Surrogate indices of insulin resistance using the Matsuda index as reference in adult men-a computational approach.

Background: Overweight and obesity, high blood pressure, hyperglycemia, hyperlipidemia, and insulin resistance (IR) are strongly associated with non-communicable diseases (NCDs), including type 2 diabetes, cardiovascular disease, stroke, and cancer. Different surrogate indices of IR are derived and validated with the euglycemic-hyperinsulinemic clamp (EHC) test. Thus, using a computational approach to predict IR with Matsuda index as reference, this study aimed to determine the optimal cutoff value and diagnosis accuracy for surrogate indices in non-diabetic young adult men. Methods: A cross-sectional descriptive study was carried out with 93 young men (ages 18-31). Serum levels of glucose and insulin were analyzed in the fasting state and during an oral glucose tolerance test (OGTT). Additionally, clinical, biochemical, hormonal, and anthropometric characteristics and body composition (DEXA) were determined. The computational approach to evaluate the IR diagnostic accuracy and cutoff value using difference parameters was examined, as well as other statistical tools to make the output robust. Results: The highest sensitivity and specificity at the optimal cutoff value, respectively, were established for the Homeostasis model assessment of insulin resistance index (HOMA-IR) (0.91; 0.98; 3.40), the Quantitative insulin sensitivity check index (QUICKI) (0.98; 0.96; 0.33), the triglyceride-glucose (TyG)-waist circumference index (TyG-WC) (1.00; 1.00; 427.77), the TyG-body mass index (TyG-BMI) (1.00; 1.00; 132.44), TyG-waist-to-height ratio (TyG-WHtR) (0.98; 1.00; 2.48), waist-to-height ratio (WHtR) (1.00; 1.00; 0.53), waist circumference (WC) (1.00; 1.00; 92.63), body mass index (BMI) (1.00; 1.00; 28.69), total body fat percentage (TFM) (%) (1.00; 1.00; 31.07), android fat (AF) (%) (1.00; 0.98; 40.33), lipid accumulation product (LAP) (0.84; 1.00; 45.49), leptin (0.91; 1.00; 16.08), leptin/adiponectin ratio (LAR) (0.84; 1.00; 1.17), and fasting insulin (0.91; 0.98; 16.01). Conclusions: The computational approach was used to determine the diagnosis accuracy and the optimal cutoff value for IR to be used in preventive healthcare.

A longitudinal study of free leptin index in pre-eclamptic pregnancies.

The ratio between circulating levels of leptin and soluble leptin receptor (sOB-R), the free leptin index (FLI), is used as a marker of leptin resistance. Therefore, the aim of our study was to investigate the FLI in mild pre-eclamptic pregnancies in a nested case-control study within a prospective observational study. Circulating levels of leptin and sOB-R levels rise significantly during pregnancy in healthy (p < 0.05) (n = 46) and pre-eclamptic pregnancies (p < 0.05) (n = 20). Serum levels of leptin were significantly higher in pre-eclamptic compared to healthy pregnancies at second and third trimesters of pregnancy (p < 0.05). Additionally, serum levels of sOB-R were significantly lower in pre-eclamptic pregnancies during the second and third trimesters of pregnancy compared to healthy pregnancies (p < 0.05). Moreover, we found that FLI did not vary significantly during pregnancy in healthy women (p > 0.05), while it increases in pre-eclamptic pregnancies (p < 0.05). Indeed, FLI was significantly higher at second and third trimesters of pregnancy in pre-eclamptic compared to healthy pregnancies (p < 0.05). In addition, FLI was significantly higher in the luteal phase compared with the follicular phase of the menstrual cycle in eumenorrheic women (p < 0.05). Receiver operating characteristic (ROC) curve analysis revealed the ability of leptin (AUC = 0.72) and FLI (AUC = 0.67) as a reliable predictor for mild pre-eclampsia during the second trimester of pregnancy. In conclusion, our findings show that FLI were significantly increased in mild pre-eclamptic pregnancies and allowed us to hypothesize that this rise might alter leptin bioavailability and bioactivity which might lead to the sympathetic hyperactivity and the hypertensive disorders during pregnancy.

Study of the Ghrelin/LEAP-2 Ratio in Humans and Rats during Different Phases of Pregnancy.

