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Biomedical subjects

S Batra

Publications and source records attributed to S Batra.

At least 127 records · Page 7Linked to original sources

Effect of 2,2'-dicarbomethoxylamino-5,5'-dibenzimidazolyl ketone on antioxidant defenses of Acanthocheilonema viteae and its laboratory host Mastomys natalensis.

The effect of the macrofilaricidal agent of 2,2'-dicarbomethoxylamino-5,5'-dibenzimidazolyl ketone (C.D.R.I. compound 82/437), on the metabolism of reactive oxygen species (ROs) in Acanthocheilonema viteae and Mastomys natalensis was measured following intraperitoneal administration at therapeutic doses. The recovered worms possessed substantially reduced levels of catalase and glutathione peroxidase (GPx), and thus were less able to detoxify H2O2. Nonetheless, the subcutaneous and adjoining muscle tissues, in which the parasites were lodged, exhibited elevated levels of antioxidant enzymes and reduced glutathione. It is concluded that compound 82/437 kills the filariid by paralysing its H2O2 detoxifying capacity without altering ROs metabolism in the tissue in which the parasite resides. Furthermore, since catalase and GPx of the liver and lungs do not show sign of inhibition, a difference appears to exist in the enzymes of the parasite and the host.

Animals↗

Effect of anthelmintics on the antioxidant system of Nippostrongylus brasiliensis.

To understand the mode of anthelmintic action of thiabendazole and methyl-[5-[[4-(2-pyridinyl)-l-piperazinyl]carbonyl]-1H-benzimidazole- 2-yl] carbamate (C.D.R.I. compound 81/470) against Nippostrongylus brasiliensis, their effect on the metabolism of reactive oxygen species in the parasite as well as in rat intestine was examined. Both drugs produced a significant depression in the levels of superoxide dismutase (SOD) and reduced glutathione (GSH) of the parasite. Release of antioxidant enzymes by the drug-treated worms was also found to be appreciably lowered. Both thiabendazole and compound 81/470 induced a depression in the levels of all five constituents of the antioxidant system of rat intestine but significant alterations were detected only in the GSH content of infected and the SOD activity of normal intestine. The production of O2- by treated intestine was, on the other hand, markedly enhanced. Increased formation of O2- by the host intestine accompanied with the reduced level of SOD and GSH in N. brasiliensis appear to have a deleterious effect on the parasite. Consequently, the drug-treated worms are unable to retain themselves in situ and are ultimately expelled. The greater effect produced on these parameters by thiabendazole compared to compound 81/470 is consistent with the relative efficacy of these anthelmintics.

Animals↗

Orchiectomy upregulates rabbit prostate peripheral benzodiazepine receptors.

The effect of orchiectomy on peripheral benzodiazepine receptors (PBZr) in the rabbit prostate was studied. The mean PBZr density in the mitochondrial fraction isolated from prostates of intact (non castrated) rabbits was 4066 fmol/mg protein which following castration increased to 7236 fmol/mg protein (p less than 0.005). The apparent dissociation constant (KD) of prostatic PBZr was higher in castrated rabbits (4.2 nM) than in intact animals (2.7 nM). These data suggest a role of androgen in the regulation of prostatic PBZr.

Androgens↗

Antioxidant system of Litomosoides carinii and Setaria cervi: effect of a macrofilaricidal agent.

Filarial parasites, Litomosoides carinii and Setaria cervi, showed great susceptibility to the oxidants generated in vitro by the xanthine/xanthine-oxidase system. In order to counteract such injurious effects, both the filariids possessed an active antioxidant enzymes system. Superoxide dismutase, catalase and glutathione peroxidase were detected in appreciable amounts but glutathione reductase and glucose-6-phosphate dehydrogenase in very low quantities. The former three enzymes were also found to be released by the parasites into the ambient medium. The released enzymes may be responsible for scavenging the host-generated oxidants present in the immediate surroundings of the parasites and thereby enabling them to live comfortably in the host. This Institute-based antifilarial agent namely Compound 82/437 which is 2,2'-dicarbomethoxylamino-5,5'-dibenzimidazolylketone, markedly inhibited catalase and glutathione peroxidase of both L. carinii and S. cervi. The compound, therefore, appears to render the filariids prone to H2O2 toxicity leading to penultimate damage.

Animals↗

Influence of arterial access sites and interventional procedures on vascular complications after cardiac catheterizations.

