Vascular photodynamic therapy : a multifactorial approach to inhibit intimal hyperplasia

The Wellman Laboratories of Photomedicine at the Massachusetts General Hospital in Boston is an internationally known institute for the development and application of laser in medicinco Besides fundamental research which investigates the interaction of light with cells and molecules, a great deal of studies arc performed towards clinical application to treat human diseases. For this reason, all known medical specialties are involved in research programmes examining the use of laser for their purposes: from ophtalmologists, using photodynamic therapy to treat choroidal neovascularization, oncologists to photochemically target and remove breast cancer cells from bone marrow, urologist to detect bladder cancer with fluorescence, gastroenterologists to treat Barret's oesophagus to dermatologists removing latloes and treating multiple skin diseases with the laser. The application of laser to treat vascular diseases was started decades ago, but more recently the concept of photodynamic therapy was introduced by the research group of Dr. LaMuraglia to prevent restenosis. As a research fellow in surgery I joined this group in 1994 and our research goal was to better understand how photodynamic therapy affects the vascular wall. The results from these investigations are presented in tllis thesis. The first part gives an outline of the problem of restenosis, the concept of photodynamic therapy and aims of the study. The following chapters describe how photodynamic therapy interacts with biological factors that regulate the vascular healing process. Finally, considerations for possible clinical use are discussed

La responsabilidad civil derivada de las actuaciones de los funcionarios del Registro Público.

El sistema registral panameño tiene como finalidad primordial el dotar de la seguridad jurídica necesaria al tráfico inmobiliario, ofreciendo garantías a quien se proponga a invertir en el mercado de los inmuebles mediante el suministro de información confiable y exacta. Pero el sistema puede fallar, ocasionando daños a los titulares de derechos inscritos o a los terceros que se atienen a las constancias registrales. Para compensar los daños así producidos por una entidad creada precisamente para ofrecer seguridad, el Código Civil panameño establece - inspirándose en este aspecto como en muchos otros concernientes a nuestro sistema registral- en la legislación española, la responsabilidad personal del Registrador, fundada principalmente en la independencia de éste al ejercer su función. No obstante, entre el régimen jurídico a que se encuentra sometido , en términos generales, el Registrador español y el nuestro existen significativas diferencias - aunque en el fondo su labor sea muy similar- que han tornado discutible esa solución, que por otra parte, en la práctica nunca ha funcionado. Además, nuestra más reciente jurisprudencia hace responsable al Estado por la deficiente prestación de servicios públicos, incluso en el caso de los funcionarios judiciales. En un mundo cuya economía se encuentra en un proceso de creciente integración y donde se acentúa la competencia por el capital, es necesario establecer efectivas garantías en el aspecto que nos ocupa. El definir claramente cuáles son las que nuestro país ofrece en este aspecto y cuáles son las que debe ofrecer, constituye el objetivo central del presente trabajo. Para ello analizamos el objetivo, naturaleza jurídica de la función registral y reglamentos operativos del Registro Público panameño, los errores registrales y las normas sobre existentes sobre la responsabilidad civil de los funcionarios registrales frente a las teorías sobre responsabilidad civil estatal, además de los elementos que conforman la responsabilidad civil en el caso específico que nos ocupa. Utilizamos el método deductivo, recurriendo asimismo al histórico y al Derecho Comparado

Gi- and Gs-coupled GPCRs show different modes of G-protein binding.

