Bariatric surgery blunts nitrate-mediated improvements in cardiovascular function of overweight women by interfering with gastric S-nitrosothiol formation.

Inorganic nitrate (NO) and nitrate-rich foods have been shown to exert antioxidative effects and lower blood pressure in experimental animal models and human clinical studies. The specific handling of nitrate, including its enterosalivary recirculation, secretion into saliva, oral microbial reduction to nitrite (NO), and the pH-dependent nitrosative capacity in the stomach have all been recognized as being important for nitrate's beneficial effects. Obesity is of major health concern worldwide and associated with increased cardiovascular risk; whether nitrate lowers blood pressure and improves endothelial function in this setting has not been investigated.

Intestinal P-gp activity is reduced in postmenopausal women under breast cancer therapy.

Intestinal P-glycoprotein (P-gp) activity plays a crucial role in modulating the oral bioavailability of its substrates. Fexofenadine has commonly been used as a P-gp probe, although it is important to note the involvement of other drug transporters like, OATP1B1, OATP1B3, and OATP2B1. In vitro studies demonstrated an upregulation of P-gp protein in response to exposure to pregnancy-related hormones.

Pharmacodynamic effect of gabapentin on central nervous system in patients with chronic low back pain: a [99mTc]Tc-ECD SPECT study.

Background: Gabapentin is an effective therapeutic alternative for chronic low back pain, indicated in several guidelines for treating neuropathic pain as first-line medication. This study aimed to describe the pharmacodynamics of gabapentin in the central nervous system of patients with chronic low back pain (CLBP) by using single-photon emission CT (SPECT) with [99mTc]Tc-ECD.

Methods: We selected 13 patients with CLBP due to lumbar disc herniation.

Efficacy of a 0.5% Propolis -0.9% Pomegranate Buccal Spray Treatment Compared with 2% Miconazole Gel for Denture Stomatitis Treatment in Elderly Patients: a Randomized Clinical Trial.

Statement Of The Problem: Natural products have attracted interest as an alternative to synthetic medi-cations for the treatment of oral diseases due to their efficacy and safety. Propolis and pomegranate extracts have both demonstrated efficacy for the treatment of denture stomatitis. However, use of the two compounds together has not been tested for this purpose.

Neurobiological substrates of chronic low back pain (CLBP): a brain [Tc]Tc-ECD SPECT study.

Background: Recent neuroimaging studies have demonstrated pathological mechanisms related to cerebral neuroplasticity in chronic low back pain (CLBP). Few studies have compared cerebral changes between patients with and without pain in the absence of an experimentally induced stimulus. We investigated the neurobiological substrates associated with chronic low back pain using [Tc]Tc-ECD brain SPECT and correlated rCBF findings with the numeric rating scale (NRS) of pain and douleur neuropathique en 4 questions (DN4).

Cohort study protocol of the Brazilian collaborative research network on COVID-19: strengthening WHO global data.

Introduction: With the COVID-19 pandemic, hospitals in low-income countries were faced with a triple challenge. First, a large number of patients required hospitalisation because of the infection's more severe symptoms. Second, there was a lack of systematic and broad testing policies for early identification of cases.

Translation, Cross-Cultural Adaptation, and Validation of the Portuguese Version of the Rotterdam Elderly Pain Observation Scale.

Introduction: This study reports on the translation, cultural adaptation, and validation of a Portuguese version of the Rotterdam Elderly Pain Observation Scale (REPOS), a Dutch scale to assess pain in patients who cannot communicate, with or without dementia.

Methods: This is a multicenter study in pain and neurological units involving Brazil (clinical phase) and the Netherlands (training phase). We performed a retrospective cross-sectional, 2-staged analysis, translating and culturally adapting the REPOS to a Portuguese version (REPOS-P) and evaluating its psychometric properties.

Efficacy of House Dust Mite Sublingual Immunotherapy in Patients with Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Sensitization to house dust mites (HDMs) is frequent in patients with atopic dermatitis.

Objective: To investigate the efficacy of sublingual immunotherapy (SLIT) with Dermatophagoides pteronyssinus extract in patients with atopic dermatitis sensitized to HDM.

Methods: In this randomized, double-blind, placebo-controlled trial, we enrolled 91 patients 3 years or older, with SCORing Atopic Dermatitis (SCORAD) score greater than or equal to 15 and positive skin test result and/or IgE to D pteronyssinus.

Metabolizer phenotype prediction in different Peruvian ethnic groups through polymorphisms.

