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Biomedical subjects

R C Mahajan

Publications and source records attributed to R C Mahajan.

At least 19 recordsLinked to original sources
PubMed1995

Plasmodium falciparum: role of activated blood monocytes in erythrocyte membrane damage and red cell loss during malaria.

The role of Plasmodium falciparum and blood monocytes in the erythrocyte damage and pathogenesis of anemia has been investigated using two strains of the parasite; one laboratory-established strain (FSJ-M) and one wild, fresh, clinical isolate (PfPGI). Peripheral blood monocyte-induced growth inhibition of the parasites, erythrocyte membrane lipid peroxidation as seen by the formation of lipid peroxide products, and sensitivity to peroxide hemolysis at atmospheric oxygen were evaluated. The growth inhibition of FSJ-M by activated blood monocytes was greater than that of PfPGI. The extent of lipid peroxidation and sensitivity to hemolysis increased significantly as the parasites matured. These adverse effects were more marked following exposure to activated monocytes, especially in synchronized, parasitized RBCs. In addition, uninfected erythrocytes within the PfPGI parasite culture revealed a significant increase in the lipid peroxide formation (P < 0.01) and susceptibility to lysis (P < 0.05) under similar oxidant stress induced by monocytes from normal healthy donors. Furthermore, there was a direct correlation between membrane lipid peroxidation and peroxide hemolysis, both before and after monocyte exposure, suggesting a primary role of membrane peroxidation in red cell lysis. The contribution of intraerythrocytic parasites and nonspecific activation of blood monocytes in the pathophysiology of erythrocyte damage and anemia of P. falciparum infection is discussed.

Adult↗
PubMed1994

Involvement of intracellular calcium stores in Giardia lamblia induced diarrhoea in mice.

The transmucosal fluxes of Na+ and Cl- were studied in Giardia lamblia-infected mice in the presence or absence of dantrolene (1-(5(p-nitrophenyl)furfurilidene-amino) hydantoin sodium hydrate). There was net secretion of Na+ and Cl- in infected animals, while in control animals there was net absorption of these ions. The addition of dantrolene resulted in significant net increase in absorption of Na+ and Cl- in control and experimental groups. Further, mouse intestinal epithelial cells were labelled with [32P]Pi and then treated with G. lamblia trophozoites and their excretory secretory products separately. The optimum time for inositol triphosphate formation was 15 min in control enterocytes as well as in treated enterocytes. A plateau was formed at higher concentrations. Since raised inositol triphosphate levels mobilize Ca2+ from intracellular stores and dantrolene traps Ca2+ within intracellular calcium stores, the present study thus suggests that intracellular calcium stores are involved in G. lamblia-induced diarrhoea in mice.

Animals↗
PubMed1994

Plasmodium falciparum and blood monocyte induced abnormalities in human erythrocyte cation homeostasis.

The role of Plasmodium falciparum and activated blood monocytes in bringing about erythrocyte membrane lipid peroxidation and in altering the enzyme activity associated with Ca2+ and K+ efflux was studied. An attempt was made to investigate the role of parasite and monocyte-mediated reactive oxygen species (ROS) in inhibiting Ca(2+)-Mg2+ ATPase and Na(+)-K+ ATPase in order to find out the cause of reported high intra-erythrocytic calcium and depleted potassium levels in parasitized erythrocytes (PRBC). The PRBC showed enhanced lipid peroxidation as indicated by increased malonyldialdehyde (MDA) formation which coincided with the maturity of the parasite. This was further enhanced following exposure of PRBC to activated blood monocytes. The Ca(2+)-Mg2+ ATPase activity was decreased as the parasite matured and was further hampered significantly in mature parasite-infected red cells exposed to activated blood monocytes. There was a good negative correlation between MDA formation and Ca(2+)-efflux from red blood cells suggesting the negative influence of ROS on Ca(2+)-efflux. The Na(+)-K+ ATPase activity did not reveal any significant change, both during parasite maturation as well as upon exposure to ROS from activated monocytes. We therefore suggest that inhibition of Ca(2+)-efflux and the resulting increased cytosolic Ca2+ in PRBC might have a role in structural and functional abnormalities of red blood cell, thus enhancing the red cell loss during P. falciparum infection.

Animals↗
PubMed1994

Increased glutathione cycling and vitamin E of P. falciparum infected erythrocytes fail to prevent spontaneous haemolysis.

