Target phosphate and calcium levels in patients undergoing hemodialysis: a post-hoc analysis of the LANDMARK study.

BACKGROUND: It is necessary to re-examine the optimal phosphate (P) and calcium (Ca) target values in the contemporary management of chronic kidney disease-mineral and bone disorder to reduce the risks of cardiovascular events in patients receiving hemodialysis. METHODS: We performed a post-hoc analysis of the LANDMARK study. The outcomes were defined as cardiovascular events and all-cause death. Data from 2135 patients receiving hemodialysis at risk of vascular calcification were analyzed using a time-dependent Cox proportional hazard model adjusted for background factors. RESULTS: On the hazard ratio (HR) curve, the ranges where the lower 95% confidence interval (CI) were below the minimum of HR (= 1.00) were as follows: P = 3.5-5.5 mg/dL; albumin-adjusted Ca < 9.1 mg/dL for cardiovascular events; and P = 3.6-5.3 mg/dL; albumin-adjusted Ca < 9.1 mg/dL for all-cause mortality. In stratified analysis, the HRs for cardiovascular events in P < 3.5 mg/dL and P ≥ 5.5 mg/dL were similar to that of P = 3.5-5.5 mg/dL (P ≥ 0.05), and albumin-adjusted Ca ≥ 9.1 mg/dL had higher HR than values < 9.1 mg/dL [1.30 (95% CI 1.00-1.68; P = 0.046)]. For all-cause mortality, the HR in P < 3.6 mg/dL was higher than that in P = 3.6-5.3 mg/dL [1.76 (95% CI 1.25-2.48; P = 0.001)], while the HRs between P ≥ 5.3 mg/dL and P = 3.6-5.3 mg/dL as well as those between albumin-adjusted Ca ≥ 9.1 and < 9.1 mg/dL were not significantly different (P ≥ 0.05). CONCLUSIONS: Managing albumin-adjusted Ca < 9.1 mg/dL may reduce the cardiovascular risk among patients undergoing hemodialysis. Hypophosphatemia < 3.6 mg/dL may be associated with mortality.

Enhanced Operational Durability of Thermally Activated Delayed Fluorescence-Based Organic Light-Emitting Diodes with a Triazine Electron Transporter.

In organic light-emitting diodes (OLEDs) based on materials that show thermally activated delayed fluorescence (TADF), the internal quantum efficiency of 100 % can be obtained without using phosphorescence-based organometallics that contain rare metals. Therefore, with TADF-based emitters, it is possible to fabricate high-performing OLEDs at a lower cost. However, compared with fluorescence- and phosphorescence-based OLEDs, an understanding of degradation mechanisms in TADF-based OLEDs is still insufficient for future commercialization. In particular, it is widely recognized that the development of electron transport materials is crucial for improving OLED characteristics, especially driving voltages and operational durability. In this study, it was demonstrated that the operational durability of TADF-based OLEDs was greatly improved by introducing a triazine-based material of 2,4,6-tris(1,1'-biphenyl-4-yl)-[1,3,5]triazine (pT2T) as a hole-blocking layer (HBL) compared with a conventional HBL material of 2,4,6-tris(biphenyl-3-yl)-[1,3,5]triazine (T2T). Several experiments were carried out to make the reasons of the improved durability clearer, and attributed the improved durability to the shift of a carrier recombination zone from the emitting layer/HBL interface and the suppressed formation of excited-state quenchers in the pT2T HBL, because of the higher electron mobility of pT2T and the better stability of its radical anion state.

Bioequivalence of perampanel fine granules and tablets in healthy Japanese subjects.

