Anemia e resistenza all'eritropoietina nel paziente uremico in dialisi

Esiste uno stretto legame tra anemia, malattia cardiovascolare e mortalità nei pazienti in dialisi. L'anemia rappresenta infatti un fattore prognostico negativo ed è associata a una scarsa sopravvivenza e a una ridotta qualità della vita nei soggetti in trattamento dialitico. Oggi, la disponibilità di numerosi agenti stimolanti l'eritropoiesi (ESAs) ha portato alla quasi completa scomparsa dell'anemia di grado severo che richiede emotrasfusioni. Nonostante questo una percentuale abbastanza consi-stente di pazienti, circa il 10%, non riesce ancora a raggiungere il valore di Hb target raccomandato dalle linee guida internazionali; il termine di Resistenza all'Eritro-poietina è stato quindi introdotto per definire quei pazienti che non raggiungono il target di Hb nonostante una dose di ESA superiore a quelle usuali o che continuamente necessitano di dosi più elevate per mantenere nel range i valori di Hb. Numerosi studi presenti in letteratura hanno evidenziato l'associazione tra incremento degli indici infiammatori e ridotta risposta agli ESA; l'infammazione cronica, mediante la produzione di citochine pro-inflammatorie determina soppressione midollare con inibizione della proliferazione e della differenziazione dei progenitori eritroidi e aumento dei livelli di una piccola proteina, l'epcidina, prodotta dal fegato in risposta a stimoli infiammatori che sembra fortemente legata al meccanismo della resistenza all'eritropoietina

Pure red cell aplasia induced by epoetin zeta

Pure red cell aplasia (PRCA) may develop in patients with chronic kidney disease receiving erythropoiesis-stimulating agents (ESA). We report on a 72-year-old patient who developed hypo-proliferative anaemia unresponsive to ESA following the administration of epoetin zeta subcutaneously for 7 months. On the basis of severe isolated hypoplasia of the erythroid line in the bone marrow and high-titre neutralizing anti-erythropoietin antibodies (Ab), a diagnosis of Ab-mediated PRCA was made. Epoetin zeta was discontinued and the patient was given steroids. This was associated with anaemia recovery. To our knowledge this is the first PRCA case related to epoetin zeta

Acute inhibition of estradiol synthesis impacts vestibulo-ocular reflex adaptation and cerebellar long-term potentiation in male rats

The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber–Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the aromatase inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF synapse in vitro, using cerebellar slices from male rats. We found that letrozole acutely impaired both gain increases and decreases adaptation of the VOR without altering basal ocular-motor performance. Moreover, letrozole prevented long-term potentiation at the PF synapse (PF-LTP) without affecting long-term depression (PF-LTD). Thus, in male rats neurosteroid E2 has a relevant impact on VOR adaptation and affects exclusively PF-LTP. These findings suggest that E2 might regulate changes in VOR adaptation by acting locally on cerebellar and extra-cerebellar synaptic plasticity sites

Jania adhaerens Primes Tomato Seed against Soil-Borne Pathogens

Managing soil-borne pathogens is complex due to the restriction of the most effective synthetic fungicides for soil treatment. In this study, we showed that seed priming with Jania adhaerens water-soluble polysaccharides (JA WSPs) was successful in protecting tomato plants from the soil-borne pathogens Rhizoctonia solani, Pythium ultimum, and Fusarium oxysporum under greenhouse conditions. WSPs were extracted from dry thallus by autoclave-assisted method, and the main functional groups were characterized by using FT-IR spectroscopy. WSPs were applied by seed treatment at 0.3, 0.6 and 1.2 mg/mL doses, and each pathogen was inoculated singly in a growing substrate before seeding/transplant. Overall, WSPs increased seedling emergence, reduced disease severity and increased plant development depending on the dose. Transcriptional expression of genes related to phenylpropanoid, chlorogenic acid, SAR and ISR pathways, and chitinase and beta-1,3 glucanase activities were investigated. Among the studied genes, HQT, HCT, and PR1 were significantly upregulated depending on the dose, while all doses increased PAL and PR2 expression as well as beta-1,3 glucanase activity. These results demonstrated that, besides their plant growth promotion activity, JA WSPs may play a protective role in triggering plant defense responses potentially correlated to disease control against soil-borne pathogens

Sensory inflow manipulation induces learning-like phenomena in motor behavior

© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: Perceptual and goal-directed behaviors may be improved by repetitive sensory stimulations without practice-based training. Focal muscle vibration (f-MV) modulating the spatiotemporal properties of proprioceptive inflow is well-suited to investigate the effectiveness of sensory stimulation in influencing motor outcomes. Thus, in this study, we verified whether optimized f-MV stimulation patterns might affect motor control of upper limb movements. Methods: To answer this question, we vibrated the slightly tonically contracted anterior deltoid (AD), posterior deltoid (PD), and pectoralis major muscles in different combinations in forty healthy subjects at a frequency of 100 Hz for 10 min in single or repetitive administrations. We evaluated the vibration effect immediately after f-MV application on upper limb targeted movements tasks, and one week later. We assessed target accuracy, movement mean and peak speed, and normalized Jerk using a 3D optoelectronic motion capture system. Besides, we evaluated AD and PD activity during the tasks using wireless electromyography. Results: We found that f-MV may induce increases (p \u3c 0.05) in movement accuracy, mean speed and smoothness, and changes (p \u3c 0.05) in the electromyographic activity. The main effects of f-MV occurred overtime after repetitive vibration of the AD and PD muscles. Conclusion: Thus, in healthy subjects, optimized f-MV stimulation patterns might over time affect the motor control of the upper limb movement. This finding implies that f-MV may improve the individual’s ability to produce expected motor outcomes and suggests that it may be used to boost motor skills and learning during training and to support functional recovery in rehabilitation

