A randomized study of coconut oil versus sunflower oil on cardiovascular risk factors in patients with stable coronary heart disease.

BACKGROUND AND RATIONALE: Coronary artery disease (CAD) and its pathological atherosclerotic process are closely related to lipids. Lipids levels are in turn influenced by dietary oils and fats. Saturated fatty acids increase the risk for atherosclerosis by increasing the cholesterol level. This study was conducted to investigate the impact of cooking oil media (coconut oil and sunflower oil) on lipid profile, antioxidant mechanism, and endothelial function in patients with established CAD. DESIGN AND METHODS: In a single center randomized study in India, patients with stable CAD on standard medical care were assigned to receive coconut oil (Group I) or sunflower oil (Group II) as cooking media for 2 years. Anthropometric measurements, serum, lipids, Lipoprotein a, apo B/A-1 ratio, antioxidants, flow-mediated vasodilation, and cardiovascular events were assessed at 3 months, 6 months, 1 year, and 2 years. RESULTS: Hundred patients in each arm completed 2 years with 98% follow-up. There was no statistically significant difference in the anthropometric, biochemical, vascular function, and in cardiovascular events after 2 years. CONCLUSION: Coconut oil even though rich in saturated fatty acids in comparison to sunflower oil when used as cooking oil media over a period of 2 years did not change the lipid-related cardiovascular risk factors and events in those receiving standard medical care.

Protective role of extracts of grape skin and grape flesh on ethanol-induced oxidative stress, inflammation and histological alterations in rat brain.

Ethanol consumption has deleterious effects on all organs and especially on brain. In our study, the radical scavenging properties of grape skin and grape flesh (contains natural antioxidants like polyphenols) was determined in vitro and for in vivo studies, male Wistar rats (16-18 week-old) and 100-120 gm weight were divided in five groups of six animals each. One group were fed with ethanol (1.6 gm/kg body weight), while second group were fed with ethanol (1.6 g/kg body weight) and grape skin extract (2.5 g/kg body weight), the third group were fed with ethanol (1.6 g/kg body weight) and grape flesh extract, daily once for 12 weeks, while the fourth group were fed with ethanol (1.6 g/kg body weight) and tocopheryl acetate (80 mg/kg/day) daily once for 12 weeks. Results of in vitro studies indicate that grape skin extracts showed significant radical scavenging properties (ROS). There was also significantly alteration of serum cytokines in our study.

Analysis of gene mutations among South Indian patients with maple syrup urine disease: identification of four novel mutations.

Maple syrup urine disease (MSUD) is predominantly caused by mutations in the BCKDHA, BCKDHB and DBT genes, which encode for the E1alpha, E1beta and E2 subunits of the branched-chain alpha-keto acid dehydrogenase complex, respectively. Because disease causing mutations play a major role in the development of the disease, prenatal diagnosis at gestational level may have significance in making decisions by parents. Thus, this study was aimed to screen South Indian MSUD patients for mutations and assess the genotype-phenotype correlation. Thirteen patients diagnosed with MSUD by conventional biochemical screening such as urine analysis by DNPH test, thin layer chromatography for amino acids and blood amino acid quantification by HPLC were selected for mutation analysis. The entire coding regions of the BCKDHA, BCKDHB and DBT genes were analyzed for mutations by PCR-based direct DNA sequencing. BCKDHA and BCKDHB mutations were seen in 43% of the total ten patients, while disease-causing DBT gene mutation was observed only in 14%. Three patients displayed no mutations. Novel mutations were c.130C>T in BCKDHA gene, c. 599C>T and c.121_122delAC in BCKDHB gene and c.190G>A in DBT gene. Notably, patients harbouring these mutations were non-responsive to thiamine supplementation and other treatment regimens and might have a worse prognosis as compared to the patients not having such mutations. Thus, identification of these mutations may have a crucial role in the treatment as well as understanding the molecular mechanisms in MSUD.

Dietary grapes (Vitis vinifera) feeding attenuates ethanol-induced oxidative stress in blood and modulates immune functions in mice.

Ethanol metabolism is known to induce overwhelming production of reactive oxygen species (ROS) and also to cause associated immune dysfunction. Several interventional agents of plant origin, in particular fruits and vegetables have been used to counteract these alterations induced by ethanol. In this study, we investigated the efficacy of dietary feeding of skin and flesh of grapes (Vitis vinifera L.) on the alterations in immune and vascular functions in mice with liver abnormalities induced by chronic ethanol consumption. Results revealed that feeding of both grape skin and flesh (2.5 g/kg body wt/day) effectively attenuated the oxidative stress and alterations in immune function and angiogenesis induced by chronic ethanol consumption (1.6 g/kg body wt/day for 12 weeks) in mice. The antioxidant actions of the grape skin and flesh as observed in this study might be attributed to the polyphenols present in the grapes.