OBJECTIVE: Perampanel is an approved anti-seizure drug. A new formulation of perampanel fine granules (FG; 1% perampanel) has been developed for patients who are unable to take tablets. Bioequivalence between the 4-mg FG and tablet perampanel formulations, as well as their safety and tolerability, were assessed. MATERIALS AND METHODS: In this phase I, single-center, open-label, 2-period, 2-sequence, crossover, bioequivalence study (NCT03399734), healthy Japanese subjects were randomized to receive single doses of the 4-mg FG perampanel and 4-mg perampanel tablet (separated by a ≥ 6-week washout period). Plasma samples for perampanel concentration analysis were collected pre-dose and at intervals up to 168 hours post-dose. The maximum observed concentration (Cmax) and area under the concentration-time curve from time zero to 168 hours (AUC(0-168h)) were used to assess the bioequivalence of the two formulations. RESULTS: The 90% confidence intervals (CIs) for the geometric mean ratio of test/reference for Cmax and AUC(0-168h) were within the bioequivalence criteria of 80 - 125% (Cmax 90% CI 90.8%, 110%; AUC(0-168h) 90% CI 98.2%, 112%; N = 21). 10/24 (41.7%) subjects with FG experienced ≥ 1 treatment-emergent adverse event (TEAE). The events were mild in severity and resolved within 4 hours of onset. There were no deaths, severe TEAEs, serious AEs, or TEAEs leading to study-drug withdrawal. CONCLUSION: Bioequivalence of 4-mg FG and 4-mg tablet of perampanel was demonstrated. Both perampanel formulations were generally safe and well tolerated. These data suggest that perampanel FG may be a suitable alternative formulation for patients with epilepsy who have difficulties taking perampanel tablets.

A first-in-human phase 1 study of ACE910, a novel factor VIII-mimetic bispecific antibody, in healthy subjects.

ACE910 is a recombinant humanized bispecific antibody that binds to activated factor IX and factor X and mimics the cofactor function of factor VIII (FVIII). This first-in-human study examined the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ACE910 in healthy male adults. A total of 40 Japanese and 24 white subjects were randomized to receive a single subcutaneous injection of ACE910 (Japanese: 0.001, 0.01, 0.1, 0.3, or 1 mg/kg; white: 0.1, 0.3, or 1 mg/kg; n = 6 per dose group) or placebo (n = 2 per dose group). ACE910 exhibited a linear PK profile and had a half-life of ∼4 to 5 weeks. In FVIII-neutralized plasma, ACE910 shortened activated partial thromboplastin time and increased peak height of thrombin generation in a dose-dependent manner. All adverse events were nonserious and did not lead to any subject's withdrawal. Neither clinical findings nor laboratory abnormalities indicating hypercoagulability were observed. Two of 48 subjects receiving ACE910 (1 Japanese and 1 white) were positive for anti-ACE910 antibodies (anti-drug antibodies [ADAs]). One subject tested positive for ADAs both before and after ACE910 administration, whereas the other became ADA positive after receiving ACE910. The PK and PD profiles of ACE910 were similar in healthy Japanese and white subjects and suggest that ACE910 will be an effective and convenient prophylactic treatment of hemophilia A. This trial was registered at www.clinicaltrials.jp as #JapicCTI-121934.

Evaluation of CYP2D6 Protein Expression and Activity in the Small Intestine to Determine Its Metabolic Capability in the Japanese Population.

CYP2D6 plays an important role in the metabolism of many drugs such as opioids and antidepressants. Polymorphisms of the CYP2D6 gene are widely observed in the Japanese population, and can affect the first-pass metabolism of orally administered drugs. Several CYP enzymes have been identified in the small intestine of Caucasians, but intestinal CYP enzymes have not been reported in the Japanese population, except for CYP3A4 and CYP2C19. In this study, we evaluated the CYP2D6 metabolic capacity by measurement of CYP2D6 mRNA and protein levels and activity in the small intestine of Japanese individuals. Normal jejunal tissues were obtained from 31 patients who had undergone pancreaticoduodenectomy, and the CYP2D6*10 variant was identified in these tissues. CYP2D6 mRNA and CYP2D6 protein levels were analyzed using real-time RT-PCR and Western blotting, respectively. Bufuralol 1'-hydroxylation, a marker of CYP2D6 activity, was analyzed using HPLC. Frequencies of the CYP2D6*1/*1, *1/*10, and *10/*10 genotypes in the jejunal tissue were 29.0% (n=9), 35.5% (n=11), and 35.5% (n=11), respectively. CYP2D6 protein and activity levels did not differ significantly between the genotypes. A positive correlation was found between CYP2D6 protein and activity levels. Furthermore, CYP2D6 protein levels and activity in the small intestine were significantly lower than those in the liver. These findings suggest that the metabolic capacity of CYP2D6 in the small intestine of the Japanese population has a relatively small effect on drug metabolism.

