Biomedical subjects

J Chakraborty

Publications and source records attributed to J Chakraborty.

At least 109 records · Page 6Linked to original sources

PubMed1987

Effects of cysteine and antioxidants on the hepatic redox-state, acetaldehyde and triglyceride levels after acute ethanol dosing.

Cysteine and the synthetic antioxidants butylated hydroxytoluene (BHT) and N,N'-diphenyl-phenylenediamine (DPPD) have been found to protect against the increase in hepatic triglycerides caused by acute ethanol administration (2 g/kg/i.p.) in rats. None of these agents affected the ethanol-induced increase in the hepatic redox-state, measured as lactate/pyruvate and 3-hydroxybutyrate/acetoacetate ratios, and there was no influence of any of the compounds on ethanol metabolism. Of the three agents tested, only cysteine was found to lower the liver acetaldehyde concentration after ethanol administration, confirming reports that trapping of acetaldehyde can protect against ethanol hepatotoxicity. The protective action of the anti-oxidants suggests that lipid peroxidation (probably initiated by acetaldehyde) is an important event in the pathogenesis of acute alcoholic fatty liver.

Acetaldehyde↗

PubMed1986

The role of the hepatocellular redox state in the hepatic triglyceride accumulation following acute ethanol administration.

The role of the increased hepatocellular redox-state [( NADH]/[NAD+] ratio) as a mechanism underlying hepatic triglyceride deposition after acute ethanol dosing has been investigated in the rat. Following a single dose of ethanol (2 g/kg i.p.) in fasted rats, increases were observed at 1.5 hr in the hepatic [lactate]/[pyruvate] (133%), [3-hydroxybutyrate]/[acetoacetate] (69%) ratios, and the liver triglyceride concentration (129%). At the same time point, ethanol increased radioactivity incorporated into hepatic total lipid and triglyceride, after an injection of [U-14C] palmitic acid, by 76% and 158% respectively. Treatment of animals with Naloxone hydrochloride (2 mg/kg i.p.) at 1.0 hr and 2.5 hr after ethanol abolished these ethanol-mediated redox-state changes, without inhibiting ethanol oxidation or affecting hepatic acetaldehyde levels. This, however, did not prevent completely the triglyceride accumulation in the liver or reverse the enhanced uptake of radio-labelled palmitate caused by ethanol. Administration of sorbitol (3.5 g/kg i.p.) caused 109%, 57% and 200% increases in the hepatic [lactate]/[pyruvate], [3-hydroxybutyrate]/[acetoacetate] ratios and glycerol-3-phosphate concentrations respectively. However, the hepatic triglyceride concentration and the incorporation of [U-14C] palmitic acid into hepatic lipids were not influenced by this treatment. In vitro studies in which rat liver slices were incubated with [1-14C] palmitic acid also indicated that the altered [NADH]/[NAD+] ratio was not responsible for the decreased rate of fatty acid oxidation seen after ethanol administration or after the addition of ethanol to the incubation medium. In conclusion, these experiments indicate that increases in the hepatic [NADH]/[NAD+] ratio resulting from ethanol oxidation may not be directly implicated in the altered hepatic fatty acid utilisation and triglyceride deposition observed after acute ethanol administration in rats.

Acetaldehyde↗

PubMed1986

Field trial of oral cholera vaccines in Bangladesh.

The protective efficacy of oral B subunit killed whole-cell (BS-WC) and killed whole-cell (WC) cholera vaccines was assessed in 63 498 Bangladeshi children aged 2-15 years and women aged over 15 years. Each received three doses of BS-WC, WC, or placebo in a randomised, double-blinded fashion. Surveillance for cases seeking medical care up to six months after the third dose revealed 26 cases of confirmed cholera in the placebo group, 4 cases in the BS-WC group (protective efficacy 85%; p less than 0.0001), and 11 cases in the WC group (protective efficacy 58%; p less than 0.01). For each vaccine protective efficacy was consistent in different age-groups (2-10 years versus greater than 10 years) and for different severities of cholera.

