Molecular design, synthesis, and hypoglycemic activity of a series of thiazolidine-2,4-diones.

A series of imidazopyridine thiazolidine-2,4-diones were designed and synthesized from their corresponding pyridines. These compounds represent conformationally restricted analogues of the novel hypoglycemic compound rosiglitazone (5). The series was evaluated for its effect on insulin-induced 3T3-L1 adipocyte differentiation in vitro and its hypoglycemic activity in the genetically diabetic KK mouse in vivo. The structure-activity relationships are discussed. On the basis of the in vivo potency, 5-[4-(5-methoxy-3-methyl-3H-imidazo[4, 5-b]pyridin-2-ylmethoxy)benzyl]thiazolidine-2,4-dione (19a) was selected as the candidate for further studies in a clinical setting.

Relationship of 31P MR spectroscopy to the histopathological grading of chronic hepatitis and response to therapy.

PURPOSE: In vivo phosphorus-31 MR spectroscopy (31P MRS) was performed in the human liver in order to investigate the relation between: the ratios of phosphorus metabolites in the liver; the histopathological grading of chronic hepatitis; and the response to therapy. MATERIAL AND METHODS: Hepatic 31P MRS using the DRESS method (depth-resolved surface-coil spectroscopy) was carried out in 45 patients with chronic viral hepatitis or autoimmune hepatitis, and in 16 control subjects. We measured the ratios of the peak areas of phosphomonoesters (PME), inorganic phosphate (Pi), or phosphodiesters (PDE) to the peak area of beta-adenosine triphosphate (ATP). RESULTS: The PDE/ATP ratio of patients with chronic hepatitis or liver cirrhosis was lower than that of control subjects (liver cirrhosis = 0.74; chronic active hepatitis = 1.13-1.21; normal = 1.43); only a small difference was found in the PME/ATP and Pi/ATP ratios. There was no correlation between the spectra and histopathological grading or response to therapy, but the response to therapy was poor when a reduced PDE/ATP ratio was present. CONCLUSION: The PDE/ATP ratio measured by 31P MRS makes it possible to identify the transition of chronic active hepatitis into liver cirrhosis with a poor response to therapy.

Interface problems between material recycling systems and plants.

A most important problem to creating a CELSS system to be used in space, for example, for a Lunar Base or Manned Mars mission, seems to be how to design and operate the various material recycling systems to be used on the missions. Recent studies of a Lunar Base habitat have identified examples of CELSS configurations to be used for the Plant Cultivation Module. Material recycling subsystems to be installed in the Plant Cultivation Modules are proposed to consist of various sub-systems, such as dehumidifiers, oxygen separation systems, catalytic wet oxidation systems, nitrogen adjusting systems, including tanks, and so on. The required performances of such various material recycling subsystems are determined based on precise metabolic data of derived from the various species of plants to be selected and investigated. The plant metabolic data, except that for wheat and potato, has not been fully collected at the present time. Therefore, much additional plant cultivation data is required to determine the performances of each material recycling subsystem introduced in Plant Cultivation Modules.

Evaluations of catalysts for wet oxidation waste management in CELSS.

A wet oxidation is considered to be one of the most effective methods of waste processing and recycling in CELSS (Controlled Ecological Life Support System). The first test using rabbit waste as raw material was conducted under a decomposition temperature of 280 degrees C for 30 minutes and an initial pure oxygen pressure of 4.9 MPa (50 kgf/cm2) before heating, and the following results were obtained. The value of COD (Chemical Oxygen Demand) was reduced 82.5% by the wet oxidation. And also the Kjeldahl nitrogen concentration was decreased 98.8%. However, the organic carbon compound in the residual solution was almost acetic acid and ammonia was produced. In order to activate the oxidation more strongly, the second tests using catalysts such as Pd, Ru and Ru+Rh were conducted. As the results of these tests, the effectiveness of catalysts for oxidizing raw material was shown as follows: COD and the Kjeldahl nitrogen values were drastically decreased 99.65% and 99.88%, respectively. Furthermore, the quantity of acetic acid and ammonia were reduced considerably. On the other hand, nitrate was showed a value 30 times as much as without catalytic oxidation.