More than two decades ago, the activation mechanism for the membrane-bound photoreceptor and prototypical G protein-coupled receptor (GPCR) rhodopsin was uncovered. Upon light-induced changes in ligand-receptor interaction, movement of specific transmembrane helices within the receptor opens a crevice at the cytoplasmic surface, allowing for coupling of heterotrimeric guanine nucleotide-binding proteins (G proteins). The general features of this activation mechanism are conserved across the GPCR superfamily. Nevertheless, GPCRs have selectivity for distinct G-protein family members, but the mechanism of selectivity remains elusive. Structures of GPCRs in complex with the stimulatory G protein, Gs, and an accessory nanobody to stabilize the complex have been reported, providing information on the intermolecular interactions. However, to reveal the structural selectivity filters, it will be necessary to determine GPCR-G protein structures involving other G-protein subtypes. In addition, it is important to obtain structures in the absence of a nanobody that may influence the structure. Here, we present a model for a rhodopsin-G protein complex derived from intermolecular distance constraints between the activated receptor and the inhibitory G protein, Gi, using electron paramagnetic resonance spectroscopy and spin-labeling methodologies. Molecular dynamics simulations demonstrated the overall stability of the modeled complex. In the rhodopsin-Gi complex, Gi engages rhodopsin in a manner distinct from previous GPCR-Gs structures, providing insight into specificity determinants

A comparison of balloon injury models of endovascular lesions in rat arteries

BACKGROUND: Balloon injury (BI) of the rat carotid artery (CCA) is widely used to study intimal hyperplasia (IH) and decrease in lumen diameter (LD), but CCA's small diameter impedes the evaluation of endovascular therapies. Therefore, we validated BI in the aorta (AA) and iliac artery (CIA) to compare it with CCA. METHODS: Rats underwent BI or a sham procedure (control). Light microscopic evaluation was performed either directly or at 1, 2, 3, 4 and 16 weeks follow-up. The area of IH and the change in LD (LD at 16 weeks minus LD post BI) were compared. RESULTS: In the BI-groups the area of IH increased to 0.14 ± 0.08 mm(2) (CCA), 0.14 ± 0.03 mm(2) (CIA) and 0.12 ± 0.04 mm(2) (AA) at 16 weeks (NS). The LD decreased with 0.49 ± 0.07 mm (CCA), compared to 0.22 ± 0.07 mm (CIA) and 0.07 ± 0.10 mm (AA) at 16 weeks (p < 0.05). The constrictive vascular remodelling (CVR = wall circumference loss combined with a decrease in LD) was -0.17 ± 0.05 mm in CIA but absent in CCA and AA. No IH, no decrease in LD and no CVR was seen in the control groups. CONCLUSIONS: BI resulted in: (1.) a decrease in LD in CCA due to IH, (2.) a decrease in LD in CIA due to IH and CVR, (3.) no change in LD in AA, (4.) Comparable IH development in all arteries, (5.) CCA has no vasa vasorum compared to CIA and AA, (6.) The CIA model combines good access for 2 F endovascular catheters with a decrease in LD due to IH and CVR after BI

Going in Thinking Process, Coming Out Transformed: Reflections and Recommendations from a Qualitative Research Course

This article presents reflections and suggestions of an instructor and students from a doctoral-level qualitative research course. Given qualitative research courses often lack guidance for best practices and the well-being of doctoral students learning qualitative research is often overlooked, the purpose of this article is threefold: 1) to provide an introductory skeleton for designing a qualitative research course that is structured for classmates to interview each other throughout the semester, what the authors call a student-as-researcher-and-participant design; 2) to provide student reflections from the course; and finally, 3) to offer recommendations for using a student-as-researcher-and participant design for a qualitative research course

