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Raltegravir (RAL) and related HIV-1 integrase (IN) strand transfer inhibitors (INSTIs) efficiently block viral replication in vitro and suppress viremia in patients. These small molecules bind to the IN active site, causing it to disengage from the deoxyadenosine at the 3' end of viral DNA. The emergence of viral strains that are highly resistant to RAL underscores the pressing need to develop ...
In the quest to investigate small airway function in a range of lung diseases, multiple-breath washout tests have been applied for their potential to represent the most peripheral air spaces [1, 2]. The aim of reducing the burden on the patient has recently also revived interest in the single-breath washout. A single-breath washout test has now been proposed which involves an inhalation of 5% S...
The sigma-2 receptor (S2R) is a potential therapeutic target for cancer and neuronal diseases. However, the identity of the S2R has remained a matter of debate. Historically, the S2R has been defined as (1) a binding site with high affinity to 1,3-di-o-tolylguanidine (DTG) and haloperidol but not to the selective sigma-1 receptor ligand (+)-pentazocine, and (2) a protein of 18-21 kDa, as shown ...
The current standard of care for human immunodeficiency virus (HIV) treatment is a three-drug regimen containing a nonnucleoside reverse transcriptase inhibitor, a protease inhibitor, or an integrase strand transfer inhibitor (INSTI) plus two nucleoside/tide reverse transcriptase inhibitors. Given their potency, safety, and distinctive mechanism of action, INSTIs represent an important advance ...
The Human Immunodeficiency Virus-1 integrase is responsible for the covalent insertion of a newly synthesized double-stranded viral DNA into the host cells, and is an emerging target for antivirus drug design. Raltegravir (RAL) and elvitegravir (EVG) are the first two integrase strand transfer inhibitors used in therapy. However, treated patients eventually develop detrimental resistance mutati...
BACKGROUND Integrase strand transfer inhibitors (INSTI) are the standard of care for naïve HIV-infected individuals due to their favourable efficacy and safety profile. The newest INSTIs, elvitegravir and dolutegravir, have not been evaluated in a head to head study; however, both have been compared to efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF) in phase III trials. Elvitegravir/cobicistat/...
BACKGROUND The Phase III VIKING-3 study demonstrated that dolutegravir (DTG) 50 mg twice daily was efficacious in antiretroviral therapy (ART)-experienced subjects harbouring raltegravir- and/or elvitegravir-resistant HIV-1. VIKING-4 (ING116529) included a placebo-controlled 7-day monotherapy phase to demonstrate that short-term antiviral activity was attributable to DTG. METHODS VIKING-4 is ...
Cardiac remodeling during heart failure development induces a significant increase in the activity of the L-type Ca(2+) channel (Cav1.2). However, the effects of enhanced Cav1.2 activity on myocyte excitation-contraction (E-C) coupling, cardiac contractility, and its regulation by the beta-adrenergic system are not clear. To recapitulate the increased Cav1.2 activity, a double transgenic (DTG) ...
This paper describes the synthesis and characterization of the copper (II) complex with the non-steroidal anti-inflammatory drug (NSAID) piroxicam. The characterization was performed by elemental analysis, FTIR spectroscopy, X-ray powder diffraction and thermal investigation. The empirical formulae of the complex, [Cu(PX)2(H2O)2]’ . H2O was determined by the mentioned methods, but especially by...
In this study, the pyrolysis procedure was used to extract oil from pomegranate peels (PP) utilizing biomass-derived sulfonated tea waste as a catalyst. FTIR, SAA, SEM, and XRD were characterize Thermo-catalytic decomposition carried out in salt bath reactor bio-oil composition determined through GC-MS. The obtained virgin PP observed contain compounds range of C5–C13, whereas catalyzed reactio...
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