Prodromal neuroinvasion of pathological α-synuclein in brainstem reticular nuclei and white matter lesions in a model of α-synucleinopathy.

Neuropathological observations in neurodegenerative synucleinopathies, including Parkinson disease, implicate a pathological role of α-synuclein accumulation in extranigral sites during the prodromal phase of the disease. In a transgenic mouse model of peripheral-to-central neuroinvasion and propagation of α-synuclein pathology (via hindlimb intramuscular inoculation with exogenous fibrillar α-synuclein: the M83 line, expressing the mutant human Ala53Thr α-synuclein), we studied the development and early-stage progression of α-synuclein pathology in the CNS of non-symptomatic (i.e. freely mobile) mice. By immunohistochemical analyses of phosphroylated α-synuclein on serine residue 129 (p-S129), our data indicate that the incipient stage of pathological α-synuclein propagation could be categorized in distinct phases: (i) initiation phase, whereby α-synuclein fibrillar inoculum induced pathological lesions in pools of premotor and motor neurons of the lumbar spinal cord, as early as 14 days post-inoculation; (ii) early central phase, whereby incipient α-synuclein pathology was predominantly detected in the reticular nuclei of the brainstem; and (iii) late central phase, characterized by additional sites of lesions in the brain including vestibular nuclei, deep cerebellar nuclei and primary motor cortex, with coincidental emergence of a sensorimotor deficit (mild degree of hindlimb clasping). Intriguingly, we also detected progressive α-synuclein pathology in premotor and motor neurons in the thoracic spinal cord, which does not directly innervate the hindlimb, as well as in the oligodendroglia within the white matter tracts of the CNS during this prodromal phase. Collectively, our data provide crucial insights into the spatiotemporal propagation of α-synuclein pathology in the nervous system of this rodent model of α-synucleinopathy following origin in periphery, and present a neuropathological context for the progression from pre-symptomatic stage to an early deficit in sensorimotor coordination. These findings also hint towards a therapeutic window for targeting the early stages of α-synuclein pathology progression in this model, and potentially facilitate the discovery of mechanisms relevant to α-synuclein proteinopathies. In a rodent model of synucleinopathy, Ferreira et al., delineate the spatiotemporal progression of incipient α-synuclein pathology (of peripheral origin) in the CNS. The authors show early affection of brainstem reticular nuclei in non-paralyzed mice, and pathological white matter lesions in relation to the neuronal pathology.

Experimental study evaluating the effect of a barrier method on postoperative intraabdominal adhesions.

The purpose of this animal study was to determine if tissue glue-coated collagen sponge is an effective barrier method to prevent localized adhesions in a modified rabbit sidewall model. Rabbits were divided into two groups and underwent laparotomy with subsequent creation of a cecal wound according to the rabbit sidewall model. Rabbits of group I (treatment group; n = 10) were treated with a TachoComb H patch placed on the defect, whereas group II animals (control group; n = 6) did not receive further treatment. All animals were sacrificed 2 weeks postoperatively and adhesions were evaluated using special adhesion score. A further six rabbits underwent TachoComb H application at the cecum to investigate the histological changes during a course of 12 weeks. The average adhesion scores were significantly (P < 0.05) reduced in the treatment group compared to the controls. Histologically the TachoComb H patch was surrounded by granulation tissue without signs of infection. Tissue glue-coated collagen sponge (TachoComb H) is effective to prevent localized intraabdominal adhesions in the modified rabbit sidewall model.

New polar-embedded stationary phase for surfactant analysis.

The separation and identification of surfactants is a challenge due to the diversity of surfactants, the complex composition of surfactant raw materials, and the complexity of the sample matrices. High-performance liquid chromatography (HPLC) is the preferred analytical technique, because it allows the characterization of surfactant raw materials according to their composition and the quantitation of individual surfactants in complex mixtures. Although many HPLC columns are available for surfactant analysis, none of these columns provide optimal selectivity for the simultaneous analysis of anionic, non-ionic, and cationic surfactants using the same mobile phase system. In this paper, we describe a new polar-embedded stationary phase for the simultaneous analysis of anionic, non-ionic, and cationic surfactants with a simple and volatile mobile phase system containing ammonium acetate buffer and acetonitrile, utilizing evaporative light-scattering detection (ELSD). Mobile phase ionic strength and pH are important for optimizing chromatographic conditions. The column offers ideal selectivity for different types of surfactants, excellent peak shapes, especially for cationic surfactants, improved resolution for oligomers in ethoxylated surfactants, and compatibility with highly aqueous mobile phases. Thus, it can be used not only for quality assurance of individual surfactants, but also for the analysis of a variety of surfactant-containing formulations.

