MicroARN circulantes y su potencialidad como futuros biomarcadores óseos / Circulating microRNAs and their potential use as future bone biomarkers / MicroRNAs circulantes e a sua potencialidade como futuros biomarcadores ósseos

Resumen El remodelamiento óseo es ejercido por la actividad de osteoblastos y osteoclastos y puede evaluarse por marcadores bioquímicos de formación y resorción ósea. Sin embargo, el nivel de los marcadores óseos está sometido a una enorme cantidad de variables y, además, carece o presenta escaso valor pronóstico. Los microARN (miARN) fueron recientemente estudiados como una alternativa potencial para ser utilizados como nuevos marcadores óseos. Los miARN son pequeñas moléculas de ARN no codificantes (15-25 nucleótidos) que, a través de la inhibición o degradación de ARN mensajeros, modifican una serie de funciones biológicas. Los miARN específicos de hueso ejercen funciones reguladoras sobre factores transcripcionales involucrados en la osteoblastogénesis y osteoclastogénesis, modificando el remodelamiento óseo. La mayoría de los miARN permanecen dentro de la célula, pero algunos son liberados a la circulación donde pueden ser dosados. Los miARN circulantes presentan gran estabilidad en fluidos biológicos, lo que los hace potenciales candidatos a ser utilizados como nuevos biomarcadores óseos. Cambios en el patrón normal de miARN circulantes específicos de hueso reflejarán modificaciones en el metabolismo óseo y señalan el posible inicio o progresión de enfermedades óseas, como la osteoporosis. Si bien es promisorio, el uso en la práctica clínica de los miARN específicos circulantes como nuevos biomarcadores óseos, ello implica primeramente cumplir con una serie de requisitos que permitan estandarizar las condiciones preanalíticas, analíticas y posanalíticas de estas moléculas. La presente revisión brinda información reciente sobre los estudios clínicos tendientes a determinar el posible uso de los miARN circulantes como nuevos biomarcadores óseos, ya que cuentan con elevada sensibilidad y especificidad diagnósticas, valor predictivo positivo y valor predictivo negativo.

Abstract Osteoblasts and osteoclasts activity determines the level of the bone remodelling process which can be assessed by biochemical markers of bone formation and resorption. However, bone marker levels are subject to a series of variables resand, furthermore, they lack or have little prognostic values. MicroRNAs (miRNAs) were recently studied as a potential alternative to be used as new bone biomarkers. The miRNAs are endogenous small noncoding RNA molecules (15-25 nucleotides) that regulate many biological functions by inhibiting or degrading specific messenger RNAs. Bone-specific miRNAs exert regulatory functions on key transcriptional factors involved in osteoblastogenesis and osteoclastogenesis, modifying the bone remodelling process. Most miRNAs remain within the cell, but some of them are released into circulation. Circulating miRNAs show great stability in biological fluids, which makes them excellent candidates to be used as new bone biomarkers. Modifications in the normal pattern of bone-specific circulating miRNA might reflect changes in bone metabolism, signalling the possible onset or progression of bone diseases, such as osteoporosis. Although promising, the use of specific circulating miRNAs as new bone biomarkers in clinical practice implies fulfilling a series of requirements that lead to standardising the pre-analytical, analytical and post-analytical conditions of these molecules. The present review gives an overview on the clinical studies related to the possible use of specific circulating miRNAs as new bone biomarkers.

Resumo A remodelação óssea é exercida pela atividade dos osteoblastos e osteoclastos e pode ser avaliada para a medição dos marcadores bioquímicos de formação e reabsorção óssea. No entanto, o nível dos marcadores ósseos está sujeito a grande quantidade de variáveis e, além disso, carece ou tem pouco valor prognóstico. Os microARN (miARN) foram estudados recentemente como uma alternativa potencial para serem utilizados como novos marcadores ósseos. Os MicroRNAs (miRNAs) são pequenas moléculas de RNA não codificantes (15-25 nucleotídeos) que, através da inibição ou degradação de RNA mensageiros modificam uma série de funções biológicas. Os miRNAs específicos de osso exercem funções reguladoras sobre fatores transcricionais envolvidos na osteoblastogênese e na osteoclastogênese, modificando o processo de remodelação óssea. A maioria dos miRNAs permanece dentro da célula, mas de RNA mensageiros alguns são liberados na circulação, onde podem ser determinados bioquimicamente. Os miRNAs circulantes apresentam grande estabilidade em fluidos biológicos, o que os torna excelentes candidatos para serem usados como novos biomarcadores ósseos. Mudanças no padrão normal de miRNA circulantes específicos do osso mostrarão mudanças no metabolismo ósseo, sinalizando o possível início ou progressão de doenças ósseas, como osteoporose. Embora promissor, o uso de miRNAs específicas circulantes na prática clínica como novos biomarcadores ósseos, implica primeiramente, atender uma série de requisitos que permitem padronizar as condições pré-analíticas, analíticas e pós-analíticas dessas moléculas. A presente revisão fornece informações recentes sobre estudos clínicos destinados a determinar o possível uso dos miRNAs circulantes como novos biomarcadores ósseos, visto que contam com elevada sensibilidade e especificidade diagnósticas, valor preditivo positivo e valor preditivo negativo.

THE THREE KEY PLAYERS IN OSTEOIMMUNOLOGY: RANK, RANKL AND OSTEOPROTEGERIN.

