Early Anti-inflammatory and Pro-angiogenic Myocardial Effects of Intravenous Serelaxin Infusion for 72 H in an Experimental Rat Model of Acute Myocardial Infarction

Sprague Dawley rats were subjected to acute myocardial infarction (AMI) by permanent ligation of the left anterior descending coronary artery. At the time of AMI, a subcutaneous mini-osmotic pump was implanted and animals were randomized into three groups, according to the intravenous therapy received during the first 72 h: placebo-treated (saline), serelaxin10-treated (SRLX10 = 10 μg/kg/day), or serelaxin30-treated (SRLX30 = 30 μg/kg/day). Treatment with SRLX30 reduced the expression of inflammatory cytokines and chemokines, as well as the infiltration of macrophages, and increased the expression of pro-angiogenic markers and vessel density in the infarcted myocardium after 7 days. SRLX30 did not reduce early myocardial fibrosis but reduced myocardial levels of sST2 and galectin-3. No significant effects were observed with SRLX10 treatment. A significant correlation was observed between plasma levels of serelaxin and effect measures. The results suggest serelaxin has a protective effect in early processes of cardiac remodeling after AMI.     

Combined actions of blueberry extract and lithium on neurochemical changes observed in an experimental model of mania: exploiting possible synergistic effects

Bipolar disorder is a psychiatric disease characterized by recurrent episodes of mania and depression. Blueberries contain bioactive compounds with important pharmacological effects such as neuroprotective and antioxidant actions. The aim of this study was to investigate the effects of blueberry extract and/or lithium on oxidative stress, and acetylcholinesterase (AChE) and Na⁺, K⁺-ATPase activity in an experimental ketamine-induced model of mania. Male Wistar rats were pretreated with vehicle, blueberry extract (200 mg/kg), and/or lithium (45 mg/kg or 22.5 mg/kg twice daily) for 14 days. Between the 8th and 14th days, the animals also received an injection of ketamine (25 mg/kg) or vehicle. On the 15th day the animals received a single injection of ketamine; after 30 min, the locomotor activity was evaluated in an open field test. Ketamine administration induced an increase in locomotor activity. In the cerebral cortex, hippocampus and striatum, ketamine also induced an increase in reactive oxygen species, lipid peroxidation and nitrite levels, as well a decrease in antioxidant enzyme activity. Pretreatment with blueberry extract or lithium was able to prevent this change. Ketamine increased the AChE and Na⁺, K⁺-ATPase activity in brain structures, while the blueberry extract partially prevented these alterations. In addition, our results showed that the neuroprotective effect was not potentiated when lithium and blueberry extract treatment were given together. In conclusion, our findings suggest that blueberry extract has a neuroprotective effect against an experimental model of mania. However, more studies should be performed to evaluate its effects as an adjuvant therapy.

     

A retrospective,observational multicenter study of 141 patients treated with ustekinumab 90 mg

A change of pricing policy in Spain have made both doses of ustekinumab (UST), 45 and 90 mg, recently available at the same price. Our primary objective was to evaluate effectiveness of UST 90 mg at 52 and 104 weeks in psoriasis patients in clinical practice; secondary objectives were to study the reasons for using this dose and to delineate its efficacy in patients previously treated with anti‐IL17 drugs. 91.8% of the 141 patients treated with UST 90 started with 45 mg and later increased their dose. Clinicians changed dose due to weight over 100 kg in 20.6% of the cases and all the other dose changes were off‐label to improve partial cutaneous or articular response or due to a previous failure of anti‐IL17 therapy. After 12 months of UST 90 treatment, absolute PASI was lower than 3 in 87.5% of patients and lower than 1 in 72.2%. Efficacy data were even better for patients with body mass index (BMI) <25. UST 90 can be effective in patients with previous use of anti‐IL17 drugs. It appears to be an alternative treatment option not only for high BMI patients, but also to increase the cutaneous or articular efficacy of the drug in patients with normal BMI.     

Influence of physical exercise and gender on acetylcholinesterase and butyrylcholinesterase activity in human blood samples

The determination of cholinesterase activity in plasma and erythrocytes serves as a useful and sensitive biomarker of exposure to organophosphorus and carbamate pesticides. However, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity may be influenced by factors such as age, gender, drugs, and physical exercise. The aim of this study was to evaluate the effects of gender and physical exercise on the activity of AChE and BuChE in healthy individuals. The values for both enzymes were lower for women. Physical exercise increased the levels of BuChE, and had no significant effect on AChE. To our knowledge, this is the first clinical study evaluating the influence of physical exercise in levels of these enzymes. Considering that cholinesterase activity is a useful parameter in assessing the exposure of individuals to pesticides, it is important to understand factors that influence the determination of the enzymes in order to avoid the erroneous interpretation of results.     

Effect of blueberry extract on energetic metabolism,levels of brain-derived neurotrophic factor,and Ca2+-ATPase activity in the hippocampus and cerebral cortex of rats submitted to ketamine-induced mania-like behavior

Metabolic Brain Disease - Bipolar disorder (BD) is a psychiatric disease characterized by mood episodes. Blueberry is rich in bioactive compounds and shows excellent therapeutic potential against...