Increased Fas and Bcl-2 Expression on Peripheral Blood T and B Lymphocytes from Juvenile-Onset Systemic Lupus Erythematosus, but not from Juvenile Rheumatoid Arthritis and Juvenile Dermatomyositis

Defective regulation of apoptosis may play a role in the development of autoimmune diseases. Fas and Bcl-2 proteins are involved in the control of apoptosis. The aims of this study were to determine the expression of Fas antigen and Bcl-2 protein on peripheral blood T and B lymphocytes from patients with juvenile-onset systemic lupus erythematosus (JSLE), juvenile rheumatoid arthritis (JRA) and juvenile dermatomyositis (JDM). Thirty-eight patients with JSLE, 19 patients with JRA, 10 patients with JDM and 25 healthy controls entered the study. Freshly isolated peripheral blood mononuclear cells (PBMC) were stained for lymphocyte markers CD3, CD4, CD8, CD19 and for Fas and Bcl-2 molecules. Expressions were measured by three-color flow cytometry. Statistical analysis was performed using Kruskal–Wallis test. Percentages of freshly isolated T lymphocytes positively stained for Fas protein from JSLE patients were significantly increased compared to healthy controls, patients with JRA and patients with JDM. Percentages of B lymphocytes positive for Fas from JSLE patients were higher than healthy controls and JRA patients. In addition, Fas expression on T cells from patients with JRA was increased compared to JDM patients. Otherwise, Fas expression on T and B cells from JRA and JDM patients were similar to healthy controls. MFI of Bcl-2 positive T lymphocytes from JSLE patients were significantly increased compared to healthy controls and JRA patients. MFI of Bcl-2 protein on B lymphocytes from JSLE patients was similar to healthy controls and patients with JRA and JDM. Bcl-2 expression did not differ between JRA and JDM patients and healthy controls. In conclusion, increased expression of Fas and Bcl-2 proteins observed in circulating T and B lymphocytes from patients with JSLE, but not from patients with JRA and JDM, suggests that abnormalities of apoptosis may be related to the pathogenesis of JSLE and probably are not a result of chronic inflammation

Effects of Neuromuscular Electrical Stimulation Training on Skeletal Muscle Anabolic Signaling in Older Adults

Neuromuscular electrical stimulation (NMES) generates involuntary muscle contraction and may be a safe and effective alternative to voluntary resistance training, which is important for those who cannot perform voluntary exercise due to age-related conditions. However, further research is needed to better understand the skeletal muscle anabolic signaling response of the mTORC1 (mammalian target of rapamycin complex 1) pathway with repeated bouts of NMES. PURPOSE: To determine changes in skeletal muscle anabolic signaling in response to a 4-week NMES intervention in older adults. METHODS: Participants (n = 7) in this clinical trial were healthy, older adults (70.4 ± 2.9 years). NMES was applied to the quadriceps muscles for 40 min/treatment, 3x/week for 4 weeks (12 sessions). On Day 1 and Day 12 of the NMES intervention, skeletal muscle biopsies were obtained from the vastus lateralis Pre-NMES and 30 minutes Post-NMES and were analyzed for phosphorylation of mammalian target of rapamycin (mTOR) and p70-S6 Kinase 1 (S6K1) anabolic signaling proteins using the SDS-PAGE Western blot technique. Phosphorylation is expressed as the ratio of phosphorylated to total protein content. Data were analyzed using paired t-tests and data are reported as mean ± SE with statistical significance set at p ≤ 0.05. RESULTS: On Day 1, phosphorylation of S6K1 increased (Pre-NMES: 0.652 ± 0.145 AU vs. Post-NMES: 0.979 ± 0.151 AU, p = 0.037) and phosphorylation of mTOR increased (Pre-NMES: 0.464 ± 0.077 AU vs. Post-NMES: 1.046 ± 0.128 AU, p = 0.006) from Pre-NMES to Post-NMES. On Day 12, phosphorylation of S6K1 increased (Pre-NMES: 0.628 ± 0.108 AU vs. Post-NMES: 1.253 ± 0.288 AU, p = 0.048) with an increasing trend for mTOR (Pre-NMES: 0.485 ± 0.044 AU vs. Post-NMES: 0.700 ± 0.154 AU, p = 0.053) from Pre-NMES to Post-NMES. Phosphorylated S6K1 and mTOR protein content were not different between Day 1 and Day 12 at Pre-NMES (p \u3e 0.05) or at Post-NMES (p \u3e 0.05). CONCLUSION: The findings of this study suggest that the anabolic signaling response to a bout of NMES remains upregulated after 4-weeks of treatment; thus, the response is not attenuated with short-term repeated bouts of NMES. Funding: Research Enhancement Program Grant to J Mettler and L Kipp; Research Accelerator Grant, Texas State University, to J Mettler

Endocrine responses to sport-related brain injury in female athletes: a narrative review and a call for action

Sport-related brain injury (SRBI) occurs when a blow to the head causes the brain to move back and forth in the skull, and can lead to neuroendocrine dysfunction. Research has shown that males and females experience and recover from SRBI differently, yet most of what is known regarding diagnosis, treatment, and recovery of SRBI is based on male normative data even though females meet or exceed incidence numbers of SRBIs compared to those of males. Females also have been known to have worse outcomes and a greater number of symptoms following SRBI than males. Research is limited as to why females have worse outcomes, but sex hormones have been suggested as a potential reason. SRBI may cause a dysregulation of the hypothalamic–pituitary–gonadal (HPG) axis, which is responsible for regulating the sex hormones estrogen and progesterone. Initial research has shown that SRBI may suppress estrogen and progesterone, and the concentration of these sex hormones could be indicative of injury severity and recovery trajectory. This review discusses the sex-specific differences in SRBI and also the future direction of research that is needed in order to identify the repercussions of SRBIs for female athletes, which will eventually lead to better clinical treatment, sideline care, and recovery profiles

Haptoglobin Phenotype, Preeclampsia Risk and the Efficacy of Vitamin C and E Supplementation to Prevent Preeclampsia in a Racially Diverse Population

Haptoglobin's (Hp) antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH). This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393) and a case-control cohort (703 cases, 1,406 controls). The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01) in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia

Phosphorus Is Associated with Coronary Artery Disease in Patients with Preserved Renal Function

High serum phosphorus levels have been associated with mortality and cardiovascular events in patients with chronic kidney disease and in the general population. In addition, high phosphorus levels have been shown to induce vascular calcification and endothelial dysfunction in vitro. The aim of this study was to evaluate the relation of phosphorus and coronary calcification and atherosclerosis in the setting of normal renal function. This was a cross-sectional study involving 290 patients with suspected coronary artery disease and undergoing elective coronary angiography, with a creatinine clearance >60 ml/min/1.73 m2. Coronary artery obstruction was assessed by the Friesinger score and coronary artery calcification by multislice computed tomography. Serum phosphorus was higher in patients with an Agatston score >10 than in those with an Agatston score ≤10 (3.63±0.55 versus 3.49±0.52 mg/dl; p = 0.02). In the patients with Friesinger scores >4, serum phosphorus was higher (3.6±0.5 versus 3.5±0.6 mg/dl, p = 0.04) and median intact fibroblast growth factor 23 was lower (40.3 pg/ml versus 45.7 pg/ml, p = 0.01). Each 0.1-mg/dl higher serum phosphate was associated with a 7.4% higher odds of having a Friesinger score >4 (p = 0.03) and a 6.1% greater risk of having an Agatston score >10 (p = 0.01). Fibroblast growth factor 23 was a negative predictor of Friesinger score (p = 0.002). In conclusion, phosphorus is positively associated with coronary artery calcification and obstruction in patients with suspected coronary artery disease and preserved renal function