Chronic Periodontitis and RANKL/OPG Ratio in Peri-Implant Mucosae Inflammation

Abstract tHistory of chronic periodontitis (CP) is a risk factor for oseointegration failure. The osteoclastogenesis system (RANK, RANKL and OPG) is critical for bone homeostatic control. We investigated the levels of OPG and RANKL in peri-implant tissues from volunteers with and without a history of CP and their association with mucosae inflammation. This is a single-blind case-contro study. Diagnosis of a history of CP and peri-implant examination was performed on 46 volunteers, divided into control (without history of CP, n=26) and CP group (with history of CP, n=20). Gingival biopsies were harvested during implant exposure. Quantitative PCR evaluated OPG/RANKL mRNA expressions. OPG and RANKL proteins were analyzed by western blot and immunohistochemistry assay. The chi-square test analyzed the significance of nominal variables between groups while continuous variables were analyzed by T-test or Mann-Whitney test, after Shapiro-Wilk test evaluation. The 2-ΔΔCT Livak method calculation evaluated the gene expression. Values of p<0.05 were considered statistically significant. Volunteers with CP history had 23 times higher chance of developing mucosae inflammation. High mucosae levels of RANKL (p=0.04) and RANKL/OPG (p=0.001) mRNA expressions were observed in CP group. CP volunteers showed increased RANKL protein levels in opposition to decreased OPG expression. Even without active periodontitis, volunteers with a history of CP had elevated gingival levels of RANKL/OPG and higher correlation with peri-implant mucosae inflammation and implant loss.

Resumo A história de periodontite crônica (CP) é um fator de risco para falhas na osseointegração. O sistema de osteoclastogênese (RANK, RANKL e OPG) é crucial para o controle da homeostase óssea. O objetivo deste estudo foi investigar os níveis de OPG e RANKL no tecido peri-implantar de voluntários com e sem histórico de CP e sua associação com inflamação da mucosa. Este é um estudo tipo caso-controle. O exame para diagnóstico de CP e na região peri-implantar foi realizado em 46 voluntários, divididos em controle (sem história CP, n=26) e grupo CP (com histórico de CP, n=20). Descartes gengivais foram obtidos durante a exposição do implante. PCR quantitativo avaliou a expressão do RNAm de OPG/RANKL. As proteínas OPG e RANKL foram analisadas por western blot e imunohistoquímica. O teste do qui-quadrado analisou a significância entre as variáveis nominais enquanto as variáveis contínuas foram analisadas pelo teste-t e Mann-Whitney, após o teste de Shapiro-wilk. O método do Livak 2--ΔΔCT avaliou a expressão gênica. Os voluntários com CP apresentaram 23 vezes mais chances de desenvolver inflamação da mucosa. Expressão elevada no RNAm de RANKL (p=0.04) e RANKL/OPG (p=0.001) foram observadas no grupo CP. Voluntários com CP mostraram aumento dos níveis da proteína RANKL em contraste com diminuída expressão de OPG. Mesmo sem periodontite ativa, voluntários com histórico de CP apresentaram elevado nível gengival de RANKL/OPG e alta correlação com inflamação peri-implantar e perda do implante.

Chronic Periodontitis and RANKL/OPG Ratio in Peri-Implant Mucosae Inflammation.

tHistory of chronic periodontitis (CP) is a risk factor for oseointegration failure. The osteoclastogenesis system (RANK, RANKL and OPG) is critical for bone homeostatic control. We investigated the levels of OPG and RANKL in peri-implant tissues from volunteers with and without a history of CP and their association with mucosae inflammation. This is a single-blind case-contro study. Diagnosis of a history of CP and peri-implant examination was performed on 46 volunteers, divided into control (without history of CP, n=26) and CP group (with history of CP, n=20). Gingival biopsies were harvested during implant exposure. Quantitative PCR evaluated OPG/RANKL mRNA expressions. OPG and RANKL proteins were analyzed by western blot and immunohistochemistry assay. The chi-square test analyzed the significance of nominal variables between groups while continuous variables were analyzed by T-test or Mann-Whitney test, after Shapiro-Wilk test evaluation. The 2-ΔΔCT Livak method calculation evaluated the gene expression. Values of p<0.05 were considered statistically significant. Volunteers with CP history had 23 times higher chance of developing mucosae inflammation. High mucosae levels of RANKL (p=0.04) and RANKL/OPG (p=0.001) mRNA expressions were observed in CP group. CP volunteers showed increased RANKL protein levels in opposition to decreased OPG expression. Even without active periodontitis, volunteers with a history of CP had elevated gingival levels of RANKL/OPG and higher correlation with peri-implant mucosae inflammation and implant loss.

MMP13, TIMP2 and TGFB3 Gene Polymorphisms in Brazilian Chronic Periodontitis and Periimplantitis Subjects.

