Oxidoreductases in early gestational monkey placenta during maternal malarial infection: histochemical localisation.

BACKGROUND & OBJECTIVES: Early gestational malaria is more deleterious than late gestational infection. Still the pathophysiology of maternofoetal organ--the placenta in malaria remains almost unexplored during early gestation. Present study dealing with oxidoreductases in early gestational placenta during maternal malarial infection of Plasmodium cynomolgi bastianellii in rhesus monkeys was anticipated to provide a better insight into the functional impairment of this organ leading to foetal abnormalities. METHODS: Three control and four experimental monkeys (Macaca mulatta) were quarantined for one month prior to experimentation. Experimental monkeys at 2- 2 1/2 months of gestation were inoculated with P. cynomolgi bastianellii. On attaining first peak of parasitaemia the placentae were collected from anesthetised animals. The snap-frozen, cryostat sections were subjected to histochemical localisation for 3 (or 17) beta-hydroxysteroid dehydrogenase (beta-HSD) [3 (or 17) beta-hydroxysteroid: NAD (P+) oxidoreductase, EC 1.1.1.51 hydroxysteroid dehydrogenases] and NADPH-tetrazolium reductase [NADPH: (acceptor) oxidoreductase, EC 1.6.99.1 NADPH-TR]. Comparative microscopy of control and malaria infected placental sections was performed and analysed. RESULTS: A localised decrease in both the enzymes was observed in syncytiotrophoblast layer of malaria infected monkey placenta. The areas showing morphological damage of syncytiotrophoblast were also depicting gross reduction in NADPH-TR activity. INTERPRETATION & CONCLUSION: The altered enzymatic activities [3 (or 17) beta-HSD and NADPH-TR] in malaria infected early gestational monkey placenta have been discussed in the light of placental function. It could be concluded by present studies that these alterations would affect the cellular metabolism especially steroidogenesis and detoxification process which in turn would affect the normal development of the foetus as well as maintenance of gestation.

Immune effector mechanisms of the nitric oxide pathway in malaria: cytotoxicity versus cytoprotection

Nitric oxide (NO) is thought to be an important mediator and critical signaling molecule for malaria immunopathology; it is also a target for therapy and for vaccine. Inducible nitric oxide synthase (iNOS) is synthesized by a number of cell types under inflammatory conditions. The most relevant known triggers for its expression are endotoxins and cytokines. To date, there have been conflicting reports concerning the clinical significance of NO in malaria. Some researchers have proposed that NO contributes to the development of severe and complicated malaria, while others have argued that NO has a protective role. Infection with parasites resistant to the microbicidal action of NO may result in high levels of NO being generated, which could then damage the host, instead of controlling parasitemia. Consequently, the host-parasite interaction is a determining factor for whether the parasite is capable of stimulating NO production; the role of NO in resistance to malaria appears to be strain specific. It is known that NO and/or its related molecules are involved in malaria, but their involvement is not independent of other immune events. NO is an important, but possibly not an essential contributor to the control of acute-phase malaria infection. The protective immune responses against malaria parasite are multifactorial; however, they necessarily involve final effector molecules, including NO, iNOS and RNI.

Syndrome enzymatique du paludisme a plasmodium falciparum

Le cycle evolutif du plasmodium falciparum implique des organes riches en activites enzymatiques. Aux fins de rechercher l'incidence de ce cycle sur les activites des enzymes couramment dosees au laboratoire; une etude portant sur des sujets impaludes et des temoins a ete conduite. Les resultats obtenus indiquent que les activites lactate deshydrogenase (LDH) et hydroxybutyrate deshydrogenase (HBDH) sont significativement augmentees. Ces augmentations de LDH et de HBDH sont correlees avec la densite parasitaire et les coefficients de correlation respectifs sont r=0;32 (p inferieur a 0;05) et r=0;39 (p inferieur a 0;01). Ces augmentations apparaissent specifiques de l'infection palustre a 93 pour cent pour la LDH et a 95 pour cent pour l'HBDH. Ces resultats pourraient permettre de considerer la LDH et l'HBDH comme marqueurs de l'infection a plasmodium falciparum

Picroliv affects gamma-glutamyl cycle in liver and brain of Mastomys natalensis infected with Plasmodium berghei.

Picroliv, the standardized preparation of iridoid glycosides from Picrorhiza kurrooa, at the dose of 6 mg/kg, po for two weeks provided significant protection against depletion of reduced glutathione levels in liver and brain of Plasmodium berghei infected Mastomys natalensis. The activation of gamma-glutamyl transpeptidase enzyme and decreased levels of cysteine, sulphydryl groups as well as glutathione synthesis in both tissues due to P. berghei infection were reversed by picroliv. Enzymatic and non enzymatic lipid peroxidation in microsomes in vitro was significantly reduced by picroliv along with the recovery of reduced glutathione.

Malaria parasites: enzymes involved in red blood cell invasion

Three enzymes have been described in malaria merozoites: a serine-protease and two phospholipases. The parasite serine-protease is necessary for parasite entry into the red blood cell. This enzyme is synthesized by intraerythrocytic schizonts as a glycolipid-anchored membrane precursor, harbouring a performed serine-protease active site but not detectable proteolytic activity. Detection of the enzymatic activity correlates with the solubilisation of the enzyme by a parasite glycolipid-specific phospholipase C in merozoites. A third enzyme has been detected with glycolipid-degrading activity, presumably a lipase A. These activities participate in a biochemical cascade originating with the attachment of the merozoite to the red blood cell, including the translocation of the phospholipase C to the membrane-bound protease, the solubilisation/activation of the protease and its secretion at the erytrocyte/parasite junction and ending with the entry of the parasite into the host cell. Both the phospholipase C and the lipase A might generate secondary messages in the merozoite. Our current knowledge concerning these enzymes is presented

Prevalences of thalassemia/hemoglobinopathies and G-6-PD deficiency in malaria patients.

It seems that thalassemia and/or hemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency (G-6-PD) have some protective effects against malaria infection. To verify this, hemoglobin typing and methehoglobin reduction test were performed on 115 malaria patients and compared with controls. It was found that the number of thalassemia/hemoglobinopathies in the malaria group and in the control group were not significantly different and also occurrence of G-6-PD deficiency in the malaria group was not different from that of the controls. Clinical manifestations of malaria in any group are quite similar. It is concluded that there is no protective effect against malaria in thalassemia/hemoglobinopathies or G-6-PD deficiency.

Glicose-6-fosfato desidrogenase: aspectos clínicos / Glucose-6-phosphate dehydrogenases: clinical aspects

In this article, the authors presente a review about the behaviour of G6PD in relation to pathologies other than hemolytic anemias, which are the many diagnostic use of the enzyme

Hepatic superoxide dismutase, catalase and lipid peroxidation products in Mastomys natalensis infected with Plasmodium berghei.

P. berghei infection in M. natalensis caused a significant reduction in the hepatic SOD and catalase activities. Cu-Zn SOD was more susceptible to infection than Mn SOD. The inhibition of enzyme activities was associated with marked increase in the levels of lipid peroxides, lipid hydroperoxides and conjugated dienes in infected M. natalensis. The alterations in the hepatic SOD, catalase and lipid peroxides are related with the severity of infection.

Catalase activity in red cell and liver of mice infected with Plasmodium berghei.

Hydrogen peroxide (H2O2) has been incriminated to have an oxidative killing malaria parasite. As P. berghei-infected mouse red cells generated H2O2 in vivo, this would result in the alteration of catalase status of the host. The present study was undertaken to determine catalase activity in red cells and liver of mice infected with P. berghei. The studies were performed in 17 samples of infected red cells as well as 20 samples of the normal red cells. Results showed that the catalase activity in red cells of the infected group was significantly lower (p less than 0.01) than that of the normal group. There was a reverse relationship between catalase activity and parasitemia. Crude parasite lysates possessed no catalase activity. Liver catalase content in the infected group was also found to be significantly lower (p less than 0.05) than that of the control group. All these findings indicated that P. berghei-infected mice caused a depressed catalase activity in red cells and liver which was possibly due to the catalatic function in detoxifying the increased H2O2 to water and free oxygen.

Acetylcholinesterase activities in cerebrospinal fluid of patients with Plasmodium falciparum cerebral malaria.

Serum cholinesterase (CHE) and acetylcholinesterase (ACHE) in cerebrospinal fluid (CSF) were determined simultaneously in 30 patients with P. falciparum cerebral malaria. Nineteen patients (63%) had low serum CHE and mean value of this serum enzyme in 30 patients was significantly lower than that of non-infected group. CSF ACHE levels were found to be significantly lower than those of normal subjects reported earlier. Post-treatment in the hospital for one week, both serum CHE and CSF ACHE levels in 9 convalescent subjects increased significantly. These findings indicated that both serum CHE and CSF ACHE levels were depressed in patients with cerebral malaria and increased on recovery.

Red cell acetylcholinesterase activity in Plasmodium falciparum malaria.

Red cell ACHE activity was determined in 19 patients with P. falciparum malaria, 13 patients during convalescence as well as in 6 normal subjects. There was no significant difference between the mean values of ACHE in red cells of these 3 groups. After separation these blood samples into 2 portions by centrifugation in 5% Ficoll solution, the parasitized red cells in the lower portion which are mostly ring forms contained the same amount of ACHE activity as those of the normal subjects and the non-parasitized red cells. However, the parasitized red cells in the upper portion which contained predominantly mature asexual forms revealed a significantly higher ACHE activity than those of the normal red cells. There was also a reverse relationship between red cell ACHE activity and the parasitaemia from this portion of blood sample. These findings indicated that although malarial parasite invaded and caused the red cell membrane damage, it did not inactivate ACHE. It may be concluded that ACHE was not responsible for the anaemia and excessive erythrocyte destruction in patients with P. falciparum malaria.