[A case of hepatic portal venous gas and upper gastrointestinal mucosal injury due to accidental ingestion of hydrogen peroxide].

A 40-year-old woman was admitted to our hospital by ambulance due to accidental ingestion of 100ml of 35% hydrogen peroxide. Although the patient suffered from frequent vomiting, abdominal distension, and abdominal pain, signs of peritonitis were not observed. An abdominal computed tomography examination demonstrated obvious gas images in the gastric wall and intrahepatic portal veins. Upper gastrointestinal endoscopy revealed mucosal redness, swelling, and erosion from the lower part of the esophagus to the duodenum. Portal venous gas and upper gastrointestinal mucosal injury due to accidental hydrogen peroxide ingestion were suspected. As the vital signs were stable and there were no signs peritoneal irritation or neurological symptoms, she was treated medically with vonoprazan, rebamipide, and sodium alginate. The next day, abdominal symptoms immediately improved and 3 days later, hepatic portal venous gas had disappeared on ultrasonography. She was discharged on the 5th day after admission. Two months later, upper gastrointestinal endoscopy showed improvement in inflammatory findings. We report a remarkable case of hepatic portal venous gas and upper gastrointestinal mucosal injury and elucidate the endoscopic findings associated with hydrogen peroxide ingestion.

Total Synthesis of Marine Polyketide Plakortone Q.

The total synthesis of the natural bicyclo[3.3.0]furanolactone polyketide, plakortone Q, was achieved in 24 steps from (R)-Roche ester. The main feature of this synthetic strategy is the stereoselective construction of a central tetrahydrofuran moiety with four consecutive stereoisomeric centers using the Upjohn dihydroxylation of oxiranyl-substituted alkenes and acid-mediated 5-endo-tet cyclization.

Synthesis and Evaluation of MGB Polyamide-Oligonucleotide Conjugates as Gene Expression Control Compounds.

MGB polyamide-oligonucleotide conjugates ON 1-4 with linked MGB polyamides at the 2-exocyclic amino group of a guanine base using aminoalkyl linkers were synthesized and evaluated in terms of binding affinity for complementary DNA containing the MGB polyamide binding sequence using T m and CD analyses. The MGB polyamides comprised pyrrole polyamides (Py4- and Py3-), which possess binding affinity for A-T base pairs, and imidazole (Im3-) and pyrrole-γ-imidazole (Py3-γ-Im3-) polyamide hairpin motifs, which possess binding affinity for C-G base pairs. It was found that the stability of modified dsDNA was greatly influenced by the linker length. Py4- and Py3-oligonucleotide conjugates (ON 1 (n = 4) and ON 2 (n = 4)) containing the 4-aminobutyl linker formed stable dsDNA with complementary DNA. Although Im3-oligonucleotide conjugate ON 3 (n = 4) containing the 4-aminobutyl linker formed stable dsDNA with complementary DNA, stabilization of dsDNA by the imidazole amide moiety of ON 3 (n = 4) was lower compared with the pyrrole amide moiety of ON 2 (n = 4). The Py3-γ-Im3-oligonucleotide conjugate ON 4 (n = 2), which possesses binding affinity for C-G base pairs via a pyrrole/imidazole combination and contains a 2-aminoethyl linker, showed high binding ability for complementary DNA. Furthermore, the DNA sequence recognition of MGB polyamide-oligonucleotide conjugates was investigated using single-base mismatch DNAs, which possess a mismatch base in the MGB polyamide binding sequence. The Py3-γ-Im3-oligonucleotide conjugate ON 4 (n = 2) showed high sequence recognition ability for complementary DNA.

Biomimetic total synthesis of plakortone Q via acid-mediated tandem cyclization.

