AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/...AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed, we screened commercially available murine microRNA libraries (SABiosciences, Qiagen Sciences, MD) to evaluate for unique miRNA profiles between these two dosing parameters. RESULTS: We distinguished numerous, unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and downregulated miRNAs, namely 574-5p, 466g, 466f-3p, 375, 29c, and 148a, have been shown to be associated with asthma in prior studies. Interestingly, a relationship between APAP and asthma has been previously well described in the literature, with an as yet unknown mechanism of pathology. There was a statistically significant increase in alanine aminotransferase levels in the lethal compared to sublethal APAP dosing groups at the 12 h time point (P < 0.001). There was 90% mortality in the lethally compared to sublethally dosed mice at the 48 h time point (P = 0.011). CONCLUSION: We identified unique plasma miRNAs both up- and downregulated in APAP poisoning which are correlated to asthma development.展开更多
Therapeutic plasma concentrations of EFV （efavirenz） are between 1,000 ng/mL and 4,000 ng/mL. Concentrations below 1000 ng/mL are associated with higher risk of treatment failure, and concentrations above 4,000 ng/m...Therapeutic plasma concentrations of EFV （efavirenz） are between 1,000 ng/mL and 4,000 ng/mL. Concentrations below 1000 ng/mL are associated with higher risk of treatment failure, and concentrations above 4,000 ng/mL are associated with toxicity. The aim of the study was to appreciate EFV plasmas concentrations profile and the association between plasma levels and various characteristics in Beninese patients treated by a 600 mg standard daily-dose. Blood samples were collected and EFV plasma levels were measured by liquid chromatography coupled with mass spectrometry detection in HIV-infected patients receiving EFV in combination with other antiretroviral drugs for at least 14 days. Adverse effects occurring during treatment were collected through a questionnaire. An over-exposure to EFV among Beninese HIV patients were observed, with 46.4% of patients presenting EFV concentration above 4,000 ng/mL, although adverse effects were tolerated indicating that antiretroviral treatment is safe. The measurement of plasma concentration at the steady-state could contribute to early detection of treatment failure and adapt treatment in subjects presenting serious adverse effects within context of therapeutic drug monitoring.展开更多
基金Supported by PHS grant DK075635 to Szabo G and McNeil Consumer Healthcare, a division of McNeil-PCC Inc. to Ward J
文摘AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed, we screened commercially available murine microRNA libraries (SABiosciences, Qiagen Sciences, MD) to evaluate for unique miRNA profiles between these two dosing parameters. RESULTS: We distinguished numerous, unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and downregulated miRNAs, namely 574-5p, 466g, 466f-3p, 375, 29c, and 148a, have been shown to be associated with asthma in prior studies. Interestingly, a relationship between APAP and asthma has been previously well described in the literature, with an as yet unknown mechanism of pathology. There was a statistically significant increase in alanine aminotransferase levels in the lethal compared to sublethal APAP dosing groups at the 12 h time point (P < 0.001). There was 90% mortality in the lethally compared to sublethally dosed mice at the 48 h time point (P = 0.011). CONCLUSION: We identified unique plasma miRNAs both up- and downregulated in APAP poisoning which are correlated to asthma development.
文摘Therapeutic plasma concentrations of EFV （efavirenz） are between 1,000 ng/mL and 4,000 ng/mL. Concentrations below 1000 ng/mL are associated with higher risk of treatment failure, and concentrations above 4,000 ng/mL are associated with toxicity. The aim of the study was to appreciate EFV plasmas concentrations profile and the association between plasma levels and various characteristics in Beninese patients treated by a 600 mg standard daily-dose. Blood samples were collected and EFV plasma levels were measured by liquid chromatography coupled with mass spectrometry detection in HIV-infected patients receiving EFV in combination with other antiretroviral drugs for at least 14 days. Adverse effects occurring during treatment were collected through a questionnaire. An over-exposure to EFV among Beninese HIV patients were observed, with 46.4% of patients presenting EFV concentration above 4,000 ng/mL, although adverse effects were tolerated indicating that antiretroviral treatment is safe. The measurement of plasma concentration at the steady-state could contribute to early detection of treatment failure and adapt treatment in subjects presenting serious adverse effects within context of therapeutic drug monitoring.
