Background and Purpose
Cannabis legalization has risen in many countries, and its use during pregnancy has increased. The endocannabinoid system is present in the CNS at early stages of embryonic ...development, and regulates functional brain maturation including areas responsible for respiratory control, data on the influence of external cannabinoids on the development of the respiratory system and possible consequences during postnatal life are limited.
Experimental Approach
We evaluated the effects of prenatal exposure to synthetic cannabinoid (WIN 55,212‐2 WIN, 0.5 mg·kg−1·day−1) on the respiratory control system in neonatal (P0, P6–7 and P12–13) and juvenile (P27–28) male and female rats.
Key Results
WIN administration to pregnant rats interfered sex‐specifically with breathing regulation of offspring, promoting a greater sensitivity to CO2 at all ages in males (except P6–7) and in juvenile females. An altered hypoxic chemoreflex was observed in P0 (hyperventilation) and P6–7 (hypoventilation) males, which was absent in females. Along with breathing alterations, brainstem analysis showed an increase in the number of catecholaminergic neurons and cannabinoid receptor type 1 (CB1) and changes in tissue respiration in the early males. A reduction in pulmonary compliance was observed in juvenile male rats. Preexposure to WIN enhanced spontaneous apnoea and reduced the number of serotoninergic (5‐HT) neurons in the raphe magnus nucleus of P0 females.
Conclusions and Implications
These data demonstrate that excess stimulation of the endocannabinoid system during gestation has prolonged and sex‐specific consequences for the respiratory control system.
Primary objectives were to analyze the prevalence of obstructive sleep apnea in (1) boys and girls, and (2) severe asthma versus moderate and mild cases. The authors hypothesized that girls and ...severe asthma would have a higher prevalence of obstructive sleep apnea.
Cross-sectional evaluation of asthmatic children attending a tertiary Pediatric Pulmonology clinic. The authors performed a history, physical examination, pulmonary function test, and home sleep apnea test.
The authors studied 80 consecutive patients, 7–18 years old, mean age of 11.6 years (standard deviation 2.7), 51.3% female, and 18.5% obese. Pulmonary function tests were obtained from 80 volunteers, 45% with obstruction pattern. Home sleep apnea tests were available from 76 volunteers, with a mean obstructive respiratory index of 1.8 events/h. Obstructive sleep apnea was found in 49 volunteers (61.2%). The authors did not find associations between obstructive sleep apnea and sex or asthma severity.
Obstructive sleep apnea was frequent among these asthmatic children. Sex and asthma severity were not risk factors. Considering the interrelationship of both diseases, it is worth keeping in mind the possibility of obstructive sleep apnea among children and teenagers with asthma.
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•Coffee husks extract (CHE) were obtained and encapsulated with PVP (ECHE) in a one-step approach.•The encapsulation of CHE increased the total phenolics content and its antioxidant ...activity.•The encapsulation of CHE tripled the quercetin extraction (compared to the non-encapsulated CHE).•Both CHE and ECHE inhibited the pancreatic α-amylase activity, but ECHE showed stronger inhibition.•ECHE delayed the increases of blood glucose after oral administration of starch in rats.
Coffee processing generates large amounts of residues of which a portion still has bioactive properties due to their richness in phenolic compounds. This study aimed to obtain a coffee husks extract (CHE) and to encapsulate it (ECHE) with polyvinylpyrrolidone using a one-step procedure of solid dispersion. The extraction and encapsulation yields were 9.1% and 92%, respectively. Thermal analyses revealed that the encapsulation increased the thermal stability of CHE and dynamic light scattering analyses showed a bimodal distribution of size with 81% of the ECHE particles measuring approximately 711 nm. Trigonelline and caffeine were the main alkaloids and quercetin the main phenolic compound in CHE, and the encapsulation tripled quercetin extraction. The total phenolics content and the antioxidant activity of ECHE, assayed with three different procedures, were higher than those of CHE. The antioxidant activity and the bioaccessibility of the phenolic compounds of ECHE were also higher than those of CHE following simulated gastrointestinal digestion (SGID). Both CHE and ECHE were not toxic against Alliumcepa cells and showed similar capacities for inhibiting the pancreatic α-amylase in vitro. After SGID, however, ECHE became a 1.9-times stronger inhibitor of the α-amylase activity in vitro (IC50 = 8.5 mg/mL) when compared to CHE. Kinetic analysis revealed a non-competitive mechanism of inhibition and in silico docking simulation suggests that quercetin could be contributing significantly to the inhibitory action of both ECHE and CHE. In addition, ECHE (400 mg/kg) was able to delay by 50% the increases of blood glucose in vivo after oral administration of starch to rats. This finding shows that ECHE may be a candidate ingredient in dietary supplements used as an adjuvant for the treatment of diabetes.
Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, generalized edema, and hyperlipidemia. It begins by changes in the glomerular filtration barrier, with increased permeability ...to plasma proteins. It affects all age groups and can progress to end-stage renal disease. NS pathophysiology is still unknown. However, the critical role of the immune system is well recognized. Animal models are useful tools for the investigation of NS. Among different experimental models proposed in the literature, disease induced by Doxorubicin has been considered helpful to the purpose of many studies. The aim of this review article is to describe the animal model of NS induced by the injection of Doxorubicin in rodents, with emphasis on action of the drug, potential mechanisms of renal injury, as well biochemical, histological, and corporal changes obtained with this model.
Pediatric obesity and sleep-disordered breathing (SDB) are strongly associated, and both promote metabolic impairments. However, the effects of a lifestyle intervention on the overall metabolic ...syndrome (MetS) are unknown. The objectives were i) to evaluate the effects of a lifestyle intervention on cardiometabolic risk (CMR), assessed with a dichotomous (MetS) and a continuous (MetScoreFM) instrument, in obese adolescents with and without SDB and ii) to compare the post-intervention cardiometabolic responses between adolescents with persistent (apnea-hypopnea index; AHI≥2) or normalized-SDB (AHI<2).
Seventy-six adolescents with obesity recruited from two specialized institutions underwent a 9–12month diet and exercise intervention. Sleep and SDB (AHI≥2) were studied by polysomnography. Anthropometric parameters, fat mass (FM), glucose, insulin, lipid and leptin profiles, blood pressure (BP), MetScoreFM and MetS were assessed pre- and post-intervention. We performed comparisons between Non-SDB and SDB groups and between Normalized-SDB and Persistent-SDB subgroups.
Fifty participants completed the study. Pre-intervention, twenty youth had SDB (40%) with higher insulin concentrations and systolic BP than Non-SDB participants (p < 0.01), for a similar degree of obesity. Post-intervention, MetScoreFM (p < 0.001) and MetS prevalence (p < 0.05) were decreased in both groups. Eleven participants (55%) normalized SDB along with a decrease in insulin concentrations and BP (p < 0.05). Triglycerides, total cholesterol and LDL-cholesterol concentrations (p < 0.01) improved equally in the Normalized and Persistent-SDB subgroups.
SDB was associated with lower insulin sensitivity and higher BP but did not affect the lipid profile. A diet and exercise lifestyle intervention is effective in decreasing the CMR whether or not SDB was normalized in obese adolescents.
•Obese adolescents with SDB have worse cardiometabolic risk profile than those without SDB.•Lipid profile is not affected by SDB.•Decrease of CMR in persistent-SDB subgroup is mediated by weight loss and improved lipid profile.•Insulin-glucose homeostasis and blood pressure are improved by SDB normalization.•A lifestyle intervention decreases SDB prevalence and CMR severity in adolescents with obesity.
To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on insomnia and other sleep disturbances in health care professionals.
A survey was distributed using social media and ...organizational emails to Brazilian active health care professionals during the COVID-19 outbreak. We explored potential associated factors including age, sex, occupation, workplace, work hours, income, previous infection with COVID-19, recent/current contact with COVID-19 patients, regional number of incident deaths, anxiety, and burnout. We evaluated new-onset/previous insomnia worsening episodes (primary outcome), new pharmacological treatments, sleep quality, duration, nightmares, and snoring (secondary outcomes).
A total of 4,384 health professionals from all regions of the country were included in the analysis (44 ± 12 years, 76% females, 53.8% physicians). Overall, 55.7% were assisting patients with COVID-19, and 9.2% had a previous COVID-19 infection. The primary outcome occurred in 32.9% of respondents in parallel to 13% new pharmacological treatments for insomnia. The sleep quality worsened for 61.4%, while 43.5% and 22.8% reported ≥ 1-hour sleep duration reduction and worsening or new-onset nightmares, respectively. Multivariate analyses showed that age (odds ratio OR: 1.008; 95% confidence interval CI 1.001-1.015), females (OR: 1.590; 95% CI 1.335-1.900), weight change (decrease: OR: 1.772; 95% CI 1.453-2.161; increase: OR: 1.468; 95% CI 1.249-1.728), prevalent anxiety (OR: 3.414; 95% CI 2.954-3.948), new-onset burnout (OR: 1.761; 95% CI 1.489-2.083), family income reduction > 30% (OR: 1.288; 95% CI 1.069-1.553), and assisting patients with COVID-19 (OR: 1.275; 95% CI 1.081-1.506) were independently associated with new-onset or worsening of previous insomnia episodes.
We observed a huge burden of insomnia episodes and other sleep disturbances in health care professionals during the COVID-19 pandemic.
Drager LF, Pachito DV, Moreno CRC, et al. Insomnia episodes, new-onset pharmacological treatments, and other sleep disturbances during the COVID-19 pandemic: a nationwide cross-sectional study in Brazilian health care professionals.
. 2022;18(2):373-382.
