Characterization of CD4/CD8+ αβ and Vγ2Vδ2+ T cells in HIV-negative individuals with different Mycobacterium tuberculosis infection statuses

BackgroundThe immune responses of T cell subsets among patients with different Mycobacterium tuberculosis (M.tb) infection statuses [i.e., active tuberculosis (ATB), latent tuberculosis infection (LTBI) and non-infection (healthy control, HC)] have not been fully elucidated in HIV-negative individuals. Specifically, data are limiting in high tuberculosis epidemic regions in China. To investigate the distributions and functions of T cell subsets (i.e., CD3+, CD4+, CD8+ αβ and Vγ2Vδ2+ T cells) in HIV-negative subjects with different M.tb infection statuses, we conducted a case-control study that enrolled 125 participants, including ATB patients (n = 46), LTBI subjects (n = 34), and HC (n = 45).ResultsAn IFN-γ release assay (IGRA) was employed to screen LTBI subjects. Whole blood cell surface staining and flow cytometry were used to detect phenotypic distributions of T cells in the peripheral blood mononuclear cells (PBMCs) and tuberculous pleural fluid mononuclear cells (PFMCs). PPD and the phosphorylated antigen HMBPP were employed as stimulators for the detection of M.tb antigen-specific T cell functions via intracellular cytokine staining (ICS). The absolute numbers of T cell subsets, including CD3+ CD4+, CD3+ CD8+ αβ and Vγ2Vδ2+ T cells, were significantly reduced in active tuberculosis compared with latent tuberculosis or the healthy controls. Importantly, PPD-specific CD3+ CD4+ and CD3+ CD8+ αβ T cells and HMBPP-specific Vγ2Vδ2+ T cells in ATB patients were also significantly reduced compared to the LTBI/HC subjects (P < 0.05). In contrast, the proportion of CD4+ T cells in PFMCs was higher compared to PBMCs, while CD8+ and Vγ2Vδ2+ T cells in PFMCs were lower compared to PBMCs (all P < 0.05). PPD-specific CD4+ T cells predominated among CD3+ T cells in PFMCs.ConclusionsCellular immune responses are impaired in ATB patients. Antigen-specific CD4+ T cell may migrate from the periphery to the lesion site, where they exert anti-tuberculosis functions.     

A distinct salivary secretory response mediated by the esophago-salivary reflex in patients with Barrett's esophagus: Its potential pathogenetic implications

PurposeA significantly compromised epidermal growth factor (EGF) secretion by basal parotid saliva may contribute to the development of Barrett's esophagus (BE). The rate of secretion of EGF as well as a wide spectrum of protective factors in total basal and stimulated saliva in BE patients remains to be explored. We therefore studied the rate of secretion of salivary buffers, glycoconjugate, protein, EGF, transforming growth factor α (TGFα) and prostaglandin E₂ (PGE₂), evoked by esophago-salivary reflex, in patients with BE and controls (CTRL).Material/methodsSalivary secretion was collected during basal condition, mastication, and intraesophageal mechanical and chemical stimulations respectively, mimicking the natural gastroesophageal reflux scenario.ResultsSalivary pH in BE was significantly lower than in controls during mechanical (p < 0.001) and chemical stimulations (p < 0.001). Bicarbonate and protein outputs in BE were significantly lower during mechanical (p < 0.05) and chemical stimulations (p < 0.01). The non-bicarbonate and glycoconjugate outputs in BE were lower during chemical stimulation (p < 0.05) and during mechanical (p < 0.05) and chemical stimulations (p < 0.05) respectively. The rate of salivary EGF output in BE was significantly lower during mechanical stimulation (p < 0.05). We observed a higher TGFα output during mastication (p < 0.05) and PGE₂ secretion during basal and masticatory condition (p < 0.05) in BE.ConclusionsPatients with BE demonstrated significantly compromised salivary pH and rate of secretion of bicarbonate, non-bicarbonate, glycoconjugate, protein and EGF. This impairment could potentially predispose to the development of accelerated esophageal mucosal injury. Potential restoration of this impairment by masticatory stimulation of salivary secretion using sugarless chewing gum justifies further clinical exploration.     

