Rapamycin Combined with α-Cyanoacrylate Contributes to Inhibiting Intimal Hyperplasia in Rat Models / Rapamicina em Combinação com α-Cianoacrilato Contribui à Inibição de Hiperplasia Intimal em Modelos em Ratos

Abstract Background: Vein graft restenosis has an adverse impact on bridge vessel circulation and patient prognosis after coronary artery bypass grafting. Objectives: We used the extravascular supporter α-cyanoacrylate (α-CA), the local application rapamycin/sirolimus (RPM), and a combination of the two (α-CA-RPM) in rat models of autogenous vein graft to stimulate vein graft change. The aim of our study was to observe the effect of α-CA, RPM, and α-CA-RPM on vein hyperplasia. Methods: Fifty healthy Sprague Dawley (SD) rats were randomized into the following 5 groups: sham, control, α-CA, RPM, and α-CA-RPM. Operating procedure as subsequently described was used to build models of grafted rat jugular vein on carotid artery on one side. The level of endothelin-1 (ET-1) was determined by enzyme-linked immunosorbent assay (ELISA). Grafted veins were observed via naked eye 4 weeks later; fresh veins were observed via microscope and image-processing software in hematoxylin-eosin (HE) staining and immunohistochemistry after having been fixed and stored" (i.e. First they were fixed and stored, and second they were observed); α-Smooth Muscle Actin (αSMA) and von Willebrand factor (vWF) were measured with reverse transcription-polymerase chain reaction (RT-PCR). Comparisons were made with single-factor analysis of variance and Fisher's least significant difference test, with p < 0.05 considered significant. Results: We found that intimal thickness of the α-CA, RPM, and α-CA-RPM groups was lower than that of the control group (p < 0.01), and the thickness of the α-CA-RPM group was notably lower than that of the α-CA and RPM groups (p < 0.05). Conclusion: RPM combined with α-CA contributes to inhibiting intimal hyperplasia in rat models and is more effective for vascular patency than individual use of either α-CA or RPM.

Resumo Fundamento: Reestenose de enxertos venosos tem um impacto adverso na circulação de pontagens e no prognóstico de pacientes após a cirurgia de revascularização miocárdica. Objetivos: Nós utilizamos α-cianoacrilato (α-CA) como suporte extravascular, rapamicina/sirolimus (RPM) como aplicação local e a combinação dos dois (α-CA-RPM) em modelos de enxerto venoso autógeno em ratos para estimular mudança no enxerto venoso. O objetivo do nosso estudo foi observar o efeito de α-CA, RPM e α-CA-RPM na hiperplasia venosa. Métodos: Cinquenta ratos Sprague Dawley (SD) saudáveis foram randomizados nos 5 grupos seguintes: sham, controle, α-CA, RPM e α-CA-RPM. O procedimento operacional descrito subsequentemente foi utilizado para construir modelos de enxertos da veia jugular na artéria carótida em ratos, em um lado. O nível de endotelina-1 (ET-1) foi determinado por ensaio de imunoabsorção enzimática (ELISA). As veias enxertadas foram observadas a olho nu 4 semanas após; as veias frescas foram observadas via microscópio e software de processamento de imagem com coloração hematoxilina-eosina (HE) e imuno-histoquímica depois de serem fixadas e armazenadas; α-actina do músculo liso (αSMA) e o fator de von Willebrand (vWF) foram medidos com reação em cadeia da polimerase-transcriptase reversa (RT-PCR). Realizaram-se as comparações com análise de variância de fator único (ANOVA) e o teste de diferença mínima significativa (LSD) de Fisher, com p < 0,05 sendo considerado estatisticamente significante. Resultados: Nós achamos que a espessura intimal nos grupos α-CA, RPM e α-CA-RPM era menor que no grupo controle (p < 0,01) e a espessura no grupo α-CA-RPM era notavelmente menor que nos grupos α-CA e RPM (p < 0,05). Conclusão: A combinação de RPM e α-CA contribui à inibição de hiperplasia em modelos em ratos e é mais efetivo para patência vascular que uso individual de α-CA ou RPM.

The effects of inhaled NO on plasma vasoactive factor and CTnI level in rabbits with acute massive pulmonary embolism

Abstract Purpose: To investigate changes in the plasma concentrations of cardiac troponin I (CTnI), thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and endothelin-1 (ET-1) in rabbits with massive pulmonary embolism (AMPE) and the impact of nitric oxide inhalation (NOI) on these indices. Methods: A total of 30 Japanese rabbits were used to construct an MPE model and were divided into 3 groups equally (n=10), including an EXP group (undergoing modeling alone), an NOI group (receiving NOI 2 h post-modeling) and a CON group (receiving intravenous physiological saline). Results: In the model group, plasma concentration of CTnI peaked at 16 h following modeling (0.46±0.10 µg/ml) and significantly decreased following NOI. Plasma levels of TXB2, PGI2 and ET-1 peaked at 12, 16 and 8 h following modeling, respectively, and significantly decreased at different time points (0, 2, 4, 8, 12, 16, 20 and 24 h) following NOI. A significant correlation was observed between the peak plasma CTnI concentration and peak TXB2, 6-keto prostaglandin F1α and ET-1 concentrations in the model and NOI groups. Conclusion: Increases in plasma TXA2, PGI2 and ET-1 levels causes myocardial damage in a rabbit model of AMPE; however, NOI effectively down regulates the plasma concentration of these molecules to produce a myocardial-protective effect.

