NADPH oxidase 4-derived hydrogen peroxide counterbalances testosterone-induced endothelial dysfunction and migration.

High levels of testosterone (Testo) are associated with cardiovascular risk by increasing reactive oxygen species (ROS) formation. NADPH oxidases (NOX) are the major source of ROS in the vasculature of cardiovascular diseases. NOX4 is a unique isotype, which produces hydrogen peroxide (H2O2), and its participation in cardiovascular biology is controversial. So far, it is unclear whether NOX4 protects from Testo-induced endothelial injury. Thus, we hypothesized that supraphysiological levels of Testo induce endothelial NOX4 expression to attenuate endothelial injury. Human mesenteric vascular endothelial cells (HMECs) and human umbilical vein endothelial cells (HUVEC) were treated with Testo (10-7 M) with or without a NOX4 inhibitor [GLX351322 (10-4 M)] or NOX4 siRNA. In vivo, 10-wk-old C57Bl/6J male mice were treated with Testo (10 mg/kg) for 30 days to study endothelial function. Testo increased mRNA and protein levels of NOX4 in HMECs and HUVECs. Testo increased superoxide anion (O2-) and H2O2 production, which were abolished by NOX1 and NOX4 inhibition, respectively. Testo also attenuated bradykinin-induced NO production, which was further impaired by NOX4 inhibition. In vivo, Testo decreased H2O2 production in aortic segments and triggered endothelial dysfunction [decreased relaxation to acetylcholine (ACh)], which was further impaired by GLX351322 and by a superoxide dismutase and catalase mimetic (EUK134). Finally, Testo led to a dysregulated endothelial cell migration, which was exacerbated by GLX351322. These data indicate that supraphysiological levels of Testo increase the endothelial expression and activity of NOX4 to counterbalance the deleterious effects caused by Testo in endothelial function.NEW & NOTEWORTHY By inducing ROS formation, high levels of testosterone play a major role in the pathogenesis of cardiovascular disease. NOXs are the major sources of ROS in the vasculature of cardiovascular diseases. Herein, we describe a novel compensatory mechanism by showing that NOX4 is a protective oxidant enzyme and counterbalances the deleterious effects of testosterone in endothelial cells by modulating hydrogen peroxide formation.

Evaluation of different body temperature measurement methods for patients in the intraoperative period.

OBJECTIVES: this study aimed at estimating and comparing the reliability of temperature measurements obtained using a peripheral infrared temporal thermometer, a central cutaneous thermometer ("Zero-Heat-Flux Cutaneous thermometer") and an esophageal or nasopharyngeal thermometer among elective surgical patients in the intraoperative period. METHOD: a longitudinal study with repeated measures carried out by convenience sampling of 99 patients, aged at least 18 years old, undergoing elective abdominal cancer surgeries, with anesthesia lasting at least one hour, with each patient having their temperature measured by all three methods. RESULTS: the intraclass correlation coefficient showed a low correlation between the measurements using the peripheral temporal thermometer and the central cutaneous (0.0324) and esophageal/nasopharyngeal (-0.138) thermometers. There was a high correlation (0.744) between the central thermometers evaluated. CONCLUSION: the data from the current study do not recommend using infrared temporal thermometers as a strategy for measuring the body temperature of patients undergoing anesthetic-surgical procedures. Central cutaneous thermometers and esophageal/nasopharyngeal thermometers are equivalent for detecting intraoperative hypothermia.

In utero exposure to maternal diabetes exacerbates dietary sodium intake-induced endothelial dysfunction by activating cyclooxygenase 2-derived prostanoids.

Prenatal exposure to maternal diabetes has been recognized as a significant cardiovascular risk factor, increasing the susceptibility to the emergence of conditions such as high blood pressure, atherosclerosis, and heart disease in later stages of life. However, it is unclear if offspring exposed to diabetes in utero have worse vascular outcomes on a high-salt (HS) diet. To test the hypothesis that in utero exposure to maternal diabetes predisposes to HS-induced vascular dysfunction, we treated adult male wild-type offspring (DM_Exp, 6 mo old) of diabetic Ins2+/C96Y mice (Akita mice) with HS (8% sodium chloride, 10 days) and analyzed endothelial function via wire myograph and cyclooxygenase (COX)-derived prostanoids pathway by ELISA, quantitative PCR, and immunochemistry. On a regular diet, DM_Exp mice did not manifest any vascular dysfunction, remodeling, or inflammation. However, HS increased aortic contractility to phenylephrine and induced endothelial dysfunction (analyzed by acetylcholine-induced endothelium-dependent relaxation), vascular hydrogen peroxide production, COX2 expression, and prostaglandin E2 (PGE2) overproduction. Interestingly, ex vivo antioxidant treatment (tempol) or COX1/2 (indomethacin) or COX2 (NS398) inhibitors improved or reverted the endothelial dysfunction in DM_Exp mice fed a HS diet. Finally, DM_Exp mice fed with HS exhibited greater circulating cytokines and chemokines accompanied by vascular inflammation. In summary, our findings indicate that prenatal exposure to maternal diabetes predisposes to HS-induced vascular dysfunction, primarily through the induction of oxidative stress and the generation of COX2-derived PGE2. This supports the concept that in utero exposure to maternal diabetes is a cardiovascular risk factor in adulthood.NEW & NOTEWORTHY Using a unique mouse model of prenatal exposure to maternal type 1 diabetes, our study demonstrates the novel observation that prenatal exposure to maternal diabetes results in a predisposition to high-salt (HS) dietary-induced vascular dysfunction and inflammation in adulthood. Mechanistically, we demonstrated that in utero exposure to maternal diabetes and HS intake induces vascular oxidative stress, cyclooxygenase-derived prostaglandin E2, and inflammation.

