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The aim of this study was to assess whether adding Ca2+ to aggregate or native forms of β -lactoglobulin alters gut hormone secretion, gastric emptying rates and energy intake in healthy men and women. Fifteen healthy adults (mean ± sd: 9M/6F, age: 24 ± 5 years) completed four trials in a randomised, double-blind, crossover design. Participants consumed test drinks consisting of 30 g of β -lactoglobulin in a native form with (NATIVE + MINERALS) and without (NATIVE) a Ca2+-rich mineral supplement and in an aggregated form both with (AGGREG + MINERALS) and without the mineral supplement (AGGREG). Arterialised blood was sampled for 120 min postprandially to determine gut hormone concentrations. Gastric emptying was determined using 13C-acetate and 13C-octanoate, and energy intake was assessed with an ad libitum meal at 120 min. A protein × mineral interaction effect was observed for total glucagon-like peptide-1 (GLP-1TOTAL) incremental AUC (iAUC; P < 0·01), whereby MINERALS + AGGREG increased GLP-1TOTAL iAUC to a greater extent than AGGREG (1882 ± 603 v. 1550 ± 456 pmol·l−1·120 min, P < 0·01), but MINERALS + NATIVE did not meaningfully alter the GLP-1 iAUC compared with NATIVE (1669 ± 547 v. 1844 ± 550 pmol·l−1·120 min, P = 0·09). A protein × minerals interaction effect was also observed for gastric emptying half-life (P < 0·01) whereby MINERALS + NATIVE increased gastric emptying half-life compared with NATIVE (83 ± 14 v. 71 ± 8 min, P < 0·01), whereas no meaningful differences were observed between MINERALS + AGGREG v. AGGREG (P = 0·70). These did not result in any meaningful changes in energy intake (protein × minerals interaction, P = 0·06). These data suggest that the potential for Ca2+ to stimulate GLP-1 secretion at moderate protein doses may depend on protein form. This study was registered at clinicaltrials.gov (NCT04659902). [ABSTRACT FROM AUTHOR]

Background: While the utility of beta-2 microglobulin (β2M) has been explored in various renal conditions to identify tubulointerstitial damage, it has not been adequately studied in nephrotic syndrome. The primary objective of the study was to compare urinary β2M levels in children with steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) in disease remission. Materials and Methods: This cross-sectional study was done at a tertiary care hospital between April 2019 and March 2020. Sixty children (2-18 years) with SSNS and SRNS (30 in each group) in remission were enrolled. SRNS patients were included after ≥1 year of treatment with calcineurin inhibitors (CNIs). Biochemical investigations were done to confirm remission; spot samples for urinary β2M were collected and estimation was done by an enzyme-linked immunosorbent assay (ELISA)-based kit. Results: Of the 60 children, 63% were boys. The median (interquartile range [IQR]) age at enrollment for SSNS and SRNS patients was 7 (4.1-9) and 11 (8.3-12) years, respectively. Urinary β2M levels were significantly higher in SRNS patients compared to SSNS patients (2.6 vs. 0.75 µg/ml, P < 0.0001). Patients who received cyclosporine for >2 years had higher median urinary β2M levels compared to those who received it for a shorter period (2.63 vs. 1.83 µg/ml, P = 0.03). Median β2M levels were higher in focal segmental glomerulosclerosis than minimal change disease (3.5 vs. 2.5 µg/ml). Conclusion: Urinary β2M levels were higher in SRNS compared to SSNS disease in remission, and β2M levels correlated well with CNI use of >2 years. It appears to be a promising noninvasive tool to identify early tubular damage and progression in patients with nephrotic syndrome, especially SRNS. [ABSTRACT FROM AUTHOR]

The 'Thomas plot' is a very helpful diagnostic tool for evaluation, monitoring and therapy of the iron status and on the hemoglobinization of the reticulocytes of patients. In 2021 Roche Diagnostics launched a second generation assay for determination of the soluble transferrin receptor (sTfR). Here we compare the old and the new assay for sTfR and analyze the consequences for the 'Thomas plot'. Measurement of sTfR, ferritin and CRP were done using a Cobas8000 system. Hemoglobin content of reticulocytes (Ret-He) was determined using a Sysmex XN9000 system. The second generation of sTfR assay showed consistently lower sTfR values compared to the first generation, which would result in a left shift of the 'Thomas plot' and may lead to false diagnosis of patients using the original cut-offs. Fifteen thousand five hundred ninty two data sets for 'Thomas plot' from 2016 to 2021 were retrospectively analyzed to estimate how many patients in our hospital would be affected. In result around 5 % of all 'Thomas plots' would be affected by the lower sTfR values of the second generation assays. Due to the lower sTfR values measured with the second generation assay new cut-offs for the Ferritin-Index (sTfR/lg Ferritin) should be used in order to correctly diagnose the iron status of patients. [ABSTRACT FROM AUTHOR]

Sickle cell disease is caused by a mutation in the beta-globin gene, leading to the formation of abnormal haemoglobin and various complications. Managing this condition during pregnancy requires a collaborative approach, involving close follow-up, patient education, and active patient involvement. The process begins with pre-conception genetic counselling and assessing the patient’s baseline health. If the disease is uncontrolled or if the patient has kidney disease, hypertension, or frequent vaso-occlusive crises, pregnancy may need to be delayed or alternative reproductive options considered. The use of hydroxyurea during pregnancy is a subject of debate and is determined on a case-by-case basis. High-dose folic acid supplementation is recommended before and during pregnancy. Medications should be carefully reviewed, and any potentially harmful drugs to the fetus should be discontinued. Low-dose aspirin and adequate hydration are used to prevent hypertensive and vaso-occlusive crises, respectively. Severe anaemia may require a blood transfusion, but haemoglobin levels are maintained below 10g/dl to prevent increased blood viscosity. Vaginal delivery can be safely performed with appropriate measures such as hydration, warmth, and nasal oxygen. Cesarean sections are reserved for obstetric indications.. [ABSTRACT FROM AUTHOR]

Background and Objectives Thalassemia is the most common monogenic disease worldwide inherited in autosomal recessive manner. Beta-thalassemia is caused by mutations in beta-globin gene. It is characterized by reduction in red blood cell indices including low MCV, low MCH, high RBC count, low HbA1 and high HbA2. Considering these symptoms, finding a relation between erythrocyte indices and kind of mutations can be used as a rapid method in mutation diagnosis and initial screening of carriers. Materials and Methods In this descriptive-analytical study after DNA extraction from 200 beta- thalassemia minors in Khuzestan province by salting out method, we amplified and sequenced beta-globin gene by Sanger sequencing. Finally, we analyzed statistically the beta-globin gene mutations and erythrocyte indices association by SPSS. Results Our results showed that IVSII-1(G > A) is the most common mutation with 22.5% frequency in this population of beta-thalassemia carriers. We found that MCV index variations have a meaningful association with beta-globin gene mutations and the highest mean of MCV (65.4 ± 3.7) was observed in IVSI-110(G > A) mutation. Conclusions The results comply with many other studies performed in this field and can be used for rapid detection of mutation in carrier parents and prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Physical Medicine & Rehabilitation Sciences is the property of Turkiye Klinikleri and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: To examine the steroid hormone effect on the physical performance of young athletes during an Olympic weightlifting competition. Methods: 26 boys and 26 girls were monitored across 2 weightlifting competitions. Pre- and post-competition testosterone (T), cortisol (C) and dehydroepiandrosterone-sulfate (DHEA-s) were measured in blood, with pre-event free T (FT) and the free androgen index (FAI) calculated. Body mass (BM) and weightlifting performance were recorded. Results: The boys had a larger BM, superior performance with more T, FT and a higher FAI than girls (p < .01). Although C (32%) and DHEA-s (8%) levels were elevated across competition, no sex differences in hormone reactivity were seen. In boys, DHEA-s correlated with performance (r = .46), but not after controlling for BM (r = .14). For girls, T correlated with performance (r = -0.51) after BM was controlled. Conclusions: The sex differences that emerge during puberty were observable, whereby the boys were larger and stronger with a more anabolic profile than girls. Individual DHEA-s (boys) and T (girls) levels were related to performance, but BM appeared to be acting as a mediating (boys) or suppressing (girls) variable. This adds new insight regarding the hormonal contribution to competitive performance in young athletes. [ABSTRACT FROM AUTHOR]

