Male versus female inflammatory response after brain death model followed by ex vivo lung perfusion.

BACKGROUND: Ex vivo lung perfusion (EVLP) is a useful tool for assessing lung grafts quality before transplantation. Studies indicate that donor sex is as an important factor for transplant outcome, as females present higher inflammatory response to brain death (BD) than males. Here, we investigated sex differences in the lungs of rats subjected to BD followed by EVLP. METHODS: Male and female Wistar rats were subjected to BD, and as controls sham animals. Arterial blood was sampled for gas analysis. Heart-lung blocks were kept in cold storage (1 h) and normothermic EVLP carried out (4 h), meanwhile ventilation parameters were recorded. Perfusate was sampled for gas analysis and IL-1ß levels. Leukocyte infiltration, myeloperoxidase presence, IL-1ß gene expression, and long-term release in lung culture (explant) were evaluated. RESULTS: Brain dead females presented a low lung function after BD, compared to BD-males; however, at the end of the EVLP period oxygenation capacity decreased in all BD groups. Overall, ventilation parameters were maintained in all groups. After EVLP lung infiltrate was higher in brain dead females, with higher neutrophil content, and accompanied by high IL-1ß levels, with increased gene expression and concentration in the culture medium (explant) 24 h after EVLP. Female rats presented higher lung inflammation after BD than male rats. Despite maintaining lung function and ventilation mechanics parameters for 4 h, EVLP was not able to alter this profile. CONCLUSION: In this context, further studies should focus on therapeutic measures to control inflammation in donor or during EVLP to increase lung quality.

As there is a shortage of viable lungs for transplantation, methods of lung preservation, such as ex vivo perfusion, are important. This method is a good alternative, as it will not only preserve the lungs, but also enable lung function assessment and treatment of the organs. Studies have showed that lungs from donors of the female sex have greater risk of being rejected, when transplanted to male receptors. However, it's not certain if sex differences in anatomy, physiology and specially in immune response could interfere with the transplant result. Females do present a greater and more efficient immune response to any hazard, however after brain death this control is lost, producing a great inflammatory response as a result. Therefore, in this study we have investigated in more detail the influence of sex on the effects of brain death followed by the preservation method. Thus, we performed a brain death model in males and females rats and placed their lungs in an ex vivo lung perfusion machine. At the end of the experiment, we analyzed lung ventilation, gas exchange, and inflammatory parameters. The obtained data indicated that overall the lung ventilation and gas exchange is maintained by the ex vivo perfusion machine. Also, that lung inflammation is influenced by the sex of the donor; where the lungs from females present greater inflammation compared to the lungs from males.

Comparative in vitro analysis of the antifungal activity of different calcium silicate-based endodontic sealers

Aim: This study aimed to perform an in vitro comparative analysis of the antifungal activity of different calcium silicate-based endodontic sealers against three fungal species. Methods: The antifungal properties of three calcium silicate-based sealers were tested: Bio-C Sealer, Cambiar a Sealer Plus BC, and MTA-Fillapex. Two commonly used sealers were used as controls: AH Plus and Endomethasone. An agar diffusion test was performed to analyze the antifungal activity of the sealers against Candida albicans, Candida glabrata, Candida tropicalis, and a mixed microbial culture medium. The results were analyzed using ANOVA (p <0.05). Results: Endomethasone exhibited the highest inhibition against all strains examined, maintaining a consistent level of inhibition throughout 7 days. MTA-Fillapex demonstrated the best performance among the calcium silicate-based sealers for the three fungal species (p < 0.05), maintaining stable values over the 7 days, surpassing that of Endomethasone. Nevertheless, MTA-Fillapex only exhibited antimicrobial effect against the mixed culture for the first 24 hours, and no antimicrobial activity was observed at 48 hours, being surpassed by all tested sealers (p < 0.05). Conclusion: Of all silicate-based sealers tested, only MTA-Fillapex exhibited promising antifungal activity. Nevertheless, care must be taken when extrapolating these results, as MTA-Fillapex exhibited poor antimicrobial activity when tested in mixed microbial cultures

American Thyroid Association and Thyroid Imaging Reporting and Data System developed by the American College of Radiology: which one is better at predicting malignancy risk?