Synthesis and Characterization of Cassava Gum Hydrogel Associated with Chlorhexidine and Evaluation of Release and Antimicrobial Activity.

Hydrogels from natural sources are attracting increasing interest due to their ability to protect biologically active molecules. Starch extracted from cassava tubers is a promising material for synthesizing these hydrogels. Copolymerization of cassava gum and incorporation of chlorhexidine digluconate (CLX) into the hydrogels is confirmed by changes in the crystallographic profile, as observed through X-ray diffraction, and a shift in the 1000 cm-1 band in the Fourier-transform infrared spectroscopy spectrum. The differential scanning calorimetry reveals changes in the decomposition temperature of the synthesized hydrogels related to CLX volatility. Micrographs illustrate the material's porosity. Release tests indicate a constant linear release over 72 h, while antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans is satisfactory, with 100% effectiveness from 0.5% CLX and the formation of inhibition halos. Toxicity and biocompatibility studies show no cytotoxicity. The continuous release of chlorhexidine is promising for components of biomedical implants and applications as it can ensure antimicrobial action according to specific therapeutic needs.

Cashew gum hydrogel as an alternative to minimize the effect of drought stress on soybean.

The use of hydrogels helpsthe production of plants in drought-stress environments. Thus, this work evaluated using different hydrogels to minimize drought stress in soybean cultivation. The treatments employed two different hydrogels, one already commercialized and the other produced with cashew gum (Anacardium occidentale), five levels (0, 30, 60, 120, and 240 mg pot-1) of the hydrogels, and two levels of drought stress in sandy soil. The growth and yield of soybeans and the levels of macro- and micronutrients in soybeans were evaluated.growth. The use of CG hydrogel promoted 12% increase in protein content in the seeds in the when soybean plants were subjected to drought stress. The levels of 30 mg pot-1, corresponding to 7.5 kg ha-1, improved the 'morphological and productive parametersof the soybeans. The increasing levels of hydrogel promoted the increase in P, K, Ca, Mg, and Fe and reduced S and Cu on an exponential scale. The use of cashew gum hydrogel increased the K and Ca contents in soybean seeds compared to commercial hydrogel.

Role of the CCL5 and Its Receptor, CCR5, in the Genesis of Aldosterone-Induced Hypertension, Vascular Dysfunction, and End-Organ Damage.

BACKGROUND: Aldosterone has been described to initiate cardiovascular diseases by triggering exacerbated sterile vascular inflammation. The functions of CCL5 (C-C motif chemokine ligand 5) and its receptor CCR5 (C-C motif chemokine receptor 5) are well known in infectious diseases, their contributions to aldosterone-induced vascular injury and hypertension remain unknown. METHODS: We analyzed the vascular profile, blood pressure, and renal damage in wild-type (CCR5+/+) and CCR5 knockout (CCR5-/-) mice treated with aldosterone (600 µg/kg per day for 14 days) while receiving 1% saline to drink. Vascular function was analyzed in aorta and mesenteric arteries, blood pressure was measured by telemetry and renal injury and inflammation were analyzed via histology and flow cytometry. Endothelial cells were used to study the molecular signaling whereby CCL5 induces endothelial dysfunction. RESULTS: Aldosterone treatment resulted in exaggerated CCL5 circulating levels and vascular CCR5 expression in CCR5+/+ mice accompanied by endothelial dysfunction, hypertension, and renal inflammation and damage. CCR5-/- mice were protected from these aldosterone-induced effects. Mechanistically, we demonstrated that CCL5 increased NOX1 (NADPH oxidase 1) expression, reactive oxygen species formation, NFκB (nuclear factor kappa B) activation, and inflammation and reduced NO production in isolated endothelial cells. These effects were abolished by antagonizing CCR5 with Maraviroc. Finally, aorta incubated with CCL5 displayed severe endothelial dysfunction, which is prevented by blocking NOX1, NFκB, or CCR5. CONCLUSIONS: Our data demonstrate that CCL5/CCR5, through activation of NFκB and NOX1, is critically involved in aldosterone-induced vascular and renal damage and hypertension placing CCL5 and CCR5 as potential therapeutic targets for conditions characterized by aldosterone excess.

