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Biomedical subjects

N K Ganguly

Publications and source records attributed to N K Ganguly.

At least 19 recordsLinked to original sources

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

Decrease of myocardial infarct size with desferrioxamine: possible role of oxygen free radicals in its ameliorative effect.

The ability of an iron chelator, desferrioxamine, to inhibit the infarct size in in vivo rat heart was assessed. Anaesthetised rats were subjected to coronary artery ligation (CAL) for 72 hr and infarct size was measured macroscopically using TTC staining. Systolic blood pressure and ECG were monitored. Desferrioxamine (10 mg/kg and 20 mg/kg i.v.) administered half an hour after CAL markedly reduced the infarct size. However, drug treatment did not alter the systolic blood pressure of animals. In addition, desferrioxamine in vitro and in vivo demonstrated an inhibition of rat PMN-evoked and luminol-enhanced chemiluminescence. The capacity of desferrioxamine to impair the generation or to scavenge directly oxygen free radicals may be responsible for its beneficial effect on myocardial infarct size in rats.

Animals

Common aetiological agent for epidemic and sporadic non-A, non-B hepatitis.

Enterovirus-like particles have been reported in the acute phase of both epidemic and sporadic non-A, non-B (NANB) hepatitis. To examine whether these particles were the causative agent in the two types of disease, 29 patients with acute viral hepatitis in a north Indian epidemic outbreak and 9 with sporadic acute disease were investigated. 25 (86%) of 29 patients with epidemic hepatitis and 5 (56%) of 9 with sporadic disease were diagnosed as having enterically-transmitted-NANB hepatitis by exclusion. Virus-like particles (VLP) of 30-34 nm were detected in stool of 1 patient with epidemic and 1 with sporadic hepatitis. The VLPs crossreacted serologically and a specific IgM response was seen in acute epidemic and sporadic serum samples. After inoculation with infected stool rhesus monkeys had a mild rise in liver enzymes, and bile samples contained VLPs. These results suggest that the aetiological agent in epidemic and sporadic disease is the same.

Animals

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

Intracellular cAMP determines the extent of degradation and not the synthesis of collagen by rat hepatocytes.

Intracellular collagen degradation in normal rat hepatocytes was exponentially stimulated by db-cAMP (10-100 microM). The effect was manifested as a decrease (p less than 0.01) in net collagen production. The extent of degradation directly co-related with the intracellular cAMP levels, only up to a threshold concentration (16.2 +/- 1.3 p moles/10(6) cells) elicited by 100 microM of db-cAMP. Higher concentrations induced no further increment. Forskolin adenylate cyclase activator (10-50 microM), produced similar effects demonstrating cAMP dependence of the phenomenon. Both db-cAMP as well as Forskolin stimulated collagen degradation (p less than 0.05) in hepatocytes from rats administered CCL4. However, the extent of stimulation was significantly (p less than 0.01) less compared to that observed in normal hepatocytes. Our data demonstrates that elevated cAMP levels regulate net collagen content by signalling intracellular collagen degradation and not synthesis.

Animals

Free radicals in myocardial injury: experimental and clinical studies.

The exposure of cardiac cells to OFR generated artificially, showed a marked decrease (p less than 0.01) in cellular utilization of glucose along with a significant decrease in calcium uptake (p less than 0.05). We have also provided evidence for a direct relationship of neutrophil OFR production with the extent of myocardial ischemia in patients of myocardial infarction. Our data provides evidence for implication of OFR in myocardial injury and the pivotal role played by modulators like calcium, ECGF and prostaglandins in potentiating damage to the myocardium.

6-Ketoprostaglandin F1 alpha

Oxygen free radicals in essential hypertension.

