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Biomedical subjects

P Sagar

Publications and source records attributed to P Sagar.

At least 37 records · Page 2Linked to original sources

Aberrations in cerebral vascular functions due to Plasmodium yoelii nigeriensis infection in mice.

Plasmodium yoelii nigeriensis infection in mice caused an increase in uptake of 125I-labeled bovine serum albumin, 51Cr-labeled erythrocytes and Evans blue dye from peripheral circulation into the brain. Isolated cerebral microvessels which were characterized in terms of their morphology under scanning electron microscope and enhancement of the specific activities of biochemical markers, viz. alkaline phosphatase, gamma-glutamyl transpeptidase, and monoamine oxidase, showed significant decrease in these activities due to P. yoelii nigeriensis infection. On the other hand, relatively minor (statistically insignificant) changes occurred in the first two enzyme specific activities in the cerebral cortex and monoamine oxidase registered an increase in this tissue due to infection. Histological examination of the cerebral tissue of infected animals by light and electron microscopy showed broken blood vessel walls and leakage of erythrocytes into extravascular space, some of which contained intraerythrocytic malarial parasite in a state of cell division.

Alkaline Phosphatase↗

Oxido-reductive functions of Entamoeba histolytica in relation to virulence.

Entamoeba histolytica can reduce nitro-blue tetrazolium (NBT) in Hank's balanced salt solution to almost the same extent as in Eagle's minimal medium. Further, this reduction was stimulated only to a minor degree by glucose, pyruvate and DL-serine, substrates known to support respiratory activity (O2 uptake) in E. histolytica. However, both NADH and NADPH increased NBT reduction several-fold, the effect being greater with NADPH. A sizeable proportion of this endogenous dye-reducing capability (in Hank's solution) was associated with low-speed sediments obtainable from amoebic homogenates, which also shared the bulk of 125I labelling (when the homogenates were prepared after surface labelling with Na 125I). Conversion of the dye to formazan was strongly inhibited by -SH blocking agents, but was not influenced by rotenone and antimycin A. The activity was also inhibited by H2O2, but stimulated by catalase. Superoxide dismutase only slightly curtailed NBT reduction in intact cells, but inhibited it in homogenates in a concentration-dependent manner to a maximal extent of 33%. Almost the same degree of curtailment of this activity was induced by anaerobic conditions. Both concanavalin A (Con A) and phorbol myristate acetate stimulated the activity in intact cells, though the effect of Con A was nullified by alpha-methyl mannoside. Both NBT-reducing capability and alcohol dehydrogenase activities were higher in the more virulent IP:106 strain, and they increased with time in cultures of NIH:200 in a cholesterol-enriched environment.

Alcohol Dehydrogenase↗

Cerebral ammonia levels and enzyme changes during Plasmodium yoelii infection in mice.

Ammonia, lactate and glutamate levels and the activities of glutamine synthetase (GS), glutamate dehydrogenase (GDH), glutaminase (GLN), aspartate transaminase (AST), phosphofructokinase (PFK) and monoamine oxidase (MAO) were compared in the brain tissue of normal and P. yoelii infected mice. The brain lactate increased by 96% at peak parasitaemia. Cerebral ammonia also exhibited an increase in infected mice which was parasitaemia dependent, while glutamate remained almost unchanged. The brain glutamine synthetase registered an increase of 35% (P < 0.001) in post-mitochondrial fractions, this effect being perceptible even at low parasitaemia, but attained constancy at parasitaemia levels higher than 20%. The activity of monoamine oxidase and phosphofructokinase increased by 105% (P < 0.02) and 41% (P < 0.05) respectively while glutamate dehydrogenase decreased by 15% (P < 0.001). Glutaminase and aspartate transaminase were not significantly influenced by infection (tested only at high parasitaemia levels). It has been postulated that cerebral hypoxia and aberrations in ammonia metabolism may both contribute towards malaria induced cerebral complications.

Ammonia↗

p53 in colorectal cancer: clinicopathological correlation and prognostic significance.

p53 protein was detected by immunohistochemistry in 42% of 52 colorectal adenocarcinomas. Positive tumours were significantly more frequent in the distal colon, and demonstrated a higher rate of cell proliferation. No correlation was found with tumour grade, Dukes' stage, presence of DNA aneuploidy or patient survival. The role of p53 in colorectal carcinogenesis is discussed with particular reference to differences between proximal and distal large bowel cancers.

Colorectal Neoplasms↗

Biochemical and ultrastructural studies induced by phanquone on Entamoeba histolytica NIH-200.

The action of phanquone on the incorporation of (14C)1-DL-valine and (14C)-8-adenine in TCA insoluble fractions of Entamoeba histolytica was examined as indices of RNA and protein synthesis respectively. The former was found to show greater sensitivity to the drug in terms of the effect manifested in the dose response curves for these parameters. Electron microscopic investigations with increasing concentrations of the drug demonstrated progressive vacuolization with concomitant dissolution of ribosomal helices. The drug had no significant effect on nucleus and plasma membrane even at concentration as high as 200 micrograms/ml.

Amebicides↗

Effect of Plasmodium yoelii infection on GABA metabolism of mouse brain.

