Increase in the prevalence of the MTHFR 677 TT polymorphism in women born since 1959: potential implications for folate requirements.

BACKGROUND/OBJECTIVES: Folate has been recognized to ensure reproductive health and there is a growing body of epidemiological evidence suggesting that the methylenetetrahydrofolate reductase (MTHFR) 677T allele and reduced dietary folate may increase the risk of cervical cancer. The main focus of our survey was to investigate the distribution of the MTHFR C677T polymorphism in relation to women's year of birth and to assess their folate intake and folic acid supplementation. SUBJECTS/METHODS: During a 6-months period, 307 healthy women of childbearing age in Catania, Italy, were enrolled in the cross-sectional study. Folate intake was estimated by a semiquantitative food frequency questionnaire and DNA extracted from blood samples for MTHFR C677T genotyping. RESULTS: A TT genotype frequency of 20.5% with an increase in the prevalence of the TT genotype in the cohort of women born since 1959 was shown. The prevalence of inadequate folate intake was 51.5%, significantly higher in non-pregnant women (83.4%) than in pregnant ones (12.3%) with a decrease during the three trimesters of pregnancy (from 25.7 to 5.0%; P=0.013). The use of folic acid supplements improved during the three trimester of pregnancy (from 71.4 to 95.0%; P=0.001). CONCLUSIONS: Healthy young women may have higher folate needs due to increasing prevalence of the T allele and reduced folate intake compared with older groups. However, clinicians should be cautious when recommending supplements to women in late pregnancy due to the possible implications in the pregnancy outcome.

Increased tumor cell multiplication after radiofrequency lesions in median hypothalamus in the mouse and rat.

A significant increase of cell multiplication in inoculated ascitic and solid tumors was demonstrated in both DBA/2 and C57BL/6 mice as well as in Wistar rats after radiofrequency lesions in the median hypothalamus (ventromedial and dorsomedial nuclei; part of arcuate nucleus). The following tests were performed: mitotic and metaphasic index, doubling time of tumor, incorporation of tritiated thymidine into DNA, cell cycle parameters and growth fraction. The increased rate of cell proliferation measured was predominantly due to the higher speed of DNA biosynthesis with a minor contribution by an increase of the growth fraction. In the animals with hypothalamic lesions we demonstrated a slight decrease in the secretory activity of the adenohypophysis. Because it is generally stated that failure of hypophysis function hinders cell multiplication in normal and neoplastic tissues, we think that heightened cell proliferation after hypothalamic lesions is due to suppression of an inhibitory mechanism located in the hypothalamus and which is independent of the hypophysis.

Radiofrequency destruction of the tuberoinfundibular region of hypothalamus permanently abrogates NK cell activity in mice.

Natural killer (NK) cells have an important role in non-adaptative resistance to tumours and their metastatic spread in vivo. Maturation of NK cells and the intensity of their activity are affected by many endogenous and external factors, as well as by regulatory cells. The possibility that some effects of the central nervous system on tumour resistance are mediated via NK activity has also been suggested. Destruction of the tuberoinfundibular region of the hypothalamus in rodents led to a significant increase in tumour growth. We show here that destruction of its ventromedial, dorsomedial and arcuate nuclei persistently abrogates NK activity in mice. By contrast, cortical lesion and operative stress depress it partially, and for a brief period only. Abrogation is the result of a block of NK lineage maturation, causing a severe decrease in the number of large granular lymphocytes (LGL), a lymphocyte population associated with NK activity. Macrophage, B- and T- lymphocyte functions, however, are not significantly affected. Agents inducing NK-cell maturation or activation such as polyinosinic-polycytidylic acid (poly(I:C], interferon (IFN) and interleukin-2 (IL-2) restore NK activity, and normalize the number of LGL.

Growth of Yoshida ascites tumor in the rat after radiofrequency destruction of the tuberoinfundibular region of the hypothalamus.

The mitotic index of Yoshida ascites tumor cells was significantly higher in rats that underwent tuberoinfundibular destruction than those lesioned in other regions of the hypothalamus or in the cerebral hemispheres or in sham-operated animals. Survival was shorter in the rats lesioned in the tubero-infundibular and posterior hypothalamic regions. The rise in the mitotic index of Yoshida ascites tumor cells is consistent with the results of previous work showing significantly increased cell proliferation in the normal tissues of animals lesioned in the tuberoinfundibular region.