The RANK, RANKL and OPG interaction plays a major role in bone resorption and remodelling. The history dates back to mid 1990s when the RANK/ RANKL interaction was found to mediate osteoblastic stromal cells to stimulate osteoclastic bone resorption. This interaction was found to induce several cytokines including the TNF superfamily, thereby activating the pathways of bone remodelling. The Osteoprotegerin (OPG) prevents the binding of RANKL to RANK, thereby preventing the excessive bone resorption. When there is an imbalance in the levels of RANK/RANKL/OPG, the metabolic activity of the bone cells gets altered and thus there is loss of balance between bone formation and resorption. Thus, studying the inter – relationship between RANK, RANKL and OPG becomes critical for assessing the osteoblastic and osteoclastic activity

Increased angiogenesis parallels cardiac tissue remodelling in experimental acute Trypanosoma cruzi infection

BACKGROUND Angiogenesis has been implicated in tissue injury in several noninfectious diseases, but its role in Chagas disease (CD) physiopathology is unclear. OBJECTIVES The present study aimed to investigate the effect of Trypanosoma cruzi infection on cardiac angiogenesis during the acute phase of experimental CD. METHODS The signalling pathway involved in blood vessel formation and cardiac remodelling was evaluated in Swiss Webster mice infected with the Y strain of T. cruzi. The levels of molecules involved in the regulation of angiogenesis, such as vascular endothelial growth factor-A (VEGF-A), Flk-1, phosphorylated extracellular-signal-regulated protein kinase (pERK), hypoxia-inducible factor-1α (HIF-1α), CD31, α-smooth muscle actin (α-SMA) and also the blood vessel growth were analysed during T. cruzi infection. Hearts were analysed using conventional histopathology, immunohistochemistry and western blotting. FINDINGS In this study, our data demonstrate that T. cruzi acute infection in mice induces exacerbated angiogenesis in the heart and parallels cardiac remodelling. In comparison with noninfected controls, the cardiac tissue of T. cruzi-infected mice presented higher levels of (i) HIF-1α, VEGF-A, Flk-1 and pERK; (ii) angiogenesis; (iii) α-SMA+ cells in the tissue; and (iv) collagen -1 deposition around blood vessels and infiltrating throughout the myocardium. MAIN CONCLUSIONS We observed cardiac angiogenesis during acute experimental T. cruzi infection parallels cardiac inflammation and remodelling.

The protective effect of naringin on cardiac injury in diabetic rats via activating Maxi K / 中国药理学通报

Aim To investigate the protective effect of naringin ( NA) on diabetic cardiomyopathy by activating the large conduction Ca2+ activated K4 channels (Maxi K ).Methods SD rats were fed with high-fat diet combined with intraperitoneal injection of strepto- zotocin (STZ) to establish a diabetic rat model.Then the rats were randomly divided into model group ( DCM) , naringin group ( NA) and naringin + Maxi K-specific inhibitor group ( NA + PAX) , with 8 rats in each group.Hats in treatment group received administration for 12 weeks and blood glucose was monitored regularly during experiments.The changes of cardiac function, morphology and fibrosis were detected after the treatment.The changes of cx and (3 subunits of Maxi K in heart were detected.Results Cardiac ultrasound results showed that NA could partially restore the cardiac function of rats.However, the cardiac protec tive function of NA was significantly reduced in diabetic rats after Maxi K was specifically blocked.Fibrosis analysis showed that the expression of collagen and fi- bronectin in rats could be decreased after NA treatment, which could be partially reversed by PAX.Western blot results showed that the expression of Maxi K a and p-subunit decreased in DCM group, but there was no significant change after NA treatment.Conclusions NA has a cardioprotective effect on diabetic rats by promoting the opening of the Maxi K channel on the membrane surface rather than increasing its expression.

Rapamycin Improves Vascular Remodelling in a Controlled Rat Model of Monocrotaline-Induced Pulmonary Hypertension

ABSTRACT Background: Pulmonary arterial hypertension (PAH) is a serious disease characterized by the progressive elevation of the pulmonary arterial resistance, leading to the right ventricular failure and death. Objective: To evaluate the effect of rapamycin (RAPA), a potent cell-cycle inhibitor, on exercise capacity, right ventricular hypertrophy and pulmonary vascular remodelling on rats. Methods: A total of 39 nine-week-old male Wistar rats (160-240 g) were divided into three groups: the control (n = 10), PAH control (n = 15) and PAH-RAPA (n = 14) groups. On the 1st day, 60 mg/kg monocrotaline was injected intraperitoneally to induce PAH in the PAH control group and PAH-RAPA groups. On the 21st day, 3 mg/kg/day RAPA was started orally, and the animals were followed for 35 days. On the 35th day, the exercise capacity of the rats was analysed through a modified forced swimming test. After measuring their right ventricular systolic pressure using an open-chest method, their hearts and lungs were excised and analysed histopathologically for right ventricular hypertrophy and pulmonary vascular remodelling. Results: Rapamycin treatment provided limited and insignificant improvements in exercise capacity, right ventricular systolic pressure and right ventricular hypertrophy of the rats. However, there was significant recovery in the rats' pulmonary artery muscular layer thickness with the RAPA treatment (p < 0.049). On the 35th day, the mortality rate was 0% in the control group, 53.1% in the PAH control group and 42.9% in the PAH-RAPA group. No statistically significant decrease was observed in their mortality rates with the RAPA treatment (p > 0.16); however, a significant recovery was noted in terms of the rats' median life span (p < 0.006). Conclusion: Pulmonary artificial hypertension is a progressive disease that is not curable with current therapies. Rapamycin may have the potential to reverse vascular remodelling and prolong life expectancy in cases of pulmonary hypertension.