Composition of plasma and atheromatous plaque among coronary artery disease subjects consuming coconut oil or sunflower oil as the cooking medium.

OBJECTIVES: Coconut oil, which is rich in medium-chain saturated fatty acids, is the principal cooking medium of the people of Kerala, India. Replacement of saturated fat with polyunsaturated fat is effective in reducing serum cholesterol levels. However, the effect of substituting coconut oil with sunflower oil on the fatty acid composition of plaque has not been thoroughly investigated. We therefore evaluated and compared the fatty acid composition of plasma and plaque among subjects consuming coconut oil or sunflower oil as the cooking medium. METHODS: Endarterectomy samples and plasma samples were obtained from subjects who underwent coronary artery bypass grafts (n = 71). The subjects were grouped based on the type of oil they were using as their cooking medium (coconut oil or sunflower oil). The fatty acid composition in the plaques and the plasma was determined by HPLC and the data were analyzed statistically. RESULTS: Sunflower oil consumers had elevated concentrations of linoleic acid (p = 0.001) in plasma, while coconut oil users had higher myristic acid levels (p = 0.011) in plasma. Medium-chain fatty acids did not differ significantly between the two groups in the plasma. Medium-chain fatty acids were detected in the plaques in both groups of subjects. In contrast to previous reports, long-chain saturated fatty acids dominated the lipid content of plaque in this population, and the fatty acid composition of plaque was not significantly different between the two groups. No correlation between fatty acids of plasma and plaque was observed in either group. CONCLUSION: A change in cooking medium, although it altered the plasma fatty acid composition, was not reflected in the plaque composition.

Effect of high fat diet without cholesterol supplementation on oxidative stress and lipid peroxidation in New Zealand white rabbits.

AIM: Dietary fats may affect coronary artery disease risk by influencing factors other than serum cholesterol. The effect of diets containing coconut oil and sunflower oil without cholesterol supplementation on oxidative stress and lipid peroxidation were studied in male New Zealand White rabbits. METHODS: Animals assigned to four groups (control, cholesterol-fed, coconut oil-fed and sunflower oil-fed), given an isocaloric diet and studied for 6 months. The lipid profile, reduced glutathione, glutathione peroxidase, superoxide dismutase, vitamin C and lipid peroxidation were evaluated at the beginning of the study, at the third month and at the end of the study period. RESULTS: Serum lipid values did not show significant variation between animals fed coconut oil and sunflower oil, but total cholesterol, triglycerides and LDL-cholesterol were significantly higher and HDL-cholesterol was reduced in cholesterol-fed animals. Lipid peroxidation was higher in cholesterol-fed and sunflower oil-fed rabbits compared to controls and coconut oil-fed rabbits. Though other parameters such as reduced glutathione, glutathione peroxidase, superoxide dismutase and ascorbate did not vary between the two oil-fed rabbit groups, cholesterol-fed rabbits showed severe oxidative stress. CONCLUSION: We conclude that in the absence of cholesterol supplementation, coconut oil intake up to 30% of daily energy supply did not cause hypercholesterolemia or oxidative stress in rabbits.

Effect of alpha-tocopherol supplementation on renal oxidative stress and Na+/K+ -adenosine triphosphatase in ethanol treated Wistar rats.

Ethanol intoxication resulted in high extent of lipid peroxidation, and reduction in antioxidant defenses (decreased GSH, GSH/GSSG ratio, and catalase, SOD and GPx activities) and (Na+/K+)-ATPase activity in kidney. Alpha-tocopherol treatment effectively protected kidney from ethanol induced oxidative challenge and improved renal (Na+/K+)-ATPase activity. Ethanol induced oxidative stress in the kidney and decreased (Na+/K+)-ATPase activity could be reversed by treatment with ascorbic acid.

Protective effects of silymarin, a milk thistle (Silybium marianum) derivative on ethanol-induced oxidative stress in liver.