Protective effect of dexmedetomidine against myocardial ischemia-reperfusion injury in rabbits

Abstract Purpose: To investigate the influence of dexmedetomidine on myocardial ischemia-reperfusion injury (IRI) in rabbits. Methods: Twenty-four New Zealand white rabbits were randomly divided into two equal-sized groups: IRI group (group IR) and dexmedetomidine group (group D). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular diastolic pressure (LVDP), +dp/dtmax, -dp/dtmax, and t-dp/dtmax were recorded and calculated at the following time points: before (T0) and after (T1) dexmedetomidine infusion, after 30-min ischemia (T2), and after 120-min reperfusion (T3). The levels of plasma endothelin 1 (ET-1), thromboxane A2 (TXA2), and platelet activating factor (PAF); area of myocardial infarction (MI); and no-reflow area were evaluated. Results: SBP, DBP, LVSP, LVEDP, LVDP, and +dp/dtmax at T3 were higher in group D than in group IR (P<0.05). The average no-reflow area in group IR was significantly smaller than that in group D (14±3% vs. 38±5%, P=0.0116). The ET-1, TXA2, and PAF levels at T2 and T3 were higher than those at T0 in both groups (P<0.05). Conclusion: Dexmedetomidine could reduce the magnitude of ischemic myocardial no-reflow area and protect the myocardium with ischemia-reperfusion injury.

Evaluation of biochemical and clinical markers of endothelial dysfunction and their correlation with urinary albumin excretion in patients with type 1 diabetes mellitus

ABSTRACT Objective Endothelial dysfunction (ED) plays an important role in the pathogenesis of diabetic nephropathy. The purpose of the study was to determine flow mediated endothelial dependent vasodilatation (FMD) measurements and serum soluble (s) endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) levels in patients with type 1 diabetes mellitus (T1DM) with or without increased urinary albumin excretion (UAE) and compare them with the healthy controls. Subjects and methods Seventy three patients with T1DM were enrolled. Patients were divided into two subgroups according to microalbumin measurements in 24-hr urine collections. The diabetic patients without microalbuminuria (41 patients) were defined as Group I and those with microalbuminuria (32 patients) were defined as group II. A hundred age and sex matched healthy subjects participated as the control group (Group III). Serum sET-1, sICAM-1, sVCAM-1 levels and FMD measurements were determined in all participants. Results Median FMD measurement was significantly lower in the diabetic groups compared with the control group (6.6, 6.4 and 7.8% in Group I, II and III, respectively) (p < 0.05). FMD was negatively correlated with age (p = 0.042). Median serum sICAM-1 level was higher in the patient groups compared to the control group (p < 0.05). Median serum sVCAM-1 level was higher in the group of patients with increased albuminuria compared to the normoalbuinuric and the control group (p < 0.05). Serum sVCAM-1 level was found to be positively correlated with degree of urinary albumin excretion (p < 0.001). Conclusion We assume that sVCAM-1 may be used as a predictive marker for risk stratification for nephropathy development and progression.

Serum big endothelin-1 as a biomarker in oral squamous cell carcinoma patients: an analytical study

Detection of abnormally elevated levels of molecules in patients with oral cancer may be useful in early diagnosis. These markers can be included in current Histopathology grading and in TNM staging systems of Oral Squamous Cell Carcinoma (OSCC) to make it more efficient. Several pro-angiogenic molecules have been assessed for the same reason. Endothelin-1 (ET-1) is a vasoactive peptide associated with the development and spread of many solid tumors, including Squamous Cell Carcinoma (SCC), but its utility in OSCC has not been confirmed.Objective This study aims to evaluate the role of the serum big ET-1 as a biomarker of OSCC, by correlating it with the clinical staging and the histopathological grading.Material and Methods Serum levels of big ET-1 measured by the sandwich Enzyme-Linked Immunosorbent Assay (ELISA) in 40 OSCC cases were compared with the levels from the control group using independent t-test. Clinical stages and histopathological grades of OSCC cases were compared in relation to their mean levels of serum big ET-1, one using the Analysis of Variance (ANOVA) test and the other the independent t-test, respectively. The significance of the mean difference between the groups was evaluated by Tukey’s multiple comparison test. All statistical analyses were performed on GraphPad statistical software version 5.0.Results By comparing the mean of the big ET-1 concentrations of cases and controls, the independent t-test revealed significant higher big ET-1 concentration of OSCC cases when compared to controls (p<0.0001). Tukey’s multiple comparison test also revealed statistically significant difference among all OSCC stages in relation to the mean levels of serum big ET-1. However, the mean of the big ET-1 concentrations of cases of grade I and of grade II did not differ statistically (p=0.729).Conclusion Serum big ET-1 levels may be useful as a diagnostic tool in OSCC and as an adjunct to OSCC staging. However, its use as a prognostic marker warrants larger prospective studies.

