Long-term sustained-released in situ gels of a water-insoluble drug amphotericin B for mycotic arthritis intra-articular administration: preparation,in vitro and in vivo evaluation

Amphotericin B (AMB) was often used in intra-articular injection administration for fungal arthritis, because it could often bring a satisfactory therapeutic efficacy and a minimum systemic toxic side effect. However, because of the multiple operations and the frequent injections, the compliance of the patients was bad. Therefore, to develop a long-term sustained-released preparation of AMB for mycotic arthritis intra-articular administration is of great significance. The purpose of present study was to develop a long-term sustained-released in situ gel of a water-insoluble drug AMB for mycotic arthritis intra-articular administration. Based on the evaluations of the in vitro properties of the formulations, the formulation containing 10% (w/w) ethanol, 15% (w/w) PG, 0.75% (w/w) HA, 5% (w/w) purified soybean oil, 0.03% (w/w) α-tocopherol, 15% (w/w) water and 55% (w/w) glyceryl monooleate was selected as a suitable intra-articular injectable in situ gel drug delivery system for water-insoluble drug AMB. Furthermore, the results of the in vivo study on rabbits showed that the selected formulation was a safe and effective long-term sustained-released intra-articular injectable AMB preparation. Therefore, the presented in situ AMB gel could reduce the frequency of the administration in the AMB treatment of fungal arthritis, and then would get a good patient compliance.     

A Longitudinal Examination of Causal Attributions and Depression Symptomatology in Rheumatoid Arthritis.

Objective: Examine longitudinal relationships between causal attributions and depression symptoms in adults with rheumatoid arthritis (RA). Study Design: Cross-lagged panel correlations tested the temporal precedence of attributions relative to depression symptoms over 1 year. Participants: Forty-two participants completed self-report instruments on 2 occasions. Main Outcome Measures: The Inventory to Diagnose Depression and the Attributional Style Questionnaire. Results: Time 1 attributions predicted increased levels of depression symptoms at Time 2 after perceived pain and disability were controlled: Time 1 depression symptoms were unrelated to Time 2 attributions. Cross-lagged correlation comparisons revealed statistical dominance for attribution-depression relationships relative to depression-attribution relationships. Conclusions: Results support cognitive diathesis conceptualizations of depression and support cognitive-behavioral treatments for depression in RA. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Dendritic Nanotheranostic for the Delivery of Infliximab: A Potential Carrier in Rheumatoid Arthritis Therapy

Antibodies are macromolecules that specifically recognize their target, making them good candidates to be employed in various therapies. The possibility of attaching a drug to an immunoglobulin makes it possible to release it specifically into the affected tissue as long as it overexpresses the target. However, chemical coupling could affect the functionality (specificity and affinity) of the antibody. It has been observed that the use of intermediaries, such as dendrimers, could resolve this issue. Because carbosilane dendrimers have aroused great interest in the field of biomedicine, this report describes the synthesis of an anionic carbosilane dendrimer with a fluorochrome on its surface that then forms a conjugate with an antibody. It has been used as immunoglobulin and infliximab, whose target is TNF-α, which is a cytokine that is overexpressed in the inflamed area or even in the blood of patients with autoimmune diseases, such as rheumatoid arthritis. In addition, the integrity and functionality of the antibody has been studied to see if they have been affected after the chemical coupling process.     

抗环瓜氨酸肽抗体阳性银屑病关节炎伴肺间质病变1例

银屑病关节炎是一种与银屑病相关的关节炎，属脊柱关节炎范畴，兼具或先后出现银屑病皮疹和关节及周围软组织疼痛、肿胀等表现。抗CC抗体是类风湿关节炎诊断及预后判断的重要指标，PsA中也有阳性报道。风湿病相关肺间质病变常见于系统性硬化症、干燥综合征、皮肌炎/肌炎、类风湿关节炎等，PsA相关肺间质病变报道少见。本文收录1例PsA患者，抗CCP抗体阳性，同时伴弥漫性肺间质病变，文献少有报道。     

Low Dietary c9t11-Conjugated Linoleic Acid Intake from Dairy Fat or Supplements Reduces Inflammation in Collagen-Induced Arthritis

Dietary cis‐9,trans‐11 (c9t11) conjugated linoleic acid (CLA) fed at 0.5 % w/w was previously shown to attenuate inflammation in the murine collagen‐induced (CA) arthritis model, and growing evidence implicates c9t11‐CLA as a major anti‐inflammatory component of dairy fat. To understand c9t11‐CLA's contribution to dairy fat's anti‐inflammatory action, the minimum amount of dietary c9t11‐CLA needed to reduce inflammation must be determined. This study had two objectives: (1) determine the minimum dietary anti‐inflammatory c9t11‐CLA intake level in the CA model, and (2) compare this to anti‐inflammatory effects of dairy fat (non‐enriched, naturally c9t11‐CLA‐enriched, or c9t11‐CLA‐supplemented). Mice received the following dietary fat treatments (w/w) post arthritis onset: corn oil (6 % CO), 0.125, 0.25, 0.375, and 0.5 % c9t11‐CLA, control butter (6 % CB), c9t11‐enriched butter (6 % EB), or c9t11‐CLA‐supplemented butter (6 % SB, containing 0.2 % c9t11‐CLA). Paw arthritic severity and pad swelling were scored and measured, respectively, over an 84‐day study period. All c9t11‐CLA and butter diets decreased the arthritic score (25–51 %, P < 0.01) and paw swelling (8–11 %, P < 0.01). Throughout the study, plasma tumor necrosis factor (TNFα) was elevated in CO‐fed arthritic mice compared to non‐arthritic (NA) mice but was reduced in 0.5 % c9t11‐CLA‐ and EB‐fed mice. Interleukin‐1β and IL‐6 were increased in arthritic CO‐fed mice compared to NA mice but were reduced in 0.5 % c9t11‐CLA‐ and EB‐fed mice through day 42. In conclusion, 0.125 % c9t11‐CLA reduced clinical arthritis as effectively as higher doses, and decreased arthritis in CB‐fed mice suggested that the minimal anti‐inflammatory levels of c9t11‐CLA might be below 0.125 %.     