Preparing Collared Peccary (Pecari tajacu Linnaeus, 1758) for Reintroduction into the Wild: A Screening for Parasites and Hemopathogens of a Captive Population.

The reintroduction of captive animals to the wild helps restore endangered species, but it risks pathogen transmission, harming wild populations. Such transmission can impact the genetic diversity and long-term viability of these populations. This study assessed parasite diversity and load in captive Pecari tajacu, a species native to the Americas and culturally significant to Brazilian indigenous culture, prior to reintroduction. Samples from 24 peccaries were analyzed for ectoparasites, hemopathogens, and stool parasites with direct and molecular analysis. Findings showed that various parasites were present. Two peccaries (8.3%) were infested by the adult tick Amblyomma sculptum. Six (25.0%) tested positive for Trypanosoma evansi, four (16.7%) for hemobacteria of the family Anaplasmataceae, twelve (50.0%) for hemotropic Mycoplasma, and seven (29.2%) for Leishmania braziliensis. Stool samples indicated multiple parasites, with sixteen (66.7%) peccaries infected by Strongylida order parasites, Spiruridae in three (12.5%), and Ascaris suum in one (4.2%) animal. Cysts of Balantidium sp. were found in twenty (83.3%), Entamoeba polecki in five (20.8%), and Iodamoeba bütschlii in two (8.3%) peccaries. To our current knowledge, this is the first global report of Leishmania braziliensis, Iodamoeba bütschlii, and Entamoeba polecki in P. tajacu, irrespective of the environment, including both captivity and wild conditions. Some of these parasites are common in domestic animals, and others are zoonotic, indicating potential interspecies pathogen transmission.

Evaluation of different body temperature measurement methods for patients in the intraoperative period / Evaluación de distintos métodos para medir la temperatura corporal de los pacientes durante el período intraoperatorio / Avaliação de diferentes métodos de mensuração da temperatura corporal de pacientes no período intraoperatório

Objectives: this study aimed at estimating and comparing the reliability of temperature measurements obtained using a peripheral infrared temporal thermometer, a central cutaneous thermometer ("Zero-Heat-Flux Cutaneous thermometer") and an esophageal or nasopharyngeal thermometer among elective surgical patients in the intraoperative period. Method: a longitudinal study with repeated measures carried out by convenience sampling of 99 patients, aged at least 18 years old, undergoing elective abdominal cancer surgeries, with anesthesia lasting at least one hour, with each patient having their temperature measured by all three methods. Results: the intraclass correlation coefficient showed a low correlation between the measurements using the peripheral temporal thermometer and the central cutaneous (0.0324) and esophageal/nasopharyngeal (-0.138) thermometers. There was a high correlation (0.744) between the central thermometers evaluated. Conclusion: the data from the current study do not recommend using infrared temporal thermometers as a strategy for measuring the body temperature of patients undergoing anesthetic-surgical procedures. Central cutaneous thermometers and esophageal/nasopharyngeal thermometers are equivalent for detecting intraoperative hypothermia.

Objetivos: el objetivo de este estudio fue estimar y comparar la confiabilidad de mediciones de temperatura obtenidas por medio de un termómetro temporal infrarrojo periférico, un termómetro cutáneo central ("Termómetro cutáneo Zero-Heat-Flux ") y un termómetro esofágico o nasofaríngeo en pacientes sometidos a cirugías electivas durante el período intraoperatorio. Método: estudio longitudinal con mediciones repetidas llevado a cabo con una muestra por conveniencia de 99 pacientes, de al menos 18 años de edad, sometidos a cirugías electivas por cáncer abdominal, con anestesia de al menos una hora de duración, y midiendo la temperatura de cada paciente con los tres métodos. Resultados: el coeficiente de correlación intraclase indicó una correlación baja entre las mediciones realizadas con el termómetro temporal periférico y los termómetros cutáneo (0,0324) y esofágico/nasofaríngeo (-0,138) centrales. Se registró una correlación alta (0,744) entre los termómetros centrales evaluados. Conclusión: los datos del presente estudio no recomiendan utilizar termómetros temporales infrarrojos como estrategia para medir la temperatura corporal de pacientes sometidos a procedimientos anestésico-quirúrgicos. Los termómetros cutáneos centrales y los esofágicos/nasofaríngeos son equivalentes para detectar hipotermia intraoperatoria.

