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S Iqbal

Publications and source records attributed to S Iqbal.

18 recordsLinked to original sources
PubMed1991

Maintenance of mixed-function oxidase and conjugation enzyme activities in hepatocyte cultures prepared from normal and diseased human liver.

Isolated hepatocytes were prepared from normal and diseased human livers and maintained in primary monolayer culture for up to 96 h. The viability and yields of cell preparations obtained from diseased livers did not differ significantly from those obtained from normal livers. During the culture period a significant increase in cell protein/DNA ratio was observed in both normal and diseased hepatocytes. The maintenance of a number of drug metabolising enzyme activities was determined in these hepatocytes during 96 h of culture. In normal hepatocytes the maintenance pattern of mixed-function oxidase activities (ethoxycoumarin-O-deethylase and ethoxyresorufin-O-deethylase) was clearly different from that of the conjugating enzymes (sulfotransferase and glutathione transferase). Whereas ethoxycoumarin-O-deethylase and ethoxyresorufin-O-deethylase activities declined sharply over the first 24 h in culture and then either totally or partially recovered, sulfotransferase and glutathione transferase activities were found to be relatively more stable initially but thereafter decline progressively. In diseased hepatocytes mixed-function oxidase activities were maintained less well than the corresponding activities in normal hepatocytes whereas conjugation enzyme activities were maintained to a similar extent.

Adolescent↗
PubMed1990

Drug metabolism in end-stage liver disease. In vitro activities of some phase I and phase II enzymes.

The activities of a number of drug metabolising enzymes were measured in liver samples obtained from three groups of subjects: normal donors, patients with primary biliary cirrhosis (PBC), and patients with other types of liver disease. In the latter group, all the enzyme activities determined were impaired relative to the normal group. In the PBC group, however, enzyme activities were altered more selectively. (a) Activities of the methyl cholanthrene-inducible forms of cytochrome P-450 were decreased compared to normal controls, whereas the activities of the phenobarbitone-inducible isozymes were relatively unaffected. (b) Sulfotransferase activities were decreased significantly compared to the normal group, whereas sulfatase activities remained unaltered.

Adolescent↗
PubMed1988

Ileal entrapment as a complication of fractured pelvis.

A case of entrapment of small bowel in a fracture of the pelvis is presented. It was found on laparotomy in the present case, but contrast enema or computerized tomography have been reported as diagnostic of this rare, life-threatening condition.

Adult↗
PubMed1987

Ileal absorption of tyrosine-conjugated bile acids in Wistar rats.

We recently reported that tyrosine-conjugated bile acids, when injected intravenously into bile-fistula rats, are extracted by the liver and secreted intact into bile with an efficiency similar to that seen for taurocholate. Now the effect of tyrosine and glycyltyrosine conjugation of bile acids on ileal absorption has been studied in Wistar rats. 125I-labelled tyrosine- and glycyltyrosine-conjugated bile acid or [14C]taurocholate was injected in 400 microliters aliquots of physiological saline buffered to pH 7.8 into the ileal lumen of bile-fistula rats. Recovery of bile salts in bile was taken as proof of ileal absorption. In comparison with taurocholate, ileal absorption was about 10% less for cholyltyrosine and chenodeoxycholyltyrosine and about 50% less for deoxycholyltyrosine. Thus, tyrosine-conjugated bile acids are absorbed by the ileum and excreted into bile and may undergo enterohepatic circulation. Low recoveries of deoxycholyltyrosine relative to deoxycholylglycine suggested that side chain structure was important for ileal absorption of 3 alpha,12 alpha-dihydroxy bile acids. Elongation of cholic acid to form cholylglycyltyrosine markedly reduced 90-min cumulative ileal absorption relative to cholyltyrosine. Although initial rates of recovery of cholylglycyltyrosine were comparable to those of the other bile acids, very little further absorption was seen in the last hour of the experiment, suggesting that this compound was rapidly degraded within the intestinal lumen.

Animals↗
PubMed1986

Synthesis and biliary excretion of tyrosine-conjugated bile salts in Wistar rats.

