Methylenetetrahydrofolate reductase (MTHFR) is one of the main regulatory enzymes of homocysteine metabolism. Previous studies revealed that a common mutation in MTHFR gene C677T is related to hyperhomocysteinemia and occlusive vascular pathology. In the current study, we determined the prevalence of a newly described mutation in the human MTHFR gene A1298C, and the already known C677T mutation, and related them to plasma total homocysteine and folate concentrations. We studied 377 Jewish subjects, including 190 men and 186 women aged 56.8 +/- 13 y (range 32-95 y). The frequency of the homozygotes for the A1298C and the C677T MTHFR mutations was common in the Jewish Israeli population (0.34 and 0.37, respectively). Subjects homozygous (TT) for the C677T mutation had significantly greater plasma total homocysteine concentrations (P < 0.01) than subjects without the mutation (CC). Homozygotes (CC) for the A1298C mutation did not have elevated plasma total homocysteine concentrations. Our study indicated that subjects with the 677CC/1298CC genotype had significantly lower concentrations (P < 0. 05) than those with a 677CC/1298AA genotype. Neither mutation (the A1298C and the C677T) was associated with established cardiovascular risk factors such as hypertension, elevated total cholesterol or body mass index.
Aging and cancer are highly correlated biological phenomena. Various cellular processes such as DNA damage responses and cellular senescence that serve as tumor suppressing mechanisms throughout life result in degenerative changes and contribute to the aging phenotype. In turn, aging is considered a pro-tumorigenic state, and constitutes the single most important risk factor for cancer development. However, the causative relations between aging and cancer is not straight forward, as these processes carry contradictory hallmarks; While aging is characterized by tissue degeneration and organ loss of function, cancer is a state of sustained cellular proliferation and gain of new functions. Here, we review the molecular and cellular pathways that stand in the base of aging related cancer. Specifically, we deal with the inflammatory perspective that link these two processes, and suggest possible molecular targets that may be exploited to modify their courses.
Contrast material caused a small but significant increase in Cr blood level in high-risk patients. There is no advantage of dopamine over adequate hydration in patients with mild to moderate renal failure or DM undergoing coronary angiography. Dopamine should be avoided in patients with PVD exposed to contrast medium.
Mutations of the methylenetetrahydrofolate reductase (MTHFR) gene have been shown to be associated with a predisposition to developing diabetic nephropathy (DN) in specific populations. The frequency of two MTHFR mutations, a recently described mutation in the human MTHFR gene A1298C and C677T, whose association with DN is already known, was determined in an Israeli Jewish population with type 2 diabetes mellitus (DM). Both A1298C and C677T are highly prevalent in the diabetic population with allele frequencies of 0.35 and 0.36, respectively. The genotype frequency and allele frequency for these two polymorphisms in patients who are normoalbuminuric (n = 55) were compared with those of patients who had either micro- or macroalbuminuria (n = 43). For both polymorphisms, there were no significant differences in either the genotype distribution or allele frequency in patients with or without DN. However, in patients with serum folate <15.4 nmol/L, there was a greater incidence of DN in those patients who were homozygous or heterozygous for the C677T mutation. For the A1298C mutation, there is evidence suggesting that the homozygous state may be protective in patients with low-normal serum folate. Folate supplementation in diabetic patients with the C677T mutation and low-normal serum folate may prevent the onset or retard the progression of DN.
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