Arsenicosis: review of recent advances.

Human health in the past and presently is influenced by the amounts and proportion of chemical elements to which humans have been exposed. Arsenic, as a therapeutic agent was known to ancient Greeks and Romans. Ehrlick introduced organic arsenicals as anti linetic agents but with advent of penicillin these have nearly become obsolete. Once considered toxic, harmful to humans, arsenic is now considered an essential ultra trace element at least in animals. Now the impact of arsenic on health is more from industrial and environmental than medicinal exposure. This article reviews human exposure to arsenic in non occupational population, mostly through drinking water which is a worldwide problem, more so in south East Asia. Sources of arsenic, normal and abnormal levels in blood and tissues levels, old and new methods of estimation of arsenic, mechanism of action of arsenic in experimental animal is briefly reviewed. Old described clinical manifestation of arsenic in humans is briefly reviewed and newly described clinical manifestations in human with special emphasis on atherosclerosis, liver and diabetes are discussed. Proposed biological mechanisms in experimental animals included up regulation of inflammatory signals like cytokines and TNF-alpha, oxidative stress, hypomethylation, decreased DNA repair and apoptosis, cell proliferation, angiogenesis, activation of several enzymes like methyl transferase which converts inorganic arsenic to MMA and DMA, and GSH in in-vivo and in-vitro in experimental rat liver slices. Experimentally NAC (N-Acetyl Cysteine) treatment attenuates oxidative stress in atherosclerosis apoptosis and liver injury. GSH probably plays an important role in deactivation of the intermediate products of arsenic metabolism and prevents peroxidation of membrane lipids. Chronic human exposure has been linked to several systems in the human body: dermal (exfoliative dermatitis, keratosis, vitiligo, skin cancer), peripheral neuropathy, encephalopathy, bronchitis, pulmonary fibrosis, hepatosplenomegaly resembling NCPF, portal hypertension, peripheral vascular disease and BFD, arteriosclerosis and cancers of lung, urinary bladder, other internal organs and diabetes. Experimental and epidemiological evidence support diabetes effect of high level arsenic exposure. Low and moderate exposure to arsenic in drinking water is widely prevalent and may play a role in diabetes prevalence and needs to be studied further. Role of arsenic in Indian arteriosclerosis, diabetes and liver diseases, (cirrhosis, NCPF), need to be studied further. Study of mechanisms and enzymes mentioned need to be studied in humans exposed to arsenic and other xenobiotics. Measuring arsenic exposure, metabolic and biologic effects by newly described and simpler urine proteomics may accelerate our understanding of arsenic on health consequences.

Malnutrition and malabsorption. Effect of nutritional rehabilitation on gastrointestinal function in kwashiorkor and marasmus--a longitudinal study.

The effects of long-term feeding of an adequate diet on the progressive changes in the biochemical parameters including gastrointestinal functions in children suffering from marasmus and kwashiorkor are presented. In both groups fasting bloos sugar, blood urea nitrogen, hemoglobin, serum total proteins and albumin at admission were significantly lower than in matched controls. These parameters improved after proper dietary therapy over a period of two years. The improvement in the biochemical parameters correlated with clinical and anthropological measurement. On admission, the gastrointestinal function as assessed by various tests was poor in both the groups. This returned to normal or near normal after nutritional rehabilitation. The return was much quicker for glucose and fat absorption than for lactose and d-xylose absorption. The rate of improvement in marasmus was slower than that in kwashiorkor.

Optimum dose of histamine for maximal acid output in underweight subjects.

The effects of increasing doses of histamine acid phosphate on the gastric secretion of acid has been studied in a randomized fashion in five normal control and 15 duodenal ulcer subjects. The dose of histamine acid phosphate used in each individual was 40, 70, 76 and 80 mug/kg. and 3.2 mg. of histamine. In 12 of 20 subjects the highest mean +/- S.D. acid output was observed after a dose of 76 mug./kg. body weight. When the acid output was expressed as the percentage of the highest response with different doses of HAP, the response was maximum with 76 mug. kg. dose. Further statistical analysis by rank totals and X2r by Friedman's two-way analysis by ranks also revealed highest acid output after a 76 mug./kg. dose of HAP. These findings suggest that 76 mug./kg. is the optimum dose for maximal acid output in underweight subjects. Only one patient showed highest acid output after a 3.2 mg. dose of histamine. The mean +/- S.D. acid output after 76 mug./kg. was higher than that after a 3.2 mg. dose of histamine. Hence, for estimating maximal acid output, a weight related dose and not a fixed dose is recommended. Further, it was shown that there was significant correlation between PAO and MAO after various doses of histamine in both the groups. Hence, for clinical purposes, estimation of one hourly poststimulatory maximal acid output after a dose of 76 mug./kg. body weight of histamine acid phosphate is recommended for underweight subjects.