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Biomedical subjects

S Ghatak

Publications and source records attributed to S Ghatak.

At least 37 records · Page 2Linked to original sources

Effect of thiabendazole & mebendazole on in vitro metabolism of Nippostrongylus brasiliensis adults.

Mebendazole and thiabendazole were found to inhibit glucose uptake and its metabolism in the adult rat hookworm (N. brasiliensis) in vitro. Rates of endogenous glycogen utilisation, and excretion of one of the end products of glycolysis viz., lactic acid, were found to be increased, when the intact N. brasiliensis adults were incubated for 60 min with mebendazole and thiabendazole, respectively.

Animals↗

Polyamine metabolism in Setaria cervi, the bovine filarial worm.

Spermine and spermidine were found to be the principal polyamines in the bovine filarial parasite Setaria cervi, whereas putrescine was observed in very low amounts. Studies conducted on the enzymes of polyamine biosynthesis revealed low activity for S-adenosyl-methionine decarboxylase, questionable and negligible activities for the decarboxylation of ornithine and arginine, and appreciable activity for ornithine aminotransferase. Uptake studies with radiolabeled putrescine, spermidine and spermine showed that these amines are rapidly taken up from the medium by an active uptake process. The uptake was temperature-sensitive and abolished at 0-4 degrees C. The questionable presence of biosynthetic enzymes such as ornithine and arginine decarboxylase and, on the other hand, an effective uptake mechanism indicate that the parasite may depend on the host for its polyamine requirement, thereby indicating a possible target for chemotherapy.

Adenosylmethionine Decarboxylase↗

Polyamine metabolism in Ancylostoma ceylanicum and Nippostrongylus brasiliensis.

Spermidine was detected as the major polyamine of Ancylostoma ceylanicum as well as Nippostrongylus brasiliensis. Spermine was present in lower amounts whereas the level of putrescine was even less. S-Adenosylmethionine decarboxylase, a rate-limiting enzyme in the biosynthetic pathway of polyamines, was demonstrated at low levels in both parasites. Decarboxylation of lysine and arginine was absent or negligible and that of ornithine questionable, as the enzyme activity was not inhibited by alpha-difluoromethylornithine while RMI 71,645, an irreversible inhibitor of ornithine aminotransferase, strongly inhibited the liberation of CO2 from ornithine. High activity of ornithine aminotransferase was observed in both the parasites and may interfere with the assay for ornithine decarboxylase. Adults of A. ceylanicum were found to rapidly take up spermidine and spermine from incubation medium while uptake of putrescine was very low. These results indicate that hookworms depend on uptake and interconversion rather than de novo synthesis for their polyamine requirement.

Ancylostoma↗

Brugia malayi: status of host during different stages of infection.

The status of glycogen, protein, lipid components, lipid peroxides and a few enzymes of energy metabolism was studied in liver of Mastomys natalensis during the development of Brugia malayi infection. Glycogen and lipid contents were decreased during the patent phase of infection while total protein was slightly altered in latent animals. Phospholipid and triglyceride contents declined at prepatent and patent phase of infection. The levels of lactate and malate dehydrogenases, as well as of adenosine triphosphatases (Na+K+, Mg2+, Ca2+), were significantly elevated and monoamine oxidase activity was decreased at patent phase of infection, while succinic dehydrogenase remained unaltered. The lipid peroxide formation was enhanced in liver during the development of filarial infection.

Adenosine Triphosphatases↗

Comparative analysis of surface components of adult, micro-filariae and infective larvae of Brugia malayi.

A comparative analysis of surface proteins of adult, microfilariae and infective larvae of Brugia malayi, the human filarial parasite, has been carried out using IODOGEN (1,3,4,6-tetrachloro-3,alpha 6 alpha-diphenyl-glycoluril) and lactoperoxidase methods. SDS-polyacrylamide gel electrophoretic and autoradiographic analyses revealed the presence of 9 proteins (15-200 kDa) in adults, while microfilariae and infective larvae showed 8 and 6 proteins (15-120 kDa), respectively. The pattern of proteins radiolabelled by IODOGEN method was very similar to that of proteins labelled by the lactoperoxidase method. Since these proteins are released by the protease treatment of whole parasites, they are likely to be present on the surface of the parasite.

Animals↗

Biochemical and histopathological alterations in golden hamster during infection with Ancylostoma ceylanicum.

Ancylostoma ceylanicum infection in golden hamsters (Mesocricetus auratus) caused marked biochemical and histopathological derangements. Jejunum, the primary site of infection, showed pronounced alterations compared with liver. Though the biochemical composition of jejunum was not significantly altered, activities of a few lysosomal enzymes were enhanced during hookworm infection. Marked damage to mitochondrial and microsomal membranes was reflected in changes in the activities of the marker enzymes from jejunal tissue. Lipid content, especially phospholipids and neutral lipids of hepatic tissue, exhibited marked elevation. Levels of hexokinase, phosphofructokinase, and lactate dehydrogenase were enhanced in jejunal as well as hepatic tissues, indicating activation of the glycolytic machinery during hookworm infection. A decrease in the levels of mucosal disaccharidases indicated damage to intestinal brush border membranes. However, alkaline phosphatase activity was increased in intestinal mucosa during the infection. Light microscopic examination of jejunal tissue revealed peeling off of the upper epithelial layer, activation of the goblet cells, and thickening of muscularis mucosa. However, hepatic tissue did not show gross alterations, except for slight necrosis in the centrilobular region.

