Enhanced reactivity towards flunarizine in cerebrovascular bed of spontaneously hypertensive rats

Cerebral blood flow (CBF) was measured and cerebrovascular resistance (CVR) was calculated in anesthetized spontaneously hypertensive rats (SHR) and normotensive rats (NR) following the administration of incremental dosages of i.v. flunarizine or papaverine. CBF and CVR changes following papaverine were the same in both groups of rats irrespective of the dose of the drug. The effect of flunarizine was much more pronounced in SHR than in NR. The results point out the greater dependency of basal cerebrovascular tone in SHR upon Ca2+ influx into vascular smooth muscle cells.     

Enhanced reactivity towards flunarizine in cerebrovascular bed of spontaneously hypertensive rats

Summary Cerebral blood flow (CBF) was measured and cerebrovascular resistance (CVR) was calculated in anesthetized spontaneously hypertensive rats (SHR) and normotensive rats (NR) following the administration of incremental dosages of i.v. flunarizine or papaverine. CBF and CVR changes following papaverine were the same in both groups of rats irrespective of the dose of the drug. The effect of flunarizine was much more pronounced in SHR than in NR. The results point out the greater dependency of basal cerebrovascular tone in SHR upon Ca²⁺ influx into vascular smooth muscle cells.     

Effects of progesterone and estradiol benzoate on superoxide dismutase activity in the brain of male rats

The activities of mitochondrial, manganese-containing superoxide dismutase (MnSOD) and cytoplasmic, copper-zinc-containing superoxide dismutase (CuZnSOD) were measured in subcellular fractions of whole brain homogenates prepared from intact and gonadectomized (GDX) male rats, untreated or treated subcutaneously (sc) with a single dose of 2 mg progesterone (P) and/or 5 g estradiol benzoate (EB). Neither MnSOD nor CuZnSOD was affected by the removal of the testes. Similarly, CuZnSOD activity was steady following systemic administration of P and/or EB to intact and GDX animals 2 h or 24 h prior to sacrifice. On the other hand, both P and EB suppressed MnSOD in the brain of either intact or GDX rats. These results suggest involvement of P and EB in the control of MnSOD activity in the brain of male rats.     

Radiation-induced changes in gentamicin pharmacokinetics

Summary Decreased clearance of i.v. or intratracheally administered gentamicin was observed in rats following single whole-body irradiation, 6 Gy⁶⁰Co, reaching its lowest rate on the 7th post-irradiation day. Simultaneously the absorption rate of gentamicin from the lungs was found to be increased.     

Cadmium-induced changes in renal hemodynamics in the domestic fowl

Low i.v. doses of cadmium chloride (15 micrograms Cd) given to pullets resulted in a significant reduction in urine flow (UF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). However, in hens treated with the heavy metal chelate FeNa EDTA prior to cadmium treatment no oliguria or reduction in GFR or ERPF was observed. It is suggested that the renal changes following the i.v. administration of cadmium to diuretic hens and alleviated in hens primed with the heavy metal chelate may result from changes in glomerular hemodynamics.     

The effect of luteineizing hormone on chicken testis and pineal gland uptake of 32P.

The glandular uptake of radioactive phosphorus (32P), administered carrier-free, was used as an endpoint for the study of the effects of luteinizing hormone (LH) on the testis and pineal gland of 3-, 10- and 13-day-old White Leghorn cockerels. Pineal uptake of 32P of the 13-day-old birds decreased and testis uptake of 32P increased following LH treatment. Maximum effects were observed when 20 mug LH was administered 4.0 h before autopsy. Although testis uptake of 32P increased following LH treatment in 3- and 10-day-old cockerels, pineal uptake of 32P remained unchanged.     

Cell transformation in vitro by transfer of isolated metaphase chromosomes]

Human and murine cells can be transformed in vitro following transfer of chromosomes (transfection) isolated from tumour (HeLa) or SV40-transformed (WI98VaD) human cells. An abortive transformation of Mouse cells is observed in soft-agar medium. An instability of the transformed phenotype is exhibited by the transfected human cells, following the isolation of colonies growing in soft-agar or low-serum medium. Nevertheless, two transformed cell lines (809 ch. VaD, Cl.5P and Cl.6P) could be established in culture.     

