Locomotion activates PKA through dopamine and adenosine in striatal neurons.

The canonical model of striatal function predicts that animal locomotion is associated with the opposing regulation of protein kinase A (PKA) in direct and indirect pathway striatal spiny projection neurons (SPNs) by dopamine1-7. However, the precise dynamics of PKA in dorsolateral SPNs during locomotion remain to be determined. It is also unclear whether other neuromodulators are involved. Here we show that PKA activity in both types of SPNs is essential for normal locomotion. Using two-photon fluorescence lifetime imaging8-10 of a PKA sensor10 through gradient index lenses, we measured PKA activity within individual SPNs of the mouse dorsolateral striatum during locomotion. Consistent with the canonical view, dopamine activated PKA activity in direct pathway SPNs during locomotion through the dopamine D1 receptor. However, indirect pathway SPNs exhibited a greater increase in PKA activity, which was largely abolished through the blockade of adenosine A2A receptors. In agreement with these results, fibre photometry measurements of an adenosine sensor11 revealed an acute increase in extracellular adenosine during locomotion. Functionally, antagonism of dopamine or adenosine receptors resulted in distinct changes in SPN PKA activity, neuronal activity and locomotion. Together, our results suggest that acute adenosine accumulation interplays with dopamine release to orchestrate PKA activity in SPNs and proper striatal function during animal locomotion.

National survey regarding the timing of endoscopic procedures during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, several questions have arisen about which endoscopic procedures (EPs) must be performed and which ones can be postponed. The aim of this study was to conduct a nationwide survey regarding the appropriate timing of EPs during the COVID-19 pandemic. METHODS: This prospective study was performed through a nationwide electronic survey. The survey consisted of 15 questions divided into three sections. The first evaluated the agreement for EPs classified as "time sensitive" and "not time sensitive". Two other sections assessed "high-priority" and "low-priority" scenarios. Agreement was considered when > 75% of respondents answered a question in the same direction. RESULTS: The response rate was 27.2% (214/784). Among the respondents, agreement for the need to perform EP in < 72 h was only reached for variceal bleeding (93.4%). Dysphagia with alarm symptoms was the scenario in which the highest percentage of physicians (95.9%) agreed that an EP needed to be performed within a month. Less than 30% of endoscopists would perform an EP within the first 72 h for patients with mild cholangitis, non-variceal upper gastrointestinal bleeding without hemodynamic instability, or severe anaemia without overt bleeding. In time-sensitive clinical scenarios suggestive of benign disease, none of the scenarios reached agreement in any sense. Among the time-sensitive clinical scenarios suggestive of malignancy, > 90% of the surveyed respondents considered that EP could not be postponed for > 8 weeks. CONCLUSIONS: There was no consensus among endoscopists about the timing of EPs in patients with pathologies considered time sensitive or in those with high-priority pathologies. Agreement was only reached in five (17%) of the evaluated clinical scenarios.

Mycobacterium tuberculosis Infection Induces BCSFB Disruption but No BBB Disruption In Vivo: Implications in the Pathophysiology of Tuberculous Meningitis.

Central nervous system (CNS) tuberculosis is the most lethal and devastating form among the diseases caused by Mycobacterium tuberculosis. The mechanisms by which M. tuberculosis bacilli enter the CNS are still unclear. However, the BBB and the BCSFB have been proposed as possible routes of access into the brain. We previously reported that certain strains of M. tuberculosis possess an enhanced ability to cause secondary CNS infection in a mouse model of progressive pulmonary tuberculosis. Here, we evaluated the morphostructural and molecular integrity of CNS barriers. For this purpose, we analyzed through transmission electron microscopy the ultrastructure of brain parenchymal microvessels and choroid plexus epithelium from animals infected with two mycobacterial strains. Additionally, we determined the expression of junctional proteins and cytokines by immunological techniques. The results showed that the presence of M. tuberculosis induced disruption of the BCSFB but no disruption of the BBB, and that the severity of such damage was related to the strain used, suggesting that variations in the ability to cause CNS disease among distinct strains of bacteria may also be linked to their capacity to cause direct or indirect disruption of these barriers. Understanding the pathophysiological mechanisms involved in CNS tuberculosis may facilitate the establishment of new biomarkers and therapeutic targets.

