The role of syndecan-1 for DIC diagnosis in hemoblastosis patients with sepsis.

Введение. Синдром диссеминированного внутрисосудистого свертывания (ДВС-синдром) является частым осложнением онкогематологических заболеваний. Известно, что повреждение эндотелия сосудов играет одну из ключевых ролей в развитии коагулопатии потребления, особенно в условиях системного воспаления. Повышение концентрации синдекана-1, одного из основных протеогликанов эндотелиального гликокаликса, в плазме крови описано при различных патологических состояниях, включая острые лейкозы и ДВС-синдром. Определение его содержания у больных гемобластозами может способствовать ранней диагностике ДВС-синдрома и своевременному назначению патогенетической терапии. Цель исследования: оценить роль протеогликана синдекан-1 в диагностике ДВС-синдрома у больных гемобластозами с сепсисом. Материалы и методы. Проведен анализ гематологических и биохимических показателей периферической крови, коагулограммы, кислотно-основного состояния и сывороточного содержания синдекана-1 у 54 больных гемобластозами с признаками системного воспаления. Острый миелоидный лейкоз диагностирован у 19 (35%), острый лимфобластный лейкоз – у 10 (18%), неходжкинская лимфома – у 13 (24%), лимфома Ходжкина – у 9 (17%), множественная миелома – у 3 (6%). Концентрацию синдекана-1 сравнивали с таковой у здоровых доноров. Наличие ДВС-синдрома определяли по шкале DIC-score Международного общества по тромбозам и гемостазу (англ. International Society on Thrombosis and Hemostasis, ISTH), степень органных дисфункций – по шкале SOFA (англ. Sequential Organ Failure Assessment). Сепсис верифицировали по критериям консенсуса «Сепсис-3». Взаимосвязь уровня синдекана-1 с показателями гемограммы, коагулограммы, биохимическими параметрами и данными шкал DIC и SOFA оценивали с использованием критерия Спирмена. Диагностическую роль синдекана-1 определяли при помощи ROC-анализа. Результаты. У больных гемобластозами выявлено повышение уровня синдекана-1 по сравнению с таковым у здоровых доноров в 5,8 раз (р = 0,008). Сепсис диагностирован у 28 (52%) пациентов, явный ДВС-синдром выявлен у 14 (25%). Концентрация синдекана-1 в сыворотке крови коррелировала со значениями активированного парциального тромбопластинового времени и протромбинового времени, количеством тромбоцитов, активностью антитромбина III, показателями шкал DIC-score и SOFA. Определена диагностическая роль синдекана-1 при развитии явного ДВС-синдрома (точка отсечения – 5,48 нг/мл, чувствительность – 73%, специфичность – 90%). Заключение. Повышенный уровень синдекана-1 (более 5,48 нг/мл) может служить дополнительным критерием развития ДВС-синдрома у больных гемобластозами с сепсисом. Background. Disseminated intravascular coagulation (DIC) is a severe complication of hemoblastosis. The key role of the vascular endothelium in hemostasis regulation is well known. Its activation and damage are the most important factors of consumption coagulopathy during systemic inflammation. Increased blood level of one of the main proteoglycans of the endothelial glycocalyx – syndecan-1 has been described in various pathological conditions, including acute leukemia and DIC. Syndecan-1 level evaluation in patients with hemoblastosis can help early DIC diagnosis and improve therapy results. Objectives: to assess the role of syndecan-1 for DIC diagnosis in hemablastosis patients with sepsis. Patients/Methods. Hematological and biochemical data of peripheral blood, coagulogram, acid-base balance and serum level of syndecan-1 were analyzed in 54 patients with hemoblastosis with signs of systemic inflammation. Acute myeloid leukemia was diagnosed in 19 (35%) patients, acute lymphoblastic leukemia – in 10 (18%), non-Hodgkin’s lymphoma – in 13 (24%), Hodgkin’s lymphoma – in 9 (17%), multiple myeloma – in 3 (6%). Syndecan-1 concentration was compared with that of healthy donors. DIC was assessed by DIC-score (ISTH, International Society on Thrombosis and Hemostasis), organ dysfunction – by SOFA (Sequential Organ Failure Assessment) score. Sepsis was verified according to the third international consensus definitions for sepsis and septic shock. Relationship of syndecan-1 level with hematological, сoagulological, biochemical data and DIC or SOFA scores was assessed by Spearman rank correlation. The diagnostic value of syndecan-1 was determined by ROC-analysis. Results. Increased level of syndecan-1 in 5.8 times was revealed in patients with hemoblastosis in comparison to healthy donors (p = 0.008). Sepsis was diagnosed in 28 (52%) patients, overt DIC – in 14 (25%). Serum syndecan-1 level correlated with activated partial thromboplastin time, prothrombin time, platelet count, antithrombin III activity, DIC and SOFA scores. The diagnostic role of syndecan-1 was determined in overt DIC (cut-off – 5.48 ng/ml, sensitivity – 73%, specificity – 90%). Conclusions. Increased syndecan-1 level (more than 5.48 ng/ml) can be additional diagnostic criterion for DIC in patients with hematological malignancies and sepsis.

