RESUMO
We investigated the in vitro antifungal activity of amphotericin B, alone and in combination with rifabutin, an inhibitor of bacterial RNA polymerase, against 26 clinical isolates of Aspergillus and 25 clinical isolates of Fusarium. Synergy or additivism between these drugs was demonstrated against all isolates tested. Amphotericin B MICs were reduced upon combination with rifabutin from a mean of 0.65 microg/ml to a mean of 0.16 microg/ml against Aspergillus, and from a mean of 0.97 microg/ml to a mean of 0.39 microLg/ml against Fusarium (P < 0.000001 for both). Similarly, the MICs of rifabutin were reduced upon combination with amphotericin B from a mean of >32 microg/ml to a mean of 1.1 microg/ml against both fungi (P < 0.000001 for both). These positive interactions were corroborated by a colony count study with two Fusarium isolates, for which treatment with the combination of subinhibitory concentrations of amphotericin B (at concentrations 2- and 4-fold less than the MIC) and rifabutin (at concentrations ranging from 4- to 64-fold less than the MIC) resulted in 3.2-log reductions in colony counts compared to those after treatment with either drug alone. Inhibition of RNA synthesis was shown to be the mechanism of antifungal activity. These results suggest that inhibition of fungal RNA synthesis might be a potential target for antifungal therapy.
Assuntos
Anfotericina B/farmacologia , Aspergillus/efeitos dos fármacos , Quimioterapia Combinada/farmacologia , Fusarium/efeitos dos fármacos , RNA Fúngico/efeitos dos fármacos , Rifabutina/farmacologia , Aspergillus/genética , Sinergismo Farmacológico , Proteínas Fúngicas/efeitos dos fármacos , Fusarium/genética , Humanos , Testes de Sensibilidade Microbiana , RNA Fúngico/biossínteseRESUMO
Outcome for 105 patients with candidemia treated with amphotericin B was correlated with amphotericin B in vitro susceptibility results. Thirty-three patients had microbiologic failure, which was defined as persistence of Candida in the bloodstream despite > or = 3 days of amphotericin B. Amphotericin B minimum inhibitory concentrations (MICs) were determined by the National Committee for Clinical Laboratory Standards methodology. After determination of MICs, the minimal lethal concentrations (MLCs) were determined. The isolates tested yielded a narrow range of amphotericin B MICs (0.06-2 microg/mL); only 5% (5/105) exhibited MICs > or = 1 microg/mL. The MLC range, on the other hand, was significantly broader (0.125 to > 16 microg/mL); 24% (25/105) exhibited MLCs > or = 1 microg/mL. The strongest predictor for microbiologic failure was 48-h MLC (P < .001), followed by 24-h MLC (P = .03) and 48-h MIC (P = .11). A resistant break point for amphotericin B of > 1 microg/mL for MLC and > or = 1 microg/mL for MIC could be inferred from this study.
Assuntos
Anfotericina B/farmacologia , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Fungemia/tratamento farmacológico , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Resistência Microbiana a Medicamentos , Humanos , Testes de Sensibilidade Microbiana , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Falha de Tratamento , Resultado do TratamentoRESUMO
The aim of this study was to investigate the effects of moxibustion at the meridian points BL-15 (Xin-shu) and BL-27 (Xiao-chang-shu) on renal function, systolic blood pressure, plasma levels of renin activity, aldosterone and atrial natriuretic peptide in spontaneously hypertensive rats. The results showed that urine volume increased significantly after moxibustion at the meridian points BL-15, but decreased at BL-27. Urinary excretion of Na+ decreased after moxibustion at the meridian points BL-15 and BL-27. Systolic blood pressure decreased after moxibustion at the meridian point BL-15. No effect was observed at BL-27. Plasma levels of aldosterone and renin activity increased significantly, but the levels of atrial natriuretic peptide decreased significantly after moxibustion at BL-15. Plasma levels of aldosterone and atrial natriuretic peptide increased significantly after moxibustion at the meridian points BL-27. These results suggest that the meridian points BL-15 and BL-27 are related to the regulation of renal function and the secretion of hormone with body fluid metabolism.
Assuntos
Pressão Sanguínea/fisiologia , Hipertensão/terapia , Rim/fisiologia , Moxibustão , Pontos de Acupuntura , Aldosterona/sangue , Animais , Fator Natriurético Atrial/sangue , Cloretos/sangue , Creatinina/urina , Modelos Animais de Doenças , Eletrólitos/urina , Hipertensão/fisiopatologia , Masculino , Potássio/sangue , Radioimunoensaio , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Renina/sangue , Sódio/sangueRESUMO
To assess the possible involvement of cholinergic mechanisms in the hypothalamic nuclei in the stimulatory effect of TRH on gastric secretion, rats were infused with thyrotropin-releasing hormone (TRH), cholinergic agonist or antagonist, and normal saline through previously implanted hypothalamic cannulae. Administration of TRH or pilocarpine into the lateral cerebral ventricle or the anterior hypothalamus caused a dose-related increase in gastric volume and acidity in rats. On the other hand, administration of either atropine or D-tubocurarine into the same brain sites caused the opposite effects. Furthermore, the stimulatory effect of TRH or pilocarpine on gastric secretion was completely abolished by pretreatment of the CSF or the anterior hypothalamus with atropine and to a lower degree, D-tubocurarine. Administration of TRH, pilocarpine, atropine or D-tubocurarine into the lateral hypothalamus produced only a slight effect on gastric volume and acidity. However, the gastric volume or acidity was not affected by administration of either TRH, pilocarpine, atropine or D-tubocurarine into the ventromedial hypothalamus in our rats. The data indicate that the cholinergic muscarinic receptor mechanisms in the anterior hypothalamus may mediate the stimulatory effect of TRH on gastric secretion in rats.