Compartmentalized Regulation of Pulmonary and Systemic Inflammation in Critical COVID-19 Patients.

Critical COVID-19 has been associated with altered patterns of cytokines. Distinct inflammatory processes in systemic and pulmonary sites have been reported, but studies comparing these two sites are still scarce. We aimed to evaluate the profile of pulmonary and systemic cytokines and chemokines in critically ill COVID-19 patients. Levels of cytokines and chemokines were measured in plasma samples and minibronchoalveolar lavage of critical COVID-19 patients within 48 h and 5-8 days after intubation. Distinct inflammatory processes were observed in the lungs and blood, which were regulated separately. Survivor patients showed higher lung cytokine levels including IFN-γ, IL-2, IL-4, G-CSF, and CCL4, while nonsurvivors displayed higher levels in the blood, which included IL-6, CXCL8, CXCL10, CCL2, and CCL4. Furthermore, our findings indicate that high TNF and CXCL8 levels in the mini-BAL were associated with better lung oxygen exchange capacity, whereas high levels of IFN-γ in plasma were associated with worse lung function, as measured using the PaO2/FiO2 ratio. These results suggest that a robust and localized inflammatory response in the lungs is protective and associated with survival, whereas a systemic inflammatory response is detrimental and associated with mortality in critical COVID-19.

Reduction in the number of neutrophils in the broncho-alveolar aspirate is associated with worse prognosis in elderly patients with severe COVID-19.

The blood levels of neutrophils are associated with the severity of COVID -19. However, their role in the pulmonary environment during COVID -19 severity is not clear. Here, we found a decrease in the neutrophil count in BAL (bronchoalveolar lavage) in non-survivors and in older patients (> 60 years). In addition, we have shown that older patients have higher serum concentration of CXCL8 and increased IL-10 expression by neutrophils.

Dysfunctional phenotype of systemic and pulmonary regulatory T cells associate with lethal COVID-19 cases.

Severe cases of COVID-19 present hyperinflammatory condition that can be fatal. Little is known about the role of regulatory responses in SARS-CoV-2 infection. In this study, we evaluated the phenotype of regulatory T cells in the blood (peripheral blood mononuclear cell) and the lungs (broncho-alveolar) of adult patients with severe COVID-19 under invasive mechanical ventilation. Our results show important dynamic variation on Treg cells phenotype during COVID-19 with changes in number and functional parameters from the day of intubation (Day 1 of intensive care unit admission) to Day 7. We observed that compared with surviving patients, non-survivors presented lower numbers of Treg cells in the blood. In addition, lung Tregs of non-survivors also displayed higher PD1 and lower FOXP3 expressions suggesting dysfunctional phenotype. Further signs of Treg dysregulation were observed in non-survivors such as limited production of IL-10 in the lungs and higher production of IL-17A in the blood and in the lungs, which were associated with increased PD1 expression. These findings were also associated with lower pulmonary levels of Treg-stimulating factors like TNF and IL-2. Tregs in the blood and lungs are profoundly dysfunctional in non-surviving COVID-19 patients.

Impact of bedside ultrasound to reduce the incidence of acute renal injury in high-risk surgical patients: a randomized clinical trial.

PURPOSE: This study aimed to determine whether performing bedside ultrasound impacts the occurrence of acute kidney injury (AKI) in the immediate postoperative period (POP) of high-risk surgery patients. METHODS: POP patients were randomly assigned to two groups: (i) ultrasound (US) group, in which hemodynamic management was guided with clinical parameters supplemented with the bedside US findings; (ii) control group, hemodynamic management based solely on clinical parameters. Two exams were performed in the first 24 h of admission. RESULTS: Fifty-one patients were randomized to the US group and 60 to the control group. There was no significant difference for incidence of AKI in both groups assessed 12 h (31.4% vs 35.0%, P = 0.84), 24 h (27.5% vs 23.3%, P = 0.66), or 7 days (17.6 vs 8.3%, P = 0.16) after surgery. No difference was found in the amounts of volume administered over the first 12 h (1000 [500-2000] vs. 1000 [500-1500], P = 0.72) and 24 h (1000 [0-1500] vs. 1000 [0-1500], P = 0.95) between the groups. Patients without AKI in the control group received higher amounts of volume during the ICU stay. CONCLUSION: The use of bedside US in the immediate postoperative period of high-risk surgery did not show benefits in reducing AKI incidence.