Micro RNAs In Periodontal Disease – A Review

@#microRNAs (miRNAs) constitute a family of small, non-coding RNA molecules that regulate gene expression and protein expression. microRNAs have influence on a broad range of physiologic and pathologic conditions. They are also considered as promising biomarkers especially when they are secreted extracellularly. In the inflammatory pathways, they dysregulate the molecular processes and contribute to the development of chronic inflammatory diseases including periodontitis. In this review, we provide an overview of miRNA characteristics, biogenesis, mechanisms of action and profiling methods. In addition, the role of miRNAs in the pathobiology of periodontitis, especially those pertaining to the cellular and molecular pathways of inflammation has been considered to enhance our understanding of the pathobiology of periodontitis.

Periostin, osteopontin and asthma / 国际儿科学杂志

Both periostin and osteopontin belong to extracellular matrix proteins and have various biological functions.Especially in allergic inflammatory diseases,they were involved in different aspects of the pathogenesis of asthma,such as airway inflammation and airway remodeling.Recent studies have shown that periostin and osteopontin play an important role in the assessment and treatment of asthma as emerging biomarkers.This article will elaborate on the new developments of the relationship between periostin,osteopontin and asthma.

2,4,6,-trihydroxy-3-geranylacetophenone (tHGA) Suppresses Chronic Allergic Airway Inflammation in Ovalbumin-Sensitized Mice via Intraperitoneal Route

@#Introduction: Asthma is a condition characterized by eosinophilic airway inflammation and remodelling that involves several pathological changes, including subepithelial fibrosis, mucus hypersecretion, smooth muscle growth, and vascular changes. The present study aimed to determine the effect of tHGA administered intraperitoneally in a chronic asthma mouse model that closely mimics the human asthma. Methods: Ovalbumin-sensitized and challenged BALB/c mice were i.p. administered with tHGA at different doses (20 and 2 mg/kg). Respiratory function was measured, and brochoalveolar lavage, blood and lung samples were then obtained and analyzed. Results: The airways of OVA-induced mice developed increased pulmonary inflammation with increased levels of cytokines, chemokines, and changes in vascular permeability. Intraperitoneal administration of tHGA in OVA-induced mice significantly and dose-dependently inhibited the airway inflammation, production of immunoglobulin E, Th2-type cytokines and chemokines, and inflammatory mediators. Treatment with tHGA also significantly reduced the airway hyperresposiveness in response to increased methacholine doses. Conclusion: This study demonstrates that the efficacy of tHGA in alleviating chronic asthmatic symptoms in mouse model improved significantly when administered intraperitoneally compared to oral route. Furthermore, this study also supports that tHGA has a therapeutic potential in chronic asthma management by acting as a cysteinyl leukotrienes (CysLT) inhibitor

Expressions of TOLL-like receptor 4 (TLR-4) and matrix metalloproteinase 9 (MMP-9)/Tissue inhibitor of metalloproteinase 1 (TIMP-1) in pulmonary blood vessels with chronic obstructive pulmonary diseases and their relationships with pulmonary vascular remodelling

SUMMARY OBJECTIVE: This study aims at investigating the expressions of TOLL-like receptor 4 (TLR-4) and matrix metalloproteinase 9 (MMP-9)/ tissue inhibitor of metalloproteinase 1 (TIMP-1) in pulmonary blood vessels with chronic obstructive pulmonary disease (COPD) and their relationships with pulmonary vascular remodelling (PVR). METHODS: 60 para-tumour tissues were divided into the COPD group and the control group (n=30); the inflammations, pulmonary artery wall area/total artery area (WA%), and wall thickness/vascular outer diameter (WT%) were compared. The expressions of TLR-4, MMP-9/TIMP-1, and PCNA in pulmonary vascular smooth muscle cells were detected, and their relationships with PVR were then analysed. RESULTS: The inflammations (1.6±0.8), WA% (44.0±6.4), and WT% (27.3±3.3) in the COPD group were higher than in the control group (0.3±0.5, 26.1±2.8, 15.6±1.8), and the expressions of TLR-4 (31.4±147) and MMP-9/TIMP-1 (2.2±2.6) were increased compared to the control group (4.7±4.5, 1.9±12). Correlation analysis: TLR-4 and MMP-9/TIMP-1 were positively correlated with the inflammations (r=0.18, P<0.01), WA% (r=0.68, P<0.01), and WT% (r=0.73, P<0.01), as well as positively correlated with the expression of PCNA (r=0.44, P<0.01); the upregulation of TLR-4 was positively correlated with the expressions of MMP-9 and TIMP-1. CONCLUSIONS: The upregulation of TLR-4 in the pulmonary arterial smooth muscle cells of COPD patients could promote the inflammations and the MMP-9 expression, thus causing abnormal degradation of extracellular matrix, so it played an important role in the process of PVR.

