RA Group Research Articles

Involvement of IL-1β on cognitive impairment after experimental pneumococcal meningitis. (INM1P.432)

Abstract Pneumococcal meningitis is associated with high rates of mortality and long-term cognitive impairment. In the current study, we evaluated the effects of an interleukin (IL)-1β receptor antagonist (IL-1Ra) on memory, cytokine, and BDNF levels in experimental pneumococcal meningitis. Adult Wistar rats were divided into four groups: control/saline, control treated with IL-1Ra, meningitis/saline and meningitis treated with IL-1Ra. The animals were killed at 24 h post-infection. In the meningitis/saline group IL-1β and CINC-1 levels increased at 24 h post-infection; however, treatment with IL-1Ra reversed these increases in the hippocampus. In a second experiment, the rats received antibiotic and were subjected to behavioural tasks (open field, step-down inhibitory avoidance and object recognition), cytokine and BDNF levels ten days after meningitis induction. In the open-field task, the meningitis group did not exhibit differences in motor and exploratory activity, indicating habituation memory impairment. The same impairment occurred in the novel object recognition memory and step-down inhibitory avoidance task (aversive memory) in the meningitis group; however, adjuvant treatment with IL-1Ra prevented memory impairment. The IL-4, IL-6, IL-10 and BDNF levels were increased in the meningitis/saline and meningitis/IL-1Ra groups. These findings illustrate a neuroprotective role of IL-1Ra inhibitor and the involvement of IL-1β on cognitive impairment after pneumococcal meningitis.

Soluble triggering receptor expressed on myeloid cells-1 is a biomarker of anti-CCP-positive, early rheumatoid arthritis.

To assess serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) levels in disease-modifying antirheumatic drug (DMARD)-naïve early rheumatoid arthritis (ERA), to investigate the association of sTREM-1 levels with Disease Activity Score in 28 joints (DAS28) and seropositivity for anti-cyclic citrullinated peptide (CCP) antibody and to determine the predictive value of sTREM-1 with respect to clinical response to DMARD therapy. Twenty-two consecutive patients with DMARD-naïve ERA were prospectively evaluated for serum sTREM-1 by means of ELISA at diagnosis and at the following clinic visit after prednisone and/or DMARD has been administered, and related to DAS28 and serum level of anti-CCP antibody. We compared the sTREM-1 level to that of 31 patients with established RA as well as to 24 controls. Serum sTREM-1 level was significantly higher in the DMARD-naïve ERA group (212.9 ± 388.9 ρg/mL) compared to established RA group (1478.0 ± 280.0 ρg/mL, P = 0.001) and normal control (34.4 ± 7.4 ρg/mL, P < 0.001). In the ERA group, elevated basal sTREM-1 level correlated with higher DAS28-CRP score (P = 0.001, HR 3.23, 95% CI 1.4-8.12), DAS28-ESR (P = 0.04, HR 2.34 95% CI 0.1-8.12), as well as predicted higher DAS28 score at the following encounter after DMARD treatment was administered (P = 0.001, HR 3.2 95% CI 1.1-7.2). Higher serum level of sTREM-1 correlated with higher titres of anti-CCP antibody (P < 0.001). Our results suggest that serum sTREM-1 may provide a novel biomarker for DMARD-naïve ERA as well as for seropositivity for anti-CCP antibody and RA activity.

Neuromuscular adaptations to water-based concurrent training in postmenopausal women: effects of intrasession exercise sequence.

