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Introduction. Gamma-glutamyltransferase (GGT) is a liver enzyme involved in inflammation and oxidative stress. It is already known that MCP-1 (Monocyte Chemoattractant Protein-1) and TNF-α (tumour necrosis factor) as inflammatory markers, ICAM-1 (Intercellular Adhesion Molecule-1) as an endothelial dysfunctional marker, and glutathione, as an antioxidant, have abnormal levels in type 2 diabetic patients. The aim of this study was to evaluate the specific biological picture of type 2 diabetic patients that also associate higher GGT activity.

Scopul acestui studiu, parte a proiectului PERSOTHER, este implementarea unei tehnici noi - hibridizarea in situ cu imunofluorescenţa (FISH) - in diagnosticul limfoamelor Burkitt (BL), pentru prima dată în ţara noastră. BL este un limfom cu celulă B de mare agresivitate clinică. Sunt recunoscute 3 variante de LB: endemică (în Africa ecuatorială), sporadică (peste tot in lume) şi asociată cu imunodeficienţa. Clasificarea Organizaţiei Mondiale a Sănătăţii din 2008 a descris o nouă formă de limfom cu celulă B, neclasificabil, cu caractere intermediare între un limfom difuz cu celulă mare B şi un BL. Deoarece tratamentul BL este foarte agresiv, cu chimioterapie in doze mari, un diagnostic corect este obligatoriu. Citologia, morfologia şi imunofenotipul (CD20+, CD10+, BCL6+, BCL2-, Ki67 98-100%) sunt tipice pentru BL. Majoritatea au o translocaţie a genei MYC, localizate pe 8q24 cu gena pentru IgH, 14q32. Demonstrarea transocaţiei MYC este necesară pentru diagnosticul de BL şi pentru diferenţierea de un DLBCL, în unele cazuri. 22 de cazuri de BL au fost evaluate prin FISH pentru translocaţia MYC. 17 cazuri au fost pozitive, un caz a fost negativ şi 4 cazuri au fost neconcludente. Aceste rezultate sunt concordante cu literatura de specialitate: autorii raportează aproximativ 10% cazuri de BL fără transocaţie MYC. În aceste cazuri pot fi implicate alterări ale micro-ARN. Studiul actual evidenţiază importanţa FISH in diagnosticul BL, identifică unele dificultăţi tehnice ale metodei şi reprezintă pentru viitor, o bază a diagnosticului de rutină, în cazuri selecţionate.

The paper attempts to attract high school pupils to practice a game (basketball), whose techniques were used as drive means for developing combined motor quality – speed regime skill - only for the experimental group (grade: 10th B). In the case of the control group (grade: 10th E), the development of speed and skill was achieved by conventional drive means, complying with the requirements of the specialized syllabus. Besides highlighting the progress achieved from one test to the other, as a hypothesis, it was also examined the extent of learning the game of basketball. The experiment took place at “Constantin Brâncoveanu - Târgovişte” Technological High School, during the 2013-2014 school year. The outcomes were compared both between the two tests (in the case of the experimental group the outcomes being significant, of p = 0.01) and between groups (the outcomes being significant for the experimental group, of p> 0.01). The manners of influencing the motor performance – speed regime skill - have proven effective, after applying the means in question an improvement being recorded in the case of the pupils belonging to the experimental group, those pupils assimilating more easily the game of basketball in comparison with the ones from the control group.