[The International Study of Burnout Syndrome among Psychiatric Trainees (BoSS International) : Findings from Statistical Analysis of the Japanese Data (BoSS Japan)].

BACKGROUND: Burnout is a psychological condition that may occur after being exposed to excessive and prolonged work-related stresses. Previous studies have demonstrated that the rate of burnout among physicians may be higher compared to other occupations ; and espe- cially psychiatric trainees would have a higher risk of burnout because of limited clinical expe- rience, the burden of heavy duties and longer work-hours etc. In this study, we report the findings from Japanese data obtained as part of the international study of burnout syndrome among psychiatric trainees (BoSS International). METHODS: This study was initiated by members of the European Federation of Psychiatric Trainees (EFPT) and the European Psychiatric Association-European Early Career Psychia- trists (EPA-EECP). The total number of participating nations was 22 countries. A national coordinator recruited study collaborators all over Japan and psychiatric trainees working at their medical institutes were invited to participate in BoSS International by e-mail. The sub- jects were requested to answer the on-line questionnaire anonymously. Consent was obtained when making a list of potential participants at each institute and reconfirmed on the first page of the on-line questionnaire. Answering the questionnaire was deemed to constitute consent. RESULTS: Total number of participants to BoSS International was 7,525 from 22 countries and regions. Of them, 1,980 psychiatric trainees fully completed answering the questionnaire (response rate (RR) 26.0%) including 95 Japanese trainees (RR 41.5%). The mean age of 95 Japanese psychiatric trainees (male rate 67.4%) enrolled in BoSS International was 31.8?4.8 year-old. Their mean clinical experience was 2.9 ?4.4 years. The mean weekly working hours were 72.3?27.1, which was the longest of the 22 participating countries/regions ; while weekly clinical supervision by a mentor was only 3.8?9.0 hours. Regarding the severity of burnout, assessed by using the Maslach Burnout Inventory-General Survey (MBI-GS) consisting of three factors (emotional exhaustion, cynicism, and low sense of professional efficacy): 41 Japanese psychiatric trainees (42.0%) meet the criteria of severe burnout syndrome in this study ; with emotional exhaustion scores of 2.20 and higher, and cynicism of 2.00 and higher. Signifi- cant differences were found on the PHQ-9 score and mean length of supervision between those participants with presence and absence of severe burnout syndrome by using Student's t-test. CONCLUSION: Statistical analyses of the whole data (n=1,980) revealed that the risk of burnout was higher for trainees who were younger, without children, and had not opted for psychiatry as a first career choice. Further analyses after adjustment for socio-demographic characteristics and country difference still demonstrated severe burnout was associated with long working hours, less supervision, and not having regular rest. The analyses of Japanese data showed similar tendencies, although statistical significance was not observed. Burnout among psychiatry trainees may be linked to drop-out from the training program and malprac- tice in clinical settings. We should be aware of the higher risk of burnout in residents and the importance of regular and sufficient supervision to prevent burnout.

[The Safety and efficacy of airway-hyperresponsiveness test for asthma using by SK-1211 (Methacholine Chloride)].