Aim: To investigate the connection of alpha‐1 acid glycoprotein inflammatory biomarker with clinical, hormonal, and metabolic characteristics in women with polycystic ovary syndrome (PCOS) and normal cycling controls. Methods: A cross‐sectional study was conducted on 235 women with PCOS and 92 normal cycling controls attended between 2008 and 2018. Alpha‐1 acid glycoprotein levels were correlated with clinical, anthropometric, anthropometric‐metabolic indexes, and hormones of women with PCOS and controls. Simple and multivariate stepwise linear regression, matched for age and body mass index confounding variables, was performed. Results: Alpha‐1 acid glycoprotein levels were higher in women with PCOS (p = 0.0016). In controls, it was positively correlated with waist circumference, fat mass, body adiposity index, and lipid accumulation product, and negatively correlated with sex hormone‐binding globulin (p < 0.005 for all comparisons). In PCOS, it was positively correlated with testosterone, most biomarkers of central adiposity, homeostatic model assessment of insulin‐resistant, erythrocyte sedimentation rate, and negatively correlated with sex hormone‐binding globulin, high‐density lipoprotein cholesterol, glucose/insulin ratio, and lymphocytes (p < 0.055 for all comparisons). After multivariate regression in women with PCOS, alpha‐1 acid glycoprotein retained a significant positive correlation with erythrocyte sedimentation rate and C‐reactive protein. Conclusions: In PCOS, alpha‐1 acid glycoprotein is correlated with biomarkers of adiposity, carbohydrate metabolism, and total testosterone. This inflammatory marker is also correlated with erythrocyte sedimentation rate, neutrophils, and lymphocytes, frequent markers of an inflammation state. [ABSTRACT FROM AUTHOR]

To determine correlations of serum beta 2-microglobulin (β2-MG) level with disease activity and renal involvement in patients with systemic lupus erythematosus (SLE). Two hundred eligible SLE patients were assigned into remission and active stage groups according to SLE disease activity index (SLEDAI) scores. They were also assigned into kidney damage and no kidney damage groups. Serum β2-MG, Scr, ALB, BUN, anti-dsDNA, complements C3, C4 and 24-h urinary total protein (UTP) were detected. Estimated glomerular filtration rate (eGFR) was calculated. Correlations of β2-MG level with SLEDAI score and eGFR were subjected to Spearman analysis. Affecting factors were explored by logistic multivariate regression analysis, and predictive values of β2-MG level for SLE, disease activity and renal damage were assessed by ROC curves. β2-MG, Scr, ALB, C3, C4, anti-dsDNA and UTP levels, eGFR and SLEDAI score were different between patients with different disease activities, and, except for eGFR, also between patients with different renal damage degrees (p<0.05). Serum β2-MG, Scr, ALB, C3, C4, anti-dsDNA, UTP, eGFR and SLEDAI score were independent factors for disease activity (p<0.05), and β2-MG, ALB, C3, UTP, eGFR and SLEDAI score were factors affecting renal damage (p<0.05). β2-MG level was correlated positively with SLEDAI score (r=0.877, p=0.000) and negatively with eGFR (r=−0.873, p=0.000). This level was highly valuable for predicting SLE, disease activity and renal damage. Serum β2-MG levels in SLE patients are correlated positively with disease activity and negatively with renal involvement, being highly sensitive and specific for predicting SLE, disease activity and eGFR. [ABSTRACT FROM AUTHOR]

Objective: It was previously shown that HLA–B27 subtypes predisposing to spondyloarthritis (SpA), i.e., B*27:02, B*27:05, and B*27:07, displayed an increased propensity to form intracellular oligomers and to accumulate at a high density in cytoplasmic vesicles, as compared to the non–SpA‐associated HLA–B*07:02 and HLA–B*27:06. This study was undertaken to characterize the nature and content of HLA–B–containing vesicles and to further examine their relevance to SpA predisposition. Methods: Vesicles containing HLA–B proteins were detected in transfected HeLa cells and in cells from SpA patients or HLA–B27/human β2‐microglobulin (hβ2m)–transgenic rats, by microscopy. The nature and content of HLA–B–containing vesicles were characterized in colocalization experiments with appropriate markers. Results: The SpA‐associated HLA–B*27:04 subtype accumulated at higher levels (P < 10−5) in cytoplasmic vesicles compared to HLA–B*27:06, from which it differs only by 2 substitutions, reinforcing the correlation between vesicle formation and SpA predisposition. Colocalization studies showed that those vesicles contained misfolded HLA–B heavy chain along with β2m and endoplasmic reticulum (ER) chaperones (calnexin, calreticulin, BiP, glucose‐regulated protein 94‐kd) and belonged to the ER but were distinct from the peptide‐loading complex (PLC). Similar vesicles were observed in immune cells from HLA–B27+ SpA patients, in greater abundance than in healthy controls (P < 0.01), and in dendritic cells from HLA–B27/hβ2m transgenic rats, correlating with SpA susceptibility. Conclusion: Accumulation of misfolded HLA–B heavy chain along with β2m and ER chaperones into ER‐derived vesicles distinct from the PLC is a characteristic feature of HLA–B27 subtypes predisposing to SpA. This phenomenon could contribute to HLA–B27 pathogenicity, via a noncanonical mechanism. [ABSTRACT FROM AUTHOR]

Aim: Sex differences have long been reported in schizophrenia leading to the hypothesis that sex hormones may be implicated in the pathophysiology of the disorder. We assessed gonadal hormones during the fasted state in drug-naïve patients with psychosis. Method: Fasting serum concentrations of follicular-stimulating hormone (FSH) and luteinizing hormone (LH), testosterone, free-testosterone, Sex Hormone Binding Globulin (SHBG) and oestradiol (E2) were compared between a group of 55 newly diagnosed, drug-naïve, first-episode men with psychosis and a group of 55 healthy controls, matched for age, smoking status and BMI. Testosterone, free-testosterone and SHBG were compared between a group of 32 drug-naïve, first-episode females with psychosis and a group of 32 healthy controls matched for age, smoking status and BMI. Results: Testosterone and free-testosterone levels were significantly lower in the patients' group and SHBG levels significantly higher in the patients' group compared to those in healthy controls. The two female groups had similar values in the hormones which were measured. Conclusion: Our findings provide evidence of lower testosterone and free-testosterone levels and increased SHBG levels in drug-naïve, first-episode males with psychosis. Reduced testosterone and free-testosterone levels in drug-naive, first-episode males with psychosis. Increased SHBG levels in drug-naive first-episode males with psychosis. No difference in FSH, LH and E2 levels between drug-naive first episode males with psychosis and controls. No difference in testosterone, free-testosterone and SHBG levels between drug-naive, first-episode women with psychosis and controls. [ABSTRACT FROM AUTHOR]

