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Biomedical subjects

P Sen

Publications and source records attributed to P Sen.

At least 127 records · Page 7Linked to original sources
PubMed1986

Nonstereoselective aspects of propranolol pharmacodynamics.

Twenty years after its discovery, the beta-adrenergic blocking agent propranolol continues to interest pharmacologists and clinicians. Its therapeutic profile has extended to areas beyond the purview of the cardiovascular system, and its ocular and central nervous system effects have been well documented. In addition, it still remains a very good pharmacological tool to map out the adrenergic beta-receptors in the body, and stereoisomers of propranolol and other beta-blockers serve as valuable agents to distinguish between the effects related to beta-adrenoceptors and those which are not. The primary purpose of this review is to summarize the evidence indicating that beta-adrenergic blocking agents lack stereoselectivity in some of their effects, including several of considerable therapeutic importance. Because many pharmacological actions of propranolol followed a nonsteroselective pattern, the involvement of beta-adrenoceptors in them was questioned and this led to the search for alternate mechanisms to explain these effects. Studies with propranolol and some related drugs indicated the involvement of a cholinergic mechanism in their antiarrhythmic, ocular hypotensive and some central effects. Also, a presynaptic inhibitory effect at the skeletal neuromuscular junction has been suggested to explain the benefical effect of propranolol and other beta-blockers in tremor. Biochemical studies with these drugs revealed their inhibitory action on the cholinesterase enzyme in blood and other tissues like myocardium and brain. It is thus hypothesized that modulation of cholinergic neurotransmission by propranolol could explain some of its nonstereoselective actions and open new vistas in propranolol pharmacodynamics.

Animals↗
PubMed1985

Effects of chloroquine on the serum complement system.

Chloroquine, a well-known anti-malarial and anti-inflammatory agent, was studied with respect to its effect on the serum complement system. The drug exhibited significant in vitro anti-complementary activity only at a very high non-therapeutic dose of 48 mg/ml. Chloroquine-induced in vitro complement consumption was observed to take place even in the absence of Ca2+ and Mg2+ ions. The drug also haemolyses rabbit erythrocytes in the presence of Mg2+-EGTA and immunoelectrophoretic studies of fresh human serum and chloroquine incubation mixture against specific anti-C3 and anti-factor B antisera have demonstrated that it cleaves both C3 and factor B. In another experiment, chloroquine failed to exert inhibitory effects on complement utilisation by immune complexes. Studies of the serum complement profile of Plasmodium falciparum-infected malaria patients receiving chloroquine therapy indicated that, in contrast to the situation in vitro, the serum C3 level is invariably decreased. Marginal reductions in the levels of C4, factor B and properdin were also found in some of these patients, while administration of chloroquine to normal human individuals failed to produce any significant change in their serum complement profile. It is, therefore, probable that malarial parasites and not chloroquine are responsible for complement activation in patients suffering from malaria.

Adult↗
PubMed1985

Characterization of G-banded chromosomes of the Indian muntjac and progression of banding patterns through different stages of condensation.

Muntjac prophase and metaphase chromosomes were G-banded following methotrexate-mediated synchronization of peripheral lymphocytes. Bands and subbands were characterized from prophase through metaphase, and the progression of band patterns from late prophase to mid-metaphase was analyzed. Extended prophase chromosomes exhibited more bands and subbands, a number of which became fused with each other, giving rise to fewer and thicker bands in the condensed metaphase chromosomes. It appeared that the dark bands condensed relatively more than the light bands. Precise delineation of the bands and subbands on extended prophase chromosomes and the usage of a proposed banding pattern nomenclature should aid in better detection and localization of induced chromosomal rearrangements with this extremely useful experimental material.

Animals↗
PubMed1985

Cholinergic involvement in the modulation of oxotremorine-tremor in mice by propranolol.

Propranolol in low doses antagonized and in higher doses facilitated oxotremorine-induced tremor (Oxo-tremor) in mice. Atropine blocked Oxo-tremor, an effect that was reversed by propranolol. Atropine pretreatment also antagonized the potentiating effect of propranolol on Oxo-tremor. Propranolol inhibited mice brain cholinesterase at doses which enhanced Oxo-tremor. Timolol and sotalol produced a dose-dependent antagonism of Oxo-tremor, whereas practolol failed to produce a similar effect. None of these three agents produced any significant enhancement of Oxo-tremor. These results suggest the involvement of a peripheral mechanism for the antagonism and a central cholinergic mechanism for the facilitation of Oxo-tremor by propranolol.

Adrenergic beta-Antagonists↗
PubMed1985

Anterior thigh pain or tenderness. A diagnostically useful manifestation of bacteremia.

In four patients with putative infectious process, anterior, bilateral proximal thigh pain and tenderness unaccompanied by generalized myalgias developed. This unusual manifestation, observed in these and other patients, was associated with demonstrable bacteremia. Aside from tenderness, no local abnormalities were found and the pain and tenderness disappeared after appropriate therapy. Creatine kinase levels, measured in three of the four patients, were elevated in only one. This manifestation is useful clinically as it strongly suggests bacteremia; attention to this finding can be lifesaving.

Abdomen↗
PubMed1985

Induction of chromosomal damage in Chinese hamster ovary cells by soluble and particulate nickel compounds: preferential fragmentation of the heterochromatic long arm of the X-chromosome by carcinogenic crystalline NiS particles.

