http://sites.google.com/a/clos.net/mini/ulcers-gastritis-and-indigestion
Ulcers Gastritis and Indigestion Dyspepsia (Indigestion) After the Mini-Gastric Bypass (Also see Gastritis, ulcer(s), indigestion, heartburn, acid stomach, upset stomach, unsettled stomach, stomachache ..., also see Bile Reflux, Esophageal Reflux, GERD Gastro Esophageal Reflux Disease...
Example: "I had surgery on April 16th, 2008 in Vegas and I think I have gastritis. What do I need to do?"
Dyspepsia is a pain or an uncomfortable feeling, usually located in the left upper middle part of your stomach. The pain might come and go, and can be made worse by certain foods (i.e. orange juice) and can be made better by Tums, Antacids and foods like Yogurt.
Dyspepsia, Gastritis, ulcer(s), indigestion, heartburn, acid stomach, upset stomach is the most common complication seen after the Mini-Gastric Bypass. It is seen in up to 5% of MGB patients similar to the rates seen in RNY Gastric Bypass (also see: Patel, Felix, Google Ulcer+RNY) patients.
Dyspepsia/Ulcer/Gastritis can lead to devastating complications such as bleeding and/or perforation which can be life threatening.
Because of this patients undergoing MGB should be well educated about the risks of Dyspepsia/Ulcer/Gastritis after MGB and follow advice to institute interventions to decrease the risks of Dyspepsia/Ulcer/Gastritis and to aggressively treat Dyspepsia/Ulcer/Gastritis when it occurs.
I. EDUCATION and AWARENESS
All MGB patients undergo an extensive preoperative education and testing procedure designed to aide them in understanding the risks of Dyspepsia/Ulcer/Gastritis, the interventions to decrease the incidence of Dyspepsia/Ulcer/Gastritis and the treatment of Dyspepsia/Ulcer/Gastritis in MGB post operative patients.
II. PREVENTATIVE MEASURES:
The MGB like the RNY and like Aspirin can increase the risk of Dyspepsia/Ulcer/Gastritis. Fortunately we know a list of factors to avoid to decrease this risk and interventions to recommend that can decrease the incidence of ulcers and gastritis.
Factors Associated with Ulcers/Gastritis
Age
Race
Gender
Heredity
Men have twice the risk of ulcers as women. Gastric ulcers peak at age 55 - 65.
Avoid:
Smoking: Gastric mucosal integrity is maintained by an interplay of some aggressive and defensive factors controlling apoptotic cell death and cell proliferation and smoking potentiates ulcer by disturbing this balance.
Alcohol
Coffee: Coffee consumption has a positive dose-response relation with active H. Pylori infection.
NSAIDS: Aspirin, Advil, Aleve, Ibuprofen and other NSAIDs (Non-steroidal anti-inflammatory drugs)
The use of NSAIDs increases the risk of peptic ulcer 300% to 500%.
Corticosteroids
Bisphosphonates are the primary agents used to treat osteoporosis. Although these agents are generally well tolerated, serious gastrointestinal adverse events, including hospitalization for gastrointestinal bleed, may arise.
Non-nitrogenous
Non-N-containing bisphosphonates:
* Etidronate (Didronel) - 1 (potency relative to that of etidronate)
* Clodronate (Bonefos, Loron) - 10
* Tiludronate (Skelid) - 10
Nitrogenous
N-containing bisphosphonates:
* Pamidronate (APD, Aredia) - 100
* Neridronate - 100
* Olpadronate - 500
* Alendronate (Fosamax) - 500
* Ibandronate (Boniva) - 1000
* Risedronate (Actonel) - 2000
* Zoledronate (Zometa, Aclasta) - 10000
Alendronate and Naproxen Are Synergistic for Development of Gastric Ulcers
David Y. Graham, MD; Hoda M. Malaty, MD, PhD Arch Intern Med. 2001;161:107-110.
Background Both alendronate sodium use and nonsteroidal anti-inflammatory drug use are associated with gastric ulcers. The aim of this study was to investigate whether alendronate and naproxen are synergistic as causes of gastric ulcers.
Methods We performed an endoscopist-blind, randomized, crossover, single-center comparison of 10 mg/d of alendronate sodium, 500 mg of naproxen sodium twice daily, or the combination taken orally for 10 days in volunteers aged 30 years or older. Videoendoscopy was used to evaluate the presence and degree of mucosal damage to the esophagus, stomach, or duodenal bulb before and after each treatment. There was a 1- to 4-week washout between evaluations.
Results Twenty-six healthy volunteers participated (18 women and 8 men), aged 30 to 50 years. Gastric ulcers were present in 2 subjects receiving ** alendronate (8%),** in 3 receiving ** naproxen (12%),** and in 10 receiving ** both (38%) ** (P<.05 for the combination vs either drug alone).
Conclusions Both alendronate and naproxen can cause gastric ulcers. The combination appears synergistic. Alendronate should be used with caution in those who simultaneously require nonsteroidal anti-inflammatory drugs.
COX-2 Selective cyclooxygenase-2 inhibitors (rofecoxib (Vioxx®) and celecoxib ( Celebrex®))
Diet and Ulcer: What You Eat Can Affect the Stomach and Your Gut
FIBER: Higher consumption of fruits and vegetables is associated with lower risk of ulcer
Total dietary fiber intake is inversely associated with the risk of ulcer
FRESH FRUITS AND VEGETABLES:
Grape seed extract may have antioxidative functions that have preventive action in ulcer disease (Grapes and Grape Juice)
Food sourced dietary vitamin C intake may protect against H. Pylori infection and ulcer and gastric cancer
"Emphasize fruits and vegetables. A diet rich in fresh fruits and vegetables, especially those high in vitamin C and beta carotene, has been shown to help protect against" H. Pylori infection and "stomach cancer. Look for deep green and dark yellow or orange fruits and vegetables, such as Swiss chard, bok choy, spinach, cantaloupe, mango, acorn or butternut squash, and sweet potatoes. Also try to eat vegetables from the cabbage family, including broccoli, brussels sprouts and cauliflower. Lycopene, a nutrient found in tomatoes and other red fruits and vegetables such as strawberries and red bell peppers, may be a particularly powerful anti-cancer chemical." From Mayo Clinic .com
FISH OIL:
Fish oil (FO) containing omega-3 polyunsaturated fatty acids may be protective of the stomach lining and prevent gastric ulcers. Fish oil causes a statistically significant increase both in mucus and phospholipid content of the gastric mucosal barrier. Fish oil showed a potent healing-promoting effect on acute gastric erosions and ulcers induced by indomethacin and significantly enhanced the mucus content of the mucosa.
H. pylori and Peptic Ulcer
Helicobacter pylori (H. pylori) is a type of bacteria. Researchers believe that H. pylori is responsible for the majority of peptic ulcers.
"The discovery of Helicobacter pylori, a spiral bacterium which lives in the inhospitable environment of the human stomach, must rank amongst the greatest medical triumphs of the twentieth century. The bacterium was discovered by two Australian doctors, Barry Marshall and Robin Warren in 1982. It took six long years for the medical profession to begin to acknowledge the importance of Marshall and Warren’s work and the first clinical treatment trial was conducted in 1987. Over half the planet’s population is reckoned to be carrying the bacteria and an estimated 5,000,000 cases of gastric cancer and duodenal ulcer occur annually as a result of the infection. From The Institute for Optimum Nutrition"
Helicobacter pylori, Yogurt and Probiotics
Probiotics: Lactobacillus- and Bifidobacterium Yogurt can improve the efficacy of therapy of Helicobacter pylori
"Helicobacter pylori infection, a highly prevalent pathogen, is a major cause of chronic gastritis and peptic ulcer and a risk factor for gastric malignancies. Antibiotics-based H. pylori eradication treatment is 90% effective. However, it is expensive and causes side effects and antibiotic resistance. Probiotics could present a low-cost, large-scale alternative solution to prevent or decrease H. pylori colonization. A literature search of the MEDLINE database (1966-2006) has been performed selecting all in vitro, animal, and human fully published English-language studies dealing with H. pylori and probiotics.
Lactobacillus- and Bifidobacterium-containing yogurt can suppress Helicobacter pylori. In a study of 138 patients were then randomly assigned to either a yogurt-plus-quadruple therapy or a quadruple therapy-only group. The yogurt-plus-quadruple therapy group had a higher H. pylori eradication rate than did the quadruple therapy-only group (intention-to-treat analysis: 90.8% compared with 76.6%, P < 0.05). 4-wk treatment with bacteria in yogurt can decrease H. pylori loads despite antimicrobial resistance, thus improving the efficacy of quadruple therapy in eradicating residual H. pylori.
Consumption of yogurt enriched with probiotics improves the eradication rate of Helicobacter pylori in peptic ulcer patients undergoing quadruple therapy after failed triple therapy, according to a study published in the American Journal of Clinical Nutrition (83, 4:864-69, 2006).
Probiotics had an in vitro inhibitory effect on H. pylori. Animal studies demonstrated that probiotic treatment is effective in reducing H. pylori-associated gastric inflammation. Seven of 9 human studies showed an improvement of H. pylori gastritis and decrease in H. pylori density after administration of probiotics. The addition of probiotics to standard antibiotic treatment improved H. pylori eradication rates (81% vs. 71%, with combination treatment vs. H. pylori-eradication treatment alone; chi(2)test: P=0.03). Probiotic treatment reduced H. pylori therapy-associated side effects (incidence of side effects: 23% vs. 46%, with combination therapy vs. H. pylori-eradication treatment alone; chi(2)test: P=0.04).
Long-term intake of products containing probiotic strains of probiotics may have a favorable effect on H. pylori infection in humans, particularly by reducing the risk of developing disorders associated with high degrees of gastric inflammation."
Other Dietary Factors/Supplements
Green tea,
Red wine,
Flavonoids,
Broccoli sprouts,
Garlic,
Probiotics and
Flavonoids are known to inhibit H. pylori colonization, decrease gastric inflammation by inhibiting cytokine and chemokine release, and repress precancerous changes
Studies have shown that "Red wine/ grapes and green tea are able to prevent H pylori-induced gastric epithelium damage."
Garlic
Capsaicin
Investigations have revealed that chili peppers and "capsaicin" are not the cause for ulcer formation but is a healing and protective agent. In contrast to what might be expected, Capsaicin does not stimulate but inhibits acid secretion. Capsaicin stimulates alkali, mucus secretions and particularly gastric mucosal blood flow which help in prevention and healing of ulcers. Capsaicin acts by stimulating afferent neurons in the stomach and signals for protection against injury. Chili and its pungent ingredient, capsaicin, have been shown to protect against experimental gastric mucosal injury induced by various necrotizing agents such as ethanol and aspirin and stress.
Melatonin
Consider asking your Dr. about supplemental melatonin 5 milligrams every night and if having dyspepsia trying 5 milligrams three times a day for two weeks.
Melatonin, formed enzymatically from L-tryptophan, has been called "the most versatile and ubiquitous hormone molecule produced not only in all animals but also in some plants."
Melatonin is synthesized not only in the pineal gland, but also in gastrointestinal tract by enterochromaffin cells (EC) and it has a gastro-protective properties.
The enterochromaffin cells of the gastrointestinal (GI) tract secrete 400 times as much melatonin as the pineal gland.
Melatonin has been shown to act by ** scavenging free radicals,** ** protecting gut ** mucosa against various irritants and ** healing of various stomach ** and bowel lesions such as stomatitis, esophagitis, gastritis and peptic ulcer.
Melatonin is abundant in the gastrointestinal tract, has been shown to inhibit gastric acid secretion, augment Gastric Blood Flow and scavenge free radicals, resulting in the attenuation of stress-induced gastric ulcers.
Studies have shown that "nocturnal secretion of melatonin in subjects with asymptomatic infection of H. pylori is higher than in patients with ulcer-like dyspepsia and with duodenal ulcer disease.
** Lower nocturnal secretion of melatonin probably may play role in pathogenesis of upper digestive tract diseases."**
"In animal studies, melatonin protects against GI ulcerations, and randomized clinical trials suggest its efficacy in treating functional dyspepsia and irritable bowel syndrome.
Melatonin administration has been shown to protect against esophageal lesions in animals. Moreover, in a randomized, single-blind clinical trial of subjects with gastroesophageal reflux disease (GERD), the combination of melatonin with other natural supplements was found to be superior to omeprazole, a proton pump inhibitor (PPI)."
The effect of the melatonin on the life span of mice, rats and fruit flies has been studied using various approaches. It has been observed that in various strains of mice long-term administration of melatonin was followed by an increase in the mean life span.
In rats, melatonin treatment increased survival of male and female rats.
Melatonin and its precursor Trptophan significantly attenuate gastric mucosal lesions induced by aspirin. Melatonin and L-tryptophan, accelerate ulcer healing probably via interaction with MT2 receptors; this ulcer healing action is caused by an enhancement by melatonin of the microcirculation at the ulcer margin possibly mediated by COX-derived PG and NO because of overexpression of iNOS and gastrin, which exhibits trophic activity in the gastric mucosa and calcitonin gene related peptide (CGRP), released from sensory nerves, may also contribute to the ulcer healing action of melatonin.
Due to its anti-inflammatory and anti-oxidant properties, melatonin may be one of the most efficient protective factors preventing the development of acute gastric damage and accelerating healing of chronic gastric ulcers probably due to reduction in proinflammatory cytokine production, scavenging of the radical oxygen species and activation of COX-PG and NOS-NO systems as well as stimulating the afferent sensory nerves in the brain-gut axis.
Treatment
Avoid Factors that Increase the Risk of Ulcers/Gastritis (See Above)
Utilize Factors/Supplements that Have Been Shown to Be Gastro-Protective (See Above)
Medical Therapy:
Antacids
(Tums Calcium Carbonate Oral, Adult Min/Max Dose: 400.0mg/5200.0mg
Antacids are attractive for rapid pain relief
Usual Adult Dose for Gastric Ulcer:
1250 to 3750 mg/day in 2 to 4 divided doses. This dose may be increased as needed and tolerated to decrease the abdominal discomfort.
Gaviscon
"In addition to the acid-neutralizing ingredients found in Gaviscon®, all Gaviscon® products contain "alginate". When chewed (Gaviscon tablets) or swallowed (Gaviscon liquid), the combination of the alginic acid and bicarbonate creates a foam barrier or "raft" that floats on the stomach acid. This raft foam barrier helps reduce the number of reflux episodes and provides longer lasting action against "heartburn" than other antacid products." From Gavison.com
* REGULAR-STRENGTH LIQUID
The usual dosage is 1 or 2 tablespoonfuls taken 4 times a day. Do not take more than 8 tablespoonfuls each 24 hours.
* EXTRA-STRENGTH LIQUID
The usual dosage is 2 to 4 teaspoonfuls taken 4 times a day. Do not take more than 16 teaspoonfuls each 24 hours.
* REGULAR AND EXTRA-STRENGTH TABLETS
The usual dosage is 2 to 4 tablets taken 4 times a day. Take the tablets after meals and at bedtime, or as needed. Do not take more than 16 tablets each 24 hours.
Metoclopramide
"Antiemetic use: Metoclopramide is commonly used to treat nausea and vomiting (emesis).
Prokinetic use: Metoclopramide increases peristalsis of the jejunum and duodenum, increases tone and amplitude of gastric contractions, and relaxes the pyloric sphincter and duodenal bulb. These prokinetic effects make metoclopramide useful in the treatment of gastric stasis (e.g. after gastric surgery or diabetic gastroparesis), It is also used in gastroesophageal reflux disease (GERD/GORD)." see Wikpedia Metaclopromide.
The recommended metoclopramide dosage for people being treated for GERD is 10 or 15 mg four times daily.
Proton Pump Inhibitors (PPIs)
Esomeprazole (Nexium®), Lansoprazole (Prevacid®), Omeprazole (Prilosec®), Pantoprazole (Protonix®), Rabeprazole (Aciphex®)
When dyspepsia/ulcer/gastritis occurs following MGB the etiology is almost always a marginal ulcer or gastritis. We routinely recommend Avoiding inciting factors, using gastroprotective supplements (see above) and the use of initial trial of high dose PPI (Proton Pump Inhibitors) usually over the counter Prilosec 20 mg tablets, 2 tabs three times a day for 2 weeks.
