Natriuretic Peptides as Biomarkers: Narrative Review and Considerations in Cardiovascular and Respiratory Dysfunctions.

Natriuretic peptides (NPs) encompass a family of structurally related hormone/paracrine factors acting through the natriuretic peptide system regulating cell proliferation, vessel tone, inflammatory processes, neurohumoral pathways, fluids, and electrolyte balance. The three most studied peptides are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-Type natriuretic peptide (CNP). ANP and BNP are the most relevant NPs as biomarkers for the diagnosis and prognosis of heart failure and underlying cardiovascular diseases, such as cardiac valvular dysfunction, hypertension, coronary artery disease, myocardial infarction, persistent arrhythmias, and cardiomyopathies. Cardiac dysfunctions related to cardiomyocytes stretching in the atria and ventricles are primary elicitors of ANP and BNP release, respectively. ANP and BNP would serve as biomarkers for differentiating cardiac versus noncardiac causes of dyspnea and as a tool for measuring the prognosis of patients with heart failure; nevertheless, BNP has been shown with the highest predictive value, particularly related to pulmonary disorders. Plasma BNP has been reported to help differentiate cardiac from pulmonary etiologies of dyspnea in adults and neonates. Studies have shown that COVID-19 infection also increases serum levels of N-terminal pro b-type natriuretic peptide (NT-proBNP) and BNP. This narrative review assesses aspects of ANP and BNP on their physiology, and predictive values as biomarkers. We present an overview of the NPs' synthesis, structure, storage, and release, as well as receptors and physiological roles. Following, considerations focus on ANP versus BNP, comparing their relevance in settings and diseases associated with respiratory dysfunctions. Finally, we compiled data from guidelines for using BNP as a biomarker in dyspneic patients with cardiac dysfunction, including its considerations in COVID-19.

Striae distensae as a diagnostic indicator for eating disorder pathologies.

OBJECTIVE: This manuscript provides a review of the relationship between patients with an underlying eating disorder (ED) and the presence of striae distensae (SD). Researchers and clinicians have recognized many different skin manifestations associated with EDs. According to the Diagnostic and Statistical Manual of Mental Disorders, EDs include, but are not limited to, anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). The presence of specific skin findings often helps clinicians conclude whether or not a patient may have an underlying ED and require further evaluation. One skin finding associated with an ED with little current literature focus is SD. SD arises from a combination of hormonal imbalances and stretching of the dermis, triggering a local inflammatory response. The presence of SD leaves patients with diminished quality of life. There is no single guideline treatment for SD; however, topical and/or light and laser therapies can be utilized. METHOD: Using online medical literature databases and the PRISMA guidelines, 11 out of 574 articles met the acceptable criteria to be analyzed, emphasizing the lack of current literature on this subject. RESULTS: Anxiety and depression were comorbidities demonstrated to be strongly related to AN and obesity, secondary to BED, in patients who developed SD. Higher degrees of suicidal ideation and insomnia, along with lower self-esteem levels, were more likely to be present in these patients. CONCLUSION: Altogether, this review highlights the importance of continued evaluation of SD and its overall impact on patient's mental health, emphasizing an underlying ED.

Resveratrol Supplants Captopril's Protective Effect on Cardiac Remodeling in a Hypertension Model Elicited by Renal Artery Stenosis.