OBJECTIVE: The aim of this study was to compare the capacity of American Thyroid Association and Thyroid Imaging Reporting and Data System developed by the American College of Radiology in predicting malignancy risk of thyroid nodules and to verify which one is better at avoiding unnecessary fine needle aspiration. METHODS: This was a cross-sectional study with 565 thyroid nodules, followed at a tertiary care hospital, in an iodine-replete area. Those were classified as American Thyroid Association and Thyroid Imaging Reporting and Data System developed by the American College of Radiology systems and stratified according to the Bethesda classification of fine needle aspiration. The values of sensibility, specificity, positive predictive value, and negative predictive value accuracy were calculated. Also, the percentage of unnecessary biopsies was presented. RESULTS: The mean age of the individuals was 58.2±13.5 [26-90] years for benign nodules and 41.7±15.6 [23-66] years for malignant nodules (p=0.002). Regarding gender, 92.6% (n=150) of the individuals with benign nodules and 85.7% (n=06) with malignant nodules were females (p=0.601). For American Thyroid Association, 90.9% of sensibility, 51.4% of specificity, 52.6% of accuracy, 10.2% of positive predictive value, and 98.9% of negative predictive value were found. For Thyroid Imaging Reporting and Data System developed by the American College of Radiology, 90.9% of sensibility, 49.7% of specificity, 52.1% of accuracy, 9.9% of positive predictive value, and 98.9% of negative predictive value were found. .Notably, 12.3% of unnecessary fine needle aspiration were found in American Thyroid Association and 44.4% were found in Thyroid Imaging Reporting and Data System developed by the American College of Radiology. CONCLUSION: Both Thyroid Imaging Reporting and Data System developed by the American College of Radiology and American Thyroid Association are able to predict the malignancy risk of thyroid nodules. Thyroid Imaging Reporting and Data System developed by the American College of Radiology was better at avoiding unnecessary fine needle aspiration.

Evaluation of the therapeutic effects of oestradiol on the systemic inflammatory response and on lung injury caused by the occlusion of the proximal descending aorta in male rats.

OBJECTIVES: Ischaemia and reperfusion-induced microvascular dysfunction is a serious problem encountered during a variety surgical procedures, leading to systemic inflammation and affecting remote organs, specially the lungs. 17ß-Oestradiol reduces pulmonary repercussions from various acute lung injury forms. Here, we focused on the 17ß-oestradiol therapeutic effects after aortic ischaemia and reperfusion (I/R) by evaluating lung inflammation. METHODS: Twenty-four Wistar rats were submitted to I/R by insufflation of a 2-F catheter in thoracic aorta for 20 min. Reperfusion took 4 h and 17ß-oestradiol (280 µg/kg, i.v.) was administered after 1 h of reperfusion. Sham-operated rats were controls. Bronchoalveolar lavage was performed and lung samples were prepared for histopathological analysis and tissue culture (explant). Interleukin (IL)-1ß, IL-10 and tumour necrosis factor-α were quantified. RESULTS: After I/R, higher number of leukocytes in bronchoalveolar lavage were reduced by 17ß-oestradiol. The treatment also decreased leukocytes in lung tissue. I/R increased lung myeloperoxidase expression, with reduction by 17ß-oestradiol. Serum cytokine-induced neutrophil chemoattractant 1 and IL-1ß increased after I/R and 17ß-oestradiol decreased cytokine-induced neutrophil chemoattractant 1. I/R increased IL-1ß and IL-10 in lung explants, reduced by 17ß-oestradiol. CONCLUSIONS: Our results showed that 17ß-oestradiol treatment performed in the period of reperfusion, modulated the systemic response and the lung repercussions of I/R by thoracic aortic occlusion. Thus, we can suggest that 17ß-oestradiol might be a supplementary approach leading the lung deterioration after aortic clamping in surgical procedures.

Comparison of acute kidney injury following brain death between male and female rats.