Near-Infrared Spectroscopy with Supervised Machine Learning as a Screening Tool for Neutropenia.

The use of non-invasive tools in conjunction with artificial intelligence (AI) to detect diseases has the potential to revolutionize healthcare. Near-infrared spectroscopy (NIR) is a technology that can be used to analyze biological samples in a non-invasive manner. This study evaluated the use of NIR spectroscopy in the fingertip to detect neutropenia in solid-tumor oncologic patients. A total of 75 patients were enrolled in the study. Fingertip NIR spectra and complete blood counts were collected from each patient. The NIR spectra were pre-processed using Savitzky-Golay smoothing and outlier detection. The pre-processed data were split into training/validation and test sets using the Kennard-Stone method. A toolbox of supervised machine learning classification algorithms was applied to the training/validation set using a stratified 5-fold cross-validation regimen. The algorithms included linear discriminant analysis (LDA), logistic regression (LR), random forest (RF), multilayer perceptron (MLP), and support vector machines (SVMs). The SVM model performed best in the validation step, with 85% sensitivity, 89% negative predictive value (NPV), and 64% accuracy. The SVM model showed 67% sensitivity, 82% NPV, and 57% accuracy on the test set. These results suggest that NIR spectroscopy in the fingertip, combined with machine learning methods, can be used to detect neutropenia in solid-tumor oncology patients in a non-invasive and timely manner. This approach could help reduce exposure to invasive tests and prevent neutropenic patients from inadvertently undergoing chemotherapy.

Risk factors for acute kidney injury after liver transplantation in intensive care unit: a retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication during the postoperative period following liver transplantation. Occurrence of AKI in intensive care unit (ICU) patients is associated with increased mortality and higher costs. OBJECTIVE: To evaluate occurrences of moderate or severe AKI among patients admitted to the ICU after liver transplantation and investigate characteristics associated with this complication. DESIGN AND SETTING: Single-center retrospective cohort study in a public hospital, Belo Horizonte, Brazil. METHODS: Forty-nine patients admitted to the ICU between January 2015 and April 2017 were included. AKI was defined from a modified Kidney Disease Improving Global Outcomes (KDIGO) score (i.e. based exclusively on serum creatinine levels). RESULTS: Eighteen patients (36.7%) developed AKI KDIGO 2 or 3; mostly KDIGO 3 (16 out of the 18 patients). Lactate level within the first six hours after ICU admission (odds ratio, OR: 1.3; 95% confidence interval, CI: 1.021-1.717; P = 0.034) and blood transfusion requirement within the first week following transplantation (OR: 8.4; 95% CI: 1.687-41.824; P = 0.009) were independently associated with development of AKI. Patients with AKI KDIGO 2 or 3 underwent more renal replacement therapy (72.2% versus 3.2%; P < 0.01), had longer hospital stay (20 days versus 15 days; P = 0.001), higher in-hospital mortality (44.4% versus 6.5%; P < 0.01) and higher mortality rate after one year (44.4% versus 9.7%; P = 0.01). CONCLUSION: Need for blood transfusion during ICU stay and hyperlactatemia within the first six postoperative hours after liver transplantation are independently associated with moderate or severe AKI. Developing AKI is apparently associated with poor outcomes.

