[A case of Hamman's syndrome associated with acute-onset type 1 diabetes mellitus presenting with abdominal pain].

A 21-year-old female presented at an emergency department with abdominal pain and nausea. Computed tomography (CT) of the chest and abdomen revealed a small amount of mediastinal emphysema in the precardiac area, but the underlying cause could not be identified. On admission, her plasma glucose was 371 mg/dl, glycated hemoglobin (HbA1c) was 14.0%, and blood pH was 6.91. These findings supported a diagnosis of Hamman's syndrome associated with diabetic ketoacidosis. Her diabetic ketoacidosis was managed with insulin and fluid therapy, and the mediastinal emphysema disappeared spontaneously by the time of discharge. Presence of free air of the chest and abdominal cavity must warrant a differential diagnosis of gastrointestinal perforation; however, when the free air is accompanied by diabetic ketoacidosis, it is not necessary to perform urgent endoscopy.

A synthesis of all stereoisomers of tenuecyclamide A employing a fluorous-Fmoc strategy.

A concise liquid-phase combinatorial synthesis of all stereoisomers of Tenuecyclamide A was achieved using a mixture of D-/L-alanine with each stereoisomer encoded by a different f-Fmoc tag. The synthetic strategy using f-Fmoc reagents as the protecting group for amino acids has been demonstrated to be a useful method for diverse polypeptide analogue synthesis.

[A case of ceftriaxone-associated pseudolithiasis in an adult patient that disappeared after the discontinuation of ceftriaxone].

We report a case of a 47-year-old female patient with ceftriaxone (CTRX)-associated pseudolithiasis. CTRX was administered at a dosage of 2g/day for 8 days because of colonic diverticulitis. A routine abdominal computed tomography (CT) scan was performed to investigate the diverticulitis. However, the CT scan demonstrated stones and sludge in the gallbladder, which had not been present before CTRX administration. Therefore, we diagnosed the patient with pseudolithiasis caused by CTRX and stopped CTRX administration. The stones and sludge disappeared 6 days after stopping CTRX administration. This underreported adverse effect of CTRX should be considered when treating both children and adult patients.

Development and application of new oxidation systems utilizing oxometalate catalysts.

This review describes our recent efforts in the development and application of new oxidation systems utilizing oxometalate catalysts. The novel use of heteropoly acid (HPA), an acidic oxometalate catalyst, in hypervalent iodine-mediated oxidations provided an effective strategy to generate cation radical species that enables a variety of direct C-H functionalizations of aromatic compounds. This strategy brought a facile biaryl synthesis and new spirodienone syntheses in aromatic oxidation chemistry. Moreover, this strategy opens up a facile synthetic route to morphinandienone alkaloids. On the other hand, the use of oxometalate catalyst together with poly(N-isopropylacrylamide) (PNIPAAm)-based polymer in the development of new solid-phase catalyst provided a novel reaction system in water. Due to the characteristic temperature-responsive intelligence of PNIPAAm, this reaction system brought a remarkable acceleration of the reactivity and ease of catalyst recovering in catalytic oxidation that uses hydrogen peroxide or oxygen gas (O2) as primary oxidant. In addition, the recovered solid-phase catalyst could be used for consecutive reactions without any significant loss of its catalytic efficacy.

Novel use of cross-linked poly(N-isopropylacrylamide) gel for organic reactions in aqueous media.

A poly(N-isopropylacrylamide) (PNIPAAm) gel cross-linked with quaternized aminoalkyls was designed. A novel recyclable system based on the external solvent-responsive oil-absorption/elution transition ability of the PNIPAAm gel matrix was then developed.

A new synthesis of dienone lactones using a combination of hypervalent iodine(III) reagent and heteropoly acid.

The oxidation of non-phenolic alkanoic acid derivatives to oxygen heterocycles was investigated; a new oxidative route to dienone lactones has been developed using a combination of hypervalent iodine(III) reagent, phenyliodine(III) bis(trifluoroacetate)(PIFA), and heteropoly acid (HPA).

Body Weight Gain and Hyperphagia After Administration of SGLT-2 Inhibitor: A Case Report.