Metabolic interactions between hyperhomocysteinemia and endothelin-1 among Tunisian patients with acute coronary diseases

BACKGROUND: Acute coronary syndromes (ACS) are complex and polygenic diseases which are a real problem of public health. These syndromes require multidisciplinary studies to understand the pathogenesis mechanisms and metabolic interactions between different risk factors.This study aimed to explore the variation of two coronary risk parameters not mentioned by Framingham cohorts, hyperhomocysteinemia and endothelin-1 (ET-1) in Tunisian coronary and the study of the variation of these parameters based on various cardiac risk factors and metabolic relationship between them.To 157 coronary and 142 healthy subjects, the concentration of homocysteine was quantified by fluorescence polarization immunoassay; the concentration of ET-1 was measured by an analytical technique, the High Performance Liquid Chromatography (HPLC) coupled with mass spectrometry. RESULTS: Our study showed that homocysteine and ET-1 were significantly higher in patients compared to healthy subjects (24.40 ± 12.5 µmol/L vs 7.44 ± 2.5 µmol/L p <0.00001) for homocysteine and (15.2 ± 5.3 nmol/L vs 7.1 ± 2.7 nmol/L, p <0.00001) for ET-1. On the other hand, homocysteine varies according to tobacco and diabetes while ET-1 depends on the sex, hypertension, smoking, obesity and dyslipidemia and a statistically negative correlation was shown between homocysteine and ET-1 in coronary patients (r = -0.66 p <0.00001. CONCLUSION: The study of the variation of these two parameters in coronary patients and metabolic exploration of the relationship between homocysteine and ET-1 according to various risk factors and the interactions between themselves facilitates the decision of therapeutic treatment.

IL-10 and ET-1 as biomarkers of rheumatic valve disease / IL-10 e ET-1 como biomarcadores de doença valvar reumática

Objective: To evaluate the immunological profile and gene expression of endothelin-1 (ET-1) in mitral valves of patients with rheumatic fever originated from a reference service in cardiovascular surgery. Methods: This was a quantitative, observational and cross-sectional study. Thirty-five subjects (divided into four groups) participated in the study, 25 patients with chronic rheumatic heart disease and ten control subjects. The mean age of the sample studied was 34.5 years. Seventeen of them (48.58%) were male and 18 (51.42%) were female. Inflammatory cytokines (TNF-α, IL-4 and IL-10) were measured and ten mitral valves of patients who underwent first valve replacement were collected for determination of gene expression of endothelin-1 by real time PCR. Results: Among the groups studied (patients vs. controls), there was a statistically significant difference in IL-10 levels (P=0.002), and no differences in other cytokines. Expression of endothelin-1 was observed in 70% of samples. Quantitatively, average of ET-1 expression was 62.85±25.63%. Conclusion: Inflammatory cytokine IL-10 participates in the maintenance of chronicity of rheumatic fever in patients who underwent valve replacement and those who are undergoing medical treatment. The expression of endothelin-1 in heart valve lesions in patients undergoing mitral valve replacement confirms its association with inflammatory activity in rheumatic fever. .

Objetivo: Avaliar o perfil imunológico e a expressão gênica de endotelina-1 em valvas mitrais de pacientes com febre reumática, originados de um serviço de referência em cirurgia cardiovascular. Métodos: Este foi um estudo quantitativo, observacional e transversal. Trinta e cinco indivíduos (divididos em quatro grupos) participaram do estudo, 25 deles com doença cardíaca reumática crônica, além de 10 controles. A média de idade da amostra estudada foi de 34,5 anos. Dezessete (48,58%) dos indivíduos eram homens, e 18 (51,42%) eram mulheres. Foram medidas algumas citocinas inflamatórias (TNF-α, IL-4 e IL-10) e coletadas 10 valvas mitrais de pacientes que se submeteram a primeira troca valvar para determinação da expressão gênica de endotelina-1 pelo PCR real-time. Resultados: Entre os grupos estudados (pacientes e controles), observou-se diferença estatisticamente significante em relação aos níveis de IL-10 (P=0,002), sem diferenças nas outras citocinas. Em relação à endotelina-1, foi observada sua expressão em 70% das amostras. Quantitativamente, a expressão média de endotelina-1 foi de 62,85±25,63%. Conclusão: A citocina inflamatória IL-10 participa da manutenção da cronicidade da febre reumática em pacientes que se submeteram a troca valvar e naqueles que estão em tratamento médico. A expressão de endotelina-1 nas lesões em valvas cardíacas de pacientes que foram submetidos à troca valvar mitral confirma sua relação com a atividade inflamatória na febre reumática. .

Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic mice

OBJECTIVE: To investigate the antifibrotic effects of crocetin in scleroderma fibroblasts and in sclerotic mice. METHODS: Skin fibroblasts that were isolated from three systemic scleroderma (SSc) patients and three healthy subjects were treated with crocetin (0.1, 1 or 10 μM). Cell proliferation was measured with an MTT assay. Alpha-smooth muscle actin was detected via an immunohistochemical method. Alpha 1 (I) procollagen (COL1A1), alpha 1 (III) procollagen (COL3A1), matrix metalloproteinase (MMP)-1 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA levels were measured using real-time PCR. SSc mice were established by the subcutaneous injection of bleomycin. Crocetin (50 mg/kg/d) was injected intraperitoneally for 14 days. Dermal thickness and lung fibrosis were assessed with Masson's trichrome staining. Plasma ET-1 was detected with an enzyme-linked immunosorbent assay (ELISA). Skin and lung ET-1 and COL1A1 mRNA levels were measured via real-time PCR. RESULTS: Crocetin inhibited the proliferation of SSc and normal fibroblasts, an effect that increased with crocetin concentration and incubation time. Crocetin decreased the expression of α-SMA and the levels of mRNA for COL1A1, COL3A1 and matrix metalloproteinase-1, while crocetin increased TIMP-1 mRNA levels in both SSc and normal fibroblasts. Skin and lung fibrosis was induced, and the levels of ET-1 in the plasma, skin and lungs were elevated in bleomycin-injected mice. Crocetin alleviated the thickening of the dermis and lung fibrosis; decreased COL1A1 mRNA levels in the skin and lung; and simultaneously decreased ET-1 concentrations in the plasma and ET-1 mRNA levels in the skin and lungs of the bleomycin-induced sclerotic mice, especially during the early phase (weeks 1-3). CONCLUSION: Crocetin inhibits cell proliferation, differentiation and collagen production in SSc fibroblasts. Crocetin alleviates skin and lung fibrosis in a bleomycin-induced SSc ...