Treatment of intact Chinese hamster ovary cells with crystalline NiS and NiCl2 resulted in the induction of chromosomal aberrations which included gaps, breaks, and exchanges. The incidence of these aberrations increased in a time- and concentration-dependent fashion. NiCl2 was more potent in inducing chromosomal aberrations in cells that were maintained with a salts/glucose medium during metal treatment than when cells were treated in culture growth medium. Chromosomal aberrations induced by NiCl2 occurred randomly among the autosomal arms; however, the heterochromatic centromeric regions of the chromosomes were preferentially damaged. In addition to inducing the same type of aberrations found with NiCl2, crystalline NiS particles also caused the selective fragmentation of the heterochromatic long arms of the X-chromosomes. This fragmentation was attributed to the difference in the mechanism of delivery of nickel ions from phagocytized crystalline NiS particles which aggregate around the nuclear membrane and release large amounts of nickel ions from a dissolving phagocytized particle. Previous studies have demonstrated that treatment of intact cells with crystalline NiS particles produces a considerably higher level of nickel in the nucleus compared with similar exposure to water-soluble NiCl2. Since heterochromatin is known to form the inside lining of the interface nucleus, nickel ions, as they are solubilized from a phagocytized particle and enter the nucleus, are likely to encounter heterochromatin before they interact with euchromatin. In contrast, nickel ions derived from NiCl2 do not preferentially accumulate in the cell, and those ions that enter the cell are taken up by a nonphagocytic mechanism. It is proposed that when cells are treated with high levels of NiCl2 in an attempt to achieve the cellular levels of nickel produced by NiS phagocytosis, this overloading results in cytotoxic responses rather than the preferential fragmentation of heterochromatin observed with particles. Since liposome-mediated delivery of NiCl2 also results in fragmentation of the long arm of the X-chromosome, the selective breakage of heterochromatin by NiS particles may be due solely to the mechanism of Ni2+ delivery in cells.

Animals↗
PubMed1984

Induction of chromosome damage by Neurospora endonuclease in repair-inhibited quiescent normal human fibroblasts.

The purpose of these experiments was to determine the role of double-strand breaks in chromosome aberration formations. Quiescent normal human fibroblasts were treated with 3 microM nitrogen mustard and then allowed to repair their DNA damage for 24 h prior to cell fusion and induction of premature chromosome condensation. The extent of chromosome damage was determined in the G1 prematurely condensed chromosomes (G1 PCC). The presence of cytosine arabinoside and hydroxyurea during the repair period in order to accumulate single-strand DNA breaks resulted in an increase in the chromosome-break frequency. Treatment of these repair-inhibited cells with single-strand-specific neurospora endonuclease during fusion to change single-strand lesions into double-strand breaks resulted in a doubling of the aberration frequency. These results support the notion that double-strand breaks are important in chromosome-aberration formation.

Cell Line↗
PubMed1984

Effect of chloroquine and some other antimalarials on the immune mechanism in experimental animals.

The effects of chloroquine and some other antimalarials on the immune responses in experimental animals have been examined. Chloroquine and quinine caused significant decrease of serum anti-SRBC haemagglutination titre. Chloroquine lowered the serum IgM level and also reduced plaque-forming cells in the spleen of mice. The delayed-type hypersensitivity responses to SRBC and the passive cutaneous anaphylaxis were also diminished in rats treated with chloroquine. Thus, the immunosuppressant activity of chloroquine may explain its efficacy in various types of immune disorders.

Adrenal Glands↗
PubMed1984

Role of vagus in the antagonism of ouabain induced arrhythmias in dogs by beta-adrenoceptor antagonists and related drugs.

The effects of propranolol and related drugs were investigated on ouabain-induced ventricular tachycardia (VT) in dogs with intact and ablated vagi. Propranolol and UM-272 completely antagonized the ouabain VT in dogs with intact vagi, whereas timolol was ineffective. Bilateral vagotomy completely abolished the effect of UM-272 and reduced the effect of propranolol. Diphenylhydantoin, however, reversed ouabain VT in dogs with both intact and ablated vagi. It is inferred that the vagus plays a significant role in the arrhythmolytic effect of propranolol and UM-272.

Adrenergic beta-Antagonists↗
PubMed1984

Kinetics and extent of repair of bleomycin-induced chromosome damage in quiescent normal human fibroblasts and human mononuclear blood cells.

The kinetics of chromosome damage repair after bleomycin treatment was studied in quiescent mononuclear human blood cells and human fibroblasts using the technique of premature chromosome condensation. Quiescent cells were treated with bleomycin for 30 min, washed free of drug, and fused with mitotic HeLa cells after various repair times. The amount of chromosome damage remaining was assayed in the G1 prematurely condensed chromosomes. The chromosome repair kinetics profile exhibited fast- and slow-repair components. The fast chromosome repair component was apparent within 2 hr after bleomycin treatment, with a significant amount of repair having occurred within 30 min. The absolute rate of chromosome repair then significantly slowed beyond 2 hr after treatment. The rate of chromosome repair was slightly dependent on dose with a higher rate observed at a higher dose. Interestingly, while quiescent fibroblasts were more sensitive to bleomycin than were mononuclear blood cells, both cell populations exhibited similar repair kinetics. These results suggest the following: (a) quiescent human fibroblasts and mononuclear blood cells show similar chromosome repair kinetics after bleomycin treatment; (b) there exist both fast- and slow-repair components after bleomycin treatment; and (c) the rate of chromosome repair is dependent on the degree of initial damage.

Bleomycin↗