Relative distribution of quadriceps head anatomical cross-sectional areas and volumes—Sensitivity to pain and to training intervention

IntroductionQuadriceps heads are important in biomechanical stabilization and in the pathogenesis osteoarthritis of the knee. This is the first study to explore the relative distribution of quadriceps head anatomical cross-sectional areas (ACSA) and volumes, and their response to pain and to training intervention.MethodsThe relative proportions of quadriceps heads were determined in 48 Osteoarthritis Initiative participants with unilateral pain (65% women; age 45–78 years). Quadriceps head volumes were also measured in 35 untrained women (45–55 years) before and after 12-week training intervention. Cross-sectional areas of the vastus medialis (VM), inter-medius (VIM), and lateralis (VL), and of the rectus femoris (RF) were determined from axial T1-weighted MR images.ResultsThe proportion of the VM on the total quadriceps ACSA increased from proximal to distal. The difference in quadriceps ACSA of painful (vs. pain-free) limbs was −5.4% for the VM (p < 0.001), −6.8% for the VL (p < 0.01), −2.8% for the VIM (p = 0.06), and +3.4% for the RF (p = 0.67) but the VM/VL ratio was not significantly altered. The muscle volume increase during training intervention was +4.2% (p < 0.05) for VM, +1.3% for VL, +2.0% for VIM (p < 0.05) and +1.6% for RF.ConclusionThe proportion of quadriceps head relative to total muscle ACSA and volume depends on the anatomical level studied. The results suggest that there may be a differential response of the quadriceps heads to pain-induced atrophy and to training-related hypertrophy. Studies in larger samples are needed to ascertain whether the observed differences in response to pain and training are statistically and clinically significant.     

Metformin limits ceramide-induced senescence in C2C12 myoblasts

High lipid and ceramide concentrations are hallmarks of obese and/or insulin resistant skeletal muscle, yet little is known about its role on cell cycle and senescence. The purpose of this study was to examine the role of ceramide on muscle senescence, and whether metformin limited this response.MethodsLow passage, proliferating C2C12 myoblasts were treated with a control, 50 μM C2-ceramide (8 h), and/or 2 mM metformin, then examined for insulin sensitivity, cell senescence, cell proliferation, cell cycle, protein expression of cell cycle regulators.ResultsCeramide treatment caused a dephosphorylation (p < 0.05) of Akt and 4E-BP1, regardless of the presence of insulin. The ceramide treated myoblasts displayed higher β-galactosidase staining (p < 0.05), reduced BrDu incorporation and total number of cells (p < 0.05), and an increased proportion of cells in G2-phase (p < 0.05) versus control cultures. Ceramide treatment also upregulated (p < 0.05) p53 and p21 protein expression, that was reversed by either pifithrin-α or shRNA for p53. Metformin limited (p < 0.05) ceramide's effects on insulin signaling, senescence, and cell cycle regulation.ConclusionsHigh ceramide concentrations reduced myoblast proliferation that was associated with aberrant cell cycle regulation and a senescent phenotype, which could provide an understanding of skeletal muscle cell adaptation during conditions of high intramuscular lipid deposition and/or obesity.     

High expression of OX40 (CD134) and 4-1BB (CD137) molecules on CD4+CD25high cells in children with type 1 diabetes

