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AbstractBackground:The majority of patients with type 2 diabetes mellitus (T2DM) are overweight or obese. Obesity is a significant risk factor for increased morbidity and mortality in people with T2DM, and increased weight has been shown to worsen glycemic control and increase the risk of diabetes progression.Methods:A search was conducted of the National Library of Medicine (PubMed) for articles published from 1990 to 2009 about the treatments of T2DM, relationship between T2DM and weight gain, obesity-related comorbidities of T2DM, and T2DM therapies associated with increased weight. Reference lists of retrieved articles were reviewed for additional publications.Findings:Results from large, prospective clinical trials have shown that weight reduction significantly improves glycemic control and blood pressure in T2DM patients and lowers the risk of progression of T2DM as well as CV disease and cancer. Treatment-related weight gain is a side effect of many oral antidiabetes agents and insulin. The thiazolidinediones (TZD), sulfonylureas, and glinides are associated with weight gain. Despite the weight gain, TZDs also redistribute fat from the central to peripheral compartments, which may lead to a beneficial effect on insulin resistance. Among insulin products, the basal insulin analog detemir is typically associated with a smaller weight increase than human insulin and insulin analog preparations, including glargine, biphasic, and prandial insulin regimens. Alpha-glucosidase inhibitors and dipeptidyl peptidase-4 inhibitors are weight neutral, whereas glucagon-like peptide1-R agonists and metformin are associated with weight loss.Discussion:An effective approach to management of the obese patient with diabetes is to communicate the significant benefits of a 1  kg reduction in body weight or prevention of weight gain on glycemic control and reduced morbidity and mortality.Limitation:This article is based on an extensive literature review rather than the prospective studies needed to define further the effect of weight gain on the management of T2DM.Conclusion:Weight management should be an integral part of a T2DM treatment strategy that includes selecting oral antidiabetes medications and insulin products that are weight beneficial. [ABSTRACT FROM AUTHOR]

In this study, thirteen sponge-derived terpenoids, including five linear furanoterpenes: furospinulosin-1 (1), furospinulosin-2 (2), furospongin-1 (3), furospongin- 4 (4), and demethylfurospongin-4 (5); four linear meroterpenes: 2-(hexaprenylmethyl)-2- methylchromenol (6), 4-hydroxy-3-octaprenylbenzoic acid (7), 4-hydroxy-3-tetraprenylphenylacetic acid (8), and heptaprenyl-p-quinol (9); a linear triterpene, squalene (10); two spongian-type diterpenes dorisenone D (11) and 11β-acetoxyspongi-12-en-16-one (12); a scalarane-type sesterterpene; 12-epi-deoxoscalarin (13), as well as an indole alkaloid, tryptophol (14) were screened for their in vitro activity against four parasitic protozoa; Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum. Cytotoxic potential of the compounds on mammalian cells was also assessed. All compounds were active against T. brucei rhodesiense, with compound 8 being the most potent (IC50 0.60 μg/mL), whereas 9 and 12 were the most active compounds against T. cruzi, with IC50 values around 4 μg/mL. Compound 12 showed the strongest leishmanicidal activity (IC50 0.75 μg/mL), which was comparable to that of miltefosine (IC50 0.20 μg/mL). The best antiplasmodial effect was exerted by compound 11 (IC50 0.43 μg/mL), followed by compounds 7, 10, and 12 with IC50 values around 1 μg/mL. Compounds 9, 11 and 12 exhibited, besides their antiprotozoal activity, also some cytotoxicity, whereas all other compounds had low or no cytotoxicity towards the mammalian cell line. This is the first report of antiprotozoal activity of marine metabolites 1-14, and points out the potential of marine sponges in discovery of new antiprotozoal lead compounds. [ABSTRACT FROM AUTHOR]

We describe the synthesis of new diaryl substituted diazabicyclo[3.2.1]octanes from diazepanes which were prepared by the reduction of diazepanones. The formation of the bicyclic system was optimized by microwave irradiation and the structures of the new compounds were established by single crystal structure analysis and NMR spectroscopy. All new compounds were tested for their potencies against Plasmodium falciparum K1and Trypanosoma b. rhodesiense, the causative organisms of malaria tropica and the East African form of sleeping sickness. [ABSTRACT FROM AUTHOR]

Abstract  5-Amino-2-azabicyclo[3.2.2]nonanes possess activity against the causative organisms of Human African trypanosomiasis and Malaria tropica. Their newly prepared N-acyl derivatives were inactive against Trypanosoma b. rhodesiense, but some of them showed good antiplasmodial activity against a multiresistant strain of Plasmodium falciparum. The results are compared to the activities of the N-unsubstituted compounds and N-sulfonyl analogues. The diastereomeric character of the formed amides was elucidated by NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Summary.  We synthesized several 4-aminobicyclo[2.2.2] octan-2-ols and 4-amino-2-azabicyclo[3.2.2]nonanes from epimerized 4-amino-bicyclo[2.2.2]octan-2-ones. The new compounds were tested for their activity against Trypanosoma b. rhodesiense, the causative organism of East African sleeping sickness, and Plasmodium falciparum K 1, a multiresistant protozoan parasite which causes Malaria tropica. The results are compared to the activities of their formerly synthesized stereoisomers and structure–activity relationships are discussed. [ABSTRACT FROM AUTHOR]

Summary.  Several 2-substituted 4-amino-2-azabicyclo [3.2.2]nonane derivatives were synthesized. The new compounds were investigated for their activities against the causative organism of East African sleeping sickness, Trypanosoma b. rhodesiense, and a protozoan parasite which causes Malaria tropica, Plasmodium falciparum K1, a strain which is resistant to chloroquine and pyrimethamine. The results are compared to the activities of 2-unsubstituted 4-amino-2-azabicyclo[3.2.2]nonanes. [ABSTRACT FROM AUTHOR]