The purpose of this study is to define the incidence of complications at the arterial access site after cardiac catheterization. The influence of the arterial access site on these complications was identified, as were the clinical characteristics of these problems. A total of 8,797 cardiac catheterizations were performed over the 3-year period of this study. Diagnostic catheterizations and percutaneous transluminal coronary angioplasties (PTCAs) were included, and the arterial access site was identified. Diagnostic catheterizations were performed via the brachial artery (group I, n = 3,137) or the femoral artery (group II, n = 4,055). PTCAs were also performed via the brachial artery (group III, n = 32) or the femoral route (group IV, n = 1,573). Ninety-five major vascular complications occurred during the course of this study. The frequency of complications was higher with brachial artery catheterization when compared with the femoral route. PTCA was associated with a higher complication rate than diagnostic studies. Brachial artery complications were primarily arterial thromboses, which were easily diagnosed and treated. Femoral artery complications were more complicated, difficult to identify, and associated with significant morbidity.

Angioplasty, Balloon, Coronary↗

Capillary network geometry during postnatal growth in rat hearts.

To determine the effects of postnatal growth on the coronary microcirculation, the geometry of capillary nets was studied in male rats at 21, 28, 60, and 240 days of age. Tissue sections were exposed to a histochemical technique that distinguished arteriolar (AC) and venular (VC) capillary regions by color. The tissue area (capillary domain) surrounding individual capillaries progressively increased with growth of the heart (P less than 0.01). In all groups, AC domain area was larger than VC domain area (P less than 0.01). The heterogeneity of capillary spacing, which is another important determinant of oxygen supply, demonstrated significant increases with age for AC regions (P less than 0.01). With increasing left ventricular mass, there was a lateral expansion of the arteriovenous capillary set, which was displayed by an increase in the number of and distance between adjacent capillaries that traversed the distance from arteriole to venule (P less than 0.01). Our data indicate that differences in the geometry of arteriolar and VC regions are present by 21 days of age. During postnatal growth, the results from both cross and longitudinal sections suggest that the geometrical conditions for oxygen supply are notably reduced.

Aging↗

Capillary length, tortuosity, and spacing in rat myocardium during cardiac cycle.

Microvascular geometry was evaluated in rat left ventricular midmyocardium (male Sprague-Dawley, n = 14), arrested in systole (S) or diastole (D), by bolus injections of CaCl2 or KCl, respectively. The histological method employed in this study allowed for the visualization of capillary pathways from arteriole to venule. Capillary length, as directly measured from terminal arteriole to collecting venule, was not significantly different between S and D groups, averaging 606 +/- 15 microns (pooled mean +/- SE). The capillary length tortuosity, defined as the ratio of the capillary length to the direct arteriovenous distance, was significantly increased in systolic-arrested hearts (S = 1.31 +/- 0.03; D = 1.18 +/- 0.02, P < 0.01). At the level of individual capillary segments, however, there was no increase in tortuosity in systolic-arrested hearts (S = 1.17 +/- 0.03; D = 1.16 +/- 0.02). Intercapillary spacing was significantly more uniform in systolic-arrested hearts. These data suggest that in systole, capillary length and tortuosity are generally preserved, and capillary spacing is more uniform, serving to maintain geometric conditions for oxygen supply during the cardiac cycle.

Animals↗

Capillary geometrical changes with fiber shortening in rat myocardium.

Capillary-to-fiber geometrical relations constitute an integral component of peripheral gas exchange. Determination of capillary length and surface area density necessitates quantification of capillary orientation (i.e., tortuosity and branching). In skeletal muscle, capillary tortuosity increases in a curvilinear fashion at reduced sarcomere length, and this compensates for decreased capillary density as fiber cross-sectional area increases. To investigate these relations in myocardium, rat hearts were glutaraldehyde perfusion-fixed in calcium- or barium-induced "systole" to provide varying degrees of fiber shortening. Morphometric techniques were used to analyze capillary geometry in subepicardium (EPI) and subendocardium (ENDO) using 1-micron sections cut transverse and longitudinal to the muscle fiber axis. Capillary density on transverse and longitudinal sections, capillary diameter, fiber cross-sectional area, and sarcomere length were determined in each region. Capillary surface density was computed, and values were related to sarcomere length and compared with published data for diastolic hearts. Sarcomere length in systole ranged from 2.06 +/- 0.03 to 1.35 +/- 0.02 microns (EPI) and from 1.93 +/- 0.04 to 1.44 +/- 0.04 microns (ENDO). Fiber cross-sectional area (EPI, 344 +/- 13 microns2; ENDO, 343 +/- 12 microns2) was significantly larger, and capillary density on transverse sections was significantly smaller (EPI, 4,105 +/- 318 mm-2; ENDO, 4,145 +/- 267 mm-2) than in hearts arrested in diastole. Compared with skeletal muscle, capillary tortuosity was substantially less increased by fiber shortening. Capillary tortuosity and branching did not differ between EPI and ENDO and contributed a maximum of 33% (range, 13-33%) to capillary length density and surface area at a sarcomere length of 1.45 +/- 0.04 microns. Compared with diastolic hearts, capillary length density decreased on average by 19.6% (EPI) and 17.7% (ENDO); similarly, capillary surface density decreased 19.9% (EPI) and 13.7% (ENDO). We conclude that, with fiber shortening in the heart, fiber cross-sectional area increases and capillary numerical density decreases as predicted from reduced sarcomere length. Combined with the minimal geometrical changes of the capillary bed at shorter fiber lengths, this results in a lower capillary length and surface area per fiber volume in systole. Consequently, the structural potential for O2 diffusion into myocytes is determined, in part, by fiber length.