The Liver-Expressed Antimicrobial Peptide 2 (LEAP-2) has emerged as an endogenous GHS-R antagonist and blunts the orexigenic action of ghrelin. This study aimed to determine the Ghrelin/LEAP-2 ratio in humans and rats during pregnancy. In humans, we conducted a nested case-control study within an observational prospective cohort. Healthy and mild preeclamptic pregnant women were studied at each trimester of gestation and three months postpartum. In addition, a group of non-pregnant women was studied into the follicular and luteal phases of the menstrual cycle. Furthermore, Ghrelin/LEAP-2 ratio was investigated in non-pregnant rats and at different periods of rat pregnancy. Human and rat serum ghrelin and LEAP-2 levels were determined using the commercially available ELISA kits. The Ghrelin/LEAP-2 ratio peak around the second trimester of gestation in healthy pregnant women (p < 0.05). Additionally, there were no statistically significant differences in Ghrelin/LEAP-2 ratio between healthy and preeclamptic pregnant women at each trimester of gestation (p > 0.05). The Ghrelin/LEAP-2 ratio in pregnant rat reached the peak around mid-gestation with a similar pattern to the human pregnancy. LEAP-2 was visualized by immunohistochemistry in human term placenta and rat placentas on days 12, 16 and 21 of pregnancy. In conclusion, this study provides the first evidence of a Ghrelin/LEAP-2 ratio peak around the half-way point of pregnancy onwards during human and rat pregnancy, and it might be associated with increased rates of weight gain during pregnancy. Thus, this study suggests that LEAP-2 and Ghrelin/LEAP-2 ratio might play an important role in maternal physiology adaptation of weight gain during pregnancy.

Maternal Fibroblast Growth Factor 21 Levels Decrease during Early Pregnancy in Normotensive Pregnant Women but Are Higher in Preeclamptic Women-A Longitudinal Study.

(1) Background: Fibroblast growth factor 21 (FGF-21) is an endocrine factor involved in glucose and lipid metabolism that exerts pleiotropic effects. The aim of this study was to investigate the serum FGF-21 profile in healthy and mild preeclamptic pregnant women at each trimester of pregnancy; (2) Methods: Serum FGF-21 levels were determined by ELISA in a nested case-control study within a longitudinal cohort study that included healthy (n = 54) and mild preeclamptic (n = 20) pregnant women, women at three months after delivery (n = 20) and eumenorrheic women during the menstrual cycle (n = 20); (3) Results: FGF-21 levels were significantly lower in the mid-luteal phase compared to the early follicular phase of the menstrual cycle in eumenorrheic women (p < 0.01). Maternal levels of FGF-21 were significantly lower in the first and second trimesters and peaked during the third trimester in healthy pregnant women (p < 0.01). Serum levels of FGF-21 in healthy pregnant were significantly lower in the first and second trimester of pregnancy compared with the follicular phase of the menstrual cycle and postpartum (p < 0.01). Serum FGF-21 levels were significantly higher in preeclamptic compared to healthy pregnant women during pregnancy (p < 0.01); (4) Conclusions: These results suggest that a peak of FGF-21 towards the end of pregnancy in healthy pregnancy and higher levels in preeclamptic women might play a critical role that contributes to protecting against the negatives effects of high concentrations of non-esterified fatty acids (NEFA) and hypertensive disorder. Furthermore, FGF-21 might play an important role in reproductive function in healthy eumenorrheic women during the menstrual cycle.

Maternal Serum Angiopoietin-Like 3 Levels in Healthy and Mild Preeclamptic Pregnant Women.