[Botulinum toxin injection for neurogenic and no neurogenic bladder dysfunction]. / Inyección de toxina botulínica en disfunción vesical neurogénica y no neurogénica.

OBJECTIVES: Botulinum toxin A (BT A) has gained popularity among urologists in the treatment of detrusor muscle dysfunctions. The aim of this article is to review our experience with this therapy METHODS: From 2001 we used BT A in 28 patients. It was injected in the bladder wall under cystoscopical vision. We analyze the indication of treatment, clinical data and urodynamics before and after treatment. RESULTS: We treated 28 patients. 71 percent had neurogenic hyperreflexic bladder, 18% idiopathic unstable bladder and 11% other diseases. No direct complications were observed. Neurogenic hyperreflexic bladder (n = 20): Mean preoperative bladder capacity was 220 cc, improving to 430 cc after treatment. Non inhibited contractions disappeared. All patients except one with multiple sclerosis, who had spontaneous voiding, required self catheterization after injection. Average time interval between injections was 8.6 months. Idiopathic unstable bladder (n = 5): a lower dose was used, with an average of 100 U. Non inhibited contractions disappeared and all patients were able to maintain spontaneous voiding with post void residuals under 50 ml. No patients required self catheterization. Bladder capacity improved from 128 ml to 370 ml. Average number of voidings per day diminished from 16 to 7 times. Other diseases (n = 3): results were poor in these patients. There were no changes in either bladder function studies or average voiding frequency (15 times per day). These patients required surgery for bladder augmentation in 2 cases and continent diversion in 1 case. CONCLUSIONS: BT A has a role in the treatment of neurogenic hyperreflexic bladder diminishing incontinence and improving bladder capacity. In cases of idiopathic unstable bladder without anatomical changes its results are promising, but a limited number of patients does not allow a definitive conclusion. In other bladder diseases with anatomical changes results are poor and its use should not be routinely recommended.

The autologous osteochondral transplantation of the knee: clinical results, radiographic findings and histological aspects.

INTRODUCTION: The osteochondral transplantation (OCT) is a well accepted treatment option for focal cartilage lesions in the knee joint, whereas the fate of the transplanted cartilage is still unclear and the clinical outcome is variable. The purpose of this study was to evaluate the histological character of autologous transplanted cartilage and to correlate technical aspects and the patients' history with the clinical outcome. MATERIAL AND METHODS: The OCT was performed in 27 patients (median age of 32 (22-43) years) with a focal chondral lesion at the medial femoral condyle. We investigated the clinical outcome after a median follow-up of 13.5 (5-28) months using the Lysholm-score and the integration of the transplanted plugs using an MRI-scoring system. Biopsy specimens from representative patients (n = 8) were evaluated with histological staining and immunohistochemistry. RESULTS: The median Lysholm-score was 80 (range 45-98). The wide range of the Lysholm-score in clinical outcome did not show significant differences in: follow-up, concomitant injuries, defect size or genesis. The MRI analysis revealed in all cases a regular osseous integration of the subchondral bone, but a failed chondral integration. The congruency of the plugs to the joint surface was often incorrect, however a correlation between the MRI-score and the clinical outcome could not be shown. Histology of the transplanted cartilage revealed small changes in immunohistochemistry after a relatively short-term follow-up, whereas the cartilage has still the typical hyaline character. Often, the surrounding cartilage consists of fibrous and granulation tissue. CONCLUSION: The congruency of the joint surface can not be restored to the original status, particularly in larger defects with irregular shapes. However, we did not find any aspects which affected the function of the knee joint following OCT. It can be assumed that remaining lesions at the surrounding cartilage could maintain the inflammatory process and therefore maintain the pain and a low knee function. Further investigations are needed to specify the effects of the OCT on the transplanted cartilage and its influence on the later clinical outcome.