BACKGROUND: In abroad, Methacholine Chloride (Provocholine®) is used to meet the indications of the diagnosis of bronchial airway hyperreactivity in subjects who do not have clinically apparent asthma. We examined efficacy, safety and pharmacokinetics of Methacholine Chloride (name of study drug: SK-1211) in order to get approved for the airway hyperresponsiveness test in Japan. METHODS: Fifteen adult healthy volunteers, fifteen adult patients with asthma and ten pediatric patients with asthma were enrolled in this study. The airway hyperresponsiveness test with SK-1211 was conducted in accordance with Japanese Society of Allergology Standard Method. RESULTS: When the threshold value of PC20 was 8 mg/mL, the sensitivity of adult patients with asthma was 66.7% (10/15 subjects) and the specificity of adult healthy volunteers was 86.7% (13/15 subjects). The sensitivity of pediatric patients with asthma was 70.0% (7/10 subjects). Not all subjects experienced some adverse reactions during inhalation of SK-1211, all of which were mild in severity and resolved soon with inhalation of a bronchodilator. There were no serious adverse reactions reported. CONCLUSION: The airway hyperresponsiveness test with SK-1211 was no specific concern with safety and useful in the diagnosis of bronchial airway hyperresponsiveness.

The Effect of Thickened Water on Ciprofloxacin Pharmacokinetics: A Comparative Study in Adult Males.

Background/Objectives: The use of food thickeners with ciprofloxacin tablets may result in a gelatinous appearance and experience delayed dissolution, which presents a challenge for the drug's efficacy, creating a healthcare economic issue. However, the pharmacokinetic impact of this compound in humans remains uncertain. Therefore, a comparative pharmacokinetic study of ciprofloxacin was conducted on healthy adult Japanese males. Methods: We compared the effects of administering tablets with water or thickened water and crushed tablets mixed with thickened water. The maximum blood concentration (Cmax) of ciprofloxacin determines the drug's efficacy. Results: There were variations in drug absorption across different administration methods. The group who took the tablets immersed in thickened water exhibited different results in the area under the blood drug concentration-time curve (AUC) and Cmax compared to the group who took the tablets in regular water. Notably, the group that consumed the crushed tablets mixed with thickened water demonstrated equivalent results for both AUC and Cmax. Conclusions: Administering crushed tablets in thickened water may yield pharmacokinetics comparable to those of tablets taken with water. However, the process of crushing tablets may result in the loss of active ingredients and compromise the formulation, necessitating a comprehensive assessment before administration.

Clinical Significance of Intraductal Carcinoma of the Prostate After High-Dose Brachytherapy With External Beam Radiation Therapy: A Single Institution Series and an Updated Meta-Analysis.

BACKGROUND: We compared oncological outcomes between prostate cancer (PCa) patients with and without intraductal carcinoma of the prostate (IDC-P) after high-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT). METHODS: We performed a retrospective analysis of 138 patients with clinically high-risk, very high-risk, or locally advanced PCa who received HDR-BT with EBRT. Of these, 70 (50.7 %) patients were diagnosed with IDC-P; 68 (49.3 %) patients with acinar adenocarcinoma of prostate. The oncological outcomes, including biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS), were assessed using Kaplan-Meier curves. Additionally, Cox proportional hazards models were used to identify significant prognostic indicators or biochemical recurrence (BCR). Meta-analysis of existing literatures was performed to evaluate the risk of BCR in patients with IDC-P after radiation therapy, compared to those without IDC-P. RESULTS: Kaplan-Meier curves demonstrated significantly inferior BCRFS and CPFS in patients with IDC-P. Multivariate analysis revealed that IDC-P and Grade Group 5 status were associated with increased BCR risk. in our meta-analysis, IDC-P was associated with BCR (HR = 2.13, P = .003). CONCLUSION: Amongst the patients who received HDR-BT, patients with IDC-P displayed significantly more rapid disease progression, compared with patients who did not have IDC-P.

Effect of a variant histology on the oncological outcomes of Japanese patients with upper tract urothelial carcinomas after radical nephroureterectomy: a multicenter retrospective study.

