Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 20-year-old male who attempted suicide by injecting subcutaneously 10 ml of Sistemin 40 (40% dimethoate) was admitted 16 h later. General weakness, muscular fibrillations and a marked inhibition of red blood cell and serum cholinesterases were the prominent signs of intoxication. The antidotal treatment of intermittent boluses of atropine, oxime HI-6 and diazepam was combined with symptomatic therapy. Cholinesterase activity decreased within the next 3 d. In contrast to the marked general improvement of the patient, the return of cholinesterase activities was very slow. The patient was discharged 24 d after the poisoning with no notable consequences which could be ascribed to the intoxication.
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PMID:A case of unusual suicidal poisoning by the organophosphorus insecticide dimethoate. 232 50

BMT has become an important therapy for many hematologic disorders. Following BMT, the recipient may develop GVHD when it appears that immunocompetent donor lymphocytes react to host antigens. Acute and chronic GVHD represent two distinct syndromes. Acute GVHD has not been associated with primary neurologic involvement. Polymyositis has been reported in 12 patients with chronic GVHD, with the most common underlying illness being aplastic anemia. The clinical, serologic, and muscle biopsy features of the myositis in GVHD have been similar to those observed in idiopathic polymyositis. Weakness was moderate to severe and responded to prednisone, sometimes with the addition of azathioprine. Prognosis depended upon the underlying disease and not on the severity of the myositis. MG occurs rarely in chronic GVHD. Most patients with MG and GVHD have had aplastic anemia; those with aplastic anemia are more likely to have anti-AchR prior to BMT. The clinical manifestations of GVHD MG have not differed from classic autoimmune MG; each patient had elevated antiacetylcholine receptor antibodies titers. All patients have responded well to cholinesterase inhibitors but have received other immunosuppressants. These observations suggest that aplastic anemia is an important host factor in the development of the autoimmune disorders seen with chronic GVHD, certainly of myositis and MG. Herpes zoster peripheral nerve infections have occurred in patients with chronic GVHD. One patient had mononeuritis multiplex. In both acute and chronic GVHD, CNS impairment is usually caused by metabolic encephalopathy or infection. Primary CNS involvement has not been recognized.
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PMID:Neurologic complications of graft-versus-host disease. 304 48

In order to clarify the later sequelae of sarin poisoning that occurred in Matsumoto City, Japan, on June 27, 1994, a cohort study was conducted on all persons (2052 Japanese people) inhabiting an area 1050 meters from north to south and 850 meters from east to west with the sarin release site in the center. Respondents numbered 1237 and 836 people when surveys were conducted at one and three years after the sarin incident, respectively. Numbers of persons with symptoms of sarin toxicity were compared between sarin victims and non-victims. Of the respondents, 58 and 46 people had symptoms associated with sarin such as fatigue, asthenia, shoulder stiffness, asthenopia and blurred vision at both points of the survey, respectively. The prevalences were low; some complained of insomnia, had bad dreams, difficulty in smoking, husky voice, slight fever and palpitation. The victims who had symptoms one year after the incident had a lower erythrocyte cholinesterase activity than did those who did not have symptoms at the early stage; such persons lived in an area with a 500 meter long axis north east from the sarin release site. The three-year cohort study clearly showed that the odds ratios of almost all of the symptoms were high in the sarin-exposed group, suggesting a positive relationship between symptoms and grades of exposure to sarin. These results suggest that symptoms reported by many victims of the sarin incident are thought to be sequelae related to sarin exposure.
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PMID:Sequelae of sarin toxicity at one and three years after exposure in Matsumoto, Japan. 1061 67

