Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies.

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrè syndrome, mostly related to halted axon regeneration. Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration. These effects involve the activation of the small GTPase RhoA/ROCK signaling pathways, which negatively modulate growth cone cytoskeleton, similarly to well stablished inhibitors of axon regeneration described so far. The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632, a selective pharmacological inhibitor of ROCK, in a mouse model of axon regeneration of peripheral nerves, where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers. Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632. Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity. In contrast, the same dose showed toxic effects on the regeneration of myelinated fibers. Interestingly, scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632. Overall, these findings confirm the in vivo participation of RhoA/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody. Our findings open the possibility of therapeutic pharmacological intervention targeting RhoA/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.

Diagnóstico de la calidad ambiental y salud / Diagnosis of environmental quality and health

Dentro de los contaminantes atmosféricos se encuentra el Material Particulado (MP). La quema de combustible en fuentes fijas y actividades extractivas, como ladrilleras, son generadoras de MP. Este compuesto posee la capacidad de afectar la salud ya que aumenta el riesgo de enfermedades cardiovasculares y pulmonares. En la presente investigación, con un diseño de triangulación concurrente y vinculación de datos mensurables y no mensurables, se planteó como objetivo general diagnosticar la calidad ambiental y su relación con patologías cardio-respiratorias en la comunidad ladrillera. Y como objetivos específicos planteamos identificar el estado general de salud de la población en estudio y grupo control; mensurar la concentración de MP sedimentable dentro del área en estudio y el área control; y reconocer la frecuencia de enfermedades cardio-respiratorias en ambos grupos. Se realizó la recolección y determinación de MP sedimentable, soluble e insoluble, según norma IRAM 29.299. A los datos obtenidos, se aplicó análisis estadístico no paramétrico. Se realizaron entrevistas semiestructuradas a los/as trabajadores/as y a un grupo control. Las mismas fueron procesadas de manera cuali/cuantitativa. También se ejecutaron anamnesis clínicas de las personas entrevistadas del grupo problema. Respecto a calidad ambiental, se identificó una diferencia significativa entre las concentraciones de MP, soluble e insoluble, entre el grupo problema y control. Existe una línea de tendencia descendiente con concentraciones mayores en colectores cercanos a los hornos hacia una menor en los colectores más alejados. Respecto al estado general de salud, se identificaron parámetros como controles médicos, lugares de atención, ambiente y salud, entre otras. No se registraron frecuencias de enfermedades de tipo cardio-respiratorias dentro del grupo problema ni grupo control. No se registró relación entre MP y la presentación de enfermedades cardio-respiratorias dentro del grupo problema.

Comprensiones en la resolución de problemas en estudiantes de Medicina: El conocimiento científico y la metodología de la investigación

Se exploran las experiencias en el tránsito formativo del tercer año de la carrera de grado, focalizándose en las comprensiones acerca de la ciencia, las formas de compresión cognitivo-emocionales acerca del conocimiento científico y sus metodologías, y los procesos de enseñanza-aprendizaje relativos a esta temática.

Osteosarcoma mandibular osteogénico / Mandibular osteogenic sarcoma

El osteosarcoma es una neoplasia maligna, poco frecuente, que se presenta de forma agresiva y sepuede originar en el hueso de la cavidad oral. Se caracteriza por la producción de osteoide tumoral(trabéculas óseas inmaduras) por parte de las células neoplásicas. Estos tumores suelen formarse en la región metafisiaria de los huesos largos de los miembros, en especial en el fémur y en la tibia. Se presenta el caso clínico de un paciente que concurre al servicio de Estomatología de la Escuela deOdontología, de la facultad de Ciencias de la Salud, Universidad Católica de Córdoba; masculino de 26 años de edad de nacionalidad peruana con diagnóstico clínico de osteosarcoma mandibular, el cual fue tratado con hemisección, quimioterapia y radioterapia en la zona mandibular sector posterior de lado izquierdo con colocación de una placa de titanio en la región.

