Crude extracts of Mexican medicinal plants were screened for trypanocidal activity against Trypanosoma cruzi, which is the etiological agent for Chagas' disease, one of the most serious protozoan diseases in Latin America. There were 43 kinds of methanolic and other organic extracts from 39 plants which were examined by the preliminary screening test to see immobilization of epimastigotes of T. cruzi in vitro. Eighteen of them showed activity at the concentration of 2 mg/ml after incubation for 2 h, while 13 showed activity at the concentration of 1 mg/ml after incubation for 48 h. Among them, the MeOH extract of roots of Aristolochia taliscana (Aristolochiaceae), locally known as "Guaco," immobilized all the epimastigotes even at lower concentration of 0.5 mg/ml (48 h). In order to identify principal compounds for this activity, the MeOH extract of Guaco was subjected to bioassay-guided fractionation. From the active fractions, four neolignans, eupomatenoid-7 (1), licarin A (2), eupomatenoid-1 (5) and licarin B (6), and two lignans, austrobailignan-7 (3) and fragransin E 1 (4) were isolated. Compounds 1-4 immobilized all the epimastigotes at the minimum concentration of 25-75 m mg/ml after incubation for 48 h, while compounds 5 and 6 were inactive. Corresponding concentration of gossypol, berberine chloride and harmine was 280 m mg/ml, 300 m mg/ml and Ͼ500 m mg/ml, respectively.
Alkaline phosphatases (APs) remove the phosphate (dephosphorylation) needed in multiple metabolic processes (from many molecules such as proteins, nucleotides, or pyrophosphate). Therefore, APs are important for bone mineralization but paradoxically they can also be deleterious for other processes, such as vascular calcification and the increasingly known cross-talk between bone and vessels. A proper balance between beneficial and harmful activities is further complicated in the context of chronic kidney disease (CKD). In this narrative review, we will briefly update the complexity of the enzyme, including its different isoforms such as the bone-specific alkaline phosphatase or the most recently discovered B1x. We will also analyze the correlations and potential discrepancies with parathyroid hormone and bone turnover and, most importantly, the valuable recent associations of AP's with cardiovascular disease and/or vascular calcification, and survival. Finally, a basic knowledge of the synthetic and degradation pathways of APs promises to open new therapeutic strategies for the treatment of the CKD-Mineral and Bone Disorder (CKD-MBD) in the near future, as well as for other processes such as sepsis, acute kidney injury, inflammation, endothelial dysfunction, metabolic syndrome or, in diabetes, cardiovascular complications. However, no studies have been done using APs as a primary therapeutic target for clinical outcomes, and therefore, AP's levels cannot yet be used alone as an isolated primary target in the treatment of CKD-MBD. Nonetheless, its diagnostic and prognostic potential should be underlined.
Chronic kidney disease-mineral and bone disorder is a new term defining a complex syndrome which underlines the need of a systemic approach to disturbances of calcium and phosphate metabolism in patients with renal failure. In recent years, the availability of new phosphorus binders and the appearance of new selective vitamin D receptor activators and calcimimetics have increased our current armamentarium and have changed previous paradigms. All these drugs can be used in combination, acting in distinct yet complementary pathways, with a resultant improvement in their individual clinical profile and reduction in secondary effects, while enhancing the achievement of clinical guideline targets. On the other hand, we should be aware that treatment costs are increasing and most of our knowledge is opinion-based. In this article, we shall consider rational recommendations on the control of calcium, phosphorus and parathyroid hormone while awaiting new evidence. We shall also briefly review some important related issues such as vascular calcification, adynamic bone disease, osteoporosis and the need of parathyroidectomy. Future guidelines may modify current recommendations, but we believe that the lack of an absolute evidence is not equivalent to the lack of awareness of the important problem which chronic kidney disease-mineral and bone disorder represents.
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