Browsing by Author "Ajit K. Saxena"

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Acrolein induces unilateral hypertrophy and associated histopathalogical changes during germ cell differentiation in mature rat ovary
(2009) Ajit K. Saxena; Divya Singh; Gajendra Singh
Acrolein is an important chemical molecule of the global environment. It has dual importance as a by product of industrial wastes, automobile exhaust, and secondly an active metabolite of cyclophosphamide metabolic pathway. Acrolein is highly reactive unsaturated three carbon aldehyde. The importance of this chemical molecule increased several folds because of high reactivity; therefore, study has been designed with the aim to evaluate the effect of low dose (1mg/kg body wt. /day), continuous exposure (i.p.) of acrolein alone or with ascorbate (5 mg/kg body wt) for 10 days to rats .Reproductive performance of the treated rats were observed by serial mating experiments with opposite sex of the same strain. Infertility (33%) was observed when compared with controls. Most interesting finding is significant reduction (P<0.001) in the size of germ cell - populations i.e. primary, secondary and graafian follicles in medulla as well as in cortex region of the ovary as observed in experimental group. In another set of experimental group where antioxidant (ascorbic acid) was supplemented along with acrolein which shows regeneration of germ cells proliferation, suggesting ascorbate help to prevent cell-damage during cell-division in female gonads. The study was also further extended to observed genetic damage in term of chromosomal aberrations assay which reveals that significant changes (p < 0.05) were observed when compared with control groups.
In vitro unusual expression of chromosome breakage under folic acid deficient culture condition in human lymphocytes associated with mentally retarded patients
(2006) Ajit K. Saxena; S. Bhattacharya; N. Bhatta; A.K. Srivastava
A fragile site is non-staining gaps and breaks present on the mammalian chromosomes. Fragile X syndrome is the most common form of inherited mental retardation in humans because of unequivocally clinical significance. The expression frequency of folate sensitive fragile site is evaluated in prometaphase \ metaphase chromosomes obtained from peripheral blood lymphocytes from clinically diagnosed mentally retarded patients. The present study shows expression frequency of such breaks in 5.8% of abnormal cell population designated as "rare" fragile site i.e. Xq27, after karyotypic correlation with standard ideogram and to the clinical features, which is slightly higher as reported earlier observations by various laboratories, suggesting that folic acid an essential component required for DNA synthesis lacking either in diet or unknown factors present in the environment.
Structural interaction between drug - DNA and protein - A novel approach for bioinformatics in medicine
(2009) Ajit K. Saxena; Divja Singh; Gajendra Singh
Drug like methotrexate were used in the present study because of dual importance, both for clinicians as well as an interest of basic scientists. Methotrexate, an antineoplastic agent is used for malignant as well as non malignant conditions and become teratogenic & mutagenic in nature. They prevent cell proliferation by incorporated into DNA during the "S"- phase of the cell- cycle and inhibit rapidly dividing normal somatic cell-division including germ cells because of antagonist of folic acid synthesis by inhibiting dihydrofolate reductase an essential enzyme required for the conversion of folic acid to tetrahydrofolic acid. The rational behind this study is to observe binding sites activity of native methotrexate structure to DNA, and dihydrofolate reductase (protein) as well as mutated structure of drug (methotrexate) using different software of structural modeling. For drug (methotrexate) - protein structure interaction, homology modeling, also known as comparative modeling, was used in the present study for constructing model of a protein from its amino acid sequence to enhance activity of the drug by structural modification. All homology modeling techniques help for the identification of one or more known protein structures (known as "templates" or "parent structures") resemble to the structure of query sequence, and on the production of an alignment, which maps residues in the query sequence. The sequence alignment and template structure are then used to produce a structural model of the target site of drug or protein. Interestingly in the present study indicates the significant interaction between the drug and DNA/proteins were noticed which could be further useful in reaching qualitative and quantitative conclusions about the query sequence of developing new molecule (drug action), especially in formulating hypotheses about why certain residues are conserved and making toxic side effects which may in turn lead to experiments to test hypotheses of drug mediated toxicity.
Unexpected segregation of chromosome and common fragile site expression induced by 5-Azacytidine exposure in human lymphocytes of Down's syndrome patients
(2007) Ajit K. Saxena; A.K. Srivastava; Gajendra Singh
Preferential breakge of chromosomes at specific sites are known as chromosomal fragile sites are distributed all over the mammalian genome. The 5-Azacytidine (5-AZC) induced expression of "common fragile sites" and other chromosomal changes were evaluated in prometaphase/ metaphase chromosomes obtained from peripheral blood lymphocytes from clinically diagnosed Down's syndrome patients. The present study possibly for the first time reveals significantly (p<0.001) high incidence of common fragile sites expression (12%), centromere breakage (6%) and more then 3% of premature condensation (PMC) of chromosomes in cell poplution when compared with controls, suggesting that high incidencec of common fragile sites expression due to demethylation action of DNA by 5 - AZC could reveal differential gene activity in mentally retarted patients.