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Local Application (local + application)
Selected AbstractsConcentration Gradient Along the Scala Tympani After Local Application of Gentamicin to the Round Window Membrane,THE LARYNGOSCOPE, Issue 7 2007Stefan K. Plontke MD Abstract Objectives: The distribution of gentamicin along the fluid spaces of the cochlea after local applications has never previously been demonstrated. Computer simulations have predicted that significant basal-apical concentration gradients might be expected, and histologic studies indicate that hair cell damage is greater at the base than at the apex after local gentamicin application. In the present study, gradients of gentamicin along the cochlea were measured. Methods: A recently developed method of sampling perilymph from the cochlear apex of guinea pigs was used in which the samples represent fluid originating from different regions along the scala tympani. Gentamicin concentration was determined in sequential apical samples that were taken after up to 3 hours of local application to the round window niche. Results: Substantial gradients of gentamicin along the length of the scala tympani were demonstrated and quantified, averaging more than 4,000 times greater concentration at the base compared with the apex at the time of sampling. Peak concentrations and gradients for gentamicin varied considerably between animals, likely resulting from variations in round window membrane permeability and rates of perilymph flow. Conclusions: The large gradients for gentamicin demonstrated here in guinea pigs account for how it is possible to suppress vestibular function in some patients with a local application of gentamicin without damaging auditory function. Variations in round window membrane permeability and in perilymph flow could account for why hearing losses are observed in some patients. [source] Local Applications of GM-CSF Induce the Recruitment of Immune Cells in Cervical Low-Grade Squamous Intraepithelial LesionsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2010Pascale Hubert Citation Hubert P, Doyen J, Capelle X, Arafa M, Renoux V, Bisig B, Seidel L, Evrard B, Bousarghin L, Gerday C, Boniver J, Foidart J-M, Delvenne P, Jacobs N. Local applications of GM-CSF induce the recruitment of immune cells in cervical low-grade squamous intraepithelial lesions. Am J Reprod Immunol 2010; 64: 126,136 Problem, Quantitative alterations of antigen-presenting cells (APC) in (pre)neoplastic lesions of the uterine cervix associated with human papillomavirus (HPV) infection suggest a diminished capacity to capture viral antigens and to induce a protective immune response. Method of study, To test whether a cervical application of GM-CSF could restore an immune response against HPV in women with cervical low-grade squamous intraepithelial lesions (LSIL), we performed two clinical trials with 11 healthy women and 15 patients with LSIL. Results, GM-CSF applications were well tolerated in all enrolled women, and no difference in toxicity between the treated and placebo groups was observed during the follow-up (until 30 months). Interestingly, in the GM-CSF treated group, a significant increase of APC and cytotoxic T-lymphocyte infiltration was observed in the cervical biopsies with no change in regulatory T cell numbers. All the HPV16+ patients exhibited an immune response against HPV16 after GM-CSF applications, as shown by NK and/or T cells producing IFN-, whereas no cellular immune response was observed before the treatment. Moreover, the anti-virus-like particles antibody titers also increased after the treatment. Conclusion, These encouraging results obtained from a limited number of subjects justify further study on the therapeutic effect of APC in cervical (pre)neoplastic lesions. [source] Activation of the basal forebrain by the orexin/hypocretin neuronesACTA PHYSIOLOGICA, Issue 3 2010E. Arrigoni Abstract The orexin neurones play an essential role in driving arousal and in maintaining normal wakefulness. Lack of orexin neurotransmission produces a chronic state of hypoarousal characterized by excessive sleepiness, frequent transitions between wake and sleep, and episodes of cataplexy. A growing body of research now suggests that the basal forebrain (BF) may be a key site through which the orexin-producing neurones promote arousal. Here we review anatomical, pharmacological and electrophysiological studies on how the orexin neurones may promote arousal by exciting cortically projecting neurones of the BF. Orexin fibres synapse on BF cholinergic neurones and orexin-A is released in the BF during waking. Local application of orexins excites BF cholinergic neurones, induces cortical release of acetylcholine and promotes wakefulness. The orexin neurones also contain and probably co-release the inhibitory neuropeptide dynorphin. We found that orexin-A and dynorphin have specific effects on different classes of BF neurones that project to the cortex. Cholinergic neurones were directly excited by orexin-A, but did not respond to dynorphin. Non-cholinergic BF neurones that project to the cortex seem to comprise at least two populations with some directly excited by orexin-A that may represent wake-active, GABAergic neurones, whereas others did not respond to orexin-A but were inhibited