Search

We analyzed the effect of Na-glucose cotransporter 2 inhibitors (SGLT2-I) in diabetic patients visiting our hospital. The study included 236 patients treated with SGLT2-I alone or with codiabetic drugs for at least two years. We analyzed overtime changes in glycosylated hemoglobin A1c (HbA1c) in the patients by repeated analyses of variance (ANOVA) and evaluated the therapeutic effect. HbA1c levels decreased significantly in the first six months after treatment. Afterward, they leveled off and increased slightly over the next two years. Six months after treatment, the mean (SD) of HbA1c was 8.19 (1.46) %; the mean difference dropped by 0.91%, and HbA1c in mild DM2 did not drop by below 8.0%. Overall, there was only a slight improvement. We performed multivariate logistic regression analysis using a model with or without improvement as the objective variable and several explanatory variables. Na and Hct were significant factors. They increased considerably over six months and then leveled off. eGFR significantly reduced in the hyperfiltration group six months after treatment. The annual decline rate in eGFR was also faster, even in the nonhyperfiltration group than in the healthy subjects, which may be a characteristic of renal clearance in SGLT2-I treatment. In conclusion, SGLT2-I is an excellent antidiabetic, nephroprotective agent to eliminate hyperfiltration, but unfortunately, SGLT2-I alone does not have enough power to reduce blood glucose levels. SGLT2-I, with insulin or insulin secretagogues, enhances insulin resistance, induces hyperinsulinemia, and exacerbates type 2 DM. In contrast, SGLT2-I, with noninsulin antidiabetic agents and a low-carbohydrate diet, may bring better results. [ABSTRACT FROM AUTHOR]

FROUNT is a cytoplasmic protein that interacts with the membrane-proximal C-terminal regions (Pro-Cs) of the CCR2 and CCR5 chemokine receptors. The interactions between FROUNT and the chemokine receptors play an important role in the migration of inflammatory immune cells. Therefore, FROUNT is a potential drug target for inflammatory diseases. However, the structural basis of the interactions between FROUNT and the chemokine receptors remains to be elucidated. We previously identified the C-terminal region (residues 532-656) of FROUNT as the structural domain responsible for the Pro-C binding, referred to as the chemokine receptor-binding domain (CRBD), and then constructed its mutant, bearing L538E/P612S mutations, with improved NMR spectral quality, referred to as CRBD_LEPS. We now report the main-chain and side-chain 1H, 13C, and 15N resonance assignments of CRBD_LEPS. The NMR signals of CRBD_LEPS were well dispersed and their intensities were uniform on the 1H-15N HSQC spectrum, and thus almost all of the main-chain and side-chain resonances were assigned. This assignment information provides the foundation for NMR studies of the three-dimensional structure of CRBD_LEPS in solution and its interactions with chemokine receptors. [ABSTRACT FROM AUTHOR]

Background: Albumin is considered a negative acute-phase protein because its concentration decreases during injury and sepsis. Hypoalbuminemia is a risk factor for mortality, postoperative complications, and prolonged hospital stay. The magnitude of the systemic inflammatory response during the perioperative period, as indicated by the acute-phase proteins—C-reactive protein (CRP) in particular—, may help identify the risk of postoperative infectious complication. The correlation between serum albumin and CRP with gastrointestinal cancer has been reported. However, it is unclear whether antecedent CRP could be utilized to predict future hypoalbuminemia in the perioperative period in colorectal surgery. The primary endpoint of this study was to reveal that antecedent CRP could be utilized to predict future hypoalbuminemia in the perioperative period of colorectal surgery. Methods: Thirty-seven patients who underwent elective open colorectal surgery were included in this study. Correlations between preoperative CRP and serum albumin on postoperative day (POD) 3, between preoperative CRP and serum albumin on POD 7 and between CRP on POD 3 and serum albumin on POD 7 were examined. Relationships between preoperative CRP and hypoalbuminemia on POD 3, between preoperative CRP and hypoalbuminemia on POD 7 and between CRP on POD 3 and hypoalbuminemia on POD 7 were examined by receiver operating characteristic analysis. Results: Three-quarters of patients were older than 65 years of age. Significant correlations were observed between preoperative CRP and serum albumin on POD 3 (p = 0.023), between preoperative CRP and serum albumin on POD 7 (p = 0.023) and between CRP on POD 3 and serum albumin on POD 7 (p < 0.001). The area under the receiver operating characteristic curve of CRP on POD 3 to development of hypoalbuminemia on POD 7 was 0.833 (95 % CI 0.679–0.987) with an optimal threshold of 12.43 mg/dL, sensitivity 75 % and specificity 80 %. Conclusions: The present study revealed that antecedent CRP was associated with future serum albumin. Additionally, CRP on POD 3 could be useful in predicting the development of hypoalbuminemia on POD 7. This result suggests that CRP on POD 3 may be a valuable indicator for early nutritional intervention. [ABSTRACT FROM AUTHOR]

