Reciprocal Fluctuations in Lipoprotein Lipase, Glycosylphosphatidylinositol-Anchored High-Density Lipoprotein-Binding Protein 1, and Hepatic Triglyceride Lipase Levels in the Peripheral Bloodstream Are Correlated with Insulin Resistance.

This study aimed to identify the regulatory system of lipoprotein lipase (LPL), glycosylphosphatidylinositol-anchored high-density lipoprotein (HDL)-binding protein 1 (GPIHBP1), and hepatic triglyceride lipase (HTGL) in the peripheral bloodstream. : In total, 207 individuals (100 males and 107 females) who were diagnosed with normal glucose tolerance or prediabetes during their comprehensive health checkup were investigated. : Circulating LPL levels were positively correlated with the GPIHBP1 and HDL-cholesterol (HDL-C) levels, and negatively correlated with body mass index (BMI), waist circumference (WC), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) scores, triglyceride-glucose index, and triglyceride, fasting insulin, ferritin, and C-reactive protein (CRP) levels.

Pharmacokinetic and Pharmacodynamic Assessment of Valganciclovir in Infants With Congenital Cytomegalovirus Infection.

Background: Valganciclovir (VGCV) is administered at a dose of 16 mg/kg 2 times daily for 6 months to treat symptomatic congenital cytomegalovirus (CMV) infections. During the treatment period, approximately 20% of the patients developed grade 3 or higher neutropenia. Currently, information on the pharmacokinetics and pharmacodynamics of ganciclovir, an active metabolite of VGCV, in infants is limited.

Neonatal metabolic alkalosis and mild diuresis resulting from torasemide self-medication by the mother: a case report.

Background: Torasemide, a loop diuretic, is rarely used for pregnant women because of the risk of reduced placental blood flow resulting from decreased circulating plasma volume. We experienced a case of a newborn with metabolic alkalosis and mild polyuria. The mother was suspected of self-medicating as we detected torasemide in the neonatal serum by LC-MS/MS method.

Pharmacokinetics of Brexpiprazole, Quetiapine, Risperidone, and Its Active Metabolite Paliperidone in a Postpartum Woman and Her Baby.

Background: Brexpiprazole is a second-generation antipsychotic approved in Japan in 2018; however, information on placental passage and breast milk transfer remains limited. In this report, the patient, a 30-year-old pregnant woman with schizophrenia, was medicated with brexpiprazole, risperidone, and quetiapine.

Methods: The study used high-performance liquid chromatography-tandem mass spectrometry to determine the concentrations of brexpiprazole, quetiapine, risperidone, and its active metabolite (paliperidone) in maternal and neonatal plasma, cord venous plasma, and breast milk.

An unusual case of fatal hypothermia involving topical diphenhydramine.

Purpose: Diphenhydramine is an antihistamine drug widely used to alleviate symptoms caused by allergies and the common cold. Diphenhydramine-involved fatalities have been reported in the past but usually involving overdose by ingestion. We report a peculiar case of fatal hypothermia during non-winter season involving topical diphenhydramine.

Local Variation and Age-Related Change in Atrial and Ventricular Myocardial Contiguity at the Atrioventricular Junction in Human Hearts.

We explored the histologic patterns of and age-related changes in atrial and ventricular myocardial contiguity at the left and right atrioventricular (AV) junction that could be a target site for catheter ablation. Twenty-three structurally normal adult hearts obtained at autopsy were studied. The 2 AV annuli were divided into 13 clinically recognized portions in which we measured distance between the atrial and ventricular myocardium at the AV junction.

[Performing integrative transcriptomic and chemical screening to identify patient-specific vulnerabilities in poor-prognosis acute myeloid leukemia].

Genetic complexity and heterogeneity have made drug discovery difficult in human malignancies. In the past few years, we aimed to find vulnerabilities in therapy-resistant and refractory acute myeloid leukemia (AML) through integrative analyses of genomic data, clinical information, and results from in vivo/in vitro cell biological assays. Through analyses, we found that the cells of patients with AML show distinct sensitivity/resistance to small inhibiting molecules for anti-apoptosis and cell cycle/division.

Potentially harmful excipients in neonatal medications: a multicenter nationwide observational study in Japan.

