Hypolipidemic activity of Achyranthus aspera Linn in normal and triton induced hyperlipemic rats.

The alcoholic extract of A. aspera, at 100 mg/kg dose lowered serum cholesterol (TC), phospholipid (PL). triglyceride (TG) and total lipids (TL) levels by 60, 51, 33 and 53% respectively in triton induced hyperlipidemic rats. The chronic administration of this drug at the same doses to normal rats for 30 days, lowered serum TC, PL, TG and TL by 56, 62, 68 and 67% respectively followed by significant reduction in the levels of hepatic lipids. The faecal excretion of cholic acid and deoxycholic acid increased by 24 and 40% respectively under the action of this drug. The possible mechanism of action of cholesterol lowering activity of A. aspera may be due to rapid excretion of bile acids causing low absorption of cholesterol.     

Hormonal studies in postpartum female camels and their neonates

The expulsion of the fetus from the mother at parturition necessitates reorganization of the endocrine status in both individuals. In this study, the patterns of hormonal changes were investigated in postpartum Dromedary camels and their neonates. Blood samples were recovered within a few hours after calving from 10 female Dromedary camels and their calves, and sampling was continued at varying intervals upto Day 21 post partum. Sera were assayed for progesterone, cortisol and thyroid hormone concentrations by specific radioimmunoassays. Progesterone concentrations in the dams varied between 0.5 and 2.0 ng/ml on the day of calving and declined steadily thereafter to become undetectable by Day 9; progesterone remained undetectable in the neonates. Cortisol concentrations were high (25 to 30 ng/ml) at parturition in both the dams and their calves. They declined to 6 to 7 ng/ml in the dams, but became undetectable in the neonates by Day 14 post partum. The thyroid hormones were low in the dams (T(4) = 70; T(3) = 1.6 ng/ml) on Day 1 post partum but then increased gradually to Day 21 (T(4) = 110; T(3) = 2.2 ng/ml). In contrast, thyroid hormone concentrations in the neonates were 4 to 5 times higher than those of their mothers at birth. They declined thereafter but nevertheless remained at almost double the concentrations found in the dams.     

Transformation of Bacillus subtilis by DNA bound on montmorillonite and effect of DNase on the transforming ability of bound DNA.

The equilibrium adsorption and binding of DNA from Bacillus subtilis on the clay mineral montmorillonite, the ability of bound DNA to transform competent cells, and the resistance of bound DNA to degradation by DNase I are reported. Maximum adsorption of DNA on the clay occurred after 90 min of contact and was followed by a plateau. Adsorption was pH dependent and was greatest at pH 1.0 (19.9 micrograms of DNA mg of clay-1) and least at pH 9.0 (10.7 micrograms of DNA mg of clay-1). The transformation frequency increased as the pH at which the clay-DNA complexes were prepared increased, and there was no transformation by clay-DNA complexes prepared at pH 1. After extensive washing with deionized distilled water (pH 5.5) or DNA buffer (pH 7.5), 21 and 28%, respectively, of the DNA remained bound. Bound DNA was capable of transforming competent cells (as was the desorbed DNA), indicating that adsorption, desorption, and binding did not alter the transforming ability of the DNA. Maximum transformation by bound DNA occurred at 37 degrees C (the other temperatures evaluated were 0, 25, and 45 degrees C). DNA bound on montmorillonite was protected against degradation by DNase, supporting the concept that "cryptic genes" may persist in the environment when bound on particulates. The concentration of DNase required to inhibit transformation by bound DNA was higher than that required to inhibit transformation by comparable amounts of free DNA, and considerably more bound than free DNase was required to inhibit transformation by the same amount of free DNA. Similarly, when DNA and DNase were bound on the same or separate samples of montmorillonite, the bound DNA was protected from the activity of DNase.     

