Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have introduced enalapril, in doses equal to or less than the 2.5 mg currently recommended, as an adjuvant to digoxin and diuretics in 17 patients of mean (SD) age 83 (5) years with severe heart failure. Only eleven patients tolerated its introduction. Unlike those reported in younger patients, all but one of the adverse drug reactions occurred 8 h or more after the first dose. Aged patients started on ACE inhibitors should be observed in hospital until stabilized on a maintenance dose. Three patients had an adverse reaction which differed in nature from those previously reported: acute confusional state, ataxia and mesenteric ischaemia. Ten patients were discharged on 5 mg or 10 mg maintenance doses of enalapril. In nine of them improvement on triple therapy was sustained for a minimum of three months. ACE inhibition was lost in the other patient when her compliance with enalapril therapy fell to around 75%: monitoring compliance is essential when ACE inhibitors are used in low dosages. Enalapril was withdrawn during follow up in three patients because of symptoms of mesenteric ischaemia and in four because of dramatic deterioration of renal function. One of the latter was found subsequently to have severe bilateral atheromatous renal artery stenosis. When isosorbide dinitrate was substituted for enalapril, symptoms of mesenteric ischaemia resolved and renal function returned to baseline. Continuing surveillance for adverse effects is essential in patients of this age group with severe heart failure, and the risk of occult renal artery stenosis requires regular biochemical screening during follow up.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of the safety of enalapril in the treatment of heart failure in the very old. 284 29

Acute and 1-month toxicity studies with SCH 31846, a nonsulfhydryl anti-hypertensive agent which acts by inhibiting angiotensin-converting enzyme, were initiated to evaluate its toxicity. The oral LD50s in mice and rats were approximately 1.8 and 2.5 g/kg, respectively, while the iv LD50 was approximately 450 mg/kg in mice and 150 mg/kg in rats. Signs of acute toxicity in rats and mice included salivation, hypoactivity, ataxia, prostration, and convulsions. In a 1-month dog study at oral doses of 25, 75, or 150 mg/kg, there was a dose-related increase in emesis between 1 and 2 hr after dosing. Absorption studies showed peak blood concentrations occurring in dogs between 0.3 and 1 hr after dosing. No other noteworthy antemortem changes were observed. In a 1-month rat study at oral doses of 30, 180, or 600 mg/kg, the hematocrit and hemoglobin values of the 600 mg/kg-dosed female rats were slightly but significantly (p less than 0.05) decreased and the blood urea nitrogen was slightly but significantly (p less than 0.05) increased in all SCH 31846-dosed male rats and the 600 mg/kg-dosed female rats. Absorption studies in male rats at doses of 30, 180, and 600 mg/kg indicate that SCH 31846 is well absorbed in rats. The 150 mg/kg-dosed dogs and the 180- and 600 mg/kg-dosed rats had a slight increase in the number of renin-containing granules in the renal juxtaglomerular cells. No other compound-related microscopic changes were observed. These data are similar to data reported for Captopril and suggest that in the dog and rat the toxicity of ACE inhibitors is not dependent upon the presence or absence of a sulfhydryl group.
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PMID:Acute and subchronic toxicity of a nonsulfhydryl angiotensin-converting enzyme inhibitor. 300 64

This review focuses on the different molecular genetic findings in migraine. Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura, which is inherited as an autosomal dominant. Half the cases of FHM are caused by point mutations in the CACNA1A gene on the short arm of chromosome 19 (19p). The gene encodes a calcium ion channel. Other mutation types cause episodic ataxia 2 (EA-2). Expansions of the CAG repeat in the 3' end bring about spinocerebellar ataxia 6 (SCA 6). Some families with FHM link to loci on the long arm of chromosome 1 (1q). The genes have not yet been identified. Some families neither link to 1q nor to 19p. Population-based family and twin studies have shown that migraine both with and without aura have a multifactorial inheritance. The CACNA1A gene may be of importance for ordinary forms of migraine in a few families. Mutations in genes on the X chromosome, dopamine receptor genes, and the ACE gene appear to be involved in migraine in a few families, whereas genes for nitric oxide synthase, serotonin receptors, and mitochondrial DNA do not seem to be involved. The positive associations have not been reproduced in other studies and therefore they should be interpreted with care. It is to be hoped that in the next few years much more will be known about the molecular genetic mechanisms of migraine with and without aura. FHM is an ion channel disorder, and many factors suggest that migraine is also an ion channel disorder, which is consistent with the paroxysmal nature of the illness.
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PMID:[Molecular genetic findings in migraine]. 1172 84

The effects of intramuscular injection of alfaxalone ([ALF] 5 mg/kg), acepromazine ([ACE] 0.05 mg/kg), and an ALF-ACE combination ([AA] 0.025 mg/kg ACE followed by 2.5 mg/kg ALF) on the sedation, echocardiographic, biochemical, and blood gas indexes and recovery were evaluated in seven cats. No sedation was obtained with ACE, and sedation scores were higher with ALF than with AA treatment. Compared with baseline, an increase in heart rate occurred after ACE, and all treatments caused a decrease in systemic arterial pressure. Decreased left ventricular internal dimension in diastole, end-diastolic volume of the left ventricle, stroke volume, and left atrial dimension were identified after AA. There were minimal changes in echocardiographic variables after ALF. Biochemical and blood gas analysis showed no significant changes after all treatments. Although the difference in quality of recovery between the AA and ALF treatment groups was insignificant, all cats treated with AA or ALF showed ataxia. The AA combination did not change the recovery score, and tremor and twitching were identified more frequently with AA than ALF. ALF had no significant effects on echocardiographic, biochemical, or blood gas variables. ALF could be considered a useful sedative option for diagnostic procedures and echocardiography in cats.
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PMID:Effects of Intramuscular Alfaxalone/Acepromazine on Echocardiographic, Biochemical, and Blood Gas Measurements in Healthy Cats. 3077 58

Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has turned out to be a formidable pandemic. Upcoming evidence from confirmed cases of COVID-19 suggests an anticipated incursion of patients with neurological manifestations in the weeks to come. An expression of the angiotensin-converting enzyme 2 (ACE 2), the cellular receptor for SARS-CoV-2 over the glial cells and neurons have made the brain a potential target. Neurotoxicity may occur as a result of direct, indirect and post-infectious complications. Attention to neurological deficits in COVID-19 is fundamental to ensure appropriate, timely, beneficial management of the affected patients. Most common neurological manifestations seen include dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizures. Anosmia and ageusia have recently been hinted as significant early symptoms in COVID-19. As cases with neurological deficits in COVID-19 emerge, the overall prognosis is yet unknown.
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PMID:Neurological manifestations of COVID-19. 3251 79