Efficacy and safety of acupuncture for chronic pain caused by gonarthrosis: A study protocol of an ongoing multi-centre randomised controlled clinical trial [ISRCTN27450856]

Background  

Controlled clinical trials produced contradictory results with respect to a specific analgesic effect of acupuncture. There is a lack of large multi-centre acupuncture trials. The German Acupuncture Trial represents the largest multi-centre study of acupuncture in the treatment of chronic pain caused by gonarthrosis up to now.     

The D‐vitamin metabolite 1,25(OH)2D in serum is associated with disease activity and Anti‐Citrullinated Protein Antibodies in active and treatment naïve,early Rheumatoid Arthritis Patients

Rationale

Sufficient levels of vitamin D seem to be essential for proper immune function, and low levels might be associated to disease activity in Rheumatoid Arthritis (RA ). Most studies investigate only 25OHD and not the physiologically active vitamin D metabolite, 1,25(OH )₂D.

Objective

To investigate associations between serum level of vitamin D metabolites and disease activity parameters in 160 inflammatory active and treatment naïve early RA patients. Serum level of vitamin D metabolites (25OHD ₂, 25OHD ₃ and 1,25(OH )₂D) was measured by isotope dilution mass spectrometry and radio‐immunoassays at baseline. Disease characteristics were gender, number of tender joints, number of swollen joints, DAS 28‐CRP , HAQ , VAS ‐scores, CRP , erosive status (Total Sharp Score; TSS ), ACPA and IgM‐RF ‐status. Associations were evaluated using Spearman's and Wilcoxon rank‐sum tests. The study was registered in clinical trials; trial registration number: NCT 00209859.

Findings

Statistically significant inverse associations were found between the active metabolite 1,25(OH )₂D and DAS 28‐CRP (P  = 0.004, rho = −0.23), HAQ (P  = 0.005, rho = −0.22), CRP (P  = 0.001, rho = −0.25), VAS _{patient‐pain} (P  = 0.008, rho = −0.21), and a positive association was found to ACPA ‐status (P  = 0.04).

Conclusion

The vitamin D metabolite 1,25(OH )₂D was inversely associated with disease activity and positively associated with ACPA in treatment naïve and inflammatory active early RA . The results indicate that in RA , both the degree of inflammatory activity, and the diagnostic sensitivity and specificity might affect—or might be affected by the level of vitamin 1,25(OH )₂D.

     

Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation

Background  

Activated microglial cells have been implicated in a number of neurodegenerative disorders, including Alzheimer's disease (AD), multiple sclerosis (MS), and HIV dementia. It is well known that inflammatory mediators such as nitric oxide (NO), cytokines, and chemokines play an important role in microglial cell-associated neuron cell damage. Our previous studies have shown that CD40 signaling is involved in pathological activation of microglial cells. Many data reveal that cannabinoids mediate suppression of inflammation in vitro and in vivo through stimulation of cannabinoid receptor 2 (CB₂).     

Role of psychiatric disorders and irritable bowel syndrome in asthma patients

OBJECTIVES:

The goals of the study were the following: 1) to determine the frequency of psychiatric disorders and irritable bowel syndrome in patients with asthma and 2) to compare the frequency of these disorders in patients with asthma to their frequency in healthy controls.

INTRODUCTION:

Patients with asthma have a higher frequency of irritable bowel syndrome and psychiatric disorders.

METHODS:

We evaluated 101 patients with bronchial asthma and 67 healthy subjects. All subjects completed the brief version of the Bowel Symptoms Questionnaire and a structured clinical interview for DSM-IV axis disorders (SCID-I/CV).

RESULTS:

There were 37 cases of irritable bowel syndrome in the group of 101 stable asthma patients (36.6%) and 12 cases in the group of 67 healthy subjects (17.9%) (p = 0.009). Irritable bowel syndrome comorbidity was not related to the severity of asthma (p = 0.15). Regardless of the presence of irritable bowel syndrome, psychiatric disorders in asthma patients (52/97; 53.6%) were more common than in the control group (22/63, 34.9%) (p = 0.02). Although psychiatric disorders were more common in asthma patients with irritable bowel syndrome (21/35, 60%) than in those without irritable bowel syndrome (31/62, 50%), the difference was not significant (p = 0.34). In asthma patients with irritable bowel syndrome and psychiatric disorders, the percentage of forced expiratory volume in 1 s (FEV₁) was lower than it was in those with no comorbidities (p = 0.02).

CONCLUSIONS:

Both irritable bowel syndrome and psychiatric disorders were more common in asthma patients than in healthy controls. Psychiatric disorders were more common in asthma patients with irritable bowel syndrome than in those without irritable bowel syndrome, although the differences failed to reach statistical significance. In asthma patients with IBS and psychiatric disorders, FEV₁s were significantly lower than in other asthma patients. It is important for clinicians to accurately recognize that these comorbid conditions are associated with additive functional impairment.     