This study investigated the effects of different exercise sequences on the neuromuscular adaptations induced by water-based concurrent training in postmenopausal women. Twenty-one healthy postmenopausal women (57.14 ± 2.43years) were randomly placed into two water-based concurrent training groups: resistance training prior to (RA, n = 10) or after (AR, n = 11) aerobic training. Subjects performed resistance and aerobic training twice a week over 12weeks, performing both exercise types in the same training session. Upper (elbow flexors) and lower-body (knee extensors) one-repetition maximal test (1RM) and peak torque (PT) (knee extensors) were evaluated. The muscle thickness (MT) of upper (biceps brachii) and lower-body (vastus lateralis) was determined by ultrasonography. Moreover, the maximal and submaximal (neuromuscular economy) electromyographic activity (EMG) of lower-body (vastus lateralis and rectus femoris) was measured. Both RA and AR groups increased the upper- and lower-body 1RM and PT, while the lower-body 1RM increases observed in the RA was greater than AR (34.62 ± 13.51 vs. 14.16 ± 13.68%). RA and AR showed similar MT increases in upper- and lower-body muscles evaluated. In addition, significant improvements in the maximal and submaximal EMG of lower-body muscles in both RA and AR were found, with no differences between groups. Both exercise sequences in water-based concurrent training presented relevant improvements to promote health and physical fitness in postmenopausal women. However, the exercise sequence resistance-aerobic optimizes the strength gains in lower limbs.

Catheter ablation of atrial fibrillation in patients with rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is associated with an increased incidence of atrial fibrillation (AF). This study evaluated the safety and efficacy of catheter ablation (CA) in the treatment of AF in patients with RA, which has not been previously reported. MethodsA total of 15 RA patients with AF who underwent CA were enrolled. For each RA patient, we selected 4 individuals (control group, 60 patients in total) who presented for AF ablation in the absence of structural heart or systemic disease and matched the RA patients with same gender, age (±2 years), type of AF, and procedure date. ResultsPatients with RA had a significantly higher C-reactive protein level (1.81±2.35mg/dl vs. 4.14±2.30mg/dl, p=0.0320), white blood cell count (5632±1200mm3 vs. 6361±1567mm3, p=0.0482), and neutrophil count (3308±973mm3 vs. 3949±1461mm3, p=0.0441). At 2-year follow-up, atrial tachyarrhythmia (ATa) recurrence rate in the RA group (33.3%, 5/15) was similar to that in the control group (31.7%, 19/60; p=0.579) after single procedure. In all the five patients from the RA group who developed recurrence, ATa relapsed within 90 days following index procedure (median recurrence time 18 days vs. 92 days in control group; p=0.0373). Multivariate Cox regression analysis showed that hypertension and left atrial diameter but not RA, C-reactive protein, white blood cell count, and neutrophil count were independent predictors of ATa recurrence. ConclusionsCatheter ablation of AF can be safely performed in patients with RA, with a success rate comparable to that of patients without RA. RA patients tend to develop early ATa recurrence after AF ablation.

Short-term reproducibility of the inflammatory phenotype in different subgroups of adult asthma cohort.

Inflammatory phenotype classification using induced sputum appears attractive as it can be applied to inflammation-based management of the patients with asthma. The aim of the study was to determine the reproducibility of inflammatory phenotype over time in patients with asthma. In 66 adults asthma was categorized as steroid-naïve (SN, n = 17), mild to moderate (MMA, n = 33), and refractory treated with oral corticosteroids (RA, n = 16). Clinical assessment, skin prick testing, spirometry, and two sputum inductions in 4–6-week interval were done. Inflammatory phenotypes were classified as eosinophilic (EA), consisting of eosinophilic and mixed granulocytic phenotypes, and noneosinophilic (NEA) consisting of paucigranulocytic and neutrophilic phenotypes. During study asthma treatment remained constant. In SN group 25% of patients changed phenotype from EA to NEA and 44% changed phenotype from NEA to EA. In MMA group 26% of patients changed phenotype from EA to NEA and 50% changed phenotype from NEA to EA. In 29% of RA patients inflammatory phenotype changed from EA to NEA and in 22% it changed from NEA to EA. Inflammatory classification, using induced sputum, is not fully reproducible in adults with asthma in short-term evaluation. EA seems to be more stable phenotype across all subgroups whereas NEA remained stable only in RA group.