The production of reactive oxygen species (ROS) is considered to be a major factor in oxidative cell injury. The antioxidant activity or the inhibition of the generation of free radicals is important in providing protection against such hepatic damage. Silymarin, derived from the milk thistle plant, Silybium marianum, has been used in traditional medicine as a remedy for diseases of the liver and biliary tract. In the present study, the effect of hepatoprotective drug silymarin on body weight and biochemical parameters, particularly, antioxidant status of ethanol-exposed rats was studied and its efficacy was compared with the potent antioxidant, ascorbic acid as well as capacity of hepatic regeneration during abstention. Ethanol, at a dose of 1.6 g/kg body wt/day for 4 wks affected body weight in 16-18 week-old male albino rats (Wistar strain weighing 200-220 g). Thiobarbituric acid reactive substance (TBARS) level, superoxide dismutase (SOD), and glutathione-s-transferase (GST) activities were significantly increased, whereas GSH content, and catalase, glutathione reductase (GR) and GPx (glutathione peroxidase) activities significantly reduced, on ethanol exposure. These changes were reversed by silybin and ascorbic acid treatment. It was also observed that abstinence from ethanol might help in hepatic regeneration. Silybin showed a significant hepatoprotective activity, but activity was less than that of ascorbic acid. Furthermore, preventive measures were more effective than curative treatment.

Effect of lecithin in the treatment of ethanol mediated free radical induced hepatotoxicity.

Alcoholic liver disease (ALD) develops as a consequence of priming and sensitizing mechanisms rendered by cross-interactions of primary mechanistic factors and secondary risk factors. Liver damage due to consumption of alcohol may be caused by oxygen radicals such as superoxide and hydroxyl radicals, generated during the metabolism of ethanol by the microsomal oxidizing system. Lecithin, an important class of phospholipids contains choline, which is considered as lipotropic factor. The effects of this lecithin as a hepatoprotective drug on body weight and antioxidant status of ethanol-exposed rats were studied. The results were compared with the effects of tocopheryl acetate. From the present study, it can be concluded that ethanol-induced stress can be partly prevented by tocopheryl acetate, and showed best result. Abstination from alcohol also involved for little hepatic regeneration. Supplementation of lecithin showed better effect compared to abstination from alcohol on reversing the effect of ethanol induced liver damage in the present study. Moreover, preventive measures were found to be better than curative treatment. Antioxidants are likely to provide beneficial effects on hepatocyes via desensitization against oxidant stress while inhibiting primary mechanism for expression of proinflammatory and cytotoxic mediators. However, abstinence from alcohol, proper nutrition, and supplementation of antioxidants, vitamins and hepatoprotective drugs are some of the therapeutic options.

Inhibition of lipid peroxidation by botanical extracts of Ocimum sanctum: in vivo and in vitro studies.

Ocimum sanctum, the Indian holy basil, has significant ability to scavenge highly reactive free radicals. Shade dried leaf powder of the plant was extracted with water and alcohol, and then fractionated with different solvents. Both extracts and their fractions have in vitro anti-lipidperoxidative activity at very low concentrations. In vivo, hypercholesterolemia-induced erythrocyte lipid peroxidation activity was inhibited by aqueous extracts of Ocimum in a dose-dependent manner in male albino rabbits. Aqueous extract feeding also provided significant liver and aortic tissue protection from hypercholesterolemia-induced peroxidative damage.

Activity of Ocimum sanctum (the traditional Indian medicinal plant) against the enteric pathogens.

Aqueous & alcoholic extracts of O. sanctum were prepared. Two concentrations of these extracts (30 mg & 60 mg) were tried against the enteric pathogens & candida albicans by Agar diffusion method. Wide zones of inhibition were observed at 60 mg concentration of extract. Aqeous extract showed wider zone of inhibition when compared to alcoholic extract. Aqueous extract showed wider zones of inhibition for Klebisella, E. Coil, Proteus & Staphylococcus aureus. Alcoholic extract showed wider zone for vibrio cholerae.

Augmentation of murine natural killer cell and antibody dependent cellular cytotoxicity activities by Phyllanthus emblica, a new immunomodulator.

When administered orally, Phyllanthus emblica, an excellent source of vitamin C (ascorbate), has been found to enhance natural killer (NK) cell activity and antibody dependent cellular cytotoxicity (ADCC) in syngeneic BALB/c mice, bearing Dalton's lymphoma ascites (DLA) tumor. P. emblica elicited a 2-fold increase in splenic NK cell activity on day 3 post tumor inoculation. Enhanced activity was highly significant on days 3, 5, 7 and 9 after tumor inoculation with respect to the untreated tumor bearing control. A significant enhancement in ADCC was documented on days 3, 7, 9, 11 and 13 in drug treated mice as compared to the control. An increase in life span (ILS) of 35% was recorded in tumor bearing mice treated with P. emblica. This increased survival was completely abrogated when NK cell and killer (K) cell activities were depleted either by cyclophosphamide or anti-asialo-GM1 antibody treatment. These results indicate: (a) an absolute requirement for a functional NK cell or K cell population in order that P. emblica can exert its effect on tumor bearing animals, and (b) the antitumor activity of P. emblica is mediated primarily through the ability of the drug to augment natural cell mediated cytotoxicity.