Rate of first recorded diagnosis of autism and other pervasive developmental disorders in United Kingdom general practice, 1988 to 2001

Background  

There has been concern that the incidence of autism and other pervasive developmental disorders (PDDs) is increasing. Previous studies have been smaller, restricted to autism (excluding other pervasive developmental disorders such as Asperger's syndrome), included boys only, or have not been based on a national sample. We investigated time trends in the rates of diagnosis of pervasive developmental disorders.     

sHLA-I Contamination,A Novel Mechanism to Explain Ex Vivo/In Vitro Modulation of IL-10 Synthesis and Release in CD8<Superscript>+</Superscript> T Lymphocytes and in Neutrophils Following Intravenous Immunoglobulin Infusion

Background  

Numerous mechanisms have been proposed to explain the beneficial action of intravenous immune globulin (IVIG) in autoimmune and systemic inflammatory disorders; among others, they could decrease pro-inflammatory cytokine levels and also induce anti-inflammatory cytokines.     

Role of platelets in neuroinflammation: a wide-angle perspective

Objectives  

This review summarizes recent developments in platelet biology relevant to neuroinflammatory disorders. Multiple sclerosis (MS) is taken as the "Poster Child" of these disorders but the implications are wide. The role of platelets in inflammation is well appreciated in the cardiovascular and cancer research communities but appears to be relatively neglected in neurological research.     

Recovery dynamics of skeletal muscle oxygen uptake during the exercise off-transient

The time course of muscle recovery from contractions (i.e., muscle off-kinetics), measured directly at the site of O₂ exchange, i.e., in the microcirculation, is unknown. Whereas biochemical models based upon creatine kinase flux rates predict slower off- than on-transients [Kushmerick, M.J., 1998. Comp. Biochem. Physiol. B: Biochem. Mol. Biol.] whole muscle data [Krustrup, et al. J. Physiol.] suggest on–off symmetry.

Purpose

We tested the hypothesis that the slowed recovery blood flow (Qm) kinetics profile in the spinotrapezius muscle [Ferreira et al., 2006. J. Physiol.] was associated with a slowed muscle recovery compared with that seen at the onset of contractions (time constant, τ  23 s, Behnke et al., 2002. Resp. Physiol.), i.e., on–off asymmetry.

Methods

Measurements of capillary red blood cell flux and microvascular pressure of O₂ (P_O2mv) were combined to resolve the temporal profile of muscle across the moderate intensity contractions-to-rest transition.

Results

Muscle decreased from an end-contracting value of 7.7 ± 0.2 ml/100 g/min to 1.7 ± 0.1 ml/100 g/min at the end of the 3 min recovery period, which was not different from pre-stimulation . Contrary to our hypothesis, muscle in recovery began to decrease immediately (i.e., time delay <2 s) and demonstrated rapid first-order kinetics (τ, 25.5 ± 2.6 s) not different (i.e., symmetrical to) to those during the on-transient. This resulted in a systematic increase in microvascular P_O2 during the recovery from contractions.

Conclusions

The slowed Qm kinetics in recovery serves to elevate the ratio and thus microvascular P_O2. Whether this Qm response is obligatory to the rapid muscle kinetics and hence speeds the repletion of high-energy phosphates by maximizing conductive and diffusive O₂ flux is an important question that awaits resolution.     

Osteoprotective effects of <Emphasis Type="Italic">Fructus Ligustri Lucidi</Emphasis> aqueous extract in aged ovariectomized rats

Background  

Fructus Ligustri Lucidi (FLL) is a commonly used herb for treating bone disorders in Chinese medicine. The present study investigates the anti-osteoporotic activity of FLL aqueous extract in the model of postmenopausal bone loss in aged ovariectomized (OVX) female rats.     

A dietary supplement to improve the quality of sleep: a randomized placebo controlled trial

Background  

To evaluate the effect of a dietary supplement containing polyunsaturated fatty acids, in association with Humulus lupulus extract, on the quality of sleep using the Leeds sleep evaluation questionnaire (LSEQ) in subjects with moderate to severe sleep disorders.     

Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia

Background  

Neuroinflammatory responses are triggered by diverse ethiologies and can provide either beneficial or harmful results. Microglial cells are the major cell type involved in neuroinflammation, releasing several mediators, which contribute to the neuronal demise in several diseases including cerebral ischemia and neurodegenerative disorders. Attenuation of microglial activation has been shown to confer protection against different types of brain injury. Recent evidence suggests that resveratrol has anti-inflammatory and potent antioxidant properties. It has been also shown that resveratrol is a potent inhibitor of cyclooxygenase (COX)-1 activity. Previous findings have demonstrated that this compound is able to reduce neuronal injury in different models, both in vitro and in vivo. The aim of this study was to examine whether resveratrol is able to reduce prostaglandin E₂ (PGE₂) and 8-iso-prostaglandin F_2α (8-iso-PGF_2α) production by lipopolysaccharide (LPS)-activated primary rat microglia.     

Psycho-education programme for temporomandibular disorders: a pilot study

Background  

Temporomandibular disorders (TMDs) are by far the most predominant condition affecting the temporomandibular joint (TMJ), however many patients have mild self-limiting symptoms and should not be referred for specialist care.     

