A high performance liquid chromatography method for determination of hydroxyzine hydrochloride in syrup

A simple isocratic method for quantification of hydroxyzine dihydrochloride by HPLC with UV detection at 232 nm in syrup has been developed and validated. Separation was achieved on a C18 column (250 x 4.6 mm, 5 μm) maintained at 90 ºC with 0.5 mol/L potassium dihydrogen phosphate buffer : acetonitrile (1:1, v/v) as mobile phase at a flow rate of 2.0 mL/min. The method was proven to be linear over the range of 80–120 μg/mL, accurate (recovery = 97.8 %), precise (coefficient of variation = 1.52 % for sample) and robust.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Brazilian network for HIV Drug Resistance Surveillance (HIV-BresNet): a survey of treatment-naive individuals

Introduction: In Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug-resistant strains and HIV subtype distribution in the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015. Methods: The HIV threshold survey methodology (HIV-THS, WHO) targeting antiretroviral-naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions. The HIV pol genotypic test was performed by genomic sequencing. Results: We analysed samples from 1568 antiretroviral-naive individuals recently diagnosed with HIV, and the overall transmitted drug resistance (TDR) prevalence was 9.5% (150 sequences). The regional prevalence of resistance according to Brazilian geographical regions was 9.4% in the northeast, 11.2% in the southeast, 6.8% in the central region, 10.2% in the north and 8.8% in the south. The inhibitor-specific TDR prevalence was 3.6% for nucleoside reverse transcriptase inhibitors (NRTIs), 5.8% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 1.6% for protease inhibitors (PIs)1.0% of individuals presented resistance to more than one class of inhibitors. Overall, subtype B was more prevalent in every region except for the southern, where subtype C prevails. Conclusions: To the best of our knowledge, this is the first TDR study conducted in Brazil with nationwide representative sampling. The TDR prevalence revealed a moderate rate in the five Brazilian geographical regions, although some cities presented higher TDR prevalence rates, reaching 14% in Sao Paulo, for example. These results further illustrate the importance of surveillance studies for designing future strategies in primary antiretroviral therapy, aiming to mitigate TDR, as well as for predicting future trends in other regions of the globe where mass antiretroviral (ARV) treatment was implemented.Brazilian Ministry of HealthUniv Fed Rio de Janeiro, Lab Virol Mol, Dept Genet IB, Rio De Janeiro, RJ, BrazilFdn Med Trop Amazonas, Manaus, Amazonas, BrazilLAPI Univ Fed Bahia, Hosp Univ Prof Edgar Santos, Lab Pesquisa, Salvador, BA, BrazilLab Cent Saude Publ Ceara Lacen CE, Fortaleza, Ceara, BrazilLab Cent Saude Publ Dist Fed, Setor Grandes Areas Norte SGAN 601, Brasilia, DF, BrazilUniv Fed Minas Gerais UFMG, Fac Med, Lab Imunol & Biol Mol DIP, Belo Horizonte, MG, BrazilLab Cent Saude Publ Mato Grosso Sul, Campo Grande, MS, BrazilLab Cent Saude Publ Pernambuco, Recife, PE, BrazilLab Municipal Curitiba, Curitiba, PR, BrazilFiocruz MS, Lab AIDS & Imunol Mol, Dept Imunol, Rio De Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, Lab Carga Viral, Rio de Janeiro, RJ, BrazilInst Biol Exercito, Rio De Janeiro, RJ, BrazilLab Cent Saude Publ Rio Grande Sul, Porto Alegre, RS, BrazilLab Hosp Nossa Senhora Conceicao, Porto Alegre, RS, BrazilLab Cent Saude Publ Santa Catarina, Florianopolis, SC, BrazilUNESP, Lab Biol Mol Hemocentro Botucatu, Fac Med, Botucatu, SP, BrazilUniv Estadual Campinas, Lab Pesquisa AIDS, Hosp Clin, Campinas, SP, BrazilInst Adolfo Lutz Sao Jose do Rio Preto, Lab Biol Mol, Sao Jose Do Rio Preto, SP, BrazilUniv Fed Sao Paulo UNIFESP, Escola Paulista Med, Lab Retrovirol, Sao Paulo, SP, BrazilInst Adolfo Lutz Cent, Lab Retrovirus, Ctr Virol, Nucleo Doencas Sanguineas & Sexuais, Sao Paulo, SP, BrazilMinist Saude, Dept Vigilancia Prevencao & Controle DST AIDS & H, Setor Adm Fed Sul SAFS 02, Secretaria Vigilancia Saude, Brasilia, DF, BrazilUniv Brasilia, Programa Pos Grad Saude Colet, Fac Med, Fac Ciencias Saude, Brasilia, DF, BrazilUniv Sao Paulo, Fac Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Escola Paulista Med, Lab Retrovirol, Sao Paulo, SP, BrazilBMH: TC 298/12Web of Scienc