Background Hepatitis C virus (HCV) and hepatic dysfunction are associated with low total and free testosterone (TT and FT) and high sex hormone-binding globulin (SHBG). However, little is known about changes in testosterone following successful HCV treatment. Methods We evaluated testosterone levels and the prevalence of low testosterone in a cohort of 327 men with chronic HCV infection (human immunodeficiency virus [HIV] coinfection = 150) and in a subset of 85 men with testosterone levels obtained pre-HCV treatment and after sustained virologic response (SVR). Median follow-up was 36 months. Results Participants with active HCV at baseline had higher TT (P <.0001) and SHBG (P <.0001) compared with participants who had achieved SVR, whereas FT did not differ. Low TT (<10.4 nmol/L) was more prevalent in participants with SVR compared with active HCV (P =.002); however, low FT (<0.1735 nmol/L) was common (50% active HCV, 43% SVR) and did not different between groups. For participants with longitudinal determinations, TT and SHBG decreased significantly (P <.0001) while FT remained unchanged post-SVR. Low FT persisted after SVR (pre-treatment 58%, post-SVR 54%, P =.72). HIV status and change in aspartate aminotrasferase-to-platelet ratio were significant independent predictors of change in FT following SVR. Conclusions During active HCV infection, testosterone deficiency may be masked due to elevated SHBG. Despite improvements in SHBG following SVR, low FT was common and persisted after HCV clearance, indicating the need for enhanced awareness and screening using estimates of FT following successful treatment of chronic HCV. Clinical Trials Registration NCT01350648. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to analyze the expression level of CRISP2, CATSPER1, PATE1 and SEMG1 genes in the sperm of men with asthenozoospermia (AZS). AZS is a cause of infertility in men in which the motility of the sperm is reduced. So far, a few genes have been associated with AZS; however, in most of the cases, its molecular etiology is unclear. Methods: A total of 35 subjects with idiopathic AZS and 35 fertile and healthy men as control were included. In study after total RNA extraction and cDNA synthesis, relative quantification was performed. B2M was used as the normalizer gene and fold change was calculated by 2-ΔΔCt method. Mann-Whitney test was used to compare the expression levels between the case and control groups with significance level of p<0.05. Results: Our results showed that CRISP2 (p=0.03) and SEMG1 (p=0.03) were significantly down- and up-regulated in AZS men respectively compared to the controls. But CATSPER1 and PATE1 did not show significant changes. Conclusion: Down-regulation of CRISP2 and up-regulation of SEMG1 were associated with AZS, which could be suggested as the potential candidate genes for the development of a diagnostic marker or potentially for more studies for treatment of AZS. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by abnormal hemoglobin production which leads to hemolytic anemia and intermittent occlusion of small blood vessels, which further leads to tissue ischemia, chronic organ damage, and organ dysfunction including urinary system. To measure the serum levels of cystatin-C and beta 2 microglobulin in pediatric patients with SCDand to investigate their significance as early biomarkers of glomerular and/or renal tubular dysfunction. This study was conducted among 70 children with SCD and 40 age and sex-matched children as a control group. All subjects underwent a full medical history, through physical examination, laboratory investigations including blood urea, serum creatinine, serum ferritin, estimated glomerular filtration rate (eGFR) using the Schwartz formula, creatinine clearance, urinary albumin/creatinine ratio, serum cystatin-C, and β-2 microglobulin levels. Pediatric patients with SCD had significantly higher serum cystatin-C and β-2 microglobulin levels compared to controls. In addition, serum cystatin-C and β-2 microglobulin levels were positively correlated with blood urea, serum creatinine, serum ferritin, urinary albumin/creatinine ratio, duration of iron chelating agents and frequency of blood transfusion/year. Serum cystatin-C and β-2 microglobulin levels were negatively correlated with hemoglobin. Our data concluded that serum cystatin-C and β-2 microglobulin had highersensitivity and specificity (91%, 90% and 85.7%, 100%, respectively) than serum creatinine (79% and85%, respectively).Serum Cystatin-C and β-2 microglobulin are early specific and sensitive biomarkers for evaluating glomerular and tubular dysfunction in children with SCD. [ABSTRACT FROM AUTHOR]

Enolase, which catalyses the conversion of 2-phospho-D-glycerate to phosphoenolpyruvate, is an important enzyme in the classic glycolysis pathway in cells. Enolase is highly conserved in organisms from bacteria to humans, indicating its importance in cells. Thus, enolase is a good target for developing new drugs. In the last decade, new functions of this enzyme have been found. Helicobacter pylori is a common human pathogen that causes gastric diseases and even gastric cancer. In this study, the sequence of H. pylori enolase (HpEno) was analysed; the conservation (at least partial) of binding sites for cofactor, plasminogen, and host extracellular RNA, as well as catalytic site, indicates that HpEno should be capable of performing the functions. Recombinant HpEno was overexpressed and purified from E. coli. Compared to the enolases from other species, HpEno had similar characteristics for its secondary structure. The temperature-induced profiles indicate that HpEno is quite stable to temperature, compared to other homologs. Regarding the kinetics of the unfolding reaction, we found that the activation enthalpy associated with the thermal unfolding reaction is equivalent to the reported activation enthalpy for yeast enolase, indicating a similar scaffold and kinetic stability. Although a wide range of experimental conditions were assayed, it was not possible to detect any enzymatic activity of HpEno. To prove the lack of activity, still a much wider range of experiments should be carried out. [ABSTRACT FROM AUTHOR]

