Tolerability of inhaled N-chlorotaurine in the pig model

<p>Abstract</p> <p>Background</p> <p>N-chlorotaurine, a long-lived oxidant produced by human leukocytes, can be applied in human medicine as an endogenous antiseptic. Its antimicrobial activity can be enhanced by ammonium chloride. This study was designed to evaluate the tolerability of inhaled N-chlorotaurine (NCT) in the pig model.</p> <p>Methods</p> <p>Anesthetized pigs inhaled test solutions of 1% (55 mM) NCT (n = 7), 5% NCT (n = 6), or 1% NCT plus 1% ammonium chloride (NH₄Cl) (n = 6), and 0.9% saline solution as a control (n = 7), respectively. Applications with 5 ml each were performed hourly within four hours. Lung function, haemodynamics, and pharmacokinetics were monitored. Bronchial lavage samples for captive bubble surfactometry and lung samples for histology and electron microscopy were removed.</p> <p>Results</p> <p>Arterial pressure of oxygen (PaO₂) decreased significantly over the observation period of 4 hours in all animals. Compared to saline, 1% NCT + 1% NH₄Cl led to significantly lower PaO₂values at the endpoint after 4 hours (62 ± 9.6 mmHg vs. 76 ± 9.2 mmHg, p = 0.014) with a corresponding increase in alveolo-arterial difference of oxygen partial pressure (AaDO₂) (p = 0.004). Interestingly, AaDO₂was lowest with 1% NCT, even lower than with saline (p = 0.016). The increase of pulmonary artery pressure (PAP) over the observation period was smallest with 1% NCT without difference to controls (p = 0.91), and higher with 5% NCT (p = 0.02), and NCT + NH₄Cl (p = 0.05).</p> <p>Histological and ultrastructural investigations revealed no differences between the test and control groups. The surfactant function remained intact. There was no systemic resorption of NCT detectable, and its local inactivation took place within 30 min. The concentration of NCT tolerated by A549 lung epithelial cells <it>in vitro </it>was similar to that known from other body cells (0.25–0.5 mM).</p> <p>Conclusion</p> <p>The endogenous antiseptic NCT was well tolerated at a concentration of 1% upon inhalation in the pig model. Addition of ammonium chloride in high concentration provokes a statistically significant impact on blood oxygenation.</p

Metabolic constituents of grapevine and grape-derived products

The numerous uses of the grapevine fruit, especially for wine and beverages, have made it one of the most important plants worldwide. The phytochemistry of grapevine is rich in a wide range of compounds. Many of them are renowned for their numerous medicinal uses. The production of grapevine metabolites is highly conditioned by many factors like environment or pathogen attack. Some grapevine phytoalexins have gained a great deal of attention due to their antimicrobial activities, being also involved in the induction of resistance in grapevine against those pathogens. Meanwhile grapevine biotechnology is still evolving, thanks to the technological advance of modern science, and biotechnologists are making huge efforts to produce grapevine cultivars of desired characteristics. In this paper, important metabolites from grapevine and grape derived products like wine will be reviewed with their health promoting effects and their role against certain stress factors in grapevine physiology

Determinación de grupos ecológicos por medio de un análisis estadístico en los pastos de puerto del Valle de Tena (Huesca)

Este trabajo tiene como fin el establecimiento de grupos ecológicos en la zona de pastos de montaña del Valle de Tena, provincia de Huesca, como un primer paso encaminado a la estimación de su capacidad ganadera. Se utiliza un método estadístico en el que se parte de las correlaciones entre las especies pratenses y una serie de variables ecológicas, utilizando más adelante las correlaciones interespecíficas. Se han deducido doce "tipos" de pastos, así como aquellos caracteres ecológicos, de entre los considerados, que determinan las exigencias ecológicas de cada uno de ellos, exigencias que deberán tenerse en cuenta en cualquier intervención racional sobre dichos pastos. (Sección 1ª. Presidente Dr. J. Cizek

