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Biomedical subjects

S Chari

Publications and source records attributed to S Chari.

At least 37 records · Page 2Linked to original sources
PubMed1994

Teratogenicity and transplacental pharmacokinetics of 13-cis-retinoic acid in rabbits.

No embryotoxic or teratogenic effects, considered to be treatment related, were observed in rabbits after daily oral doses of 3 mg/kg of 13-cis-retinoic acid (13-cis-RA) from Day 8 to Day 11 of gestation. In contrast, treatment with 15 mg/kg/day significantly increased the rate of fetal resorptions (22%) and 13 out of 68 surviving fetuses (16%) were malformed. Pharmacokinetic studies with both dosing regimens of 13-cis-RA in pregnant rabbits showed that on Day 11 of gestation, high concentrations of parent compound, 13-cis-RA, and its major metabolite, 13-cis-4-oxoRA, existed in maternal plasma. Much lower concentrations were found for all-trans-4-oxoRA and all-trans-RA. The area under the concentration-time curve (AUC) of all-trans-RA following the 15 mg/kg/day dosing regimen of 13-cis-RA was only 1.2% that of parent compound 13-cis-RA. At this dose, embryo levels of 13-cis-RA, 13-cis-4-oxoRA, and all-trans-4-oxoRA were 2.5-, 4.7-, and 3.6-fold higher by AUC comparison (24-hr period of Day 11) compared with the dose of 3 mg/kg. However, embryo levels of all-trans-RA were virtually identical at both doses and were, in fact, somewhat lower than endogenous concentrations measured in untreated rabbit embryos. In contrast to mice, where isomerization from 13-cis- to all-trans-RA was suggested to be crucial for the teratogenic action of 13-cis-RA, we found that the teratogenic action of 13-cis-RA (15 mg/kg/day) in rabbits is characterized by increased whole embryo concentrations of 13-cis-RA, 13-cis-4-oxoRA, and all-trans-4-oxoRA, but not of all-trans-RA.

Abnormalities, Drug-Induced↗
PubMed1993

Alcohol and gastric acid secretion in humans.

The secretory response of gastric acid to pure ethanol and alcoholic beverages may be different because the action of the non-ethanolic contents of the beverage may overwhelm that of ethanol. Pure ethanol in low concentrations (< 5% vol/vol) is a mild stimulant of acid secretion whereas at higher concentrations it has either no effect or a mildly inhibitory one. Pure ethanol given by any route does not cause release of gastrin in humans. Alcoholic beverages with low ethanol content (beer and wine) are strong stimulants of gastric acid secretion and gastrin release, the effect of beer being equal to the maximal acid output. Beverages with a higher ethanol content (whisky, gin, cognac) do not stimulate gastric acid secretion or release of gastrin. The powerful stimulants of gastric acid secretion present in beer, which are yet to be identified, are thermostable and anionic polar substances. The effect of chronic alcohol abuse on gastric acid secretion is not as predictable. Chronic alcoholic patients may have normal, enhanced, or diminished acid secretory capacity; hypochlorhydria being associated histologically with atrophic gastritis. There are no studies on the acute effect of alcohol intake on gastric acid secretion in chronic alcoholic patients. The acid stimulatory component of beer and wine needs to be characterised and its possible role in the causation of alcohol induced gastrointestinal diseases needs to be investigated.

Alcohol Drinking↗
PubMed1993

[Pathophysiologic concepts and protective possibilities in experimental pancreatic lesions].

Experimental pancreatic lesions can be induced by a number of different procedures, e.g. pancreatic hyperstimulation, intraductal application of bile acids, feeding choline deficient diet, obstruction of pancreatic duct, or reducing pancreatic blood flow. The pathogenetic mechanisms leading to pancreatic lesions include basolateral enzyme secretion, acinar cell polarisation defect, intracellular activation of proteases, and the production of free radicals and other active metabolites. The importance of these individual mechanisms in the production and progression of different experimentally-induced pancreatic lesions remains speculative. These pathogenetic concepts have inspired the study of a number of substances likely to protect the pancreas and prevent the pancreatic lesions. This paper gives an overview of the pathogenetic concepts of development of and protection against experimental pancreatic lesions produced in animal models. Special mention has been made of an animal model of pancreatic lesion produced by immunosuppressives.