Big endotelina-1 e óxido nítrico em pacientes idosos hipertensos com e sem síndrome da apneia-hipopneia obstrutiva do sono / Big endothelin-1 and nitric oxide in hypertensive elderly patients with and without obstructive sleep apnea-hypopnea syndrome

FUNDAMENTO: O papel do estresse oxidativo em pacientes idosos hipertensos com síndrome de apneia-hipopneia obstrutiva do sono (SAHOS) é desconhecido. Objetivo: O objetivo foi avaliar os níveis de Big Endotelina-1 (Big ET-1) e Óxido Nítrico (NO) em pacientes idosos hipertensos com e sem SAHOS moderada a grave. MÉTODOS: Os voluntários permaneceram internados durante 24 horas. Obtivemos os seguintes dados: índice de massa corporal (IMC), Monitorização Ambulatorial da Pressão Arterial (MAPA) - 24 horas, e medicação atual. Sangue arterial foi coletado às 7:00 h e às 19:00 h para determinar níveis plasmáticos de NO e Big ET-1. A oximetria de pulso foi realizada durante o sono. A correlação de Pearson, Spearman e análise de variância univariada foram utilizadas para a análise estatística. RESULTADOS: Foram estudados 25 sujeitos com SAHOS (grupo 1) e 12 sem SAHOS (grupo 2), com idades de 67,0 ± 6,5 anos, 67,8 ± 6,8 anos, respectivamente. Não foram observadas diferenças significativas entre os grupos em IMC; no número de horas de sono; PA diastólica e sistólica em 24 h; PA de vigília; PA no sono; ou medicamentos usados para controlar a PA. Não foram detectadas diferenças nos níveis de NO e Big ET-1 plasmáticos às 19:00 h, mas às 7:00 h os níveis de de Big ET-1 foram mais altos (p = 0,03). No grupo 1, correlação negativa também foi observada entre a saturação de oxihemoglobina arterial média e a PA sistólica - 24 horas (p = 0,03, r = -0,44), e Big ET-1 (p = 0,04, r = 0,41). CONCLUSÕES: Na comparação entre idosos hipertensos com e sem SAHOS com PA e IMC semelhantes, observou-se níveis mais elevados de Big ET-1 após o sono no grupo SAHOS. Os níveis de NO não diferiram entre os pacientes hipertensos com ou sem SAHOS.

BACKGROUND: The role of oxidative stress in hypertensive elderly patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) is unknown. OBJECTIVE: The purpose was to evaluate the levels of big endothelin-1 (Big ET-1) and nitric oxide (NO) in elderly hypertensive patients with and without moderate to severe OSAHS. METHODS: Volunteers were hospitalized for 24 h. We obtained the following data: body mass index (BMI); 24-ambulatory blood pressure monitoring; and current medication. Arterial blood was collected at 7pm and 7am for determining plasma NO and Big ET-1 levels. Pulse oximetry was performed during sleep. Pearson's or Spearman's correlation and univariate analysis of variance were used for statistical analysis. RESULTS: We studied 25 subjects with OSAHS (group 1) and 12 without OSAHS (group 2) aged 67.0 ± 6.5 years and 67.8±6.8 years, respectively. No significant differences were observed between the groups in BMI; number of hours of sleep; 24-h systolic and diastolic BPs; awake BP, sleep BP and medications to control BP between groups. No differences were detected in plasma Big ET-1 and NO levels at 19:00 h, but plasma Big ET-1 levels at 7:00 h were higher in group 1 (p =0.03). In group 1, a negative correlation was also observed between the mean arterial oxyhemoglobin saturation level, 24-h systolic BP (p = 0.03, r = -0.44), and Big ET-1 (p = 0.04, r = -0.41). CONCLUSIONS: On comparing elderly hypertensive patients with and without OSAHS having similar BP and BMI, we observed higher Big ET-1 levels After sleep in the OSAHS group. NO levels did not differ between the hypertensive patients with or without OSAHS.

