Manipal Life science Center

Manipala, India

Manipal Life science Center

Manipala, India

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Kalavathi V.,University of Madras | Chandra N.,University of Madras | Renjini Nambiar G.,University of Madras | Shanker J.,University of Madras | And 7 more authors.
International Journal of Human Genetics | Year: 2010

Primary amenorrhea refers to absence of spontaneous menarche even after the age of 16 while in secondary amenorrhea, the condition follows a period of normal menstruation. Cytogenetic data in cases with primary (n=852) (PA) or secondary (n=127) amenorrhea (SA) investigated at the Department of Genetics, Dr. A.L. Mudaliar Post Graduate Institute of Basic Medical Sciences, University of Madras, during the 25-year period 1979 to 2004 was reviewed. Routine GTG-band analysis of metaphases from peripheral blood leucocytes revealed the incidence of chromosomal abnormalities in individuals with PA and SA to be 25.82% and 7.09% respectively. In addition to numerical abnormalities, the various structural aberrations of the X chromosome encountered were deletions, isochromosome for the long arm, translocations and ring chromosomes. Ascertainment of the karyotype aided in confirmation of the provisional diagnosis, a better phenotype-genotype correlation to understand clinical heterogeneity and in genetic counseling. © Kamla-Raj 2010.

PubMed | University of the West Indies, MSU GEF International Medical School and Manipal Life Science Center
Type: Journal Article | Journal: Cognitive neurodynamics | Year: 2015

In chronic renal failure there is a gradual retention of substances in the tissues and body fluids, called as uremic retention toxins, which can bring about a number of biochemical activities in the body. Chronic renal insufficiency also leads to progressive behavioural conflict. Uremic toxins can affect both the central and the peripheral nervous system. Uremic encephalopathy is also associated with problems in cognition and memory. To study the psychomotor functional disorders in rats with progressive chronic renal failure surgical nephrectomy was done by resection method. The animals were grouped into two control groups, Sham control (SC) and normal control (NC) and two uremic groups, moderate uremia (GM) and severe uremia (GS). Psychomotor analysis was done by passive avoidance and open field in these animals at 4, 8, 12, and 16weeks. After the incubation period, the nephrectomised groups (GM and GS) showed significant changes in exploratory, locomotor and emotional behaviour when compared to the controls (NC and SC). Psychomotor changes involve poor cognition, reduced memory, reduced locomotor activity and decreased exploratory drive and emotional disturbance like increased fear during the initial stages. During the later stages a restless behaviour was noticed, associated with diminished fear.

Kodandapani S.,Kasturba Medical College | Pai M.V.,Kasturba Medical College | Nambiar J.,Kasturba Medical College | Moka R.,Manipal Life science Center
Journal of Human Reproductive Sciences | Year: 2011

Genetic aberrations comprise one-third of women with premature ovarian aging (POA). X chromosome abnormalities are seen in these women. We report a case of a 29-year-old lady with primary infertility and POA. She was phenotypically normal and her basal follicle stimulating hormone level was above the age-specific cut-off. Karyotype was triple X syndrome.

Tharoor H.,Schizophrenia Research Foundation | Tharoor H.,Manipal University India | Kotambail A.,Manipal Life science Center | Jain S.,National Institute of Mental Health and Neuro Sciences | And 2 more authors.
Psychiatric Genetics | Year: 2013

The 5-hydroxy tryptamine transporter (5-HTT) gene has been previously implicated in lithium response, but the roles of the triallelic 5-HTT linked promoter region (5-HTTLPR) and variable number tandem repeats in the second intron [serotonin transporter intron 2 (STin2)] have not been reported. We examined these polymorphisms in 122 patients with bipolar I disorder, among which 49 patients were classified as good responders, 49 as nonresponders, and 24 as partial responders to lithium prophylaxis. We observed significant variation in the genotype frequencies of STin2 polymorphism among the response groups (P=0.02). There was also a significant association of haplotype consisting of the S allele of 5-HTTLPR and 10 repeat allele of STin2 with lithium response (P=0.01) and no such relationship was found with 5-HTTLPR variants. Our data support preliminary information of a possible association of STin2 and its combined effect with 5-HTTLPR variants with lithium response and also suggest that lithium is likely to be more effective for patients carrying 5-HTT polymorphisms associated with reduced transcriptional activity.Copyright © Lippincott Williams & Wilkins.

Rao U.S.C.,Jawaharlal Institute of Postgraduate Medical Education & Research | Devendran A.,Jawaharlal Institute of Postgraduate Medical Education & Research | Satyamoorthy K.,Manipal Life science Center | Shewade D.G.,Jawaharlal Institute of Postgraduate Medical Education & Research | And 2 more authors.
Molecular Biology Reports | Year: 2011

CYP2C19 is an enzyme involved in the metabolism of several clinically important drugs. The variations in the CYP2C19 promoter region may alter the transcription of the gene by altering the interaction between the trans and cis-acting elements. In the present study, CYP2C19 promoter region with different variant alleles were cloned into a pGL-3 basic luciferase reporter vector and transfected into HepG2 cell lines. Subsequently, dual luciferase activity was measured to evaluate the activity of the promoter region. Gel shift assays with predicted binding sites for CCAAT displacement protein, activating transcription factor-2 and glucocorticoid receptor were performed. Results from this study indicate that few variations present in the putative cis-acting elements of the CYP2C19 promoter region such as -1442T>C, -779A>C and -98T>C -1498T>G and -828del>T alter the transcription of the gene. Specific binding with nuclear proteins was also observed in gel shift assays. This may account for the interindividual variations in gene expression and genotype dependant differences in gene transcription. The results also suggest the role of activating transcription factor-2 and CCAAT displacement repressor protein on CYP2C19 gene transcription. © Springer Science+Business Media B.V. 2010.