The Combined Use of Melatonin and an Indoleamine 2,3-Dioxygenase-1 Inhibitor Enhances Vaccine-Induced Protective Cellular Immunity to HPV16-Associated Tumors

Immunotherapy has become an important ally in the fight against distinct types of cancer. However, the metabolic plasticity of the tumor environment frequently influences the efficacy of therapeutic procedures, including those based on immunological tools. In this scenario, immunometabolic adjuvants arise as an alternative toward the development of more efficient cancer therapies. Here we demonstrated that the combination of melatonin, a neuroimmunomodulator molecule, and an indoleamine 2,3-dioxygenase (IDO) inhibitor (1-methyl-DL-tryptophan, DL-1MT) improves the efficacy of an immunotherapy (gDE7) targeting human papillomavirus (HPV)-associated tumors. Melatonin or IDO inhibitors (D-1MT and DL-1MT) directly reduced proliferation, migration, adhesion and viability of a tumor cell line (TC-1), capable to express the HPV-16 E6 and E7 oncoproteins, but could not confer in vivo antitumor protection effects. Nonetheless, combination of gDE7 with melatonin or D-1MT or DL-1MT enhanced the antitumor protective immunity of gDE7-based vaccine in mice. Notably, expression of IDO1 in stromal cells and/or immune cells, but not in tumor cells, inhibited the antitumor effects of the gDE7, as demonstrated in IDO1-deficient mice. Finally, co-administration of gDE7, melatonin and DL-1MT further improved the protective antitumor effects and the numbers of circulating E7-specific CD8+ T cells in mice previously transplanted with TC-1 cells. The unprecedented combination of melatonin and IDO inhibitors, as immunometabolic adjuvants, thus, represents a new and promising alternative for improving the efficacy of immunotherapeutic treatments of HPV-associated tumors

Transmission of MRSA between Companion Animals and Infected Human Patients Presenting to Outpatient Medical Care Facilities

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen in both human and veterinary medicine. The importance of companion animals as reservoirs of human infections is currently unknown. The companion animals of 49 MRSA-infected outpatients (cases) were screened for MRSA carriage, and their bacterial isolates were compared with those of the infected patients using Pulsed-Field Gel Electrophoresis (PFGE). Rates of MRSA among the companion animals of MRSA-infected patients were compared to rates of MRSA among companion animals of pet guardians attending a “veterinary wellness clinic” (controls). MRSA was isolated from at least one companion animal in 4/49 (8.2%) households of MRSA-infected outpatients vs. none of the pets of the 50 uninfected human controls. Using PFGE, patient-pets MRSA isolates were identical for three pairs and discordant for one pair (suggested MRSA inter-specie transmission p-value = 0.1175). These results suggest that companion animals of MRSA-infected patients can be culture-positive for MRSA, representing a potential source of infection or re-infection for humans. Further studies are required to better understand the epidemiology of MRSA human-animal inter-specie transmission

Primary brain calcification: an international study reporting novel variants and associated phenotypes.

Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with a wide spectrum of motor, cognitive, and neuropsychiatric symptoms. It is typically inherited as an autosomal-dominant trait with four causative genes identified so far: SLC20A2, PDGFRB, PDGFB, and XPR1. Our study aimed at screening the coding regions of these genes in a series of 177 unrelated probands that fulfilled the diagnostic criteria for primary brain calcification regardless of their family history. Sequence variants were classified as pathogenic, likely pathogenic, or of uncertain significance (VUS), based on the ACMG-AMP recommendations. We identified 45 probands (25.4%) carrying either pathogenic or likely pathogenic variants (n = 34, 19.2%) or VUS (n = 11, 6.2%). SLC20A2 provided the highest contribution (16.9%), followed by XPR1 and PDGFB (3.4% each), and PDGFRB (1.7%). A total of 81.5% of carriers were symptomatic and the most recurrent symptoms were parkinsonism, cognitive impairment, and psychiatric disturbances (52.3%, 40.9%, and 38.6% of symptomatic individuals, respectively), with a wide range of age at onset (from childhood to 81 years). While the pathogenic and likely pathogenic variants identified in this study can be used for genetic counseling, the VUS will require additional evidence, such as recurrence in unrelated patients, in order to be classified as pathogenic