Neutrophil Activated by the Famous and Potent PMA (Phorbol Myristate Acetate).

This review will briefly outline the major signaling pathways in PMA-activated neutrophils. PMA is widely used to understand neutrophil pathways and formation of NETs. PMA activates PKC; however, we highlight some isoforms that contribute to specific functions. PKC α, ß and δ contribute to ROS production while PKC ßII and PKC ζ are involved in cytoskeleton remodeling. Actin polymerization is important for the chemotaxis of neutrophils and its remodeling is connected to ROS balance. We suggest that, although ROS and production of NETs are usually observed together in PMA-activated neutrophils, there might be a regulatory mechanism balancing both. Interestingly, we suggest that serine proteases might determine the PAD4 action. PAD4 could be responsible for the activation of the NF-κB pathway that leads to IL-1ß release, triggering the cleavage of gasdermin D by serine proteases such as elastase, leading to pore formation contributing to release of NETs. On the other hand, when serine proteases are inhibited, NETs are formed by citrullination through the PAD4 pathway. This review puts together results from the last 31 years of research on the effects of PMA on the neutrophil and proposes new insights on their interpretation.

Assistência farmacêutica na pandemia da Covid-19: uma pesquisa documental / Pharmaceutical assistance in the Covid-19 pandemic: a documentary research / Asistencia farmacéutica en la pandemia de Covid-19: una investigación documental

Resumo Este artigo objetivou discutir as propostas de reorganização da assistência farmacêutica durante a pandemia da Coronavirus disease-19 (Covid-19) pelas secretarias de saúde dos estados brasileiros e do Distrito Federal. Para tanto, foi realizada uma pesquisa documental dos arquivos disponibilizados nos sites das secretarias. A interpretação dos dados revelou três categorias de discussão sobre a reorganização da assistência farmacêutica do Sistema Único de Saúde: garantia do acesso às tecnologias em saúde, telefarmácia e promoção do uso racional de medicamentos e segurança na dispensação. Além de oferecer um sistema de abastecimento de tecnologias indispensáveis para o funcionamento dos serviços de saúde, as ações de assistência farmacêutica foram citadas como estratégicas para a difusão de informações fundamentadas em evidências, colaborando para a integralidade, a resolubilidade e a eficiência das intervenções em saúde.

Abstract This article aimed to discuss the proposals for reorganizing pharmaceutical assistance during the Coronavirus disease-19 (COVID-19) pandemic by the health departments of the Brazilian states and the Federal District. To this end, a documentary search of the files made available on the websites of the aforementioned departments was carried out. The interpretation of the data showed three categories of discussion on the reorganization of pharmaceutical assistance in the Unified Health System: ensuring access to health technologies, tele-pharmacy and promoting the rational use of medicines and safety in dispensing. In addition to offering a system of supply of essential technologies for the functioning of health services, pharmaceutical assistance actions were cited as strategic for the dissemination of evidence-based information, contributing to the completeness, resolvability and efficiency of health interventions.

Resumen Este artículo objetiva discutir las propuestas de reorganización de la asistencia farmacéutica durante la pandemia de Coronavirus-19 (Covid-19) por parte de las secretarías de salud de los estados brasileños y del Distrito Federal. Con este fin, se llevó a cabo una búsqueda documental de los archivos disponibles en los sitios web de las secretarías. La interpretación de los datos reveló tres categorías de discusión sobre la reorganización de la atención farmacéutica del Sistema Único de Salud: garantizar el acceso a las tecnologías de salud, telefarmacia y promover el uso racional de los medicamentos y la seguridad en la dispensación. Además de ofrecer un sistema de suministro de tecnologías indispensables para el funcionamiento de los servicios de salud, las acciones de asistencia farmacéutica fueron citadas como estratégicas para la difusión de informaciones fundamentales basadas en evidencias, colaborando para la integridad, resolución y eficiencia de las intervenciones de salud.

Paternal Resistance Training Modulates Calcaneal Tendon Proteome in the Offspring Exposed to High-Fat Diet.

The increase in high-energy dietary intakes is a well-known risk factor for many diseases, and can also negatively impact the tendon. Ancestral lifestyle can mitigate the metabolic harmful effects of offspring exposed to high-fat diet (HF). However, the influence of paternal exercise on molecular pathways associated to offspring tendon remodeling remains to be determined. We investigated the effects of 8 weeks of paternal resistance training (RT) on offspring tendon proteome exposed to standard diet or HF diet. Wistar rats were randomly divided into two groups: sedentary fathers and trained fathers (8 weeks, three times per week, with 8-12 dynamic movements per climb in a stair climbing apparatus). The offspring were obtained by mating with sedentary females. Upon weaning, male offspring were divided into four groups (five animals per group): offspring from sedentary fathers were exposed either to control diet (SFO-C), or to high-fat diet (SFO-HF); offspring from trained fathers were exposed to control diet (TFO-C) or to a high-fat diet (TFO-HF). The Nano-LC-MS/MS analysis revealed 383 regulated proteins among offspring groups. HF diet induced a decrease of abundance in tendon proteins related to extracellular matrix organization, transport, immune response and translation. On the other hand, the changes in the offspring tendon proteome in response to paternal RT were more pronounced when the offspring were exposed to HF diet, resulting in positive regulation of proteins essential for the maintenance of tendon integrity. Most of the modulated proteins are associated to biological pathways related to tendon protection and damage recovery, such as extracellular matrix organization and transport. The present study demonstrated that the father's lifestyle could be crucial for tendon homeostasis in the first generation. Our results provide important insights into the molecular mechanisms involved in paternal intergenerational effects and potential protective outcomes of paternal RT.