Potential utility of melatonin as an antioxidant therapy in the management of sickle cell anemia

This study aimed to assess antioxidant effects of melatonin treatment compared to N‐acetylcysteine (NAC) and to their combination in a sickle cell suspension. Sickle erythrocytes were suspended in phosphate‐buffered saline, pH 7.4, composing external control group. They were also suspended and incubated at 37°C either in the absence (experimental control group) or in the presence of NAC, melatonin and their combination at concentrations of 100 pm , 100 nm and 100 μm for 1 hr (treatment groups). The melatonin influences were evaluated by spectrophotometric [hemolysis degree, catalase (CAT), glutathione S‐transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), glucose‐6‐phosphate dehydrogenase (G6PDH), and superoxide dismutase (SOD) activities] and chromatographic methods [glutathione (GSH) and malondialdehyde (MDA) levels]. Incubation period was able to cause a rise about 64% on hemolysis degree as well as practically doubled the lipid peroxidation levels (P < 0.01). However, almost all antioxidants tested treatments neutralized this incubation effect observed in MDA levels. Among the antioxidant biomarkers evaluated, we observed a modulating effect of combined treatment on GPx and SOD activities (P < 0.01), which showed ~25% decrease in their activities. In addition, we found an antioxidant dose‐dependent effect for melatonin on lipid peroxidation (r = ?0.29; P = 0.03) and for combined antioxidant treatments also on MDA levels (r = ?0.37; P = 0.01) and on SOD activity (r = ?0.54; P < 0.01). Hence, these findings contribute with important insight that melatonin individually or in combination with NAC may be useful for sickle cell anemia management.     

Association between Tomographic Characteristics of the Temporal Bone and Transtemporal Window Quality on Transcranial Color Doppler Ultrasound in Patients with Stroke or Transient Ischemic Attack

Transcranial color-coded Doppler (TCCD) is an ultrasonographic technique used to obtain and evaluate images of the cerebral parenchyma and to assess blood flow velocities of the intracranial vessels. One of the major limitations of TCCD is the failure to insonate through the transtemporal window, which occurs in about 5%–44% of patients. Temporal bone thickness has been strongly associated with transtemporal window failure (TWF). The aims of the study were to evaluate the association between TWF on TCCD and radiologic findings on computed tomography of the skull along with the demographic characteristics of patients with acute stroke or transient ischemic attack (TIA), and to propose a classification for transcranial window quality (TWQ) on B-mode scan of TCCD. A total of 187 consecutive patients with acute stroke or TIA were included. Among them, 21.9% had TWF and 34.8% had TWQ categorized as insufficient on B-mode scan of TCCD. On logistic regression, age (odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.03–1.12, p < 0.001), female sex (OR = 5.99, 95% CI: 2.09–17.16, p = 0.001), pneumatized temporal bone (OR = 7.90, 95% CI: 1.95–32.03, p = 0.004) and temporal bone thickness (OR = 3.04, 95% CI: 1.73–5.35, p < 0.001) were independent predictors of TWF, even after adjusting for confounders. These findings may help to select patients in whom echogenic contrast or even other imaging methods could be used to assess intracranial vessels.     

COX-2 inhibition does not reverse the increased sympathetic modulation in MSG obese rats

We evaluate the effects of chronic treatment with celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, on blood pressure (BP) and heart rate variability (HRV) in obese rats induced by neonatal monosodium glutamate (MSG). The animals were treated with celecoxib or saline for 30 days (from the 60th to the 90th day of age). On the 90th day, the MSG obesity induced an increase in the low-frequency (LF) component (CTR=5.69±18.30ms(2), MSG=38.49±6.27ms(2)) and a decrease in the high-frequency (HF) component of HRV (CTR=71.48±6.22ms(2), MSG=50.94±7.03ms(2)), which were unchanged by celecoxib treatment. We suggest that HRV in MSG obesity involves a greater sympathetic modulation not related with COX-2 products.     

Xylarenones C-E from an endophytic fungus isolated from Alibertia macrophylla

Xylarenones C-E (2-4), three new eremophilane sesquiterpenes, have been isolated from solid substrate cultures of a Camarops-like endophytic fungus isolated from Alibertia macrophylla. The structures were elucidated by analysis of spectroscopic data. Compounds were evaluated in subtilisin and pepsin protease assays, and compound 2 showed potent inhibitory activity against both proteases.     