A novel magnetic levitation train system can be constructed by using a long-stator controlled-PM linear synchronous motor having propulsion and attractive-mode levitation functions and minimum loss. Realizing this system requires simplifying manufacture of the log-stator guideway. In the long-stator on the ground, semiclosed large slots are adapted and designed for one-turn coils of a waveform to be easily installed. The large slots cause of the PM LSM detent forces to give strong influences on dynamic operations of the running vehicle. A two-dimensional FEM used for the dynamics simulations is capable of precisely analyzing the detent forces produced between the stator teeth and the PMs. This paper presents FEM dynamics simulations and experiments in mass-reduced-control mode of ½ scale model magnetic levitation vehicle supported by small rubber rollers. The simulation model developed here includes the vehicle speed performance, position sensors and drag force due to friction between rubber roller and rail. The detent force problem in propulsion motion is successfully solved by adapting the feedback control of the vehicle propulsion based on the I10-controlled method. The trajectory control is thus accomplished for the vehicle to follow speed and position patterns. The dynamics simulations are verified from the experiments. The simulation program proposed here enables us to investigate the magnetic levitation train system, including LSM design and vehicle dynamic operations. [ABSTRACT FROM AUTHOR]

Background: Clinical decision support systems (CDSS) are reported to be useful in preventing dosage errors in renally excreted drugs by alerting hospital pharmacists to inadequate dosages for hospitalized patients with decreased GFR. However, it is unclear whether CDSS can reduce dosage errors in renally excreted drugs in hospitalized patients. To prevent dosage errors in renally excreted drugs, we introduced a prescription checking system (PCS) for in-hospital prescriptions. This retrospective study aimed to evaluate whether a prescription audit by hospital pharmacists using the PCS reduced the rate of dosage errors in renally excreted drugs., Methods: The target drugs were allopurinol, cibenzoline, famotidine, and pilsicainide. Interrupted time series analysis was used to evaluate trends in the 4-weekly dosage error rates over 52 weeks before PCS implementation and 52 weeks after PCS implementation., Results: Before and after PCS implementation, 474 and 331 prescriptions containing one of the targeted drugs, respectively, were generated. The estimated baseline level of the 4-weekly dosage error rates was 34%. The trend before the PCS implementation was stable with no observable trend. The estimated level change from the last point in the pre-PCS implementation to the first point in the PCS implementation was -20% ( P <0.001). There was no change in the trend after PCS implementation., Conclusions: We demonstrated that a prescription audit by hospital pharmacists using the PCS reduced the rate of dosage errors in the target renally excreted drugs in hospitalized patients. Although further studies are needed to confirm whether our results can be generalized to other health facilities, our findings highlight the need for a PCS to prevent the overdose of renally excreted drugs., Competing Interests: T. Irie reports having patents or royalties with the Safety Medical System Laboratory Corporation. Y. Ishitsuka reports having patents or royalties with the Safety Medical System Laboratory Corporation. Y. Kondo reports receiving research funding from AYUMI Pharmaceutical Corporation and Safety Medical System Laboratory Corporation; having patents or royalties with the Safety Medical System Laboratory Corporation; and serving in an advisory or leadership role for Safety Medical System Laboratory Corporation (unpaid). All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

An administration plan for vancomycin (VCM) in bedridden elderly patients has not been established. This retrospective study aimed to evaluate the prediction accuracy of the area under the concentration-time curve (AUC) of VCM by the Bayesian approach using creatinine-based equations of estimated kidney function in such patients. Kidney function was estimated using the Japanese equation of estimated glomerular filtration rate (eGFR) and the Cockcroft-Gault equation of estimated creatinine clearance (eCCr). eCCr (serum creatinine (SCr) + 0.2) was calculated by substituting the SCr level +0.2 mg/dL into the Cockcroft-Gault equation. For eGFR/0.789, eGFR, eCCr, and eCCr (SCr + 0.2), the AUC values were calculated by the Bayesian approach using the therapeutic drug monitoring (TDM) software, BMs-Pod (ver 8.06) and denoted as AUC eGFR/0.789 , AUC eGFR , AUC eCCr , and AUC eCCr (SCr + 0.2) respectively. The reference AUC (AUC REF ) was calculated by applying VCM's peak and trough steady-state concentrations to first-order pharmacokinetic equations. The medians (range) of AUC eGFR/0.789 /AUC REF , AUC eGFR /AUC REF , AUC eCCr /AUC REF , and AUC eCCr (SCr + 0.2) /AUC REF were 0.88 (0.74-0.93), 0.90 (0.79-1.04), 0.92 (0.81-1.07), and 1.00 (0.88-1.11), respectively. Moreover, the percentage of patients within 10% of the AUC REF , defined as |Bayesian-estimated AUC - AUC REF | < AUC REF  × 0.1, was the highest (86%) in AUC eCCr (SCr + 0.2) . These results suggest that the Bayesian approach using eCCr (SCr + 0.2) has the highest prediction accuracy for the AUC REF in bedridden elderly patients. Although further studies are required with more accurate determination methods of the CCr and AUC, our findings highlight the potential of eCCr (SCr + 0.2) for estimating VCM's AUC by the Bayesian approach in such patients.