RESUMO OBJETIVO: Este estudo tem como objetivo investigar as expressões de TOLL-like receptor 4 (TLR-4) e metaloproteinase 9 da matriz (MMP-9)/inibidor de tecido da metaloproteinase 1 (TIMP-1) em vasos sanguíneos pulmonares com doença pulmonar obstrutiva crônica (DPOC) e suas relações com o remodelamento vascular pulmonar (PVR). MÉTODOS: Sessenta tecidos paratumorais foram divididos em grupo COPD e o grupo controle (n = 30). Foram comparadas as inflamações, área da parede da artéria pulmonar/área da artéria total (WA%) e espessura da parede/diâmetro externo vascular (WT%). As expressões de TLR-4, MMP-9/TIMP-1 e PCNA em células de músculo liso vascular pulmonar foram detectadas, e suas relações com PVR foram então analisadas. RESULTADOS: As inflamações (1,6 ± 0,8), WA% (44,0 ± 6,4) e WT% (27,3 ± 3,3) no grupo COPD foram maiores que no grupo controle (0,3 ± 0,5; 26,1 ± 2,8; 15,6 ± 1,8). E as expressões de TLR-4 (31,4 ± 14,7) e MMP-9/TIMP-1 (2,2 ± 2,6) foram aumentadas em relação ao grupo controle (4,7 ± 4,5, 1,9 ± 1,2). Na análise de correlação, TLR-4 e MMP-9/TIMP-1 foram positivamente correlacionadas com as inflamações (r = 0,18; P <0,01), WA% (r = 0,68; P <0,01) e WT% (r = 0,73; P <0,01), bem como correlacionadas positivamente com a expressão de PCNA (r = 0,44; P <0,01). A elevação da TLR-4 foi correlacionada positivamente com as expressões de MMP-9 e TIMP-1. CONCLUSÕES: A regulação positiva do TLR-4 nas células do músculo liso arterial pulmonar de pacientes com DPOC poderia promover as inflamações e a expressão de MMP-9, causando assim uma degradação anormal da matriz extracelular, por isso desempenhou um papel importante no processo de PVR.

Valor pronóstico de los niveles de propéptido N-terminal del procolágeno tipos I y III asociados al remodelamiento ventricular en pacientes con insuficiencia cardiaca crónica / Prognostic value of procollagen types I and III N-terminal propeptide as regards ventricular remodelling in patients with chronic heart failure

Resumen Introducción: La insuficiencia cardiaca constituye el estadio final de muchas cardiopatias. Aunque los cambios en la composición de la matriz extracelular relacionados con el proceso de remodelamiento ventricular han sido descritos, ni la evolución ni el impacto clínico de la fibrogénesis miocárdica en pacientes con IC están completamente entendidos. Objetivo: Determinar si los precursores de la síntesis y degradación del colágeno son útiles en la predicción de hospitalización, muerte o necesidad de trasplante cardiaco en pacientes con insuficiencia cardiaca crónica. Métodos: Se estudiaron 204 pacientes con insuficiencia cardiaca crónica entre 2015 y 2016; 106 con miocardiopatía isquémica y 98 con miocardiopatía dilatada. Se midieron los niveles séricos de noradrenalina, fracción N-terminal del propéptido natriurético cerebral, propéptido N-terminal del procolágeno tipo I (PINP) y propéptido N-terminal del procolágeno tipo III (PIIINP). Se determinaron volúmenes y fracción de eyección del ventrículo izquierdo, clase funcional y tratamiento médico. Resultados: Durante el seguimiento hubo 55 hospitalizaciones, 7 muertes y 9 trasplantes. La edad (p < 0,001), los niveles de PINP (p = 0,04), PIIINP (p = 0,016) y volúmenes del ventrículo izquierdo (p < 0,05), fueron significativamente mayores en los pacientes que alcanzaron el desenlace primario. En pacientes con dilatación severa del ventrículo izquierdo (IVTDVI > 110ml/m2, IVTSVI > 50ml/m2), niveles de PIIINP > 6,2 (g/L y PINP > 40 (g/L se asociaron con mayor riesgo de hospitalización, muerte o necesidad de trasplante (sobrevida libre de eventos a 12 meses: 45% versus 95%, p < 0,0001). Conclusiones: Los niveles circulantes de PINP y PIIINP, se correlacionan con el remodelamiento del ventrículo izquierdo y predicen desenlaces en pacientes con insuficiencia cardiaca crónica.

Abstract Introduction: Heart failure (HF) is the end-stage of many heart diseases. Although the changes in the composition of the extracellular matrix associated with the ventricular remodelling process have been described, neither the evolution nor the clinical impact of the myocardial fibrogenesis in patients with HF are completely understood. Objective: To determine if the precursors of the synthesis and degradation of collagen are useful in the prediction of hospital admissions, death, or the need for a heart transplant in patients with chronic heart failure (CHF). Methods: A total of 204 patients with chronic heart failure were studied between the years 2015 and 2016, of whom 106 had ischaemic heart disease, and 98 had dilated cardiomyopathy. Measurements were made of the serum levels of noradrenaline, N-terminal pro-B-type natriuretic peptide, procollagen type I N-terminal propeptide, and procollagen type III N-terminal propeptide (PIIINP). The left ventricular volumes and ejection fraction were determined, as well a record made of the functional class and medical treatment. Results: During follow-up, there were 55 hospital admissions, 7 deaths and 9 transplants. Age (p<0,001), PINP levels (p=0,04), PIIINP levels (p=0,016), and left ventricular volumes (p<0,05), were significantly higher in patients who achieved the primary outcome. In patients with severe dilation of the left ventricle (LV diastolic volume index, LVDVI > 110 ml/m2, LV systolic volume index, LVTSVI > 50 ml/m2), PIIINP levels > 6.2 (g/L and a PINP > 40 (g/L, were associated with a higher risk of hospital admission, death, or need of a transplant (event-free survival at 12 months: 45% versus 95%, p<0,0001). Conclusions: The circulating levels of PINP and PIIINP are associated with left ventricular remodelling, and predict the outcomes in patients with chronic heart failure.