Animals↗
PubMed1992

Isolation of luteinising hormone receptor binding inhibitor from bovine corpus luteum.

A luteinising hormone receptor binding inhibitor (LHRBI) has been purified from bovine corpus luteum (CL). Steroid-free extract of the CL was subjected to successive chromatographies on Sephadex G-50, Q-Sepharose, Orange A dye and metal chelate affinity columns followed by high performance-reverse phase and gel filtration columns. Purification was monitored by the ability of the fractions to inhibit the binding of 125I-human chorionic gonadotropin (hCG) to porcine granulosa cells in vitro. The final isolate showed an 8000-fold enrichment of activity. It was also capable of inhibiting porcine granulosa cell secretion of estradiol and progesterone (P) in vitro. Administration of LHRBI into follicle-stimulating hormone (FSH)-stimulated, immature rats strongly inhibited the ovarian ovulatory response to hCG as revealed by decreased P levels and the number of ova released. The M(r) of LHRBI as assessed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis was ca. 15 kDa and the pI was between 5.0 and 5.5.

Animals↗
PubMed1990

Plasma glucagon responses in tropical fibrocalculous pancreatic diabetes.

Plasma insulin and glucagon responses to a glucose load were measured in a group of patients with fibrocalculous pancreatic diabetes (FCPD) and compared with patients with noninsulin-dependent diabetes mellitus (NIDDM) and control subjects. Both diabetic groups had markedly diminished insulin responses but the differences between FCPD and NIDDM groups were not significant. In control subjects, in response to the glucose load, plasma glucagon levels decreased while they increased in NIDDM patients. In FCPD patients there was no significant change in glucagon levels in response to the glucose load. The study shows that FCPD patients lack pancreatic alpha-cell responses to a glucose load. This may play a role in protecting these patients against ketosis.

Adult↗
PubMed1990

Fibrocalculous pancreatic diabetes and obesity.

Fibrocalculous pancreatic diabetes (FCPD) is a form of diabetes secondary to chronic pancreatitis that is found in tropical countries. Most patients with FCPD are lean and many are frankly undernourished. Four patients with FCPD who were obese are reported in this paper and this is the first report of obesity in FCPD patients.

Adult↗
PubMed1989

Exocrine pancreatic function in tropical fibrocalculous pancreatic diabetes.

Exocrine pancreatic function was studied by fecal chymotrypsin test in three groups of diabetic patients seen in southern India. Exocrine pancreatic insufficiency, as shown by low fecal chymotrypsin levels, was seen in 87.5% of patients with fibrocalculous pancreatic diabetes (FCPD), in 23.5% of insulin-dependent diabetes mellitus patients, and in 4.5% of non-insulin-dependent diabetes mellitus patients. There was no correlation between fecal chymotrypsin levels and serum amylase, serum lipase, age, body mass index, duration of diabetes, fasting plasma glucose, or glycosylated hemoglobin levels. The fecal chymotrypsin test is a useful additional investigation for the diagnosis of FCPD found in tropical countries.

Adult↗
PubMed1988

Young v adult cirrhotics: a prospective, comparative analysis of the clinical profile, natural course and survival.

In order to assess the frequency and profile of cirrhosis in the young, 169 consecutive patients with cirrhosis were studied. Sixty three (37%) patients of less than or equal to 35 years age were defined as young and the remaining 106 (63%) patients (greater than 35 years) as adult cirrhotics. Men predominated significantly (p less than 0.01) in the young cirrhotic group. The aetiology, the frequency of positive hepatitis B markers and initial clinical presentation were similar in the two groups. During the follow up period (30.6 +/- 29.7 months for the young and 25.8 +/- 21.7 months for the adult group), except for abdominal distension and pedal oedema which occurred significantly more often in the adult compared with the young cirrhotics, no difference was noted in the two groups. Twenty seven (39.7%) deaths (40% as a result of hepatic failure and 52% due to variceal bleeding) occurred in the young and 47 (44.3%) deaths (63.8% because of hepatic failure and 26% because of variceal bleeding) occurred in the adult cirrhotics during the follow up (difference NS). The five year survival (61.9% v 55.7%) and the probability of survival within the same Child's grade of liver disease were comparable. In both the groups, however, the probability of survival was significantly higher in Child's A compared with Child's B and C and in Child's B compared with Child's C grade of liver disease. Survival was not influenced by sex of the patient and aetiology of cirrhosis. Results of this prospective study indicate that cirrhosis is not uncommon in young adults. The aetiology, clinical presentation, natural history of the disease and the survival rates in young cirrhotics do not differ significantly from adult cirrhotics.

