Non enzymatic glycosylation of alpha-1-proteinase inhibitor of human plasma.

Human plasma contains inhibitors, which control the activity of proteolytic enzymes. Alpha-1-proteinase inhibitor and alpha-2-macroglobulin are two of them present in high concentration in human plasma, which inhibit action of trypsin among other proteinases. The trypsin inhibitory capacity (TIC) of human plasma is observed to be decreased in pathological conditions like diabetes mellitus. The mechanisms of decrease in TIC was due to nonenzymatic glycosylation of alpha-1-proteinase inhibitor (A1PI). A1PI was partially purified from normal human plasma by steps involving ammonium sulphate precipitation, DEAE Sepharose CL6B chromatography, Concanavalin A Sepharose Chromatography and Sephadex G-100 Gel filtration. Purified inhibitor was glycosylated in vitro by incubating it with varying glucose concentrations, under nitrogen for different periods of time in reducing conditions. After glycosylation, the molecular weight of inhibitor increased from 52 kDa to 57 KDa because of binding with glucose molecules. The percent free amino groups in the protein decreased with increasing glucose concentration and days of incubation. The TIC of such modified inhibitor decreased significantly. Decrease in TIC was dependent on the glucose concentration and period of incubation used during in-vitro glycosylation of native inhibitor.

Hypolipidemic effects of synthetic gugulsterones in normal rats and assessment of its long-term toxicity at cellular levels in various organs.

Synthetic gugulsterones when administered to rats for a period of 3 weeks in dose of 5.0 mg/kg body weight/day caused a reduction in levels of total cholesterol by 30%, LDL-chol. by 40%, Tg by 40%. VLDL-chol. by 40% and HDL-chol. by 35%. The drug when administered to rats for a period of 16 weeks with increasing dose upto 1150 mg/kg body weight/day, reduced VLDL-chol. and Tg. by 55% and 50% respectively (P < 0.001) and LDL-chol by 33% (P < 0.05), whereas HDL-chol. was increased by 25% (P < 0.001). Histopathological studies on liver, spleen, intestine, lung, kidney, stomach and adrenal gland revealed drug related changes in a few animals upon exposure to high dose of the drug.

Contraceptive potential of an antiprogestin ZK 98.734: reversal of ZK 98.734--induced blockade of folliculogenesis with FSH and LH and their differential effects in bonnet monkeys.

Studies were undertaken in adult bonnet monkeys to investigate whether treatment with an antiprogestin ZK 98.734 at weekly intervals, starting from day one of menstrual cycle, could arrest ovulation and also to determine if ZK 98.734 induced blockade of ovulation could be reversed with gonadotropins. Adult animals have ovulatory menstrual cycles of normal duration were treated at weekly intervals with ZK 98.734 (25 mg/dose, sc, oil base) for 10 consecutive weeks and its effects on serum levels of estradiol, bioactive LH and progesterone, and endometrial histology were investigated. Following treatment with the antiprogestin they were treated with hMG or hFSH alone. Ovulation was blocked during treatment period in all the animals (n = 14). Typical follicular phase rise in estradiol levels was inhibited, mid cycle surge in the levels of bioactive LH was abolished and serum progesterone levels remained below 1 ng/ml throughout the treatment period. However, prolonged treatment had no significant effect on the basal levels of estradiol which were around 50 pg/ml. ZK 98.734 also had no significant effect on cortisol levels. In animals (n = 4) followed for recovery after the last dose, the treatment cycle length was increased to 117.8 + 6.8 days. In three animals the treatment cycles were anovulatory, whereas in one delayed ovulation with luteal insufficiency was observed. The endometrium had become atrophic. Treatment with hMG (Pergonal: 35 I.U. hLH and 35 I.U. hFSH) or hFSH (Metrodin, 35 I.U.) for 7 consecutive days initiated folliculogenesis and the animals ovulated either spontaneously or after a single im injection of hCG (100 I.U.) on day 8 in ZK 98.734 treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Spectrum of pediatric urolithiasis in western India.

