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PURPOSE: The separation between the inside and outside through the skin was fundamental for the evolution of prevertebrates, which grow through extrapituitary circuits, to vertebrates, which grow through the somatotrophic axis, namely pituitary growth hormone (GH). and circulating IGF1.Individuals with untreated isolated growth hormone (GH) deficiency (IGHD) due to a mutation in the GH-releasing hormone receptor (GHRH) gene, residing in Itabaianinha, Brazil, are vulnerable to skin cancer and have reduced sweating. However other aspects of their skin physiology are still unknown. Our objectives were to evaluate the number of skin cancers, skin aging, and functional aspects of the skin in this IGHD cohort. METHODS: Twenty-six IGHD individuals and 26 controls matched by age, sex, ethnicity, and occupation were submitted to a biochemical, dermatological and a functional skin assessment by the Multi Probe Adapter Cutometer® MPA 580. RESULTS: There was no difference in the number of skin cancers and in the degrees of photodamage between the groups. The melanin content in the forearm was similar between the groups but was lower in the buttocks (p = 0.005), as well as skin resistance (p < 0.0001) and elasticity (p = 0.003), lower in the IGHD. There was no difference in hydration and sebum content between the two groups. CONCLUSION: IGHD is apparently associated with a neutral profile in terms of skin cancer and photodamage, with similar melanin on the forearm and lower buttocks, lower skin resistance and elasticity, with hydration and sebum similar to controls.

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BACKGROUND: Endotoxemia is a severe and dangerous clinical syndrome that results in elevated morbidity, especially in intensive care units. Neonates are particularly susceptible to endotoxemia due to their immature immune systems. There are few effective treatments for neonatal endotoxemia. One group of compounds with potential in the treatment of neonatal inflammatory diseases such as endotoxemia is the flavonoids, mainly due to their antioxidant and anti-inflammatory properties. Among these, naringenin (NGN) is a citrus flavonoid which has already been reported to have anti-inflammatory, antioxidant, anti-nociceptive and anti-cancer effects. Unfortunately, its clinical application is limited by its low solubility and bioavailability. However, cyclodextrins (CDs) have been widely used to improve the solubility of nonpolar drugs and enhance the bioavailability of these natural products. OBJECTIVE: We, therefore, aimed to investigate the effects of NGN non-complexed and complexed with hydroxypropyl-ß-cyclodextrin (HPßCD) on neonatal endotoxemia injuries in a rodent model and describe the probable molecular mechanisms involved in NGN activities. METHOD: We used exposure to a bacterial lipopolysaccharide (LPS) to induce neonatal endotoxemia in the mice. RESULTS: It was found that NGN (100 mg/kg i.p.) exposure during the neonatal period reduced leukocyte migration and decreased pro-inflammatory cytokine (TNF-α, IL-1ß and IL-6) levels in the lungs, heart, kidneys or cerebral cortex. In addition, NGN upregulated IL-10 production in the lungs and kidneys of neonate mice. The administration of NGN also enhanced antioxidant enzyme catalase and SOD activity, reduced lipid peroxidation and protein carbonylation and increased the reduced sulfhydryl groups in an organ-dependent manner, attenuating the oxidative damage caused by LPS exposure. NGN decreased ERK1/2, p38MAPK and COX-2 activation in the lungs of neonate mice. Moreover, NGN complexed with HPßCD was able to increase the animal survival rate. CONCLUSION: NGN attenuated inflammatory and oxidative damage in the lungs, heart and kidneys caused by neonatal endotoxemia through the MAPK signaling pathways regulation. Our results show that NGN has beneficial effects against neonatal endotoxemia and could be useful in the treatment of neonatal inflammatory injuries.

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BACKGROUND: Arrhythmias are one manifestation of the cardiotoxicity that results from doxorubicin (Doxo) administration. Although cardiotoxicity is an anticipated outcome in anticancer therapies, there is still a lack of treatment options available for its effective management. This study sought to evaluate the possible cardioprotective effect of complex d-limonene (DL) plus hydroxypropyl-ß-cyclodextrin (HßDL) during treatment with Doxo, focusing on the arrhythmic feature. METHODS: Cardiotoxicity was induced in Swiss mice with Doxo 20 mg/kg, with 10 mg/kg of HßDL being administered 30 min before the Doxo. Plasma CK-MB and LDH levels were analyzed. Cellular excitability and susceptibility to cardiac and cardiomyocyte arrhythmias were evaluated using in vivo (pharmacological cardiac stress) and in vitro (burst pacing) ECG protocols. Ca2+ dynamics were also investigated. The expression of CaMKII and its activation by phosphorylation and oxidation were evaluated by western blot, and molecular docking was used to analyze the possible interaction between DL and CaMKII. RESULTS: Electrocardiograms showed that administration of 10 mg/kg of HßDL prevented Doxo-induced widening of the QRS complex and QT interval. HßDL also prevented cardiomyocyte electrophysiological changes that trigger cellular arrhythmias, such as increases in action potential duration and variability; decreased the occurrence of delayed afterdepolarizations (DADs) and triggered activities (TAs), and reduced the incidence of arrhythmia in vivo. Ca2+ waves and CaMKII overactivation caused by phosphorylation and oxidation were also decreased. In the in silico study, DL showed potential inhibitory interaction with CaMKII. CONCLUSION: Our results show that 10 mg/kg of ßDL protects the heart against Doxo-induced cardiotoxicity arrhythmias, and that this is probably due to its inhibitory effect on CaMKII hyperactivation.