Adolescent↗
PubMed1987

Intravariceal versus paravariceal sclerotherapy: a prospective, controlled, randomised trial.

Fifty four consecutive patients with oesophageal variceal bleeding were randomised to undergo intravariceal (28 patients) or paravariceal (26 patients) sclerotherapy, every three weeks. Intravariceal technique was found significantly (p less than 0.01) more effective in controlling active variceal bleeding than the paravariceal technique (91% v 18.7% respectively). The mean (+/- SD) time taken for variceal eradication by intravariceal sclerotherapy (15.4 +/- 5.3 weeks) was significantly (p less than 0.001) less than paravariceal (26.8 +/- 6.6 weeks) technique. The number of sclerotherapy sessions needed with intravariceal technique were also significantly less. Rebleeding was seen in 38.5% patients after para and 14.3% after intravariceal injections (NS). Except for retrosternal pain, which occurred more often (p less than 0.01) with paravariceal technique, there was no difference in the incidence of other complications or mortality between the two groups. Variceal recurrence was seen in seven patients (25%) in the intra and one (3.9%) patient in the paravariceal group (p less than 0.01) after a mean follow up of 29.4 +/- 9.1 weeks. Intravariceal sclerotherapy was superior to paravariceal in the control of active variceal bleeding and for total variceal obliteration, but was associated with a higher variceal recurrence.

Adolescent↗
PubMed1985

Simplification of the method of in vitro fertilization: sonographic measurements of follicular diameter as the sole index of follicular maturity.

As a simplification of the in vitro fertilization (IVF) procedure, repeated sonographic scanning of follicular diameters in stimulated cycles was performed, until the largest visible follicle reached a mean diameter of at least 20 mm, at which time human chorionic gonadotropin (hCG) was administered. Follicle puncture was performed either guided by sonography or by laparoscopy 34-36 hr after the hCG injection, and following insemination oocytes were cultured for 48-60 hr before embryo transfer (ET). Serum levels of luteinizing hormone (LH), prolactin (PRL), and estradiol-17 beta (E2) at the time of hCG injection as well as follicular fluid levels of follicle stimulating hormone (FSH), LH, and PRL as well as progesterone (P), testosterone (T), and E2 at the time of puncture were determined in retrospect using specific radioimmunoassay (RIA). It was found that the knowledge of a single value of LH or E2 in serum should have been of little additional value for the decision to give hCG in all stimulation models used: clomiphene + hCG, human menopausal gonadotropin (hMG) + hCG, and clomiphene + hMG + hCG. The concentrations of the three steroids measured in follicular fluid were, in a high proportion of the follicles, within a normal range in all stimulation models. The group receiving clomiphene + hMG + hCG appeared promising through its higher proportion of estrogenic follicles. It is concluded that sonographic measurement of follicular diameters may be used as the sole index of follicular maturity in an IVF program.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Regulators of steroid secretion and inhibin activity in human ovarian follicular fluid.

Inhibin activity from human follicular fluid was purified by successive chromatographies on Sephadex G-50, DEAE-Biogel A and orange A dye matrix. Inhibin activity was associated only with the protein(s) that bound to orange A (OrA-2). Daily injection of OrA-2, 1 h prior to hMG into 10-day-old female rats for 4 days caused a significant inhibition of hMG-induced estradiol secretion. In vitro, OrA-2 dose-dependently inhibited the amounts of estradiol secreted by porcine granulosa cells during a 3-h incubation. Orange A-unbound proteins, on the other hand, induced a dose-dependent increase in estradiol as well as progesterone secretion by porcine granulosa cells in vitro. Separation of stimulator from the inhibitor by orange A chromatography led to an increase in the relative inhibin activity (25-50-fold) as well as aromatisation-suppressing activity (60-fold). The results indicate a possible local action of hFF inhibin to regulate aromatisation activity.

