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Biomedical subjects

A M Sipahi

Publications and source records attributed to A M Sipahi.

At least 19 recordsLinked to original sources
PubMed2004

Effect of a selective nonsteroidal anti-inflammatory inhibitor of cyclooxygenase-2 on the small bowel of rats.

The pathogenesis of nonsteroidal anti-inflammatory drug (NSAID) enteropathy is a complex process involving the uncoupling of mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase (COX). Rofecoxib, a selective inhibitor of COX-2, has shown less gastric damage, but the same beneficial effect is not clear in the case of the small bowel. Fifty-seven male Wistar rats (250-350 g) were divided into three groups (N=19 each) to evaluate the effect of this NSAID on the rat intestine. The groups received 2.5 mg/kg rofecoxib, 7.5 mg/kg indomethacin or water with 5% DMSO (control) given as a single dose by gavage 24 h before the beginning of the experiment. A macroscopic score was used to quantify intestinal lesions and intestinal permeability was measured using [51Cr]-ethylenediaminetetraacetic acid ([51Cr]-EDTA). The extent of intestinal lesion, indicated by a macroscopic score, was significantly lower when rofecoxib was administered compared to indomethacin (rofecoxib=0.0 vs indomethacin=63.6 +/- 25.9; P<0.05) and did not differ from control. The intestinal permeability to [51Cr]-EDTA was significantly increased after indomethacin (control=1.82 +/- 0.4 vs indomethacin=9.12 +/- 0.8%; P<0.0001), but not after rofecoxib, whose effect did not differ significantly from control (control=1.82 +/- 0.4 vs rofecoxib=2.17 +/- 0.4%; ns), but was significantly different from indomethacin (indomethacin=9.12 +/- 0.8 vs rofecoxib=2.17 +/- 0.4%; P<0.001). In conclusion, the present data show that rofecoxib is safer than indomethacin in rats because it does not induce macroscopic intestinal damage or increased intestinal permeability.

Animals↗
PubMed2003

Lack of evidence for the pathogenic role of iron and HFE gene mutations in Brazilian patients with nonalcoholic steatohepatitis.

The hypothesis of the role of iron overload associated with HFE gene mutations in the pathogenesis of nonalcoholic steatohepatitis (NASH) has been raised in recent years. In the present study, biochemical and histopathological evidence of iron overload and HFE mutations was investigated in NASH patients. Thirty-two NASH patients, 19 females (59%), average 49.2 years, 72% Caucasians, 12% Mulattoes and 12% Asians, were submitted to serum aminotransferase and iron profile determinations. Liver biopsies were analyzed for necroinflammatory activity, architectural damage and iron deposition. In 31 of the patients, C282Y and H63D mutations were tested by PCR-RFLP. Alanine aminotransferase levels were increased in 30 patients, 2.42 1.12 times the upper normal limit on average. Serum iron concentration, transferrin saturation and ferritin averages were 99.4 31.3 g/dl, 33.1 12.7% and 219.8 163.8 g/dl, respectively, corresponding to normal values in 93.5, 68.7 and 78.1% of the patients. Hepatic siderosis was observed in three patients and was not associated with architectural damage (P = 0.53) or with necroinflammatory activity (P = 0.27). The allelic frequencies (N = 31) found were 1.6 and 14.1% for C282Y and H63D, respectively, which were compatible with those described for the local population. In conclusion, no evidence of an association of hepatic iron overload and HFE mutations with NASH was found. Brazilian NASH patients comprise a heterogeneous group with many associated conditions such as hyperinsulinism, environmental hepatotoxin exposure and drugs, but not hepatic iron overload, and their disease susceptibility could be related to genetic and environmental features other than HFE mutations.

Adult↗
PubMed2001

Protective effect of metronidazole on uncoupling mitochondrial oxidative phosphorylation induced by NSAID: a new mechanism.

BACKGROUND: The pathogenesis of non-steroidal anti-inflammatory drug (NSAID) enteropathy is complex. It involves uncoupling of mitochondrial oxidative phosphorylation which alters the intercellular junction and increases intestinal permeability with consequent intestinal damage. Metronidazole diminishes the inflammation induced by indomethacin but the mechanisms remain speculative. A direct effect on luminal bacteria has traditionally been thought to account for the protective effect of metronidazole. However, a protective effect of metronidazole on mitochondrial oxidative phosphorylation has never been tested. AIMS: To assess the protective effect of metronidazole on mitochondrial uncoupling induced by indomethacin and also on the increased intestinal permeability and macroscopic damage. MATERIAL AND METHODS: The protective effect of metronidazole was evaluated in rats given indomethacin; a macroscopic score was devised to quantify intestinal lesions, and intestinal permeability was measured by means of (51)Cr-ethylenediaminetetraacetic acid. The protective effect of metronidazole against mitochondrial uncoupling induced by indomethacin was assessed using isolated coupled rat liver mitochondria obtained from rats pretreated with metronidazole or saline. RESULTS: Metronidazole significantly reduced the macroscopic intestinal damage and increase in intestinal permeability induced by indomethacin; furthermore, at the mitochondrial level, it significantly reduced the increase in oxygen consumption in state 4 induced by indomethacin and caused less reduction of the respiratory control rate. CONCLUSION: Our study confirmed the beneficial effects of metronidazole on intestinal damage and intestinal permeability, and demonstrated, for the first time, a direct protective effect of metronidazole on uncoupling of mitochondrial oxidative phosphorylation caused by NSAIDs.

Animals↗
PubMed2001

Intestinal permeability in strongyloidiasis.

The objective of the present study was to assess intestinal permeability in patients with infection caused by Strongyloides stercoralis. Twenty-six patients (16 women and 10 men), mean age 45.9, with a diagnosis of strongyloidiasis were evaluated. For comparison, 25 healthy volunteers (18 women and 7 men), mean age 44.9, without digestive disorders or intestinal parasites served as normal controls. Intestinal permeability was measured on the basis of urinary radioactivity levels during the 24 h following oral administration of chromium-labeled ethylenediaminetetraacetic acid ((51)Cr-EDTA) expressed as percentage of the ingested dose. The urinary excretion of (51)Cr-EDTA was significantly reduced in patients with strongyloidiasis compared to controls (1.60 +/- 0.74 and 3.10 +/- 1.40, respectively, P = 0.0001). Intestinal permeability is diminished in strongyloidiasis. Abnormalities in mucus secretion and intestinal motility and loss of macromolecules could explain the impaired intestinal permeability.

Adult↗
PubMed1997

Effects of colectomy on gallbladder motility in patients with ulcerative colitis.

In order to gain insight into the possible mechanisms involved in gallstone formation in colectomized ulcerative colitis patients, we studied gallbladder motility by means of ultrasonography in three groups of subjects: controls (N = 40) and ulcerative colitis patients without (N = 30) and with (N = 20) colectomy. Impaired gallbladder emptying after a liquid fatty meal stimulus was observed in ulcerative colitis patients with colectomy compared with those obtained in ulcerative colitis patients without colectomy and controls (P = 0.001). The maximum percentage of gallbladder emptying also, was significantly lower (59.8%) than those seen in ulcerative colitis patients without colectomy (74.5%) and controls (77.8%) (P = 0.001). Diminished gallbladder emptying with ensuing stasis might be a contributory factor to the increased prevalence of gallstones in colectomized patients.

Adult↗
PubMed1997

Gallbladder hypokinesia in Crohn's disease.

For the purpose of shedding some light upon the possible mechanisms involved in gallstone formation in patients with Crohn's disease, we have investigated gallbladder emptying by means of ultrasonography in two groups of subjects: controls (n = 40) and Crohn's disease (n = 30). Diminished gallbladder emptying after a liquid fatty-meal stimulus was observed in patients with Crohn's disease when compared with controls (p < 0.001). Also, the values for the residual gallbladder volume (RGV) and maximal decrease in gallbladder volume (MDGV), both in milliliters and percentage were, respectively, increased (RGV = 9.6 ml) and diminished (MDGV = 14.8 ml; MDGV = 60.9%) in patients with Crohn's disease when compared with controls (RGV = 5.9 ml, p < 0.001; MDGV = 19.9 ml, p = 0.003; MDGV = 77.8%, p < 0.001). Hence, reduced gallbladder emptying with consequent stasis might be a contributory factor to the increased prevalence of gallstones in Crohn's disease.

Adult↗
PubMed1995

Experimental evaluation of a model for predicting micellar composition and concentration of monomeric species in bile salt binary mixtures.

