Exploratory investigation on nitro- and phospho-proteome cerebellum changes in hyperammonemia and hepatic encephalopathy rat models

Hepatic encephalopathy (HE) is a neurological disease associated with hepatic dysfunction. Current knowledge suggests that hyperammonemia, related to liver failure, is a main factor contributing to the cerebral alterations in HE and that hyperammonemia might impair signal transduction associated with post-translational modification of proteins such as tyrosine-nitration and phosphorylation. However, the molecular bases of the HE remain unclear and very little is known about the occurrence of post-translational modification on in vivo proteins. In this exploratory study we look for evidence of post-translation modifications of proteins in the cerebellum of experimental HE rat models using a proteomic approach. For the first time we showed that hyperammonemia without liver failure (HA rats) and experimental HE with liver failure due to portacaval shunt (PCS rats) lead to a reduced protein nitration in rat cerebellum, where the undernitrated proteins were involved in energy metabolism and cytoskeleton remodelling. Moreover we showed that tyrosine nitration loss of these proteins was not necessarily associated to a change in their phosphorylation state as result of the disease. Interestingly the rat cerebellum phosphoproteome was mainly perturbed in PCS rats, whereas HA rats did not shown appreciable changes in their phosphoprotein profile. Since the protein nitration level decreased similarly in the cerebellum of both HA and PCS rats, this implies that the two disease models share common effects but also present some differential signalling effects in the cerebellum of the same animals. This study highlights the interest for studying the concerted action of multiple signalling pathways in HE development.     

Exposure to second-hand smoke and reproductive outcomes depending on maternal asthma

Tobacco consumption and exposure to second-hand smoke (SHS) are associated with reduced birth weight. One issue that has not been clarified previously is that of the potential higher risk of this outcome in mothers with asthma. We assessed the role of prenatal maternal tobacco use and SHS on reproductive outcomes and assessed the interaction with maternal history of asthma. Data was collected from the INMA study, a maternal birth cohort selected from the general population established in Spain in 2002. We measured cotinine at the 32nd week of pregnancy in 2,219 females. Diagnosed maternal asthma was self-reported during pregnancy. 35% of mothers reported not being exposed to smoking or SHS during pregnancy. Active smoking (i.e. self-reported or cotinine >50 ng·mL(-1)) was related to a 134 g decrease in birth weight and a relative risk of 1.8 for small for gestational age and fetal growth restriction. These results were not modified by maternal asthma. Maternal asthma had a similar frequency in all exposure groups. Non SHS-exposed females had the lowest prevalence of asthma. SHS (i.e. cotinine 20-50 ng·mL(-1)) decreased birth weight by 32 g among those without maternal asthma, but these differences were not statistically significant (95% CI -88.76-24.76). Maternal asthma did not promote these effects. Maternal history of asthma did not modify the effects of smoking on reproductive outcomes in a cohort sampled from the general population.     

Risk factors for the development of vertebral fractures after percutaneous vertebroplasty

We have recently observed an increased risk for vertebral fractures (VF) in a randomized controlled trial comparing the analgesic effect of vertebroplasty (VP) versus conservative treatment in symptomatic VF. The aim of the present study was to evaluate the risk factors related to the development of VF after VP in these patients. We evaluated risk factors including age, gender, bone mineral density, the number, type, and severity of vertebral deformities at baseline, the number of vertebral bodies treated, the presence and location of disk cement leakage, bone remodeling (determining bone turnover markers) and 25 hydroxyvitamin D [25(OH)D] levels at baseline in all patients. Twenty‐nine radiologically new VF were observed in 17 of 57 patients undergoing VP, 72% adjacent to the VP. Patients developing VF after VP showed an increased prevalence of 25(OH)D deficiency (<20 ng/mL) and higher P1NP values. The principal factor related to the development of VF after VP in multivariate analysis was 25(OH)D levels < 20 ng/mL (RR, 15.47; 95% CI, 2.99–79.86, p < 0.0001), whereas age >80 years (RR, 3.20; 95% CI, 1.70–6.03, p = 0.0007) and glucocorticoid therapy (RR, 3.64; 95% CI, 1.61–8.26, p = 0.0055) constituted the principal factors in the overall study population. Increased risk of VF after VP was also associated with cement leakage into the inferior disk (RR, 6.14; 95% CI, 1.65–22.78, p = 0.044) and more than one vertebral body treated during VP (RR, 4.19; 95% CI, 1.03–34.3, p = 0.044). In conclusion, nearly 30% of patients with osteoporotic VF treated with VP had a new VF after the procedure. Age, especially >80 years, the presence of inferior disk cement leakage after the procedure, the number of cemented vertebrae, and low 25(OH)D serum levels were related to the development of new VF in these patients, with the latter indicating the need to correct vitamin D deficiency prior to performing VP.     

