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.

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 percent 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 percent; 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 percent; ns), but was significantly different from indomethacin (indomethacin = 9.12 ± 0.8 vs rofecoxib = 2.17 ± 0.4 percent; 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.

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.

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 (51Cr-EDTA) expressed as percentage of the ingested dose. The urinary excretion of 51Cr-EDTA was significantly reduced in patients with strongyloidiasis compared to controls (1.60 + or - 0.74 and 3.10 + or - 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

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.

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.

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.

Reproducibility of the ultrasound method for measurement of gallbladder volume.

Gallbladder motility has largely been studied in recent years. Since the ultrasonographic method can be used in gallbladder emptying studies, we investigated the reproducibility of the ultrasound method for measurement of gallbladder volume. The ultrasonographic method was highly reproducible (r = 0.97) and, due to its safeness and lack of use of radioactive agents, it is attractive option for gallbladder motility studies in conditions associated with increased frequency of cholelithiasis.

Measurement of gastric emptying time by real-time ultrasonography in patients with Crohn's disease.

In order to gain some insight into the possible influence of gastric emptying on gallbladder hypomotility in patients with Crohn's disease, the gastric emptying time (GET) was measured by means of ultrasonography in 10 healthy controls and 10 patients with Crohn's disease. No significant difference was observed between both mean values for GET studies (GET: controls, 165.0 min +/- 12.8; Crohn, 142.0 min +/- 11.5; p = 0.208) after ingestion of a liquid meal. Thus, the gallbladder hypomotility described in patients with Crohn's disease, after a liquid fatty-meal stimulus, can not be explained by prolonged gastric emptying time.

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.

Protein-losing enteropathy in systemic lupus erythematosus

Enteropatia perdedora de proteina no lupus eritematoso sistemico. O caso de uma jovem de 23 anos com lupus eritematoso sistemico e enteropatia perdedora de proteina e descrito. A biopsia de delgado revelou linfangiectasia. O quadro regrediu com o uso de prednisona. A enteropatia perdedora de proteina deve ser suspeitada nos casos de lupus eritematoso sistemico com hipoalbuminemia e funcoes hepatica e renal preservadas. A revisao da literatura e apresentada salientando-se os aspectos fisiopatologicos envolvidos.

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.

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.

[Postoperative jaundice syndrome after mitral valve replacement. A case report]. / Síndrome de icterícia pós-operatória após substituição valvar mitral. Relato de caso.

A 52-year old woman was submitted to mitral valve replacement. The operation proceeded without complications. Jaundice had been noted since the first postoperative (po) day and increased progressively due to conjugated bilirubin. Abdominal examination was normal and no signs of infection or circulatory failure were noted. Conjugated bilirubin levels increased from 6 mg/dl on the second po day to 20.4 mg/dl on the sixth po day and to 32 mg/dl on the tenth po day. Gammaglutamyl transferase levels were 600 U/L (normal up to 18 U/L) and lactate dehydrogenase levels were 396 U/L (normal) up to 240 U/L) on the seventh po day. Alkaline phosphatase levels were 1880 U/L (normal up to 170 U/L) whereas glutamic oxalacetic transaminase levels were 60 U/L (normal up to 15 U/L) and glutamic pyruvic transaminase levels were 66 U/L (normal up to 17 U/L) on the tenth po day. Abdominal ultrasonography did not disclose dilatation of intra and extra-hepatic biliary system. The patient died after a percutaneous hepatic biopsy procedure. The jaundice was attributed to a cholestatic syndrome after cardiac surgery and cardiopulmonary bypass, due to an impairment of the excretory function of the hepatocyte.

[Salicylic derivatives in the clinical treatment of inflammatory bowel disease: new perspectives]. / Derivados salicílicos no tratamento clínico da doença inflamatória intestinal: novas perspectivas.

Sulfasalazine is one of the most used drugs in the clinical management of inflammatory bowel disease. Nevertheless up to 30% of the patients experiment side effects related to the drug and end up having the drug diminished or withdrawn. The new salicylic-derivate compounds emerge as a reliable alternative for these patients. The authors review the new preparations and discuss their characteristics, indications and side effects.

[Chylomicron metabolism in experimental cholestasis]. / Metabolismo de quilomícros na colestase experimental.

Cholesterol and triglyceride plasma levels are usually increased in cholestasis. The excess of cholesterol and that of triglyceride are carried in abnormal low-density lipoproteins (LP) named LP-X and beta 2-LP respectively. It has been assumed that chylomicron metabolism is involved in these alterations. To gain insight into the LP disturbances in this pathology, artificial chylomicrons (AC) were prepared in protein-free aqueous solutions containing lecithin, cholesteryl-oleate, cholesterol and triolein. AC were labelled simultaneously with cholesteryl--14C-oleate (14C-CO) and 3H-triolein (3H-TO) and pulse injected intra-arterially in rats subjected to total obstruction of the bile duct for 48 hours and sham-operated rats. Blood was collected at 2-minute intervals during 10 minutes for radioactivity determination. Fractional clearance rates of 3H-TO and 14C-CO were diminished. Since plasma decay of 3H-TO reflects predominantly the rate of lipolysis (L) whereas chylomicron remnant removal (CRR) by the liver is represented by the 14C-CO decay, our data suggest that in cholestasis both L and CRR are defective.

[Chylomicron metabolism]. / Metabolismo de quilomicros.

The liver is known to play a central role in the chylomicron metabolism. It synthesizes apolipoproteins (e.g., apo A I, apo C II, apo E), lecithin cholesterol acyltransferase, hepatic lipase and is responsible for the chylomicron remnant removal. Not surprisingly then the chylomicron metabolism is compromised in liver diseases such as acute hepatitis, cirrhosis and cholestasis. The authors reviewed the normal features of the chylomicron metabolism which are essential for a better understanding of the lipoprotein disturbance in liver diseases.