- Hollow mesoporous structured molecularly imprinted polymer as adsorbent in pipette-tip solid-phase extraction for the determination of antiretrovirals from plasma of HIV-infected patients. [Journal Article]
- EElectrophoresis 2018 May 17
- In this work a hollow mesoporous structured molecularly imprinted polymer was synthetized and used as adsorbent in pipette-tip solid-phase extraction for the determination of lamivudine (3TC), zidovu...
In this work a hollow mesoporous structured molecularly imprinted polymer was synthetized and used as adsorbent in pipette-tip solid-phase extraction for the determination of lamivudine (3TC), zidovudine (AZT) and efavirenz (EFZ) from plasma of human immunodeficiency virus (HIV) infected patients by high-performance liquid chromatography (HPLC). All parameters that influence the recovery of the pipette tip based on hollow mesoporous molecularly imprinted polymer solid-phase extraction (PT-HM-MIP-SPE) method were systematically studied and discussed in detail. The adsorbent material was prepared using methacrylic acid and 4-vinylpyridine as functional monomers, ethylene glycol dimethacrylate as crosslinker, acetonitrile as solvent, 4,4'-azobis(4-cyanovaleric acid) as radical initiator, benzalkonium chloride as surfactant), 3TC, and AZT as templates. The simultaneous separation of 3TC, AZT and EFZ by HPLC-UV was performed using a Gemini C18 Phenomenexࣨ column (250 mm × 4.6 mm, 5 μm) and mobile phase consisting of acetonitrile: water pH 3.2 (68:32, v/v), flow rate of 1.0 mL min-1 and λ = 260 nm. The method was linear over the concentration range from 0.25 to 10 μg mL-1 for 3TC and EFZ, and 0.05 to 2.0 μg mL-1 for AZT, with correlation coefficients larger than 0.99 for all analytes. Recovery ± relative standard deviations (RSDs %) were 41.99±2.38 %, 82.29±1.63 %, and 83.72±7.52 % for 3TC, AZT, and EFZ, respectively. The RSDs and relative errors (REs) were lower than 15 % for intra and interday assays. The method has been successfully applied for monitoring HIV-infected patients outside the therapeutic dosage.2 This article is protected by copyright. All rights reserved.
- Anemia and thrombocytopenia in the cohort of HIV-infected adults in northwest Ethiopia: a facility-based cross-sectional study. [Journal Article]
- EEJIFCC 2018; 29(1):36-47
- CONCLUSIONS: We found an overall high prevalence of anemia in the cohort of HIV-infected adults in northwest Ethiopia. HAART naïve subjects and those with CD4 count less than 200 cells/µl were found to be at higher risk for developing anemia. This data has an important implication for management of hematological abnormalities in HIV patients and highlights the need for early initiation of HAART to reduce the burden of anemia.
- Engineered mixed oxide-based polymeric composites for enhanced antimicrobial activity and sustained release of antiretroviral drug. [Journal Article]
- IJInt J Biol Macromol 2018 May 12
- Here, pH-responsive engineered polymeric composites were fabricated from sodium alginate and mixed Cu/Zn oxides. The resulting alginate-CuxZn1-xO composites were characterized by FTIR, SEM and XRD, t...
Here, pH-responsive engineered polymeric composites were fabricated from sodium alginate and mixed Cu/Zn oxides. The resulting alginate-CuxZn1-xO composites were characterized by FTIR, SEM and XRD, then used as an efficient carrier for the antiretroviral drug (zidovudine, AZT) and exhibited remarkable antibacterial properties. The resulting polymeric composites had specific surface areas of 185.2-198.6 m2/g as confirmed by the Brunauer-Emmett-Teller analysis. The metal oxide distribution within the alginate matrix was confirmed from the X-ray diffraction and scanning electron microscopy analyses. The zidovudine, an antiretroviral drug was encapsulated in 30 mg of alginate-Cu0.7Zn0.3O with 68% encapsulation efficiency. The release of AZT in simulated intestinal fluid (pH 7.4) was studied, a slow and sustained release of AZT (~96.2%) was observed. The AZT release kinetics is sufficiently described by the Korsmeyer-Peppas model and follows the Fickian transport profile. Results herein demonstrated that A-Cu0.7Zn0.3O, A-Cu0.3Zn0.7O and Cu0.5Zn0.5O exhibited excellent bacterial devastation property. A dose of 8 μg/mL A-Cu0.7Zn0.3O and 13 μg/mL A-Cu0.3Zn0.7O are sufficient to completely killed E. coli DH5a and S. aureus NSUHS-151 within 24 h.