PurposeDespite the rapidly rising incidence of diabetes in children, with the highest rise in children < 5 years of age, data on mechanisms that trigger severe beta-cells damage are limited. The aim of the study was to assess the frequency of OX40 (CD134) or 4-1BB (CD137) positive cells in the peripheral blood of children with newly diagnosed type 1 diabetes (T1D) in comparison to healthy controls.Material/methodsThe study included 33 children (mean age 7.3 ± 5.4 years) with newly diagnosed T1D and 39 age-matched healthy controls. Separate analysis was performed in children < 5 years. Flow cytometric analysis was performed using the following markers: CD4, CD25, CD137, and CD134. Fasting C-peptide level was assessed as well.ResultsThe frequency of CD4⁺CD25^highOX40⁺ was higher in T1D children than in controls (median value 3.58% vs. 1.1%, respectively; p = 0.003). Moreover, T1D children had higher frequency of CD4⁺CD25^high4-1BB⁺ cells than healthy subjects (median value 5.76% vs. 3.74%, respectively; p = 0.037). A significant correlation was noted between the age of diabetic children and the C-peptide level (r = 0.54, 95% CI [0.19–0.77], p = 0.004). In comparison with age-matched controls, children < 5 years had higher frequency of CD4⁺CD25^highOX40⁺ (p = 0.004) and CD4⁺CD25^high4-1BB⁺ cells (p = 0.079).ConclusionsOur study showed higher frequency of both OX40 and 4-1BB positive cells in T1D children in comparison to controls. It seems that observed differences might be more pronounced in children < 5 years of age than in older subjects. Further clinical studies are needed to determine the age-related differences in the immune system, in the pathogenesis of T1D.     

Analyses and comparisons of telomerase activity and telomere length in human T and B cells: Insights for epidemiology of telomere maintenance

Telomeres are the DNA–protein complexes that protect the ends of eukaryotic chromosomes. The cellular enzyme telomerase counteracts telomere shortening by adding telomeric DNA. A growing body of literature links shorter telomere length and lower telomerase activity with various age-related diseases and earlier mortality. Thus, leukocyte telomere length (LTL) and telomerase activity are emerging both as biomarkers and contributing factors for age-related diseases. However, no clinical study has directly examined telomerase activity and telomere length in different lymphocyte subtypes isolated from the same donors, which could offer insight into the summary measure of leukocyte telomere maintenance.We report the first quantitative data in humans examining both levels of telomerase activity and telomere length in four lymphocyte subpopulations from the same donors—CD4+, CD8+CD28+ and CD8+CD28? T cells and B cells, as well as total PBMCs—in a cohort of healthy women. We found that B cells had the highest telomerase activity and longest telomere length; CD4+ T cells had slightly higher telomerase activity than CD8+CD28+ T cells, and similar telomere length. Consistent with earlier reports that CD8+CD28? T cells are replicatively senescent cells, they had the lowest telomerase activity and shortest telomere length. In addition, a higher percentage of CD8+CD28? T cells correlated with shorter total PBMC TL (r = ? 0.26, p = 0.05). Interestingly, telomerase activities of CD4+ and CD8+CD28+ T cells from the same individual were strongly correlated (r = 0.55, r < 0.001), indicating possible common mechanisms for telomerase activity regulation in these two cell subtypes. These data will facilitate the understanding of leukocyte aging and its relationship to human health.     

Disclosing genetic risk of Alzheimer’s disease to cognitively impaired patients and visit companions: Findings from the REVEAL Study

ObjectiveTo describe the impact of genetic information on Alzheimer’s disease (AD) risk communication to patients with mild cognitive impairment (MCI) and their visit companions.MethodsParticipants of the fourth REVEAL Study trial were randomized to receive AD risk assessments with or without genotype results. We coded 79 audio recorded risk disclosure sessions with the Roter Interaction Analysis System. Multilevel analyses explored differences in communication when disclosed risks were based on age and MCI diagnosis alone or in addition to APOE genotype status.ResultsThe addition of genotype results diminished the patient-centered nature of the sessions (p < 0.001). When ε4 positive relative to ε4 negative results were disclosed, visit companions were more verbally active (p < 0.05), disclosed more medical information (p < 0.05), were more positive verbally and non-verbally (p < 0.05) and were more proactive in setting the visit agenda (p < 0.05).ConclusionsDelivery of complex genetic risk information reduces the patient-centeredness of disclosure sessions. Visit companions are more actively engaged in session communication when patients are at increased genetic risk for AD.Practice implicationsAD risk discussions can be improved by supporting the positive role of visit companions and addressing the challenges inherent in the delivery of complex genetic information in a patient-centered manner.     