Mechanical thrombectomy with solitaire stent retrieval for acute ischemic stroke in a Brazilian population

OBJECTIVE:

Large vessel occlusion in acute ischemic stroke is associated with low recanalization rates under intravenous thrombolysis. We evaluated the safety and efficacy of the Solitaire AB stent in treating acute ischemic stroke.

METHODS:

Patients presenting with acute ischemic stroke were prospectively evaluated. The neurological outcomes were assessed using the National Institutes of Health Stroke Scale and the modified Rankin Scale. Time was recorded from the symptom onset to the recanalization and procedure time. Recanalization was assessed using the thrombolysis in cerebral infarction score.

RESULTS:

Twenty-one patients were evaluated. The mean patient age was 65, and the National Institutes of Health Stroke Scale scores ranged from 7 to 28 (average 17±6.36) at presentation. The vessel occlusions occurred in the middle cerebral artery (61.9%), distal internal carotid artery (14.3%), tandem carotid occlusion (14.3%), and basilar artery (9.5%). Primary thrombectomy, rescue treatment and a bridging approach represented 66.6%, 28.6%, and 4.8% of the performed procedures, respectively. The mean time from symptom onset to recanalization was 356.5±107.8 minutes (range, 80-586 minutes). The mean procedure time was 60.4±58.8 minutes (range, 14-240 minutes). The overall recanalization rate (thrombolysis in cerebral infarction scores of 3 or 2b) was 90.4%, and the symptomatic intracranial hemorrhage rate was 14.2%. The National Institutes of Health Stroke Scale scores at discharge ranged from 0 to 25 (average 6.9±7). At three months, 61.9% of the patients had a modified Rankin Scale score of 0 to 2, with an overall mortality rate of 9.5%.

CONCLUSIONS:

Intra-arterial thrombectomy with the Solitaire AB device appears to be safe and effective. Large randomized trials are necessary to confirm the benefits of this approach in acute ischemic stroke.     

Effect of exercise on epicardial adipose tissue in adults: a systematic review and meta-analyses

Heart Failure Reviews - According to previous epidemiological studies, we can reduce the thickness of epicardial fat and improve cardiovascular risk factors through exercise, and the changes may...     

From the Cover: Anti-inflammatory lipoxin A4 is an endogenous allosteric enhancer of CB1 cannabinoid receptor

Allosteric modulation of G-protein–coupled receptors represents a key goal of current pharmacology. In particular, endogenous allosteric modulators might represent important targets of interventions aimed at maximizing therapeutic efficacy and reducing side effects of drugs. Here we show that the anti-inflammatory lipid lipoxin A₄ is an endogenous allosteric enhancer of the CB₁ cannabinoid receptor. Lipoxin A₄ was detected in brain tissues, did not compete for the orthosteric binding site of the CB₁ receptor (vs. ³H-SR141716A), and did not alter endocannabinoid metabolism (as opposed to URB597 and MAFP), but it enhanced affinity of anandamide at the CB1 receptor, thereby potentiating the effects of this endocannabinoid both in vitro and in vivo. In addition, lipoxin A₄ displayed a CB₁ receptor-dependent protective effect against β-amyloid (1–40)-induced spatial memory impairment in mice. The discovery of lipoxins as a class of endogenous allosteric modulators of CB₁ receptors may foster the therapeutic exploitation of the endocannabinoid system, in particular for the treatment of neurodegenerative disorders.     

Neurocognitive functioning in children with developmental dyslexia and attention-deficit/hyperactivity disorder: Multiple deficits and diagnostic accuracy

Introduction: This study aimed to investigate the neurocognitive functioning of children with developmental dyslexia (DD) and attention-deficit/hyperactivity disorder (ADHD). Method: Four groups of children between the ages of 8 and 10 years participated in the study: typically developing children (TDC; N = 34), children with DD-only (N = 32), children with ADHD-only (N = 32), and children with DD+ADHD (N = 18). Results: Children with DD and ADHD exhibited significant weaknesses on almost all neurocognitive measures compared with TDC. Large effect sizes were observed for naming speed and phonological awareness. The comorbid group showed deficits consistent with both DD and ADHD without additional impairments. Results from binary logistic regression and receiver-operating characteristic (ROC) curve analyses suggested that some neurocognitive measures revealed an adequate sensitivity for the clinical diagnosis of both neurodevelopmental disorders. Specifically, naming speed and phonological awareness were the strongest predictors to correctly discriminate both disorders. Conclusions: Taken together, the results lend support to the multiple cognitive deficit hypothesis showing a considerable overlap of neurocognitive deficits between both disorders.