Urinary N-terminal pro-B-type natriuretic peptide as a biomarker for cardiovascular events in a general Japanese population: the Hisayama Study

BACKGROUND@#Epidemiological evidence has shown that serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, a diagnostic biomarker for heart failure, are positively associated with cardiovascular risk. Since NT-proBNP in serum is excreted in urine, it is hypothesized that urinary NT-proBNP concentrations are correlated with serum concentrations and linked with cardiovascular risk in the general population.@*METHODS@#A total of 3060 community-dwelling residents aged ≥ 40 years without history of cardiovascular disease (CVD) were followed up for a median of 8.3 years (2007-2015). Serum and urinary concentrations of NT-proBNP at baseline were compared. The hazard ratios (HRs) and their 95% confidence intervals (CIs) for the association between NT-proBNP concentrations and the risk of developing CVD were computed using the Cox proportional hazards model.@*RESULTS@#The median values (interquartile ranges) of serum and urinary NT-proBNP concentrations at baseline were 56 (32-104) pg/mL and 20 (18-25) pg/mL, respectively. There was a strong quadratic correlation between the serum and urinary concentrations of NT-proBNP (coefficient of determination [R@*CONCLUSIONS@#The present study demonstrated that urinary NT-proBNP concentrations were well-correlated with serum concentrations and were positively associated with cardiovascular risk. Given that urine sampling is noninvasive and does not require specially trained personnel, urinary NT-proBNP concentrations have the potential to be an easy and useful biomarker for detecting people at higher cardiovascular risk.

The protective arm of the renin -angiotensin system may counteract the intense inflammatory process in fetuses with posterior urethral valves / O braço protetor do sistema renina-angiotensina pode contrapor-se ao intenso processo inflamatório em fetos com válvula de uretra posterior

Abstract Objective: Posterior urethral valve is the most common lower urinary tract obstruction in male children. A high percentage of patients with posterior urethral valve evolve to end‐stage renal disease. Previous studies showed that cytokines, chemokines, and components of the renin-angiotensin system contribute to the renal damage in obstructive uropathies. The authors recently found that urine samples from fetuses with posterior urethral valve have increased levels of inflammatory molecules. The aim of this study was to measure renin-angiotensin system molecules and to investigate their correlation with previously detected inflammatory markers in the same urine samples of fetuses with posterior urethral valve. Methods: Urine samples from 24 fetuses with posterior urethral valve were collected and compared to those from 22 healthy male newborns at the same gestational age (controls). Renin-angiotensin system components levels were measured by enzyme‐linked immunosorbent assay. Results: Fetuses with posterior urethral valve presented increased urinary levels of angiotensin (Ang) I, Ang‐(1‐7) and angiotensin‐converting enzyme 2 in comparison with controls. ACE levels were significantly reduced and Ang II levels were similar in fetuses with posterior urethral valve in comparison with controls. Conclusions: Increased urinary levels of angiotensin‐converting enzyme 2 and of Ang‐(1‐7) in fetuses with posterior urethral valve could represent a regulatory response to the intense inflammatory process triggered by posterior urethral valve.

Resumo Objetivo: A válvula de uretra posterior é a obstrução do trato urinário inferior mais comum em crianças do sexo masculino. Uma alta porcentagem de pacientes com válvula de uretra posterior evolui para doença renal em estágio final. Estudos anteriores mostraram que citocinas, quimiocinas e componentes do sistema renina-angiotensina contribuem para o dano renal em uropatias obstrutivas. Recentemente, descobrimos que amostras de urina de fetos com válvula de uretra posterior tinham níveis aumentados de moléculas inflamatórias. O objetivo deste estudo foi medir as moléculas de renina-angiotensina e investigar sua correlação com marcadores inflamatórios previamente detectados nas mesmas amostras de urina de fetos com válvula de uretra posterior. Métodos: Amostras de urina de 24 fetos com válvula de uretra posterior foram coletadas e comparadas com amostras de urina de 22 recém-nascidos saudáveis de mesma idade gestacional (controles). Os níveis dos componentes de SRA foram medidos por ensaio de imunoabsorção enzimática. Resultados: Os fetos com válvula de uretra posterior apresentaram níveis urinários aumentados de angiotensina (Ang) I, Ang-(1-7) e enzima conversora de angiotensina 2 em comparação com os controles. Os níveis de enzima conversora de angiotensina eram significativamente menores e os níveis de Ang II eram semelhantes nos fetos com válvula de uretra posterior em comparação com os controles. Conclusões: O aumento dos níveis urinários de enzima conversora de angiotensina 2 e de Ang-(1-7) em fetos com válvula de uretra posterior poderia representar uma resposta regulatória ao intenso processo inflamatório desencadeado pela válvula de uretra posterior.

