The enigma of arsenic carcinogenesis: role of metabolism

Inorganic arsenic is considered a high-priority hazard, particularly because of its potential to be a human carcinogen. In exposed human populations, arsenic is associated with tumors of the lung, skin, bladder, and liver. While it is known to be a human carcinogen, carcinogenesis in laboratory animals by this metalloid has never been convincingly demonstrated. Therefore, no animal models exist for studying molecular mechanisms of arsenic carcinogenesis. The apparent human sensitivity, combined with our incomplete understanding about mechanisms of carcinogenic action, create important public health concerns and challenges in risk assessment, which could be met by understanding the role of metabolism in arsenic toxicity and carcinogenesis. This symposium summary covers three critical major areas involving arsenic metabolism: its biodiversity, the role of arsenic metabolism in molecular mechanisms of carcinogenesis, and the impact of arsenic metabolism on human risk assessment. In mammals, arsenic is metabolized to mono- and dimethylated species by methyltransferase enzymes in reactions that require S-adenosyl- methionine (SAM) as the methyl donating cofactor. A remarkable species diversity in arsenic methyltransferase activity may account for the wide variability in sensitivity of humans and animals to arsenic toxicity. Arsenic interferes with DNA methyltransferases, resulting in inactivation of tumor suppressor genes through DNA hypermethylation. Other studies suggest that arsenic-induced malignant transformation is linked to DNA hypomethylation subsequent to depletion of SAM, which results in aberrant gene activation, including oncogenes. Urinary profiles of arsenic metabolites may be a valuable tool for assessing human susceptibility to arsenic carcinogenesis. While controversial, the idea that unique arsenic metabolic properties may explain the apparent non-linear threshold response for arsenic carcinogenesis in humans. In order to address these outstanding issues, further efforts are required to identify an appropriate animal model to elucidate carcinogenic mechanisms of action, and to define dose-response relationships.      

Predictors of psychosis severity in individuals with primary stimulant addictions

The goal of this study is to define the factors that could contribute to the development, severity, and persistence of psychotic symptoms in individuals with stimulant addiction. We hypothesize that particular drug use variables may contribute to the severity of psychiatric symptoms. Thirty-seven stimulant users, abstinent for > 30 days were recruited from the community. Previous drug use and current and past psychiatric symptoms were assessed using validated objective rating scales and several self-report questionnaires. Age at first use of the stimulant drug was inversely related to the Beck Anxiety Inventory score, and the subjects with more than 5 years duration of chronic use exhibited greater severity of symptoms on the PANSS Positive and General Scales and total score. The method of drug administration, duration of abstinence, latency from first use to regular use, and prior solicitation of treatment were not related to PANSS total and subscale scores or other clinical variables. Severity of psychosis appears to be related to earlier and longer exposure to stimulants, consistent with a “threshold” effect of stimulant use on the development of psychotic symptoms. The association may also suggest a critical developmental period that is most susceptible to the deleterious effects of stimulant exposure.     

Clinical profile of special children at asha centre

Background: The care of special children suffering from cerebral palsy, deaf mutism, mental retardation (MR) and post encephalitic sequelae etc. is done in the armed forces at “ASHA” centre supported by Army Wives Welfare Association (AWWA).     

Extended endoscopic endonasal transsphenoidal approaches in skull base Surgery Article in Russian

The article deals with endoscopic endonasal transsphenoidal surgery, which has gained great interest among the modem trends of neurosurgery. Application of extended endoscopic endonasal transsphenoidal approaches significantly advances capabilities of transsphenoidal surgery. Pituitary adenomas and some other sellar tumors which traditionally require transcranial procedure now can be removed via endonasal route.     

Neurological mechanisms of migraine: potential of the gap-junction modulator tonabersat in prevention of migraine

Migraine is a neurovascular disorder characterized by recurrent episodic headaches, and is caused by abnormal processing of sensory information due to peripheral and/or central sensitization. The exact pathophysiological mechanism underlying migraine is not fully understood; however, cortical spreading depression (CSD) is thought to provide the basis for migraine aura and may serve as a trigger of migraine pain. CSD depends on neuronal–glial cell communication, which is mediated by intercellular transfer of messengers through connexin-containing gap junctions, as well as messengers released into the extracellular space by non-junctional connexin-containing hemichannels. These processes are believed to be important in peripheral sensitization within the trigeminal ganglion and to lead to central sensitization. The novel benzopyran compound tonabersat binds selectively to a unique site in the brain. In preclinical studies, tonabersat markedly reduced CSD and CSD-associated events and inhibited gap-junction communication between neurons and satellite glial cells in the trigeminal ganglion. Together, these findings suggest that tonabersat should have clinical application in preventing migraine attacks.     