Table 1
Proton Pump Inhibitors
Adult Maximum Daily Acute Dose
DRUG
MAXIMUM DOSE
Esomeprazole
(Nexium®)
erosive esophagitis: 40 mg/day
GERD: 20 mg/day
H. pylori eradication: 40 mg/day
Lansoprazole
(Prevacid®)
duodenal ulcer: 15 mg/day
gastric ulcer: 30 mg/day
gastric ulcer associated with NSAIDs: 30 mg/day
GERD: 15 mg/day
H. pylori eradication:
triple therapy – 60 mg/day
dual therapy – 90 mg/day
hypersecretory conditions: 180 mg/day
erosive esophagitis: 30 mg/day
Omeprazole
(Prilosec®)
duodenal ulcer: 20 mg/day
gastric ulcer: 40 mg/day
H. pylori eradication:
triple therapy – 40 mg/day in divided doses
dual therapy – 40 mg/day
hypersecretory conditions: 360 mg/day
GERD, esophagitis: 20 mg/day
upper GI bleeding risk reduction (Zegerid® only): 40 mg/day
Pantoprazole
(Protonix®)
erosive esophagitis associated with GERD: 40 mg/day
hypersecretory conditions: 240 mg/day
Rabeprazole
(Aciphex®)
duodenal ulcer: 20 mg/day
hypersecretory conditions: 120 mg/day
H. pylori eradication: 40 mg/day
GERD: 20 mg/day
erosive esophagitis: 20 mg/day
From MEDICAID DRUG USE REVIEW CRITERIA FOR OUTPATIENT USE
Safety note: A few studies have linked PPIs to a higher risk of pneumonia and infection with a bacterium called C. difficile, and in December 2006 a study found that long–term use of PPIs may be associated with an increased risk of hip fractures. Talk with your doctor about these risks, especially if you must take a PPI over a long period of time.
People aged 65 and over, and people with chronic medical conditions, who take a PPI should get vaccinated against pneumonia and get a flu shot every year.
Bile Reflux Gastritis.
The Mini-Gastric Bypass is a Billroth II Loop Gastrojejunostomy, that is to say the stomach is connected to the side of the small intestine, to the "loop" of small bowel. Many physicians fear the risk that this will lead to a very high incidence of bile reflux gastritis. Bile is a normal part of the digestion in the gut. It is poweful detergent and can irritate the stomach, especially if there is some acid damage to the lining of the stomach from an acid ulcer or gastritis. In most MGB cases anti-ACID therapy resolves the ulcers and gastritis that follows the surgery but in some cases attention to the bile can be helpful as well.
Several treatments have been found to aide in decreaseing the irritaion caused by the detergent bile in the stomach. Lowered recirculation of bile acids results in utilization of cholesterol to synthesize bile acid and reduced fat absorption.
1. Actigall (ursodeoxycholic acid)
which changes bile acid composition. This is less irritating than the patient's own bile acids on the gastric remnant. In a study by Stefaniwsky AB, Tint GS, Speck J, Shefer S, Salen G. "12 patients with symptomatic alkaline (bile) reflux gastritis were treated for 1 mo with placebo and for 1 mo with ursodeoxycholic acid, 1000 mg/day. Before treatment, all patients were symptomatic and manifested epigastric pain, nausea, and bilious vomiting. The gastric mucosa was erythematous, friable, and bile stained, and the histology revealed chronic inflammation. No significant change in symptoms was noted during administration of placebo. In contrast, ursodeoxycholic acid treatment resulted in a profound decrease in the intensity and frequency of pain and almost abolished nausea and vomiting. During bile acid therapy the proportion of ursodeoxycholic acid in gastric bile rose to 50% of total bile acids, whereas cholic and deoxycholic acids decreased and chenodeoxycholic acid remained unchanged."
2. Cholestyramine
Cholestyramine resin adsorbs 90+% of all bile salts tested. The addition of cholestyramine to duodenal contents inhibits their ulcerogenic action of bile in the stomach of rats challenged by bile and acid. "Cholestyramine protects the gastric mucosa from ulceration by blocking the barrier breaking action of bile salts" The recommended maintenance dose for all QUESTRAN powdered products is 2 to 4 packets or scoopfuls daily (8-16 grams anhydrous cholestyramine resin) divided doses. The recommended starting dose is 1 single-dose packet or 1 level scoopful, 1 to 2 times daily.
3. Fiber
Citrucel (cellulose) has been reported as the most active in capturing and inactivating biliary acids: this constitutes a cytoprotective action on the stomach mucosa. In a study by Paniagua M, Piñol F, and Cendan A. "50 patients with bile reflux gastritisreceived cellulose 5 g/day during three months. The results showed that total biliary acids in gastric content decreased at the end of treatment mostly in patients treated with cellulose..." "there was a an excellent response in pain, vomiting and heartburn after cellulose treatment."
4. Aluminum Containing Antacids
Aluminum Containing Antacids can bind bile acids.
Many antacids are available today that contain aluminum hydroxide.
* Aluminum carbonate (Basaljel)
* Aluminum hydroxide (ALternaGEL, Alu-Cap, Alu-Tab, Amphojel, Dialume, Nephrox)
* Aluminum hydroxide/magnesium carbonate (Duracid)
* Aluminum hydroxide/magnesium hydroxide (Alamag, Almacone, Aludrox, Gaviscon Liquid, Gelusil, Kudrox, Maalox, Magalox, Mintox, Mylanta, Rulox)
* Aluminum hydroxide/magnesium hydroxide/calcium carbonate (Tempo)
* Aluminum hydroxide/magnesium trisilicate (Alenic Alka, Gaviscon, Genaton, Foamicon)
5. Sucralfate Carafate
A drug used to treat ulcers. It adheres to proteins at the ulcer site and forms a protective coating over the ulcer. Sucralfate also binds bile acids and may be useful in treat bile reflux gastritis. The recommended adult oral dosage for duodenal ulcer is 1 g four times per day on an empty stomach.
6. Green and Leafy Vegetables
In a study by Kahlon TS, Chiu MC, Chapman MH at Western Regional Research Center, USDA-ARS, Albany, CA found that "relative to cholestyramine, in vitro bile acid binding was for the collard greens, kale, and mustard greens, 13%; broccoli, 10%; Brussels sprouts and spinach, 8%; green bell pepper, 7%; and cabbage, 5%.
"Steam cooking significantly improved the bile acid binding of collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage compared with previously observed bile acid binding values for these vegetables raw (uncooked).
"Inclusion of steam-cooked collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage in our daily diet as health-promoting vegetables should be emphasized. These green/leafy vegetables, when consumed regularly after steam cooking, would lower the risk of cardiovascular disease and cancer, advance human nutrition research, and improve public health."
Other Gastroprotective Agents:
Amino Acids:
7. Taurine
Protective effect of taurine against alendronate-induced gastric damage in rats.
Sener G, Sehirli O, Cetinel S, Midillioğlu S, Gedik N, Ayanoğlu-Dülger G. Fundam Clin Pharmacol. 2005 Feb;19(1):93-100.
Alendronate (Fosamax) causes serious gastrointestinal adverse effects.
The aim of this study was to investigate whether taurine, a semi-essential amino acid and an antioxidant, improves the alendronate-induced gastric injury.
Rats were administered 20 mg/kg Alendrolate by gavage for 4 days, either alone or following treatment with Taurine (50 mg/kg, i.p.).
On the last day of treatment, following drug administration, pylorus ligation was performed and 2 h later, rats were killed and stomachs were removed.
Gastric acidity and tissue ulcer index values, lipid peroxidation and glutathione (GSH) levels, myeloperoxidase (MPO) activity as well as the histologic appearance of the stomach tissues were determined.
Chronic oral administration of Alendrolate induced significant gastric damage, increasing lipid peroxidation, MPO activity and collagen content, as well as decreasing tissue GSH levels.
Treatment with Taurine prevented the damage and also the changes in biochemical parameters.
Findings of the present study suggest that Alendrolate induces oxidative gastric damage by a local irritant effect, and that Taurine ameliorates this damage by its antioxidant and/or membrane-stabilizing effects.
Modulation of indomethacin-induced gastric injury by spermine and taurine in rats.
Motawi TK, Abd Elgawad HM, Shahin NN. J Biochem Mol Toxicol. 2007;21(5):280-8.
This study investigated the involvement of neutrophil infiltration, nitric oxide (NO) generation, and oxidative stress in indomethacin-induced ulcer and the possible gastroprotective potentials of taurine, known for antioxidant effects.
Rats were allocated into a normal control group, ulcer control group (received a single dose of indomethacin 40 mg-kg p.o.), and ulcer group pretreated with taurine (250 mg-kg i.p. for three consecutive days before ulcer induction).
6 h after indomethacin administration, and the gastric juice, serum, and mucosal tissue were used for gastric injury evaluation.
Taurine significantly ameliorated the indomethacin-induced gastric lesions in glandular mucosa.
Taurine was able to decrease the elevated levels of gastric myeloperoxidase, conjugated diene, and serum NO. The lowered tissue NO content was markedly elevated by taurine.
The antioxidant action of taurine was illustrated by restoration of the depressed content of glutathione, normalization of the inhibited activities of glutathione reductase, and superoxide dismutase.
These results suggest that taurine confers significant gastroprotection against indomethacin-induced gastric injury
Effect of taurine on ulcerogenic response and impaired ulcer healing induced by monochloramine in rat stomachs.
Kato S, Umeda M, Takeeda M, Kanatsu K, Takeuchi K. Aliment Pharmacol Ther. 2002 Apr;16 Suppl 2:35-43.
BACKGROUND: It is well known that neutrophil-derived hypochlorous acid interacts with ammonia (NH4OH) to generate monochloramine (NH2Cl) and that NH2Cl irritates the gastric mucosa and impairs ulcer healing.
AIM: To examine the effect of taurine, a hypochlorous acid scavenger, on the mucosal ulcerogenic and the impaired healing response induced by NH2Cl in rat stomachs, in comparison with those of methionine and glycine.
METHODS AND RESULTS: Under anaesthesia, oral administration of NH2Cl (120 mmol/L) produced severe lesions in male Sprague-Dawley rat stomachs.
Taurine (10-100 mg/kg) given p.o. 30 min prior to NH2Cl dose-dependently prevented these lesions in response to NH2Cl.
This action was mimicked by methionine (3-30 mg/kg) but not by glycine (10-100 mg/kg).
Under urethane anaesthesia, mucosal exposure to NH4OH (120 mmol/L) caused a marked reduction of potential difference (PD) in the ex vivo chambered stomachs after induction of ischaemia, resulting in severe lesions.
These ulcerogenic and PD responses by NH4OH plus ischaemia were also mitigated by taurine and methionine, but not glycine, applied to the chamber 20 min before the onset of NH4OH plus ischaemia.
Moreover, oral administration of 100% ethanol produced severe haemorrhagic lesions in rat stomachs, all of which rapidly healed within 7 days after lesion induction.
Daily administration of NH2Cl (20 mmol/L) significantly delayed the healing of these lesions, but recovery of this impaired healing response was obtained by concurrent administration of taurine.
Both taurine and methionine showed a potent scavenging effect against NH2Cl in vitro.
CONCLUSIONS: (1) NH2Cl generated either exogenously or endogenously damages the gastric mucosa and impairs the healing response;
(2) taurine exerts a prophylactic effect against the deleterious effects of NH2Cl, mainly due to its scavenging action against NH2Cl; and
(3) this effect of taurine may be useful for treatment of gastritis associated with Helicobacter pylori infection.
Effect of taurine on gastric oxidative stress and hemorrhagic erosion in brain ischemic rats.
Hung CR. Chin J Physiol. 2006 Jun 30;49(3):152-9.
The effect of taurine on gastric hemorrhage and mucosal erosion in the brain ischemia is unknown.
The aim of the research was to study the involvement of gastric oxidative stress in hemorrhagic erosion produced in brain ischemia rats.
The protective effect of taurine on this erosion model was evaluated.
Male Wistar rats were deprived of food for 24 h. Under chloral hydrate -anesthesia, bilateral carotid artery ligation was performed 12, 18 and 21 h after removal of food to obtain 12, 6 and 3 h of brain ischemia duration.
The pylorus and carotid esophagus of rats also were ligated. The stomachs were then irrigated for 3 h with normal saline or simulated gastric juice containing 100 mM HCl plus 17.4 mM pepsin and 54 mM NaCl. The stomach was dissected. Gastric samples were harvested. The rat brain was dissected for examination of ischemia by using triphenyltetrazolium chloride staining method.
Changes in gastric ulcerogenic parameters, such as decreased mucosal GSH level as well as enhanced gastric acid back-diffusion, mucosal lipid peroxide generation, histamine concentration, luminal hemoglobin content and mucosal erosion in gastric samples were measured.
The results indicated that bilateral carotid artery ligation could produce severe brain ischemia in rats.
Moreover, a brain ischemia- duration-dependent exacerbation of various ulcerogenic parameters also was observed in these rats.
Intraperitoneal taurine (0-300 mg/kg) dose-dependently ameliorated gastric oxidative stress and hemorrhagic erosion in brain ischemia rats.
Taken together, brain ischemia could produce gastric oxidative stress and hemorrhagic erosions that was ameliorated by taurine through stimulation of GSH biosynthesis and inhibition of oxidative stress.
Taurine ameliorates water avoidance stress-induced degenerations of gastrointestinal tract and liver. Zeybek A, Ercan F, Cetinel S, Cikler E, Sağlam B, Sener G. Dig Dis Sci. 2006 Oct;51(10):1853-61.
We investigated the role of taurine, is a potent free radical scavenger, on water avoidance stress-induced degeneration of the gastric, ileal, and colonic mucosa and liver parenchyma.
Wistar rats were exposed to chronic water avoidance stress (water avoidance stress group) 2 hr daily for 5 days. After exposing animals to chronic water avoidance stress (water avoidance stress + taurine group), 50 mg/kg taurine was injected IP for 3 days. Control animals received vehicle solution only.
The stomach, ileum, colon, and liver samples were investigated under light microscope for histopathologic changes.
To demonstrate the topography of the luminal mucosa of the stomach, ileum, and colon, scanning electron microscope was used and for hepatocyte ultastructure transmission electron microscope was used. Malondialdehyde (MDA, a biomarker of oxidative damage) and glutathione (GSH, a biomarker of protective oxidative injury) levels were also determined in all tissues.
In the water avoidance stress group, the stomach epithelium showed ulceration in some areas, dilatations of the gastric glands, and degeneration of gastric glandular cells; prominent congestion of the capillaries was apparent.
In the water avoidance stress group, severe vascular congestion was observed along with degeneration of ileal and colonic epithelium.
Prominent vascular congestion and dilated sinusoids, activated Kupffer cells, dilated granular endoplasmic reticulum membranes, and focal pyknotic nuclei were observed in liver parenchyma. MDA levels (stomach, P < 0.01; ileum, colon, and liver P < 0.05) were increased and GSH levels (P < 0.01) were decreased in all tissues in the water avoidance stress group compared with the control group.
The morphology of gastric, ileal, and colonic mucosa and liver parenchyma in the water avoidance stress + taurine group (stomach and ileum, P < 0.05; colon and liver, P < 0.01) showed a significant amelioration when compared to the water avoidance stress group. Increased MDA and decreased GSH levels in the water avoidance stress group were ameliorated with taurine treatment.
Based on the results, taurine supplementation effectively attenuates the oxidative damage of gastrointestinal mucosa and liver because of water avoidance stress induction possibly by its antioxidant effects.
Sunday, July 19, 2009
Gallstones: Prevention
Scand J Gastroenterol Suppl. 1995;212:63-78.Links
Cholesterol gallstone formation in man and potential treatments of the gallbladder motility defect.
Portincasa P, Stolk MF, van Erpecum KJ, Palasciano G, van Berge-Henegouwen GP.
Dept. of Gastroenterology, University Hospital Utrecht, The Netherlands.
Cholelithiasis affects 10-15% of the adult population in Western society, and about 75% of gallstones are of cholesterol type. Hepatic hypersecretion of cholesterol with the formation of instable cholesterol-rich vesicles in bile, an imbalance between nucleation-inhibiting and nucleation-promoting proteins with further aggregation of cholesterol crystals in a gallbladder with a motility defect (stasis), all play a role in the pathogenesis of cholesterol gallstones. Experimental animal models suggest that gallstone formation can be prevented by improving gallbladder emptying. Thus, a better understanding of the causes underlying the impaired gallbladder motor function in patients with gallstones might lead to the selection of therapeutic approaches for those individuals who are at increased risk for the formation or recurrence of gallstones. The present article focuses on current concepts and theories on the pathogenesis of cholesterol gallstones with emphasis on the gallbladder motility defect. Several treatment strategies for the correction of gallbladder hypomotility are also discussed.