Osteosarcoma is a malignant, rare and aggressive neoplasm that originates in the bone of the oralcavity. It is characterized by the production of tumor osteoid (immature bone trabeculae) by neoplasticcells. These tumors usually originate in metaphyseal region of long limb bones, especially in femurand tibia.Case report: 26-year-old peruvian male patient attending the Stomatology service at the School ofDentistry, Faculty of Health Sciences, Catholic University of Cordoba. The patient was clinically diagnosedwith mandibular osteosarcoma, treated with hemisection, chemotherapy, radiotherapy onmandibular zone posterior sector of left side and fixation of a titanium bone plate.

[Vaginal Follicular dendritic cell sarcoma in patient with previous urinary tract carcinoma. Case Report].

INTRODUCTION: follicular dendritic cell sarcoma (FDC sarcoma) is an uncommon neoplasm derived from FDC present in lymphoid follicles. It usually presents in lymph nodes, being extranodal location a very unusual event. CASE REPORT: A 78 year old female, with prior left nephrectomy for invasive urothelial carcinoma, consulted for genitorragia. At examination, a polypoid vaginal lesion, measuring 3.5 cm in diameter was discovered. It was reported as squamous cell carcinoma in incisional biopsy. A polipectomy was performed. Examination of resected specimen showed a tumor having pushing edges, arranged in a solid pattern with spindle and epithelioid cells, having a syncytial appearance, diffusely sprinkled with numerous lymphocytes and granulocytes. At immunohistochemistry neoplastic cells were positive for vimentin, CD 68, CD 21 and fascine, and focally positive for S-100 and CD45. Occasional scattered neoplastic cells expressed CD30 and CD 23. They were negative for CD3, CD20, myeloperoxidase, AE1 / AE3, EMA, HMB45, Melan A, desmin, Chromogranin, CD1a and CD35. Infiltrating lymphocites were mainly of T cell lineage (CD3 +). DISCUSSION: We report a case of FDC sarcoma in an unusual location, being to our knowledge, the first one at this site. The fact of having a prior neoplasia posed additional difficulties in differential diagnosis. Histological findings with expression of a specific marker of FDC (in this case CD21) allowed us to establish an accurate diagnosis.

Progression of choroidal metastasis of ovarian serous cystoadenocarcinoma after intravitreal bevacizumab treatment.

A 57-year-old woman presented to her ophthalmologist because of rapid deterioration in vision. Dilated funduscopic examination of the right eye showed an elevated, yellow-orange choroidal mass temporal to the fovea; a complete retinal detachment was present in the left eye. The patient was referred to an oncologist. Computerized tomography of the brain, thorax, abdomen, and pelvis were obtained. They revealed an 11-mm mass in the right parietal lobe, a 30-mm mass in the left temporal lobe, 23-mm mass in the right kidney, and multiple nodules in both lungs. Supported by published experience with intravitreal bevacizumab for choroidal metastasis, the patient was injected into the vitreous through the pars plana of the left eye. The tumor mass did not show signs of regression and the visual acuity was unchanged. The patient suffered from end-state complications tumor metastasis and expired one month after the invitreal injection.

Detection of the risk of adenocarcinoma in Barrett's esophagus by means of tumor markers (p53 and Ki67).

The rising incidence of adenocarcinoma in Barrett's esophagus has intensified the research into methods of early recognition of cancer risk, detecting cytological and architectural changes (dysplasia) or using biomarkers as predictive tests. The aim of this paper is to evaluate the involvement of two tumor markers: p53 (tumor suppressor gene) and Ki67 (proliferation marker), by means of immunohistochemical analysis with monoclonal antibodies designed for the specific localization of p53 and Ki67 antigens, in esophageal biopsies with columnar metaplasia of patients with and without dysplasia and adenocarcinoma, and to anticipate which ones are liable to suffer it in the future. Both markers were positive in all intestinal metaplasia patients with high-grade dysplasia and adenocarcinoma, and even in some cases with low grade or without dysplasia. In contrast, in those who have gastric metaplasia, tumor markers were negative. Expression of biomarkers next to dysplasia reduces interobserver variation. Patients with these abnormalities have to be included into a surveillance protocol.

Splenic autoimplantation in omentum and stomach, hematoimmunological follow-up and B-cell repertoire in the graft.