Risk factors for acute kidney injury after liver transplantation in intensive care unit: a retrospective cohort study

ABSTRACT BACKGROUND: Acute kidney injury (AKI) is a frequent complication during the postoperative period following liver transplantation. Occurrence of AKI in intensive care unit (ICU) patients is associated with increased mortality and higher costs. OBJECTIVE: To evaluate occurrences of moderate or severe AKI among patients admitted to the ICU after liver transplantation and investigate characteristics associated with this complication. DESIGN AND SETTING: Single-center retrospective cohort study in a public hospital, Belo Horizonte, Brazil. METHODS: Forty-nine patients admitted to the ICU between January 2015 and April 2017 were included. AKI was defined from a modified Kidney Disease Improving Global Outcomes (KDIGO) score (i.e. based exclusively on serum creatinine levels). RESULTS: Eighteen patients (36.7%) developed AKI KDIGO 2 or 3; mostly KDIGO 3 (16 out of the 18 patients). Lactate level within the first six hours after ICU admission (odds ratio, OR: 1.3; 95% confidence interval, CI: 1.021-1.717; P = 0.034) and blood transfusion requirement within the first week following transplantation (OR: 8.4; 95% CI: 1.687-41.824; P = 0.009) were independently associated with development of AKI. Patients with AKI KDIGO 2 or 3 underwent more renal replacement therapy (72.2% versus 3.2%; P < 0.01), had longer hospital stay (20 days versus 15 days; P = 0.001), higher in-hospital mortality (44.4% versus 6.5%; P < 0.01) and higher mortality rate after one year (44.4% versus 9.7%; P = 0.01). CONCLUSION: Need for blood transfusion during ICU stay and hyperlactatemia within the first six postoperative hours after liver transplantation are independently associated with moderate or severe AKI. Developing AKI is apparently associated with poor outcomes.

Rapid diagnosis of COVID-19 using FT-IR ATR spectroscopy and machine learning.

Early diagnosis of COVID-19 in suspected patients is essential for contagion control and damage reduction strategies. We investigated the applicability of attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy associated with machine learning in oropharyngeal swab suspension fluid to predict COVID-19 positive samples. The study included samples of 243 patients from two Brazilian States. Samples were transported by using different viral transport mediums (liquid 1 or 2). Clinical COVID-19 diagnosis was performed by the RT-PCR. We built a classification model based on partial least squares (PLS) associated with cosine k-nearest neighbours (KNN). Our analysis led to 84% and 87% sensitivity, 66% and 64% specificity, and 76.9% and 78.4% accuracy for samples of liquids 1 and 2, respectively. Based on this proof-of-concept study, we believe this method could offer a simple, label-free, cost-effective solution for high-throughput screening of suspect patients for COVID-19 in health care centres and emergency departments.

Properties and Application of Cell-Free DNA as a Clinical Biomarker.

Biomarkers are valuable tools in clinical practice. In 2001, the National Institutes of Health (NIH) standardized the definition of a biomarker as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. A biomarker has clinical relevance when it presents precision, standardization and reproducibility, suitability to the patient, straightforward interpretation by clinicians, and high sensitivity and/or specificity by the parameter it proposes to identify. Thus, serum biomarkers should have advantages related to the simplicity of the procedures and to the fact that venous blood collection is commonplace in clinical practice. We described the potentiality of cfDNA as a general clinical biomarker and focused on endothelial dysfunction. Circulating cell-free DNA (cfDNA) refers to extracellular DNA present in body fluid that may be derived from both normal and diseased cells. An increasing number of studies demonstrate the potential use of cfDNA as a noninvasive biomarker to determine physiologic and pathologic conditions. However, although still scarce, increasing evidence has been reported regarding using cfDNA in cardiovascular diseases. Here, we have reviewed the history of cfDNA, its source, molecular features, and release mechanism. We also show recent studies that have investigated cfDNA as a possible marker of endothelial damage in clinical settings. In the cardiovascular system, the studies are quite new, and although interesting, stronger evidence is still needed. However, some drawbacks in cfDNA methodologies should be overcome before its recommendation as a biomarker in the clinical setting.

Ultrasound as an alternative bedside tool to quickly confirm the position of the enteral catheter in the context of the COVID-19 pandemic.

