José Carlos Saraiva Gonçalves

Vitamin A deficiency in patients with hepatitis C virus-related chronic liver disease

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 HCV-related 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 μmol/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.

Glyceridic esters of p‐methoxycinnamic acid. A new sunscreen of the cinnamate class

Synopsis

Pharmacokinetic/pharmacodynamic Modeling of Psychomotor Impairment Induced by Oral Clonazepam in Healthy Volunteers

This study was undertaken to model the relationship between clonazepam plasma concentrations and a central nervous system adverse effect (impairment of the psychomotor performance) following the oral administration of immediate-release tablets of clonazepam in healthy volunteers. Such a (P)pharmacokinetic/(P)pharmacodynamic (PK/PD) study is important to interpret properly the consequences of determined levels of plasma concentrations of psychoactive therapeutic drugs reported to be involved in road-traffic accidents. Twenty-three male subjects received a single oral dose of 4 mg clonazepam. Plasma concentration, determined by on-line solid phase extraction coupled with high-performance liquid chromatography tandem mass spectrometry, and psychomotor performance, quantified through the Digit Symbol Substitution Test, were monitored for 72 hours. A 2-compartment open model with first order absorption and lag-time better fitted the plasma clonazepam concentrations. Clonazepam decreased the psychomotor performance by 72 ± 3.7% (observed maximum effect), 1.5 to 4 hours (25th-75th percentile) after drug administration. A simultaneous population PK/PD model based on a sigmoid Emax model with time-dependent tolerance described well the time course of effect. Such acute tolerance could minimize the risk of accident as a result of impairment of motor skill after a single dose of clonazepam. However, an individual analysis of the data revealed a great interindividual variation in the relationship between clonazepam effect and plasma concentration, indicating that the phenomenon of acute tolerance can be predicted at a population, but not individual, level.

Randomized Clinical Trial Comparing the Pharmacokinetics of Standard- and Increased-Dosage Lopinavir-Ritonavir Coformulation Tablets in HIV-Positive Pregnant Women

ABSTRACT 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 μg/ml in the second and third trimesters and postpartum, respectively. The increased-dose group exhibited values of 7.9, 6.9, and 9.2 μg/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.)

Assessment of the Relative Dose-Response Test as Indicators of Hepatic Vitamin A Stores in Various Stages of Chronic Liver Disease

Hepatic vitamin A stores should be the best early indicator of vitamin A status because more than 90% of total body vitamin A is stored in the liver. The objective of the present study was to evaluate the hepatic vitamin A stores in all stages of chronic liver disease (CLD), including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). One hundred forty-four patients (age 55.34 ± 9.38 years) were evaluated in a cross-sectional study. Vitamin A nutrition status was analyzed by serum retinol levels and relative dose-response (RDR) method. Patients with cholestasis were excluded from the sample group. Biochemical, clinical, and anthropometric evaluations were performed. Vitamin A deficiency (VAD) was detected in 51.4% of all patients. Patients with adequate levels of serum retinol presented adequate liver vitamin A reserves; in contrast, nearly half the patients with low serum retinol levels presented adequate levels of retinol in the liver, although none of the patients with hepatitis had this condition. Therefore, the effectiveness of the RDR method for evaluating vitamin A nutrition status was limited in patients with cirrhosis and HCC, perhaps due to the advanced age of these patients, since those in the chronic hepatitis group, who were younger, responded adequately to the test. Thus, the RDR method should be modified when applied to later stages of CLD, considering the time and dose of retinyl palmitate supplementation, as VAD may be a risk factor for the progression of the disease.

Usefulness of serotoninergic challenge with oral citalopram

OBJECTIVE Challenge tests designed to evaluate serotoninergic pathways have widely used intravenous citalopram. Oral citalopram has also been used, but unsatisfactory results were obtained with a dose of 20 mg. The objective of this study was to determine whether a higher oral dose would reproduce similar to those described for intravenous administration. To that end, we evaluated cortisol, growth hormone and prolactin levels. METHOD Eight healthy male volunteers were evaluated in a randomized crossover challenge test with 40 mg of oral citalopram or placebo. RESULTS Cortisol levels increased at 2-4h after the oral citalopram intake, with a small amplitude peak occurring in two-thirds of the subjects. Levels of prolactin and growth hormone remained unchanged throughout the study. CONCLUSION The use of oral citalopram might present an alternative in serotoninergic challenge tests, but higher doses are required.

A Rapid and Simple HPLC Method for Therapeutic Monitoring of Vancomycin

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.

Fully-Automated “Timed Up and Go” and “30-Second Chair Stand” Tests Assessment: A Low Cost Approach Based on Arduino and LabVIEW

In this paper it is described the prototyping of an instrumented chair that allows to fully-automate the “Timed Up and Go” and “30-Second Chair Stand” tests assessment. The presented functional chair prototype is a low cost approach that uses inexpensive sensors and the Arduino platform as the data acquisition board, with its software developed resorting to LabVIEW. The “Timed up and go test” consists in measuring the time spent in the task execution of standing up from a chair, walk three meters with a maximum speed without running, turn a cone and going back to the initial position. The “30-Second Chair Stand” test consists in the count of the number of completed chair stands in 30 seconds. It are agility and strength tests easy to setup and execute although they lack of repeatability, whenever the measures are taken manually, due to the rough errors that are introduced.

Technological Dynamics and National Innovation System: A Quantitative Focus of a Neoschumpeterian Approach

This paper aims at analyzing the dynamic technological transition of a Naional Innovation System (subsequently abbreviated as NIS) through a theoretical model of complex system, presented in a non-linear difference equation. This paper shall also specify the way through which a hypothetical technological paradigm may be explored and the forces that shape the economical, social and institutional spheres.Putting together the results presented by the analysis of the complexity with the characteristics proposed by the evolutionist theory related to technologic dynamics inside the NIS, it is possible to systemize in a better way the results of the variation in the time of the economical changes presented.