Quality Evaluation of Gentamicin Sulfate Reference Standards in Japanese Pharmacopoeia Using Hydrophilic Interaction Chromatography Combined With Tandem Mass Spectrometry.

Background: Through the recent development of analytical technology, antibiotics quantification in the Japanese Pharmacopoeia (JP) has changed from traditional microbiological assays to physicochemical methods with high specificity and precision. However, for several multicomponent antibiotics without typical UV absorption, potency cannot be directly determined using instrumental methods such as high-performance liquid chromatography; therefore, traditional microbiological assays are still used. Gentamicin sulfate (GmS), which consists of three major components, C1, C1a, and C2, is such a typical antibiotic, and its antimicrobial potency continues to be assayed using microbiological methods in JP monographs.

Intragastric administration of cinnamaldehyde induces changes in body temperature via TRPA1.

The transient receptor potential (TRP) channel family, including TRPA1, is known to be involved in temperature sensing and response. Previous studies have shown that intragastric administration of cinnamaldehyde (a typical TRPA1 agonist) can change body temperature, but the role of TRPA1 in this response is not clear. In this study, we found that intragastric administration of cinnamaldehyde increased in the intrascapular brown adipose tissue (IBAT) and rectal temperatures.

Humoral and cellular factors inhibit phosphate-induced vascular calcification during the growth period.

Hyperphosphatemia is an independent and non-classical risk factor of cardiovascular disease and mortality in patients with chronic kidney disease (CKD). Increased levels of extracellular inorganic phosphate (Pi) are known to directly induce vascular calcification, but the detailed underlying mechanism has not been clarified. Although serum Pi levels during the growth period are as high as those observed in hyperphosphatemia in adult CKD, vascular calcification does not usually occur during growth.

Validation of a dietary balance score in middle-aged and older community-dwelling Japanese.

This study assessed the validity of dietary balance scores (DBSs) by investigating the association between DBSs and nutrient adequacy (NA) in two Japanese populations. The participants were 65 community-dwelling Japanese from Tokushima Prefecture and 2,330 community-dwelling Japanese from Aichi Prefecture. Based on food frequency questionnaires or 3-day dietary records, we obtained 18 food groups.

Forodesine Enhances Immune Responses through Guanosine-Mediated TLR7 Activation while Preventing Graft-versus-Host Disease.

Recent evidence indicates that specific types of nuclear acids, including guanosine and its derivatives, act as natural ligands for TLR7. This led us to hypothesize that purine nucleoside phosphorylase inhibitors not only can induce apoptosis of T cells but also can lead to TLR7 activation by accumulation of guanine nucleosides, in particular under systemic inflammation, where damaged tissues release a large amount of nucleotides. We demonstrate in the present study that a purine nucleoside phosphorylase inhibitor, forodesine, can reduce the disease severity and prolong the survival in a xenogeneic mouse model of graft-versus-host disease (GVHD).

Interplay of UDP-Glucuronosyltransferase and CYP2C8 for CYP2C8 Mediated Drug Oxidation and Its Impact on Drug-Drug Interaction Produced by Standardized CYP2C8 Inhibitors, Clopidogrel and Gemfibrozil.

Background And Objective: Early investigations into drug-drug interactions (DDIs) involving cytochrome P450 2C8 (CYP2C8) have highlighted the complexity of interactions between CYP2C8 substrate drugs, including montelukast, desloratadine, pioglitazone, repaglinide, and cerivastatin (the latter two being OATP1B1 substrates), and standardized CYP2C8 inhibitors such as clopidogrel (Clop) and gemfibrozil (Gem). These interactions have proven challenging to predict based solely on simple CYP inhibition. A hypothesis has emerged suggesting that these substrate drugs first distribute to UDP-glucuronosyltransferase (UGT) before undergoing oxidation by CYP2C8, resulting in bidirectional elimination.

Isolation and Purification of Harpagogenin as an Nrf2-ARE Activator from the Tubers of Chinese Artichoke (Stachys sieboldii).

Chinese artichoke tuber (Stachys sieboldii Miq.) is used as an herbal medicine as well as edible food. This study examined the effect of the Chinese artichoke extracts on the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway that induces the expression of antioxidant enzymes to explore its novel characteristics.

Development of new scores for atherosclerotic cardiovascular disease using specific medical examination items: the Suita Study.