Inhibitory effect of some heteropolyanions on potato virus X

Summary Heteropolyanions like 12-tungstozincic acid (i.i.), potassium 13-vanadomanganate (i.v.), potassium 13-vanadonickelate (i.v.) and sodium tungstoborate produced an inhibitory effect on potato virus X. Amongst these, tungstozincic acid was found to be the most potent.The authors are thankful to Prof. R. P. Rastogi, Head of the Chemistry Department, University of Gorakhpur for providing necessary facilities. The financial support by Council of Science and Technology, U.P., Lucknow is gratefully acknowledged.     

Accumulation of taurine in the nasal mucosa and the olfactory bulb

Using whole-body autoradiography of 14C-taurine in mice we have observed a high concentration in the nasal mucosa followed by accumulation in the olfactory bulb at longer survival times. When 14C-taurine was administered in the nasal cavity unilaterally, a high accumulation was observed in the ipsilateral olfactory bulb.     

Cadmium-induced changes in renal hemodynamics in the domestic fowl

Summary Low i.v. doses of cadmium chloride (15 g Cd) given to pullets resulted in a significant reduction in urine flow (UF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). However, in hens treated with the heavy metal chelate FeNa EDTA prior to cadmium treatment no oliguria or reduction in GFR or ERPF was observed.It is suggested that the renal changes following the i. v. administration of cadmium to diuretic hens and alleviated in hens primed with the heavy metal chelate may result from changes in glomerular hemodynamics.     

The glucose dependence of pancreatic endocrine responses to 2-deoxyglucose in the calf

Summary The initial plasma glucose concentration of unanesthetized calves with cut splanchnic nerves, given 2-deoxyglucose (1.2 mmoles/kg, i.v.), was either lowered by prior starvation, or raised by a continuous infusion of exogenous glucose. Raising the initial plasma glucose concentration completely suppressed the release of pancreatic glucagon and pancreatic polypeptide but substantially enhanced the release of insulin in response to 2-deoxyglucose.This work has been supported by the Medical Research Council and the Leverhulme Trust. We are also indebted to Mr P.M.M. Bircham and Mr G.P. Macgregor for their skilled technical assistance.     

Arousal deficit shown in aged rat's quantitative EEG and ameliorative action of pramiracetam compared to piracetam

Summary The basal EEG profile of the aged Fisher-344 rat was consistently different from that of the young rat, showing dominant high voltage slow-wave components. These slow waves were present in both the frontal cerebral cortex and dorsal hippocampus. Absent or greatly attenuated in the aged rat's hippocampal EEG was rhythmic theta activity, which was always dominant in the young awake rat's hippocampus. These EEG differences were clearly apparent only under basal test conditions, i.e, following habituation to the test situation. Pramiracetam sulfate acted strongly to normalize the aged rat's EEG, while the action of piracetam was weak and appeared to undergo tolerance development.     

Arousal deficit shown in aged rat's quantitative EEG and ameliorative action of pramiracetam compared to piracetam

The basal EEG profile of the aged Fisher-344 rat was consistently different from that of the young rat, showing dominant high voltage slow-wave components. These slow waves were present in both the frontal cerebral cortex and dorsal hippocampus. Absent or greatly attenuated in the aged rat's hippocampal EEG was rhythmic theta activity, which was always dominant in the young awake rat's hippocampus. These EEG differences were clearly apparent only under basal test conditions, i.e., following habituation to the test situation. Pramiracetam sulfate acted strongly to normalize the aged rat's EEG, while the action of piracetam was weak and appeared to undergo tolerance development.     

Effect of antiblastokinin on rabbit pregnancy

On different days following coitus, i.e., during the first stages of pregnancy, adult female rabbits were treated with antiblastokinin obtained from a chicken. A high prenatal mortality was observed and a reduction of the weight in the stillborn of the rabbits treated. The antiblastokinin produces evident biological effect about the 4th day following coitus, during the period of maximum production of blastokinin by the endometrium in vivo.     

