The purpose of this study was to assess whether an alternative treatment approach that targets angiogenesis, delivered through ligand-targeted nanotherapy, would ameliorate inflammatory arthritis. Arthritis was induced using the K/BxN mouse model of inflammatory arthritis. After arthritis was clearly established, mice received three consecutive daily doses of alpha(v)beta(3)-targeted fumagillin nanoparticles. Control groups received no treatment or alpha(v)beta(3)-targeted nanoparticles without drugs. Disease score and paw thickness were measured daily. Mice that received alpha(v)beta(3)-targeted fumagillin nanoparticles showed a significantly lower disease activity score (mean score of 1.4+/-0.4; P<0.001) and change in ankle thickness (mean increase of 0.17+/-0.05 mm; P<0.001) 7 d after arthritis induction, whereas the group that received alpha(v)beta(3)-targeted nanoparticles without drugs exhibited a mean arthritic score of 9.0 +/- 0.3 and mean change in ankle thickness of 1.01 +/- 0.09 mm. Meanwhile, the group that received no treatment showed a mean arthritic score of 9.8 +/- 0.5 and mean change in ankle thickness of 1.05 +/- 0.10 mm. Synovial tissues from animals treated with targeted fumagillin nanoparticles also showed significant decrease in inflammation and angiogenesis and preserved proteoglycan integrity. Ligand-targeted nanotherapy to deliver antiangiogenic agents may represent an effective way to treat inflammatory arthritis.

The role of innate immunity in the pathogenesis of asthma is unclear. Although increased presence of neutrophils is associated with persistent asthma and asthma exacerbations, how neutrophils participate in the pathogenesis of asthma remains controversial. In this study, we show that the absence of dipeptidyl peptidase I (DPPI), a lysosomal cysteine protease found in neutrophils, dampens the acute inflammatory response and the subsequent mucous cell metaplasia that accompanies the asthma phenotype induced by Sendai virus infection. This attenuated phenotype is accompanied by a significant decrease in the accumulation of neutrophils and the local production of CXCL2, TNF, IL-1β, and IL-6 in the lung of infected DPPI−/− mice. Adoptive transfer of DPPI-sufficient neutrophils into DPPI−/− mice restored the levels of CXCL2 and enhanced cytokine production on day 4 postinfection and subsequent mucous cell metaplasia on day 21 postinfection. These results indicate that DPPI and neutrophils play a critical role in Sendai virus-induced asthma phenotype as a result of a DPPI-dependent neutrophil recruitment and cytokine response.

Pityriasis rubra pilaris (PRP) is a rare group of hyperkeratotic, papulosquamous disease that can be acquired or inherited. There have been reported cases of rheumatologic associations, mainly arthritis and dermatomyositis. In this review article, we will explore the clinical presentation and classification, rheumatologic associations and treatment modalities of PRP. In addition, we will also report a case of PRP with seronegative arthritis.Keywords: Pityriasis rubra pilaris; Review; Arthritis; Rheumatologic; Treatment CASE REPORTA 50-year-old East Indian male with a 2-year history of nonspecific knee arthritis presented to his primary care doctor with a new scaly and pruritic rash. It began on the extensor surfaces of the elbow and bilaterally spread onto the forearms. Similar lesions began to appear over the scalp, trunk, axilla and knee. His nails became thickened and hyperpigmented. The patient was diagnosed with psoriasis. With the appearance of the lesions, his knee pain intensified, especially when ascending the stairs. The pain would awaken him at night. During this period, he had stiffening of his extremities. Besides fatigue, he denied any recent acute illnesses, constitutional symptoms, and mucocutaneous or ocular lesions. His past medical history included hypothyroidism and seasonal allergies. He denied food, drug and environmental allergies. His medication list at presentation included levothyroxine and glucosamine and chondroitin. He smoked tobacco occasionally and owned a cat. He had not traveled outside the country recently. His mother had nonspecific arthritis. On physical examination, his vitals were normal. There were no lymphadenopathy, oral lesions and hepatosplenomegaly. Neither joint deformity nor synovitis was appreciated. He had tenderness of the right knee on palpation with mild patellar laxity. He had multiple sharply demarcated redorange scaly plaques over the extensor surfaces of the forearms, axillae, knees and trunk. The plaques were nearly confluent on his trunk with the exception of islands of normal skin. The skin of his palms was thick and dry. Bilaterally, his second and third fingernails were hyperkeratotic with pitting and hyperpigmentation.X-rays of the hands and knees were normal. Complete blood count, complete metabolic panel and urinalysis were normal. The erythrocyte sedimentary rate was 15; antinuclear antibody was 1:160 with a nucleolar pattern. Thyroid stimulating hormone, immunoglobulin and complement levels were normal. Rheumatoid factor, hepatitis panel and RPR were negative. He did not respond to the conventional psoriatic treatment with ultraviolet light therapy UVA and UVB. Eventually, a punch biopsy was performed, and a diagnosis of pityriasis rubra pilaris (PRP) was made. The patient was placed on methotrexate therapy and his arthritis and skin lesions subsequently resolved.

Although specific criteria for diagnosing the antiphospholipid syndrome (APS) exist (the Sapporo Criteria), most physicians are not aware these include repeat testing and documentation of either a lupus anticoagulant or medium to high levels of anti-cardiolipin antibody. Incorrect diagnosis of APS may result in unnecessary long-term anticoagulation. The purpose of this study was to determine the clinical and serological characteristics of patients being treated for APS and concordance with published criteria. This cross-sectional study identified APS patients who were being treated with warfarin at one of three university-based anticoagulation clinics. Levels of anticardiolipin antibody were classified as low-positive if abnormal but < 40 GPL/MPL units and medium/high-positive if > or = 40 units. Strength of meeting Sapporo criteria was graded as definite, possible, and not meeting criteria. Of 103 cases, 97 had clinical and laboratory data available. Only 10 cases (10%, 95% Confidence Interval 5 - 19) met criteria for definite APS, 16 (16%, 10 - 26) had a possible diagnosis, and 71 (73%, 63 - 81) did not meet criteria. Of 70 cases that had abnormal anticardiolipin antibody results, only 32 (46%, 34 - 58) had medium/high-positive levels. Repeat laboratory testing was performed in only 49 cases (51%, 40 - 61). We conclude that few patients treated forAPS met Sapporo criteria. Abnormal levels of anticardiolipin antibody were frequently in the low-positive range, and repeat testing was often absent. A quality improvement program that includes review of cases referred for chronic anticoagulation care is recommended to ensure appropriate testing and treatment of patients with suspected APS.

2016-12-23T18:47:23