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Lung Ultrasound Can Predict the Clinical Course and Severity of COVID-19 Disease.

Coronavirus disease 2019 (COVID-19) compromises the lung in large numbers of people. The development of minimally invasive methods to determine the severity of pulmonary extension is desired. This study aimed to describe the characteristics of sequential lung ultrasound and to test the prognostic usefulness of this exam in a group of patients admitted to the hospital with COVID-19. We prospectively evaluated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted to our hospital between April and August 2020. Bedside lung ultrasound exams were performed at three time points: at inclusion in the study, after 48 h and on the seventh day of follow-up. Lung ultrasound scores were quantified according to the aeration loss in each of eight zones scanned. Sixty-six participants were included: 42 (63.6%) in the intensive care unit and 24 (36.3%) in the ward. Lung ultrasound scores were higher in participants admitted to the intensive care unit than in those admitted to the ward at the time of inclusion (16 [13-17] vs. 10 [4-14], p < 0.001), after 48 h (15.5 [13-17] vs. 12.5 [8.2-14.7], p = 0.001) and on the seventh day (16 [14-17] vs. 7 [4.5-13.7], p < 0.001) respectively. Lung ultrasound score measured at the time of inclusion in the study was independently associated with the need for admission to the intensive care unit (odds ratio = 1.480; 95% confidence interval, 1.093-2.004; p = 0.011) adjusted by the Sequential Organ Failure Assessment score.

Ultrarapid On-Site Detection of SARS-CoV-2 Infection Using Simple ATR-FTIR Spectroscopy and an Analysis Algorithm: High Sensitivity and Specificity.

There is an urgent need for ultrarapid testing regimens to detect the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infections in real-time within seconds to stop its spread. Current testing approaches for this RNA virus focus primarily on diagnosis by RT-qPCR, which is time-consuming, costly, often inaccurate, and impractical for general population rollout due to the need for laboratory processing. The latency until the test result arrives with the patient has led to further virus spread. Furthermore, latest antigen rapid tests still require 15-30 min processing time and are challenging to handle. Despite increased polymerase chain reaction (PCR)-test and antigen-test efforts, the pandemic continues to evolve worldwide. Herein, we developed a superfast, reagent-free, and nondestructive approach of attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy with subsequent chemometric analysis toward the prescreening of virus-infected samples. Contrived saliva samples spiked with inactivated γ-irradiated COVID-19 virus particles at levels down to 1582 copies/mL generated infrared (IR) spectra with a good signal-to-noise ratio. Predominant virus spectral peaks are tentatively associated with nucleic acid bands, including RNA. At low copy numbers, the presence of a virus particle was found to be capable of modifying the IR spectral signature of saliva, again with discriminating wavenumbers primarily associated with RNA. Discrimination was also achievable following ATR-FTIR spectral analysis of swabs immersed in saliva variously spiked with virus. Next, we nested our test system in a clinical setting wherein participants were recruited to provide demographic details, symptoms, parallel RT-qPCR testing, and the acquisition of pharyngeal swabs for ATR-FTIR spectral analysis. Initial categorization of swab samples into negative versus positive COVID-19 infection was based on symptoms and PCR results (n = 111 negatives and 70 positives). Following training and validation (using n = 61 negatives and 20 positives) of a genetic algorithm-linear discriminant analysis (GA-LDA) algorithm, a blind sensitivity of 95% and specificity of 89% was achieved. This prompt approach generates results within 2 min and is applicable in areas with increased people traffic that require sudden test results such as airports, events, or gate controls.

Lipopolysaccharide exposure modulates the contractile and migratory phenotypes of vascular smooth muscle cells.

