ROLE OF VITAMIN-D3 AND RETINOIC ACID IN A HUMAN THP-1 MACROPHAGE MODEL OF MYCOBACTERIUM TUBERCULOSIS INFECTION

Mycobacterium tuberculosis (Mtb) replicates within the human macrophages and we investigated the activating effects of retinoic acid (RA) and vitamin D3 (VD) on macrophages in relation to the viability of Mtb. A combination of these vitamins (RAVD) enhanced the receptors on THP-1 macrophage (Mannose receptor and DC-SIGN) that increased mycobacterial uptake but inhibited thesubsequent intracellular growth of Mtb by inducing reactive oxygen species (ROS) and autophagy. RAVD also enhanced antigen presenting and homing receptors in THPs that suggested an activated phenotype for THPs following RAVD treatment. RAVD mediated activation was also associated with a marked phenotypic change in Mtb infected THPs that fused with adjacent cells to formmultinucleate giant cells (MNGCs). Typically MNGCs occurred over 30 days of in vitro culture and contained non-replicating persisting Mtb for as long as 60 days in culture. We propose that the RAVD mediated inhibition of replicating Mtb leading to persistence of non-replicating Mtb within THPs may provide a novel human macrophage model simulating formation of MNGCs in humanlungs.

Food Politics: How the Food Industry Influences Nutrition and Health, Revised and Expanded Edition

A review of Food Politics: How the Food Industry Influences Nutrition, and Health, Revised and Expanded Edition.

Neural tube defects in Mexican-Americans living on the US-Mexico border: The effects of folic acid and dietary folate

Neural tube defects (NTDs) are malformations of the developing brain and spinal cord; the most common are anencephaly and spina bifida. Evidence from many populations suggests that 50% of NTDs can be prevented through daily consumption of folic acid. A recent study has reported that folic acid may not protect populations of Mexican descent. This finding has serious implications for women living along the US-Mexico border. Not only is risk high in these Mexican American women compared with other US women; they also differ markedly in supplemental folic acid and dietary folate consumption, and in NTD-related risks (e.g., obesity, diabetes). This case-control study investigated whether folic acid supplements and dietary folate reduces NTDs in Mexican Americans. Cases included liveborn, stillborn, electively and spontaneously aborted NTD-affected fetuses and infants occurring in the 14-county Texas-Mexico border. Controls were randomly selected from unaffected live births, frequency matched to cases by hospital and year. An in-person interview of 110 case and 113 control mothers solicited data on folic acid supplements, dietary folate, and other covariates. Consumption of folic acid-containing vitamins before conception was only 5% for both case and control women. Taking vitamins the trimester before conception had no apparent effect, after adjusting for covariates [odds ratio (OR) = 1.0, 95% confidence interval (CI) = 0.3–3.4]. Combining folate from vitamins and diet showed a 20% risk reduction for women consuming at least 400 μg of folate daily [OR = 0.8, 95% CI = 0.5–1.5]; however, this estimate is statistically indistinguishable from the null. Although consistent with an inherent ineffectiveness of supplemental folic acid, that so few women consumed multivitamins during the critical time severely limited the assessment of folic acid in this population. A reduced folate response in Mexican descent women may be due to a genetic heterogeneity for metabolizing folate. Alternatively, folate intakes may be insufficient to overcome other underlying risk factors. In conclusion, determining whether folic acid reduces NTD risk in Mexican American women requires further study in populations with higher folic acid exposures. Meanwhile, we should pursue all recommended prevention strategies to reduce risk, including motivating Mexican American women of childbearing age to take folic acid routinely. ^

Modification of mutagen sensitivity by chemopreventive agents {\it in vitro\/}

The clinical application of chemopreventive agents is expected to prevent the appearance of cancer by arresting carcinogenesis or reversing it in the precancerous stages. The hypothesis of the present investigations was that chemopreventive agents (retinoids and antioxidant vitamins) may counteract the clastogenic effects of bleomycin in vitro in both lymphoblastoid cell lines and primary lymphocyte cultures and that a similar phenomenon can be detected in lymphocytes from individuals treated with 13-cis-retinoic acid. The efficacy of 13-cis-retinoic acid, n-(4-hydroxyphenyl)-retinamide, ascorbic acid, n-acetyl-l-cysteine, alpha-tocopherol, and alpha-tocopherol-acid succinate was tested against bleomycin-induced chromosomal breakage.^ The results provided direct evidence of the concentration-related protective effects of these agents against bleomycin-induced clastogenicity in cultures of human lymphoblastoid cell lines in vitro. Similar anticlastogenic protection was demonstrated with 13-cis-retinoic acid, ascorbic acid, n-acetyl-l-cysteine, and alpha-tocopherol-acid succinate in primary lymphocyte cultures in vitro. The in vitro anticlastogenic effect of 13-cis-retinoic acid was also demonstrated in lymphocyte cultures from peripheral blood samples from patients treated with this retinoid.^ An important consideration is that the concentrations used in the present investigations are comparable to those achieved in clinical situations.^ The in vitro anticlastogenic effect of these retinoids and antioxidants may constitute an important element of their chemopreventive properties. The results corroborate the hypothesis that these compounds may be effective in clinical chemoprevention trials. The bleomycin-assay may also be used as a short-term test to evaluate the antimutagenic effects of various agents. ^

AN ESTIMATION OF IN UTERO DRUG EXPOSURE BY DETERMINANTS OF FREQUENCY AND DISTRIBUTION OF MATERNAL DRUG CONSUMPTION

Data derived from 1,194 gravidas presenting at the observation unit of a city/county hospital between October 11, 1979 through December 7, 1979 were evaluated with respect to the proportion ingesting drugs during pregnancy. The mean age of the mother at the time of the interview was 22.0 years; 43.0 percent were Black; 34.0 percent Latin-American, 21.0 percent White and 2.0 percent other; mean gravida was 2.5 pregnancies; mean parity was 1.0; and mean number of previous abortions was 0.34. Completed interview data was available for 1,119 gravida, corresponding urinalyses for 997 subjects. Ninety and one-tenth percent (90.1 percent) of the subjects reported ingestion of one or more drug preparation(s) (prescription, OTC, or substances used for recreational purposes) during pregnancy with a range of 0 to 11 substances and a mean of 2.7. Dietary supplements (vitamins and minerals) were most frequently reported followed by non-narcotic analgesics. Seventy-six and one tenth percent (76.1 percent) of the population reported consumption of prescription medication, 42.5 percent reported consumption of over-the-counter medications, 45.7 percent reported consumption of a substance for recreational purposes and 4.3 percent reported illicit consumption of a substance. For selected substances, no measurable difference was found between obtaining the information from the interview method or from a urinalysis assay. ^