Aliment Pharmacol Ther. 2000 May;14 Suppl 2:39-47. Links
Review: pathogenesis of gallstones.
Dowling RH.
Gastroenterology Unit, Guy's, King's & St Thomas' School of Medicine, London, UK. h.dowling@umds.ac.uk
The aim of this article is to review selected aspects of the pathogenesis of cholesterol-rich, gall-bladder stones (GBS)--with emphasis on recent developments in biliary cholesterol saturation, cholesterol microcrystal nucleation, statis within the gall-bladder and, particularly, on the roles of intestinal transit and altered deoxycholic acid (DCA) metabolism, in GBS development. In biliary cholesterol secretion, transport and saturation, recent developments include evidence in humans and animals, that bile lipid secretion is under genetic control. Thus in mice the md-2 gene, and in humans the MDR-3 gene, encodes for a canalicular protein that acts as a 'flippase' transporting phospholipids from the inner to the outer hemi-leaflet of the canalicular membrane. In the absence of this gene, there is virtually no phospholipid or cholesterol secretion into bile. Furthermore, when inbred strains of mice that have 'lith genes' are fed a lithogenic diet, they become susceptible to high rates of GBS formation. The precipitation/nucleation of cholesterol microcrystals from supersaturated bile remains a critical step in gallstone formation. methods of studying this phenomenon have now been refined from the original 'nucleation time' to measurement of cholesterol appearance/detection times, and crystal growth assays. Furthermore, the results of recent studies indicate that, in addition to classical Rhomboid-shape monohydrate crystals, cholesterol can also crystallize, transiently, as needle-, spiral- and tubule-shaped crystals of anhydrous cholesterol. A lengthy list of promoters, and a shorter list of inhibitors, has now been defined. There are many situations where GB stasis in humans is associated with an increased risk of gallstone formation--including iatrogenic stone formation in acromegalic patients treated chronically with octreotide (OT). As well as GB stasis, however, OT-treated patients all have 'bad' bile which is supersaturated with cholesterol, has excess cholesterol in vesicles, rapid microcrystal mulceation times and a two-fold increase in the percentage DCA in bile. This increase in the proportion of DCA seems to be due to OT-induced prolongation of large bowel transit time (LBTT). Thus LBTT is linearly related to (i) the percentage of DCA in serum; (ii) the DCA pool size; and (III) the DCA input or 'synthesis' rate. Furthermore, the intestinal prokinetic, cisapride, counters the adverse effects of OT on intestinal transit, and 'normalizes' the percentage of DCA in serum/bile. Patients with spontaneous gallstone disease also have prolonged LBTTs, more colonic gram-positive anaerobes, increased bile acid metabolizing enzymes and higher intracolonic pH values, than stone-free controls. Together, these changes lead to increased DCA formation, solubilization and absorption, Thus, in addition to the 'lithogenic liver' and 'guilty gall-bladder' one must now add the 'indolent intestine' to the list of culprits in cholesterol gallstone formation.
Liver Int. 2008 Aug;28(7):935-47. Links
Comment in:
Liver Int. 2008 Aug;28(7):906-7.
Ezetimibe prevents cholesterol gallstone formation in mice.
Zúñiga S, Molina H, Azocar L, Amigo L, Nervi F, Pimentel F, Jarufe N, Arrese M, Lammert F, Miquel JF.
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
BACKGROUND: Intestinal cholesterol absorption may influence gallstone formation and its modulation could be a useful therapeutic strategy for gallstone disease (GSD). Ezetimibe (EZET) is a cholesterol-lowering agent that specifically inhibits intestinal cholesterol absorption. AIMS: To test whether EZET can prevent gallstone formation in mice. METHODS/RESULTS: Gallstone-susceptible C57BL/6 inbred mice were fed control and lithogenic diets with or without simultaneous EZET administration. Lithogenic diet increased biliary cholesterol content and secretion, and induced sludge or gallstone formation in 100% of the animals. EZET administration reduced intestinal cholesterol absorption by 90% in control animals and by 35% in mice receiving the lithogenic diet. EZET prevented the appearance of cholesterol crystals and gallstones. In addition, mice fed the lithogenic diet plus EZET exhibited a 60% reduction in biliary cholesterol saturation index. Of note, EZET treatment caused a significant increase in bile flow (+50%, P<0.01) as well as bile salt, phospholipid and glutathione secretion rates (+60%, +44% and +100%, respectively, P<0.01), which was associated with a moderately increased expression of hepatic bile salt transporters. In addition, relative expression levels of Nieman-Pick C1 like 1 (NPC1L1) in the enterohepatic axis in humans were assessed. Expression levels of NPC1L1 were 15- to 30-fold higher in the duodenum compared with the liver at transcript and protein levels, respectively, suggesting preferential action of EZET on intestinal cholesterol absorption in humans. CONCLUSIONS: In a murine model of GSD, EZET prevented gallstone formation by reducing intestinal cholesterol absorption and increasing bile salt-dependent and -independent bile flow. EZET could be useful in preventing GSD disease in susceptible patients.
Gastroenterology. 2008 Jun;134(7):2101-10. Epub 2008 Mar 10. Links
Effect of ezetimibe on the prevention and dissolution of cholesterol gallstones.
Wang HH, Portincasa P, Mendez-Sanchez N, Uribe M, Wang DQ.
Department of Medicine, Liver Center and Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
BACKGROUND & AIMS: Cholesterol cholelithiasis is one of the most prevalent and most costly digestive diseases in developed countries and its incidence has increased markedly in Asian countries owing to the adoption of Western-type dietary habits. Because animal experiments showed that high efficiency of intestinal cholesterol absorption contributes to gallstone formation, we explored whether the potent cholesterol absorption inhibitor ezetimibe could prevent gallstones and promote gallstone dissolution in mice and reduce biliary cholesterol content in human beings. METHODS: Male gallstone-susceptible C57L mice were fed a lithogenic diet and concomitantly administered with ezetimibe at 0, 0.8, 4, or 8 mg/kg/day for 8 or 12 weeks. Gallbladder biles and gallstones were examined by microscopy. Gallbladder emptying in response to cholecystokinin octapeptide was measured gravimetrically. Biliary lipid outputs were analyzed by physical-chemical methods. Cholesterol absorption efficiency was determined by fecal dual-isotope ratio and mass balance methods. Lipid changes in gallbladder biles of gallstone patients vs overweight subjects without gallstones were examined before (day 0) and at 30 days after ezetimibe treatment (20 mg/day). RESULTS: Ezetimibe prevented gallstones by effectively reducing intestinal cholesterol absorption and biliary cholesterol secretion, and protected gallbladder motility function by desaturating bile in mice. Treatment with ezetimibe promoted the dissolution of gallstones by forming an abundance of unsaturated micelles. Furthermore, ezetimibe significantly reduced biliary cholesterol saturation and retarded cholesterol crystallization in biles of patients with gallstones. CONCLUSIONS: Ezetimibe is a novel approach to reduce biliary cholesterol content and a promising strategy for preventing or treating cholesterol gallstones by inhibiting intestinal cholesterol absorption.
Hepatology. 1992 Oct;16(4):960-7.Links
Dietary N-3 polyunsaturated fatty acids decrease biliary cholesterol saturation in gallstone disease.
Berr F, Holl J, Jüngst D, Fischer S, Richter WO, Seifferth B, Paumgartner G.
Department of Medicine II, Klinikum Grosshadern, University of Munich, Germany.
Because fatty acid composition of biliary phospholipids influences cholesterol secretion into bile, we investigated whether replacement of n-1 monounsaturated or n-6 polyunsaturated fatty acids with n-3 polyunsaturated fatty acids in biliary phosphatidylcholines reduces supersaturation with cholesterol and prevents precipitation of cholesterol crystals in bile of gallstone patients. Seven patients with radiolucent gallstones in functioning gallbladders were studied before (control) and after 5 wk of dietary supplementation with marine fish oil (11.3 gm/day = 3.75 gm n-3 polyunsaturated fatty acids/day). Duodenal bile was collected for analysis during intravenous infusion of cholecystokinin. Gallbladder emptying in response to cholecystokinin was comparable before and during intake of n-3 polyunsaturated fatty acids. Intake of n-3 polyunsaturated fatty acids increased (p less than 0.001) the fractions of eicosapentaenoic and docosahexaenoic acids and decreased the fractions of linoleic (p less than 0.001) and arachidonic acids (p less than 0.02) in biliary phospholipids. Concomitantly, the molar ratio of cholesterol to phospholipids decreased (-19%; p less than 0.05). As a consequence, the cholesterol saturation index was reduced by -25% (p = 0.01), from 1.60 +/- 0.44 to 1.24 +/- 0.38. However, in vitro nucleation time of duodenal bile was not prolonged. The decrease in cholesterol saturation was not sufficient to prevent nucleation of cholesterol crystals in bile of gallstone patients. In conclusion, our data suggest that cholesterol saturation can be influenced by the fatty acid composition of the phosphatidylcholines secreted in bile.
Cas Lek Cesk. 2007;146(1):24-34.Links
[Effect of hypolipidemic treatment on the composition of bile and the risk or cholesterol gallstone disease]
[Article in Czech]
Zák A, Zeman M, Hrubant K, Vecka M, Tvrzická E.
IV interní klinika 1. LF UK a VFN, Praha. azak@vfn.cz
Obesity, diabetes mellitus type 2 and dyslipidemia, characterized by hypertriglyceridemia and low HDL-cholesterol levels, are risk factors for cholesterol gallstone disease. The common denominator of above-mentioned states is insulin resistance. Hypolipidemic treatment significantly influences not only the biliary lipid composition, but also other etiopathogenetic mechanisms of the disease. Three principal defects are involved in gallstone formation - cholesterol supersaturation, accelerated nucleation, and gallbladder dysmotility. The degree of cholesterol saturation in gallbladder bile is the most important predictor of cholesterol crystal formation. Cholesterol, lecithin and bile acids are the major components in bile. According to the molar ratios of the three main components, simple or mixed micelles, unstable unilamellar or multilamellar vesicles are formed in the bile. The cholesterol supersaturation of the gallbladder bile and cholesterol crystal formation from the unstable multilamellar vesicles initiates the onset of cholesterol cholelithiasis. The pool of unesterified cholesterol is the source for VLDL synthesis; together with HDL-cholesterol, it is also the source for cholesterol secretion into the bile. The main metabolic products of cholesterol degradation are bile acids, which are synthesized predominantly from LDL-cholesterol. The rate of the production of primary bile acids is principally regulated by cholesterol 7alpha-hydroxylase (CYP7A 1). The treatment of dyslipidemia with niacin and resins does not influence the saturation of bile with cholesterol or the incidence of cholelithiasis. The effects of ezetimibe in human patients with the respect of cholesterol cholelithiasis have not been published. The fibrate treatment is associated with increased cholesterol saturation of bile due to inhibition of CYP7A1 activity, enhanced flux of cholesterol via HDL and increased secretion of cholesterol into bile. The clinical studies describe cholesterol supersaturation in bile and increased frequency of cholelithiasis as well. The administration of pravastatin and simvastatin led to reduced cholesterol saturation indexes. The patients with endogenous hypertriglyceridemia and low HDL-cholesterol being administered with polyunsaturated fatty acids of n-3 family had decreased cholesterol concentration in bile. Other authors described beneficial effect of fish oil on the biliary cholesterol nucleation time, improvement of gallbladder sensitivity to cholecystokinin and the prevention of cholesterol gallstone formations caused by rapid weight loss.
Surgery. 2007 Aug;142(2):228-33. Links
Ezetimibe ameliorates cholecystosteatosis.
Mathur A, Walker JJ, Al-Azzawi HH, Lu D, Swartz-Basile DA, Nakeeb A, Pitt HA.
Department of Surgery, Indiana University School of Medicine, Indianapolis, Ind, USA.
BACKGROUND: Cholecystosteatosis is the accumulation of gallbladder wall fats leading to decreased gallbladder emptying. Ezetimibe inhibits intestinal fat absorption and prevents murine gallstone formation. However, the influence of ezetimibe on gallbladder emptying and cholecystosteatosis has not been studied. Therefore, we tested the hypothesis that ezetimibe would improve gallbladder motility by preventing the buildup of fats in the gallbladder wall. METHODS: Forty lean female mice were fed either a control diet or a lithogenic diet for 6 weeks. Half of the mice on each diet received ezetimibe. At 11 weeks of age, all mice were fasted overnight and underwent gallbladder ultrasonography to determine ejection fraction. One week later, the mice were fasted and underwent cholecystectomy. Bile was examined for cholesterol crystals. The gallbladders were snap-frozen for lipid analysis. RESULTS: The lithogenic diet significantly (P < 0.05) increased serum cholesterol, biliary crystals, gallbladder wall cholesterol and cholesterol/phospholipid ratio, and decreased gallbladder ejection fraction. All of these abnormalities were reversed (P < 0.05) by the addition of ezetimibe to the diet. CONCLUSIONS: These data suggest that ezetimibe lowers serum cholesterol, prevents biliary crystals, and normalizes gallbladder wall fat and function. We conclude that ezetimibe ameliorates cholecystosteatosis and may be an effective agent for gallstone prevention.
Atherosclerosis. 2008 May;198(1):77-84. Epub 2007 Dec 3. Links
Inhibition of intestinal absorption of cholesterol by ezetimibe or bile acids by SC-435 alters lipoprotein metabolism and extends the lifespan of SR-BI/apoE double knockout mice.
Braun A, Yesilaltay A, Acton S, Broschat KO, Krul ES, Napawan N, Stagliano N, Krieger M.
Department of Biology, Massachusetts Institute of Technology, Building 68-483, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
SR-BI/apoE double knockout (dKO) mice exhibit many features of human coronary heart disease (CHD), including hypercholesterolemia, occlusive coronary atherosclerosis, cardiac hypertrophy, myocardial infarctions, cardiac dysfunction and premature death. Ezetimibe is a FDA-approved, intestinal cholesterol absorption inhibitor that lowers plasma LDL cholesterol in humans and animals and inhibits aortic root atherosclerosis in apoE KO mice, but has not been proven to reduce CHD. Three-week-ezetimibe treatment of dKO mice (0.005% (w/w) in standard chow administered from weaning) resulted in a 35% decrease in cholesterol in IDL/LDL-size lipoproteins, but not in VLDL- and HDL-size lipoproteins. Ezetimibe treatment significantly reduced aortic root (57%) and coronary arterial (68%) atherosclerosis, cardiomegaly (24%) and cardiac fibrosis (57%), and prolonged the lives of the mice (27%). This represents the first demonstration of beneficial effects of ezetimibe treatment on CHD. The dKO mice were similarly treated with SC-435 (0.01% (w/w)), an apical sodium codependent bile acid transporter (ASBT) inhibitor, that blocks intestinal absorption of bile acids, lowers plasma cholesterol in animals, and reduces aortic root atherosclerosis in apoE KO mice. The effects of SC-435 treatment were similar to those of ezetimibe: 37% decrease in ILD/LDL-size lipoprotein cholesterol and 57% prolongation in median lifespan. Thus, inhibition of intestinal absorption of either cholesterol (ezetimibe) or bile acids (SC-435) significantly reduced plasma IDL/LDL-size lipoprotein cholesterol levels and improved survival of SR-BI/apoE dKO mice. The SR-BI/apoE dKO murine model of atherosclerotic occlusive, arterial CHD appears to provide a useful system to evaluate compounds that modulate cholesterol homeostasis and atherosclerosis.
Hepatology. 2000 Sep;32(3):455-60. Links
Comment in:
Hepatology. 2000 Sep;32(3):670-1.
Melatonin prevents pigment gallstone formation induced by bile duct ligation in guinea pigs.
Shiesh SC, Chen CY, Lin XZ, Liu ZA, Tsao HC.
