Autopsy-Confirmed Undifferentiated Carcinoma of the Liver With Rapid Bone Metastasis.

A male in his late 70s, with progressive hip pain, was diagnosed with a metastatic iliac bone tumor, initially misinterpreted as septic arthritis. Despite extensive imaging, the primary tumor site was undetected until autopsy, which confirmed undifferentiated carcinoma of the liver with secondary lung involvement. The patient's poor performance status and rapid health decline precluded aggressive treatment, leading to his demise.

[Tolvaptan, a vasopressin V receptor antagonist, is the world's first approved drug for treatment of autosomal dominant polycystic kidney disease (ADPKD)].

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease. Fluid-filled cysts develop and enlarge in both kidneys, eventually leading to kidney failure. Tolvaptan is a selective vasopressin V receptor antagonist and the first and only drug approved for treatment of ADPKD.

Detecting a subendocardial infarction in a child with coronary anomaly by three-dimensional late gadolinium enhancement MRI using compressed sensing.

Three-dimensional high-resolution late gadolinium enhancement (3D HR LGE) magnetic resonance imaging (MRI) using compressed sensing can help detect small myocardial infarcts. We discuss the case of an 11-year-old child with an anomalous aortic origin of the left coronary artery. Since he was suspected to have coronary stenosis due to anomalous aortic origin of the left coronary artery, cardiovascular MRI, including conventional two-dimensional (2D) LGE MRI and HR 3D LGE MRI, was conducted.

Analysis of 307 cases with drug-induced liver injury between 2010 and 2018 in Japan.

Aim: In order to know the present status of drug-induced liver injury (DILI) in Japan, we present the data of prospectively collected DILI cases between 2010 and 2018 from 27 hospitals.

Methods: Drug-induced liver injury cases diagnosed by DILI experts from 27 hospitals all over Japan have been prospectively collected since 2010. Alanine aminotransferase level ≥150 U/L and/or alkaline phosphatase ≥2× upper limit of normal were inclusion criteria.

Synthesis and evaluation of a potent, well-balanced EP/EP dual agonist.

A highly potent and well-balanced dual agonist for the EP and EP receptors is described. Optimization of the lead compound was accomplished in consideration of the relative agonist activity against each EP subtype receptor and the pharmacokinetic profile. As the result, 2-[(2-{(1R,2R)-2-[(1E,4S)-5-cyclopentyl-4-hydroxy-4-methyl-1-penten-1-yl]-5-oxocyclopentyl}eth-yl)thio]-1,3-thiazole-4-carboxylic acid (10) showed excellent potency (human EC EP = 1.

Severe Respiratory Event Initially Thought to be Inadvertent Endobronchial Intubation: Possible Complications From Using of a Topical Metered-Dose of 8% Lidocaine Pump Spray.

Introduction: Pulmonary collapse after intubation is common, and it is caused by a variety of factors.

Case Presentation: A 21-year-old man presented at our operation room to undergo an appendectomy. Except for a history of cigarette smoking, his history was negative.

The Lateral Position Improved Airway Patency in Anesthetized Patient With Burn-Induced Cervico-Mento-Sternal Scar Contracture.

A 78-year-old woman with burn-induced cervico-mento-sternal scar contracture was scheduled for laparoscopic cholecystectomy. During inhalational induction of sevoflurane, her airway patency deteriorated. The right lateral position and assist ventilation using a breathing bag dramatically improved her airway patency.

Discovery of highly potent dual EP(2) and EP(3) agonists with subtype selectivity.

The cyclic carbamate derivatives, 2-{[2-((4S)-4-{(1E,3R)-8-fluoro-3-hydroxy-4,4-dimethyl-1-octenyl}-2-oxo-1,3-oxazolidin-3-yl)ethyl]sulfanyl}-1,3-thiazole-4-carboxylic acid (5) and 2-{[2-((4S)-4-{(1E,3R)-3-[1-(4-fluorobutyl)cyclobutyl]-3-hydroxy-1-propenyl}-2-oxo-1,3-oxazolidin-3-yl)ethyl]sulfanyl}-1,3-thiazole-4-carboxylic acid (7) were identified as the first potent dual EP2 and EP3 agonists with selectivity against the EP1 and EP4 subtypes. Compounds 5 and 7 demonstrated highly potent dual EP2 and EP3 agonist activity with EC50 values of 10nM or less. In addition, these compounds possess structural features distinct from natural prostaglandins, such as a cyclic carbamate moiety, a dimethyl or cyclobutyl group and a terminal fluorine atom.