Enriched Environment Contributes to the Recovery from Neurotoxin-Induced Parkinson's Disease Pathology.

Parkinson's disease (PD) is a neurological disorder that affects dopaminergic neurons. The lack of understanding of the underlying molecular mechanisms of PD pathology makes treating it a challenge. Several pieces of evidence support the protective role of enriched environment (EE) and exercise on dopaminergic neurons. The specific aspect(s) of neuroprotection after exposure to EE have not been identified. Therefore, we have investigated the protective role of EE on dopamine dysregulation and subsequent downregulation of DJ1 protein using in vitro and in vivo models of PD. Our study for the first time demonstrated that DJ1 expression has a direct correlation with dopamine downregulation in PD models and exposure to EE has a significant impact on improving the behavioral changes in PD mice. This research provides evidence that exercise in EE has a positive effect on PD without interfering with the current line of therapy.

Central Nervous System Tuberculosis in a Murine Model: Neurotropic Strains or a New Pathway of Infection?

Tuberculosis (TB) of the central nervous system (CNS) is a lethal and incapacitating disease. Several studies have been performed to understand the mechanism of bacterial arrival to CNS, however, it remains unclear. Although the interaction of the host, the pathogen, and the environment trigger the course of the disease, in TB the characteristics of these factors seem to be more relevant in the genesis of the clinical features of each patient. We previously tested three mycobacterial clinical isolates with distinctive genotypes obtained from the cerebrospinal fluid of patients with meningeal TB and showed that these strains disseminated extensively to the brain after intratracheal inoculation and pulmonary infection in BALB/c mice. In this present study, BALB/c mice were infected through the intranasal route. One of these strains reaches the olfactory bulb at the early stage of the infection and infects the brain before the lungs, but the histological study of the nasal mucosa did not show any alteration. This observation suggests that some mycobacteria strains can arrive directly at the brain, apparently toward the olfactory nerve after infecting the nasal mucosa, and guides us to study in more detail during mycobacteria infection the nasal mucosa, the associated connective tissue, and nervous structures of the cribriform plate, which connect the nasal cavity with the olfactory bulb.

Long-term safety and durability of novel intra-aortic percutaneous mechanical circulatory support device.

An unmet need exists for minimally invasive percutaneous mechanical circulatory support (pMCS) devices to provide partial support and promote cardiac rest and recovery in non-end-stage heart failure patients. This indication requires safe, long-term, ambulatory use with standard anticoagulation. The Aortix pump (Procyrion, Houston, Texas, USA) is a percutaneously deployed intra-aortic pump currently being clinically evaluated for subacute use and has the potential to provide extended therapy for non-end-stage heart failure patients. The device has demonstrated hemocompatibility and hemodynamic impact and has features well suited for home use. To evaluate the Aortix pump for long-term, ambulatory use, pumps were implanted in 4 untethered sheep. Pumps operated for 90 to 142 days and were stopped electively. Pump bearing components were found to have only superficial wear. No clinically significant hemolysis was observed and aorta and kidney histopathology showed no device-related findings or adhesions, suggesting Aortix is suitable for long-term (>6 months) ambulatory use.

[Obesity, symptoms of gastroesophageal reflux and endoscopic findings in a referral hospital]. / Obesidad, sintomas de reflujo gastroesofágico y hallazgos endoscópicos en un hospital de referencia.

