Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice

Background:

Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like effects. However, the antipsychotic properties of repeated CBD treatment have been poorly investigated. Behavioral changes induced by repeated treatment with glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been proposed as an animal model of schizophrenia-like signs. In the present study, we evaluated if repeated treatment with CBD would attenuate the behavioral and molecular modifications induced by chronic administration of one of these antagonists, MK-801.

Methods:

Male C57BL/6J mice received daily i.p. injections of MK-801 (0.1, 0.5, or 1mg/kg) for 14, 21, or 28 days. Twenty-four hours after the last injection, animals were submitted to the prepulse inhibition (PPI) test. After that, we investigated if repeated treatment with CBD (15, 30, and 60mg/kg) would attenuate the PPI impairment induced by chronic treatment with MK-801 (1mg/kg; 28 days). CBD treatment began on the 6th day after the start of MK-801 administration and continued until the end of the treatment. Immediately after the PPI, the mice brains were removed and processed to evaluate the molecular changes. We measured changes in FosB/ΔFosB and parvalbumin (PV) expression, a marker of neuronal activity and a calcium-binding protein expressed in a subclass of GABAergic interneurons, respectively. Changes in mRNA expression of the NMDAR GluN1 subunit gene (GRN1) were also evaluated. CBD effects were compared to those induced by the atypical antipsychotic clozapine.

Results:

MK-801 administration at the dose of 1mg/kg for 28 days impaired PPI responses. Chronic treatment with CBD (30 and 60mg/kg) attenuated PPI impairment. MK-801 treatment increased FosB/ΔFosB expression and decreased PV expression in the medial prefrontal cortex. A decreased mRNA level of GRN1 in the hippocampus was also observed. All the molecular changes were attenuated by CBD. CBD by itself did not induce any effect. Moreover, CBD effects were similar to those induced by repeated clozapine treatment.

Conclusions:

These results indicate that repeated treatment with CBD, similar to clozapine, reverses the psychotomimetic-like effects and attenuates molecular changes observed after chronic administration of an NMDAR antagonist. These data support the view that CBD may have antipsychotic properties.     

Choosing drugs for the treatment of diabetic neuropathy

Introduction: Diabetic sensorimotor polyneuropathy (DSP) affects 50% of diabetes patients and is painful in about 26%. Although disease-modifying therapies are not available for DSP, symptomatic treatments for painful diabetic neuropathy (PDN) are effective.

Areas covered: We performed a MEDLINE search on PubMed using the search terms: treatment diabetic neuropathy and treatment PDN. This review outlines the problem posed by DSP, the clinical presentation and the characterization of PDN. A discussion of disease-modifying interventions, including the benefits of strict glycemic control, is followed by a focus on interventions for PDN including antidepressants, anticonvulsants and other treatments.

Expert opinion: Disease modification in DSP remains an unmet need in clinical medicine affecting a large percentage of the population with concomitant healthcare costs. Strict glycemic control and attention to potential risk factors such as hypertension, hyperlipidemia and obesity may minimize DSP. Many patients benefit from treatment of their painful symptoms with anticonvulsants or antidepressants, but all are associated with significant side effects that limit their usefulness. There is a need for treatments of PDN with fewer side effects and more effective pain relief.     

Critical preparedness and operational response actions directed for the acute and post-acute COVID-19 pandemic in Brazil: the experience of a nationwide outpatient healthcare group

While the new Coronavirus Disease 2019 (COVID-19) pandemic rapidly spread across the world, South America was reached later in relation to Asia, Europe and the United States of America (USA). Brazil concentrates now the largest number of cases in the continent and, as the disease speedily progressed throughout the country, prompt and challenging operational strategies had to be taken by institutions caring for COVID-19 and non-COVID-19 patients in order to assure optimal workflows, triage, and management. Although hospitals in the USA, Europe and Asia have shared their experience on this subject, little has been discussed about such strategies in South America or by the perspective of outpatient centers, which are paramount in the radiology field. This article shares the guidelines adopted early in the pandemic by a nationwide outpatient healthcare center composed by a network of more than 200 patient service centers and nearly 2,000 radiologists in Brazil, discussing operational and patient management strategies, staff protection, changes adopted in the fellowship program, and the effectiveness of such measures.     

Percepção Inadequada do Risco Cardiovascular e Baixo Conhecimento sobre Hipercolesterolemia Familiar em Indivíduos com Hipercolesterolemia Grave

BackgroundIndividuals with severe hypercholesterolemia are at a high risk of developing atherosclerotic cardiovascular disease (ASCVD). Many of them have familial hypercholesterolemia (FH).ObjectivesTo assess from a patient perspective the degree of awareness about severe hypercholesterolemia, especially FH, ASCVD risk perception, cascade screening performance, and treatment of individuals participating in a routine health evaluation program.MethodsFrom a database of 70,000 Brazilian individuals evaluated between 2006 and 2016, 1,987 (2.8%) met the inclusion criteria (age ≥ 18 years and LDL-C ≥ 190 mg/dL or ≥ 160 mg/dL, respectively, if not in use of statins or on statin therapy). Two-hundred individuals were randomly invited to complete an extensive questionnaire. FH was diagnosed if suspected by the attending physician.ResultsAlthough 97% of the sample (age 48±9 years; 16% women; 95% college/university education; 88% primary prevention; LDL-C 209±47 mg/dL) had severe hypercholesterolemia, only 18% and 29.5% believed to be at high ASCVD risk and reported knowledge of their recommended LDL-C goal, respectively. Fifty-eight percent reported being informed that high cholesterol could be a family disease, 24.5% (n = 49) had ever heard about FH, and merely 14% (n = 29) had been previously identified as suspected of having FH (age at FH diagnosis 35±12 years; 79% and 31% diagnosed, respectively, > 30 and > 40 years old). Only 2.5% underwent genetic tests, 17% underwent cascade screening, and 17% were not in use of pharmacological treatment.ConclusionsAn important gap in risk perception, cholesterol management, and aspects related to FH was encountered in individuals with severe hypercholesterolemia. (Arq Bras Cardiol. 2021; [online].ahead print, PP.0-0)     

The effects of resistance training in patients with primary Sjogren’s syndrome

Clinical Rheumatology - Resistance training (RT) is well tolerated and has shown promise for decreasing fatigue. However, the effects of RT have never been examined in primary Sjogren’s...     

Human rhinovirus C infections in pediatric hematology and oncology patients

Children with cancer and HSCT recipients are at high risk for common viral infections. We sought to define the viral etiology of ARI and identify risk factors. Nasal wash samples were collected from pediatric hematology–oncology patients and HSCT recipients with ARI during the 2003–2005 winter seasons. Real‐time RT‐PCR was performed to detect Flu A, influenza B, RSV, PIV 1‐3, human MPV, and HRV. HRV specimens were sequenced and genotyped. Seventy‐eight samples from 62 children were included. Viruses were detected in 31 of 78 samples (40%). HRV were detected most frequently, in 16 (52%) including five HRVC; followed by seven (22%) RSV, five (16%) Flu A, four (13%) MPV, and two (6%) PIV2. There was a trend toward higher risk of viral infection for children in day care. Only 8% of the study children had received influenza vaccine. HRV, including the recently discovered HRVC, are an important cause of infection in pediatric oncology and HSCT patients. Molecular testing is superior to conventional methods and should be standard of care, as HRV are not detected by conventional methods.