Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in nonhuman primates.

Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)-rich protein aggregates [termed "Lewy bodies" (LBs)], is a well-established characteristic of Parkinson's disease (PD). Much evidence, accumulated from multiple experimental models, has suggested that α-syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here, we have used a machine learning-based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct α-syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular α-syn aggregates is as toxic as larger amyloid fibrils present in the LBs, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD, as multiple causes can induce a similar outcome regarding dopaminergic neurodegeneration.

I Conferencia Nacional de Consenso sobre el Injerto Óseo del Seno Maxilar / 1st National Consensus Conference on maxillar sinus bone grafts

Objetivo: El objetivo de la I Conferencia Española de Consenso sobre el Injerto Óseo Sinusal era intentar llegar a puntos de acuerdo sobre las principales controversias de esta técnica, aplicada de forma muy variada y con el empleo de materiales muy diversos, y conseguir plasmar los mismos en un documento resumen consensuado por todos los autores. Material y método: Durante los días 17 y 18 de octubre de 2008 se celebró en Oviedo la citada conferencia, auspiciada por la Sociedad Española de Cirugía Oral y Maxilofacial. En ella se dieron cita un total de 50 ponentes de reconocido prestigio nacional e internacional que repasaron en 6 mesas de trabajo las principales controversias sobre los injertos óseos sinusales. Tras las conferencias de los ponentes, los moderadores establecían las principales conclusiones de cada mesa y se abría un turno de debate donde participaban todos los asistentes. Resultado: Este documento y sus conclusiones emanan de las presentaciones realizadas por los ponentes y de las deliberaciones y acuerdos de cada mesa de trabajo. Ambos han sido aprobados tras varias correcciones por todos los autores antes de ser enviados para su publicación. Además, han obtenido el reconocimiento científico oficial de la Sociedad Española de Cirugía Oral y Maxilofacial y deben servir como base para futuros estudios y reuniones científicas. Conclusiones: El objetivo fundamental cuando se realiza un injerto óseo sinusal es la formación de hueso vital en el seno maxilar, para conseguir la supervivencia a largo plazo de los implantes tras su carga protésica. Para ello, la técnica y la secuencia de tratamiento deben orientarse a conseguir resultados predecibles y estables en el tiempo, aunque esto suponga un mayor tiempo de espera hasta la colocación de la prótesis. La estabilidad inicial del implante es el factor clave para la osteointegración y debe ser el principal criterio para indicar implantes simultáneos o diferidos en el seno maxilar(AU)

Objective: The objectives of the first Spanish Consensus Conference on Sinus Bone Graft were trying to reach agreements points on the major controversies of this technique, and translate them in a summary document. Material and method: During the 17th and 18th of October of 2008 took place in Oviedo (Spain) the Conference, sponsored by the Spanish Society of Oral and Maxillofacial Surgery. There, 50 national and international speakers reviewed in 6 workshops the major controversies of sinus bone grafts. Following the conferences, the moderators proposed the main conclusions of each workshop and opened a round of discussion where all attendees participated. Results: This document and its conclusions emanate from the presentations made by the speakers and the discussions and agreements of each workshop. Both have been approved after several corrections by all authors before being submitted for publication. They have also obtained the official scientific recognition of the Spanish Society of Oral and Maxillofacial Surgery and should serve as a basis for future scientific studies and meetings. Conclusions: The main objective when we perform a sinus bone graft is vital bone formation in the maxillary sinus, to achieve long-term survival of the implants after prosthetic loading. To do this, the technique and sequence of treatment should aim to achieve predictable and stable results over time, although this involves a longer waiting time. The initial implant stability is the key factor for osseointegration and should be the main criterion to indicate simultaneous or delayed implants in the maxillary sinus(AU)

¿Participa la histamia mastocitaria en el reflejo periférico que modula la actividad simpática en la rata? / It participates the histamine mast cell in the outlying reflection that it modulates the nice activity in the rat?

