8-Hydroxy-2-(1H-1,2,3-triazol-1-yl)-1,4-naphtoquinone derivatives inhibited P2X7 Receptor-Induced dye uptake into murine Macrophages.

Extracellular adenosine 5'-triphosphate (ATP) triggers the P2X7 receptor (P2X7R) ionic channel to stimulate the release of the interleukin-IL-1ß cytokine into macrophages. The current study explored the reaction of six structurally diverse triazole derivatives on P2X7-mediated dye uptake into murine peritoneal macrophages. P2X7R activity determined by ATP-evoked fluorescent dye uptake. Triazole derivatives toxicity measured using dextran rhodamine exclusion based colorimetric assay. A740004 and BBG, both P2X7R antagonist, inhibited ATP-induced dye uptake. In contrast, the derivatives 5a, 5b, 5e, and 5f did not diminish P2X7R activity in concentrations until 100 µM. 5c and 5d analogs caused a potent inhibitory activity on P2X7-induced dye uptake. Dextran Rhodamine exclusion measurements after 24 h of continuous treatment with triazole derivatives indicated a moderated toxicity for all molecules. In conclusion, this study showed that a series of new hybrid 1,2,3-triazolic naphthoquinones reduces P2X7R-induced dye uptake into murine macrophages. In silico analysis indicates a good pharmacokinetic profile and molecular docking results of these analogs indicate the potential to bind into an allosteric site located into the P2X7R pore and juxtaposed with the ATP binding pocket. In this manner, the compounds 5c and 5d may be used as a scaffold for new P2X7R inhibitors with reduced toxicity, and good anti-inflammatory activity.

Changes in cardiovascular performance, biochemistry, gastric motility and muscle temperature induced by acute exercise on a treadmill in healthy military dogs.

Changes in physiological parameters that are induced by acute exercise on a treadmill in healthy military dogs have not been thoroughly investigated, especially with regard to age. This study investigated the effects of acute exercise on a treadmill on cardiovascular function, biochemical parameters and gastric antral motility in military dogs. Thermography was used to assess variations in superficial hindlimb muscle temperature. Nine healthy dogs were distributed into three groups according to their age (Group I: 25 ± 7 months; Group II: 51 ± 12 months; Group III: 95 ± 10 months) and sequentially subjected to running exercise on a treadmill for 12 min (3.2 km/h at 0° incline for 4 min, 6.4 km/h at 0° incline for 4 min and 6.4 km/h at 10° incline for 4 min). Heart rate, systolic and diastolic arterial pressure (DAP), gastric motility, haematocrit and biochemical analyses were performed at rest and after each session of treadmill exercise. Infrared thermographic images of muscles in the pelvic member were taken. Exercise decreased DAP in Group I, increased systolic arterial pressure in Groups II and III and increased mean arterial pressure in Group III (all p < 0.05). After the exercise protocol, plasma creatine kinase and aspartate aminotransferase levels increased only in Group I (p < 0.05). Exercise increased heart rate and decreased the gastric motility of a solid meal at 180 min in all groups (all p < 0.05). Exercise also elevated temperature in the femoral biceps muscles in Group I compared with the older dogs. The results indicate that acute exercise decreased gastric motility in dogs, regardless of age, and caused more pronounced cardiovascular changes in older dogs than in younger dogs. Acute exercise also altered biochemical parameters and superficial hindlimb muscle temperature in younger military dogs.

Searching for a potential antibacterial lead structure against bacterial biofilms among new naphthoquinone compounds.