Objective: Angiopoietin-like protein 3(ANGPTL3) is an important regulator of lipoprotein metabolism in the fed state by inhibiting the enzyme lipoprotein lipase in oxidative tissues. However, the possible role of ANGPTL3 throughout gestation and its relationship with hormonal and biochemical variables are still unknown. The aim of this study was to determinate serum ANGPTL3 level in healthy non-pregnant women, during healthy and preeclamptic pregnancy and postpartum. Methods: Serum ANGPTL3 was analyzed by enzyme-linked immunosorbent assay (ELISA), in a prospective cohort of healthy pregnant women (n = 52) and women with mild preeclampsia (n = 21), and women at three months postpartum (n = 20) and healthy non-pregnant women (n = 20). The results obtained were correlated with biochemical, hormonal and anthropometric variables and insulin resistance indices. Results: Levels of ANGPTL3 were not different between the follicular and the luteal phases of the cycle in healthy non-pregnant women. There was a significant reduction in serum ANGPTL3 levels from the first to the third trimester in healthy pregnant women compared with healthy non-pregnant and postpartum women (p <0.01). ANGPTL3 levels do not differ significantly during the three trimesters of pregnancy neither in healthy women nor in preeclamptic women. The serum levels of ANGPTL3 in women who developed preeclampsia are not statistically different from those observed in healthy pregnant women in each trimester of pregnancy. A significant lineal positive correlation was observed between serum ANGPTL3 levels and triglyceride (P =0.0186, r =0.52), very low-density lipoprotein cholesterol (P =0.0224, r =0.50), and total cholesterol levels (P =0.0220, r =0.50) in healthy non-pregnant women (P 0.05). Besides, there were no significant correlations between serum ANGPTL3 and body mass index (BMI), high-density lipoprotein cholesterol, glucose, insulin, leptin, or HOMA-IR (P >0.05). Conclusions: We describe for the first time the profile of ANGPTL3 throughout pregnancy and postpartum as well as and discussed about explore their potential contribution interactions with lipoprotein metabolism throughout pregnancy and postpartum. Thus, low levels of ANGPTL3 during pregnancy might favor lipid uptake in oxidative tissues as the main maternal energy source, while may helping to preserve glucose for use by the fetus and placenta.

Effect of neural therapy on NGF and BDNF serum levels in patients with chronic pain. A pilot study / Efecto de la terapia neural sobre los niveles séricos del NGF y el BDNF en pacientes con dolor crónico. Estudio piloto

Abstract Introduction: Neurotrophins (NT) are a family of proteins consisting of the nerve growth factor (NGF), the brain-derived neurotrophic factor (BDNF) and NT-3 and NT-4/5. These proteins play an essential role in neuronal survival, differentiation, and proliferation. Objectives: To analyze the variations of NGF and BDNF serum levels in patients with chronic pain after undergoing neural therapy and to establish the effects of this type of intervention on their quality of life. Materials and methods: Prospective pilot study conducted in 10 patients with chronic pain treated with neural therapy between July 2017 and April 2018 in Bogotá D.C., Colombia. Three consultations were performed (one in which the intervention was initiated, and two follow-up visits every three weeks). During each consultation, the patients' quality of life was assessed using the SF-12 scale and their NGF and BDNF serum levels were measured. Data were analyzed by means of descriptive statistics, using medians and interquartile ranges for quantitative variables, and absolute frequencies and percentages for qualitative variables. Results: The median score on the SF-12 scale tended to improve in the first and second follow-up visits compared with the baseline score (pre-intervention), particularly during the first follow-up visit (consultation No. 1: 34.5; follow-up No. 1: 39.5, and follow-up No. 2: 38). Median NGF serum levels had a downward trend after the intervention, particularly in the first follow-up visit (157.6, 42.95, and 237.8, respectively), and in the case of BNDF, an overall downward trend was also found (29.96, 19.24 and 20.43, respectively). An improvement in quality of life related to the decrease in the serum levels of both neurotrophins was observed. Conclusion: Neural therapy intervention reduced NGF and BDNF serum levels and improved the quality of life of the participants. Therefore, the behavior of these neurotrophins could become a biomarker for the diagnosis, treatment, and follow-up of patients with chronic pain.