Bone marrow adipose tissue——A kind of special adipose tissue / 中华内分泌代谢杂志

Bone marrow adipose tissue (MAT) is formed by the accumulation of adipocytes in the bone marrow cavity. Previously, the function of MAT is mainly considered to be filled with bone marrow cavity for the mechanical support. However,with the in-depth study of MAT,it has been gradually understood that MAT is not only a part of the bone marrow microenvironment,may also be a new endocrine "organ". The main component of bone marrow adipocytes(BMA) plays a regulatory role in bone marrow and systemic metabolism through the autocrine and paracrine secretion of adiponectin, leptin, interleukin-6, and a series of cytokines. Though its biological characteristics are somewhat similar with white fat adipose tissue(WAT) and brown adipose tissue(BAT),there are some significant differences,so MAT is thought to be a special adipose tissue. MAT is also involved in the development of hematological diseases,metabolic diseases,degenerative diseases,and may affect their outcomes. MAT may be the auxiliary diagnostic criteria and treatment targets of such diseases. This article will review the MAT's own biological characteristics,the differences and associations among three types of adipose tissue and the link between MAT and the diseases,which aims to explore the new research direction through the profound understanding of MAT.

Síndrome cardiorrenal / Cardiorenal syndrome

Resumen La insuficiencia cardiaca origina inicialmente una lesión miocárdica que conlleva remodelamiento ventricular, lo cual induce a la activación de mecanismos compensadores, entre los cuales el riñón es pieza fundamental ya que regula la homeostasis hidroelectrolítica y así el volumen circulante. El sistema nervioso simpático y el sistema renina-angiotensina-aldosterona aportan una retención de sodio y agua que afecta negativamente la función cardiaca y conduce a compromiso cardiovascular, miocárdico y renal; de allí nace la definición clínica de síndrome cardiorrenal que se clasifica de acuerdo con su forma de presentación y componentes fisiopatológicos. Esto motivó la definición y conceptualización del síndrome cardiorrenal, que incluye interacciones bidireccionales, en la que alteraciones, tanto agudas como crónicas de cualquier órgano, pueden afectar de manera funcional o estructural la función ventricular, la renal o ambas.

Abstract Heart failure initially causes myocardial damage that leads to ventricular remodelling. This, in turn, leads to activation of compensatory mechanisms where the kidney plays a fundamental role, as it regulates electrolyte homeostasis and thus the circulating volume. The sympathetic nervous system and the renin angiotensin-aldosterone system lead to the retention of sodium and water, which adversely affects cardiac function. This leads to cardiovascular, renal and myocardial compromise, or a cardiorenal syndrome, which is classified according to its presentation and pathophysiological components. The definition and conceptualization of cardiorenal syndrome includes two-way interactions, where acute and chronic changes of any organ can functionally or structurally affect the ventricular and/or renal function

Osteoporosis and periodontitis: a bidirectional relationship / Osteoporose e periodontite: uma relação bidirecional

Osteoporosis is a condition of compromised bone strength that predisposes an individual to increased risk of fracture and is a major cause of morbidity in older susceptible individuals. Osteoporosis is related to various endocrinal abnormalities, metabolic and nutritional factors, postmenopausal hormonal changes and consumption of certain drugs such as cortisone. Emerging clinical and molecular evidence suggests that inflammation also exerts significant influence on osteoporotic bone changes. Numerous pro-inflammatory cytokines have been shown to be associated with regulation of osteoblast and osteoclast differentiation. Chronic inflammatory conditions causing immune system remodeling may serve as pathological risk factors for osteoporosis. The present article reviews the current perspective on the interaction between bone morphology and immune system in the inflammatory condition (periodontitis), unleashing the link between two chronic conditions. (AU)

A osteoporose é uma condição de resistência óssea comprometida que predispõe um indivíduo ao risco aumentado de fratura e é uma das principais causas de morbidade em indivíduos susceptíveis mais velhos. A osteoporose está relacionada a várias anomalias endócrinas, fatores metabólicos e nutricionais, alterações hormonais pós-menopausa e consumo de certos medicamentos como a cortisona. Evidências clínicas e moleculares emergentes sugerem que a inflamação também exerce uma influência significativa sobre as alterações ósseas osteoporóticas. Numerosas citoquinas pró-inflamatórias demonstraram estar associadas à regulação da osteoblastos e da diferenciação osteoclástica. As condições inflamatórias crónicas, que provocam a remodelação do sistema imunitário, podem servir como factores de risco patológicos para a osteoporose. O presente artigo apresenta uma revisão da perspectiva atual sobre a interação entre a morfologia óssea e o sistema imunológico na condição inflamatória (periodontite), desencadeando a ligação entre duas condições crônicas (AU)

