Evaluation of Lung Adverse Events Associated With Lenvatinib: A Post-marketing Surveillance Study.

Background/aim: Despite the seriousness of lung adverse events (AEs) associated with lenvatinib, comprehensive data on these events remain limited. This study was conducted to examine the disproportionality, time to onset, incidence rates, and outcomes of lenvatinib-associated lung AEs using the Japanese Adverse Drug Event Report database.

Patients And Methods: We analysed data for the period from April 2004 to May 2023.

Disproportionality Analysis of Hepatotoxic and Gastrointestinal Adverse Events Associated With Nintedanib Using the Japanese Adverse Drug Event Report (JADER) Database.

Background/aim: Nintedanib may cause adverse events such as elevated liver enzyme levels, diarrhea, and decreased appetite. These adverse events should be managed appropriately as they affect the quality of life of patients. This study has aimed to analyze patient characteristics and time-to-onset of adverse events caused by nintedanib using the Japanese Adverse Drug Event Report (JADER) database.

Evaluation of Times-to-onset and Outcomes of Lung Adverse Events Associated With Sorafenib Using JADER.

Background/aim: Despite the seriousness of lung adverse events (AEs) associated with sorafenib, comprehensive data are limited. This study was conducted to examine the disproportionality, times to onset, incidence rates, and outcomes of sorafenib-associated lung AEs, using the Japanese Adverse Drug Event Report database.

Patients And Methods: Data for the period between April 2004 and May 2023 were analyzed.

Red-light Emitting Orthogonally Trireactive Gold Nanoclusters for the Synthesis of Multifunctionalized Nanomaterials.

For the development of highly multifunctionalized nanomaterials, the introduction of functional molecules on gold nanoclusters containing thiols preinstalled with connecting groupsconstitutes a promising approach. However, the uniform introduction of multiple connecting groups while avoiding side reactions is a challenging task. Herein, the synthesis of gold nanoclusters (ca.

Synthetic Studies of Javaberine A Based on Intramolecular Hydroamination of Alkenes.

A total synthesis of javaberine A was achieved through a lithium amide-mediated intramolecular hydroamination of an N-allyl aminoalkene. The desired hydroamination was accomplished using an excess of i-PrNH with a substoichiometric amount of n-BuLi. Using an excess of both n-BuLi and i-PrNH led to tandem cyclization, however, resulting in the construction of a tricyclic structure through the formation of one C-N and two C-C bonds in a single operation.

Lifestyle Behaviors of Childhood and Adolescence: Contributing Factors, Health Consequences, and Potential Interventions.

In this narrative review, we summarized evidence from peer-reviewed articles, published before February 2024, that investigated lifestyle behaviors among children (≤12 years) and adolescents (13-18 years) representing different geographic descents. These behaviors included dietary patterns, screen time, physical activity, smoking, alcohol consumption, oral hygiene, unsafe sex, and sleep duration and quality. We documented the significant impacts of parental, school, and sociodemographic factors on the adoption of numerous lifestyle behaviors in this age category.

Synthesis of Novel Pseudo-Enantiomeric Phase-Transfer Catalysts from Cinchona Alkaloids and Application to the Hydrolytic Dynamic Kinetic Resolution of Racemic 3-Phenyl-2-oxetanone.

Naturally occurring Cinchona alkaloids such as quinidine (QD)/cinchonine (CN) and their diastereomers, quinine (QN)/cinchonidine (CD), have been recognized as pseudo-enantiomeric pairs. Utilizing these pseudo-enantiomeric alkaloids as chiral resources provides complementary enantioselectivity in many asymmetric reactions. During the screening of Cinchona alkaloid phase-transfer catalysts (PTCs) in the hydrolytic dynamic kinetic resolution of racemic 3-phenyl-2-oxetanone (1) to tropic acid (2), we found that the introduction of a 4-trifluoromethylphenyl group at the vinyl terminus of BnQN significantly reduced the enantioselectivity to 41% enantiomeric excess (ee).

Tumoral Pharmacokinetic-Pharmacodynamic Simulation of Doxorubicin-Encapsulated Polymeric Micelles Using a Tissue-Isolated Tumor Perfusion System.

Pharmacokinetic (PK) elucidation of polymeric micelles delivering anticancer drugs is crucial for accurate antitumor PK-pharmacodynamic (PK-PD) simulations. Particularly, establishing a methodology to quantify the tumor inflow and outflow of anticancer drugs encapsulated in polymeric micelles is an essential challenge. General tumor biodistribution experiments are disadvantageous in that inflow quantification is easy, but outflow quantification is challenging.

Suppressing the expression of steroidogenic acute regulatory protein (StAR) in the myocardium by spironolactone contributes to the improvement of right ventricular remodeling in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive condition that frequently leads to right ventricular (RV) remodeling. Aldosterone promotes vascular and RV remodeling. The upregulation of steroidogenic acute regulatory protein (StAR) stimulates aldosterone synthesis.

