succimer and Skin-Diseases

The cytotoxicity of the arsenical vesicant Lewisite was assessed in first passage cultures of proliferating neonatal human skin keratinocytes. Both munitions grade and distilled Lewisite were extremely toxic with LC(50) values in the low ng/ml range, with no significant differences between them. This similarity in toxicity was also mirrored with respect to their toxic effects on hairless guinea pig skin. Two-, 4- and 6-min vapour exposures of these agents resulted in similar and severe skin injury that was obvious by 3-5h post-exposure and almost maximal at 24h. The toxicity of Lewisite in culture was temperature dependent, with a >10-fold reduction in 24h LC(50) values as the incubation temperature was reduced from 37 to 25 degrees C. However, this cooling induced protection was not persistent. In contrast, cooling of Lewisite exposed hairless guinea pig skin at approximately 10 degrees C for as little as 30 min post-exposure resulted in dramatic and permanent protection, with 4h of cooling almost completely eliminating Lewisite induced skin injury. Further, significant protection was also evident even when cooling was delayed for as long as 2h post-Lewisite exposure. In an effort to investigate whether cooling might also increase the window in which chelation therapy against this vesicant agent would be useful, we examined the protective effects of the heavy metal chelator dimercaptosuccinic acid (DMSA). Topical application to Lewisite exposed skin was extremely protective, even when delayed for 2h after Lewisite. Cooling of Lewisite exposed skin for 2h, followed by DMSA topical application resulted in decreased skin injury compared to either treatment in isolation. It appears that the simple and non-invasive application of cooling measures may provide not only significant therapeutic relief to Lewisite exposed skin, but that it may also increase the therapeutic window in which medical countermeasures against this vesicant agent are useful.

Topics: Animals; Arsenicals; Cell Survival; Cells, Cultured; Chelating Agents; Chemical Warfare Agents; Guinea Pigs; Humans; Hypothermia, Induced; Keratinocytes; Male; Skin Diseases; Succimer

Chronic arsenic toxicity due to drinking arsenic-contaminated water has been one of the worst environmental health hazards affecting eight districts of West Bengal since the early eighties. Detailed clinical examination and investigation of 248 such patients revealed protean clinical manifestations of such toxicity. Over and above hyperpigmentation and keratosis, weakness, anaemia, burning sensation of eyes, solid swelling of legs, liver fibrosis, chronic lung disease, gangrene of toes, neuropathy, and skin cancer are some of the other manifestations. A cross-sectional survey involving 7683 participants of all ages was conducted in an arsenic-affected region between April 1995 and March 1996. Out of a population of 7683 surveyed, 3467 and 4216 people consumed water containing As below and above 0.05 mg/L, respectively. Except pain abdomen the prevalence of all other clinical manifestations tested (e.g., pigmentation, keratosis, hepatomegaly, weakness, nausea, lung disease and neuropathy) were found to be significantly higher in As exposed people (water As > 0.05 mg/L) compared to control population (water As level < 0.05 mg/L). The prevalence of pigmentation and keratosis, hepatomegaly, chronic respiratory disease and weakness rose significantly with increasing arsenic concentrations in drinking water. The respiratory effects were most pronounced in individuals with high arsenic water concentrations who also had skin lesion. Therapy with chelating agent DMSA was not found to be superior to placebo effect. However, therapy with DMPS caused significant improvement of clinical condition of chronic arsenicosis patients as evidenced by significant reduction of total clinical scores from 8.90 +/- 2.84 to 3.27 +/- 1.73; p < 0.0001. Efficacy of specific chelation therapy for patients suffering from chronic As toxicity has further need to be fully substantiated. However, supportive treatment could help in reducing many symptoms of the patients. Treatment in hospital with good nutritious diet has been found to reduce symptom score in a subset of placebo treated patients in West Bengal during the course of DMSA and DMPS trial. People should be advised to stop drinking As contaminated water or exposure to As from any other source. The various clinical manifestations should be treated symptomatically.

Topics: Abdominal Pain; Adult; Arsenic Poisoning; Chelating Agents; Chemical and Drug Induced Liver Injury; Cross-Sectional Studies; Female; Humans; India; Male; Middle Aged; Nausea; Nervous System Diseases; Nutritional Support; Pulmonary Fibrosis; Skin Diseases; Succimer; Water Supply