Knee laxity of Malaysian adults: Gender differentials,and association with age and anthropometric measures

BackgroundKnee laxity measurements have been shown to be associated with some medical conditions such as chronic joint pain and collagen tissue diseases. The aim of this study was to determine the effects of demographic factors and anthropometric measures on knee laxity.Materials and methodsData were collected from 521 visitors, staffs and students from the University Malaya Medical Centre and University of Malaya between December 2009 and May 2010. Knee laxity was measured using a KT-1000 arthrometer. Multiple regression analysis was used to find the association of knee laxity with age and anthropometric measures.ResultsUsing ANOVA, knee laxity did not show significant differences among ethnic groups for both genders. The average knee laxity in men was 3.47 mm (right) and 3.49 mm (left); while in women were 3.90 mm (right) and 3.67 mm (left). Knee laxity in women was significantly higher (right knee p < 0.01 and left knee p < 0.05) than men. Right knee laxity of men was negatively associated with height (p < 0.05) and BMI (p < 0.05); also a negative association was observed between left knee laxity and BMI (p < 0.05). Overweight and obese men had less knee laxity than normal weight and underweight individuals. Elderly men and women (age 55 and above) had lower knee laxity (p < 0.01) than young adults (ages 21–39).ConclusionThese results suggest that age and body size are important factors in predicting knee laxity.     

Anti-Tax antibody levels in asymptomatic carriers,oligosymptomatic carriers,patients with rheumatologic disease or with HAM/TSP do not correlate with HTLV-1 proviral load

BackgroundHTLV-1 infects millions of people around the world and induces myelopathy (HAM/TSP), adult T-cell leukemia (ATL) or other inflammatory or rheumatologic diseases. The host–virus interaction causes asymptomatic carriers to develop HAM/TSP. Biomarkers are needed to predict patients who are at risk for HAM/TSP. Tax is highly immunogenic and is a major target protein recognized by cytotoxic T lymphocytes. Anti-Tax antibodies are involved in HAM/TSP pathogenesis.ObjectivesTo assess anti-Tax IgG reactivity with a flow cytometry assay (FCA) using an infection/transfection system with Vaccinia virus and pLW44/Tax-expressing Tax and to correlate the anti-Tax response and the HTLV-1 proviral load.Study design: We enrolled 81 individuals: 9 HTLV-1 seronegative (NP) and 72 HTLV-1 positive (23 HTLV-1 asymptomatic carriers (AC), 12 oligosymptomatic patients (OL), 7 with rheumatologic diseases (DR) and 30 with HAM/TSP (HT)). Anti-Tax reactivity was assessed by FCA, and HTLV-1 proviral load was measured with real time PCR.ResultsThe HT and DR groups showed greater anti-Tax IgG reactivity (p < 0.001 and p < 0.05 comparing HT to the OL and AC group, respectively; p < 0.05 comparing DR to the OL group), and the reactivity in the DR + HT group was significantly different when compared to the AC group (p < 0.05) and to the OL group (p < 0.001). The proviral load was higher in the HT group compared to the OL (p < 0.001) and in the HT + DR group compared to OL (p < 0.001). There was no correlation between anti-Tax IgG reactivity and proviral load in any of the HTLV-1-infected groups.ConclusionThese findings suggest that although anti-Tax IgG reactivity and the HTLV-1 proviral load are important markers of the development of HTLV-1-associated diseases, their levels are not correlated.     

Specifying the effects of physician's communication on patients’ outcomes: A randomised controlled trial

