Background: Atazanavir, an antiretroviral drug of the protease inhibitor class, is co-administered with ritonavir to inhibit atazanavir metabolism and decrease pharmacokinetic variability. Atazanavir is metabolised mainly by CYP3A4/5 enzymes. High CYP3A intersubject variability has been documented in most cases on a genetic basis. The CYP3A5*3 allele affects splicing defect and protein truncation. Recently a new intronic variant, CYP3A4*22, was found associated with reduced CYP3A4 activity. To assess whether an altered CYP3A activity impairs the metabolism of atazanavir, we investigated the two functional polymorphisms. To the best of our knowledge, this is the first case report showing that overexposure to ATV is associated with CYP3A poor phenotype and nephrolithiasis. Further study is needed in order to confirm this interesting observation. Case Presentation: We describe the case of a 43 year-old HIV-1-infected man treated with atazanavir/ritonavir plus lamivudine who experienced early and recurrent severe episodes of kidney stones. Atazanavir plasma trough concentrations showed a value higher than the normal range, thus we investigated the two polymorphisms that are known to affect CYP3A4/5 activity. This analysis revealed that our patient was a CYP3A poor metabolizer since he carried CYP3A4*1/*22 and CYP3A5*3/*3 genotypes. Conclusion: We suggest that screening of CYP3A functional variants is an appropriate approach, helping in treatment choice and potential dosage adjustment of protease inhibitors.
Objective: The aim of the present study was to investigate the antidiabetic potential of Pergularia daemiamethanolic extract (PD) on alloxan-induced diabetic mice. Methods: Diabetes was induced using alloxan (150mg/kg). Different doses of the methanolic extract of P. daemia were prepared and administered orally. The alloxan-induced diabetic mice were treated with 200, 400 and 1000 mg/kg body weight (b.w.) methanolic extract of Pergularia daemia and the blood glucose levels were measured over 4 hrs. Results: All doses of the extract (200, 400 and 1000 mg/kg b.w) significantly (p<0.0001) lowered fasting blood glucose level after treatment. The hypoglycaemic effect of the methanolic extract was also compared with that of an oral dose of glibenclamide under the same conditions. The extract showed significant (p<0.05) hypoglycemic effect in alloxan-induced diabetic mice. The glucose half-life (t1/2G) (p<0.0001), Mean Glucose Residence Time (MRTG) (p<0.0001), and the area under glucose concentration time curve (AUC0-4hG) (p<0.05) were high in control group compared to the alloxan-induced mice treated with P. daemia extract. Conclusion: The results of this study indicate that methanolic extract of the plant of Pegularia daemiapossess hypoglycaemic activity.
Aim: This paper analyses the global and European responses to the break out of the H1N1 virus in 2009 and highlights the major deficiencies of the European authorization procedure of vaccines against H1N1 pandemic flu. Study Design: The study analyses the institutional reactions to the spread of the H1N1 pandemic flu (commonly called swine flu). The study reports the fundamental steps undertaken by global and European Institutions since 2009 to face the spreading of the H1N1 flu. Methodology: The study applies a legal methodology proceeding from formal rules towards the substantial effects taking place in the specific health protection field considered. Results: The analysis of the European authorization procedure of vaccines against H1N1 pandemic flu shows the lack of coordination between Member States and the European Union, as well as coordination between the European Medicines Agency (EMA) and the European Office of the World Health Organization (WHO); moreover, a fundamental violation of the precautionary principle emerged. In the European context, in fact, the principle does not coincide with the temporary nature of the measures, but reflects the fundamental distinction between assessment and risk management. Conclusions: The supranational mediation of the European Union has offered in many cases the guarantee of health protection within contexts in which the multiplicity of involved interests increases the level of conflict. That mediation has definitely failed in the case of swine flu because of the lack of supranational constituency representation within the European Medicines Agency that allows the intergovernmental component and the underlying unilateral protection of economic interests to resurface. In the case of swine flu, the trust relationships between global and European bodies have been affected by the lack of transparency of the responsible organizations (WHO and EMA) and the lack of pluralistic openness to different interests in the decision-making procedures.
Aims:Emblica officinalis, locally known as Amla, is a highly nutritious seasonal fruit. The processed fruit could be an important dietary source of natural vitamin C with potent antioxidant activity. The aim of present investigation was to study factors influencing antioxidant potential of Amla and its products. Methodology: Three Indian varieties of Amla fruits in three ripening states (unripe, semi ripe and fully ripe) were analyzed for total phenolic contents, vitamin C as well as antioxidant potential. Two Amla products were studied over a period of 33 days for these parameters. Results: In the present data, the fully ripe stage of Amla had the highest value of vitamin C (804.4±0.8mg/100g) and polyphenols (1300.3±99.6mg/100g) than the unripe, semi ripe stages. The DPPH Scavenging activity was found to be highest in semi ripe stage. ABTS radical scavenging (IC50 values) of unripe, semi ripe and ripe were 18.5±0.0071, 34.7±0.026, 21.9±0.024 respectively. The stability study for syrup and pickle, processed from Amla fruit, demonstrated sharper decrease of the vitamin C content for pickle than decrease for syrup over the time 33 days but the polyphenols and the free radical scavenging activity remained the same over the time. Conclusion: The present study suggested that ripening stages influence the antioxidant potential of Amla fruit. The contents of vitamin C showed a significant decrease over time in syrup and pickle but the antioxidant potential remained unaffected.
Introduction:Kwatha (decoction) preparations are one among commonest practiced Ayurvedic dosage forms, which are highly effective, but they are to be used when freshly prepared due to short shelf life (i.e. 1/2- 1 day), and they are often overlooked due to the preparation method and palatability. In present study, Guduchyadi Kwatha, a known Ayurvedic formulation used in Jwara (~pyrexia), was converted into a different dosage form for instant use by Rasakriya method (to convert into semi solid state), to make it easy to dispense, increase the shelf life, make it palatable, for dose fixation, etc. Aims and Objectives: To evaluate physico-chemical profile of fresh Guduchyadi Kwatha (GKF) and Guduchyadi Kwatha for instant use (GKI). Materials and Methods: Five batches of GKI and GKF were prepared and findings were systematically recorded. Organoleptic evaluation (Hedonic scale method) Physicochemical parameters (Loss on drying, Ash value, Acid insoluble ash, pH, Total solid content, Specific gravity, Water and Methanol soluble extractive, solubility and dissolution rate tests), High performance thin layer chromatography (HPTLC) profile, and microbial over load were carried out. Results and Conclusion: Comparative organoleptic screening of GKF and GKI showed no major differences in color and smell. In GKF, pH value, total solid content, specific gravity, and surface tension were found as 6.0, 95.14%, 1.009 w/w and 27.19 dynes/cm respectively. In finished product (GKI), pH value, loss on drying, Ash value, water soluble and alcohol soluble extractives were obtained as 6.16, 1.93% w/w, 7.90% w/w, 63.69% w/w and 37.29% w/w respectively. No microbial overload was detected in the sample.