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.

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.

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.

Purpose: Valproic acid (VPA) is not only an antiepileptic drug but also a mood stabilizer for patients with bipolar disorder. Long-term VPA therapy can cause carnitine deficiency, which may result in an increase in the blood ammonia level, in patients with epilepsy. However, information about this effect in patients with bipolar disorder is limited. The aim of this study was to investigate the associations between the serum VPA level and the carnitine and ammonia levels in psychiatric adult patients with epilepsy. Methods: The subjects were 182 consecutive Japanese adult patients (mean age 54.3 ± 19.5 years) diagnosed with bipolar disorder and treated with VPA. The serum VPA level, carnitine fraction, and plasma ammonia level were measured. Furthermore, the free carnitine and acylcarnitine fractions were measured using an enzyme cycling method. Results: Sixty-nine patients (38%) had a low free carnitine level. There were significant differences in sex, height, VPA dose, serum VPA level, total carnitine level, acylcarnitine level, and acylcarnitine/free carnitine ratio between patients with a low free carnitine level and those with a normal range of free carnitine. The simple and multiple regression analyses revealed that the VPA dose and the serum VPA level were inversely and significantly correlated with the free carnitine level. The plasma ammonia level was correlated with the VPA dose, serum VPA level, and acylcarnitine level but not with the free carnitine level. Conclusions: These findings suggest that carnitine deficiency is associated with the VPA dose and the serum VPA level in patients with bipolar disorder. However, it is unlikely that carnitine deficiency is associated with hyperammonemia in patients with bipolar disorder.

The results of the present study suggest that adjunctive treatment with carbamazepine reduces the concentration of paliperidone in a dose-dependent manner, most likely because of the induction of several drug-metabolizing enzymes and several drug transporters.

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The prevalence of Borna disease virus (BDV)-specific antibodies among patients with psychiatric disorders and healthy individuals has varied in several reports using several different serological assay methods. A reliable and specific method for anti-BDV antibodies needs to be developed to clarify the pathological significance of BDV infections in humans. We developed a new electrochemiluminescence immunoassay (ECLIA) for the antibody to BDV that uses two recombinant proteins of BDV, p40 and p24 (full length). Using this ECLIA, we examined 3,476 serum samples from humans with various diseases and 917 sera from blood donors in Japan for the presence of anti-BDV antibodies. By ECLIA, 26 (3.08%) of 845 schizophrenia patients and 9 (3.59%) of 251 patients with mood disorders were seropositive for BDV. Among 323 patients with other psychiatric diseases, 114 with neurological diseases, 75 with chronic fatigue syndrome, 85 human immunodeficiency virus-infected patients, 50 with autoimmune diseases including rheumatoid arthritis and systemic lupus erythematosis and 17 with leprosy, there was no positive case except one case each with alcohol addiction, AIDS, and dementia. Although 19 (1.36%) of 1,393 patients with various ocular diseases, 10 (1.09%) of 917 blood donors, and 3 (4.55%) of 66 multitransfused patients were seropositive for BDV-specific antigen, high levels of seroprevalence in schizophrenia patients and young patients (16 to 59 years old) with mood disorders were statistically significant. The immunoreactivity of seropositive sera could be verified for specificity by blocking with soluble p40 and/or p24 recombinant protein. Anti-p24 antibody was more frequent than p40 antibody in most cases, and in some psychotic patients antibody profiles showed only p40 antibody. Although serum positive for both p40 and p24 antibodies was not found in this study, the p40 ECLIA count in schizophrenia patients was higher than that of blood donors. Furthermore, we examined 90 sera from Japanese feral horses. Antibody profiles of control human samples are similar to that of naturally BDV-infected feral horses. We concluded that BDV infection was associated in some way with psychiatric disorders.