Resumen Introducción. Las neurotrofinas (NT) son una familia de proteínas conformada por el factor de crecimiento nervioso (NGF), el factor neurotrófico derivado del cerebro (BDNF) y las neurotrofinas NT-3 y NT-4/5; estas proteínas tienen un papel esencial en la supervivencia, diferenciación y proliferación neuronal. Objetivos. Analizar las variaciones de los niveles séricos del NGF y el BDNF en pacientes con dolor crónico luego de recibir terapia neural y establecer los efectos de este tipo de intervención en su calidad de vida. Materiales y métodos. Estudio piloto prospectivo realizado en 10 pacientes con dolor crónico tratados con terapia neural entre julio de 2017 y abril de 2018 en Bogotá D.C., Colombia. Se realizaron 3 consultas (una en la que se inició la intervención y dos de control cada tres semanas) y en cada una se evaluó la calidad de vida mediante el cuestionario de salud SF-12 y se midieron los niveles séricos del NGF y el BDNF. Los datos se analizaron mediante estadística descriptiva, utilizando medianas y rangos intercuartiles para las variables cuantitativas, y frecuencias absolutas y porcentajes para las cualitativas. Resultados. La mediana de puntaje del cuestionario SF-12 tendió a mejorar en el primer y segundo control comparada con la puntuación inicial (antes de la intervención), en particular en el primer control (consulta 1: 34.5; control 1: 39.5, y control 2: 38). La mediana de los niveles séricos del NGF tendió a disminuir luego de la intervención, en particular en el primer control (157.6, 42.95 y 62.2, respectivamente), y en el caso del BNDF, la tendencia global también fue hacia la disminución (29.96, 19.24 y 20.43, respectivamente). Se observó una mejora en la calidad de vida relacionada con la disminución de los niveles séricos de ambas neurotrofinas. Conclusión. La intervención de terapia neural produjo una reducción en los niveles séricos del NGF y el BDNF y mejoró la calidad de vida de los participantes; por tanto, el comportamiento de estas neurotro-finas podría convertirse en un biomarcador para el diagnóstico, tratamiento y seguimiento de pacientes con dolor crónico.

Molecular study of sticky platelet syndrome using exorne sequencing / Estudio molecular del síndrome de plaqueta pegajosa mediante secuenciación del exoma

Abstract Introduction: Sticky platelet syndrome (SPS) is a prothrombotic condition characterized by increased platelet aggregation that causes arterial and venous thrombosis. Its diagnosis is reached by identifying increased aggregation using low concentrations of adenosine diphosphate and epinephrine in platelet aggregation tests. Objectives: To identify common mutations through exome sequencing in two patients from the same family diagnosed with SPS and, thus, contribute to the molecular study of this disease. Materials and methods: Descriptive study. In January 2018, exome sequencing was performed in a 10-year-old patient treated at Fundación HOMI (Bogotá D.C., Colombia), index case, and in one of his adult first-degree relatives, both with a history of thrombotic disease and diagnosed with SPS. Exome sequencing was performed at the Complexo Hospitalario Universitario de Santiago de Compostela (Spain) using the SureSelect Clinical Research Exome V2 software by Agilent. Results: Exome sequencing led to detect genetic variants in both cases when compared with the reference sequence. The following variant was identified in the two samples: a cytosine to thymine transition at position c.236 (NM_000174.4) of the glycoprotein (GP)Ib-IX-V complex platelet membrane receptor, which causes a heterozygous transition of the amino acid threonine to isoleucine (i.e., a transition from hydrophilic amino acid to a hydrophobic amino acid) at position p. 79 of the extracellular leucine-rich repeat domain of GPIba subunit of the (GP)Ib-IX complex, involving a conformational change of the main receptor of ligands IB alpha, which might result in platelet hyperaggregation and thrombosis. This variant has not been described in patients with SPS to date. Conclusion: The mutation identified in both samples could be related to SPS considering the importance of glycoprotein IX in platelet function.

Resumen Introducción. El síndrome de plaqueta pegajosa (SPP) es una condición protrombótica caracterizada por un incremento de la agregabilidad plaquetaria que causa trombosis arterial y venosa. Su diagnóstico se realiza al identificar el aumento de la agregabilidad utilizando bajas concentraciones de adenosín difosfato y epinefrina en pruebas de agregación plaquetaria. Objetivos. Identificar mutaciones comunes mediante secuenciación del exoma en dos pacientes de una misma familia con diagnóstico de SPP y, de esta forma, contribuir al estudio molecular de esta enfermedad. Materiales y métodos. Estudio descriptivo en el que se realizó secuenciación del exoma en un paciente de 10 años atendido en la Fundación HOMI (Bogotá, Colombia), caso índice, y en uno de sus familiares adultos en primer grado, ambos con antecedente de enfermedad trombótica y diagnosticados con SPP. La secuenciación del exoma se realizó en el Complexo Hospitalario Universitario de Santiago de Compostela (España) con el programa SureSelect Clinical Research Exome V2 de Agilent. Resultados. En la secuenciación del exoma se detectaron variantes genéticas en ambos casos en comparación con la secuencia de referencia. En las muestras de ambos pacientes se identificó una variante heterocigota consistente en una transición de citosina a timina en la posición c.236 (NM_000174.4) que provoca el cambio del aminoácido treonina por isoleucina en la posición p.79 del dominio extracelular repetitivo rico en leucina (subunidad GPIba del complejo de la glicoproteína Ib-IX-V) y que podría provocar el cambio conformacional del receptor principal del ligando Ib alfa, así como hiperagregación plaquetaria y trombosis. Esta variante no ha sido descrita previamente en pacientes con SPP. Conclusión. La mutación identificada en las muestras estudiadas podría estar relacionada con el SPP considerando la importancia de la glicoproteína IX en las funciones plaquetarias.