Plakortone Q and plakdiepoxide are natural polyketides isolated from the marine sponge Plakortis simplex. Bicyclo[3.3.0]furanolactone compounds, including plakortone Q, are expected to exhibit a wide range of pharmacological activities. Therefore, developing a simple and versatile synthetic method to produce these compounds is an important research goal. We have achieved the first total synthesis of plakortone Q and plakdiepoxide through an efficient protecting-group-free strategy. The key transformation was an acid-mediated tandem 5-endo-tet/5-endo-tet cyclization of vicinal diepoxide to build the tetrahydrofuran-γ-lactone motif.

Total syntheses of ent-hypocoprin A and ent-hypocoprin B.

This study reports the stereoselective total syntheses of the antipodes of the unique 3/10 bicyclic skeletal sesquiterpenoids, namely, hypocoprin A and hypocoprin B. The synthesis involved conjugate addition accelerated by trimethylsilyl chloride, construction of the ten-membered ring via the intramolecular SN2 reaction promoted by 1,8-diazabicyclo[5.4.0]undec-7-ene, and osmium-mediated π-facial selective dihydroxylation to functionalize the 1,1-disubstituted alkene.

Observational Study on Unhealthy Eating Behavior and the Effect of Sodium-Glucose Cotransporter 2 Inhibitors: The Luseogliflozin Ehime Diabetes Study.

INTRODUCTION: Luseogliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. Unhealthy eating behavior is associated with diabetes, hypertension, and obesity. However, evidence regarding the effect of medications, including SGLT2 inhibitors, on unhealthy eating behavior is limited. This study investigated the association between unhealthy eating behavior and the laboratory and physical findings of Japanese patients with type 2 diabetes given luseogliflozin once daily for 24 weeks. METHODS: Twenty-nine patients with type 2 diabetes mellitus were enrolled in a 24-week prospective, open-label, single-arm pilot study. The information regarding unhealthy eating behaviors (eating fast, late dinner, nighttime snack, skipping breakfast, and eating until full) was obtained using self-reported questionnaires. RESULTS: The baseline rate of eating fast, late dinner, nighttime snack, skipping breakfast, and eating until full was 51.7%, 24.1%, 24.1%, 10.3% and 55.2%, respectively. After administration of luseogliflozin, fasting plasma glucose, HbA1c, aspartate aminotransferase (ALT), weight, body mass index, and waist measurement all decreased significantly. High-density lipoprotein cholesterol and hematocrit increased significantly. In the healthy eating behavior group, the improvements of fasting plasma glucose and ALT, but not other variables, were attenuated. HbA1c level was significantly improved in patients with eating fast, while other unhealthy eating behaviors attenuated the effect of luseogliflozin for HbA1c. The effect of leseogliflozin on the relationship between eating behavior and weight reduction was inconsistent after administration luseogliflozin. CONCLUSION: Luseogliflozin might be more effective for controlling plasma glucose in patients with type 2 diabetes who have a tendency to eat fast, but it might have less effect on those with other unhealthy eating habits.

Total Synthesis of Chlorinated Oxylipin Eiseniachloride B.

Eiseniachloride B is a marine chlorinated oxylipin isolated from the brown alga Eisenia bicyclis. This natural product contains cyclopentane, chlorohydrin, and 14-membered lactone systems that incorporate five stereogenic centers. In this paper, we report on the total synthesis of structurally unique oxylipin eiseniachloride B from optically active lactol via ecklonialactone B in a linear sequence comprising 11 steps with a 12.1% overall yield.

Cordyceps militaris Fruit Body Extract Decreases Testosterone Catabolism and Testosterone-Stimulated Prostate Hypertrophy.