Non-dipping pattern of nocturnal blood pressure in obstructive sleep apnea syndrome: possible role of oxidative stress and endothelin-1 precursor

There is growing evidence suggesting that obstructive sleep apnea OSA is linked to the occurrence of cardiovascular disorders. Lack of normal nocturnal dipping of blood pressure has also been considered a risk factor for the occurrence of cardiovascular disorders. Non-dipping has been described in patients with OSA and is attributed to autonomic dysfunction. However, the search for a causal link between OSA and cardiovascular disease is still underway. To evaluate the occurrence of non-dipping pattern of nocturnal blood pressure, and the possible role of oxidative stress and ET-1 precursor in patients with OSA. Thirty eight patients with OSA and fourteen normal control subjects were enrolled in this study and were subjected to history taking, clinical examination, early morning blood samplings for the measurement of serum malondialdehyde [MDA] and endothelin 1 precursor [ET-1 precursor]. All patients with OSA were subjected to full polysomnographic study and monitoring of nocturnal blood pressure changes. Nocturnal blood pressure measurement of all patients revealed that thirty six patients [94.7%] were non-dippers, 15 patients [39.5%] suffered from ischemic heart disease. Serum endothelin-1 precursor and serum malondialdehyde levels were significantly higher in patients with OSA than in the control group. The systolic blood pressure measured before sleep was also significantly higher in patients than in the control group. The Epworth sleepiness scale and the clinical apnea score were significantly higher in patients than in the control group. The high incidence of non-dipping pattern of nocturnal blood pressure in both normotensive and hypertensive patients with OSA may be considered a warning sign for the occurrence of cardiovascular complications in these patients. Both increased oxidative stress and ET-1 precursor may be among the causative factors responsible for the high prevalence of the non-dipping pattern through increasing sympathetic nervous system activity

The effect of serum magnesium levels and serum Endothelin-1 levels on bone mineral density in protein energy malnutrition / Efecto de los niveles séricos de magnesio y los niveles séricos de Endotelina-1 sobre la densidad mineral osea en la malnutrición calórico-proteica

An inadequate and imbalanced intake of protein and energy results in protein-energy malnutrition (PEM). It is known that bone mineral density and serum magnesium levels are low in malnourished children. However, the roles of serum magnesium and endothelin-1 (ET-1) levels in the pathophysiology of bone mineralization are obscure. Thus, the relationships between serum magnesium and ET-1 levels and the changes in bone mineral density were investigated in this study. There was a total of 32 subjects, 25 of them had PEM and seven were controls. While mean serum ET-1 levels of the children with kwashiorkor and marasmus showed no statistically significant difference, mean serum ET-1 levels of both groups were significantly higher than that of the control group. Serum magnesium levels were lower than normal value in 9 (36%) of 25 malnourished children. Malnourished children included in this study were divided into two subgroups according to their serum magnesium levels. While mean serum ET-1 levels in the group with low magnesium levels were significantly higher than that of the group with normal magnesium levels (p < 0.05), mean bone mineral density and bone mineral content levels were significantly lower (p < 0.05). In conclusion, many factors play a role in the pathophysiology of changes in bone mineral density in malnutrition. Our study suggested that lower magnesium levels and higher ET-1 levels might be important factors in changes of bone mineral density in malnutrition. We recommend that the malnourished patients, especially with hypomagnesaemia, should be treated with magnesium early.

El consumo inadecuado y desbalanceado de proteínas y calorías energía conduce a la malnutrición calórico-proteica (MCP). Se sabe que la densidad mineral ósea y los niveles séricos de magnesio son bajos en los ninos malnutridos. Sin embargo, no está claro el papel que desempenan los niveles séricos de magnesio y los niveles séricos de endotelina-1 (ET-1) en la patofisiología de la mineralización del hueso. Por consiguiente, las relaciones entre los niveles séricos de magnesio y los niveles séricos de ET-1, y los cambios en la densidad mineral ósea, constituyen el objeto de investigación de este estudio. Hubo un total de 32 sujetos; 25 de ellos tenían DCP y 7 eran considerados. Si bien los niveles séricos promedios de ET-1 de los ninos con kwashiorkor y marasmo no mostraron diferencia estadística significativa, los niveles séricos promedio de ET-1 de ambos grupos fueron significativamente más altos que los del grupo de control. Los niveles séricos de magnesio estuvieron por debajo del valor normal en 9 (36%) de 25 ninos malnutridos. Los ninos malnutridos incluidos en este estudio fueron divididos en dos sub-grupos según sus niveles de magnesio en suero. Mientras que los niveles séricos promedio de ET-1 en el grupo con niveles bajos de magnesio fueron significativamente más altos que los del grupo con niveles normales de magnesio (p < 0.05), la densidad mineral ósea promedio y los niveles promedio del contenido mineral óseo fueron significativamente más bajos (p < 0.05). En conclusión, muchos factores juegan un papel en la patofisiología de los cambios en la densidad mineral ósea por la malnutrición. Nuestro estudio sugirió niveles más bajos de magnesio y niveles más altos de ET-1 podrían ser factores importantes en los cambios de densidad mineral ósea en la malnutrición. Se recomienda que los pacientes malnutridos, especialmente a causa de hipomagnesemia, sean tratados con magnesio lo más pronto posible.

