Valproic acid radiosensitizes anaplastic thyroid cells through a decrease of the DNA damage repair capacity.

BACKGROUND: Anaplastic thyroid cancer (ATC) represents a rare lethal human malignancy with poor prognosis. Multimodality treatment, including radiotherapy, is recommended to improve local control and survival. Valproic acid (VA) is a clinically available histone deacetylase inhibitor with a well-documented side effect profile. In this study, we aim to investigate the combined effect of VA with photon irradiation in vitro. METHODS: Anaplastic thyroid cancer cells (8505c) were used to investigate the radiosensitizing effect of VA. RESULTS: VA sensitized cells to photon irradiation. VA increased radiation-induced apoptosis and radiation-induced DNA damage measured by γH2AX foci induction. Furthermore, VA prolonged γH2AX foci disappearance over time in irradiated cells and decreased the radiation-induced levels of mRNA of key DNA damage repair proteins of the homologous recombination (HR) and the nonhomologous end joining (NHEJ) pathways. CONCLUSIONS: VA at a clinically safe dose enhance the radiosensitivity of 8505c cells through an increase in radiation-induced apoptosis and a disruption in the molecular mechanism of HR and NHEJ DNA damage repair pathways.

Robotic versus laparoscopic surgery for rectal cancer: a comparative cost-effectiveness study.

BACKGROUND: The differences between the costs of robotic rectal resection and of the laparoscopic approach are still not well known. The aim of this study was to evaluate the cost-effectiveness of robotic versus laparoscopic surgery. METHODS: We conducted an observational, comparative, prospective, non-randomized study on patients having laparoscopic and robotic rectal resection between February 2014 and March 2018 at the Sanchinarro University Hospital, Madrid. Outcome parameters included surgical and post-operative costs, quality adjusted life years (QALY) and incremental cost per QALY gained or the incremental cost effectiveness ratio (ICER). The primary endpoint was to compare cost effectiveness in the robotic and laparoscopic surgery groups. A willingness-to-pay of 20,000€ and 30,000€ per QALY was used as a threshold to determine the most cost-effective treatment. RESULTS: A total of 81 RRR and 104 LRR were included. The mean operative costs were higher for RRR (4307.09€ versus 3834.58€; p = 0.04), although mean overall costs were similar (7272.03€ for RRR and 6968.63€ for the LLR; p = 0.44). Mean QALYs at 1 year for the RRR group (0.8482) was higher than that associated with LRR (0.6532) (p = 0.018). At a willingness-to-pay threshold of 20,000€ and 30,000€ there was a 95.54% and 97.18% probability, respectively, that RRR was more cost-effective than LRR. CONCLUSIONS: Our data regarding the cost-effectiveness of RRR versus LRR shows a benefit for RRR.

Robotic-assisted gastrectomy compared with open resection: a comparative study of clinical outcomes and cost-effectiveness analysis.

In the last decade, there have clearly been important changes in the surgical approach of gastric cancer treatment due to an increased interest in the minimally invasive surgical approach (MIS). The higher cost of robotic surgery procedures remains an important issue of debate. The objective of the study is to compare the main operative and clinical outcomes and to assess the incremental cost-effectiveness ratios (ICERs) of the two techniques. This is a prospective cost-effectiveness and clinical study when comparing the robotic gastrectomy (RG) technique with open gastrectomy (OG) in gastric cancer. Outcome parameters included surgical and post-operative costs, quality-adjusted life years (QALY) and incremental cost per QALY gained or the incremental cost-effectiveness ratio (ICER). The incremental utility was 0.038 QALYs and the estimated ICER for patients was dominated by robotic approach. The probability that the robotic approach was cost effective was 94.04% and 94.20%, respectively, at a WTP threshold of 20,000€ and 30,000€ per QALY gained. RG for gastric cancer represents a cost-effective procedure compared with the standard OG.

Functionalization of gum arabic including glycoprotein and polysaccharides for the removal of boron.