Department of Medical Technology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China. hsieh@mail.ncku.edu.tw
Free radical-mediated oxidative stress has been implicated in the genesis of gallstone in vitro. This study was designed to examine the oxidative stress changes during pigment gallstone formation and to investigate whether melatonin (MLT) could act as a chemopreventive agent for cholelithiasis in a guinea pig model. The common bile duct of guinea pigs was ligated with or without MLT pretreatment. Animals were studied on day 7, 9, 12, and 14 after surgery. Stone and/or sludge developed in ligated guinea pigs without MLT. Fourier transform infrared spectra of the sludge showed the presence of calcium bilirubinate, whose peak height per milligram of sludge gradually increased with time after ligation. Total antioxidant activity (TAA) in bile of guinea pigs at day 14 after ligation reduced to one third of the level in sham-operated controls (P <.001). In addition, the bile of ligated guinea pigs had increased pH (P <.001), bile salts (P <.01), and malondialdehyde (MDA) (P <.05), compared to sham controls. Pretreatment of guinea pigs with MLT at a dose of 1,000 microg/kg significantly decreased the incidence of pigment gallstone formation at day 14 after ligation, as compared to no pretreatment (0/7 vs. 8/10). MLT also reverted the ligation-induced changes in biliary bile salts, pH, MDA, and TAA to control levels. These in vivo findings support a causative role of oxidative stress in the bile duct ligation-induced pigment gallstone formation. Antioxidants may prove useful in preventing pigment gallstone formation in humans.
J Physiol Pharmacol. 2007 Sep;58(3):381-405. Links
Localization and biological activities of melatonin in intact and diseased gastrointestinal tract (GIT).
Konturek SJ, Konturek PC, Brzozowska I, Pawlik M, Sliwowski Z, Cześnikiewicz-Guzik M, Kwiecień S, Brzozowski T, Bubenik GA, Pawlik WW.
Department of Physiology, Jagiellonian University Medical College, Cracow, Poland. mpkontur@cyf-kr.edu.pl
Melatonin (MT), an indole formed enzymatically from L-trytophan (Trp), was first discovered in the bovine pineal gland in 1958 by Lerner et al. Melatonin is the most versatile and ubiquitous hormonal molecule produced not only in the pineal gland but also in various other tissues of invertebrates and vertebrates, particularly in the gastrointestinal tract (GIT). This review focuses on the localization, production, metabolism and the functions of MT in GIT and the duodenal unit (liver, biliary routes and pancreas), where multi-step biosynthetic pathways of this indole, similar to those in pinealocytes, have been identified. These biosynthetic steps of MT, including two major rate limiting enzymes; arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), transforming L-tryptophan (Trp), originally identified in pinealocytes, have been also detected in entero-endocrine (EE) cells of GIT, where this indole appears to act in endocrine, paracrine and/or luminal pathway directly or through G-protein coupled MT receptors. Studies of the distribution of MT in GIT mucosa showed that this indole is generated in GIT in much larger amounts than it is produced in the pineal gland. Melatonin acts in GIT, partly locally in paracrine fashion and is partly released into portal circulation, to be taken up by the liver. It is then metabolized and excreted with the bile to small bowel and finally returns to liver through entero-hepatic circulation. The production of MT by the pineal gland shows circadian rhythm with high night-time surge, especially at younger age, followed by the fall during the day-light time. As a highly lipophylic substance, MT reaches all body cells within minutes, thus, serving as a convenient circadian timing signal. Following pinealectomy, the light/dark cycle of plasma MT levels disappears, while its day-time blood concentration is maintained mainly due to its release from the GIT. According to our experience, after oral application of Trp, the plasma MT increases in dose-dependent manner both in intact and pinealectomized animals and humans, indicating that GIT but not the pineal gland is a source of this indole. In GIT MT exhibits a wide spectrum of activities such as circadian entrainment, antioxidant and free radicals scavenging activity, Melatonin (MT), an indole formed enzymatically from L-trytophan (Trp), was first discovered in the bovine pineal gland in 1958 by Lerner et al. Melatonin is the most versatile and ubiquitous hormonal molecule produced not only in the pineal gland but also in various other tissues of invertebrates and vertebrates, particularly in the gastrointestinal tract (GIT). This review focuses on the localization, production, metabolism and the functions of MT in GIT and the duodenal unit (liver, biliary routes and pancreas), where multi-step biosynthetic pathways of this indole, similar to those in pinealocytes, have been identified. These biosynthetic steps of MT, including two major rate limiting enzymes; arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), transforming L-tryptophan (Trp), originally identified in pinealocytes, have been also detected in entero-endocrine (EE) cells of GIT, where this indole appears to act in endocrine, paracrine and/or luminal pathway directly or through G-protein coupled MT receptors. Studies of the distribution of MT in GIT mucosa showed that this indole is generated in GIT in much larger amounts than it is produced in the pineal gland. Melatonin acts in GIT, partly locally in paracrine fashion and is partly released into portal circulation, to be taken up by the liver. It is then metabolized and excreted with the bile to small bowel and finally returns to liver through entero-hepatic circulation. The production of MT by the pineal gland shows circadian rhythm with high night-time surge, especially at younger age, followed by the fall during the day-light time. As a highly lipophylic substance, MT reaches all body cells within minutes, thus, serving as a convenient circadian timing signal. Following pinealectomy, the light/dark cycle of plasma MT levels disappears, while its day-time blood concentration is maintained mainly due to its release from the GIT. According to our experience, after oral application of Trp, the plasma MT increases in dose-dependent manner both in intact and pinealectomized animals and humans, indicating that GIT but not the pineal gland is a source of this indole. In GIT MT exhibits a wide spectrum of activities such as circadian entrainment, antioxidant and free radicals scavenging activity, cytoprotective, anti-inflammatory and healing efficacy of various GIT lesions such as esophagitis, gastritis, peptic ulcer, pancreatitis and colitis. This review concentrates on the generation and pathophysiological implication of MT in GIT and related organs.
J Physiol Pharmacol. 2008 Aug;59 Suppl 2:33-51. Links
Thirty four years since the discovery of gastrointestinal melatonin.
Bubenik GA.
Department of Integrative Biology, University of Guelph, Guelph, Ontario, Canada. gbubenik@uoguelph.ca
After the discovery of melatonin in the pineal gland by Lerner and co-workers in 1958, melatonin was also detected in the retina and the human appendix. Later, melatonin was confirmed immunohistologically in all segments of the gastrointestinal tract (GIT), in the guts of bovine embryos and in the GIT of low vertebrates. Melatonin was also confirmed in the pancreas and the hepatobiliary system. Melatonin is produced in the enteroendocrine cells of the GIT mucosa. The concentrations of melatonin in the GIT are 10-100x higher than in the plasma and the total amount of melatonin in the GIT is around 400x higher than the amount of melatonin in the pineal gland. Similar to pineal melatonin, GIT melatonin is a multifunctional compound which exhibits some general as well as some specific effects, depending on the organ and the location of GIT tissue. In the GIT, melatonin exhibits endocrine, paracrine, autocrine and luminal actions. Generally, the episodic secretion of melatonin from the GIT is related to the intake and digestion of food and to the prevention of tissue damage caused by hydrochloric acid and digestive enzymes. Some actions, such as the scavenging of hydroxyl free radicals, immunoenhancement and antioxidant effects are of general nature, whereas others, such as an increase of mucosal blood flow, the reduction of peristalsis and the regulation of fecal water content, are specific to the tubular GIT. Generally, melatonin actions oppose those of serotonin. Laboratory and clinical studies indicate that the utilization of melatonin can prevent or treat pathological conditions such as esophageal and gastric ulcers, pancreatitis, colitis, irritable bowel disease, and colon cancer.
J Pineal Res. 2004 Nov;37(4):267-75. Links
Melatonin protects against pancreaticobiliary inflammation and associated remote organ injury in rats: role of neutrophils.
Barlas A, Cevik H, Arbak S, Bangir D, Sener G, Yeğen C, Yeğen BC.
Department of General Surgery, Marmara University School of Medicine, Istanbul, Turkey.
Although the role of oxidative stress in acute pancreatitis (AP) has been studied in several animal models, little data are available regarding AP induced by pancreatic duct obstruction. We characterized the protective effects of melatonin on pancreaticobiliary inflammation and associated remote organ injury. In Sprague-Dawley rats, either the common pancreaticobiliary duct (PBDL; n = 28) or bile duct (BDL; n = 28) was ligated or a sham operation was applied (n = 14). Either melatonin (10 mg/kg) or vehicle (saline; 1 mL/kg) was administered intraperitoneally (i.p.) immediately before the surgery and twice a day until the rats were decapitated at 6 or 72 h. The pancreas, liver, kidneys and lungs were removed and tissue samples were stored for the determination of malondialdehyde (MDA) and glutathione (GSH) levels and myelopreoxidase activity. The results demonstrate that pathogenesis of acute obstructive pancreatitis involves not only the oxidative damage of the pancreatic and hepatic tissues, as assessed by increased MDA and reduced GSH levels, but the lungs and kidneys are also challenged by oxidant injury. Similarly, hepatic oxidative injury caused by cholestasis was also accompanied by pulmonary, renal and even pancreatic damage. The biochemical findings were also verified histologically. Melatonin, probably because of its free-radical scavenging and antioxidant activity, which involves an inhibitory effect on tissue neutrophil infiltration, protected all the affected tissues.
World J Gastroenterol. 2005 Apr 7;11(13):1951-6. Links
Protective effect of low dose of melatonin against cholestatic oxidative stress after common bile duct ligation in rats.
Esrefoglu M, Gül M, Emre MH, Polat A, Selimoglu MA.
Department of Histology and Embryology, Faculty of Medicine, Inonu University, 44280 Malatya, Turkey. drmukaddes@hotmail.com
AIM: To investigate the role of oxidative injury and the effect of exogenous melatonin administration on liver damage induced by bile duct ligation (BDL), and second, to evaluate the role of nitric oxide (NO), a free oxygen radical, in oxidative injury. METHODS: Thirty-two Sprague-Dawley rats were assigned to four groups: sham operation (SO), BDL, BDL+melatonin, and BDL+vehicle. Cholestasis was achieved by double ligature of the common bile duct. Melatonin was injected intraperitoneally 500 microg/(kg.d) for 8 d. Hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA), and reduced GSH. Total nitrite (NOX) concentrations were determined in hepatic homogenates. Histopathological examination was performed using a histological scoring system. RESULTS: The histopathological changes including portal inflammation, necrosis, apoptosis, focal inflammation and fibrosis were severe in the BDL and BDL+vehicle groups. There were numerous large areas of coagulation necrosis. Histological Activity Index scores of these groups were significantly higher than that of the SO group. Treatment with melatonin reduced these alterations significantly. The degree of necro-inflammation and fibrosis showed significant difference between the BDL and BDL+melatonin groups. BDL was accompanied by a significant increase in MDA and NOX, and a significant decrease in GSH levels. Mean+/-SE values of MDA, GSH and NOX levels of SO group were 147.47+/-6.69, 0.88+/-0.33 micromol/g and 180.70+/-6.58 nm/g, respectively. The values of BDL group were 200.14+/-21.30, 0.65+/-0.02 micromol/g, and 400.46+/-48.89 nm/g, respectively, whereas the values of BDL+melatonin group were 115.93+/-6.8, 0.74+/-0.02 micromol/g, and 290.38+/-32.32 nm/g, respectively. Melatonin treatment was associated with a significant recovery of MDA, GSH and NOX levels. CONCLUSION: We have concluded that oxidative stress is associated with the pathogenesis of cholestatic liver damage and NO contributes to oxidative damage. Melatonin, even at low dose, is an efficient agent in reducing negative parameters of cholestasis.
J Pineal Res. 2008 Apr;44(3):250-60. Links
Protective effect of melatonin on Ca2+ homeostasis and contractility in acute cholecystitis.
Gomez-Pinilla PJ, Camello PJ, Pozo MJ.
Department of Physiology, Nursing School, University of Extremadura, Caceres, Spain.
Impaired Ca2+ homeostasis and smooth muscle contractility co-exist in acute cholecystitis (AC) leading to gallbladder dysfunction. There is no pharmacological treatment for this pathological condition. Our aim was to evaluate the effects of melatonin treatment on Ca2+ signaling pathways and contractility altered by cholecystitis. [Ca2+]i was determined by epifluorescence microscopy in fura-2 loaded isolated gallbladder smooth muscle cells, and isometric tension was recorded from gallbladder muscle strips. Malondialdehyde (MDA) and reduced glutathione (GSH) contents were determined by spectrophotometry and cycloxygenase-2 (COX-2) expression was quantified by western blot. Melatonin was tested in two experimental groups, one of which underwent common bile duct ligation for 2 days and another that was later de-ligated for 2 days. Inflammation-induced impairment of Ca2+ responses to cholecystokinin and caffeine were recovered by melatonin treatment (30 mg/kg). This treatment also ameliorated the detrimental effects of AC on Ca2+ influx through both L-type and capacitative Ca2+ channels, and it was effective in preserving the pharmacological phenotype of these channels. Despite its effects on Ca2+ homeostasis, melatonin did not improve contractility. After de-ligation, Ca2+ influx and contractility were still impaired, but both were recovered by melatonin. These effects of melatonin were associated to a reduction of MDA levels, an increase in GSH content and a decrease in COX-2 expression. These findings indicate that melatonin restores Ca2+ homeostasis during AC and resolves inflammation. In addition, this indoleamine helps in the subsequent recovery of functionality.
J Physiol Pharmacol. 2007 Dec;58 Suppl 6:23-52. Links
Role of melatonin in upper gastrointestinal tract.
Konturek SJ, Konturek PC, Brzozowski T, Bubenik GA.
Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, Cracow, Poland. mpkontur@cyf-kr.edu.pl
Melatonin, an indole formed enzymatically from L-tryptophan, is the most versatile and ubiquitous hormone molecule produced not only in all animals but also in some plants. This review focuses on the role of melatonin in upper portion of gastrointestinal tract (GIT), including oral cavity, esophagus, stomach and duodenum, where this indole is generated and released into the GIT lumen and into the portal circulation to be uptaken, metabolized by liver and released with bile into the duodenum. The biosynthetic steps of melatonin with two major rate limiting enzymes, arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), transforming tryptophan to melatonin, originally identified in pinealocytes have been also detected in entero-endocrine (EE) cells of GIT wall, where this indole may act via endocrine, paracrine and/or luminal pathway through G-protein coupled receptors. Melatonin in GIT was shown to be generated in about 500 times larger amounts than it is produced in pineal gland. The production of melatonin by pineal gland shows circadian rhythm with high night-time peak, especially at younger age, followed by the fall during the day-light time. As a highly lipophilic substance, melatonin reaches all body cells within minutes, to serve as a convenient circadian timing signal for alteration of numerous body functions.. Following pinealectomy, the light/dark cycle of plasma melatonin levels disappears, while its day-time blood concentrations are attenuated but sustained mainly due to its release from the GIT. After oral application of tryptophan, the plasma melatonin increases in dose-dependent manner both in intact and pinealectomized animals, indicating that extrapineal sources such as GIT rather than pineal gland are the major producers of this indole. In the upper portion of GIT, melatonin exhibits a wide spectrum of activities such as circadian entrainment, free radicals scavenging activity, protection of mucosa against various irritants and healing of various GIT lesions such as stomatitis, esophagitis, gastritis and peptic ulcer. This review concentrates on the generation and pathophysiological implication of melatonin in upper GIT
Scand J Gastroenterol Suppl. 1995;212:63-78.Links
Cholesterol gallstone formation in man and potential treatments of the gallbladder motility defect.
Portincasa P, Stolk MF, van Erpecum KJ, Palasciano G, van Berge-Henegouwen GP.
Dept. of Gastroenterology, University Hospital Utrecht, The Netherlands.
Cholelithiasis affects 10-15% of the adult population in Western society, and about 75% of gallstones are of cholesterol type. Hepatic hypersecretion of cholesterol with the formation of instable cholesterol-rich vesicles in bile, an imbalance between nucleation-inhibiting and nucleation-promoting proteins with further aggregation of cholesterol crystals in a gallbladder with a motility defect (stasis), all play a role in the pathogenesis of cholesterol gallstones. Experimental animal models suggest that gallstone formation can be prevented by improving gallbladder emptying. Thus, a better understanding of the causes underlying the impaired gallbladder motor function in patients with gallstones might lead to the selection of therapeutic approaches for those individuals who are at increased risk for the formation or recurrence of gallstones. The present article focuses on current concepts and theories on the pathogenesis of cholesterol gallstones with emphasis on the gallbladder motility defect. Several treatment strategies for the correction of gallbladder hypomotility are also discussed.