Passiflora quadrangularis L. prevents experimental hypertension and vascular remodelling in rats exposed to nitric oxide deficit / Passiflora quadrangularis L. previene la hipertensión experimental y el remodelado vascular en ratas expuestas a déficit de óxido nítrico

Background: Passiflora quadrangularis L. is among the species used in Colombian folk medicine for hypertension, but until now it has not been studied in experimental models. Objectives: To assess the capacity of P. quadrangularis L. EtOH extract to prevent the hypertension and vascular remodelling induced by nitric oxide (NO) deficit in Wistar rats. Methods: The nitric oxide (NO) synthase inhibitor L-NAME (10 mg/kg, i.p (intraperitoneal), every 48h) was administered for seven weeks to the following groups of rats: P. quadrangularis L.75, 150 and 300 mg/kg/d, p.o. (oral route); enalapril as reference agent, 10 mg/kg/d, p.o. and vehicle as control (mixture of propylene glycol 10%, glycerine 10% and polysorbate 2%). Arterial blood pressure (BP) and heart rate (HR) were measured twice a week. After sacrifice, the aortic rings were isolated, contraction was triggered with phenylephrine (PE 10-6 M) and then the relaxant response achieved with cumulative concentrations of acetylcholine (ACh, 10-10 ­ 10-5 M) or sodium nitroprusside (SNP, 10-10 ­ 10-5 M) was assessed. Histopathologic measures of thickness/lumen ratio from both the left ventricle and aorta walls, as well as phytochemical screening, were also performed. Results: As for enalapril, all doses of P. quadrangularis L. prevented the hypertension induced by L-NAME (122±1.2 versus 155±1.3 mmHg at seventh week). P. quadrangularis L. significantly increased the relaxant effect induced by ACh in isolated aorta and decreased the thickness/lumen ratio of aorta wall specimens. Conclusions: P. quadrangularis L. prevents experimental hypertension induced in rats with nitric oxide deficits improving the endothelium vasodilatation response and protecting against vascular remodelling.

Antecedentes: Passiflora quadrangularis L. es una de las especies utilizadas en medicina tradicional en Colombia para la hipertensión pero hasta el momento no se ha evaluado en modelos experimentales. Objetivos: Evaluar la capacidad del extracto etanólico de P. quadrangularis L. para prevenir la hipertensión y el remodelado vascular inducidos por déficit de óxido nítrico (NO) en ratas Wistar. Métodos: El inhibidor de la óxido nítrico (NO) sintasa L-NAME (10 mg/kg, i.p, cada 48 h) se administró durante siete semanas a los siguientes grupos de tratamiento: P. quadrangularis L. 75, 150 y 300 mg/kg/d, p.o; Enalapril como agente de referencia, 10 mg/kg/d, p.o., y vehículo como control (mezcla de propilenglicol 10%, glicerina 10% y polisorbato 2%). Se midió la presión arterial (BP) y la frecuencia cardiaca (HR) dos veces por semana. Después del sacrificio, se aislaron los anillos aórticos, se desencadenó la contracción con fenilefrina (PE 10-6 M) y la respuesta relajante con concentraciones acumulativas de acetilcolina (ACh, 10-10 ­ 10-5 M) o nitroprusiato de sodio (SNP, 10-10 ­ 10-5 M). También se realizaron estudios histopatológicos de la relación entre el espesor y el lumen tanto en el ventrículo izquierdo como en las paredes de la aorta, así como un cribado fitoquímico. Resultados: Enalapril y todas las dosis de P. quadrangularis L. evitaron la hipertensión inducida por L-NAME (122 ± 1,2 frente a 155 ± 1,3 mm Hg a la séptima semana). P. quadrangularis L. aumentó significativamente el efecto relajante inducido por ACh en la aorta aislada y disminuyó la relación entre el espesor y la luz de los especímenes en la pared de la aorta. Conclusiones: P. quadrangularis L. previene la hipertensión experimental inducida por déficit de óxido nítrico en ratas, mejorando la respuesta del endotelio y protegiendo frente al remodelado vascular.

Conexiones entre tejido óseo y tejido graso: efecto de la obesidad sobre la salud ósea / Bone and fat connection: obesity effect on bone health / Conexões entre tecido ósseo e tecido gorduroso: efeito da obesidade na saúde óssea

La prevalencia de dos desórdenes crónicos como la osteoporosis y la obesidad se encuentra en aumento. La fisiopatología de ambas alteraciones metabólicas es multifactorial e incluye factores genéticos, factores ambientales y hormonales. Diversos estudios clínicos y experimentales demuestran la existencia de una interacción entre el tejido adiposo y el esqueleto, similar a la que ocurre entre las patologías mencionadas. Si bien se pensaba que la obesidad protegía al hueso, actualmente se postula que un exceso de tejido graso, fundamentalmente grasa abdominal, sería un factor de riesgo para el desarrollo de osteoporosis y fracturas por fragilidad. Diversos factores secretados por el tejido graso incrementados por efecto de la obesidad jugarían un rol clave en la salud ósea. Las adipoquinas, citokinas y ácidos grasos libres regulan el remodelamiento óseo, disminuyendo la formación e incrementando la resorción, al mismo tiempo que inducen estrés oxidativo e hiperglucemia, que exacerba el efecto negativo sobre la masa ósea. Esta revisión trata de profundizar el conocimiento de las interacciones entre hueso y tejido adiposo y de las implicancias clínicas que surgen de la interrelación entre obesidad y osteoporosis.