Objetivos: este estudo teve como objetivo estimar e comparar a confiabilidade das medições de temperatura obtidas com um termômetro temporal infravermelho periférico, um termômetro cutâneo central (" Zero-Heat-Flux ") e um termômetro esofágico ou nasofaríngeo entre pacientes cirúrgicos eletivos no período intraoperatório. Método: estudo longitudinal com medidas repetidas realizado por amostragem de conveniência de 99 pacientes, com 18 anos ou mais, submetidos a cirurgia eletiva de câncer abdominal, com duração de anestesia de pelo menos uma hora, com cada paciente tendo sua temperatura medida pelos três métodos. Resultados: o coeficiente de correlação intraclasse mostrou uma baixa correlação entre as medições usando o termômetro temporal periférico e os termômetros cutâneo central (0,0324) e esofágico/nasofaríngeo (-0,138). Houve uma alta correlação (0,744) entre os termômetros centrais avaliados. Conclusão: os dados do presente estudo não recomendam o uso de um termômetro infravermelho temporal como estratégia para medir a temperatura corporal de pacientes submetidos a procedimentos anestésico-cirúrgicos. O termômetro cutâneo central e o termômetro esofágico/nasofaríngeo são equivalentes para detectar hipotermia intraoperatória.

Adjusted vascular contractility relies on integrity of progranulin pathway: Insights into mitochondrial function.

Objective: Cardiovascular disease (CVD) is a global health crisis and a leading cause of mortality. The intricate interplay between vascular contractility and mitochondrial function is central to CVD pathogenesis. The progranulin gene (GRN) encodes glycoprotein progranulin (PGRN), a ubiquitous molecule with known anti-inflammatory property. However, the role of PGRN in CVD remains enigmatic. In this study, we sought to dissect the significance of PGRN in the regulation vascular contractility and investigate the interface between PGRN and mitochondrial quality. Method: Our investigation utilized aortae from male and female C57BL6/J wild-type (PGRN+/+) and B6(Cg)-Grntm1.1Aidi/J (PGRN-/-) mice, encompassing wire myograph assays to assess vascular contractility and primary aortic vascular smooth muscle cells (VSMCs) for mechanistic insights. Results: Our results showed suppression of contractile activity in PGRN-/- VSMCs and aorta, followed by reduced α-smooth muscle actin expression. Mechanistically, PGRN deficiency impaired mitochondrial oxygen consumption rate (OCR), complex I activity, mitochondrial turnover, and mitochondrial redox signaling, while restoration of PGRN levels in aortae from PGRN-/- mice via lentivirus delivery ameliorated contractility and boosted OCR. In addition, VSMC overexpressing PGRN displayed higher mitochondrial respiration and complex I activity accompanied by cellular hypercontractility. Furthermore, increased PGRN triggered lysosome biogenesis by regulating transcription factor EB and accelerated mitophagy flux in VSMC, while treatment with spermidine, an autophagy inducer, improved mitochondrial phenotype and enhanced vascular contractility. Finally, angiotensin II failed to induce vascular contractility in PGRN-/- suggesting a key role of PGRN to maintain the vascular tone. Conclusion: Our findings suggest that PGRN preserves the vascular contractility via regulating mitophagy flux, mitochondrial complex I activity, and redox signaling. Therefore, loss of PGRN function appears as a pivotal risk factor in CVD development.

Vascular injury associated with ethanol intake is driven by AT1 receptor and mitochondrial dysfunction.

BACKGROUND: Renin-angiotensin (Ang II)-aldosterone system (RAAS) is crucial for the cardiovascular risk associated with excessive ethanol consumption. Disturbs in mitochondria have been implicated in multiple cardiovascular diseases. However, if mitochondria dysfunction contributes to ethanol-induced vascular dysfunction is still unknown. We investigated whether ethanol leads to vascular dysfunction via RAAS activation, mitochondria dysfunction, and mitochondrial reactive oxygen species (mtROS). METHODS: Male C57/BL6J or mt-keima mice (6-8-weeks old) were treated with ethanol (20% vol./vol.) for 12 weeks with or without Losartan (10 mg/kg/day). RESULTS: Ethanol induced aortic hypercontractility in an endothelium-dependent manner. PGC1α (a marker of biogenesis), Mfn2, (an essential protein for mitochondria fusion), as well as Pink-1 and Parkin (markers of mitophagy), were reduced in aortas from ethanol-treated mice. Disturb in mitophagy flux was further confirmed in arteries from mt-keima mice. Additionally, ethanol increased mtROS and reduced SOD2 expression. Strikingly, losartan prevented vascular hypercontractility, mitochondrial dysfunction, mtROS, and restored SOD2 expression. Both MnTMPyP (SOD2 mimetic) and CCCP (a mitochondrial uncoupler) reverted ethanol-induced vascular dysfunction. Moreover, L-NAME (NOS inhibitor) and EUK 134 (superoxide dismutase/catalase mimetic) did not affect vascular response in ethanol group, suggesting that ethanol reduces aortic nitric oxide (NO) and H2O2 bioavailability. These responses were prevented by losartan. CONCLUSION: AT1 receptor modulates ethanol-induced vascular hypercontractility by promoting mitochondrial dysfunction, mtROS, and reduction of NO and H2O2 bioavailability. Our findings shed a new light in our understanding of ethanol-induced vascular toxicity and open perspectives of new therapeutic approaches for patients with disorder associated with abusive ethanol drinking.

