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Biomedical subjects

M A Rahman

Publications and source records attributed to M A Rahman.

At least 127 records · Page 7Linked to original sources

Immune complex effects on glomerular eicosanoid production and renal hemodynamics.

We examined the effect of glomerular immune complex (IC) deposition on glomerular eicosanoid synthesis and the role of the eicosanoids in glomerular pathophysiology. Rats received daily 10 mg i.v. injections of native bovine gamma-globulin (NBGG) or cationic bovine gamma-globulin (CBGG) for 21 days; age-matched controls were maintained. Immunofluorescence and electron microscopy showed mesangial deposits of IC in the NBGG group and capillary wall deposits in the CBGG group, without light or electron microscopic evidence of leukocyte infiltration. One week after the last antigen dose, GFR was similar in all three groups, but RPF increased in the rats given CBGG; (8.37 +/- 0.90 vs. control 5.54 +/- 0.56 ml/min, P less than 0.05). Glomerular synthesis of prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) was normal in animals that received NBGG. Rats given CBGG had increased glomerular production of PGE2, (2.23 +/- 0.37 vs. control 1.03 +/- 0.16 ng/mg glomerular dry wt, P less than 0.05) and TxB2 (3.12 +/- 0.50 vs. control 0.48 +/- 0.07 ng/mg glomerular dry wt, P less than 0.001). Proteinuria only developed in the rats given CBGG, 86.6 +/- 18 mg/24 hr, which correlated with glomerular TxA2 synthesis, r = 0.82, P = 0.01. Acute administration of the TxA2 synthesis inhibitor, UK-38,485, and a TxA2 receptor antagonist, EP-092, to rats given CBGG did not affect GFR or RPF. The cyclo-oxygenase inhibitor, indomethacin, reduced both GFR and RPF by up to 40% in CBGG-immunized rats. Oral administration of UK-38,485 for six days to nephrotic rats did not result in a statistically significant reduction of proteinuria despite 85% inhibition of glomerular TxB2. We conclude that cationic antigen induces a glomerular disease pathologically similar to membranous nephropathy. The increment of RPF is most probably due to increased glomerular PGE2. The increased TxA2 has no effect on glomerular hemodynamics and probably is not a component in the pathogenesis of proteinuria.

Animals↗

The roles of eicosanoids in experimental glomerulonephritis.

There is accumulating evidence showing alterations of renal eicosanoid synthesis in glomerular disease. Despite the complexity of their role in glomerulonephritis, these compounds appear to play a major part in the inflammatory response and in control of renal hemodynamics. The role of eicosanoids in the filtration of macromolecules has not been established, but there is indirect evidence of their involvement in mediating proteinuria. Dietary manipulation, either by high EPA, high linoleic acid, or EFA-deficient diet, in experimental glomerulonephritis have shown promising results as summarized in Table 1. The therapeutic potential of alterations in dietary fatty acid to modulate the inflammatory response appears to be of great value. Table 2 summarizes the effects of different dietary fatty acid alterations on eicosanoid synthesis. Nonetheless, we should point out that most of the studies of alterations in dietary fatty acids did not document changes in glomerular synthesis of prostaglandin, thromboxane, or HETES. Further studies examining the effects of different fatty acid regimens on glomerular eicosanoid synthesis and the role of these eicosanoids in the development of glomerulonephritis will provide valuable information. These findings could determine the specific type of dietary manipulation to inhibit or stimulate the production of selected eicosanoids.

Alprostadil↗

Eicosanoids in experimental and human renal disease.

The renal prostaglandins and thromboxanes are powerful autacoids with potential effects on renal hemodynamics, salt and water metabolism, and the immune system. The possibility of adverse effects on renal function in certain patients with renal disease due to cyclooxygenase inhibition with nonsteroidal anti-inflammatory drugs has long been appreciated. Experimental evidence indicates that renal prostaglandin and thromboxane production is increased in several models of renal disease and that similar decrements in renal function occur with cyclooxygenase inhibition and may be due to inhibition of vasodilator prostaglandins. Additionally, several investigators have shown that administration of prostaglandins may be therapeutic in some forms of renal disease, particularly immunologically mediated diseases. Dietary modification to affect prostaglandin production has also been promising in certain experimental models. In contrast to vasodilator prostaglandins, thromboxane is a potent vasoconstrictor and would be expected to have adverse effects on renal function. Despite demonstration of elevated glomerular thromboxane, studies using inhibitors of thromboxane synthesis in immunologically mediated glomerular disease have been disappointing. There is some evidence, however, that these drugs may be of benefit in ureteric obstruction and renal transplant rejection.

Acute Kidney Injury↗

Changes in urinary composition of calcium oxalate stone formers.

