Efficacy and safety of perioperative melatonin for postoperative delirium in patients undergoing surgery: a systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of perioperative melatonin and melatonin agonists in preventing postoperative delirium (POD). METHODS: We conducted a systematic search for randomized controlled trials (RCTs) published through December 2022. The primary outcome was efficacy based on the incidence of POD (POD-I). Secondary outcomes included efficacy and safety according to the length of hospital or intensive care unit stay, in-hospital mortality, and adverse events. Subgroup analyses of POD-I were based on the type and dose of drug (low- and high-dose melatonin, ramelteon), the postoperative period (early or late), and the type of surgery. RESULTS: In the analysis (16 RCTs, 1981 patients), POD-I was lower in the treatment group than in the control group (risk ratio [RR] = 0.57). POD-I was lower in the high-dose melatonin group than in the control group (RR = 0.41), whereas no benefit was observed in the low-dose melatonin and ramelteon groups. POD-I was lower in the melatonin group in the early postoperative period (RR = 0.35) and in patients undergoing cardiopulmonary surgery (RR = 0.54). CONCLUSION: Perioperative melatonin or melatonin agonist treatment suppressed POD without severe adverse events, particularly at higher doses, during the early postoperative period, and after cardiopulmonary surgery.

A single-center prospective study regarding time to return to activities of daily living after craniotomy for brain tumors.

BACKGROUND: There are few studies on the time to return to activities of daily living (ADL) after craniotomy in patients with brain tumors. This study aimed to investigate the duration before returning to ADLs after craniotomy for brain tumors and present data that can provide information and guidelines on the appropriate time needed. METHODS: Patients (n = 183 of 234) who underwent craniotomy for brain tumors between April 2021 and July 2021 capable of self-care upon discharge were enrolled, and data of 158 were collected. The start time of 85 ADL items was prospectively investigated for 4 months postoperatively, using the self-recording sheet. RESULTS: Over 89% and 87% of the patients performed basic ADL items within a month and instrumental ADL items within 2 months (medians: within 18 days), except for a few. Regarding work, 50% of the patients returned within 4 months. Washing hair with a wound was performed at 18 days of median value, after 4 months of dyeing/perming hair, 6 days of drinking coffee/tea, after 4 months of air travel, and 40 days of complementary and alternative medicine. In patients with infratentorial tumors or surgical problems, return times were much later for various items. CONCLUSIONS: It is possible to provide practical information and guidelines on the duration to return to ADL after craniotomy in brain tumor patients. These study findings also reduce uncertainty about recovery and daily life and help patients return to their daily life at the appropriate time, thereby maintaining function and daily well-being after surgery.

Pharmacokinetic comparison of a fixed-dose combination versus concomitant administration of amlodipine, olmesartan, and rosuvastatin in healthy adult subjects.

Objective: The aim of this study was to compare the pharmacokinetic (PK) and safety profiles of a fixed dose combination (FDC) formulation and co-administration of amlodipine, olmesartan, and rosuvastatin. Materials and methods: This study was an open-label, randomized, cross-over design conducted in healthy male volunteers. All subjects received either a single FDC tablet containing amlodipine 10 mg/olmesartan 40 mg/rosuvastatin 20 mg, or were co-administered an FDC tablet containing amlodipine 10 mg/olmesartan 40 mg and a tablet containing rosuvastatin 20 mg, for each period, with 14-day washout periods. Plasma concentrations of amlodipine, olmesartan, and rosuvastatin were measured by liquid chromatography tandem mass spectrometry. Safety was evaluated by measuring vital signs, clinical laboratory parameters, physical examinations, and medical interviews. Results: Sixty-four subjects were enrolled, and 54 completed the study. The geometric mean ratios and 90% CI for the maximum plasma concentration (Cmax) and area under the curve from time zero to the last sampling time (AUCt) were 1.0716 (1.0369,1.1074) and 1.0497 (1.0243,1.0757) for amlodipine, 1.0396 (0.9818,1.1009) and 1.0138 (0.9716,1.0578) for olmesartan, and 1.0257 (0.9433,1.1152) and 1.0043 (0.9453,1.0669) for rosuvastatin. Fourteen cases of adverse events occurred in 12 subjects. There was no statistically significant clinical difference between the formulation groups. Conclusion: The 90% CI of the primary PK parameters were within the acceptance bioequivalence criteria, which is ln (0.8) and ln (1.25). These results indicate that the FDC formulation and co-administration of amlodipine, olmesartan and rosuvastatin are pharmacokinetically bioequivalent and have similar safety profiles.

Metabolic profiling of tyrosine, tryptophan, and glutamate in human urine using gas chromatography-tandem mass spectrometry combined with single SPE cleanup.

The tyrosine, tryptophan, and glutamate metabolic pathways play key roles on pathological state of neuronal functions and the change of their levels in biological systems reflects the progress degree of neuronal diseases. Comprehensive profiling of these metabolites is important to find new biomarkers for diagnosis or prognosis of various neuronal diseases. However, the overall profiling analysis of various neurochemicals in biological sample is confronted with several limitations due to their low concentration and physicochemical properties and the coexistence of matrices. We developed an efficient and feasible method using gas chromatography-tandem mass spectrometry (GC-MS/MS). Wide-bore mixed cation exchange (MCX) SPE process enables a rapid and effective cleanup of 20 neurochemicals even including acidic and basic neurochemicals in a single SPE cartridge by using different composition of eluents. Selective derivatization of various types of metabolites was applied to achieve highly chromatographic separation and sensitive mass detection. Appropriate selection of precursor and product transition ions used in multiple reaction-monitoring (MRM) mode based on the MS/MS fragmentations of the derivatized neurochemicals could be significantly minimized the matrix effects and enhanced the reliability of quantification results. The developed method was validated in terms of linearity, limits of detection, precision, accuracy, and matrix effects. The intra- and inter-assay analytical variations were less than 10%. The overall linearity for all of the targets was excellent (R2≥0.996). The detection limits ranged between 0.38 and 8.13ng/mL for the acidic neurochemicals and between 0.02 and 11.1ng/mL for the basic neurochemicals. The developed protocol will be expected to be a promising tool for the understanding of the pathological state and diagnosis of various neuronal diseases.

