Ameliorative Effects of a Polyphenolic Fraction of Cinnamomum zeylanicum L. Bark in Animal Models of Inflammation and Arthritis

Cinnamon bark (Cinnamomum zeylanicum Syn C. verum, family: Lauraceae) is one of the oldest traditional medicines for inflammatory- and pain-related disorders. The objective of the present study was to evaluate the efficacy of the polyphenol fraction from Cinnamomum zeylanicum bark (CPP) in animal models of inflammation and rheumatoid arthritis. Dose-response studies of CPP (50, 100, and 200 mg/kg) used in a separate set of in vivo experiments were conducted in acute (carrageenan-induced rat paw edema), subacute (cotton pellet-induced granuloma), and sub-chronic (AIA, adjuvant-induced established polyarthrtis) models of inflammation in rats and the acetic acid-induced writhing model of pain in mice. Effects of CPP on cytokine (IL-2, IL-4, and IFNγ) release from Concanavalin (ConA)-stimulated lymphocytes were also evaluated in vitro. CPP showed a strong and dose-dependent reduction in paw volume, weight loss reversal effects against carrageenan-induced paw edema, and cotton pellet-induced granuloma models in rats. CPP (200 mg/kg p.o. for 10 days) showed a significant reduction in elevated serum TNF-α concentration without causing gastric ulcerogenicity in the AIA model in rats. CPP also demonstrated mild analgesic effects during acute treatment as evidenced by the reduction in the writhing and paw withdrawal threshold of the inflamed rat paw during the acetic acid-induced writhing model and Randall-Selitto test. CPP was found to inhibit cytokine (IL-2, IL-4, and IFNγ) release from ConA-stimulated lymphocytes in vitro. In conclusion, CPP demonstrated prominent action in animal models of inflammation and arthritis and therefore can be considered as a potential anti-rheumatic agent with disease-modifying action.     

艾灸对佐剂性关节炎大鼠免疫介导物质β-内啡肽含量的影响

目的通过观察艾灸对佐剂性关节炎大鼠免疫介导物质β-内啡肽含量的影响,揭示针灸调节免疫功能的机理。方法将40只大鼠分为空白组、模型组、灸命门组、灸关元组,灸非穴组,除空白组外,其余大鼠于右后足跖皮内注射弗氏完全佐剂造模,模型组造模后不做任何处理,灸命门组灸命门穴、灸关元组灸关元穴、灸非穴组灸关元穴左侧旁开0.5cm处。观察足爪肿胀率并观测血浆、下丘脑、垂体和淋巴结中β-内啡肽(β-EP)含量。结果与模型组比较,灸命门组与灸非穴组右足足爪肿胀率明显降低(P<0.01);与灸命门组比较,灸关元组与灸非穴组右足足爪肿胀率明显升高(P<0.05)。与空白组比较,模型组左足足爪肿胀率明显升高(P<0.05),灸命门组与灸关元组左足组爪肿胀率明显升高(P<0.05);与模型组比较,灸命门组、灸关元组、灸非穴组左足足爪肿胀率明显降低(P<0.01)。与空白组比较,模型组、灸命门组、灸关元组、灸非穴组大鼠血浆中β-EP含量明显降低(P<0.05);与空白组比较,模型组大鼠下丘脑中β-EP含量明显升高(P<0.05);与空白组比较,灸关元组、灸非穴组大鼠垂体中β-EP含量明显升高(P<0.05);与模型组比较,灸关元组、灸非穴组大鼠垂体中β-EP含量明显升高(P<0.05);与模型组比较,灸命门组、灸关元组、灸非穴组大鼠淋巴结中的β-EP含量明显升高(P<0.05)。结论灸命门穴和非穴对右足原发性炎症有抑制作用;灸命门穴、关元穴、非穴对左足继发性炎症有抑制作用。推测艾灸上述穴位对机体免疫炎症的调整作用是通过提高淋巴结β-EP含量、调动中枢内β-EP而实现的。     

The effects of an orally administered probiotic on sulfasalazine metabolism in individuals with rheumatoid arthritis: a preliminary study

