Recommendations for the use of transcranial Doppler ultrasonography to determine the existence of cerebral circulatory arrest as diagnostic support for brain death.

Introduction: The clinical criteria for brain death consist of the demonstration of the absence of any clinical sign of encephalic activity. Confirmatory testing is usually not required for the diagnosis of brain death, except in some special situations that Spanish law details. In these situations demonstrating cerebral circulatory arrest (CCA) by cerebral flow studies is necessary to support the diagnosis of brain death.

siRNA applications in nanomedicine.

The ability to specifically silence genes using RNA interference (RNAi) has wide therapeutic applications for the treatment of disease or the augmentation of tissue formation. RNAi is the sequence-specific gene silencing mediated by a 21-25 nucleotide double-stranded small interfering RNA (siRNA) molecule. siRNAs are incorporated into the RNA-induced silencing complex (RISC), which mediates mRNA sequence-specific binding and cleavage.

A novel intracellular protein delivery platform based on single-protein nanocapsules.

An average cell contains thousands of proteins that participate in normal cellular functions, and most diseases are somehow related to the malfunctioning of one or more of these proteins. Protein therapy, which delivers proteins into the cell to replace the dysfunctional protein, is considered the most direct and safe approach for treating disease. However, the effectiveness of this method has been limited by its low delivery efficiency and poor stability against proteases in the cell, which digest the protein.

The phosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2) by engineered surfaces with electrostatically or covalently immobilized VEGF.

Growth factors are a class of signaling proteins that direct cell fate through interaction with cell-surface receptors. Although a myriad of possible cell fates stems from a growth factor binding to its receptor, the signaling cascades that result in one fate over another are still being elucidated. One possible mechanism by which nature modulates growth factor signaling is through the method of presentation of the growth factor--soluble or immobilized (matrix bound).

Novel C-6 substituted and unsubstituted pregnane derivatives as 5alpha-reductase inhibitors and their effect on hamster flank organs diameter size.

The present study is addressed to ascertain the inhibitory effect of several progesterone derivatives having a chlorine substituent at C-6 (12a-12d), 15 with a bromine substituent at C-6 and 14a-14d, without any halogen atom at C-6 all having an ester side chain at C-17 (benzoate ester bearing a Cl, F and a Br atom at C-4 position of the phenyl ring) on the 5alpha-reductase enzyme activity present in human prostate. In addition, it was also of interest to investigate the pharmacological effect on hamster flank organs diameter size. In order to study the structure-activity relationships of steroids 12a-12d, 14a-14d and 15 we determined the concentration of these steroids that inhibited 50% of the activity of human prostate 5alpha-reductase enzyme (IC(50)), as well as the in vivo effect of these compounds in the hamster flank organs diameter size.

Endothelial dysfunction, vascular disease and stroke: the ARTICO study.

Endothelial dysfunction is a fundamental step in the atherosclerotic disease process. Its presence is a risk factor for the development of clinical events, and may represent a marker of atherothrombotic burden. Also, endothelial dysfunction contributes to enhanced plaque vulnerability, may trigger plaque rupture, and favors thrombus formation.

Engineering clustered ligand binding into nonviral vectors: alphavbeta3 targeting as an example.

The development of techniques to efficiently deliver genes using nonviral approaches can broaden the application of gene delivery in medical applications without the safety concerns associated with viral vectors. Here, we designed a clustered integrin-binding platform to enhance the efficiency and targetability of nonviral gene transfer to HeLa cells with low and high densities of alpha(v)beta(3) integrin receptors. Arg-Gly-Asp (RGD) nanoclusters were formed using gold nanoparticles functionalized with RGD peptides and used to modify the surface of DNA/poly(ethylene imine) (PEI) polyplexes.

Inflammation as therapeutic objective in stroke.

Ischemic stroke is the most frequent cause of persistent neurologic disability in modern Western societies. Albeit it is still not clear whether inflammation is merely an epiphenomenon or rather has a disease-promoting function, accumulating evidence implicates inflammation in many forms of acute neurodegenerative disorders including ischemia. The immune cell influx during a neuropathological event is thought to be elicited by glial cells, especially microglia.

DNA delivery from matrix metalloproteinase degradable poly(ethylene glycol) hydrogels to mouse cloned mesenchymal stem cells.

The ability to genetically modify mesenchymal stem cells (MSCs) seeded inside synthetic hydrogel scaffolds would offer an alternative approach to guide MSC differentiation and to study molecular pathways in three dimensions than protein delivery. In this report, we explored gene transfer to infiltrating MSCs into matrix metalloproteinase (MMP) degradable hydrogels that were loaded with DNA/poly(ethylene imine) (PEI) polyplexes. DNA/PEI polyplexes were encapsulated inside poly(ethylene glycol) (PEG) hydrogels crosslinked with MMP-degradable peptides via Michael addition chemistry.

Aromatic esters of progesterone as 5alpha-reductase and prostate growth inhibitors.

The aim of this study was to determine the biological activity of 4 steroidal derivatives (9a, 9b and 10a, 10b) prepared from the commercially available 17alpha acetoxyprogesterone, where 9a, 9b, have the Delta(4)-3-oxo structure and 10a and 10b an epoxy group at C-4 and C-5. These steroids were tested as inhibitors of 5alpha-reductase enzyme, which is present in androgen-dependent tissues and converts testosterone to its more active reduced metabolite dihydrotestosterone. The pharmacological effect of these steroids was demonstrated by the significant decrease of the weight of the prostate gland of gonadectomized hamsters treated with testosterone plus finasteride or with steroids 10a and 10b.