Subjects susceptible to chronic periodontitis (CP) show a high risk for the development of periimplantitis (PI). Both diseases are multifactorial, presenting similarities in their pathophysiology and polygenic profile. MMP-13 (matrix metalloproteinases 13/ collagenase 3) is a collagenolytic enzyme, which expression is induced by TGF beta 3 (transforming growth factor type 3) in human gingival fibroblasts and inhibited by TIMP-2 (tissue inhibitor of metalloproteinase type 2). The aim of this study was to investigate the occurrence of periimplantitis (PI) in subjects with history of chronic periodontitis (CP) and polymorphisms frequency in MMP13, TIMP2 and TGFB3 genes. One hundred and sixty-three volunteers received dental implant placement were submitted to oral and radiographic examination in order to identify past history of CP or presence of PI. Volunteers were divided into 4 groups: Control (without PI and CP, n=72), CP (with CP and without PI, n=28), PI (with PI and without CP, n=28) and diseased (with CP and PI, n=35). The chi-square test correlated genotypes in specific regions of MMP13 (rs2252070), TIMP2 (rs7501477) and TGFB3 (rs2268626) genes, considering the interaction between CP and PI. The results showed that volunteers with CP had 3.2 times more susceptibility to develop PI (p=0.0004) compared to those without CP. No significant association was observed in MMP13, TIMP2 and TGFB3 genes with CP or PI. CP is a risk factor to develop PI, however, there is no association of both diseases with polymorphisms in the MMP13, TIMP2 and TGFB3 genes.

MMP13, TIMP2 and TGFB3 Gene Polymorphisms in Brazilian Chronic Periodontitis and Periimplantitis Subjects

Abstract Subjects susceptible to chronic periodontitis (CP) show a high risk for the development of peiimplantitis (PI). Both diseases are multifactorial, presenting similarities in their pathophysiology and polygenic profile. MMP-13 (matrix metalloproteinases 13/ collagenase 3) is a collagenolytic enzyme, which expression is induced by TGF beta 3 (transforming growth factor type 3) in human gingival fibroblasts and inhibited by TIMP-2 (tissue inhibitor of metalloproteinase type 2). The aim of this study was to investigate the occurrence of peiimplantitis (PI) in subjects with history of chronic periodontitis (CP) and polymorphisms frequency in MMP13, TIMP2 and TGFB3 genes. One hundred and sixty-three volunteers received dental implant placement were submitted to oral and radiographic examination in order to identify past history of CP or presence of PI. Volunteers were divided into 4 groups: Control (without PI and CP, n=72), CP (with CP and without PI, n=28), PI (with PI and without CP, n=28) and diseased (with CP and PI, n=35). The chi-square test correlated genotypes in specific regions of MMP13 (rs2252070), TIMP2 (rs7501477) and TGFB3 (rs2268626) genes, considering the interaction between CP and PI. The results showed that volunteers with CP had 3.2 times more susceptibility to develop PI (p=0.0004) compared to those without CP. No significant association was observed in MMP13, TIMP2 and TGFB3 genes with CP or PI. CP is a risk factor to develop PI, however, there is no association of both diseases with polymorphisms in the MMP13, TIMP2 and TGFB3 genes.

Resumo Indivíduos susceptíveis à periodontite crônica (CP) apresentam alto risco para o desenvolvimento de periimplantite (PI). Ambas doenças são multifatoriais e apresentam similaridades na patofisiologia e perfil poligênico. A MMP-13 (metaloproteinase da matriz tipo 13) é uma enzima colagenolítica cuja expressão é induzida por TGF beta 3 (fator transformador do crescimento tipo 3) nos fibroblastos gengivais humanos e inibida por TIMP-2 (inibidor tecidual de metaloproteinase tipo 2). O objetivo deste estudo foi investigar a ocorrência de periimplantite em sujeitos com periodontite crônica e a frequência dos polimorfismos nos genes MMP13, TIMP2 e TGFB3. Cento e sessenta e três voluntários submetidos à instalação de implantes endósseos foram analisados clínica e radiograficamente quanto à presença de histórico de CP e PI, sendo divididos em 4 grupos: Controle (sem história de CP e PI, n=72), CP (com CP e sem PI, n=28), PI (com PI e sem CP, n=28) e Doentes (com CP e PI, n=35). O teste do qui-quadrado correlacionou os genótipos nas regiões dos genes MMP13 (rs2252070), TIMP2 (rs7501477) e TGFB3 (rs2268626), considerando a interação entre CP e PI. Os resultados mostraram que voluntários com CP possuem 3.2 vezes mais chances de desenvolver PI (p=0.0004) comparados aos sem CP. Nenhuma associação significativa foi observada entre os genes MMP13, TIMP2 e TGFB3 e CP ou PI. A CP é um fator de risco ao desenvolvimento de PI, no entanto, não há associação entre ambas as doenças com polimorfismos nos genes MMP13, TIMP2 e TGFB3.

Use of tranexamic acid for controlling bleeding in thoracolumbar scoliosis surgery with posterior instrumentation.

OBJECTIVE: Scoliosis surgery involves major blood loss and frequently requires blood transfusion. The cost and risks involved in using allogeneic blood have motivated investigation of methods capable of reducing patients' bleeding during operations. One of these methods is to use antifibrinolytic drugs, and tranexamic acid is among these. The aim of this study was to assess the use of this drug for controlling bleeding in surgery to treat idiopathic scoliosis. METHODS: This was a retrospective study in which the medical files of 40 patients who underwent thoracolumbar arthrodesis by means of a posterior route were analyzed. Of these cases, 21 used tranexamic acid and were placed in the test group. The others were placed in the control group. The mean volumes of bleeding during and after the operation and the need for blood transfusion were compared between the two groups. RESULTS: The group that used tranexamic acid had significantly less bleeding during the operation than the control group. There was no significant difference between the groups regarding postoperative bleeding and the need for blood transfusion. CONCLUSIONS: Tranexamic acid was effective in reducing bleeding during the operation, as demonstrated in other studies. The correlation between its use and the reduction in the need for blood transfusion is multifactorial and could not be established in this study. We believe that tranexamic acid may be a useful resource and that it deserves greater attention in randomized double-blind prospective series, with proper control over variables that directly influence blood loss.