In an attempt to understand the pathogenesis of anaemia in Plasmodium falciparum infection, the status of erythrocyte glutathione and vitamin E content in relation to the susceptibility of infected red cells to peroxide haemolysis was examined. Synchronized cultures of the parasite with either ring-, trophozoite or schizont-infected red cells showed a gradual increase in the reduced glutathione content which was significantly higher (p < 0.05) in schizont-infected cells. Trophozoite-infected cells revealed significant increase in oxidized glutathione (p < 0.01) suggesting an increase in glutathione utilization during active erythrocytic schizogony of the parasites. The membrane antioxidant vitamin E also showed an increased accumulation in trophozoite- and schizont-infected red cells (p < 0.05) but not in the uninfected or ring-infected erythrocytes. Despite a favourable change in these antioxidants, the infected as well as uninfected red cells from parasite cultures showed enhanced peroxide haemolysis (uninfected, p < 0.05; ring-rich, p < 0.05, trophozoite- and schizont-rich, p < 0.001). The study provided direct evidence for enhanced susceptibility of red cells to lysis, including those of uninfected cells exposed to parasite products. This might explain the cause for much higher red cell loss and anaemia during P. falciparum infection than all the infected cells put together.

Animals↗
PubMed1993

Leishmania donovani: in vitro evidence of hepatocyte damage by Kupffer cells and immigrant macrophages in a murine model.

Infection with Leishmania donovani leads to activation of liver macrophages. The role of different macrophage populations of liver in this infection is not clearly defined. Thus, the mechanism involved in hepatocyte damage was studied by coculturing hepatocytes with two populations of liver macrophages, the kupffer cells and immigrant macrophages. The results indicated maximum tissue damage at peak infection in both the macrophage populations cocultured with hepatocytes (P < 0.001). Kupffer cell-hepatocyte coculture treated with scavengers of reactive oxygen intermediates failed to inhibit the hepatocyte damage (P > 0.05). But with heparin and phenylmethylsulfonyl fluoride, a sharp decrease in the damage was noticed (P < 0.001). In contrast, immigrant macrophage-hepatocyte coculture showed a significant reduction in tissue damage when treated with both the scavengers of reactive oxygen intermediates and enzyme inhibitors (P < 0.001). Therefore the murine infection with L. donovani is speculated to involve two distinct subpopulations of liver macrophages with marked differences in morphology and functional capabilities.

Animals↗
PubMed1993

Effect of nifedipine on calcium status and chemiluminescence response of phagocytes during Plasmodium berghei infection in mice.

The macrophages and neutrophils from nifedipine-treated mice, both Plasmodium berghei-infected and uninfected, showed suppressed capacity to generate oxygen free radicals as compared with untreated controls. Nifedipine treatment did not affect resting state free calcium levels in these cells. But the rise in intracellular calcium levels of macrophages and neutrophils following P. berghei infection was significantly less (P < 0.05) in nifedipine-treated mice as compared with untreated groups at various parasitaemia levels. Probably this reflects a more potent effect of nifedipine on these cells in the depolarized state. Similarly, the rise in intracellular calcium levels of these cells following formyl-Met-Leu-Phe (fMLP) stimulation was also significantly less in nifedipine-treated groups than in untreated controls at different parasitaemia levels. A positive correlation between this fMLP-stimulated rise in calcium levels and the chemiluminescence response of macrophages and neutrophils was observed in nifedipine-treated and untreated groups at various parasitaemia levels. Thus the respiratory-burst responses of these cells during P. berghei infection depend on the calcium homeostasis in the cells. The disturbances of the calcium-regulating mechanisms by nifedipine treatment resulted in subnormal phagocytic cell responses which lead to more severe and rapidly fatal P. berghei infection in these animals.

Amino Acid Sequence↗
PubMed1993

Macrophage-mediated enterocyte damage in BALB/c mice infected with different strains of Giardia lamblia.

The mechanism of mucosal injury in Giardia lamblia-infected animals and humans is not well understood, although the role of gut macrophages in killing the trophozoites is well known. It is speculated, however, that macrophage products have a role in tissue injury and inflammatory response during infection, as in other inflammatory diseases. Therefore, in the present study an attempt was made to examine the mechanism involved in enterocyte damage during giardiasis. This was achieved using co-culture of enterocytes and gut macrophages obtained from infected BALB/c mice. The extent of tissue damage was assessed by measuring the marker enzyme of enterocyte damage, lactate dehydrogenase. To investigate the role of the various proteases and free oxygen radicals released by activated macrophages on enterocyte damage, inhibitors of various proteases and free oxygen radicals were used. Superoxide radical and certain proteases were found to have important roles in bringing about enterocyte damage during this infection in mice. Parasite load, lactate dehydrogenase release, and extent of lipid peroxidation were more pronounced in mice infected with symptomatic strains than in asymptomatic ones. The theory of inflammatory cell-mediated enterocyte damage in Giardia lamblia infection is proposed.

Animals↗
PubMed1993

Changes in glycosylation of microvillus membranes in Giardia lamblia infected mice intestine.