Aliment Pharmacol Ther. 2000 May;14 Suppl 2:39-47. Links
Review: pathogenesis of gallstones.
Dowling RH.
Gastroenterology Unit, Guy's, King's & St Thomas' School of Medicine, London, UK. h.dowling@umds.ac.uk
The aim of this article is to review selected aspects of the pathogenesis of cholesterol-rich, gall-bladder stones (GBS)--with emphasis on recent developments in biliary cholesterol saturation, cholesterol microcrystal nucleation, statis within the gall-bladder and, particularly, on the roles of intestinal transit and altered deoxycholic acid (DCA) metabolism, in GBS development. In biliary cholesterol secretion, transport and saturation, recent developments include evidence in humans and animals, that bile lipid secretion is under genetic control. Thus in mice the md-2 gene, and in humans the MDR-3 gene, encodes for a canalicular protein that acts as a 'flippase' transporting phospholipids from the inner to the outer hemi-leaflet of the canalicular membrane. In the absence of this gene, there is virtually no phospholipid or cholesterol secretion into bile. Furthermore, when inbred strains of mice that have 'lith genes' are fed a lithogenic diet, they become susceptible to high rates of GBS formation. The precipitation/nucleation of cholesterol microcrystals from supersaturated bile remains a critical step in gallstone formation. methods of studying this phenomenon have now been refined from the original 'nucleation time' to measurement of cholesterol appearance/detection times, and crystal growth assays. Furthermore, the results of recent studies indicate that, in addition to classical Rhomboid-shape monohydrate crystals, cholesterol can also crystallize, transiently, as needle-, spiral- and tubule-shaped crystals of anhydrous cholesterol. A lengthy list of promoters, and a shorter list of inhibitors, has now been defined. There are many situations where GB stasis in humans is associated with an increased risk of gallstone formation--including iatrogenic stone formation in acromegalic patients treated chronically with octreotide (OT). As well as GB stasis, however, OT-treated patients all have 'bad' bile which is supersaturated with cholesterol, has excess cholesterol in vesicles, rapid microcrystal mulceation times and a two-fold increase in the percentage DCA in bile. This increase in the proportion of DCA seems to be due to OT-induced prolongation of large bowel transit time (LBTT). Thus LBTT is linearly related to (i) the percentage of DCA in serum; (ii) the DCA pool size; and (III) the DCA input or 'synthesis' rate. Furthermore, the intestinal prokinetic, cisapride, counters the adverse effects of OT on intestinal transit, and 'normalizes' the percentage of DCA in serum/bile. Patients with spontaneous gallstone disease also have prolonged LBTTs, more colonic gram-positive anaerobes, increased bile acid metabolizing enzymes and higher intracolonic pH values, than stone-free controls. Together, these changes lead to increased DCA formation, solubilization and absorption, Thus, in addition to the 'lithogenic liver' and 'guilty gall-bladder' one must now add the 'indolent intestine' to the list of culprits in cholesterol gallstone formation.
Liver Int. 2008 Aug;28(7):935-47. Links
Comment in:
Liver Int. 2008 Aug;28(7):906-7.
Ezetimibe prevents cholesterol gallstone formation in mice.
Zúñiga S, Molina H, Azocar L, Amigo L, Nervi F, Pimentel F, Jarufe N, Arrese M, Lammert F, Miquel JF.
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
BACKGROUND: Intestinal cholesterol absorption may influence gallstone formation and its modulation could be a useful therapeutic strategy for gallstone disease (GSD). Ezetimibe (EZET) is a cholesterol-lowering agent that specifically inhibits intestinal cholesterol absorption. AIMS: To test whether EZET can prevent gallstone formation in mice. METHODS/RESULTS: Gallstone-susceptible C57BL/6 inbred mice were fed control and lithogenic diets with or without simultaneous EZET administration. Lithogenic diet increased biliary cholesterol content and secretion, and induced sludge or gallstone formation in 100% of the animals. EZET administration reduced intestinal cholesterol absorption by 90% in control animals and by 35% in mice receiving the lithogenic diet. EZET prevented the appearance of cholesterol crystals and gallstones. In addition, mice fed the lithogenic diet plus EZET exhibited a 60% reduction in biliary cholesterol saturation index. Of note, EZET treatment caused a significant increase in bile flow (+50%, P<0.01) as well as bile salt, phospholipid and glutathione secretion rates (+60%, +44% and +100%, respectively, P<0.01), which was associated with a moderately increased expression of hepatic bile salt transporters. In addition, relative expression levels of Nieman-Pick C1 like 1 (NPC1L1) in the enterohepatic axis in humans were assessed. Expression levels of NPC1L1 were 15- to 30-fold higher in the duodenum compared with the liver at transcript and protein levels, respectively, suggesting preferential action of EZET on intestinal cholesterol absorption in humans. CONCLUSIONS: In a murine model of GSD, EZET prevented gallstone formation by reducing intestinal cholesterol absorption and increasing bile salt-dependent and -independent bile flow. EZET could be useful in preventing GSD disease in susceptible patients.
Gastroenterology. 2008 Jun;134(7):2101-10. Epub 2008 Mar 10. Links
Effect of ezetimibe on the prevention and dissolution of cholesterol gallstones.
Wang HH, Portincasa P, Mendez-Sanchez N, Uribe M, Wang DQ.
Department of Medicine, Liver Center and Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
BACKGROUND & AIMS: Cholesterol cholelithiasis is one of the most prevalent and most costly digestive diseases in developed countries and its incidence has increased markedly in Asian countries owing to the adoption of Western-type dietary habits. Because animal experiments showed that high efficiency of intestinal cholesterol absorption contributes to gallstone formation, we explored whether the potent cholesterol absorption inhibitor ezetimibe could prevent gallstones and promote gallstone dissolution in mice and reduce biliary cholesterol content in human beings. METHODS: Male gallstone-susceptible C57L mice were fed a lithogenic diet and concomitantly administered with ezetimibe at 0, 0.8, 4, or 8 mg/kg/day for 8 or 12 weeks. Gallbladder biles and gallstones were examined by microscopy. Gallbladder emptying in response to cholecystokinin octapeptide was measured gravimetrically. Biliary lipid outputs were analyzed by physical-chemical methods. Cholesterol absorption efficiency was determined by fecal dual-isotope ratio and mass balance methods. Lipid changes in gallbladder biles of gallstone patients vs overweight subjects without gallstones were examined before (day 0) and at 30 days after ezetimibe treatment (20 mg/day). RESULTS: Ezetimibe prevented gallstones by effectively reducing intestinal cholesterol absorption and biliary cholesterol secretion, and protected gallbladder motility function by desaturating bile in mice. Treatment with ezetimibe promoted the dissolution of gallstones by forming an abundance of unsaturated micelles. Furthermore, ezetimibe significantly reduced biliary cholesterol saturation and retarded cholesterol crystallization in biles of patients with gallstones. CONCLUSIONS: Ezetimibe is a novel approach to reduce biliary cholesterol content and a promising strategy for preventing or treating cholesterol gallstones by inhibiting intestinal cholesterol absorption.
Hepatology. 1992 Oct;16(4):960-7.Links
Dietary N-3 polyunsaturated fatty acids decrease biliary cholesterol saturation in gallstone disease.
Berr F, Holl J, Jüngst D, Fischer S, Richter WO, Seifferth B, Paumgartner G.
Department of Medicine II, Klinikum Grosshadern, University of Munich, Germany.
Because fatty acid composition of biliary phospholipids influences cholesterol secretion into bile, we investigated whether replacement of n-1 monounsaturated or n-6 polyunsaturated fatty acids with n-3 polyunsaturated fatty acids in biliary phosphatidylcholines reduces supersaturation with cholesterol and prevents precipitation of cholesterol crystals in bile of gallstone patients. Seven patients with radiolucent gallstones in functioning gallbladders were studied before (control) and after 5 wk of dietary supplementation with marine fish oil (11.3 gm/day = 3.75 gm n-3 polyunsaturated fatty acids/day). Duodenal bile was collected for analysis during intravenous infusion of cholecystokinin. Gallbladder emptying in response to cholecystokinin was comparable before and during intake of n-3 polyunsaturated fatty acids. Intake of n-3 polyunsaturated fatty acids increased (p less than 0.001) the fractions of eicosapentaenoic and docosahexaenoic acids and decreased the fractions of linoleic (p less than 0.001) and arachidonic acids (p less than 0.02) in biliary phospholipids. Concomitantly, the molar ratio of cholesterol to phospholipids decreased (-19%; p less than 0.05). As a consequence, the cholesterol saturation index was reduced by -25% (p = 0.01), from 1.60 +/- 0.44 to 1.24 +/- 0.38. However, in vitro nucleation time of duodenal bile was not prolonged. The decrease in cholesterol saturation was not sufficient to prevent nucleation of cholesterol crystals in bile of gallstone patients. In conclusion, our data suggest that cholesterol saturation can be influenced by the fatty acid composition of the phosphatidylcholines secreted in bile.
Cas Lek Cesk. 2007;146(1):24-34.Links
[Effect of hypolipidemic treatment on the composition of bile and the risk or cholesterol gallstone disease]
[Article in Czech]
Zák A, Zeman M, Hrubant K, Vecka M, Tvrzická E.
IV interní klinika 1. LF UK a VFN, Praha. azak@vfn.cz
Obesity, diabetes mellitus type 2 and dyslipidemia, characterized by hypertriglyceridemia and low HDL-cholesterol levels, are risk factors for cholesterol gallstone disease. The common denominator of above-mentioned states is insulin resistance. Hypolipidemic treatment significantly influences not only the biliary lipid composition, but also other etiopathogenetic mechanisms of the disease. Three principal defects are involved in gallstone formation - cholesterol supersaturation, accelerated nucleation, and gallbladder dysmotility. The degree of cholesterol saturation in gallbladder bile is the most important predictor of cholesterol crystal formation. Cholesterol, lecithin and bile acids are the major components in bile. According to the molar ratios of the three main components, simple or mixed micelles, unstable unilamellar or multilamellar vesicles are formed in the bile. The cholesterol supersaturation of the gallbladder bile and cholesterol crystal formation from the unstable multilamellar vesicles initiates the onset of cholesterol cholelithiasis. The pool of unesterified cholesterol is the source for VLDL synthesis; together with HDL-cholesterol, it is also the source for cholesterol secretion into the bile. The main metabolic products of cholesterol degradation are bile acids, which are synthesized predominantly from LDL-cholesterol. The rate of the production of primary bile acids is principally regulated by cholesterol 7alpha-hydroxylase (CYP7A 1). The treatment of dyslipidemia with niacin and resins does not influence the saturation of bile with cholesterol or the incidence of cholelithiasis. The effects of ezetimibe in human patients with the respect of cholesterol cholelithiasis have not been published. The fibrate treatment is associated with increased cholesterol saturation of bile due to inhibition of CYP7A1 activity, enhanced flux of cholesterol via HDL and increased secretion of cholesterol into bile. The clinical studies describe cholesterol supersaturation in bile and increased frequency of cholelithiasis as well. The administration of pravastatin and simvastatin led to reduced cholesterol saturation indexes. The patients with endogenous hypertriglyceridemia and low HDL-cholesterol being administered with polyunsaturated fatty acids of n-3 family had decreased cholesterol concentration in bile. Other authors described beneficial effect of fish oil on the biliary cholesterol nucleation time, improvement of gallbladder sensitivity to cholecystokinin and the prevention of cholesterol gallstone formations caused by rapid weight loss.
Surgery. 2007 Aug;142(2):228-33. Links
Ezetimibe ameliorates cholecystosteatosis.
Mathur A, Walker JJ, Al-Azzawi HH, Lu D, Swartz-Basile DA, Nakeeb A, Pitt HA.
Department of Surgery, Indiana University School of Medicine, Indianapolis, Ind, USA.
BACKGROUND: Cholecystosteatosis is the accumulation of gallbladder wall fats leading to decreased gallbladder emptying. Ezetimibe inhibits intestinal fat absorption and prevents murine gallstone formation. However, the influence of ezetimibe on gallbladder emptying and cholecystosteatosis has not been studied. Therefore, we tested the hypothesis that ezetimibe would improve gallbladder motility by preventing the buildup of fats in the gallbladder wall. METHODS: Forty lean female mice were fed either a control diet or a lithogenic diet for 6 weeks. Half of the mice on each diet received ezetimibe. At 11 weeks of age, all mice were fasted overnight and underwent gallbladder ultrasonography to determine ejection fraction. One week later, the mice were fasted and underwent cholecystectomy. Bile was examined for cholesterol crystals. The gallbladders were snap-frozen for lipid analysis. RESULTS: The lithogenic diet significantly (P < 0.05) increased serum cholesterol, biliary crystals, gallbladder wall cholesterol and cholesterol/phospholipid ratio, and decreased gallbladder ejection fraction. All of these abnormalities were reversed (P < 0.05) by the addition of ezetimibe to the diet. CONCLUSIONS: These data suggest that ezetimibe lowers serum cholesterol, prevents biliary crystals, and normalizes gallbladder wall fat and function. We conclude that ezetimibe ameliorates cholecystosteatosis and may be an effective agent for gallstone prevention.
Atherosclerosis. 2008 May;198(1):77-84. Epub 2007 Dec 3. Links
Inhibition of intestinal absorption of cholesterol by ezetimibe or bile acids by SC-435 alters lipoprotein metabolism and extends the lifespan of SR-BI/apoE double knockout mice.
Braun A, Yesilaltay A, Acton S, Broschat KO, Krul ES, Napawan N, Stagliano N, Krieger M.
Department of Biology, Massachusetts Institute of Technology, Building 68-483, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
SR-BI/apoE double knockout (dKO) mice exhibit many features of human coronary heart disease (CHD), including hypercholesterolemia, occlusive coronary atherosclerosis, cardiac hypertrophy, myocardial infarctions, cardiac dysfunction and premature death. Ezetimibe is a FDA-approved, intestinal cholesterol absorption inhibitor that lowers plasma LDL cholesterol in humans and animals and inhibits aortic root atherosclerosis in apoE KO mice, but has not been proven to reduce CHD. Three-week-ezetimibe treatment of dKO mice (0.005% (w/w) in standard chow administered from weaning) resulted in a 35% decrease in cholesterol in IDL/LDL-size lipoproteins, but not in VLDL- and HDL-size lipoproteins. Ezetimibe treatment significantly reduced aortic root (57%) and coronary arterial (68%) atherosclerosis, cardiomegaly (24%) and cardiac fibrosis (57%), and prolonged the lives of the mice (27%). This represents the first demonstration of beneficial effects of ezetimibe treatment on CHD. The dKO mice were similarly treated with SC-435 (0.01% (w/w)), an apical sodium codependent bile acid transporter (ASBT) inhibitor, that blocks intestinal absorption of bile acids, lowers plasma cholesterol in animals, and reduces aortic root atherosclerosis in apoE KO mice. The effects of SC-435 treatment were similar to those of ezetimibe: 37% decrease in ILD/LDL-size lipoprotein cholesterol and 57% prolongation in median lifespan. Thus, inhibition of intestinal absorption of either cholesterol (ezetimibe) or bile acids (SC-435) significantly reduced plasma IDL/LDL-size lipoprotein cholesterol levels and improved survival of SR-BI/apoE dKO mice. The SR-BI/apoE dKO murine model of atherosclerotic occlusive, arterial CHD appears to provide a useful system to evaluate compounds that modulate cholesterol homeostasis and atherosclerosis.
Hepatology. 2000 Sep;32(3):455-60. Links
Comment in:
Hepatology. 2000 Sep;32(3):670-1.
Melatonin prevents pigment gallstone formation induced by bile duct ligation in guinea pigs.
Shiesh SC, Chen CY, Lin XZ, Liu ZA, Tsao HC.
