Risk of colorectal cancer associated with the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in the Kashmiri population.

Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA synthesis, DNA repair and DNA methylation. The two common functional polymorphisms of MTHFR, 677 C→T and 1298 A→C, have been shown to impact various diseases, including cancer. The 677 C→T polymorphism has been widely investigated in different cancers and has been implicated as a risk factor for the development of various cancers. We investigated MTHFR C677T genotype frequency in colorectal cancer cases in the Kashmiri population and correlated this information with the known clinicopathological characters of colorectal cancer, in a case-control study. Eighty-six colorectal cancer cases were studied for MTHFR C677T polymorphism, compared to 160 controls taken from the general population, employing the PCR-RFLP technique. We found the frequency of the three different genotypes of MTHFR in our ethnic Kashmir population, i.e., CC, CT and TT, to be 68.6, 20.9 and 10.4% among colorectal cancer cases and 75.6, 16.9 and 7.5% among the general control population, respectively. There was a significant association between the MTHFR TT genotype and colorectal cancer in the higher age group. We conclude that the MTHFR C677T polymorphism slightly increases the risk for colorectal cancer development in our ethnic Kashmir population.

Study on Prevalence of lodine Deficiency Disorder and Salt Consumption Patterns in Jammu Region.

RESEARCH QUESTION: What is the situation of iodine deficiency disorder (IDD) and salt consumption in Jammu region? HYPOTHESIS: The prevalence of IDD has decreased markedly as a result of medical as well as socio-economic factors. OBJECTIVE: To assess the magnitude of IDD in Jammu region and also assess the salt consumption patterns in the region. DESIGN: Cross-sectional study. SETTING: Primary schools in both urban and rural areas. STUDY TOOLS: Clinical examination of study population for goiter, laboratory assessment of casual urine sample for urinary iodine estimation of I(2) content of salt samples collected from sub-samples of study population. PARTICIPANTS: School children in the age group of 6-12 years were selected for study using WHO 30-cluster methodology, urine samples were collected from 15% of selected children and salt samples from 5% of sub-sample. ETHICAL CONCERN: No ethical issues were involved. RESULTS: An overall goiter prevalence of 11.98% was observed in the region. Females had a prevalence of 16.1% and males 10.1%. The median urinary iodine excretion in the region was 96.5 mug/l (range: 29.0-190.0 mug/l). Forty-nine percent of subjects had biochemical iodine deficiency with 6.7% having moderate and 42.53% mild iodine deficiency. In Jammu region, 74.47% of households consume powdered salt with 98.17% powdered salt samples having an I(2) content of greater than 15 ppm. CONCLUSION: Iodine deficiency remains a public health problem in the region, though the region seems to be in a state of nutritional transition from iodine deficiency to iodine sufficiency.

Effect of exogenous copper on lipid peroxidation in rat hepatocytes. Possible involvement of protein kinase C.

We have investigated the direct effect of copper on malondialdehyde formation in rat isolated hepatocytes. Copper was found to decrease the cell viability with concomitant production of malondialdehyde in a time related manner. In addition the protein kinase C activator, PMA, was found to have a synergistic effect with copper on rat hepatocytes. These results indicate that protein kinase C may be important in mediating hepatotoxicity after exposure to copper.

Intracellular cAMP determines the extent of degradation and not the synthesis of collagen by rat hepatocytes.

Intracellular collagen degradation in normal rat hepatocytes was exponentially stimulated by db-cAMP (10-100 microM). The effect was manifested as a decrease (p less than 0.01) in net collagen production. The extent of degradation directly co-related with the intracellular cAMP levels, only up to a threshold concentration (16.2 +/- 1.3 p moles/10(6) cells) elicited by 100 microM of db-cAMP. Higher concentrations induced no further increment. Forskolin adenylate cyclase activator (10-50 microM), produced similar effects demonstrating cAMP dependence of the phenomenon. Both db-cAMP as well as Forskolin stimulated collagen degradation (p less than 0.05) in hepatocytes from rats administered CCL4. However, the extent of stimulation was significantly (p less than 0.01) less compared to that observed in normal hepatocytes. Our data demonstrates that elevated cAMP levels regulate net collagen content by signalling intracellular collagen degradation and not synthesis.

Collagen-stimulated superoxide production: evidence for coupled mobilization of calcium.

Superoxide production by human neutrophils was stimulated by rat liver collagen. The stimulation was exponentially related to the collagen concentration, with maximal effect at 150 micrograms/ml. The collagen-induced effect was significantly enhanced by the presence of Ca2+ in the medium. Verapamil--a calcium channel blocker--caused a dose-dependent inhibition of superoxide production by collagen-stimulated neutrophils. Collagen-induced stimulation was associated with a transient rise in cytosolic free Ca2+ independent of the presence of Ca2+ in the medium. Depletion of intracellular calcium caused a significant decrease in superoxide activity; however, replenishment of Ca2+ in the medium significantly overcame the inhibition. These changes were associated with a direct binding of [14C]collagen with the neutrophils. Our data suggest that collagen-neutrophil interaction couples superoxide production with the process of Ca2+ mobilization and that this interaction may play a physiologic role in neutrophil stimulation.