Giardia lamblia infection has been shown to modify the glycosylation process of microvillus membranes in mice intestine. Sialic acid content of the membranes was enhanced 3-fold but there was no change in fucose content of infected animals compared to the controls. The binding of 125I-wheat germ agglutinin was augmented and that of Ulex Europeus agglutinin was unaltered to infected membranes. The binding of 125I-peanut agglutinin to brush borders was however, significantly reduced in Giardia infected mice. Kinetic analysis revealed that the observed binding of peanut agglutinin to the membrane was associated with reduced number of the lectin reactive sites (control = 649 and infected 380 nmole/protein) with no change in the affinity constant (Ka = 95.7 nmole/ml) in Giardia infected mice intestine.

Animals↗
PubMed1993

Altered course of Plasmodium berghei infection by nifedipine treatment.

The effect of nifedipine (a calcium channel blocker) on the course of P. berghei infection was examined. It was observed that mice receiving a daily dose of 0.015 mg/kg of nifedipine had significantly shorter prepatent, patent and survival periods as compared to untreated P. berghei-infected animals (p < 0.001). This shows that the calcium channel blockers, in addition to possessing the property of reversing drug resistance during combined therapy with chloroquine, may also alter the pathophysiology of malaria infection. The decreased resistance of the host to the invading parasite suggests that the effect of CCB on the host-parasite interaction in human malaria needs to be investigated further before CCB can be used in combination with chloroquine for the treatment of chloroquine-resistant malaria or for chemoprophylaxis.

Animals↗
PubMed1993

Generation of reactive oxygen species by blood monocytes during acute Plasmodium knowlesi infection in rhesus monkeys.

The status and kinetics of monocyte activation during acute P. knowlesi infection was investigated by latex-induced, luminol-dependent chemiluminescence (CL) response. The contribution of various reactive oxygen species (ROS) to CL response was estimated before infection and at peak parasitaemia (day 7 post infection) by using scavengers of ROS (benzoate, catalase and superoxide dismutase). The chemiluminescence index (CLI) was not found to be significantly different from controls on day 2 postinfection, but was significantly higher on days 5 and 7 postinfection. Hydroxyl radical (OH.) production was considerably elevated, whereas superoxide anion (O2-.) and hydrogen peroxide (H2O2) production dropped following infection. These changes in generation of ROS are discussed in relation to the progression of parasitaemia to high levels, immunopathology and immunosuppression during acute P. knowlesi infection.

Animals↗
PubMed1992

Plasmodium falciparum induced perturbations of the erythrocyte antioxidant system.

Erythrocyte antioxidants catalase, superoxide dismutase, reduced glutathione and glutathione peroxidase were studied in cells harbouring different growth stages of Plasmodium falciparum. Catalase and superoxide dismutase showed significant decrease during parasite maturation indicating hampered metabolism of hydrogen peroxide and superoxide anions. Glutathione peroxidase also exhibited a downward trend during the growth of P. falciparum, while there was a moderate accumulation of reduced glutathione. These findings suggest decreased utilization of the reduction potential in detoxification of reactive oxygen species. The fall in all three antioxidant enzymes studied was highly significant (P less than 0.001) in erythrocytes with mature stages of the parasite (trophozoites, schizonts). The increased vulnerability of erythrocytes to damage, which parallels the growth phases of the parasite emphasizes the need for early treatment of P. falciparum malaria to minimise red cell destruction and the resulting anaemia.

Animals↗
PubMed1992

Study on the mechanism of Giardia lamblia induced diarrhoea in mice.

The transmucosal fluxes of Na+ and Cl- were studied in Giardia lamblia infected mice in the presence or absence of phorbol-12-myristate-13-acetate (PMA), the activator of protein kinase C (PKC) or 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H-7), the inhibitor of PKC or Ca(2+)-calmodulin. There was net secretion of Na+ and Cl- in infected animals, while in control animals there was net absorption of these ions. The addition of ionophore or PMA resulted in net secretion of Na+ and Cl- in the control group while in the infected group there was no change in the fluxes of these ions. The selective potent inhibitor of protein kinase C, H-7, reversed the secretion of Na+ and Cl- in infected group to absorption. The addition of PMA and Ca(2+)-ionophore together in the infected group had a partial additive effect. This study suggests that G. lamblia induced fluid secretion involves protein kinase C and further protein kinase C acts in synergism with calcium.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Oxidative damage of erythrocytes infected with Plasmodium falciparum. An in vitro study.