OBJECTIVE: To determine association between obesity, gastroesophageal reflux symptoms, hiatus hernia and erosive esophagitis. METHODS: Consecutive patients who underwent upper endoscopies at our center were studied. Before endoscopy, through a direct interview all subjects were asked to complete the Carlsson-Dent questionnaire. Weight and height of all patients were determined. Body mass index was calculated. At endoscopy it was looked for the presence of hiatus hernia and erosive esofagitis. We excluded patients with some of the following conditions: Pregnancy, ascitis, esophageal varices, esophageal, gastric or duodenal stenosis, and patient who required an emergency or therapeutic endoscopy. We compared prevalence of symptomatic GERD, hiatus hernia and erosive esophagitis between normal weight patients, overweight and obese. RESULTS: A total of 196 patients were included for analysis, 122 women and 74 men, mean age 52.5 years, 40.3% were overweight and 28.1% were obese. There were 124 patients (63.3%) with symptoms of GERD determined by the C-D Questionnaire obtained. Hiatus hernia was observed in 87 patients (44.4%), and erosive esophagitis in 69 patients (35.7%). Prevalence of GERD symptoms in obese or overweight patients were similar to those normal-weight patients (66.4% and 56.5% respectively, p = 0.20) OR 1.52 (IC 95%, 0.82-2.82). Among obese or overweight hiatus hernia was observed in 47% compared to 38.7% of those normal-weight (p = 0.28) OR 1.40 (IC 95%, 0.76-2.59). Prevalence of erosive esofagitis was also similar in both groups 37.3% and 32.3% respectively (p = 0.52) OR 1.25 (IC 95%, 0.66-2.36). CONCLUSIONS: This study didn't show association between symptoms of GERD, hiatus hernia or erosive esofagitis and overweight or obesity.

[Appropriate use of diagnostic esophagogastroduodenoscopy and its relation with positive results]. / Uso appropriado de las esofagogastroduodenoscopia diagnóstica y su relación con hallazgos positivos.

INTRODUCTION: Upper gastrointestinal endoscopy is a sensitive and safe procedure, but expensive and with certain risks. The range of inappropriate use of upper gastrointestinal endoscopy in open access system is between 5.6 to 61.7%. In our department we use restricted access system. OBJECTIVE: To determine the accuracy of Gastrointestinal Endoscopy American Society guidelines in the diagnosis through the upper gastrointestinal endoscopies performed in a reference hospital setting with restricted access. METHODS: We review requests for diagnostic upper gastrointestinal endoscopies and their reports between March 1st 2003 and February 29th 2004. It was defined as an appropriate diagnostic esophagogastroduodenoscopy which followed the American Gastrointestinal Endoscopy society guidelines. It was done statistical descriptive analysis. RESULTS: A total of 3033 requests and reports of upper gastrointestinal endoscopies were reviewed. The proportion of clinical diagnoses that followed the guidelines was 74.3%. We found a 56.3% of abnormal positive endoscopy findings, concordance between clinical diagnosis and abnormal positive endoscopy findings was 46.8%. CONCLUSION: The proportion of upper gastrointestinal endoscopies that follow the American Gastrointestinal Endoscopy Society guidelines in our restricted access system is low.

[Prevalence of periampullary diverticular, its association with choledocolithiasis and technical sucess with ERCP]. / Prevalencia del divertículo periampular, su asociación con coledocolitiasis y el éxito técnico de la colangiopancreatografia endoscópica.

BACKGROUND: Periampullary diverticula (DP) are thought to be associated with bile duct stones; they may influence the index of success or failure at endoscopic retrograde cholangiopancreatography (CPE) and may increase the risk of its complications. AIM: Assess the association between DP with bile duct stones and its contribution with the technical success at CPE. METHODS: Two hundred and forty five consecutive patients who were undergoing CPE between April 1st and September 23th were prospectively entered into a database. Patients with and without DP were identified and compared. DP prevalence, its association with bile duct stones and with the technical success at CPE, and immediate complications were determined. Chi squared, Student t and Fisher exact test were used. RESULTS: A total of 205 cases were included. DP prevalence was 10. 7% (IC 95% 8.6-12.8) Mean age of patients with DP (68 vs. 52 years) (p = 0.001) and the incidence of choledocholithiasis (81% vs. 49%) (p = 0.004) were greater in DP group. There were no significant differences found between DP group and the control group in terms of successful duct cannulation (90% vs. 89%), satisfactory sphincterotomies (95% vs. 93%) or stone extraction (77% vs. 75%). There was an increased frequency of hemorrhage in the DP group (9% vs. 4%) however the difference was no significant. CONCLUSIONS: DP is associated with an increased incidence of choledocholithiasis. DP did not cause any major technical difficulties at CPE.

3D modeling of human cancer: A PEG-fibrin hydrogel system to study the role of tumor microenvironment and recapitulate the in vivo effect of oncolytic adenovirus.