Administration, Oral↗

PubMed1986

Determination of the urinary metabolites of caffeine and theophylline by high-performance liquid chromatography. A comparative study of a direct injection and an ion-pair extraction procedure.

Chromatographic separation of methylxanthine metabolites was achieved using a Hypersil octadecylsilane column with a simple concave gradient elution programme of 0-12.75% acetonitrile in 1% tetrahydrofuran, pH 4.8, and the eluted components were detected by monitoring their absorption at 280 nm. An extraction procedure involving the formation of an ion-pair complex was developed which gave significant improvements over previously described methods including a shorter chromatographic run of 20 min. A thorough comparison of this procedure with a more convenient alternative involving direct injection of diluted urine specimens showed that the latter analysis was adequate for the quantitation of the major urinary metabolites of caffeine and theophylline.

Caffeine↗

PubMed1986

Effects of experimental torsion of the spermatic cord on Leydig cell function in the guinea pig testis: an ultrastructural stereological analysis.

An ultrastructural stereological analysis of Leydig cells of the guinea pig testis was carried out following surgically induced testicular torsion. Morphometric analyses of the Leydig cells of the experimental group of animals revealed an increase in the nuclear and mitochondrial volume and a decrease in the lipid volume, in comparison to those in the Leydig cells of the control group of animals. We believe that these changes in the Leydig cells of the experimental group of animals are indicative of cellular hypertrophy. The possible mechanisms of the Leydig cell hypertrophy in the guinea pig testis following the induction of spermatic cord torsion are discussed.

Animals↗

PubMed1986

Torsion of the spermatic cord--a long term study of the contralateral testis.

The object of the present investigation was to study the long-term effects of the unilateral torsion of the spermatic cord on the contralateral testis. Eighteen guinea pigs were divided into 3 groups. In group I of six animals, unilateral torsion of the spermatic cords was maintained until the time of sacrifice. In group II of six animals, torsion of the spermatic cords was maintained for 8-12 h, then the spermatic cords were untwisted and the animals were maintained until the day of sacrifice. Group III six animals, received an injection of pentobarbital, which served as control. All animals were sacrificed after 16 months. Extensive light and electron microscopic studies were carried out. In the contralateral testes of the experimental group of animals, several degenerative changes were noted, which included excessive intraepithelial vacuolization, a loss of germ cells and the presence of tubules containing only Sertoli cells and a few spermatogonia. 10.6% and 19.5% seminiferous tubules were damaged in the contralateral testes of torsion maintained and the torsion reversed groups of animals, respectively in comparison to 3.1% tubular damage (indicated only by occasional presence of intraepithelial vacuoles and necrotic germ cells), in the control testis. It was concluded that long-term effect of unilateral torsion of the spermatic cord is permanent and irreversible in nature.

Animals↗

PubMed1986

Annulate lamellae in guinea pig Sertoli cells.

Unilateral torsion of the spermatic cord was surgically induced in 24 Hartley strain guinea pigs. Groups of six animals were sacrificed 4, 8, 12, and 16 months after the surgery and testes were excised. Nine animals has severely damaged testes. Extensive study on the Sertoli cells of each of these nine animals was carried out after testicular tissues were processed for electron microscopy following the usual procedure. The majority of the affected seminiferous tubules contained a single layer of Sertoli cells without any differentiating germ cells. The Sertoli cells were vacuolated and contained highly lobulated nuclei. Each nucleus contained a nucleolus. The Sertoli cells contained an elaborate annulate lamellae system. The membranous portion of the annulate lamellae was associated with the rough and smooth endoplasmic reticulum. Close association of the annulate lamellae with the lysosomes and lipid droplets was found to be a consistent feature. Although it was not possible for us to predict the functional significance of these annulate lamellae, the present investigation clearly established for the first time, the presence of an annulate lamellae system in the Sertoli cell of a rodent species.