Estudios previos realizados por Campos y colaboradores han demostrado la presencia de un reflejo periférico que modula inhibitoriamente la actividad simpática en el conducto deferente de la rata. Una modulación inhibitoria similar fue encontrada en el corazón del perro. En este reflejo periférico de asa corta parece estar involucrada una interacción entre neuronas noradrenérgicas y neuronas que contienen histamina, en el cual la histamina neural parece estar modulando la actividad simpática y la presión arterial de una manera inhibitoria. En este sentido, intervenciones quirúrgicas de la vía neuronal que contiene histamina, la cual es adyacente a los niveles simpáticos del conducto deferente de la rata, causan una facilitación local de la actividad simpática. Además, Campos y colaboradores demostraron también un incremento de la actividad de la L-histidina descarboxilasa, marcador de la neurona que contiene histamina, por estimulación de la vía simpática, e inhibición de la enzima causó una facilitación de la actividad simpática e hipertensión arterial en la rata, sugiriendo la existencia de un mecanismo generalizado modulador de la actividad simpática. Condiciones estresantes que aumentan la actividad simpática incrementan los niveles sanguíneos de histamina en la rata y en humanos, por lo que se piensa que concomitantemente con la descarga simpática hay una liberación de histamina neuronal periférica como fenómeno reflejo compensador. Teniendo en cuenta estos hallazgos, en este trabajo se procedió explorar si hay participación de la histamina mastocitaria en el reflejo periférico de autorregulación de la actividad simpática. Para ello, ratas machos Srague-dawley recibieron 0.75 mg/kg, i.p. del compuesto 48/80, diariamente por 12 días; tratamiento que produce una marcada desgranulación mastocitaria. Se determinó la presión arterial media y la frecuencia cardíaca usando un plestimógrafo de cola, encontrándose que los parámetros cardiovasculares no cambiaron ni en el curso ni al final de la desgranulación con el compuesto 48/80. De estos estudios se desprende que la histamina mastocitaria tiene un papel secundario en la regulación funcional de la actividad simpática

Availability of HIV care in Central America.

Central America is an area with a growing human immunodeficiency virus (HIV) epidemic, but with marked limitations in its health care infrastructure. Estimated adult HIV infection rates range from 0.20% in Nicaragua to 2.01% in Belize. Hospitals and clinicians with experience in HIV care exist mainly, if not only, in capital cities and principal economic centers. Nationally sponsored social security systems in each country consistently offer a wider range of services than do ministry of health systems. Estimated access to the social security system ranges from 0% in Belize and 10% of the population in Honduras to 95% in Costa Rica. Combination antiretroviral therapy is not available through the ministries of health and zidovudine is only sporadically available for prevention of perinatal transmission. Combination therapy is available through the social security system in the countries of Guatemala, Panama, and Costa Rica only. A wide variety of antiretroviral agents are available through private pharmacies in all countries except Belize. With the exception of Costa Ricans, most people with HIV infection in Central America have limited access to HIV-specific health services and limited or no access to antiretroviral agents.

Neurochemical and electrophysiological evidence that 5-HT4 receptors exert a state-dependent facilitatory control in vivo on nigrostriatal, but not mesoaccumbal, dopaminergic function.

In this study we investigated, using in vivo microdialysis and single unit recordings, the role of serotonin4 (5-HT4) receptors in the control of nigrostriatal and mesoaccumbal dopaminergic (DA) pathway activity. In freely moving rats, the 5-HT4 antagonist GR 125487 (1 mg/kg, i.p.), without effect on its own, significantly reduced the enhancement of striatal DA outflow induced by 0.01 (-35%) and 0.1 (-66%), but not 1 mg/kg, s.c. haloperidol (HAL). Intrastriatal infusion of GR 125487 (1 microM) had no influence on basal DA outflow, but attenuated (-49%) the effect of 0.01 mg/kg HAL. Systemic administration of GR 125487 modified neither basal nor 0.01 mg/kg HAL-stimulated accumbal DA outflow. In halothane-anaesthetized rats, 1 or 10 mg/kg GR 125487, without effect by itself, failed to modify the changes in accumbal and striatal DA outflow elicited by electrical stimulation (300 microA, 1 ms, 20 Hz, 15 min) of the dorsal raphe nucleus. Finally, GR 125487 (444 microg/kg, i.v.), whilst not affecting basal firing of DA neurons within either the substantia nigra or the ventral tegmental area, reduced HAL-stimulated (1--300 microg/kg, i.v.) impulse flow of nigrostriatal DA neurons only. These results indicate that 5-HT4 receptors exert a facilitatory control on both striatal DA release and nigral DA neuron impulse flow only when nigrostriatal DA transmission is under activated conditions. Furthermore, they indicate that the striatum constitutes a major site for the expression of the control exerted by 5-HT4 receptors on DA release. In contrast, 5-HT4 receptors have no influence on mesoaccumbal DA activity in either basal or activated conditions.

Endogenous serotonin enhances the release of dopamine in the striatum only when nigro-striatal dopaminergic transmission is activated.