Discovery of Gemilukast (ONO-6950), a Dual CysLT1 and CysLT2 Antagonist As a Therapeutic Agent for Asthma.

An orally active dual CysLT1 and CysLT2 antagonist possessing a distinctive structure which consists of triple bond and dicarboxylic acid moieties is described. Gemilukast (ONO-6950) was generated via isomerization of the core indole and the incorporation of a triple bond into a lead compound. Gemilukast exhibited antagonist activities with IC50 values of 1.

Anti-stress effects of ONO-2952, a novel translocator protein 18 kDa antagonist, in rats.

Accumulating evidence has shown the pathophysiological significance of the translocator protein 18 kDa (TSPO) in the central nervous system. In this study, we evaluated the beneficial effects of ONO-2952, a novel TSPO antagonist in rat stress models. ONO-2952 potently bound both rat and human TSPO (Ki=0.

Combination therapy with ONO-KK1-300-01, a cathepsin K inhibitor, and parathyroid hormone results in additive beneficial effect on bone mineral density in ovariectomized rats.

This study examined the effects of a novel cathepsin K inhibitor, ONO-KK1-300-01 (KK1-300), used concurrently with parathyroid hormone (PTH) in ovariectomized (OVX) rats. KK1-300 (3 mg/kg, twice daily), alendronate (1 mg/kg, once daily) or vehicle were orally administered to OVX rats for 56 days, starting the day after ovariectomy, followed by combination treatment with or without PTH (3 μg/kg, subcutaneously three times a week) for another 28 days. OVX control animals exhibited a significant increase in both bone resorption (urinary deoxypyridinoline; DPD) and formation markers (serum osteocalcin) as well as microstructural changes associated with decreased bone mineral density (BMD).

Tolvaptan delays the onset of end-stage renal disease in a polycystic kidney disease model by suppressing increases in kidney volume and renal injury.

Tolvaptan, a selective vasopressin V2 receptor antagonist, slows the increase in total kidney volume and the decline in kidney function in patients with the results of the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Outcome (TEMPO) 3:4 trial. However, it was unclear which dose of tolvaptan was optimal or whether tolvaptan was able to delay progression to end-stage renal disease (ESRD). Here we examined the relationship with aquaresis and the inhibitory effect on cyst development in short-term treatment and mortality as an index of ESRD in long-term treatment with tolvaptan using DBA/2FG-pcy mice, an animal model of nephronophthisis.

ONO-5334, a cathepsin K inhibitor, improves bone strength by preferentially increasing cortical bone mass in ovariectomized rats.

This study compared the effects of ONO-5334, a cathepsin K inhibitor, with those of alendronate on bone mass and strength in ovariectomized rats. Ovariectomy resulted in significant elevation in urinary deoxypyridinoline and plasma C-terminal cross-linking telopeptide of type I collagen (CTX) 8 weeks after surgery. Peripheral quantitative computed tomography analysis showed that total, trabecular, and cortical bone mineral content (BMC) decreased in the proximal tibia, which was paralleled with a significant decline in bone strength.

Complications of radiofrequency ablation for hepatocellular carcinoma in a multicenter study: An analysis of 16 346 treated nodules in 13 283 patients.

Aim:   We surveyed multiple centers to identify types and frequency of complications and mortality rate associated with radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC).

Methods:   We distributed a questionnaire developed by members of the Chugoku-Shikoku Society for the Local Ablation Therapy of Hepatocellular Carcinoma to 20 centers and analyzed types and frequency of complications and mortality rate.

Results:   In total, 16 346 nodules were treated in 13 283 patients between January 1999 and November 2010.

Genetic screening for regulators of Prz1, a transcriptional factor acting downstream of calcineurin in fission yeast.

Calcineurin phosphatase plays crucial roles in a wide variety of cell types and organisms. Dephosphorylation of the nuclear factor of activated T-cell (NFAT) family of transcriptional factors by calcineurin is essential for activating immune-responsive genes in mammals. NFAT activity is also regulated by diverse signaling pathways, which affect NFAT kinases and nuclear partner proteins.