Key role for spinal dorsal horn microglial kinin B<Subscript>1</Subscript>receptor in early diabetic pain neuropathy

Background  

The pro-nociceptive kinin B₁ receptor (B₁R) is upregulated on sensory C-fibres, astrocytes and microglia in the spinal cord of streptozotocin (STZ)-diabetic rat. This study aims at defining the role of microglial kinin B₁R in diabetic pain neuropathy.     

Population-based study of genetic variation in individuals with autism spectrum disorders from Croatia

Background  

Genome-wide studies on autism spectrum disorders (ASDs) have mostly focused on large-scale population samples, but examination of rare variations in isolated populations may provide additional insights into the disease pathogenesis.     

Dipyrithione inhibits IFN-γ-induced JAK/STAT1 signaling pathway activation and IP-10/CXCL10 expression in RAW264.7 cells

Objective  

This study investigates the effects of dipyrithione (PTS2) on the expression of IP-10/CXCL10, which has been observed in a wide variety of chronic inflammatory disorders and autoimmune conditions.     

Contribution of bone marrow-derived cells to the pro-inflammatory effects of protease-activated receptor-2 in colitis

Objective  

Our aim was to determine the contribution of proteinase-activated receptor-2 (PAR₂)-expressing bone marrow-derived cells on the development of colonic inflammation.     

Aquaporin-4 autoantibodies in neuromyelitis optica spectrum disorders: comparison between tissue-based and cell-based indirect immunofluorescence assays

Background  

Neuromyelitis optica spectrum disorders (NMOSD) are severe central nervous system inflammatory demyelinating disorders (CNS IDD) characterized by monophasic or relapsing, longitudinally extensive transverse myelitis (LETM) and/or optic neuritis (ON). A significant proportion of NMOSD patients are seropositive for aquaporin-4 (AQP4) autoantibodies. We compared the AQP4 autoantibody detection rates of tissue-based indirect immunofluorescence assay (IIFA) and cell-based IIFA.     

<Emphasis Type="Italic">E. coli</Emphasis> lipopolysaccharide attenuates adenosine A<Subscript>1</Subscript> receptor-mediated increase in plasma exudation from the hamster cheek pouch

Objective and design  

To determine whether exposure to E. coli lipopolysaccharide (LPS) modulates adenosine A₁ receptor-induced increase in plasma exudation from the intact hamster cheek pouch microcirculation.     

Dupilumab is effective in type 2-high asthma patients receiving high-dose inhaled corticosteroids at baseline

Background

Dupilumab blocks the shared receptor component for interleukin (IL)-4/IL-13, key drivers of type 2 inflammation. In phase 2b (NCT01854047) and phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200/300 mg every 2 weeks (q2w) reduced severe exacerbations, improved prebronchodilator (pre-BD) forced expiratory volume in 1 second (FEV₁) and quality of life measures, and it was generally well tolerated in patients with uncontrolled, persistent (phase 2b), or moderate-to-severe (phase 3) asthma.

Methods

In patients on high-dose inhaled corticosteroids (ICS) with type 2-high asthma (subgroups including baseline blood eosinophils ≥150/300 cells/µL and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb), annualized severe exacerbation rates over the treatment period, changes from baseline in pre-BD FEV₁ and asthma control (5-item asthma control questionnaire [ACQ-5]) were analyzed.

Results

In high-dose ICS type 2-high subgroups, dupilumab 200/300 mg q2w vs placebo in the phase 2b (24 weeks) and phase 3 (52 weeks) studies significantly reduced severe exacerbations by 55%-69%/57%-60% (all P<.05) and 53%-69%/48%-66% (all P < .001), respectively, except in patients with ≥ 300 eosinophils/µL in phase 2b study (24%/50% (P = .52/0.15). Across subgroups, pre-BD FEV₁ improved by 0.18-0.22 L/0.19-0.24 L (all P < .05) and 0.23-0.36 L/0.15-0.25 L (all P < .01) and ACQ-5 scores were reduced by 0.46-0.55/0.47-0.85 (all P < .05) and 0.38-0.50/0.24-0.30 (all P < .05), respectively, except dupilumab 200 mg q2w in phase 2b in patients with FeNO ≥ 25 ppb (0.41; P = .09). Dupilumab was also effective in patients taking medium-dose ICS.

Conclusion

Dupilumab significantly reduced severe exacerbations and improved lung function and asthma control in patients with type 2-high asthma on high-dose ICS at baseline.

     

Effects of 1,25-(OH)<Subscript>2</Subscript>D<Subscript>3</Subscript> on the expressions of vitamin D receptor,STAT5 and cytoskeletal rearrangement in human monocytes incubated with sera from type 2 diabetes patients and diabetic nephropathy patients with uremia

Objective  

To explore the effects of 1,25-(OH)₂D₃ and lipopolysaccharide (LPS) plus human recombinant interleukin-15 (IL-15) on expression of vitamin D receptor (VDR) and STAT5, and cytoskeletal rearrangement in human monocytes incubated with sera from type 2 diabetes (T2DM) patients and diabetic nephropathy (DN) patients with uremia.