MicroCT Analysis of Micro-Nano Titanium Implant Surface on the Osseointegration.

This study was to investigate the effects of micro-nano titanium implant surface on the osseointegration. A total of 36 screw-shaped implants were used. The implant surfaces were classified into 3 groups (n = 12): machined surface (M group), nanosurface which is nanotube formation on the machined surface (MA group) and nano-micro surface which is nanotube formation on the RBM surface (RA group). Anodic oxidation was performed at a 20 V for 10 min with 1 M H3PO4 and 1.5 wt% HF solutions. The implants were installed on the humerus on 6 beagles. After 4 and 12 weeks, the morphometric analysis with micro CT (skyscan 1172, SKYSCAN, Antwerpen, Belgium) was done. The data were statistically analyzed with two-way ANOVA. Bone mineral density and bone volume were significantly increased depending on time. RA group showed the highest bone mineral density and bone volume at 4 weeks and 12 weeks significantly. It indicated that nano-micro titanium implant surface showed faster and more mature osseointegration.

Inhibition on JAK-STAT3 Signaling Transduction Cascade Is Taken by Bioactive Peptide Alpha-S2 Casein Protein from Goat Ethawah Breed Milk.

Background:RA is a systemic inflammatory disease that causes developing comorbidity conditions. This condition can cause by overproduction of pro-inflammatory cytokine. In a previous study, we have found bioactive peptide CSN1S2 from Ethawah goat milk for anti-inflammatory for repair the ileum destruction. However, the signaling transduction cascade of bioactive peptides inhibits inflammation still not clear yet. Therefore, we analyzed the signaling transduction cascade via JAK-STAT3 pathway by in vivo and in silico.Methods:The ileum was isolated DNA and amplification with specific primer. The sequence was analyzed using the Sanger sequencing method. Modeling 3D-structure was predicted by SWISS-MODEL and virtual interaction was analyzed by docking system using Pymol and Discovery Studio 4.0 software.Results:This study showed that STAT3 has target gene 480bp. The normal group and normal treating- CSN1S2 of goat milk have similarity from gene bank. Whereas, RA group had transversion mutation that the purine change into pyrimidine even cause frameshift mutation. Interestingly, after treating with the CSN1S2 protein of goat milk shows reverse to the normal acid sequence group. Based on in silico study, from eight peptides, only three peptides of CSN1S2 protein, which carried by PePT1 to enter the small intestine. The fragments are PepT1-41-NMAIHPR-47; PepT1-182-KISQYYQK-189 and PepT1-214-TNAIPYVR-221. We have found just one bioactive peptide of f182-KISQYYQK-189 is able bind to STAT3. The energy binding of f182-KISQYYQK-189 and RA-STAT3 amino acid, it was Σ = -402.43 kJ/mol and the energy binding of f182-KISQYYQK-189 and RAS-STAT3 amino acid is decreasing into Σ = -407.09 kJ/mol.Conclusion:This study suggested that the fragment 182-KISQYYQK-189 peptides from Ethawah goat milk may act as an anti-inflammatory agent via JAK-STAT3 signal transduction cascade at the cellular level.

Effect of a self-etching primer and phosphoric acid etching on the bond strength of 4-META/MMA-TBB resin to human enamel.

The purpose of this study was to evaluate the shear bond strength and durability of 4-META/MMA-TBB resin to human enamel. A self-etching primer that contained 4-META (Teeth Primer, TP) and 35-45% or 60-65% concentrations of phosphoric acid (K-Etchant Gel, KE, and Super Bond C&B Red Activator, RA) were used as the surface treatment agents. A methyl methacrylate (MMA)-based self-polymerizing resin (Super-Bond C&B) was used as a luting agent. The shear bond strength was determined both pre and post thermocycling. The results were statistically analyzed with a non-parametric procedure. The post-thermocycling shear bond strength of the TP group was significantly higher than that of other groups, and that of the KE group was significantly higher compared with the RA group. These results demonstrated that 4-META was effective. Furthermore, when the degree of tooth demineralization was compared, surface treatment with less demineralization using TP was the most effective treatment.