Effect of slow-release urea on intake, ingestive behavior, digestibility, nitrogen metabolism, microbial protein production, blood and ruminal parameters of sheep.

We conducted two experiments. The first aimed to obtain and characterize microparticles of slow-release urea (SRU) using calcium alginate as the encapsulating agent. The second experiment evaluated their inclusion in sheep diets. In the first experiment, four treatments from a completely randomized design were employed to develop an SRU through the ionic gelification technique testing two drying methods (oven and lyophilizer) and addition or no of sulfur (S): SRU oven-dried with sulfur (MUSO) and without sulfur (MUO), SRU freeze-dried/lyophilized with (MUSL), and without sulfur (MUL). MUO exhibited better yield and encapsulation efficiency among these formulations than the others. Therefore, the second experiment was conducted to compare free urea (U) as control and three proportions (1%, 1.5%, and 2% of total dry matter) of MUO in the diet of sheep. Twenty-four non-castrated male Santa Ines lambs, with an average body weight of 22 ± 3.0 kg, were used and distributed in a completely randomized design with four treatments and six replications. The inclusion of 1% alginate-encapsulated urea (MUO1%) resulted in higher dry matter (DM) intake than free urea (p ≤ 0.05). MUO2% inclusion promoted higher NDF digestibility than U and MUO1%. MUO1% showed higher DM than MUO2% and higher NFC digestibility than U and MUO2% (p ≤ 0.05). Sheep fed MUO1.5% and MUO2% exhibited similar nutrient intake and digestibility. Sheep receiving MUO1% had higher N-intake, N-urinary, N-excretion total, N-digested, and N-retained compared to U. Sheep fed MUO1% showed greater N-retained (as % ingested and digested), microbial protein production, and efficiency when compared to other treatments (p ≤ 0.05). MUO2% addition (SRU) promoted the lowest microbial protein production and efficiency in sheep. MUO dietary inclusion increased feeding time and reduced idleness time compared to U, regardless of the MUO level (p ≤ 0.05). Adding MUO1% improved the intake efficiency of DM and NDF and resulted in more feed boli than the other MUO levels (p ≤ 0.05). Sheep receiving U had (4 h after fending) higher NH3-N, pH, and blood urea nitrogen (BUN) and lower TGL serum compared to sheep fed MUO (p ≤ 0.05), without significant difference among MUO levels (p > 0.05), except NH3-N was higher in MUO1.5% and MUO2% compared to MUO1.0%. The external ionic gelation technique proved suitable for urea microencapsulation in calcium alginate (3%), demonstrating high quality, efficiency, and yield. MUO represents a promising slow-release urea for ruminants and is recommended for sheep diets at an inclusion level of 1.0%. This inclusion level improves intake efficiency and nutrient digestibility, increases rumen nitrogen retention, and reduces BUN without compromising sheep health.

Role Of The C-C Motif Chemokine Ligand 5 (CCL5) And Its Receptor, C-C Motif Chemokine Receptor 5 (CCR5) In The Genesis Of Aldosterone-induced Hypertension, Vascular Dysfunction, And End-organ Damage.

Background: Aldosterone, a mineralocorticoid steroid hormone, has been described to initiate cardiovascular diseases by triggering exacerbated sterile vascular inflammation. The functions of C-C Motif Chemokine Ligand 5 (CCL5) and its receptor, C-C Motif Chemokine Receptor 5 (CCR5), are well known in infectious diseases, but their roles in the genesis of aldosterone-induced vascular injury and hypertension are unknown. Methods: We analyzed the vascular profile, blood pressure, and renal damage in wild-type (CCR5+/+) and CCR5 knockout (CCR5-/-) mice treated with aldosterone (600 µg/kg/day for 14 days) while receiving 1% saline to drink. Results: Here, we show that CCR5 plays a central role in aldosterone-induced vascular injury, hypertension, and renal damage. Long-term infusion of aldosterone in CCR5+/+ mice resulted in exaggerated CCL5 circulating levels and vascular CCR5 expression. Aldosterone treatment also triggered vascular injury, characterized by endothelial dysfunction and inflammation, hypertension, and renal damage. Mice lacking CCR5 were protected from aldosterone-induced vascular damage, hypertension, and renal injury. Mechanistically, we demonstrated that CCL5 increased NADPH oxidase 1 (Nox1) expression, reactive oxygen species (ROS) formation, NFκB activation, and inflammation and reduced nitric oxide production in isolated endothelial cells. These effects were abolished by antagonizing CCR5 with Maraviroc. Finally, aortae incubated with CCL5 displayed severe endothelial dysfunction, which is prevented by blocking Nox1, NFκB, or with Maraviroc treatment. Conclusions: Our data demonstrate that CCL5/CCR5, through activation of NFkB and Nox1, is critically involved in aldosterone-induced vascular and renal damage and hypertension. Our data place CCL5 and CCR5 as potential targets for therapeutic interventions in conditions with aldosterone excess.