Inyección de toxina botulínica en disfunción vesical neurogénica y no neurogénica / Botulinum toxin injection for neurogenic and no neurogenic bladder dysfunction

OBJETIVO: La Toxina Botulínica A(TB A)ha ganado popularidad entre los urólogos para el tratamientode las disfunciones del detrusor. El propósitode este artículo es revisar nuestra experiencia con estetratamiento.MÉTODOS: Desde el año 2001 hemos tratado 28pacientes con TB A. Se ha inyectado bajo visión cistoscópicaen la pared vesical. Se analiza la indicacióndel tratamiento, con la información clínica y urodinámicapre y post tratamiento.RESULTADOS: Se han tratado 28 pacientes. 71% convejiga neurogénica hiperrefléxica, 18% con vejiga inestableidiopática y 11% con otras patologías. No seobservaron complicaciones directas por el uso de latoxina. Vejiga neurogénica hiperrefléctica (n:20): Lacapacidad vesical preoperatoria promedio fue 220cc,la que mejoró post-tratamiento a 430cc. Las contraccionesno inhibidas desaparecieron. Todos los pacientes,excepto una paciente con esclerosis múltiple, queorinaba en forma espontánea, requirieron autocateterismopost-inyección, todos se hicieron continentes. Elpromedio de los intervalos entre inyección fue de 8,6meses. Vejiga inestable idiopática (n:5) : Se usó unadosis menor, con un promedio de 100 U. Las contraccionesno inhibidas desaparecieron y todos pudieronmantener micción espontánea con residuos postmiccionalesmenores de 50 ml. Ningún paciente requirióde autocateterismo. La capacidad vesical mejoródesde 128 ml a 370ml. El promedio de micciones pordía bajó de 16 a 7 veces. Otras patologías (n:3): Enestos pacientes los resultados fueron pobres. No hubocambios en los estudios de función vesical ni en la frecuenciamiccional promedio (15 veces por día). Estospacientes requirieron de cirugía de ampliación vesicalen 2 casos y de una derivación continente en 1 caso.DISCUSIÓN: TB A tiene un papel en el tratamiento dela Vejiga Hiperrefléctica Neurogénica, disminuyendo laincontinencia y mejorando la capacidad vesical. EnVejiga Inestable Idiopática sin cambios anatómicos susresultados son prometedores, pero el número limitadode pacientes no permite una conclusión definitiva. Enotras patologías vesicales con cambios anatómicos claros,sus resultados son malos y su uso no debiera serrecomendado de rutina

OBJECTIVES: Botulinum toxin A (BT A) has gained popularity among urologists in the treatment of detrusor muscle dysfunctions. The aim of this article is to review our experience with this therapy. METHODS: From 2001 we used BT A in 28 patients. It was injected in the bladder wall under cystoscopical vision. We analyze the indication of treatment, clinical data and urodynamics before and after treatment. RESULTS: We treated 28 patients. 71 percent had neurogenic hyperreflexic bladder, 18% idiopathic unstable bladder and 11% other diseases. No direct complications were observed. Neurogenic hyperreflexic bladder (n = 20): Mean preoperative bladder capacity was 220 cc, improving to 430 cc after treatment. Non inhibited contractions disappeared. All patients except one with multiple sclerosis, who had spontaneous voiding, required self catheterization after injection. Average time interval between injections was 8.6 months. Idiopathic unstable bladder (n = 5): a lower dose was used, with an average of 100 U. Non inhibited contractions disappeared and all patients were able to maintain spontaneous voiding with post void residuals under 50 ml. No patients required self catheterization. Bladder capacity improved from 128 ml to 370 ml. Average number of voidings per day diminished from 16 to 7 times. Other diseases (n = 3): results were poor in these patients. There were no changes in either bladder function studies or average voiding frequency (15 times per day). These patients required surgery for bladder augmentation in 2 cases and continent diversion in 1 case. CONCLUSIONS: BT A has a role in the treatment of neurogenic hyperreflexic bladder diminishing incontinence and improving bladder capacity. In cases of idiopathic unstable bladder without anatomical changes its results are promising, but a limited number of patients does not allow a definitive conclusion. In other bladder diseases with anatomical changes results are poor and its use should not be routinely recommended

The role of the carbachol test and concomitant diseases in patients with nonobstructive urinary retention undergoing sacral neuromodulation.

The aim of this study was to evaluate the percutaneous nerve evaluation (PNE) test success in patients with nonobstructive urinary retention. A total of 24 PNE tests were performed in patients with nonobstructive urinary retention and in 18 patients, a carbachol test was performed during urodynamics. The diagnosis relating to the acontractile detrusor was also assessed and compared to the outcome of the PNE test. The PNE test was successful in eight of 24 patients (33.3%) with the the highest success rate being observed in patients after hysterectomy (80%). It was successful in five of 12 patients with negative carbachol tests and in three of six patients with positive carbachol tests. We conclude that sacral neuromodulation is an effective treatment option in patients with nonobstructive urinary retention. PNE tests should be performed in all patients with therapy resistant nonobstructive urinary retention, because predictive factors do not exist.