According to the cholinergic hypothesis, the impairment of cognitive function and the behavioural disturbances that affect patients with Alzheimer's disease are mainly due to cortical deficiencies in cholinergic transmission. Numerous cholinesterase inhibitors have been investigated for treatment of this disease, the rationale being to support the cholinergic system by blocking the degradation of acetylcholine released from presynaptic neurons. These drugs can be classified as reversible (tacrine, donepezil and galantamine), pseudo-reversible (physostigmine, eptastigmine and rivastigmine) or irreversible (metrifonate) enzyme inhibitors. This article reviews efficacy and tolerability results from 6-month placebo-controlled studies of 7 cholinesterase inhibitors: tacrine (80 to 160 mg/day), donepezil (5 to 10 mg/day), rivastigmine (1 to 12 mg/day), metrifonate (30 to 80 mg/day), eptastigmine (30 to 60 mg/day), physostigmine (30 to 36 mg/day) and galantamine (8 to 32 mg/day). All these agents have demonstrated a statistically significant, although modest, effect versus placebo on the cognitive and global performance of patients with Alzheimer's disease. Dramatic clinical response has been seen in only 3 to 5% of patients. There are no major differences in terms of efficacy between the different drugs. The mean difference between drug and placebo effects on standardised psychometric scales is about 2 to 4 points on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog; a 70-point cognitive scale) and 0.2 to 0.5 points on the Clinician's Interview-Based Impression of Change with Caregiver Input (CIBIC-Plus; a 7-point global scale), or 5 to 14% of the average value of the scales. The most common adverse effects observed after administration of cholinesterase inhibitors are nausea, vomiting, diarrhoea, dizziness, asthenia and anorexia, all symptoms linked to cholinergic overstimulation. These effects are dose related and largely depend on the degree of cholinesterase inhibition. Also important is the rate of onset of cholinesterase inhibition, which depends on the kinetics of enzyme inhibition, the presence and rate of titration, and the pharmacodynamic peak-to-trough fluctuations. A model predicting the incidence of nausea based on acetylcholinesterase inhibition and the half-life of acetylcholinesterase recovery is proposed. In conclusion, cholinesterase inhibitors are the only pharmacological agents proved to be effective for the treatment of Alzheimer's disease in large, long term, double-blind, placebo-controlled trials. While the efficacy of different cholinesterase inhibitors is similar, their tolerability profiles differ. For example, the incidence of nausea (in excess of that seen with placebo) at cognitively effective dosages ranges from 1% with eptastigmine 60 mg/day to 53% with physostigmine 30 mg/day. Differences in tolerability profile may be due to the extent of peripheral acetylcholinesterase inhibition needed to reach clinical efficacy. Other contributing pharmacodynamic factors are the rate of onset of and fluctuations in acetylcholinesterase inhibition at steady state.
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PMID:Pharmacodynamic-tolerability relationships of cholinesterase inhibitors for Alzheimer's disease. 1147 43

Two terrorist attacks with the nerve agent Sarin affected citizens in Matsumoto and Tokyo, Japan in 1994 and 1995, killing 19 and injuring more the 6000. Sarin, a very potent organophosphate nerve agent, inhibits acetylcholinesterase (AchE) activity within the central, peripheral, and autonomic nervous systems. Acute and long-term Sarin effects upon humans were well documented in these two events. Sarin gas inhalation caused instantaneous death by respiratory arrest in 4 victims in Matsumoto. In Tokyo, two died in station yards and another ten victims died in hospitals within a few hours to 3 months after poisoning. Six victims with serum ChE below 20% of the lowest normal were resuscitated from cardiopulmonary arrest (CPA) or coma with generalized convulsion. Five recovered completely and one remained in vegetative state due to anoxic brain damage. EEG abnormalities persisted for up to 5 years. Miosis and copious secretions from the respiratory and GI tracts (muscarinic effects) were common in severely to slightly affected victims. Weakness and twitches of muscles (nicotinic effects) appeared in severely affected victims. Neuropathy and ataxia were observed in small number (less than 10%) of victims, which findings disappeared between 3 days and 3 months. Leukocytosis and high serum CK levels were common. Hyperglycemia, ketonuria, low serum triglyceride, hypopotassemia were observed in severely affected victims, which abnormalities were attributed to damage of the adrenal medulla. Oximes, atropine sulphate, diazepam and ample intravenous infusion were effective treatments. Pralidoxime iodide IV reversed cholinesterase and symptoms quickly even if administered 6 h after exposure. Post Traumatic Stress Disorder (PTSD) was less than 8% after 5 years. However, psychological symptoms continue in victims of both incidents. In summary, both potent toxicity and quick recovery from critical ill conditions were prominent features. Conventional therapies proved effective in Sarin incidents in Japan.
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PMID:Sarin experiences in Japan: acute toxicity and long-term effects. 1696 40