Manganese (Mn), a neurotoxin causing Manganism a Parkinsons‐like disease, disrupts dopamine (DA) neurons, but the neurotoxic mechanism is not fully resolved. Reports postulate it more related to DA neuron dysfunction than degeneration. Lateral gill cilia of Crassostrea virginica are controlled by serotonergic‐dopaminergic innervations from their ganglia. DA causes cilio‐inhibition, serotonin (HT) cilio‐excitation. We showed post‐synaptic DA receptors in gill lateral cells are D2 type and Mn blocks effects of DA by blocking DA post‐synaptic receptors. The adenylyl cyclase component of the D2 signal transduction pathway was not effected by Mn. Phospholipase C (PLC), another component of the D2 signal transduction pathway, is inactivated by DA. We hypothesized PLC is not effected by Mn. We measured cilia beating using stroboscopic microscopy. Adding HT (10‐6 ‐ 10‐3M) to gill increased beating to 25 beats/min. Adding DA (10‐6 ‐ 10‐3M) decreased rates to 0. Mn (100 µM) prevented the cilio‐inhibitory response. m3M3FBS (10‐6 ‐ 10‐3M), a PLC activator, increased beating. U73122 (10‐6 ‐ 10‐4M), a PLC inhibitor, decreased beating. Mn (100 µM) had no effect on the actions of either drug. The study helps elucidate the neurotoxic mechanism of action of Mn by showing Mn disrupts dopamine’s actions at D2 post‐synaptic receptors, but not at the level of adenylyl cyclase or PLC in the signal transduction pathway. Grant Funding Source: NIH‐ 2R25GM0600309, NSF‐ 0622197, NYSED‐ 0516041071
Journal of Patient-Centered Research and Reviews ( JPCRR) is a peerreviewed scientific journal whose mission is to communicate clinical and bench research findings, with the goal of improving the quality of human health, the care of the individual patient, and the care of populations. used, including variants of delirium, altered mental status, acute confusional state, acute brain syndrome, acute brain failure, metabolic encephalopathy, predict, predictive, prediction, models, modeling, scores, scoring, tests, testing, rules, index and indices. The bibliographies of included studies were examined, and no additional articles were referenced. Results: To appropriately extract data from the 12 studies meeting inclusion criteria, the following parameters were used: study description, study population, delirium assessment method, incidence of delirium, and risk factors for delirium. Quality for cohort studies was assessed using "NewcastleOttawa Quality Assessment Scale" ranging from 1 to 9 (1 = poor quality, 9 = high quality). Overall incidence of delirium in the studies ranged from 4% to 26%. Most common risk factors for delirium were dementia, decreased functional status, blood urea nitrogen to creatinine ratio, infection and severe illness. Other variables less common were alcohol, malignancy, history of delirium, older age, medications, physical restraints, malnutrition, admitted from other than home and an iatrogenic event. The quality of studies ranged from 4 to 8. Conclusion: This systematic review summarizes the medical literature on risk prediction models for delirium in hospitalized older patients. We will use this information to develop an EHRgenerated delirium risk prediction model to be used by the "Hospital Elder Life Program" to reduce delirium incidence.
MEDICAL JOURNAL823 of the society more than a third suffered from nutriti9nal anaemia. Can that be without effect on output? Those who hearken to vapourings about "all being well" and "there is no malnutrition in the country" live in a world of their own. What a chance for the iron-containing wheatmeal bread could be found among those munition workers! But Lord Woolton has decided it is not necessary. When will the Ministry of Health direct matters of nutrition?-I am, etc.,
Lateral gill cilia of Crassostrea virginica are controlled by a serotonin‐dopamine (DA) innervation. DA is an inhibitory transmitter at gill causing cilio‐inhibition. Manganese (Mn) is a neurotoxin causing Manganism in people exposed to high levels in air. Clinical interventions for Manganism have not been successful. Recently, p‐aminosalicylic acid (PAS) was reported to provide effective treatment of Manganism. PAS is an anti‐inflammatory drug with chelating properties. We showed treatments of C. virginica with Mn disrupts DA innervation of gill. Pre‐or co‐treatments with PAS or EDTA prevented it. We hypothesized chelating agents would be effective in reversing neurotoxic effects of Mn when applied after Mn. We used gills of C. virginica to measure lateral cilia beating rates of preparations treated first with Mn followed by treatments with either PAS, EDTA or DMSA (meso‐2,3‐dimercaptosuccinic acid). Dose responses of PAS, EDTA and DMSA (10−11–10−4M) against beating were conducted after 100 FM of Mn was added to gill. All 3 drugs reversed the neurotoxic effects of Mn in a dose‐dependent manner. DMSA was the most potent. The study demonstrates these chelators are effective in reversing acute neurtoxicity of Mn. This information should be of interest to those designing therapeutic drug treatments for Manganism. Supported by 2R25GM06003 of NIGMS, 0516041171 of NYSDOE and 0622197 of NSF.
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