Acupuncture for Frequent Migraine: A Randomized, Patient/Assessor Blinded, Controlled Trial with One-Year Follow-Up.

Objectives. This study aimed to evaluate the efficacy and safety of manual acupuncture as a prophylaxis for frequent migraine. Methods. Fifty frequent migraineurs were randomly allocated to receive 16 sessions of either real acupuncture (RA = 26) or sham acupuncture (SA = 24) during 20 weeks. The primary outcomes were days with migraine over four weeks, duration, and intensity of migraine and the number of responders with more than 50% reduction of migraine days. The secondary outcomes were the relief medication, quality of migraine, quality of life, and pressure pain thresholds. Results. The two groups were comparable at baseline. At the end of the treatment, when compared with the SA group, the RA group reported significant less migraine days (RA: 5.2 ± 5.0; SA: 10.1 ± 7.1; P = 0.008), less severe migraine (RA: 2.18 ± 1.05; SA: 2.93 ± 0.61; P = 0.004), more responders (RA: 19 versus SA: 7), and increased pressure pain thresholds. No other group difference was found. Group differences were maintained at the end of the three-month follow-up, but not at the one-year follow-up. No severe adverse event was reported. Blinding was successful. Discussion. Manual acupuncture was an effective and safe treatment for short-term relief of frequent migraine in adults. Larger trials are warranted.

Efficacy of Levofloxacin Based Triple and High-Dose PPI-Amoxicillin Dual Eradication Therapy for Helicobacter pylori after Failures of First- and Second-Line Therapies.

Objectives. The aim of this study was to investigate and compare the eradication rate of Helicobacter pylori as the third-line triple therapy with rabeprazole (RPZ) + amoxicillin (AMPC) + levofloxacin (LVFX) and high-dose RPZ + AMPC. Methods. 51 patients who failed Japanese first-line (proton pump inhibitor (PPI) + AMPC + clarithromycin) and second-line (PPI + AMPC + metronidazole) eradication therapy were randomly assigned at a 1 : 1 ratio to one of the following third-line eradication groups: (1) RAL group: RPZ 10 mg (b.i.d.), AMPC 750 mg (b.i.d.), and LVFX 500 mg (o.d.) for 10 days; (2) RA group: RPZ 10 mg (q.i.d.) and AMPC 500 mg (q.i.d.) for 14 days. Patients who failed to respond to third-line eradication therapy received salvage therapy. Results. The rates of eradication success, based on intention to treat (ITT) analysis, were 45.8% in the RAL group and 40.7% in the RA group. The overall eradication rates were 73.9% in the RAL group and 64.0% in the RA group. There was no significant difference between the two groups. Conclusions. The third-line triple therapy with RPZ, AMPC, and LVFX was as effective as that with high-dose RPZ and AMPC.

Anti-cyclic citrullinated peptide antibodies and paraoxonase-1 polymorphism in rheumatoid arthritis.