Background: Renovascular hypertension elicits cardiac damage and remodeling. Two-kidney, one-clip (2K1C) is an experimental model used to study hypertension pathophysiology. In this model, the renin-angiotensin-system (RAS) is overactive due to renal artery stenosis, leading to cardiac remodeling. Redox mechanisms underlying RAS activation mediate hypertension-induced cardiovascular damage. Preclinical studies and clinical trials demonstrated resveratrol's protective effects in cardiovascular diseases, mainly attributed to its antioxidant properties. We hypothesized resveratrol alone or in combination with an angiotensin-converting enzyme (ACE) inhibitor would be beneficial against cardiac damage caused by renovascular hypertension. Objective: We investigated the benefits of resveratrol against cardiac remodeling in 2K1C rats compared with captopril. Methods: Male Wistar rats underwent unilateral renal stenosis - 2K1C Goldblatt model of hypertension. Systolic Blood Pressure (SBP) was measured before and 6 weeks after surgery. Hypertensive 2K1C rats presented SBP≥160 mmHg. From the 6th week after the surgery, the animals received oral resveratrol (20 mg/kg), captopril (12 mg/kg), or their combination for 3 times per week for 3 weeks. Whole heart hypertrophy was evaluated. Histological assays assessed left ventricle hypertrophy and fibrosis. Results: Renovascular hypertension caused cardiac hypertrophy, accompanied by increased myocyte diameter and collagen deposition. Resveratrol reduced 2K1C rats' SBP and whole heart hypertrophy, independently of captopril. Resveratrol caused a higher reduction in ventricular hypertrophy than captopril. Collagen deposition was greater reduced by 2K1C treated only with resveratrol than with captopril alone or combined with resveratrol. Conclusion: Independent of captopril, resveratrol prompts cardioprotective effects on cardiomyocyte remodeling and fibrosis resulting from renovascular hypertension in 2K1C rats.

Formative assessment scores in tutorial sessions correlates with OSCE and progress testing scores in a PBL medical curriculum.

BACKGROUND: Effective assessments programs are a challenge in problem-based learning (PBL). One of the main principles of this educational setting is the Formative Assessment (FA). We hypothesized that students' performance assessed by FA in tutorial sessions in a PBL curriculum is related to other summative assessments. OBJECTIVE: To investigate the correlation among FA in tutorial sessions with grades obtained in Objective Structured Clinical Evaluation (OSCE) and Progress Testing (PT) to better understand the assessment process in PBL medical teaching approach and to predict student's future performance. DESIGN: An observational cross-sectional study was conducted comparing FA, OSCE and PT scores from 4th to 8th semester medical students. Correlation analyses were performed using pooled and separate data from the 4th and 8th semesters. RESULTS: From the 5th to 8th semester, OSCE scores were smaller compared to the FA, while PT scores were lower in all stages. In the pooled data, the correlation analysis showed a significant positive relationship between grades on FA and OSCE, FA and PT and OSCE and PT. A significant correlation among the three assessments strategies was also detected in the 8th semester, but not in the 4th semester. CONCLUSIONS: Assessment strategies in PBL approach, including FA, OSCE and PT, have positive correlations, which increases as the medical course becomes more complex.

Could Carlos Chagas' assumption on the relationship between goiter and chronic Chagas heart disease be correct? A historical reappraisal.

In 1910, Chagas divided the clinical manifestations of the chronic form of Chagas disease according to heart, Central Nervous System, and thyroid involvement, particularly the presence of goiter. Chagas emphasized the association of goiter with poor houses infested with kissing bugs, the similarity of the clinical picture with that of patients underwent partial thyroidectomy, and with the presence of thyroid sclerosis (inflammation) on histological examination. In addition, Chagas observed that all people living in poor houses infested by sucking bugs had goiter, contrasting with persons who lived in the same region, drinking the same water, but living in good houses, which did not have goiter. Furthermore, Chagas stressed the fact that people without any evidence of thyroid disease that migrated to live in poor houses in areas infested by sucking bugs developed thyroid disease some time later. Finally, and more importantly, Chagas emphasized the association of goiter with cardiac abnormalities in 80% of patients with chronic Chagas heart disease. Despite this, other authors working in different regions did not confirm such an association. A reappraisal of data from a work published in 1949 clearly shows that the presence of goiter was statistically associated with chronic Chagas heart disease and with chronic Chagas disease. Our paper highlights once more the grandiosity of Chagas' work, which has been proved to be correct even in the history of goiter, and justifies our claim for a posthumous Nobel Prize inasmuch as his work was not perceived by the Karolinska Institute.