ObjectiveTo experimentally test the effects of physician's affect-oriented communication and inducing expectations on outcomes in patients with menstrual pain.MethodsUsing a 2 × 2 RCT design, four videotaped simulated medical consultations were used, depicting a physician and a patient with menstrual pain. In the videos, two elements of physician's communication were manipulated: (1) affect-oriented communication (positive: warm, emphatic; versus negative: cold, formal), and (2) outcome expectation induction (positive versus uncertain). Participants (293 women with menstrual pain), acting as analogue patients, viewed one of the four videos. Pre- and post video participants’ outcomes (anxiety, mood, self-efficacy, outcome expectations, and satisfaction) were assessed.ResultsPositive affect-oriented communication reduced anxiety (p < 0.001), negative mood (p = 0.001), and increased satisfaction (p < 0.001) compared to negative affect-oriented communication. Positive expectations increased feelings of self-efficacy (p < 0.001) and outcome expectancies (p < 0.001), compared to uncertain expectations, but did not reduce anxiety. The combination of positive affect-oriented communication and a positive expectation reduced anxiety (p = 0.02), increased outcome expectancies (p = 0.01) and satisfaction (p = 0.001).ConclusionBeing empathic and inducing positive expectations have distinct and combined effects, demonstrating that both are needed to influence patients’ outcomes for the best.Practice implicationsContinued medical training is needed to harness placebo-effects of medical communication into practice.     

CD4 and CD4/CD8 ratio progression in HIV-HCV infected patients after achievement of SVR

BackgroundIn HIV-HCV co-infected patients, the long-term effects of HCV eradication on HIV disease progression are still unclear.ObjectivesThis study aims to determine if CD4 and CD4/CD8 ratio slopes improved after anti-HCV treatment in patients achieving a sustained virological response (SVR).Study designA total of 116 HIV-HCV co-infected patients, previously treated with Peg-IFN/RBV, were divided into two groups: SVR (55 patients who had achieved SVR), and non-SVR (61 patients). Retrospective data before and after anti-HCV therapy were obtained for all patients, with a median 8 year-follow-up. Multilevel mixed models were fitted to assess the trends over time of FIB-4 score, APRI score, CD4, CD8 cell count and CD4/CD8 ratio.ResultsMedian HIV-infection duration, HCV-RNA and GGT baseline levels were higher in non-SVR compared to the SVR group. A significantly decreased FIB-4 (p < 0.001) and APRI trend (p < 0.001) after SVR was observed in SVR patients compared to those non-SVR. After adjustment for HIV duration, there was no significant difference between the two groups for absolute CD4 (p = 0.08) or percentage CD4 slope (p = 0.6) over time. The CD4/CD8 ratio trend also demonstrated a similar progressive increase in both groups (p = 0.2). During follow-up, six deaths were reported in the non-SVR group versus no death for the SVR group, while no difference in AIDS and non-AIDS events was observed.ConclusionsAchievement of SVR determines an important beneficial impact in terms of liver-related mortality and fibrosis regression, but does not seem to alter neither the slope of long term CD4 gain nor the CD4/CD8 ratio evolution in ART-treated HIV-HCV co-infected patients.     

Effect of the immunosuppressive regimen on the incidence of cytomegalovirus infection in 378 heart transplant recipients: A single centre,prospective cohort study

BackgroundCytomegalovirus (CMV) infection is a major complication of immunosuppression after heart transplant. Recent studies suggest the actual immunosuppressive regimen may affect the risk of CMV infection.ObjectivesTo evaluate incidence, risk factors and clinical consequences of CMV infection and assess the possible differential effect of distinct immunosuppressive protocols.Study designSingle centre, prospective cohort study of 378 consecutive heart transplant recipients undergoing CMV monitoring. Preemptive treatment was the standard of care. Patients were grouped as follows: group A, without any CMV infection; group B, with CMV infection not requiring pre-emptive treatment; group C, treated for CMV infection or disease.ResultsMost recipients never required antiviral therapy because of no CMV infection/disease (group A, 31%) or CMV levels below the cut-off for pre-emptive treatment (group B, 28%). Group C recipients (41%) were significantly older than group A patients (49.1 ± 13.2 vs. 44.8 ± 15.1 years; p = 0.028). Most cases occurred within the second month post-transplant. CMV viremia was detected in 77% and 62% of patients primed with thymoglobulin or ATG Fresenius, respectively, (OR 2.06, 95% C.I. 1.27–3.34; p = 0.0034). Use of everolimus was associated with a significantly lower rate of CMV infection compared to azathioprine or mycophenolate (OR 0.19, 95% C.I. 0.09–0.39; p < 0.0001). Major opportunistic infections were significantly more common in groups B and C.ConclusionIn a large and homogeneous cohort of heart transplant recipients, we observed a strong relationship between the immune suppressive regimen and CMV infection, as well as an increased incidence of other opportunistic infections in recipients with CMV infection/disease.     