Recurrent stroke and massive right-to-left shunt: results from the prospective Spanish multicenter (CODICIA) study.

Background And Purpose: Few studies have prospectively examined the risk of recurrent stroke associated with patent foramen ovale. We present the results of the Spanish right-to-left shunt (RLSh) multicenter study.

Methods: Four hundred eighty-six patients with cryptogenic stoke were included at 17 participating hospitals.

[Pharmacology of neuroprotection in acute ischemic stroke].

Introduction: Stroke leads the list of causes of disability in adults and represents the second leading cause of death worldwide. Knowledge about the pathophysiology of ischemic stroke has improved substantially over the past 25 years, and, as a result of this, new therapeutic strategies have been developed with two main aims: restoration of cerebral flow and the minimization of the deleterious effects of ischemia on neurons. Although so far there are no drugs approved for the neuroprotection therapy in stroke, there are some compounds with promising results.

Recommendations and treatment strategies for the management of acute ischemic stroke.

Background: Stroke is one of the leading causes of mortality and disability worldwide. From the establishment of the penumbra concept, ischemic stroke has been recognized as a dynamic process and two main therapeutic strategies have been designed: one that tries to reopen the occluded artery and the second aims to protect the penumbra brain tissue until the physiologic mechanisms-or the treatment-stop the ischemia.

Objective: To review the most recent, high-quality evidence for acute stroke treatment.

Stroke pathophysiology: management challenges and new treatment advances.

Stroke is the second leading cause of death and the first cause of lost disability-adjusted years in developed countries. During the past decade, new developments in thrombolytic therapy have led to the implementation of emergency intervention protocols for the treatment of ischemic stroke, replacing the widespread sense of therapeutic nihilism in the past. Treatment with rtPA has shown to be effective within the first 3 hours following stroke onset and the FDA and the European Medical Agency (EMEA) have approved its use.

[Intravenous thrombolytic treatment in acute ischemic stroke: initial results in the Complejo Hospitalario Universitario de Albacete].

Aim: To analyze the safety profile and clinical outcome of patients with acute cerebral ischemia who received open treatment with tissue plasminogen activator (rt-PA) in a hospital without previous experience.

Patients And Methods: This prospective and observational study were realized from January 2004 to January 2007. A total of 1,704 consecutive patients with ischemic stroke were attended.

The effect of enzymatically degradable poly(ethylene glycol) hydrogels on smooth muscle cell phenotype.

The formation of scar tissue due to dedifferentiation of smooth muscle cells (SMCs) is one of the major issues faced when engineering bladder tissue. Furthermore, cell sources for regenerating the SMC layer are also limiting. Here we explore if human mesenchymal stem cells (MCSs), cultured in enzymatically degradable poly(ethylene glycol) (PEG) hydrogel scaffolds can be differentiated into SMC-like cells.

[Recommendations of the use of transcranial Doppler to determine the existence of cerebral circulatory arrest as diagnostic support of brain death].

Introduction: The clinical criteria for brain death consist of the demonstration of the absence of any clinical sign of encephalic activity. Confirmatory testing is usually not required for the diagnosis of brain death, except in some special situations that the Spanish law details. In these situations demonstrating cerebral circulatory arrest (CCA) by cerebral flow studies is necessary to support the diagnosis of brain death.

Steroids with a carbamate function at C-17, a novel class of inhibitors for human and hamster steroid 5alpha-reductase.

In order to study the biological activity of the two novel steroidal carbamates derivatives: 8a and 8b, we determined the concentration of both compounds that inhibit the 50% of the activity of human prostate 5alpha-reductase enzyme, as well as the in vivo effect of these compounds in the weight of hamster prostate and flank organs diameter size. We determined also, the capacity of these steroids to bind to the androgen receptors present in the rat prostate cytosol. Furthermore the activity of these compounds on the mRNA expression of glycerol 3-phosphate acyl transferase (GPAT) in flank organs was analyzed by RT-PCR.

RNA interference targeting hypoxia inducible factor 1alpha reduces post-operative adhesions in rats.

Background: To investigate the use of RNA interference mediated gene down-regulation targeting hypoxia inducible factor 1alpha (HIF-1alpha) and plasminogen activator inhibitor 1 (PAI-1) in an effort to prevent abdominal adhesion formation.

Materials And Methods: Real time PCR and a PAI-1 protein activity assay were used in vitro to determine the efficacy of small interfering RNAs (siRNAs). For in vivo experiments, 57 white female rats were operated to generate ischemic and serosal injury to the uterine horns, and treated with saline, siRNA(Lamin A/C) (negative control), siRNA(HIF-1alpha), siRNA(PAI-1), or siRNA(HIF-1alpha) plus siRNA(PAI-1).

Synthesis and in vitro characterization of an ABC triblock copolymer for siRNA delivery.

The ability to specifically down-regulate gene expression using the RNAi pathway in mammalian cells has tremendous potential in therapy and in basic science. However, delivery systems capable of efficient and biocompatible delivery of siRNA to target cells are not yet satisfactory. Here, we report the synthesis and in vitro characterization of ABC triblock copolymers that self-assemble with siRNA based on electrostatics and with each other by hydrophobic interactions.