A major goal of this study was to determine whether serum protein fractions of healthy Florida manatees differ with age, sex, or living environments (wild versus housed). A second goal was to determine which serum protein fractions vary in diseased versus healthy manatees. Serum protein fractions were determined using agarose gel electrophoresis. Healthy adults had slightly higher total serum protein and total globulin concentrations than younger animals. This largely resulted from an increase in gamma globulins with age. Total serum protein, albumin, alpha-1 globulin, beta globulin, and total globulin concentrations were slightly higher in housed manatees compared to wild manatees, but there was no significant difference in the albumin/globulin (A/G) ratio, suggesting a difference in hydration between these groups. No significant differences were attributable to sex or pregnancy. Serum albumin concentrations and A/G ratios were significantly lower for manatees with boat trauma, entanglements, emaciation, or cold stress compared to healthy manatees. Variable increases were seen in alpha-1globulins, alpha-2 globulins, beta globulins, and gamma globulins. These globulin fractions contain positive acute-phase proteins and immunoglobulins, and their increases may reflect acute or chronic active inflammation. Changes in serum protein fractions were not consistent enough to justify the use of serum protein electrophoresis as a routine diagnostic test for manatees. However, serum (or plasma) protein electrophoresis is required when accurate values for albumin and globulins are needed in manatees and in determining which protein fractions may account for a hyperproteinemia or hypoproteinemia reported in a clinical chemistry panel. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to investigate the effects of serum beta-2 microglobulin (B2M) on the risks of major cardiovascular events (MACEs) and all-cause death in Chinese elderly isolated systolic hypertension (ISH) patients without severe renal insufficiency (estimated glomerular filtration rate [eGFR] <30 ml/min/1.73 m²). Materials and Methods: Serum B2M concentration, creatinine-eGFR, and blood pressure variability were evaluated in 460 elderly patients (mean age, 82.6 years; 28 women) with ISH in this observational study. The Cox proportional hazard model was adopted to calculate adjusted hazard ratios (HRs) of risk factors for cardiovascular events and all-cause deaths. Results: During a median follow-up period of 37.6 months, 63 patients (13.7%) died, and 65 patients (14.1%) had MACEs. Multivariable analysis showed that the higher serum B2M concentration (B2M ≥0.28 mg/dl) was an independent predictor of increased risk of MACEs (nonfatal acute myocardial infarction, acute heart failure, ischemic stroke, and cardiovascular deaths) and all-cause death (HR: 2.62, 95% confidence interval [CI]: 1.46-4.69, P = 0.001 and HR: 3.40, 95% CI: 1.78-6.48, P < 0.001, respectively) adjusting for other multiple confounders including creatinine-eGFR and cystatin C. In addition, blood pressure variability derived from ambulatory blood pressure measurement was not associated with incidence of MACEs and all-cause mortality (P > 0.05). Conclusion: Our data suggest that serum B2M concentration may be individually associated with MACEs and all-cause death in elderly ISH patients without severe renal insufficiency even after adjusted for creatinine-eGFR and cystatin C. [ABSTRACT FROM AUTHOR]

Objective. To explore the effect and mechanism of ShiZhiFang on uric acid metabolism. Methods. 40 rats were divided into normal group, model group, ShiZhiFang group, and benzbromarone group. The hyperuricemic rat model was induced by yeast gavage at 15 g/kg and potassium oxonate intraperitoneal injection at 600 mg/kg for two weeks. During the next two weeks, ShiZhiFang group rats were given ShiZhiFang by gavage, and benzbromarone group rats were given benzbromarone by gavage. The serum uric acid, creatinine, blood urea nitrogen, XOD activity, urinary uric acid, urinary β2-MG, and histopathological changes were observed in the rats of each group after treatment. Results. The hyperuricemic model was established successfully and did not show the increase of serum creatinine and blood urea nitrogen. Compared with the model group, the serum uric acid, serum XOD activity, and urinary β2-MG were significantly decreased (p<0.05), and 24 h urinary uric acid excretion was significantly decreased (p<0.01) in ShiZhiFang group, whereas the two treatment groups were of no statistical significant in above indicators (p>0.05); renal histopathology showed that the lesions in two treatment groups were reduced compared to the model groups. The gene and protein expression of uric acid anion transporters rOAT1 and rOAT3 in the kidney was significantly higher than that in model group (p<0.01). Conclusion. The model is suitable for the study of primary hyperuricemia. The mechanisms of ShiZhiFang on uric acid metabolism in hyperuricemic rats may be involved in reducing the activity of serum XOD and promoting the transcription and expression of rOAT1 and rOAT3 in the kidney. [ABSTRACT FROM AUTHOR]

Nerve growth factor (NGF) is an endogenously produced protein with the capacity to induce central nervous system (CNS) neuronal differentiation and repair. NGF signaling involves its binding to tropomyosin-related kinase (Trk) receptors, internalization, and initiation of phosphorylation cascades which cause microtubule reorganization and neuronal outgrowth. Because NGF cannot cross the blood-brain barrier, its therapeutic use is limited. Synthetic peptides that can act as NGF receptor agonists (NGF mimetics) are known to attenuate neurodegenerative pathologies in experimental models of Alzheimer’s disease and Parkinson’s disease; however, the existence of plant-based NGF mimetics is uncertain. For this reason, we recently completed a high throughput screening of over 1100 nutraceuticals (vitamins, herbal plant parts, polyphenolics, teas, fruits, and vegetables) to identify neuritogenic factor using a PC-12 cell model. Remarkably we found only one, commonly known as the seed of Gac plant (Momordica cochinchinensis) (MCS). In the current study, we further investigated this seed for its neuritogenic effect using bioactivity-guided chemical separations. The data show no biological neuritogenic activity in any chemical solvent fraction, where activity was exclusive to the crude protein. MSC crude proteins were then separated by 1D electrophoresis, where the active neuritogenic activity was confirmed to have a molecular mass of approximately 17 kDa. Subsequently, the 17kDa band was excised, digested, and run on a UPLC-MS/MS with a Q Exactive Hybrid Quadrupole-Orbitrap Mass Spectrometer with data evaluated diverse tools such as X! Tandem, OMS, and K-score algorithms. Proteomic evaluation of the 17kDa band confirmed evidence for 11S globulin subunit beta, napin, oleosin, Momordica trypsin inhibitors (TI) MCoTI-I /II, and many isoforms of Two Inhibitor Peptide Topologies (TIPTOPs). While all peptides identified correspond to the genus/species, Momordica cochinchinensis and Cucumis Sativus, a significant limitation of the analysis is the nonexistence of full annotation for the Momordica cochinchinensis proteome. In conclusion, these findings demonstrate that there is a stable protein within MCS having a mass of 17kDa with the capacity to induce neurite outgrowth. Future work will be required to establish the therapeutic value of the MCS for the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background: Dialysis-related destructive spondyloarthropathy caused by beta-2 microglobulin (β2M) amyloid deposits in intervertebral discs is a major burden for patients undergoing long-term dialysis. This study aimed to quantify the presence of β2M amyloid deposits in the intervertebral disc tissue of such patients and analyze whether there was a significant correlation between β2M accumulation and the duration of dialysis. Methods: Two groups of patients who had undergone surgery for degenerative spinal pathologies were selected: the dialysis group (n = 29) with long-term dialysis and the control group (n = 10) with no renal impairment. Tissue sections were prepared from specimens of intervertebral disc tissue obtained during spinal surgery and analyzed via histological staining, including immunohistochemistry (IHC) and Congo red. Results: There was a statistically significant multifold increase of β2M expression in the disc tissue of long-term dialysis patients when compared to non-dialysis patients, as shown by both IHC (0.019 ± 0.023 µm² vs. 0.00020 ± 0.00033 µm², respectively; p = 0.012) and Congo red staining (0.027 ± 0.041 µm² vs. 9.240 x 10-5 ± 5.261 x 10-5 µm², respectively; p = 0.047). We also note a moderate strength positive correlation between the duration of dialysis and positive IHC (r = 0.39; p = 0.015) and Congo-red staining (r = 0.42; p = 0.007). Conclusions: The problem of β2M amyloidosis in long-term dialysis patients remains unresolved even with predominant use of high-flux dialysis membranes. This highlights the insufficiency of current dialysis modalities to effectively filter β2M. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to describe salivary beta-2 microglobulin (sB2M) levels in our setting and to assess the performance of sB2M for the diagnosis of Sjögren's syndrome (SS). Patients and methods: This cross-sectional, comparative study included 192 SS patients (2 males, 190 females; mean age 53.1 years; range 23 to 84 years) and 64 healthy controls (1 male, 63 females; mean age 46.9 years; range 21 to 82 years). Patients were divided into three groups as those with primary SS, secondary SS, and sicca non-Sjögren's syndrome (snSS). sB2M was measured by enzyme-linked immunosorbent assay in whole unstimulated saliva (ng/mL). Differences in sB2M were evaluated using the Kruskal-Wallis test. Receiver operating curves were generated to determine the performance of sB2M for distinguishing between SS and non-autoimmune snSS groups, and between SS group and healthy controls. Results: The primary SS and secondary SS groups had a significantly higher concentration of sB2M than the other two groups. There was no significant difference in the concentration of sB2M between primary SS and secondary SS groups, and neither between snSS group and healthy controls. The receiver operating curve analysis for distinguishing SS and snSS showed an area under the curve of 0.661 (95% confidence interval 0.590-0.728, p=0.0001) with an optimal cutoff value of 0.582 ng/mL. Sensitivity, specificity, positive predictive value, and negative predictive value were 68.7%, 59.3%, 20.2%, and 92.7%, respectively. The reported prevalence of SS in Mexico was considered when calculating the last two values. Conclusion: In our setting, sB2M effectively distinguished between SS patients and non-autoimmune sicca symptoms. Including sB2M in our conventional diagnostic arsenal may assist in the evaluation of patients in whom SS is suspected; however, further studies are needed to clarify this hypothesis. [ABSTRACT FROM AUTHOR]

