Asociación de la fuerza muscular con marcadores tempranos de riesgo cardiovascular en adultos sedentarios

ObjectiveTo assess the association between muscle strength and early cardiovascular risk (CVR) markers in sedentary adults.Materials and methodsA total of 176 sedentary subjects aged 18-30 years were enrolled. Body mass index and fat percentage were calculated, and waist circumference, grip strength by dynamometry, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and maximal oxygen uptake by VO_2max were measured as CVR markers. A multivariate logistic regression analysis was used to assess associations between muscle strength and CVR markers.ResultsInverse correlations were found between muscle strength and adiposity (r = -.317; P = .001), waist circumference (r = -.309; P = .001), systolic blood pressure (r = -.401; P = .001), and mean arterial pressure (r = -.256; P = .001). Subjects with lower levels of muscle strength had a 5.79-fold (95% CI 1.57 to 9.34; P = .008) risk of having higher adiposity levels (≥ 25%) and a 9.67-fold (95% CI = 3.86 to 19.22; P < .001) risk of having lower physical capacity values for VO_2max (≤ 31.5 mL/kg/min^-1).ConclusionsIn sedentary adults, muscle strength is associated to early manifestations of CVR. It is suggested that muscle strength testing is added to routine measurement of VO_2max and traditional risk factors for prevention and treatment of cardiovascular risk.     

In vitro activity of amphotericin B cochleates against Leishmania chagasi

Cochleate delivery vehicles are a novel lipid-based system with potential for delivery of amphotericin B (AmB). In this study, the efficacy of cochleates was evaluated by examining the in vitro activity of AmB cochleates (CAMB) against Leishmania chagasi in a macrophage model of infection. We demonstrate that CAMB is nontoxic to macrophages at concentrations as high as 2.5 μg/mL, whereas the conventional formulation, AmB deoxycholate, showed high toxicity at this concentration. The in vitro activity of CAMB against L. chagasi was found to be similar to that of the reference drug AmB deoxycholate, with ED50s of 0.017 μg/mL and 0.021 μg/mL, respectively. Considering that L. chagasi affects organs amenable to cochleate-mediated delivery of AmB, we hypothesize that CAMB will be an effective lipid system for the treatment of visceral leishmaniasis.     

In Vitro and In Vivo Analysis of RTK Inhibitor Efficacy and Identification of Its Novel Targets in Glioblastomas

Treatment for glioblastoma consists of radiotherapy and temozolomide-based chemotherapy. However, virtually all patients recur, leading to a fatal outcome. Receptor tyrosine kinase (RTK)-targeted therapy has been the focus of attention in novel treatment options for these patients. Here, we compared the efficacy of imatinib, sunitinib, and cediranib in glioblastoma models. In the present work, the biologic effect of the drugs was screened by viability, cell cycle, apoptosis, migration, and invasion in vitro assays or in vivo by chick chorioallantoic membrane assay. Intracellular signaling was assessed by Western blot and the RTK targets were identified using phospho-RTK arrays. The amplified status of KIT, PDGFRA, and VEGFR2 genes was assessed by quantitative polymerase chain reaction. In a panel of 10 glioblastoma cell lines, we showed that cediranib was the most potent. In addition, cediranib and sunitinib synergistically sensitize the cells to temozolomide. Cediranib efficacy was shown to associate with higher cytostatic and unique cytotoxic effects in vitro and both antitumoral and antiangiogenic activity in vivo, which could associate with its great capacity to inhibit mitogen-activated protein kinase (MAPK) and AKT pathways. The molecular status of KIT, PDGFRA, and VEGFR2 did not predict glioblastoma cell responsiveness to any of the RTK inhibitors. Importantly, phospho-RTK arrays revealed novel targets for cediranib and sunitinib therapy. In conclusion, the novel targets found may be of value as future biomarkers for therapy response in glioblastoma and lead to the rational selection of patients for effective molecular targeted treatment.     

Ultrasensitive detection of adrenocorticotropin hormone (ACTH) using disposable phenylboronic-modified electrochemical immunosensors

This work reports for the first time an electrochemical immunosensor for the determination of adrenocorticotropin hormone (ACTH). The immunoelectrode design involves the use of amino phenylboronic acid for the oriented immobilization of anti-ACTH antibodies onto screen-printed carbon modified electrode surfaces. A competitive immunoassay between the antigen and the biotinylated hormone for the binding sites of the immobilized antibody was performed. The electroanalytical response was generated by using alkaline phosphatase-labelled streptavidin and 1-naphtyl phosphate as the enzyme substrate. The electrochemical oxidation of the enzyme reaction product, 1-naphtol, measured by differential pulse voltammetry was employed to monitor the affinity reaction. Under the optimized working conditions, an extremely low detection limit of 18 pg/L was obtained. Cross-reactivity was evaluated against other hormones (cortisol, estradiol, testosterone, progesterone, hGH and prolactin) and the obtained results demonstrated an excellent selectivity. The developed immunosensor was applied to a human serum sample containing a certified amount of ACTH with good results.     