Background: A multicenter investigation of neonate exposure to potentially harmful excipients (PHEs) in neonatal intensive care units (NICUs) in Japan has not been conducted.

Methods: A multicenter nationwide observational study was conducted. Neonate patient demographic data and information on all medicines prescribed and administered during hospitalization on 1 day between November 2019 and March 2021 were extracted from the medical records.

High-throughput identification and determination of aminoglycoside antibiotics in human plasma using UPLC-Q-ToF-MS.

Aminoglycosides are a class of broad-spectrum antibiotics with several clinical uses. Owing to the ototoxicity and nephrotoxicity of aminoglycosides, therapeutic drug monitoring is required. This study aimed to devise a high-throughput method for identification and quantitative determination of aminoglycoside antibiotics in human plasma samples using ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q-ToF-MS).

Targeting critical kinases and anti-apoptotic molecules overcomes steroid resistance in MLL-rearranged leukaemia.

Background: Acute lymphoblastic leukaemia with mixed lineage leukaemia gene rearrangement (MLL-ALL) frequently affects infants and is associated with a poor prognosis. Primary refractory and relapsed disease due to resistance to glucocorticoids (GCs) remains a substantial hurdle to improving clinical outcomes. In this study, we aimed to overcome GC resistance of MLL-ALL.

Pharmacokinetic assessment of alprazolam-induced neonatal abstinence syndrome using physiologically based pharmacokinetic model.

Sustained benzodiazepine use during pregnancy can induce neonatal abstinence syndrome (NAS). In this study, the association between NAS and plasma alprazolam concentration was examined using the measured neonatal concentrations in the time series as well as simulated plasma concentrations of pregnant woman and neonate by physiologically based pharmacokinetic (PBPK) modeling. A neonate born to a mother taking alprazolam daily throughout pregnancy exhibited symptoms such as apnea and vomiting from 9 h to 4 days after birth.

Relationship of oral conditions to the incidence of infective endocarditis in periodontitis patients with valvular heart disease: a cross-sectional study.

Objectives: Infective endocarditis (IE) is a life-threatening infectious disease, but the pathogenesis of the disease remains uncertain. The objective of this study was to examine whether oral infectious conditions are associated with the occurrence of IE in valvular heart disease (VHD) patients.

Materials And Methods: A total of 119 periodontitis (P) patients with or without VHD were enrolled, and cross-sectional analyses were performed.

Evaluation for optimal dosing of vancomycin in patients with different physical types.

The sufficient dose to obtain an optimal trough concentration of vancomycin (VCM) in patients with non-standard physical types remains controversial. In this study, we examined the relationship between the dose and physical type in patients in whom an optimal trough concentration was obtained among VCM-treated patients. We retrospectively investigated the dose of VCM and physical type in patients treated with VCM between January 2012 and January 2017 at two medical institutions (n = 272).

Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism.

Although "genomically" humanized animals are invaluable tools for generating human disease models as well as for biomedical research, their development has been mainly restricted to mice via established transgenic-based and embryonic stem cell-based technologies. Since rats are widely used for studying human disease and for drug efficacy and toxicity testing, humanized rat models would be preferred over mice for several applications. However, the development of sophisticated humanized rat models has been hampered by the difficulty of complex genetic manipulations in rats.

Differentiated HASTR/ci35 cells: A promising in vitro human astrocyte model for facilitating CNS drug development studies.

Astrocytes have shown longstanding promise as therapeutic targets for various central nervous system diseases. To facilitate drug development targeting astrocytes, we have recently developed a new conditionally immortalized human astrocyte cell line, termed HASTR/ci35 cells. In this study, in order to further increase their chances to contribute to various astrocyte studies, we report on the development of a culture method that improves HASTR/ci35 cell differentiation status and provide several proofs related to their astrocyte characteristics.

Evaluation of 4β-Hydroxycholesterol and 25-Hydroxycholesterol as Endogenous Biomarkers of CYP3A4: Study with CYP3A-Humanized Mice.

Cytochrome P450 3A (CYP3A) enzymes metabolize approximately half of all drugs on the market. Since the endogenous compounds 4β-hydroxycholesterol (4β-HC) and 25-hydroxycholesterol (25-HC) are generated from cholesterol via CYP3A enzymes, we examined whether the plasma levels of 4β-HC and 25-HC reflect hepatic CYP3A4 activity by using a CYP3A-humanized mouse model, in which the function of endogenous Cyp3a was genetically replaced by human CYP3A. CYP3A-humanized mice have great advantages for evaluation of the relationship between hepatic CYP3A protein levels and plasma and hepatic levels of 4β-HC and 25-HC.