Osteoporosis and obesity are chronic disorders that are increasing in prevalence. The pathophysiology of these diseases is multifactorial and it includes genetic, environmental and hormonal determinants. Basic and clinical studies support an important interaction between adipose tissue and the skeleton similar to that found in osteoporosis and obesity. The belief that obesity is protective for bone has recently been revised. In fact, excess of fat mass might be a risk factor for osteoporosis and fragility fractures. Increasing evidence seems to indicate that different factors released by the fat tissue could play a key role in skeletal health. Adipokines, cytokines and free-fatty acids secreted by the obese fat mass can regulate bone remodelling decreasing bone formation and increasing bone resorption. Moreover they increase oxidative stress, increasing even more the negative effect on bone mass. This review considers literature data to understand bone-fat interactions and the clinical implications of linking obesity to osteoporosis.

A prevalência de duas doenças crônicas, como a osteoporose e a obesidade estão aumentando. A fisiopatologia de ambas as doenças metabólicas é multifatorial e inclui fatores genéticos, fatores ambientais e hormonais. Estudos clínicos e experimentais demonstram a existência de interação entre o tecido adiposo e o esqueleto, semelhante ao encontrado nas patologias mencionadas. Embora exista a crença de que a obesidade protegia o osso, atualmente se postula que um excesso de tecido gorduroso, fundamentalmente gordura abdominal seria um fator de risco para desenvolver osteoporose e fraturas por fragilidade. Diversos fatores secretados pelo tecido gorduroso aumentado por efeito da obesidade teria um papel chave na saúde óssea. As adipocinas, citocinas e ácidos graxos livres regulam a remodelação óssea, diminuindo a formação e aumentando a reabsorção, ao mesmo tempo que eles induzem estresse oxidativo e hiperglicemia, aumentando ainda mais o efeito negativo sobre a massa óssea. Esta revisão visa aprofundar o conhecimento das interações entre o osso e o tecido adiposo e nas implicações clínicas que surgem da interação entre obesidade a osteoporose.

Effect of Shensong Yangxin Capsule on Cardiac Remodelling of Myocardial Infarction Mouse Model / 医药导报

Objective To investigate the effect of Shensong Yangxin capsule on cardiac remodelling of myocardial infarction mouse model and the possible molecular mechanisms. Methods Adult male C57BL/6J mice were divided into sham operation group(n=10), model control group(n=20)and Shensong Yangxin group(n=20)according to random number table. Left anterior descending branch of coronary artery was ligated to establish myocardic infarction model in the model control group and Shensong Yangxin group. From the 2nd day after the surgery, Shensong Yangxin ( 400 mg . kg-1 ) was intragastrically administered, and the death rate of the mice was observed.Four weeks after the surgery, echocardiography was used to measure the cardiac function;myocardiac infarction area was detected by pathological staining;the expression levels of cardiac remodelling markers and extracellular matrix proteins were detected by RT-PCR. The possible molecular mechanisms were screened by Western blotting. Results As compared with the model control group, Shensong Yangxin significantly reduced the mortality after myocardial infarction in mice(P<0.05), as well as the myocardial infarct size(P<0.05).The mRNA expression levels of cardiac remodelling markers ANP, BNP, and β-MHC and the extracellular matrix proteins(collagenⅠ, collagen Ⅲ, CTGF, TGFβ) decreased significantly in the Shensong Yangxin group as compared with the model control group. Western blotting showed that Shensong Yangxin significantly decreased activation of smad3, and reduced expression level of smad4. Conclusion Shensong Yangxin attenuates cardiac remodelling after myocardial infarction and the mechanism may be related with blockage of smad signaling pathway.

Differential Expression Patterns of Leukaemia Associated Genes in Leukaemia Cell Lines Compared to Healthy Controls

Introduction: The phenotype and genotype of cancer cells portray hallmarks of cancer which may have clinical value. Cancer cell lines are ideal models to study and confirm these characteristics. We previously established two subtracted cDNA libraries with differentially expressed genes from an acute myeloid leukaemia patient with poor prognosis (PP) and good prognosis (GP). Objective: To compare gene expression of the leukaemia associated genes with selected biological characteristics in leukaemia cell lines and normal controls. Methodology: Expression of 28 PP genes associated with early fetal/embryonic development, HOX-related genes, hematopoiesis and aerobic glycolysis/ hypoxia genes and 36 GP genes involved in oxidative phosphorylation, protein synthesis, chromatin remodelling and cell motility were examined in B-lymphoid (BV173, Reh and RS4;11) and myeloid (HL-60, K562) leukaemia cell lines after 72h in culture as well as peripheral blood mononuclear cells from healthy controls (N=5) using semi-quantitative polymerase chain reaction (PCR) method. Cell cycle profiles were analysed on flow cytometry while MTT cytotoxicity assay was used to determine drug resistance to epirubicin. Results: Genes expressed significantly higher in B-lymphoid leukaemia cell lines compared to healthy controls were mostly of the GP library i.e. oxidative phosphorylation (3/10), protein synthesis (4/11), chromatin remodelling (3/3) and actin cytoskeleton genes (1/5). Only two genes with significant difference were from the PP library. Cancer associated genes, HSPA9 and PSPH (GP library) and BCAP31 (PP library) were significantly higher in the B-lymphoid leukemia cell lines. No significant difference was observed between myeloid cell lines and healthy controls. This may also be due heterogeneity of cell lines studied. PBMC from healthy controls were not in cell cycle. G2/M profiles and growth curves showed B-lymphoid cells just reaching plateau after 72 hour culture while myeloid cells were declining. IC50 values from cytotoxicity assay revealed myeloid cell lines had an average 13-fold higher drug resistance to epirubicin compared to B-lymphoid cell lines. Only CCL1, was expressed at least two-fold higher in myeloid compared to B-lymphoid cell lines. In contrast, MTRNR2, EEF1A1, PTMA, HLA-DR, C6orf115, PBX3, ENPP4, SELL, and IL3Ra were expressed more than 2-fold higher in B-lymphoid compared to myeloid cell lines studied here. Conclusion: Thus, B-lymphoid leukaemia cell lines here exhibited active, proliferating characteristics closer to GP genes. Higher expression of several genes in B-lymphoid compared to myeloid leukaemia cell lines may be useful markers to study biological differences including drug resistance between lineages.