Serum angiopoietin-like 3 levels are elevated in obese non diabetic men but are unaffected during an oral glucose tolerance test.

This study aimed to determine ANGPTL3 serum levels in healthy young lean and obese non-diabetic men during an oral glucose tolerance test (OGTT) and correlate them with anthropometric, biochemical and hormonal parameters. A case-control study was carried out and 30 young obese non-diabetic (23.90 ± 3.84 years and BMI 37.92 ± 4.85 kg/m2) and 28 age-matched healthy lean (24.56 ± 3.50 years and BMI of 22.10 ± 1.72 kg/m2) men were included in this study. The primary outcome measures were serum basal ANGPTL3 and ANGPTL3-area under the curve (AUC) levels. The percentage of body fat was measured by dual-energy X-ray absorptiometry and biochemical, hormonal and insulin resistance indices were determined. Basal ANGPTL3 and ANGPTL3-AUC levels were significantly elevated (p < 0.05) in young obese subjects compared with lean subjects and were positively and significantly associated with different anthropometric measurements. Fasting ANGPTL3 serum levels were positively correlated with fasting insulin, leptin, Leptin/Adiponectin index and triglyceride-glucose index. Moreover, ANGPTL3-AUC was negatively correlated with Matsuda index. In this regard, chronically high ANGPTL3 levels in young obese subjects might favor triglyceride-rich lipoprotein clearance to replenish triglyceride stores by white adipose tissue rather than oxidative tissues.

Triglycerides/Glucose and Triglyceride/High-Density Lipoprotein Cholesterol Indices in Normal and Preeclamptic Pregnancies: A Longitudinal Study.

Metabolic changes have been correlated with adverse pregnancy outcomes. The aim of the present study is to determine the TyG and TG/HDL-c indices in a cohort of healthy pregnant (n = 142), preeclamptic (n = 18), and healthy nonpregnant women (n = 56). Preeclamptic women were selected from the same cohort. Pregnant women were followed during three periods of pregnancy and postpartum. The results showed a significant increase in the values of TyG and TG/HDL-c (p < 0.01) as pregnancy progresses, without significant differences between healthy and preeclamptic women. TyG and TG/HDL-c indices are significantly low in nonpregnant and three months' postpartum women when compared with each gestational period studied. TyG and TG/HDL-c indices are positively correlated with HOMA-IR in the early and middle pregnancy (p < 0.05). Multiple linear regression using the TyG and TG/HDL-c indices as dependent variables showed that TyG index was significantly associated with HOMA-IR, gestational age, HDL-c, TC, LDL, fasting insulin, and mean BP (p < 0.001); meanwhile, TG/HDL-c index was only associated with HOMA-IR (p < 0.0242) and gestational age (p < 0.001). In conclusion, the TyG and TG/HDL-c indices could be useful in monitoring insulin resistance during pregnancy.

Serum 25-hydroxyvitamin D levels throughout pregnancy: a longitudinal study in healthy and preeclamptic pregnant women.