Hemopexin protects against heme toxicity in hemolytic diseases and conditions, sepsis, and sickle cell disease. This protection is sustained by heme-hemopexin complexes in biological fluids that resist oxidative damage during heme-driven inflammation. However, apo-hemopexin is vulnerable to inactivation by reactive nitrogen (RNS) and oxygen species (ROS) that covalently modify amino acids. The resultant nitration of amino acids is considered a specific effect reflecting biological events. Using LC-MS, we discovered low endogenous levels of tyrosine nitration in the peptide YYCFQGNQFLR in the heme-binding site of human hemopexin, which was similarly nitrated in rabbit and rat hemopexins. Immunoblotting and selective reaction monitoring were used to quantify tyrosine nitration of in vivo samples and when hemopexin was incubated in vitro with nitrating nitrite/myeloperoxidase/glucose oxidase. Significantly, heme binding by hemopexin declined as tyrosine nitration proceeded in vitro. Three nitrated tyrosines reside in the heme-binding site of hemopexin, and we found that one, Tyr-199, interacts directly with thehemeringDpropionate. Investigating the oxidative modifications of amino acids after incubation with tert-butyl hydroperoxide and hypochlorous acid in vitro, we identified additional covalent oxidative modificationsonfour tyrosine residues and one tryptophan residue of hemopexin. Importantly, three of the four modified tyrosines, some of which have more than one modification, cluster in the heme-binding site, supporting a hierarchy of vulnerable amino acids. We propose that during inflammation, apo-hemopexin is nitrated and oxidated in niches of the body containing activated RNS- and ROS-generating immune and endothelial cells, potentially impairing hemopexin's protective extracellular antioxidant function. [ABSTRACT FROM AUTHOR]

Background: Deficiency of complement factor H-related plasma proteins and complement factor H autoantibody-positive hemolytic uremic syndrome (DEAP-HUS), which is characterized by the deficiency of complement-factor H-related (CFHR) plasma proteins and the subsequent formation of autoantibodies against complement factor H (CFH), has been reported to have an adverse outcome in one third of patients. Therapy options include prompt removal of antibodies by plasma exchange and immunosuppressive therapy. Recently, restoration of complement control using the monoclonal antibody eculizumab has been shown to be effective as first- and as second-line therapy in cases of therapy resistance or severe side effects of the applied therapy. Diagnosis/treatment: Here, we report a 6-year-old girl with DEAP-HUS and first-line therapy with eculizumab under immunosuppressive therapy with glucocorticoids and mycophenolate mofetil (MMF). This therapy led to a prompt and sustained clinical recovery, to a stable reduction of complement activation, and to a rapid decline in autoantibody titer. A second increase in the autoantibody titer was successfully treated with methylprednisolone and the child remained in remission. After 8.3 months of sustained complement control and 4.5 months of stable antibody suppression, eculizumab was successfully discontinued without any sign of relapse. Conclusions: To our knowledge, this is the first reported case of a child with DEAP-HUS treated with the combination of eculizumab and immunosuppression as first-line therapy avoiding any HUS- or therapy-related complications and resulting in prompt clinical recovery. Importantly, clinical remission is maintained after discontinuation of eculizumab under stable immunosuppression. [ABSTRACT FROM AUTHOR]

The article focuses on the Chronic hepatitis C infection (HCV) has been associated with multiple extrahepatic comorbidities, such as coronary artery disease, diabetes mellitus, osteoporosis, renal insufficiency, depression, and cognitive impairment. It mentions that hypogonadism has been well documented in HCV-infected men; and also mentions the assessment of the hypothalamic-pituitary-gonadal (HPG) axis in HCV-infected men is often complicated by high concentrations of sex hormone.

Monoclonal gammopathy of undetermined significance does not have end organ damage, but a proportion of cases manifest with renal injury when it is called monoclonal gammopathy of renal significance (MGRS). Herein, we describe a case of acute hepatitis E infection, which precipitated the development of MGRS. The patient underwent kidney biopsy for elevated creatinine with clinical suspicion of drug-induced interstitial nephritis. On light microscopy, there were periodic acid--Schiff negative-fractured casts in tubules with giant cell reaction around them. The tubular epithelial cells showed intracytoplasmic bile pigment. On direct immunofluorescence, casts showed kappa restriction. A diagnosis of bilirubin proximal tubulopathy and light chain cast nephropathy was made, and possibility of myeloma was suggested. On further evaluation, κ:λ ratio was 27, β2 microglobulin was 8036 ng/ml, and bone marrow examination showed 5% plasma cells. There were no bony lesions, and serum calcium was 8.6 mg/dl. The present case is unique in two aspects. First, the patient developed MGRS triggered by acute hepatitis E in less than a month. Second, the MGRS lesion was manifested in the form of light chain cast nephropathy. [ABSTRACT FROM AUTHOR]

To examine the site-specific osteogenic effect of upper limb impact-loading activity we compared the forearm and arm bone mineral density (BMD) of male boxers to that of active controls. A cross-sectional study was performed with 30 amateur male boxers (aged 18-44 years) and 32 age-matched, non-boxing, active controls. Participants had their regional and whole body BMD and bone mineral content (BMC) assessed by dual-energy X-ray absorptiometry. Hand grip strength, testosterone, oestradiol, sex hormone-binding globulin, vitamin D, lean and fat mass, and past and current physical activity were also assessed. Forearm and arm BMD were 1.5-2.2 % higher in boxers than the control group although this was not statistically significant (p > 0.05), with no significant difference for BMC (p > 0.05). There were no differences between groups for spine, hip, or whole body BMD or BMC, or for body composition or hormone status. Within the arms, lean mass was associated with BMD and BMC in both boxers and the control group (BMD, r = 0.60-0.76, p < 0.001; BMC, r = 0.67-0.82, p < 0.001). There were no significant differences between amateur boxers and the control group for upper limb BMD and BMC. However, muscle mass appears to be particularly important to bone health of the upper limbs. [ABSTRACT FROM AUTHOR]