The androgens testosterone and dihydrotestosterone (DHT) are essential for a variety of systemic functions in mature males. Alteration of these hormones results in late-onset hypogonadism (LOH) and benign prostate hyperplasia (BPH). The fruit bodies of fungi of the genus Cordyceps have been regarded as folk medicine or health food with tonic and antifatigue effects. The extract from the fruit body of Cordyceps militaris parasitizing Samia cynthia ricini (CM) was evaluated as a novel-candidate natural product for ameliorating male andropause symptoms. To explore the effects of CM on LOH and BPH, CM was applied to rat models and cultured testicular cells and prostate cells. The concentrations of androgens in the serum and culture media were determined by ELISA. Expression of steroidogenic enzymes and androgen-related genes was evaluated by qPCR, and prostatic cell proliferation was assessed with the cell-viability assay. CM maintained the serum levels of testosterone and DHT, but inhibited testosterone-induced prostate hypertrophy. CM also increased the secretion of testosterone and DHT by primary testicular cells, with no changes in the mRNA expression of steroidogenic enzymes, but decreased the growth of prostatic cell lines. Our data suggest that CM could improve both LOH and BPH in males.

Total synthesis of squafosacin F: stereodivergent approach to mono-tetrahydrofuran acetogenins.

Annonaceous acetogenins have a wide range of potential biological activities. The development of simple and diversity-oriented approaches to their synthesis is therefore important. We have achieved the first total synthesis of squafosacin F and assigned its absolute configuration. The key steps were an acid-mediated tandem intramolecular double cyclization to build the hydroxy-flanked mono-tetrahydrofuran core and decoration with the desired functionalities of the target natural product via highly stereoselective reactions.

Ipragliflozin Ameliorates Liver Damage in Non-alcoholic Fatty Liver Disease.

BACKGROUND: There are few effective medications for non-alcoholic steatohepatitis (NASH). We investigated the efficacy of ipragliflozin (selective sodium-glucose cotransporter-2 inhibitor [SGLT2I]) for the treatment of patients with type 2 diabetes mellitus (T2DM) complicated by non-alcoholic fatty liver disease (NAFLD). METHODS: We prospectively enrolled patients with T2DM complicated by NAFLD treated at our institutions from January 2015 to December 2016. Patients received oral ipragliflozin (50 mg/day) once daily for 24 weeks. Body composition was evaluated using an InBody720 analyzer. We used transient elastography to measure liver stiffness and the controlled attenuation parameter for the quantification of liver steatosis in patients with NASH. RESULTS: Forty-three patients with T2DM and NAFLD were enrolled (12 with biopsy-proven NASH and 31 with NAFLD diagnosed by ultrasonography). After 24 weeks, body weight, hemoglobin A1c (HbA1c), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase, body fat mass, and steatosis were significantly decreased compared to baseline measurements in patients with NASH. However, muscle mass was not reduced, and liver stiffness showed a statistically insignificant tendency to decrease. NAFLD patients also showed a significant reduction in body weight, HbA1c, AST, and ALT compared to baseline measurements. CONCLUSION: Ipragliflozin may be effective in patients with T2DM complicated by NAFLD.

Formal synthesis of cis-solamin: acid-catalyzed one-step construction of 2,5-disubstituted tetrahydrofuran.

A divergent strategy has been used for the concise and efficient enantioselective formal synthesis of Annonaceous acetogenin cis-solamin. Our synthetic strategy comprises concise preparation of the diepoxyester via an 11-membered silaketal constructed by ring-closing metathesis after the dimerization of chiral epoxides, and uses an acid-catalyzed tandem intramolecular SN2-like reaction to construct the threo-cis-threo configuration of the tetrahydrofuran-diol moiety.

Cigarette smoking is a risk factor for the onset of fatty liver disease in nondrinkers: A longitudinal cohort study.