BACKGROUND: A detailed description is given of a case we encountered in which unexpectedly marked weight gain occurred following a treatment switch from a GLP-1 receptor agonist to an SGLT-2 inhibitor CASE REPORT: The patient, a 44-year-old man with type 2 diabetes mellitus, had gained about 10 kg in weight in the previous year. Therefore, metformin was replaced with liraglutide to obtain reduction of body weight. Although the patient lost about 8 kg (7%), during the 18-month period on the medication, the weight loss stabilized; therefore, the treatment was again switched to tofogliflozin to obtain further reduction of body weight. However, the patient reported increasing hunger and an exaggerated appetite from week 3 onward after the start of tofogliflozin, and gained about 9 kg in weight within 2 weeks, associated with a tendency towards increased HbA1c; therefore, tofogliflozin was discontinued. Immediate reinstitution of liraglutide resulted in reduction of the increased appetite, weight, and HbA1c level. CONCLUSIONS: Caution should be exercised against hyperphagia and weight gain due to hunger that may occur following discontinuation of a GLP-1 receptor agonist and/or initiation of an SGLT-2 inhibitor.

Analyzing the Factors Contributing to Withdrawal from Insulin Therapy Following Additional Administration of Alogliptin: Retrospective Study after Removing Glucotoxicity with Insulin.

We attempted to examine whether withdrawal from insulin therapy is or is not possible with administration of additional alogliptin and identify the contributing factors. The subjects were 43 adult patients with type 2 diabetes undergoing insulin therapy after admission. After glucotoxicity was removed, 25 mg alogliptin was additionally administered. Insulin was reduced by 15.6 ± 13.0 units (mean ± SD), and 17 patients (39.5%) completely withdrew from insulin therapy. Several factors were compared between the two groups of patients: those who could withdraw from insulin therapy and those who could not. The former group showed lower HbA1c levels on admission, a lower insulin dose before adding alogliptin, lower injection frequencies, and longer treatment histories prior to admission. Logistic regression analysis showed that lower insulin dose contributed significantly to withdrawal. These results suggest that a lower insulin dose is the best predictor for withdrawal from insulin therapy after adding alogliptin.

A novel and efficient oxidative biaryl coupling reaction of phenol ether derivatives using a combination of hypervalent iodine(III) reagent and heteropoly acid.

A novel and efficient oxidative biaryl coupling reaction of phenol ether derivatives using a combination of hypervalent iodine(III) reagent, phenyliodine(III) bis(trifluoroacetate) (PIFA), and heteropoly acid has been developed.

Structure-function analysis of vitamin D 24-hydroxylase (CYP24A1) by site-directed mutagenesis: amino acid residues responsible for species-based difference of CYP24A1 between humans and rats.

Our previous studies revealed the species-based difference of CYP24A1-dependent vitamin D metabolism. Although human CYP24A1 catalyzes both C-23 and C-24 oxidation pathways, rat CYP24A1 shows almost no C-23 oxidation pathway. We tried to identify amino acid residues that cause the species-based difference by site-directed mutagenesis. In the putative substrate-binding regions, amino acid residue of rat CYP24A1 was converted to the corresponding residue of human CYP24A1. Among eight mutants examined, T416M and I500T showed C-23 oxidation pathway. In addition, the mutant I500F showed quite a different metabolism of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] from both human and rat CYP24A1. These results strongly suggest that the amino acid residues at positions 416 and 500 play a crucial role in substrate binding and greatly affect substrate orientation. A three-dimensional model of CYP24A1 indicated that the A-ring and triene part of 1alpha,25(OH)2D3 could be located close to amino acid residues at positions 416 and 500, respectively. Our findings provide useful information for the development of new vitamin D analogs for clinical use.

Metabolism of 2 alpha-propoxy-1 alpha,25-dihydroxyvitamin D3 and 2 alpha-(3-hydroxypropoxy)-1 alpha,25-dihydroxyvitamin D3 by human CYP27A1 and CYP24A1.

Recently, we demonstrated that some A-ring-modified vitamin D3 analogs had unique biological activity. Of these analogs, 2alpha-propoxy-1alpha,25(OH)2D3 (C3O1) and 2alpha-(3-hydroxypropoxy)-1alpha,25(OH)2D3 (O2C3) were examined for metabolism by CYP27A1 and CYP24A1. Surprisingly, CYP27A1 catalyzed the conversion from C3O1 to O2C3, which has 3 times more affinity for vitamin D receptor than C3O1. Thus, the conversion from C3O1 to O2C3 by CYP27A1 is considered to be a metabolic activation process. Five metabolites were detected in the metabolism of C3O1 and O2C3 by human CYP24A1 including both C-23 and C-24 oxidation pathways. On the other hand, three metabolites of the C-24 oxidation pathway were detected in their metabolism by rat CYP24A1, indicating a species-based difference in the CYP24A1-dependent metabolism of C3O1 and O2C3 between humans and rats. Kinetic analysis revealed that the Km and kcat values of human CYP24A1 for O2C3 are, respectively, approximately 16 times more and 3 times less than those for 1alpha,25(OH)2D3. Thus, the catalytic efficiency, kcat/Km, of human CYP24A1 for O2C3 is only 2% of 1alpha,25(OH)2D3. These results and a high calcium effect of C3O1 and O2C3 in animal experiments using rats suggest that C3O1 and O2C3 are promising for clinical treatment of osteoporosis.