Interactions between malignant and stromal cells and the 3D spatial architecture of the tumor both substantially modify tumor behavior, including the responses to small molecule drugs and biological therapies. Conventional 2D culture systems cannot replicate this complexity. To overcome these limitations and more accurately model solid tumors, we developed a highly versatile 3D PEG-fibrin hydrogel model of human lung adenocarcinoma. Our model relevantly recapitulates the effect of oncolytic adenovirus; tumor responses in this setting nearly reproduce those observed in vivo. We have also validated the use of this model for complex, long-term, 3D cultures of cancer cells and their stroma (fibroblasts and endothelial cells). Both tumor proliferation and invasiveness were enhanced in the presence of stromal components. These results validate our 3D hydrogel model as a relevant platform to study cancer biology and tumor responses to biological treatments.

[Intragastric migration of a plastic prosthesis placed for repair of a diaphragmatic perforation. Case report]. / Migración intragástrica de una prótesis plástica colocada para reparación de una perforación diafragmática. Reporte de un caso.

CASE: We report the case of a 21-year old female with multiple surgeries. Her problem began after last surgery, which got complicated by a diaphragmatic perforation on the left side so it was necessary to repair the defect with a plastic prosthesis, since that time she complained of abdominal pain. In an abdominal computed axial tomography prosthesis was observed and by endoscopy its presence into stomach was confirmed, because its size and rigidity its endoscopic extraction was impossible, so it was surgically extracted. One and half month after surgery the patient's evolution was satisfactory. DISCUSSION: Migration is one of the most common complications of medical prosthesis placed into abdominal cavity. However precise incidence is unknown, neither intraluminal migration to the gastrointestinal tract. We didn't find previews reports about intragastric migration of a prosthesis that was used to repair a diaphragmatic defect.

[Association between symptomatic gastroesophageal reflux and Barrett's esophagus]. / Asociación entre reflujo gastroesofágico sintomático y esófago de Barrett.

BACKGROUND DATA: Barrett esophagus is a proximal displacement of the squamocolumnar junction relative to the gastroesophageal junction with intestinal metaplasia, it has been linked to gastroesophageal reflux disease. However, it has been observed in individuals without gastroesophageal reflux symptoms, with prevalence up to 25% in 50 years older men. OBJECTIVE: Assess the association between symptomatic gastroesophageal reflux and Barrett's esophagus. METHODS: Consecutive patients undergoing endoscopy at our center were studied. Before endoscopy, through a direct interview all subjects were asked to complete the Carlsson-Dent questionnaire for determining 2 groups (patients with and without gastroesophageal reflux symptoms). Those subjects with suggestive image of Barrett's esophagus, biopsy specimens were obtained from the distal esophageal mucosa with the intention of find intestinal metaplasia. We compared prevalence of Barrett's esophagus between groups. RESULTS: One hundred and nine patients were studied. Prevalence of symptomatic gastroesophageal reflux disease was 37.6%. Barrett's esophagus was found in 9.7% of symptomatic gastroesophageal reflux disease patients and in 9.6% of subjects without symptoms of gastroesophageal reflux disease (p = 0.87). Gender and age were similar between groups. Prevalence of hernia hiatal was bigger in patients with Barrett's esophagus (90 vs. 42%) (p = 0.004). CONCLUSION: Our study didn't show association between symptomatic gastroesophageal reflux detected by a questionnaire and Barrett's esophagus.

Capillary-like network formation by human amniotic fluid-derived stem cells within fibrin/poly(ethylene glycol) hydrogels.

