Discovery of Benzopyrrolizidines as Promising Antigiardiasic Agents.

Current treatments for giardiasis include drugs with undesirable side effects, which increase the levels of therapeutic desertion and promote drug resistance in the parasites. Herein, we describe the antigiardiasic evaluation on Giardia lamblia trophozoites of a structurally diverse collection of 74 molecules. Among these scaffolds, we discovered a benzopyrrolizidine derivative with higher antigiardiasic activity (IC50 = 11 µM) and lower cytotoxicity in human cell cultures (IC50 = 130 µM) than those displayed by the current gold-standard drugs (metronidazole and tinidazole). Furthermore, this compound produced morphologic modifications of trophozoites, with occasional loss of one of the nuclei, among other changes not observed with standard giardicidal drugs, suggesting that it might act through a novel mechanism of action.

Circulating Concentrations of Advanced Glycation end Products, its Association With the Development of Diabetes Mellitus.

BACKGROUND: Diabetes Mellitus (DM) is characterized by the production and accumulation of advanced glycation end products (AGEs), which are one of the key mechanisms in the development of its chronic complications. AIMS OF THE STUDY: To assess the serum AGEs concentration by a radioimmunoassay (RIA) developed in our laboratory, to establish reference values in healthy population and to evaluate the diagnostic potential of measuring longitudinal changes in circulating AGEs concentrations to predict the development of DM. METHODS: Clinical and metabolic parameters were obtained from a cohort of 781 Mexican people, initially and then seven years later. AGEs were quantified by a specific RIA. Associations of the changes in circulating levels of AGEs with the appearance of impaired fasting glucose (IFG), and the development of DM were evaluated. RESULTS: Diabetic subjects had higher circulating levels of AGEs than normoglycemic subjects or individuals with IFG in both samples studied (471 vs. 246 and 342 µU/mL, p <0.001; and 912 vs. 428 and 519 µU/mL, p <0.001; respectively). A multinomial logistic regression analysis showed that subjects who had AGEs concentration ≥400 µU/mL in the baseline sample had a relative risk ratio of 1.98 to develop IFG seven years later (p = 0.003). While the subjects who had AGEs concentration ≥450 µU/mL in the baseline sample had a relative risk ratio of 10.7 to develop DM seven years later (p <0.001). CONCLUSIONS: Circulating AGEs concentration is a good early marker to predict risk of developing DM.