13 research outputs found
Effectiveness and safety of generic version of abacavir/lamivudine and efavirenz in treatment naive HIV-infected patients: a nonrandomized, open-label, phase IV study in Cali-Colombia, 2011-2012
Background: Generic drug policies are often associated with concerns about the quality and effectiveness of these
products. Phase IV clinical trials may be a suitable design to assess the effectiveness and safety of generic drugs.
The objective of this study was to describe the effectiveness and the safety of the generic abacavir/lamivudine and
efavirenz in treatment-naïve HIV-infected patients.
Methods: A monocentric, nonrandomized, open-label, phase IV study in treatment naïve HIV-infected patients
18 years or older with indication to receive abacavir/lamivudine and efavirenz were recruited from a program that
provides comprehensive outpatient consultation and continuing care. The primary end-point was to achieve viral load
<40 copies/mL at 12 months after baseline to assess effectiveness. Secondary end-point of the study were 1) to asses
increasing in T-CD4 lymphocytes levels as accompaniment to asses effectiveness, and 2) to assess both gastrointestinal,
skin, and central nervous system symptoms, and lipid profile, cardiovascular risk, renal, and hepatic function as safety
profile. Data were determined at baseline, 3, 6, and 12 months. Close clinical monitoring and pharmaceutical care were
used for data collection. Wilcoxon matched-pairs signed-rank test was used to compare proportions or medians.
Results: Sixty patients were invited to participate in the study; 42 were enrolled and 33 completed the follow-up. Of
the nine patients excluded from the study, only one was withdrawn due to adverse events. At 12 months, 31 of 42
patients (73.8 % in intention-to-treat analysis) achieved a viral load of HIV1 RNA <40 copies/mL. There was a significant
increase (172 cells/mm3) in the median for CD4 T lymphocyte count. The adverse events were mild and met the safety
profile for this antiretroviral regimen, mainly of central nervous system symptoms, skin rash, lipid abnormalities, and an
increase of 2 % in the median of the percentage of cardiovascular risk.
Conclusions: The clinical outcomes of generic version of abacavir/lamivudine and efavirenz in HIV treatment naïve
patients showed the expected safety and effectiveness profile of proprietary ARV drugs.
Trial registration: Registro Público Cubano de Ensayos Clínicos (RPCEC) ID: RPCEC00000202. Registered 19 November
2015.This research was made possible by contribution from the Corporación de
Lucha Contra el SIDA, Cali-Colombia, and Comité para el Desarrollo de la
Investigación (CODI), Universidad de Antioquia, Medellín, Colombia. In
addition, Humax Pharmaceutical S.A. provided the antiretroviral drugs
A Deep Insight into the Sialotranscriptome of the Gulf Coast Tick, Amblyomma maculatum
Background: Saliva of blood sucking arthropods contains compounds that antagonize their hosts ’ hemostasis, which include platelet aggregation, vasoconstriction and blood clotting; saliva of these organisms also has anti-inflammatory and immunomodullatory properties. Perhaps because hosts mount an active immune response against these compounds, the diversity of these compounds is large even among related blood sucking species. Because of these properties, saliva helps blood feeding as well as help the establishment of pathogens that can be transmitted during blood feeding. Methodology/Principal Findings: We have obtained 1,626,969 reads by pyrosequencing a salivary gland cDNA library from adult females Amblyomma maculatum ticks at different times of feeding. Assembly of this data produced 72,441 sequences larger than 149 nucleotides from which 15,914 coding sequences were extracted. Of these, 5,353 had.75 % coverage to their best match in the non-redundant database from the National Center for Biotechnology information, allowing for the deposition of 4,850 sequences to GenBank. The annotated data sets are available as hyperlinked spreadsheets. Putative secreted proteins were classified in 133 families, most of which have no known function. Conclusions/Significance: This data set of proteins constitutes a mining platform for novel pharmacologically activ
A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction
Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acidinduced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5dihydroxybenzoic acid to a range of 2,5substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholineinduced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF2 and H2DCFDA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RTPCR and western blotting were utilized to measure Akt, eNOS, Nrf2, NQO1 and HO1 expression. Results: Ex vivo endotheliumdependent relaxation was significantly improved by the glycomimetics under palmitateinduced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitateinduced oxidative stress and enhanced NO production. We demonstrate that the protective effects of preincubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROSinduced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease