Differential sensitivity of naïve and subsets of memory CD4+ and CD8+ T cells to hydrogen peroxide-induced apoptosis

CD4+ and CD8+ memory T cells are identified into central and effector memory subsets, which are characterized by distinct homing patterns and functions. In this investigation, we show that na?ve and central memory CD4+ and CD8+ T cells are sensitive to hydrogen peroxide (H2O2)-induced apoptosis, whereas effector memory CD4+ and CD8+ T cells are relatively resistant to H2O2-induced apoptosis. Apoptosis in na?ve and central memory CD4+ and CD8+ is associated with the release of cytochrome c and activation of caspase-9 and caspase-3, upregulation of Bax and voltage-dependent anion channel (VDAC) expression, and decreased intracellular glutathione (GSH). In vitro GSH and a superoxide dismutase mimetic Mn(III) tetrakis (1-methyl-4-pyridyl) porphyrin inhibited H2O2-induced apoptosis in both na?ve and central memory CD4+ and CD8+ T cells. Furthermore, VDAC inhibitor 4,4'-diisothiocynostilbene-2,2'-disulfonic acid blocked H2O2-induced apoptosis. These data demonstrate that H2O2 induces apoptosis preferentially in human na?ve and central memory CD4+ and CD8+ T cells via the mitochondrial pathway by regulating intracellular GSH and the expression of Bax and VDAC.     

下颌第一磨牙牙合向受力时整体下颌骨应力有限元分析

目的:采用有限元方法分析正常下颌第一磨牙咬合面受力时,下颌骨局部及整体应力变化,为种植牙对的影响提供理论依据。方法:CT扫描1例正常成年人下颌骨,Mimics14.11软件建立下颌骨模型,下颌第一磨牙面给予100 N的垂直力,有限元分析软件ABAQUS6.9-3分析整个下颌骨应力的变化。结果:下颌第一磨牙垂直受力时,下颌第一磨牙周围骨质应力应变最大处为底部偏向颊侧;整个下颌骨受力分析中,应力应变主要集中在受力的下颌第一磨牙处,其次在对侧下颌角位置,应力应变沿着下颌骨外斜线传导至髁突,显示了髁突部分应力应变的变化。结论:采用有限元方法,分析下颌第一磨牙正常咬合力时下颌骨应力应变变化,为下颌第一磨牙种植修复提供生物力学依据,以便获得最佳临床修复效果。     

Serum sex hormone-binding globulin levels are independently associated with nonalcoholic fatty liver disease in people with type 2 diabetes

Aim

To clarify the association between serum sex hormone-binding globulin (SHBG) levels and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes.

Methods

Two hundred seventy nine patients with type 2 diabetes were consecutively enrolled and metabolic parameters were checked. High-grade NAFLD was defined as moderate or severe fatty liver disease, measured using liver ultrasound. SHBG, testosterone, and estradiol levels were measured.

Results

SHBG levels were lower in patients with high-grade NAFLD than in those with normal ultrasound and decreased significantly based on the severity of fatty liver disease. SHBG levels were negatively correlated with hypertension, body mass index (BMI), waist circumference, high-grade NAFLD, triglycerides, alanine aminotransferase (ALT), γ-glutamyltransferase (γGT), homeostasis model assessment-estimated insulin resistance (HOMA-IR), and C-reactive protein (CRP) and were positively correlated with testosterone and estradiol levels. The odds ratios (ORs) predicting the presence of high-grade NAFLD in men and women decreased significantly with increasing SHBG tertile. The ORs remained significant even after further adjusting for BMI, waist circumference, hypertension, triglycerides, γGT, ALT, CRP, HOMA-IR, testosterone, estradiol, and anti-diabetic medications.

Conclusions

Serum SHBG levels were independently associated with the high-grade NAFLD in patients with type 2 diabetes.     

Osteomusculocutaneous flap for clavicular reconstruction: a case report

Radiotherapy for tumors can cause soft tissue necrosis, osteonecrosis, and pathologic fractures. A 47-year-old woman presented with a pathologic fracture of the left clavicle 10 years after radiotherapy following radical mastectomy for breast cancer. She was treated with a compound rib-latissimus dorsi osteomusculocutaneous flap with a 4-cm segment of the sixth rib. Fusion of the bones was achieved in three months. Donor site morbidity was cosmetically acceptable and function of the shoulder was improved. The Constant shoulder score which was 36 preoperatively increased to 88 after 38 months of follow-up.     

Clinical features of chronic granulomatous disease: a series of 26 patients from a single center

Chronic granulomatous disease is a genetically determined immunodeficiency disorder affecting phagocytic cells rendering them unable to kill certain bacteria and fungi. The present study is a single-center retrospective study that aimed to document the clinical course of 26 children, with a median age of 2.5 years, from 21 families diagnosed as chronic granulomatous disease from 1989-2008. A median delay of 39 months was observed between the onset of infections and age at diagnosis. Pneumonia was the most common initial manifestation of the disease followed by lymphadenitis, skin abscess and diarrhea. An AR inheritance was predominant in the study group. All patients received antibacterial and antifungal prophylaxis, resulting in a marked decrease in the incidence of infections. Overall mortality was 19.2%. These results showed that all features in our group (clinical, progression and outcome) were similar to the literature except for the predominance of autosomal recessive form.     

Homoarginine in the cardiovascular system: Pathophysiology and recent developments

Upcoming experimental and epidemiological data have identified the endogenous non-proteinogenic amino acid L-homoarginine (L-hArg) not only as a novel biomarker for cardiovascular disease but also as being directly involved in the pathogenesis of cardiac dysfunction. The association of low L-hArg levels with adverse cardiovascular events and mortality has proposed the idea of nutritional supplementation to rescue pathways inversely associated with cardiovascular health. Subsequent clinical and experimental studies contributed significantly to our knowledge of potential effects on the cardiorenal axis, acting either as a biomarker or a cardiovascular active agent. In this review article, we provide a comprehensive summary of the L-hArg metabolism, pathophysiological aspects, and current developments in the field of experimental and clinical evidence in favor of protective cardiovascular effects. Establishing a reliable biomarker to identify patients at high risk to die of cardiovascular disease represents one of the main goals for tackling this disease and providing individual therapeutic guidance.     

Hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: The ADVANCE-CIDP 1 randomized controlled trial

Background and Aims

ADVANCE-CIDP 1 evaluated facilitated subcutaneous immunoglobulin (fSCIG; human immunoglobulin G 10% with recombinant human hyaluronidase) efficacy and safety in preventing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) relapse.

Methods

ADVANCE-CIDP 1 was a phase 3, double-blind, placebo-controlled trial conducted at 54 sites in 21 countries. Eligible adults had definite or probable CIDP and adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores of 0–7 (inclusive), and received stable intravenous immunoglobulin (IVIG) for ≥12 weeks before screening. After stopping IVIG, patients were randomized 1:1 to fSCIG 10% or placebo for 6 months or until relapse/discontinuation. fSCIG 10% was administered at the same dose (or matching placebo volume) and interval as pre-randomization IVIG. The primary outcome was patient proportion experiencing CIDP relapse (≥1-point increase in adjusted INCAT score from pre-subcutaneous treatment baseline) in the modified intention-to-treat population. Secondary outcomes included time to relapse and safety endpoints.

Results

Overall, 132 patients (mean age 54.4 years, 56.1% male) received fSCIG 10% (n = 62) or placebo (n = 70). CIDP relapse was reduced with fSCIG 10% versus placebo (n = 6 [9.7%; 95% confidence interval 4.5%, 19.6%] vs n = 22 [31.4%; 21.8%, 43.0%], respectively; absolute difference: −21.8% [−34.5%, −7.9%], p = .0045). Relapse probability was higher with placebo versus fSCIG 10% over time (p = .002). Adverse events (AEs) were more frequent with fSCIG 10% (79.0% of patients) than placebo (57.1%), but severe (1.6% vs 8.6%) and serious AEs (3.2% vs 7.1%) were less common.

Interpretation

fSCIG 10% more effectively prevented CIDP relapse than placebo, supporting its potential use as maintenance CIDP treatment.