Quantification of Bone Histomorphometric Parameters Using the Weibel Technique in Animals

Bone histomorphometric measurements are required to understand the efficacy of treatment on bone remodelling. Previous studies used the Weibel technique as a quantitative stereological method to determine bone cellular and dynamic changes. However, there was no description on how this technique was applied. This studyaimed to provide a full picture about the utilization of the Weibel technique to measure static and dynamic bone histomorphometric indices. Technical expertise, processing of bone samples, randomization of the trabecular sections and an adequate number of analysed images for each section are required to achieve reliable results with a low possibility of errors.

Hallazgos ecocardiográficos en pacientes con preeclampsia en la Unidad de alta dependencia obstétrica en el Hospital Universitario de San José, 2012-2014 / Echographic findings in patients with pre-eclampsia see at the critical obstetrics unit of the San Jose Children's Teaching Hospital, 2012-2014

Objetivo: describir las alteraciones ecocardiográficas encontradas en pacientes con diagnóstico de preeclampsia severa.Materiales y métodos: estudio de corte transversal. Se describen los hallazgos ecocardiográficos en las pacientes con preeclampsia severa (PS), de acuerdo con los criterios del Congreso Americano de Obstetras y Ginecólogos, atendidas en un hospital universitario de referencia ubicado en Bogotá (Colombia), entre enero 1 de 2012 y junio 30 de 2014. Se excluyeron las pacientes con control adecuado de tensión arterial o con patología cardiaca estructural previa conocida. Se describen las variables sociodemográficas, clínicas y los hallazgos ecocardiográficos más frecuentes, globalmente y por momento de aparición. Se presentan los datos mediante estadística descriptiva.Resultados: se diagnosticaron 228 pacientes con PS. A 124 se les realizó ecocardiograma: en 8 de ellas el informe de ecocardiografía fue no concluyente. Se hallaron 78 pacientes (67 %) con alguna alteración. Los principales hallazgos fueron: hipertensión pulmonar leve, n = 34 (29 %); hipertrofia del ventrículo izquierdo, n = 32 (27 %); hipertensión pulmonar moderada, n = 21 (18 %); disfunción diastólica, n = 16 (13 %). Las pacientes con PS pretérmino (69 %) presentaron alteraciones ecocardiográficas más frecuentes que las pacientes a término (20 %) y que las que comenzaron con PS en el puerperio (11 %). La disfunción diastólica se presentó más en pacientes con preeclampsia que comenzó en el puerperio.Conclusiones: la prevalencia de alteraciones ecocardiográficas en PS es del 67 %, con mayor frecuencia de hipertensión pulmonar e hipertrofia ventricular izquierda. Se requieren más estudios que validen estos hallazgos regionalmente.

Objective: To describe echographic abnormalities found in patients diagnosed with severe preeclampsia.Materials and methods: Cross-sectional study describing ultrasound findings in patients with severe preeclampsia (SP) in accordance with the criteria of the American Congress of Obstetricians and Gynecologists. The patients were seen in a referral teaching hospital in Bogota (Colombia), between January 1, 2012 and June 30, 2014. Patients with adequate blood pressure control or with known pre-existing structural heart disease were excluded. Social, demographic and clinical variables are described, as well as the most frequent global echographic findings, also by time of onset. The data are presented using descriptive statistics.Results: Overall, 228 patients were diagnosed with SP. An echographic examination was performed in 124 and in 8 of them the echographic report was non-conclusive. Some form of abnormality was found in 78 patients (67 %). Mild pulmonary hypertension [n=34 (29 %)], left-ventricular hypertrophy [n=32 (27 %)], moderate pulmonary hy per tension [n=21 (18 %)] and diastolic dysfunction [n= 16 (13 %)] were the main findings observed. Echographic abnormalities were found more frequently in patients with pre-term SP (69 %) than in term patients (20 %) or those who developed SP during the post-partum period (11 %). Diastolic dysfunction was found to occur more frequently in patients who developed preeclampsia in the post-partum period.Conclusions: The prevalence of echographic abnormalities in SP is 67 %, the most frequent being pulmonary hypertension and left ventricular hypertrophy. More studies are needed in order to validate these findings regionally.