Effect of a preparation from Viscum album on tumor development in vitro and in mice.

The effect of Iscador, a commercial preparation made from Viscum album was studied on several cell lines using in vitro tissue culture as well as tumor-bearing animals. Iscador was found to be cytotoxic to animal tumor cells such as Dalton's lymphoma ascites cells (DLA cells) and Ehrlich ascites cells in vitro and inhibited the growth of lung fibroblasts (LB cells), Chinese hamster ovary cells (CHO cells) and human nasopharyngeal carcinoma cells (KB cells) at very low concentrations. Moreover, administration of Iscador was found to reduce ascites tumours and solid tumours produced by DLA cells and Ehrlich ascites cells. The effect of the drug could be seen when the drug was given either simultaneously, after tumour development or when given prophylactically, indicating a mechanism of action very different from other chemotherapeutic drugs. Iscador was not found to be cytotoxic to lymphocytes.

Presence of a receptor for the active component of Iscador in ascites fluid of tumour bearing mice.

Tumour bearing mice exhibit a specific "receptor" in the ascites fluid which binds with the active component isolated from Iscador. This "receptor" was found to be a protein which inhibited the cytotoxicity of Iscador and its isolated active component at low concentration. The receptor protein was also found in the sonicates of tumour cells which are susceptible to the action of Iscador but not in lymphocytes which were not susceptible to Iscador or its isolated active component. The receptor was separated on a Sephadex G-50 column. Activity was lost upon heat denaturation and dialysis.

An alternative pathogenetic pathway for oral submucous fibrosis (OSMF).

Oral submucous fibrosis is a potent pre-cancerous condition which occurs almost exclusively in Indians but cases have been reported from several countries. The definite aetiology of OSMF is still unknown and there is no known treatment for it. Chilles, tobacco use, vitamin deficiencies and betel quid chewing have been implicated. Ramanathan is of the view that OSMF seems to be the Asian version of sideropenic dysphagia. He suggests that OSMF appears to be an altered oral mucosa following prolonged period of chronic deficiency of iron and/or vitamin "B" complex especially folic acid. This changed state of the oral mucosa subsequently appears to develop more easily a hypersensitivity to oral irritants such as spices especially chillies and to the betel quid. We hold that the hypersensitivity caused by local irritants and the resultant persistent juxta epithelial inflammatory response noted in OSMF (in a host system already primed by an intrinsic genetic defect) act as the initiating factor leading to a defective inflammatory--reparative response, culminating in fibrotic healing. The role of iron and "B"complex together with others may be contributory (promotor) to this pre-existing pathologic response of the lamina propria.

Isolation and identification of a tumour reducing component from mistletoe extract (Iscador).

Using a combination of gel filtration and paper chromatography, a tumour reducing component from mistletoe extract (Iscador) was isolated and identified to be a peptide of approximate molecular weight 5000. The isolated peptide reduced the solid tumour induced by Dalton's lymphoma ascites tumour cells (DLA cells) in mice. The isolated component was very cytotoxic to the DLA cells but was not cytotoxic to normal lymphocytes, indicating a cell dependent specificity.

Preliminary studies on the immunopotentiating action of some ayurvedic preparations.

Ten healthy controls, 9 Rheumatoid Arthritis patients and 5 cancer patients were studied for T and B cells in peripheral circulation. T cell count in cancer patients showed a slight enhancement after receiving Ayurvedic Treatment; but the B cell count remained the same. In Rheumatoid Arthritis patients no significant change was noticed either in T cell or cell count.

Tissue binding patterns of lectins in premalignant and malignant lesions of the oral cavity.

Lectins from the seeds of Jackfruit (Artocarpus integrifolia) and winged bean (Psophocarpus tetragonolobus) were isolated using an immobilized N-acetyl D-galactosamine column and conjugated to type VI horse radish peroxidase. The purified conjugate was used for the study of tissue specificities using diaminobenzidine as the substrate on dewaxed tissue sections of normal, oral leukoplakia, oral submucous fibrosis, verucous carcinoma and squamous cell carcinoma of the oral cavity. In spite of having a common inhibitory sugar, winged bean lectin did not bind to any lectins whereas Jackfruit lectin showed varying degrees of binding towards the above tissues. The difference in the nature and intensity of binding of the Jackfruit lectin suggest the utilizing this lectin in the differential diagnosis of the premalignant and malignant lesions of the oral cavity.