Plasmodium yoelii infection in albino mice decreased the activity of brain glutamic acid decarboxylase (GAD) by about 30 and 48% in crude homogenate and its synaptosomal fraction, respectively. The decrease was evident from 20% parasitemia and remained more or less constant up to 80% parasitemia. The Km values of GAD in normal and infected animals were 1.2 x 10(-2) and 3.3 x 10(-2) mM, respectively, indicating a decrease in enzyme substrate affinity due to infection. The lowered GAD activity rose to slightly above normal by treatment of infected animals with chloroquine. Decrease in GAD activity reflected lower gamma-aminobutyric acid (GABA) levels in the infected brain; however, GABA-transaminase activity was not significantly influenced by infection. It has been proposed that impaired GABA synthesis may be due to hypoxia induced by malarial infection.

4-Aminobutyrate Transaminase↗

Specific features of phosphomonoesterase of Entamoeba histolytica (NIH-200).

Axenically grown E. histolytica possess significant acid phosphatase activity. The Km of the enzyme was found to be 7.1 x 10(-3) and was maximally active at pH 4.5. Acid phosphatase activity was significantly inhibited by Cu2+, cysteine and was activated by tartrate and fluoride. It was found that E. histolytica acid phosphatase differs in some properties as compared to the enzyme reported from other sources.

Animals↗

Action of metronidazole on Entamoeba histolytica: an ultrastructural study.

Metronidazole (19 micrograms/ml) caused progressive increase in vacuolization in Entamoeba histolytica cells with disintegration of its plasma membrane leading to almost complete disappearance of the latter within 3 hours. The drug also induced formation of helical ribosomal aggregates in the cytoplasm and disappearance of button like structures inside the nucleus.

Animals↗

Evidence for selection of virulent sub-populations of Entamoeba histolytica by cholesterol.

Quantitatively much higher Concanavalin A (Con. A) agglutinability, haemolytic potency, and activities of acid hydrolases, namely phosphatase (EC 3.1.3.2), ribonuclease (EC 2.7.7.16), deoxyribonuclease (EC 3.1.4.5) and proteinase--were observed in a virulent strain of Entamoeba histolytica (IP-106), as compared to attenuated and avirulent strains (200-NIH) and DKB respectively. In addition, significant differences in these parameters were observed among clonal cultures derived from the latter two cultures by cultivation of single amoebic cells picked out by micromanipulation. Repeated sub-culturing of parent cultures of both these strains in cholesterol-enriched medium resulted in marked enhancement of all the above activities, but no such change occurred in the derived clonal cultures following similar cholesterol treatment. The implication of these findings in relation to enhancement of the virulence of E. histolytica by cholesterol is discussed.

Acid Phosphatase↗

In vitro insulin action on erythrocyte glucose metabolism in normal and diabetic rats.

Alloxan-induced diabetes in rats significantly impaired the capacity of the erythrocytes to metabolise glucose in vitro to either lactic acid or CO2. Both these metabolic activities were initially insensitive to insulin in normal as well as in diabetic animals; but became responsive when these cells were subjected to insulin and glucose 'starvation' for 1 h through incubation in their absence. This action of insulin in starved cells showed concentration dependence and required preincubation with the hormone prior to addition of glucose.

Animals↗

Action of praziquantel on calcium transport in Hymenolepis diminuta.

Effect of praziquantel on inward and outward Ca++ fluxes was investigated in Hymenolepis diminuta in glucose supplemented balanced electrolyte solution and under conditions of glucose/Mg++ deficiency. The 45Ca++ uptake in freshly isolated worms presented, generally, a biphasic kinetics. This comprised of an initial fast uptake phase, followed by a continued slower influx. The initial fast kinetics showed insensitivity to or slight stimulation by praziquantel depending on its concentration, and such stimulatory action was particularly prominent under Mg++ deficient condition (P less than 0.01). The subsequent slower 45Ca++ uptake was, however, markedly inhibited by the drug under both these conditions (P less than 0.01). Glucose starvation of the worms resulted in abolition of the fast 45Ca++ influx phase and uniform inhibition by the praziquantel without any indication of initial stimulatory effect (P less than 0.01). The extrusion of 45Ca++ from the label preloaded worms was stimulated by praziquantel under all the conditions investigated (P less than 0.01).

Animals↗

Sensitivity of protein and RNA synthesis to emetine in axenic Entamoeba histolytica.

The action of emetine on the incorporation of (14C)1-DL-valine and (14C)-8-adenine in TCA insoluble fraction of axenic Entamoeba histolytica was investigated. These compounds were almost exclusively incorporated in the 'protein' and 'RNA' fractions, respectively. Incorporation of the purine showed a significantly higher sensitivity to emetine. While the percentage inhibition of valine incorporation by emetine decreased with increasing pH, the susceptibility of adenine incorporation was greater in the alkaline range.

Adenine↗

Cholesterol induced changes in glucose-6-phosphate generating enzymes, concanavalin A agglutinability and haemolytic activity of axenic Entamoeba histolytica.

Repeated passage of the 200-NIH strain of Entamoeba histolytica through cholesterol-enriched axenic growth medium induced marked increases in cholesterol, phosphoglucomutase and hexokinase levels and a less prominent rise in the protein content of amoebic cells. There was also pronounced enhancement of haemolytic activity and Concanavalin A (Con A) agglutinability of the culture, but no significant change was observed in glucose phosphate isomerase. These cholesterol-induced effects persisted to a large extent when amoebae were subsequently repassaged through normal axenic medium lacking exogenous cholesterol, but changes in cellular cholesterol and protein levels did not persist. Qualitatively similar results were obtained whether the sterol was layered as a film on the glass walls of the culture tubes or supplied as sonicated micells, but the latter was in general more effective.

Agglutination↗