In psoriasis, CD28/B7 costimulatory molecules are well characterized. Here, using the severe combined immunodeficient (SCID) mouse-psoriasis xenograft model, we report therapeutic efficacy of a humanized anti-CD28 monoclonal antibody (FR255734; Astellas Pharmaceuticals Inc., Tokyo, Japan). Transplanted psoriasis plaques on the SCID mouse were treated weekly for 4 weeks with intraperitoneal injections of FR255734 at 10, 3, and 1-mg kg(-1) doses. Groups treated with doses of 10 and 3 mg kg(-1) had significant thinning of the epidermis and reduced HLA-DR-positive lymphocytic infiltrates. The length of the rete pegs changed from 415.2+/-59.6 to 231.4+/-40.4 microm (P<0.005) in the 10-mg kg(-1) group, and from 323.4+/-69.6 to 237.5+/-73.6 microm in the 3-mg kg(-1) group (P=0.002). Positive controls treated with CTLA4-Ig and cyclosporine had significant histological improvement, whereas plaques treated with saline and isotype controls (human and mouse IgG2) remained unchanged. In vitro studies have shown that FR255734 effectively blocked T-cell proliferation and proinflammatory cytokine production. These observations warrant studies to evaluate the efficacy of FR255734 in human autoimmune diseases.
FK734 is a partial agonist of CD28 signaling that can reduce human T cell alloresponses in the presence of strong costimulation by B7 molecules in vitro and can reduce T cell-mediated skin allograft rejection in vivo.
BackgroundLong-acting injectable antipsychotics (LAIs) are regarded as an important alternative to oral medication for patients with schizophrenia. However, LAIs remain under-utilized in clinical practice.AimsThe aims of this investigation were to 1) obtain information on patients’ attitudes toward LAIs and 2) assess factors associated with patients’ acceptance of LAIs, and 3) identify predictors of the discrepancy between patients and referring psychiatrists’ opinions regarding the appropriateness for LAIs.MethodsAnonymized data were collected from a questionnaire distributed to 159 patients with schizophrenia and their referring psychiatrists at three psychiatric hospitals between February 2014 and July 2014. The patients completed an original questionnaire developed to evaluate their attitudes regarding LAIs. Regarding the appropriateness of LAI prescription, patients and their referring psychiatrists were asked to rate, on a 5-point scale, how appropriate they felt the depot prescription was for the patients. The participants also answered instruments to assess symptom severity, antipsychotic-induced extrapyramidal symptoms, functions, quality of life, and self-esteem levels.ResultsPatients currently on LAIs have favorable attitudes toward LAIs with respect to side effects, relapse prevention, efficacy, pain, and cost. Expectation of relapse prevention was significantly associated with patients’ acceptance of LAIs (answering that those drugs are appropriate for their own treatment). In addition, the discrepancy between the patients’ and referring psychiatrists’ opinions regarding the appropriateness of LAI treatment was significantly associated with symptom severity, expectation of relapse prevention, belief that LAIs are painful, and belief that LAIs offer a reduced range of antipsychotic choices.ConclusionAttitudes toward LAIs need to be considered when deciding whether to prescribe this formulation. Access to information on LAIs, including their benefit in relapse prevention, might enhance the acceptance and use of this formulation among patients with schizophrenia.
BackgroundRecently, a relationship between obesity and schizophrenia has been reported. The prediction of resting energy expenditure (REE) is important to determine the energy expenditure of patients with schizophrenia. However, there is a lack of research concerning the most accurate REE predictive equations among Asian patients with schizophrenia. The purpose of the study reported here was to compare the validity of four REE equations for patients with schizophrenia taking antipsychotics.MethodsFor this cross-sectional study, we recruited patients (n=110) who had a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, diagnosis of schizophrenia and were admitted to four psychiatric hospitals. The mean (± standard deviation) age of these patients was 45.9±13.2 years. Anthropometric measurements (of height, weight, body mass index) were taken at the beginning of the study. REE was measured using indirect calorimetry. Comparisons between the measured and estimated REEs from the four equations (Harris–Benedict, Mifflin–St Jeor, Food and Agriculture Organization/World Health Organization/United Nations University, and Schofield) were performed using simple linear regression analysis and Bland–Altman analysis.ResultsSignificant trends were found between the measured and predicted REEs for all four equations (P<0.001), with the Harris–Benedict equation demonstrating the strongest correlation in both men and women (r=0.617, P<0.001). In all participants, Bland–Altman analysis revealed that the Harris–Benedict and Mifflin–St Jeor equations did not show a significant bias in the prediction of REE, however, a significant overestimation error was shown for the Food and Agriculture Organization/World Health Organization/United Nations University and Schofield equations.ConclusionWhen estimating REE in patients with schizophrenia taking antipsychotics, the Harris–Benedict equation appears to be the most appropriate for clinical use.
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