Aim: To carry out a pilot study to investigate the effect of short‐term oral probiotic administration on the metabolism of sulfasalazine (SSZ) in patients with rheumatoid arthritis (RA) stabilized on SSZ. Methods: Twelve subjects with RA taking stable doses of SSZ for a minimum of 3 months prior to the study, received a probiotic preparation contained three strains of bacteria (1.8 × 10⁹ CFU/day) twice daily for 1 week. Single point blood and 12‐h urine samples were taken before and after probiotic treatment and 3 weeks following discontinuation of probiotics, for determination of SSZ and its metabolites. The presence of the probiotic bacteria in the feces of patients was investigated by denaturing gradient gel electrophoresis (DGGE). Results: Adverse events recorded were three instances of gastrointestinal disturbance and one flare of RA. Plasma and urinary levels of SSZ and its metabolites showed no statistically significant changes after probiotic administration and the incidence of gastrointestinal disturbance did not appear to be ascribed to higher sulfapyridine plasma levels. Probiotic‐specific DGGE bands were detected in the feces of some patients after the treatment period. Conclusions: Short‐term treatment of RA patients with a multi‐strain probiotic did not significantly influence SSZ metabolism as has been demonstrated in animal models.     

Analysis of clinical,radiological and laboratory variables in psoriatic arthritis with 25 Japanese patients

Psoriatic arthritis (PsA) has many clinical and radiological manifestations but lacks a specific laboratory marker. The aim of the present study was to identify noteworthy features in PsA patients on routine clinical examinations. The subjects were 25 PsA patients who were classified based on the Classification of Psoriatic Arthritis (CASPAR) criteria. The clinical and radiological findings and laboratory parameters were analyzed by retrospective chart review. On clinical examination, dactylitis was present in 13 (52%) of 25 patients, swollen and/or tender Achilles tendons were present in nine (36%), and sacroiliitis was present in eight (32%). Of the radiological features, juxta‐articular new bone formation (JANF) was seen in 12 (48%), extra‐articular new bone formation was seen in nine (36%) and sacroiliitis was seen in six (24%). Dactylitis and JANF had the highest prevalence rates. The Psoriasis Area and Severity Index score, swollen and/or tender joint count, erythrocyte sedimentation rate, C‐reactive protein, and matrix metalloproteinase‐3 were higher in patients with sacroiliitis than in those without sacroiliitis (P < 0.05). Dactylitis, JANF and sacroiliitis may be noteworthy manifestations in Japanese patients with PsA.     

Activating NK‐cell receptors co‐stimulate CD4+CD28− T cells in patients with rheumatoid arthritis

Effector T‐cell responses can be modulated by competing positive or negative signals transduced by NK‐cell receptors (NKR). In the CD4⁺ T‐cell population, the expression of NKR is primarily found in the CD4⁺CD28⁻ T‐cell subset, also known as CD28^null T cells. These T cells are frequently found in rheumatoid arthritis (RA) and other inflammatory disorders, suggesting that signaling through NKR may play a role in the autoimmune reaction. Here we aimed to dissect the phenotype and function of NKR‐expressing CD4⁺CD28⁻ T cells in patients with RA. By analyzing a broad array of NKR on CD4⁺CD28⁻ T cells we found a significant expression of the co‐activating receptors 2B4 (CD244), DNAM‐1 (CD226), and CRACC. Pair‐wise ligations of 2B4 with DNAM‐1 and/or NKG2D lead to increased effector functions of primary CD4⁺CD28⁻ T cells to suboptimal levels of anti‐CD3 stimulation. Using multi‐parameter flow cytometry, we demonstrate that such co‐ligation led to an increased magnitude in overall responsiveness without changing qualitative aspects of the response. Altogether these results demonstrate a pattern of additive effects in NKR‐mediated functional modulation of CD4⁺CD28⁻ T cells in RA. This may have consequences for the inflammatory responses imposed by these cells, thus influencing disease manifestations.     

Are fibromyalgia patients as inactive as they say they are?