- Missed opportunities for prevention of vertical HIV transmission in Canada, 1997-2016: a surveillance study. [Journal Article]
- COCMAJ Open 2018 May 10; 6(2):E202-E210
- CONCLUSIONS: Efforts to improve timely access to care, HIV screening and treatment for all women, combined with enhanced resources targeting populations at increased risk for HIV infection, will be needed if vertical HIV transmission is to be eliminated in Canada.
- Innovation and trends in the development and approval of antiviral medicines: 1987-2017 and beyond. [Review]
- ARAntiviral Res 2018 May 15; 155:76-88
- 2017 marked the 30th anniversary of the approval of zidovudine (AZT) as the first HIV/AIDS therapy. Since then, more than eighty antiviral drugs have received FDA approval, half of which treat HIV in...
2017 marked the 30th anniversary of the approval of zidovudine (AZT) as the first HIV/AIDS therapy. Since then, more than eighty antiviral drugs have received FDA approval, half of which treat HIV infection. Here, we provide a retrospective analysis of approved antiviral drugs, including therapeutics against other major chronic infections such as hepatitis B and C, and herpes viruses, over the last thirty years. During this time, only a few drugs were approved to treat acute viral infections, mainly influenza. Analysis of these approved antiviral drugs based on molecular class and mode of action shows that a large majority are small molecules and direct-acting agents as opposed to proteins, peptides, or oligonucleotides and host-targeting therapies. In addition, approvals of combination therapies accelerated over the last five years. We also provide a prospective study of future potential antiviral therapies, based on current clinical research pipelines across the pharmaceutical industry. Comparing past drug approvals with current clinical candidates hints at the future evolution in antiviral therapies and reveals how antiviral medicines are often discovered. Overall, this work helps forecast future trends and innovation in the field of antiviral research and development.
- Occurrence, fate and removal of pharmaceuticals, personal care products and pesticides in wastewater stabilization ponds and receiving rivers in the Nzoia Basin, Kenya. [Journal Article]
- STSci Total Environ 2018 May 08; 637-638:336-348
- Although there is increased global environmental concern about emerging organic micropollutants (EOMPs) such as pharmaceuticals, personal care products (PPCPs) and polar pesticides, limited informati...
Although there is increased global environmental concern about emerging organic micropollutants (EOMPs) such as pharmaceuticals, personal care products (PPCPs) and polar pesticides, limited information is available on their occurrence in Africa. This study presents unique data on concentrations and loads of 31 PPCPs and 10 pesticides in four wastewater stabilization ponds (WSPs) and receiving rivers (flowing through urban centres) in Kenya. The WSPs indicate a high potential to remove pharmaceutically active compounds (PhACs) with removals by up to >4 orders of magnitude (>99.99% removal), mainly occurring at the facultative stage. However, there are large differences in removal among the different classes, and a shift in the relative PhACs occurrence is observed during wastewater treatment. Whereas the influent is dominated by high-consumption PhACs like anti-inflammatory drugs (e.g. paracetamol and ibuprofen, up to 1000 μg L-1), the most recalcitrant PhACs including mainly antibiotics (e.g. sulfadoxin and sulfamethoxazole) and antiretrovirals (e.g. lamivudine and nevirapine) are largely abundant (up to 100 μg L-1) in treated effluent. Overall, concentrations of EOMPs in the Nzoia Basin rivers are the highest in dry season (except pesticides) and in small tributaries. They are of the same order of magnitude as those measured in the western world, but clearly lower than what we recently measured in the Ngong River, Nairobi region. Based on the specific consumption patterns and recalcitrant behavior, high concentrations (>1000 ng L-1) are observed in the rivers for PPCPs like lamivudine, zidovudine, sulfamethoxazole and methylparaben. Concentration levels of pesticides are in general one order of magnitude lower (<250 ng L-1). Our data suggest a continuous input of EOMPs to the rivers from both point (WSPs) and diffuse (urban centres) sources. To better understand and manage the impact of both sources, EOMP removal mechanisms in WSPs and their attenuation in rivers merit further research.
