Hypercholesterolemia-induced oxidative stress in heart and its prevention by vitamin E

Oxygen-free radicals have been implicated in hypercholesteolemic atherosclerosis. It is possible that hypercholesterolemia produces oxidative stress in myocardium. We therefore investigated the effects of a high cholesterol diet in the absence or presence of vitamin E on serum cholesterol and lipid peroxidation product malondialdehyde (MDA), chemiluminescence (M-CL), a measure of antioxidant reserve, and activity of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-P_x)] in cardiac muscles of rabbits. Rabbits were divided into four groups: Group I, regular rabbit chow diet; Group II, same as Group I + vitamin E; Group III, high cholesterol diet; Group IV, high cholesterol + vitamin E. The heart was removed under anesthesia at the end of 4 months on their respective diets for various biochemical measurements. Serum cholesterol in Groups III and IV increased to a similar extent. There was an increase in the levels of MDA, M-CL, GSH-P_x activity and a decrease in SOD activity in hypercholesterolemic rabbits in the absence of vitamin E. Vitamin E prevented the hypercholesterolemia-induced changes in cardiac MDA, M-CL, and GSH-P_x. These results suggest that hypercholesterolemia produces oxidative stress in the myocardium which may be due to a decrease in the antioxidant reserve, and that vitamin E is effective in preventing hypercholesterolemia-induced oxidative stress on the myocardium.     

Effects of platelet-activating factor on cardiovascular function,oxygen free radical status,and blood chemistry

Platelet-activating factor (PAF) is released in numerous clinical situations. PAF primes or directly activates polymorphonuclear (PMN) leukocytes, which results in release of oxyradicals (O ₂ ^– , H₂O₂, .OH) and hypochlorous acid (HOCl). The authors investigated the effects of PAF (1 µg/kg IV) in the absence and in the presence of antioxidants (superoxide dismutase [SOD], catalase [CAT], dimethylthiourea [DMTU]) and methionine, a quencher of HOCl, on cardiac function and contractility; blood lactate, gases, and pH levels; serum creatine kinase activity (CK); chemiluminescent activity of PMN leukocytes; and cardiac tissue malondialdehyde (MDA) in anesthetized dogs. Hemodynamic measurements and collection of blood samples for various biochemical measurements were made before and at various intervals up to two hours after PAF administration in the presence and absence of various antioxidants.PAF produced a decrease in indices of cardiac function and contractility and an increase in systemic and pulmonary vascular resistance. There were decreases in the blood pH and PMN leukocyte chemiluminescence and increases in blood lactate, serum CK activity, and tissue MDA content. SOD plus catalase or DMTU plus methionine reduced the effects of PAF on cardiac function and contractility, blood lactate and pH, serum CK, and cardiac tissue MDA. The antioxidants only partially antagonized the deleterious effects of PAF. The combination of SOD + CAT was superior to that of DMTU + methionine in reducing the deleterious effects of PAF.These results suggest that PAF-induced depression of cardiac function and contractility, and the increase in systemic and pulmonary vascular resistance, may be partly mediated by the release of oxyradicals and HOCl from PMN leukocytes. Antioxidants may be beneficial in reducing the deleterious effects of PAF on the cardiovascular system.     

The Plasmodium falciparum cysteine protease falcipain-2 captures its substrate, hemoglobin, via a unique motif

Falcipain-2 (FP2) is a papain family cysteine protease and important hemoglobinase of erythrocytic Plasmodium falciparum parasites. Inhibitors of FP2 block hemoglobin hydrolysis and parasite development, suggesting that this enzyme is a promising target for antimalarial chemotherapy. FP2 and related plasmodial cysteine proteases have an unusual 14-aa motif near the C terminus of the catalytic domain. Recent solution of the structure of FP2 showed this motif to form a beta-hairpin that is distant from the enzyme active site and protrudes out from the protein. To evaluate the function of this motif, we compared the activity of the wild-type enzyme with that of a mutant lacking 10 aa of the motif (Delta10FP2). Delta10FP2 had nearly identical activity to that of the wild-type enzyme against peptide substrates and the protein substrates casein and gelatin. However, Delta10FP2 demonstrated negligible activity against hemoglobin or globin. FP2 that was inhibited with trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane (FP2E-64) formed a complex with hemoglobin, but Delta10FP2E-64 did not, indicating that the motif mediates binding to hemoglobin independent of the active site. A peptide encoding the motif blocked hemoglobin hydrolysis, but not the hydrolysis of casein. Kinetics for the inhibition of Delta10FP2 were very similar to those for FP2 with peptidyl and protein inhibitors, but Delta10FP2 was poorly inhibited by the inhibitory prodomain of FP2. Our results indicate that FP2 utilizes an unusual motif for two specific functions, interaction with hemoglobin, its natural substrate, and interaction with the prodomain, its natural inhibitor.     

Establishing Cranio-Dental Keys for Human and Non-Human Primates: Implication in Forensic Investigations

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Establishing species identity in wildlife forensics and anthropology is pre-requisite fo prosecution of the...     

Iron status of children aged 9-36 months in an urban slum Integrated Child Development Services project in Delhi

OBJECTIVE: To assess the magnitude/severity and possible etiology of anemia and iron deficiency among children 9-36 months of age. METHODS: A population-based study on the prevalence, etiology of anemia and iron status in 545 children, 9-36 months of age, was conducted in an urban slum ICDS (Integrated Child Development Services) project in North-East Delhi. Hemoglobin and serum ferritin was estimated and information on socio-economic, demographic, parasitic infection/infestation and dietary intake was collected. RESULTS: Prevalence of anemia (using WHO cut-off values of Hb >11.0 g/dl) among children, 9-36 months of age, was 64%, of these 7.8% had severe anemia (Hb >7.0 g/dl). Using 10.0 g/dl as the Hb cut-off point 44% children less than 18 months of age in the present study population were anemic. On a sub-sample study, 88% children were estimated to be iron deficient, with serum ferritin concentration less than 12 microg/L. The peripheral smear red cell morphology showed 33.9% as microcytic-hypochromic and 37.1% as dimorphic. Dimorphic anemia was 55% in moderate anemia group. The energy and iron intakes were 56% and 45%, respectively of the Recommended Dietary Allowances (RDA). The parasitic infestation/infection was not related to the prevalence or severity of anemia. CONCLUSION: In Delhi, high prevalence of moderate to severe anemia and iron deficiency with vitamins folate and/or B12 among children under 3 years of age in an ICDS block in operation for 20 years is of concern. Dietary origin was the main cause of anemia in this age group.     

Progressive supranuclear palsy-like phenotype associated with bilateral hypoxic-ischemic striopallidal lesions.

A progressive supranuclear palsy (PSP)-like syndrome due to vascular or anoxic brain insult is rare. We describe a 65-year-old man with a progressive PSP-like phenotype associated with hypoxic-ischemic bilateral striopallidal lesions, secondary to rupture of and subsequent surgery for a thoracic aortic aneurysm. After early extrapyramidal features, 10 months later he started to fall, and developed levator inhibition. A supranuclear gaze palsy for downgaze was documented 5.5 years after the insult.     

Cavernous haemangioma of hypopharynx

A case of cavernous haemangioma of hypopharynx in a 20 year old male is reported. The tumour was removed by surgical diathermy through anterior pharyngotomy approach.