Strenuous exercise induces proteinuria which is related to the intensity of exercise. However, renal responses to each type of exercise during a middle-distance triathlon have not been reported. The present study, carried out on 7 healthy athletes, investigated renal function at rest and after each exercise of a half-triathlon race. Blood and urine samples were collected at rest and after each specific event. Protein excretion and renal clearances were determined on each sample. Compared with resting values, albuminuria was increased by a factor of 30 (p<0.05) after swimming but did not differ from the resting value after cycling and running (p>0.05). Rates of β2-microglobulin and retinol-binding protein excretion did not change throughout the triathlon (p>0.05). Glomerular filtration rate (expressed as creatinine clearance) remained stable after each exercise event, whereas tubular reabsorption rate (expressed as urea clearance) was reduced by 50, 40 and 65% after swimming, cycling and running, respectively, compared to pre-exercise values (p<0.05). Glomerular membrane permeability (expressed as albumin clearance) was significantly increased by the swimming event (13 times, p<0.05). These results suggest that middle-distance triathlon has a noticeable impact on the glomerular membrane permeability (albumin clearance) and elimination of protein waste (urea clearance) depending on exercise type. [ABSTRACT FROM AUTHOR]

Although collagenolytic matrix metalloproteinases (MMPs) possess common domain organizations, there are subtle differences in their processing of collagenous triple-helical substrates. In this study, we have incorporated peptoid residues into collagen model triple-helical peptides and examined MMP activities toward these peptomeric chimeras. Several different peptoid residues were incorporated into triple-helical substrates at subsites P3, P1, P1', and P10' individually or in combination, and the effects of the peptoid residues were evaluated on the activities of full-length MMP-1, MMP-8, MMP-13, and MMP-14/MT1-MMP. Most peptomers showed little discrimination between MMPs. However, a peptomer containing N-methyl Gly (sarcosine) in the P1' subsite and N-isobutyl Gly (NLeu) in the P10' subsite was hydrolyzed efficiently only by MMP-13 [nomenclature relative to the α1(I)772-786 sequence]. Cleavage site analysis showed hydrolysis at the Gly-Gln bond, indicating a shifted binding of the triple helix compared to the parent sequence. Favorable hydrolysis by MMP-13 was not due to sequence specificity or instability of the substrate triple helix but rather was based on the specific interactions of the P7' peptoid residue with the MMP-13 hemopexin-like domain. A fluorescence resonance energy transfer triple-helical peptomer was constructed and found to be readily processed by MMP-13, not cleaved by MMP-1 and MMP-8, and weakly hydrolyzed by MT1-MMP. The influence of the triple-helical structure containing peptoid residues on the interaction between MMP subsites and individual substrate residues may provide additional information about the mechanism of collagenolysis, the understanding of collagen specificity, and the design of selective MMP probes. [ABSTRACT FROM AUTHOR]

Summary Nonalcoholic fatty liver disease (NAFLD) has a variety of causes including calorie over-intake, an unbalanced diet, and/or genetic dysfunction of lipid metabolism. We hypothesized that NAFLD symptoms could be mitigated by specific nutritional factors. Here, we show that the potential for soy β-conglycinin (βCG) to improve obesity-induced metabolic abnormalities in the Otsuka Long Evans Tokushima fatty (OLETF) rat model of NAFLD. Long Evans Tokushima Otsuka ( i.e. , wild-type) and OLETF rats were provided a normal diet containing 20% casein for 4 weeks as a control. In a third (βCG) group, OLETF rats were fed a diet in which half of the casein was replaced by βCG. There was no difference in food intake between groups. Rats in the βCG group had decreased liver weight and lipid content (triglycerides, cholesterol, and phospholipids) compared to controls. In addition, βCG consumption decreased fatty acid synthase gene expression and enzymatic activity. These findings indicate that dietary intake of βCG can improve obesity-induced metabolic dysfunction, possibly via suppression of de novo fatty acid synthesis. [ABSTRACT FROM AUTHOR]

β-thalassemia is a common hereditary disorder, particularly in Middle Eastern countries. More than 200 mutations in the β globin gene have been reported; most are point mutations in functionally important regions (HBB; OMIM #141900)). The spectrum of mutations varies significantly between different geographical regions; only a few common mutations of β-globin cause β-thalassemia in each population. The aim of this study was to determine the spectrum of mutations that cause β-thalassemia in the North Coast of Egypt and to investigate their correlation with the phenotypic severity of β-thalassemia. We carried out our study with a total of 47 Egyptian patients (25 male and 22 female) confirmed to have β-thalassemia. Evaluation of β-thalassemia mutations revealed the presence of 10 β-globin mutations. The most frequently encountered mutations were intronic: IVS 1.6 [T>C] (27.66%) and IVS 1.110 [G>A] (22.35%), followed by IVS 2.848 [C>A], IVS 1.1 (G>A), and IVS 2.745 [C>G]. We observed the exonic and promoter mutations less frequently. A homozygous mutation was found in 24 patients (51%) and compound heterozygous mutations were found in 13 patients (28%). However, in 9 patients (19%), we identified only 1 mutation. In 1 patient (2%), we detected no mutation. The detection rate of the method that we used in our population was 88% (83 of the tested 94 alleles). The results we obtained did not reveal any correlation between genotype and phenotype among patients with β-thalassemia. [ABSTRACT FROM AUTHOR]

Background and Objective: Elevated serum beta-2 microglobulin (β2-M) has previously been reported in non-Hodgkin lymphoma (NHL) patients. This study examined the association between serum β2-M and the prognosis of NHL and analyzed its predictive value. Method: A total of 287 NHL patients from Taiyuan, Shanxi, China, participated in a prospective cohort study between 2008 and 2011. Overall survival (OS) was compared between NHL patients with high and normal β2-M levels using the log-rank test. Three standard Cox regression models including the International Prognostic Index (IPI) score, β2-M or IPI score + β2-M as independent variables were constructed. The time-dependent receiver operating characteristic curves method and C index were used to examine the tendency of the models' predictive accuracy over time. Results: NHL patients with elevated β2-M values had worse OS (p < 0.001) and higher mortality risk (HR = 1.93, 95% CI 1.37-2.77, p < 0.001) than patients with normal β2-M values. There were statistically significant differences between the C indexes for the models with IPI + β2-M, IPI or β2-M alone (p < 0.001). Conclusion: Our results demonstrated an association between serum β2-M and NHL prognosis. Combining β2-M with IPI may help to improve the prognostic accuracy of NHL. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective A fundamental metric in the diagnosis of arthropathies is the pattern of joint involvement, including differences in proximal versus distal joints and patterns of symmetric or asymmetric disease. The basis for joint selectivity among arthritides and/or within a defined disease such as rheumatoid arthritis remains enigmatic. Coagulation and fibrinolytic activity are observed in both experimental animals with inflammatory joint disease and patients with inflammatory arthritis. However, the contribution of specific hemostatic factors to joint disease is not fully defined. We sought to determine the contribution of the fibrinolytic protease, plasminogen, to tumor necrosis factor α (TNFα)-driven arthritis in distinct joints in mice. Methods The impact of plasminogen and/or fibrinogen genetic deficiencies on arthritis progression was evaluated in Tg197 mice genetically predisposed to spontaneous, nonabating, and erosive polyarthritis due to exuberant human TNFα expression. Results Elimination of plasminogen in Tg197 mice significantly exacerbated the incidence and severity of arthritis within the paw joints, but simultaneously and dramatically diminished the entire spectrum of pathologies within the knee joints of the same animals. These opposing outcomes were both mechanistically linked to fibrin(ogen), in that superimposing fibrinogen deficiency reversed both the proarthritic phenotype in the paws and arthritis resistance in the knees of plasminogen-deficient mice. Intriguingly, the change in disease severity in the knees, but not the paws, was associated with a plasminogen-dependent reduction in matrix metalloproteinase 9 activity. Conclusion Plasminogen is a key molecular determinant of inflammatory joint disease capable of simultaneously driving or ameliorating arthritis pathogenesis in distinct anatomic locations in the same subject. [ABSTRACT FROM AUTHOR]