- Age- and genotype-dependent variability in the protein abundance and activity of six major uridine diphosphate-glucuronosyltransferases in human liver. [Journal Article]
- CPClin Pharmacol Ther 2018 May 08
- The ontogeny of hepatic uridine diphosphate-glucuronosyltransferases (UGTs) was investigated by LC-MS/MS proteomics to determine UGT protein abundance in human liver microsomes isolated from 136 pedi...
The ontogeny of hepatic uridine diphosphate-glucuronosyltransferases (UGTs) was investigated by LC-MS/MS proteomics to determine UGT protein abundance in human liver microsomes isolated from 136 pediatric (0-18 years) and 35 adult (age 18-67 years) donors. Microsomal protein abundances of UGT1A1, UGT1A4, UGT1A6, UGT1A9, UGT2B7 and UGT2B15 increased by ∼8, 55, 35, 33, 8 and 3-fold from neonates to adults, respectively. The estimated age at which 50% of the adult protein abundance is observed for UGT isoforms was between 2.6 to 10.3 years. Measured in vitro activity was generally consistent with the protein data. UGT1A1 protein abundance was associated with multiple genetic variants possessing noticeable ontogeny-genotype interplay. UGT2B15 rs1902023 (*2) was associated with decreased protein activity without any change in protein abundance. Taken together, these data are invaluable to facilitate the prediction of drug disposition in children using physiologically based pharmacokinetic modeling as demonstrated for zidovudine and morphine. This article is protected by copyright. All rights reserved.
- Similar HIV protection from four weeks of zidovudine versus nevirapine prophylaxis among formula-fed infants in Botswana. [Journal Article]
- SASouth Afr J HIV Med 2018; 19(1):751
- CONCLUSIONS: Both ZDV and NVP resulted in low intrapartum transmission rates and no significant differences in severe infant haematologic toxicity (DAIDS Grade 3 or Grade 4) among formula-fed full-term infants with a birthweight ≥ 2500 g.
- Abundance of Phase I and II Drug Metabolizing Enzymes in Alcoholic and Hepatitis C Cirrhotic Livers: A Quantitative Targeted Proteomics Study. [Journal Article]
- DMDrug Metab Dispos 2018 Apr 25
- To predict the impact of liver cirrhosis on hepatic drug clearance using physiologically based pharmacokinetic (PBPK) modeling, we compared the protein abundance of various Phase I and Phase II drug ...
To predict the impact of liver cirrhosis on hepatic drug clearance using physiologically based pharmacokinetic (PBPK) modeling, we compared the protein abundance of various Phase I and Phase II drug metabolizing enzymes (DMEs) in S9 fractions of alcoholic (n=27) or hepatitis C (HCV, n=30) cirrhotic vs. non-cirrhotic (control) livers (n=25). The S9 total protein content was significantly lower in alcoholic or HCV cirrhotic vs. control livers (i.e., 38.3 ± 8.3, 32.3 ± 12.8 vs. 51.1 ± 20.7 mg/g liver, respectively). In general, alcoholic cirrhosis was associated with a larger decrease in the DME abundance than HCV cirrhosis. However, only the abundance of UGT1A4, ADH1A and ADH1B was significantly lower in alcoholic vs. HCV cirrhotic livers. When normalized to per gram of tissue, the abundance of nine DMEs (UGT1A6, UGT1A4, CYP3A4, UGT2B7, CYP1A2, ADH1A, ADH1B, AOX1 and CES1) in alcoholic cirrhosis and five DMEs (UGT1A6, UGT1A4, CYP3A4, UGT2B7, and CYP1A2) in HCV cirrhosis was <25% of that in control livers. The abundance of the majority of DMEs in cirrhotic livers was 25-50% of control livers. CES2 abundance was not affected by cirrhosis. Integration of UGT2B7 abundance in cirrhotic livers into the liver cirrhosis (Child Pugh C) model of Simcyp improved the prediction of zidovudine and morphine PK in subjects with Child Pugh C liver cirrhosis. These data demonstrate that protein abundance data, combined with PBPK modeling and simulation, can be a powerful tool to predict drug disposition in special populations.
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- Birth Outcomes for Pregnant Women with HIV Using Tenofovir-Emtricitabine. [Journal Article]
- NEJMN Engl J Med 2018 04 26; 378(17):1593-1603
- CONCLUSIONS: The risk of adverse birth outcomes was not higher with TDF-FTC-LPV/r than with ZDV-3TC-LPV/r or TDF-FTC-ATV/r among HIV-infected women and their infants in the United States, although power was limited for some comparisons. (Funded by the National Institutes of Health and others.).