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.     

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.     

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.     

Co-delivery of Vorinostat and Etoposide <Emphasis Type="Italic">Via</Emphasis> Disulfide Cross-Linked Biodegradable Polymeric Nanogels: Synthesis,Characterization, Biodegradation,and Anticancer Activity

Treatment regimens for cancer patients using single chemotherapeutic agents often lead to undesirable toxicity, drug resistance, reduced uptake etc. Combination of two or more drugs is therefore becoming an imperative strategy to overcome these limitations. A step forward can be taken through delivery of the drugs used in combination via nanoparticles. Co-administration of chemotherapeutic drugs encapsulated in nanoparticles has been shown to result in synergistic effects and enhanced therapeutic efficacy. In present study, we explored the combination treatment of histone deacetylase inhibitor vorinostat (VOR) and topoisomerase II inhibitor etoposide (ETOP). The concurrent combination treatment of VOR and ETOP resulted in synergistic effect on human cervical HeLa cancer cells. VOR and ETOP were encapsulated into poly(ethylene glycol) monomethacrylate (POEOMA)-based disulfide cross-linked nanogels. The nanogels were synthesized using atom transfer radical polymerization (ATRP) via cyclohexane/water inverse mini-emulsion and were degradable in presence of intracellular glutathione (GSH) concentration. Both the drugs were loaded into the nanogels by physical encapsulation method and characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD), dynamic light scattering (DLS), and differential scanning calorimetry (DSC). Both VOR- and ETOP-loaded nanogels showed sustained release profile. Furthermore, combination treatment drugs encapsulated of POEOMA nanogel demonstrated enhanced synergistic cytotoxic effect compared with combination of free drugs. Enhanced synergistic cell killing efficiency of drug-loaded POEOMA nanogels was due to increased apoptosis via caspase 3/7 activation. Therefore, combination of VOR- and ETOP-loaded PEG-based biodegradable nanogels may provide a promising therapy with enhanced anticancer effect.     

Complex effects of Ayurvedic formulation: <Emphasis Type="Italic">Guduchi</Emphasis> and <Emphasis Type="Italic">Madhuyashti</Emphasis> on different components of life history may elude the elixir effect

Formulations from the traditional Indian medicine, Ayurveda, have long been considered to have potent life-style-enhancing effects, possibly by their effect(s) on key life-history attributes. Although several studies have reported beneficial effects of these formulations on different components of life history, few have investigated their concurrent influence on various life-history traits. Here, we report the results of an investigation showing the effect of two well-known Ayurvedic formulations, Guduchi and Madhuyashti, on fecundity and longevity of Drosophila melanogaster. Flies were either grown (i.e., larval exposure) and/or maintained (i.e., adult exposure) on standard food supplemented with 0.5% Guduchi or 0.5% Madhuyashti. It was observed that the longevity of adult flies of both sexes was not affected on feeding Guduchi food, but fecundity of the females was greatly enhanced. Fecundity was also found to be affected by the adult food and whether their mates were grown on Guduchi or normal food. Madhuyashti, on the other hand, significantly reduced mean longevity and had a stimulatory effect on female fecundity. This fecundity enhancing effect however seemed to be mediated through its effect on the males. Interestingly, much of these effects interacted with age in a complex way, making it difficult to generalize the overall effect of these formulations on the reproductive output of the flies. Our study underlines the importance of evaluating the interacting effects of these (and similar) formulations on a range of life-history traits in a holistic way to understand their utility better.     

Presence of “Ra” and “P”-site receptors for adenosine coupled to adenylate cyclase in cultured vascular smooth muscle cells

The existence of adenosine receptors coupled to adenylate cyclase in cultured vascular smooth muscle cells from rat aorta is demonstrated in these studies. Adenosine, N⁶-phenylisopropyladenosine, adenosine N′-oxide and 2-chloroadenosine stimulated adenylate cyclase in a concentration dependent manner. The stimulation was dependent on the presence of guanine nucleotides and was blocked by 3-isobutyl-1-methylxanthine. In contrast, 2′ deoxyadenosine inhibited adenylate cyclase activity. Adenosine and 2-chloroadenosine showed a biphasic effect on adenylate cyclase, stimulation occurred at low concentrations. The activation of adenylate cyclase by N⁶-phenylisopropyladenosine was also dependent on the Mg²⁺ concentration. The data suggest that vascular smooth muscle cells have both “Ra” and “P” receptors for adenosine, and it can be postulated that the relaxant effect of adenosine on vascular smooth muscle may be mediated by its interaction with “Ra” receptors associated with adenylate cyclase.     

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.     

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.