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This study estimated the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in urban cleaning and solid waste management workers during the transmission of the Omicron variant in one of the poorest regions of Brazil (the state of Sergipe). Nasopharyngeal swabs were collected from 494 workers, and the presence of SARS-CoV-2 RNA was tested by quantitative reverse-transcriptase polymerase chain reaction. Data on socio-demographic characteristics, comorbidities, vaccination status, mask use, and use of public transport to commute to the workplace were collected. The prevalence with a 95% confidence interval (CI) was calculated from the proportion of SARS-CoV-2 positive cases among the total number of individuals tested. The prevalence ratio (PR) with a 95% CI was the measure of association used to evaluate the relationship between SARS-CoV-2 infection and the exposure variables. The prevalence of SARS-CoV-2 infection was 22.5% (95% CI, 19.0 to 26.4). Individuals under the age of 40 had a higher prevalence of infection (PR, 1.53; 95% CI, 1.03 to 2.30) as well as those who did not believe in the protective effect of vaccines (PR, 1.78; 95% CI, 1.05 to 2.89). Our results indicate the need for better guidance on preventive measures against coronavirus disease 2019 among urban cleaning and solid waste management workers.

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In this household-based seroepidemiological survey, we analyzed the dynamics of SARS-CoV-2 seroprevalence during the first year of the COVID-19 pandemic in Sergipe State, Northeast Brazil, the poorest region of the country. A total of 16,547 individuals were tested using a rapid IgM-IgG antibody test and fluorescence immunoassay (FIA). Seroprevalence rates were presented according to age, sex, and geographic region. A comparative analysis was performed between the results obtained in July 2020 (peak of the first wave), August - November 2020 (end of the first wave), and February - March 2021 (beginning of the second wave). Seroprevalence rates in the three phases were estimated at 9.3% (95% CI 8.5-10.1), 12.0% (95% CI 11.2-12.9) and 15.4% (95% CI 14.5-16.4). At the end of the first wave, there was a rise in seroprevalence in the countryside (p < 0.001). At the beginning of the second wave, we found an increase in seroprevalence among women (p < 0.001), adults aged 20 to 59 years (p < 0.001), and the elderly (p < 0.001). In this phase, we found an increase in estimates both in metropolitan areas and in the countryside (p < 0.001). This study showed an increase in SARS-CoV-2 seroprevalence over the first year of the pandemic, with approximately one in six people having anti-SARS-CoV-2 antibodies at the beginning of the second wave of COVID-19. Furthermore, our results suggest a rapid spread of COVID-19 from metropolitan areas to the countryside during the first months of the pandemic.

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Parkinson's disease (PD) is identified by the loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc), and is correlated to aggregates of proteins such as α-synuclein, Lewy's bodies. Although the PD etiology remains poorly understood, evidence suggests a main role of oxidative stress on this process. Lippia grata Schauer, known as "alecrim-do-mato", "alecrim-de-vaqueiro", "alecrim-da-chapada", is a native bush from tropical areas mainly distributed throughout the Central and South America. This plant species is commonly used in traditional medicine for relief of pain and inflammation conditions, and that has proven antioxidant effects. We evaluated the effects of essential oil of the L. grata after its complexed with ß-cyclodextrin (LIP) on PD animal model induced by reserpine (RES). Behavioral assessments were performed across the treatment. Upon completion the treatment, the animals were euthanized, afterwards their brains were isolated and processed for immunohistochemical and oxidative stress analysis. The LIP treatment delayed the onset of the behavior of catalepsy, decreased the number of oral movements and prevented the memory impairment on the novel object recognition task. In addition, the treatment with LIP protected against dopaminergic depletion in the SNpc and dorsal striatum (STRd), and decreased the α-syn immunoreactivity in the SNpc and hippocampus (HIP). Moreover, there was reduction of the oxidative stability index. These findings demonstrated that the LIP treatment has neuroprotective effect in a progressive parkinsonism model, suggesting that LIP could be an important source for novel treatment approaches in PD.

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