OBJETIVO: A cirurgia de escoliose envolve elevada perda sanguínea e necessita frequentemente de hemotransfusão. O custo e os riscos envolvidos no uso do sangue alogênico têm motivado pesquisas de métodos capazes de reduzir o sangramento operatório nos pacientes. Um desses métodos é o uso de drogas antifibrinolíticas, entre as quais está o ácido tranexâmico (ATX). O objetivo deste estudo foi verificar o uso dessa droga no controle do sangramento em cirurgias de escoliose idiopática. MÉTODOS: Estudo retrospectivo no qual foram analisados os prontuários de 40 pacientes submetidos à artrodese toracolombar por via posterior. Desses, apenas 21 usaram o ATX e foram relacionados no grupo teste. Os demais foram relacionados no grupo controle. Foram comparadas as médias de sangramento per e pós-operatório e a necessidade de hemotransfusão entre os dois grupos. RESULTADOS: O grupo que usou o ATX teve sangramento peroperatório significativamente menor do que o grupo controle. Não houve diferença significativa entre os grupos para o sangramento pós-operatório e a necessidade de hemotransfusão. CONCLUSÕES: O ATX foi eficaz na redução do sangramento peroperatório, conforme demostrado em outros estudos. A correlação entre o seu uso e a redução da necessidade de hemotransfusão é multifatorial e não pôde ser estabelecida neste trabalho. Acreditamos que o ácido tranexâmico possa ser um recurso útil e merece maior atenção em séries prospectivas, duplo-cegas, randomizadas, com o devido controle das variáveis que interferem diretamente na perda sanguínea.

Effects of resistance exercise training on acyl-ghrelin and obestatin levels in hemodialysis patients.

BACKGROUND: Patients undergoing hemodialysis (HD) present altered levels of appetite hormones such as acyl-ghrelin (orexigenic) and obestatin (anorexigenic), which may contribute to anorexia. Physical exercise may affect these hormones and improve appetite in these patients. OBJECTIVES: The objective of this study is to evaluate the effects of a resistance exercise program in appetite hormones, body composition, and nutritional status in HD patients. DESIGN: Intervention study with the control group. SUBJECTS: Fifty-two patients on regular HD program were enrolled into two groups: 37 patients performed exercises (56.7% male, 45 ± 12.8 years, 57 (9-192) months on HD) and 15 patients comprised the control group (66.7% men, 50 ± 10.6 years, 57 (11-153) months on HD). MEASUREMENTS: Exercise program (performed with elastic bands and ankle cuffs in both lower limbs) was supervised three times a week during 6 months (72 sessions). Patients had their blood drawn in a regular HD day after overnight fasting, before and after 6 months of exercise program. Obestatin, acyl-ghrelin, routine biochemical parameters, quality of life, and anthropometric data were collected and analyzed before and after 6 months. RESULTS: After 6 months of exercise, obestatin levels reduced [from 3.0 ng/mL (2.3-3.4) to 1.9 ng/mL (0.6-3.4)] and acyl-ghrelin levels increased [from 21.5 pg/mL (1.3-77.7) to 37.2 pg/mL (16.7-94.1)] and the control group presented no significant differences in both plasma levels of hormones. Body composition and physical functional assessed by SF-36 and albumin levels (3.7 ± 0.3 to 3.9 ± 0.2, p < 0.05) improved after exercises. CONCLUSION: Six months of resistance exercises contributed to changes in plasma appetite hormones, body composition, and nutritional status in hemodialysis patients.

Use of tranexamic acid for controlling bleeding in thoracolumbar scoliosis surgery with posterior instrumentation / Uso do ácido tranexâmico no controle do sangramento em cirurgias de escoliose toracolombar com instrumentação posterior

OBJECTIVE: Scoliosis surgery involves major blood loss and frequently requires blood transfusion. The cost and risks involved in using allogeneic blood have motivated investigation of methods capable of reducing patients' bleeding during operations. One of these methods is to use antifibrinolytic drugs, and tranexamic acid is among these. The aim of this study was to assess the use of this drug for controlling bleeding in surgery to treat idiopathic scoliosis. METHODS: This was a retrospective study in which the medical files of 40 patients who underwent thoracolumbar arthrodesis by means of a posterior route were analyzed. Of these cases, 21 used tranexamic acid and were placed in the test group. The others were placed in the control group. The mean volumes of bleeding during and after the operation and the need for blood transfusion were compared between the two groups. RESULTS: The group that used tranexamic acid had significantly less bleeding during the operation than the control group. There was no significant difference between the groups regarding postoperative bleeding and the need for blood transfusion. CONCLUSIONS: Tranexamic acid was effective in reducing bleeding during the operation, as demonstrated in other studies. The correlation between its use and the reduction in the need for blood transfusion is multifactorial and could not be established in this study. We believe that tranexamic acid may be a useful resource and that it deserves greater attention in randomized double-blind prospective series, with proper control over variables that directly influence blood loss. .