High-Efficiency Postdilution Online Hemodiafiltration Reduces All-Cause Mortality in Hemodialysis Patients

Retrospective studies suggest that online hemodiafiltration (OL-HDF) may reduce the risk of mortality compared with standard hemodialysis in patients with ESRD. We conducted a multicenter, open-label, randomized controlled trial in which we assigned 906 chronic hemodialysis patients either to continue hemodialysis (n=450) or to switch to high-efficiency postdilution OL-HDF (n=456). The primary outcome was all-cause mortality, and secondary outcomes included cardiovascular mortality, all-cause hospitalization, treatment tolerability, and laboratory data. Compared with patients who continued on hemodialysis, those assigned to OL-HDF had a 30% lower risk of all-cause mortality (hazard ratio [HR], 0.70; 95% confidence interval [95% CI], 0.53–0.92; P=0.01), a 33% lower risk of cardiovascular mortality (HR, 0.67; 95% CI, 0.44–1.02; P=0.06), and a 55% lower risk of infection-related mortality (HR, 0.45; 95% CI, 0.21–0.96; P=0.03). The estimated number needed to treat suggested that switching eight patients from hemodialysis to OL-HDF may prevent one annual death. The incidence rates of dialysis sessions complicated by hypotension and of all-cause hospitalization were lower in patients assigned to OL-HDF. In conclusion, high-efficiency postdilution OL-HDF reduces all-cause mortality compared with conventional hemodialysis.In the last decades, renal replacement therapy with hemodialysis has become a standard of care for patients with ESRD. Despite continuous improvement, annual mortality among these patients ranges between 15% and 25%.^1,2 Hemodialysis techniques are based on the ability of molecules to diffuse across a semipermeable membrane, which allows adequate clearance of low molecular weight particles. To increase the clearance of middle-to-large molecules, synthetic membranes with high water permeability (high-flux membranes) were introduced years ago. The anticipated benefit of high-flux over low-flux hemodialysis on patient survival was not confirmed in the Hemodialysis (HEMO) study.³ However, the Membrane Permeability Outcome (MPO) study,⁴ as well as a post hoc analysis in diabetic patients, showed that high-flux hemodialysis improved long-term survival in patients with hypoalbuminemia.Clearance of middle-to-large molecules can be increased by combining diffusive and convective transport through hemodiafiltration. The introduction of online hemodiafiltration (OL-HDF) using ultrapure dialysate as the source of the replacement fluid has allowed the convective volume to be increased and has reduced the cost of the procedure.⁵ Randomized studies with limited sample sizes and nonrandomized studies have shown that OL-HDF improves hemodynamic stability and response to erythropoietic-stimulating agents (ESAs) and reduces the incidence of hemodialysis-associated amyloidosis and chronic inflammation.^6–11 The effect of OL-HDF on patient survival is derived from noncontrolled studies. The European Dialysis Outcomes and Practice Pattern Study was associated with a mortality risk reduction of 35% in patients treated with high-efficiency hemodiafiltration compared with those treated with conventional hemodialysis.¹² These results were confirmed in other noncontrolled studies conducted in several European countries,^13–15 although two recent, randomized studies failed to show differences in patient survival^16,17In 2007, the Catalonian Health Authorities approved a specific additional reimbursement for OL-HDF to dialysis care providers and the Catalonian Society of Nephrology promoted this randomized study (On-Line Hemodiafiltration Survival Study, or Estudio de Supervivencia de Hemodiafiltración On-Line [ESHOL]) to compare the effect of OL-HDF over hemodialysis on patient survival.¹⁸     

European Species of Hebeloma Section Theobromina

This paper addresses section Theobromina within the genus Hebeloma (Agaricales). We recognise seven European species within this section, three of which are described as new: Hebeloma alboerumpens, H. griseopruinatum and H. parvicystidiatum. The first two of these species appear to be ectomycorrhizal with Cistaceae: Cistus and Helianthemum. Hebeloma parvicystidiatum is more likely to be in mycorrhizal association with Quercus spp. We also provide a key to the European species within sect. Theobromina and an updated key of known Hebeloma associates of Cistus. Molecular analyses based on multiple loci further illustrate the distinctness of the newly described taxa and provide molecular evidence, supporting the morphological evidence, for the relationship that exists among species of this section. The ITS is the only one from the sequenced loci that, alongside with morphology, distinguishes among all of the species of sect. Theobromina. The section gains most of its molecular support from the MCM7 locus, followed by RPB2.     

Hand and wrist arthralgia in systemic lupus erythematosus is associated to ultrasonographic abnormalities

ObjectiveSystemic lupus erythematosus (SLE) is an autoimmune disease which may has joint impairment. Often, SLE patients complain of hand and wrist arthralgia (HA). Usually, these patients do not show any swelling in the physical exam. Our aim was to demonstrate Power Doppler Ultrasound (PDUS) abnormalities in SLE patients with HA.MethodsWe recruited 58 consecutive SLE patients and divided them into two groups: case group (n = 28) were patients with HA, and control group (n = 30) were patients without HA. We also collected socio-demographic and disease activity data, biological markers and SLEDAI index. We evaluated disability and quality of life by mHAQ and SF-12, respectively. We performed a bilateral hand and wrist PDUS on all patients. PDUS findings were based in OMERACT-7 group criteria.ResultsWe found PDUS abnormalities in most of SLE patients who suffered HA, when compared to SLE controls (P < 0.001). The main findings in Case Group were: tenosynovitis (39.2%), synovial effusion or hypertrophy (25%) and active synovitis (14.2%). SLEDAI score and dsDNA antibodies were related to the presence of PDUS abnormalities (P < 0.05 and P < 0.001, respectively). We also found worse physical SF-12 (P < 0.05) and mHAQ (NS) scores in case group.ConclusionsSLE patients who present HA have more PDUS abnormalities. These findings are associated with a higher SLEDAI score and dsDNA antibodies. This articular affection may contribute to a worsened functional ability and a lower quality of life. PDUS seems to be a reliable tool in the assessment of SLE patients with HA.