Suppression of protein aggregation is a subject of growing importance in the treatment of protein aggregation diseases, an urgent worldwide human health problem, and the production of therapeutic proteins, such as antibody drugs. We previously reported a method to identify compounds that suppress aggregation, based on screening using multiple terminal deletion mutants. We now present a method to determine the aggregation contact sites of proteins, using such solubilizing compounds, to design monodispersed mutants. We applied this strategy to the chemokine receptor-binding domain (CRBD) of FROUNT, which binds to the membrane-proximal C-terminal intracellular region of CCR2. Initially, the backbone NMR signals were assigned to a certain extent by available methods, and the putative locations of five α-helices were identified. Based on NMR chemical shift perturbations upon varying the protein concentrations, the first and third helices were found to contain the aggregation contact sites. The two helices are amphiphilic, and based on an NMR titration with 1,6-hexanediol, a CRBD solubilizing compound, the contact sites were identified as the hydrophobic patches located on the hydrophilic sides of the two helices. Subsequently, we designed multiple mutants targeting amino acid residues on the contact sites. Based on their NMR spectra, a doubly mutated CRBD (L538E/P612S) was selected from the designed mutants, and its monodispersed nature was confirmed by other biophysical methods. We then assessed the CCR2-binding activities of the mutants. Our method is useful for the protein structural analyses, the treatment of protein aggregation diseases, and the improvement of therapeutic proteins.

Background: The aims of this study were to investigate predictive factors involved in effectiveness and safety of enoxaparin for prevention of postoperative venous thromboembolism in aged Japanese total knee arthroplasty (TKA) patients., Methods: Japanese patients over 65 years old who were administered enoxaparin for TKA were enrolled in this study. Their medical records were retrospectively reviewed. Data were corrected at the Izumi Regional Medical Center, from September 2009 to March 2014. Patients were stratified into groups according to whether enoxaparin was effective (no deep vein thrombosis event up to postoperative day 7) or not, and whether they had an adverse drug event (ADE) or not., Results: A total of 128 patients were included in this study. One hundred five (82.0%) patients were in the effective group and 20 (15.6%) in the adverse drug event (ADE) group. Anemia (13 patients), abnormalities in liver function tests (4 patients), clinically relevant non-major bleeding (4 patients) and urticaria (1 patient) were observed as ADEs. Multivariate logistic regression analysis showed that the serum total protein level at postoperative day 1 (POD1, before enoxaparin administration), was associated with effectiveness of enoxaparin, while the serum total protein and hemoglobin level at POD1 were involved in ADE caused by enoxaparin., Conclusions: Although further large scale studies will be warranted, our results suggest that serum total protein level just before enoxaparin treatment for TKA relates to the effectiveness and safety of enoxaparin in a Japanese aged population. In addition, the results indicate that the development of anemia should be carefully monitored during enoxaparin treatment for TKA, particularly in patients with lower levels of serum hemoglobin before treatment.

We previously reported lower lymphocyte vitamin C levels in individuals with type 2 diabetes mellitus and in individuals with severe Parkinson's disease. Oxidative stress has been proposed to play a key role in the progression of Alzheimer's disease. Thus, the objective of this study was to investigate the association between peripheral levels of vitamin C and the progression of cognitive dysfunction in Alzheimer's disease. Fifty individuals with Alzheimer's disease being treated at Shizuoka General Hospital were consecutively enrolled in this study from December 2009 to March 2015 (76.0±9.7 y of age [mean±SD]; 32 men and 18 women; Mini-Mental State Examination Japanese version (MMSE-J) score range, 8-27). Plasma and lymphocyte vitamin C levels in fasting blood samples were measured. The association between the MMSE-J scores and vitamin C levels was estimated using Spearman's rank correlation coefficient (ρ) and the criteria defined by Swinscow. Spearman's ρ for the relationship between peripheral vitamin C levels and the MMSE-J score was ρ=0.17 for plasma vitamin C and ρ=0.26 for lymphocyte vitamin C. Thus, the associations were relatively weak based on the criteria. In contrast with type 2 diabetes mellitus and Parkinson's disease, lymphocyte vitamin C levels in the peripheral blood may not directly reflect the progression of cognitive dysfunction in Alzheimer's disease. Additional longitudinal studies are needed to evaluate the clinical importance of changes of peripheral vitamin C status in Alzheimer's disease.