INTRODUCTION: Splenic autoimplantation appears to be the only alternative to preserve splenic tissue after splenectomy; however, its relevance is still controversial We intended to study splenic autoimplantation in the greater omentum and stomach wall of rabbits and analyze its hematoimmunological performance and the preservation of original structures. METHODS: New Zealand rabbits were divided in two groups: autoimplanted (A) (n=13) and splenectomized (S) (n=4). The animals of group A underwent autoimplantation of splenic fragments in the greater omentum and gastric wall Both groups were evaluated by hemocytological tests, scintigraphy, immunoglobulin and C3 dosages, before the surgery and 2 and 4 months afterwards. After 4 months, the grafts were removed and histological examination and gen rearrangement of B-lymphocytes receptors by polymerase chain reaction (PCR) were performed to assess the cellular diversity of clones. RESULTS: The histological analysis demonstrated the presence of splenic tissue in 10 of the 13 cases (77%) with evident size reduction. The gastric location did not develop complications and demonstrated higher morphological correspondence to the autoimplanted tissue. Both groups showed significant decrease of IgM and increase of C3, without considerable differences between both of them during follow up. From the 8 grafts studied with PCR, 3 cases presented polyclonality and 5 oligoclonality. CONCLUSIONS: The revascularized grafts evidenced splenic regenerating tissue, probably associated to the oligoclonality detected by PCR. Consequently, we consider that autoimplantation is a reasonable alternative for splenectomized patients, even though the stomach placement and the high frequency of oligoclonality justify further investigation.

Secretory Leukoprotease Inhibitor: A Native Antimicrobial Protein in the Innate Immune Response in a Rat Model of S. aureus Keratitis.

Purpose. To describe the presence of secretory leukocyte protease inhibitor (SLPI), a cationic peptide with antimicrobial and antiprotease activity in the innate immune reaction in a rat model of Staphylococcus aureus keratitis. Methods. Forty female Lewis rats were divided into 2 groups: the infectious keratitis and the epithelial defect groups. Eyes were processed for immunohistochemical studies for SLPI, interleukin-1, interleukin-6, tumor necrosis factor-alpha, and matrix metalloproteinase-8. Results. Immunohistochemical studies confirmed high levels of SLPI, IL-1, IL-6, TNF-alpha, and MMP-8 expression in eyes with S. aureus keratitis and with epithelial defects, in contrast to undetectable SLPI expression in the normal control corneas. Conclusions. To our knowledge, this paper is the first to demonstrate the presence of SLPI with increased amounts of proinflammatory cytokines in inflamed and infected corneas.

Vantris, a biocompatible, synthetic, non-biodegradable, easy-to-inject bulking substance. Evaluation of local tissular reaction, localized migration and long-distance migration.

Biodegradable injectable bulking agents of animal origin present a fast rate of bio-reabsorption and may cause an allergic reaction. Biodegradable elements of synthetic origin have a high rate of reabsorption after a year. Non-biodegradable agents of synthetic origin lead to the formation of a fibrotic capsule, giving stability and long-term permanence. VANTRIS is categorized into this last group; it belongs to the family of Acrylics, particles of polyacrylate polyalcohol copolymer immersed in a glycerol and physiological solution carrier. Molecular mass is very high. When injected in soft tissues, this material causes a bulkiness that remains stable through time. The carrier is a 40% glycerol solution with a pH of 6. Once injected, the carrier is eliminated by the reticular system through the kidneys, without metabolizing. Particles of this polyacrylate polyalcohol with glycerol are highly deformable by compression, and may be injected using a 23-gauge needle. The average of particles size is 320 mm. Once implanted, particles are covered by a fibrotic capsule of up to 70 microns. Particles of this new material are anionic with high superficial electronegativity, thus promoting a low cellular interaction and low fibrotic growth. The new polyacrylate polyalcohol copolymer with glycerol was tested for biocompatibility according to ISO 10993-1:2003 in vitro, showing that they are not mutagenic for the Salmonella T. strains analyzed. The extract turned out to be non-cytotoxic for cell lines in culture and non-genotoxic for mice. In in vivo studies, acrylate did not cause sensitization in mice. The macroscopic reaction of tissue irritation was not significant in subcutaneous implants and in urethras of rabbits. Seven female dogs were injected transurethrally with VANTRIS to evaluate short and long-term migration (13 weeks and 12 months respectively). No particles or signs of inflammation or necrosis are observed in any of the organs examined 13 weeks and 12 months after implantation. To conclude, this new material meets the conditions of ideal tissue bulking material.