Avaliação da capilaroscopia usando Endotelina-1 como um marcador de ativação endotelial na lesão microvascular e úlceras cutâneas / Evaluation of the capillaroscopy using endothelin-1 as a marker of endothelial activation in microvascular injury and cutaneous ulcerations

OBJETIVO: Avaliar a presença da ET-1 em pacientes portadores de esclerodermia e a sua correlação com o nível de atividade da doença; verificar se os níveis de endotelina estão associados com o perfil clínico e de autoanticorpos da esclerodermia e, ainda, se há associação com lesão microvascular detectada pela capilaroscopia periungueal. MÉTODOS: Um total de 74 pacientes, sendo 37 portadores de esclerodermia e o restante controle, foram submetidos à dosagem de ET-1 por meio de teste de ELISA. Pacientes com esclerodermia foram analisados através de um questionário sobre características da doença e pesquisa de autoanticorpos. A gravidade da doença foi definida pelos critérios de Medsger e a doença microvascular foi acessada através de capilaroscopia periungueal. RESULTADOS: Dos 37 pacientes com esclerodermia três (8,1%) eram homens e 34 (91,89%) mulheres, com idade média de 48,97 ? 13,36 anos e tempo médio de doença de 42,54 ? 13,35 anos. Os valores da ET-1 nos controles foram de 0,41 a 5,65 pg/ml (mediana de 2,26 pg/ml) e nos com esclerodermia de 0,41 a 8.82 pg/ml (mediana de 0,41 pg/ml) com p de 0,0007. Não houve correlação com o tempo de doença, idade do paciente e com o nível de acometimento cutâneo. Não encontrou-se correlação entre nível de ET-1 sérica e gravidade da doença (p=0,13). Níveis maiores de ET-1 foram observados na forma de superposição (1,49 a 6,82 pg/ml). CONCLUSÃO: Os níveis de ET-1 em esclerodérmicos mostraram-se inferiores aos controles. Não houve associação dos níveis de ET-1 com as variáveis estudadas.

Objectives: To evaluate the presence of ET-1 in patients with scleroderma and its correlation with the level of disease activity; to verify if the levels of endothelin are associated with the clinical profile and autoantibodies of scleroderma, and even if there is an association with microvascular injury detected by nailfold capillaroscopy. METHODS: A total of 74 patients, 37 patients with scleroderma, the remaining being controls, were subjected to measurement of ET-1 by ELISA. Patients with scleroderma were evaluated through a questionnaire about characteristics of the disease and determination of autoantibodies. Disease severity was defined by the criteria of Medsger and microvascular disease was accessed through nailfold capillaroscopy. RESULTS: Of the 37 patients with scleroderma, three (8.1%) were men and 34 (91.89%) women, with a mean age of 48.97 ± 13.36 years and mean disease duration of 42.54 ± 13, 35. The amounts of ET-1 in the controls was 0.41 to 5.65 pg / ml (median of 2.26 pg / ml) and, in the scleroderma group, from 0.41 to 8.82 pg / ml (median, 0.41 pg / ml), with p = 0.0007. There was no correlation with disease duration, patient age and the degree of skin involvement. No correlation was found between serum levels of ET-1 and disease severity (p = 0.13). Higher levels of ET-1 were observed in the form of overlap (1.49 to 6.82 pg / ml). CONCLUSION: The levels of ET-1 in scleroderma were inferior to controls. There was no association of ET-1 levels with the variables studied.

role of the biomarker and the genetic polymorphism of endothelin-1 in pulmonary arterial hypertension among Egyptians

This study analyses for the first time endothelin-1 [ET-1] level, and gene polymorphisms for endothelin-1 [EDN1 gene] in patients with pulmonary arterial hypertension [PAH] in Egypt. Cross-sectional study. Large, tertiary care, Alexandria university teaching hospital, Chest Department. Thirty subjects with PAH with 30 control subjects. Subjects were divided into two groups of matched age and sex were allocated. The first group consisted of thirty subjects, >/=18 years one group with no apparent evidence of disease free from pulmonary hypertension after full medical history, examination, and selected investigations [control group]. The second group consisted of thirty subjects, >/=18 years, suffering from pulmonary hypertension. All subjects who had a documented pulmonary hypertension with routine Echodoppler study were screened for endothelin-1[ET-1] and Gene polymorphism. Measurements and results: This study analyzed the frequency and the potential role of endothelin- 1 and gene polymorphisms, the +134 del/insA, located in the gene encoding for endothelin-1 [EDN1] in PAH. Thirty patients with pulmonary hypertension [12 [40%] men] were included in the study [Table 1]. The mean age of the patients was 53.5 +/- 12.8 years range from 34 to 72 years. The two groups of patients and control subjects were matched as regard the age and gender. The endothelin-1 mean was 1.8 +/- 1.3 fmol/ml with range from 0.3 to 3.8 fmol/ml in the patients group. The endothelin-1 mean was 0.7 +/- 0.05 fmol/ml with range from 0.6 to 0.75 fmol/ml in the patients group. There was a significantly higher level of endothelin-1 in the group of pulmonary hypertension [p < 0.001]. For the groups of polymorphisms studied, there was three genotypes [GT, TT, and GG], no substantial differences in genotype and allele distributions for +134 del/insA located in EDN1 gene, between PAH patients and control population, were observed [DF = 1; C.I. = 95.0; and p= 0.226]. The genotype GG show the highest level of endothelin while the TT type show the lowest value of endothelin-1. Also, we found a significant relation between the higher endothelin-1 level and the lower oxygen saturation [p= 0.049], and the higher meanPAP [p =0.004]. In conclusion, our findings suggest a potential link between endothelin-1 level and specific genotypes in the EDN1 gene and susceptibility for PAH with a worse haemodynamic profile. Further investigations are warranted to understand the molecular basis and to confirm the potential clinical importance of these findings on larger cohorts of patients with PAH. This will impact on the management of PAH of Egyptian patients in the near future

