Food-induced stimulation of the antisecretory factor to improve symptoms in Meniere's disease: our results.

PURPOSE: Specially processed cereals (SPC) that increase endogenous antisecretory factor (AF) synthesis have been proposed to improve symptoms of Meniere's disease (MD) with controversial results. The aim of this study was to evaluate the effects of SPC in patients with definite unilateral MD and compare the results to a treatment protocol with intravenous glycerol and dexamethasone. METHODS: Thirteen patients with unilateral MD were treated with SPC and 13 patients were treated with intravenous glycerol and dexamethasone for 12 months. Audio-vestibular evaluation was performed before (T0) and at the end of the treatments (T12). The number of vertigo spells were evaluated before and after therapy and the Efficacy Index (EI) was calculated. Questionnaires for hearing loss (HHIA), tinnitus (THI) and quality of life (TFL) were administered. RESULTS: EI decreased in the SPC group in the second semester compared to the first although not significantly (p = 0.6323). There was a significant reduction for THI score in the SPC group at T12 (p = 0.0325). No significant differences were found between the two groups at T0 (p = 0.4723), while a significant difference was found at T12 (p = 0.0041). Quality of life showed an improvement in daily activities in the SPC group compared to infusion therapy group. CONCLUSION: Our study shows a reduced number of vertigo attacks and a positive effect on the discomfort generated by tinnitus and quality of life in patients with unilateral MD treated with SPC and when compared to patients treated with intravenous glycerol and dexamethasone. No effects on hearing thresholds were noted in both groups.

Peripheral nervous system effects in the PS19 tau transgenic mouse model of tauopathy.

It is well known that transgenic mice overexpressing human tau protein with P301S mutation driven by the mouse prion protein promoter show clasping and limb retraction, hunched back and paralysis, followed by inability to feed that results in death around 12 months of age. To understand these motor deficits, we have carried out rotarod tests on PS19 line and demonstrated how they worsened during aging. Then, we have analyzed if these phenotypic characteristics correlate with sciatic nerve degeneration. We first demonstrated by western blot and immunohistochemistry that the sciatic nerve expresses the transgenic tau protein; then, electron microscopy studies showed alterations in myelin, mainly a detachment of myelin lamellae at Schmidt-Lanterman clefts. Similar motor deficits and myelin alterations have been previously reported in tau knockout and overexpressing transgenic mice; taking into account that PS19 model is widely used to study tauopathies, we suggest that analyzing the expression of transgenic tau protein and myelin abnormalities in the sciatic nerve should be considered when studying some features as motor performance or survival.

In-stream attenuation of neuro-active pharmaceuticals and their metabolites.

In-stream attenuation was determined for 14 neuro-active pharmaceuticals and associated metabolites. Lagrangian sampling, which follows a parcel of water as it moves downstream, was used to link hydrological and chemical transformation processes. Wastewater loading of neuro-active compounds varied considerably over a span of several hours, and thus a sampling regime was used to verify that the Lagrangian parcel was being sampled and a mechanism was developed to correct measured concentrations if it was not. In-stream attenuation over the 5.4-km evaluated reach could be modeled as pseudo-first-order decay for 11 of the 14 evaluated neuro-active pharmaceutical compounds, illustrating the capacity of streams to reduce conveyance of neuro-active compounds downstream. Fluoxetine and N-desmethyl citalopram were the most rapidly attenuated compounds (t1/2 = 3.6 ± 0.3 h, 4.0 ± 0.2 h, respectively). Lamotrigine, 10,11,-dihydro-10,11,-dihydroxy-carbamazepine, and carbamazepine were the most persistent (t1/2 = 12 ± 2.0 h, 12 ± 2.6 h, 21 ± 4.5 h, respectively). Parent compounds (e.g., buproprion, carbamazepine, lamotrigine) generally were more persistent relative to their metabolites. Several compounds (citalopram, venlafaxine, O-desmethyl-venlafaxine) were not attenuated. It was postulated that the primary mechanism of removal for these compounds was interaction with bed sediments and stream biofilms, based on measured concentrations in stream biofilms and a column experiment using stream sediments.