Animals↗

PubMed1986

Pleomorphism of human prostatic cancer cells (DU 145) in culture--the role of cytoskeleton.

The role of cytoskeletal structure in the alteration of cell shape, multinucleation, and intracellular transport of human prostatic carcinoma cells DU 145 was investigated by light microscopy, scanning and transmission electron microscopy, and by immunofluorescence microscopy. It was confirmed that alterations in cell shape and surface topography, multinucleation, and intracellular transport of these cultured cells were regulated by a microfilament system composed of actin. The presence of prekeratin confirmed the epithelial nature of these cells. It was noted for the first time that these cells were highly motile and contained fewer microtubules, a moderate amount of intermediate filaments, and a large amount of microfilaments. "Displastic" cells were quite common in long-term culture. DU 145 cells are excellent in vitro models for further research on human prostatic cancer cells.

Actin Cytoskeleton↗

PubMed1986

The biotransformation and urinary excretion of dexamethasone in equine male castrates.

The pro-drugs of dexamethasone, a potent glucocorticoid, are frequently used as anti-inflammatory steroids in equine veterinary practice. In the present study the biotransformation and urinary excretion of tritium labelled dexamethasone were investigated in cross-bred castrated male horses after therapeutic doses. Between 40-50% of the administered radioactivity was excreted in the urine within 24 h; a further 10% being excreted over the next 3 days. The urinary radioactivity was largely excreted in the unconjugated steroid fraction. In the first 24 h urine sample, 26-36% of the total dose was recovered in the unconjugated fraction, 8-13% in the conjugated fraction and about 5% was unextractable from the urine. The metabolites identified by microchemical transformations and thin-layer chromatography were unchanged dexamethasone, 17-oxodexamethasone, 11-dehydrodexamethasone, 20-dihydrodexamethasone, 6-hydroxydexamethasone and 6-hydroxy-17-oxodexamethasone together accounting for approx 60% of the urinary activity. About 25% of the urinary radioactivity associated with polar metabolites still remains unidentified.

Acetylation↗

PubMed1986

Urinary metabolites of caffeine in pregnant women.

In a study of caffeine and its metabolites in pregnant and non-pregnant women, on average 56.8% of the administered caffeine dose was recovered in the urine in both groups. However, compared to the controls, the pregnant subjects produced smaller amounts of 1-methylxanthine and 1-methyluric acid, whereas the excretion of most of the other metabolites, particularly 3,7-dimethylxanthine and 3-methylxanthine tended to be greater. It is suggested that hormonal influences on the hepatic caffeine metabolising enzymes might be implicated.

Caffeine↗

PubMed1985

The effect of methylene blue on the hepatocellular redox state and liver lipid content during chronic ethanol feeding in the rat.

Feeding of ethanol in a liquid diet to male Wistar rats caused decreases in the hepatic cytosolic and mitochondrial [NAD+]/[NADH] ratios. This redox-state change was attenuated after 16 days of feeding ethanol as 36% of the total energy intake. Supplementation of the ethanol-containing liquid diet with Methylene Blue largely prevented the ethanol-induced redox state changes, but did not significantly decrease the severity of the hepatic lipid accumulation that resulted from ethanol ingestion. Methylene Blue did not affect body-weight gain, ethanol intake or serum ethanol concentrations in ethanol-fed rats, nor did the compound influence the hepatic redox state or liver lipid content of appropriate pair-fed control animals. These findings suggest that the altered hepatic redox state that results from ethanol oxidation is not primarily responsible for the production of fatty liver after long-term ethanol feeding in the rat.

Animals↗

PubMed1985

The roles of the hepatocellular redox state and the hepatic acetaldehyde concentration in determining the ethanol elimination rate in fasted rats.