Consequences of hypoxia-reoxygenation phenomena in patients with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome [OSAS] is a common disorder characterized by numerous episodes of absence of respiratory flow during sleep, which can be followed by a decrease in SaO2, which is rapidly normalized when ventilation resumes. We hypothesize that this hypoxia-reoxygenation phenomena may affect the generation of vascular endothelial growth factor [VEGF], erythropoietin [EPO], endothelin-1 [ENDO-1], and inducible nitric oxide synthase [iNOS]. Prospective, patients referred to sleep disorders center. The presence and severity of OSAS were determined using the standard overnight polysomnography. Diagnosis of OSAS was made when the apnea-hypopnea index [AHI] was >/= 15, independent of the appearance of symptoms. Serum levels of VEGF, EPO, ENDO-1, and nitrite-nitrate were measured after overnight fasting in 69 patients with OSAS and in 17 healthy control subjects. Serum levels of VEGF and nitrite-nitrate were measured again after 12 weeks of treatment with continuous positive airway pressure [CPAP] in OSAS patients. Serum VEGF levels were found to be significantly higher and nitrite-nitrate levels were found to be significantly lower in OSAS patients than in controls [P=.003, .008, respectively], but no differences in EPO and ENDO-1 levels were found between the groups. We demonstrated that in OSAS patients, the serum VEGF levels were decreased and nitrate levels were increased after 12 weeks of CPAP treatment [P=.001, .002, respectively]. According to our data, it is likely that hypoxia-reoxygenation phenomena affect the VEGF and nitrite-nitrate levels, which may be pathogenic factors in generating cardiovascular complications in OSAS

Plasma C-Reactive Protein and Endothelin-1 Level in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension

Pulmonary hypertension is a frequent complication of chronic obstructive pulmonary disease (COPD) and associated with a worse survival and increased risk of hospitalization for exacerbation of COPD. However, little information exists regarding the potential role of systemic inflammation in pulmonary hypertension of COPD. The purpose of the present study was to investigate the degree of C-reactive protein (CRP) and endothelin-1 (ET-1) levels in COPD patient with and without pulmonary hypertension. The levels of CRP and ET-1 were investigated in 58 COPD patient with pulmonary hypertension and 50 patients without pulmonary hypertension. Pulmonary hypertension was defined as a systolic pulmonary artery pressure (Ppa) > or =35 mmHg assessed by Doppler echocardiography. Plasma CRP and ET-1 levels were significantly higher in patients with pulmonary hypertension than in patients without hypertension. There were significant positive correlations between the plasma ET-1 level and CRP level in the whole study groups. For COPD patients, systolic Ppa correlated significantly with plasma CRP levels and plasma ET-1 levels. These findings support a possibility that CRP and ET-1 correlate to pulmonary hypertension in COPD patients.

Plasma stable nitric oxide end products and endothelin-1 states in patients undergoing hemodialysis due to chronic end stage rena disease

In patients with end-stage renal disease [ESRD], it is essential to mandate an active screening for high risk factors of coronary atherosclerosis through periodical clinical examination and determination of the traditional and non traditional risk factors for cardiovascular disease [CVD]. Determination of two novel biochemical atherogenic risk factors: plasma nitric oxide [NO] metabolites [nitrite: NO2 and nitrate: NO3] and endothelin-1 [ET-1] concentrations in patients with end stage renal disease who were undergoing hemodialysis. The present study population was classified into: [i] A healthy reference [control] group which comprised 13 clinically healthy blood donors or patients' relatives and [ii] ESRD group which comprised 19 patients with chronic end stage renal failure [ESRD] who were undergoing intermittent hemodialysis [HD] All patients and controls were subjected for determination of plasma native NO-2/NO-3 concentrations by a colorimetric assay and plasma ET-1 concentrations using an enzyme immunometric immunoassay [EIA]. Plasma total nitrites [NO-2,+NO-3], native nitrites and calculated nitrates [umol/mi] and plasma ET-l [pg/mi] levels were significantly higher in ESRD patients both before and after dialysis sessions than their corresponding levels of healthy controls. Hemodialysis sessions induced non significant increase of NO metabolites [NOx, NO2 and NO3] and ET-1 levels above the predialysis values. However, nitrate: native nitrite ratios in the HD-patients both before and after dialysis [1.7: 1 and 1.5: 1] were significantly lower than the corresponding normal ratio [3.1:1]. Plasma total nitrites comprised 21.2% native nitrites in healthy subjects. The native nitrites fraction increased to 37.0% and 40.0% of the total nitrites in ESRF patients immediately before and after HD sessions, respectively. Patients with ESRD who were undergoing hemodialysis presented significant increase of novel vasoactive CVD risk factors [NO and PT-I] when compared with the corresponding healthy reference values. Although there was a significant correlation between No meyabolites and ET-1, plasma NO metabolites concentrations did not necessarily reflect the hemodynamically active plasma NO component

Plasma endothelin-1, homocysteine, and nitric oxide levels in a multiethnic hypertensive cohort from the United Arab Emirates