A specific immune tolerance toward offspring cells is to exist after the mother lymphocyte infusion

PurposeTo examine immune tolerance between maternal lymphocytes and offspring tissue after a donor lymphocyte infusion.MethodsMouse models were established by mating female BALB/c mice with male C57BL mice. Splenic lymphocytes from donors of different genetic backgrounds were labeled with carboxyfluorescein succinimidyl ester (CFSE), and 1 × 10⁷ of the labeled cells were intravenously injected into a recipient. At 6 h, 24 h, 72 h and 120 h after the infusion, mononuclear cells in recipient spleen, liver, thymus, lymph nodes, and peripheral blood were collected. CFSE+, CFSE-, CD3+, CD8+, CD4+, CD19+, NK1.1+, CD25+, and CD127+ lymphocytes in those samples were analyzed by flow cytometry. The distribution of donor T cells, B cells, NK cells, helper T cells, cytotoxic T cells, and recipient regulatory T cells in the tissues were then analyzed.ResultsMaternal lymphocytes were more likely to survive in offspring. At 120 h after infusion, the percentages of maternal cells in the offspring were 0.52 ± 0.11% in lymph nodes, 0.97 ± 0.04% in peripheral blood, and 0.97 ± 0.11% in the spleen. Few donor cells, if any, were detected in these tissues at 120 h after aunt to child, father to child, and unrelated allogeneic infusions were performed. The subtype proportion of donor lymphocytes changed significantly in the recipient tissues. Recipient Treg cells increased in the mother to child group, but not in the aunt to child, father to child, and unrelated allogeneic groups, suggesting a decreased cellular immune response to allogeneic cells in the mother to child group. At 120 h after the infusion, no donor cells were detected in the recipient livers and thymuses of all groups, implying that donor cells were barely able to colonize in the liver and thymus.ConclusionSpecific immune tolerance to maternal lymphocytes exists in offspring. An infusion of maternal donor lymphocytes may produce a relatively persistent effect of adoptive immunotherapy with reduced side-effects.     

Effects of supervised whole body vibration exercise on fall risk factors,functional dependence and health-related quality of life in nursing home residents aged 80+

ObjectiveTo test the feasibility and effectiveness of whole-body vibration (WBV) therapy on fall risk, functional dependence and health-related quality of life in nursing home residents aged 80+ years.DesignTwenty-nine 80–95 years old volunteers, nursing home residents were randomized to an eight-week WBV intervention group) (n = 15) or control group (n = 14). Functional mobility was assessed using the timed up and go (TUG) test. Lower limb performance was evaluated using the 30-s Chair Sit to Stand (30-s CSTS) test. Postural stability was measured using a force platform. The Barthel Index was used to assess functional dependence and the EuroQol (EQ-5D) was used to evaluate Health-Related Quality of Life. All outcome measures were assessed at baseline and at a follow-up after 8 weeks.ResultsAt the 8-week follow up, TUG test (p < 0.001), 30-s CSTS number of times (p = 0.006), EQ-5Dmobility (p < 0.001), EQ-5DVAS (p < 0.014), EQ-5Dutility (p < 0.001) and Barthel index (p = 0.003) improved in the WBV intervention group when compared to the control group.ConclusionsAn 8-week WBV-based intervention in a nursing home setting is effective in reducing fall risk factors and quality of life in nursing home residents aged 80+.     

Can pre-operative measures predict quadruple hamstring graft diameter?