Membrane abnormalities in essential hypertensives (EH) are well known. The respiratory burst enzyme, NADPH oxidase is located in the cell membrane of the neutrophil (PMNLs) and its activity is important in generation of oxygen derived free radical (OFR). Recently OFR have been implicated in vascular changes in variety of conditions. An attempt was made to delineate the status of OFR and antioxidants in EH. Ten, age and sex-matched, healthy controls (GpI) and 26 untreated EH (Gp IIA mild-8, Gp IIB Moderate-8, Gp IIC Severe-10) were studied. After clinical examination and basic laboratory evaluation of subjects, neutrophils isolated from their blood were studied. Chemiluminescence (CL) emitted by PMNLs after stimulation was measured (counts/min) in a luminometer and was taken as measure of OFR production and thereby of NADPH oxidase activity. The levels of antioxidants, superoxide dismutase (SOD) and reduced glutathione (GSH), were also estimated. Chemiluminescence was increased significantly (p less than 0.01) in Gp IIC (243.04 +/- 24.9 x 10(3) counts per minute) as compared to Gp IIA (2.80 +/- 1.87), Gp IIB (34.54 +/- 30.24) and Gp I (0.52 +/- 0.15) and SOD was reduced significantly (p less than 0.05) in all EH (Gp IIA 3.9 +/- 0.3 units per mg protein, Gp IIB 3.5 +/- 0.3 and Gp IIC 3.12 +/- 0.3) as compared to controls (4.1 +/- 0.2). Similarly GSH was reduced (p less than 0.05) in EH (Gp IIA 11.2 +/- 1.7 mg per gm protein, Gp IIB 8.5 +/- 1.1 and Gp IIC 6.6 +/- 0.3) as compared to Gp I (13.5 +/- 2.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

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

Immunopathogenesis of Takayasu arteritis.

Takayasu arteritis is a common cause of renovascular hypertension in India. Sensitization to infective agents, particularly mycobacterium tuberculosis or autoimmune disturbances have been incriminated in its pathogenesis. Twenty patients of Takayasu arteritis along with groups of normal individuals, patients of essential hypertension, autoimmune disorders, tuberculosis, and healthy tuberculin reactors were studied. Besides detailed immunological profiles including LE cell phenomenon, serum complement C3 levels, antibodies to single (SS) and double stranded (DS) DNA, rheumatoid factor, lymphocyte subsets, blast transformation to antigens including, phytohemagglutinin, PPD, pokeweed, and purified human aortal antigen (PHAA) were examined. Soluble protein from human aorta was fractionated into 9 peaks by DEASE-52 and Sephadex G-75 chromatography, and 25 micrograms of major protein fraction-II was used for blast transformation study. Blast transformation by PHAA was higher in Takayasu arteritis as compared to all other groups (P < 0.05). Blast transformation to PPD showed wide variation in all the groups, and was significantly higher only in tuberculin reactors as compared to controls. These observations support aortal sensitization to PHAA playing a role in pathogenesis of Takayasu arteritis and do not relate tuberculosis to Takayasu arteritis, at least immunologically. In addition, the ratio of CD-4 positive to CD-8 positive lymphocytes changing in favor of the former and the concomitant increase in B lymphocytes favor the presence of autoimmune disturbances in Takayasu arteritis.

Adolescent

Microbiological studies in mid-trimester abortion with Emcredil versus normal saline.

In 40 mid-trimester abortion seekers, in whom abortion was induced by extra-amniotic normal saline or Emcredil, microbiological studies were carried out before induction and at 24 hours. It was observed that there was no difference in the isolation of organisms from vagina and cervix of these subjects between 0 hours and 24 hours. Thus, this study shows that leaving the catheter in the extra-amniotic space until it is expelled spontaneously does not increase the risk of ascending infection. At the same time, leaving the catheter in-situ until it is expelled spontaneously reduces the induction-abortion interval appreciably.

Abortion, Induced

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

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

Frequency of D8/17 B lymphocyte alloantigen in north Indian patients with rheumatic heart disease.

Ninety patients with rheumatic heart disease and 50 age- and sex-matched healthy human volunteers representing a North Indian population were typed for the B cell alloantigen D8/17 using a monoclonal antibody and a single step immunofluorescence technique. This alloantigen was expressed in 66.44% patients with RHD as compared with 14% of the normal population. A high relative risk (RR = 11.13) indicated a strong association of D8/17 B cell alloantigen with rheumatic heart disease. Increase in the frequency of the marker was observed with increasing age up to the fifth decade (40-49 years) in these patients. However, the frequency of this alloantigen, in the present study, in North Indian patients with rheumatic heart disease is lower than that reported in the American population.