Progranulin Maintains Blood Pressure and Vascular Tone Dependent on EphrinA2 and Sortilin1 Receptors and Endothelial Nitric Oxide Synthase Activation.

Background The mechanisms determining vascular tone are still not completely understood, even though it is a significant factor in blood pressure management. Many circulating proteins have a significant impact on controlling vascular tone. Progranulin displays anti-inflammatory effects and has been extensively studied in neurodegenerative illnesses. We investigated whether progranulin sustains the vascular tone that helps regulate blood pressure. Methods and Results We used male and female C57BL6/J wild type (progranulin+/+) and B6(Cg)-Grntm1.1Aidi/J (progranulin-/-) to understand the impact of progranulin on vascular contractility and blood pressure. We found that progranulin-/- mice display elevated blood pressure followed by hypercontractility to noradrenaline in mesenteric arteries, which is restored by supplementing the mice with recombinant progranulin. In ex vivo experiments, recombinant progranulin attenuated the vascular contractility to noradrenaline in male and female progranulin+/+ arteries, which was blunted by blocking EphrinA2 or Sortilin1. To understand the mechanisms whereby progranulin evokes anticontractile effects, we inhibited endothelial factors. N(gamma)-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor) prevented the progranulin effects, whereas indomethacin (cyclooxygenase inhibitor) affected only the contractility in arteries incubated with vehicle, indicating that progranulin increases nitric oxide and decreases contractile prostanoids. Finally, recombinant progranulin induced endothelial nitric oxide synthase phosphorylation and nitric oxide production in isolated mesenteric endothelial cells. Conclusions Circulating progranulin regulates vascular tone and blood pressure via EphrinA2 and Sortilin1 receptors and endothelial nitric oxide synthase activation. Collectively, our data suggest that deficiency in progranulin is a cardiovascular risk factor and that progranulin might be a new therapeutic avenue to treat high blood pressure.

Suppressed vascular Rho-kinase activation is a protective cardiovascular mechanism in obese female mice.

BACKGROUND: Obesity is the number one cardiovascular risk factor for both men and women and is a complex condition. Although a sex dimorphism on vascular function has already been noted, the underlying processes remain unclear. The Rho-kinase pathway has a unique role in controlling vascular tone, and in obese male mice, hyperactivation of this system results in worsened vascular constriction. We investigated whether female mice exhibit decreased Rho-kinase activation as a protective mechanism in obesity. METHODS: We exposed male and female mice to a high-fat diet (HFD) for 14 weeks. At the end, energy expenditure, glucose tolerance, adipose tissue inflammation, and vascular function were investigated. RESULTS: Male mice were more sensitive to HFD-induced body weight gain, glucose tolerance, and inflammation than female mice. After establishing obesity, female mice demonstrated increase in energy expenditure, characterized by an increase in heat, whereas male mice did not. Interestingly, obese female mice, but not male, displayed attenuated vascular contractility to different agonists, such difference was blunted by inhibition of Rho-kinase, which was accompanied by a suppressed Rho-kinase activation, measured by Western blot. Finally, aortae from obese male mice displayed an exacerbated inflammation, whereas obese female demonstrated a mild vascular inflammation. CONCLUSION: In obesity, female mice demonstrate a vascular protective mechanism-suppression of vascular Rho-kinase-to minimize the cardiovascular risk associated with obesity, whereas male mice do not generate any adaptive response. Future investigations can help to understand how Rho-kinase becomes suppressed in female during obesity.

PROGRESSION OF VASCULAR FUNCTION AND BLOOD PRESSURE IN A MOUSE MODEL OF KAWASAKI DISEASE.

ABSTRACT: Kawasaki disease (KD) is a systemic vasculitis of childhood characterized by vascular damage in the acute stage, which can persist into the late stage. The vascular mechanisms in the cardiovascular risk of KD are not fully studied. We investigated the vascular function and blood pressure in a murine model of KD. We used the Candida albicans water-soluble (CAWS) fraction model. Mice were injected with 4 mg CAWS for 5 consecutive days and separated into three groups. Control, CAWS 7 days (C7), and CAWS 28 days (C28). Hearts and arteries were harvested for vascular characterization. Rat aortic smooth muscle cells were used to studies in vitro. C7 presented elevated inflammatory markers in the coronary area and abdominal aortas, whereas C28 showed severe vasculitis. No difference was found in blood pressure parameters. Vascular dysfunction characterized by higher contractility to norepinephrine in C7 and C28 in aortic rings was abolished by blocking nitric oxide (NO), reactive oxygen species, and cyclooxygenase (COX)-derived products. The CAWS complex increased COX2 expression in rat aortic smooth muscle cells, which was prevented by Toll-like receptor 4 antagonist. Our data indicate that the murine model of KD is associated with vascular dysfunction likely dependent on COX-derived products, oxidant properties, and NO bioavailability. Furthermore, vascular smooth muscle cell may present an important role in the genesis of vascular dysfunction and vasculitis via the Toll-like receptor 4 pathway. Finally, the CAWS model seems not to be appropriate to study KD-associated shock. More studies are necessary to understand whether vascular dysfunction and COXs are triggers for vasculitis.