Calcium oxalate is the most important constituent of urinary calculi and the excretion pattern of calcium and oxalate is not consistent with stone formation. The increase in urinary calcium and oxalate in calcium oxalate stone formers has been found to be associated with the increase in uric acid and uromucoids along with the increase in inorganic phosphate and magnesium (in adults only) whilst citrate was decreased (in children only). The role of uric acid and uromucoids in the genesis of calcium oxalate stone is indicated.

Adolescent↗

Studies on serum mucoproteins in patients with urinary calculi.

A significant increase in serum mucoproteins in stone patients has been observed previously. The present study describes the variation of the constituents of mucoproteins obtained on hydrolysis. The serum mucoproteins of 31 patients with urinary calculi (13 with kidney stone, 7 with bladder stone and 11 with stones in other sites) were analysed and compared with that of 15 healthy control subjects, who had no personal or family history of calculi. The mucoproteins, glycosylated serum proteins, hexosamine and sialic acid were increased in all patients irrespective of the site of stone, while uronic acid decreased as compared with the control subjects. Serum fucose increased in all patients except in kidney stone formers. Uronic acid decreased in all stone formers irrespective of the site of the stone. It is suggested that a different type of mucoprotein is present in such patients.

Adolescent↗

Second generation alpha-enones from a pyranosidic alpha-enone.

The Diels-Alder product from the reaction of methyl 2,3,6-trideoxy-alpha-D-glycero-hex-2-enopyranosid-4-ulose (1b) with trans-1-methoxy-3-tert-butyl-dimethylsilyloxy-1,3-butadiene is 3b (93%). Reaction of 3b wih sodium borohydride causes reduction of the C-4 carbonyl group only, but, with lithium aluminum hydride, further reactions occur which can be rationalized by fragmentation brought about by hydride cleavage on the silicon-oxygen bond, with simultaneous ejection of the beta-methoxyl group complexed to a trivalent aluminum species. The enone resulting from this fragmentation also reacts further with lithium aluminum hydride, and several products result. The behavior of postulated intermediates, which have been prepared separately and subjected to the reaction conditions, supports the proposed reaction mechanisms. The "second generation" enone (methyl 2,3,6-trideoxy-alpha-D-talopyranosido)-[3,2-d]-2-cyclohexenone+ ++ (10a), arising from the first generation precursors 1b, has been prepare by two routes.

Chemical Phenomena↗

Mechanism of contamination from agricultural chemicals in mammals.

Chemicals in the form of pharmaceuticals are used to extend the life of man. It is ironic that other chemicals are also required to poison the pests that compete for the food supply so that man will have enough to eat during his extended lifetime. Now these poisons are reaching levels in the environment where the life span of man is again being shortened by both immediate and long-term effects caused by these pesticides. Hundreds of thousands of people are incapacitated and killed by insecticide poisoning each year, many of them in developing countries, from the chemicals no longer allowed for use in the western nations that produce them. Continuous monitoring and surveillance are required to avoid misuse of pesticides, because many of the hazards associated with these chemicals can be reduced substantially, if not eliminated completely.

Adipose Tissue↗

Studies on cataractogenesis in humans and in rats with alloxan-induced diabetes. I. Cation transport and sodium-potassium-dependent ATPase.

Changes in the cation balance cause hydration and initiate the process of lens opacification. Such alterations were studied in human cataractous lenses and during the development of alloxan-induced diabetic cataract in rats by biochemical and histochemical techniques. The development of alloxan-induced cataract in rats was examined in vivo which showed cortical opacities beginning after 32 days. These opacities did progress to maturity after 64 days and finally the lenses were completely opacified after 96 days of alloxan treatment. The histochemical localization of sodium-potassium-activated adenosine triphosphatase using three different methods provided information on the possible role of this enzyme in normal and cataractous lenses. In human cataractous lenses, sodium-potassium adenosine triphosphatase activity was found to be considerably decreased, whereas no activity of this enzyme was localized in human diabetic cataractous lenses. An animal model provided evidence that an apparent decrease of sodium-potassium adenosine triphosphatase may be involved in the initiation of alloxan-induced diabetic cataract in rats.

Animals↗

Studies on cataractogenesis in humans and in rats with alloxan-induced diabetes. II. Histochemical evaluation of lenticular enzymes.