The critical micellar concentration (cmc) values of some mixed systems containing two bile salts were determined by a maximum pressure bubble method and compared with those derived from a theoretical model developed for nonionic surfactants to assess the applicability of this model to such systems. Some assumptions on which the presumed validity of this model was based are discussed. The following binary mixtures were investigated: sodium chenodeoxycholate with cholate, ursocholate and ursodeoxycholate, either unconjugated or conjugated with taurine and glycine at different mole fractions (0, 0.25, 0.5, 0.75, 1) in 0.15 M NaCl. For these mixtures, experimentally determined data were in good agreement with values predicted by the theoretical model: both the cmc and the surface tension at this concentration of the mixtures were intermediate between those of the two pure bile salts; also, as the total bile salt concentration increased, the mixed micelles became enriched with the bile salt having the highest cmc, whereas the total monomer activity, determined by a potentiometric method employing a bile salt-selective electrode, increased only slightly. To test this model in an in vitro system, surface tension was also measured in ox bile samples that were enriched by 50% with sodium ursodeoxycholate, chenodeoxycholate, or their taurine amidates. The cmc and the surface tension at this concentration of the artificial bile increased when enriched with a bile salt with a cmc higher than that of endogenous salts (e.g. ursodeoxycholate versus taurocholate), whereas the reverse occurred for mixtures enriched with a bile salt with a lower cmc, such as chenodeoxycholate.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Acids and Salts↗
PubMed1993

Chylomicron metabolism in experimental cirrhosis and cholestasis.

Recently it has been demonstrated that artificial emulsions made of lecithin, cholesterol, cholesteryl-oleate and triolein simulate the metabolism of the natural chylomicra. Artificial-chylomicron delipidation and remnant disappearance from plasma were investigated in rats with carbon tetrachloride-induced hepatic cirrhosis or with cholestasis due to bile-duct ligation. Artificial chylomicra were labelled simultaneously with glyceryl tri [9, 10 (N)-3H] oleate and cholesteryl [1-14C] oleate and injected intra-arterially. Simultaneous chylomicron delipidation and remnant removal by the liver were calculated from the plasma radioactivity decay curves: that of glyceryl tri [9, 10 (N)-3H] oleate signifying the combined delipidation and particle-removal processes, whereas that of cholesteryl [1-14C] oleate representing the particle disappearance rate from plasma. Particle delipidation was increased in cirrhosis and decreased in cholestasis, implying faster and slower lipolysis rates respectively. On the other hand, the remnant removal rate by the liver slowed down in both experimental pathologies.

Animals↗
PubMed1991

Small bowel bacterial overgrowth in strongyloidiasis.

Small bowel bacterial growth was studied in patients with strongyloidiasis, and the results were compared to controls. We concluded that in strongyloidiasis there is small bowel bacterial overgrowth, and so it should be considered in the pathogenesis of some of the gastrointestinal manifestations and complications of strongyloidiasis.

Adolescent↗
PubMed1990

Bile acids do not regulate the intestinal mucosal cholesterol synthesis: studies in the chronic bile duct-ureter fistula rat model.

Control male Wistar rats with intact bile circulation, animals with a bile duct-right ureter fistula, and bile duct-right ureter fistula rats fed taurocholic acid (5.5 mg/day) were maintained on a cholesterol-free pellet diet and pulse labeled subcutaneously with radioactive cholesterol. Bile acid feeding did not interfere with the synthesis of cholesterol by the intestinal mucosa or by the whole body in spite of markedly lowering the production of bile acids. Of the total fecal cholesterol mass in bile fistula animals roughly 25% originated from plasma filtration and 75% was ascribed to local mucosal cholesterol synthesis.

Animals↗
PubMed1989

Origin of intestinal lymph cholesterol in rats: contribution from luminal absorption, mucosal synthesis and filtration from plasma.

Measurement of cholesterol transport from plasma to intestinal lymph based on i.v. labeling with radioactive beta-sitosterol was validated by the simultaneous i.v. administration of 4-14C-beta-sitosterol and of 1,2-3H-cholesterol to two rats with bile duct, intestinal lymph, duodenum and jugular vein cannulations. In 11 other rats undergoing intestinal lymph duct cannulation, each potential source of lymph cholesterol was determined 2-3 weeks after i.v. pulse administration of 1,2-3H-beta-sitosterol and 4-14C-cholesterol. For this purpose, lymph fat, after an intragastric infusion of cottonseed oil (1900mg), was used as a marker for total cholesterol mass transported into intestinal lymph. In these two experimental groups of rats, namely, in the absence and in the presence of supplemental dietary cholesterol, filtration of cholesterol from plasma to lymph and absorption of cholesterol derived from bile did not change in the presence of exogenous cholesterol. In other words, absorption of cholesterol based on the amount of cholesterol in intestinal lymph by direct measurement was comparable to the level obtained by the isotopic procedure based upon lowering of the lymph/plasma ratio of 4-14C-cholesterol specific activity (d.p.m./mg of cholesterol). Plasma cholesterol appearing in intestinal lymph was transported mainly in lymph lipoproteins at a density below 1.006 (i.e., chylomicrons). Esterification was not necessary for luminal cholesterol absorption under these experimental conditions.