Brazilian medical students' perceptions of expert versus non-expert facilitators in a (non) problem-based learning environment.

BACKGROUND: In problem-based learning (PBL), the facilitator plays an important role in guiding the student learning process. However, although content expertise is generally regarded as a useful but non-essential prerequisite for effective PBL facilitation, the perceived importance of content knowledge may be subject to cultural, contextual, and/or experiential influences. AIM: We sought to examine medical students' perceptions of subject-matter expertise among PBL facilitators in a region of the world (Brazil) where such active learning pedagogies are not widely used in university or pre-university settings. RESULTS: Of the 252 Brazilian medical students surveyed, significantly (p≤0.001) greater proportions viewed content expert facilitators to be more effective than their non-expert counterparts at building knowledge (95% vs. 6%), guiding the learning process (93% vs. 7%), achieving cognitive learning (92% vs. 18%), generating learning goals (87% vs. 15%), and motivating self-study (80% vs. 15%). DISCUSSION/CONCLUSION: According to Brazilian medical students, subject-matter expertise among PBL facilitators is essential to the learning process. We believe this widespread perception is due, in large part, to the relative lack of prior educational exposure to such pedagogies.

Vascular relaxation induced by C-type natriuretic peptide involves the ca2+/NO-synthase/NO pathway.

AIMS: C-type natriuretic peptide (CNP) and nitric oxide (NO) are endothelium-derived factors that play important roles in the regulation of vascular tone and arterial blood pressure. We hypothesized that NO produced by the endothelial NO-synthase (NOS-3) contributes to the relaxation induced by CNP in isolated rat aorta via activation of endothelial NPR-C receptor. Therefore, the aim of this study was to investigate the putative contribution of NO through NPR-C activation in the CNP induced relaxation in isolated conductance artery. MAIN METHODS: Concentration-effect curves for CNP were constructed in aortic rings isolated from rats. Confocal microscopy was used to analyze the cytosolic calcium mobilization induced by CNP. The phosphorylation of the residue Ser1177 of NOS was analyzed by Western blot and the expression and localization of NPR-C receptors was analyzed by immunohistochemistry. KEY FINDINGS: CNP was less potent in inducing relaxation in denuded endothelium aortic rings than in intact ones. L-NAME attenuated the potency of CNP and similar results were obtained in the presence of hydroxocobalamin, an intracellular NO0 scavenger. CNP did not change the phosphorylation of Ser1177, the activation site of NOS-3, when compared with control. The addition of CNP produced an increase in [Ca2+]c in endothelial cells and a decrease in [Ca2+]c in vascular smooth muscle cells. The NPR-C-receptors are expressed in endothelial and adventitial rat aortas. SIGNIFICANCE: These results suggest that CNP-induced relaxation in intact aorta isolated from rats involves NO production due to [Ca2+]c increase in endothelial cells possibly through NPR-C activation expressed in these cells. The present study provides a breakthrough in the understanding of the close relationship between the vascular actions of nitric oxide and CNP.

The effect of extracellular pH changes on intracellular pH and nitric oxide concentration in endothelial and smooth muscle cells from rat aorta.

AIMS: It has been known for more than a century that pH changes can alter vascular tone. However, there is no consensus about the effects of pH changes on vascular response. In this study, we investigated the effects of extracellular pH (pHo) changes on intracellular pH (pHi) and intracellular nitric oxide concentration ([NO]i) in freshly isolated endothelial cells and cross sections from rat aorta. MAIN METHODS: The HCl was used to reduce the pHo from 7.4 to 7.0 and from 7.4 to 6.5; the NaOH was used to increase the pHo from 7.4 to 8.0 and from 7.4 to 8.5. The fluorescent dyes 5-(and-6)-carboxy SNARF-1, acetoxymethyl ester, acetate (SNARF-1) and diaminofluorescein-FM diacetate (DAF-FM DA) were employed to measure the pHi and [NO]i, respectively. The fluorescence intensity was measured in freshly isolated endothelial cells by flow cytometry and in freshly obtained aorta cross sections by confocal microscopy. KEY FINDINGS: The endothelial and vascular smooth muscle pHi was increased at pHo 8.5. The extracellular acidification did not change the endothelial pHi, but the smooth muscle pHi was reduced at pHo 7.0. At pHo 8.5 and pHo 6.5, the endothelial [NO]i was increased. Both extracellular alkalinization and acidification increased the vascular smooth muscle [NO]i. SIGNIFICANCE: Not all changes in pHo did result in pHi changes, but disruption of acid-base balance in both directions induced NO synthesis in the endothelium and/or vascular smooth muscle.