Utilización de un método fitológico en la determinación del valor nutritivo de pastos

En este trabajo se comparan los resultados obtenidos por dos métodos, uno químico y otro fitológico, en 48 pastos de montaña correspondientes a doce agrupaciones pascícolas distintas, evidenciando la estrecha correlación existente entre\ el llamado Valor Pastoral (VP), de DE VRIES y KLAPP, y las Unidades Forrajeras (UP) calculadas de los resultados del análisis químico. El valor nutritivo de un pasto medido en UP puede ser, pues, deducido de un análisis fitosociológico, junto con la determinación de la producción en verde y de la materia seca. Este procedimiento facilitaría en gran medida la estimación del valor nutritivo de pasto

Henificación en la depresión media prepirenaica; producciones, mermas y calidad

Este trabajo presenta datos globales sobre producción, calidad y mermas por henificación en cultivos forrajeros de la Canal de Berdún (Depresión Media Prepirenaica), a partir de controles en 43 parcelas durante 3 años (1981-83). Estos datos, que se refieren a lo que se obtiene en la práctica agronómica real actual, constituyen una base de partida para poder cuantificar las posibilidades forrajeras de la zona que es hoy fundamentalmente cerealícola, a pesar de que, por su situación, clima, etc., debería integrarse en el sistema de explotación ganadera del Pirineo inmediato, cuyos pastos estivales son actualmente infrautilizados. Los resultados del estudio muestran notables producciones forrajeras pero con mermas por henificación elevadas (34 %). En cuanto a calidad, la de la alfalfa resulta alta, mientras que es muy baja la de la esparceta; la de las praderas de regadío, tanto artificiales como naturales, acusa un sistema de explotación (abonados, siegas) deficiente

Rendimientos y calidad de alfalfares en regadío y en secano, en la Depresión Prepirenaica

Este trabajo presenta los resultados de los controles de producción y calidad de alfalfares de la Depresión Prepirenaica occidental, en regadío y secano, realizados entre 1981 y 1983. El estudio se justifica debido a la carencia de información concreta cuantificada en este sentido en la zona, que, sin embargo, resulta imprescindible para un estudio económico de su potencial forrajero como complemento para la ganadería pirenaica.Los resultados muestran un notable potencial (12.100 Kg. MS/Ha. media anual en regadío y 7.635 Kg. MS/Ha. en secano) en cuanto a producción bruta, aunque se evidencian las altas mermas por inadecuado proceso de henificación así como el incorrecto régimen de abonado, con despilfarro de N y escasez de P y K, sobre todo en regadío. Se especifican asimismo los regímenes de instalación y explotación, y se dan la producción y calidad por años y por aprovechamientos dentro del año

Effectiveness of Botulinum Toxin on Pain in Stroke Patients Suffering from Upper Limb Spastic Dystonia

open11noThis observational study aimed at investigating pain in stroke patients with upper limb spastic dystonia. Forty-one consecutive patients were enrolled. A 0–10 numeric rating scale was used to evaluate pain at rest and during muscle tone assessment. Patients were asked to indicate the most painful joint at passive mobilization (shoulder, elbow, wrist-fingers). The DN4 questionnaire was administered to disclose neuropathic pain. All patients were assessed just before and 1 month after incobotulinumtoxin-A treatment. Pain was present in 22 patients, worsened or triggered by passive muscle stretching. DN4 scored &lt; 4 in 20 patients. The most painful joints were wrist–fingers in 12 patients, elbow in 5 patients and shoulder in the remaining 5 patients. Both elbow and wrist– fingers pain correlated with muscle tone. BoNT-A treatment reduced pain in all the joints, including the shoulder. We discussed that nociceptive pain is present in a vast proportion of patients with upper limb spastic dystonia. BoNT-A treatment reduced both spastic dystonia and pain in all the joints but the shoulder, where the effect on pain could be mediated by the reduction of pathological postures involving the other joints.openTrompetto C.; Marinelli L.; Mori L.; Puce L.; Avanti C.; Saretti E.; Biasotti G.; Amella R.; Cotellessa F.; Restivo D.A.; Curra A.Trompetto, C.; Marinelli, L.; Mori, L.; Puce, L.; Avanti, C.; Saretti, E.; Biasotti, G.; Amella, R.; Cotellessa, F.; Restivo, D. A.; Curra, A

Transcription factor binding sites downstream of the human immunodeficiency virus type 1 transcription start site are important for virus infectivity.