Associations of Sarcopenia and Sarcopenic Obesity With Metabolic Syndrome Considering Both Muscle Mass and Muscle Strength.

OBJECTIVES: We investigated the associations of sarcopenia-defined both in terms of muscle mass and muscle strength-and sarcopenic obesity with metabolic syndrome. METHODS: Secondary data pertaining to 309 subjects (85 men and 224 women) were collected from participants in exercise programs at a health center in a suburban area. Muscle mass was measured using bioelectrical impedance analysis, and muscle strength was measured via handgrip strength. Sarcopenia based on muscle mass alone was defined as a weight-adjusted skeletal muscle mass index more than two standard deviations below the mean of a sex-specific young reference group (class II sarcopenia). Two cut-off values for low handgrip strength were used: the first criteria were <26 kg for men and <18 kg for women, and the second criteria were the lowest quintile of handgrip strength among the study subjects. Sarcopenic obesity was defined as the combination of class II sarcopenia and being in the two highest quintiles of total body fat percentage among the subjects. The associations of sarcopenia and sarcopenic obesity with metabolic syndrome were evaluated using logistic regression models. RESULTS: The age-adjusted risk ratios (RRs) of metabolic syndrome being compared in people with or without sarcopenia defined in terms of muscle mass were 1.25 (95% confidence interval [CI], 1.06 to 1.47, p=0.008) in men and 1.12 (95% CI, 1.06 to 1.19, p<0.001) in women, which were found to be statistically significant relationships. The RRs of metabolic syndrome being compared in people with or without sarcopenic obesity were 1.31 in men (95% CI, 1.10 to 1.56, p=0.003) and 1.17 in women (95% CI, 1.10 to 1.25, p<0.001), which were likewise found to be statistically significant relationships. CONCLUSIONS: The associations of sarcopenia defined in terms of muscle mass and sarcopenic obesity with metabolic syndrome were statistically significant in both men and women. Therefore, sarcopenia and sarcopenic obesity must be considered as part of the community-based management of non-communicable diseases.

Comprehensive profiling analysis of bioamines and their acidic metabolites in human urine by gas chromatography/mass spectrometry combined with selective derivatization.

A comprehensive analytical method was developed for the profiling of biogenic amines in human urine using GC/MS in SIM mode. Biogenic amines and their acidic metabolites were converted into their volatile O-trimethylsilyl/N-heptafluorobutyryl (OTMS/-NHFBA) derivatives for GC/MS analysis. Dual hexamethyldisilazane (HMDS)/-N-methyl-bis-heptafluorobutyramide (MBHFBA) derivatizations have been shown to be quite effective, with high derivatization yields and the absence of side products for primary biogenic amines. In this study, selective derivatization conditions by HMDS/MBHFBA were optimized in terms of the reagent amount, reaction temperature and reaction time period. The highest derivatization reaction yield was obtained at 40°C for 10min for OTMS derivatization and 80°C for 5min for N-HFBA derivatization. The use of MCX SPE cartridges with different SPE elution solvents was effective for the pre-concentration and selective cleanup of the biogenic amines and their acidic metabolites in human urine. The selection of appropriate ions in SIM mode provided reliable quantification and identification and a reduction in background effects. The established method was validated in terms of linearity, limits of detection (LOD), limits of quantification (LOQ), precision, and accuracy. The present method was linear (r(2)>0.996), reproducible (relative standard deviation range 1.1-6.9%), and accurate (range 87.9-111.9%), with LOQs of 0.17-17.84ng/mL. The biogenic amine profiling of human urine was successfully accomplished by GC/MS in SIM mode combined with selective HMDS/MBHFBA derivatization and MCX SPE cleanup.

Serum deprivation increases the expression of low density lipoprotein receptor-related protein in primary cultured rat astrocytes.

The low density lipoprotein receptor (LDLR)-related protein (LRP) is a multifunctional receptor which mediates the endocytic uptake of several ligands implicated in Alzheimer's disease pathophysiology. Although LRP, as a member of the LDLR family, is likely to be regulated in response to various cellular stresses, this regulation has not been fully understood yet. In the present study we studied the regulation of LRP expression in primary cultured rat astrocytes in response to serum deprivation as a general cellular stress. A significant increase in LRP expression was detected after serum deprivation and this increase was blocked by treatment of U0126, an inhibitor of MAP kinase. This serum deprivation action was partially reversed by either serum or D-glucose supplementation, but further augmented by glutamine. This result contrasted with a finding that glutamine suppressed gadd153 protein induced by serum deprivation. Taken together, the present data suggest that serum deprivation induces dramatically LRP expression in astrocytes partly by MAPK signaling pathways and by signaling pathways apparently distinct from gadd153 induction.