Ethanol administration (2 g/kg i.p.) to fasted male Wistar rats caused, on average, a 64% decrease in the cytosolic free NAD+:NADH ratio and a 41% decrease in the mitochondrial free NAD+:NADH ratio measured 90 min after ethanol was injected. Treatment of animals with either Naloxone (2 mg/kg i.p.) 1 hr after ethanol or 3-palmitoyl-(+)-catechin (100 mg/kg p.o. 1 hr before ethanol) prevented these ethanol induced redox state changes, without affecting the ethanol elimination rate or the hepatic acetaldehyde concentration measured at 90 min after ethanol administration. The thiol compounds cysteine and malotilate (diisopropyl-1,3-dithiol-2-ylidene malonic acid) significantly lowered the hepatic acetaldehyde concentrations measured at 0.75, 1.5 and 6.0 hr after ethanol, and caused a 29% and 12% increase respectively in the ethanol elimination rate, without affecting the ethanol induced alterations in the NAD+:NADH ratio. Pretreatment of animals with the aldehyde dehydrogenase inhibitor, cyanamide (1 mg/kg or 15 mg/kg p.o. one hour before ethanol), caused increases of up to 23-fold in the hepatic acetaldehyde level, without influencing the cytosolic NAD+:NADH ratio in ethanol dosed rats, while significantly reducing the ethanol elimination rate by up to 44%, compared with controls. These results suggest that ethanol oxidation by cytosolic alcohol dehydrogenase may be regulated in part by the hepatic acetaldehyde concentration achieved during ethanol metabolism rather than NADH reoxidation, either to supply NAD for the dehydrogenase, or to reduce inhibition of the enzyme by NADH, being a rate-limiting factor in ethanol metabolism in fasted rats.

Acetaldehyde↗

PubMed1985

Germ cell quantitation in human testicular biopsy.

Quantitative analysis of human seminiferous epithelium was carried out using an improved method of glutaraldehyde and osmium fixation with plastic embedding. Part of each biopsy specimen was fixed in Bouin's fixative and embedded in paraffin for comparison. Epon embedded tissue had very little artifactual damage compared with paraffin embedded tissue sections. The germ cell to Sertoli cell ratios were determined by counting the various germ cells per "unit" tubular area. Data obtained by this method reflect a remarkable stability of Sertoli cell number and germ cell-Sertoli cell ratios both between biopsies from different individuals and between biopsies from right and left testes from the same individual. Agreement between the present results and those of earlier studies based on paraffin embedded testicular specimens supports the validity of this method of germ cell quantitation of human testicular biopsy samples.

Adolescent↗

PubMed1985

High-dose methylprednisolone sodium succinate (pulse therapy) in the treatment of renal disease: plasma and urine concentrations.

Methylprednisolone hemisuccinate (MPS) and methylprednisolone (MP) concentrations in plasma and urine were monitored in renal transplant and glomerulonephritis patients who were given i.v. infusions of 0.5 g or 1 g of MPS. A marked individual variation of peak plasma levels of both MPS and MP was observed after the same dose and MPS disappeared from plasma more rapidly than MP. Their clearances from the circulation, however, did not appear to be significantly influenced by the peak plasma levels of the drug, creatinine clearance, administration of previous pulses of MPS or the urinary excretion of unconjugated MPS and MP. Even in patients with profoundly reduced renal function, no accumulation of the drug was apparent when repeated doses of MPS were administered at 48-h intervals.

Adult↗

PubMed1985

Quantitative evaluation of testicular biopsies from men with unilateral torsion of spermatic cord.

Torsion of the spermatic cord is not uncommon among young men. Various abnormalities in the histology of the contralateral testis have been reported due to unilateral torsion of the spermatic cord. We quantitatively estimated the germ cells from three groups of men: normal individual (Group I), men with unilateral torsion of short duration (Group II), and men with unilateral torsion of long duration or some other condition such as varicocele or intermittent torsion to the contralateral testis (Group III). No significant difference in the number of spermatogonia, spermatocytes, and spermatids of Groups I and II patients was observed. This observation indicates that there was no pre-existing morphophysiologic defect in the testis of Group II patients. Severe damage in the contralateral testis was noted in Group III patients. This indicates that if a damaged testis is retained in the body for a long time, the contralateral testis may be affected. Contralateral testis may also be affected by intermittent torsion or varicocele.

