Intravital Microscopy Evidence That Methylene Blue Should Be a Vasopressor-Sparing Agent in Sepsis Vasoplegia.

Microvasculature failure is expected in sepsis and at higher amine concentrations. Therefore, special attention focused individually on microcirculation is needed. Here, we present that methylene blue can prevent leukocytes from adhering to the endothelium in a rat model of lipopolysaccharide-induced endotoxemia. As hypothesis evidence, an intravital microscopy image is presented.

Smooth muscle contraction of the fundus of stomach, duodenum and bladder from mice exposed to a stress-based model of depression.

Several reports have demonstrated that depressive disorder is related to somatic symptoms including gastrointestinal or genitourinary alterations. The pathophysiological mechanisms underlying the gastrointestinal or genitourinary alterations associated with the depression are still not fully understood. Therefore, this study aimed to evaluate the motor activity of gastrointestinal (fundus of stomach and duodenum) and genitourinary tract (bladder) in a stress-based animal model of depression. Adult male mice were submitted to uncontrollable and unpredictable stress (learned helplessness model), controllable stress and non-stressful situations (control). Then, animals were euthanized and the fundus of stomach, duodenum segments or whole bladder were isolated and mounted in a standard organ bath preparation. We evaluated the contractile effects induced by KCl 80 mM for 5 min or carbachol (acetylcholine receptor agonist). The relaxant effects of isoproterenol (ß-adrenoceptor agonist) were also checked. Animals submitted to the learned helplessness model developed a helpless (depressive-like behavior) or resilient (does not exhibit depressive-like behavior) phenotype. The contractions induced by carbachol were diminished in fundus of stomach isolated from helpless and resilient animals. The isoproterenol-induced fundus of stomach relaxation was reduced in resilient but not helpless mice. The contractions/relaxation of duodenum segments isolated from helpless or resilient animals were not altered. Both helpless and resilient animals showed an increase in the bladder contractions induced by carbachol while the relaxant effects of isoproterenol were reduced when compared to control. Conversely, mice underwent a controllable stress situation did not exhibit alterations in the fundus of stomach or duodenum contraction/relaxation induced by pharmacological agents although a decrease in the bladder contraction induced by carbachol was found. In conclusion, incontrollable and unpredictable stress and not depressive phenotype (helpless animals) or controllable stress could be related to the alterations in motor activity of the fundus of stomach and bladder.

Effects of histamine on the contractility of the rat distal cauda epididymis.

The motor activity of the epididymis duct is an essential process for male fertility and it is regulated by hormonal, neuronal and epithelial mechanisms. However, although there is evidence for the presence of histamine in the epididymis, its effects on epididymal motor activity are unknown. This study sought to evaluate the contractile effects of histamine on the rat distal cauda epididymis duct. Segments of the distal cauda epididymis duct from male Wistar rats were isolated and used in isolated organ bath experiments to evaluate the contractile effects of histamine in the absence or presence of antagonists of histamine receptors, α1-adrenoceptors and muscarinic acetylcholine receptors. The effects of histamine on noradrenaline induced contractions were also investigated. Histamine was able to induce phasic contractions on rat distal cauda epididymis duct which were prevented by promethazine 10-1000 nM (H1 receptor antagonist), ranitidine 1-100 µM (H2 receptor antagonist), atropine 100 nM (muscarinic antagonist), and prazosin 100 nM (α1-adrenoceptor antagonist). In addition, histamine was also able to modify noradrenaline-induced contractions possibly via activation of H1 and H2 receptors. In conclusion, this study demonstrates that histamine can induce phasic contractions of rat distal cauda epididymis via H2 receptors and autonomic neurotransmitters. Histamine may also exert modulatory actions on contractions of rat distal cauda epididymis duct induced by adrenergic receptor agonists. Further studies are necessary to unveil the localization of histamine receptors within the epididymal duct and the consequences of manipulation of the histaminergic system on epididymal function and male fertility.

Effects of dipyrone and acetylsalicylic acid on contractions of distal cauda epididymis duct, serum testosterone and sperm count in rats.

The effects of dipyrone and acetylsalicylic acid (ASA) on male fertility are still not fully understood, mainly considering the epididymis as a putative target for their anti-fertility effects. Therefore, this study aimed to investigate the effects of dipyrone and ASA on the contractions of distal cauda epididymis duct, serum testosterone levels and sperm parameters in rats. Firstly, we checked the in vitro effects of dipyrone and ASA (10-1000 µM) on the contractions of distal cauda epididymis duct by pharmacological experiments. We also evaluated the effects of in vivo treatment with dipyrone and ASA 100 mg/kg (p.o.) for 15 days on epididymal duct contractions, serum testosterone levels and sperm parameters. In vitro dipyrone or ASA decreased the epididymal duct contractions induced by phenylephrine or carbachol. We observed that in vivo treatment with both drugs decreased the daily sperm production, serum testosterone levels and sperm count through epididymis without altering the epididymal duct contractions and sperm transit time through epididymis. In conclusion, in vitro dipyrone and ASA were able to diminish the contractions of epididymal duct, whilst in vivo administration decreased the sperm count throughout epididymis as a consequence of a low sperm production caused by reduced testosterone levels.

Effect of high-intensity interval training on metabolic parameters in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Our aim was to assess the effect of high-intensity interval training (HIIT) on metabolic parameters and body composition in women with polycystic ovary syndrome (PCOS). METHODS AND ANALYSIS: A systematic review and meta-analysis of randomized controlled trials was conducted using Embase, MEDLINE (via Ovid), PubMed, Sport Discus, Scopus, Web of Science, Cochrane Library and Google Scholar (advanced feature) up to September 2020. Two authors independently screened citations and determined the risk of bias and quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Meta-analyses were conducted using random effects model. RESULTS: Seven trials (n = 423) were included in the systematic review. The studies included HIIT interventions vs. moderate exercise or control groups. Most studies were small (average 32, range 24-110 participants) and of relatively short duration (10-16 weeks). The training intensity was performed between 90% and 95% of the maximum heart rate, three times a week, for at least 10 weeks. Insulin resistance, measured using homeostatic model assessment for insulin resistance (HOMA-IR), and body mass index (BMI) showed a significant decrease (MD -0.57; 95% CI, -0.98 to -0.16, p = 0.01), (MD -1.90, 95% CI -3.37, -0.42, p = 0.01) with moderate and high certainty of evidence, respectively. CONCLUSION: Results support that HIIT alone is effective for reducing HOMA-IR and BMI in women with PCOS. However, evidence is limited to discern the effect of HIIT on other outcomes. Future studies with a longer duration (> 16 weeks), larger sample sizes and other outcomes are needed.