Estimulación de nervio periférico en el tratamiento de diferentes tipo de cefaleas / Peripheral nerve stimulation in the treatment of various types of headache

Introducción. La cefalea constituye una enfermedad con gran impacto en la calidad de vida y la economía de los países industriales. Una de las teorías fisiopatológicas se encuentra la activación de las fibras aferentes cervicales de los nervios C2-C3. La neuroestimulación periférica aferente de C2-C3, que se provoca en la estimulación del nervio occipital, parece aliviar la cefalea a través de las conexiones trigeminocervicales, y ser una de las causas principales de su eficacia. Material y métodos. Estudio multicéntrico retrospectivo entre abril 2005 y mayo 2009. Se incluyó a los pacientes con cefalea crónica mayor que fueron tratados con neuroestimulación. En todos los pacientes se valoró el tipo de cefalea, el grado de dolor mediante una escala numérica simple, tratamiento médico y episodios de cefalea. Se analizó el porcentaje de test negativos. En los portadores del generador definitivo se valoró la eficacia de la técnica mediante el análisis de la escala numérica simple y el análisis del porcentaje de mejoría subjetiva de los pacientes al mes, 3 meses, 6 meses y 12 meses. Se analizó el grado de cobertura, la satisfacción, la disminución de los episodios y la medicación y las complicaciones. Resultados. Se incluyeron 31 pacientes. El resultado del test fue positivo en el 87%. Existió una disminución significativa (p < 0,001) del dolor desde el momento basal con una mejoría mayor del 50% sostenido del 85,2% y un descenso en la puntuación de la escala numérica simple > 2 puntos en un 96,3% de los casos. Todos los pacientes estaban satisfechos durante el estudio. El 56% de la muestra no tuvo episodios de cefaleas tras el año de estudio y el 47% dejo de tomar medicación. La complicación más frecuente fue la migración del electrodo (AU)

Background and objective. Headache has a great impact on patients quality of life and in industrialized countries there is economic impact as well. One of the pathophysiologic theories to explain headache is activation of afferent C2-C3 nerve fibers. Afferent peripheral nerve stimulation by occipital nerve provocation at C2-C3 seems to alleviate headache by acting on the trigeminocervical complex, which would largely explain the effectiveness of this modality. The aim of this study was to describe peripheral nerve stimulation as an alternative therapy in patients who do not respond to other headache treatments. Material and methods. Multicenter retrospective study between April 2005 and May 2009, analyzing cases of patients treated with nerve stimulation for severe chronic headache. In all patients the medical history included type of headache, intensity of pain on a numerical scale, medical treatment used, and number of headache episodes. We recorded the percentage of patients with negative tests. Patients implanted with a generator assessed effectiveness on the numerical scale; we analyzed the percentage of perceived improvement at 1, 3, 6, and 12 months. We also analyzed the extent of coverage provided by the electrodes, patient satisfaction, reduction in the number of episodes and medication, and complications. Results. Of 31 patients, 87% had positive results, with a significant decrease in pain from baseline (P <. 001); 85.2% reported sustained improvement of >50%, and 96.3% reported a decrease of > 2 points on the pain scale. All patients expressed satisfaction during the period of follow-up. Fifty-six percent had no headaches after a year and 47% had stopped taking medication. The most frequent complication was electrode migration (AU)

Synthesis and biological evaluation of novel peripherally active morphiceptin analogs.

Morphiceptin (Tyr-Pro-Phe-Pro-NH(2)), a tetrapeptide present in the enzymatic digest of bovine beta-casein, is a selective ligand of the mu-opioid receptor. In the present study, we describe the synthesis of a series of novel morphiceptin analogs modified in positions 1-3. Two of the obtained analogs, [Dmt(1), D-Ala(2), D-1-Nal(3)]morphiceptin and [Dmt(1), D-NMeAla(2), D-1-Nal(3)]morphiceptin (Dmt-2',6'-dimethyltyrosine and d-1-Nal-3-(1-naphthyl)-D-alanine)) displayed very high mu-receptor affinity, resistance to enzymatic degradation, and remarkable supraspinally mediated analgesia, as shown in the hot-plate test after intracerebroventricular but not intravenous administration, which indicated that they could not cross the blood-brain barrier. Therefore, these two analogs were further tested in vitro and in vivo towards their possible peripheral analgesic activity and inhibitory effect on gastrointestinal (GI) motility. We report that both peptides showed strong antinociceptive effect in the writhing test after intraperitoneal administration, inhibited smooth muscle contractility in vitro and GI motility in vivo. Taken together, these findings indicate that the novel morphiceptin analogs which induce peripheral, but not central antinociception, inhibit GI transit, and possess exceptional metabolic stability, may provide an interesting approach to the development of peripherally restricted agents for the treatment of GI motility disorders, such as diarrhea or diarrhea-predominant irritable bowel syndrome.