Antioxidant and antifungal potential of methanol extracts of Phellinus spp. from Sonora, Mexico

BackgroundAmong the potential natural sources of bioactive compounds, those of the macroscopic fungi Phellinus spp. have been identified by previous researches. Phenolic compounds are among the major antioxidant and antimicrobial contributors due to their bioactive properties.AimsThe goal of this study was to determine the total phenolic and flavonoid contents, and its relation with the antioxidant and antifungal activity of methanolic extracts of Phellinus gilvus, Phellinus rimosus and Phellinus badius, respectively.MethodsThe collected and identified organisms of Phellinus spp. were treated with methanol and the generated aqueous extract was analyzed to quantified total phenolic compounds, total flavonoids, radical scavenging activity against DPPH, trolox equivalent antioxidant capacity, and oxygen absorbance capacity. The antifungal property of the extracts was evaluated against Alternaria alternata.ResultsThe content of phenolic compounds was of 49.31, 46.51 and 44.7 mg of gallic acid equivalents/g, for P. gilvus, P. rimosus and P. badius, respectively. The total flavonoid content followed the same pattern with values of 30.58, 28, and 26.48 mg of quercetin equivalents/g for P. gilvus, P. rimosus and P. badius, respectively. The variation on the content of phenolic components was reflected on the antioxidant activity of every organism. The antioxidant activity ranked as follows: P. gilvus > P. rimosus > P. badius. The antifungal effect of the different extracts against A. alternata showed a significant effect, all of them, inhibiting the growth of this pathogen.ConclusionsP. gilvus showed the best potential to inactivate free radicals, being all the tested fungi effective to inhibit A. alternata growth.     

Land use and nitrogen export in the Piracicaba River basin, Southeast Brazil

Anthropogenic N inputs and riverine export were determined for a meso-scale river basin in one of the most developed and economically important regions of South America. The Piracicaba River basin is located in southeastern Brazil and drains into a tributary of the Paraná River. The basin supports over 3 million people (about 2% of the population of Brazil) with intensive agricultural and industrial activities. During two years from 1995 to 1997, biweekly samples were collected at 10 stations along the Piracicaba River and its tributaries for analyses of dissolved and particulate N. The average annual flux of dissolved inorganic N and total N increased by a factor of 15 and 20 times, respectively, from the headwaters to the lower reaches of the main channel, whereas discharge increased by only 7 times. On a per area basis, the export of TN varied according to land use and was significantly correlated to the net input of anthropogenic N. Among 10 sub-catchments composing the basin, areas mostly covered by pasture and forest had the lowest export, whereas more agricultural and urban areas had higher export. The amount of N exported from each sub-catchment varied widely, but inputs were consistently higher than fluvial outputs. Losses and retention of N occurred throughout the basin but were especially high in the sub-catchment with a main-stem reservoir, suggesting that aquatic processing plays an important role in controlling riverine N export. Total net anthropogenic input to the Piracicaba River basin was 4,500 (± 900) kg N km^–2 yr^–1 of which about 40% was exported via fluvial outputs.     

Structure/function relationships of several biopolymers as related to invertase stability in dehydrated systems

Structure/function relationships of different biopolymers (alginate, dextran, or beta-cyclodextrin) were analyzed as single excipients or combined with trehalose in relation to their efficiency as enzyme stabilizers in freeze-dried formulations and compared to trehalose. Particularly, a novel synthesized polymer beta-cyclodextrin-branched alginate (beta-CD-A) was employed as excipient. During freeze-drying, the polymers or their mixtures did not confer better protection to invertase compared to trehalose. Beta-CD-A (with or without trehalose), beta-cyclodextrin (beta-CD), or dextran with trehalose were the best protective agents during thermal treatment, while beta-CD and alginate showed a negative effect on invertase activity preservation. The beta-CD linked alginate combined the physical stability provided by alginate with the stabilization of hydrophobic regions of the enzyme provided by cyclodextrin. Beta-CD-A was effective even at conditions at which trehalose lost its protective effect. A relatively simple covalent combination of two biopolymers significantly affected their functionalities and, consequently, their interactions with proteins, modifying enzyme stability patterns.