Leishmania protozoans are the causal agents of neglected diseases that represent an important public health issue worldwide. The growing occurrence of drug-resistant strains of Leishmania and severe ...side effects of available treatments represent an important challenge for the leishmaniases treatment. We have previously reported the leishmanicidal activity of phylloseptin-1 (PSN-1), a peptide found in the skin secretion of Phyllomedusa azurea (=Pithecopus azureus), against Leishmania amazonensis promastigotes. However, its impact on the amastigote form of L. amazonensis and its impact on infected macrophages are unknown. In this work, we evaluated the effects of PSN-1 on amastigotes of L. amazonensis inside macrophages infected in vitro. We assessed the production of hydrogen peroxide and nitric oxide, as well as the levels of inflammatory and immunomodulatory markers (TGF-β, TNF-α and IL-12), in infected and non-infected macrophages treated with PSN-1. Treatment with PSN-1 decreased the number of infected cells and the number of ingested amastigotes per cell when compared with the untreated cells. At 32 µM (64 µg/mL), PSN-1 reduced hydrogen peroxide levels in both infected and uninfected macrophages, whereas it had little effect on NO production or TGF-β release. The effect of PSN-1 on IL-12 and TNF-α secretion depended on its concentration, but, in general, their levels tended to increase as PSN-1 concentration increased. Further in vitro and in vivo studies are needed to clarify the mechanisms of action of PSN-1 and its interaction with the immune system aiming to develop pharmacological applications.
Arthropod-borne viruses belonging to the flavivirus genus possess an enormous relevance in public health. Neotropical non-human primates (NPs) have been proposed to be susceptible to flavivirus ...infections due to their arboreal and diurnal habits, their genetic similarity to humans, and their relative closeness to humans. However, the only known flavivirus in the American continent maintained by sylvatic cycles involving NPs is yellow fever virus (YFV), and NPs’ role as potential hosts of other flaviviruses is still unknown. Here, we examined flavivirus exposure in 86 serum samples including 83.7% samples from free-range and 16.3% from captive NPs living in flavivirus-endemic regions of Costa Rica. Serum samples were opportunistically collected throughout Costa Rica in 2000–2015. We used a highly specific micro-plaque reduction neutralization test (micro-PRNT) to determine the presence of antibodies against YFV, dengue virus 1–4 (DENV), Zika virus, West Nile virus (WNV), and Saint Louis encephalitis virus (SLEV). We found evidence of seropositive NPs with homotypic reactivity to SLEV 11.6% (10/86), DENV 10.5% (9/86), and WNV 2.3% (2/86). Heterotypic reactivity was determined in 3.5% (3/86) of individuals against DENV, 1.2% (1/86) against SLEV, and 1.2% (1/86) against WNV. We found that 13.9% (12/86) of NPs were positive for an undetermined flavivirus species. No antibodies against DENV-3, DENV-4, YFV, or ZIKV were found. This work provides compelling serological evidence of flavivirus exposure in Costa Rican NPs, in particular to DENV, SLEV, and WNV. The range of years of sampling and the region from where positives were detected coincide with those in which peaks of DENV in human populations were registered, suggesting bidirectional exposure due to human–wildlife contact or bridging vectors. Our work suggests the continuous exposure of wildlife populations to various flaviviruses of public health importance and underscores the necessity of further surveillance of flaviviruses at the human–wildlife interface in Central America.
Sleep‐related phenotypes have been frequently reported in early on‐set epileptic encephalopathies and in developmental delay syndromes, in particular in syndromes related to autism spectrum disorder. ...Yet the convergent pathogenetic mechanisms between these comorbidities are largely unknown. We first performed a gene enrichment study that identified shared risk genes among rare epileptic encephalopathies/neurodevelopmental disorders, rare developmental delay genetic syndromes and sleep disturbances. We then determined cellular and molecular pathways enriched among genes shared between sleep phenotypes and those two early onset mental illnesses, aiming to identify genetic disparities and commonalities among these phenotypic groups. The sleep gene set was observed as significantly overlapped with the two gene lists associated to rare genetic syndromes (i.e., epileptic encephalopathies/neurodevelopmental disorders and developmental delay gene sets), suggesting shared genetic contribution. Similarities across significantly enriched pathways between the two intersect lists comprehended mostly synapse‐related pathways, such as retrograde endocannabinoid signaling, serotonergic, and GABAergic synapse. Network analysis indicates epileptic encephalopathies/neurodevelopmental disorders versus sleep‐specific clusters and developmental delay versus sleep‐specific clusters related to synaptic and transcriptional regulation, respectively. Longstanding functional patterns previously described in epileptic encephalopathies and neurodevelopmental disorders genetic architecture were recaptured after dissecting the overlap between the genes associated to those developmental phenotypes and sleep disturbances, suggesting that during neurodevelopment different molecular and functional mechanisms are related to alterations on circadian rhythm. The overlapping gene set and biological pathways highlighted by this study may serve as a primer for new functional investigations of shared molecular mechanisms between sleep disturbances and rare developmental syndromes.
There is significant overlap between sleep‐ and neurodevelopment‐associated genes, with divergencies and commonalities in biological processes involved in sleep and rare genetic syndromes related to early on‐set epileptic encephalopathies and developmental delay conditions.
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