Animals↗

Microvascular geometry of the rat heart. Arteriolar and venular capillary regions.

The importance of realistic data regarding microvascular geometry for the understanding of oxygen transport to tissue cannot be underestimated. The purpose of the present investigation was therefore to determine the pattern of capillarization in rat myocardium. The histochemical method used in this study was novel in that it allowed for the discrimination of arteriolar capillary (AC) and venular capillary (VC) regions on the basis of color. Our preeminent finding was that systematic differences exist in microvascular geometry from arteriolar to venular capillary regions in normal rat myocardium. Specifically, VC regions are characterized by greater capillary density; more uniform capillary spacing; shorter segment lengths; and increased capillary diameter. These differences translate to significantly greater capillary length, surface and volume densities on the venular side of the capillary bed. In the face of lower PO2 values towards venules, this distinctive geometry would serve to provide advantageous geometric conditions for oxygen diffusion.

Animals↗

Effect of five-membered heterocycles against Leishmania donovani infection.

Impact of change of heteroatom in pentavalent heterocycles, viz., pyrroles, isoxazoles, imidazoles and crotonates on the profile of antileishmanial activity against amastigotes of L. donovani using in vivo test system and macrophage-amastigote culture system has been studied. Sixty-three compounds were tested. Nine imidazoles showed marginal activity in vivo, whereas 3 out of 10 compounds of isoxazolone series and 2 out of 4 substituted aminocrotonates exhibited antileishmanial activity. Of the 30 substituted pyrroles, except 8 all showed antileishmanial activity in vivo on day 7 post treatment.

Animals↗

Effect of calcium and calcium antagonists on 45Ca influx and cellular growth of human prostatic tumor cells.

Calcium and calmodulin play significant roles in DNA synthesis and cell proliferation. In this work the effects of verapamil, trifluoperazine, and tamoxifen on 45Ca uptake and cell growth in human prostatic tumor cells (DU 145) and human fibroblast cells (1 BR) were studied. Although the maximum proliferation was achieved at a concentration of around 2 mM CaCl2 in both DU 145 and 1 BR, growth of DU 145 cells was considerably greater than 1 BR at all calcium concentrations (0.1-4 mM). Calcium uptake experiments, using 45Ca, revealed that the unstimulated 45Ca uptake in 1 BR fibroblasts was 4-5 times higher than in DU 145 cancer cells. Depolarization with high extracellular K caused a 2-3-fold increase in 45Ca influx in 1 BR but only 25-55% increase in DU 145 cells. Verapamil caused a significant inhibition of cell growth with an IC50 value of 55 microM. Verapamil paradoxically increased 45Ca uptake in both unstimulated and K-stimulated DU 145 cells. Whereas unstimulated 45Ca uptake could be blocked by very low concentrations of lathanum (10 microM), much higher concentrations (1-10 mM) were required to completely block uptake in K-depolarized cells. Both trifluoperazine and tamoxifen also inhibited cell proliferation with an IC50 concentration of approximately 5 microM. These drugs, had, however, no effect on 45Ca uptake either in unstimulated or depolarized cells. The results suggest that voltage-gated calcium channels exist in both DU 145 cancer cells and fibroblasts. However, verapamil, in contrast to 1 BR, failed to block these channels in DU 145 cells. The mechanism of antiproliferative action of verapamil may be related to the observed, although paradoxical, increase in cellular calcium. The effect of trifluoperazine and tamoxifen does not involve changes in transmembrane calcium movements but could be mediated by their inhibition of calmodulin-mediated reactions within the cell.