Objectives: The gene have three common alleles, , and , associated with different homozygous ( and ) and heterozygous ( and ) genotypes, which in turn are related to extensive (EM), intermediate (IM) and poor (PM) metabolizers. Likewise, the inter-ethnic variability was intimately associated with different drug metabolism. Therefore, the aim of the present study was predict the metabolizer phenotypes in different Peruvian ethnic groups from lowland (<2,500 m) and highland (>2,500 m).

Meningococcal disease epidemiology in Brazil (2005-2018) and impact of MenC vaccination.

Background: Meningococcal disease (MD) presents a substantial public health problem in Brazil. Meningococcal C conjugate (MenC) vaccination was introduced into the routine infant immunization program in 2010, followed by adolescent vaccination in 2017. We evaluated changes in national and regional MD incidence and mortality between 2005 and 2018, serogroup distribution and vaccine coverage.

Nifedipine Does Not Alter the Pharmacokinetics of Venlafaxine Enantiomers in Healthy Subjects Phenotyped for CYP2D6, CYP2C19, and CYP3A.

Venlafaxine (VEN) is a P-glycoprotein (P-gp) substrate, and nifedipine has been described by in vitro and experimental studies as a P-gp inhibitor. The present study aimed to investigate whether nifedipine alters the kinetic disposition of VEN enantiomers and their metabolites in healthy subjects. A crossover study was conducted in 10 healthy subjects phenotyped as extensive metabolizers for cytochrome P450 (CYP) 2D6, CYP2C19, and CYP3A.

Estimating resting energy expenditure from dual-energy X-ray absorptiometry: A cross-sectional study in healthy young adults.

Objective: To qualify a 3C approach model of dual-energy X-ray absorptiometry (DXA) to estimate multicomponent resting energy expenditure (REE) referenced by indirect calorimetry (IC).

Methods: A sample of 155 college students, of both sexes (18-30 years old) was evaluated. Anthropometric measures, REE by IC, and whole-body DXA-scans were performed.

Direct chiral LC-MS/MS analysis of fexofenadine enantiomers in plasma and urine with application in a maternal-fetal pharmacokinetic study.

This study shows the development and validation of two enantioselective LC-MS/MS methods for the determination of fexofenadine in biological matrices including the elution order determination. Plasma (200 µL) or urine (50 µL) aliquots were added to the internal standard solution [(S)-(-)-metoprolol] and extracted in the acid medium with chloroform. Resolution of the (R)-(+)- and (S)-(-)-fexofenadine enantiomers was performed in a Chirobiotic V column.

Limited Sampling Modeling for Estimation of Phenotypic Metrics for CYP Enzymes and the ABCB1 Transporter Using a Cocktail Approach.

Plasma concentration data points (n = 2,640) from 16 healthy adults were used to develop and validate limited sampling strategies (LSS) for estimation of phenotypic metrics for CYP enzymes and the ABCB1 transporter, using a cocktail of subtherapeutic doses of the selective probes caffeine (CYP1A2), metoprolol (CYP2D6), midazolam (CYP3A), losartan (CYP2C9), omeprazole (CYP2C19), and fexofenadine (ABCB1). All-subsets linear regression modelling was applied to estimate the AUC for caffeine, fexofenadine, and midazolam, and the AUC ratio of metoprolol: α-OH metoprolol and omeprazole:5-OH omeprazole. LSS-derived metrics were compared with the parameters' 'best estimates' obtained by non-compartmental analysis using all plasma concentration data points.

Hormonal status affects plasma exposure of tamoxifen and its main metabolites in tamoxifen-treated breast cancer patients.

Background: Tamoxifen is considered a prodrug of its active metabolite endoxifen, which is dependent on the CYP2D6 and CYP3A enzymes. Tamoxifen pharmacokinetic variability influences endoxifen exposure and, consequently, its clinical outcome. This study investigated the impact of hormonal status on the pharmacokinetics of tamoxifen and its metabolites in TAM-treated breast cancer patients.

Effect of Lercanidipine on the Pharmacokinetics-Pharmacodynamics of Carvedilol Enantiomers in Patients With Chronic Kidney Disease.

This study evaluates the carvedilol-lercanidipine drug interaction, and the influence of chronic kidney disease (CKD) on both drugs. Patients with high blood pressure (8 with normal renal function [control] and 8 with CKD with estimated glomerular filtration rate categories of G3b to G5 [12-38 mL/min/1.73 m ]) were included and prescribed 3 different treatment regimens, a single oral dose of racemic carvedilol 25 mg (CAR), a single oral dose of racemic lercanidipine 20 mg (LER), and single oral doses of CAR plus LER.