Context.—Hemoglobin (Hb) Austin was defined in 1977, using amino acid sequencing of samples from 3 unrelated Mexican-Americans, as a substitution of serine for arginine at position 40 of the b-globin chain (Arg40Ser). Its electrophoretic migration on both cellulose acetate (pH 8.4) and citrate agar (pH 6.2) was reported between Hb F and Hb A, and this description persists in reference literature. Objectives.—To review the clinical features and redefine the diagnostic characteristics of Hb Austin. Design.—Eight samples from 6 unrelated individuals and 2 siblings, all with Hispanic surnames, were submitted for abnormal Hb identification between June 2010 and September 2011. High-performance liquid chromatography, isoelectric focusing (IEF), citrate agar electrophoresis, and bidirectional DNA sequencing of the entire b-globin gene were performed. Results.—DNA sequencing confirmed all 8 individuals to be heterozygous for Hb Austin (Arg40Ser). Retention time on high-performance liquid chromatography and migration on citrate agar electrophoresis were consistent with that identification. Migration on IEF, however, was not between Hb F and Hb A, as predicted from the report of cellulose acetate electrophoresis. By IEF, Hb Austin migrated anodal to (‘‘faster than’’) Hb A. Conclusions.—Hemoglobin Austin (Arg40Ser) appears on IEF as a ‘‘fast,’’ anodally migrating, Hb variant, just as would be expected from its amino acid substitution. The cited historic report is, at best, not applicable to IEF and is probably erroneous. Our observation of 8 cases in 16 months suggests that this variant may be relatively common in some Hispanic populations, making its recognition important. Furthermore, gene sequencing is proving itself a powerful and reliable tool for definitive identification of Hb variants. [ABSTRACT FROM AUTHOR]

Protein electrophoresis is commonly used to assess the different protein fractions in vertebrates. This information can provide important clinical information regarding the health status of an individual patient or a population of animals. The objective of this study was to evaluate plasma protein fractions of clinically normal, captive, male adult Nile crocodiles (Crocodilus niloticus) over a 12 month period. Blood was collected from the ventral coccygeal vein into heparinized syringes and immediately placed into vacutainer tubes. Samples were centrifuged, plasma removed, and the total protein content of each sample determined using the biuret method. Plasma proteins were separated using gel electrophoresis and scanned using a laser densitometer. No changes in total protein concentration were detected over time. Albumin values were significantly higher in December through March and lower from April through September. Beta globulin values were significantly higher in August through September and significantly lower in December through April. Gamma globulin values were significantly higher in March through May and again in June. The albumin/globulin (AG) ratio for January was significantly different from April through December. February and March AG ratios were both significantly higher than values collected in April through September. April through September AG ratios were significantly lower than were November and December AG ratios. The significant differences noted in the protein electrophoresis values suggest that seasonal changes occur in the healthy animals and should be taken into consideration when evaluating a clinical case involving a crocodilian. [ABSTRACT FROM AUTHOR]

The present study investigated dietary intake, glucose metabolism and sex hormones in women with polycystic ovary syndrome (PCOS). A total of forty-five women (aged 25–40 years) with PCOS and 161 control women (aged 25–43 years) with non-PCOS-related infertility were recruited. Anthropometry, glucose tolerance and sex hormones were determined and dietary intake was assessed. Women with PCOS had lower serum sex hormone-binding globulin and increased BMI, waist:hip ratio, luteinising hormone, ratio of luteinising hormone:follicle-stimulating hormone, testosterone and free androgen index (FAI). Postprandial glucose, fasting insulin and insulin resistance were elevated in women with PCOS. Women with PCOS had reduced energy and carbohydrate intake but higher fat intake. Serum sex hormone-binding globulin level was negatively associated with BMI in both groups and negatively correlated with macronutrient intake in the PCOS group with hyperandrogenism. However, FAI was positively correlated with BMI, waist circumference and glucose metabolic parameters in both groups. Therefore, women with PCOS consume lower energy and carbohydrate compared with those with non-PCOS-related infertility and macronutrient intake is only negatively associated with serum sex hormone-binding globulin level in the PCOS group with hyperandrogenism. [ABSTRACT FROM PUBLISHER]

Background Avian tuberculosis is an important disease affecting all species of birds and is most often caused by Mycobacterium avium or Mycobacterium genavense. Blood proteins are important diagnostic constituents in gastrointestinal, hepatic, renal, and infectious diseases. Objective The aim of the study was to compare serum protein profiles of domestic pigeons ( Columba livia var. domestica) infected with Mycobacterium avium subsp. avium ( MAA), with healthy pigeons. Methods Serum samples were collected from 80 pigeons with clinical signs of tuberculosis, all kept in the same loft. All birds were necropsied and cultured for mycobacteriosis; positive cultures were typed for MAA by PCR reactions targeting 16S rRNA, IS901 and IS1245. The concentration of total serum proteins was determined by the biuret method and spectrophotometry. Individual protein fractions were analyzed by cellulose acetate electrophoresis and extrapolated based on total protein concentration. For statistical analysis, the infected birds were compared with healthy pigeons. Results A total of 37 pigeons with culture results positive for MAA were selected and allocated to 2 groups, a culture-positive group with macroscopic lesions of tuberculosis and another without macroscopic lesions. Six protein fractions were identified: prealbumin, albumin, alpha-1, alpha-2, and beta globulins and gamma globulins. Concentrations of total protein, beta globulins and gamma globulins were statistically significantly higher in the infected pigeons when compared with the control group. There were no significant differences between the groups of birds with or without macroscopic lesions. Conclusions Statistically significant differences in total protein, and beta and gamma globulin concentrations in all infected pigeons suggest that serum protein electrophoresis represents a nonspecific but valuable indicator for tuberculosis in pigeons. [ABSTRACT FROM AUTHOR]