Combination therapy of curcumin and alendronate modulates bone turnover markers and enhances bone mineral density in postmenopausal women with osteoporosis

ABSTRACT Objective: This study evaluated the effects of combination therapy of curcumin and alendronate on BMD and bone turnover markers in postmenopausal women with osteoporosis. Subjects and methods: In a randomized, double-blind trial study, 60 postmenopausal women were divided into three groups: control, alendronate, and alendronate + curcumin. Each group included 20 patients. Total body, total hip, lumbar spine and femoral neck BMDs were measured by dual-energy X-ray absorptiometry (DXA) at baseline and after 12 months of therapy. Bone turnover markers such as bone-specific alkaline phosphatase (BALP), osteocalcin and C-terminal cross-linking telopeptide of type I collagen (CTx) were measured at the outset and 6 months later. Results: Patients in the control group suffered a significant decrease in BMD and increased bone turnover markers at the end of study. The group treated with only alendronate showed significantly decreased levels of BALP and CTx and increased levels of osteocalcin compared to the control group. The alendronate group also showed significant increases in the total body, total hip, lumbar spine and femoral neck BMDs at the end of study compared to the control group. In the curcumin + alendronate group, BALP and CTx levels decreased and osteocalcin levels increased significantly at the end of study compared to the control and alendronate groups. BMD indexes also increased in four areas significantly at the end of study compared to the control and alendronate groups. Conclusion: The combination of curcumin and alendronate has beneficial effects on BMD and bone turnover markers among postmenopausal women with osteoporosis. Arch Endocrinol Metab. 2018;62(4):438-45

Inhalation Therapy of Calcitonin Relieves Osteoarthritis of the Knee

This study was conducted to determine if nasal salmon calcitonin has additional beneficial effects on clinical symptoms, serum NO, IL-1beta, matrix metalloproteinase 3, urinary C-terminal telopeptide type II collagen (CTX-II) levels and MRI findings in knee osteoarthritis (OA) when used concomitantly with exercise therapy. Fifty female patients with knee OA were randomized into two groups. The first group (n = 30) received 200 IU/day nasal salmon calcitonin and a home exercise program; the second group (n = 20) received a home exercise program for 6 months. Compared with baseline,while significant improvements were observed in visual analogue scale (VAS), WOMAC pain, physical function scores, 20-m walking time (P < 0.001) and WOMAC stiffness score (P = 0.041) in the first group, walking and resting VAS, and WOMAC physical function scores were improved (P = 0.029) in the second group after treatment. Significantly increased levels of serum NO and urinary CTX-II (P < 0.001) and significant improvements in the area of medial femoral condyle (P < 0.05) were noted only in the first group. There were significant differences in VAS activation values (P = 0.032) and NO levels (P < 0.001) in the favor of the first group. In conclusion, nasal salmon calcitonin may have possible chondroprotective effects besides its known effects on symptoms in patients with knee OA.