BACKGROUND: Worldwide there is a high prevalence of 25-hydroxyvitamin D (25OHD) deficiency and has been associated with adverse outcomes during pregnancy. OBJECTIVE: This is a nested, case-control study in a longitudinal cohort to compare the serum 25OHD levels and other biomarkers throughout pregnancy in a group of 20 preeclamptic women and 61 healthy pregnant women. An additional group of 29 healthy non-pregnant women were also studied during the two phases of the menstrual cycle. RESULTS: Mean 25OHD levels in non-pregnant women were 31.9 ng/mL and 34.9 ng/mL during follicular and luteal phase, respectively (P < 0.01). Mean serum 25OHD levels in healthy pregnant women were 26.5, 30.1 and 31.9 ng/mL, at first, second and third trimester, respectively (P < 0.001). The first trimester levels of 25OHD were lower than those of healthy non-pregnant women (P < 0.001), showing a significant recovery at third trimester. In the group of healthy pregnant women, the 25OHD levels were 25.7 ng/mL and 27.2 ng/mL at 3 and 6 months postpartum, respectively; both values were lower than those observed in the non-pregnant women (P < 0.001). In preeclamptic women, 25OHD serum levels were similar to those of healthy pregnant women; nevertheless, they remained almost unchanged throughout pregnancy. CONCLUSION: There were no significant differences between healthy and preeclamptic pregnant women in terms of 25OHD levels throughout the pregnancy. Serum 25OHD levels in non-pregnant women were higher during luteal phase compared with follicular phase. The 25OHD levels of non-pregnant women tended to be higher than those of pregnant women.

Estudio molecular de la inversión de los intrones 1 y 22 del factor VIII de la coagulación en niños con hemofilia A severa utilizando técnica de PCR de larga distancia / Molecular study in children with hemophilia A in Colombia: analysis of Intron 1 and 22 inversion using long-distance PCR technique

Resumen Introducción. La hemofilia A es una enfermedad recesiva ligada al cromosoma X, con una incidencia de 1 en 5 000 a 10 000 varones y es el trastorno hemostático congénito más frecuente en varones. En pacientes con fenotipo severo, las inversiones de los intrones 22 y 1 son las mutaciones más comunes con una prevalencia del 45% a 50% y del 1% al 5% de los pacientes, respectivamente. Objetivo. Determinar la frecuencia de la inversión de los intrones 1 y 22 del gen del factor VIII de la coagulación en menores de 18 años con hemofilia A severa en Bogotá D.C. Materiales y métodos. Estudio descriptivo y transversal. La identificación de la inversión de los intrones 1 y 22 del gen del factor VIII se realizó mediante técnicas de reacción en cadena de polimerasa de larga distancia. Resultados. Se estudiaron 30 pacientes y se encontró inversión del intrón 22 en 12 pacientes (40%) e inversión 1 en 3 pacientes, cifras similares a las observadas en otros estudios. Conclusiones. Se encontraron las inversiones de los intrones 1 y 22 en la mitad de los pacientes evaluados. Los resultados son reproducibles, por lo que constituyen una herramienta útil para la identificación de las dos mutaciones más frecuentes en hemofilia A severa.

Abstract Introduction: Hemophilia A is an X-linked recessive disease with an incidence of 1 in 5 000 to 10 000 males. It is the most common congenital hemostatic disorder in men. The inversion of introns 1 and 22 in patients with a severe phenotype is considered the most frequent abnormality, with a prevalence of 1 to 5% and 45 to 50%, respectively. Objective: To determine the frequency of introns 1 and 22 inversions in factor VIII gene in children under 18 years with severe hemophilia A in Bogotá. Materials and methods: This is a non-experimental, descriptive, transverse study. The inversions of introns 1 and 22 for factor VIII gene were identified using long-distance polymerase chain reaction techniques in pediatric patients with severe Hemophilia A treated in different centers of Bogotá, Colombia. Results: Thirty patients were analyzed. Inversion of intron 22 was found in 12 patients (40%), while inversion of intron 1 was observed in 3 patients. These findings are similar to other studies. Conclusions: Inversions of intron 22 and 1 were found in half of this group of patients. These results are reproducible and useful to identify the two most frequent mutations in severe hemophilia A patients.

Serum endoglin levels in patients suffering from systemic sclerosis and elevated systolic pulmonary arterial pressure.