Vantris®, a biocompatible, synthetic, non-biodegradable, easy-to-onject bulking substance. Evaluation of local tissular reaction, localized migration and long-distance migration / Vantris® una sustancia inyectable biocompatible, sintética, no biodegradable y fácil de aplicar: Evaluación de la reacción tisular local, y de la migración local y a larga distancia

Biodegradable injectable bulking agents of animal origin present a fast rate of bio-reabsorption and may cause an allergic reaction. Biodegradable elements of synthetic origin have a high rate of reabsorption after a year. Non-biodegradable agents of synthetic origin lead to the formation of a fibrotic capsule, giving stability and long-term permanence. VANTRIS® is categorized into this last group; it belongs to the family of Acrylics, particles of polyacrylate polyalcohol copolymer immersed in a glycerol and physiological solution carrier. Molecular mass is very high. When injected in soft tissues, this material causes a bulkiness that remains stable through time. The carrier is a 40% glycerol solution with a pH of 6. Once injected, the carrier is eliminated by the reticular system through the kidneys, without metabolizing. Particles of this polyacrylate polyalcohol with glycerol are highly deformable by compression, and may be injected using a 23-gauge needle. The average of particles size is 320 mm. Once implanted, particles are covered by a fibrotic capsule of up to 70 microns. Particles of this new material are anionic with high superficial electronegativity, thus promoting a low cellular interaction and low fibrotic growth. The new polyacrylate polyalcohol copolymer with glycerol was tested for biocompatibility according to ISO 10993-1:2003 in vitro, showing that they are not mutagenic for the Salmonella T. strains analyzed. The extract turned out to be non-cytotoxic for cell lines in culture and non-genotoxic for mice. In in vivo studies, acrylate did not cause sensitization in mice. The macroscopic reaction of tissue irritation was not significant in subcutaneous implants and in urethras of rabbits. Seven female dogs were injected transurethrally with VANTRIS® to evaluate short and long-term migration (13 weeks and 12 months respectively). No particles or signs of inflammation or necrosis are observed in any of the organs examined 13 weeks and 12 months after implantation. To conclude, this new material meets the conditions of ideal tissue bulking material (AU)

Los agentes inyectables biodegradables de origen animal presentan una tasa rápida de bioreabsorción y pueden provocar reacciones alérgicas. Los elementos biodegradables de origen sintético tienen una alta tasa de reabsorción después de un año. Los agentes no-biodegradables de origen sintético dan lugar a la formación de una cápsula fibrótica, dando estabilidad y permanencia a largo plazo. VANTRIS® se clasifica en este último grupo; pertenece a la familia de los acrílicos, partículas de copolímero poliacrida polialcohol inmersas en una solución vehiculante de glicerol y fisiológico. Su masa molecular es muy alta. Cuando se inyecta en tejidos blandos, este material produce un abultamiento que permanece estable a lo largo del tiempo. El vehículo contiene un 40% de solución de glicerol con un pH de 6. Una vez inyectada, el vehículo es eliminado por el sistema reticular a través de los riñones, sin metabólizar. Las partículas de este poliacrilato polialcohol con glicerol son altamente deformables por compresión, y pueden inyectarse utilizando una aguja del 23 Gauge. El tamaño medio de las partículas es de 320 mm. Una vez implantadas, las partículas se recubren de una cápsula fibrótica de hasta 70 micrones. Las partículas de este nuevo material son aniónicas y tienen una gran electronegatividad en superficie, promoviendo así una baja interacción celular y un bajo crecimiento fibrótico. El nuevo copolímero de poliacrilato polialcohol con glicerol fue sometido a pruebas de biocompatibilidad in vitro de acuerdo con la normal ISO 10993-1:2003, mostrando que no es mutagénico para las cepas de salmonela T. analizadas. El extracto no fue citotóxico en cultivos de líneas celulares ni en ratones. En los estudios in vivo, el acrilato no produjo sensibilización en ratones. Los implantes subcutáneos y en uretra de conejos no produjeron reacción de irritación tisular macroscópica significativa. Para evaluar la migración a corto y largo plazo se inyectó Vantris® por vía transuretral en siete hembras de perro (13 semanas y 12 meses respectivamente). No se observaron partículas o signos de inflamación con necrosis en ninguno de los órganos examinados ni a las 13 semanas ni a las 12 meses del implante. En conclusión, este nuevo material cumple con las condiciones del material inyectable tisular ideal

