Factors Influencing the Intracellular Concentrations of the Sofosbuvir Metabolite GS-331007 (in PBMCs) at 30 Days of Therapy.

Sofosbuvir (SOF) is an HCV NS5B polymerase inhibitor, and GS-331007 is its major metabolite. The aim of this study was to investigate whether clinical and pharmacological factors could influence GS-331007 intracellular (IC) concentrations in peripheral blood mononuclear cells (PBMCs) associated with a sustained virological response in patients treated with SOF and ribavirin (RBV). Drug levels were analyzed using liquid chromatography at different days of therapy, whereas variants in genes encoding transporters and nuclear factors were investigated using real-time PCR.

Pharmacogenetic determinants of kidney-associated urinary and serum abnormalities in antiretroviral-treated HIV-positive patients.

Tenofovir disoproxyl fumarate (TDF) has been associated with renal tubular abnormalities, phosphaturia and proteinuria (retinol binding protein, RBP, loss): vitamin D (VD) and PTH affect these markers. Aim was to understand if some single nucleotide polymorphisms (SNPs) were predictors of renal abnormalities in an Italian cohort of HIV-affected patients. DNA was analyzed through real-time PCR, urinary RBP corrected by creatinine (uRBP/Cr).

Influence of Vitamin D in Advanced Non-Small Cell Lung Cancer Patients Treated with Nivolumab.

Nivolumab is one of the most commonly used monoclonal antibodies for advanced non-small cell lung cancer treatment, to the extent that the presence of its anti-antibody is considered a negative prognostic factor. Vitamin D (VD) modulates expression of the genes involved in drug metabolism and elimination. Immune system regulation and immunodeficiency is frequent in non-small cell lung cancer patients.

Development and validation of an HPLC-UV method for quantification of elvitegravir and two other new antiretrovirals, dolutegravir and rilpivirine, in the plasma of HIV-positive patients.

Therapeutic drug monitoring may be crucial in selected clinical conditions for the management of HIV infection. In recent years, new antiretrovirals have been introduced and in particular elvitegravir (EVG) is now recommended for first-line and simplification treatment as well as dolutegravir (DTG) and rilpivirine (RPV). The aim of this study was to develop and validate a high-performance liquid chromatography-ultraviolet (HPLC-UV) method for determining EVG and new antiretrovirals DTG and RPV in human plasma.

Comparison of efficacy and safety between individualized and empiric dose regimen of amitriptyline in the treatment of major depressive episode.

The most efficient method for amitriptyline dose individualization has not been established as yet. For this purpose the authors developed and clinically assessed the modified Bayesian method supported by original basic computer program. Twenty-one male and 39 female subjects (32-65 years old), with major depressive disorder (International Classification of Diseases, 10th revision), were randomly assigned and single-blinded to take individualized (experimental group, n = 30) or empiric (control group, n = 30) doses of amitriptyline for 8 weeks.

Relaxant effect of oxytocin on isolated human oviduct.

Aim: Oxytocin produces concentration-dependent relaxation of isolated isthmus and ampulla of human oviduct precontracted by histamine. The aim of our study was to investigate whether this oxytocin effect was specific and by which receptors it was mediated.

Methods: We investigated effects of oxytocin and its antagonists on isolated isthmus and ampulla of the uterine tubes from 20 women who underwent surgery for uterine fibroids.

Service quality in public and private pharmacies in the city of Kragujevac, fr Yugoslavia.

Aim: To compare the service quality in public and private pharmacies in the city of Kragujevac by measuring patient care and health facility indicators.

Methods: The patient care indicators and health facility indicators, established by the World Health Organization in 1995, were measured prospectively in 7 public and 7 private pharmacies in Kragujevac, Yugoslavia, during November and December 1999. A sample of 100 patient-visits was analyzed in each pharmacy.

Effects of nicotine, dimethylphenylpiperazinium and tetramethylammonium on smooth muscles from feline and human gastric corpus.

Both excitatory and inhibitory intrinsic neurons could be found within the gastric wall, both of them receiving innervation from vagal fibres and being sensitive to nicotine. The effects of three nicotine receptor agonists, nicotine, tetramethylammonium (TMA) and 1,1-dimethyl-4-phenylpiperazinium (DMPP), on contractile activity of preparations isolated from feline and human gastric corpus wall were investigated. While DMPP (3.

The control of hair growth.

The hair follicle is one of a few human tissues containing stem cells. The stem cells are interspersed within the basal layer of the outer root sheath and in an area called the bulge. From this reservoir stem cells migrate to hair matrix and start to divide and differentiate.

The effects of excitatory amino acids on isolated gut segments of the rat.

Glutamate and aspartate are excitatory neurotransmitters in both central and peripheral nervous systems, acting on ionotropic and metabotropic receptors. In our study we have examined the effects of glutamate, aspartate, N-methyl-d-aspartate (NMDA), kainic acid and (+/-)-1-aminocyclopentane-cis-1,3-dicarboxylic acid (ACPD) on tone and spontaneous activity of isolated rat gastric fundus, jejunum, ileum, ascending colon and rectum. Both glutamate and aspartate produced concentration-dependent tonic contractions of rat fundus and rectum; the other gut segments used in the study were not responsive.

Schild's equation and the best estimate of pA2 value and dissociation constant of an antagonist.

Calculation of the pA2 value and dissociation constants for an antagonist from the effects observed on isolated smooth muscles can be done in two ways: using Schild's plot procedure or Schild's equation. In our study we used the effects of muscarinic antagonists observed in experiments on isolated human and feline stomach and rat gastric fundus. Only the estimates of pA2 values and dissociation constants made using the Schild's equation on the basis of the lowest antagonist concentrations were not significantly different from the values calculated using the Schild's plot procedure.