TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations.

JAK2V617F and MPLW515L/K represent recently identified mutations in myeloproliferative disorders (MPD) that cause dysregulated JAK-STAT signaling, which is implicated in MPD pathogenesis. We developed TG101209, an orally bioavailable small molecule that potently inhibits JAK2 (IC(50)=6 nM), FLT3 (IC(50)=25 nM) and RET (IC(50)=17 nM) kinases, with significantly less activity against other tyrosine kinases including JAK3 (IC(50)=169 nM). TG101209 inhibited growth of Ba/F3 cells expressing JAK2V617F or MPLW515L mutations with an IC(50) of approximately 200 nM. In a human JAK2V617F-expressing acute myeloid leukemia cell line, TG101209-induced cell cycle arrest and apoptosis, and inhibited phosphorylation of JAK2V617F, STAT5 and STAT3. Therapeutic efficacy of TG101209 was demonstrated in a nude mouse model. Furthermore, TG101209 suppressed growth of hematopoietic colonies from primary progenitor cells harboring JAK2V617F or MPL515 mutations.

Ocorrência de Campylobacter spp. em carne e miúdos de frango expostos ao consumo em Belém, Pará / Occurence of Campylobacter spp. in chicken meat and giblets exposed to consumption in Northern Brazil

In order to study Campylobacter in chicken meat exposed to consumption in the city of Belém, state of Pará, Brazil, 16 samples (four of liver, four of gizzard, two of heart, two of skin, one of neck, two of carcass and a mixture of neck skin and fragments of the abdominal cavity), collected in clandestine butcher shops, fair-free and supermarkets were submitted to isolation and identification according to the recommended methods. In high percentage, the foods exposed to consumption were contaminated by this agent, meaning a potential risk to the human health.

Isoform-selective PI3K inhibitors as novel therapeutics for the treatment of acute myocardial infarction.

In the present paper, we review the preclinical development of TG100-115, a PI3K (phosphoinositide 3-kinase) gamma/delta isoform-specific inhibitor currently in clinical trials for the reduction of acute MI (myocardial infarction). An overview is presented outlining the pathogenesis of acute MI and the rationale for clinical use of PI3K gamma/delta-specific inhibitors in this indication. TG100-115's broad anti-inflammatory activities are described, as well as its ability to discriminate between cellular signalling pathways downstream of receptor tyrosine kinase ligands such as vascular endothelial growth factor. Finally, we review TG100-115's potent cardioprotective activities as revealed in rigorous animal models of acute MI, and, based on these data, this compound's potential for clinical utility.

[Patient satisfaction at a university hospital]. / A satisfação do usuário em hospital universitário.

The results of a research project into the level of satisfaction/dissatisfaction of 158 first-time patients attending by an University hospital, Brazil, are presented. The interviews were carried out by first year medical students as part of a comprehensive project concerned with the restructuring of the Medical Curriculum. Its prime objective was to expose the students to patients/consumers as early as possible in their studies. After an introductory training program, the students asked the patients arriving at the hospital out-patient clinic for permission to observe them throughout the attendance given. A questionnaire was used which covered the various aspects of the consumers relationship with a medical institution (socio-economic variables, "art of care", outcome of the medical encounter and suggestions for improvement). Both patients and students were able to perceive the different problems that patients confront in the course of their dealings with a medical institution (reception, registration, nursing, social service and medical attention). The data showed a difference of opinion between students and patients regarding several aspects of the satisfaction/dissatisfaction items, partly because of their different social class status and party due to the different expectations regarding medical care.