Department of Medical Technology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China. hsieh@mail.ncku.edu.tw
Free radical-mediated oxidative stress has been implicated in the genesis of gallstone in vitro. This study was designed to examine the oxidative stress changes during pigment gallstone formation and to investigate whether melatonin (MLT) could act as a chemopreventive agent for cholelithiasis in a guinea pig model. The common bile duct of guinea pigs was ligated with or without MLT pretreatment. Animals were studied on day 7, 9, 12, and 14 after surgery. Stone and/or sludge developed in ligated guinea pigs without MLT. Fourier transform infrared spectra of the sludge showed the presence of calcium bilirubinate, whose peak height per milligram of sludge gradually increased with time after ligation. Total antioxidant activity (TAA) in bile of guinea pigs at day 14 after ligation reduced to one third of the level in sham-operated controls (P <.001). In addition, the bile of ligated guinea pigs had increased pH (P <.001), bile salts (P <.01), and malondialdehyde (MDA) (P <.05), compared to sham controls. Pretreatment of guinea pigs with MLT at a dose of 1,000 microg/kg significantly decreased the incidence of pigment gallstone formation at day 14 after ligation, as compared to no pretreatment (0/7 vs. 8/10). MLT also reverted the ligation-induced changes in biliary bile salts, pH, MDA, and TAA to control levels. These in vivo findings support a causative role of oxidative stress in the bile duct ligation-induced pigment gallstone formation. Antioxidants may prove useful in preventing pigment gallstone formation in humans.
J Physiol Pharmacol. 2007 Sep;58(3):381-405. Links
Localization and biological activities of melatonin in intact and diseased gastrointestinal tract (GIT).
Konturek SJ, Konturek PC, Brzozowska I, Pawlik M, Sliwowski Z, Cześnikiewicz-Guzik M, Kwiecień S, Brzozowski T, Bubenik GA, Pawlik WW.
Department of Physiology, Jagiellonian University Medical College, Cracow, Poland. mpkontur@cyf-kr.edu.pl
Melatonin (MT), an indole formed enzymatically from L-trytophan (Trp), was first discovered in the bovine pineal gland in 1958 by Lerner et al. Melatonin is the most versatile and ubiquitous hormonal molecule produced not only in the pineal gland but also in various other tissues of invertebrates and vertebrates, particularly in the gastrointestinal tract (GIT). This review focuses on the localization, production, metabolism and the functions of MT in GIT and the duodenal unit (liver, biliary routes and pancreas), where multi-step biosynthetic pathways of this indole, similar to those in pinealocytes, have been identified. These biosynthetic steps of MT, including two major rate limiting enzymes; arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), transforming L-tryptophan (Trp), originally identified in pinealocytes, have been also detected in entero-endocrine (EE) cells of GIT, where this indole appears to act in endocrine, paracrine and/or luminal pathway directly or through G-protein coupled MT receptors. Studies of the distribution of MT in GIT mucosa showed that this indole is generated in GIT in much larger amounts than it is produced in the pineal gland. Melatonin acts in GIT, partly locally in paracrine fashion and is partly released into portal circulation, to be taken up by the liver. It is then metabolized and excreted with the bile to small bowel and finally returns to liver through entero-hepatic circulation. The production of MT by the pineal gland shows circadian rhythm with high night-time surge, especially at younger age, followed by the fall during the day-light time. As a highly lipophylic substance, MT reaches all body cells within minutes, thus, serving as a convenient circadian timing signal. Following pinealectomy, the light/dark cycle of plasma MT levels disappears, while its day-time blood concentration is maintained mainly due to its release from the GIT. According to our experience, after oral application of Trp, the plasma MT increases in dose-dependent manner both in intact and pinealectomized animals and humans, indicating that GIT but not the pineal gland is a source of this indole. In GIT MT exhibits a wide spectrum of activities such as circadian entrainment, antioxidant and free radicals scavenging activity, Melatonin (MT), an indole formed enzymatically from L-trytophan (Trp), was first discovered in the bovine pineal gland in 1958 by Lerner et al. Melatonin is the most versatile and ubiquitous hormonal molecule produced not only in the pineal gland but also in various other tissues of invertebrates and vertebrates, particularly in the gastrointestinal tract (GIT). This review focuses on the localization, production, metabolism and the functions of MT in GIT and the duodenal unit (liver, biliary routes and pancreas), where multi-step biosynthetic pathways of this indole, similar to those in pinealocytes, have been identified. These biosynthetic steps of MT, including two major rate limiting enzymes; arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), transforming L-tryptophan (Trp), originally identified in pinealocytes, have been also detected in entero-endocrine (EE) cells of GIT, where this indole appears to act in endocrine, paracrine and/or luminal pathway directly or through G-protein coupled MT receptors. Studies of the distribution of MT in GIT mucosa showed that this indole is generated in GIT in much larger amounts than it is produced in the pineal gland. Melatonin acts in GIT, partly locally in paracrine fashion and is partly released into portal circulation, to be taken up by the liver. It is then metabolized and excreted with the bile to small bowel and finally returns to liver through entero-hepatic circulation. The production of MT by the pineal gland shows circadian rhythm with high night-time surge, especially at younger age, followed by the fall during the day-light time. As a highly lipophylic substance, MT reaches all body cells within minutes, thus, serving as a convenient circadian timing signal. Following pinealectomy, the light/dark cycle of plasma MT levels disappears, while its day-time blood concentration is maintained mainly due to its release from the GIT. According to our experience, after oral application of Trp, the plasma MT increases in dose-dependent manner both in intact and pinealectomized animals and humans, indicating that GIT but not the pineal gland is a source of this indole. In GIT MT exhibits a wide spectrum of activities such as circadian entrainment, antioxidant and free radicals scavenging activity, cytoprotective, anti-inflammatory and healing efficacy of various GIT lesions such as esophagitis, gastritis, peptic ulcer, pancreatitis and colitis. This review concentrates on the generation and pathophysiological implication of MT in GIT and related organs.
J Physiol Pharmacol. 2008 Aug;59 Suppl 2:33-51. Links
Thirty four years since the discovery of gastrointestinal melatonin.
Bubenik GA.
Department of Integrative Biology, University of Guelph, Guelph, Ontario, Canada. gbubenik@uoguelph.ca
After the discovery of melatonin in the pineal gland by Lerner and co-workers in 1958, melatonin was also detected in the retina and the human appendix. Later, melatonin was confirmed immunohistologically in all segments of the gastrointestinal tract (GIT), in the guts of bovine embryos and in the GIT of low vertebrates. Melatonin was also confirmed in the pancreas and the hepatobiliary system. Melatonin is produced in the enteroendocrine cells of the GIT mucosa. The concentrations of melatonin in the GIT are 10-100x higher than in the plasma and the total amount of melatonin in the GIT is around 400x higher than the amount of melatonin in the pineal gland. Similar to pineal melatonin, GIT melatonin is a multifunctional compound which exhibits some general as well as some specific effects, depending on the organ and the location of GIT tissue. In the GIT, melatonin exhibits endocrine, paracrine, autocrine and luminal actions. Generally, the episodic secretion of melatonin from the GIT is related to the intake and digestion of food and to the prevention of tissue damage caused by hydrochloric acid and digestive enzymes. Some actions, such as the scavenging of hydroxyl free radicals, immunoenhancement and antioxidant effects are of general nature, whereas others, such as an increase of mucosal blood flow, the reduction of peristalsis and the regulation of fecal water content, are specific to the tubular GIT. Generally, melatonin actions oppose those of serotonin. Laboratory and clinical studies indicate that the utilization of melatonin can prevent or treat pathological conditions such as esophageal and gastric ulcers, pancreatitis, colitis, irritable bowel disease, and colon cancer.
J Pineal Res. 2004 Nov;37(4):267-75. Links
Melatonin protects against pancreaticobiliary inflammation and associated remote organ injury in rats: role of neutrophils.
Barlas A, Cevik H, Arbak S, Bangir D, Sener G, Yeğen C, Yeğen BC.
Department of General Surgery, Marmara University School of Medicine, Istanbul, Turkey.
Although the role of oxidative stress in acute pancreatitis (AP) has been studied in several animal models, little data are available regarding AP induced by pancreatic duct obstruction. We characterized the protective effects of melatonin on pancreaticobiliary inflammation and associated remote organ injury. In Sprague-Dawley rats, either the common pancreaticobiliary duct (PBDL; n = 28) or bile duct (BDL; n = 28) was ligated or a sham operation was applied (n = 14). Either melatonin (10 mg/kg) or vehicle (saline; 1 mL/kg) was administered intraperitoneally (i.p.) immediately before the surgery and twice a day until the rats were decapitated at 6 or 72 h. The pancreas, liver, kidneys and lungs were removed and tissue samples were stored for the determination of malondialdehyde (MDA) and glutathione (GSH) levels and myelopreoxidase activity. The results demonstrate that pathogenesis of acute obstructive pancreatitis involves not only the oxidative damage of the pancreatic and hepatic tissues, as assessed by increased MDA and reduced GSH levels, but the lungs and kidneys are also challenged by oxidant injury. Similarly, hepatic oxidative injury caused by cholestasis was also accompanied by pulmonary, renal and even pancreatic damage. The biochemical findings were also verified histologically. Melatonin, probably because of its free-radical scavenging and antioxidant activity, which involves an inhibitory effect on tissue neutrophil infiltration, protected all the affected tissues.
World J Gastroenterol. 2005 Apr 7;11(13):1951-6. Links
Protective effect of low dose of melatonin against cholestatic oxidative stress after common bile duct ligation in rats.
Esrefoglu M, Gül M, Emre MH, Polat A, Selimoglu MA.
Department of Histology and Embryology, Faculty of Medicine, Inonu University, 44280 Malatya, Turkey. drmukaddes@hotmail.com
AIM: To investigate the role of oxidative injury and the effect of exogenous melatonin administration on liver damage induced by bile duct ligation (BDL), and second, to evaluate the role of nitric oxide (NO), a free oxygen radical, in oxidative injury. METHODS: Thirty-two Sprague-Dawley rats were assigned to four groups: sham operation (SO), BDL, BDL+melatonin, and BDL+vehicle. Cholestasis was achieved by double ligature of the common bile duct. Melatonin was injected intraperitoneally 500 microg/(kg.d) for 8 d. Hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides, measured as malondialdehyde (MDA), and reduced GSH. Total nitrite (NOX) concentrations were determined in hepatic homogenates. Histopathological examination was performed using a histological scoring system. RESULTS: The histopathological changes including portal inflammation, necrosis, apoptosis, focal inflammation and fibrosis were severe in the BDL and BDL+vehicle groups. There were numerous large areas of coagulation necrosis. Histological Activity Index scores of these groups were significantly higher than that of the SO group. Treatment with melatonin reduced these alterations significantly. The degree of necro-inflammation and fibrosis showed significant difference between the BDL and BDL+melatonin groups. BDL was accompanied by a significant increase in MDA and NOX, and a significant decrease in GSH levels. Mean+/-SE values of MDA, GSH and NOX levels of SO group were 147.47+/-6.69, 0.88+/-0.33 micromol/g and 180.70+/-6.58 nm/g, respectively. The values of BDL group were 200.14+/-21.30, 0.65+/-0.02 micromol/g, and 400.46+/-48.89 nm/g, respectively, whereas the values of BDL+melatonin group were 115.93+/-6.8, 0.74+/-0.02 micromol/g, and 290.38+/-32.32 nm/g, respectively. Melatonin treatment was associated with a significant recovery of MDA, GSH and NOX levels. CONCLUSION: We have concluded that oxidative stress is associated with the pathogenesis of cholestatic liver damage and NO contributes to oxidative damage. Melatonin, even at low dose, is an efficient agent in reducing negative parameters of cholestasis.
J Pineal Res. 2008 Apr;44(3):250-60. Links
Protective effect of melatonin on Ca2+ homeostasis and contractility in acute cholecystitis.
Gomez-Pinilla PJ, Camello PJ, Pozo MJ.
Department of Physiology, Nursing School, University of Extremadura, Caceres, Spain.
Impaired Ca2+ homeostasis and smooth muscle contractility co-exist in acute cholecystitis (AC) leading to gallbladder dysfunction. There is no pharmacological treatment for this pathological condition. Our aim was to evaluate the effects of melatonin treatment on Ca2+ signaling pathways and contractility altered by cholecystitis. [Ca2+]i was determined by epifluorescence microscopy in fura-2 loaded isolated gallbladder smooth muscle cells, and isometric tension was recorded from gallbladder muscle strips. Malondialdehyde (MDA) and reduced glutathione (GSH) contents were determined by spectrophotometry and cycloxygenase-2 (COX-2) expression was quantified by western blot. Melatonin was tested in two experimental groups, one of which underwent common bile duct ligation for 2 days and another that was later de-ligated for 2 days. Inflammation-induced impairment of Ca2+ responses to cholecystokinin and caffeine were recovered by melatonin treatment (30 mg/kg). This treatment also ameliorated the detrimental effects of AC on Ca2+ influx through both L-type and capacitative Ca2+ channels, and it was effective in preserving the pharmacological phenotype of these channels. Despite its effects on Ca2+ homeostasis, melatonin did not improve contractility. After de-ligation, Ca2+ influx and contractility were still impaired, but both were recovered by melatonin. These effects of melatonin were associated to a reduction of MDA levels, an increase in GSH content and a decrease in COX-2 expression. These findings indicate that melatonin restores Ca2+ homeostasis during AC and resolves inflammation. In addition, this indoleamine helps in the subsequent recovery of functionality.
J Physiol Pharmacol. 2007 Dec;58 Suppl 6:23-52. Links
Role of melatonin in upper gastrointestinal tract.
Konturek SJ, Konturek PC, Brzozowski T, Bubenik GA.
Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, Cracow, Poland. mpkontur@cyf-kr.edu.pl
Melatonin, an indole formed enzymatically from L-tryptophan, is the most versatile and ubiquitous hormone molecule produced not only in all animals but also in some plants. This review focuses on the role of melatonin in upper portion of gastrointestinal tract (GIT), including oral cavity, esophagus, stomach and duodenum, where this indole is generated and released into the GIT lumen and into the portal circulation to be uptaken, metabolized by liver and released with bile into the duodenum. The biosynthetic steps of melatonin with two major rate limiting enzymes, arylalkylamine-N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), transforming tryptophan to melatonin, originally identified in pinealocytes have been also detected in entero-endocrine (EE) cells of GIT wall, where this indole may act via endocrine, paracrine and/or luminal pathway through G-protein coupled receptors. Melatonin in GIT was shown to be generated in about 500 times larger amounts than it is produced in pineal gland. The production of melatonin by pineal gland shows circadian rhythm with high night-time peak, especially at younger age, followed by the fall during the day-light time. As a highly lipophilic substance, melatonin reaches all body cells within minutes, to serve as a convenient circadian timing signal for alteration of numerous body functions.. Following pinealectomy, the light/dark cycle of plasma melatonin levels disappears, while its day-time blood concentrations are attenuated but sustained mainly due to its release from the GIT. After oral application of tryptophan, the plasma melatonin increases in dose-dependent manner both in intact and pinealectomized animals, indicating that extrapineal sources such as GIT rather than pineal gland are the major producers of this indole. In the upper portion of GIT, melatonin exhibits a wide spectrum of activities such as circadian entrainment, free radicals scavenging activity, protection of mucosa against various irritants and healing of various GIT lesions such as stomatitis, esophagitis, gastritis and peptic ulcer. This review concentrates on the generation and pathophysiological implication of melatonin in upper GIT
Colleen said:
"Those of us that have had the surgery cannot thank this great man enough. If you're trying to decide to have MGB get off your feet and do it. I was 303 and am now 125-128 depending on what I ate the day before. My cholesterol is not 1000 anymore-187. Energy abounds, spring in my steps. I look great in clothes; saving for the plastic surgery. But I can play with my grand daughters, jump the waves for an hour, be on my feet teaching without them swelling, no longer snore and am no longer diabetic. Yahooee!!! My teenage boys & the rest 0f my family can't believe the sdfference in me, nor can my husband. I was at a party with people I hadn't seen in 10 years and noone recognized me. How great is that! Thank you forever"
"Those of us that have had the surgery cannot thank this great man enough. If you're trying to decide to have MGB get off your feet and do it. I was 303 and am now 125-128 depending on what I ate the day before. My cholesterol is not 1000 anymore-187. Energy abounds, spring in my steps. I look great in clothes; saving for the plastic surgery. But I can play with my grand daughters, jump the waves for an hour, be on my feet teaching without them swelling, no longer snore and am no longer diabetic. Yahooee!!! My teenage boys & the rest 0f my family can't believe the sdfference in me, nor can my husband. I was at a party with people I hadn't seen in 10 years and noone recognized me. How great is that! Thank you forever"
Brenda :
"I am almost 10 years out and I have had no problems, there are lots of people I worked with that have had different types and they have had all kinds of problems..