BackgroundRheumatoid arthritis (RA) is the most common chronic inflammatory joint disease, with a worldwide prevalence of 0.5% to 1%. Anti-cyclic citrullinated peptide antibody (anti-CCP-2 Ab) is a marker of choice for diagnosing early and late RA. Anti-oxidant enzymes activity decreases in RA patients. Till now, the relationship between the rheumatoid factor (RF) and anti-CCP-2 Ab, anti-oxidant activity and polymorphism of paraoxenase-1 (PON-1) 192 Q/R in patients with RA has not been investigated. In this study, we aimed to determine the serum level of RF and anti-CCP-2 Ab, PON-1 activity and 192 Q/R polymorphism and arylesterase (ARE) activity in patients with RA. Also, we studied RA markers in different genotypes of PON-1 of RA patients.MethodsA total of 120 RA patients and 90 healthy persons were subjected to full clinical examinations and routine laboratory tests. PON-1 and ARE activities were determined using an enzymatic spectrophotometric method. PON-1 192 gene polymorphism was determined using polymerase chain reaction based restriction fragment analysis. RF was measured by immunoturbidimetry method and anti-CCP-2 Ab was assayed by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using SPSS for windows 20.0.ResultsThe sensitivity and specificity of anti-CCP-2 Ab for the diagnosis of RA were 76.2% and 100% respectively. PON-1 and ARE activities were statistically lower (P <0.001) in the RA group compared to the control group. A negative correlation between RF and anti-CCP-2 Ab levels and PON-1 and ARE activities was found. No significant difference in the genotype distribution between RA patients and healthy persons was detected. RF and anti-CCP-2 Ab levels were higher in RA patients carried RR genotype than in those carried QQ genotype.ConclusionHigh RF and anti-CCP-2 antibody serum levels were found to be associated with decreased PON-1 and ARE activities with no correlation between PON-1 polymorphism and serum levels of RF and anti-CCP-2 Ab in patients with RA. These results may indicate an implication between antioxidant enzymes activity and serum levels of RF and anti-CCP-2 Ab.

Radiation therapy of anal canal cancer: from conformal therapy to volumetric modulated arc therapy.

BackgroundTo appraise the role of volumetric modulated arc (RapidArc, RA) in the treatment of anal canal carcinoma (ACC).MethodsA retrospective analysis has been conducted on 36 patients treated with RA since 2009 comparing outcome against a group of 28 patients treated with conformal therapy (CRT). RA treatments were prescribed with SIB technique with 59.4 Gy to the primary tumor and nodes and 49.5 Gy to the elective nodes. CRT was sequentially delivered with 45 Gy to the pelvic target and a boost of 14.4 Gy to the primary tumor.ResultsMedian age of patients was 65 yrs for RA (59 yrs for CRT); 90% had Stage II-III (93% in the CRT group). No statistically significant differences were observed concerning survival or control. 5 yrs disease specific survival was 85.7% and 81.2%, loco-regional control was of 78.1% and 82.1% for RA and CRT respectively. RA treatments lead to lower incidence of higher grade of toxicity events (all retrospectively retrieved from charts as worse events). Grade 2–3 toxicity, compared to CRT, reduced from 89% to 68% for GI, from 39% to 33% for GU and from 82% to 75% for the skin. Late toxicity was as follows: 5/36 (14%) and 3/36 (8%) patients had G1 or G2 GI toxicity in the RA group (1/28 (4%) and 4/28 (14%) in the CRT group). GU late toxicity was observed only in 4/28 (14%) patients of the CRT group: 3/28 (11%) had G2 and 1/28 (4%) had G1.ConclusionsRA treatments of ACC patients proved to be equally effective than CRT but it was associated to a reduction of toxicity.

Cardiovascular autonomic neuropathy in rheumatoid arthritis assessed by cardiovascular autonomic function tests: A cross-sectional survey.

Objective:In this study, we aimed to evaluate cardiovascular autonomic neuropathy (CAN) in RA patients by cardiovascular autonomic function tests. Because CAN was reported of patients with automimmune rheumatic diseases those may in sudden death or myocardial infarction.Methods:A total of 44 patients with RA and 44 age-and sex-matched healthy volunteers participated in this cross-sectional study. Assessment of CAN was performed using cardiovascular reflex tests. These five tests were: 1) beat-to-beat heart rate variation during deep breathing; 2) heart rate response to standing up; 3) heart rate response to the Valsalva maneuver; 4) blood pressure response to standing up; and 5) blood pressure response to sustained handgrip.Results:The mean age was 43.15 (SD, 12.18) years (range, 23-68 years) in the RA group, and 38 were women. In beat-to-beat heart rate variation during deep breathing, expiration-to-inspiration ratio was abnormal in 3 cases with RA (6.8%) but in 1 (2.3%) control subject (p=0.3), and maximum minus minimum heart rate was abnormal in 8 patients (18.2%) and in 3 (6.8%) control subjects (p=0.1). 2) In heart rate response to standing up, all patients and controls had normal results. Valsalva ratio was abnormal in 7 RA patients (15.9%) and in 7 control subjects (15.9%). Blood pressure response to standing up was normal in RA patients but abnormal in 1 (2.3%) control subject (p=0.4). Blood pressure response to sustained handgrip was abnormal in 5 RA patients (11.4%) and 2 (4.6%) control subjects (p=0.2).Conclusion:Our study failed to show any statistically significant difference between cardiovascular autonomic function tests in RA patients with control subjects by our test done.