BACKGROUND: The effect of cigarette smoking on the onset of nonalcoholic fatty liver disease (NAFLD) is unclear, especially that associated with drinking small amounts of alcohol. We conducted a longitudinal study to investigate the relationship between cigarette smoking and NAFLD onset, which was stratified according to the amount of alcohol consumed. METHODS: We enrolled 7,905 Japanese subjects who had received annual health checkups more than twice between April 2003 and August 2013, 4,045 of whom met at least one of the following exclusion criteria and were excluded: (a) fatty liver at baseline; (b) hepatitis B or hepatitis C; (c) alcohol consumption (men: ≥210 g/wk; women: ≥140 g/wk); (d) change in alcohol drinking status between baseline and the study's endpoint; (e) change in cigarette smoking habits between baseline and the study's endpoint; or (f) current treatment with antidiabetic agents, antihypertensive agents, and/or lipid-lowering agents. The remaining 3,860 subjects (1,512 men, 2,348 women) were divided into two groups based on average alcohol consumption. RESULTS: After adjusting for the variables associated with metabolic disease, smoking was associated with fatty liver disease onset compared with nonsmokers in nondrinkers (adjusted hazard ratio = 1.988, 95% confidence interval 1.057-3.595; p = 0.034). No association was found between smoking and fatty liver disease onset in the low alcohol consumption group (men: <210 g alcohol/week; women: <140 g alcohol/week). The fatty liver disease incidence increased significantly among the nondrinkers as the number of cigarettes smoked increased (p = 0.001). CONCLUSIONS: Cigarette smoking may be a significant risk factor associated with NAFLD onset in nondrinkers. These results may help clinicians to identify patients who are at a high risk of developing NAFLD and to prevent the progression of NAFLD by promoting earlier interventions that help people discontinue unhealthy lifestyle habits.

Total Synthesis of ent-Ascospiroketal B.

Ascospiroketal B was isolated from a marine-derived fungus as a structurally unique polyketide possessing a rare tricyclic core including 5,5-spiroketal-γ-lactone. An asymmetric total synthesis of ent-ascospiroketal B was achieved using an original synthetic route. The synthesis included the stereoselective construction of 5,5-spiroketal for ascospiroketal B and stereocontrolled construction of a quaternary asymmetric carbon by rearrangement of a trisubstituted epoxide.

Nocturia and Prevalence of Depressive Symptoms in Japanese Adult Patients With Type 2 Diabetes Mellitus: The Dogo Study.

OBJECTIVES: No studies have investigated the association between nocturia and depressive symptoms in patients with type 2 diabetes mellitus. Because nocturia and depressive symptoms are common in patients with type 2 diabetes, we examined this association in Japanese patients with type 2 diabetes. METHODS: We studied 762 Japanese patients with type 2 diabetes. A self-administered questionnaire was used to collect information about the variables under study. The subjects were divided into 3 groups according to their nocturnal micturition: 1) no nocturia; 2) mild nocturia (1 void per night) and 3) moderate to severe nocturia (2 or more voids per night). Depressive symptoms were defined as being present when a subject had a Self-Rating Depression Scale score higher than 49. RESULTS: The prevalence values of mild nocturia, moderate to severe nocturia and depressive symptoms were 39.5%, 41.9% and 16.8%, respectively. Both mild nocturia and moderate to severe nocturia were independently positively associated with depressive symptoms in all patients; the adjusted ORs were 1.96 (95% CI 1.06 to 3.77) and 2.58 (95% CI 1.38 to 5.04). In female patients, both mild nocturia and moderate to severe nocturia were independently associated with depressive symptoms; the adjusted ORs were 5.26 (95% CI 1.73 to 20.61) and 6.91 (95% CI 2.15 to 28.54), respectively. In male patients, neither mild nocturia nor moderate to severe nocturia was significantly related to depressive symptoms. CONCLUSIONS: In Japanese female patients with type 2 diabetes, nocturia may be positively associated with depressive symptoms.

Eating Behaviours and Prevalence of Gastroesophageal Reflux Disease in Japanese Adult Patients With Type 2 Diabetes Mellitus: The Dogo Study.