A major limitation in tissue engineering strategies for congenital birth defects is the inability to provide a significant source of oxygen, nutrient, and waste transport in an avascular scaffold. Successful vascularization requires a reliable method to generate vascular cells and a scaffold capable of supporting vessel formation. The broad potential for differentiation, high proliferation rates, and autologous availability for neonatal surgeries make amniotic fluid-derived stem cells (AFSC) well suited for regenerative medicine strategies. AFSC-derived endothelial cells (AFSC-EC) express key proteins and functional phenotypes associated with endothelial cells. Fibrin-based hydrogels were shown to stimulate AFSC-derived network formation in vitro but were limited by rapid degradation. Incorporation of poly(ethylene glycol) (PEG) provided mechanical stability (65%±9% weight retention vs. 0% for fibrin-only at day 14) while retaining key benefits of fibrin-based scaffolds-quick formation (10±3 s), biocompatibility (88%±5% viability), and vasculogenic stimulation. To determine the feasibility of AFSC-derived microvasculature, we compared AFSC-EC as a vascular cell source and AFSC as a perivascular cell source to established sources of these cell types-human umbilical vein endothelial cells (HUVEC) and mesenchymal stem cells (MSC), respectively. Cocultures were seeded at a 4:1 endothelial-to-perivascular cell ratio, and gels were incubated at 37°C for 2 weeks. Mechanical testing was performed using a stress-controlled rheometer (G'=95±10 Pa), and cell-seeded hydrogels were assessed based on morphology. Network formation was analyzed based on key parameters such as vessel thickness, length, and area, as well as the degree of branching. There was no statistical difference between individual cultures of AFSC-EC and HUVEC in regard to these parameters, suggesting the vasculogenic potential of AFSC-EC; however, the development of robust vessels required the presence of both an endothelial and a perivascular cell source and was seen in AFSC cocultures (70%±20% vessel length, 90%±10% vessel area, and 105%±10% vessel thickness compared to HUVEC/MSC). At a fixed seeding density, the coculture of AFSC with AFSC-EC resulted in a synergistic effect on network parameters similar to MSC (150% vessel length, 147% vessel area, 150% vessel thickness, and 155% branching). These results suggest that AFSC-EC and AFSC have significant vasculogenic and perivasculogenic potential, respectively, and are suited for in vivo evaluation.

In situ vascularization of injectable fibrin/poly(ethylene glycol) hydrogels by human amniotic fluid-derived stem cells.

One of the greatest challenges in regenerative medicine is generating clinically relevant engineered tissues with functional blood vessels. Vascularization is a key hurdle faced in designing tissue constructs larger than the in vivo limit of oxygen diffusion. In this study, we utilized fibrin-based hydrogels to serve as a foundation for vascular formation, poly(ethylene glycol) (PEG) to modify fibrinogen and increase scaffold longevity, and human amniotic fluid-derived stem cells (AFSC) as a source of vascular cell types (AFSC-EC). AFSC hold great potential for use in regenerative medicine strategies, especially those involving autologous congenital applications, and we have shown previously that AFSC-seeded fibrin-PEG hydrogels have the potential to form three-dimensional vascular-like networks in vitro. We hypothesized that subcutaneously injecting these hydrogels in immunodeficient mice would both induce a fibrin-driven angiogenic host response and promote in situ AFSC-derived neovascularization. Two weeks postinjection, hydrogels were sectioned, and the following was demonstrated: the average maximum invasion distance of host murine cells into the subcutaneous fibrin/PEG scaffold was 147 ± 90 µm after 1 week and 395 ± 138 µm after 2 weeks; the average number of cell-lined lumen per square millimeter was significantly higher in hydrogels seeded with stem cells or cocultures containing stem cells (MSC, 36.5 ± 11.4; AFSC, 47.0 ± 18.9; AFSC/AFSC-EC, 32.8 ± 11.6; and MSC/HUVEC, 43.1 ± 25.1) versus endothelial cell types alone (AFSC-EC, 9.7 ± 6.1; HUVEC, 14.2 ± 8.8); and a subset of these lumen were characterized by the presence of red blood cells. Select areas of cell-seeded hydrogels contained CD31(+) lumen surrounded by α-smooth muscle cell support cells, whereas control hydrogels with no cells only showed infiltration of α-smooth muscle cell-positive host cells.

Use of myocardial matrix in a chitosan-based full-thickness heart patch.