Bio hybrid material supported multifunctional (hydroxyproline with enriched glycoprotein) has been shown to be efficient in chelation with boron and can be used for removal of boron at ppm levels. Gum arabic (GUM) is biodegradable and nontoxic biopolymer. GUM includes GA-GP-GA-glycoprotein and polysaccharides. Hollow silica spheres (HSS) gain increasing attention, thanks to low density, high specific surface and good adsorption performance. In this study, sol-gel process was used for the preparation of HSS and was modified with epoxy group. The resulted epoxidized HSS (HSEPC) was reacted with GUM to obtain a poly saccharide derivative functional hollow silica sphere (HSGUM) for removal of boron. Characterizations of HSGUM were performed by FT-IR and SEM techniques. Adsorption isotherm and kinetic models were also applied to adsorption of boron onto HSGUM. The resulting sorbent HSGUM has been demonstrated efficient and the maximum boron sorption capacity at monolayer coverage (qmax) was found as average 4.10 mmol g-1.

First case of complete full robotic surgical resection of leiomyosarcoma of the right renal vein.

BACKGROUND: Leiomyosarcomas present high postoperative morbidity and poor prognosis [1]. In the literature, only few cases of localized small leiomyosarcoma have been described [2, 3]. These cases might benefit from a minimally invasive approach. Robotic surgery has been claimed to have several advantages over laparoscopy such as enhanced vision and instruments movements which might make more feasible the execution of this type of surgery where partial renal resection is required. METHODS: A 53-year-old female with a medical history of myeloid leukemia and with chronic renal failure (creatinine: 2.6) was referred to our hospital for an incidental finding of right perirenal tumor of almost 3 cm compatible with leiomyosarcoma arising from the right renal vein. RESULTS: The operation was performed using a Da Vinci Robotic Surgical System model Si (Intuitive Surgical, Sunnyvale, CA, USA).Robotic ports were placed in a standard configuration for minimally invasive right nephrectomy. The dissection started with the partial mobilization of the right liver and Kocher maneuver. After the identification of the inferior vena cava the tumor was finally localized and dissected. Resection ended with a partial right vein resection and suture. Pathological final exam confirmed the diagnosis with margins free from tumor. CONCLUSIONS: In selected cases, robotic resection of leiomyosarcoma might be a safe and feasible procedure in experienced hands.

Robotic versus laparoscopic surgery for rectal cancer: a comparative study of clinical outcomes and costs.

PURPOSE: The costs involved in performing robotic surgery present a critical issue which has not been well addressed yet. The aims of this study are to compare the clinical outcomes and cost differences of robotic versus laparoscopic surgery in the treatment of rectal cancer and to conduct a literature review of the cost analysis. METHODS: This is an observational, comparative study whereby data were abstracted from a retrospective database of patients who underwent laparoscopic and robotic rectal resection from October 2010 to March 2017, at Sanchinarro University Hospital, Madrid. An independent company performed the financial analysis, and fixed costs were excluded. RESULTS: A total of 86 robotic and 112 laparoscopic rectal resections were included. The mean operative time was significantly lower in the laparoscopic approach (336 versus 283 min; p = 0.001). The main pre-operative data, overall morbidity, hospital stay and oncological outcomes were similar in both groups, except for the readmission rate (robotic: 5.8%, laparoscopic: 11.6%; p = 0.001). The mean operative costs were higher for robotic surgery (4285.16 versus 3506.11€; p = 0.04); however, the mean overall costs were similar (7279.31€ for robotic and 6879.8€ for the laparoscopic approach; p = 0.44). We found four studies reporting costs, three comparing robotic versus laparoscopy costs, with all of them reporting a higher overall cost for the robotic rectal resection. CONCLUSION: Robotic rectal resection has similar clinical outcomes to that of the conventional laparoscopic approach. Despite the higher operative costs of robotic rectal resection, overall mean costs were similar in our series.

Dynamics of ultra-thin polystyrene with and without a (artificial) dead layer studied by resonance enhanced dynamic light scattering.

