Hyperkalemia Caused by Potassium-Enriched Salt in a Hospitalized Patient.

Hyperkalemia is a potentially life-threatening condition, particularly in patients with chronic kidney disease (CKD). Potassium-enriched salt substitutes are increasingly promoted as a dietary intervention for hypertension, but may pose risks in patients with impaired renal function. We report the case of an 88-year-old male with CKD who developed asymptomatic but marked hyperkalemia (7.

Development of selective RyR2 inhibitors with a pharmacophore containing a parabanic acid skeleton.

Gene mutations resulting in dysfunction of the ryanodine receptor type 2 (RyR2), a huge Ca release channel that controls the concentration of Ca in the cytosol of cardiac muscle cells, can cause fatal heart arrhythmias. However, no RyR2 inhibitors have yet been developed for clinical usage. In this work, we discovered an isoform-selective RyR2 inhibitor 1 with a parabanic acid skeleton by screening a large chemical library.

Improved visibility of palisade vessels within Barrett's esophagus using red dichromatic imaging: a retrospective cross-sectional study in Japan.

Background/aims: Visualization of palisade vessels (PVs) in Barrett's esophagus is crucial for proper assessment. This study aimed to determine whether red dichromatic imaging (RDI) improves PV visibility compared with white-light imaging (WLI) and narrow-band imaging (NBI).

Methods: Five expert and trainee endoscopists evaluated the PV visibility in Barrett's esophagus using WLI, NBI, and RDI on 66 images from 22 patients.

Olmesartan-associated Gastritis Observed Over Time.

A 61-year-old woman who had been taking olmesartan for 7 years complained of epigastric pain, diarrhea, loss of appetite, and weight loss. Esophagogastroduodenoscopy revealed roughened mucosa and erosions in the stomach and duodenum. An endoscopic biopsy failed to identify the cause of the mucosal disorder.

Impaired Consciousness Due to Hyperammonemia During S-1 Administration for Unresectable Pancreatic Cancer.

A 71-year-old woman diagnosed with unresectable locally advanced pancreatic cancer was initially treated with gemcitabine and nab-paclitaxel as first-line therapy. The tumor exhibited no significant progression; however, after 12 cycles, the patient developed drug-induced interstitial pneumonia, leading to the discontinuation of gemcitabine and nab-paclitaxel therapy. Following recovery from pneumonia, S-1 therapy was initiated as second-line treatment.

Discovery and Structure-Activity Relationship of a Ryanodine Receptor 2 Inhibitor.

Ryanodine receptor 2 (RyR2) is a large Ca-release channel in the sarcoplasmic reticulum (SR) of cardiac muscle cells. It serves to release Ca from the SR into the cytosol to initiate muscle contraction. RyR2 overactivation is associated with arrhythmogenic cardiac disease, but few specific inhibitors have been reported so far.

Anti-Inflammatory Effects of a Novel Nuclear Factor-B Inhibitory Derivative Derived from Pyrazolo[3,4-]Pyrimidine in Three Inflammation Models.

Nuclear factor-B (NF-B) plays a central role in inflammatory responses, and its physiologic functions are essential for cell survival and proliferation. Currently, drugs targeting NF-B inhibition have not yet been applied in clinical practice. We investigated the physiologic effect of a novel NF-B inhibitory compound, 1-pyrazolo[3,4-]pyrimidin-4-amine derivative (INH #1), on three inflammatory animal models.

Shell-Driven Localized Oxide Nanoparticles Determine the Thermal Stability of Microencapsulated Phase Change Material.

Not all encapsulation techniques are universally apt for every type of phase change material (PCM), highlighting the imperative for methodological precision. This study addresses the challenges of microencapsulated PCM (MEPCM) arising from the immiscible pairing of α-AlO nanoparticles with Sn microparticles. The high-speed impact blending (HIB) dry synthesis technique is employed, facilitating large-volume production of Sn@α-AlO MEPCMs.

A potent and selective cis-amide inhibitor of ryanodine receptor 2 as a candidate for cardiac arrhythmia treatment.

Ryanodine receptor 2 (RyR2) is a Ca release channel mainly located on the sarcoplasmic reticulum (SR) membrane of heart muscle cells and regulates the concentration of Ca in the cytosol. RyR2 overactivation causes potentially lethal cardiac arrhythmias, but no specific inhibitor is yet available. Herein we developed the first highly potent and selective RyR2 inhibitor, TMDJ-035, containing 3,5-difluoro substituents on the A ring and a 4-fluoro substituent on the B ring, based on a comprehensive structure-activity relationship (SAR) study of tetrazole compound 1.

Screening for Novel Type 2 Ryanodine Receptor Inhibitors by Endoplasmic Reticulum Ca Monitoring.