A novel cardiac scaffold comprised of decellularized porcine heart matrix was investigated for use as a biodegradable patch with a potential for surgical reconstruction of the right ventricular outflow tract. Powdered heart matrix solution was blended with chitosan and lyophilized to form three-dimensional scaffolds. For this investigation, we examined the influence of different blending ratios of heart matrix to chitosan on porosity and mechanical properties, then gene expression and electrophysiological function of invading neonatal rat ventricular myocytes (NRVM) compared to type-A gelatin/chitosan composite scaffolds. Heart matrix/chitosan-blended hydrogels (1.6 mg/mL heart matrix) had similar porosity (109±34 µm), and elastic modulus (13.2±4.0 kPa) as previously published gelatin/chitosan scaffolds. Heart matrix/chitosan hydrogels maintained>80% viability and had higher NRVM retention (∼1000 cells/mm(2)) than gelatin/chitosan scaffolds. There was a significant increase in α-myosin heavy chain and connexin-43 expression in NRVM cultured on heart matrix/chitosan scaffolds after 14 days compared with gelatin/chitosan scaffolds. Further, heart matrix/chitosan scaffolds had significantly higher conduction velocity (12.6±4.9 cm/s) and contractile stress (0.79±0.13 mN/mm(2)) than gelatin/chitosan scaffolds. In summary, NRVM cultured on heart matrix scaffold showed improvements in contractile and electrophysiological function.

Biocompatible carbon nanotube-chitosan scaffold matching the electrical conductivity of the heart.

The major limitation of current engineered myocardial patches for the repair of heart defects is that insulating polymeric scaffold walls hinder the transfer of electrical signals between cardiomyocytes. This loss in signal transduction results in arrhythmias when the scaffolds are implanted. We report that small, subtoxic concentrations of single-walled carbon nanotubes, on the order of tens of parts per million, incorporated in a gelatin-chitosan hydrogel act as electrical nanobridges between cardiomyocytes, resulting in enhanced electrical coupling, synchronous beating, and cardiomyocyte function. These engineered tissues achieve excitation conduction velocities similar to native myocardial tissue (22 ± 9 cm/s) and could function as a full-thickness patch for several cardiovascular defect repair procedures, such as right ventricular outflow track repair for Tetralogy of Fallot, atrial and ventricular septal defect repair, and other cardiac defects, without the risk of inducing cardiac arrhythmias.

Reconstrucción endovascular de aneurisma intracraneal mediante dispositivo diversor de flujo Pipeline®. Reporte de 2 casos y revisión de la literatura / Endovascular reconstruction of intracranial aneurysm using a Pipeline® flow diversifier device

Resumen Introducción: Los aneurismas intracraneales son anomalías vasculares cerebrales con una prevalencia aproximada a nivel mundial del 2-3%. Son la principal causa de hemorragia subaracnoidea no traumática, el diagnóstico y tratamiento preventivo de esta entidad puede reducir considerablemente la morbimortalidad que de ella deviene. Con la aparición de nuevos dispositivos de terapia endovascular cerebral como los diversores de flujo se ha logrado ofrecer al paciente un procedimiento menos invasivo que no requiere cirugía convencional, y una importante reducción en el número de días de estancia intrahospitalaria y de recuperación, con alto grado de seguridad. El tratamiento endovascular para aneurismas intracraneales ha evolucionado sustancialmente en las últimas dos décadas, convirtiéndose en el tratamiento de elección en diversas situaciones clínicas. Reporte de caso: Caso 1: Varón de 62 años edad que ingresa a unidad hospitalaria después de sufrir un traumatismo craneoencefálico moderado con pérdida transitoria del estado de alerta y cefalea holocraneana. Se realizó una tomografía de cráneo simple y con contraste ante la sospecha de hemorragia subaracnoidea. Se evidenció la presencia de un aneurisma intracraneal en la arteria carótida interna izquierda, segmento comunicante posterior de 4 x 3 mm con cuello de 3 mm. Se realizó tratamiento mediante la colocación de dispositivo diversor de flujo Pipeline®, así como control angiográfico a los 3 meses post-tratamiento con una evolución satisfactoria. Caso 2: Mujer de 59 años de edad que acudió por presentar hemiparesia facial y brazo ipsilateral, con incremento gradual de la intensidad y duración. Se inició protocolo de estudio con resonancia magnética. Se evidenció la presencia de aneurisma intracraneal de 15 mm de diámetro en el segmento comunicante de la arteria carótida interna derecha y otro de 8 mm contralateral. Fue programada para colocación de dispositivo diversor de flujo Pipeline® con adecuada evolución. Conclusión: El uso de dispositivos diversores de flujo es una excelente alternativa para el tratamiento de aneurismas intracraneales incidentales, con importantes ventajas de costo-efectividad, reduciendo tiempos quirúrgicos, de estancia hospitalaria y de recuperación. Además de tener un porcentaje de curación superior al 95% a 5 años.