Ancylostomiasis↗

Altered drug metabolism in parasitic diseases.

While the immune system represents the main line of host defence against parasite infections, mixed function oxidase (MFO) systems (Box 1) offer the main line of defence against drugs and other biologically active substances. But, as this review shows, many parasites can exert a profound effect on the host MFO system by altering the microsomal drug-metabolizing enzymes and electron transport carriers such as cytochrome P-450. This can markedly affect the host's ability to metabolize biologically active compounds, often with adverse physiological, pharmacological and toxicological consequences. In mammals, drug metabolism occurs predominantly in the liver, and to a lesser extent in the spleen, lungs, kidneys, intestine and cerebral tissues. Thus those parasites that occupy sites in these tissues - such as amoebae, Fasciola, schistosomes and malaria - tend to be those with greatest effects on the host's ability to metabolize drugs. The effects can modify the host response to substances unrelated to the infection, and to drugs which may be administered under a chemotherapeutic regime.

Journal Article↗

Ancylostoma ceylanicum: I. Protein and antigenic composition of adult and larval stages.

The protein and antigenic composition of adult and larval stages of Ancylostoma ceylanicum, a human hookworm maintained in golden hamsters (Mesocricetus auratus), was studied employing immunochemical techniques. SDS-polyacrylamide gel electrophoresis revealed the presence of 47 and 43 protein bands in adult worms and infective larvae respectively in the molecular weight range of 10-170 kD. Crossed immunoelectrophoretic analysis, using immune rabbit sera, showed the presence of 32 antigenic peaks in adults and 19 in infective larval stage. Most of the antigens were common between adult and larval stage as evidenced by cross-line immunoelectrophoresis, although some stage specific antigens were also identified. These studies also demonstrate the complex nature of adult worms as compared to larvae.

Ancylostoma↗

Suppression of release of microfilariae in vitro from Setaria cervi (Nematoda: Filariodeae) by chlorpromazine.

Chlorpromazine (CPZ) caused suppression in release of microfilariae in vitro from Setaria cervi at 10(-5) M concentration. The inhibitory effect of CPZ was further stimulated by Ca2+ (2 mM), whereas addition of EGTA (2 mM) resulted in partial reversal. Addition of dopamine (1 mM) along with CPZ (10(-5) M) caused similar inhibition as was observed in the presence of CPZ (10(-5) M) alone. CPZ did not effect in vitro oxygen uptake by worm homogenates up to 0.5 mM concentration. The results indicate the Ca2+/calmodulin-dependent anthelmintic action of CPZ on S. cervi.

Animals↗

Effect of Plasmodium yoelii nigeriensis infection and chloroquine on the hepatic mixed function oxidase system of mice.

Plasmodium yoelii nigeriensis infection in albino mice significantly altered the hepatic microsomal mixed function oxidase system. Cytochrome P-450 (the terminal monooxygenase) and other monooxygenases, viz. aniline hydroxylase, aminopyrine-N-demethylase and benzo(a)pyrene hydroxylase were significantly lowered while microsomal heme showed 4-fold increase at 80% parasitaemia. Noticeable impairment in the other components like NADH:cytochrome b5 reductase, NADPH:cytochrome c reductase, cytochrome b5 and glucose-6-phosphatase was also observed. Oral treatment of normal and P. y. nigeriensis infected mice with chloroquine (64 mg per kg body weight for 4 days) caused lowering of mixed function oxidase activities which however showed a recovering trend, a week after cessation of treatment.

Animals↗

T-cell-receptor beta- and I-A beta-chain genes of normal SWR mice are linked with the development of lupus nephritis in NZB x SWR crosses.

The incidence of nephritis in autoimmune New Zealand Black (NZB) mice is low, but when they are crossed with normal SWR mice, almost 100% of the female F1 hybrids (SNF1) develop lethal glomerulonephritis. To define the contribution of the normal SWR strain to the development of nephritis, we analyzed the association of the I-A beta-chain gene of Ia-encoding region, the T-cell-receptor beta (TcR beta)-chain gene, and immunoglobulin heavy-chain allotype (IgH) with the development of lupus nephritis in 165 NZB X SWR crosses. We found that genes linked to the TcR and Ir gene loci of the normal SWR mice interacted with NZB-derived genes, leading to the development of accelerated and severe nephritis in the NZB X SWR crosses.

Animals↗

Identification of antigenic proteins of setaria cervi by immunoblotting technique.

Identification and characterization of antigenic proteins of Setaria cervi (bovine filarial parasite) adults and microfilariae was done by immunoblotting technique using hyperimmune rabbit sera against S. cervi and Brugia malayi. The antigens recognized by these sera were detected by using 125I protein-A followed by autoradiography. Fifteen different antigens were observed to be common between adult and microfilarial stages of the parasite. Some stage specific antigens were also identified. Many antigens of S. cervi adults and microfilariae were also recognized by rabbit anti-B.malayi serum showing the existence of common antigenic determinants between the bovine and human filarial parasites.

Animals↗