Tyrosine-labelled free and glycine-conjugated bile acids were synthesized and radiolabelled with 125I to high purity. The synthetic method utilized excess tyrosine methyl ester hydrochloride (1.4 equiv.) and bile acid (one equiv.) via dicyclohexylcarbodiimide (1.4 equiv.) with yields of 90-93% for tyrosine bile acid conjugates and glycyltyrosine conjugates and 56-60% yields for the glycylglycyltyrosine conjugates. All of the eight iodinated tyrosine bile acids tested were rapidly excreted into bile following intravenous injection. In bile duct-cannulated rats with ligated renal pedicles under pentobarbital anaesthesia the percentages of injected dose recovered from bile within 20 min were as follows: cholylglycine ([14C]cholylGly), 81.2 +/- 1.3%; taurocholate ([14C]taurocholate), 94.3 +/- 1.0%; cholyltyrosine (125I-cholylTyr), 85.5 +/- 3.3%; deoxycholyltyrosine (125I-deoxycholylTyr), 87.9 +/- 6.3%; chenodeoxycholyltyrosine (125I-chenodeoxycholylTyr), 93.4 +/- 2.9; cholylglycyltyrosine (125I-cholylGlyTyr), 95.7 +/- 6.7%; deoxycholylglycyltyrosine (125I-deoxylcholylGlyTyr), 92.5 +/- 3.2%; chenodeoxycholylglycyltyrosine (125I-chenodeoxycholylGlyTyr), 94.1 +/- 3.1%; cholyldiglycyltyrosine (125I-cholylGlyGlyTyr), 85.2 +/- 3.6%, and deoxycholyldiglycyltyrosine (125I-deoxycholylGlyGlyTyr), 85.5 +/- 2.7%. Values are means +/- SD. Thus the biliary excretion of 125I-chenodeoxycholylGlyTyr, 125I-chenodeoxycholylTyr, 125I-deoxycholylGlyTyr and 125I-cholylGlyTyr was similar to that of [14C]taurocholate, the major naturally occurring bile acid in the rat, and the biliary excretion of all the tyrosine conjugates was similar to or exceeded that of [14C]cholylglycine. Conjugation with tyrosine enhanced the efficiency of plasma-to-bile transport of most naturally occurring bile acids. Comparison of glycyltyrosine conjugates with glycylglycyltyrosine conjugates suggests that any additional benefit derived by elongation of the side-chain is probably negated by obscuring the 12 alpha-hydroxyl function on the steroid nucleus in the bile acid glycylglycyltyrosine conjugates.

Animals↗
PubMed1986

Iodinated cholylglycyltyrosine: a new agent for hepatobiliary imaging.

The characteristics of radiolabelled cholylglycyltyrosine (CGT), a recently synthesised bile acid, were studied. 125I-CGT-Na was found to have a short plasma half-life of 1.6 +/- 0.4 min in rats and 3.1 +/- 0.7 min in dogs. Biliary clearance studies showed the cumulative biliary output of the tracer over 20 min in rats to be 95.7% of the total dose administered, with a mean biliary transit time (50% retention time) of 4.0 +/- 0.1 min, i.e. similar to the biliary kinetics of taurocholate. 131I-CGT-Na proved to be satisfactory for hepatobiliary imaging in rats and dogs at doses of 35 microCi (1.3 MBq) in rats and 90 microCi (3.3 MBq) in dogs. Satisfactory hepatic images were also obtained in rats that had high bilirubin levels produced by obstruction or the recycling of bile. These results show that CGT has better pharmacokinetics than currently used hepatobiliary imaging agents, and that this new compound may be useful in scintigraphy even in the presence of jaundice.

Animals↗
PubMed1985

Selectively reduced biliary excretion of cholyldiglycylhistamine but not of cholyltetraglycylhistamine in ethinyl estradiol-treated rats. A possible indicator of increased bile canalicular permeability.

A series of bile acid derivatives were synthesized, purified and radiolabelled. These were [125I]cholylglycylhistamine [( 125I]CGH), [125I] cholyldiglycylhistamine [( 125I]CG2H), [125I]cholyltriglycylhistamine [( 125I]CG3H), and [125I]cholyltetraglycylhistamine [( 125I]CG4H). These derivatives were rapidly excreted unchanged into the bile of bile-fistula rats. In normal rats the 30-min cumulative excretion following intravenous administration was only 39.0 +/- 0.7% for [125I]CGH but greater than 80% for the three larger compounds. This marked difference in biliary recovery between CGH and the other larger compounds could be due to a threshold biliary permeability, and we postulated that the critical molecular weight threshold for effective biliary retention of such compounds falls between [125I]CGH (MW 683) and [125I]CG2H (MW 740). Increased permeability, involving a shift to a higher molecular weight threshold would then be anticipated to diminish biliary excretion of [125I]CG2H (MW 740) before exerting a major influence on the biliary excretion of [125I]CG4H (MW 854). We previously reported functional and morphological studies which suggest that ethinyl estradiol (EE) may alter the permeability of bile canalicular tight junctions. In this study we have looked for further evidence of a progressive permeability change in EE-induced cholestasis by observing the biliary excretion of CG2H and CG4H in rats. Treatment with EE (5 mg/kg/day) for 3 days (EE3) or with the injection vehicle propylene glycol for 7 days (C7) reduced biliary excretion to a significant extent when compared to 3-day controls (C3) but had no differential effect on the 30-min recoveries from bile of CG2H and CG4H, respectively: C3 (81.2 +/- 1.8% and 81.7 +/- 2.1%, P = CN): C7 (72.3 +/- 3.0% and 73.5 +/- 3.6%, P = NS): EE3 61.8 +/- 2.5% and 61.9 +/- 2.7%, P = NS). However, treatment with EE for 7 days significantly reduced the biliary recovery of CG2H (46.8 +/- 9%) compared to EE3 rats (P less than 0.0025) but there was no significant change of biliary CG4H recovery (61.0 +/- 2.5%, P = NS) compared with EE3 rats. These results are compatible with our hypothesis that EE-induced cholestasis is associated with a change of biliary permeability which, as it progresses, affects successively larger molecules.

