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Summary: A head-to-head comparison of once-monthly oral bisphosphonates minodronate (MIN) and risedronate (RIS) in patients with rheumatoid arthritis (RA) demonstrated that MIN has the same effect as RIS on increase in bone mineral density (BMD) and a stronger effect on inhibition of bone resorption than RIS, suggesting that MIN is a promising treatment option for osteoporosis patients with RA.Introduction: To evaluate the effect of once-monthly oral MIN in patients with RA, a prospective, randomized, open-label, head-to-head comparison with once-monthly oral RIS was conducted.Methods: A total of 83 patients with RA were randomly assigned to either once-monthly oral MIN 50 mg (n = 42) or once-monthly oral RIS 75 mg (n = 41). Serial BMD and bone turnover markers were measured and compared between the treatment groups.Results: BMD (lumbar spine, total hip, femoral neck) increased significantly after 12 months of treatment with MIN (3.8, 2.0, and 2.2%, respectively, P < 0.05) and RIS (3.6, 1.9, and 1.9%, respectively, P < 0.05). There were no significant differences between the treatment groups. Percent changes of bone turnover markers from baseline to 12 months in the MIN group were significantly greater than those in the RIS group (TRACP-5b: − 36.3 vs − 19.3%, P < 0.05; NTX: − 27.1 vs − 17.3%, P < 0.05; BAP: −30.2 vs −19.4%, P < 0.05).Conclusions: The present study of RA patients demonstrated that MIN has the same effect as RIS on increase in BMD and a stronger effect on inhibition of bone resorption than RIS. The results suggest that MIN is a promising treatment option for osteoporosis patients with RA. [ABSTRACT FROM AUTHOR]

Nuclear factor (NF)-κB is a transcription factor that regulates cytokine and chemokine production in various inflammatory diseases, including bronchial asthma. IκB kinase (IKK) β is important for NF-κB activation in inflammatory conditions, and is possibly related to airway remodelling. Thus, inhibition of the IKKβ-NF-κB pathway may be an ideal strategy for the management of airway remodelling. We examined the effects of a newly synthesized IKKβ inhibitor, IMD-0354, in a chronic allergen exposure model of bronchial asthma in mice. A chronic mouse model was generated by challenge with house dust mite antigen ( Dermatophagoides pteronyssinus). IMD-0354 was administrated intraperitoneally in therapeutic groups. Lung histopathology, hyperresponsiveness and the concentrations of mediators and molecules in supernatants of lung homogenates were determined. NF-κB activation was inhibited by prolonged periods of IMD-0354 administration. IMD-0354 reduced the numbers of bronchial eosinophils. IMD-0354 also inhibited the pathological features of airway remodelling, including goblet cell hyperplasia, subepithelial fibrosis, collagen deposition and smooth muscle hypertrophy. Inhibition of these structural changes by IMD-0354 was the result of the suppressing the production and activation of remodelling-related mediators, such as TGF-β, via inhibition of IKKβ. IMD-0354 inhibited IL-13 and IL-1β production, and it restored the production of IFN-γ. It also ameliorated airway hyperresponsiveness. IKKβ plays crucial roles in airway inflammation and remodelling in a chronic mouse model of asthma. A specific IKKβ inhibitor, IMD-0354, may be therapeutically beneficial for treating airway inflammation and remodelling in chronic asthma. Cite this as: H. Ogawa, M. Azuma, S. Muto, Y. Nishioka, A. Honjo, T. Tezuka, H. Uehara, K. Izumi, A. Itai and S. Sone, Clinical & Experimental Allergy, 2011 (41) 104-115. [ABSTRACT FROM AUTHOR]

The Fcγ receptor IIIb (FcγRIIIb), a receptor for the Fcγ region of IgG, is specifically expressed on neutrophils. It has two allelic polymorphisms, NA1 and NA2, which are highly immunogenic and act as targets in alloimmune or autoimmune neutropenia. Thus, neutrophil antigens (NA) compatibility of donor/recipient pairs might be expected to affect the engraftment of neutrophils after allogeneic SCT (allo-SCT). Here, the impact of NA compatibility of 17 patients and their donors undergoing allo-SCT with a myeloablative regimen was determined. Leukocyte depletion filters were used for all transfusions before and post-SCT; most patients received G-CSF after transplant. Major mismatches for NA1 and NA2 were present in 1 and 7 patient/donor pairs, respectively. These eight patients receiving NA major-mismatched allo-SCT were compared with nine patients who received NA compatible allo-SCT. Engraftment of neutrophils and the incidence of post-engraftment neutropenia were found to be identical in the two groups. Despite the limitations in statistical power because of the small number of patients analyzed, these observations suggest that the major mismatching for NA2 antigen has little impact on the engraftment of neutrophils after myeloablative allo-SCT, at least in patients transfused using leukocyte depletion filters and receiving G-CSF after transplantation.Bone Marrow Transplantation (2009) 43, 229–235; doi:10.1038/bmt.2008.311; published online 22 September 2008 [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a rare but notoriously recalcitrant cutaneous diseases. Therefore, there have been few reports of more than ten patients with GPP who were treated at the same institution. The severity of this disease and its response to each therapeutic modality vary among patients. In some GPP is life-threatening, but in others it may show a benign, chronic course for a long period of time. Before starting treatment, a knowledge of the therapeutic efficacy and side effects of each drug used in the treatment of GPP is necessary. In our multicenter study, we compared the effectiveness of and adverse reactions to several systemically administered drugs. Following the development of a unique classification of the disease severity based on scoring the clinical symptoms and the laboratory findings, we propose here therapeutic guidelines for the treatment of GPP. [ABSTRACT FROM AUTHOR]

We report a 20-month-old boy with acute lymphoblastic leukemia with the 11q23 translocation whose blasts markedly increased in peripheral blood after intravenous granulocyte colony-stimulating factor (G-CSF) administration, but disappeared after stopping G-CSF. The in vitro study showed that the leukemic cells separated from this patient expressed G-CSF receptor (G-CSFR) and an addition of G-CSF stimulated their proliferation by 3H-thymidine incorporation assay (stimulation index, 4.9). To clarify whether or not leukemic cells with 11q23 translocations generally express G-CSFR and show proliferative response to G-CSF, we performed the similar in vitro experiments using eight leukemic cell lines with 11q23 translocations. We found that all cell lines examined expressed G-CSFR (20-98%) and proliferation of seven leukemic cell lines was significantly enhanced in response to G-CSF (stimulation index >1.5 in five cell lines), suggesting a possible participation of the G-CSF/G-CSFR interaction in the process of growth regulation of leukemic cells with 11q23 translocations. [ABSTRACT FROM AUTHOR]