Animals↗
PubMed1985

On the identity of bovine seminal plasma inhibin.

In light of current discussions on multiple forms of inhibin, it was thought of interest to ascertain the identity of the postulated 'iso-hormones' of bull seminal plasma inhibin (Chari et al., 1978). By subjecting the biologically active fraction, obtained by Sephadex G-100 gel filtration of bull seminal plasma acetone powder, to extensive dialysis in distilled water adjusted to pH 5.8, it was possible to remove the bulk of inert protein as a precipitate. The resulting active preparation could be readily fractionated by preparative iso-electric focusing in the pH range 4.0-6.5 yielding 2 distinct homogeneous peptides, alpha and beta, capable of suppressing hCG-induced uterine weight increase in immature mice, in a 'reversed Steelman-Pohley' assay design. However, of these, alpha alone was able to suppress post-castrational serum gonadotropin rise in appropriate animal models. This peptide is highly acidic in nature (iso-electric point congruent to 2.2) and has a molecular weight (Mr) of 18200 and a Stokes radius of 1.90 nm. On the basis of currently available evidence, it is concluded that the molecule consists of a single peptide chain.

Animals↗
PubMed1985

Oocyte maturation as regulated by follicular factors.

Follicular fluid (FFl), obtained from 24 women treated with clomiphene/hCG in an in vitro fertilization program, was characterized with respect to steroid hormone levels and oocyte maturation inhibitor (OMI) activity. Three FFl samples apparently were derived from cystic follicles and contained low steroid levels and no OMI activity in an in vitro rat oocyte assay. The remaining 21 follicles contained normal preovulatory steroid levels and mature and generally fertilizable oocytes. In 7 of these follicles the FFl (at 50% concentration) significantly inhibited rat oocyte meiosis, while 14 exerted no OMI activity. The results confirm earlier work on porcine and human FFl, suggesting that the putative OMI activity declines with follicular maturation.

Animals↗
PubMed1984

[Sex hormones and fertility following portacaval anastomosis in rats].

Portocaval anastomosis (PCA) in the normal male rat causes profound alterations in testicular morphology and function and in plasma levels of sex steroids as well as of gonadotropins. Testicular atrophy is accompanied by a significant decrease of plasma testosterone (0.03 ng/ml versus 0.99 ng/ml) and an increase of estradiol (76.2 pg/ml versus 39.7 pg/ml) and estrone (68. pg/ml versus 45.5 pg/ml). Plasma levels of gonadotropins (LH, FSH) and prolactin are lowered too (LH: 15 ng/ml versus 28.5 ng/ml, FSH:119 versus 182 ng/ml, prolactin:53 versus 109 ng/ml). The altered sex hormone metabolism is reflected in marked changes of the morphology and nucleic acid content of the metabolizing organs i.e. liver, gonades and kidney. The results of this study are consistent with the hypothesis that portosystemic shunt per se plays an important role in the pathogenesis of the disturbed metabolism of sex hormones observed in patients with liver cirrhosis and portal hypertension.

Adrenal Glands↗
PubMed1983

In vitro inhibition of rat oocyte meiosis by human follicular fluid fractions.

We studied the effect of low molecular weight fractions of human follicular fluid (FF1) on rat oocyte meiosis and progesterone secretion by the granulosa cells. Steroid-free FF1 extracts were filtered through Sephadex G50 gel. One highly retarded fraction was obtained (GF-3), which was either used for testing or further purified by filtration on Sephadex G10, the G10-3 fraction of which was used for experiments. The GF-3 and G10-3 fractions of FF1 inhibited (in a dose-dependent and reversible manner) meiosis of isolated rat oocytes during a 4-h culture. Similarly treated fractions of serum had no effect. The inhibition was not abolished by ether extraction, trypsin treatment, heating to 56 degrees C for 1 h or boiling for 5 min, whereas heating to 105 degrees C for 18 h decreased the effect. Gonadotropin-stimulated progesterone secretion by cumulus and mural granulosa cells was also dose-dependently and reversibly inhibited by the GF-3 fractions. Our results confirm those obtained in earlier studies on porcine oocyte maturation inhibitor (OMI).

Animals↗