Rationale & Objective: Coronary artery calcification (CAC) progresses rapidly in people with chronic kidney disease (CKD) compared with the general population. We studied the association between CAC progression and higher risks of atherosclerotic cardiovascular disease (CVD), congestive heart failure, and all-cause mortality among adults with CKD., Study Design: Prospective cohort study., Setting: & Participants: 1,310 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had at least one CAC scan with no prior history of CVD and with observed or imputed data on changes in CAC over time., Exposure: Observed or imputed CAC progression, categorized as incident CAC among participants with zero CAC on the baseline scan, or progressive CAC when the baseline scan demonstrated CAC and there was an increase in CAC ≥50 Agatston units per year., Outcomes: Atherosclerotic CVD (myocardial infarction or stroke), congestive heart failure, and all-cause mortality., Analytical Approach: Cause-specific Cox proportional hazards regression, stratified by presence of CAC at baseline., Results: A total of 545 participants without and 765 with prevalent CAC at baseline were included. During a mean 3.3 years between CAC assessments, 177 (32.5%) participants without baseline CAC developed incident CAC while 270 participants (35.3%) with baseline CAC developed a ≥50 Agatston units per year increase in CAC. After multivariable adjustment, incident CAC was associated with 2.42-fold higher rate of atherosclerotic CVD (95% confidence interval [CI]: 1.23-4.79) and 1.82-fold higher rate of all-cause mortality (95% CI: 1.03-3.22). Progressive CAC (≥50 units per year) was not associated with atherosclerotic CVD (hazard ratio [HR]: 1.42; 95% CI: 0.85-2.35) but was associated with a 1.73-fold higher rate of all-cause mortality (95% CI: 1.31-2.28). Progressive CAC was not associated with incident heart failure., Limitations: Residual confounding and limited statistical power for some outcomes., Conclusions: Among adults with CKD stages 2-4, CAC progression over a mean 3.3 years was associated with higher risk of atherosclerotic CVD and all-cause mortality. The associations were strongest among participants without CAC at baseline., (Copyright © 2024. Published by Elsevier Inc.)

Purpose of Review: Cardiomyopathy in chronic kidney disease (CKD) is a complex condition with multiple triggers and poor prognosis. This review provides an overview of recent advances in CKD-associated cardiomyopathy, with a focus on pathophysiology, newly discovered biomarkers and potential therapeutic targets., Recent Findings: CKD is associated with a specific pattern of myocardial hypertrophy and fibrosis, resulting in diastolic and systolic dysfunction, and often triggered by nonatherosclerotic processes. Novel biomarkers, including amino-terminal type III procollagen peptide (PIIINP), carboxy-terminal type I procollagen peptide (PICP), FGF23, marinobufagenin, and several miRNAs, show promise for early detection and risk stratification. Treatment options for CKD-associated cardiomyopathy are limited. Sodium glucose cotransporter-2 inhibitors have been shown to reduce left ventricle hypertrophy and improve ejection fraction in individuals with diabetes and mild CKD, and are currently under investigation for more advanced stages of CKD. In hemodialysis patients calcimimetic etelcalcetide resulted in a significant reduction in left ventricular mass., Summary: CKD-associated cardiomyopathy is a common and severe complication in CKD. The identification of novel biomarkers may lead to future therapeutic targets. Randomized clinical trials in individuals with more advanced CKD would be well posed to expand treatment options for this debilitating condition., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

People living with HIV (PLWH) who are immune nonresponders (INRs) are at greater risk of comorbidity and mortality than are immune responders (IRs) who restore their CD4+ T cell count after antiretroviral therapy (ART). INRs have low CD4+ T cell counts (<350 c/μL), heightened systemic inflammation, and increased CD4+ T cell cycling (Ki67+). Here, we report the findings that memory CD4+ T cells and plasma samples of INRs from several cohorts are enriched in gut-derived bacterial solutes p-cresol sulfate (PCS) and indoxyl sulfate (IS) that both negatively correlated with CD4+ T cell counts. In vitro PCS or IS blocked CD4+ T cell proliferation, induced apoptosis, and diminished the expression of mitochondrial proteins. Electron microscopy imaging revealed perturbations of mitochondrial networks similar to those found in INRs following incubation of healthy memory CD4+ T cells with PCS. Using bacterial 16S rDNA, INR stool samples were found enriched in proteolytic bacterial genera that metabolize tyrosine and phenylalanine to produce PCS. We propose that toxic solutes from the gut bacterial flora may impair CD4+ T cell recovery during ART and may contribute to CD4+ T cell lymphopenia characteristic of INRs.