Anti-arthritic activity of luteolin in Freund’s complete adjuvant-induced arthritis in rats by suppressing P2X4 pathway

To investigate anti-arthritic activity of luteolin (Lut) in Freund’s complete adjuvant (FCA)-induced arthritis (AA) in rats. AA was induced by injecting with Freund’s complete adjuvant (FCA). Male rats were randomly divided into five groups with 10 mice in each group: (1) control group (saline), (2) AA group, (3) AA+Diclofenac Sodium (AA+DS, 5mg/kg), (4) AA+Lut (20mg/kg), (5) AA+Lut (40mg/kg). Male SD rats were subjected to treatment with Lut at 10 and 20mg/kg from days 18 to 24 after immunization. Arthritic scores, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-17 (IL-17), paw histopathology and the proteins of P2X4 pathway were assessed at the end of the experiment. Lut reduced the severity of arthritic scores during the experimental period as compared with positive control (RA). Lut significantly suppressed TNF-α, IL-6, IL-1β and IL-17 as compared with RA group. Histopathological examination indicated that Lut alleviated infiltration of inflammatory cells and synovial hyperplasia as well as protected joint destruction. Lut significantly suppressed P2X4, NLRP1, ASC, and Caspase-1p10. Lut may be a potential preventive or therapeutic candidate for the treatment of inflammation and arthritis.

Overexpression of extracellular superoxide dismutase protects against brain injury induced by chronic hypoxia.

Extracellular superoxide dismutase (EC-SOD) is an isoform of SOD normally found both intra- and extra-cellularly and accounting for most SOD activity in blood vessels. Here we explored the role of EC-SOD in protecting against brain damage induced by chronic hypoxia. EC-SOD Transgenic mice, were exposed to hypoxia (FiO2.1%) for 10 days (H-KI) and compared to transgenic animals housed in room air (RA-KI), wild type animals exposed to hypoxia (H-WT or wild type mice housed in room air (RA-WT). Overall brain metabolism evaluated by positron emission tomography (PET) showed that H-WT mice had significantly higher uptake of 18FDG in the brain particularly the hippocampus, hypothalamus, and cerebellum. H-KI mice had comparable uptake to the RA-KI and RA-WT groups. To investigate the functional state of the hippocampus, electrophysiological techniques in ex vivo hippocampal slices were performed and showed that H-KI had normal synaptic plasticity, whereas H-WT were severely affected. Markers of oxidative stress, GFAP, IBA1, MIF, and pAMPK showed similar values in the H-KI and RA-WT groups, but were significantly increased in the H-WT group. Caspase-3 assay and histopathological studies showed significant apoptosis/cell damage in the H-WT group, but no significant difference in the H-KI group compared to the RA groups. The data suggest that EC-SOD has potential prophylactic and therapeutic roles in diseases with compromised brain oxygenation.