Urinary ethyl glucuronide for the assessment of alcohol consumption during pregnancy: Comparison between biochemical data and screening questionnaires

Background: Ethyl glucuronide (EtG) is a metabolite of ethanol used as a marker of alcohol drinking and is identified in urine. Gestational alcohol drinking harms the fetus, so, disclosing any form of use and abuse of this substance during pregnancy is crucial. Many discovery methods have been planned to overcome this question, including that of using screening questionnaires as the AUDIT-C, T-ACE/TACER-3, and TWEAK. Aim: The aim and novelties of this study were to compare biochemical data from urinary EtG assays (cut-off 100 ng/mL for risking drinking behavior) with the outcome of questionnaires and of a food diary routinely used in our hospital; moreover, for the first time, we analyzed in pregnant women the EtG values normalized by the amount of creatinine excreted according to methods previously established [1]. Methods: Random urine samples were collected from 309 pregnant women immediately after being interviewed. EtG was quantified using an enzyme immunoassay and urinary creatinine was assessed using an enzymatic colorimetric method. Women that had not exhaustively answered one of the questionnaires, or that refused to provide urine samples were excluded. In the end, 309 women had a complete set of data and were considered for this study. Urine creatinine measurements were performed to determine if urine dilution might have resulted in false negatives in the challenge study. In order to accomplish this objective, as urinary creatinine concentrations are, on average, approximately 1 mg/mL, we used a normalized value of 100 ng EtG/mg Creatinine [1]. Results: Our data show that 20.4% of the pregnant women in the study were over the established normalized cut-off value. Poor to null concordance (unweighted k < 0.2) was found between EtG data and the screening interviews, that show, on average, lower levels of alcohol consumption. Conclusion: In conclusion, this study provides evidence that the assessment of maternal alcohol consumption during pregnancy, only indirectly estimated with questionnaires and food diary, can produce misleading ratings.

The hypertriglyceridemic-waist phenotype as a valuable and integrative mirror of metabolic syndrome traits

Rates of non-communicable diseases (NCDs), such as obesity, diabetes, cardiovascular events and cancer, continue to rise worldwide, which require objective instruments for preventive and management actions. Diverse anthropometric and biochemical markers have been used to qualitatively evaluate degrees of disease, metabolic traits and evolution of nutritional status. The aim of this study was to integrate and assess the interactions between an anthropometric measurement, such as waist circumference (WC), and biochemical data, such as the triglyceride glucose index (TyG), in order to individually characterize metabolic syndrome (MetS) features considering the hypertriglyceridemic waist phenotype as a marker. An ancillary cross-sectional study was conducted using anthropometric measurements, such as weight, height, waist and hip circumferences, as well as fasting biochemical data of 314 participants. Different indices based on WC (WC, WC*TG and WC*TyG) were estimated to compute MetS components and accompanying comorbidities. ROC curves were fitted to define the strength of the analyses and the validity of the relationships. Associations were confirmed between anthropometric, biochemical and combined indices with some chronic disease manifestations, including hyperglycemia, hypertension and dyslipidemia. Both WC*TG and WC*TyG indices showed similar performance in diagnosing MetS (area under the ROC curve = 0.81). Interestingly, when participants were categorized according to a reference value of the WC*TyG index (842.7 cm*mg/dl), our results evidenced that subjects classified over this limit presented statistically higher prevalence of MetS and accompanying individual components with clinical relevance for interventions. These results revealed that WC*TyG mirrors the hypertriglyceridemic phenotype, which suggests may serve as a good indicator to define the metabolic syndrome phenotype and a suitable, sensitive, and simple proxy to complement others. A reference point was proposed with a good clinical performance and maximized sensitivity and specificity values.

