Use of glucocorticoids and azithromycin in the therapy of COVID-19.

In December 2019, a new variant coronavirus, SARS-CoV-2, emerged in China, which was initially described as a pneumonia of an unknown agent. The new coronavirus spreads mainly by person-to-person transmission through close contact. The pathophysiology of COVID-19 is related to a complex immune system response that varies between people and, in severe cases of the disease, is characterized by excessive responses called "cytokine storms," which are associated with complications that can lead to a state of hypercoagulation and death. Glucocorticoids and azithromycin are drugs that may be effective in the treatment. This review aims to highlight the clinical findings that demonstrate the effectiveness of glucocorticoid and azithromycin therapy in the treatment of COVID-19. To date, many drugs have been studied for use in combination therapy, and the rapid expansion of knowledge about the virology of SARS-CoV-2 generates a more accurate direction in therapy.

Effects of an extract obtained from fruits of Euterpe oleracea Mart. in the components of metabolic syndrome induced in C57BL/6J mice fed a high-fat diet.

Previously, we have demonstrated that the seed of Euterpe oleracea Mart. (açaí) from the Amazon region exerts vasodilator and antihypertensive actions. The aim of our study was to assess the effects of oral chronic treatment with açaí seed extract (ASE, 300 mg · kg(-1) · d(-1)) on high-fat (HF) diet­induced metabolic syndrome (MS) in C57BL/6J mice. Four groups of C57BL/6 mice were fed with control diet (10% fat), ASE (10% fat), HF (60% fat), and HF + ASE (60% fat plus ASE) for 12 weeks. The vasodilator effects of acetylcholine (ACh) and nitroglycerine (NG) were studied in perfused mesenteric arterial bed. Body weight, plasma total cholesterol, triglyceride, glucose and insulin levels, oral glucose tolerance test, and oxidative damage were determined, and the insulin resistance measured by Homeostatic Model Assessment (HOMA) index. Vasodilator response to ACh but not to NG was reduced in HF mice, and ASE restored the response. Increased plasma malondialdehyde levels, body weight, plasma triglyceride, total cholesterol, glucose levels, and insulin resistance were observed in HF mice and reduced by ASE. Treatment with ASE also reduced glucose intolerance observed by oral glucose tolerance test in HF mice. In conclusion, ASE protected C57BL/6J mice fed HF diet from phenotypic and metabolic characteristics of MS, providing an alternative nutritional resource for prevention of MS.

Relaxant effects of sildenafil on the human isolated bladder neck.

OBJECTIVE: To evaluate potential in vitro relaxant actions of sildenafil on human isolated bladder neck smooth muscle. METHODS: Bladder neck strips were sampled from patients (aged 55-77 years) submitted to prostatic surgery (6 adenomectomies and 1 radical prostatectomy). These were carefully dissected into 1-2 x 0.5-cm pieces and suspended in an organ bath containing 30 mL of a modified Krebs Henseleit solution, bubbled with 95% O(2)/5% CO(2). After tissue stabilization and viability test with KCl, the tissue was precontracted with phenylephrine, and a concentration-response relaxant curve to sildenafil was constructed. The effect of sildenafil was also assessed in tissues treated with N(omega)-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) (inhibitors of nitric oxide synthase and guanylyl cyclase, respectively). RESULT: Sildenafil induced significant bladder neck relaxation at all concentrations tested. The maximum relaxation was 86.97% +/- 6.69%, obtained with a high concentration of sildenafil (5.1 x 10(-4) M). Both L-NAME and ODQ significantly reduced sildenafil-induced relaxation. CONCLUSIONS: Sildenafil was effective in inducing bladder neck smooth muscle relaxation in vitro. This effect was almost abolished by L-NAME and ODQ, clearly demonstrating a dependence of the nitric oxide-cyclic guanosine monophosphate pathway. Our in-vitro results suggest that sildenafil might be useful in improving lower urinary tract symptoms due to benign prostatic hyperplasia.

Inhibitory effect of sildenafil on the human isolated seminal vesicle.

OBJECTIVE: To investigate the effects of sildenafil on noradrenaline- and potassium-induced contractions of isolated human seminal vesicles (SVs), as premature ejaculation is a relatively common male sexual dysfunction that currently lacks an adequate therapy, and recent in vitro tests showed that sildenafil induces relaxation of rodent isolated SVs, but it is not known whether it also inhibits isolated human SV. MATERIAL AND METHODS: Isolated strips of human SVs were suspended in an organ bath and cumulative concentration-response curves to either noradrenaline or KCl were constructed in the presence and absence of sildenafil to evaluate its inhibitory actions. RESULTS: Sildenafil (25-100 microm) induced concentration-dependent inhibitory effects on the human SV contracted by either noradrenaline or KCl. These actions of sildenafil do not therefore appear to be mediated via a competitive antagonism of alpha-adrenoceptors and are consistent with its recognized ability to inhibit phosphodiesterase-5. CONCLUSIONS: The present results show an important inhibitory action of sildenafil in the isolated human SV, supporting the therapeutic indication of this drug for treating premature ejaculation.