Animals↗
PubMed1985

Biliary permeability during ethinyl estradiol-induced cholestasis studied by segmented retrograde intrabiliary injections in rats.

The influence of ethinyl estradiol (EE) treatment on the permeability of the biliary tree in rats has been assessed by the segmented retrograde intrabiliary injection (SRII) technique. Three pairs of compounds were studied, inert [14C]sucrose and [3H]inulin; [14C]taurocholic acid (TC) and [14C]glycocholic acid (GC) and the non-ionic bile acid derivatives [125I]cholyldiglycylhistamine (CG2H) and [131I]cholyltetraglycylhistamine (CG4H). In control rats recovery in bile after SRII was always greater for the larger of any pair of compounds, confirming that the biliary tree acts as a filter, and that decreased recovery from bile during this technique is an index of greater biliary permeability. After EE treatment recovery of all compounds was significantly reduced, thus confirming that EE increases biliary permeability. Recovery of sucrose and inulin fell from 55-65% of the administered dose in controls to 8-9% in EE rats. Recoveries of TC, GC, CG2H and CG4H was also reduced, but their biliary recovery profiles were consistent with marked re-excretion into bile of that portion which had initially passed out of the biliary system by filtration. During the later phase of the experiment excretion of the negatively charged bile acids TC and GC was greater than that of the non-ionic bile acid derivatives CG2H and CG4H. Although the site at which these permeability changes have occurred is unknown, our results are compatible with previous data implicating increased tight junction permeability as a mechanism of EE-induced cholestasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Dermatoglyphics in vitiligo.

One hundred probands of vitiligo were studied for palmar dermatoglyphics, both qualitatively and quantitatively, and were compared with those of 100 phenotypically normal control subjects. Ulnar loop pattern was the most common digital pattern observed in both probands and controls. An increased incidence of whorls and arches in men and women probands, respectively, was found to be statistically significant when compared with those of controls. Simian crease and Sydney line also have been observed in the present study, which has not been previously reported. A statistically highly significant reduction has been observed in total finger ridge count (TFRC) and a-b ridge count in both sexes of vitiligo cases when compared with those of controls. No significant changes was observed in the values of atd angle and position of axial triradius.

Adolescent↗
PubMed1985

A new method of complete biliary retention.

We describe a new modified method of producing non-obstructive complete internal biliary retention in the rat by draining bile into the caudal vena cava. This relatively simple method has the additional advantage that restraining cages are not necessary.

Animals↗
PubMed1983

Increased tight junction permeability: a possible mechanism of oestrogen cholestasis.

Ethinyl oestradiol increased rat biliary permeability for 3H-inulin and 14C-sucrose, and significantly raised serum concentrations of bile acids after 3 and 7 days' treatment (P less than 0.0005) and bilirubin after 7 days (P less than 0.005) but not after 3 days. Following intravenous infusion of bromsulphthalein or phenolphthalein, ethinyl oestradiol-treated rats had elevated plasma concentrations of the three bile constituents, bromsulphthalein (P less than 0.0005 after 3 and 7 days), bromsulphthalein-glutathione conjugate (P less than 0.005 after 3 days; P less than 0.0005 after 7 days) and phenolphthalein glucuronide (P less than 0.005 after 3 days; P less than 0.0005 after 7 days), but the plasma concentration of unconjugated phenolphthalein, which was undetectable in bile, was unchanged. Similar changes followed partial biliary obstruction produced by bile cannula elevation. This pattern suggests that biliary constituents are refluxing from bile to plasma via the paracellular pathway, a concept further supported by structural changes in tight junction morphology in the oestrogen-treated rats. 'Leakiness' of canalicular tight junctions may explain the pathophysiology of oestrogen-induced cholestasis.

Animals↗
PubMed1979

Membranes and bile formation. Composition of several mammalian biles and their membrane-damaging properties.

The total content and profile of bile salts and phospholipids are reported for several mammalian biles. Rabbit and guinea-pig biles are characterized by high proportions of conjugated dihydroxy bile salts with respect to trihydroxy bile salts, but contain relatively little phospholipid. Both rabbit and guinea-pig biles exhibit little evidence of hepatic cell damage, even though they are able to cause membrane damage (as evidenced by lysis of human erythrocytes) at low (2--3 mM) concentrations of bile salts; this lytic behaviour is also a property of their predominant bile salts. Addition of phosphatidylcholine to the bile or bile salt is able to decrease the lytic behaviour. Perhaps the most significant observation is that these biles, and their predominant bile salts, are dramatically less lytic towards sheep erythrocytes, indicating that some factor(s) in membrane composition and structure may partly explain the resistance of membranes of the biliary tract to the presence of high concentrations of potentially membrane-damaging bile salts.

Animals↗