Brexpiprazole: A new option in treating agitation in Alzheimer's dementia-Insights from transgenic mouse models.

Aim: Brexpiprazole is the first FDA-approved treatment for agitation associated with dementia due to Alzheimer's disease. Agitation in Alzheimer's dementia (AAD) occurs in high prevalence and is a great burden for patients and caregivers. Efficacy, safety, and tolerability of brexpiprazole were demonstrated in the AAD clinical trials.

Synergistic anti-depressive effect of combination treatment of Brexpiprazole and selective serotonin reuptake inhibitors on forced swimming test in mice.

Aim: Selective serotonin reuptake inhibitors (SSRIs) are used to treat major depressive disorder (MDD) and other psychiatric disorders (e.g., obsessive compulsive disorder, social anxiety disorder, and panic disorder).

Prenatal methotrexate injection increases behaviors possibly associated with depression and/or autism in rat offspring; A new animal model for mental disorder, based on folate metabolism deficit during pregnancy.

Background: Deficiency of folate, an essential vitamin for DNA synthesis and methylation, is reported as a risk factor for mental disorders. Considering a possibility that folate metabolism deficit during pregnancy may disturb CNS development and increase mental disorders in offspring, we treated pregnant rats with methotrexate (MTX), an inhibitor of folate metabolic enzyme, and evaluated offspring behaviors.

Methods: Saline or MTX was intraperitoneally administered to female SD rats on gestational day 17.

Perceived outcomes of psychedelic microdosing as self-managed therapies for mental and substance use disorders.

Rationale: The regular consumption of very small doses of psychedelic drugs (known as microdosing) has been a source of growing media and community attention in recent years. However, there is currently limited clinical and social research evidence on the potential role of microdosing as therapies for mental and substance use disorders.

Objectives: This paper examined subjective experiences of microdosing psychedelics to improve mental health or to cease or reduce substance use, and examined sociodemographic and other covariates of perceived improvements in mental health that individuals attributed to microdosing.

Microdosing psychedelics: Motivations, subjective effects and harm reduction.

Background: In recent years there has been growing media attention on microdosing psychedelics (e.g., LSD, psilocybin).

Psychedelic Microdosing: A Subreddit Analysis.

Self-administration of very low doses of psychedelic drugs to improve mental health and wellbeing and enhance cognitive function, known as microdosing, has received recent media attention, but little research has been conducted. We conducted a content analysis of discussions about microdosing from the online forum Reddit. We examined motivations, dosing practices, and perceived benefits and limitations of microdosing.

Brexpiprazole has a low risk of dopamine D receptor sensitization and inhibits rebound phenomena related to D and serotonin 5-HT receptors in rats.

Background: Long-term antipsychotic treatment in patients with schizophrenia can induce supersensitivity psychosis and tardive dyskinesia which is thought to be caused by dopamine D receptor sensitization. We evaluated the effects of brexpiprazole on D receptor sensitivity after subchronic treatment in rats. We also evaluated whether brexpiprazole could suppress enhanced response to D receptors in rats subchronically dosed with another atypical antipsychotic.

A Prospective Randomized, Comparative Trial of High-Dose Mizoribine Versus Mycophenolate Mofetil in Combination With Tacrolimus and Basiliximab for Living Donor Renal Transplant: A Multicenter Trial.

Objectives: Our objectives were to compare the clinical outcomes of mizoribine (12 mg/kg/d) and mycophenolate mofetil (2000 mg/d) in combination with tacrolimus, basiliximab, and corticosteroids.

Materials And Methods: We enrolled 83 recipients of living-donor renal transplant (performed between 2008 and 2013) in this study. This prospective multi-institutional randomized comparative study compared mizoribine (n = 41) and mycophenolate mofetil (n = 42) in combination with tacrolimus, basiliximab, and corticosteroids for living-donor renal transplant recipients.

A Prospective Randomized, Comparative Trial of High-Dose Mizoribine Versus Mycophenolate Mofetil in Combination With Tacrolimus and Basiliximab for Living Donor Renal Transplant: A Multicenter Trial.

