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.

Shelter-housed cats show no evidence of faecal shedding of canine parvovirus DNA.

Canine parvovirus (CPV) and feline panleukopenia virus (FPV) are deoxyriboncucleic acid (DNA) viruses in the taxon Carnivore protoparvovirus 1. Exposure of cats to either CPV or FPV results in productive infection and faecal shedding of virus. Asymptomatic shedding of CPVs by one-third of shelter-housed cats in a UK study suggests that cats may be an important reservoir for parvoviral disease in dogs. The aim of this cross-sectional study was to determine the prevalence of faecal shedding of CPVs in asymptomatic shelter-housed cats in Australia. Faecal samples (n=218) were collected from cats housed in three shelters receiving both cats and dogs, in Queensland and NSW. Molecular testing for Carnivore protoparvovirus 1 DNA was performed by polymerase chain reaction (PCR) amplification followed by DNA sequencing of the VP2 region to differentiate CPV from FPV. Carnivore protoparvovirus 1 DNA was detected in only four (1.8%, 95% confidence interval 0.49-4.53%) faecal samples from a single shelter. Sequencing identified all four positive samples as FPV. Faecal shedding of CPV by shelter-cats was not detected in this study. While the potential for cross-species transmission of CPV between cats and dogs is high, this study found no evidence of a role for cats in maintaining CPV in cat and dog populations through faecal shedding in the regions tested.

Recent avian influenza virus A/H5N1 evolution in vaccinated and unvaccinated poultry from farms in Southern Vietnam, January-March 2010.

We report 15 new avian influenza virus A/H5N1 haemagglutinin (HA) sequences sampled from visibly sick domestic poultry in southern Vietnam, between 1 January 2010 and 6 March 2010. These HA sequences form a new sub-clade of the clade 1 H5N1 viruses that have been circulating in Vietnam since 2003/2004. The viruses are characterized by a change from isoleucine to valine at position 514 (I514V) and are 1.8% divergent at the nucleotide level from HA sequences sampled in Vietnam in 2007. Five new amino acid changes were observed at previously identified antigenic sites, and three were located within structural elements of the receptor-binding domain. One new mutation removed a potential N-linked glycosylation site, and a methionine insertion was observed in one virus at the polybasic cleavage site. Five of these viruses were sampled from farms where poultry were vaccinated against H5N1, but there was no association between observed amino acid changes and flock vaccination status. Despite the current lack of evidence for antigenic drift or immune escape in Vietnamese H5N1 viruses, continued surveillance remains a high priority.

Clinical aspects of acute vs persistent diarrhea in Ho Chi Minh City, Vietnam.

A retrospective clinical study of acute and persistent diarrhea in children younger than three years of age was conducted for 12 months (October 1989 to September 1990) in a Pediatric Hospital in Ho Chi Minh City, South Vietnam. Most of the 3833 episodes of diarrhea identified were of short duration, with 77.7% lasting only 1-7 days. Only 5.3% of episodes lasted more than 14 days. Episodes of longer duration were associated with young age (0-5 months). Bloody stool was present in more than 40% of persistent episodes. Severe malnutrition was associated with persistent episodes that lasted 14-21 days (33%) or more than 22 days (59%). It is important that all patients with diarrhea have appropriate dietary management in addition to fluid therapy, and that future analysis examines etiologic factors to determine the optimal treatment of bloody diarrhea.