Modulation of adenylate cyclase activity by Ca2+, phospholipid-dependent protein kinase in rat brain striatum

Summary The effects of purified Ca²⁺, phospholipid-dependent protein kinase (C-kinase) were studied on adenylate cyclase activity from rat brain striatum. C-kinase treatment of the membranes stimulated adenylate cyclase activity, the maximal stimulation between 50–80% was observed at 3.5 U/ml, whereas the catalytic subunit of cAMP dependent protein kinase did not show any effect on enzyme activity. The inclusion of Ca²⁺ and phosphatidyl serine did not augment the percent stimulation of adenylate cyclase by C-kinase, however EGTA inhibited the stimulatory effect of C-kinase on enzyme activity. Furthermore, the known inhibitors of C-kinase such as polymyxin-B and 1-(5-Isoquinoline sulfonyl)-2-methylpiperazine dihydrochloride (H-7) also inhibited the stimulatory effect of C-kinase on adenylate cyclase activity. In addition, in the presence of GTP the stimulatory effects of C-kinase on basal and N-Ethylcarboxamide adenosine- (NECA-), dopamine-(DA) and forskolin- (FSK) sensitive adenylate cyclase activities were augmented. On the other hand, the inhibitory effect of high concentrations of GTP on enzyme activity was attenuated by C-kinase treatment. In addition, oxotremorine inhibited adenylate cyclase activity in a concentration dependent manner, with an apparent Ki of about 10 µM and C-kinase treatment almost completely abolished this inhibition. These data suggest that C-kinase may play an important role in the regulation of adenylate cyclase activity possibly by interacting with a guanine nucleotide regulatory protein.Abbreviations C-kinase Ca^2– phospholipid-dependent protein kinase - NECA N-Ethylcarboxamide adenosine - DA Dopamine - FSK Forskolin - PMA Phorbol 12-(-Myristate), 13-Acetate, H-7, 1-(5-isoquinoline sulfonyl)-2-methylpiperazine dihydrochloride Presented in part at the VIth International Conference on Cyclic nucleotides, calcium and protein phosphorylation signal transduction in biological systems. September 2-6, 1986, Bethesda, MD (USA).M.B.A.-S. was Canadian Heart Foundation Scholar during the course of these studies.     

Refinement of diagnostic assays for a probable causal mutation for porcine and human malignant hyperthermia.

The substitutions of T for C1843 in the porcine ryanodine receptor (RYR1) gene, which deletes a HinPI restriction endonuclease site and creates a HgiAI site, and of T for C1840 in human RYR1, which deletes a RsaI site, lead to Cys for Arg substitutions in the ryanodine receptors and are probable causal mutations for malignant hyperthermia (MH). To improve the restriction endonuclease assay of these sites, thereby providing an accurate, reliable diagnosis for MH, introns flanking the exon containing the mutation were sequenced, permitting identification and PCR amplification of a 659-bp porcine gene sequence that contains both constant and variant HgiAI sites and a 922-bp human gene sequence that contains both constant and variant RsaI sites. As a result, these PCR-amplified sequences contain constant internal controls for the reliable differentiation by restriction endonuclease digestion of normal, heterozygous, and MH genotypes.     

Immunological Changes in Azir-Mutants of Bradyrhizobium sp. (Cajanus)

Antigenic constitution of an efficient nitrogen fixing strain of Bradyrhizobium sp. (Cajanus) ARS39 was compared with its six azide resistant mutants. The wild type strain contained minimum six antigens. Five of them were bound antigens and reacted only when they were released by sonication of cells followed by heat treatment. Azide resistance caused changes at minimum of three antigenic sites in the mutants. This led to the deletion of two most slow diffusing antigens and further resolution of a strain specific, moderately diffusing antigen. No change was observed in fast diffusing antigens which are considered species/group-specific. All the six mutants showed identical antigenic constitution though they were selected independently.     