Objectives: Our objectives were to compare the clinical outcomes of mizoribine (12 mg/kg/d) and mycophenolate mofetil (2000 mg/d) in combination with tacrolimus, basiliximab, and corticosteroids.

Materials And Methods: We enrolled 83 recipients of living-donor renal transplant (performed between 2008 and 2013) in this study. This prospective multi-institutional randomized comparative study compared mizoribine (n = 41) and mycophenolate mofetil (n = 42) in combination with tacrolimus, basiliximab, and corticosteroids for living-donor renal transplant recipients.

Mortality rates and walking ability transition after lower limb major amputation in hemodialysis patients.

Objective: The number of hemodialysis patients with peripheral artery disease is increasing, and critical limb ischemia develops in some of these patients. The clinical outcomes in such patients after major amputation remain unclear. We therefore examined the mortality rates after major amputation in hemodialysis patients.

A Low Mortality, High Morbidity Reduced Intensity Status Epilepticus (RISE) Model of Epilepsy and Epileptogenesis in the Rat.

Animal models of acquired epilepsies aim to provide researchers with tools for use in understanding the processes underlying the acquisition, development and establishment of the disorder. Typically, following a systemic or local insult, vulnerable brain regions undergo a process leading to the development, over time, of spontaneous recurrent seizures. Many such models make use of a period of intense seizure activity or status epilepticus, and this may be associated with high mortality and/or global damage to large areas of the brain.

Limited utility of blood cultures in the management of febrile outpatient kidney transplant recipients.

Background/purpose: Blood cultures for patients suspected of having bacteremia are standard practice, although several studies demonstrate that blood cultures have limited utility because of a low true-positive rate and infrequent resultant changes in antibiotic treatment. However, most reports exclude immunocompromised patients such as transplant recipients. We assessed the utility of blood cultures in transplant recipients hospitalized for community-acquired infections and evaluated clinical characteristics to predict bacteremia.

MK-801-induced deficits in social recognition in rats: reversal by aripiprazole, but not olanzapine, risperidone, or cannabidiol.

Deficiencies in social activities are hallmarks of numerous brain disorders. With respect to schizophrenia, social withdrawal belongs to the category of negative symptoms and is associated with deficits in the cognitive domain. Here, we used the N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801) for induction of social withdrawal in rats and assessed the efficacy of several atypical antipsychotics with different pharmacological profiles as putative treatment.

Global Trends in Alzheimer Disease Clinical Development: Increasing the Probability of Success.

Purpose: Alzheimer disease (AD) is a growing global health and economic issue as elderly populations increase dramatically across the world. Despite the many clinical trials conducted, currently no approved disease-modifying treatment exists. In this commentary, the present status of AD drug development and the grounds for collaborations between government, academia, and industry to accelerate the development of disease-modifying AD therapies are discussed.

Right versus left retroperitoneoscopic living-donor nephrectomy.

Purpose: To compare the safety and efficacy of right-side and left-side retroperitoneoscopic donor nephrectomy (RDN) using our hybrid technique.

Methods: We retrospectively reviewed the data obtained from 151 consecutive patients who underwent RDN between May 2005 and July 2013. Right and left nephrectomies were performed in 87 and 64 patients, respectively.

Pretransplant HbA1c Is a Useful Predictor for the Development of New-Onset Diabetes in Renal Transplant Recipients Receiving No or Low-Dose Erythropoietin.

Aims. To evaluate the predictive power of pretransplant HbA1c for new-onset diabetes after transplantation (NODAT) in kidney transplant candidates, who had several predispositions for fluctuated HbA1c levels. Methods.

Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator.

Brexpiprazole (OPC-34712, 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)-one) is a novel drug candidate in clinical development for psychiatric disorders with high affinity for serotonin, dopamine, and noradrenaline receptors. In particular, it bound with high affinity (Ki < 1 nM) to human serotonin 1A (h5-HT1A)-, h5-HT2A-, long form of human D2 (hD2L)-, hα1B-, and hα2C-adrenergic receptors. It displayed partial agonism at h5-HT1A and hD2 receptors in cloned receptor systems and potent antagonism of h5-HT2A receptors and hα1B/2C-adrenoceptors.

