Development of a Scalable Synthesis of Tofogliflozin.

An efficient and scalable synthesis of an antidiabetic drug, tofogliflozin (1), which was identified as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor, is described. A key factor in the synthesis of 1 was the selection of the purpose-designed protecting group, which plays a strategic role in protection, chemoselective activation, and crystalline purification. The developed and optimized method made it possible to prepare 1 on a multidecagram scale without any column chromatography.

Assessing the effects of severe rainstorm-induced mixing on a subtropical, subalpine lake.

Severe rainstorms cause vertical mixing that modifies the internal dynamics (e.g., internal seiche, thermal structure, and velocity filed) in warm polymictic lakes. Yuan Yang Lake (YYL), a subtropical, subalpine, and seasonally stratified small lake in the north-central region of Taiwan, is normally affected by typhoons accompanied with strong wind and heavy rainfall during the summer and fall. In this study, we used the field data, statistical analysis, spectral analysis, and numerical modeling to investigate severe rainstorm-induced mixing in the lake. Statistical determination of the key meteorological and environmental conditions underlying the observed vertical mixing suggests that the vertical mixing, caused by heat loss during severe rainstorms, was likely larger than wind-induced mixing and that high inflow discharge strongly increased heat loss through advection heat. Spectral analysis revealed that internal seiches at the basin scale occurred under non-rainstorm meteorological conditions and that the internal seiches under the rainstorm were modified on the increase of the internal seiche frequencies. Based upon observed frequencies of the internal seiches, a two-dimensional model was simulated and then appropriate velocity patterns of the internal seiches were determined under non-rainstorm conditions. Moreover, the model implemented with inflow boundary condition was conducted for rainstorm events. The model results showed that the severe rainstorms promoted thermal destratification and changed vertical circulation of the basin-scale, internal seiche motion into riverine flow.

Particle release transport in Danshuei River estuarine system and adjacent coastal ocean: a modeling assessment.

A three-dimensional hydrodynamic model was created to study the Danshuei River estuarine system and adjacent coastal ocean in Taiwan. The model was verified using measurements of the time-series water surface elevation, tidal current, and salinity from 1999. We conclude that our model is consistent with these observations. Our particle-tracking model was also used to explore the transport of particles released from the Hsin-Hai Bridge, an area that is heavily polluted. The results suggest that it takes a much longer time for the estuary to be flushed out under low freshwater discharge conditions than with high freshwater discharge. We conclude that the northeast and southwest winds minimally impact particle dispersion in the estuary. The particles fail to settle to the bottom in the absence of density-induced circulation. Our model was also used to simulate the ocean outfall at the Bali. Our experimental results suggest that the tidal current dominates the particle trajectories and influences the transport properties in the absence of a wind stress condition. The particles tend to move northeast or southwest along the coast when northeast or southwest winds prevail. Our data suggest that wind-driven currents and tidal currents play important roles in water movement as linked with ocean outfall in the context of the Danshuei River.

Impact of phosphorus load reduction on water quality in a stratified reservoir-eutrophication modeling study.

Monitoring data collected from the Mingder Reservoir in Taiwan indicate that the water quality is between mesotrophic and eutrophic. Chlorophyll a concentration is higher in the summer and anoxic conditions occur in the bottom. The data also reveal that a pronounced vertical thermal gradient in summer and vertical mixing the end of fall. A vertical two-dimensional, laterally averaged hydrodynamic and water quality model (CE-QUAL-W2) was adopted to simulate the water surface elevation, water temperature, and water quality conditions in the water column. The modeling effort was supported with monitoring data collected in the field for a 2-year period in the reservoir. The hydrodynamic model reproduced the time series water surface elevation. Spatial and temporal distributions of temperature in the water column of the reservoir were also well reproduced by the hydrodynamic model. Model-calculated concentrations of key water quality constituents such as nutrients, dissolved oxygen, and algal biomass matched the measured values closely in the reservoir. The calibrated model was then applied to simulate water quality response to various nutrient reduction scenarios. Results of the model scenario runs reveal that a 20% and 80% reduction of the phosphorus loads will improve the water quality from eutrophic to mesotrophic and oligotrophic conditions, respectively. The modeling effort has yielded valuable information that can be used by decision makers for the evaluation of different management strategies of reducing watershed nutrient loads.