A novel and useful oxidative intramolecular coupling reaction of phenol ether derivatives on treatment with a combination of hypervalent iodine(III) reagent and heteropoly acid.

The oxidative intramolecular coupling reaction of phenol ether derivatives (nonphenolic derivatives) on treatment with a novel combination of a hypervalent iodine(III) reagent, phenyliodine bis(trifluoroacetate) (PIFA), and heteropoly acid (HPA) was studied. Biaryl compounds were obtained in excellent yields on treatment of highly substituted phenol ethers. On the other hand, spirodienones were specifically formed when one of the preferred arylic coupling sites was substituted with a methoxy group in the para position.

The efficient synthesis of morphinandienone alkaloids by using a combination of hypervalent iodine(III) reagent and heteropoly acid.

The non-phenolic coupling reaction of benzyltetrahydroisoquinolines (laudanosine derivatives) by using a hypervalent iodine(III) reagent is described. In general, chemical oxidation of laudanosine gives glaucine. In contrast to general chemical oxidizing reagent systems, the novel use of reagent combination of phenyliodine bis(trifluoroacetate) (PIFA), and heteropoly acid (HPA) afforded morphinandienone alkaloids in excellent yields. In order to achieve the coupling reaction with simple reaction procedure, the use of HPA supported on silica gel instead of HPA was demonstrated and sufficient yield was exerted again. The present reagent system, PIFA/HPA, was also applied to the oxidation of other non-phenolic benzyltetrahydroisoquinolines and the high yield conversion to morphinandienones was accomplished.

A novel and concise synthesis of spirodienone alkaloids using hypervalent iodine(III) reagents.

Intramolecular oxidative coupling reaction of N-protected benzyltetrahydroisoquinoline derivatives using hypervalent iodine(III) reagents was investigated. The use of remarkable combination of phenyliodine bis (trifluoroacetate) (PIFA) and heteropoly acid (HPA) in wet acetonitrile smoothly afforded morphinandienone alkaloids, while neospirinedienone alkaloids were obtained in high yield under anhydrous conditions.

ST-segment re-elevation unrelated to left ventricular ejection fraction or volume after anterior wall acute myocardial infarction treated with successful reperfusion.

Ventricular remodeling is a major determinant of the long-term prognosis of patients with acute myocardial infarction (AMI). No previous study examined the relation of ST-segment re-elevation to left ventricular (LV) volume and function in patients with successful reperfusion. We examined the relation of ST-segment re-elevation to LV function and volume indices in 51 patients with anterior wall AMI who underwent successful reperfusion by direct coronary angioplasty. A 12-lead electrocardiogram was recorded once a day until 7 days after the onset of AMI. ST-segment shift was measured and Sigma ST was defined as the sum of ST-segment elevation obtained from leads V2, V3, and V4. ST-segment re-elevation was defined as present when the difference between maximal and minimal Sigma ST (Delta ST) was >0.3mV. LV indices were obtained from left ventriculography performed approximately 1 month after the onset of AMI. ST-segment re-elevation was observed in 15 patients (29%). No significant differences were observed between the ST- re-elevation group and non-ST-re-elevation group in LV ejection fraction (49.4+/-14.0 vs. 51.2+/-11.5%), LV end-systolic volume index (35.8+/-13.1 vs. 33.8+/-12.5 mL/m(2)) or LV end-diastolic volume index (69.7+/-12.8 vs. 68.3+/-14.4 mL/m(2)). The difference between maximal and minimal Sigma ST (Delta ST) was not significantly correlated with any LV index examined. In conclusion, the present study revealed that ST-segment re-elevation after successful reperfusion in anterior wall AMI patients was not related to LV volume or function, indicating that ST-re-elevation is not a clinically meaningful indicator of LV remodeling.