A comparison of balloon injury models of endovascular lesions in rat arteries

BACKGROUND: Balloon injury (BI) of the rat carotid artery (CCA) is widely used to study intimal hyperplasia (IH) and decrease in lumen diameter (LD), but CCA's small diameter impedes the evaluation of endovascular therapies. Therefore, we validated BI in the aorta (AA) and iliac artery (CIA) to compare it with CCA. METHODS: Rats underwent BI or a sham procedure (control). Light microscopic evaluation was performed either directly or at 1, 2, 3, 4 and 16 weeks follow-up. The area of IH and the change in LD (LD at 16 weeks minus LD post BI) were compared. RESULTS: In the BI-groups the area of IH increased to 0.14 +/- 0.08 mm2 (CCA), 0.14 +/- 0.03 mm2 (CIA) and 0.12 +/- 0.04 mm2 (AA) at 16 weeks (NS). The LD decreased with 0.49 +/- 0.07 mm (CCA), compared to 0.22 +/- 0.07 mm (CIA) and 0.07 +/- 0.10 mm (AA) at 16 weeks (p < 0.05). The constrictive vascular remodelling (CVR = wall circumference loss combined with a decrease in LD) was -0.17 +/- 0.05 mm in CIA but absent in CCA and AA. No IH, no decrease in LD and no CVR was seen in the control groups. CONCLUSIONS: BI resulted in: (1.) a decrease in LD in CCA due to IH, (2.) a decrease in LD in CIA due to IH and CVR, (3.) no change in LD in AA, (4.) Comparable IH development in all arteries, (5.) CCA has no vasa vasorum compared to CIA and AA, (6.) The CIA model combines good access for 2 F endovascular catheters with a decrease in LD due to IH and CVR after BI

Nationwide Study to Predict Colonic Ischemia after Abdominal Aortic Aneurysm Repair in The Netherlands

BACKGROUND: Colonic ischemia remains a severe complication after abdominal aortic aneurysm (AAA) repair and is associated with a high mortality. With open repair being one of the main risk factors of colonic ischemia, deciding between endovascular or open aneurysm repair should be based on tailor-made medicine. This study aims to identify high-risk patients of colonic ischemia, a risk that can be taken into account while deciding on AAA treatment strategy.METHODS: A nationwide population-based cohort study of 9,433 patients who underwent an AAA operation between 2014 and 2016 was conducted. Potential risk factors were determined by reviewing prior studies and univariate analysis. With logistic regression analysis, independent predictors of intestinal ischemia were established. These variables were used to form a prediction model.RESULTS: Intestinal ischemia occurred in 267 patients (2.8%). Occurrence of intestinal ischemia was seen significantly more in open repair versus endovascular aneurysm repair (7.6% vs. 0.9%; P &lt; 0.001). This difference remained significant after stratification by urgency of the procedure, in both intact open (4.2% vs. 0.4%; P &lt; 0.001) and ruptured open repair (15.0% vs. 6.2%); P &lt; 0.001). Rupture of the AAA was the most important predictor of developing intestinal ischemia (odds ratio [OR], 5.9, 95% confidence interval [CI] 4.4-8.0), followed by having a suprarenal AAA (OR 3.4; CI 1.1-10.6). Associated procedural factors were open repair (OR 2.8; 95% CI 1.9-4.2), blood loss &gt;1L (OR 3.6; 95% CI 1.7-7.5), and prolonged operating time (OR 2.0; 95% CI 1.4-2.8). Patient characteristics included having peripheral arterial disease (OR 2.4; 95% CI 1.3-4.4), female gender (OR 1.7; 95% CI 1.2-2.4), renal insufficiency (OR 1.7; 1.3-2.2), and pulmonary history (OR 1.6; 95% CI 1.2-2.2). Age &lt;68 years proved to be a protective factor (OR 0.5; 95% CI 0.4-0.8). Associated mortality was higher in patients with intestinal ischemia versus patients without (50.6% vs. 5.1%, P &lt; 0.001). Each predictor was given a score between 1 and 4. Patients with a score of ≥10 proved to be at high risk. A prediction model with an excellent AUC = 0.873 (95% CI 0.855-0.892) could be formed.CONCLUSIONS: One of the main risk factors is open repair. Several other risk factors can contribute to developing colonic ischemia after AAA repair. The proposed prediction model can be used to identify patients at high risk for developing colonic ischemia. With the current trend in AAA repair leaning toward open repair for better long-term results, our prediction model allows a better informed decision can be made in AAA treatment strategy.</p

The Influence of Aortic Wall Elasticity on the False Lumen in Aortic Dissection: An In Vitro Study

Cardiovascular Aspects of Radiolog