RESUMEN
The nickel-iron carbon monoxide dehydrogenase (CODH) enzyme uses a heterometallic nickel-iron-sulfur ([NiFe4S4]) cluster to catalyze the reversible interconversion of carbon dioxide (CO2) and carbon monoxide (CO). These reactions are essential for maintaining the global carbon cycle and offer a route towards sustainable greenhouse gas conversion but have not been successfully replicated in synthetic models, in part due to a poor understanding of the natural system. Though the general protein architecture of CODH is known, the electronic structure of the active site is not well-understood, and the mechanism of catalysis remains unresolved. To better understand the CODH enzyme, we have developed a protein-based model containing a heterometallic [NiFe3S4] cluster in the Pyrococcus furiosus (Pf) ferredoxin (Fd). This model binds small molecules such as carbon monoxide and cyanide, analogous to CODH. Multiple redox- and ligand-bound states of [NiFe3S4] Fd (NiFd) have been investigated using a suite of spectroscopic techniques, including resonance Raman, Ni and Fe K-edge X-ray absorption spectroscopy, and electron paramagnetic resonance, to resolve charge and spin delocalization across the cluster, site-specific electron density, and ligand activation. The facile movement of charge through the cluster highlights the fluidity of electron density within iron-sulfur clusters and suggests an electronic basis by which CN- inhibits the native system while the CO-bound state continues to elude isolation in CODH. The detailed characterization of isolable states that are accessible in our CODH model system provides valuable insight into unresolved enzymatic intermediates and offers design principles towards developing functional mimics of CODH.
RESUMEN
PURPOSE: Local excision of malignant rectal tumors remains controversial due to the lack of prospective studies. The principal aim of this paper is to analyze survival and recurrence of patients with rectal cancer who were operated by transanal endoscopic microsurgery with curative intention. METHODS: In 1997, we started a prospective protocol for patients who had T1/T2 rectal tumors: transanal local full-thickness excision was considered curative in T1 low risk (group A); patients with T1 high-risk and T2 low-risk tumors received postoperative radiotherapy (group B). From 1997 to 2006, 88 patients were enrolled. Sixty eight entered the study after the preoperative workup and 20 patients with an initial diagnosis of adenoma after postoperative definitive pathological assessment. RESULTS: After definitive histological findings, 54 patients were to group A, 28 to group B, and 6 had immediate radical surgery. One patient was lost for follow-up. At a mean follow-up of 71 months, 7 (4 from group A and 3 from group B) out of 81 patients recurred. Five-year overall survival was of 94% and cancer-specific survival of 96%. CONCLUSIONS: Our data support that transanal endoscopic microsurgery is an adequate treatment for T1 low-risk tumor, and no additional measures are required. For T2 low-risk lesions, our study showed a higher local recurrence rate than that reported after radical surgery but a similar survival outcome.
Asunto(s)
Canal Anal/cirugía , Endoscopía , Microcirugia/métodos , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Cuidados Preoperatorios , Neoplasias del Recto/patología , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Gluten-free pasta enriched with fish can support a nutritive and suitable option for people with celiac disease that allows achieving the benefits of fish consumption, especially the consumption of Ω-3 fatty acids; however, this requires that the pasta has adequate technological and sensory properties. For this purpose, four optimal formulations, obtained with an iterative process, were analyzed to determine the effect of the different ingredients (yellow corn flour, white corn flour, and rice flour) in gluten-free pasta compared to commercial wheat pasta. An evaluation of the color, texture, and technological properties were conducted, and the pasta was sensorially characterized. The enriched gluten-free pasta required shorter cooking times (≈3 min) and was characterized by lower hardness, springiness, gumminess, chewiness, and fracturability, and had higher values of adhesiveness than wheat pasta. In addition, the incorporation of yellow corn gives gluten-free pasta a similarity in color to commercial pasta, with a value of ∆E between 5.5 and 8.0. Regarding the sensory analysis, gluten-free pasta was characterized by slight fishy aromas and flavors with some aftertaste compared to commercial pasta. Finally, the use of different cereals to obtain gluten-free pasta could be a good and feasible alternative despite the technological and sensory modifications observed.