Background: We previously developed risk models predicting stroke, coronary heart disease (CHD), and cardiovascular disease (CVD) among Japanese people from the Suita Study. Yet, applying these models at the national level was challenging because some of the included risk factors differed from those collected in the Japanese governmental health check-ups, such as Tokutei-Kenshin. We, therefore, conducted this study to develop new risk models for stroke, CHD, and atherosclerotic CVD (ASCVD), based on data from the Suita Study.

The association between the estimated glomerular filtration rate and cognitive impairment: the Suita Study.

This cross-sectional study investigated the association between the estimated glomerular filtration rate (eGFR), a measure of chronic kidney disease (CKD), and cognitive impairment. We used data from 6215 Japanese individuals registered in the Suita Study. Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score of ≤ 26.

Rab32 and Rab38 maintain bone homeostasis by regulating intracellular traffic in osteoclasts.

Osteoclasts play a crucial role in bone homeostasis by forming resorption pits on bone surfaces, resulting in bone resorption. The osteoclast expression of Rab38 protein is highly induced during differentiation from macrophages. Here we generated mice with double knockout (DKO) of Rab38 and its paralogue, Rab32, to investigate the roles of these proteins in osteoclasts.

The Crucial Role of the Interstitial Cells of Cajal in Neurointestinal Diseases.

Neurointestinal diseases result from dysregulated interactions between the nervous system and the gastrointestinal (GI) tract, leading to conditions such as Hirschsprung's disease and irritable bowel syndrome. These disorders affect many people, significantly diminishing their quality of life and overall health. Central to GI motility are the interstitial cells of Cajal (ICC), which play a key role in muscle contractions and neuromuscular transmission.

Improvement of Medication Guidance Sheet for Total Body Irradiation/Cyclophosphamide Followed by Allogeneic Hematopoietic Stem Cell Transplantation Based on Real Monitoring Data.

Background/aim: Adverse events (AEs) must be managed during cancer therapy. We had previously developed a medication guidance sheet (MGS) to monitor AEs after conditioning therapy with allogeneic hematopoietic stem cell transplantation (HSCT). However, it remains unclear whether this sheet can accurately predict the type, onset, and duration of AEs in clinical practice.

Gastroparesis Worsens Indomethacin-Induced Gastric Antral Ulcers by Bile Reflux via Activation of 5-HT and Dopamine D Receptors in Mice.

Background/aims: We examined the contributions of gastric emptying and duodenogastric bile reflux in the formation of gastric antral ulcers induced by NSAIDs in mice.

Methods: We used the murine re-fed indomethacin (IND) experimental ulcer model. Outcome measures included the appearance of gastric lesions 24 h after IND treatment and the assessment of gastric contents and the concentration of bile acids 1.

Characterization of Rab32- and Rab38-positive lysosome-related organelles in osteoclasts and macrophages.

Both the biogenesis and functions of osteoclasts and macrophages involves dynamic membrane traffic. We screened transcript levels for Rab family small GTPases related to osteoclasts and identified Rab38. Rab38 expression is upregulated during osteoclast differentiation and maturation.

Evaluation of Time to Onset and Outcome of Cardiac Adverse Events Associated with Nilotinib using Post-Marketing Surveillance.

Introduction: Cardiac adverse events (CAEs) have become a concern as serious adverse events (AEs) of nilotinib administration. No reports have described the incidence of CAEs associated with nilotinib in Japanese patients. Thus, we conducted this study to evaluate the risk of nilotinib-induced CAEs, time to onset, incidence rates, and post hoc outcomes using the Japanese Adverse Drug Event Report database.

Effect of the combination of cationic lipid and phospholipid on gene-knockdown using siRNA lipoplexes in breast tumor cells and mouse lungs.

Previously, using three types of cationic lipids, the effect of phospholipids in liposomal formulations on gene-knockdown efficacy was determined after and transfection with small interfering RNA (siRNA)/cationic liposome complexes (siRNA lipoplexes) containing various cationic lipids and phospholipids. In the present study, six other types of cationic lipids, namely -dimethyl--tetradecyltetradecan-1-aminium bromide, -hexadecyl--dimethylhexadecan-1-aminium bromide (DC-1-16), 2-[bis{2-(tetradecanoyloxy)ethyl}amino]--trimethyl-2-oxoethan-1-aminium chloride (DC-6-14), 1,2-di--octadecenyl-3-trimethylammonium propane chloride (DOTMA), 1,2-distearoyl-3-trimethylammonium-propane chloride (DSTAP) and 1,2-dioleoyl-3-dimethylammonium-propane were selected, and the effect of phospholipids in liposomal formulations containing each cationic lipid on gene-knockdown was evaluated. A total of 30 types of cationic liposomes composed of each cationic lipid with phosphatidylethanolamine containing unsaturated or saturated diacyl chains (C14, C16 or C18) were prepared.