OBJECTIVES: In the general population, late-night dinner is positively associated with gastroesophageal reflux disease (GERD). No evidence exists regarding the relationship between eating behaviours and GERD in patients with type 2 diabetes mellitus, though the prevalence of GERD in patients with type 2 diabetes is higher than in those without diabetes. We conducted this study to investigate the association between eating behaviours and GERD in Japanese patients with type 2 diabetes. METHODS: The study's subjects were 817 Japanese patients with type 2 diabetes. GERD was defined as being present when a subject had a Quality of Life and Utility Evaluation Survey Technology (QUEST) score of 4 or higher. The assessment of eating behaviour was performed by self-administered questionnaire. Subjects were considered positive for late-night dinner if they answered yes to the question "Do you eat dinner within 2 hours before bedtime at least 3 times per week? RESULTS: The prevalence values of GERD, skipping breakfast, bedtime snacking, late-night dinner and fast eating were 32.0%, 13.7%, 27.1%, 28.8%, and 44.4%, respectively. Late-night dinner was independently positively associated with GERD in patients with type 2 diabetes; the adjusted odds ratio was 1.46 (95% CI 1.03 to 2.05). No relationships were found between skipping breakfast, bedtime snacking or fast eating and GERD. CONCLUSIONS: Late-night dinner may be positively associated with GERD in Japanese patients with type 2 diabetes.

Dietary intake habits and the prevalence of nocturia in Japanese patients with type 2 diabetes mellitus.

AIMS/INTRODUCTION: No reports have been published on the association between dietary intake habits and nocturia in the diabetes population. We therefore evaluated this issue among Japanese patients with diabetes mellitus. MATERIALS AND METHODS: Study participants in the present study were 785 Japanese patients with type 2 diabetes mellitus. Self-administered questionnaires were used to assess each type of dietary intake habit. Vegetable intake habit was assessed by the following question: "Do you have vegetables or seaweed every day?" We used the following two outcomes: (i) nocturia: ≥2 voids per night; and (ii) severe nocturia: ≥3 voids per night. Adjustment was made for age, sex, body mass index, glycated hemoglobin, hypertension, dyslipidemia, smoking, drinking, exercise habit, stroke, ischemic artery disease, diabetic nephropathy, diabetic neuropathy and diabetic retinopathy. RESULTS: The prevalence of nocturia, severe nocturia, and vegetable intake habit was 39.9%, 14.4% and 67.3%, respectively. After adjusting for confounding factors, vegetable intake habit was independently inversely associated with nocturia and severe nocturia: the adjusted odds ratios were 0.67 (95% confidence interval [CI] 0.48-0.94) and 0.46 (95% CI 0.30-0.71), respectively. Among male patients, vegetable intake habit was independently inversely associated with severe nocturia, but not nocturia: the adjusted OR was 0.51 (95% CI 0.29-0.88). Among female patients, vegetable intake habit was independently inversely associated with nocturia and severe nocturia: the adjusted ORs were 0.44 (95% CI 0.24-0.79) and 0.34 (95% CI 0.15-0.78), respectively. CONCLUSIONS: We found an inverse association between vegetable intake habit and nocturia in Japanese patients with type 2 diabetes mellitus.

Physical activity and prevalence of erectile dysfunction in Japanese patients with type 2 diabetes mellitus: The Dogo Study.

AIMS/INTRODUCTION: To date, there is no evidence regarding the association between physical activity (PA) and erectile dysfunction (ED) among Japanese patients with type 2 diabetes mellitus. We investigated this issue among Japanese patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Study participants were 460 male Japanese patients with type 2 diabetes mellitus. The definitions of exercise habit, walking habit and fast walking were based on a self-administered questionnaire regarding PA behavior. Participants were classified into one of four PA levels based on the number of 'Yes' answers to the three questions in the questionnaire: (i) lowest; (ii) lower; (iii) moderate; and (iv) higher. Severe ED and moderate-to-severe ED were based on Sexual Health Inventory for Men score <8 and <12, respectively. RESULTS: The prevalence of moderate-to-severe ED, severe ED, exercise habit, walking habit, and fast walking was 64.6, 51.1, 36.3, 41.3 and 37.6%, respectively. Walking habit was independently inversely associated with moderate-to-severe ED and severe ED. Exercise habit was independently inversely associated with severe ED, but not moderate-to-severe ED. Higher PA was independently inversely associated with moderate-to-severe ED and severe ED (adjusted odds ratio 0.42, 95% confidence interval 0.21-0.85; and adjusted odds ratio 0.38, 95% CI: 0.19-0.73, respectively). There was a statistically significant inverse exposure-response relationship between the PA level and moderate-to-severe ED and severe ED (P for trend = 0.02 and 0.005), respectively. CONCLUSIONS: PA might be inversely associated with ED in Japanese patients with type 2 diabetes mellitus.