RESUMEN
OBJECTIVE: Removing rectal adenomas not only relieves symptoms, but also eradicates the incidence of carcinoma. There are many techniques for local removal of rectal polyps. Transanal endoscopic microsurgery (TEM) is the most recent. The purpose of this study is to present our long-term results using TEM for rectal adenomas, paying special attention to the risk factors of harboring a malignancy. METHODS: Data from all patients undergoing TEM from December 1995 to December 2005 were collected prospectively. The selection criteria were benign sessile adenomas below the peritoneal reflection. In the study period, 173 patients were operated on for an apparently benign rectal adenoma. The mean distance of lower tumor was 7.6 cm (range, 1-18 cm), and the mean distance to upper edge was 11 cm (2-20 cm). Full-thickness local excision was performed in all procedures. Patients were followed for a minimum of 1 year. RESULTS: According to the histologic findings, 14% of the specimens were invasive carcinomas. No statistical differences were found when comparing the histologic findings by tumor size, distance to the anal verge, or location.In 10 (5.8%) cases, the dissection was considered uncompleted because of a normal mucosa margin smaller than 1 mm. The mean hospital stay was 4 days (2-30 days). The morbidity rate was 14.5%. There was 1 postoperative death (0.6%). There were 9 (5.4%) histologically proven recurrences. Four of the patients with recurrence had uncompleted microscopic circumferential resection (P = 0.001). At a mean follow-up of 35 months (range, 12-82 months), all carcinoma patients were alive with no evidence of disease. CONCLUSIONS: In conclusion, a significant number of adenomas that we assumed preoperatively to be benign were already carcinomas and we were unable to find any reliable predictor to identify them. TEM full-thickness excision provided a low rate of postoperative morbidity and potentially avoided a significant number of major abdominal operations and local recurrences.
Asunto(s)
Adenoma/cirugía , Neoplasias del Recto/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Canal Anal , Femenino , Humanos , Masculino , Microcirugia , Persona de Mediana Edad , Proctoscopía , Factores de Riesgo , Adulto JovenRESUMEN
Local surgery for rectal tumors has been traditionally limited due to technical issues for lower risk lesions. In the 1980s, Buess described the transanal endoscopic microsurgery (TEM) technique that enabled excision of lesions that were larger and in a higher location. TEM in a short time became the gold standard for the excision of large adenomas and early rectal carcinomas. Since the advent of TEM, and due to advances in minimal invasive technology, new devices and procedures have come to the surgical armamentarium, in many cases with only very slight differences between them. However, local surgery for rectal cancer still remains a challenge. An overview of the current status of minimal transanal invasive techniques is presented here and sheds some light on the controversies that the local management of rectal cancer still raises.
Asunto(s)
Neoplasias del Recto/cirugía , Microcirugía Endoscópica Transanal/métodos , HumanosRESUMEN
Human butyrylcholinesterase (BuChE) is being developed as a new therapeutic for protection against the toxicity of organophosphorus agents and cocaine. The purified BuChE consists predominantly of 340 kDa tetramers and contains less than 5% monomers and dimers. Our goal was to determine whether BuChE crosses the blood-cerebrospinal fluid (CSF) barrier. Rats were injected intraperitoneally with 1mg of purified human BuChE. Plasma BuChE activity increased nearly 400-fold, while BuChE activity in the CSF increased three-fold. Sucrose density centrifugation showed that the human BuChE molecule in the rat CSF was a tetramer. Immunoprecipitation confirmed the identity of the CSF BuChE as human BuChE. The lower amount of human BuChE in the CSF (0.04%) than of smaller proteins (0.1-1%), with respect to their levels in plasma, supports the idea that passage through the blood-CSF barrier depends on molecular size. BuChE in the CSF could serve to protect the brain from the neurotoxicity of organophosphorus pesticides and cocaine.
Asunto(s)
Butirilcolinesterasa/administración & dosificación , Líquido Cefalorraquídeo/efectos de los fármacos , Acetilcolina/sangre , Acetilcolina/líquido cefalorraquídeo , Animales , Butirilcolinesterasa/sangre , Butirilcolinesterasa/líquido cefalorraquídeo , Líquido Cefalorraquídeo/enzimología , Humanos , Inmunoprecipitación/métodos , Inyecciones Intraperitoneales/métodos , Masculino , Peso Molecular , Plasma/efectos de los fármacos , Plasma/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
A statistically acceptable epidemiological investigation of the prevalence of Chagas' Disease was made by sampling in the cities of Resistencia, Barranqueras, and Vilelas, of a population of 61,697, 1,641 (2.66 percent) persons aged 6 or more were surveyed. The margin of security obtained from 99 percent (of the 1,641 covered by the survey, 1,625 were investigated) is highly plausible, for it confirms the value of the survey
The investigation consisted of a complement fixation test, background history of the disease, clinical examination, and electrocardiogram. Moreover, an investigation of the tuberculosis prevalence and rate, made in the same area in 1961, showed that 10.8 percent of the 8,276 persons examined suffered from cardiac enlargement
The serological rate was 5.17 percent and the persons examined showed a very high percentage of electrocardiographic alterations (38.53 percent); only 1.65 percent of the population examined were considered to have abnormal electrocardiograms imputable to Chagas' Disease
Of the 84 seropositives, 50 percent had electrocardigraphic alteration, and in one of three of the latter group such alteration was considered to be imputable to the disease. As expected, the percentage distribution (rate) of abnormal electrocardiograms showed a tendency to increase from childhood to old age. The percentage rates for seropositives according to age group were high, ... (AU)