Ligand-based discovery of new potential acetylcholinesterase inhibitors for Alzheimer's disease treatment.

The enzyme acetylcholinesterase (AChE) is currently a therapeutic target for the treatment of neurodegenerative diseases. These diseases have highly variable causes but irreversible evolutions. Although the treatments are palliative, they help relieve symptoms and allow a better quality of life, so the search for new therapeutic alternatives is the focus of many scientists worldwide. In this study, a QSAR-SVM classification model was developed by using the MATLAB numerical computation system and the molecular descriptors implemented in the Dragon software. The obtained parameters are adequate with accuracy of 88.63% for training set, 81.13% for cross-validation experiment and 81.15% for prediction set. In addition, its application domain was determined to guarantee the reliability of the predictions. Finally, the model was used to predict AChE inhibition by a group of quinazolinones and benzothiadiazine 1,1-dioxides obtained by chemical synthesis, resulting in 14 drug candidates with in silico activity comparable to acetylcholine.

Genetic analysis of resistance to blast in the Vietnamese rice cultivar 'Chiembac'.

The resistance to rice blast disease in the Vietnamese traditional rice cultivar 'Chiembac' was studied. The blast resistance spectrum in 'Chiembac' and 15 rice differentials carrying different known resistance genes was identified using 25 Pyricularia grisea isolates derived from 15 AFLP lineages from the North, Center and South of Vietnam. None of the differential lines carrying a single resistance gene could effectively control all tested Vietnamese blast isolates. 'Chiembac' showed a different resistance pattern compared to that of the differential lines. A cross between 'Chiembac' and 'CR203', an improved rice cultivar, was made and the F2 population was used for characterization and mapping of the resistance genes in 'Chiembac'. Genetic analysis showed that the resistance against two representative isolates from two predominant lineages, VT7 and 12, in 'Chiembac' was controlled by the single dominant genes Pi-VT7 and Pi-I2. The resistance gene Pi-VT7 was closely linked to Pi-I2 and was mapped to chromosome 12 using the framework mapping population 'IR64' x 'Azucena' of 124 double haploid progenies. The resistance to the Vietnamese blast isolate VT7 in 'IR64' was also studied. The latter was controlled by one locus with major effect located on chromosome 12 and mapped closely to the AFLP marker NIN080, which was also tightly linked to the resistance gene Pi-VT7 in 'Chiembac'. Thus, the resistance locus Pi-VT7 and the resistance locus in 'IR64' probably belong to a cluster of resistance genes.

Elimination of caffeine interference in HPLC determination of urinary nicotine and cotinine.

We report an analytical reversed-phase liquid-chromatographic procedure for quantifying nicotine and cotinine in urine, taking into account the presence of interfering caffeine frequently encountered in such specimens. These analytes are extracted from the alkalinized urine with chloroform. After evaporation of the chloroform, the residue is dissolved in methanol and injected into a chromatographic C18 column. Extraction recoveries averaged 80% to 97%. Chromatographic conditions were investigated to obviate caffeine interference. The proposed eluent mobile phase is a polar mixture of water, acetonitrile, methanol, and a pH 4 acetoacetate buffer (65/2/29/4 by vol) adjusted to pH 4.30 +/- 0.02 with triethylamine. High resolution and linearity were obtained for each analyte up to a concentration of 200 mg/L. The minimum detectable amount of each compound was 20 ng per injection, corresponding to 10 micrograms per liter of urine. Correlation with results of gas-liquid chromatography was excellent (r = 0.99). This simple, rapid procedure allows routine screening of tobacco exposure with acceptable precision: within- and between-run coefficients of variation were less than 2% and less than 5%, respectively.

[Measurement of CK-BB isoenzyme after cardiac surgery (author's transl)]. / La créatine kinase après chirurgie cardiaque. Dosage de la fraction BB.

We measured the BB isoenzyme of creatine kinase in the serum of 135 patients following cardiac surgery with cardiopulmonary bypass: 64 infants, 48 children and 23 adults, 56 of them have had, at least, one positive result. The duration of anaesthesia do not have any influence; we have found the same proportion of positive results in the two groups with anaesthesia less or more than 8 hours. Severity and complexity of the surgical procedure induce the CK-BB increase. In many cases, a high serum concentration of CK-BB is not related to clinical cerebral damage. Under this circumstances, it is possible that the rise in CK-BB concentration is not specific of central nervous system lesion.