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Biomedical subjects

P Sen

Publications and source records attributed to P Sen.

At least 109 records · Page 6Linked to original sources
PubMed1987

Comparison of the localization of chromosome damage induced by calcium chromate and nickel compounds.

Chromosomal aberrations were studied in Chinese hamster ovary cells and in C3H10T1/2 cells following treatment with NiCl2, crystalline NiS, and CaCrO4. All three compounds caused an increase in chromosomal aberrations in a concentration- and time-dependent fashion. The chromosomal aberrations induced by NiCl2 and crystalline NiS occurred predominantly in heterochromatic regions of the chromosomes. Additionally, treatment of cells with crystalline NiS and to a smaller extent long-term treatment with NiCl2 caused a preferential effect on the condensation state of the heterochromatic long arm of the X-chromosome in hamster cells. In contrast, treatment of cells with CaCrO4 did not induce aberrations preferentially in heterochromatin. These results are interesting because nickel(II), which is thought to be the ultimate carcinogen of nickel compounds, binds poorly to DNA, is weakly mutagenic, but induces chromosome damage, probably because of its interaction with nuclear proteins in heterochromatin. Chromate binds to DNA, is mutagenic, and interacts with chromatin randomly.

Calcium Compounds↗
PubMed1987

Involvement of brain transmitters in the modulation of shock-induced aggression in rats by propranolol and related drugs.

(+/-)Propranolol (1, 3, 10 and 30 mg/kg) exhibited a differential effect on footshock aggression (FSA) in rats. Lower doses (1 and 3 mg/kg) of the drug facilitated FSA, whereas an inhibitory effect was observed with higher doses (10 and 30 mg/kg) of the same. (+)Propranolol (30 mg/kg) and UM-272 (1 and 10 mg/kg) as well as physostigmine (0.1 and 0.5 mg/kg) all produced inhibition of FSA. Similar FSA inhibitory effects were also observed with salbutamol (1 and 5 mg/kg). Pretreatment with atropine and not methylatropine attenuated the anti-aggressive effect of (+/-)propranolol (10 mg/kg) without appreciably altering the facilitatory effect (1 mg/kg) of the drug on FSA. In addition, at the anti-aggressive doses, (+/-)propranolol (10 mg/kg) and UM-272 (10 mg/kg), significantly inhibited brain cholinesterase enzyme activity when compared to saline controls. (+/-)Propranolol (10 mg/kg) also inhibited significantly the aggression induced by reserpine-apomorphine treatment. It is inferred that a central cholinergic and dopaminergic mechanism is involved in the anti-aggressive effect of (+/-)propranolol, whereas the low dose induced facilitation of affective aggression could be attributed to central beta-adrenoceptor blockade.

Acetylcholinesterase↗
PubMed1986

Pathway of nickel uptake influences its interaction with heterochromatic DNA.

Exposure of intact Chinese hamster ovary cells to water-soluble NiCl2 and to particulate crystalline NiS induced a concentration-dependent incidence of chromosomal aberrations which included gaps, breaks, and exchanges. Exposure of cells to crystalline NiS particles caused a high incidence of chromatid exchanges and dicentrics and produced what appears to be an effect on the condensation state of the heterochromatic long arm of the X chromosome. Treatment of cells with NiCl2 did not cause any significant effect on the long arm of the X chromosome, and there was a much lower incidence of the dicentric type of chromosomal aberrations compared to NiS. To examine whether the fragmentation/decondensation of the long arm of the X chromosome produced by crystalline NiS particles was due to a phagocytic pathway of uptake of NiS particles, cells were treated with NiCl2-albumin complexes that had been encapsulated in liposomes. Although treatment of cells with NiCl2-albumin complexes yielded higher intracellular nickel levels than were obtained by treatment of cells with NiCl2, at comparable intracellular levels fragmentation/decondensation of the heterochromatic long arm of the X chromosome was observed when nickel (II) was delivered by way of a liposome but not when cells were treated with unencapsulated NiCl2. Ionic nickel alone irrespective of its delivery mechanism exhibited some preference for heterochromatin, since there was a higher incidence of aberrations observed in the heterochromatic centromeric region of chromosomes. These observations suggest that the pathway of delivery of Ni2+ from NiS particles may be responsible for a preferential interaction of this metal with heterochromatin leading to an effect on the condensation state/fragmentation of the heterochromatic long arm of the X chromosome.

Animals↗
PubMed1986

Antagonistic effect of magnesium chloride on the nickel chloride-induced inhibition of DNA replication in Chinese hamster ovary cells.

