Design and testing of an optical instrument for skin flap monitoring.

Flap procedures are complex surgical tools widely used in reconstructive surgery. Flap ischemia is one of the most dangerous complications, both during the surgical procedure and during the patient's recovery, which can quickly lead to tissue necrosis (flap loss) with serious medical and psychological consequences. Today, bedside clinical assessment remains the gold standard for flap monitoring, but timely detection of flap ischemia is a difficult and challenging task, so auxiliary techniques are needed to support flap monitoring. Here we present a prototype of a new optical diagnostic tool, based on visible light absorption in diffuse reflectance spectroscopy, for non-invasive, continuous, real-time monitoring of flaps. The proposed approach is assessed by monitoring flap ischemic scenarios induced on pig animal models. The results obtained support that the proposed approach has great potential, not only for prompt detection of ischemia (in seconds), but also for clear differentiation between an arterial occlusion and venous occlusion.

Theranostic Contribution of Extracellular Matrix Metalloprotease Inducer-Paramagnetic Nanoparticles Against Acute Myocardial Infarction in a Pig Model of Coronary Ischemia-Reperfusion.

BACKGROUND: Rapid screening and accurate diagnosis of acute myocardial infarction are critical to reduce the progression of myocardial necrosis, in which proteolytic degradation of myocardial extracellular matrix plays a major role. In previous studies, we found that targeting the extracellular matrix metalloprotease inducer (EMMPRIN) by injecting nanoparticles conjugated with the specific EMMPRIN-binding peptide AP9 significantly improved cardiac function in mice subjected to ischemia/reperfusion. METHODS: In a porcine model of coronary ischemia/reperfusion, we tested the theragnostic effects of administering 0.1 mg/kg gadolinium-containing nanoparticles conjugated with AP9 (NAP9), a synthetic peptide that targets EMMPRIN or a control nanoparticle (NAPSC). Cardiac magnetic resonance assessment of the infarct progression, ventricular function, and nanoparticle distribution was performed the next 7 days. We also measured the infarcted area of the heart and cardiac remodeling at 7 or 21 days after ischemia/reperfusion. RESULTS: After 21 days of ischemia/reperfusion, NAP9 reduced the extension of cardiac necrosis (14.1±9.7 versus 35.5±1.8) and the levels of collagenolytic activity of MMPs (matrix metalloproteases), along with a significant reduction in collagen deposition (7.5±4.5 versus 41.3±20); including the ratio of type I versus III collagen fibers in the necrotic myocardium. In terms of cardiac function, the response to NAP9 administration resulted in a significant improvement of cardiac performance overtime, as evidenced by the left ventricle ejection fraction (64.0±7.8), when compared with those present in the NAPSC group (47.3±4.7). As shown by magnetic resonance imaging, noninvasive molecular imaging of NAP9 enabled us to find a significant reduction in cardiac necrosis, myocardial edema, hemorrhage, and microvascular obstruction, suggesting that NAP9 may reduce myocardial injury and preserve left ventricular function, at least, by preventing the effect of EMMPRIN on extracellular matrix degradation. CONCLUSIONS: Our data point towards NAP9 as a promising theragnostic tool in managing acute myocardial infarction, by inhibiting EMMPRIN-induced extracellular matrix degradation and allowing noninvasive visualization of cardiac necrosis progression over time.

Graft infusion of adipose-derived mesenchymal stromal cells to prevent rejection in experimental intestinal transplantation: A feasibility study.

BACKGROUND: Mesenchymal stromal cells (MSC) have been proposed as a promising complement to standard immunosuppression in solid organ transplantation because of their immunomodulatory properties. The present work addresses the role of adipose-derived MSC (Ad-MSC) in an experimental model of acute rejection in small bowel transplantation (SBT). MATERIAL/METHODS: Heterotopic allogeneic SBT was performed. A single dose of 1.5x106 Ad-MSC was intra-arterially delivered just before graft reperfusion. Animals were divided into CONTROL (CTRL), CONTROL+Ad-MSC (CTRL_MSC), tacrolimus (TAC), and TAC+Ad-MSC (TAC_MSC) groups. Each Ad-MSC groups was subdivided in autologous and allogeneic third-party groups. RESULTS: Rejection rate and severity were similar in MSC-treated and untreated animals. CTRL_MSC animals showed a decrease in macrophages, T-cell (CD4, CD8, and Foxp3 subsets) and B-cell counts in the graft compared with CTRL, this decrease was attenuated in TAC_MSC animals. Pro- and anti-inflammatory cytokines and some chemokines and growth factors increased in CTRL_MSC animals, especially in the allogeneic group, whereas milder changes were seen in the TAC groups. CONCLUSION: Ad-MSC did not prevent rejection when administered just before reperfusion. However, they showed immunomodulatory effects that could be relevant for a longer-term outcome. Interference between tacrolimus and the MSC effects should be addressed in further studies.

First steps for the development of silk fibroin-based 3D biohybrid retina for age-related macular degeneration (AMD).

Age-related macular degeneration is an incurable chronic neurodegenerative disease, causing progressive loss of the central vision and even blindness. Up-to-date therapeutic approaches can only slow down he progression of the disease. OBJECTIVE: Feasibility study for a multilayered, silk fibroin-based, 3D biohybrid retina. APPROACH: Fabrication of silk fibroin-based biofilms; culture of different types of cells: retinal pigment epithelium, retinal neurons, Müller and mesenchymal stem cells ; creation of a layered structure glued with silk fibroin hydrogel. MAIN RESULTS: In vitro evidence for the feasibility of layered 3D biohybrid retinas; primary culture neurons grow and develop neurites on silk fibroin biofilms, either alone or in presence of other cells cultivated on the same biomaterial; cell organization and cellular phenotypes are maintained in vitro for the seven days of the experiment. SIGNIFICANCE: 3D biohybrid retina can be built using silk silkworm fibroin films and hydrogels to be used in cell replacement therapy for AMD and similar retinal neurodegenerative diseases.