OBJETIVO: A cirurgia de escoliose envolve elevada perda sanguínea e necessita frequentemente de hemotransfusão. O custo e os riscos envolvidos no uso do sangue alogênico têm motivado pesquisas de métodos capazes de reduzir o sangramento operatório nos pacientes. Um desses métodos é o uso de drogas antifibrinolíticas, entre as quais está o ácido tranexâmico (ATX). O objetivo deste estudo foi verificar o uso dessa droga no controle do sangramento em cirurgias de escoliose idiopática. MÉTODOS: Estudo retrospectivo no qual foram analisados os prontuários de 40 pacientes submetidos à artrodese toracolombar por via posterior. Desses, apenas 21 usaram o ATX e foram relacionados no grupo teste. Os demais foram relacionados no grupo controle. Foram comparadas as médias de sangramento per e pós-operatório e a necessidade de hemotransfusão entre os dois grupos. RESULTADOS: O grupo que usou o ATX teve sangramento peroperatório significativamente menor do que o grupo controle. Não houve diferença significativa entre os grupos para o sangramento pós-operatório e a necessidade de hemotransfusão. CONCLUSÕES: O ATX foi eficaz na redução do sangramento peroperatório, conforme demostrado em outros estudos. A correlação entre o seu uso e a redução da necessidade de hemotransfusão é multifatorial e não pôde ser estabelecida neste trabalho. Acreditamos que o ácido tranexâmico possa ser um recurso útil e merece maior atenção em séries prospectivas, duplo-cegas, randomizadas, com o devido controle das variáveis que interferem diretamente na perda sanguínea. .

Fructose intake: is there an association with uric acid levels in nondialysis-dependent chronic kidney disease patients? / La ingesta de fructosa: ¿existe una asociación con los niveles de ácido úrico en pacientes con enfermedad renal crónica no dependiente de diálisis?

Introduction: Fructose intake has increased dramatically in consequence of the consumption of fructose-based sweetened foods and beverages. Research suggests that high fructose intake has a strong association with uric acid (UA) levels and worse prognosis of chronic kidney disease (CKD). Objective: The aim of this study was to investigate the influence of fructose intake on plasma UA levels in nondialysis- dependent CKD patients. Methods: Fifty-two patients on stages 3-5 (64.2 ± 9.6 years, 24 men, glomerular filtration rate of 30.5 ± 10.3ml/ min) were divided into two groups: high fructose intake (>50g/d, n=29, 61.7 ± 9.3years) and low fructose intake (<50g/d, n=23, 65.8 ± 9.7years). Blood samples were collected to determine lipid profile and plasma levels of UA, inflammatory (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP)) and cardiovascular markers (monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)). The energy, protein and fructose intake was estimated using 3-day 24-hour food recall. Results: High fructose intake was observed in 55.8% of patients and the mean UA levels were 7.7 ± 1.3 and 6.2 ± 1.6mg/dl in patients with high and low fructose intake, respectively (p<0.05). According to the regression analysis, fructose intake was the only variable able to affect the AU levels (b=0.42, p=0.016) after adjustment for gender, BMI, energy and protein intake, cardiovascular markers and lipid profile. Conclusions: These findings support a potential role for fructose in hyperuricemia in these patients (AU)

Introducción: El consumo de fructosa ha aumentado dramáticamente en consecuencia del consumo de alimentos y bebidas azucaradas a base de fructosa. Pesquisas sugieren que el alto consumo de fructosa tiene una fuerte asociación con niveles de ácido úrico (AU) y empeora el pronóstico de la enfermedad renal crónica (ERC). Objetivo: El objetivo de este estudio fue investigar la influencia del consumo de fructosa en los niveles plasmáticos de ácido úrico en pacientes con ERC que no son dependiente de diálisis. Métodos: Cincuenta y dos pacientes en fases 3-5 (64,2±9,6 años, 24 hombres, tasa de filtración glomerular de 30,5±10,3ml/min) se dividieron en dos grupos: alto consumo de fructosa (>50g/día, n=29, 61,7± 9,3 años) y bajo consumo de fructosa (<50g/día, n=23, 65,8±9,7 años). Muestras de sangre fueron recogidas para determinación del perfil lipídico y niveles plasmáticos de AU, citocinas inflamatorias (interleucina-6 (IL-6), factor de necrosis tumoral-α (TNF-α), proteína C-reactiva (CRP)), y marcadores cardiovasculares (proteína quimiotáctica de monocitos-1 (MCP-1), molécula de adhesión intercelular- 1 (ICAM-1) y molécula de adhesión vascular-1 (VCAM-1)). El consumo de energía, proteína y fructosa fue estimulado utilizando 3 días de recordatorio alimentar de 24 horas. Resultados: El alto consumo de fructosa fue observado en el 55,8% de los pacientes y los niveles medios de AU fueron 7,7±1,3 y 6,2±1,6mg/dl en pacientes con alto y bajo consumo de fructosa, respectivamente (p<0,05). De acuerdo con el análisis de regresión, el consumo de fructosa fue la única variable capaz de afectar los niveles de AU (b=0,42, p=0,016) después del ajuste para el género, composición corporal, energía y proteína, marcadores cardiovasculares y el perfil lipídico. Conclusiones: Estos resultados apoyan un papel potencial de la fructosa ocasionando la hiperuricemia en estos pacientes (AU)

New strategy to control cell migration and metastasis regulated by CCN2/CTGF.