Detection of Chemical Engagement of Solute Carrier Proteins by a Cellular Thermal Shift Assay.

Solute carriers (SLCs) are transmembrane proteins that transport various nutrients, metabolites, and drugs across cellular membranes. Despite the relevance of SLCs to cell homeostasis, metabolism, and disease states, for the majority of SLCs we lack experimental evidence regarding the nature of the cognate ligands, whether endobiotic or xenobiotic. Moreover, even for the roughly 20 SLCs for which inhibitors have been characterized, engagement assays in cells are limited to the accessibility of radiolabeled or fluorescent probes.

Postmortem angiography revealing traumatic rupture of the intracranial internal carotid artery.

Diagnosis of traumatic subarachnoid hemorrhage (SAH), although relatively rare, is important in forensic medicine. It is mostly associated with rupture of the vertebrobasilar artery. Traumatic aneurysm of the intracranial part of the internal carotid artery (ICA) is also rare but has been reported in several studies.

Frequency and influencing factors of cardiopulmonary resuscitation-related injuries during implementation of the American Heart Association 2010 Guidelines: a retrospective study based on autopsy and postmortem computed tomography.

Aim: To determine the frequency of cardiopulmonary resuscitation (CPR)-related injuries and factors involved in their occurrence, data based on forensic autopsy and postmortem computed tomography (PMCT) during implementation of the 2010 American Heart Association Guidelines for CPR were studied.

Methods: We retrospectively evaluated data on adult patients with non-traumatic deaths who had undergone manual CPR and autopsy from January 2012 to December 2014. CPR-related injuries were analyzed on autopsy records and PMCT images and compared with results of previous studies.

Stature estimation in a contemporary Japanese population based on clavicular measurements using multidetector computed tomography.

The aims of this study was to assess the correlation between stature and clavicular measurements in a contemporary Japanese population using three-dimensional (3D) computed tomographic (CT) images, and to establish regression equations for predicting stature. A total of 249 cadavers (131 males, 118 females) underwent postmortem CT scanning and subsequent forensic autopsy between October 2011 and May 2016 in our department. Four clavicular variables (linear distances between the superior margins of the left and right sternal facets to the anterior points of the left and right acromial ends and between the superior margins of the left and right sternal facets to the left and right conoid tubercles) were measured using 3D CT reconstructed images that extracted only bone data.

Involvement of ESE-3, epithelial-specific ETS factor family member 3, in transactivation of the ABCB1 gene via pregnane X receptor in intestine-derived LS180 cells but not in liver-derived HepG2 cells.

Pregnane X receptor (PXR) is involved in the transactivation of ABCB1 gene by rifampicin (RIF). However, we found that increase in ABCB1 mRNA by RIF was observed in LS180 cells but not in HepG2 cells. Since both cell lines expressed PXR equally, we hypothesized that a factor(s) other than PXR is responsible for PXR-mediated transactivation of the ABCB1 gene.

Sexual determination based on multidetector computed tomographic measurements of the second cervical vertebra in a contemporary Japanese population.

Accurate sex estimation is important in forensic investigation to determine the identity of unknown individuals. The aim of this study was to investigate the accuracy of sex assessment based on measurements of the second cervical vertebra (C2) using computed tomographic (CT) images in a Japanese population and to develop discriminant function formulae. The data were collected from 224 Japanese cadavers (112 male subjects, 112 female subjects) on which postmortem CT scanning and subsequent forensic autopsy were performed.

A rare autopsy case of traumatic rhabdomyolysis associated with intermittent assault.

Traumatic rhabdomyolysis generally occurs after severe blunt trauma and is acute in onset, associated with severe disease, and potentially lethal. Accordingly, diagnosis of traumatic rhabdomyolysis in patients without massive subcutaneous or intramuscular hemorrhage is difficult, especially in the postmortem period, which is limited in terms of the availability of biochemical examination tools and accurate history of illness. To the best of our knowledge, there are no previous reports of death from traumatic rhabdomyolysis among individuals who did not pursue medical consultation.