INTRODUCTION: Sepsis survivors are at higher risk for cardiovascular events. Lipopolysaccharide (LPS) activates Toll-like receptor 4 (TLR4) in sepsis. Activation of TLR4 modulates vascular smooth muscle cells (VSMCs) phenotype and contributes to cardiovascular changes after sepsis. AIM: Investigate changes in VSMCs phenotype caused by LPS-induced TLR4 activation. METHODS: Rat VSMCs were incubated with LPS. Two incubation conditions were used in cell contraction and migration assays: acute stimulation - LPS stimulus was initiated at the beginning of the assay and maintained throughout; and preconditioning - LPS stimulation was applied prior to the assay then discontinued. Nitric oxide (NO) production, mRNA expression of cytokines and phenotype markers, and interleukin (IL)-6 production were evaluated. KEY FINDINGS: LPS increased gene expression of IL-1ß, IL-6, TNFα and MCP-1 (p < .001), of secretory phenotype markers collagen and vimentin (p < .0479) and of the contractile marker smooth muscle 22α (SM22α) (p = .0067). LPS exposure increased IL-6 secretion after 24 and 48 h (p < .0001), and NO at 8 and 24 h (p < .0249) via inducible nitric oxide synthase (iNOS), as demonstrated by a decrease in NO after incubation with aminoguanidine. Acute stimulation with LPS reduced migration and contraction in a NO-dependent manner, while preconditioning with LPS increased both in an IL-6-dependent manner. SIGNIFICANCE: LPS affects VSMCs by modulating their secretory, contractile and migratory phenotypes. LPS acute stimulation of VSMCs promoted a NO-dependent reduction in migration and contraction, while preconditioning with LPS promoted IL-6-dependent increases in migration and contraction, evidencing that VSMCs can present phenotype modifications that persist after sepsis, thereby contributing to postsepsis cardiovascular events.

Effects of direct high sodium exposure at endothelial cell migration.

The present study aimed to test the hypothesis that high sodium affects the migratory phenotype of endothelial cells (EC) and investigates mechanisms involved independently of hemodynamic factors. Cell migration was evaluated by Wound-Healing at conditions: High Sodium (HS; 160 mM) and Control (CT; 140 mM). O2- production was evaluated by DHE. NADPH oxidase activity was determined by chemiluminescence assay. Expression of adhesion molecules was analyzed by RT-PCR. Shear Stress was performed using a rhythmic shake. Nitric oxide production was measured by Griess reaction. HS-induced impairment in EC migration while both Candesartan and DPI prevented it. HS increased NADPH oxidase activity, which was blocked by Candesartan. Also, HS increased O2- production that was inhibited by Candesartan. HS decreased adhesion molecules expression via ROS (Integrin Alpha 5, Integrin Beta 1, Integrin Beta 3, VE-Cadherin and PECAM) and via AT1R (PECAM). The nitric oxide production induced by shear stress was decreased after EC exposure to HS while both Candesartan and DPI prevented it. Conclusion: This study demonstrated that HS reduced EC migration by AT1R and ROS derived from NADPH Oxidase and mitochondria. The HS reduction in adhesion molecules expression modulated by ROS and AT1R may help to explain the impairment in migration capacity. Also, HS affected EC functionality by reducing their nitric oxide production in response to shear stress.

Influence of Long-Term Salt Diets on Cardiac Ca2+ Handling and Contractility Proteins in Hypertensive Rats.