Connective tissue growth factor (CTGF)/CCN family member 2 (CCN2) is a CCN family member of matricellular signaling modulators. It has been shown that CCN2/CTGF mediates cell adhesion, aggregation and migration in a large variety of cell types, including vascular endothelial cells, fibroblasts, epithelial cells, aortic smooth muscle and also pluripotent stem cells. Others matricellular proteins are capable of interacting with CCN2/CTGF to mediate its function. Cell migration is a key feature for tumor cell invasion and metastasis. CCN2/CTGF seems to be a prognostic marker for cancer. In addition, here we intend to discuss recent discoveries and a new strategy to develop therapies against CCN2/CTGF, in order to treat cancer metastasis.

Role of altered intestinal microbiota in systemic inflammation and cardiovascular disease in chronic kidney disease.

The normal intestinal microbiota plays a major role in the maintenance of health and disease prevention. In fact, the alteration of the intestinal microbiota has been shown to contribute to the pathogenesis of several pathological conditions, including obesity and insulin resistance, among others. Recent studies have revealed profound alterations of the gut microbial flora in patients and animals with chronic kidney disease (CKD). Alterations in the composition of the microbiome in CKD may contribute to the systemic inflammation and accumulation of gut-derived uremic toxins, which play a central role in the pathogenesis of accelerated cardiovascular disease and numerous other CKD-associated complications. This review is intended to provide a concise description of the potential role of the CKD-associated changes in the gut microbiome and its potential role the pathogenesis of inflammation and uremic toxicity. In addition, the potential efficacy of pre- and pro-biotics in the restoration of the microbiome is briefly described.

Brazil nut (Bertholletia excelsa, H.B.K.) improves oxidative stress and inflammation biomarkers in hemodialysis patients.

Cumulative evidence indicates that oxidative stress and inflammation frequently occurs in patients undergoing maintenance hemodialysis (HD) and as a result of overproduction of reactive oxygen species (ROS) and a decrease of antioxidant defenses such as selenium (Se). Previous studies in our laboratory showed that the supplementation of 1 unit of Brazil nut (the richest known food source of Se) a day during 3 months is effective to improve Se status and increase glutathione peroxidase (GPx) levels in HD patients. The aim of this study was to evaluate the effect of Brazil nut supplementation on oxidative stress and inflammation markers in HD patients. Forty HD patients from Rio de Janeiro, Brazil were studied. All patients received one nut per day for 3 months. The Se plasma levels and GPx, 8-isoprostane, 8-hydroxy-2-deoxyguanosine (8-OHdG), and cytokine (TNF-α and IL-6) levels and lipid profile were determined before and after 3 months of supplementation. The plasma Se and GPx activity increased, while cytokines, 8-OHdG, and 8-isoprostane plasma levels decreased significantly after 3 months supplementation. HDL-c levels increased and LDL-c levels decreased significantly. These data suggest that the consumption of only one Brazil nut per day during 3 months was effective to reduce the inflammation, oxidative stress markers, and the atherogenic risk, thereby increasing the antioxidant defenses in HD patients. Our results indicate that Brazil nut as Se source plays an important role as an anti-inflammatory and antioxidant agent in HD patients.

Fructose intake: is there an association with uric acid levels in nondialysis-dependent chronic kidney disease patients?

INTRODUCTION: Fructose intake has increased dramatically in consequence of the consumption of fructose-based sweetened foods and beverages. Research suggests that high fructose intake has a strong association with uric acid (UA) levels and worse prognosis of chronic kidney disease (CKD). OBJECTIVE: The aim of this study was to investigate the influence of fructose intake on plasma UA levels in nondialysis- dependent CKD patients. METHODS: Fifty-two patients on stages 3-5 (64.2 ± 9.6 years, 24 men, glomerular filtration rate of 30.5 ± 10.3 ml/ min) were divided into two groups: high fructose intake (>50 g/d, n=29, 61.7 ± 9.3 years) and low fructose intake (

Introducción: El consumo de fructosa ha aumentado dramáticamente en consecuencia del consumo de alimentos y bebidas azucaradas a base de fructosa. Pesquisas sugieren que el alto consumo de fructosa tiene una fuerte asociación con niveles de ácido úrico (AU) y empeora el pronóstico de la enfermedad renal crónica (ERC). Objetivo: El objetivo de este estudio fue investigar la influencia del consumo de fructosa en los niveles plasmáticos de ácido úrico en pacientes con ERC que no son dependiente de diálisis. Métodos: Cincuenta y dos pacientes en fases 3-5 (64,2±9,6 años, 24 hombres, tasa de filtración glomerular de 30,5±10,3ml/min) se dividieron en dos grupos: alto consumo de fructosa (>50g/día, n=29, 61,7± 9,3 años) y bajo consumo de fructosa (

Is there association between acyl-ghrelin and inflammation in hemodialysis patients?