Calcium↗

Geometry of capillary networks in hypertrophied rat heart.

Capillary geometry was examined in normal and hypertrophic myocardium. Hypertrophy was induced by aortic constriction in neonatal rats. Morphometric data were obtained from tissue sections exposed to a staining technique that distinguished the arteriolar and venular portions of capillaries by color. In sham-operated controls, the theoretical tissue region supplied by a single capillary decreased from the arteriolar to venular side (499 +/- 3 microns 2 and 456 +/- 5 microns 2, P less than 0.05; mean +/- SE) of capillaries. In hypertrophy, only arteriolar capillary tissue regions increased in size, thus enlarging the difference between arteriolar and venular ends (547 +/- 6 microns 2 and 464 +/- 5 microns 2, P less than 0.01). Intercapillary distances, measured at various levels along the capillary path length, decreased in a stepwise manner in both normal and hypertrophic hearts. In hypertrophic hearts, mean capillary path length was significantly longer than in controls, but the total length of the individual capillary nets was reduced. In both groups, arteriolar capillary segment length was longer (P less than 0.01) than venular capillary segment length. Given that PO2 values are lower on the venular side of capillaries, this spatially distinctive geometry in normal myocardium: smaller domains, shorter intercapillary distances and segment lengths, would provide favorable geometric conditions for oxygen diffusion. In hypertrophy, average intercapillary distance increased, and the distinction between arteriolar and venular portions of capillaries was further exacerbated.

Animals↗

Geometry of capillary networks in volume overloaded rat heart.

Volume overload cardiac hypertrophy was induced in male Sprague-Dawley rats by experimental aortocaval fistula. This procedure resulted in considerable increases in left ventricular mass (70%) by 21-23 days. Our objective was to study the effect of volume overload on the geometry of coronary capillaries in the left ventricular midmyocardium. Tissue sections were stained according to a protocol that distinguished arteriolar (AC) and venular (VC) capillary regions by color. Morphometric data were then collected and compared between AC and VC regions. In sham-operated controls (CON; n = 8), the tissue area (capillary domain) supplied by a single capillary decreased from AC to VC regions (AC = 505 +/- 5 microns 2: VC = 452 +/- 7 microns 2; P less than 0.01; mean +/- SE). In volume overloaded hearts (VOL; n = 8), only VC domain areas were reduced from control values (P less than 0.01) and the differences between AC and VC regions were preserved (AC = 480 +/- 5 microns 2; VC = 395 +/- 6 microns 2; P less than 0.01). Minimal capillary length was significantly longer in volume overloaded hearts (VOL = 723 +/- 18; CON = 581 +/- 20 microns; P less than 0.01). In the control group, AC segment length was longer than VC segment length (AC = 93 +/- 2 microns: VC = 74 +/- 2 microns; P less than 0.01). In volume overload, AC segment length was also longer than VC segment length, but the divergence between AC and VC regions was increased (AC = 108 +/- 3 microns; VC = 71 +/- 2 microns; P less than 0.01). These changes in capillary geometry may be secondary to specific changes in the arrangement and dimension of myocytes in the left ventricular wall following volume overload hypertrophy.

Animals↗

Capillarization of the hypertrophic heart: discrepancy of the results obtained by the triangulation and domain methods.

The geometry of capillary networks was examined in pressure-overloaded hypertrophic rat myocardium. All hearts were exposed to a staining protocol that distinguished the arteriolar (AC) and venular (VC) regions of capillaries. In control hearts, the triangulation method (one-dimensional distance between neighboring capillaries) and the domain method (two-dimensional area surrounding capillaries) exhibited similar results, showing increased capillarization for the venular region of capillaries networks. In hypertrophic hearts, the triangulation method did not demonstrate differences between arteriolar and venular capillaries (AC = 27.2 +/- 0.4 microns, VC = 27.0 +/- 0.2 microns, p = 0.56). However, the domain method still detected smaller tissue supply regions for venular capillaries (AC = 547 +/- 6 microns 2, VC = 464 +/- 5 microns 2, p less than 0.01). To resolve this discrepancy in hypertrophic heart, we have measured capillary spacing from longitudinal sections at discrete intervals along the A-V path length. These results indicate a stepwise decrease in intercapillary distance from arteriole to venule for both groups, which would support results obtained by the domain method. A possible explanation for the discrepancy between these two methods, specific to hypertrophic heart, may be changes in the clustering patterns of arteriolar and venular capillaries.

Animals↗