Adiponectin Induces Oncostatin M Expression in Osteoblasts through the PI3K/Akt Signaling Pathway

Rheumatoid arthritis (RA), a common autoimmune disorder, is associated with a chronic inflammatory response and unbalanced bone metabolism within the articular microenvironment. Adiponectin, an adipokine secreted by adipocytes, is involved in multiple functions, including lipid metabolism and pro-inflammatory activity. However, the mechanism of adiponectin performance within arthritic inflammation remains unclear. In this study, we observed the effect of adiponectin on the expression of oncostatin M (OSM), a pro-inflammatory cytokine, in human osteoblastic cells. Pretreatment of cells with inhibitors of phosphatidylinositol 3-kinase (PI3K), Akt, and nuclear factor (NF)-κB reduced the adiponectin-induced OSM expression in osteoblasts. Stimulation of the cells with adiponectin increased phosphorylation of PI3K, Akt, and p65. Adiponectin treatment of osteoblasts increased OSM-luciferase activity and p65 binding to NF-κB on the OSM promoter. Our results indicate that adiponectin increased OSM expression via the PI3K, Akt, and NF-κB signaling pathways in osteoblastic cells, suggesting that adiponectin is a novel target for arthritis treatment.     

Matrine Exerts a Strong Anti-Arthritic Effect on Type II Collagen-Induced Arthritis in Rats by Inhibiting Inflammatory Responses

To investigate anti-arthritic effects of matrine isolated from the roots of S. flavescens on type II collagen-induced arthritis (CIA) in rats and to explore its related potential mechanisms, CIA rats were established and administered with matrine (20, 40 or 80 mg/kg/days, for 30 days). Subsequently, blood was collected to determine serum levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, IL-10, MMP-2, MMP-3 and MMP-9, and hind paws and knee joints were collected for histopathological examination. Furthermore, indices of the thymus and spleen were determined, and synovial tissues were collected to determine the protein expressions of p-IκB, IκB, Cox-2 and iNOS. Our results indicated that matrine significantly suppressed inflammatory reactions and synovial tissue destruction. Matrine inhibited paw swelling, arthritis indices and weight loss in CIA rats. Additionally, matrine decreased the levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, MMP-2, MMP-3 and MMP-9. Matrine also down-regulated expressions of p-IκB, Cox-2, and iNOS but up-regulated IκB in synovial tissues in CIA rats. The results suggested matrine possesses an anti-arthritic effect in CIA rats via inhibiting the release of pro-inflammatory cytokines and proteins that promote the NF-κB pathway.     

Development of a shortened center for epidemiological studies depression scale for assessment of depression in rheumatoid arthritis.

Objective: The purpose was to develop a short-form version of the Center for Epidemiologic Studies Depression Scale (CES-D) for the identification of persons with major depressive disorder (MDD) within a population with rheumatoid arthritis (RA). Study Design: Data were analyzed from 337 persons with RA. Forty-six participants met the diagnostic criteria for MDD; 291 participants were classified in the non-MDD category (including 21 participants with dysthymia and 18 participants with minor depressive disorder). A short-form version of the CES-D was developed, and multiple cutoff scores were examined. Results: A cutoff score of ≥5 from a 9-item, short-form CES-D was found to be generally as efficient as the more commonly used full-scale cutoff score of ≥16 for classifying participants with MDD within an RA population. Although the shortened CES-D scale (cutoff score ≥5) was slightly more sensitive, it also exhibited slightly less specificity than the full-scale cutoff score of ≥16. Conclusion: The results suggest that a short-form CES-D can be used to screen for MDD within an RA sample with a degree of efficiency that is generally comparable to that of the full-scale instrument. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Identification of potent human anti-IL-1RI antagonist antibodies

Interleukin-1 (IL-1) blockade by IL-1 receptor antagonist benefits some arthritis patients by reducing joint damage. This fact inspired us to develop antagonist human therapeutic antibodies against IL-1R(I) using phage libraries that display single-chain variable fragment (scFv) antibody fragments. Panning libraries against human IL-1R(I) generated 39 unique scFv-phage whose binding to IL-1R(I) was competed by IL-1 ligands. Fifteen of these scFv-phage, identified using IL-1R(I)-binding assays and dissociation rate ranking, were reformatted as scFv-Fc and IgG(4) molecules. The ease of producing antibodies in the scFv-Fc format permitted rapid identification of four lead clones (C10, C13, C14, C15) that inhibit NF-kappaB nuclear translocation induced by IL-1. Reformatting these clones as IgG(4) molecules increased their inhibition potency by 相似文献