INTRODUCTION AND OBJECTIVES: Patients with chronic kidney disease (CKD) present anorexia, which may be related with the chronic inflammatory process. Thus the objective of this study was to evaluate if there is association between inflammation and the orexigenic hormone, acyl-ghrelin, in CKD patients undergoing hemodialysis (HD). METHODS: Thirty-six patients were studied (61.1% men, 46.7 ± 14.9 years, BMI 22.9 ± 3.9 kg/m²) in regular HD program (65.0 ± 46.8 months). Plasma levels of acyl-ghrelin and inflammatory markers TNF-α, IL-6 and CRP were measured by enzyme immunoassay (ELI-SA, Enzyme Linked Immunosorbent Assay). Anthropometric parameters were collected for assessment of nutritional status and dietary intake was assessed by food recall. RESULTS: The patients presented elevated plasma levels of IL-6 (83 ± 10 pg/mL), TNF-α (21.06 pg/mL [20.6-40.0]) and CRP (2.7 pg/mL [1.73.4]) compared to normal values. Acylghrelin plasma levels were (18.0 [1.3 to 77.7 pg/mL]) low when compared to healthy individuals. However, patients with high BMI (> 25 kg/m²) presented lower acyl-ghrelin plasma levels (13.6 [1.3 to 30.5] pg/mL) when compared to patients with BMI < 25 kg/m² (21.7 [7.4 to 77.7] pg/mL) (p < 0.05). Acylghrelin and BMI were negatively correlated (r = -0.38, p = 0.02) and there was no significant correlation between acyl-ghrelin and inflammatory markers. CONCLUSIONS: Hemodialysis patients showed low acyl-ghrelin levels and seem to present an acyl-ghrelin resistance and there was no correlation between inflammation and this orexigenic hormone.

Há associação entre acyl-grelina e inflamação em pacientes em hemodiálise? / Is there association between acyl-ghrelin and inflammation in hemodialysis patients?

INTRODUÇÃO E OBJETIVOS: Pacientes com doença renal crônica (DRC) apresentam um quadro de anorexia que pode estar relacionado com o processo inflamatório crônico, característico desta população. Assim, o presente estudo teve como objetivo avaliar se há associação entre inflamação e o hormônio orexígeno, acyl-grelina, em pacientes com DRC em hemodiálise (HD). MÉTODOS: Foram estudados 36 pacientes (61,1% homens; 46,7 ± 14,9 anos; IMC 22,9 ± 3,9 kg/m²) em programa regular de HD (65,0 ± 46,8 meses em HD). Os níveis plasmáticos de acyl-grelina e dos marcadores inflamatórios (TNF-α, IL-6 e PCR) foram medidos com o uso do método imunoenzimático (ELISA, Enzyme Linked Immunosorbent Assay). Dados antropométricos foram coletados para avaliação do estado nutricional e a ingestão alimentar foi analisada por meio de recordatório alimentar de 24h de 2 dias. RESULTADOS: Os pacientes apresentaram elevados níveis de IL-6 (83 ± 10 pg/mL), TNF-α (21,06 pg/mL [20,6-40,0]) e PCR (2,7 pg/mL [1,7-3,4]) quando comparados a valores normais. Os níveis plasmáticos de acyl-grelina (18,0 pg/mL [1,3-77,7 pg/mL]) foram baixos comparados com valores de indivíduos saudáveis. Porém, pacientes com elevado IMC (> 25 kg/m²) apresentaram menores concentrações plasmáticas de acyl-grelina (13,6 [1,3-30,5] pg/mL) em relação aos pacientes com IMC < 25 kg/m² (21,7 [7,4-77,7] pg/mL (p < 0,05). Houve correlação negativa entre o IMC e acyl-grelina (r = -0,38; p = 0,02), porém, não houve correlação significativa entre acyl-grelina e os marcadores inflamatórios. CONCLUSÃO: Apesar dos pacientes em HD apresentarem baixas concentrações de acyl-grelina e uma provável resistência a este hormônio, não houve associação entre inflamação e acyl-grelina.

INTRODUCTION AND OBJECTIVES: Patients with chronic kidney disease (CKD) present anorexia, which may be related with the chronic inflammatory process. Thus the objective of this study was to evaluate if there is association between inflammation and the orexigenic hormone, acyl-ghrelin, in CKD patients undergoing hemodialysis (HD). METHODS: Thirty-six patients were studied (61.1% men, 46.7 ± 14.9 years, BMI 22.9 ± 3.9 kg/m²) in regular HD program (65.0 ± 46.8 months). Plasma levels of acyl-ghrelin and inflammatory markers TNF-α, IL-6 and CRP were measured by enzyme immunoassay (ELI-SA, Enzyme Linked Immunosorbent Assay). Anthropometric parameters were collected for assessment of nutritional status and dietary intake was assessed by food recall. RESULTS: The patients presented elevated plasma levels of IL-6 (83 ± 10 pg/mL), TNF-α (21.06 pg/mL [20.6-40.0]) and CRP (2.7 pg/mL [1.73.4]) compared to normal values. Acylghrelin plasma levels were (18.0 [1.3 to 77.7 pg/mL]) low when compared to healthy individuals. However, patients with high BMI (> 25 kg/m²) presented lower acyl-ghrelin plasma levels (13.6 [1.3 to 30.5] pg/mL) when compared to patients with BMI < 25 kg/m² (21.7 [7.4 to 77.7] pg/mL) (p < 0.05). Acylghrelin and BMI were negatively correlated (r = -0.38, p = 0.02) and there was no significant correlation between acyl-ghrelin and inflammatory markers. CONCLUSIONS: Hemodialysis patients showed low acyl-ghrelin levels and seem to present an acyl-ghrelin resistance and there was no correlation between inflammation and this orexigenic hormone.

Reduced plasma zinc levels, lipid peroxidation, and inflammation biomarkers levels in hemodialysis patients: implications to cardiovascular mortality.