短程兰索拉唑、克拉霉素和阿莫西林三联疗法根除幽门螺杆菌在东南亚患者中的

测定和比较含兰索拉唑、克拉霉和阿莫西林的5日tid疗法和7日bid疗法根除幽门螺杆菌（H.pylori)疗效,方法：本研究为随机,双盲,对照研究。胃窦和胃体部活检经组织学检查和快速尿素酶试验确诊为H．pylori感染的患者内入研究,患者分别接受克拉霉素500mgtid,阿莫西林500mgtid和兰索拉唑每日30mg治疗5天（LAC5组）或克拉霉素500mgbid,阿莫西林500mgbid和兰索拉唑每日30mg治疗7天（LAC7组）。治疗结束至少4周后,用组织学检查和快速尿酶素试验评估H．pylori是否成功除,胃窦和胃体部活检H．pylori阴性定义为H．pylor根除,结果：108例胃患者纳入研究,LAC5组有4例患者失访;LAC7组2例患者失访,2例患者对药物不能依从。按意图治疗分析,LAC5组的根除率为85．2％[46/54,95%可信区间（CI):72.9%,93.4%],LAC7组的根除率为87．0％（47／54,95％CI：75．1,94.6%).按方案分析,LAC5组的根除率为92．90％（46／50,95％CI：80．8％,97．8％）,LAC7组的根除率为94．0％（47／50,95％CI：83.5%,98.7%),两种疗效对患者均很适宜,除LAC7组2例外,其余患者均服完规定的药物,两种疗法的副作用均较轻微,没有患者因对药物不耐受而中断治疗,最常见的副作用是味觉改变（LAC5组：64．7％,LAC7组：78．8％）。少数患者有腹泻,恶心和厌食,结论：LAC5tid疗法和LAC7bid疗法均有具有良好受性的治疗方案,根除H．pylor的疗效高。     

短程兰索拉唑、克拉霉素和阿莫西林三联疗法根除幽门螺杆菌在东南亚患者中的疗效——5日一日三次疗法和7日一日两次疗法

目的:测定和比较含兰索拉唑、克拉霉素和阿莫西林的5日tid疗法和7日bid疗法根除幽门螺杆菌(H.pylori)的疗效.方法:本研究为随机、双盲、对照研究.胃窦和胃体部活检经组织学检查和快速尿素酶试验确诊为H.pylori感染的患者纳入研究.患者分别接受克拉霉素500 mg tid、阿莫西林500 mg tid和兰索拉唑每日30 mg治疗5天(LAC5组)或克抗雷素500 mg bid、阿莫西林500 mg bid和兰索拉唑每日30 mg治疗7天(LAC7组).治疗结束至少4周后,用组织字检应查和快速尿素酶试验评估H.Pylori是否成功根除,胃窦和胃体部活检H.Pylori阴性定义为H.Pylori根除.结果:108例患者纳入研究.LAC5组有4例患者失访;LAC7组2例患者失访,2例患者对药物不能依从.按意图治疗分析,LAC5组的根除率为85.2%[46/54,95%可信区间(CI):72.9%,93.4%],LAC7组的根除率为87.0%(47/54,95%CI:75.1%,94.6%);按方案分析,LAC5组的根除率为92.0%(46/50,95%CI:80.8%,97.8%),LAC7组的根除率为94.0%(47/50,95%CI:83.5%,98.7%).两种疗法对患者均很适宜,除LAC7组2例外,其余患者均服完规定的药物.两种疗法的副作用均较轻微,没有患者因对药物不耐受而中断治疗.最常见的副作用是味觉改变(LAC5组:64.7%,LAC7组:78.8%).少数患者有腹泻、恶心和厌食.结论:LAC5 tid疗法和LAC7 bid疗法均为具有良好耐受性的治疗方案,根除H.Pylori的疗效高.