Manipal University

About: Manipal University is a education organization based out in Manipal, Karnataka, India. It is known for research contribution in the topics: Population & Medicine. The organization has 9525 authors who have published 11207 publications receiving 110687 citations.

Age-associated deficit of mitochondrial oxidative phosphorylation in skeletal muscle: role of carnitine and lipoic acid.

Abstract: Mitochondrial damage has implicated a major contributor for ageing process. In the present study, we measured mitochondrial membrane swelling, mitochondrial respiration (state 3 and 4) by using oxygen electrode in skeletal muscle of young (3–4 months old) and aged rats (above 24 months old) with supplementation of l-carnitine and dl-α-lipoic acid. Our results shows that the mitochondrial membrane swelling and state 4 respiration were increased more in skeletal muscle mitochondria of aged rats than in young control rats, whereas the state 3 respiration, respiratory control ratio (RCR) and ADP:O ratio decreased more in aged rats than in young rats. After supplementation of carnitine and lipoic acid to aged rats for 30 days, the state 3 respiration and RCR were increased, whereas the state 4 and mitochondrial membrane swelling were decreased to near normal rats. From our results, we conclude that combined supplementation of carnitine and lipoic acids to aged rats increases the skeletal muscle mitochondrial respiration, thereby increasing the level of ATP. (Mol Cell Biochem xxx: 83–89, 2005)

Risk factors for malnutrition among preschool children in rural Karnataka: a case-control study

Abstract: The prevalence of malnutrition among children in developing countries is very high. As a step towards reducing the prevalence of malnutrition, there is a need to identify the important determinants of malnutrition in the specific population so that preventive and control measures can be implemented. The objective of the study is to determine the risk factors for malnutrition among preschool children in Rural Karnataka, South India. A case-control study was carried out among preschool children, aged between three to six years, attending the Anganwadi centers and their mothers’ in Udupi district of Karnataka, India. A total of 570 children (190 cases and 380 controls) were selected by multistage cluster sampling technique. A semi-structured risk factors questionnaire was used to identify the risk factors for malnutrition among children. The majority (45.8 and 45.5%) of the children in the study were in the age group of 3.0 to 4.0 years in case and control groups respectively. There was a slight preponderance of illiterate parents among cases in comparison to the controls. Largely, 87.4% of the children belonged to poor socio-economic status in the case groups compared to 82.4% in the control group. After adjusting for the confounders, underweight was significantly associated with socio-economic status of the parents (aOR: 2.05, 95% CI: 1.06, 3.96), birth weight < 2000 g (aOR: 25, 95% CI: 0.10, 0.59), recurrent diarrhoea (aOR: 2.74, 95% CI: 1.56, 4.83), recurrent cold and cough (aOR: 3.88, 95% CI: 1.96, 7.67), worm infestation (aOR: 2.0, 95% CI: 1.19, 3.38) and prelacteal feed given (aOR: 3.64, 95% CI: 2.27, 5.86). Parental education, childhood illness, short birth interval, open defecation, type of weaning and complimentary food given to children were some of the significant determinants of underweight that were found in the study. Information, Education and Communication (IEC) campaigns alleviating food habits and taboos and promoting birth spacing is the need of the hour for preventing the occurrence of undernutrition among preschool children.

NAD(P)HX dehydratase (NAXD) deficiency: a novel neurodegenerative disorder exacerbated by febrile illnesses.

Abstract: Physical stress, including high temperatures, may damage the central metabolic nicotinamide nucleotide cofactors [NAD(P)H], generating toxic derivatives [NAD(P)HX]. The highly conserved enzyme NAD(P)HX dehydratase (NAXD) is essential for intracellular repair of NAD(P)HX. Here we present a series of infants and children who suffered episodes of febrile illness-induced neurodegeneration or cardiac failure and early death. Whole-exome or whole-genome sequencing identified recessive NAXD variants in each case. Variants were predicted to be potentially deleterious through in silico analysis. Reverse-transcription PCR confirmed altered splicing in one case. Subject fibroblasts showed highly elevated concentrations of the damaged cofactors S-NADHX, R-NADHX and cyclic NADHX. NADHX accumulation was abrogated by lentiviral transduction of subject cells with wild-type NAXD. Subject fibroblasts and muscle biopsies showed impaired mitochondrial function, higher sensitivity to metabolic stress in media containing galactose and azide, but not glucose, and decreased mitochondrial reactive oxygen species production. Recombinant NAXD protein harbouring two missense variants leading to the amino acid changes p.(Gly63Ser) and p.(Arg608Cys) were thermolabile and showed a decrease in Vmax and increase in KM for the ATP-dependent NADHX dehydratase activity. This is the first study to identify pathogenic variants in NAXD and to link deficient NADHX repair with mitochondrial dysfunction. The results show that NAXD deficiency can be classified as a metabolite repair disorder in which accumulation of damaged metabolites likely triggers devastating effects in tissues such as the brain and the heart, eventually leading to early childhood death.

Click chemistry approach for bis-chromenyl triazole hybrids and their antitubercular activity.

Abstract: 1,4-Disubstituted bis-chromenyl triazole hybrids 5a–m have been synthesized in a three-step reaction sequence from 4-(bromomethyl)-2H-chromen- 2-ones 3a–m. The intermediate azides 4a–m underwent a regioselective 1,3-dipolar cycloaddition with a 2H-chromen-2-one linked acetylenic dipolarophile in the presence of Cu (II)/ascorbate/ water/n-butanol reaction medium. Three compounds 5h–j exhibited 6.25 lg/mL MIC against M. tuberculosis. Among the compounds screened for antifungal activity, lowest MIC of 6.25 lg/mL was observed for 5c against A. niger that also exhibited DNA cleavage observed by agarose gel electrophoresis. All the compounds were moderately active against both Gram-positive and Gramnegative bacterial strains. The cytotoxic effect of potent compounds on normal cells (V79 and HBL100) was assessed by MTT assay.

Aloe vera Inhibits Proliferation of Human Breast and Cervical Cancer Cells and Acts Synergistically with Cisplatin

Abstract: Many of the anti-cancer agents currently used have an origin in natural sources including plants. Aloe vera is one such plant being studied extensively for its diverse health benefits, including cancer prevention. In this study, the cytotoxic potential of Aloe vera crude extract (ACE) alone or in combination with cisplatin in human breast (MCF-7) and cervical (HeLa) cancer cells was studied by cell viability assay, nuclear morphological examination and cell cycle analysis. Effects were correlated with modulation of expression of genes involved in cell cycle regulation, apoptosis and drug metabolism by RT-PCR. Exposure of cells to ACE resulted in considerable loss of cell viability in a dose- and time-dependent fashion, which was found to be mediated by through the apoptotic pathway as evidenced by changes in the nuclear morphology and the distribution of cells in the different phases of the cell cycle. Interestingly, ACE did not have any significant cytotoxicity towards normal cells, thus placing it in the category of safe chemopreventive agent. Further, the effects were correlated with the downregulation of cyclin D1, CYP 1A1, CYP 1A2 and increased expression of bax and p21 in MCF-7 and HeLa cells. In addition, low dose combination of ACE and cisplatin showed a combination index less than 1, indicating synergistic growth inhibition compared to the agents applied individually. In conclusion, these results signify that Aloe vera may be an effective anti-neoplastic agent to inhibit cancer cell growth and increase the therapeutic efficacy of conventional drugs like cispolatin. Thus promoting the development of plant-derived therapeutic agents appears warranted for novel cancer treatment strategies.