Effects of high altitude stay on the incidence of common diseases in man

Prolonged stay at high altitude significantly lowers the incidence of some of the diseases commonly encountered at sea level. This conclusion is based on a study involving 130,700 men stationed on plains between 760 m and sea level and 20,000 men stationed at altitudes between 3692 and 5538 m during the period 1965 to 1972. When yearwise differences in morbidity rates were determined for this period it was found that apart from amoebic hepatitis, goitre and lobar pneumonia, which show a higher incidence, the incidence of infections of bacterial, viral and protozoal origin, diabetes mellitus, hypertension and ischaemic heart disease, asthma and rheumatoid arthritis, gastric disorders, skin diseases, psychiatric ailments and anaemia was significantly lower at high altitude than at sea level. When the trend in morbidity rates was compared over the two subperiods of 1965 to 1968 and 1969 to 1972 it was found that generally increasing or decreasing trends on plains were reflected at high altitude. The overall incidence at high altitude however remained low. Part I of our communication deals with epidemiological data and these findings. Part II surveys the available literature and attempts to explain how improved hormonal state, enhanced fibrinolytic activity, accelerated humoral and cellular immune responses, favourable haemodynamics, better cardiac and cerebral functions, improved metabolic functions, and a relatively stable, dry and cold climate favourably influence the incidence of diseases at high altitude.     

Modulation of alcohol dehydrogenase and ethanol metabolism by sex hormones in the spontaneously hypertensive rat. Effect of chronic ethanol administration

In young (4-week-old) male and female spontaneously hypertensive (SH) rats, ethanol metabolic rate in vivo and hepatic alcohol dehydrogenase activity in vitro are high and not different in the two sexes. In males, ethanol metabolic rate falls markedly between 4 and 10 weeks of age, which coincides with the time of development of sexual maturity in the rat. Alcohol dehydrogenase activity is also markedly diminished in the male SH rat and correlates well with the changes in ethanol metabolism. There is virtually no influence of age on ethanol metabolic rate and alcohol dehydrogenase activity in the female SH rat. Castration of male SH rats prevents the marked decrease in ethanol metabolic rate and alcohol dehydrogenase activity, whereas ovariectomy has no effect on these parameters in female SH rats. Chronic administration of testosterone to castrated male SH rats and to female SH rats decreases ethanol metabolic rate and alcohol dehydrogenase activity to values similar to those found in mature males. Chronic administration of oestradiol-17β to male SH rats results in marked stimulation of ethanol metabolic rate and alcohol dehydrogenase activity to values similar to those found in female SH rats. Chronic administration of ethanol to male SH rats from 4 to 11 weeks of age prevents the marked age-dependent decreases in ethanol metabolic rate and alcohol dehydrogenase activity, but has virtually no effect in castrated rats. In the intoxicated chronically ethanol-fed male SH rats, serum testosterone concentrations are significantly depressed. In vitro, testosterone has no effect on hepatic alcohol dehydrogenase activity of young male and female SH rats. In conclusion, in the male SH rat, ethanol metabolic rate appears to be limited by alcohol dehydrogenase activity and is modulated by testosterone. Testosterone has an inhibitory effect and oestradiol has a testosterone-dependent stimulatory effect on alcohol dehydrogenase activity and ethanol metabolic rate in these animals.     

Contribution of dissolved dinitrogen in culture solutions to growth of Rhodopseudomonas capsulata with various sources of combined nitrogen

Fixation of dissolved dinitrogen in culture solutions by the photosynthetic bacterium Rhodopseudomonas capsulata, strain B10, reduced the lag phase associated with growth with glutamate. A comparable effect was not observed with ammonium chloride. This strain assimilated nitrate but nitrogen fixation was depressed during early growth on nitrate. It is shown that nitrite, the first product of nitrate assimilation, inhibits nitrogen fixation during the early stages of cell growth.     

Effect of p-chlorophenylalanine on development of cross-tolerance between pentobarbital and ethanol.

Rats developed cross-tolerance to the motor-impairing effects of ethanol after daily oral administration of pentobarbital. Chronic administration of p-chlorophenylalanine (p-CPA), in a dosage regimen previously demonstrated to maintain extensive brain serotonin (5-HT) depletion, slowed down cross-tolerance development. p-CPA did not appear to exert this effect by altering the disposition of ethanol, since blood ethanol levels measured 20 min after ethanol administration were not affected by p-CPA treatment. This study extends our previous findings with respect to the inhibitory effects of p-CPA on tolerance development to ethanol and pentobarbital, and suggests that 5-HT may play a role in cross-tolerance development between ethanol and pentobarbital.