Low Creatininuria due to Hyponatremia Is Reversible in Many Patients

<b><i>Background:</i></b> Chronic hyponatremia has been reported to be associated with low solute intake and low creatinine excretion (reflecting likely sarcopenia). We wanted to study the effect, on the long term, of correction of hyponatremia on solute and creatinine excretion in chronic SIADH. <b><i>Methods:</i></b> We made a retrospective review of clinical and biochemical data of patients with euvolemic hyponatremia. We analyzed 24-h urine solute and creatinine excretion in volunteers with hyponatremia induced by dDAVP over 4 days, in 12 patients with chronic SIADH (&#x3e;1 month) before and after a few days of SNa correction and in 12 patients (6 women and 6 men) before and after 3 months of SNa correction by a vaptan or urea. <b><i>Results:</i></b> We confirm a low urine creatinine and solute excretion only in patients with chronic hyponatremia (&#x3e;1 month). Correction of SNa (from 127 ± 2.3 mEq/L to 139 ± 2.8 mEq/L) for &#x3e;3 months, in the 12 patients (mean age 58 ± 18), was associated with an increase in 24-h creatinine excretion (from 986 ± 239 to 1,238 ± 220 mg; <i>p</i> &#x3c; 0.02) and in patients treated with a vaptan (<i>n</i> = 5) solute excretion increased from 656 ± 207 mmol/24 h to 960 ± 193 mmol/24 h (<i>p</i> &#x3c; 0.02). Sodium excretion increased also in the 12 patients (from 100 ± 53 mEq/24 h to 169 ± 38 mEq/24 h; <i>p</i> &#x3c; 0.01). <b><i>Conclusion:</i></b> Chronic hyponatremia (&#x3e;1 month) is associated with a decrease in solute output (or intake) and in creatinine excretion. In many patients, these abnormalities are reversible in the long term.

Evaluation of preoperative ultrasonographic parameters to predict renal recovery in long-term survivors after treatment of feline ureteral obstructions: 2012–2019

Objectives The aim of this study was to determine whether preoperative ultrasound imaging characteristic(s) in cats suffering from unilateral benign ureteral obstructions are predictive of outcome after successful renal decompression with a subcutaneous ureteral bypass (SUB) device. Methods This was a retrospective study of 37 cats with unilateral, benign ureteral obstruction. Preoperative imaging characteristics (including renal pelvis diameter, parenchymal thickness [transverse plane], renal length and pelvic size:overall renal size) and biochemical data were evaluated for all cats diagnosed with a unilateral ureteral obstruction treated with a SUB device. Any patient with bilateral obstructions or documented bacteriuria/infection in the data collection period was excluded. All patients were followed between 3 and 6 months postoperatively to obtain postoperative biochemical data. Long-term outcome was defined as serum creatinine concentration at 3–6 months postoperatively. Results No preoperative imaging characteristics or biochemical findings were found to be significantly associated with long-term serum creatinine concentrations. The length of the kidney was found to be associated with change in blood urea nitrogen and creatinine with decompression but not with long-term renal values. Conclusions and relevance In this study, long-term renal function based on preoperative ultrasound imaging findings could not be predicted in cats with unilateral ureteral obstruction, regardless of the severity of the biochemical parameters, renal pelvic dilation (large or small pelvis), kidney size or thickness of renal parenchyma assessed.

YbeY, éminence grise of ribosome biogenesis

YbeY is an ultraconserved small protein belonging to the unique heritage shared by most existing bacteria and eukaryotic organelles of bacterial origin, mitochondria and chloroplasts. Studied in more than a dozen of evolutionarily distant species, YbeY is invariably critical for cellular physiology. However, the exact mechanisms by which it exerts such penetrating influence are not completely understood. In this review, we attempt a transversal analysis of the current knowledge about YbeY, based on genetic, structural, and biochemical data from a wide variety of models. We propose that YbeY, in association with the ribosomal protein uS11 and the assembly GTPase Era, plays a critical role in the biogenesis of the small ribosomal subunit, and more specifically its platform region, in diverse genetic systems of bacterial type.

Crystal structures of an E1–E2–ubiquitin thioester mimetic reveal molecular mechanisms of transthioesterification

E1 enzymes function as gatekeepers of ubiquitin (Ub) signaling by catalyzing activation and transfer of Ub to tens of cognate E2 conjugating enzymes in a process called E1–E2 transthioesterification. The molecular mechanisms of transthioesterification and the overall architecture of the E1–E2–Ub complex during catalysis are unknown. Here, we determine the structure of a covalently trapped E1–E2–ubiquitin thioester mimetic. Two distinct architectures of the complex are observed, one in which the Ub thioester (Ub(t)) contacts E1 in an open conformation and another in which Ub(t) instead contacts E2 in a drastically different, closed conformation. Altogether our structural and biochemical data suggest that these two conformational states represent snapshots of the E1–E2–Ub complex pre- and post-thioester transfer, and are consistent with a model in which catalysis is enhanced by a Ub(t)-mediated affinity switch that drives the reaction forward by promoting productive complex formation or product release depending on the conformational state.

Response to Comment on “Structural evidence for a dynamic metallocofactor during N2 reduction by Mo-nitrogenase”

Peters et al. comment on our report of the dynamic structure of the nitrogenase metallocofactor during N2 reduction. Their claim that their independent structural refinement and consideration of biochemical data contradict our finding is incorrect and is strongly refuted by our biochemical and structural data that collectively and conclusively point to the binding of dinitrogen species to the nitrogenase cofactor.