The impact of early intra-articular administration of interleukin-1 receptor antagonist on lubricin metabolism and cartilage degeneration in an anterior cruciate ligament transection model

Study the impact of intra-articular interleukin-1 receptor antagonist (IL-1 ra) treatment onlubricin biosynthesis following anterior cruciate ligament transection (ACLT) in the rat and evaluate the effect of combined IL-1 ra and recombinant human lubricin (rhPRG4) treatments on chondrocyte apoptosis. ACLT was performed in male Lewis rats. Treatments included IL-1 ra or vehicle (n=36 in each group). IL-1 ra intra-articular dosing was performed on days 1, 3, 5 and 7 following ACLT using Anakinra (150mg/ml; 40μl). At 3 and 5 weeks, animals were sacrificed and RNA was isolated. Histological analyses included Safranin O and H&E. Lubricin synovial fluid (SF) lavage concentrations were determined at 5 weeks. ACLT animals were treated with a single injection of vehicle, IL-1 ra (75mg/ml; 40μl), rhPRG4 (200μg/ml; 40μl), or IL-1 ra+rhPRG4 (75mg/ml+200μg/ml; 40μl) (n=6 in each group) on day 7 following ACLT and cartilage was probed for cleaved caspase-3 at 5 weeks. IL-1 ra treatment improved lubricin expression (P<0.001) and lubricin SF lavage concentrations in the IL-1 ra group was higher (P=0.005) than the vehicle. IL-1 ra treatment reduced cartilage and synovial scores (P<0.001) compared to vehicle. IL-1 ra and rhPRG4 acted synergistically to reduce caspase-3 positive chondrocytes (P<0.001) compared to individual treatments. IL-1 ra treatment preserved lubricin following ACLT and a combined treatment of IL-1 ra+rhPRG4 may act synergistically to reduce cartilage catabolism.

Efeitos do Treinamento Combinado Resistido-Aeróbio no Ventrículo Esquerdo de Rato Wistar

The objective of this work was to determine the effects of combined resistance- aerobic training on the left ventricle (LV) weight, LV wall thickness and LV cavity dimension in rats. One group of rats (n=5), the combined resistance-aerobic group (RA) were submitted to exercise and a sedentary control group (C) (n=5) was included. Rats were trained to climb a 1.1 m vertical (80° incline) ladder with weights tied to their tails, which were progressively augmented. After each resistance training session, the animals were trained to run 1 hour/day on the treadmill. Exercise training was performed 5 times weekly for 8 weeks. After the sacrifice, the myocardium was perfused with glutaralde hyde and the LV was isolated and weighed. Themid-zone of the LV free wall was incised transversely obtaining a ring with a thickness of 0.5 cm, which was included in Epon resin yielding blocksf or performing histological sections transversely to the long axisof the cavity with 0.5 µm thick that weres tained with to luidine blue and used to measure the diameter of the cavity and the thickness of the wall. The results showed that the values of the LV weight was 10.5% larger in the RA group (P< 0.05), compared with the C group, the LV wall thickness was 8% larger in the RA group (P<0.05), than in C group and the LV internal diameter was 4.5% larger in RA group (P <0.05), than in C group. Conclusion: The resistance-aerobic trainingused in this studyinducedthe developmentof aspecific typeof hypertrophyof the LV wall, which combinesthe effects ofaerobic trainingandresistance training. The resistance-aerobic training increases the ventricular cavity while increasing wall thickness.

Intranasal nerve growth factor attenuates tau phosphorylation in brain after traumatic brain injury in rats