Using non-invasive, marker-free resonance enhanced dynamic light scattering, the dynamics of capillary waves on ultrathin polystyrene films' coupling to the viscoelastic and mechanical properties have been studied. The dynamics of ultrathin polymer films is still debated. In particular the question of what influence either the solid substrate and/or the fluid-gas interface has on the dynamics and the mechanical properties of films of glass forming liquids as polymers is in the focus of the present research. As a consequence, e.g., viscosity close to interfaces and thus the average viscosity of very thin films are prone to change. This study is focused on atactic, non-entangled polystyrene thin films on the gold surface. A slow dynamic mode was observed with Vogel-Fulcher-Tammann temperature dependence, slowing down with decreasing film thickness. We tentatively attribute this relaxation mode to overdamped capillary waves because of its temperature dependence and the dispersion with a wave vector which was found. No signs of a more mobile layer at the air/polymer interface or of a "dead layer" at the solid/polymer interface were found. Therefore we investigated the influence of an artificially created dead layer on the capillary wave dynamics by introducing covalently bound polystyrene polymer brushes as anchors. The dynamics was slowed down to a degree more than expected from theoretical work on the increase of density close to the solid liquid interface-instead of a "dead layer" of 2 nm, the interaction seems to extend more than 10 nm into the polymer.

Comportamiento morfológico y electroquímico de un recubrimiento Dip Coating policaprolactona-quitosano-colágeno sobre Ti6Al4V / Morphological and electrochemical behavior of polycaprolactone-chitosan-collagen film fabricated by Dip Coating on Ti6Al4V

Resumen: En este trabajo se presenta, la caracterización mediante las técnica de Infrarrojo, Microscopía de Fuerza Atómica, Microscopía Electrónica de Barrido y ángulo de contacto de los recubrimientos poliméricos de la mezcla binaria de policaprolactona-quitosano y su modificación tras la adición de colágeno que fueron depositados mediante la técnica de Dip Coating sobre la aleación de Ti6Al4V; además, se evaluó mediante la técnica de Espectroscopía de Impedancia Electroquímica la aleación Ti6Al4V recubierta por las mezclas de polímeros a cero días de inmersión en Fluido Corporal Simulado y la capacidad de adsorción de calcio a 21 días de inmersión. De esta manera, se encontraron efectos representativos sobre el papel del colágeno para el aumento de la rugosidad superficial, mayores valores en la resistencia a la polarización del Ti6Al4V, mejor comportamiento en los parámetros de energía libre, adsorción atómica de calcio y la consolidación de una nueva interfase asociada a la monocapa de calcio simulada mediante circuitos equivalentes y observada por Microscopía Electrónica de Barrido.

Abstract: This paper presents the characterization by the infrared technique, atomic force microscopy, scanning electron microscopy and contact angle of the polymer coatings of the binary mixture of polycaprolactone-chitosan and its modification after addition of collagen were deposited by the technique of Dip Coating on Ti6Al4V alloy; also by the technique of Electrochemical Impedance Spectroscopy were evaluated the Ti6Al4V alloy coated by polymer blends zero days immersion in Simulate Bode Fluid and of adsorptivity calcium to 21 days immersion. Thus, representative effects on the role of collagen to increase the surface roughness, higher values in the polarization resistance of Ti6Al4V, better behavior parameters free energy, atomic adsorption of calcium and the consolidation of a found new interface associated with the monolayer calcium simulated by equivalent circuits and observed by Scanning Electron Microscopy.

Total pancreatoduodenectomy en bloc with superior mesenteric artery and vein resection after gemcitabine and nab-paclitaxel neoadjuvancy.

BACKGROUND: Pancreatectomy for locally advanced adenocarcinoma affecting the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) is still under discussion [1]. However, in selected cases, in light of the advancement of recent neoadjuvant treatments, it must be taken into account [2,3]. This video demonstrates some of the technical aspects of SMA and SMV resection as well as some tips of vascular reconstruction. METHODS: A 48-year-old man with a large adenocarcinoma of the uncinated process affecting the SMA and SMV underwent 3 cycles of gemcitabine and nab-paclitaxel neoadjuvancy. Post chemotherapy studies showed no disease progression with a normalization of CA 19.9 and SUV of FDG PET CT scan and a downsizing of the tumor, as well. Therefore, an en bloc total spleno-pancreato-duodenectomy with resection of SMA and SMV was planned. RESULTS: Through a bilateral subcostal incision, an "arterial first approach" [3] was performed. Considering the large length of the vascular resection, the replacement of the resected SMA and SMV was performed using two PTFE grafts, as showed in the video. Postoperative pathology showed margins free from disease with an important pathological response (grade 2 of Ryan classification adapted from rectal cancer) [4]. The post-operative course was uneventful and the patient is still free from disease at 31 months from surgery. CONCLUSIONS: This case is part of a large experience our group have acquired since we started neoadjuvancy in 2010. In our experience, we gathered 25 cases of locally advanced pancreatic tumors, of which 12 underwent to pancreatic resection after good response to the neoadjuvant treatment. In 5 of them concomitant SMA and SMV resection was required and post-operative mortality occurred in 1 of them. Morbidities and mortalities are higher compared with standard pancreatectomies, specially related to the vascular reconstruction (bleeding, graft thrombosis) [5]. However, in some circumstances like young age, great radiological and biological response to neoadjuvancy (such as the case herein presented), surgery might be considered the best option of care providing the only possibility to increase survival for these types of locally advanced tumors. However, further studies are needed to know which patients might benefit from this approach. En bloc total spleno-pancreato-duodenectomy with resection of SMA and SMV might be considered as an effective procedure in selected cases of pancreatic adenocarcinoma with good response to preoperative treatment.