Phellilane L, Sesquiterpene Metabolite of Phellinus linteus: Isolation, Structure Elucidation, and Asymmetric Total Synthesis.

A new cyclopropane-containing sesquiterpenoid, phellilane L (1), was isolated from the medicinal mushroom Phellinus linteus ("Meshimakobu" in Japanese), a member of the Hymenochaetaceae family and a well-known fungus that is widely used in East Asia. The planar structure of 1 was determined on the basis of spectroscopic analysis. The authors achieved the first total synthesis of 1. Our protecting group-free synthesis features a highly stereoselective one-pot synthesis involving an intermolecular alkylation/cyclization/lactonization strategy for construction of the key cyclopropane-γ-lactone intermediate. Additionally, our synthesis determined the absolute configuration of phellilane L (1).

B-type natriuretic peptide and renal function in Japanese patients with type 2 diabetes mellitus: The Dogo Study.

Among patients with type 2 diabetes mellitus, the association between B-type natriuretic peptide (BNP) and renal function remains controversial. We therefore investigated this issue among Japanese patients with type 2 diabetes mellitus. This study included 687 Japanese patients with type 2 diabetes mellitus. BNP levels were divided at quartile points on the basis of the distribution. We used four outcomes regarding the renal function: 1) chronic kidney disease (CKD): estimated glomerular filtration rate (eGFR) < 60ml/min/1.72m2, 2) advanced CKD: eGFR < 30ml/min/1.72m2, 3) microalbuminuria: urinary albumin creatinine ratio (UACR) ≥ 30 mg/g creatinine, and 4) macroalbuminuria: UACR ≥ 300 mg/g creatinine. The prevalence values of CKD, advanced CKD, microalbuminuria, and macroalbuminuria were 27.4％, 2.5%, 31.4%, and 9.3%, respectively. Highest BNP (≥ 39.2 ng/ml) was independently positively associated with microalbuminuria and macroalbuminuria (adjusted ORs, 2.61 [95% CI: 1.53-4.49] and 3.45 [95% CI: 1.46-8.72], respectively). High BNP was not associated with advanced CKD or CKD. There was a statistically significant positive exposure-response relationships between the BNP level and advanced CKD, microalbuminuria, and macroalbuminuria (p for trend = 0.047, 0.001, and 0.003, respectively). BNP level may be independently positively associated with advanced CKD, microalbuminuria, and macroalbuminuria but not CKD in Japanese patients with type 2 diabetes mellitus.

Primary Type3 (Non-ABC, Non-GCB) Subtype of Extranodal Diffuse Large B-Cell Lymphoma of the Thyroid Bearing No MYD88 Mutation by Padlock Probe Hybridization.

Primary extranodal malignant lymphoma of the thyroid is a rare entity composed of mostly neoplastic transformation of germinal center-like B cells (GCB) or memory B cells. Other B-cell-type malignancies arising primarily in the thyroid have rarely been described. Immunohistochemical examination of autopsied primary malignant lymphoma of the thyroid in an 83-year-old Japanese female revealed the presence of a non-GCB subtype of diffuse large B-cell lymphoma (DLBCL) without the typical codon 206 or 265 missense mutation of MYD88. The lack of the highly oncogenic MYD88 gene mutation, frequently observed in DLBCL of the activated B-cell (ABC) subtype, and the detection of an extremely aggressive yet local clinical phenotype demonstrated that the present case was an exceptional entity of the type3 (non-GCB and non-ABC) subtype.