Both fibromyalgia and rheumatoid arthritis (RA) patients self-report similar disability. These diseases are viewed differently by the medical profession as one has ample evidence of tissue damage and inflammation and the other does not. We were interested to see if an objective measure produced similar results. Twelve patients with RA were matched with 12 fibromyalgia patients by sex, age, and Health Assessment Questionnaire (HAQ) score. The 24-h ambulatory activity of these patients was recorded using the Numact monitor. Statistical analysis was performed using independent group t test for the ambulatory activity data and Spearman’s correlation coefficients for HAQ and total energy. There were no significant differences found between the two groups in terms of total activity. Other compared analyses for activity included the number of steps taken, vigor of steps, and time spent standing, which were not statistically different. The correlation coefficients of HAQ and total ambulatory activity for the fibromyalgia group were ρ = −0.638 (p = 0.026). Patients with RA and fibromyalgia displaying similar levels of self-reported disability have objective evidence of similar levels of total ambulatory activity. There is a statistically significant correlation between self-reported and objective measurements of disability for the fibromyalgia patients. Either of these measures merits further study as outcome measures for fibromyalgia.     

Gait abnormalities differentially indicate pain or structural joint damage in monoarticular antigen-induced arthritis

Gait abnormalities have been suggested to provide an objective measure for joint pain in animal models. Here, we aimed to assess whether parameters of gait analysis correlate with measures of pain-related behavior in experimental monoarthritis. For this purpose, antigen-induced arthritis was induced in the left knee joints of 68 female Lewis rats, of which 30 were treated with tumor necrosis factor-alpha(TNF)-neutralizing compounds. During the course of arthritis, paw print analysis parameters and measures for mechanical and thermal hyperalgesia were obtained. Knee joints harvested on either day 3 or day 21 were scored histologically for signs of inflammation and cartilage and bone destructions. Data were compared to those obtained from 33 immunized control rats and correlated for days 3 and 21. Arthritic rats showed distinct asymmetric gait abnormalities. In the acute stage of antigen-induced arthritis, but not in the chronic phase, there was a significant correlation between the gait parameter ‘left–right distance’ and measures of primary and secondary hyperalgesia. Both in the acute and chronic phases, however, the gait parameter ‘angle between paws’ indicating outward rotation of paws mainly correlated with joint destruction as assessed using histology. Etanercept treatment exhibited pronounced anti-nociceptive and pro-locomotional effects, but the described correlations remained. In conclusion, some parameters of gait analysis may represent a good measure for arthritis pain, mainly in acute inflammation, while others are increasingly influenced by mechanical joint deformation as indicated by cartilage and bone destructions. Thus, gait abnormalities may not unequivocally be suitable for objective pain assessment in all stages of experimental arthritis.     

Endoscopic Facet Debridement for the treatment of facet arthritic pain - a novel new technique

Study design: Retrospective, observational, open label.Objective: We investigated the efficacy of facet debridement for the treatment of facet joint pain.Summary of background data: Facet joint disease, often due to degenerative arthritis, is common cause of chronic back pain. In patients that don''t respond to conservative measures, nerve ablation may provide significant improvement. Due to the ability of peripheral nerves to regenerate, ablative techniques of the dorsal nerve roots often provide only temporary relief. In theory, ablation of the nerve end plates in the facet joint capsule should prevent reinnervation.Methods: All patients treated with endoscopic facet debridement at our clinic from 2003-2007 with at least 3 years follow-up were included in the analysis. Primary outcome measure was percent change in facet-related pain as measured by Visual Analog Scale (VAS) score at final follow-up visit.Results: A total of 174 people (77 women, 97 men; mean age 64, range 22-89) were included. Location of facet pain was cervical in 45, thoracic in 15, and lumbar in 114 patients. At final follow-up, 77%, 73%, and 68% of patients with cervical, thoracic, or lumbar disease, respectively, showed at least 50% improvement in pain. Mean operating time per joint was 17 minutes (range, 10-42). Mean blood loss was 40 ml (range, 10-100). Complications included suture failure in two patients, requiring reclosure of the incision. No infection or nerve damage beyond what was intended occurred.Conclusions: Our results demonstrate a comparable efficacy of endoscopic facet debridement compared to radiofrequency ablation of the dorsal nerve branch, with durable results. Large scale, randomized trials are warranted to further evaluate the relative efficacy of this surgical treatment in patients with facet joint disease.