BACKGROUND: High sodium intake contributes to the pathogenesis of hypertension and adversely affects cardiac function. Conversely, sodium reduction is associated with a blood pressure decrease and improved cardiovascular function. However, the mechanisms that underlie the cardiac effects induced by salt intake in hypertension have not been fully elucidated. Ca2+ handling is critical for efficient myocardial function; thus, we aimed to investigate the long-term effects of diets with different salt contents on cardiac function and Ca2+ handling proteins in spontaneously hypertensive rats (SHRs). METHODS: Cardiac function was evaluated by catheterization. Ca2+ handling and contractile proteins were evaluated by immunoblotting in hearts from SHRs fed for 6 months with diets containing high (HS, 3%), low (LS, 0.03%), or normal salt content (NS, 0.3%). Diets were introduced immediately after weaning. Tail cuff pletismography was assessed at the 3rd and 7th months of follow-up. RESULTS: Compared to the NS group, the HS group exhibited worsened hypertension, increased cardiac expression of ß-myosin heavy chain (MHC), a decreased α/ß-MHC ratio and reduced expression of both phospholamban (PLB) and Na+/Ca2+ exchanger (NCX). LS intake attenuated the blood pressure increase and left ventricle hypertrophy, slightly decreased the cardiac contractility and relaxation index, and increased the α/ß-MHC ratio. These effects were accompanied by increased cardiac PLB expression and decreased Ca2+ L-type channel and NCX expression. CONCLUSIONS: These findings indicate that the modulation of Ca2+ handling may be one of the molecular mechanisms underlying the effect of salt intake on myocardial function in hypertension.

Xanthine Oxidase Activation Modulates the Endothelial (Vascular) Dysfunction Related to HgCl2 Exposure Plus Myocardial Infarction in Rats.

Heavy metal exposure is associated with cardiovascular diseases such as myocardial infarction (MI). Vascular dysfunction is related to both the causes and the consequences of MI. We investigated whether chronic exposure to low doses of mercury chloride (HgCl2) worsens MI-induced endothelial dysfunction 7 days after MI. Male Wistar rats were divided into four groups: Control (vehicle), HgCl2 (4 weeks of exposure), surgically induced MI and combined HgCl2-MI. Morphological and hemodynamic measurements were used to characterize the MI model 7 days after the insult. Vascular reactivity was evaluated in aortic rings. Chronic HgCl2 exposure did not cause more heart injury than MI alone in terms of the morphological or hemodynamic parameters. Vascular reactivity increased in all groups, but the combination of HgCl2-MI increased the vasorelaxation induced by ACh compared with the HgCl2 and MI groups. Results showed reduced endothelial nitric oxide synthase (eNOS) protein expression in the MI group; increased iNOS activity in the HgCl2-MI group, although without enough magnitude to reverse the reduction in NO bioavailability; and increased phenylephrine response in the HgCl2-MI group due to an increase in ROS production, notably via xanthine oxidase (XO). Results suggest that the combination of 1 month pre-exposure of HgCl2 before MI changed the endothelial generation of oxidative stress induced by mercury exposure from NADPH oxidase pathway to XO (xanthine oxidase)-dependent ROS production.

Effects of controlled doses of Oxyelite Pro on physical performance in rats.

BACKGROUND: OxyElite Pro (OEP) is a dietary supplement to increase metabolism which contains as key stimulant the ingredient 1,3-dimethylamylamine (DMAA). Serious adverse effects have been reported after OEP consumption however, these effects are related to poisoning or overdose. To our knowledge, no one studied the effects of OEP at controlled doses. Thus, the aim of this study was to evaluate acute and chronic OEP affects, at controlled doses in Wistar rats, on physical performance, metabolic parameters, liver injury markers and oxidative stress markers and mitochondrial biogenesis in skeletal muscle. METHODS: Rats were divided in control, 4.3 mg OEP/kg, 12.9 mg OEP/kg and 25.8 mg OEP/kg. All groups were submitted to supplementation with OEP for 4 weeks and the experimental protocols were performed 30 min after the first OEP administration (acute response) and 30 min after the last OEP administration at the end of the forth week (chronic response). RESULTS: Running distance and running time increased after acute administration of 12.9 mg OEP/kg (2.6-fold) and 25.8 mg OEP/kg (2.8-fold). Since no effect on the exercise tolerance test was observed at the lower OEP dose (4.3 mg OEP/kg), this group was removed from further analyzes. On other hand, running distance and running time decreased after daily supplementation for 4 weeks also in both groups (64% in 12.9 mg OEP/kg and 72% in 25.8 mg OEP/kg). Chronic supplementation at both 12.9 and 25.8 mg OEP/kg decreased TBARS levels in soleus muscle (36 and 31%) and liver (43 and 25%). AOPP was also decreased by both doses in the liver (39 and 45%). Chronic administration of the highest dose, 25.8 mg OEP/kg, was able to reduce mRNA expression of PGC-1α in soleus muscle (25%). No effect was found in other analyses such as spontaneous physical activity, body weight, food and water intake, hepatic toxicity, cardiac oxidative stress and mitochondrial DNA amount. CONCLUSION: Maximum and not recommended doses of OEP ingested acutely presented stimulating effect on the ability to exercise. However, its daily consumption for 4 weeks showed antioxidant effects in soleus muscle and liver which may have decreased the PGC-1α mRNA expression on soleus muscle and contributed to the impaired performance in the exercise tolerance test.