Background: β-thalassaemia is one of the most common single-gene disorders worldwide. Each ethnic population has its own common mutations, accounting for the majority of cases, with a small number of mutations for the rarer alleles. Due to the heterogeneity of β-thalassaemia and the multi-ethnicity of Malaysians, molecular diagnostics may be expensive and time consuming. Methods: A simple polymerase chain reaction (PCR) approach involving a multiplex amplification refractory mutation system (MARMS) and one amplification refractory mutation system (ARMS), consisting of 20 β-globin gene mutations, were designed and employed to investigate β-thalassaemia patients and carriers. Results: Out of 169 carriers tested with the MARMS, Cd 41/42 (−TTCT), Cd 26 (A-G) HbE, IVS 1-1 (G-T), and IVS 1-5 (G-C) were the most common mutations, accounting for 78.1%. Among the Malays, Cd 26 (A-G) HbE, Cd 41/42 (−TTCT), IVS 1-1 (G-T), and IVS 1-5 (G-C) were the most common mutations, accounting for 81.4%, whereas Cd 41/42 (−TTCT) and IVS 2-654 (C-T) were most common among the Chinese (79.1%). Conclusion: We propose the use of this cheap, easy to interpret, and simple system for the molecular diagnostics of β-thalassaemia among Malaysians at the Institute for Medical Research (IMR). [ABSTRACT FROM AUTHOR]

Hepatitis includes a wide range of clinical and pathological conditions. The beta-2 microglobulin (β2M), as part of the HLA complex, is responsible for transmission of viral antigens on the surface of liver cells. The purpose of this study is to determine the concentration of salivary β2M as a marker of viral proliferation in subjects who are HbsAg+, HBV DNA PCR+ compared with those who are HbsAg+ HBV DNA PCR-. Materials and Methods: In this case-control study, we enrolled 25 patients who were Hbs Ag+ HBV DNA PCR+ in addition to 21 patients who were Hbs Ag+, HBV DNA PCR-. We obtained sputum samples from all patients and measured salivary β2M levels by nephelometry. Data analyses were performed by the descriptive, student's t- and chi-square tests. Results: There were 25 men (54.3%) and 21 women (45.7%) with a mean age of 35.72 ±11.86 years who participated. Of PCR+ patients, 72% were on medication, however 85.7% of the PCR- patients did not take medication (p<0.001). Salivary β2M concentration in the PCR+ patients (5.284±5.45) was greater than observed in the PCR- patients (1.51: ±0.77), of which this difference was statistically significant (p<0.003). Conclusion: Salivary β2M levels, as a marker of viral replication, could be used in patients with hepatitis B. [ABSTRACT FROM AUTHOR]

Mastocytosis comprises a heterogeneous group of disorders characterized by the presence of clonal mast cells (MC) in organs such as skin, bone marrow (BM), and gastrointestinal tract, among other tissues. The clonal nature of the disease can be established in most adult patients by the demonstration of activating KIT mutations in their BM MC. When highly sensitive techniques capable of identifying cells present at very low frequencies in a sample are applied, BM MC from virtually all systemic mastocytosis patients display unique immunophenotypical features, particularly the aberrant expression of CD25. By contrast, large, multifocal BM MC aggregates (the only World Health Organization major criterion for systemic mastocytosis) are absent in a significant proportion of patients fulfilling at least three minor criteria for systemic mastocytosis, particularly in subjects studied at early stages of the disease with very low MC burden. Moreover, recent molecular and immunophenotypical investigations of BM MC from patients with indolent systemic mastocytosis have revealed a close association of some biological features (e.g., multilineage involvement of hematopoiesis by the KIT mutation and an immature mast cell immunophenotype) with an increased risk for disease progression. These observations support the fact that, although the current consensus diagnostic criteria for systemic mastocytosis have been a major advance for the diagnosis and classification of the disease, rationale usage of the most sensitive diagnostic techniques available nowadays is needed to improve the diagnosis, refine the classification, and reach objective prognostic stratification of adult mastocytosis. [ABSTRACT FROM AUTHOR]

Objective Inhibition of inflammation and destruction, but not of osteoproliferation, in patients with spondylarthritis (SpA) treated with anti-tumor necrosis factor raises the question of how these three processes are interrelated. This study was undertaken to analyze this relationship in a rat model of SpA. Methods Histologic spine and joint samples from HLA-B27/human β2-microglobulin (hβ2m)-transgenic rats were analyzed for signs of spondylitis and destructive arthritis and semiquantitatively scored as showing mild, moderate, or severe inflammation. Results In rats exhibiting spondylitis, mildly inflamed sections displayed lymphocyte infiltration in connective tissue adjacent to the junction of the anulus fibrosus and vertebral bone but not at the enthesis. Moderately inflamed tissue samples contained osteoclasts eroding bone outside the cartilage end plate. In sections from rats with severe inflammation, the cartilage end plate and underlying bone marrow were also affected. End-stage disease was characterized by complete destruction of the intervertebral disc and vertebrae, with ongoing infiltration. Osteoproliferation was not observed in samples from rats with no or mild inflammation, but was present at the edge of the vertebrae in sections with moderate inflammation and persisted during severe inflammation and end-stage destruction. Osteoproliferation occurred at the border of inflammation, at a distance from bone destruction. A strong correlation between the extent of inflammation, destruction, and osteoproliferation was observed. Sections from rats with arthritis displayed a similar pattern of synovial inflammation associated with bone destruction, and simultaneous but topographically distinct osteoproliferation starting from the periosteum. Conclusion SpA in B27/hβ2m-transgenic rats is characterized by destructive inflammatory pannus tissue rather than by enthesitis or osteitis. Destruction and osteoproliferation occur simultaneously but at distinct sites in joints with moderate to severe inflammation. [ABSTRACT FROM AUTHOR]

Objective HLA-B27/human β2-microglobulin-transgenic (B27-transgenic) rats, a model of spondylarthritis (SpA), develop spontaneous colitis and arthritis under conventional conditions. CD4+ T cells are pivotal in the development of inflammation in B27-transgenic rats. This study was undertaken to characterize the phenotype of CD4+ T cells in this model and to determine whether dendritic cells (DCs) induce proinflammatory T cells. Methods The phenotype of CD4+ T cells from rat lymph nodes (LNs) draining the sites of inflammation was analyzed by flow cytometry. Immunostaining was used to detect interleukin-17 (IL-17)-producing cells in the rat joints. DCs from B27-transgenic or control rats (transgenic for HLA-B7 or nontransgenic) were cocultured with control CD4+ T cells and stimulated with anti-T cell receptor α/β. Results IL-17A- and tumor necrosis factor α (TNFα)-producing CD4+ T cells were expanded in mesenteric and popliteal LNs from B27-transgenic rats. The accumulation of Th17 cells correlated with disease development, in contrast to Th1 or Treg cells. IL-17-positive mononuclear cells were detected in the arthritic joints of B27-transgenic rats but not in the joints of control rats. Finally, in vitro cocultures demonstrated that Th17 cells were preferentially induced and expanded by DCs from B27-transgenic rats, by a process that may involve defective engagement of costimulatory molecules. Conclusion Our findings indicate that expanded CD4+ T cells in B27-transgenic rats exhibit a proinflammatory Th17 phenotype characterized by IL-17A and TNFα production. Furthermore, this population is preferentially induced by DCs from B27-transgenic rats. These data point toward an induction of Th17 cells as a possible pathogenic mechanism in this model of SpA. However, their pathogenic role still needs to be shown. [ABSTRACT FROM AUTHOR]