Predictive prognostic value of local and distant recurrence of F-fluorodeoxyglucose positron emission tomography for pancreatic neuroendocrine tumors with reference to World Health Organization classifications (2004, 2010). Case series study.

BACKGROUND: F-flurodeoxyglucose positron emission tomography (FDG-PET) have been claimed to be an important prognostic tool in different malignancies. However, its predictive prognostic value on pancreatic neuroendocrine tumors (PNETs) is still under investigation. AIM: We study the prognostic impact of FDG-PET scan in neuroendocrine pancreatic tumors. METHODOLOGY: Between 2007 and 2012, 26 patients with no metastastatic histologically confirmed PNETs (mean age: 57 years) were examined with FDG-PET. We studied its captation in relation with the well established hystopathological prognostic markers assessed in the tumoral resected specimen according to the WHO 2004 and ENETS/WHO 2010 classification. RESULTS: FDG-PET captation was positive in 17 cases (65.4%). The median follow-up period was 34.4 months and recurrences occurred in 4 cases (15.4%). We found a significant correlation between this captation and Ki 67 index (p = 0.032), mitotic index (p = 0.002), tumor grade (p = 0.017) and tumor size (p = 0.01). CONCLUSIONS: FDG-PET provides a good prognostic value for PNETs. Present results must be further validated with larger sample studies.

Preoperative treatment with gemcitabine plus nab-paclitaxel is a safe and effective chemotherapy for pancreatic adenocarcinoma.

INTRODUCTION: Recently, novel chemotherapeutic agents like nab-paclitaxel and gemcitabine demonstrated a survival benefit over gemcitabine alone in metastatic pancreatic cancer. However, there are limited clinical results using this chemotherapy in potentially resectable pancreatic adenocarcinoma. Our aim is to report the oncological results of patients affected by potentially resectable pancreatic adenocarcinoma that underwent surgery after a combination of gemcitabine and nab-paclitaxel. METHODS: A total of 25 patients have been included. We evaluated: (1) Drug toxicity; (2) tumoral response (tumoral size at CT scan, SUV of FDG PET-CT scan and CA 19.9; (3) resection rate; (4) R0 resection rate and histopathological response and (5) survival and disease free survival. RESULTS: Overall treatment was well tolerated. Treatment resulted in a statistical decrease of CA19-9 (p = 0.019) tumoral size (p = 0.04) and SUV (p = 0.004). The resection rate was 68% (17/25 patients). All specimens were R0 and 13 of 17 specimens had major pathological regressions (complete and important response). Median survival and medial disease free survival of patients that underwent surgery was 21 months and 19 months, respectively at a mean follow up of 38.5 months. CONCLUSIONS: This data suggests that nab-paclitaxel and gemcitabine is a safe and effective neoadjuvant treatment for potentially resectable pancreatic adenocarcinoma. This promising data should be confirmed in larger, randomized studies.

Is "small for size syndrome" a relatively new complication after the ALPPS procedure?

Aim of this study is to assess the incidence and outcome of small for size syndrome after ALPPS procedure. This novel procedure is claimed to induce accelerated and increased growth of future liver remnant after major hepatectomies. We prospectively collected data on nine consecutive patients undergoing ALPPS procedure at our center. Main patients' characteristics, outcome and postoperative complications, including small for size syndrome were analyzed. Main interval between two stages of ALPPS was 15.1 days. Mean future liver remnant hypertrophy was 93.2%. Severe complications occurred in 44.4% of patients and mortality occurred in two cases (22.2%). Small for size syndrome occurred in two cases (22.2%). The first one was detected intraoperatively during first stage. It was successfully managed by spleno-renal venous shunt. Second case was not promptly detected and died on postoperative day 64. This case series provides evidence that SFFS can be an important complication after ALPPS procedure. If it is not promptly detected and properly managed it can be a cause of death as occurred in our case.

