A combined ligand and target-based virtual screening strategy to repurpose drugs as putrescine uptake inhibitors with trypanocidal activity.

Chagas disease, also known as American trypanosomiasis, is a neglected tropical disease caused by the protozoa Trypanosoma cruzi, affecting nearly 7 million people only in the Americas. Polyamines are essential compounds for parasite growth, survival, and differentiation. However, because trypanosomatids are auxotrophic for polyamines, they must be obtained from the host by specific transporters.

Broadening the spectrum of ivermectin: Its effect on and related trypanosomatids.

Chagas disease is an endemic American parasitosis, caused by . The current therapies, benznidazole (BZN) and nifurtimox (NFX), show limited efficacy and multiple side effects. Thus, there is a need to develop new trypanocidal strategies.

GLYT1 encephalopathy: Further delineation of disease phenotype and discussion of pathophysiological mechanisms.

GLYT1 encephalopathy is a form of glycine encephalopathy caused by disturbance of glycine transport. The phenotypic spectrum of the disease has not yet been completely described, as only four unrelated families with the disorder have been reported to date. Common features of affected patients include neonatal hypotonia, respiratory failure, encephalopathy, myoclonic jerks, dysmorphic features, and musculoeskeletal anomalies.

A structure-based approach towards the identification of novel antichagasic compounds: carbonic anhydrase inhibitors.

carbonic anhydrase (CA) has recently emerged as an interesting target for the design of new compounds to treat Chagas disease. In this study we report the results of a structure-based virtual screening campaign to identify novel and selective CA inhibitors. The combination of properly validated computational methodologies such as comparative modelling, molecular dynamics and docking simulations allowed us to find high potency hits, with K values in the nanomolar range.

Cascade Ligand- and Structure-Based Virtual Screening to Identify New Trypanocidal Compounds Inhibiting Putrescine Uptake.

Chagas disease is a neglected tropical disease endemic to Latin America, though migratory movements have recently spread it to other regions. Here, we have applied a cascade virtual screening campaign combining ligand- and structure-based methods. In order to find novel inhibitors of putrescine uptake in , an ensemble of linear ligand-based classifiers obtained by has been applied as initial screening filter, followed by docking into a homology model of the putrescine permease PAT12.

[Presacral tumors. Analysis of 20 surgically treated patients].

Introduction: Presacral tumors are a rare and little known pathology. We present our experience in its surgical treatment.

Methods: Analysis of a series (1995-2008).

[Obstructive defecation. Diagnostic methods and treatment].

Obstructive defecation is observed in approximately half of all patients with functional constipation. Functional constipation has been related to alterations in intestinal motility (slow transit constipation) and to pelvic floor disorders leading to obstructive defecation associated with anatomical alterations of the pelvic floor (rectocele, posterior perineal hernia, enterocele and sigmoidocele, internal rectal intussusception, occult mucosal prolapse, solitary rectal ulcer and descending perineum syndrome), or obstructive defecation without anatomical alterations (pelvic floor dyssynergy or anismus). The diagnostic methods used (history and physical examination, colonic transit time, balloon expulsion test, proctography, anorectal manometry and electromyography) are reviewed.

[Novel techniques in the treatment of anal incontinence].

Fecal incontinence can negatively affect the patient's occupational and social life. Until recently, most patients with severe anal incontinence unresponsive to conservative medical and/or surgical treatments underwent colostomy. Currently, these patients can benefit from one of the innovative techniques that have recently been developed.