The effect of cataractogenesis on the behavior of some enzymes involved in glucose metabolism was examined histochemically both in human lenses and in rat lenses from rats with alloxan-induced diabetes. Several modifications in the currently available techniques were made in order to localize glucose-6-phosphate dehydrogenase, aldose reductase, sorbitol dehydrogenase, hexokinase and ketohexokinase in ocular lens. Human cataractous lenses showed a precipitous drop in glucose-6-phosphate dehydrogenase activity, whereas the lenticular tissues of alloxan-treated rats showed a gradual decrease of this enzyme with the prolongation of diabetes. Aldose reductase activity increased in hypermature and senile diabetic cataracts, whereas sorbitol dehydrogenase activity decreased in these lenses. Similarly, in alloxan-diabetic rat lenses the activity of aldose reductase increased while that of sorbitol dehydrogenase decreased with the prolongation of diabetes. Attempts were made to localize hexokinase and ketohexokinase in ocular lens.

Aldehyde Reductase↗

Glomerular arachidonate lipoxygenation in rat nephrotoxic serum nephritis.

Arachidonate lipoxygenation to monohydroxylated eicosatetraenoic acids (HETE) was studied in rat nephrotoxic serum nephritis (NSN). A single infusion of nephrotoxic serum enhanced conversion of [3H]arachidonic acid ([3H]C20:4) to [3H]12-HETE in glomeruli isolated from nephritic rats compared with controls. The percent conversion of [3H]arachidonic acid was 1.95 +/- 0.2% in control glomeruli and 14.2 +/- 2% in nephritic glomeruli 2 d after induction of disease. No significant changes in the conversion of [3H]C20:4 to [3H]5-, 8-, and 9-HETE were noted. Extraction of glomerular HETE by alkaline hydrolysis, to evaluate possible reacylation of HETE after their production, confirmed the presence of 12-HETE and did not provide evidence of 5-HETE synthesis. Increased glomerular 12-HETE synthesis in nephritic rats was also demonstrated by high pressure liquid chromatography-UV detection and by 12-HETE radioimmunoassay. The enhanced glomerular 12-HETE synthesis commenced as early as 3-5 h after administration of nephrotoxic serum and peaked at day 2 with 10-fold enhancement of 12-HETE production. Increments of glomerular 12-HETE persisted on day 7 and returned toward control levels by day 14. Platelet depletion, induced by antiplatelet antisera, did not decrease glomerular 12-HETE synthesis in NSN, thereby eliminating platelets as the cellular origin of 12-HETE. Glomerular epithelial and mesangial cells are the most likely sources of enhanced 12-lipoxygenase activity. The enhanced arachidonate 12-lipoxygenation in glomerular immune injury could have important proinflammatory effects in the evolution of glomerulonephritis since 12-HETE has important effects on leukocyte function.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Studies on xylitol-induced insulin secretion in vitro.

A comparative study on the insulinotropic effect of xylitol and glucose was undertaken using isolated rat islets of Langerhans. Xylitol and glucose showed equal insulinotropic effects when compared at equivalent dose levels. Xylitol-induced insulin release was not inhibited by either mannoheptulose or 2-deoxy-D-glucose whereas glucose-induced insulin release was significantly inhibited. Glucagon, caffeine and cyclic-AMP enhanced the insulinotropic effect of glucose and leucine significantly, but insulin release in response to xylitol was not affected. Arginine did not potentiate the insulin releasing effect of xylitol though leucine showed an additive effect. These findings suggest that the mode of action of xylitol may be different from that of glucose.

Animals↗

Trace elements in serum from Pakistani patients with acute and chronic ischemic heart disease and hypertension.

We examined sera from 159 patients with ischemic heart disease and hypertension and from 50 apparently healthy control subjects for content of trace elements, cholesterol, triglyceride, and enzymes. Concentrations of copper, cobalt, cholesterol, and triglyceride were increased in all patients, but calcium was decreased in patients with hypertension, acute myocardial ischemia, and acute myocardial infarction. Also accompanying acute myocardial infarction were decreased concentrations of zinc and iron but increases in nickel, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase. Magnesium concentration was lower in patients with acute myocardial ischemia. In acute myocardial infarction, the concentrations of copper, zinc, and iron were higher after 21-30 h (as compared with the values at 0-10 h), by which time concentrations of calcium, magnesium, cobalt, and alanine aminotransferase had decreased. The variation in concentration of trace elements in serum from cases of ischemic heart disease and hypertension corresponds to the severity of the disorder.

Adult↗

Partial purification and characterization of lenticular S-adenosylmethionine synthetase.

Lenticular S-adenosylmethionine synthetase has been partially purified and characterized. Lower levels of S-adenosylmethionine synthetase were detected by a sensitive radioactive assay procedure in the lenticular extract obtained from the pooled lenses of alloxan-treated rats 96 days of age as compared to the nontreated controls. With respect to chromatographic behavior and kinetic analysis, lenticular S-adenosylmethionine synthetase closely resembled that of the corresponding liver enzyme.

Alloxan↗