An organizational model to improve the robotic system among general surgeons.

INTRODUCTION: Robotic surgery has gained wide acceptance in recent years. However its development is slower and the lack of high level experience with this technique is an important limitation. This manuscript discusses some of the reasons of it and aims to describe the organizational system we have progressively established in our center in order to improve the development of Robotic program in our surgical area. METHODS: Some points may be required to improve the robotic program development in a general surgical department, including: a broad availability of robotic system in a surgical area; an ideal setting area with mainly oncological and hepato-biliary-pancreatic disease; the need of a mainly young team; a broad application of the robotic system in more general surgical fields; a high motivation on robotic use; a departmental and institutional economical effort. We have tried to achieve these goals before starting the robotic program in our department at October 2010. RESULTS: From October 2010 until November 2013 a total of 170 procedures have been performed, 92% of them for malignant diseases. Conversion rate and overall morbidity was 5% and 19%, respectively. CONCLUSIONS: The organizational model defined in our center is facilitating the constant and progressive development of the robotic program. A broad and flexible availability of the robotic system, a progressive increase of young surgeons joining this technology as well as the institutional and departmental economical effort are the points with which the robotic system may increase its development in a surgical department.

Análisis de variables epidemiológicas, clínicas e histopatológicas del cáncer de piel en el Hospital Regional de Arica, Chile (2007-2011) / Analysis of epidemiological, clinical and histopathological variables of skin cancer in the Regional Hospital of Arica, Chile (2007-2011)

Introducción: el cáncer cutáneo es un problema de salud pública. Múltiples factores influyen en el desarrollo de esta neoplasia. El nortede Chile y particularmente Arica, tienen condiciones diferentes al restodel país, presentan mayores niveles de radiación solar, elevada foto exposición y un importante número de población amerindia. Objetivo: Determinar las tasas de incidencia de Carcinoma Basocelular (CBC),Carcinoma Espinocelular CEC y Melanoma Maligno (MM) en la población beneficiaria del Hospital Regional de Arica entre 2007 y 2011 ycaracterizar los tumores utilizando variables clínicas e histopatológicas. Metodología: Se analizaron 22.787 informes histopatológicos de biopsiasen el Hospital Regional de Arica, durante los años 2007 - 2011.Se obtuvieron 288 informes compatibles con cáncer de piel. Se analizaronlas variables de sexo, edad, raza, localización anatómica y tipo histológico. El análisis estadístico se realizó mediante test de Fisher considerando un valor de p menor a 0,05 significativo. Resultados: Se obtuvieron 183 pacientes (64%) con CBC, 93 (32%) con CEC y 12 (4%)de MM. Las tasas de incidencia en total presentaron fluctuaciones,con un patrón decreciente, en CBC (44,03/ 100.000 en 2007, a 13.68/100.000 en 2011) y CEC (16,08/100.000 en 2007 a 8,92/ 100.000 en2011). La localización más frecuente fue cabeza y cuello, 154 pacientespara CBC (84%) y 44 con CEC (47%). En cuanto MM la ubicación más frecuente fue tronco en varones y extremidades superiores e inferiores,en mujeres...

Introduction: skin cancer is a public health problem. Multiplefactors contribute to its appearance. Northern Chile, particularly Arica, has different conditions to the rest of the countryand showed higher levels of solar radiation, a higher sunexposure and a significant number of Amerindian population. Objetive: Determine the incidence rates of Basal Cell Carcinoma( BCC), Squamous cell carcinoma (SCC) and Malignantmelanoma (MM ) in the target population of Arica RegionalHospital, between 2007 and 2011 and characterize the skintumors according to the clinical and histopathological variables. Methodology: 22,787 histopathological reports from the Regional Hospital of Arica, during 2007-2011 were analyzed.288 reports compatible with skin cancer (BCC, SCC and MM)were obtained. For each tumor the variables of sex, age, race,anatomical location and histological type were analyzed. The statistical analysis was performed by the test of Fisher. Results:183 patients, 64% BCC, 32 % SCC and 4% MM wereobtained. Incidence rates of all skin cancer showed fluctuations with decreasing pattern in BCC (ranging from 44.03 /100,000 in 2007, to 13.68 / 100,000 in 2011) and SCC (rangingfrom 16.08 / 100,000 the year 2007 to 8.92 / 100,000 in2011). The most frequent location was head and neck, 154for BCC (84%) and 44 with SCC (47%). The most frequent location of MM was trunk in males and upper and lower limbsin females...

