Posttranslational nitro-glycative modifications of albumin in Alzheimer's disease: implications in cytotoxicity and amyloid-ß peptide aggregation.

Glycation and nitrotyrosination are pathological posttranslational modifications that make proteins prone to losing their physiological properties. Since both modifications are increased in Alzheimer's disease (AD) due to amyloid-ß peptide (Aß) accumulation, we have studied their effect on albumin, the most abundant protein in cerebrospinal fluid and blood. Brain and plasmatic levels of glycated and nitrated albumin were significantly higher in AD patients than in controls. In vitro turbidometry and electron microscopy analyses demonstrated that glycation and nitrotyrosination promote changes in albumin structure and biochemical properties. Glycated albumin was more resistant to proteolysis and less uptake by hepatoma cells occurred. Glycated albumin also reduced the osmolarity expected for a solution containing native albumin. Both glycation and nitrotyrosination turned albumin cytotoxic in a cell type-dependent manner for cerebral and vascular cells. Finally, of particular relevance to AD, these modified albumins were significantly less effective in avoiding Aß aggregation than native albumin. In summary, nitrotyrosination and especially glycation alter albumin structural and biochemical properties, and these modifications might contribute for the progression of AD.

Enemas de factor de crecimiento epidérmico para inducir la remisión de la colitis ulcerosa izquierda / Epidermal growth factor enemas for induction of remission in left-sided ulcerative colitis

Introducción: la colitis ulcerosa es una enfermedad inflamatoria crónica de etiología poco conocida, que afecta la mucosa del colon. El efecto positivo del factor de crecimiento epidérmico fue reportado en estudio previo con uso de enema para tratamiento de la manifestación izquierda leve o moderada de la enfermedad. Este antecedente sirvió de base para evaluar la eficacia y perfil de seguridad de una solución viscosa del producto.Métodos: fueron aleatorizados 31 pacientes hacia tres grupos de tratamiento diario durante 14 días. Doce recibieron enemas de 10 mg de factor de crecimiento epidérmico en 100 mL de solución viscosa, mientras nueve fueron tratados con enemas placebo conteniendo solamente solución viscosa. Ambos grupos recibieron además 1,2 g diarios de mesalacina oral. El tercer grupo incluyó 10 pacientes con mesalacina en enemas de 3g / 100 mL. La variable principal de eficacia fue la respuesta clínica al finalizar las dos semanas de tratamiento, definida como la disminución de, al menos tres puntos, el índice basal de actividad de la enfermedad acompañada de mejoría endoscópica o histológica.Resultados: se alcanzó remisión de la enfermedad en todos los pacientes que recibieron factor de crecimiento epidérmico y en seis de los grupos mesalacina enema y placebo. Todas las comparaciones entre grupos mostraron superioridad estadísticamente significativa para el factor de crecimiento epidérmico, único producto que logró la reducción significativa del índice de actividad de la enfermedad y de la presencia e intensidad de los síntomas digestivos en los pacientes luego del tratamiento. Ningún evento adverso fue reportado.Conclusiones: estos resultados son consistentes con las anteriores evidencias moleculares y clínicas que señalan al factor de crecimiento...

Introduction: ulcerative colitis is a little known chronic inflammatory disease in colonic mucosa. The positive effect of epidermal growth factor was shown in a previous report, with enema use for treatment of mild to moderate left-sided manifestation of the disease. This evidence provided the basis for evaluating the efficacy and safety profile of a viscous solution of this product. Methods: thirty-one patients were randomized to three groups for daily medications during 14 days. Twelve received one 10 mg enema of epidermal growth factor dissolved in 100 mL of viscous solution whereas nine were treated with placebo enema; both groups also received 1.2 g of oral mesalamine per day. The other group included ten patients with 3 g / 100 mL of mesalamine enema. Primary end point was clinical responses after two weeks of treatment, defined as a decreased of, at least three points from baseline, the Disease Activity Index and endoscopic or histological evidences of improvement. Results: remission of disease was observed in all patients in the epidermal growth factor group, and six in both, mesalamine enema and placebo group. All the comparisons between groups showed statistically significant superiority for epidermal growth factor, the only product with significant reduction in disease activity index as well as the presence and intensity of digestive symptoms in patients after treatment. None adverse event was reported. Conclusions: the results agree with previous molecular and clinical evidences, indicating that the epidermal growth factor is effective to reduce disease activity and to induce remission. A new study involving more patients should be conducted to confirm the efficacy of the epidermal growth factor enemas

Preoperative antithrombin supplementation in cardiac surgery: a randomized controlled trial.

OBJECTIVES: Purified antithrombin supplementation in cardiac surgery has been suggested for the treatment of heparin resistance and the prevention of thromboembolic complications. This study is a randomized controlled trial of preoperative purified antithrombin supplementation, with the primary end point of avoiding low (<58%) postoperative antithrombin activity levels and secondary end points including avoidance of heparin resistance, clinical outcome, and safety end points. METHODS: Two hundred patients were randomly allocated to the antithrombin group and the control group. Patients in the antithrombin group received a dose of purified antithrombin to reach an antithrombin activity value of 120%, whereas patients in the control group did not receive antithrombin. RESULTS: The antithrombin activity values were significantly higher in the antithrombin group at all postoperative determinations until discharge. Antithrombin activity levels <58% at admission to the intensive care unit were found in 26.6% of patients in the control group versus none in the antithrombin group (P = .001). Heparin resistance rate was significantly (P = .001) higher in the control group (38.2%) versus the antithrombin group (17%). Patients in the antithrombin group had a significant but clinically irrelevant (8 mL/hour) higher postoperative bleeding, with no differences in transfusion rates. No differences were found for clinical outcomes, and no safety issues were identified. CONCLUSIONS: Preoperative antithrombin supplementation prevents heparin resistance and avoids excessive postoperative decrease of antithrombin activity.