BACKGROUND: Clinical reports associate kidneys from female donors with worse prognostic in male recipients. Brain Death (BD) produces immunological and hemodynamic disorders that affect organ viability. Following BD, female rats are associated with increased renal inflammation interrelated with female sex hormone reduction. Here, the aim was to investigate the effects of sex on BD-induced Acute Kidney Injury (AKI) using an Isolated Perfused rat Kidney (IPK) model. METHODS: Wistar rats, females, and males (8 weeks old), were maintained for 4h after BD. A left nephrectomy was performed and the kidney was preserved in a cold saline solution (30 min). IPK was performed under normothermic temperature (37°C) for 90 min using WME as perfusion solution. AKI was assessed by morphological analyses, staining of complement system components and inflammatory cell markers, perfusion flow, and creatinine clearance. RESULTS: BD-male kidneys had decreased perfusion flow on IPK, a phenomenon that was not observed in the kidneys of BD-females (p < 0.0001). BD-male kidneys presented greater proximal (p = 0.0311) and distal tubule (p = 0.0029) necrosis. However, BD-female kidneys presented higher expression of eNOS (p = 0.0060) and greater upregulation of inflammatory mediators, iNOS (p = 0.0051), and Caspase-3 (p = 0.0099). In addition, both sexes had increased complement system formation (C5b-9) (p=0.0005), glomerular edema (p = 0.0003), and nNOS (p = 0.0051). CONCLUSION: The present data revealed an important sex difference in renal perfusion in the IPK model, evidenced by a pronounced reduction in perfusate flow and low eNOS expression in the BD-male group. Nonetheless, the upregulation of genes related to the proinflammatory cascade suggests a progressive inflammatory process in BD-female kidneys.

Use of carminic acid immobilized in agarose gel as a binding phase for DGT: A new approach for determinations of rare earth elements.

Recently, rare-earth elements (REEs) have attracted great interest due to their importance in several fields, such as the high-technology and medicine industries. Due to the recent intensification of the use of REEs in the world and the resulting potential impact on the environment, new analytical approaches for their determination, fractionation and speciation are needed. Diffusive gradients in thin films are a passive technique already used for sampling labile REEs, providing in situ analyte concentration, fractionation and, consequently, remarkable information on REE geochemistry. However, data based on DGT measurements until now have been based exclusively on the use of a single binding phase (Chelex-100, immobilized in APA gel). The present work proposes a new method for the determination of rare earth elements using an inductively coupled plasma‒mass spectrometry technique and a diffusive gradients in thin films (DGT) technique for application in aquatic environments. New binding gels were tested for DGT using carminic acid as the binding agent. It was concluded that acid dispersion directly in agarose gel presented the best performance, offering a simpler, faster, and greener method for measuring labile REEs compared to the existing DGT binding phase. Deployment curves obtained by immersion tests in the laboratory show that 13 REEs had linearity in their retention by the developed binding agent (retention x time), confirming the main premise of the DGT technique obeying the first Fick's diffusion law. For the first time, the diffusion coefficients were obtained in agarose gels (diffusion medium) and carminic acid immobilized in agarose as the binding phase for La, Ce, Pr, Nd, Sm, Eu, Gd, Dy, Ho, Er, Tm, Yb and Lu, which were 3.94 × 10-6, 3.87 × 10-6, 3.90 × 10-6, 3.79 × 10-6, 3.71 × 10-6, 4.13 × 10-6, 3.75 × 10-6, 3.94 × 10-6, 3.45 × 10-6, 3.97 × 10-6, 3.25 × 10-6, 4.06 × 10-6, and 3.50 × 10-6 cm2 s-1, respectively. Furthermore, the proposed DGT devices were tested in solutions with different pH values (3.5, 5.0, 6.5 and 8) and ionic strengths (I = 0.005 mol L-1, 0.01 mol L-1, 0.05 mol L-1 and 0.1 mol L-1 - NaNO3). The results of these studies showed an average variation in the analyte retention for all elements at a maximum of approximately 20% in the pH tests. This variation is considerably lower than those previously reported when using Chelex resin as a binding agent, particularly for lower pH values. For the ionic strength, the maximum average variation was approximately 20% for all elements (except for I = 0.005 mol L-1). These results indicate the possibility of a wide range of the proposed approach to be used for in situ deployment without the use of correction based on apparent diffusion coefficients (as required for using the conventional approach). In laboratory deployments using acid mine drainage water samples (treated and untreated), it was shown that the proposed approach presents excellent accuracy compared with data obtained from Chelex resin as a binding agent.

MiRNA-30d and miR-770-5p as potential clinical risk predictors of Vasoplegic Syndrome in Patients undergoing on-pump coronary artery bypass grafting.