Biochar Obtained from Caryocar brasiliense Endocarp for Removal of Dyes from the Aqueous Medium.

Given the increase in environmental pollution, especially of water, the emergence of studies that seek to develop strategies to mitigate/treat such effects have gained prominence in the world scientific community. Among the numerous adsorption processes, those made from biochar production stand out. This study analyzed the adsorption properties of the blue methylene model dye in the aqueous solution of biochar and activated biochar developed from pequi (Caryocar brasiliense) endocarp. The biochar was characterized, before and after adsorption, by infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffractometry (XRD), and thermogravimetric analysis (TG). The surface load of the materials was performed by the point of zero charge (pHPZC) method. The study also included analyses of contact time parameters and adsorbed concentration in the adsorption process. Morphological analysis showed that a more significant and profound number of fissures and pores appeared in the activated biochar compared to the biochar. Residual mass analysis evidenced that biochar lost about 15% more mass than the activated biochar, indicating that activation occurred satisfactorily. The adsorption process was well adjusted by pseudo-second-order kinetics and Langmuir's isothermal model. The activated biochar achieved an excellent adsorption capacity of 476.19 mg.g-1, thus demonstrating to be a sound system for removing dyes from an aqueous medium.

Essential oils for healing and/or preventing infection of surgical wounds: a systematic review.

OBJECTIVE: To analyze the evidence available in the literature on the use of essential oils for healing and/or preventing infection in surgical wounds. METHOD: Systematic review according to the JBI model and PRISMA statement. The search was carried out in November/2020 and updated in December/2021, using descriptors and keywords, in the CINAHL, LILACS, CENTRAL, EMBASE, PUBMED, Scopus, and Web of Science databases. The quality of the evidence was assessed using the JBI critical appraisal tool for randomized controlled trials. RESULTS: Five publications were included. Three studies evaluated healing and the presence of infection after episiotomy using the Redness-Edema-Ecchymosis-Discharge-Approximation (REEDA) scale; one study evaluated healing after periodontal surgery using the plaque index and Modified Gingival Index; the other four studies considered the presence of infection after episiotomy. Most studies used lavender oil, associated or not with other oils (80%). Two studies showed an improvement in healing. The infection outcome, although mentioned by 60% of studies, was not assessed as a primary outcome. CONCLUSION: The promising efficacy of essential oils, especially lavender, was verified in the healing of surgical wounds, especially in episiotomies.

Instruments to Identify Delirium in Patients Recovering From Anesthesia: A Scoping Review.

PURPOSE: To identify the validated instruments used for screening and detecting postoperative delirium (POD) during Post Anesthesia Recovery (PAR) period, and the incidence and associated risk factors with POD. DESIGN: A scoping review. METHODS: The study search occurred in May 2021 in the PubMed, Embase, Scopus, CINAHL, Web of Science and LILACS databases. Primary studies that used validated instruments for screening and detecting POD in the PAR period were included. FINDINGS: A total of 38 articles were included. The most used instruments were CAM-ICU, Nu-DESC, and RASS. The instruments that screened and detected delirium earliest were the Nu-DESC and CAM-ICU. POD incidence was up to 20% in more than half of the included studies. Cardiovascular comorbidities, chronic kidney disease, low functional reserve, chronic obstructive pulmonary disease and postoperative pain were among the primary risk factors. CONCLUSION: The instrumentsshowing the greatest accuracy for screening and detecting POD in the PAR period were the Nu-DESC and CAM-ICU.

CCR5 antagonist treatment inhibits vascular injury by regulating NADPH oxidase 1.

BACKGROUND: Chemokine (C- Cmotif) ligand 5 (CCL5) and its receptor C-C motif chemokine receptor 5 (CCR5), have been broadly studied in conjunction with infectious pathogens, however, their involvement in cardiovascular disease is not completely understood. NADPH oxidases (Noxs) are the major source of reactive oxygen species (ROS) in the vasculature. Whether the activation of Noxs is CCL5/CCR5 sensitive and whether such interaction initiates vascular injury is unknown. We investigated whether CCL5/CCR5 leads to vascular damage by activating Noxs. MATERIAL AND METHODS: We used rat aortic smooth muscle cells (RASMC) to investigate the molecular mechanisms by which CCL5 leads to vascular damage and carotid ligation (CL) to analyze the effects of blocking CCR5 on vascular injury. RESULTS: CCL5 induced Nox1 expression in concentration and time-dependent manners, with no changes in Nox2 or Nox4. Maraviroc pre-treatment (CCR5 antagonist, 40uM) blunted CCL5-induced Nox1 expression. Furthermore, CCL5 incubation led to ROS production and activation of Erk1/2 and NFkB, followed by increased vascular cell migration, proliferation, and inflammatory markers. Notably, Nox1 inhibition (GKT771, 10uM) blocked CCL5-dependent effects. In vivo, CL induced pathological vascular remodeling and inflammatory genes and increased Nox1 and CCR5 expression. Maraviroc treatment (25 mg/Kg/day) reduced pathological vascular growth and Nox1 expression. CONCLUSIONS: Our findings suggest that CCL5 activates Nox1 in the vasculature, leading to vascular injury likely via NFkB and Erk1/2. Herein, we place CCR5 antagonists and/or Nox1 inhibitors might be preeminent antiproliferative compounds to reduce the cardiovascular risk associated with medical procedures (e.g. angioplasty) and vascular diseases associated with vascular hyperproliferation.