Thanks Dr. R..I have maintained for years without even thinking about it..I am not obsessed and it does not rule my life..I eat, but after 10 years, I still can only eat small portions..Sweets and bread are my downfall..It is different for everybody but in the end the goal is to have a happy normal eating life, and if we just happen to look good in the end then that is just icing on the cake..Take care all,
Zoey"
"I am almost 10 years out and I have had no problems, there are lots of people I worked with that have had different types and they have had all kinds of problems..
Thanks Dr. R..I have maintained for years without even thinking about it..I am not obsessed and it does not rule my life..I eat, but after 10 years, I still can only eat small portions..Sweets and bread are my downfall..It is different for everybody but in the end the goal is to have a happy normal eating life, and if we just happen to look good in the end then that is just icing on the cake..Take care all,
Zoey"
Nancy commented
"on 8/31 I will have my 3 year anniverary. Thank you, Dr. Rutledge and team, for giving me this new life."
To see the comment thread, follow the link below:
http://ping.fm/YHpLX
Thanks,
The Facebook Team
"on 8/31 I will have my 3 year anniverary. Thank you, Dr. Rutledge and team, for giving me this new life."
To see the comment thread, follow the link below:
http://ping.fm/YHpLX
Thanks,
The Facebook Team
Friday, July 17, 2009
Surgeon and hospital procedure volume have an inverse relationship with in-hospital complications and mortality.
Ann Surg. 2007 May;245(5):699-706.
Links
A state-wide review of contemporary outcomes of gastric bypass in Florida: does provider volume impact outcomes?
Murr MM, Martin T, Haines K, Torrella T, Dragotti R, Kandil A, Gallagher SF, Harmsen S.
Department of Surgery, University of South Florida Health Sciences Center, c/o Tampa General Hospital, Tampa, FL 33601, USA. mmurr@health.usf.edu
OBJECTIVES: To report contemporary outcomes of gastric bypass for obesity and to assess the relationship between provider volume and outcomes. BACKGROUND: Certain Florida-based insurers are denying patients access to bariatric surgery because of alleged high morbidity and mortality. SETTINGS AND PATIENTS: The prospectively collected and mandatory-reported Florida-wide hospital discharge database was analyzed. Restrictive procedures such as adjustable gastric banding and gastroplasty were excluded. RESULTS: The overall complication and in-hospital mortality rates in 19,174 patients who underwent gastric bypass from 1999 to 2003 were 9.3% (8.9-9.7) and 0.28% (0.21-0.36), respectively. Age and male gender were associated with increased duration of hospital stay (P < 0.001), increased in-hospital complications [age: odds ratio (OR) = 1.11, CI: 1.08-1.13; male: OR = 1.53, CI: 0.36-1.72] and increased in-hospital mortality (age: OR = 1.51, CI: 1.32-1.73; male: CI = 2.66, CI: 1.53-4.63), all P < 0.001. The odds of in-hospital complications significantly increased with diminishing surgeon or hospital procedure volume (surgeon: OR = 2.0, CI: 1.3-3.1; P < 0.001, 1-5 procedures relative to >500 procedures; hospital volume: OR = 2.1, CI: 1.2-3.5; P < 0.001, 1-9 procedures relative to >500 procedures). The percent change of in-hospital mortality in later years of the study was lowest, indicating higher mortality rates, for surgeons or hospitals with fewer (< or =100) compared with higher (> or =500) procedures. CONCLUSION: Increased utilization of bariatric surgery in Florida is associated with overall favorable short-term outcomes. Older age and male gender were associated with increased morbidity and mortality. Surgeon and hospital procedure volume have an inverse relationship with in-hospital complications and mortality.
Ann Surg. 2007 May;245(5):699-706.
Links
A state-wide review of contemporary outcomes of gastric bypass in Florida: does provider volume impact outcomes?
Murr MM, Martin T, Haines K, Torrella T, Dragotti R, Kandil A, Gallagher SF, Harmsen S.
Department of Surgery, University of South Florida Health Sciences Center, c/o Tampa General Hospital, Tampa, FL 33601, USA. mmurr@health.usf.edu
OBJECTIVES: To report contemporary outcomes of gastric bypass for obesity and to assess the relationship between provider volume and outcomes. BACKGROUND: Certain Florida-based insurers are denying patients access to bariatric surgery because of alleged high morbidity and mortality. SETTINGS AND PATIENTS: The prospectively collected and mandatory-reported Florida-wide hospital discharge database was analyzed. Restrictive procedures such as adjustable gastric banding and gastroplasty were excluded. RESULTS: The overall complication and in-hospital mortality rates in 19,174 patients who underwent gastric bypass from 1999 to 2003 were 9.3% (8.9-9.7) and 0.28% (0.21-0.36), respectively. Age and male gender were associated with increased duration of hospital stay (P < 0.001), increased in-hospital complications [age: odds ratio (OR) = 1.11, CI: 1.08-1.13; male: OR = 1.53, CI: 0.36-1.72] and increased in-hospital mortality (age: OR = 1.51, CI: 1.32-1.73; male: CI = 2.66, CI: 1.53-4.63), all P < 0.001. The odds of in-hospital complications significantly increased with diminishing surgeon or hospital procedure volume (surgeon: OR = 2.0, CI: 1.3-3.1; P < 0.001, 1-5 procedures relative to >500 procedures; hospital volume: OR = 2.1, CI: 1.2-3.5; P < 0.001, 1-9 procedures relative to >500 procedures). The percent change of in-hospital mortality in later years of the study was lowest, indicating higher mortality rates, for surgeons or hospitals with fewer (< or =100) compared with higher (> or =500) procedures. CONCLUSION: Increased utilization of bariatric surgery in Florida is associated with overall favorable short-term outcomes. Older age and male gender were associated with increased morbidity and mortality. Surgeon and hospital procedure volume have an inverse relationship with in-hospital complications and mortality.
Controlling for other factors, patients treated by low- and medium-volume surgeons (OR 3.7, P = .002; OR 2.8, P = .015) and hospitals (OR 2.3, P = .01; OR 2.44, P = .017) had increased odds of 30-day mortality versus high-volume surgeons and hospitals. LOS was significantly shorter at high-volume hospitals as well.
CONCLUSIONS: In Pennsylvania, high volume is associated with decreased mortality and LOS.
CONCLUSIONS: In Pennsylvania, high volume is associated with decreased mortality and LOS.
Designation as a bariatric surgery center of excellence does not ensure better outcomes. Neither does high annual procedure volume. Extra expenses associated with center of excellence designation may not be warranted.
Arch Surg. 2009 Apr;144(4):319-25; discussion 325.
Links
Bariatric surgery outcomes at designated centers of excellence vs nondesignated programs.
Livingston EH.
Division of Gastrointestinal and Endocrine Surgery, University of Texas Southwestern School of Medicine, 5323 Harry Hines Blvd, Rm E7-126, Dallas, TX 75390-9156, USA. edward.livingston@utsouthwestern.edu
OBJECTIVE: To compare outcomes of patients undergoing bariatric procedures in hospitals designated as centers of excellence compared with nondesignated hospitals. DESIGN: The 2005 National Inpatient Survey was used to compare outcomes at designated vs nondesignated hospitals. In addition to conventional null-hypothesis statistical testing to assess differences, effect sizes were calculated to estimate the clinical significance for observed differences. RESULTS: Centers of excellence performed substantially more operations than nondesignated centers. Despite this, outcomes were equivalent at centers of excellence and hospitals without this designation. Volume-outcome modeling attempting to identify the optimal number for a minimum volume threshold for bariatric operations revealed that annual procedure volume has a weak effect on outcomes. Similarly, many variables that were statistically significantly different between centers and noncenters proved to be clinically unimportant by effect size analysis. Risk adjustment was effectively achieved by using the Agency for Healthcare Research and Quality-supplied variables all-payer severity-adjusted diagnostic related group expected charges and deaths. CONCLUSIONS: Designation as a bariatric surgery center of excellence does not ensure better outcomes. Neither does high annual procedure volume. Extra expenses associated with center of excellence designation may not be warranted.
Arch Surg. 2009 Apr;144(4):319-25; discussion 325.
Links
Bariatric surgery outcomes at designated centers of excellence vs nondesignated programs.
Livingston EH.
Division of Gastrointestinal and Endocrine Surgery, University of Texas Southwestern School of Medicine, 5323 Harry Hines Blvd, Rm E7-126, Dallas, TX 75390-9156, USA. edward.livingston@utsouthwestern.edu
OBJECTIVE: To compare outcomes of patients undergoing bariatric procedures in hospitals designated as centers of excellence compared with nondesignated hospitals. DESIGN: The 2005 National Inpatient Survey was used to compare outcomes at designated vs nondesignated hospitals. In addition to conventional null-hypothesis statistical testing to assess differences, effect sizes were calculated to estimate the clinical significance for observed differences. RESULTS: Centers of excellence performed substantially more operations than nondesignated centers. Despite this, outcomes were equivalent at centers of excellence and hospitals without this designation. Volume-outcome modeling attempting to identify the optimal number for a minimum volume threshold for bariatric operations revealed that annual procedure volume has a weak effect on outcomes. Similarly, many variables that were statistically significantly different between centers and noncenters proved to be clinically unimportant by effect size analysis. Risk adjustment was effectively achieved by using the Agency for Healthcare Research and Quality-supplied variables all-payer severity-adjusted diagnostic related group expected charges and deaths. CONCLUSIONS: Designation as a bariatric surgery center of excellence does not ensure better outcomes. Neither does high annual procedure volume. Extra expenses associated with center of excellence designation may not be warranted.
Gastric banding or bypass? (Neither is Very Good).
Weight loss outcomes strongly favored Roux-en-Y gastric bypass over laparoscopic adjustable gastric banding. Patients treated with laparoscopic adjustable gastric banding had lower short-term morbidity than those treated with Roux-en-Y gastric bypass, but reoperation rates were higher among patients who received laparoscopic adjustable gastric banding.
Am J Med. 2008 Oct;121(10):885-93.
Gastric banding or bypass? A systematic review comparing the two most popular bariatric procedures.
Tice JA, Karliner L, Walsh J, Petersen AJ, Feldman MD.
Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143-1732, USA. jtice@medicine.ucsf.edu
Weight loss outcomes strongly favored Roux-en-Y gastric bypass over laparoscopic adjustable gastric banding. Patients treated with laparoscopic adjustable gastric banding had lower short-term morbidity than those treated with Roux-en-Y gastric bypass, but reoperation rates were higher among patients who received laparoscopic adjustable gastric banding.
Am J Med. 2008 Oct;121(10):885-93.
Gastric banding or bypass? A systematic review comparing the two most popular bariatric procedures.
Tice JA, Karliner L, Walsh J, Petersen AJ, Feldman MD.
Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143-1732, USA. jtice@medicine.ucsf.edu
Roux-en-Y gastric bypass is superior to gastric banding, There is mounting and convincing evidence that laparoscopic gastric banding is suboptimal
University of Toronto, Department of Surgery, Toronto, ON, M3N 1N1, Canada. uguller@yahoo.com.
ABSTRACT: BACKGROUND: The use of bariatric surgery in the management of morbid obesity is rapidly increasing. The two most frequently performed procedures are laparoscopic Roux-en-Y bypass and laparoscopic gastric banding. The objective of this short overview is to provide a critical appraisal of the most relevant scientific evidence comparing laparoscopic gastric banding versus laparoscopic Roux-en-Y bypass in the treatment of morbidly obese patients. RESULTS AND DISCUSSION: There is mounting and convincing evidence that laparoscopic gastric banding is suboptimal at best in the management of morbid obesity. Although short-term morbidity is low and hospital length of stay is short, the rates of long-term complications and band removals are high, and failure to lose weight after laparoscopic gastric banding is prevalent. CONCLUSION: The placement of a gastric band appears to be a disservice to many morbidly obese patients and therefore, in the current culture of evidence based medicine, the prevalent use of laparoscopic gastric banding can no longer be justified. Based on the current scientific literature, the laparoscopic gastric bypass should be considered the treatment of choice in the management of morbidly obese patients.
Patient Saf Surg. 2009 May 29;3(1):10.
University of Toronto, Department of Surgery, Toronto, ON, M3N 1N1, Canada. uguller@yahoo.com.
ABSTRACT: BACKGROUND: The use of bariatric surgery in the management of morbid obesity is rapidly increasing. The two most frequently performed procedures are laparoscopic Roux-en-Y bypass and laparoscopic gastric banding. The objective of this short overview is to provide a critical appraisal of the most relevant scientific evidence comparing laparoscopic gastric banding versus laparoscopic Roux-en-Y bypass in the treatment of morbidly obese patients. RESULTS AND DISCUSSION: There is mounting and convincing evidence that laparoscopic gastric banding is suboptimal at best in the management of morbid obesity. Although short-term morbidity is low and hospital length of stay is short, the rates of long-term complications and band removals are high, and failure to lose weight after laparoscopic gastric banding is prevalent. CONCLUSION: The placement of a gastric band appears to be a disservice to many morbidly obese patients and therefore, in the current culture of evidence based medicine, the prevalent use of laparoscopic gastric banding can no longer be justified. Based on the current scientific literature, the laparoscopic gastric bypass should be considered the treatment of choice in the management of morbidly obese patients.
Patient Saf Surg. 2009 May 29;3(1):10.
Debra H. to Mini-Gastric-B.
Jul 16
Hello to all…..
Just checking in on my 6 year anniversary! Can’t believe it has already been 6 years! The journey has been great! No complications, maintaining my weight… well up and down 5-8 pounds at times. The MGB and Dr. R truly changed my life! Life is good!
Those considering gastric by pass, do your research and make a decision that is best for you, I know for me the MGB was far above all others. My step daughter had an RNY and has had complications. Just last month at 2 years out from her RNY she had emergency surgery due to complications.
MGB is truly life changing. The health improvements have been the most important changes. Sometimes I forget I was obese, but then I see the discrimination and ridicule obese people face and it makes me remember the emotional pain I felt when I was obese. It makes me angry. I truly believe obesity is the last discrimination tolerated in our society.
I am proof the MGB when used as a tool works long term weight loss and maintenance.
I can honestly say…. 6 years into my MGB journey life is great!
God Bless,
Debra H. in San Antonio, TX
Dr. R. 7-16-03
240 high 212 day of surgery… NOW… 132 size 6 & 4
Jul 16
Hello to all…..
Just checking in on my 6 year anniversary! Can’t believe it has already been 6 years! The journey has been great! No complications, maintaining my weight… well up and down 5-8 pounds at times. The MGB and Dr. R truly changed my life! Life is good!
Those considering gastric by pass, do your research and make a decision that is best for you, I know for me the MGB was far above all others. My step daughter had an RNY and has had complications. Just last month at 2 years out from her RNY she had emergency surgery due to complications.
MGB is truly life changing. The health improvements have been the most important changes. Sometimes I forget I was obese, but then I see the discrimination and ridicule obese people face and it makes me remember the emotional pain I felt when I was obese. It makes me angry. I truly believe obesity is the last discrimination tolerated in our society.
I am proof the MGB when used as a tool works long term weight loss and maintenance.
I can honestly say…. 6 years into my MGB journey life is great!