In this study, we use in vivo microdialysis to investigate the influence of endogenous serotonin (5-HT) on striatal dopamine (DA) and 5-hydroxyidoleacetic acid (5-HIAA) efflux in both basal and activated conditions. The selective serotonin reuptake inhibitors citalopram and fluoxetine were used to mobilize endogenous 5-HT. In halothane-anaesthetized rats, citalopram (5 mg/kg, i.p.), administered either alone or in combination with the 5-HT(1A) receptor antagonist WAY 100635 (0.1 mg/kg, s.c.), while reducing striatal 5-HIAA outflow (-25 and -15%, respectively), had no effect on basal DA output. When locally applied into the striatum, citalopram had no effect at 1 microM concentration, but enhanced DA release after its perfusion at 25 and 100 mircroM concentrations (+27% and +67%, respectively). However, the injection of the neurotoxin 5,7-dihydroxytryptamine into the dorsal raphe nucleus, which markedly depleted 5-HT in the striatum, failed to modify the effect of 25 microM citalopram. In freely-moving rats, the intrastriatal infusion of citalopram or fluoxetine (1 microM each), had no effect on its own, but significantly enhanced the increase in DA outflow induced by the subcutaneous administration of 0.01 mg/kg haloperidol (+31% and +30% for citalopram and fluoxetine, respectively). These findings indicate that, in the striatum, endogenous 5-HT has no influence on DA release under basal conditions, but positively modulates DA outflow when nigro-striatal DA transmission is activated.

Selecting the surgical procedure for simple and complicated esophageal achalasia in children.

BACKGROUND/PURPOSE: Surgical experience in children who have achalasia is limited. Surgical treatment requires esophagocardiomyotomy and an antireflux procedure. However, when these operations fail, other procedures are needed. To summarize the experience treating children who have this condition, the authors reviewed retrospectively all case histories of patients treated from 1971 to 1996 at their hospital. METHODS: Three boys and a girl, ranging in age from 18 months to 11 years, were treated. All had multiple previous dilatations. Two then underwent operation using an abdominal approach for a Heller procedure and a posterior fundoplasty (Guarner operation). Two children were previously treated in another hospital. One underwent a Heller operation complicated by perforation of the anterior mucosa. The other had undergone three previous abdominal approaches for esophagocardiomyotomy and a Nissen fundoplication. Symptoms persisted and imaging and endoscopy showed stenosis in both patients. In the first patient an esophagocardioplasty with transverse closure (Wendel procedure) and a posterior fundoplasty was performed. In the second child, the three previous abdominal surgical approaches mandated a transthoracic approach with transdiaphragmatic latero-lateral esophagogastric anastomosis (Heyrowsky operation) and a modified Guarner operation using the remaining fundus and gastric body. RESULTS: There were no intraoperative or postoperative complications. Follow-up time ranged from 3 months to 17 years. All patients experienced dramatic relief of symptoms and satisfactory weight gain. No recurrence of symptomatology has occurred. CONCLUSIONS: Esophagocardiotomy associated with an antireflux procedure may be the first option in the surgical treatment of children who have achalasia. However, if this fails, esophagocardioplasty and the latero-lateral esophagogastric anastomosis associated with antireflux procedure may be successful alternatives.

[Ocular toxoplasmosis in human immunodeficiency virus infected patients without concurrent central nervous system infection. Report of two cases]. / Toxoplasmosis ocular sin afectación del SNC en pacientes con infección por el VIH. Presentación de dos casos.

Ocular toxoplasmosis is an uncommon complication of acquired immunodeficiency syndrome (AIDS), and it is generally described associated with central nervous system (CNS) lesions. We describe two cases of ocular toxoplasmosis in human immunodeficiency virus (HIV) infected patients, without concurrent CNS infection. Both developed bilateral or unilateral choriorretinitis with favorable response to antitoxoplasma therapy. None of them presented toxoplasmosis of the CNS coexisting with ocular lesions. Ocular toxoplasmosis should be considered in HIV infected patients although no involvement of the CNS is found.

Análisis de 1,000 histerectomías: simplificaciones técnicas y reflexiones, hospitales del ISSSTE / Analysis of 1,000 hysterectomies. Technical simplifications and reflexions, ISSSTE's hospitals

Se informa acerca de 1,000 histerectomías realizadas por el autor en un lapso de 20 años en cuatro hospitales del ISSSTE. Se analizaron algunos parámetros clínicopatológicos, morbi-mortalidad, etc. Se informa de los resultados obtenidos utilizando simplificaciones en las técnicas quirúrgicas. Los síntomas más frecuentes fueron trastornos menstruales, y el diagnóstico más frecuente fue la miomatosis con (61.2 por ciento), la media de edad entre los 35-45 años. Todas las histerectomías fueron totales, 92.6 por ciento intrafasciales y 74.8 por ciento abdominales, Llamó la atención que 7.2 por ciento de las pacientes presentaron síndrome de congestión pélvica post oclusión tubaria y la asociación de adenomiosis. La mortalidad global fue de 12.2 por ciento predominando la del tipo urosepsis. La mortalidad se presentó en un caso por mioma intraligamentario gigante y coagulopatía por consumo. Se utilizó sangre sólo en 4.2 por ciento. Se piensa que la simplificación quirúrgica aquí enunciada, permite ofrecer mayor seguridad, menor morbilidad, mínimo sangrado y tiempo quirúrgico-anestésico breve. Además se realizó un análisis crítico del uso y abuso de este tipo de intervención quirúrgica