The aims of this study were to perform pre-surgery miRNA profiling of patients who develop Vasoplegic syndrome (VS) after coronary artery bypass grafting (CABG) and identify those miRNAs that could be used as VS prognostic tools and biomarkers. The levels of 754 microRNAs (miRNAs) were measured in whole blood samples from a cohort of patients collected right before the coronary artery bypass grafting (CABG) surgery. We compared the miRNA levels of those who developed VS (VASO group) with those who did not (NONVASO group) after surgery. Six miRNAs (hsa-miR-548c-3p, -199b-5p, -383-5p -571 -183-3p, -30d-5p) were increased and two (hsa-1236-3p, and hsa-miR770-5p) were decreased in blood of VASO compared to NONVASO groups. Receiver Operating Characteristic (ROC) curve analysis revealed that a combination of the miRNAs, hsa-miR-30d-5p and hsa-miR-770-5p can be used as VS predictors (AUC = 0.9615, p < 0.0001). The computational and functional analyses were performed to gain insights into the potential role of these dysregulated miRNAs in VS and have identified the "Apelin Liver Signaling Pathway" as the canonical pathway containing the most target genes regulated by these miRNAs. The expression of the combined miRNAs hsa-miR-30d and hsa-miR-770-5p allowed the ability to distinguish between patients who could and could not develop VS, representing a potential predictive biomarker of VS.

Comparison of acute kidney injury following brain death between male and female rats

Abstract Background Clinical reports associate kidneys from female donors with worse prognostic in male recipients. Brain Death (BD) produces immunological and hemodynamic disorders that affect organ viability. Following BD, female rats are associated with increased renal inflammation interrelated with female sex hormone reduction. Here, the aim was to investigate the effects of sex on BD-induced Acute Kidney Injury (AKI) using an Isolated Perfused rat Kidney (IPK) model. Methods Wistar rats, females, and males (8 weeks old), were maintained for 4h after BD. A left nephrectomy was performed and the kidney was preserved in a cold saline solution (30 min). IPK was performed under normothermic temperature (37°C) for 90 min using WME as perfusion solution. AKI was assessed by morphological analyses, staining of complement system components and inflammatory cell markers, perfusion flow, and creatinine clearance. Results BD-male kidneys had decreased perfusion flow on IPK, a phenomenon that was not observed in the kidneys of BD-females (p< 0.0001). BD-male kidneys presented greater proximal (p= 0.0311) and distal tubule (p= 0.0029) necrosis. However, BD-female kidneys presented higher expression of eNOS (p= 0.0060) and greater upregulation of inflammatory mediators, iNOS (p= 0.0051), and Caspase-3 (p= 0.0099). In addition, both sexes had increased complement system formation (C5b-9) (p=0.0005), glomerular edema (p= 0.0003), and nNOS (p= 0.0051). Conclusion The present data revealed an important sex difference in renal perfusion in the IPK model, evidenced by a pronounced reduction in perfusate flow and low eNOS expression in the BD-male group. Nonetheless, the upregulation of genes related to the proinflammatory cascade suggests a progressive inflammatory process in BD-female kidneys.

American Thyroid Association and Thyroid Imaging Reporting and Data System developed by the American College of Radiology: which one is better at predicting malignancy risk?

SUMMARY OBJECTIVE: The aim of this study was to compare the capacity of American Thyroid Association and Thyroid Imaging Reporting and Data System developed by the American College of Radiology in predicting malignancy risk of thyroid nodules and to verify which one is better at avoiding unnecessary fine needle aspiration. METHODS: This was a cross-sectional study with 565 thyroid nodules, followed at a tertiary care hospital, in an iodine-replete area. Those were classified as American Thyroid Association and Thyroid Imaging Reporting and Data System developed by the American College of Radiology systems and stratified according to the Bethesda classification of fine needle aspiration. The values of sensibility, specificity, positive predictive value, and negative predictive value accuracy were calculated. Also, the percentage of unnecessary biopsies was presented. RESULTS: The mean age of the individuals was 58.2±13.5 [26-90] years for benign nodules and 41.7±15.6 [23-66] years for malignant nodules (p=0.002). Regarding gender, 92.6% (n=150) of the individuals with benign nodules and 85.7% (n=06) with malignant nodules were females (p=0.601). For American Thyroid Association, 90.9% of sensibility, 51.4% of specificity, 52.6% of accuracy, 10.2% of positive predictive value, and 98.9% of negative predictive value were found. For Thyroid Imaging Reporting and Data System developed by the American College of Radiology, 90.9% of sensibility, 49.7% of specificity, 52.1% of accuracy, 9.9% of positive predictive value, and 98.9% of negative predictive value were found. .Notably, 12.3% of unnecessary fine needle aspiration were found in American Thyroid Association and 44.4% were found in Thyroid Imaging Reporting and Data System developed by the American College of Radiology. CONCLUSION: Both Thyroid Imaging Reporting and Data System developed by the American College of Radiology and American Thyroid Association are able to predict the malignancy risk of thyroid nodules. Thyroid Imaging Reporting and Data System developed by the American College of Radiology was better at avoiding unnecessary fine needle aspiration.