Traumatic brain injury (TBI) is a considerable cause of mild cognitive impairment and dementia. Intranasal administration of nerve growth factor (NGF) has previously been found to improve cognitive function after TBI, but the mechanism remains unclear. This study aimed to investigate the effects of intranasal NGF on the tau hyperphosphorylation following TBI. A modified Feeney's weight-drop model was used to induce TBI. Rats were randomly divided into control group, TBI group, TBI+NGF group, TBI+PDTC group and TBI+IL-1ra group. Rats in TBI+NGF group were administered with NGF (5μg/d) for 3d before surgery. Hyperphosphorylated tau protein was remarkable in the peri-contusional cortex area with TBI. Both western blotting and immunostaining results displayed intranasal pretreatment of NGF significantly reduced tau phosphorylation. To evaluate the underlying mechanism, the levels of glycogen synthase kinase 3β (GSK-3β), interleukin-1β (IL-1β), and the DNA binding activity of nuclear factor-κB (NF-κB) were assayed. NGF markedly inhibited GSK-3β. NGF also reduced TBI-induced elevation of IL-1β and NF-κB DNA binding activity. Furthermore, PDTC and IL-1ra were injected to prove a potential signaling pathway among NF-κB, IL-1β and GSK-3β. Taken together, these findings demonstrated that intranasal NGF could effectively attenuate the hyperphosphorylation of tau after TBI, which might involve an integrated signaling pathway related to NF-κB.

Effects of aerobic training, resistance training, or combined resistance-aerobic training on the left ventricular myocardium in a rat model.

This study follows the left ventricular (LV) hypertrophy in rats undergoing aerobic training alone (A), resistance training alone (R), or combined resistance and aerobic training (RA) (usually referred as concurrent training) program. A sedentary control group (C) was included. LV remodeling was evaluated using electron and light microscopy. The LV weight to body weight (LVW: BW) increased 11.4% in A group, 35% in the R group, and 18% in the RA group compared to the C group. The LV thickness increased 6% in the A group, 17% in the R group, and 10% in the RA group. The LV internal diameter increased 19% in the A group, 3% in the R group, and 8% in the RA group compared with the C group. The cross-sectional area of cardiomyocyte increased by 1% with the A group, 27% with R group, and 12% with RA training. The capillary density increased by 5.4% with A training, 11.0% with R training, and 7.7% with RA training compared with the C group. The volume fraction of interstitial collagen increased by 0.4% with training A, increased by 2.8% with R training, and 0.9% with RA training. In conclusion, except for the LV internal diameter, which increased more in the A group, the cardiac parameters increased more in the R group than in the other groups and in RA group than in A group. Collagen density increased from 5.4 ± 0.8% in the C group to 5.8 ± 0.6% in the A group (n. s.) (P > 0.05), to 8.2 ± 0.7% in the R group (P < 0.05), and to 6.3 ± 0.4% in the RA group (P < 0.05). These results demonstrate a significant increase for collagen content in the LV with R and RA exercise, but the increase was higher with R training alone than with RA training.

Associations between serum 25-hydroxyvitamin D and disease activity, inflammatory cytokines and bone loss in patients with rheumatoid arthritis.

The aim of this study was to describe the associations between serum levels of 25-hydroxyvitamin D [25(OH)D] and disease activity, inflammatory cytokines and bone loss/erosions in patients with RA. The study included 130 patients with RA and 80 healthy controls. Serum 25(OH)D, IL-17 and IL-23 levels were detected by ELISA. Radiographic bone erosion was assessed using the van der Heijde modified Sharp score and BMD was measured using DXA. There were no significant differences in age, gender and BMI between the RA and control groups. Serum level of 25(OH)D was markedly lower in the RA group than in the control group [43.12 nmol/l (s.d. 15.59) vs 57.93 (15.95), P < 0.01]. In RA patients, 25(OH)D levels were significantly and negatively associated with clinical parameters of disease activity including swollen joint count, tender joint count, joint pain degree, morning stiffness time and HAQ score and laboratory measures including platelets and ESR after adjustment for gender, age and BMI. They were also negatively associated with serum levels of IL-17 and IL-23. While 25(OH)D levels were not associated with radiographic bone erosions of RA, they were significantly lower in those with osteopenia and osteoporosis than in those with normal BMD (P < 0.01). 25(OH)D levels were reduced in patients with RA and were negatively associated with disease activity, IL-17/IL-23 and bone loss in RA. These suggest that vitamin D deficiency may play a role in the aetiology of RA.