Background: An earlier systematic review and meta-analysis found that patients with a certain histological variant of upper tract urothelial carcinoma (UTUC) exhibited more advanced disease and poorer survival than those with pure UTUC. A difference in the clinicopathological UTUC characteristics of Caucasian and Japanese patients has been reported, but few studies have investigated the clinical impact of the variant histology in Japanese UTUC patients. Methods: We retrospectively enrolled 824 Japanese patients with pTa-4N0-1M0 UTUCs who underwent radical nephroureterectomy without neoadjuvant chemotherapy. Subsequently, we explored the effects of the variant histology on disease aggressiveness and the oncological outcomes. We used Cox's proportional hazards models to identify significant predictors of oncological outcomes, specifically intravesical recurrence-free survival (IVRFS), recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results: Of the 824 UTUC patients, 32 (3.9%) exhibited a variant histology that correlated significantly with a higher pathological T stage and lymphovascular invasion (LVI). Univariate analysis revealed that the variant histology was an independent risk factor for suboptimal RFS, CSS, and OS. However, significance was lost on multivariate analyses. Conclusions: The variant histology does not add to the prognostic information imparted by the pathological findings after radical nephroureterectomy, particularly in Japanese UTUC patients.

Genetic characteristics of CTX-M-type extended-spectrum-ß-lactamase (ESBL)-producing enterobacteriaceae involved in mastitis cases on Japanese dairy farms, 2007 to 2011.

Sixty-five CTX-M-2/15/14 extended-spectrum-ß-lactamase-producing Enterobacteriaceae were isolated from 258,888 mastitic milk samples from Japanese dairy farms between 2007 and 2011. CTX-M-2-producing Klebsiella pneumoniae and CTX-M-15-producing Escherichia coli were the predominant strains isolated. There was no predominant clonal type, and clonal diversity was found even in strains isolated from a single farm.

Cholinergic involvement and synaptic dynamin 1 expression in Yokukansan-mediated improvement of spatial memory in a rat model of early Alzheimer's disease.

The aim of this study was to investigate the effect of Yokukansan (YKS) on the impairment of spatial memory and cholinergic involvement in a rat model of early-phase Alzheimer's disease (AD). In this model, rats underwent four-vessel transient cerebral ischemia and then were treated with beta amyloid oligomers injected intracerebroventricularly once daily for 7 days. These animals showed memory impairment in an eight-arm radial maze task without histological evidence of apoptosis but with a decrease in expression of hippocampal dynamin 1, an important factor in synaptic vesicle endocytosis. Oral administration of YKS for 2 weeks significantly increased the number of correct choices and decreased the number of error choices in the eight-arm radial maze task (P < 0.05). Moreover, YKS significantly increased high K⁺-evoked potentiation of acetylcholine (ACh) release (P < 0.05) and significantly increased the expression of dynamin 1 (P < 0.01) in the hippocampus. The ameliorative effect of YKS on spatial memory impairment in our rat model of early-phase AD may be mediated in part by an increase in ACh release and modulation of dynamin 1 expression, leading to improved synaptic function. Future studies will determine whether YKS is similarly useful in the treatment of memory defects in patients diagnosed with early-stage AD.

Urinary profiles of methoxyphenamine and its metabolite after inhalation of methoxyphenamine smoke in humans: aiming to distinguish between active and passive exposure.

PURPOSE: Methamphetamine (METH) is commonly abused through smoking. However, the lack of evidence regarding differences in urinary METH excretion after its active and passive inhalation has resulted in complications where the accused claims passive exposure. This study aimed to determine the differences in urinary excretion after active and passive inhalation of the drug, using methoxyphenamine (MPA) as a model for METH. METHODS: Body temperature and locomotor activity were measured in mice as indicators of central nervous system toxicity. Six healthy adult male subjects were exposed to passive or active inhalation of MPA smoke in a small room, and urine samples were taken. MPA concentrations were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: There were no signs of toxicity in mice exposed to MPA smoke, ensuring the safety of the clinical study. Urinary MPA concentrations were significantly lower with passive inhalation compared with those of active inhalation. The maximum urinary MPA concentration in passive inhalation was 13.4 ng/mL, which was 1/60 of active inhalation with 800 ng/mL. The urinary excretion in passive inhalation until 24 h was 8.21 µg, which was 1/76 of active inhalation with 625 µg. CONCLUSIONS: Since METH and MPA are expected to be excreted similarly, urinary METH concentrations in passively exposed persons are expected to be lower than the cutoff value of the screening kit. If the urine screening test is positive, the suspect should be considered a METH user. TRIAL REGISTRATION NUMBER: jRCTs031210604, registration date: Feb. 9, 2022.