Type 2 ryanodine receptor (RyR2) is a Ca release channel on the endoplasmic (ER)/sarcoplasmic reticulum that plays a central role in the excitation-contraction coupling in the heart. Hyperactivity of RyR2 has been linked to ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia and heart failure, where spontaneous Ca release via hyperactivated RyR2 depolarizes diastolic membrane potential to induce triggered activity. In such cases, drugs that suppress RyR2 activity are expected to prevent the arrhythmias, but there is no clinically available RyR2 inhibitors at present.

Fatal Severe Fever with Thrombocytopenia Syndrome Virus and Pasteurella multocida Coinfection.

We herein report a case of severe fever with thrombocytopenia syndrome (SFTS) with Pasteurella multilocida bacteremia in a 65-year-old man with alcoholic cirrhosis who was admitted to our hospital with anorexia and severe fatigue. Laboratory tests revealed pancytopenia and liver and kidney dysfunction. After admission, he developed impaired consciousness, mucosal hemorrhaging, and septic shock.

Targeting Cellular Retinoic Acid Binding Protein 1 with Retinoic Acid-like Compounds to Mitigate Motor Neuron Degeneration.

All-trans-retinoic Acid (atRA) is the principal active metabolite of Vitamin A, essential for various biological processes. The activities of atRA are mediated by nuclear RA receptors (RARs) to alter gene expression (canonical activities) or by cellular retinoic acid binding protein 1 (CRABP1) to rapidly (minutes) modulate cytosolic kinase signaling, including calcium calmodulin-activated kinase 2 (CaMKII) (non-canonical activities). Clinically, atRA-like compounds have been extensively studied for therapeutic applications; however, RAR-mediated toxicity severely hindered the progress.

Drug development for the treatment of RyR1-related skeletal muscle diseases.

Type 1 ryanodine receptor (RyR1) is an intracellular Ca release channel on the sarcoplasmic reticulum of skeletal muscle, and it plays a central role in excitation-contraction (E-C) coupling. Mutations in RyR1 are implicated in various muscle diseases including malignant hyperthermia, central core disease, and myopathies. Currently, no specific treatment exists for most of these diseases.

A reconstituted depolarization-induced Ca2+ release platform for validation of skeletal muscle disease mutations and drug discovery.

In skeletal muscle excitation-contraction (E-C) coupling, depolarization of the plasma membrane triggers Ca2+ release from the sarcoplasmic reticulum (SR), referred to as depolarization-induced Ca2+ release (DICR). DICR occurs through the type 1 ryanodine receptor (RyR1), which physically interacts with the dihydropyridine receptor Cav1.1 subunit in specific machinery formed with additional essential components including β1a, Stac3 adaptor protein, and junctophilins.

Development of a water-soluble ryanodine receptor 1 inhibitor.

Ryanodine receptor 1 (RyR1) is a Ca-release channel expressed on the sarcoplasmic reticulum (SR) membrane. RyR1 mediates release of Ca from the SR to the cytoplasm to induce muscle contraction, and mutations associated with overactivation of RyR1 cause lethal muscle diseases. Dantrolene sodium salt (dantrolene Na) is the only approved RyR inhibitor to treat malignant hyperthermia patients with RyR1 mutations, but is poorly water-soluble.

Mice with R2509C-RYR1 mutation exhibit dysfunctional Ca2+ dynamics in primary skeletal myocytes.

Type 1 ryanodine receptor (RYR1) is a Ca2+ release channel in the sarcoplasmic reticulum (SR) of the skeletal muscle and plays a critical role in excitation-contraction coupling. Mutations in RYR1 cause severe muscle diseases, such as malignant hyperthermia, a disorder of Ca2+-induced Ca2+ release (CICR) through RYR1 from the SR. We recently reported that volatile anesthetics induce malignant hyperthermia (MH)-like episodes through enhanced CICR in heterozygous R2509C-RYR1 mice.

Synthesis and Structure-Activity relationships of cyclin-dependent kinase 11 inhibitors based on a diaminothiazole scaffold.

Cyclin-dependent kinases (CDK) are attractive targets for drug discovery due to their wide range of cellular functions. CDK11 is an understudied CDK with roles in transcription and splicing, cell cycle regulation, neuronal function, and apoptosis. In this study, we describe a medicinal chemistry campaign to identify a CDK11 inhibitor.

A case of lip edema caused by the accidental ingestion of a bar of soap.

The most common symptom following the accidental ingestion of a soap is lip edema. Although most cases are asymptomatic or exhibit mild symptoms, in some cases, aspiration pneumonia, oropharyngeal edema, and bronchial obstruction may be fatal.

Beta-catenin-activated hepatocellular adenoma in a male.

Beta-catenin-activated hepatocellular adenoma is potentially malignant and warrants careful follow-up and surgical resection. Here, we report a 48-year-old man in whom a 55 mm single liver tumor was incidentally detected in the S1 segment. Contrast-enhanced computed tomography scans showed no enhancement in the early phase and a slight defection in the late phase.