Protocolo combinado de 99mTc-Ciprofloxacina y 99mTc-MDP en el diagnóstico de osteomielitis y prótesis articular infectada / 99mTc-ciprofloxacin/99mTc-MDP combined protocol in the diagnosis of osteomyelitis and infected joint prosthesis

Introducción. El centellograma óseo con 99mTc-MDP es una técnica útil en el diagnóstico de osteomielitis, sin embargo, presenta especificidad limitada en presencia de patología ósea previa (osteomielitis complicada). La 99mTc-ciprofloxacina es uno de los radiofármacos más difundidos para la detección de infecciones óseas, aunque persisten controversias sobre su rendimiento diagnóstico. Objetivo. Determinar el valor clínico del protocolo combinado de centellograma con 99mTc-ciprofloxacina y 99mTc-MDP en el diagnóstico de osteomielitis complicada y prótesis articular infectada. Materiales y métodos 37 pacientes con sospecha clínica de osteomielitis complicada o prótesis infectada fueron estudiados mediante centellograma con 99mTc-ciprofloxacina y 99mTc-MDP. 26/37 pacientes presentaban fractura previa, 7 prótesis de rodilla y 4 prótesis de cadera. En todos ellos se realizó seguimiento clínico y bacteriológico. Resultados. El método presentó sensibilidad de 94 por ciento, especificidad de 79 por ciento, valor predictivo positivo de 81 por ciento y valor predictivo negativo de 94 por ciento, con una exactitud de 86 por ciento. Conclusiones. El protocolo combinado de 99mTc-ciprofloxacina y 99mTc-MDP presenta elevado rendimiento para el diagnóstico de osteomielitis complicada y prótesis articular infectada.

Introduction. Bone scintigraphy with 99mTc-MDP is a useful technique in the diagnosis of osteomyelitis, however, has limited specificity in the presence of previous bone pathology (complicated osteomyelitis). 99mTc-ciprofloxacin is one of the most widely used radiotracers for the detection of bone infection, although controversies persist on its diagnostic performance. Objective To determine the clinical value of 99mTc-ciprofloxacin/99mTc-MDP combined protocol in the diagnosis of complicated osteomyelitis and infected joint prosthesis. Materials and methods 37 patients with clinically suspected complicated osteomyelitis or infected prosthesis were studied with 99mTc-ciprofloxacin and 99mTc-MDP scintigraphy. 26/37 patients had previous fractures, 7 had knee replacements and 4 had hip replacements. All of the patients underwent clinical and bacteriological follow-up. Results. The method presented sensitivity of 94 percent, 79 percent specificity, 81 percent positive predictive value and 94 percent negative predictive value, with an accuracy of 86 percent. Conclusions. The combined protocol using 99mTc-ciprofloxacin/99mTc-MDP showed high diagnostic performance in complicated osteomyelitis and infected joint prosthesis.

[99mTc-OCTREOTIDE in patients with neuroendocrine tumors from the GI tract]. / 99mTc-OCTREOTIDE en pacientes con tumores neuroendócrinos gastroenteropancreáticos.

INTRODUCTION: It has been demonstrated that scintigraphy with somatostatin analogues is useful for the diagnosis, staging and follow up of patients with neuroendocrine tumors from the gastrointestinal tract (NET-GIT). Some studies suggest that the use of 99mTc-Hydrazinonicotinyl-Tyr3-octreotide (99mTc-HYNIC-TOC) yields similar diagnostic results than the use of 111In-DTPA-octreotide. OBJECTIVE: To determine the clinical value of scintigraphy using 99mTc-HYNIC-TOC for the detection of primary and secondary lesions in patients with NET-GIT. METHODS: From September 2004 to May 2009, 32 patients (17 women, age range 18 to 82 years old) with histologically proven or clinically suspected NET-GIT underwent scintigraphy using 99mTc-HYNIC-TOC Patients underwent a whole body scan, with additional static images of abdomen and pelvis, followed by SPECT at 4-hrs post injection of 925 MBq of the tracer. Patients underwent clinical, imaging and histopathology follow-up during 3 to 18 months. RESULTS: Histopathology demonstrated carcinoid tumor in 20 patients, insulinoma in 2, gastrinoma in 2 and non-specific NET-GIT in 6. Total sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 87%, 100%, 100%, 89% and 94%, respectively. To detect the primary lesion, the values were 94%, 100% 100%, 94% and 97%, respectively and to detect secondary lesions, 79%, 100%, 100%, 86% and 91%, respectively. CONCLUSIONS: 99mTc-HYNIC-TOC is a specific somatostatin analog, with high affinity to receptor subtype SST-2, widely available and affordable by Latin American countries. It has a good performance to be used for diagnosis, staging and follow-up of patients with NET-GIT.