A modified hydrogel production protocol to decrease cellular content.

PURPOSE: To analyze the cytotoxicity and cell in porcine-derived decellularized skin matrix. METHODS: We analyzed the effect of multiple decellularization processes by histological analysis, DNA quantification, and flow cytometry. Subsequently, we analyzed the most appropriate hydrogel concentration to minimize cytotoxicity on fibroblast culture and to maximize cell proliferation. RESULTS: After the fourth decellularization, the DNA quantification showed the lowest DNA concentration (< 50 ng/mg). Histological analysis showed no cell components in the hydrogel. Moreover, hematoxylin and eosin showed a heterogeneous structure of collagen fibers. The best hydrogel concentration ranged from 3 to 25%, and there was no significant difference between the 24 hours and seven days. CONCLUSIONS: The process of hydrogel production was effective for removing cells and DNA elements. The best hydrogel concentration ranged from 3 to 25%.

Modulatory effects of 17ß-estradiol on acute lung inflammation after total occlusion of the descending aorta in male rats.

As a consequence of systemic inflammation caused by ischemia and reperfusion (I/R) due to aortic occlusion, the lungs can exhibit increased microvascular permeability, local release of pro-inflammatory mediators, and leukocyte infiltration. Lung tissue infiltration by activated neutrophils is followed by acute respiratory distress syndrome, which is linked to acute pulmonary microvascular damage, high mortality rates, and organ dysfunction. Previous studies have demonstrated that female sex hormones modulate the inflammatory response and that prophylactic treatment with 17ß-estradiol (E2) can prevent fatalities and preserve mesenteric perfusion and intestinal integrity after ischemia/reperfusion induced by aortic occlusion. In this study, we focused on the protective effects of estradiol after aortic ischemia/reperfusion by evaluating lung injury and endothelial alterations. Upon anesthesia and mechanical ventilation, male rats were subjected to aortic occlusion for 20 min, followed by 2 h of reperfusion. In parallel, one group of rats received a single injection of estradiol (280 µg/kg, i.v.) 30 min before ischemia. We observed increased serum concentrations of IL-1ß, IL-6 and IL-10 in the I/R rats and E2 was able to reduce them. E2 effects after 2 h of reperfusion resulted mainly in decreasing of edema, iNOS expression and preventing leukocyte infiltration. Overall, our data indicate that estradiol might be a supplementary approach to deal with systemic processes and lung deterioration.

Ischemic preconditioning does not prevent placental dysfunction induced by fetal cardiac bypass.

BACKGROUND: Remote ischemic preconditioning (rIPC) has been applied to attenuate tissue injury. We tested the hypothesis that rIPC applied to fetal lambs undergoing cardiac bypass (CB) reduces fetal systemic inflammation and placental dysfunction. METHODS: Eighteen fetal lambs were divided into three groups: sham, CB control, and CB rIPC. CB rIPC fetuses had a hindlimb tourniquet applied to occlude blood flow for four cycles of a 5-min period, followed by a 2-min reperfusion period. Both study groups underwent 30 min of normothermic CB. Fetal inflammatory markers, gas exchange, and placental and fetal lung morphological changes were assessed. RESULTS: The CB rIPC group achieved higher bypass flow rates (p < .001). After CB start, both study groups developed significant decreases in PaO2 , mixed acidosis, and increased lactate levels (p < .0004). No significant differences in tissular edema were observed on fetal lungs and placenta (p > .391). Expression of Toll-like receptor 4 and intercellular adhesion molecule-1 in the placenta and fetal lungs did not differ among the three groups, as well as with vascular cell adhesion molecule-1 (VCAM-1) of fetal lungs (p > .225). Placental VCAM-1 expression was lower in the rIPC group (p < .05). Fetal interleukin-1 (IL-1) and thromboxane A2 (TXA2) levels were lower at 60 min post-CB in the CB rIPC group (p < .05). There were no significant differences in tumor necrosis factor-α, prostaglandin E2, IL-6, and IL-10 plasma levels of the three groups at 60-min post-bypass (p > .133). CONCLUSION: Although rIPC allowed increased blood flow during fetal CB and decreased IL-1 and TXA2 levels and placental VCAM-1, it did not prevent placental dysfunction in fetal lambs undergoing CB.

