GH levels and insulin sensitivity are differently associated with biomarkers of cardiovascular disease in active acromegaly

Context: Acromegaly is characterized by GH excess and insulin resistance. It is not known which of these disorders is responsible for the increased atherogenic risk in these patients. Objective: To analyse the associations of GH and homoeostasis model assessment (HOMA) with biomarkers of cardiovascular disease and to compare the above-mentioned variables between patients with active acromegaly and controls. Design and setting: This open cross-sectional study was conducted at a University Hospital. Patients: Twenty-two outpatients were compared with sex- and age-matched control subjects. Main outcomes: Included clinical features, hormonal status, markers of insulin resistance, lipoprotein profile and biomarkers of cardiovascular disease. Results: Patients presented higher triglyceride (median [IQR]) (1·2[1·1-1·6] vs 0·9[0·6-1·1] mm, P < 0·05), low-density lipoprotein-cholesterol (LDL-C) (mean ± SD) (3·5 ± 0·9 vs 3·0 ± 0·7mm, P < 0·05), apoB (0·98 ± 0·23 vs 0·77 ± 0·22 g/l, P < 0·05), free fatty acid (0·69 ± 0·2 vs 0·54 ± 0·2 mM, P < 0·05), oxidized-LDL (120 ± 22 vs 85 ± 19 U/l, P < 0·05) and endothelin-1 (0·90 ± 0·23 vs 0·72 ± 0·17 ng/l, P < 0·05) levels, increased cholesteryl ester transfer protein (CETP) activity (179 ± 27 vs 138 ± 30%/ml/h, P < 0·01) and lower C reactive protein (CRP) (0·25[0·1-0·9] vs 0·85[0·4-1·4] mg/l; P < 0·05) levels than control subjects. Vascular cell adhesion molecule (VCAM-1) concentration was not different. By multiple linear regression analyses, HOMA explained the variability of triglycerides (25%), high-density lipoprotein-cholesterol (HDL-C) (30%) and CETP activity (28%), while GH independently predicted LDL-C (18%), oxidized-LDL (40%) and endothelin-1 levels (19%). Conclusions: In patients with active acromegaly, GH excess contributes to the development of insulin resistance, and the interaction between both disturbances would be responsible for the appearance of atherogenic pro-oxidative and pro-inflammatory factors. Insulin resistance would be preferably associated with an atherogenic lipoprotein profile and to high CETP activity, while high GH levels would independently predict the increase in LDL-C, ox-LDL and endothelin-1

Association of common variants in JAK2 gene with reduced risk of metabolic syndrome and related disorders

<p>Abstract</p> <p>Background</p> <p>Disturbances in leptin and insulin signaling pathways are related to obesity and metabolic syndrome (MS) with increased risk of diabetes and cardiovascular disease. Janus kinase 2 (JAK2) is a tyrosine kinase involved in the activation of mechanisms that mediate leptin and insulin actions. We conducted a population cross-sectional study to explore the association between two common variants in JAK2 gene and MS related traits in 724 Argentinean healthy male subjects.</p> <p>Methods</p> <p>A total of 724 unrelated men aged 37.11 ± 10.91 yr were included in a cross-sectional study. Physical examination, anthropometric measurements and biochemical analysis were determined by a standardized protocol. rs7849191 and rs3780378 were genotyped. Analyses were done separately for each SNP and followed up by haplotype analysis.</p> <p>Results</p> <p>rs7849191 and rs3780378 were both associated with reduced risk of MS [p = 0.005; OR (95%CI) = 0.52 (0.33-0.80) and p = 0.006; OR (95% CI) = 0.59 (0.40-0.86) respectively, assuming a dominant model]. rs3780378 T allele was associated with triglyceridemia values under 150 mg/dl [p = 0.007; OR (95%CI) = 0.610 (0.429-0.868)] and TT carriers showed lower triglycerides (p = 0.017), triglycerides/HDL-C ratio (p = 0.022) and lipid accumulation product (p = 0.007) compared to allele C carriers. The two-SNPs-haplotype analysis was consistent with single locus analysis.</p> <p>Conclusions</p> <p>It was found for the first time, significant associations of JAK2 common variants and related haplotypes with reduced risk of MS. These findings could be explained by the role of JAK2 in insulin and/or leptin signaling.</p

MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C

Cirrhosis likely shares common pathophysiological pathways despite arising from a variety of liver diseases. A recent GWAS identified rs641738, a polymorphism in the MBOAT7 locus, as being associated with the development of alcoholic cirrhosis. Here we explore the role of this variant on liver inflammation and fibrosis in two cohorts of patients with chronic hepatitis C. In 2,051 patients, rs641738 associated with severe hepatic inflammation and increased risk of fibrosis, as well as fast fibrosis progression. At functional level, rs641738 associated with MBOAT7 transcript and protein levels in liver and blood, and with serum inflammatory, oxidative stress and macrophage activation markers. MBOAT7 was expressed in immune cell subsets, implying a role in hepatic inflammation. We conclude that the MBOAT7 rs641738 polymorphism is a novel risk variant for liver inflammation in hepatitis C, and thereby for liver fibrosis

HOMA-IR and non-HDL-C as predictors of high cholesteryl ester transfer protein activity in patients at risk for type 2 diabetes

Background and aims: Metabolic syndrome (MS) and type 2 diabetes are highly associated with an abnormal lipoprotein profile, which may be generated and accentuated by high cholesteryl ester transfer protein (CETP) activity. Given the difficulty in measuring CETP activity, the aim was to identify simple biochemical predictors of high CETP activity. Design and methods: Eighty five subjects at risk for type 2 diabetes were classified according to the presence of MS. Lipoprotein profile, HOMA-IR and endogenous CETP activity were evaluated. Results: As expected, MS patients presented higher concentration of glucose, insulin, triglycerides and non-HDL-C and lower HDL-C levels. Moreover, MS patients exhibited increased HOMA-IR and CETP activity. Employing a ROC curve for MS, high CETP activity was defined as >250%ml⁻¹ h⁻¹. The predictive variables of high CETP were non-HDL-C≥160mg/dl (OR=11.1;95%IC=3.3-38.2;p2.1 (OR=4.4;95%IC=1.3-14.8;p<0.05). Conclusions: High non-HDL-C and insulin resistance were predictors for increased CETP activity which measurement is not accessible for clinical laboratories

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Age-related differences in integrin expression in peripheral blood lymphocytes

Alpha integrins play an important role in cell to cell and cell to extra-cellular matrix interactions required for an effective T-lymphocyte-mediated immune response, however little is known about age related differences in expression of alpha integrins on T-cells in humans. We here measured alpha-4 (α4) integrin (CD49d) expression on T-lymphocytes via peripheral blood sampling, comparing parameters between cohorts of young and old adults. No age-related differences were found for the absolute numbers of T-cells, although the percentage of CD4+ T-cells in older adults was significantly greater and the percentage of CD8+ T-cells lower than in younger cohorts. Percentage and absolute numbers of CD3+ T-cells co-expressing CD49d were significantly lower in older adults compared to younger cohorts, and the percentage of gated CD4+ and CD8+ cells that co-labelled positively for CD49d was also reduced in this group. There were no age-related differences in circulating levels of cytokines (Type I interferons) that are known to regulate cell surface integrin expression. Reduced expression of alpha integrins on T-cells may be an early indicator of the loss of homeostatic control that occurs with ageing, contributing to diminished effector T-cell responses during senescence

Adenoma pleomórfico metastásico de glándula parótida. Reporte de un caso y estudio descriptivo retrospectivo de la literatura en inglés