Adolescent↗

PubMed1985

Effect of experimental torsion of the spermatic cord on sustentacular cells in the guinea-pig testis.

Torsion of the spermatic cord is not an extremely rare occurrence among prepubertal and adolescent boys. Although it is known that torsion of the spermatic cord may lead to germ cell degeneration in the affected as well as in the contralateral testis, nothing is known regarding the response of sustentacular cells to this condition. During the present investigation, we studied the effect of experimental torsion on the sustentacular cells of guinea pig testes. Light-microscopic examination revealed that, although all types of germ cells, except a few spermatogonia, were degenerated in the guinea pig testes with torsion, sustentacular cells did not degenerate. This observation was confirmed from the quantitation data which indicated that the number of these cells remained unchanged when compared to the control and/or the contralateral testis of the same animal with unilateral torsion. Therefore, sustentacular cells of the damaged testis from guinea pigs can be used as reference cells for germ cell quantitation. The striking ultrastructural change in the sustentacular cells of damaged testes was characterized by the presence of well-developed annulate lamellae, which was not reported before in any other rodent species. Lobulated nuclei, numerous tight junctional complexes and lysosomes were other characteristic features of the sustentacular cells of damaged testes.

Animals↗

PubMed1985

Calcium, parathyroid hormone and phospholipid turnover of human red blood cells.

PTH enhances entry of calcium into RBC, stimulates their Ca ATPase and increases osmotic fragility. The effect on the latter occurs only in the presence of calcium. The mechanisms of action of PTH and those mediating their increased calcium influx into RBC are not evident. It is possible that calcium, PTH or both affects phospholipid turnover of RBC and results in production of ionophoric compounds such as phosphatidic acid which in turn allows calcium movement. The present study examined the effect of calcium (1 mM), 1-84 PTH (50 U/ml) and calcium and PTH on phospholipid contents and 32P incorporation into phosphoinositides of human RBC and RBC ghosts. Calcium produced significant decrements in 32P incorporation into phosphatidylinositol, di- and triphosphatidylinositol and an increase into phosphatidic acid. PTH decreased the 32P into phosphatidylinositol only. Both PTH or calcium caused a significant increase in RBC content of phosphatidylserine. The data show that calcium alone alters phospholipid turnover of RBC and such an effect may mediate the PTH-induced calcium influx. Alternatively, PTH may enhance entry of calcium into RBC independent of the effect of calcium on phospholipid turnover and the increase in cytosolic calcium would then alter phospholipid turnover which in turn would further facilitate the effect of PTH on calcium influx. The increase of phosphatidylserine by PTH may increase rigidity of RBC membrane and enhance osmotic fragility.

Calcium↗

PubMed1985

The effect of naloxone on the hepatocellular redox state and serum ethanol concentrations following acute ethanol administration.

Naloxone hydrochloride (2.0 mg/kg) has been found to reverse the significant decreases in the hepatic cytosolic and mitochondrial [NAD+]/[NADH] ratios observed after acute ethanol administration in rats. This correction of the ethanol-induced changes in the hepatocellular redox state by naloxone was, however, not associated with any lowering of serum ethanol concentrations or an observable reduction in the extent of intoxication. This lack of antagonism of alcohol intoxication by naloxone was not affected by the feeding status of the animals, the time point after naloxone administration at which serum ethanol concentration was determined or the method used for ethanol analysis. Thus this study has failed to confirm that naloxone antagonises acute alcohol intoxication, in spite of its potent ability to reverse the ethanol-induced changes in the hepatic redox state.

Alcoholic Intoxication↗