Chikungunya, Zika and Dengue seroprevalence rates among pregnant women in a hospital of southeastern Brazil / Soroprevalência de chikungunya, zika e dengue em gestantes de um hospital do sudeste do Brasil / Seroprevalencia de chikungunya, zika y dengue en mujeres embarazadas en un hospital del sureste de Brasil

Background and objectives: For decades, dengue outbreaks have been affecting vast territories of the Americas. In 2010's decade, Chikungunya and Zika virus (CHIKV and ZIKV) emerged as new arboviruses in the region. While several seroprevalence rates have been reported for dengue virus (DENV) infection in Brazil, serological surveys for the latest are scarce. We aimed to evaluate the seroprevalence of CHIKV, ZIKV, and DENV infections in pregnant women at admission to a public maternity hospital of Nova Iguaçu, state of Rio de Janeiro. Methods: A simple questionnaire was applied, containing limited demographic, obstetric, and clinical data, alongside with blood collection. Different commercial test kits, based on enzyme-linked immunosorbent assay (ELISA), were used. Results: Among 349 pregnant women enrolled from July to December 2017, there was a 28.4% seroreactivity for CHIKV, 47.2% for ZIKV, and 88.8% for DENV. Conclusion: These findings reflect the high dengue endemicity scenario and suggest a significant reach of the recent outbreaks of ZIKV and CHIKV infections in the region.(AU)

Justificativas e objetivos: Há décadas, surtos de dengue afetam vastos territórios das Américas. Na década de 2010, os vírus Chikungunya e Zika (CHIKV e ZIKV) surgiram como arbovírus emergentes na região. Embora diversas taxas de soroprevalência tenham sido relatadas para a infecção pelo vírus da dengue (DENV) no Brasil, pesquisas sorológicas para chikungunya e zika são escassas. Objetivou-se avaliar a soroprevalência das infecções por CHIKV, ZIKV e DENV em gestantes admitidas em uma maternidade pública de Nova Iguaçu, estado do Rio de Janeiro. Métodos: Foi aplicado um questionário simples, contendo dados demográficos, obstétricos e clínicos limitados, sendo realizada coleta de sangue na mesma visita. Diferentes kits de teste comerciais, baseados em ensaio imunoenzimático (ELISA), foram utilizados. Resultados: De 349 gestantes recrutadas de julho a dezembro de 2017, houve sororreatividade de 28,4% para CHIKV, 47,2% para ZIKV e 88,8% para DENV. Conclusão: Esses achados refletem o cenário de alta endemicidade da dengue e sugerem um alcance significativo dos surtos recentes causados por ZIKV e CHIKV na região.(AU)

Justificación y objetivos: Durante décadas, los brotes de dengue han afectado a vastos territorios de las Américas. En la década de 2010, los virus Chikungunya y Zika (CHIKV y ZIKV) surgieron como arbovirus emergentes en la región. Aunque se han reportadas varias tasas de seroprevalencia para la infección por el virus del dengue (DENV) en Brasil, la investigación serológica para el chikungunya y el Zika es escasa. Este estudio tuvo como objetivo evaluar la seroprevalencia de infecciones por CHIKV, ZIKV y DENV en mujeres embarazadas ingresadas en una maternidad pública en Nova Iguaçu, estado de Rio de Janeiro. Métodos: Se aplicó un sencillo cuestionario, que contenía datos demográficos, obstétricos y clínicos limitados, y se extrajo sangre en la misma visita. Se utilizaron diferentes kits de prueba comerciales basados en el ensayo inmunoabsorbente ligado a enzimas (ELISA). Resultados: De 349 mujeres embarazadas reclutadas de julio a diciembre de 2017, hubo serorreactividad de 28,4% para CHIKV, 47,2% para ZIKV y 88,8% para DENV. Conclusión: Estos hallazgos reflejan el escenario de alta endemicidad para el dengue y sugieren una variedad significativa de brotes recientes causados por ZIKV y CHIKV en la región.(AU)