Background. Pulmonary arterial hypertension (PAH) is the main cause of morbimortality in systemic sclerosis (SSc). Increased Eng expression has been demonstrated in SSc patients. Objective. Ascertaining serum levels of Eng in SSc patients with and without elevated systolic pulmonary arterial pressure (sPAP) and comparing them with that of healthy volunteers. Methods. A cross-sectional study was carried out. A commercial ELISA kit was used for measuring serum concentrations of Eng in 60 subjects: 40 patients with SSc with and without elevated sPAP, compared to 20 healthy control subjects. Elevated sPAP was detected by echocardiogram. Results. No association between positive Eng and elevated sPAP was found when compared to the SSc without elevated sPAP group (OR = 2.85; 0.65-12.88 95% CI; P = .11); however, an association was found between positive Eng and elevated sPAP compared to healthy controls (OR = 23.22; 2.46-1050.33 95% CI; P = .001), and weak association was found between the positive Eng with SSc without elevated sPAP group compared to healthy controls (OR = 8.14, 0.8-393.74 95% CI; P = .046). Conclusion. Raised serum levels of Eng in SSc patients compared to healthy controls were found, suggesting a role for Eng in SSc vasculopathy and not just in elevated sPAP. However, prospective studies are needed to verify such observations.

Adiponectin receptor 2 is regulated by nutritional status, leptin and pregnancy in a tissue-specific manner.

The aim of the present work was to study the regulation of circulating adiponectin levels and the expression of adiponectin receptor 2 (Adipo-R2) in several rat tissues in relation to fasting, leptin challenge, pregnancy, and chronic undernutrition. Using real-time PCR, we found Adipo-R2 mRNA expression in the liver, stomach, white and brown adipose tissues (WAT and BAT) of adult rats. Immunohistochemical studies confirmed protein expression in the same tissues. Adipo-R2 mRNA levels were decreased in liver after fasting, with no changes in the other tissues. Leptin decreased Adipo-R2 expression in liver and stomach, but increased its expression in WAT and BAT. Chronic caloric restriction in normal rats increased Adipo-R2 gene expression in stomach, while it decreased hepatic Adipo-R2 levels in pregnant rats. Using radioimmunoassay, we found that plasma adiponectin levels were diminished by fasting and leptin. Conversely, circulating adiponectin was increased in food-restricted rats, whereas its levels decreased in food-restricted pregnant rats by the end of gestation. In conclusion our findings provide the first evidence that (a) Adipo-R2 mRNA is regulated in a tissue-specific manner by fasting, but leptin is not responsible for those changes; (b) chronic caloric restriction in normal and pregnant rats also regulate Adipo-R2 mRNA in a tissue-specific manner; and (c) Adipo-R2 mRNA does not show a clear correlation with plasma adiponectin levels.

Potential biomarkers for detecting pulmonary arterial hypertension in patients with systemic sclerosis.

Pulmonary arterial hypertension (PAH) is the major complication of systemic sclerosis (SSc) and the main cause of morbi-mortality. It is important to find predictors for this vascular problem. The objective of this study was to determine the serum levels of different biomarkers in patients with SSc and secondary PAH and to compare them with those of healthy control subjects to define their potential role as predictors of PAH. Cross-section study in which 20 patients with SSc were included. PAH was diagnosed by echocardiogram. The optical densities of endoglin (Eng), endothelin-1 (ET-1), platelet-derived growth factor (PDGF), tumoral necrosis factor alpha (TNF-alpha), Transforming growth factor beta 2 (TGF-beta2) and Interleukin 8 (IL-8) were measured in 20 patients with SSc and 20 healthy controls matched by sex. The differences found between the group of patients with PAH and the control group were (mean or median and range): ET-1 (0.20; 0.10-0.35 vs. 0.16; 0.10-0.24; P = 0.0276), IL-8 (195.7; 45.5-504 vs. 118.9; 23-299.5; P = 0.0364), TNF-alpha (0.70; 0.50-0.96 vs. 0.48; 0.38-0.65; P = 1 x 10(-8)) and Eng (0.95; 0.57-1.72 vs. 0.75; 0.57-0.89; P = 0.0028). A correlation was found between the progression of the disease and the development of Raynaud's phenomenon (Rho: 0.67 and P = 0.0011), ET-1 and Eng (Rho: 0.53 and P = 0.0196), and between IL-8 and Eng (Rho: 0.68 and P = 0.0019). In conclusions, the elevation of the serum levels of Eng and ET-1 could represent a useful tool as PAH biomarkers. Nevertheless, the diagnostic value of these markers needs to be determined by prospective studies.