Secretory leukocyte protease inhibitor is an inducible antimicrobial peptide expressed in Staphylococcus aureus endophthalmitis.

PURPOSE: To describe the presence of secretory leukocyte protease inhibitor (SLPI), a cationic peptide with antimicrobial and antiprotease activity, in the innate ocular immune reaction in a rat model of Staphylococcus aureus endophthalmitis. METHODS: Seventy-five female Lewis rats were divided into three groups: the endophthalmitis group received an intravitreal injection of 65 colony-forming units of viable S. aureus, the vehicle-injected group received balanced sterile saline solution (BSS), and the control group was not injected. Eyes were enucleated at 24 and 48 hours and processed for immunohistochemical staining and Western blot studies for SLPI. RESULTS: In S. aureus endophthalmitis eyes, there was strong immunostaining for SLPI in the retina and vitreous with associated neutrophilic infiltrates. At 48 hours, corneas also stained for SLPI. Western blots confirmed increased SLPI expression in all infected eyes. By immunohistochemical assays, SLPI was absent in the BSS and control eyes. The causative pathogen was identified in all samples from the endophthalmitis group by traditional culture methods. CONCLUSIONS: To our knowledge, this report is the first to demonstrate the presence of SLPI in the inflamed cornea, vitreous, and retina tissues of rat eyes with S. aureus endophthalmitis, suggesting that SLPI has an active role in the innate immunity of the eye. Release of SLPI by inflammatory cells in the anterior and posterior segments may contribute to the host defense response against infectious endophthalmitis.

Pielonefritis xantogranulomatosa asociada a flora polimicrobiana / Xantothogranulomatous pyelonephritis associated with polymicrobian flora

La pielonefritis xantogranulomatosa (PX) es una rara infección crónica y severa del parénquima renal. Debido a que sus manifestaciones simulan una neoplasia, el diagnóstico preoperatorio es dificultoso. Habitualmente se asocia a infección bacteriana monomicrobiana. Nosotros comunicamos el caso de PX asociada a infección polimicrobiana, una de las cuales es un microorganismo anaeróbico

Organismos tipo campylobacter en el esofago de Barrett / Organisms type campylobacter in Barrett esofhagus

Esta claro que el CP está presente en mayor o menor grado en diversa patología gastroduodenal, fundamentalmente en gastritis crónica superficial activa, úlcera gástrica y úlcera duodenal con metaplasia gástrica. Tambien se lo encuentra en gastritis crónica atrófica y en menor porcentaje si ésta tiene metaplasia intestinal, así como en algunos estómagos normales. No se lo halla en duodeno histológicamente normal ni en esófago. Como nos llamó la atención que no se hubiera realizado ninguna publicación en EB, nos dispusimos a realizar retrospectivamente, la búsqueda del CP en la metaplasia columnar del esófago distal. Su incidencia resultó elevada, 88.88% aún en aquellos casos con metaplasia intestinal, y con úlcera de Barret. Utilizamos coloración de Gram y Warthin-Starry con Alcian-Blue, y clasificándolos dentro de los Grados establecidos por Marshall y Warren. Elaboramos asimismo la discusión sobre algunos hechos fisiopatológicos, como la presencia de infiltrado PMN en todos los casos, y su importancia en el mantenimiento de la metaplasia, de las úlceras de Barrett y su posible papel en el desarrolo del adenocarcinoma