Diabetes confers a vasoprotective role to the neurocompensatory response elicited by carotid balloon injury: consequences on contralateral carotid tone and blood flow.

The purpose from this study was to investigate the consequences of sensory neurocompensation to carotid balloon injury in diabetic rats on angiotensin II-induced contraction and basal blood flow in contralateral carotid. Concentration-response curves for angiotensin II and blood flow were obtained in contralateral carotid from non-treated or capsaicin-treated streptozotocin-induced diabetic rats that underwent carotid balloon injury. Diabetes increased angiotensin II-induced contraction and impaired the blood flow in non-operated rat carotid. In diabetic rats, balloon injury led to neointima formation, which reduced the blood flow in ipsilateral carotid. Carotid balloon injury in diabetic rats reduced angiotensin II-induced contraction and restored the blood flow in contralateral carotid when compared to diabetic non-operated rat carotid. Capsaicin inhibited the effects evoked by carotid balloon injury on diabetic rat contralateral carotid. Endothelium removal, PEG-catalase (hydrogen peroxide scavenger) or l-NPA (neuronal nitric oxide synthase, nNOS, inhibitor) increased angiotensin II-induced contraction in contralateral carotid from diabetic operated rats to the levels observed in diabetic non-operated rat carotid. Our findings suggest that carotid balloon injury in diabetic rats elicits a neurocompensation that attenuates the diabetic hyperreactivity to angiotensin II in contralateral carotid by a sensory nerves-dependent mechanism mediated by hydrogen peroxide derived from endothelial nNOS. This sensory mechanism also restored the blood flow in this vessel, compensating the impaired blood flow in diabetic rat ipsilateral carotid. Thus, our major conclusions are that Diabetes confers a vasoprotective significance to the neurocompensation to carotid balloon injury in preventing further damage at carotid cerebral irrigation after angioplasty in diabetic subjects.

Automedicação em acadêmicos do curso de medicina / Self-medication in academics from medical school

Objetivo: Avaliar a automedicação em estudantes do curso de Medicina da Universidade de RibeirãoPreto (UNAERP) no ano de 2008. Métodos: Estudo transversal quantitativo, realizado no ano de 2008, no qual 200 alunos do curso de Medicina da UNAERP responderam a um questionário autoaplicado, contendo questões de múltipla escolha sobre a prática da automedicação, no intuito de conhecer aspectos do consumo de medicamentos. Para análise estatística foi empregado o teste de correlação de Pearson. Considerou-se como base o intervalo de confiança de 95%. O estudo foi aprovado pelo Comitê de Ética da UNAERP. Resultados: Observaram-se 58,5% de participantes do sexo feminino. A média de idade foi de 21,5 anos. A prevalência da automedicação foi de 92,0%. As prevalências entre os alunos das diferentes etapas do curso não foram significativamente diferentes: 86,6%, 90,0%, 93,3%,94,4% e 97,1%, respectivamente, entre os alunos do 1º ao 4º ano e internato. A aquisição de medicamentos controlados, sem apresentação da prescrição, ocorreu entre 6,5% dos alunos e 69,5% responderam já terem indicado medicamentos para outras pessoas...