Brexpiprazole II: antipsychotic-like and procognitive effects of a novel serotonin-dopamine activity modulator.

Brexpiprazole (OPC-34712, 7-{4-[4-(1-benzothiophen-4-yl)piperazin-1-yl]butoxy}quinolin-2(1H)-one) is a novel serotonin-dopamine activity modulator with partial agonist activity at serotonin 1A (5-HT1A) and D2/3 receptors, combined with potent antagonist effects on 5-HT2A, α1B-, and α2C-adrenergic receptors. Brexpiprazole inhibited conditioned avoidance response (ED50 = 6.0 mg/kg), apomorphine- or d-amphetamine-induced hyperactivity (ED50 = 2.

Medication compliance in renal transplant patients during the Great East Japan Earthquake.

Introduction: Oral immunosuppressant suspension induces renal graft dysfunction in renal transplant patients. After the Great East Japan Earthquake, not only were drugs lost in the tsunami, but visiting hospitals became difficult owing to information and transportation network disruption. We investigated medication compliance in renal transplant patients and actions taken immediately after the earthquake.

Effects of elevated tacrolimus trough levels in association with infectious enteritis on graft function in renal transplant recipients.

Background: The bioavailability of oral tacrolimus is influenced by enterocyte metabolism, which involves CYP3A and P-glycoprotein. Viral infection-induced intestinal inflammation damages the enterocytes and causes unfavorable elevations in blood tacrolimus levels in transplant recipients, which may lead to nephrotoxicity.

Methods: From May 2000 to May 2011, 56 renal transplant recipients receiving tacrolimus at our hospital suffered from infectious enteritis with diarrhea.

Insulin resistance as a risk factor for new-onset diabetes after kidney transplantation.

Introduction: New-onset diabetes after transplantation (NODAT) is a serious and common complication after kidney transplantation. Insulin resistance, together with β-cell dysfunction, plays an essential role in the development of diabetes. Homeostasis model assessment of insulin resistance (HOMA-IR), which is calculated as [fasting plasma glucose (mmol/L) × fasting insulin (mU/L)]/22.

The 5-time point oral glucose tolerance test as a predictor of new-onset diabetes after kidney transplantation.

Aims: To evaluate the predictive power of the 5-time point oral glucose tolerance test (OGTT) for new-onset diabetes after kidney transplantation (NODAT).

Methods: We performed a retrospective study of 145 patients without diabetes who received kidney transplantations at our hospital. The 5-time point OGTT was performed before transplantation.

Cannabidivarin (CBDV) suppresses pentylenetetrazole (PTZ)-induced increases in epilepsy-related gene expression.

To date, anticonvulsant effects of the plant cannabinoid, cannabidivarin (CBDV), have been reported in several animal models of seizure. However, these behaviourally observed anticonvulsant effects have not been confirmed at the molecular level. To examine changes to epilepsy-related gene expression following chemical convulsant treatment and their subsequent control by phytocannabinoid administration, we behaviourally evaluated effects of CBDV (400 mg/kg, p.

Retroperitoneoscopic living donor nephrectomy: short learning curve and our original hybrid technique.

Objective: To evaluate the effect of the learning curve for the hybrid technique of retroperitoneoscopic living donor nephrectomy (RDN) on donor and recipient outcomes.

Methods: We retrospectively reviewed 120 consecutive patients who underwent RDN, performed by a laparoscopic surgeon, at Sendai Shakaihoken Hospital between May 2005 and September 2011. A new hybrid technique, in which 2 laparoscopic ports were inserted through a hand-port device and all the procedures except mobilization and taping of ureter and extracting kidney were performed with nonhand-assisted technique, was used.

Body fat percentage as a marker of new-onset diabetes mellitus after kidney transplantation.

Background: New-onset diabetes after transplantation (NODAT) is a serious metabolic complication that can follow kidney transplantation. Several risk factors, including obesity, have been related to NODAT development. Obesity is defined as an excessive accumulation of body fat, and body fat percentage (BF%) has been commonly measured by different techniques, including bioelectrical impedance analysis.