Background: Individuals with CKD may be at high risk for atherosclerotic cardiovascular disease (ASCVD). However, there are no ASCVD risk prediction models developed in CKD populations to inform clinical care and prevention., Methods: We developed and validated 10-year ASCVD risk prediction models in patients with CKD that included participants without self-reported cardiovascular disease from the Chronic Renal Insufficiency Cohort (CRIC) study. ASCVD was defined as the first occurrence of adjudicated fatal and nonfatal stroke or myocardial infarction. Our models used clinically available variables and novel biomarkers. Model performance was evaluated based on discrimination, calibration, and net reclassification improvement., Results: Of 2604 participants (mean age 55.8 years; 52.0% male) included in the analyses, 252 had incident ASCVD within 10 years of baseline. Compared with the American College of Cardiology/American Heart Association pooled cohort equations (area under the receiver operating characteristic curve [AUC]=0.730), a model with coefficients estimated within the CRIC sample had higher discrimination ( P =0.03), achieving an AUC of 0.736 (95% confidence interval [CI], 0.649 to 0.826). The CRIC model developed using clinically available variables had an AUC of 0.760 (95% CI, 0.678 to 0.851). The CRIC biomarker-enriched model had an AUC of 0.771 (95% CI, 0.674 to 0.853), which was significantly higher than the clinical model ( P =0.001). Both the clinical and biomarker-enriched models were well-calibrated and improved reclassification of nonevents compared with the pooled cohort equations (6.6%; 95% CI, 3.7% to 9.6% and 10.0%; 95% CI, 6.8% to 13.3%, respectively)., Conclusions: The 10-year ASCVD risk prediction models developed in patients with CKD, including novel kidney and cardiac biomarkers, performed better than equations developed for the general population using only traditional risk factors., (Copyright © 2022 by the American Society of Nephrology.)

Rationale & Objective: Metabolic acidosis associated with chronic kidney disease (CKD) may contribute to muscle dysfunction and bone disease. We aimed to test whether treatment with sodium bicarbonate improves muscle and bone outcomes., Study Design: Multicenter, randomized, placebo-controlled, clinical trial., Setting & Participants: 149 patients with CKD stages 3 and 4 between July 2011 and April 2016 at 3 centers in Cleveland, OH, and the Bronx, NY., Intervention: Sodium bicarbonate (0.4 mEq per kg of ideal body weight per day) (n=74) or identical-appearing placebo (n=75)., Outcomes: Dual primary outcomes were muscle function assessed using sit-to-stand test and bone mineral density. Muscle biopsies were performed at baseline and 2 months. Participants were seen at baseline and 2, 6, 12, and 24 months., Results: Mean baseline serum bicarbonate level was 24.0±2.2 (SD) mEq/L and mean baseline estimated glomerular filtration rate was 36.3±11.2mL/min/1.73m 2 . Baseline characteristics did not differ between groups. Mean serum bicarbonate levels in the intervention arm during follow-up were 26.4±2.2, 25.5±2.3, 25.6±2.6, and 24.4±2.8 mEq/L (at 2, 6, 12, and 24 months). These were significantly higher than in the placebo group (P<0.001). Compared to the placebo group, participants randomly assigned to sodium bicarbonate treatment had no significant differences in sit-to-stand time (5 repetitions: P=0.1; and 10 repetitions P=0.07) or bone mineral density (P=0.3). Sodium bicarbonate treatment caused a decrease in serum potassium levels that was of borderline statistical significance (P=0.05). There were no significant differences in estimated glomerular filtration rates, blood pressure, weight, serious adverse events, or levels of muscle gene expression between the randomly assigned groups., Limitations: Initial mean serum bicarbonate level was in the normal range., Conclusions: Sodium bicarbonate therapy in patients with CKD stages 3 and 4 significantly increases serum bicarbonate and decreases potassium levels. No differences were found in muscle function or bone mineral density between the randomly assigned groups. Larger trials are required to evaluate effects on kidney function., Funding: National Institutes of Health grant., Trial Registration: Registered at ClinicalTrials.gov with study number NCT01452412., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Patients with CKD are at high risk for cardiovascular disease, ESKD, and mortality. Vascular calcification is one pathway through which cardiovascular disease risks are increased. We hypothesized that a novel measure of serum calcification propensity is associated with cardiovascular disease events, ESKD, and all-cause mortality among patients with CKD stages 2-4., Design, Setting, Participants, & Measurements: Among 3404 participants from the prospective, longitudinal Chronic Renal Insufficiency Cohort Study, we quantified calcification propensity as the transformation time (T 50 ) from primary to secondary calciprotein particles, with lower T 50 corresponding to higher calcification propensity. We used multivariable-adjusted Cox proportional hazards regression models to assess the associations of T 50 with risks of adjudicated atherosclerotic cardiovascular disease events (myocardial infarction, stroke, and peripheral artery disease), adjudicated heart failure, ESKD, and mortality., Results: The mean T 50 was 313 (SD 79) minutes. Over an average 7.1 (SD 3.1) years of follow-up, we observed 571 atherosclerotic cardiovascular disease events, 633 heart failure events, 887 ESKD events, and 924 deaths. With adjustment for traditional cardiovascular disease risk factors, lower T 50 was significantly associated with higher risk of atherosclerotic cardiovascular disease (hazard ratio [HR] per SD lower T 50 , 1.14; 95% confidence interval [95% CI], 1.05 to 1.25), ESKD within 3 years from baseline (HR per SD lower T 50 , 1.68; 95% CI, 1.52 to 1.86), and all-cause mortality (HR per SD lower T 50 , 1.16; 95% CI, 1.09 to 1.24), but not heart failure (HR per SD lower T 50 , 1.06; 95% CI, 0.97 to 1.15). After adjustment for eGFR and 24-hour urinary protein, T 50 was not associated with risks of atherosclerotic cardiovascular disease, ESKD, and mortality., Conclusions: Among patients with CKD stages 2-4, higher serum calcification propensity is associated with atherosclerotic cardiovascular disease events, ESKD, and all-cause mortality, but this association was not independent of kidney function., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019&#95;10&#95;28&#95;CJN04710419.mp3., (Copyright © 2019 by the American Society of Nephrology.)

