Frequency of amantadine-resistant influenza A viruses during two seasons featuring cocirculation of H1N1 and H3N2.
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In two influenza seasons during which H1N1 and H3N2 cocirculated, resistance was more frequent in H3N2 strains than in H1N1 strains after amantadine treatment. Predominant amino acid substitutions in M2 protein occurred at position 31 (serine to asparagine) in H3N2 strains and at position 27 (valine to alanine) in H1N1 strains. (+info)
High frequency of resistant viruses harboring different mutations in amantadine-treated children with influenza.
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Clinical samples from 15 amantadine-treated children were collected serially-before, during, and/or after treatment-and were studied to determine the actual prevalence, timing, and clinical implications of M2 mutational events. After viral RNA extraction and reverse-transcriptase polymerase chain reaction amplification of the viral RNA encoding the M2 protein, the products were cloned into plasmids, and their sequences were determined. Five mutations known to confer amantadine resistance in clinical samples were identified in 12 (80%) of 15 evaluable patients, and 9 patients had >1 (2-4) mutant virus. The pattern of emergence of mutant strains was clarified from the study of 6 patients with at least 4 serial samples. Although viruses with M2 mutations tended to become the dominant populations, in 2 cases, wild-type viruses became dominant after decreasing to low levels. These results suggest that resistant viruses emerge in a much higher proportion of amantadine-treated patients than has been suggested by previous studies. (+info)
Effect of combined treatment with imipramine and amantadine on the central dopamine D2 and D3 receptors in rats.
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In spite of intensive research, the problem of treating antidepressant-resistant depressive patients has not yet been solved. Our previous studies demonstrated that joint administration of a tricyclic antidepressant drug, imipramine (IMI) with the uncompetitive antagonist of NMDA receptors, amantadine (AMA), produced stronger "antidepressant" effect in the forced swimming test (Porsolt's test) than the treatment with either drug alone given. Since it has been suggested that dopamine receptors, among others, may play a role in anti-immobility effect of IMI, in the present study we examined the effect of AMA (10 mg/kg) and IMI (5 and 10 mg/kg) given separately or jointly, as a single dose or repeatedly (twice daily for 14 days) on the dopamine D2 and D3 receptors in the rat brain, using receptor autoradiography. Following repeated administration of AMA alone or given in combination with IMI (5 mg/kg), the binding of [3H]quinpirole (dopamine D2/D3 receptors agonist) was increased, and similar changes were observed at the level of mRNA encoding dopamine D2 receptors. We used [3H]7-OH-DPAT to selectively label the dopamine D3 receptors. This experiment has shown that AMA given repeatedly did not induce statistically significant changes in the D3 receptor binding, while IMI at both used doses, increased the [3H]7-OH-DPAT binding, and this effect was still observed after repeated joint administration of AMA with both doses of IMI. However, using both radioligands, we did not observe any synergistic or even additive effects in the binding studies after joint administration of AMA and IMI. Nevertheless, we can conclude that repeated administration of AMA, given together with IMI, induces the up-regulation of dopamine D2 and D3 receptors in the rat brain, and this effect may explain their synergistic action observed in the behavioral studies involving dopaminergic transmission. (+info)
Effect of combined treatment with selective sigma ligands and amantadine in the forced swimming test in rats.
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The obtained results showed that the selective sigma, receptor agonist, SA4503 (but not siramesine, the sigma2 receptor agonist), given alone, exerted an antidepressant-like activity in the forced swimming test in rats. Amantadine (an uncompetitive NMDA receptor antagonist) potentiated or revealed the effect of SA4503 or siramesine, respectively, in this model. (+info)
Effect of joint administration of imipramine and amantadine on binding of [3H]7-OH-DPAT to dopamine D3 receptors in peripheral blood lymphocytes of the patients with drug-resistant unipolar depression.
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Treatment of the patients suffering from therapy-resistant unipolar depression with joint administration of imipramine (twice daily, 100-150 mg/day) and amantadine (twice daily, 150 mg/day) for four to six weeks resulted in the significant increase in the binding of [3H]7-OH-DPAT to dopamine D3 receptors in the peripheral blood lymphocytes. This effect correlated well with the clinical improvement, estimated with Hamilton's Depression Rating Scale. In the light of the above data, it seems justified to postulate that joint therapy with imipramine and amantadine may be successful in the treatment-resistant unipolar depression. (+info)
'Tako-Tsubo cardiomyopathy' associated with syndrome malin: reversible left ventricular dysfunction.
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A 66-year-old man developed a fever and had a syncopal attack during treatment with imipramine and amantadine for depression and Parkinson's disease. His muscular enzyme levels were very high, so he was diagnosed with incomplete syndrome malin and given hydration therapy. The electrocardiogram recorded an ST segment elevation like acute myocardial infarction in most leads, and the echocardiogram revealed left ventricular dysfunction with severe hypokinesis to dyskinesis of the anterior and apical wall regions, and hyperkinesis of the basal wall. One month from onset, the left ventricular contractility had not changed despite normal coronary arteries. Thallium-201((201)Tl) myocardial scintigraphy showed a perfusion defect and there was no accumulation of iodine-123((123)I) metaiodobenzylguanidine (MIBG) in the entire apex of the heart. Left ventricular function returned to normal and repeat (201)Tl scintigraphy showed recovery by the 4th month. However, there was still an absence of cardiac MIBG uptake. There are a number of reports from Japan of a syndrome demonstrating such reversible left ventricular dysfunction, called 'tako-tsubo cardiomyopathy', but the present case is the first to be associated with syndrome malin. A coronary microvascular abnormality and cardiac sympathetic denervation probably both play an important role in tako-tsubo cardiomyopathy. (+info)
Proton conduction through the M2 protein of the influenza A virus; a quantitative, mechanistic analysis of experimental data.
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The M2 proton channel from influenza A virus forms proton-selective ion channels, which are the target of the drug amantadine. Here, existing experimental data are quantitatively examined for insights into mechanisms to account for the pH- and voltage-dependences of M2 proton conduction. The analysis shows that a model involving protonation equilibria of His37, including pH-dependent changes in the relative rates of diffusion on either side of the pore, is quantitatively able to account for recently reported electrophysiological data examining the pH- and voltage-dependences of Rostock and Weybridge strain M2 proton conduction. (+info)
Prevention and control of influenza. Recommendations of the Immunization Practices Advisory Committee (ACIP).
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These recommendations update information on the vaccine and antiviral agents available for controlling influenza during the 1992-1993 influenza season (superseding the MMWR 1991; 40(no. RR-6): 1-15.) The primary changes include statements about vaccination of persons with known hypersensitivity to eggs or other components of the influenza vaccine, the optimal timing of influenza vaccination, and the influenza strains in the trivalent vaccine for 1992-1993. (+info)