The pleomorphic adenoma (PA) -ICD-O-8940/0- is the most common benign epithelial tumor of salivary glands, of pleomorphic histological appearance with ductal cells and myoepitheliocytes and hyalinized, chondroids and myxoids stromal areas. The metastasizing pleomorphic adenoma (MPA) it is an extremely rare tumor with an aggressive behavior since it produces metastasis but retains its benign phenotype. In the fourth edition (year 2017) of the Classification of head and neck tumors of the WHO occupies a subcategory of PA within the session of benign tumors. In this communication, we present a rare case of MPA of the parotid gland with multiple lung metastases. The histopathological study (H/E) of the surgical piece of total parotidectomy and lymphoid nodes was performed and a PA was diagnosed. In a routine control, a chest radiograph was requested, where multiple nodular images were observed in both lungs consistent with metastasis. A lung biopsy was performed, identifying tumor formations similar to the parotid tumor.The majority of published cases occur after surgery of a primary or recurrent tumor and several authors suggest that surgical manipulation can cause tumor cell separation, hematogenous spread and subsequent implantation in distant sites.El adenoma pleomórfico (AP) -ICD-O- 8940/0- es el tumor epitelial benigno más común de glándulas salivales, de apariencia histológica pleomórfica con células ductales y mioepiteliocitos y áreas estromales hialinizadas, condroides y mixoides. El adenoma pleomórfico metastásico (APM) es un tumor extremadamente raro con un comportamiento agresivo ya que produce metástasis pero conserva su fenotipo benigno. En la cuarta edición (año 2017) de la “Clasificación de tumores de cabeza y cuello” de la Organización Mundial de la Salud (OMS) ocupa una subcategoría de AP dentro de la sesión de tumores benignos. En esta comunicación presentamos un raro caso de APM de glándula parótida con múltiples metástasis en pulmón. Se realizó el estudio histopatológico (H/E) de la pieza quirúrgica de parotidectomía total y nodos linfoides y se diagnosticó adenoma pleomórfico. En un control de rutina se le solicitó radiografía de tórax donde se observaron imágenes nodulares múltiples en ambos pulmones consistentes con metástasis. Se hizo una punción biopsia de pulmón identificándose formaciones tumorales similares al tumor parotídeo. La mayoría de los casos publicados ocurren después de la cirugía de un tumor primario o recurrente y diversos autores sugieren que la manipulación quirúrgica puede causar separación de células tumorales, propagación hematógena y posterior implantación en sitios distantes

Direct Identification of the Meloidogyne incognita Secretome Reveals Proteins with Host Cell Reprogramming Potential

The root knot nematode, Meloidogyne incognita, is an obligate parasite that causes significant damage to a broad range of host plants. Infection is associated with secretion of proteins surrounded by proliferating cells. Many parasites are known to secrete effectors that interfere with plant innate immunity, enabling infection to occur; they can also release pathogen-associated molecular patterns (PAMPs, e.g., flagellin) that trigger basal immunity through the nematode stylet into the plant cell. This leads to suppression of innate immunity and reprogramming of plant cells to form a feeding structure containing multinucleate giant cells. Effectors have generally been discovered using genetics or bioinformatics, but M. incognita is non-sexual and its genome sequence has not yet been reported. To partially overcome these limitations, we have used mass spectrometry to directly identify 486 proteins secreted by M. incognita. These proteins contain at least segmental sequence identity to those found in our 3 reference databases (published nematode proteins; unpublished M. incognita ESTs; published plant proteins). Several secreted proteins are homologous to plant proteins, which they may mimic, and they contain domains that suggest known effector functions (e.g., regulating the plant cell cycle or growth). Others have regulatory domains that could reprogram cells. Using in situ hybridization we observed that most secreted proteins were produced by the subventral glands, but we found that phasmids also secreted proteins. We annotated the functions of the secreted proteins and classified them according to roles they may play in the development of root knot disease. Our results show that parasite secretomes can be partially characterized without cognate genomic DNA sequence. We observed that the M. incognita secretome overlaps the reported secretome of mammalian parasitic nematodes (e.g., Brugia malayi), suggesting a common parasitic behavior and a possible conservation of function between metazoan parasites of plants and animals

The Euclid mission: status after launch and early operations

During its 6-year nominal mission, Euclid shall survey one third of the sky, enabling us to examine the spatial distributions of dark and luminous matter during the past 10 Gyr of cosmic history. The Euclid satellite was successfully launched on a SpaceX Falcon 9 launcher from Cape Canaveral on 1 July 2023 and is fully operational in a halo orbit around the Second Sun-Earth Lagrange point. We present an overview of the expected and unexpected findings during the early phases of the mission, in the context of technological heritage and lessons learnt. The first months of the mission were dedicated to the commissioning of the spacecraft, telescope and instruments, followed by a phase to verify the scientific performance and to carry out the in-orbit calibrations. We report that the key enabling scientific elements, the 1.2-meter telescope and the two scientific instruments, a visual imager (VIS) and a near-infrared spectrometer and photometer (NISP), show an inorbit performance in line with the expectations from ground tests. The scientific analysis of the observations from the Early Release Observations (ERO) program done before the start of the nominal mission showed sensitivities better than the prelaunch requirements. The nominal mission started in December 2023, and we allocated a 6-month early survey operations phase to closely monitor the performance of the sky survey. We conclude with an outlook of the activities for the remaining mission in the light of the in-orbit performance