Therapeutics for mitochondrial dysfunction-linked diseases in Down syndrome.

Genome-wide deregulation contributes to mitochondrial dysfunction and impairment in oxidative phosphorylation (OXPHOS) mechanism resulting in oxidative stress, increased production of reactive oxygen species (ROS) and cell death in individuals with Down syndrome (DS). The cells, which require more energy, such as muscles, brain and heart are greatly affected. Impairment in mitochondrial network has a direct link with patho-mechanism at cellular and systemic levels at the backdrop of generalized metabolic perturbations in individuals with DS.

Spectrum of stable and unstable rearrangements in lymphocytic chromosomes investigated in Bhopal population 30 years post MIC disaster amid co-exposure to lifestyle, living, and occupational hazards.

Immediate assessment of genetic damage in methyl isocyanate (MIC) gas-exposed population in small and heterogeneous samples using diversified study designs and solid-stained metaphases could not depict the actual genetic impact of MIC on accidentally exposed individuals. The outcome of the then large multi-center genetic screening program was not available to the public and scientific community. Also, the routine and regular epidemiological health survey does not capture the genetic and long-term effect of MIC.

Effects of tyrosine kinase inhibitors for controlling Ph+ clone and additional clonal abnormalities in a chronic myeloid leukemia.

Purpose: The chronic myeloid leukemia (CML) is characterized by the presence of t(9;22)(q34;q11) that results in chimerization of BCR and ABL genes on the rearranged chromosome 22 or Philadelphia chromosome (Ph). Imatinib has been established as the first line of therapy for CML; in case of Imatinib failure or resistance, other second or third generation tyrosine kinase inhibitors (TKIs) are considered. However, acquisition of additional clonal abnormalities (ACAs) interferes in management of CML.

Triplication of HSA21 on alterations in structure and function of mitochondria.

Triplication of genes encoded in human chromosome 21 (HSA21) is responsible for the phenotypes of Down syndrome (DS). The dosage-imbalance of the nuclear genes and the extra-nuclear mitochondrial DNA (mtDNA) jointly contributes to patho-mechanisms in DS. The mitochondrial organelles are the power house of cells for generation of ATP and maintaining cellular calcium and redox homeostasis, and cellular energy-metabolism processes.

Green Synthesis to Develop Iron-Nano Formulations and Its Toxicity Assays.

Objectives: In the past few years, herbal medicines have gained popularity over synthetic drugs because of their natural source and minimal side effects which has led to a tremendous growth of phytopharmaceuticals usage. With the development of nanotechnology, it provides alternative approaches to overcome several limitations using nano-formulations. In spite of considerable quantity of antianemic preparations with different iron forms available, currently additives are used and represented in modern pharmaceutical market.

Age-related disease burden in Indian population.

Objectives: Aging is not just a consequence of wear-and-tear, but it is the inappropriate regenerative mechanism of the stem cells. Aging is directly proportional to increase in health-problems involving all organs and physiological systems - more of non-communicable types. On the other hand, medical advancement and awareness about health-care are increasing the life expectancy, which could outnumber the young generation or the mainstream of work-force gradually.

Effect of age at exposure on chromosome abnormalities in MIC-exposed Bhopal population detected 30 years post-disaster.

Follow-up cytogenetic study was carried out on 145 individuals from areas stratified by Indian Council of Medical Research, for evaluation of the effect of age-at-exposure and its interaction with exposure status on chromosomal aberrations (CA) in blood-lymphocytes. CA was presented as abnormal cell (Abc), aberrations (Abn) and number of aberration/abnormal cell (Abn/Abc), and correlated with age-at-exposure (childhood: <1-10 years; young: 11-26 years; adult: >27 years). Age related increase in abnormalities (Abc, Abn, Abn/Abc) was observed in all exposure strata, except moderately exposed adult-group, which has exhibited lower Abn/Abc than similarly exposed childhood and young age-groups.

Spectrum of health condition in methyl isocyanate (MIC)-exposed survivors measured after 30 years of disaster.

Health effects of methyl isocyanate (MIC) exposure were mostly reported on the one-time acute exposure in Bhopal population. Epidemiological survey conducted by the Indian apex body of health research has been reported as Technical Reports, which were lacking in peer review by the expert epidemiologic scientists. The present pilot survey was aimed to measure the health effects 30 years post disaster in MIC-exposed survivors.

Complexity of chromosomal rearrangements in Down syndrome leukemia.

Reports on imbalanced HSA21 gene expression and chromosomal rearrangements on leukemogenesis, drug sensitivity, and treatment outcome of leukemia in Down syndrome (DS) are limited. DS has been recognized as one of the most common leukemia-predisposing syndromes with unique clinical features, significant differences in treatment outcome and treatment-related toxicity profiles. Acute myeloid leukemia (AML), especially acute megakaryocytic leukemia, is reported with high cure rates presenting 80%-100% event-free survivals (EFSs); however, acute lymphoid leukemia indicates a worse prognosis in DS patients compared to non-DS children.

Spectrum of complex chromosomal aberrations in a myelodysplastic syndrome and a brief review.

Myelodysplastic syndrome (MDS) is a heterogeneous premalignant condition characterized by cytopenia, ineffective hematopoiesis, dysplastic marrow, and risk of progression to acute myeloid leukemia. Cytogenetic abnormalities, including del(3q/5q/7q/11q/12p/20q), monosomy 5/7, trisomy 8/19, i(17q), and -Y, are the indicators of diagnosis and risk stratification. The present case with bicytopenia detected with highly complex chromosome rearrangements with variability in numerical and structural combinations.

Clinical expression of an inherited unbalanced translocation in chromosome 6.

Unbalanced chromosomal rearrangements are not common; however, they have a significant clinical expression. The parental balanced translocation produces unbalanced chromosome, which is transmitted to next generation through fertilization of gametes carrying the derivative chromosome. The carriers of balanced rearrangements mostly do not have recognizable phenotypic expression.

Conventional and fluorescence in situ hybridization analysis of three-way complex BCR-ABL rearrangement in a chronic myeloid leukemia patient.

Chromosomal analysis was carried out in bone marrow sample of an 11-year-old girl suspected of myeloproliferative disorder. Conventional G-banding study detected a complex three-way translocation involving 7, 9 and 22, which has resulted in the formation of a variant Philadelphia chromosome causing rearrangement of abl and bcr genes in 87% cells. Fluorescence in situ hybridization (FISH) confirmed the fusion of bcr-abl oncogene.