When transcriptionally active, the human immunodeficiency virus (HIV) promoter contains a nucleosome-free region encompassing both the promoter/enhancer region and a large region (255 nucleotides [nt]) downstream of the transcription start site. We have previously identified new binding sites for transcription factors downstream of the transcription start site (nt 465 to 720): three AP-1 sites (I, II, and III), an AP3-like motif (AP3-L), a downstream binding factor (DBF) site, and juxtaposed Sp1 sites. Here, we show that the DBF site is an interferon-responsive factor (IRF) binding site and that the AP3-L motif binds the T-cell-specific factor NF-AT. Mutations that abolish the binding of each factor to its cognate site are introduced in an infectious HIV-1 molecular clone to study their effect on HIV-1 transcription and replication. Individual mutation of the DBF or AP3-L site as well as the double mutation AP-1(III)/AP3-L did not affect HIV-1 replication compared to that of the wild-type virus. In contrast, proviruses carrying mutations in the Sp1 sites were totally defective in terms of replication. Virus production occurred with slightly delayed kinetics for viruses containing combined mutations in the AP-1(III), AP3-L, and DBF sites and in the AP3-L and DBF-sites, whereas viruses mutated in the AP-1(I,II,III) and AP3-L sites and in the AP-1(I,II,III), AP3-L, and DBF sites exhibited a severely defective replicative phenotype. No RNA-packaging defect could be measured for any of the mutant viruses as determined by quantification of their HIV genomic RNA. Measurement of the transcriptional activity of the HIV-1 promoter after transient transfection of the HIV-1 provirus DNA or of long terminal repeat-luciferase constructs showed a positive correlation between the transcriptional and the replication defects for most mutants

Spatial and temporal dynamics of innervation during the development of fetal human pancreas.

The delineation of pancreatic nerve innervations during fetal life may contribute to our understanding of pancreatic pain modalities after birth. The aim of this study was to characterize the spatial and temporal distribution of nerve structures in the human pancreas throughout gestation. Computer-based image morphometry with piecewise polynomial interpolation analysis was performed to quantify nervous structures in the head, body and tail of the pancreas. Nerve structures were detected by automatic immunostaining techniques using a polyclonal antibody against two S-100 proteins that reacts strongly with human S100A and B that are detected in Schwann cells. Immunoreactivity was found in the parenchyma of head, body and tail of the pancreas with the relative density being head> body> tail. In addition to this extensive set of nerve fibers terminating in the pancreas there were large bundles of en passant nerve fibers in the dorsal region of the pancreas that were 3D reconstructed and were associated with the superior mesenteric plexus. If at first glance, the perimeter and the width of the nerve fibers seem to increase at a continuous rate up to term in all three regions of the pancreas, spatial and temporal co-analysis identified that the head of the pancreas shows a two-peak growth increase at 14 and 22 weeks of gestation with regard to the area, perimeter and width of the nerve structures, while the body and tail regions show a unique peak at 20 weeks. A developmental deceleration was found between the 22nd and the 36th week of gestation for the head region only. This is the first systematic study of nerve innervation of the human pancreas throughout gestation. The developmental dynamics of the pancreas nerve innervation corresponds approximately to the remodeling of the intrahepatic biliary system. Understanding the factors and disease states that may alter the distribution of nerve structures can be of significance for the development of therapies in pancreatic disorders of child- and adulthood