Despite the fact that low plasma zinc (Zn) levels play important roles in the oxidative stress, the relationships between lipid peroxidation and inflammation biomarkers with low plasma Zn levels have not been investigated in chronic kidney disease (CKD) patients. The aim of this study was to evaluate the Zn plasma levels, electronegative LDL [LDL(-)] levels, and inflammation markers as predictors of cardiovascular (CV) mortality in hemodialysis (HD) patients. Forty-five HD patients (28 men, 54.2 ± 12.7 years, 62.2 ± 51.4 months on dialysis and BMI 24.3 ± 4.1 kg/m(2)) were studied and compared to 20 healthy individuals (9 men, 51.6 ± 15.6 years, BMI 25.2 ± 3.9 kg/m(2)) and followed for 24 months to investigate the risks for CV mortality. LDL(-) levels were measured by ELISA, plasma Zn levels by atomic absorption spectrophotometry, C-reactive protein (CRP) level by immunoturbidimetric method, and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1) levels by a multiplex assay kit. HD patients presented low plasma Zn levels (54.9 ± 16.1 µg/dL) and high-LDL(-) (0.18 ± 0.12 U/L) and TNF-α (5.5 ± 2.2 pg/mL) levels when compared to healthy subjects (78.8 ± 9.4µ g/dL, 0.10 ± 0.08U/L, 2.4 ± 1.1 pg/mL, respectively, p < 0.05). Zn plasma levels were negatively correlated to TNF-α (r = -0.49; p = 0.0001) and LDL(-) (r = -0.33; p = 0.008). During the 2 years, 24.4% of the patients died, all due to CV disease. Analysis by the Cox model showed that high CRP, TNF-α, IL-6 levels, and long duration of HD were significant predictors of mortality. In conclusion, reduced Zn levels were associated with lipid peroxidation and inflammation, and we confirm here in a Brazilian cohort of HD patients that inflammation markers are strong predictors of CV death.

Is there association between uric acid and inflammation in hemodialysis patients?

BACKGROUND: Elevated serum uric acid has been associated with a variety of cardiovascular disease and with inflammation, but these have been little explored in chronic kidney disease (CKD). Elevated uric acid levels are common in CKD patients and could be involved in inflammatory milieu; our aim was to analyze the association between uric acid and inflammatory markers in hemodialysis (HD) patients. DESIGN: This was a cross-sectional study. SETTING: This study was conducted from private clinic, Rio de Janeiro, Brazil. PATIENTS: This study included 50 HD patients and 21 healthy subjects. METHODS AND PROCEDURES: This study included 50 HD patients [62% men, 54.3 ± 12.6 years, 57.5 ± 50.1 months on dialysis, and body mass index (BMI), 24.4 ± 4.1 kg/m2] and 21 healthy individuals (45% men, 50.7 ± 15.7 years and BMI, 25.5 ± 4 kg/m2). Uric acid was measured using uricase-PAP method; inflammatory [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP)] and atherosclerosis markers [intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1)] were measured by a multiplexed assay. RESULTS: PATIENTS presented high levels of TNF-α, IL-6, CRP, VCAM-1, ICAM-1 (5.5 ± 2.1 pg/mL, 4.1 ± 1.6 pg/mL, 0.32 ± 0.30 mg/mL, 48.5 ± 8.5 ng/mL, 20.5 ± 15.9 ng/mL, respectively), compared with healthy individuals (2.4 ± 1.1 pg/mL, 2.7 ± 0.4 pg/mL, 0.11 ± 0.12 mg/mL, 23.8 ± 5.5 ng/mL, 7.2 ± 1.2 ng/mL, respectively) ( p < 0.04). Uric acid levels were also higher in HD patients (5.4 ± 1.3 mg/dL) than in healthy individuals (3.9 ± 0.9 mg/dL) ( p < 0.02). There was a positive correlation between uric acid and inflammatory markers, IL-6 (r = 0.30, p = 0.01), CRP (r = 0.37, p = 0.003), TNF-α (r = 0.40, p = 0.001), ICAM-1 (r = 0.53, p = 0.0001), and VCAM-1 (r = 0.45, p = 0.0001). CONCLUSION: These original data suggest that uric acid may have a role in inflammation and atherosclerosis in HD patients. However, further prospective studies involving intervention trials should be conducted in order to search for actual causality relationship between these markers.

Zinc-α2-glycoprotein: is there association between this new adipokine and body composition in hemodialysis patients?

Peptides involved in the regulation of body composition are of interest in hemodialysis (HD) patients because protein wasting associated with high fat mass (FM) is present in these patients. Zinc-α2-glycoprotein (ZAG), a new adipokine, is involved in the regulation of lipid metabolism, adiposity, and energy balance. The purpose of this study was to evaluate ZAG levels and its relationship with body composition and dietary intake in HD patients. Forty-nine HD patients (28 men, 53.1 ± 12.5 years, and BMI 24.0 ± 4.3 kg/m2) were studied and compared with 20 healthy subjects (9 men, 49.5 ± 15.2 years, and BMI 25.6 ± 4.1 kg/m(2)). Plasma ZAG levels were measured using the ELISA methods and body composition was evaluated through anthropometric data. Dietary intake was assessed 3 days by 24-hour food recall. Although most of the HD patients (59.2%) were eutrophic according to BMI, 92.3% presented high percentage of body fat (BF), and 43.5%, reduced fat-free mass according to midarm muscle circumference values. ZAG levels were ∼2.5-fold higher in HD patients (135.9 ± 40.9 mg/L) compared with healthy individuals (54.6 ± 23.0 mg/L) (p < 0.0001). Circulating ZAG was not associated with dietary intake; however, this peptide was negatively correlated with %BF and, for each 1% reduction in BF, ZAG levels increased by 2.4 mg/L (p = 0.02). In summary, circulating ZAG is increased and inversely correlated with adiposity in HD patients; however, in spite of its higher plasma levels, the majority of HD patients did not show low BF.

