A thermophilic, acidophilic procaryote lacking a cell wall has been isolated from a coal refuse pile which had undergone self-heating. Electron micrographs, chemical assays for hexosamine, and the inability of vancomycin to inhibit growth confirm the lack of a cell wall. The apparent ability of the organism to reproduce by budding and the low guanine plus cytosine content of its DNA indicate a relation to the mycoplasmas. The temperature optimum of the organism is 59 degrees C, and growth occurs over a range of 45 degrees to 62 degrees C. No growth occurs at 37 degrees C or at 65 degrees C. The optimum pH for growth is between 1 and 2, and growth occurs between pH 0.96 and 3.5 but does not occur at pH 0.35 and only poorly at pH 4.0. We propose to call this organism Thermoplasma acidophila. The existence of this organism extends considerably the range of habitats in which mycoplasma may occur.
SUMMARYFourteen cultures of thermophilic acidophilic bacteria have been isolated from a variety of thermal acid environments by enrichment at elevated temperatures and low pH. Morphological and physiological properties suggest that the bacteria are members of a homogeneous group of aerobic spore-forming rods. The base composition of the DNA is about 62 % guanine plus cytosine, and this fact together with the physiological properties suggests that relationship to other species in the genus Bacillus is rather distant. The isolates are hence classified in a new species, Bacillus acidocaldarius.The species is characterized by the ability to grow at temperatures from 45" to 70" (optimum 60" to 65") and at pH values from 2.0 to 6.0 (optimum 3 to 4).
Without inhibiting COX-2 enzyme, META060 reduces the inflammation by inhibiting multiple kinases involved in NF-kappaB pathway, and may have potential as a safe anti-inflammatory therapeutic.
Aims/HypothesisWe developed KDT501, a novel substituted 1,3-cyclopentadione chemically derived from hop extracts, and evaluated it in various in vitro and in vivo models of diabetes and insulin sensitivity.MethodsKDT501 was evaluated for anti-inflammatory effects in monocyte/macrophage cells; agonistic activity for peroxisome proliferator-activated receptors (PPAR); lipogenesis and gene expression profile in human subcutaneous adipocytes. Body composition, glucose, insulin sensitivity, and lipids were assessed in diet-induced obesity (DIO) mice and Zucker Diabetic Fatty (ZDF) rats after oral administration.ResultsKDT501 mediated lipogenesis in 3T3L1 and human subcutaneous adipocytes; however, the gene expression profile of KDT501 differed from that of the full PPARγ agonist rosiglitazone, suggesting that KDT501 has pleiotropic biological activities. In addition, KDT501 showed only modest, partial PPARγ agonist activity and exhibited anti-inflammatory effects in monocytes/macrophages that were not observed with rosiglitazone. In a DIO mouse model, oral administration of KDT501 significantly reduced fed blood glucose, glucose/insulin AUC following an oral glucose bolus, and body fat. In ZDF rats, oral administration of KDT501 significantly reduced fed glucose, fasting plasma glucose, and glucose AUC after an oral glucose bolus. Significant, dose-dependent reductions of plasma hemoglobin A1c, weight gain, total cholesterol, and triglycerides were also observed in animals receiving KDT501.ConclusionThese results indicate that KDT501 produces a unique anti-diabetic profile that is distinct in its spectrum of pharmacological effects and biological mechanism from both metformin and pioglitazone. KDT501 may thus constitute a novel therapeutic agent for the treatment of Type 2 diabetes and associated conditions.
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