Contribution of direct InhA inhibitors to novel drug regimens in a mouse model of tuberculosis.

Isoniazid is an important first-line medicine to treat tuberculosis (TB). Isoniazid resistance increases the risk of poor treatment outcomes and development of multidrug resistance, and is driven primarily by mutations involving , encoding the prodrug-activating enzyme, rather than its validated target, InhA. The chemical tractability of InhA has fostered efforts to discover direct inhibitors of InhA (DIIs).

Adaptation and validation of a method for evaluating the bactericidal activity of ethyl alcohol in gel format 70% (w/w).

Ethyl alcohol 70% (w/w) is a broad-spectrum bactericidal agent that is mandatorily marketed as a gel in Brazil since 2002. However, there is no method described for the microbiological quality control of surface disinfectants in the form of gel, which makes it impossible to monitor the effectiveness of these products by the Health Surveillance. Thus, the present study aimed to adapt an analytical method and validate it so that it is possible to evaluate the bactericidal activity of ethyl alcohol-based disinfectants at 70% (w/w) in gel form.

Polymyxin B Heteroresistance and Adaptive Resistance in Multidrug- and Extremely Drug-Resistant Acinetobacter baumannii.

Acinetobacter baumannii is an emerging pathogen associated with nosocomial infections and multidrug resistance. Polymyxin B has been used to treat infections caused by multidrug-resistant (MDR) A. baumannii but an increase in polymyxin B resistance has been observed.

Influence of substrate orientation on tadpoles' feeding efficiency.

In nature, tadpoles encounter food on substrates oriented at different angles (e.g. vertically along stems, horizontally on the bottom of the pond).

Assessing Pharmacodynamic Interactions in Mice Using the Multistate Tuberculosis Pharmacometric and General Pharmacodynamic Interaction Models.

The aim of this study was to investigate pharmacodynamic (PD) interactions in mice infected with Mycobacterium tuberculosis using population pharmacokinetics (PKs), the Multistate Tuberculosis Pharmacometric (MTP) model, and the General Pharmacodynamic Interaction (GPDI) model. Rifampicin, isoniazid, ethambutol, or pyrazinamide were administered in monotherapy for 4 weeks. Rifampicin and isoniazid showed effects in monotherapy, whereas the animals became moribund after 7 days with ethambutol or pyrazinamide alone.

Differential effects of temperature on the feeding kinematics of the tadpoles of two sympatric anuran species.

Temperature impacts ectotherm performance by influencing many biochemical and physiological processes. When well adapted to their environment, ectotherms should perform most efficiently at the temperatures they most commonly encounter. In the present study, we tested how differences in temperature affects the feeding kinematics of tadpoles of two anuran species: the benthic tadpole of Rhinella schneideri and the nektonic tadpole of Trachycephalus typhonius.

Tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide and N-benzyl-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3.

Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide (THPP) and N-benzyl-6',7'-dihydrospiro[piperidine-4,4'-thieno[3,2-c]pyran] (Spiro) analogues were recently identified against Mycobacterium tuberculosis and Mycobacterium bovis BCG through a high-throughput whole-cell screening campaign.

Comparative feeding kinematics of tropical hylid tadpoles.

Anuran larvae, which are otherwise simple in shape, typically have complex keratinized mouthparts (i.e. labial teeth and jaw sheaths) that allow them to graze upon surfaces.