Adolescent Persistent Atrial Fibrillation Concomitant with Pectus Excavatum.

A 19-year-old man with pectus excavatum developed symptomatic persistent atrial fibrillation (AF). He had no remarkable medical history or comorbidities and had not exercised intensely during childhood. Electrical cardioversion and pre-treatment with amiodarone for two months failed to maintain sinus rhythm. Computed tomography before ablation revealed compression of the right and left atria between the sternal bone and vertebral bodies. Voltage mapping revealed that the right and left atrial voltages were preserved within the normal limit. However, radiofrequency catheter ablation successfully eliminated recurrent persistent AF. No recurrence was observed during eight months of follow-up.

Ability of older male caregivers to seek help when caring for a wife or mother with dementia living at home.

Objective: We aimed to clarify factors associated with the ability to seek help among older male caregivers who care for women with dementia in their families. Patients and Methods: This information will inform strategies to support their continued provision of long-term care. Participants were 364 male caregivers recruited from three places: The study period was 2017-2018. We obtained ethical approval for this study from the relevant ethics committee. Results: The ability to seek help for care problems among male caregivers was normally distributed. We found that more than 90% of older male caregivers did not actively seek help to resolve care problems, suggesting that older male caregivers had problems with long-term care. In the high score group, health status and the number of emotional support persons in the household were significantly and somewhat strongly positively correlated. The low score group showed a significant and rather weak positive correlation between economic status and health status, and the number of emotional supporters inside and outside the household. Positive correlations for the high score group were self-esteem and depressive symptoms, and self-esteem and resources. Positive correlations for the low score group were self-esteem and depressive symptoms, self-esteem and resources, and resources and depressive symptoms. Conclusion: Male caregivers are more likely to seek help if they are employed or play a role in their community. Nurses also need to support male caregivers with positive words and praise to help them use available support and resources and continue to provide long-term care. It is important for healthcare professionals to observe whether a caregiver presents with depressive symptoms or has long-term care problems because older male caregivers do not seek help. Collaboration between caregivers and medical, long-term care, and welfare professionals is necessary. Direct and timely intervention is needed.

Effect of vitamin D receptor activators on cardiovascular events in patients on hemodialysis-A post hoc analysis of the LANDMARK study.

INTRODUCTION: The clinical benefit of vitamin D receptor activators (VDRA) in patients with well-controlled secondary hyperparathyroidism undergoing dialysis remains unclear. METHODS: This post hoc analysis of the LANDMARK study investigates if VDRA use is associated with cardiovascular benefits. Data of 2135 patients undergoing hemodialysis who were at risk for vascular calcification were analyzed using a Cox proportional hazards model with propensity-score matching. RESULTS: The hazard ratio (HR) for VDRA use was 0.99 (95% confidence interval [CI]: 0.67-1.46; p = 0.945) for cardiovascular events and 0.89 (95% CI: 0.62-1.28; p = 0.541) for all-cause mortality at baseline. Among patients who always used VDRA, the HR was 1.12 (95% CI: 0.67-1.89; p = 0.666) for cardiovascular events and 1.11 (95% CI: 0.67-1.85; p = 0.688) for all-cause mortality compared to those who never used VDRA. CONCLUSION: The use of VDRA does not reduce the risks of cardiovascular events or all-cause mortality in patients on dialysis with well-controlled secondary hyperparathyroidism.

A Study on Pharmacokinetics of Acetylsalicylic Acid Mini-Tablets in Healthy Adult Males-Comparison with the Powder Formulation.