The use of autologous grafts such as the quadrupled semitendinosus and gracilis tendon is very common in anterior cruciate ligament (ACL) reconstruction. The diameter of such grafts can be variable and thus unpredictable prior to surgery. In this study, we hypothesized that parameters such as gender, height, age, and body mass index (BMI) can be used pre-operatively to reveal the true graft diameter. All hamstring ACL reconstructions from 1994 to 2002 were reviewed. 536 cases (302 females, 234 males) met the inclusion criteria. Quadruple hamstring constructs and femoral tunnel diameters were measured using 1 mm increment graft sizers. Pre-operative measures of height, weight, body mass index, gender, and age were obtained. Multiple regression analysis was used to build a predictive model of the quadruple hamstring graft diameter. The results of the study demonstrated that males had significantly larger grafts than females (8.1 ± 0.8 vs. 7.5 ± 0.6 mm). Multiple regression analysis on the entire group showed that pre-operative height (p < 0.0002) and gender (p < 0.0047), but not age (p < 0.06) or weight (p < 0.019) were significant predictors of graft diameter. Height (p < 0.0001) was a specific predictor solely in men. In females, none of the pre-operative measures were predictive of graft diameters. Patient height and gender can be used as pre-operative indicators of in vivo quadrupled hamstring graft diameter. Regardless of other variables, 42% of females will have tunnel diameters of 7 mm or less. An alternative graft choice should be discussed pre-operatively if graft sizes may be of concern for the tall and large female patients.     

Prolonged survival effects induced by immature dendritic cells and regulatory T cells in a rat liver transplantation model

BackgroundDendritic cells (DCs) and regulatory T (Treg) cells are crucial for inducing immune tolerance. However, the suppressive function of infused Treg cells and immature DCs (imDCs) following solid organ transplantation remains unclear.MethodsImDCs derived from DA-donor rats and Treg cells isolated from spleens of Lewis rats were prepared. A heterotopic liver transplantation model was established to examine the immune tolerance effects of infusion of Treg-imDCs, imDCs and Treg cells individually. Th1/Th2 cytokines and TRAL were detected by ELISA. The overall rejection grade was assessed and the rejection activity index (RAI) was calculated. TUNEL-positive lymphocytes were detected in the portal area in liver sections.ResultsThe infusion of Treg-imDCs was more effective than imDCs or Treg cells individually. Moreover, the expression of IL-10 and TGF-β1 was significantly up-regulated, and IL-12 expression was significantly down-regulated, especially in the Treg-imDCs group. The percentage of TUNEL-positive cells was significantly higher in the Treg cells and imDCs groups. The RAI values in Treg-imDCs group on days 3 and 7 were lower than control, imDCs and Treg cells groups individually (p < 0.05). Both TBIL and ALT levels in the Treg-imDCs and imDCs groups were significantly lower than those of the control and Treg cells groups, and serum TRAL levels increased significantly 10 days after transplantation in the imDC and Treg-imDC groups compared with the control and Treg cells groups (P < 0.001).ConclusionThese data demonstrated that infusion of Treg cells and/or imDCs induces alloantigen tolerance and prolongs liver allograft survival. The infusion of Treg-imDCs was more effective than imDCs or Treg cells individually. ImDCs synergize with Treg cells in inducing and maintaining the feedback loop between imDCs and Treg cells in vivo.     

Guided self-determination improves life skills with Type 1 diabetes and A1C in randomized controlled trial

ObjectiveTo report 1-year results of newly developed method, guided self-determination (GSD), applied in group training (GSD-GT) for Type 1 diabetes patients with persistent poor glycaemic control.MethodsGSD was designed on the basis of qualitative research to help patients develop life skills with diabetes using worksheets filled in at home and coached by nurses in mutual reflection. We randomized 18–49-year-old adults at a Danish university hospital to either 16 h GSD-GT in 2001 or to similar training 1 year later. Inclusion criteria: mean A1C ≥ 8.0% for at least 2 years, disease onset ≤40 years and insulin treatment from onset.ResultsThirty GSD-GT patients and 20 controls completed the study. GSD-GT patients did better than control patients in terms of (a) increased autonomy support perceived from health professionals (p < 0.01); (b) higher frequency of self-monitored blood glucoses (p < 0.001); (c) increased perceived competence in managing diabetes (p < 0.01); (d) fewer diabetes-related problems (p < 0.05); and (e) improved glycaemic control (p < 0.01).ConclusionGSD was effective in improving life skills with diabetes, including A1C, over a period of 1 year.Practice implicationsGSD is a worthy candidate for further research. We consider it adjustable to people with type 2 diabetes and other chronic conditions.     