Of 1,211 patients with urolithiasis treated at this institution over a nine years period, there were 77 (6.4%) pediatric cases. The commonest age group was 6-10 years (55.8%). Male:female ratio was 7.6:1. Hindus constituted 72.7% of the patients. There was no significant seasonal variation. The commonest site was urinary bladder (67.5%). The upper: lower urinary tract stone ratio was 1:2.85. Majority belonged to the lower-middle or poor income groups having a cereal based diet with minimal or poor protein intake. The common constituents of stones were calcium (98.7%), oxalate (87%), phosphate (84.4%) and uric acid (76.6%). Of all these, uric acid had the richest concentration (grade of ++ or more) in 93.2%. Only 4 stones (5.2%) were "pure": calcium oxalate--3 and calcium phosphate--1; whereas 73 (94.8%) were mixed stones. Of these, 9 (11.7%) were "predominant" mixed stones, with only one constituent having rich concentration (grade of ++ or more) and all others being either trace or +. The rest 64 (83.1%) were "heterogenous" mixed stones having rich concentration of more than one constituent.

Altered kinetic properties of rat heart mitochondrial enzymes following experimental-thyrotoxicosis.

Effects of T3- and T4-induced thyrotoxicosis on temperature-dependent Arrhenius kinetics of succinate oxidase and Mg2+- and Mg2+ + 2,4-dinitrophenoldependent ATPase activities in rat heart mitochondria were examined, For succinate oxidase system, treatment with T3 and T4 caused increase in the energy of activation in high temperature range in a dose-dependent manner. For low temperature range, increase in energy of activation was apparent only with higher doses of the hormones; with low doses a small but reproducible decrease was evinced. The phase transition temperature decreased significantly under these conditions. For the Mg2+- and Mg2++2,4-dintrophenol- dependent-ATPase activities, the activation energy values in high temperature range decreased in general. Activation energy values in low temperature range recorded a generalized increase in the Mg2+-ATPase enzyme system while the value did not change significantly for the Mg2+ + 2,4-dinitrophenol-ATPase; phase transition temperature registered a small but reproducible decrease under these conditions. The results are suggestive of increased membrane fluidization possibly through increased proportion of unsaturated fatty acids. The differential effects seen for succinate oxidase and ATPase systems are consistent with different lipid protein domains of these enzyme systems.

Effect of experimentally induced thyrotoxicosis on oxidative energy metabolism in rat heart mitochondria.

Treatment of rats with T3 resulted in a significant decrease in body weight, while the heart weight increased. T4 treatment had less marked effect on body weights but resulted in decreased heart weights. Serum T4 levels decreased significantly with simultaneous increase of T3 level following T3 treatment, whereas with T4 treatment, levels of both T4 and T3 increased in the serum. Low doses of T3 (0·5 μg) caused decrease in mitochondrial protein content while high dose of T4 (1 μg), caused significant increase in mitochondrial mass. The state 3 respiration rates were significantly depressed following T3 and T4 treatments, in a substrate specific manner with the effects being more pronounced with T3; these responses with T4 were dose-dependent for succinate and ascorbate + N,N,N',N'-tetramethyl-p-phenylenedίamme. State 4 respiration rates also exhibited similar corresponding changes. ADP/O ratios were not changed but ADP-phosphorylation rates were decreased significantly particularly so with the T3-treated animals. Treatment with T3 also resulted in lowering of intramitochondrial cytochrome contents. Similar effects were seen also with higher doses of T4. The results thus indicate that T3- and T4- thyrotoxicosis results in impaired energy metabolism in heart mitochondria.

Acute pancreatitis and reduction of H+ ion concentration in gastric secretions in experimental acute myocarditis produced by Indian red scorpion, Buthus tamulus, venom.

Crude venom (4 mg/kg) of scorpion (B. tamulus) was given in saline to anaesthetized dogs and rabbits. It produced a reduction in gastric H+ ion concentration in dogs with acute myocarditis. Simultaneously an increase in circulating amylase and lipase level was also observed. However 60% venom poisoned rabbits showed an elevated lipase level without a parallel increase in amylase. It is suggested that the venom acts directly on exocrine pancreas to cause acute pancreatitis.

Hepatic drug metabolizing capacity of patients of cirrhosis before and after clinico-biochemical recovery.

The present study was undertaken to determine whether, along with clinico-biochemical recovery there was associated restoration of hepatic drug metabolizing capacity in patients of cirrhosis after treatment of their cirrhosis, using serum antipyrine half life, the ideal index. Estimation of serum antipyrine half life before (26.34 +/- 2.4 hr) and after (18.83 +/- 2 hr) clinico-biochemical recovery showed significant (P less than 0.01) improvement in drug metabolizing capacity of liver. Biochemical parameters of liver function tests except serum total proteins and prothrombin time showed simultaneous improvement.