Abstract Introduction: Intracranial aneurysms are cerebral vascular anomalies with an approximate global prevalence of 2 to 3% and are the main cause of non-traumatic subarachnoid hemorrhage. Diagnosis and preventive treatment of this entity can considerably reduce morbidity and mortality. With the advent of new devices for cerebral endovascular therapy such as flow diverters, the patient now has the option of choosing a less invasive procedure, which does not require conventional surgery. This represents a significant reduction in the number of days of in hospital stay and recovery. The procedure has showed a high degree of security. The endovascular treatment for intracranial aneurysms has evolved substantially in the last two decades, and has become the treatment of choice. Case report: Case 1: A 62-year-old male was admitted in the hospital after a moderate cranioencephalic trauma with transient loss of conscious and a holocranial headache. A cerebral angiography was performed to rule out subarachnoid hemorrhage. The angiography showed an intracranial aneurysm. It was localized in left internal carotid-posterior communicating artery. The measures were of 4mm X 3mm with a 3mm neck. The treatment was performed with a pipeline flow-diverting device, as well as an angiographic control 3 months after the treatment with a satisfactory evolution. Case 2: A 59-year-old female patient with facial hemiparesis and ipsilateral arm, that showed a gradual increase in intensity and duration. A magnetic resonance study protocol was initiated and an intracranial aneurysm was observed in the communicating segment of the right internal carotid artery. The diameter of the aneurysmal sac was of 15 mm and also, a contralateral of 8 mm. Placement of a flow-diverting device was programmed. Conclusion: The use of flow-diverting devices is an excellent alternative for the treatment of incidental intracranial aneurysms, with important cost-effectiveness advantages, surgical time, hospital stay and recovery reduction. In addition to having a recovery percentage of 95% in 5 years.

Evaluation of endothelial cells differentiated from amniotic fluid-derived stem cells.

Amniotic fluid holds great promise as a stem cell source, especially in neonatal applications where autologous cells can be isolated and used. This study examined chemical-mediated differentiation of amniotic fluid-derived stem cells (AFSC) into endothelial cells and verified the function of AFSC-derived endothelial cells (AFSC-EC). AFSC were isolated from amniotic fluid obtained from second trimester amnioreduction as part of therapeutic intervention from pregnancies affected with twin-twin transfusion syndrome. Undifferentiated AFSC were of normal karyotype with a subpopulation of cells positive for the embryonic stem cell marker SSEA4, hematopoietic stem cell marker c-kit, and mesenchymal stem cell markers CD29, CD44, CD73, CD90, and CD105. Additionally, these cells were negative for the endothelial marker CD31 and hematopoietic differentiation marker CD45. AFSC were cultured in endothelial growth media with concentrations of vascular endothelial growth factor (VEGF) ranging from 1 to 100 ng/mL. After 2 weeks, AFSC-EC expressed von Willebrand factor, endothelial nitric oxide synthase, CD31, VE-cadherin, and VEGF receptor 2. Additionally, the percentage of cells expressing CD31 was positively correlated with VEGF concentration up to 50 ng/mL, with no increase at higher concentrations. AFSC-EC showed a decrease in stem cells markers c-kit and SSEA4 and were morphologically similar to human umbilical vein endothelial cells (HUVEC). In functional assays, AFSC-EC formed networks and metabolized acetylated low-density lipoprotein, also characteristic of HUVEC. Nitrate levels for AFSC-EC, an indirect measure of nitric oxide synthesis, were significantly higher than undifferentiated controls and significantly lower than HUVEC. These results indicate that AFSC can differentiate into functional endothelial-like cells and may have the potential to provide vascularization for constructs used in regenerative medicine strategies.