Beneficial effect of combination therapy with antihypertensive drugs in patients with hypertension.

BACKGROUND: Cardiac hypertrophy and failure are major complications of hypertension. OBJECTIVES: The beneficial effect of treatment with antihypertensive drugs on serum levels of brain natriuretic peptide (BNP) was examined in patients with essential hypertension. METHODS: Antihypertensive drugs were administered to 88 hypertensive patients (44 diabetic and 44 nondiabetic) whose systolic blood pressure was greater than 140 mmHg and/or diastolic blood pressure was greater than 90 mmHg. Other antihypertensive drugs were added every two months until the blood pressure fell below 130/85 mmHg. Candesartan, benidipine, bisoprolol or celiprolol, and bunazosin were administered in this order. RESULTS: The mean systolic blood pressure was reduced from 163.7+/-11.6 mmHg to 121.8+/-7.5 mmHg after 12 months in patients with diabetes and from 167.6+/-12.3 mmHg to 122.8+/-7.5 mmHg in patients without diabetes. The mean diastolic blood pressure was also significantly reduced in patients with and without diabetes. Serum BNP levels were reduced from 52.2+/-38.8 pg/mL to 38.8+/-30.9 pg/mL in patients with diabetes and from 47.1+/-34.2 pg/mL to 35.8+/-22.5 pg/mL in patients without diabetes. In patients older than 70 years of age, serum BNP levels were reduced from 56.3+/-39.3 pg/mL to 40.2+/-23.0 pg/mL in those with diabetes and from 54.6+/-32.9 pg/mL to 38.0+/-16.0 pg/mL in those without diabetes. CONCLUSIONS: These results indicate that combination therapy with antihypertensive drugs is usually necessary to reduce blood pressure to below 130/85 mmHg and to improve serum BNP levels.

Cardiovascular disorders in patients with diabetes mellitus.

Diabetes mellitus is a disease with multiorgan involvement. Besides retinopathy, nephropathy and peripheral neuropathy induced by microangiopathy, both cardiovascular and cerebrovascular complications are significant. Both cardiomyopathy and coronary artery disease are observed in patients with diabetes, and the latter is clinically more important because of its high incidence and seriousness.

Risk factors for coronary artery sclerosis in patients with diabetes.

OBJECTIVE: To examine risk factors for coronary artery sclerosis in patients with diabetes mellitus. METHODS: Patients with diabetes were divided into two groups based on whether their electrocardiogram (ECG) showed ischemic changes. In addition to traditional risk factors, other parameters (ie, serum levels of serotonin, homocysteine, thrombomodulin, plasminogen activator inhibitor-1, tissue plasminogen activator, vascular endothelial growth factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and endothelial-leukocyte adhesion molecule-1) were measured in both groups. RESULTS: In the group with ischemic ECG changes (n=13), systolic blood pressure was significantly higher than in the group with no changes (n=18). There were no significant differences in the serum levels of other factors; however, body mass index, hemoglobin A1c, total cholesterol, low density lipoprotein cholesterol and triglyceride levels tended to be higher in the group with ischemic ECG changes. CONCLUSIONS: Although the sample of patients was limited, these results suggest that strict control of traditional risk factors, especially high blood pressure, is important for preventing coronary artery sclerosis in patients with diabetes mellitus.

Enantioselective deprotonation of meso-cycloheptanone derivative: application to the synthesis of a potential intermediate for pseudomonic acid B.

[reaction: see text] A novel synthetic path to a potential intermediate for the synthesis of pseudomonic acid B was established by employing enantioselective deprotonation of a meso-cycloheptanone derivative bearing hydroxy groups at the 3,4,5,6-positions with lithium (S,S')-alpha,alpha'-dimethyldibenzylamide as a key step.