The extent of reduced glutathione, activity of glutathione peroxidase, amount of membrane lipid peroxidation products, and the extent of hemoglobin release from host erythrocytes during in vitro Plasmodium falciparum growth was studied. Highly synchronized parasite cultures were studied to examine the alterations caused by different growth stages of the parasite. There was a moderate increase in the reduced glutathione content as the parasite matured, which was significant only in schizont-rich erythrocyte lysates (p < 0.05) whereas the activity of glutathione peroxidase was significantly low in all the parasitized red blood cells (ring-infected RBC, p < 0.005; trophozoite- and schizont-infected RBC, p < 0.001). The lipid peroxidation product, malonyldialdehyde, of the host red cells increased gradually to more than fourfold in schizont-rich cells as compared with normal erythrocytes (p < 0.001). The hemoglobin release from cultured cells was significantly higher in all parasitized red cell cultures as well as in uninfected cells kept in in vitro, as compared with normal erythrocytes. The consequence of such changes induced by the malarial parasites in the host red cells in the pathogenesis of erythrocyte destruction and anemia of P. falciparum malaria is discussed.

Erythrocytes↗
PubMed1992

Effect of nifedipine treatment on oxidative metabolism of peritoneal macrophages and neutrophils of Plasmodium berghei-infected mice.

The oxidative metabolism of peritoneal macrophages (PM) and neutrophils from nifedipine (calcium channel blocker)-treated, Plasmodium berghei (NK 65)-infected and normal infected Swiss Albino mice was studied. A significant fall in oxidative metabolism as evidenced by decreased chemiluminescence (CL) response (P less than 0.001) was recorded both in PM and neutrophils from nifedipine-treated mice compared to the control animals. When the oxidative metabolism of these phagocytes was studied after infection of the host, higher CL response was recorded from both PM and neutrophils isolated during the early course of infection (0-1 and 5-10% parasitaemia) when compared to uninfected mice (P less than 0.001). A similar pattern was observed in the case of nifedipine-treated and infected mice even though the CL response was much lower. The increasing parasite load not only resulted in subnormal CL response but also prolonged the time required for the phagocytes to exhibit peak oxidative activity both in normal infected and CCB-treated infected mice, but the time taken to show peak CL response was shortened following drug administration compared to controls. These observations revealed the profound in vivo effect of CCB on the functioning of phagocytic leucocytes and thereby questions the use of CCB in combination with chloroquine for reversal of drug resistance.

Animals↗
PubMed1992

An experimental model of ameboma in guinea pig.

Among the wide variety of clinicopathological manifestations of intestinal amebiasis, amebomas occur rarely and their pathogenesis is not well understood. When cholesterol-fed, 2- to 4-week-old guinea pigs were infected intracecally with a virulent, monoaxenic strain of Entamoeba histolytica, gross and histologically characteristic amebomas developed in 85% of the animals by the 3rd day, in 94% by the 9th day, and in 96% by the 12th day postinfection, by which time most of them had died. Amebomas were confirmed by histopathology. Thus, a model of consistent production of amebomas was documented.

Animals↗
PubMed1992

Effect of sodium stibogluconate and pentamidine on in vitro multiplication of Leishmania donovani in peritoneal macrophages from infected and drug-treated BALB/c mice.

The in vitro antileishmanial activity of sodium stibogluconate (SSG) and pentamidine in peritoneal macrophages from three different groups of animals (i.e. normal, Leishmania donovani-infected and drug-treated BALB/c mice) is reported. Peritoneal macrophages were extracted from all these animals and infected in vitro with L. donovani promastigotes. After 24 h, the infected macrophages (with amastigotes) were exposed to various concentrations of SSG (10-90 micrograms/mL) and pentamidine (0.1-5.0 micrograms/mL). The in vitro infection could be cured readily with 80 micrograms/mL of SSG and 4 micrograms/mL of pentamidine in macrophages from normal animals. But even higher dosages of these drugs added in vitro could not reduce the amastigote loads in macrophages from infected animals. In contrast, incubation in vitro of infected macrophages with very low dosages of these drugs (40 micrograms/mL of SSG and 1.0 mu/mL of pentamidine) could eliminate the parasites present within macrophages obtained from drug-treated animals. This was probably because the macrophages from drug-treated animals tackled the parasites themselves by their microbicidal mechanisms and the in vitro infection was tackled by the drug in vitro. This implies that a well-developed specific immunity in leishmaniasis helps in the antileishmanial activity of these drugs.

Animals↗
PubMed1992

Response of mast cells against filarial antigens from experimentally infected Mastomys natelensis with Brugia malayi.

The role of antigens of Brugia malayi adult worms in induction of histamine release from mast cells was studied. Both peritoneal and lung mast cells were passively sensitized using immune serum collected from Mastomys natelensis on different days after infection with B. malayi. A significant release of histamine both with crude worm and 60-kD antigens was shown. However, the role of the 43-kD antigen in histamine release was comparable to that of control. When the sera were heat inactivated, the histamine release was minimal, thus indicating the heat-labile nature of the antibodies. Furthermore, the responses of peritoneal and lung mast cells to filarial antigens were similar.

Animals↗