Predicting erythropoietin resistance in hemodialysis patients with type 2 diabetes

<p>Background: Resistance to ESAs (erythropoietin stimulating agents) is highly prevalent in hemodialysis patients with diabetes and associated with an increased mortality. The aim of this study was to identify predictors for ESA resistance and to develop a prediction model for the risk stratification in these patients.</p> <p>Methods: A post-hoc analysis was conducted of the 4D study, including 1015 patients with type 2 diabetes undergoing hemodialysis. Determinants of ESA resistance were identified by univariate logistic regression analyses. Subsequently, multivariate models were performed with stepwise inclusion of significant predictors from clinical parameters, routine laboratory and specific biomarkers.</p> <p>Results: In the model restricted to clinical parameters, male sex, shorter dialysis vintage, lower BMI, history of CHF, use of ACE-inhibitors and a higher heart rate were identified as independent predictors of ESA resistance. In regard to routine laboratory markers, lower albumin, lower iron saturation, higher creatinine and higher potassium levels were independently associated with ESA resistance. With respect to specific biomarkers, higher ADMA and CRP levels as well as lower Osteocalcin levels were predictors of ESA resistance.</p> <p>Conclusions: Easily obtainable clinical parameters and routine laboratory parameters can predict ESA resistance in diabetic hemodialysis patients with good discrimination. Specific biomarkers did not meaningfully further improve the risk prediction of ESA resistance. Routinely assessed data can be used in clinical practice to stratify patients according to the risk of ESA resistance, which may help to assign appropriate treatment strategies.</p&gt

Soluble tumor necrosis factor receptor 1 and 2 predict outcomes in advanced chronic kidney disease : a prospective cohort study

Background : Soluble tumor necrosis factor receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated to progression of renal failure, end stage renal disease and mortality in early stages of chronic kidney disease (CKD), mostly in the context of diabetic nephropathy. The predictive value of these markers in advanced stages of CKD irrespective of the specific causes of kidney disease has not yet been defined. In this study, the relationship between sTNFR1 and sTNFR2 and the risk for adverse cardiovascular events (CVE) and all-cause mortality was investigated in a population with CKD stage 4-5, not yet on dialysis, to minimize the confounding by renal function. Patients and methods : In 131 patients, CKD stage 4-5, sTNFR1, sTNFR2 were analysed for their association to a composite endpoint of all-cause mortality or first non-fatal CVE by univariate and multivariate Cox proportional hazards models. In the multivariate models, age, gender, CRP, eGFR and significant comorbidities were included as covariates. Results : During a median follow-up of 33 months, 40 events (30.5%) occurred of which 29 deaths (22.1%) and 11 (8.4%) first non-fatal CVE. In univariate analysis, the hazard ratios (HR) of sTNFR1 and sTNFR2 for negative outcome were 1.49 (95% confidence interval (CI): 1.28-1.75) and 1.13 (95% CI: 1.06-1.20) respectively. After adjustment for clinical covariables (age, CRP, diabetes and a history of cardiovascular disease) both sTNFRs remained independently associated to outcomes (HR: sTNFR1: 1.51, 95% CI: 1.30-1.77; sTNFR2: 1.13, 95% CI: 1.06-1.20). A subanalysis of the non-diabetic patients in the study population confirmed these findings, especially for sTNFR1. Conclusion : sTNFR1 and sTNFR2 are independently associated to all-cause mortality or an increased risk for cardiovascular events in advanced CKD irrespective of the cause of kidney disease

The social cost of chronic kidney disease in Italy

This study aims to estimate the mean annual social cost per patient with chronic kidney disease (CKD) by stages 4 and 5 pre-dialyses and cost components in Italy. The multicenter cross-sectional study included all adult outpatients in charge of the 14 main Nephrology Centers of Tuscany Region during 7 weeks from 2012 to 2013. Direct medical costs have been estimated using tariffs for laboratory tests, diagnostic exams, visits, hospitalization and prices for drugs. Non-medical costs included expenses of low-protein special foods, travel, and formal and informal care. Patients' and caregivers' losses of productivity have been estimated as indirect costs using the human capital approach. Costs have been expressed in Euros (2016). Totals of 279 patients in stage 4 and 205 patients in stage 5 have been enrolled. The estimated mean annual social cost of a patient with CKD were a,notsign7422 (+/- a,notsign6255) for stage 4 and a,notsign8971 (+/- a,notsign6503) for stage 5 (p < 0.05). Direct medical costs were higher in stage 5 as compared to stage 4; direct non-medical costs and indirect costs accounted, respectively, for 41 and 5 % of the total social cost of CKD stage 4 and for 33 and 9 % of CKD stage 5. In Italy, the overall annual social cost of CKD was a,notsign1,809,552,398 representing 0.11 % of the Gross Domestic Product. Direct non-medical costs and indirect costs were weighted on the social cost of CKD almost as much as the direct medical cost. Patients, their families and the productivity system sustain the burden of the disease almost as much as the healthcare system. © 2016, The Author(s)