Anti-edematous effects of tolvaptan in experimental rodent models.

Purpose: The aim of this study was to evaluate the therapeutic efficacy of tolvaptan, a vasopressin V(2) receptor antagonist, on edema in two rat models: 1) histamine-induced vascular hyperpermeability of the dorsal skin and 2) carrageenan-induced paw edema.

Methods: In the skin vascular hyperpermeability model, 3 h after oral administration of tolvaptan or the natriuretic agent furosemide, rats were intravenously injected with Evans Blue (EB), followed by intradermal injection of 10 μg of histamine into the dorsal skin. One hour later, blood was collected to measure serum parameters.

Chronic hyponatremia impairs memory in rats: effects of vasopressin antagonist tolvaptan.

The effects of stable chronic hyponatremia on the central nervous system are largely unknown, clinically, or in experimental animals. The aim of this study was to identify and characterize these effects in rats. Tolvaptan, a vasopressin V(2) receptor antagonist, was used to correct hyponatremia and determine any potential benefits of such treatment in this condition.

Comparison of therapeutic effects between radiofrequency ablation and percutaneous microwave coagulation therapy for small hepatocellular carcinomas.

Background: Although thermal ablation therapies have gained fairly wide acceptance as an effective treatment for small hepatocellular carcinoma (HCC), there have been only a few clinical studies comparing the response to radiofrequency ablation (RFA) and percutaneous microwave coagulation therapy (PMCT). We evaluated the therapeutic efficacy and safety of these two procedures for the treatment of small HCC measuring < or = 2 cm in diameter.

Methods: Thirty-four patients who had 37 nodules were treated by RFA and were compared with 49 patients (56 nodules) who underwent PMCT.

[Pyogenic liver abscess complicated by gastric fistula and bacterial meningitis].

A 77-year-old woman was admitted suffering from fever and headache. On laboratory examination, bacterial meningitis and sepsis due to Klebsiella pneumoniae were diagnosed. In addition, a hepatic cystic lesion measuring 13 cm in diameter in the left lobe was indicated on diagnostic imaging.

Radiofrequency ablation versus percutaneous microwave coagulation therapy for small hepatocellular carcinomas: a retrospective comparative study.

Background/aims: Although local ablation procedures are useful in eradication treatment for small hepatocellular carcinoma (HCC), there have only been a few clinical studies comparing the response to radiofrequency ablation (RFA) and percutaneous microwave coagulation therapy (PMCT). We evaluated the clinical effect and safety of these two procedures for the treatment of small HCCs measuring 2cm or less in diameter.

Methodology: Twenty-four patients with HCC who were treated by RFA and were compared with 39 patients with HCC who underwent PMCT.

[Hepatocellular carcinoma occurring after 11 year-long sustained viral response to interferon therapy for chronic hepatitis C].

The patient was a 61-year-old man with chronic hepatitis C who achieved a sustained virological response to interferon therapy in 1993. As a result, the status of his liver improved pathologically from F2A2 to F1A1. Eleven years later, however, a tumor measuring 15 mm in diameter in segment 6 of the liver was indicated by CT.

Indole diterpene synthetic studies: development of a second-generation synthetic strategy for (+)-nodulisporic acids A and B.

A second-generation strategy for construction of (+)-nodulisporic acids A and B based on the development of a new, effective modular indole synthesis exploiting a sequential Stille cross-coupling/Buchwald-Hartwig union/cyclization tactic is disclosed. This strategy evolved due to the considerable acid instability of the C(24) hydroxyl group observed in several advanced intermediates during our first-generation approach.

Indole diterpene synthetic studies. Total synthesis of (+)-nodulisporic acid F and construction of the heptacyclic cores of (+)-nodulisporic acids A and B and (-)-nodulisporic acid D.

A first-generation strategy for construction of (+)-nodulisporic acids A (1) and B (2) is described. The strategy entails union of the eastern and western hemisphere subtargets via the indole synthesis protocol developed in our laboratory. Subsequent elaboration of rings E and F, however, revealed the considerable acid instability of the C(24) hydroxyl, thereby preventing further advancement.