Synthesis, antileishmanial activity and QSAR studies of 2-chloro- N -arylacetamides

ABSTRACT We describe herein the synthesis and evaluation of the antileishmanial activity against promastigote forms of Leishmania amazonensis and cytotoxicity to murine macrophages of a series of 2-chloro-N-arylacetamide derivatives. All compounds were active, except one (compound 3). Compound 5 presented the most promising results, showing good antileishmanial activity (CI50=5.39±0.67 µM) and moderate selectivity (SI=6.36), indicating that further development of this class is worthwhile. Preliminary QSAR studies, although not predictive, furnished some insights on the importance of electronic character of aryl substituent to biological activity, as well as an indirect influence of hydrophobicity on activity

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Direct detection of Mycobacterium tuberculosis complex in bovine and bubaline tissues through nested-PCR

Post-mortem bacterial culture and specific biochemical tests are currently performed to characterize the etiologic agent of bovine tuberculosis. Cultures take up to 90 days to develop. A diagnosis by molecular tests such as PCR can provide fast and reliable results while significantly decreasing the time of confirmation. In the present study, a nested-PCR system, targeting rv2807, with conventional PCR followed by real-time PCR, was developed to detect Mycobacterium tuberculosis complex (MTC) organisms directly from bovine and bubaline tissue homogenates. The sensitivity and specificity of the reactions were assessed with DNA samples extracted from tuberculous and non-tuberculous mycobacteria, as well as other Actinomycetales species and DNA samples extracted directly from bovine and bubaline tissue homogenates. Regarding the analytical sensitivity, DNA of the M. bovis AN5 strain was detected up to 1.5 pg by nested-PCR, whereas DNA of M. tuberculosis H37Rv strain was detected up to 6.1 pg. The nested-PCR system showed 100% analytical specificity for MTC when tested with DNA of reference strains of non-tuberculous mycobacteria and closely-related Actinomycetales. A clinical sensitivity level of 76.7% was detected with tissues samples positive for MTC by means of the culture and conventional PCR. A clinical specificity of 100% was detected with DNA from tissue samples of cattle with negative results in the comparative intradermal tuberculin test. These cattle exhibited no visible lesions and were negative in the culture for MTC. The use of the nested-PCR assay to detect M. tuberculosis complex in tissue homogenates provided a rapid diagnosis of bovine and bubaline tuberculosis

Inventário da família Orchidaceae na Amazônia Brasileira: parte I Preliminary results of an inventory of the Orchidaceae family in the Brazilian Amazon

São apresentados os resultados parciais de um levantamento sistematizado da família Orchidaceae na Amazônia brasileira. O objetivo do trabalho é conhecer a diversidade específica e aspectos da biologia, biogeografia e ecologia desta família. Foi registrado, até o momento, um total de 378 espécies distribuídas entre 99 gêneros. Destas, algumas são espécies novas para a ciência, cuja a descrição foi feita com base em material tipo coletado pelos autores. Outras são novas citações para a flora brasileira.<br>A total of 378 species of 99 genera were registered, some of these species are new to science while and others are new records for the Brazilian flora

ESCAPE pain trial - The effects of Curcumin in pain relief in women diagnosed with primary dysmenorrhea: A triple blinded, placebo-controlled, phase II, randomized clinical trial protocol

ntroduction: Primary dysmenorrhea affects many women, being a major cause of absenteeism and reduced productivity at work and at school. Although non-steroidal anti-inflammatory drugs (NSAIDs) are a good treatment option, up to 18% of women show no response or present allergic reactions and adverse events. Curcumin has antispasmodic, antinociceptive and both specific and nonspecific anti-inflammatory effects, with good tolerability and safety. To date, no previous trial involving curcumin and dysmenorrhea pain has been performed. Therefore, our main goal is to assess the efficacy of curcumin for pain relief among women with primary dysmenorrhea, along with determining curcumin\u2019s adverse effects and tolerability profile. Methods:A phase II, single-center, randomized, triple-blinded, placebo-controlled, parallel-group, superiority trial to evaluate the effect of curcumin (500 mg/12h) in pain reduction in women (18 to 35-year-old) with primary dysmenorrhea. A first cycle will be used for a passive, observational run-in phase. A sample of 108 participants (54 per group) is necessary to detect a 30% difference in pain sensitivity between groups assessed by visual analogue scale (VAS). Secondary outcomes include side effects, Cox Menstrual Symptom Scale (CMSS), and use of rescue drugs for pain relief. Discussion: Clinical evidence has shown analgesic and anti-inflammatory effects of curcumin and in view of dysmenorrhea\u2019s physiopathology being related to those mechanisms targeted by curcumin, we hypothesize its use could represent an innovative and effective therapy to reduce the severity of this disease and its symptoms.Keywords:primary dysmenorrhea, Curcumin, pain relief, Visual Analogue Scale, Cox Menstrual Sympto