Hyaluronan degrading silica nanoparticles for skin cancer therapy.

We report the first nanoformulation of Hyaluronidase (Hyal) and its enhanced adjuvant effect over the free enzyme. Hyaluronic acid (HA) degrading enzyme Hyal was immobilized on 250 nm silica nanoparticles (SiNP) maintaining specific activity of the enzyme via the layer-by-layer self-assembly technique. This process was characterized by dynamic light scattering (DLS), zeta potential, infrared and UV-Vis spectroscopy, transmission electron microscopy (TEM) and enzymatic activity measurements. The nanoparticles were tested in vivo as adjuvants of carboplatin (CP), peritumorally injected in A375 human melanoma bearing mice and compared with the non-immobilized enzyme, on the basis of equal enzymatic activity. Alcian Blue staining of A375 tumors indicated large overexpression of hyaluronan. At the end of the experiment, tumor volume reduction with SiNP-immobilized Hyal was significantly enhanced compared to non-immobilized Hyal. Field emission scanning electron microscopy (FE-SEM) images together with energy dispersive X-ray spectroscopy (EDS) spectra confirmed the presence of SiNP on the tumor. We mean a proof of concept: this extracellular matrix (ECM) degrading enzyme, immobilized on SiNP, is a more effective local adjuvant of cancer drugs than the non-immobilized enzyme. This could prove useful in future therapies using other or a combination of ECM degrading enzymes.

Biological effects of brachytherapy using a (32)P-patch on the skin of Sencar mice.

In recent years, specially designed patches containing beta emitters have been developed for contact brachytherapy of skin lesions. The aim of the present work was to evaluate the biological effects of the (32)P-patch on the skin of Sencar mice as a result of a brachytherapy treatment. For this purpose, a (32)P-patch was prepared with Chromic (32)P-phosphate and silicone and the classical model of two-stage skin carcinogenesis was reproduced in Sencar mice. Animals were divided in six groups. Four groups received the contact brachytherapy treatments using a scheme of a single session of 40 and 60Gy (SD40 and SD60) and a scheme of two sessions of 40 and 60Gy each (FD40 and FD60). The other two groups were used as controls of the single (CSD) and the fractionated (CFD) treatments. Radiation doses were estimated with equations derived from the MIRD DOSE scheme, and biologically effective doses (BED) were calculated according to equations derived from the linear-quadratic model. The endpoint to evaluate the treatments effects was tumor size after a follow-up period of 44 days. Finally, animals were sacrificed in order to get samples of all tumors for histological analysis and PCNA staining. Erythema, dermatitis and skin ulceration developed in almost all treated animals, but they gradually healed with regeneration of tissue during the follow-up period. Radiation effects on the skin of SD40, SD60, FD40 and FD60 showed a significant reduction of the tumor size with regard to controls, independently of the scheme and the radiation dose considered. PCNA staining scores of control groups were higher than for treated groups, independently of the scheme and the radiation dose considered. This radioactive (32)P-silicone-patch which is easy to prepare and use in the treatment of skin diseases, seems promising as a radioactive device for clinical use.

Enfermedad de Moyamoya, a propósito de dos casos / Moyamoya disease, 2 case-report

Moyamoya Disease is a progressive occlusive cerebrovascular disease of both internal carotid arteries and their branches, with compensatory development of a fine collateral vascular network. The etiology of the disease is unknown; however, several studies have suggested involvement of genetic and environmental factors in its pathogenesis. In children, it causes transient ischemic attacks and cerebral infarction, while bleeding is more frequent in adults. In Japan, where the disease is most frequently observed, the development of magnetic resonance with angiography has allowed diagnosis in asymptomatic Moyamoya Disease. Revascularization surgery is believed to reduce the incidence of new ischemic events and improve long term prognosis in these patients. We present 2 children with Moyamoya Disease treated in our Clinic between 1998 and 2007.