The relationship between apelin and parathyroid hormone in hemodialysis patients.

Both apelin and parathyroid hormone (PTH) are endogenous ligands for G-protein-coupled receptors. Apelin acts as a mitogenic agent for osteoblasts, and metabolic bone abnormalities are frequently seen in hemodialysis (HD) patients because of hyperparathyroidism. The aim of this study was to analyze plasma apelin levels in HD patients and to determine whether they are related to PTH concentrations. A total of 23 HD patients [15 men and 8 women, with a mean (SD) age of 54.2 (4.4) years and a mean body mass index (BMI) of 25.0 (4.1) kg/m(2)] were studied and compared with 15 healthy subjects [6 men and 9 women, with a mean (SD) age of 51.3 (13.6) years and a BMI of 27.0 (4.3) kg/m(2)]. Plasma apelin-36 was measured using an enzyme immunometric assay method and PTH was measured by ELISA. There was no significant difference in apelin levels between the patients [0.80 (0.6) ng/mL] and the healthy subjects [0.83 (0.23) ng/mL]. There was a positive correlation between apelin and PTH (r = 0.66, p = 0.0001). The patients with PTH >300 pg/mL had significantly higher plasma apelin levels [1.17 (0.7) ng/mL] compared with the patients with PTH <300 pg/mL [0.50 (0.15) ng/mL] (p = 0.003). In conclusion, HD patients with secondary hyperparathyroidism have high plasma apelin levels, which suggest that apelin may protect bone in HD patients by acting as an osteoblastic factor.

Relationship between zinc levels and plasma leptin in hemodialysis patients.

UNLABELLED: Recent evidences suggested a possible relationship between zinc deficiency and leptin levels in pathogenesis of anorexia in chronic kidney disease. The present study addressed the relationship between zinc and leptin in hemodialysis (HD) patients. METHODS: Fifty HD patients (54.3±12.7years old, 62% men) were studied and compared to 21 healthy volunteers (50.7±15.7years old, 43% men). Biochemical data, serum zinc, plasma leptin, IL-6, TNF-α and C-Reactive Protein levels were determined. Anthropometric parameters, food intake and appetite score were also assessed. RESULTS: The leptin levels were higher in HD patients (16.1µg/mL (0.21-118.25) vs 6.0µg/mL (0.50-23.10)) in healthy volunteers (p=0.04), whereas serum zinc levels were lower (54.5±16.3µg/dL) compared to healthy volunteers (78.4±9.4µg/dL) (p=0.0001). The plasma leptin was correlated negatively with plasma zinc (r=-0.33; p=0.007), energy (r=-0.38; p=0.002) and protein intake (r=-0.34; p=0.006) and, positively correlated with BMI (r=0.54; p=0.0001), % body fat (r=0.70; p=0.0001) and conicity index (r=0.46; p=0.001). Plasma zinc was associated with hemoglobin (r=0.30; p=0.04) and negatively associated with TNF-α (r=-0.37; p=0.002) and C-Reactive Protein (r=-0.37; p=0.004). There was no correlation among Zn, leptin and appetite score in these patients. CONCLUSION: This study showed that low plasma zinc levels are negatively associated with high leptin levels in HD patients.

Is a body mass index of 23 kg/m² a reliable marker of protein-energy wasting in hemodialysis patients?

OBJECTIVE: To evaluate the body composition and inflammatory status in patients on hemodialysis (HD) according to the cutoff of 23 kg/m² for the body mass index (BMI). METHODS: Forty-seven patients (30 men, 11 diabetics, 53.8 ± 12.2 y of age, 58.2 ± 50.9 mo on HD) were studied. Anthropometric data and handgrip strength were evaluated. C-reactive protein, tumor necrosis factor-α, leptin, and interleukin-6 were measured. Mortality was assessed after 24 mo of follow-up. RESULTS: Nineteen patients (40.4%) presented BMI values lower than 23 kg/m² and leptin levels, midarm muscle area, and free-fat mass were significantly lower in these patients. The prevalence of functional muscle loss according to handgrip strength was not different between the BMI groups. The sum of skinfold thicknesses, the percentage of body fat, fat mass, the fat mass/free-fat mass ratio, and waist circumference were significantly lower in patients with a BMI lower than 23 kg/m², but the mean values did not indicate energy wasting. Patients with a BMI higher than 23 kg/m² presented a higher prevalence of inflammation and higher waist circumference and body fat values. The adiposity parameters were correlated with C-reactive protein and leptin. A Cox multivariate regression analysis demonstrated that C-reactive protein, tumor necrosis factor-α, and interleukin-6 predict cardiovascular mortality. CONCLUSION: Patients on HD with a BMI lower than 23 kg/m² did not present signs of energy wasting, whereas those with a BMI higher than 23 kg/m² had more inflammation, probably because of a greater adiposity. Thus, the BMI value of 23 kg/m² does not seem to be a reliable marker of protein-energy wasting in patients on HD.