The role of perireceptor events in vertebrate olfaction

The perception of odours and pheromones is mediated by small soluble carrier proteins that belong to the family of lipocalins. Those secreted by the nasal mucosa are called odorant-binding proteins (OBPs) for their binding activity towards volatile compounds. Proteins of similar structure, which we call pheromone-binding proteins (PBPs), help to deliver volatile pheromones in the environment. They are present in high concentration in biological fluids, such as urine, saliva and vaginal discharge, involved in chemical communication between conspecifics. Several subclasses of OBPs have been identified in the same animal species, each best related to a particular group of PBPs. Such similarities, together with anatomical and behavioural evidence, suggest that OBPs may be involved in the perception of pheromones.     

Nanoparticle-based drug delivery: case studies for cancer and cardiovascular applications

Nanoparticles (NPs) comprised of nanoengineered complexes are providing new opportunities for enabling targeted delivery of a range of therapeutics and combinations. A range of functionalities can be included within a nanoparticle complex, including surface chemistry that allows attachment of cell-specific ligands for targeted delivery, surface coatings to increase circulation times for enhanced bioavailability, specific materials on the surface or in the nanoparticle core that enable storage of a therapeutic cargo until the target site is reached, and materials sensitive to local or remote actuation cues that allow controlled delivery of therapeutics to the target cells. However, despite the potential benefits of NPs as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of NP materials, as well as their size and shape. The need to validate each NP for safety and efficacy with each therapeutic compound or combination of therapeutics is an enormous challenge, which forces industry to focus mainly on those nanoparticle materials where data on safety and efficacy already exists, i.e., predominantly polymer NPs. However, the enhanced functionality affordable by inclusion of metallic materials as part of nanoengineered particles provides a wealth of new opportunity for innovation and new, more effective, and safer therapeutics for applications such as cancer and cardiovascular diseases, which require selective targeting of the therapeutic to maximize effectiveness while avoiding adverse effects on non-target tissues.     

Acute effect of hypophysectomy on the natriuresis following saline infusion in dogs.

The natriuresis following an i.v. isotonic saline loading corresponding to 10% of body wt. was markedly decreased after acute hypophysectomy, due to lowered urinary sodium concentration, in anaesthetized dogs. A role of the pituitary in such a homeostatic natriuresis is suggested.     

Stimulation parameters determine role of GABAB receptors in long-term potentiation

Blockade of GABA_B receptors was reported to improve cognitive performance in mammals. The physiological basis of this effect is poorly understood. We investigated the effect of the GABA_B receptor antagonist CGP 35348 on long-term potentiation (LTP) in the CA1 area of the hippocampus in vitro and in vivo. In vitro the effect of CGP 35348 on LTP, induced either by two non-primed tetanic stimulations or by two primed bursts of stimuli, was investigated. In the presence of 1 mM CGP 35348 LTP was significantly facilitated following two non-primed tetanic trains, but was impaired following two primed burst stimulations. In vivo LTP was induced by applying non-primed trains of stimuli of increasing duration to the Schaffer collateral/commissural fibers. The potentiation of the population spike recorded in CA1 was significantly facilitated by CGP 35348 (100 mg/kg i.v.). In conclusion these findings demonstrate that the GABA_B antagonist CGP 35348 facilitates LTP in vitro and in vivo if induced by non-primed tetanic stimulation. In vitro, the mode of stimulation determines the effect of the GABA_B antagonist on LTP.     

Studies on chemically induced tumors in rats: I. Heterogeneity of tumor cells and establishment of syngeneic, tumor-specific cytotoxic T cell clones

Sarcoma P1 was induced in DA rats by DMBA. Anti-P1 antibodies were produced in DA rats, purified via fixed tumor cells and used to induce anti-idiotypic antibodies in syngeneic rats. The anti-idiotypic antibodies were used to generate cytotoxic, P1 specific DA T cells in vitro. These cytotoxic T cells and P1 tumor cells were cloned by limiting dilution. Using the DA anti-P1 specific cytotoxic T cell clones, we were able to characterize 2 types of P1 tumor cell clones, namely those which were susceptible and those which were resistant to the P1 specific cytotoxic T cells. Cytotoxic T cell injected i.v. into syngeneic DA rats could not prevent the development of lethal P1 tumors.