Hypertension is a major cause of morbidity and mortality in the United Arab Emirates [UAE]. However, little is known regarding vasoactive biomarkers and lipid profiles in hypertensives versus normotensives in this heterogeneous ethnic population. This study aimed to evaluate plasma endothelin-1 [ET-1], homocysteine [Hcy], nitric oxide [NO], and lipid parameters among hypertensive subjects and normotensives controls in a heterogeneous ethnic population from the UAE. We collected venous samples from 164 hypertensive and 112 normotensive subjects matched for age, gender and ethnicity to determine their plasma levels of ET-1, Hcy and NO as well as their lipid profile. Hypertensive subjects displayed significantly higher plasma levels of ET-1 [p < 0.001] and NO [p < 0.001] but lower insulin levels [P<0.006] than normotensives. In contrast, there was no statistically significant difference with regard to Hcy concentrations. Very low-density lipoprotein [VLDL] and triglycerides [TG] levels were significantly [p < 0.01] higher in hypertensives than controls. Total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], and non-esterified fatty acids [NEFA] were significantly lower [p < 0.01] in hypertensives than normotensives. In our heterogeneous ethnic population, levels of ET-1 and NO, but not of Hcy, were found to be associated with hypertension and may possibly contribute to an increased systemic vascular resistance among hypertensives. Whether the elevated ET-1 results are because of overproduction or decreased clearance remains to be ascertained Elevated levels of TG and VLDL, alongside with unaltered TC levels, seem to indicate the presence of type IV hypertriglyceridaemia

Endothelin-1 and leptin as markers of intrauterine growth restriction.

Objective. To explore the role of endothelin-1 (ET-1) and leptin in intrauterine growth restriction (IUGR) among preeclamptic and non-pre-eclamptic women. Methods. Forty three patients with a pregnancy complicated by IUGR, 23 cases with severe pre-eclampsia and 20 cases of non-pre-eclamptic were enrolled. Control group comprised 15 cases with uncomplicated pregnancy. Blood samples from umbilical artery and maternal venous blood were collected at the time of delivery for analysis of ET-1 and leptin levels. Mode of delivery, birth weight and Apgar score were also recorded. Results. The mean maternal and fetal ET-1 level was significantly higher in pregnancies complicated by IUGR than in control group. The mean maternal leptin level was significantly higher in pre-eclamptic patients when compared to nonpreeclamptic and control groups. Mean fetal leptin level was significantly lower in patients compared to control; however, when fetal leptin corrected to fetal weight, it was insignificantly different in the both groups. Conclusion. Maternal plasma ET-1 and leptin correlate with the degree of fetal growth restriction originating from deterioration of placental function. Maternal plasma leptin and ET-1 levels may reflect deterioration in fetal growth.

Hyperdynamic circulatory response to iron deficiency, thalassaemia and sickle cell a anaemias

One of the most interesting areas of research in erythrocyte physiology is the interaction of haemoglobin with nitric oxide [NO]. These two molecules independently fulfill diverse and complex physiological roles, while together they delicately modulate microvascular perfusion in response to second-by-second changes in local metabolic demand, contributing to hypoxic vasodilatation. To highlight on pathophysiological mechanisms of hyperdynamic state in anemic patients as well as to investigate the relation between haemoglobin, NO, endothelin-1 [ET-1], cyclic guanosine monophosphate [c GMP] and endotoxins with hyperdynamic circulatory states in different anaemic patients. Forty five anaemic patients categorized in three groups each fifteen [Iron Deficiency Anaemic, Thalassaemic and Sickle Cell Anaemic patients] in addition to ten healthy controls. Pulse rate, systolic and diastolic blood pressure values were recorded for all subjects. Also, Haemoglobin types and level, serum iron and TIBC, NO, ET-1, c GMP and Endotoxin levels were measured for all. Significant increase in pulse rate and pressure, decrease in diastolic pressure in addition to elevation of NO, cGMP and Endotoxins whereas ET-1 significantly decline in all anemic patients. NO levels when correlated with Hb, ET-1 levels and diastolic blood pressure showed negative significant correlation, while. It was positively correlated with c GMP, Endotoxins, systolic blood pressure and pulse pressure in different anemic groups. Vasodilatation, the main cause of hyperdynamic accompanying anemia contributed to increase NO levels joint with reduction of ET-1 which mediated through c GMP pathway. Besides, en do endotoxemia may have some role in amplifying of NO production

Endothelin-1 and Interleukin-18 with polycystic ovary syndrome

The aim of this study is to evaluate the serum level of the endothilin-1 and the interleukin-18 In patients with polycystic ovary syndrome. A Case Control Study. Ain Shams University Maternity Hospital and Ahmed Maher Teaching Hospital. 45 women will participate in the study divided to two groups. Group A [30 with Polycystic Ovarian Syndrome]. Group B [15 controls]. Patients with PCOS will be recruited from the infertility and gynecological clinics. Control subjects are healthy volunteers with a normal menstrual cycle and with no clinical or biochemical features of hyperandrogenism, thereby excluding the diagnosis of PCOS in this group. Blood Samples will be collected and examined by in-vivo enzyme immunoassay for detection of total human lnterleukin-18 and Endothelin-1 in complex biological body fluids. Results shows that the PCO cases had a higher serum Endotheline-1 level than that of the controls with statistically significant difference; [p <0.001.] and results show that the serum level of Interleukin-18 is greater in PCO patients than that of the controls with statistically significant difference; p = 0.038. PCOS induce an increase in serum IL-18 levels and the endotheline-1 concentration