Thoracic bilateral sympathectomy attenuates oxidative stress and prevents ventricular remodelling in experimental pulmonary hypertension.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a cardiopulmonary disease that affects the pulmonary vasculature, leading to increased afterload and eventually right ventricular (RV) remodelling and failure. Bilateral sympathectomy (BS) has shown promising results in dampening cardiac remodelling and dysfunction in several heart failure models. In the present study, we investigated whether BS reduces pulmonary arterial remodelling and mitigates RV remodelling and failure. METHODS: PAH was induced in male Wistar rats by intraperitoneal injection of monocrotaline. Rats were divided into 3 groups, involving untreated PAH (n = 15), BS-treated PAH (n = 13) and non-manipulated control rats (n = 13). Three weeks after PAH induction, the rats were anaesthetized and RV function was assessed via the pressure-volume loop catheter approach. Upon completion of the experiment, the lungs and heart were harvested for further analyses. RESULTS: BS was found to prevent pulmonary artery remodelling, with a clear reduction in α-smooth muscle actin and endothelin-1 expression. RV end-systolic pressure was reduced in the BS group, and preload recruitable stroke work was preserved. BS, therefore, mitigated RV remodelling and cardiomyocyte hypertrophy and diminished oxidative stress. CONCLUSIONS: We showed that thoracic BS may be an important treatment option for PAH patients. Blockade of the sympathetic pathway can prevent pulmonary remodelling and protect the RV from oxidative stress, myocardial remodelling and function decay.

Cardiac MicroRNA Expression Profile After Experimental Brain Death Is Associated With Myocardial Dysfunction and Can Be Modulated by Hypertonic Saline.

BACKGROUND: Brain death (BD) is associated with systemic inflammatory compromise, which might affect the quality of the transplanted organs. This study investigated the expression profile of cardiac microRNAs (miRNAs) after BD, and their relationship with the observed decline in myocardial function and with the changes induced by hypertonic saline solution (HSS) treatment. METHODS: Wistar rats were assigned to sham-operation (SHAM) or submitted to BD with and without the administration of HSS. Cardiac function was assessed for 6 h with left ventricular (LV) pressure-volume analysis. We screened 641 rodent miRNAs to identify differentially expressed miRNAs in the heart, and computational and functional analyses were performed to compare the differentially expressed miRNAs and find their putative targets and their related enriched canonical pathways. RESULTS: An enhanced expression in canonical pathways related to inflammation and myocardial apoptosis was observed in BD induced group, with 2 miRNAs, miR-30a-3p, and miR-467f, correlating with the level of LV dysfunction observed after BD. Conversely, HSS treated after BD and SHAM groups showed similar enriched pathways related to the maintenance of heart homeostasis regulation, in agreement with the observation that both groups did not have significant changes in LV function. CONCLUSIONS: These findings highlight the potential of miRNAs as biomarkers for assessing damage in BD donor hearts and to monitor the changes induced by therapeutic measures like HSS, opening a perspective to improve graft quality and to better understand the pathophysiology of BD. The possible relation of BD-induced miRNA's on early and late cardiac allograft function must be investigated.

Protective effects of 17ß-oestradiol on coagulation and systemic inflammation after total occlusion of the descending aorta in male rats.