Rationale & Objective: Coronary artery calcification (CAC) is prevalent among patients with chronic kidney disease (CKD) and increases risks for cardiovascular disease events and mortality. We hypothesized that a novel serum measure of calcification propensity is associated with CAC among patients with CKD stages 2 to 4., Study Design: Prospective cohort study., Setting & Participants: Participants from the Chronic Renal Insufficiency Cohort (CRIC) Study with baseline (n=1,274) and follow-up (n=780) CAC measurements., Predictors: Calcification propensity, quantified as transformation time (T 50 ) from primary to secondary calciprotein particles, with lower T 50 corresponding to higher calcification propensity. Covariates included age, sex, race/ethnicity, clinical site, estimated glomerular filtration rate, proteinuria, diabetes, systolic blood pressure, number of antihypertensive medications, current smoking, history of cardiovascular disease, total cholesterol level, and use of statin medications., Outcomes: CAC prevalence, severity, incidence, and progression., Analytical Approach: Multivariable-adjusted generalized linear models., Results: At baseline, 824 (65%) participants had prevalent CAC. After multivariable adjustment, T 50 was not associated with CAC prevalence but was significantly associated with greater CAC severity among participants with prevalent CAC: 1-SD lower T 50 was associated with 21% (95% CI, 6%-38%) greater CAC severity. Among 780 participants followed up an average of 3 years later, 65 (20%) without baseline CAC developed incident CAC, while 89 (19%) with baseline CAC had progression, defined as annual increase≥100 Agatston units. After multivariable adjustment, T 50 was not associated with incident CAC but was significantly associated with CAC progression: 1-SD lower T 50 was associated with 28% (95% CI, 7%-53%) higher risk for CAC progression., Limitations: Potential selection bias in follow-up analyses; inability to distinguish intimal from medial calcification., Conclusions: Among patients with CKD stages 2 to 4, higher serum calcification propensity is associated with more severe CAC and CAC progression., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Large size, protein binding and intracellular sequestration are well known to limit dialytic removal of compounds. In studying the normal renal and dialytic handling of trimethylamine oxide (TMAO), a molecule associated with cardiovascular disease in the general population, we discovered two largely unrecognized additional limitations to sustained reduction of a solute by chronic hemodialysis. We measured solute levels and handling in subjects on chronic hemodialysis (ESRD, n = 7) and compared these with levels and clearance in normal controls (NLS, n = 6). The ESRD patients had much higher peak predialysis plasma levels of TMAO than NLS (77 ± 26 vs 2±1 μM, mean ± SD, p<0.05). For comparison, predialysis BUN levels in ESRD subjects were 45±11 mg/dl and 15±3 mg/dl in NLS. Thus TMAO levels in ESRD average about 40 fold those in NLS while BUN is 3 fold NLS. However, the fractional reduction of TMAO concentration during dialysis, was in fact greater than that of urea (86±3 vs 74±6%, TMAO vs urea, p < 0.05) and its dialytic clearance while somewhat lower than that of urea was comparable to creatinine's. Also production rates were similar (533±272 vs 606 ± 220 μ moles/day, ESRD vs NLS, p>0.05). However, TMAO has a volume of distribution about one half that of urea. Also in NLS the urinary clearance of TMAO was high (219±78 ml/min) compared to the urinary urea and creatinine clearances (55±14 and 119±21 ml/min, respectively). Thus, TMAO levels achieve multiples of normal much greater than those of urea due mainly to 1) TMAO's high clearance by the normal kidney relative to urea and 2) its smaller volume of distribution. Modelling suggests that only much more frequent dialysis would be required to lower levels Thus, additional strategies such as reducing production should be explored. Furthermore, using urea as the sole marker of dialysis adequacy may be misleading since a molecule, TMAO, that is dialyzed readily accumulates to much higher multiples of normal with urea based dialysis prescriptions.