The association between antenatal coffee consumption and preeclampsia: a systematic review and meta-analysis.

Background: A growing body of evidence has documented unfavorable maternal outcomes attributed to excessive antenatal coffee consumption. Preeclampsia is one of the most common hypertensive disorders of pregnancy with several adverse maternal and neonatal outcomes. However, the association between antenatal coffee consumption and preeclampsia remains debatable.

Risk Factor for Rash in Patients Receiving Cytarabine and Idarubicin Induction Therapy for Acute Myeloid Leukemia.

Background/aim: Rash is a common adverse event (AE) observed during cytarabine and idarubicin induction therapy in patients with acute myeloid leukemia (AML). Previous studies have highlighted the challenge in predicting the onset and duration of rash. This study aimed to determine the factors that affect the onset of rash in patients receiving induction therapy for AML.

Results of the JRS-I LRA0401 and LRB0402 Japan Rhabdomyosarcoma Study Group trials for low-risk embryonal rhabdomyosarcoma.

Background: Failure-free survival (FFS) rates of low-risk patients with rhabdomyosarcoma improved in Intergroup Rhabdomyosarcoma Study IV after the escalation of cyclophosphamide total dose to 26.4 g/m. However, this dose may increase the risk of adverse events, including infertility, in some patients.

Exploring the multiple effects of nifedipine and captopril administration in spontaneously hypertensive rats through pharmacokinetic-pharmacodynamic analyses.

This study assessed the pharmacokinetics (PKs) and pharmacodynamics (PDs) of two antihypertensive drugs, nifedipine and captopril, by exploring their main (blood pressure [BP]) and secondary effects (heart rate [HR] and QT interval [QT]) in spontaneously hypertensive rats. This study aimed to assess the relationship between PKs and PDs. Using these PD parameters, BP, HR, and QT during coadministration were estimated.

High amphipathicity of α-helical peptides enhances unmethylated CpG DNA-induced activation of mouse macrophage-like RAW264.7 cells.

The α-helical antimicrobial peptide Kn2-7 enhances the activation of mouse macrophage-like RAW264.7 induced by DNA containing unmethylated cytosine-guanine motifs (CpG DNA). This enhancement is related to increased cellular uptake of DNA by Kn2-7, but the relevant properties of Kn2-7 are unknown.

Global Associations of the Traditional Japanese Diet Score with Hypertension Prevalence and Systolic Blood Pressure from 2009 to 2019: A Cross-Sectional and Longitudinal Ecological Study.

Objective: Prevention and improvement of hypertension is one of the most important health issues worldwide. The traditional Japanese diet contributes to the prevention of some non-communicable diseases associated with hypertension. However, whether traditional Japanese dietary patterns are associated with hypertension prevalence and systolic blood pressure (SBP) worldwide remains unknown.

Structural and biophysical analysis of cytochrome P450 2C9*14 and *27 variants in complex with losartan.

The human cytochrome P450 (CYP) 1, 2 and 3 families of enzymes are responsible for the biotransformation of a majority of the currently available pharmaceutical drugs. The highly polymorphic CYP2C9 predominantly metabolizes many drugs including anticoagulant S-warfarin, anti-hypertensive losartan, anti-diabetic tolbutamide, analgesic ibuprofen, etc. There are >80 single nucleotide changes identified in CYP2C9, many of which significantly alter the clearance of important drugs.

Pharmacokinetic-Pharmacodynamic Analysis of pH-Responsive Doxorubicin-Releasing Micelles with Anticancer Activity.

This study aimed to investigate the effect of pH-responsive doxorubicin (DOX) release and the targetability of pilot molecules in folic acid (FA)-modified micelles using a pharmacokinetic-pharmacodynamic (PK-PD) model. The time profiles of intratumoral DOX concentrations in Walker256 tumor-bearing rats were monitored using a microdialysis probe, followed by compartmental analysis, to evaluate intratumoral tissue pharmacokinetics. Maximal DOX was released from micelles 350 min after the administration of pH-responsive DOX-releasing micelles.

Left-Right Difference in Brain Pharmacokinetics Following Nasal Administration Via One-Site Nostrils.

The olfactory and trigeminal pathways are direct delivery pathways between the nose and brain. To determine the effect of direct delivery on drug distribution in the brain, two model drugs with different physical properties, antipyrine (ANP), with high membrane permeability, and ranitidine (RNT), with low membrane permeability, were selected. For ANP, direct delivery from the nose to the brain was observed only in the olfactory bulb beside the nasal cavity, with a direct transport percentage (DTP) of approximately 45 %, whereas in the frontal and occipital brains, the contribution from the systemic circulation to the brain was observed as the primary route of brain distribution.