Geographic distribution of the 3435C>T polymorphism of the MDR1 gene in Peruvian populations.

Background The MDR1 gene presents several genetic polymorphisms with pharmacological implications. Therefore, the aim of the present study is to establish the genotype and allele frequencies of 3435C>T polymorphism of MDR1 gene into Peruvian populations (Coastal, Andean and Amazonian ecoregions), even considering the altitude (lowland <2500 m and highland >2500 m). Methods The polymorphism was analyzed by TaqMan genotyping assays in a group of 181 healthy unrelated Peruvian individuals.

Pertussis epidemiological pattern and disease burden in Brazil: an analysis of national public health surveillance data.

We described pertussis epidemiological trends in Brazil between 2010 and 2015. We also assessed tetanus, diphtheria and acellular pertussis (Tdap) vaccine coverage among pregnant women from 2014, the year of the introduction of Tdap maternal immunization recommendation in Brazil, to 2016. Epidemiological data for incidence, prevalence, hospitalization, mortality, and maternal vaccination coverage were calculated based on the Brazilian public surveillance databases.

LC-MS/MS analysis of the plasma concentrations of a cocktail of 5 cytochrome P450 and P-glycoprotein probe substrates and their metabolites using subtherapeutic doses.

Drug transporters and CYP enzymes are important sources of pharmacokinetics (PK) variability in drug responses and can cause various pharmacological and toxicological consequences, leading to either toxicity or an insufficient pharmacological effect. In recent years, the cocktail approach was developed to determine in vivo CYP and transporters activities, but these approaches are somewhat limited. We described the development and validation of three sensitive and specific LC-MS/MS assays for the determination of P-gp and major human CYP isoenzyme activities following oral administration of a drug cocktail of subtherapeutic doses (lower than 10 times) of caffeine (CAF), omeprazole (OME), losartan (LOS), midazolam (MDZ), metoprolol (METO) and fexofenadine (FEX) in healthy volunteers.

Analysis of unbound plasma concentration of oxcarbazepine and the 10-hydroxycarbazepine enantiomers by liquid chromatography with tandem mass spectrometry in healthy volunteers.

This study describes the development and validation of a method for the analysis of unbound plasma concentrations of oxcarbazepine (OXC) and of the enantiomers of its active metabolite 10-hydroxycarbazepine (MHD) [S-(+)- and R-(-)-MHD] using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Additionally, the free fraction of the drug is described in healthy volunteers (n=12) after the oral administration of 300mg OXC/12h for 5days. Plasma aliquots of 200μL were submitted to ultrafiltration procedure and 50μL of the ultrafiltrate were extracted with a mixture of tert-butyl methyl ether:dichloromethane (2:1, v/v).

The Diterpene Sclareol Vascular Effect in Normotensive and Hypertensive Rats.

Background:: The diterpene Sclareol has antimicrobial action, cytotoxic and cytostatic effects and anti-tumor activities. However, researches on the cardiovascular system are scarce.

Objective:: This study was designed to investigate the mechanisms involved in the Sclareol cardiovascular effect in normotensive and hypertensive rats.

Population pharmacokinetics of oxcarbazepine and its metabolite 10-hydroxycarbazepine in healthy subjects.

Oxcarbazepine is indicated for the treatment of partial or generalised tonic-clonic seizures. Most of the absorbed oxcarbazepine is converted into its active metabolite, 10-hydroxycarbazepine (MHD), which can exist as R-(-)- and S-(+)-MHD enantiomers. Here we describe the influence of the P-glycoprotein (P-gp) inhibitor verapamil, on the disposition of oxcarbazepine and MHD enantiomers, both of which are P-gp substrates.

Enantioselectivity in the Metabolism of Cyclophosphamide in Patients With Multiple or Systemic Sclerosis.

The aim of this study was to evaluate the enantioselective pharmacokinetics of cyclophosphamide and its metabolites 4-hydroxycyclophosphamide and carboxyethylphosphoramide mustard in patients with systemic or multiple sclerosis. Patients with systemic sclerosis (n = 10) or multiple sclerosis (n = 10), genotyped for the allelic variants of CYP2C9*2 and CYP2C9*3 and of the CYP2B6 G516T polymorphism, were treated with 50 mg cyclophosphamide/kg daily for 4 days. Serial blood samples were collected up to 24 hours after administration of the last cyclophosphamide dose.