Despite the increase in obesity among women of reproductive ages, few studies have considered maternal obesity as a risk factor for breast-feeding success. We tested the hypothesis that women who are obese (BMI = 30-34.9) and very obese (BMI >or=35) before pregnancy are less likely to initiate and maintain breast-feeding than are their normal-weight counterparts (BMI = 18.5-24.9) among white and black women. Data from 2000 to 2005 South Carolina Pregnancy Risk Assessment Monitoring System (PRAMS) were used. The overall response rate was 71.0%; there were 3,517 white and 2,846 black respondents. Black women were less likely to initiate breast-feeding and breast-fed their babies for a shorter duration than white women. Compared to normal-weight white women, very obese white women were less likely to initiate breast-feeding (odds ratio: 0.63; 95% confidence interval (CI) = 0.42, 0.94) and more likely to discontinue breast-feeding within the first 6 months (hazard ratio (HR) = 1.89; 95% CI: 1.39, 2.58). Among black women, prepregnancy BMI was neither associated with breast-feeding initiation nor with breast-feeding continuation within the first 6 months. Because very obese white women are less likely to initiate or continue breast-feeding than other white women, health professionals should be aware that very obese white women need additional breast-feeding support. Lower rates of breast-feeding among black women suggest that they should continue to be the focus of the programs and policies aimed at breast-feeding promotion in the United States.

In an attempt to find a direct method for the determination of circulating immune complexes in pathological sera we studied the ability of Cibacron Blue 3GA covalently bound to Sepharose 4B to bind heat- or antigen-aggregated human IgG. Blue-Sepharose was found to bind significant amounts of aggregated IgG (about 1.5 mg/ml packed gel) but very low amounts of monomeric IgG (about 0.1 mg/ml gel). The ability of Blue-Sepharose to bind immune complexes was tested on human pathological sera containing variable amounts of circulating immune complexes. Using both a turbidimetric measurement and Barkas' method we found that Blue-Sepharose is able to remove a very high percent of circulating immune complexes (greater than 80%) from sera. Considering the above observations a new method is described for the direct determination of circulating immune complexes using Blue-Sepharose as serum adsorbent and either 125I-labeled protein A or 125I-labeled rabbit IgG anti-human IgG to demonstrate the binding of immune complexes.

Rabbit liver cells were able to bind cytophilic monomeric and polymeric homologous IgG via their Fc receptor binding sites (FcR). On the other hand, non-cytophilic rabbit IgG did not bind to hepatocytes, even after its aggregation. The present findings suggest that FcR on rabbit liver cells are specific for cytophilic monomeric IgG but do not significantly bind non-cytophilic, polymeric IgG.

Nuclei isolated from rabbit liver are able to bind cytophilic monomeric and polymeric homologous IgG while non-cytophilic rabbit IgG are not bound by nuclei even after its aggregation. The present finding suggests that the rabbit hepatocyte nuclear envelope is similar to the liver cell membrane as regards the specific binding of monomeric cytophilic IgG via a selective binding site for the Fc fragment of IgG. Therefore, the Fc receptor is not restricted to the external membrane of the hepatocyte but exists also on the nuclear envelope.