Lean soft tissue contributes more to bone health than fat mass independent of physical activity in women across the lifespan

ObjectivesTo investigate the association between lean soft tissue (LST) and fat mass (FM) on bone health variables in women across the lifespan, while taking into account the influence of objectively measured habitual physical activity (PA).Study designA total of 104 women, 37 young (23.3 ± 2.6 years), 28 middle-age (49.2 ± 5.4 years), and 39 old (68.3 ± 6.4 years) participated in this cross-sectional study. All underwent a DXA scan and wore a pedometer for 7 days.Main outcome measuresBone mineral content (BMC) and BMD of the whole body (WB), lumbar spine (LS) and proximal femur (PF), and body composition (FM and LST) were assessed with DXA and PA (steps/day) was assessed from 7 day pedometer counts.ResultsLST was significantly and positively associated with PF and LS BMD (r = 0.34; 0.67, p < 0.05), and WB, PF and LS BMC (r range = 0.41–0.59, p < 0.05) in all age groups and WB BMD in the middle-age group (r = 0.72, p < 0.05) independent of PA, FM, and hormonal status. FM was not positively associated with any bone variable in any age group when adjusted for PA, LST, and hormonal status. PA was significantly associated with WB BMD in the middle-age group (r = 0.60, p < 0.05), independent of LST, FM, and hormonal status.ConclusionsLST contributes more to bone health in women across the lifespan than FM, independent of PA and hormonal status.     

The role of oxidative stress and inflammatory response in high-fat diet induced peripheral neuropathy

ObjectiveEarlier studies suggest that high-calorie diet is an important risk factor for neuronal damage resulting from oxidative stress of lipid metabolism. In our experimental study of rats under high-fat diet, oxidative stress markers and axonal degeneration parameters were used to observe the sciatic nerve neuropathy. The aim of this study is to evaluate the pathophysiology of neuropathy induced by high-fat diet.MethodsA total of 14 male rats (Wistar albino) were randomly divided into two experimental groups as follows; control group (n = 7) and the model group (n = 7); while control group was fed with standard diet; where the model group was fed with a high-fat diet for 12 weeks. At the end of 12 weeks, the lipid profile and blood glucose levels, interleukin-1β (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) levels were studied. Tissue malondialdehyde (MDA), nitric oxide (NO) levels and super-oxide dismutase (SOD), paraoxonase-1 (PON-1) and glutathione peroxidase (GPx) activities were studied. The distal blocks of the left sciatic nerves were evaluated for histomorphological analysis (including mean axon area, axon numbers, nerve fiber diameters, axon diameters, and thickness of myelin sheets).ResultsBody weights, serum glucose and high-density lipoprotein (HDL) levels of rats were found not statistically significantly different compared between the model and the control groups (p > 0.05). Serum cholesterol, triglyceride, TGF-β and TNF-α levels were significantly higher in the model group when compared with the control group (p < 0.05). IL-1 and IL-6 levels were not statistically significantly different compared between the model group and the control group (p > 0.05). The MDA and NO levels and the SOD and GPx activities of the sciatic nerves in model group were statistically significantly higher than the control group (p < 0.05). In addition, the activities of PON-1 were statistically significantly lower in the model group when compared with the control group (p < 0.05). The difference in the total number of myelinated axons between the control group and the model group was not statistically significant (p > 0.05). The nerve fiber diameter and the thickness of the myelin sheet were statistically significantly lower in the model group when compared with the control group (p < 0.05). The axon diameter and area were significantly decreased in the model group when compared with the control group (p < 0.05).ConclusionOur results support that dyslipidemia is an independent risk factor for the development of neuropathy. In addition, we postulated that oxidative stress and inflammatory response may play an important role in the pathogenesis of high-fat diet induced neuropathy.