Hepatitis C virus (HCV) infection is associated with oxidative stress and vitamin A possesses antioxidant activity. The objective of the present study was to investigate vitamin A nutritional status in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC), according to biochemical, functional and dietetic indicators correlating these findings with liver function, liver damage and death. Vitamin A nutritional status was analysed by serum retinol levels, dietetic indicators and functional indicators. A total of 140 patients with HCVrelated liver disease were enrolled. Vitamin A deficiency was detected in 54·3 % of all patients, and there was a progressive drop in serum retinol levels from chronic hepatitis C patients towards cirrhosis and HCC patients. Increased total bilirubin, liver transaminases and prothrombin time, presence of hepatic encephalopathy and ascites were related to reduced serum retinol levels, and values #0·78 mmol/l of serum retinol were associated with liver-related death. A high prevalence of inadequate intake of vitamin A was observed in all stages of chronic liver disease. The functional indicator was not an adequate parameter for evaluating the vitamin A nutritional status. Therefore, serum retinol concentration is related to severity of the disease, liver complications and mortality. The effectiveness of nutritional counselling and measures of intervention in this group in improving vitamin A nutritional status should be examined further in a controlled study.
A lopinavir-ritonavir (LPV/r)-based regimen is recommended during pregnancy to reduce the risk of HIV mother-to-child transmission, but the appropriate dose is controversial. We compared the pharmacokinetics of standard and increased LPV/r doses during pregnancy. This randomized, open-label prospective study enrolled 60 pregnant women between gestational weeks 14 and 30. The participants received either the standard dose (400/100 mg twice a day [BID]) or increased dose (600/150 mg BID) of LPV/r tablets during pregnancy and the standard dose for 6 weeks after childbirth. Pharmacokinetics analysis was performed using a high-performance liquid chromatography-tandem mass spectrometry method. Adherent participants who received the standard dose presented minimum LPV concentrations of 4.4, 4.3, and 6.1 g/ml in the second and third trimesters and postpartum, respectively. The increased-dose group exhibited values of 7.9, 6.9, and 9.2 g/ml at the same three time points. Although LPV exposure was significantly higher in the increased-dose group, the standard dose produced therapeutic levels of LPV against wild-type virus in all adherent participants, except one patient in the third trimester; 50%, 37.5%, and 25%, and 0%, 15%, and 0% of the participants in the standard-and increased-dose groups failed to achieve therapeutic levels against resistant viruses during the second and third trimesters and after childbirth, respectively. After 12 weeks of treatment and after childbirth, all adherent participants achieved undetectable HIV viral loads, and their babies (49/54) were uninfected. No serious drug-related adverse events were observed. We conclude that the standard dose is appropriate for use during pregnancy and that an increased dose may be necessary for women harboring resistant HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT00605098.)
Therapeutic monitoring of the antibiotic vancomycin is important to achieve specific plasma concentration and prevent toxic effects. Several assays have been described for vancomycin determination in clinical practice, but high-performance liquid chromatography is still considered the gold standard for the quantification of vancomycin. In this study, we developed a new and rapid high-performance liquid chromatography method requiring 50 μL of plasma for the quantification of vancomycin. Acetonitrile was used for processing plasma by protein precipitation (1:2.5). Isocratic chromatographic analysis was carried out on a C18 silica-based (2.7 μm) column with the mobile phase containing 20 mM ammonium acetate/formic acid buffer (pH 4.0):methanol 88:12 (v/v). A diode array detector was used for UV detection at 240 nm. This method was validated according to the Brazilian Health Surveillance Agency legislation and International Conference on Harmonization guidelines. The measurement range was 1-100 μg/mL, analysis time was 8 min, and intermediate precision was <12%, supporting the present method as a fast, simple, and effective alternative for therapeutic monitoring of vancomycin.
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