A method for the determination and removal of circulating immune complexes in pathological sera was developed using human secretory or dimeric myeloma IgA covalently bound to Sepharose 4B. IgA-Sepharose 4B was able to selectively bind heat or antigen-aggregated human IgG (circulating immune complexes) but not monomeric IgG. The absorbent was also able to remove a very high proportion (95%) of circulating immune complexes from pathological sera as determined by a turbidimetric technique. An immunoradiometric assay for the direct measurement of circulating immune complexes is described. The assay uses IgA-Sepharose 4B as an absorbent (for the binding of IgG immune complexes from sera) and 125I-rabbit anti-IgG antibody (for the quantitation of IgG immune complexes bound to IgA-Sepharose 4B). The mean value obtained for pathological sera (27.1 +/- 0.9) was significantly higher than that of normal sera (4.8 +/- 0.5).

Specific surface receptors for the Fc region of human immunoglobulin A (Fc alpha R) were identified on the thymus cells of all 15 patients affected by myasthenia gravis. A large variation of the percentage of Fc alpha R bearing thymus cells was recorded (9 . 5-66 . 0%; mean value 27 . 9 +/- 17 . 8) the high values being associated in most cases with the thymus hyperplasia and the low values with a lipomatosis of the organ. Even the lowest percentage of Fc alpha R bearing cells recorded in myasthenia gravis are considerably higher than those found in normal subjects (0 . 4-4 . 1; mean value 1 . 8) demonstrating that the expression of Fc alpha R on the thymus cells is the consequence of the disease. No attempts were made to identify the cell population bearing Fc alpha R but indirect results indicate that the cells belong to E-rosette forming population, and, in some cases, to a null cell population devoid of the ability to form E and EAC rosettes, Fc alpha R can bind various IgA ligands and the binding is confined to a small fraction of IgA (not more than 5%) considered as cytophilic IgA.

Protein A containing staphylococci were saturated with human monomeric IgG (mIgG) and cross-linked with glutaraldehyde. The resulting material (SMG) preferentially bound aggregated IgG (aIgG) and soluble immune complexes (CIC). One milliliter of a 10% suspension of SMG bound approximately 30 micrograms of mIgG and 1000 micrograms of aIgG and CIC. The binding of aIgG to SMG was reduced to approximately 50% at a 20-fold excess of mIgG over aIgG. CIC and aIgG could be released from SMG by elution with 3 M KSCN. The results indicate that SMG can be used for identification and removal of CIC in patient plasma.

About 15% of rabbit IgG loaded on a column of Con A-Sepharose 4B was found to be specifically bound to the column due to a structural variation in its carbohydrate moiety. The Con A-retained rabbit IgG contained a higher amount of neutral hexoses than the initial IgG but its molecular weight, antigenic structure and half-life were identical or similar. The Con A-retained rabbit IgG has an affinity for the Fc receptor-bearing homologous macrophages which is 10 times higher than that of the initial IgG. The IgG fraction not retained on Con A-Sepharose is practically devoid of binding ability. These results suggest that the Con A-bound IgG may represent the cytophilic fraction of monomeric IgG responsible for the binding of IgG to Fc receptor-bearing cells.

In the course of two chronic experiments including the administration of N-2-acetylaminofluorene (N-A-AF) to male Wistar rats, alterations were observed in the fine structure of the nuclei isolated from the liver. After the first 3 to 4 months of ingestion of the carcinogen, the heterochromatin became uniformly distributed throughout the nucleus, with dissociation of the nucleolus-associated heterochromatin. At longer intervals (7 months) evidence was found in the nucleus of various types of inclusions, chiefly granular virus-like bodies. Subsequently, the frequency of inclusions diminished but the liver cell nucleus remained large, with numerous large nucleoli. This suggested the existence of a stage of metabolic activation of the liver cell nucleus in the course of experimental induction of hepatocarcinoma with N-A-AF, giving rise to an increase in the nuclear and nucleolar volume by accumulation of synthesis products and disorders in nucleo-cytoplasmic exchanges.