Renal Effects and Underlying Molecular Mechanisms of Long-Term Salt Content Diets in Spontaneously Hypertensive Rats.

Several evidences have shown that salt excess is an important determinant of cardiovascular and renal derangement in hypertension. The present study aimed to investigate the renal effects of chronic high or low salt intake in the context of hypertension and to elucidate the molecular mechanisms underlying such effects. To this end, newly weaned male SHR were fed with diets only differing in NaCl content: normal salt (NS: 0.3%), low salt (LS: 0.03%), and high salt diet (HS: 3%) until 7 months of age. Analysis of renal function, morphology, and evaluation of the expression of the main molecular components involved in the renal handling of albumin, including podocyte slit-diaphragm proteins and proximal tubule endocytic receptors were performed. The relationship between diets and the balance of the renal angiotensin-converting enzyme (ACE) and ACE2 enzymes was also examined. HS produced glomerular hypertrophy and decreased ACE2 and nephrin expressions, loss of morphological integrity of the podocyte processes, and increased proteinuria, characterized by loss of albumin and high molecular weight proteins. Conversely, severe hypertension was attenuated and renal dysfunction was prevented by LS since proteinuria was much lower than in the NS SHRs. This was associated with a decrease in kidney ACE/ACE2 protein and activity ratio and increased cubilin renal expression. Taken together, these results suggest that LS attenuates hypertension progression in SHRs and preserves renal function. The mechanisms partially explaining these findings include modulation of the intrarenal ACE/ACE2 balance and the increased cubilin expression. Importantly, HS worsens hypertensive kidney injury and decreases the expression nephrin, a key component of the slit diaphragm.

SERCA-2a is involved in the right ventricular function following myocardial infarction in rats.

AIMS: Right ventricular (RV) function is considered an independent predictor of mortality and development of heart failure (HF) in patients with left ventricle dysfunction following myocardial infarction (MI). The functional and molecular mechanisms that may explain the RV dysfunction are still poorly understood. Our study was conducted to investigate RV contractility and the myocardium protein involved in the calcium handling following MI in rats. MAIN METHODS: MI was surgically induced in male Wistar rats to create transmural infarctions involving 40-60% of the left ventricle surface. Infarcted rats were divided into two groups: those that presented classical signs of congestive heart failure (HF group) and those that did not (INF group), and compared to control animals (Sham). RV contractility was studied using isometric contraction in isolated strips and isovolumetric pressure in isolated heart. KEY FINDINGS: Inotropic responses in RV strips were preserved in the INF group but were reduced in the HF group (3.75 mM Ca(2+) treatment: Sham = 163 ± 18; INF = 148 ± 19; HF = 68 ± 11 g/g*; *p < 0.05; 5 × 10(-5) M isoproterenol: Sham = 151 ± 15, INF = 134 ± 17, HF = 52 ± 7 g/g*; *p < 0.05). An increase in SERCA-2a protein expression in the RV was observed in the INF group but not in the HF group, which could explain the preserved inotropic response in these animals. SIGNIFICANCE: Increased SERCA-2a protein expression may play a role in the preservation of RV function post-MI. Therefore, therapeutic strategies that attempt to increase SERCA protein expression levels may be useful for the treatment of HF.