La enfermedad de Moyamoya es una enfermedad cerebrovascular oclusiva, progresiva de ambas arterias carótidas internas o sus ramas, compensada por el desarrollo de una fina red vascular colateral. Su etiología es desconocida, aunque distintos estudios han asociado su patogénesis a factores genéticos y ambientales. En Pediatría se manifiesta generalmente como crisis isquémicas transitorias o infartos cerebrales, mientras que en adultos es más frecuente la hemorragia cerebral. En países donde es más frecuente, como Japón, se ha logrado hacer un diagnóstico precoz en pacientes aún asintomáticos, gracias al desarrollo de la Resonancia magnética con angiografía cerebral. La cirugía de revascularización lograría reducir la incidencia de nuevos episodios isquémicos y mejorar el pronóstico a largo plazo de los pacientes que padecen esta patología. Presentamos a continuación dos casos que han llegado a nuestro centro en un período de 9 años.

Design and bioevaluation of a 32P-patch for brachytherapy of skin diseases.

The purpose of this study was to design and evaluate a 32P patch for brachytherapy of skin diseases. We employed Phosphoric-32P-acid and Chromic 32P-phosphate in combination with natural rubber or silicone to produce the patches. Stability studies in vitro to evaluate the leakage of radioactivity, autoradiographic studies to evaluate homogeneity and shielding, as well as therapeutic efficacy in an animal model of skin cancer of the selected 32P patch were performed. The 32P-silicone-patch demonstrated its safety for external application. Tumor growth was arrest and complete regressions of tumors were seen in some other cases with 40 Gy applied in a single-dose scheme. In conclusion, the 32P-silicone-patch is easy to prepare and use in the treatment of skin diseases.

Kinetic and inhibition studies of cinnamoyl-CoA reductase 1 from Arabidopsis thaliana.

Cinnamoyl coenzyme A reductase (CCR, EC 1.2.1.44), one of the key enzymes in the biosynthesis of lignin monomers, catalyzes the NADPH-dependent reduction of cinnamoyl-CoA esters to their corresponding cinnamaldehydes. AtCCR1, one of the two distinct isoforms isolated from Arabidopsis thaliana, was shown to be involved in lignin biosynthesis during development. Here, we report on the purification of the recombinant AtCCR1 protein expressed in Escherichia coli and the subsequent determination of its kinetic properties (K(m) and k(cat)/K(m) values) towards its main substrates i.e. feruloyl-CoA, sinapoyl-CoA, and p-coumaroyl-CoA esters. In addition, the potential inhibitory effect of five substrate-like analogs possessing an N-acetylcysteamine thioester group was tested on CCR activity using either feruloyl-CoA or sinapoyl-CoA as substrates. The K(i) values were in the range of 4.4-502 microM and the type of inhibition was found to be either uncompetitive or noncompetitive. Interestingly, for compounds 3 and 5, the type of inhibition was found to be different depending on the substrate used to monitor the enzyme activity. The best inhibitors were those possessing the feruloyl (compound 3) and sinapoyl (compound 5) aromatic moiety (4.1 and 7.1 microM) while the enzyme activity was monitored using the corresponding substrates.

Aggregation during coniferyl alcohol polymerization in pectin solution: a biomimetic approach of the first steps of lignification.

Coniferyl alcohol was polymerized in pectin solution in order to mimic the lignification that is the final step of biosynthesis of plant cell wall. Dehydrogenated polymers (DHP = coniferyl alcohol polymers = synthetic lignin) interact with pectin to form hydrophobic clusters as monitored by pyrene fluorescence spectroscopy. The structure of these clusters was studied during the polymerization of synthetic lignin by static and quasielastic light scattering and small angle neutron scattering experiments. We show that synthetic lignin and pectin contribute to the same clusters, but the inner structure of these clusters is very heterogeneous and displays three phases. One observes a segregation between well separated pectin and lignin rich phases at length scales below approximately 30 nm. As a corollary of this segregation, clusters embody a large amount of solvent. On average, the density of the polymer rich phase (lignin plus pectin) inside clusters increases while its specific surface area decreases throughout the polymerization process. These results are discussed with respect to in vivo lignification of the plant cell wall.