Kumar D.,Manipal University India | Upadhya D.,Manipal University India | Salian S.R.,Manipal University India | Rao S.B.S.,Manipal Life science Center | And 3 more authors.
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2013

Objectives: To study the post-natal characteristics and the survival of offspring derived from DNA damaged sperm. Study design: This experimental prospective study was conducted on Swiss Albino mice (Mus musculus). Sperm DNA damage was induced by different doses of γ-irradiation in male mice who were then mated with healthy female mice. The post-natal characteristics including the survival of first generation offspring were studied and then correlated with the amount of paternal sperm DNA damage. Results: A significant reduction of survival in the early post-natal period was observed in the first generation offspring derived from the DNA damaged sperm, and a strong association was observed between the extent of sperm DNA damage and the survival of the offspring. Conclusion: The DNA damage load in sperm at the time of fertilization influences early post-natal survival of the mouse offspring. © 2012 Elsevier Ireland Ltd.

Dutta A.,Manipal Life science Center | Shetty P.,Manipal Life science Center | Bhat S.,Manipal Life science Center | Ramachandra Y.,Manipal Life science Center | Hegde S.,Manipal Life science Center
Journal of Biomolecular Techniques | Year: 2012

A solvent system that extracts a maximum number of metabolites belonging to diverse chemical classes from complex biofluids, such as plasma, may offer useful inputs to understand the metabolic and physiological state of an individual. The present study compared seven solvent systems for extraction of metabolites from plasma. The extracts were analyzed by mass spectrometry (MS) and MS/MS (MS2) using a quadrupole time-of-flight liquid chromatography/MS system in positive and negative modes of ionization. Metabolites with molecular mass below 400 were identified using Human Metabolome Database MS2 and MS search interfaces. Theacetone/isopropanol(2: 1)system yielded promising results in positive ionizationmode, asthe maximum number of MS and MS2 features was detected in the extract. It was found to be superior in extraction of various classes of metabolites, especially organic acids, nucleosides and nucleoside derivatives, and heterocyclic molecules. Glycerophosphocholines in the mass range of 400-700 were found to be efficiently extracted by the methanol/chloroform/water (8: 1: 1) system. In negative mode as well, the maximum number of MS2 features was detected in methanol/chloroform/water and acetone/isopropanol extracts. The fingerprints of molecular features obtained in the negative and positive modes differed from each other to a significant extent. © 2012 ABRF.

Adiga S.K.,Manipal University India | Upadhya D.,Manipal University India | Kalthur G.,Manipal University India | Bola Sadashiva S.R.,Manipal Life Science Center | Kumar P.,Manipal University India
Fertility and Sterility | Year: 2010

Objective: To report a more quantitative approach to study the influence of varying levels of sperm DNA damage on transgenerational changes in genomic instability in a mouse model. Design: Experimental prospective study. Setting: Embryology research laboratory. Animal(s): Swiss albino mice. Intervention(s): The sperm DNA damage was induced by different doses of γ-irradiation to male mice followed by mating with healthy female mice. Main Outcome Measure(s): Genomic integrity in embryos, fetus, and spermatozoa of F1 mice derived from the DNA-damaged sperm. Result(s): The transgenerational changes in genetic integrity were attributed by a dose-dependent increase in the frequency of micronuclei in preimplantation embryos and a concomitant increase in genomic instability in fetal liver cells and sperm chromatin modifications in F1 males. A strong positive correlation was observed between the extent of sperm DNA damage and somatic and germ-line genomic instability. Conclusion(s): Sperm-mediated transgenerational genomic instability is dependent on the amount of DNA damage present in the sire's sperm at the time of fertilization. © 2010 American Society for Reproductive Medicine.

The present study was aimed to evaluate the anti-tumor efficacy and systemic toxicity of chitosan-based plumbagin microspheres in comparison to free plumbagin. The optimized formulation had a mean particle size of 106.35 mum with an encapsulation efficiency of 80.12%. Pharmacokinetic studies showed a 22.2-fold increase in elimination half-life (t(1/2)) of plumbagin from chitosan microspheres as compared to free plumbagin. Administration of plumbagin microspheres resulted in a significant tumor growth inhibition and reduced systemic toxicity. These results suggest that chitosan-based microspheres could be a promising strategy for the systemic delivery of anti-cancer agents like plumbagin.

PubMed | Manipal Life science Center
Type: Comparative Study | Journal: Drug delivery | Year: 2011

Plumbagin (2-methyl, 5-hydroxy, 1, 4-naphthoquinone), an anticancer agent is encapsulated either as conventional or long circulating liposomal formulations to enhance its biological half-life and antitumor efficacy.The liposomes were prepared by thin film hydration method and in vitro characterization was carried out to examine the particle size, zeta potential, drug encapsulation efficiency and in vitro release. The optimized formulations were tested for pharmacokinetic and pharmacodynamic efficacy against mice bearing B16F1 melanoma. Also in vivo toxicity studies were carried out.The optimum particle size and entrapment efficiency was observed at drug to lipid molar ratio of 1:20. The in-vitro release of plumbagin from the liposomal formulations in phosphate-buffered saline (pH 7.4) showed biphasic release with an initial burst release followed by sustained release phase. Elimination half life (T()) of pegylated, conventional and free plumbagin was 1305.76278.16, 346.8733.82 and 35.897.95min respectively. Further, plumbagin exhibited better antitumor efficacy in vivo when administered as long circulating liposomes with no signs of normal tissue toxicity.It can be concluded that the pegylated liposomes could provide a promising parenteral platform for plumbagin with enhanced plasma half-life and therapeutic efficacy.

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