Inhalation Therapy of Calcitonin Relieves Osteoarthritis of the Knee

This study was conducted to determine if nasal salmon calcitonin has additional beneficial effects on clinical symptoms, serum NO, IL-1beta, matrix metalloproteinase 3, urinary C-terminal telopeptide type II collagen (CTX-II) levels and MRI findings in knee osteoarthritis (OA) when used concomitantly with exercise therapy. Fifty female patients with knee OA were randomized into two groups. The first group (n = 30) received 200 IU/day nasal salmon calcitonin and a home exercise program; the second group (n = 20) received a home exercise program for 6 months. Compared with baseline,while significant improvements were observed in visual analogue scale (VAS), WOMAC pain, physical function scores, 20-m walking time (P < 0.001) and WOMAC stiffness score (P = 0.041) in the first group, walking and resting VAS, and WOMAC physical function scores were improved (P = 0.029) in the second group after treatment. Significantly increased levels of serum NO and urinary CTX-II (P < 0.001) and significant improvements in the area of medial femoral condyle (P < 0.05) were noted only in the first group. There were significant differences in VAS activation values (P = 0.032) and NO levels (P < 0.001) in the favor of the first group. In conclusion, nasal salmon calcitonin may have possible chondroprotective effects besides its known effects on symptoms in patients with knee OA.

Niveles urinarios de angiotensina-(1-7) y angiotensina II en pacientes con estenosis aórtica de importante repercusión hemodinámica / Urinary levels of angiotensin-(1-7) and angiotensin II in patients with severe aortic stenosis

Objetivo:Reforzar el conocimiento sobre la fisiopatología de la estenosis aórtica. Métodos: Se compararon los niveles urinarios de angiotensina II y angiotensina-(1-7) entre dos muestras: a) 45 pacientes con estenosis aórtica de importante repercusión hemodinámica, sin hipertensión arterial sistémica y con funciones renal y sistólica ventricular izquierda normales; b) grupo de control con 21 voluntarios sin patología cardiovascular. Hipótesis nula: no habría diferencia entre los niveles urinarios. Resultados:El promedio de la concentración urinaria de angiotensina-(1-7) en pacientes con estenosis aórtica fue 2.102 pmoles/mL y de 5.591 pmoles/mL para el grupo control. La media obtenida en concentración urinaria de angiotensina II fue de 0.704 pmoles/mL en los pacientes con estenosis aórtica y 0.185 pmoles/mL en el grupo control. Utilizando la prueba t de Student determinamos que la diferencia en la concentración urinaria de angiotensina-(1-7) (p = 0.633) y la diferencia en la concentración urinaria de angiotensina II (p = 0.631), fueron estadísticamente significativas. Conclusión:Se documentó una diferencia estadísticamente significativa en los niveles urinarios de angiotensina II y angiotensina-(1-7) dentro del grupo de pacientes con estenosis aórtica de importante repercusión hemodinámica.

Objective:Strengthen knowledge about the pathophysiology of aortic stenosis. Methods: Urinary levels of angiotensin-(1-7) and angiotensin II were compared between two samples: A) forty five patients with severe aortic stenosis, without systemic arterial hypertension and with normal kidney and normal left ventricular systolic function; B) control group: twenty one persons without cardiovascular disease. Null hypothesis: there would be no difference between urinary levels. Results: The average of angiotensin-(1-7) urinary concentration in severe aortic stenosis patients was 2.102 pmol/mL and 5.591 pmol/mL for the control group. The average of Ang II was 0.704 pmol/mL and 0.185 pmol/mL respectively. Using t-Student test, we determine that the difference in urinary concentration of angiotensin-(1-7) [p = 0.633] and the difference of angiotensin II (p = 0.631), were statistically significant. Conclusion:documented a statistically significant difference in urinary levels angiotensin II and angiotensin-(1-7) within the group of patients with severe aortic stenosis.

O papel dos marcadores bioquímicos do metabolismo ósseo no diagnóstico e seguimento laboratorial das doenças ósteo-metabólicas / The role of bone biochemical markers in the diagnosis and follow-up bone metabolic diseases

Os novos marcadores bioquímicos do metabolismo ósseo säo um novo recurso laboratorial com aplicaçöes cada vez mais amplas. Podem ser divididos em dois grupos principais: os de formaçäo óssea, representados principalmente pela fosfatase alcalina óssea e pela osteocalcina, e os de reabsorçäo óssea, representados basicamente pelos métodos que avaliam a excreçäo de fragmentos específicos produzidos pela hidrólise do colágeno tipo 1 (piridinolina, deoxipiridinolina, NTX, CTX). Suas aplicaçöes práticas se estendem desde a avaliaçäo da resposta terapêutica obtida pela introduçäo de terapêutica específica.