Children with Kawasaki disease are prescribed acetylsalicylic acid powder as an antipyretic analgesic and antiplatelet agent; however, some of it remains in the mouth, leading to a bitter or sour taste. To address this issue, an in-hospital mini-tablet formulation of acetylsalicylic acid was developed. In order to use the mini-tablets safely and effectively, dissolution tests alone are not sufficient. Therefore, an open-label crossover study on six healthy participants was conducted to evaluate comparative pharmacokinetic parameters. The pharmacokinetic parameters of salicylic acid were Cmax: 4.80 ± 0.79 mg/L (powder; P), 5.03 ± 0.97 mg/L (mini-tablet; MT), AUC0-12: 18.0 ± 3.03 mg-h/L (P), 18.9 ± 4.59 mg-h/L (MT), those of acetylsalicylic acid Cmax: 0.50 ± 0.20 mg/L (P), 0.41 ± 0.24 mg/L (MT), AUC0-12: 0.71 ± 0.27 mg-h/L (P), 0.61 ± 0.36 mg-h/L (MT), with no significant differences between the mini-tablet and powder formulations. Although pharmacokinetic results obtained from adults cannot be directly applied to children, the results of this study are important for predicting pharmacokinetics. Furthermore, a formulation that can improve medication adherence in children who have difficulty taking acetylsalicylic acid powder, thus contributing to pediatric drug therapy.

Sedation Therapy in Intensive Care Units: Harnessing the Power of Antioxidants to Combat Oxidative Stress.

In critically ill patients requiring intensive care, increased oxidative stress plays an important role in pathogenesis. Sedatives are widely used for sedation in many of these patients. Some sedatives are known antioxidants. However, no studies have evaluated the direct scavenging activity of various sedative agents on different free radicals. This study aimed to determine whether common sedatives (propofol, thiopental, and dexmedetomidine (DEX)) have direct free radical scavenging activity against various free radicals using in vitro electron spin resonance. Superoxide, hydroxyl radical, singlet oxygen, and nitric oxide (NO) direct scavenging activities were measured. All sedatives scavenged different types of free radicals. DEX, a new sedative, also scavenged hydroxyl radicals. Thiopental scavenged all types of free radicals, including NO, whereas propofol did not scavenge superoxide radicals. In this retrospective analysis, we observed changes in oxidative antioxidant markers following the administration of thiopental in patients with severe head trauma. We identified the direct radical-scavenging activity of various sedatives used in clinical settings. Furthermore, we reported a representative case of traumatic brain injury wherein thiopental administration dramatically affected oxidative-stress-related biomarkers. This study suggests that, in the future, sedatives containing thiopental may be redeveloped as an antioxidant therapy through further clinical research.

Ameliorative effects of telmisartan on the inflammatory response and impaired spatial memory in a rat model of Alzheimer's disease incorporating additional cerebrovascular disease factors.

Telmisartan, an angiotensin type 1 receptor blocker, is used in the management of hypertension to control blood pressure. In addition, telmisartan has a partial agonistic effect on peroxisome proliferator activated receptor γ (PPARγ). Recently, the effects of telmisartan on spatial memory or the inflammatory response were monitored in a mouse model of Alzheimer's disease (AD). However, to date, no studies have investigated the ameliorative effects of telmisartan on impaired spatial memory and the inflammatory response in an AD animal model incorporating additional cerebrovascular disease factors. In this study, we examined the effect of telmisartan on spatial memory impairment and the inflammatory response in a rat model of AD incorporating additional cerebrovascular disease factors. Rats were subjected to cerebral ischemia and an intracerebroventricular injection of oligomeric or aggregated amyloid-ß (Aß). Oral administration of telmisartan (0.3, 1, 3 mg/kg/d) seven days after ischemia and Aß treatment resulted in better performance in the eight arm radial maze task in a dose-dependent manner. Telmisartan also reduced tumor necrosis factor α mRNA expression in the hippocampal region of rats with impaired spatial memory. These effects of telmisartan were antagonized by GW9662, an antagonist of PPARγ. These results suggest that telmisartan has ameliorative effects on the impairment of spatial memory in a rat model of AD incorporating additional cerebrovascular disease factors via its anti-inflammatory effect.