God Bless,
Debra H. in San Antonio, TX
Dr. R. 7-16-03
240 high 212 day of surgery… NOW… 132 size 6 & 4
Monday, June 29, 2009
http://ping.fm/XoaOW
Address the public health problem of liver injury related to the use of acetaminophen (Tylenol)
Acetaminophen is one of the most commonly used drugs in the United States,1 yet it is also an important cause of serious liver injury. Acetaminophen is the generic name of a drug found in many common brand name over-the-counter (OTC) products, such as Tylenol
Address the public health problem of liver injury related to the use of acetaminophen (Tylenol)
Acetaminophen is one of the most commonly used drugs in the United States,1 yet it is also an important cause of serious liver injury. Acetaminophen is the generic name of a drug found in many common brand name over-the-counter (OTC) products, such as Tylenol
http://ping.fm/7fdRZ
FDA Requires Additional Labeling For Over-the-Counter Pain Relievers And Fever Reducers To Help Consumers Use Products Safely
Over-the-counter (OTC) pain relievers and fever reducers to revise their labeling to include warnings about potential safety risks, such as internal bleeding and liver damage
FDA Requires Additional Labeling For Over-the-Counter Pain Relievers And Fever Reducers To Help Consumers Use Products Safely
Over-the-counter (OTC) pain relievers and fever reducers to revise their labeling to include warnings about potential safety risks, such as internal bleeding and liver damage
http://ping.fm/TIbFE
FDA Recommends Tougher Standards for Acetaminophen: when taken over the maximum amount of 4 grams per day, acetaminophen can cause liver damage, ranging from abnormalities in blood tests used to assess liver function to acute liver failure (ALF), and even death
FDA Recommends Tougher Standards for Acetaminophen: when taken over the maximum amount of 4 grams per day, acetaminophen can cause liver damage, ranging from abnormalities in blood tests used to assess liver function to acute liver failure (ALF), and even death
Tuesday, April 28, 2009
American Society for Metabolic and Bariatric Surgery centers of excellence Don't Deliver!
http://ping.fm/Oc5Rb
doesn't reduce a patient's risk of complications or death!!!
http://ping.fm/Oc5Rb
doesn't reduce a patient's risk of complications or death!!!
Sunday, January 01, 2006
From: "Nancy Monroe"
Date: Sun Jan 1, 2006 4:49pm
Subject: RE: [OSSG-MiniGastricBypass] NEED CONTACTS
I had the surgery on 7/19/02 with Dr. Robert Rutledge, weighing 285 lbs. I
had been heavy all my life, trying different diets and diet pills just to
lose the weight and regain it all back plus more. I couldn't sit in a booth
at a restaurant and would have to ask for a table, couldn't climb stairs
without being out of breath, ask for an extension belt on a plane and
couldn't even enjoy playing with my grandchild. I felt so worthless and had
very low self esteem. This was my last chance for a healthy life.
My surgery took 45 minutes because I had some scar tissue from having a
spleen removed in 1989. I had no nausea after surgery and only used the
pain pump once to get some sleep. I was up walking in the hall by late
evening. My girlfriend picked me up the next morning and stayed with me for
the weekend.
It took several weeks for me to get my energy back. During this time, I was
hired for CLOS. The staff is very compassionate to patient needs and care
and we are here to answer any questions or concerns you may have.
Our doctors are very skilled, knowledgeable, compassionate surgeons and have
all been trained by the pioneer of the MGB, Dr. Robert Rutledge.
The hospital staff is also great. Everyone is understanding to your needs
and very caring.
Would I do it again? In a heartbeat. The first 2-3 months are the hardest
because there are so many changes taking place. It is quite a challenge to
see what your body will tolerate after surgery.
Do I have any regrets? Yes, just one..My only regret is that I couldn't
have had the surgery years ago. WOW, what a difference it would have made
in my life.
This is a very special gift that has been given to me by Dr. Rutledge and I
will forever grateful to him. I have lost 145 lbs. and I thank God that it
has changed my life.
Nancy Monroe
Human Resource Administrator
704-682-0260 (cell)
704-871-0031
npm@...
www.clos.net
Date: Sun Jan 1, 2006 4:49pm
Subject: RE: [OSSG-MiniGastricBypass] NEED CONTACTS
I had the surgery on 7/19/02 with Dr. Robert Rutledge, weighing 285 lbs. I
had been heavy all my life, trying different diets and diet pills just to
lose the weight and regain it all back plus more. I couldn't sit in a booth
at a restaurant and would have to ask for a table, couldn't climb stairs
without being out of breath, ask for an extension belt on a plane and
couldn't even enjoy playing with my grandchild. I felt so worthless and had
very low self esteem. This was my last chance for a healthy life.
My surgery took 45 minutes because I had some scar tissue from having a
spleen removed in 1989. I had no nausea after surgery and only used the
pain pump once to get some sleep. I was up walking in the hall by late
evening. My girlfriend picked me up the next morning and stayed with me for
the weekend.
It took several weeks for me to get my energy back. During this time, I was
hired for CLOS. The staff is very compassionate to patient needs and care
and we are here to answer any questions or concerns you may have.
Our doctors are very skilled, knowledgeable, compassionate surgeons and have
all been trained by the pioneer of the MGB, Dr. Robert Rutledge.
The hospital staff is also great. Everyone is understanding to your needs
and very caring.
Would I do it again? In a heartbeat. The first 2-3 months are the hardest
because there are so many changes taking place. It is quite a challenge to
see what your body will tolerate after surgery.
Do I have any regrets? Yes, just one..My only regret is that I couldn't
have had the surgery years ago. WOW, what a difference it would have made
in my life.
This is a very special gift that has been given to me by Dr. Rutledge and I
will forever grateful to him. I have lost 145 lbs. and I thank God that it
has changed my life.
Nancy Monroe
Human Resource Administrator
704-682-0260 (cell)
704-871-0031
npm@...
www.clos.net
| From: "Susan E. G Date: Sun Jan 1, 2006 4:21pm Subject: RE: [OSSG-MiniGastricBypass] What's best to eat right after surgery | |
>1 ). Do the hospital give you a list of recomdations on what would be
>good choices to eat. I know yogurt, chiken noodle soup, saltine
>crackers can be eaten right after but what else. Same question for
>Stage 2, whats good.
At the hospital, they brought me yogurt, chicken broth, saltines and
Gatorade a few hours after surgery. Same thing the next day. When I came
back to my hotel, I stayed with that, plus V8, and 'classic' (not cream)
tomato soup. There was a Wild Oats market with fresh, hot soups nearby, and
I ate some of the strained, non-creamy broths from the vegetable soups.
I'm three weeks post-op, and I still stick mostly with the stage 1 foods,
plus some runny mashed potatoes made with lactose-free milk, some applesauce
and a tiny bit of guacamole on saltines. I also eat the noodles from the
chicken soup and tried a bit of butternut squash soup diluted down with more
chicken broth. I did eat a little baked fish the other night, which tasted
pretty good, and yesterday I ate a graham cracker with a thin layer of
creamy peanut butter on it. Yogurt is still a mainstay---good source of
calcium and protein and very easy on your new stomach connections.
The first week or so I lost about ten pounds, and since then, seem to be
consistently losing about half a pound a day, so today I'm down 20 lbs from
pre-op. I feel good, have plenty of energy and can happily jog two miles
five days a week---and no, I WASN'T doing that pre-surgery.
I know this sounds pretty dull, but your tastes and appetites *will* change
after surgery. Believe me, I love good food, but post-surgery, you really
are (or at least I am) pretty ho-hum about food. It recedes back into a
mildly interesting fuel source, not the central driving force of your
universe. You'll lose the craving to drive twenty miles for a favorite
meal, be able to drive past the pizza joint down the street without drooling
and will have to remind yourself to go find a bite or two of something,
rather than fighting with yourself to order the medium fries instead of the
super-size with a double cheeseburger.
Don't worry about being satisfied with food post-op---you will be, even on a
fairly restricted regimen at first. Food loses its magical (dominating)
attraction and you really will be perfectly satisfied with a few ounces of
yogurt or a cup of brothy something or other. Don't look at post-op as "I
have to stay on this really boring diet". Look at it as "food no longer has
a hold over me." That really is how it feels on the other side.
Good luck, I know you'll do great.
Susan G
Dr. Rutledge, Las Vegas 12/14/05
249/229/?
Saturday, December 31, 2005
Hello Dr. Rutledge,
Just thought you might like to hear from a long past patient. You did my surgery about 7 years ago. I now realize I was quite ill and on my way to the grave. At the time of my surgery, I was at about 290 but at times was well over 300.
I came to the clinic in NC for my wife, but realized I needed the surgery more than she did. Within a year of having the surgery, I stopped losing at 165 pounds and I am still at that same weight.
I eat anything I want and I am as happy and as healthy as I have ever been in my life. I do have problems with Iron Deficiency but all else is great. My blood pressure and cholesterol are great. The only medications I take are Prilosec and iron.
No more B/P medications, no more sleep apnea and life is wonderful. You may recall, my wife had the surgery also and she is currently at 140 pounds. We both are still nurses and currently live in South Carolina.
The surgery saved my life and I am grateful every day that there are people like you who were willing to see that the possible side effects of a drastic measure such as surgery outweigh the alternative of a life of misery or death.
I still visit your web site on occasion to make sure you are still around and helping others.
Keep up the great work.
Homer B., RN, MSN
Just thought you might like to hear from a long past patient. You did my surgery about 7 years ago. I now realize I was quite ill and on my way to the grave. At the time of my surgery, I was at about 290 but at times was well over 300.
I came to the clinic in NC for my wife, but realized I needed the surgery more than she did. Within a year of having the surgery, I stopped losing at 165 pounds and I am still at that same weight.
I eat anything I want and I am as happy and as healthy as I have ever been in my life. I do have problems with Iron Deficiency but all else is great. My blood pressure and cholesterol are great. The only medications I take are Prilosec and iron.
No more B/P medications, no more sleep apnea and life is wonderful. You may recall, my wife had the surgery also and she is currently at 140 pounds. We both are still nurses and currently live in South Carolina.
The surgery saved my life and I am grateful every day that there are people like you who were willing to see that the possible side effects of a drastic measure such as surgery outweigh the alternative of a life of misery or death.
I still visit your web site on occasion to make sure you are still around and helping others.
Keep up the great work.
Homer B., RN, MSN
Ann Surg. 2005 Jul;242(1):20-8. Related Articles, Links
Laparoscopic Roux-en-Y versus mini-gastric bypass for the treatment of morbid obesity: a prospective randomized controlled clinical trial.
Lee WJ, Yu PJ, Wang W, Chen TC, Wei PL, Huang MT.
Department of Surgery, En-Chu Kong Hospital and School of Nursing, Taiwan. wjlee@km.eck.org.tw
OBJECTIVES: This prospective, randomized trial compared the safety and effectiveness of laparoscopic Roux-en-Y gastric bypass (LRYGBP) and laparoscopic mini-gastric bypass (LMGBP) in the treatment of morbid obesity.- SUMMARY BACKGROUND DATA: LRYGBP has been the gold standard for the treatment of morbid obesity. While LMGBP has been reported to be a simple and effective treatment, data from a randomized trial are lacking.
- METHODS: Eighty patients who met the NIH criteria were recruited and randomized to receive either LRYGBP (n = 40) or LMGBP (n = 40). The minimum postoperative follow-up was 2 years (mean, 31.3 months). Perioperative data were assessed. Late complication, excess weight loss, BMI, quality of life, and comorbidities were determined. Changes in quality of life were assessed using the Gastro-Intestinal Quality of Life Index (GIQLI).
- RESULTS: There was one conversion (2.5%) in the LRYGBP group. Operation time was shorter in LMGBP group (205 versus 148, P <>
- CONCLUSION: Both LRYGBP and LMGBP are effective for morbid obesity with similar results for resolution of metabolic syndrome and improvement of quality of life. LMGBP is a simpler and safer procedure that has no disadvantage compared with LRYGBP at 2 years of follow-up.
Publication Types:
MeSH Terms:- Adult
- Anastomosis, Roux-en-Y
- Body Mass Index
- Comparative Study
- Female
- Gastric Bypass/methods*
- Humans
- Laparoscopy/methods*
- Male
- Obesity, Morbid/diagnosis*
- Obesity, Morbid/surgery*
- Pain, Postoperative
- Patient Satisfaction
- Postoperative Complications
- Probability
- Prospective Studies
- Quality of Life*
- Reference Values
- Risk Assessment
- Severity of Illness Index
- Surgical Procedures, Minimally Invasive/methods
- Treatment Outcome
- Weight Loss
PMID: 15973097 [PubMed - indexed for MEDLINE]
From: "Julie C."
Date: Sat Dec 31, 2005 7:39pm
Subject: A week of many firsts and thank yous
This week has been filled with several poignant moments for me that have thrilled me beyond believe that I had to share them with you all and say thanks.
This week I reached and past my doctor's goal weight, a weight I haven't seen in 24 years and I skated and tobaggoned for the first time in 24 years. A few minor injuries but still had the energy to get back up and dust myself off. The icing on my cake to end this most fabulous year of firsts was going to buy new jeans today and walking out of the store with 2 pairs of size 6. I have never in my life been a size 6 and tears can to my eyes when the clerk handed them to me and they fit.
For such a personal journey I can't believe how many new people have become a part of my life and who without their help and support I never could have had such an amazing week and year. 2005 started off to be one of the worst years of my life and now 12 months later I look back and think wow, how blessed am I.
Now for my Oscar acceptance speech...I would first like to say thank you to the very first group of MGB ladies (Donna and Donna) that I meet when I attended my first support meeting in Welland in September 2004, you really helped me to get the ball rolling. A huge thank you to Kim Hazen and Dr. Fiala for being my role models and helping me make the decision to take back control of my life and showing me that there really is a light at the end of the tunnel. A great big thank you to all that supported me online when I was new to the group. To those who listened to my troubles with my doctor/OHIP and offered me solutions to my problems, Gloria, Miriam, Alexandra, Martha, Tricia, Ann, Joan and anyone else I may have forgetten. Thank you to the wonderful people at OHIP for approving my surgery, without them, well I don't even want to think about where I would be. Thank you to the wonderful Michigan support group for all your support and suggestions the day before my surgery. I look forward to coming to Michigan again and enjoying something other then soup with you all.
Thank you to Dr. Rutledge for pioneering this amazing surgery, Dr. Doroghazi (my new hero) for giving me the greatest tool to use in taking back my life. Again to Kim Hazen for her shoulder to cry on when I was emotionally distraught and petrified to leave Michigan. A great big thank you to my step mom (my support person) who was there for me the entire time and still is my number one support person. A huge thank you and hug to my dearest friend Donna Giles who without her ongoing support from day one I never could have made it this far.
And last but not least to everyone in all the support groups who have helped, inspired, supported me and everyone else in this group, a very huge and heartfelt thank you to you all.
Happy New Year
Julie C.
Penetanguishene, Ontario Canada
March 22, 2005
Dr. Doroghazi Bay City Michigan
300/290/156
Date: Sat Dec 31, 2005 7:39pm
Subject: A week of many firsts and thank yous
This week has been filled with several poignant moments for me that have thrilled me beyond believe that I had to share them with you all and say thanks.
This week I reached and past my doctor's goal weight, a weight I haven't seen in 24 years and I skated and tobaggoned for the first time in 24 years. A few minor injuries but still had the energy to get back up and dust myself off. The icing on my cake to end this most fabulous year of firsts was going to buy new jeans today and walking out of the store with 2 pairs of size 6. I have never in my life been a size 6 and tears can to my eyes when the clerk handed them to me and they fit.
For such a personal journey I can't believe how many new people have become a part of my life and who without their help and support I never could have had such an amazing week and year. 2005 started off to be one of the worst years of my life and now 12 months later I look back and think wow, how blessed am I.
Now for my Oscar acceptance speech...I would first like to say thank you to the very first group of MGB ladies (Donna and Donna) that I meet when I attended my first support meeting in Welland in September 2004, you really helped me to get the ball rolling. A huge thank you to Kim Hazen and Dr. Fiala for being my role models and helping me make the decision to take back control of my life and showing me that there really is a light at the end of the tunnel. A great big thank you to all that supported me online when I was new to the group. To those who listened to my troubles with my doctor/OHIP and offered me solutions to my problems, Gloria, Miriam, Alexandra, Martha, Tricia, Ann, Joan and anyone else I may have forgetten. Thank you to the wonderful people at OHIP for approving my surgery, without them, well I don't even want to think about where I would be. Thank you to the wonderful Michigan support group for all your support and suggestions the day before my surgery. I look forward to coming to Michigan again and enjoying something other then soup with you all.
Thank you to Dr. Rutledge for pioneering this amazing surgery, Dr. Doroghazi (my new hero) for giving me the greatest tool to use in taking back my life. Again to Kim Hazen for her shoulder to cry on when I was emotionally distraught and petrified to leave Michigan. A great big thank you to my step mom (my support person) who was there for me the entire time and still is my number one support person. A huge thank you and hug to my dearest friend Donna Giles who without her ongoing support from day one I never could have made it this far.
And last but not least to everyone in all the support groups who have helped, inspired, supported me and everyone else in this group, a very huge and heartfelt thank you to you all.
Happy New Year
Julie C.
Penetanguishene, Ontario Canada
March 22, 2005
Dr. Doroghazi Bay City Michigan
300/290/156
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