Dronedarone blockage of the tumor-related Kv10.1 channel: a comparison with amiodarone.

Kv10.1 (Eag1, or KCNH1) is a human potassium-selective channel associated with tumor development. In this work, we study the interaction of the drug dronedarone with Kv10.1. Dronedarone presents two chemical modifications aimed to lessen side effects produced by its parent molecule, the antiarrhythmic amiodarone. Hence, our observations are discussed within the framework of a previously reported interaction of amiodarone with Kv10.1. Additionally, we show new data regarding the interaction of amiodarone with the channels. We found that, unexpectedly, the effect of dronedarone on Kv10.1 differs both quantitatively and qualitatively to that of amiodarone. Among other observations, we found that dronedarone seems to be an open-pore blocker, in contrast to the reported behavior of amiodarone, which seems to inhibit from both open and closed states. Additionally, herein we provide evidence showing that, in spite of their chemical similarity, these molecules inhibit the K+ conductance by binding to non-overlapping, independent (non-allosterically related) sites. Also, we show that, while amiodarone inhibits the Cole-Moore shift, dronedarone is unable to inhibit this voltage-dependent characteristic of Kv10.1.

Development of new hCaM-Alexa Fluor® biosensors for a wide range of ligands.

Eight new fluorescent biosensors of human calmodulin (hCaM) using Alexa Fluor® 350, 488, 532, and 555 dyes were constructed. These biosensors are thermodynamically stable, functional, and highly sensitive to ligands of the CaM. They resolve the problem of CaM ligands with similar spectroscopic properties to the intrinsic and extrinsic fluorophores of other biosensors previously reported. Additionally, they can be used in studies of protein-protein interaction through Förster resonance energy transfer (FRET). The variation in Tm (range 78.07-81.47 °C; 79.05 to WT) is no larger than two degrees in all cases in regards to CaM WT. The Kds calculated with all biosensors for CPZ and BIMI (a new inhibitor of CaM) are in the range of 0.45-1.86 and 0.69-1.54 µm respectively. All biosensors retain their ability to activate Calcineurin about 70%. Structural models built "in silico" show their possible conformation taking the fluorophores in protein thus we can predict system stability. Finally, these new biosensors represent a biotechnological development applied to an analytical problem, which aims to determine accurately the affinity of inhibitors of CaM without possible interference, to be put forward as possible drugs related to CaM.

Postprandial glycaemia and inhibition of α-glucosidase activity by aqueous extract from Coriandrum sativum.

The antihyperglycaemic properties of the aqueous extract from the leaves and stems of Coriandrum sativum L. were evaluated in normoglycaemic rats, and on α-glucosidase activity from Saccharomyces cerevisiae, in order to validate its use in folk medicine. In in vivo experiments rats were administered with the aqueous extract of the plant at 100, 300 and 500 mg/kg, to observe the effect on oral sucrose tolerance test. The aqueous extract exhibited significant antihyperglycaemic activity at the three tested doses. In vitro experiments with α-glucosidase exhibited a competitive-type inhibition. These results confirm the antidiabetic properties of the extract of C. sativum L., probably by the inhibition of α-glucosidase in the gastrointestinal tract.

Aqueous extract of Annona macroprophyllata: a potential α-glucosidase inhibitor.

Annona genus contains plants used in folk medicine for the treatment of diabetes. In the present study, an aqueous extract prepared from Annona macroprophyllata (Annonaceae, also known as A. diversifolia) leaves was evaluated on both the activity of yeast α -glucosidase (an in vitro assay) and sucrose tolerance in Wistar rats. The results have shown that the aqueous extract from A. macroprophyllata inhibits the yeast α -glucosidase with an IC50 = 1.18 mg/mL, in a competitive manner with a K(i) = 0.97 mg/mL, a similar value to that of acarbose (K(i) = 0.79 mg/mL). The inhibitory activity of A. macroprophyllata was reinforced by its antihyperglycemic effect, at doses of 100, 300, and 500 mg/kg in rats. Chromatographic analysis identified the flavonoids rutin and isoquercitrin in the most polar fractions of A. macroprophyllata crude extract, suggesting that these flavonoids are part of the active constituents in the plant. Our results support the use of A. macroprophyllata in Mexican folk medicine to control postprandial glycemia in people with diabetes mellitus, involving active constituents of flavonoid nature.

[Salmonella serotypes identified in Mexican health services]. / Serotipos de Salmonella identificados en los servicios de salud de México.

OBJECTIVE: To identify the different Salmonella strain serotypes isolated at public and private laboratories in Mexico and at the Institute for Epidemiologic Diagnosis and Referral (InDRE). MATERIAL AND METHODS: A total of 24,394 Salmonella strains collected from 1972 to 1999 in public and private health laboratories of Mexico were analyzed with the Kauffmann-White method, using antisera produced by InDRE, according to Centers for Disease Control and Prevention (CDC, Atlanta, GA) standards; 15,843 (64.9%) samples were from human sources and 8,551 (35.1%) from non-human sources. RESULTS: One hundred ninety nine different serotypes were identified. The most frequent serotype in human beings was S. Typhimurium (20.4%), followed by S. Enteritidis (18.3%). In the past few years, the frequency of S. Enteritidis has been increasing, surpassing that of S. Typhimurium since 1991. Presently S. Enteritidis is the most frequently isolated serotype. In non-human sources, S. Derby (13.8%) and S. Anatum (8.5%) are the most frequent strains. CONCLUSIONS: Salmonella serotypes most frequently isolated in Mexico are: S. Typhimurium, S. Enteritidis, S. Derby, S. Agona y S. Anatum. From the epidemiologic standpoint, it is necessary to identify circulating and emerging Salmonella serotypes in order to target pertinent preventative interventions.