OBJECTIVES: The surgical treatment for diseases of the descending aorta is related to a high mortality rate because of the activation of a systemic inflammatory process due to ischaemia and reperfusion (I/R) injury. Activation of coagulation can contribute to the inflammatory process, resulting in microcirculatory damage and multiple organ failure. Our goal was to evaluate the role of prophylactic intravenous 17ß-oestradiol (E2) in coagulation, the inflammatory response and hepatic injury after occlusion of the descendent proximal aorta in male rats. METHODS: Wistar male rats were randomized and allocated to 3 groups (n = 8 per group): sham, surgically manipulated; IR, animals subjected to I/R; and E2, animals treated with E2 (280 µg/kg, intravenously) before I/R. I/R was induced by insertion of a 2-Fr Fogarty arterial embolectomy catheter in the descending aorta, which was occluded for 20 min, followed by a reperfusion period of 2 h. Serological markers, platelet aggregation, hepatic vascular flow, systemic and liver inflammatory response and apoptosis were analysed. The coagulation process was evaluated by thromboelastometry. RESULTS: The aortic occlusion led to a reduction in plasma fibrinogen concentration in parallel with increased clotting time, greater clot firmness and reduced lysis. E2 treatment was able to increase fibrinogen, prevent the increase in clotting time and normalize clot firmness, but it exerted only a mild effect on clot lysis. Platelet aggregation was increased by IR, and E2 treatment was able to reduce it. There was a reduction in flow percentage in the IR group that was not prevented by E2. In parallel, higher aggregate formation was observed in the vessels of the IR group of animals. There was increased systemic release of interleukin-1-ß, interleukin-6 and interleukin-10 in the IR group, which was reduced in the treated animals. CONCLUSIONS: The current results suggest that pretreatment with E2 before an ischaemic period induced by occlusion of the proximal descending aorta is effective in preventing alterations in coagulation and systemic inflammation due to I/R injury.

Protective role of 17ß-estradiol treatment in renal injury on female rats submitted to brain death.

BACKGROUND: Clinical and experimental data highlight the consequences of brain death on the quality of organs and demonstrate the importance of donor state to the results of transplantation. Female rats show higher cardio-pulmonary injury linked to decreased concentrations of female sex hormones after brain-dead (BD). This study evaluated the effect of 17ß-estradiol on brain death induced renal injury in female rats. METHODS: Female Wistar rats were randomically allocated into 4 groups: false-operation (Sham), BD, treatment with 17ß-estradiol (50 µg/mL, 2 mL/h) 3 h after brain death (E2-T3), or immediately after brain death confirmation (E2-T0). Creatinine, urea, cytokines, and complement system components were quantified. Renal injury markers, such as KIM-1, Caspase-3, BCL-2 and MMP2/9 were evaluated. RESULTS: Brain death leads to increased kidney KIM-1 expression and longer 17ß-estradiol treatment resulted in downregulation (P<0.0001). There was increase of neutrophil numbers in kidney from BD rats and E2 treatment was able to reduce it (P=0.018). Regarding complement elements, E2-T3 group evidenced E2 therapeutic effects, reducing C5b-9 (P=0.0004), C3aR (P=0.054) and C5aR (P=0.019). In parallel, there were 17ß-estradiol effects in reducing MMP2 (P=0.0043), MMP9 (P=0.011), and IL-6 (P=0.024). Moreover, E2-T3 group improved renal function in comparison to BD group (P=0.0938). CONCLUSIONS: 17ß-estradiol treatment was able to reduce acute kidney damage in BD female rats owing to its ability to prevent tissue damage, formation of C5b-9, and local synthesis of inflammatory mediators.

Long-term lung inflammation is reduced by estradiol treatment in brain dead female rats.

OBJECTIVES: Lung transplantation is limited by the systemic repercussions of brain death (BD). Studies have shown the potential protective role of 17ß-estradiol on the lungs. Here, we aimed to investigate the effect of estradiol on the long-lasting lung inflammatory state to understand a possible therapeutic application in lung donors with BD. METHODS: Female Wistar rats were separated into 3 groups: BD, subjected to brain death (6h); E2-T0, treated with 17ß-estradiol (50 µg/mL, 2 mL/h) immediately after brain death; and E2-T3, treated with 17ß-estradiol (50 µg/ml, 2 ml/h) after 3h of BD. Complement system activity and macrophage presence were analyzed. TNF-α, IL-1ß, IL-10, and IL-6 gene expression (RT-PCR) and levels in 24h lung culture medium were quantified. Finally, analysis of caspase-3 gene and protein expression in the lung was performed. RESULTS: Estradiol reduced complement C3 protein and gene expression. The presence of lung macrophages was not modified by estradiol, but the release of inflammatory mediators was reduced and TNF-α and IL-1ß gene expression were reduced in the E2-T3 group. In addition, caspase-3 protein expression was reduced by estradiol in the same group. CONCLUSIONS: Brain death-induced lung inflammation in females is modulated by estradiol treatment. Study data suggest that estradiol can control the inflammatory response by modulating the release of mediators after brain death in the long term. These results strengthen the idea of estradiol as a therapy for donor lungs and improving transplant outcomes.