Pharmacist Interventions for Adverse Drug Reactions in Palliative Care: A Multicentre Pilot Study.

This study aimed to investigate adverse reactions to medications administered during palliative care and compare the responses of Board-Certified Pharmacists in Palliative Pharmacy (BCPPP) and non-BCPPP professionals. : This multicentre prospective survey included hospital and community pharmacists who are members of the Japanese Society for Pharmaceutical Palliative Care and Sciences. Study participants included patients who experienced new drug reactions during the study period and responded to the requested survey items.

Evaluation of Time to Onset and Outcome of Lung Adverse Events Related to Pembrolizumab Using Marketing Surveillance.

Background: Pembrolizumab has been widely used in patients since its release, but detailed information on lung-specific adverse events (AEs) from post-marketing monitoring has not been reported.

Objectives: This study was undertaken to determine the risk of pembrolizumab-induced lung AEs, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database.

Method: We analyzed data for the period between April 2004 and March 2022.

GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-Activated Human CD4 T Cells Exhibiting Varied Levels of and Expression.

Immune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4 T cells, we investigated the mRNA expression of the α7 subunit and the human-specific dupα7 nAChR subunit, which functions as a dominant-negative regulator of ion channel function, under resting conditions and T cell receptor (TCR)-activation.

Anti-Inflammatory Effects of Dietary Polyphenols through Inhibitory Activity against Metalloproteinases.

Matrix metalloproteinases (MMPs) are zinc-dependent metalloproteinases that play important roles in a variety of diseases, including cancer, cardiovascular disease, diabetes, obesity, and brain diseases. Dietary polyphenols are thought to have a variety of beneficial effects on these diseases characterized by inflammation. Clinical studies have demonstrated that MMPs are in most cases upregulated in various inflammatory diseases, including osteoarthritis, rheumatoid arthritis, inflammatory bowel disease, and Alzheimer's disease.

Multicenter prospective observational study on hospital pharmacist interventions to reduce inappropriate medications.

In Japan, the involvement of hospital pharmacists in inappropriate medications (IMs) practices has not been sufficiently reported. Therefore, this prospective study described the interventions of hospital pharmacists in discontinuing inappropriate drugs or reducing drug doses. We conducted a prospective, multicenter, observational study to investigate the intervention of hospital pharmacists in inappropriate prescriptions for inpatients in September 2018.

Comparison of the conventional and immersing powdered crude drugs (IPCD) methods for color and extraction of quantitative indicator ingredients in the Kampo formula decoction of daiokanzoto.

Aim: The immersing powdered crude drugs (IPCD) method is a quick and simple method for preparing decoctions. Here, the conventional and IPCD methods were compared for the color and extraction of quantitative indicator ingredients in the daiokanzoto decoction solution, and the suitability of the IPCD method was assessed.

Methods: The color of decoction solutions was visually observed, and the Commission Internationale de L'éclairage (CIE) L*a*b*color parameters were measured using conventional and IPCD methods.

Development of Real-world Data-based Medication Instruction Sheet for Acute Myeloid Leukemia Patients Receiving High-dose Cytarabine Consolidation Therapy.

Background/aim: For quick and accurate monitoring of potential adverse events (AEs) during concurrent chemotherapy, we had previously developed innovative medication instruction sheets (MIS) for a variety of chemotherapy regimens. However, it is still unclear whether these sheets correctly predict the type and time course of the onset and recovery of AEs. Therefore, we monitored AEs in patients with acute myeloid leukemia (AML) receiving high-dose cytarabine (HD-AraC) using the original MIS.

Quality assessment of Rheum species cultivated in Japan by focusing on M2 polarization of microglia.

In traditional Japanese medicine, Rhei Rhizoma is used as a purgative, blood stasis-resolving and antipsychotic drug. The latter two properties are possibly related to anti-inflammatory effects. Microglia regulate inflammation in the central nervous system.