Ivabradine in acute heart failure: Effects on heart rate and hemodynamic parameters in a randomized and controlled swine trial.

BACKGROUND: Acute heart failure patients could benefit from heart rate reduction, as myocardial consumption and oxidative stress are related to tachycardia. Ivabradine could have a clinical role attenuating catecholamine-induced tachycardia. The aim of this study was to evaluate hemodynamic effects of ivabradine in a swine model of acute heart failure. METHODS: Myocardial infarction was induced by 45 min left anterior descending artery balloon occlusion in 18 anesthetized pigs. An infusion of dobutamine and noradrenaline was maintained aiming to preserve adequate hemodynamic support, accompanied by fluid administration to obtain a pulmonary wedged pressure ≥ 18 mmHg. After reperfusion, rhythm and hemodynamic stabilization, the animals were randomized to 0.3 mg/kg ivabradine intravenously (n = 9) or placebo (n = 9). Hemodynamic parameters were observed over a 60 min period. RESULTS: Ivabradine was associated with a significant reduction in heart rate (88.4 ± 12.0 bpm vs. 122.7 ± 17.3 bpm after 15 min of ivabradine/placebo infusion, p < 0.01) and an increase in stroke volume (68.8 ± 13.7 mL vs. 52.4 ± 11.5 mL after 15 min, p = 0.01). There were no significant differences in systemic or pulmonary arterial pressure, or significant changes in pulmonary capillary pressure. However, after 15 min, cardiac output was significantly reduced with ivabradine (-5.2% vs. +15.0% variation in ivabradine/placebo group, p = 0.03), and central venous pressure increased (+4.2% vs. -19.7% variation, p < 0.01). CONCLUSIONS: Ivabradine reduces heart rate and increases stroke volume without modifying systemic or left filling pressures in a swine model of acute heart failure. However, an excessive heart rate reduction could lead to a decrease in cardiac output and an increase in right filling pressures. Future studies with specific heart rate targets are needed.

Uso de toxina botulínica paravertebral para detener la progresión de escoliosis en pollos pinealectomizados: la columna vertebral como sistema de tensegridad / Use of paravertebral injection of botulinum toxin to control scoliosis progression in pinealectomized chicken: the spine as a tensegrity system

Antecedentes y Objetivos. La escoliosis idiopática infantil no tiene un tratamiento satisfactorio que permita reducir la importante morbilidad y mortalidad asociada a los casos más severos y progresivos de la enfermedad. El desarrollo de procedimientos que puedan ralentizar la progresión de la enfermedad durante el desarrollo del niño puede influir favorablemente en el crecimiento y retrasar el tratamiento definitivo de la deformidad al momento de la madurez músculoesquelética. Presentamos un estudio sobre la influencia de la toxina botulínica en el desarrollo de deformidad en un modelo animal de escoliosis progresiva. Material y Método. Utilizamos 52 pollos Broiler hembra, en los que se practicó pinealectomía para producir escoliosis. Comparamos la evolución de la deformidad entre un grupo control y un grupo intervención asignado a recibir toxina botulínica paravertebral en la concavidad de la curva, bajo control electromiográfico. Realizamos estudios radiográficos y anatomopatológicos de los animales para evaluar los resultados. El grado de escoliosis se midió utilizando el método del ángulo de Cobb. Resultados. Cinco animales no sobrevivieron al estudio (1 en el grupo control y 4 en el de intervención). En el grupo control observamos una deformidad media de 32.9º (n= 25) y en el grupo intervención de 18.8º (n=22), encontrando diferencias estadísticamente significativas (p<0.05). Por tanto, la aplicación de toxina botulínica en la concavidad de la deformidad de pollos pinealectomizados frena la progresión de escoliosis. Conclusiones. La consideración de la columna vertebral y sus tejidos blandos asociados como una estructura de tensegridad puede explicar el fenómeno mediante el desequilibrio generado entre los componentes de tensión (músculos y ligamentos) y compresión (vértebras) que conforman el sistema. Estos resultados justifican nuevos estudios en investigación clínica para explorar una nueva alternativa para el tratamiento de la escoliosis idiopática infantil (AU)

Background and Objectives. Severe and progressive adolescent idiopathic scoliosis has no satisfactory treatment since high rates of morbidity and mortality are associated. Development of procedures that might slow down the progression of the deformity in the growing children may postpone definitive surgery to the end of musculoskeletal maturity period. A study about the influence of botulinum toxin in the development of deformity in a progressive scoliosis animal model is reported. Methods. Surgical pinealectomy was performed in 52 Broiler chickens to induce progressive scoliosis. Scoliosis progression among a control group and an intervention group assigned to paravertebral injection of botulinum toxin in curve´s concavity electromyographycally assisted is compared. Conventional x-ray and anatomopathologic studies were conducted to evaluate results. Cobb angle method was used to measure spine deformation. Results. Five animals died (1 in the control group and 4 in the intervention group). Mean scoliosis values observed were 32.9 degrees (n= 25) and 18.8 degrees (n= 22) for control and intervention groups respectively (p<0.05). Therefore, the use of botulinum toxin in the deformity´s concavity restrains scoliosis progression in pinealectomized chickens. Conclusions. The assumption of the spine and its associated soft tissues as a tensegrity structure may explain these results, through the induced imbalance between the tension (muscles and ligaments) and compression (vertebrae) components that shape the system. Further studies are necessary to determine clinical applications of this therapy in adolescent idiopathic scoliosis (AU)