The degree of inhibition of semiconservative DNA replication induced by nickel chloride (NiCl2) was analyzed by radiolabeled-thymidine incorporation alone or with cesium chloride (CsCl) density gradient centrifugation. The onset and duration of this Ni2+-induced inhibition was time- and concentration-dependent, but the degree of inhibition was not. A maximal reduction in the rate of DNA synthesis was observed within the first hour of treatment with 2.5 mM NiCl2, which was the highest noncytotoxic concentration utilized. After six hours, 500 microM and 1 mM as well as 2.5 mM NiCl2 all produced the same 50% to 60% reduction in [3H]-thymidine incorporation into DNA. The inhibitory effect of nickel ions on DNA synthesis was reversible. The rate of DNA synthesis following a 500 microM or 1 mM NiCl2 treatment began to increase after washout of nickel, but a six-hour exposure of cells to 2.5 mM NiCl2 produced a sustained 50% to 60% suppression of DNA synthetic activity for at least 36 hours. At all concentrations of NiCl2 used in this study, some inhibition of DNA synthesis persisted for at least 48 hours, but by 72 hours after treatment, the rate of [3H]-thymidine incorporation was actually 10% above the control. Examination of autoradiographic slides of cells treated with 2.5 mM NiCl2 for six hours demonstrated a 60% reduction of silver grains, but there was no preferential reduction in the quantity of grains in the nucleolus or any other region. Cesium chloride density gradient analysis of the replication of nucleolar DNA in cells treated with 2.5 mM nickel supported the autoradiographic findings. The inhibitory effect of NiCl2 on DNA replication was prevented by the addition of magnesium chloride (MgCl2) to cells maintained in a simple salts/glucose medium (SGM). This effect did not appear to be due to an antagonism of the cellular uptake of nickel by Mg2+, since the maximally effective dose of Mg2+ reduced 63Ni2+ uptake by no more than 25% while the inhibition of replication was completely reversed.

Animals↗
PubMed1986

Incidence and localization of sister chromatid exchanges induced by nickel and chromium compounds.

Carcinogenic nickel compounds enhanced the incidence of sister chromatid exchanges (SCEs) in a concentration-dependent fashion in intact Chinese hamster ovary cells. There was a preferential induction of these exchanges in the heterochromatic regions of the chromosomes. CaCrO4 also caused a dose-dependent induction of SCEs. However, in contrast to NiCl2, the exchanges induced by CaCrO4 were not localized in any particular chromosomal region. The total incidence of exchanges was higher with CaCrO4 than with NiCl2. CaCrO4, crystalline NiS and NiCl2 enhanced the incidence of SCEs at concentrations below the threshold of DNA damage as detected by the technique of alkaline elution. Additionally, following treatment time intervals of 24-48 h, there was an increase in SCEs at concentrations of NiCl2 or CaCrO4 that produced little disruption of cell cycle progression. These results are consistent with the hypothesis that potently carcinogenic nickel compounds which are not very mutagenic exert selective effects on genetically inactive heterochromatin, while potently mutagenic and carcinogenic chromate do not appear to produce a similar predominance of SCEs in heterochromatic regions.

Cell Cycle↗
PubMed1986

Tissue cholinesterase inhibition by propranolol and related drugs.

The effect of (+/-)-propranolol and some related drugs have been investigated on the cholinesterase (ChE) enzyme activity of heart and brain tissues of the rat. Brain homogenates hydrolysed more methacholine than benzoylcholine and the reverse was true for the heart tissue. In-vitro, (+/-)-, (+)- and (-)-propranolol, as well as its quaternary analogue, UM-272, all significantly inhibited heart and brain ChE. Timolol and sotalol, however, were less potent. In-vivo, (+/-)-propranolol (30 mumol kg-1) significantly inhibited brain ChE activity in rats when compared with saline controls. It is inferred that propranolol inhibits brain and heart ChE enzyme in a non-stereoselective manner and that this cholinomimetic action could be involved in the mediation of some of its therapeutic effects.

Animals↗
PubMed1986

Autonomic regulation involved in the ocular hypotensive action of beta-adrenergic blocking agents.

The effects of racemic propranolol and some related drugs on the intraocular pressure (IOP) were studied after topical application in rabbits. These drugs produced a significant reduction in IOP with the following order of potency: (-)-propranolol greater than timolol greater than (+/-)-propranolol greater than sotalol greater than (+)-propranolol greater than pranolium. Pretreatment of rabbit eyes with atropine significantly antagonized the ocular hypotensive action of (+/-)-propranolol, timolol and pranolium. Both (+/-)-propranolol and timolol produced a significant increase in pupil diameter in the presence of a submydriatic dose of atropine. The activities of monoamine oxidase and carbonic anhydrase were unaffected by (+/-)-propranolol, timolol and pranolium in-vitro. It is concluded from the results that both cholinergic and adrenergic mechanisms may be involved in the ocular hypotensive effects of the drugs.

Adrenergic beta-Antagonists↗