AIMS: The aims of this study were to design, synthesize and to evaluate 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones against Gram-negative and Gram-positive bacterial strains, including methicillin-resistant Staphylococcus aureus (MRSA) and its biofilm, to probe for potential lead structures. METHODS AND RESULTS: Thirty-six new analogues were prepared with good yields using a simple, fast, operational three-procedure reaction and a thiol addition to an ο-quinone methide using microwave irradiation. All compounds were tested against Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Proteus mirabilis ATCC 15290, Serratia marcescens ATCC 14756, Klebsiella pneumoniae ATCC 4352, Enterobacter cloacae ATCC 23355, Enterococcus faecalis ATCC 29212, S. aureus ATCC 25923, Staphylococcus simulans ATCC 27851, Staphylococcus epidermidis ATCC 12228 and a hospital strain of MRSA. Their antibacterial activity was determined using the disc diffusion method, revealing the activity of 19 compounds, mainly against Gram-positive strains. Interestingly, the minimal inhibitory concentration ranges detected for the hit molecules (32-128 µg ml-1 ) were within Clinical and Laboratory Standards Institute levels. Promisingly, compound 15 affected the MRSA strain, with a reduction of up to 50% in biofilm formation, which is better than vancomycin as biofilm forms a barrier against the antibiotic that avoids its action. CONCLUSIONS: After probing 36 naphthoquinones for a potential antibacterial lead structure against the bacterial biofilm, we found that compound 15 should be explored further and also should be structurally modified in the near future to test against Gram-negative strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Since vancomycin is one of the last treatment options currently available, and it is unable to inhibit biofilm, the research of new antimicrobials is urgent. In this context, 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones proved to be a promising lead structure against MRSA and bacterial biofilm.

Impacto do estresse térmico na reprodução da fêmea bovina / Heat stress impact on reproduction of bovine female

Com o objetivo de melhorar os índices de produtividade de seus rebanhos, muitos criadores de regiões tropicais têm optado pela aquisição de animais especializados oriundos de regiões de clima temperado com condições climáticas bem diferenciadas das dos trópicos. Devido às altas temperaturas tropicais, estes animais estão constantemente susceptíveis ao estresse térmico, uma vez que não são dotados de mecanismos anatomo-fisiológicos necessários para manter a homeotermia, resultando em prejuízos para a produção e reprodução animal. Portanto, esta revisão tem por objetivo discorrer sobre os efeitos negativos do estresse térmico sobre a reprodução, enfocando aspectos relacionados à atividade ovariana e à mortalidade embrionária.(AU)

Aiming to improve the productivity rates of their herds, many farmers in tropical regions have opted for the acquisition of specialized animals come from temperate regions with weather conditions so different from those found in the tropics. Due to high tropical temperatures, these animals are constantly susceptible to heat stress; because they do not have anatomical and physiological mechanisms to maintain efficiently its homeostasis, resulting in prejudices to production and reproduction performances. This review aims to discuss the adverse effects of heat stress on female reproduction, emphasizing some aspects involved in ovarian activity and embryo mortality.(AU)

Impacto do estresse térmico na reprodução da fêmea bovina / Heat stress impact on reproduction of bovine female

Com o objetivo de melhorar os índices de produtividade de seus rebanhos, muitos criadores de regiões tropicais têm optado pela aquisição de animais especializados oriundos de regiões de clima temperado com condições climáticas bem diferenciadas das dos trópicos. Devido às altas temperaturas tropicais, estes animais estão constantemente susceptíveis ao estresse térmico, uma vez que não são dotados de mecanismos anatomo-fisiológicos necessários para manter a homeotermia, resultando em prejuízos para a produção e reprodução animal. Portanto, esta revisão tem por objetivo discorrer sobre os efeitos negativos do estresse térmico sobre a reprodução, enfocando aspectos relacionados à atividade ovariana e à mortalidade embrionária.

Aiming to improve the productivity rates of their herds, many farmers in tropical regions have opted for the acquisition of specialized animals come from temperate regions with weather conditions so different from those found in the tropics. Due to high tropical temperatures, these animals are constantly susceptible to heat stress; because they do not have anatomical and physiological mechanisms to maintain efficiently its homeostasis, resulting in prejudices to production and reproduction performances. This review aims to discuss the adverse effects of heat stress on female reproduction, emphasizing some aspects involved in ovarian activity and embryo mortality.