Adolescent

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

Use of hepatitis B vaccine alone or in combination with hepatitis B immunoglobulin for immunoprophylaxis of perinatal hepatitis B infection.

The efficacy of hepatitis B vaccine alone or in combination with immunoglobulin in neonates born to HBsAG positive mothers was investigated. Twenty-four infants were given three doses (at 0, 1, 2 months) of the vaccine alone, while 27 infants were given hepatitis B immunoglobulin (HBIG) and three doses of the vaccine. Fifty-eight infants born to HBsAg positive mothers who did not agree for vaccination or could not come for follow-up constituted the control group. The overall seroprotection rates (anti-HBS levels > or = 10 IU/l) were almost similar in both the groups at 6 months (81 and 76 per cent, respectively). However, the seroprotection rates in babies born to HBeAg positive mothers were better with combination of HBIG and vaccine (71 v. 57 per cent, respectively). It was also observed that seroprotection rates in babies born to anti-HBe positive mothers were even better (100 and 90 per cent in vaccine alone and combination group, respectively). No chronic carrier was detected in babies born to anti-HBe positive mothers.

Carrier State

Ca2+ transport in unstimulated platelets of essential hypertensives and their blood relatives.

OBJECTIVE: Intracellular free Ca2+ concentration has been shown to be elevated in platelets from essential hypertensive patients. This study was designed to characterize Ca2+ homeostasis in platelets of essential hypertensives. DESIGN: A double-blind study was carried out. Untreated and treated (propranolol therapy) essential hypertensives were studied in comparison with normotensive control subjects. First-degree blood relatives of essential hypertensives were also studied. The various procedures used in the study were already standardized and well-established methods. METHOD: For Ca2+ uptake and efflux studies, 45Ca was used. For intracellular free Ca2+ concentration studies the fluorescent Ca2+ chelator dye fura-2/acetoxymethyl ester (fura-2/AM) was used. RESULTS: The uptake of 45Ca by unstimulated platelets of untreated essential hypertensives and their relatives was significantly higher than for controls. However, essential hypertensives treated with a beta-blocker drug showed no significant difference in Ca2+ uptake compared with controls. A significantly decreased Ca2+ efflux was observed in essential hypertensives (both untreated and treated) compared with controls. Relatives also showed a depressed Ca2+ efflux compared with controls. CONCLUSIONS: It appears that the elevated intracellular free Ca2+ concentration levels in platelets (also observed by us) may be due to both an enhanced uptake into, and decreased efflux of Ca2+ from, the cell. Beta-blocker therapy may help to normalize the elevated intracellular free Ca2+ concentration levels observed in essential hypertensives. Relatives exhibit a state predisposed towards the development of hypertension.

Adolescent

Adherence of Streptococcus pyogenes M type 5 to pharyngeal and buccal cells of patients with rheumatic fever and rheumatic heart disease during a one-year follow-up.

In vitro adherence of Streptococcus pyogenes M type 5 to isolated pharyngeal and buccal epithelial cells was studied in patients with acute recurrent rheumatic fever (n = 21), chronic rheumatic heart disease (n = 33), streptococcal pharyngitis (n = 12), and in normal controls. Patients were investigated at admission and one, six and 12 months later. Streptococci adhered significantly more to the pharyngeal cells of patients with rheumatic fever and rheumatic heart disease than to the pharyngeal cells of controls. Adherence of streptococci to pharyngeal cells of patients with pharyngitis was not different from age-matched controls. The adherence of streptococci to the pharyngeal cells of patients with acute rheumatic fever fell during follow-up but even after one year remained significantly higher than in the control group. These findings suggest that host factor(s) controlling streptococcal adhesion and colonization at the pharyngeal mucosa may be important in the pathogenesis of acute rheumatic fever.

Acute Disease

Effect of exogenous copper on lipid peroxidation in rat hepatocytes. Possible involvement of protein kinase C.

We have investigated the direct effect of copper on malondialdehyde formation in rat isolated hepatocytes. Copper was found to decrease the cell viability with concomitant production of malondialdehyde in a time related manner. In addition the protein kinase C activator, PMA, was found to have a synergistic effect with copper on rat hepatocytes. These results indicate that protein kinase C may be important in mediating hepatotoxicity after exposure to copper.

Animals