Objective: Evaluate the self-medication by students of University of Medicine of Ribeirão Preto (UNAERP) in 2008. Methods: A quantitative cross-sectional study conducted throughout 2008 in with 200 medicine students, who answered a self-administered questionnaire containing multiple choice questions regarding self-medication and consumption of medicines. Statistical analysis was employed to test Pearson correlation. The confidence interval considered was of 95%. The study was approved by UNAERP Ethics Committee. Results: There were 58.5% of female participants. The age average was 21.5 years old. The prevalence of self-medication was 92.0%. The prevalence among students from different stages of the course was not significantly different: 86.6%, 90.0%, 93.3%, 94.4% and 97.1%, among the students from, respectively, the 1st to 4th year and from the internship...

Acidosis induces relaxation mediated by nitric oxide and potassium channels in rat thoracic aorta.

We investigated the mechanism by which extracellular acidification promotes relaxation in rat thoracic aorta. The relaxation response to HCl-induced extracellular acidification (7.4 to 6.5) was measured in aortic rings pre-contracted with phenylephrine (Phe, 10(-6) M) or KCl (45mM). The vascular reactivity experiments were performed in endothelium-intact and denuded rings, in the presence or absence of indomethacin (10(-5) M), L-NAME (10(-4) M), apamin (10(-6) M), and glibenclamide (10(-5) M). The effect of extracellular acidosis (pH 7.0 and 6.5) on nitric oxide (NO) production was evaluated in isolated endothelial cells loaded with diaminofluorescein-FM diacetate (DAF-FM DA, 5µM). The extracellular acidosis failed to induce any changes in the vascular tone of aortic rings pre-contracted with KCl, however, it caused endothelium-dependent and independent relaxation in rings pre-contracted with Phe. This acidosis induced-relaxation was inhibited by L-NAME, apamin, and glibenclamide, but not by indomethacin. The acidosis (pH 7.0 and 6.5) also promoted a time-dependent increase in the NO production by the isolated endothelial cells. These results suggest that extracellular acidosis promotes vasodilation mediated by NO, K(ATP) and SK(Ca), and maybe other K(+) channels in isolated rat thoracic aorta.

Decreased number of caveolae in endothelial cells impairs the relaxation induced by acetylcholine in hypertensive rat aortas.

The present study was designed to investigate the contribution of endothelial cell caveolae to vascular relaxation in aortas from a normotensive (2K) and renal hypertensive (2K-1C) rat. For that purpose, concentration-effect curves to acetylcholine were constructed in 2K and 2K-1C intact endothelium aortic rings, in the absence or in the presence of the caveolae disassembler methyl-beta-ciclodextrin. The potency (pD(2)) and the maximum relaxant effect to acetylcholine were greater in 2K than in 2K-1C aortas. Methyl-beta-ciclodextrin reduced the pD(2) in 2K and the maximum relaxant effect in both 2K and 2K-1C. The quantification of the caveolae number by electronic microscopy has shown a larger number of caveolae in 2K than in 2K-1C endothelial cells, which was reduced by methyl-beta-ciclodextrin in both 2K and 2K-1C. The production of NO stimulated with acetylcholine was greater in 2K than in 2K-1C endothelial cells, and this effect was impaired by methyl-beta-ciclodextrin in both 2K and 2K-1C. The cytosolic Ca(2+) concentration ([Ca(2+)]c) was simultaneously measured in endothelial and smooth muscle cells stimulated with acetylcholine by confocal image of aortic slices. Acetylcholine produced a greater [Ca(2+)]c increase in 2K than in 2K-1C endothelial cells, which response was inhibited by methyl-beta-ciclodextrin only in 2K cells. In smooth muscle cells the reduction of [Ca(2+)]c was higher in 2K than in 2K-1C. This effect was inhibited by methyl-beta-ciclodextrin only in 2K cells. Taken together, our results suggest that the decreased number of caveolae in the endothelial cells from 2K-1C rat aortas is involved in the impaired effect of acetylcholine on [Ca(2+)]c and NO.