Essential oils for healing and/or preventing infection of surgical wounds: a systematic review / Aceites esenciales para la cicatrización y/o prevención de infecciones de heridas quirúrgicas: una revisión sistemática / Óleos essenciais para a cicatrização e/ou prevenção de infecção de feridas cirúrgicas: revisão sistemática

ABSTRACT Objective: To analyze the evidence available in the literature on the use of essential oils for healing and/or preventing infection in surgical wounds. Method: Systematic review according to the JBI model and PRISMA statement. The search was carried out in November/2020 and updated in December/2021, using descriptors and keywords, in the CINAHL, LILACS, CENTRAL, EMBASE, PUBMED, Scopus, and Web of Science databases. The quality of the evidence was assessed using the JBI critical appraisal tool for randomized controlled trials. Results: Five publications were included. Three studies evaluated healing and the presence of infection after episiotomy using the Redness-Edema-Ecchymosis-Discharge-Approximation (REEDA) scale; one study evaluated healing after periodontal surgery using the plaque index and Modified Gingival Index; the other four studies considered the presence of infection after episiotomy. Most studies used lavender oil, associated or not with other oils (80%). Two studies showed an improvement in healing. The infection outcome, although mentioned by 60% of studies, was not assessed as a primary outcome. Conclusion: The promising efficacy of essential oils, especially lavender, was verified in the healing of surgical wounds, especially in episiotomies.

RESUMEN Objetivo: Analizar la evidencia en la literatura sobre el uso de aceites esenciales para la cicatrización y/o prevención de infecciones en heridas quirúrgicas. Método: Revisión sistemática de acuerdo con el modelo JBI y el PRISMA. Se realizó una búsqueda en las bases de datos CINAHL, LILACS, CENTRAL, EMBASE, PUBMED, Scopus y Web of Science, en el periodo de noviembre/2020, con actualizaciones en diciembre/2021, utilizando descriptores y palabras clave. La calidad de la evidencia se evaluó por la herramienta JBI critical appraisal para ensayos controlados aleatorizados. Resultados: Se incluyeron cinco publicaciones. Tres estudios evaluaron la curación y la presencia de infección tras episiotomía mediante la escala REEDA (Redness-Edema-Ecchimosis-Discharge-Approximation); uno evaluó la curación después de cirugía periodontal utilizando el índice de placa y el índice gingival modificado; y los demás consideraron la presencia de infección posterior a la episiotomía. La mayoría de los estudios utilizaron aceite de lavanda, asociado a otros aceites o no (80%). Dos estudios demostraron mejorar la cicatrización. El resultado infección, aunque mencionado por el 60% de los estudios, no se evaluó como resultado primario. Conclusión: Se verificó la prometedora eficacia de los aceites esenciales, especialmente el de lavanda, en la cicatrización de heridas quirúrgicas, especialmente en episiotomías.

RESUMO Objetivo: Analisar as evidências disponíveis na literatura sobre o uso de óleos essenciais para a cicatrização e/ou prevenção de infecção em feridas cirúrgicas. Método: Revisão sistemática segundo modelo JBI e declaração PRISMA. Busca realizada em novembro/2020 e atualizada em dezembro/2021, utilizando-se descritores e palavras-chave, nas bases CINAHL, LILACS, CENTRAL, EMBASE, PUBMED, Scopus e Web of Science. A qualidade das evidências foi avaliada usando a ferramenta JBI critical appraisal para ensaios clínicos randomizados. Resultados: Cinco publicações foram incluídas. Três estudos avaliaram a cicatrização e presença de infecção após episiotomia por meio da escala REEDA (Redness-Edema-Ecchymosis-Discharge-Approximation); um avaliou cicatrização após cirurgia periodontal por meio do índice de placa e Índice Gengival Modificado; o restante considerou a presença de infecção após episiotomia. A maioria dos estudos utilizou o óleo de lavanda, associado ou não a outros óleos (80%). Em dois estudos houve melhora da cicatrização. O desfecho infecção, embora mencionado por 60% estudos, não foi avaliado como primário. Conclusão: Verificou-se a eficácia promissora de óleos essenciais, sobretudo do de lavanda, na cicatrização de feridas cirúrgicas, especialmente em episiotomias.