Animals↗
PubMed1989

Contribution of plasma protein and lipoproteins to intestinal lymph: comparison of long-chain with medium-chain triglyceride duodenal infusion.

In rats with intestinal lymph-fistula and electrolyte and protein losses continuously replaced by I.V. infusion, the plasma to lymph filtration of total protein, albumin, and cholesterol was similar after duodenal infusion of either long-chain (LCT) or medium-chain (MCT) triglyceride. Filtration of cholesterol into intestinal lacteals was also measured after pulsed I.V. administration of 14C-beta-sitosterol as an indirect marker for passage of lipoproteins into the lymph system. During intraduodenal administration of LCT and constant I.V. infusion of 125I-apo high density lipoprotein (HDL), intact plasma HDL appeared in lymph and contributed apo-LP to chylomicron formation. Nevertheless, most lymph apo-LP originated from local mucosal synthesis.

Animals↗
PubMed1979

Origin of cholesterol transported in intestinal lymph: studies in patients with filarial chyluria.

In subjects fed a cholesterol-free diet there are three possible sources of intestinal lymph cholesterol: a) mucosal synthesis; b) absorption of endogenous (biliary) cholesterol; and c) transudation of plasma lipoproteins into the lacteals of the intestinal wall. To test these possibilities, the extent of transudation was measured by means of [3H]beta-sitosterol administered intravenously as a marker. Absorption of biliary cholesterol was reduced by oral administration of beta-sitosterol (9 g/day), and mucosal synthesis of cholesterol was evaluated by comparisons of plasma/lymph [14C]cholesterol specific activity ratios after intravenous administration of a single dose of labeled cholesterol. Studies were carried out on six patients with filarial chyluria. In five patients fed a cholesterol-free diet the results indicated that lymph cholesterol was largely derived by transudation of plasma lipoproteins into the lacteals from the intestinal blood supply, without contribution from de novo mucosal synthesis or from absorption of endogenous cholesterol. The intestinal lymph of one patient fed cholesterol (2 g/day) contained cholesterol originating mostly from plasma transudation and from dietary absorption, with little contribution from absorbed endogenous cholesterol. In all experiments the larger part of the cholesterol transported away from the intestine in the lymph was carried in chylomicrons, even though it had its origin in plasma lipoproteins.

Adolescent↗
PubMedDate not supplied

Ursodeoxycholic acid does not interfere with in vivo Helicobacter pylori colonization.

A low frequency of Helicobacter pylori in the gastric mucosa of patients with alkaline gastritis has been reported. At the same time, it can be noted that the growth of bacteria can be inhibited by bile acids. We studied 40 patients with chronic gastritis related to Helicobacter pylori in order to determine the effect of ursodeoxycholic acid on this infection. Diagnoses of the infection and the inflammatory process were obtained by histologic study of gastric biopsies collected during endoscopy. Two groups were studied: group I received ursodeoxycholic acid - 300 mg/day, and group II received the placebo, twice a day, both for 28 days. The colonization by Helicobacter pylori and the intensity of the mononuclear and polymorphonuclear inflammatory infiltrate were determined before (time 1) and after (time 2) treatment. Ursodeoxycholic acid had no effect on the Helicobacter pylori infection. A significant reduction in the intensity of the mononuclear inflammatory infiltrate of the gastric antrum mucosa was observed in patients from group I, when we compared not only times 1 and 2 but also groups I and II. However, this was not the case with the body mucosa. We concluded that ursodeoxycholic acid had no action on the colonization by Helicobacter pylori or on the polymorphonuclear inflammatory infiltrate, but it caused a significant reduction in the intensity of the mononuclear inflammatory infiltrate of the gastric antrum.

Adult↗
PubMedDate not supplied

Protein-losing enteropathy in systemic lupus erythematosus.

We describe a 23-year old Brazilian woman with systemic lupus erythematosus and protein-losing enteropathy. Small intestinal biopsy revealed lymphangiectasia. Protein-losing enteropathy responded to corticosteroid therapy and should be suspected in cases of systemic lupus erythematosus with hypoalbuminemia without proteinuria and liver failure. A review of the English literature is presented with comments on pathogenesis.

Adult↗