by dynorphin and may be sleep-active, GABAergic neurones. This evidence suggests that the BF is a key site through which orexins activate the cortex and promote behavioural arousal. In addition, orexins and dynorphin may act synergistically in the BF to promote arousal and improve cognitive performance. [source] Biodegradable poly(D,L -lactide) coating of implants for continuous release of growth factorsJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 4 2001G. Schmidmaier Abstract Local application of growth factors like insulin like growth factor-I (IGF-I) and transforming growth factor-beta 1 (TGF-,1) from a biodegradable thin layer of poly(D,L -lactide) (PDLLA) coated implants could stimulate fracture healing. A new "cold coating technique" for metallic implants was established to produce a biodegradable coating with a high mechanical stability that provides a continuous release of incorporated growth factors. The properties of this bioactive coating were investigated in vitro and in vivo. Scanning electron microscope analysis revealed a coating thickness of in average 14.8 ,m on titanium and 10.7 ,m on steel wires. Intramedullary implantation and extraction experiments depicted a loss of PDLLA coating from titanium and steel implants of less than 5%. After explantation of the implants, the coating displayed a complete and regular layer without any defects of PDLLA uncovering the metallic surface. Smear tests demonstrate that the coating can be performed under sterile conditions. The PDLLA depicted a reduction of about 8% within 6 weeks in vitro and in vivo. The growth factors were incorporated in a stable form and demonstrated a loss of stability of less than 3% within 42 days and less than 5% within one year. In an elution experiment, 54% IGF-I and 48% TGF-,1 were released within the first 48 h. After 42 days, 76% of IGF-I and 71% of TGF-,1 were detected in the elution fluid by ELISA. Comparable results were obtained in the in vivo experiments after 42 days. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 449,455, 2001 [source] Evaluation of implants coated with rhBMP-2 using two different coating strategies: a critical-size supraalveolar peri-implant defect study in dogsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2010Jaebum Lee Lee J, Decker JF, Polimeni G, Cortella CA, Rohrer MD, Wozney JM, Hall J, Susin C, Wikesjö UME. Evaluation of implants coated with rhBMP-2 using two different coating strategies: a critical-size supraalveolar peri-implant defect study in dogs. J Clin Periodontol 2010; 37: 582,590. doi: 10.1111/j.1600-051X.2010.01557.x. Abstract Background: Implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce relevant bone formation but also resident bone remodelling. Objectives: To compare the effect of implants fully or partially coated with rhBMP-2 on new bone formation and resident bone remodelling. Materials and Methods: Twelve, male, adult, Hound Labrador mongrel dogs were used. Critical-size, supraalveolar, peri-implant defects received titanium porous oxide surface implants coated in their most coronal aspect with rhBMP-2 (coronal-load/six animals) or by immersion of the entire implant in an rhBMP-2 solution (soak-load/six animals) for a total of 30 ,g rhBMP-2/implant. All implants were air-dried. The animals were euthanized at 8 weeks for histometric evaluation. Results: Clinical healing was uneventful. Supraalveolar bone formation was not significantly affected by the rhBMP-2 application protocol. New bone height and area averaged (± SE) 3.4 ± 0.2 versus 3.5 ± 0.4 mm and 2.6 ± 0.4 versus 2.5 ± 0.7 mm2 for coronal-load and soak-load implants, respectively (p>0.05). The corresponding bone density and bone,implant contact (BIC) recordings averaged 38.0 ± 3.8%versus 34.4 ± 5.6% and 25.0 ± 3.8%versus 31.2 ± 3.3% (p>0.05). In contrast, resident bone remodelling was significantly influenced by the rhBMP-2 application protocol. Bone density outside the implants threads averaged 74.7 ± 3.8% and 50.8 ± 4.1% for coronal-load and soak-load implants, respectively (p<0.05); bone density within the thread area averaged 51.8 ± 1.2% and 37.8 ± 2.9%, and BIC 70.1 ± 6.7% and 43.3 ± 3.9% (p<0.05). Conclusion: Local application of rhBMP-2 appears to be a viable technology to support local bone formation and osseointegration. Coronal-load implants obviate resident bone remodelling without compromising new bone formation. [source] Deproteinized bovine bone and gentamicin as an adjunct to GTR in the treatment of intrabony defects: a randomized controlled clinical studyJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2003A. Stavropoulos Abstract Objectives: To evaluate whether Bio-Oss® used as an adjunct to guided tissue regeneration (GTR) improves the healing of 1- or 2-wall intrabony defects as compared with GTR alone, and to examine whether impregnation of Bio-Oss® with gentamicin may have an added effect. Material and methods: Sixty patients, with at least one interproximal intrabony defect with probing pocket depth (PPD) 7 mm and radiographic evidence of an intrabony component (IC) 4 mm, were treated at random with either a resorbable membrane (GTR), a resorbable membrane in combination with Bio-Oss® impregnated with saline (DBB,), a resorbable membrane in combination with Bio-Oss® impregnated with gentamicin (DBB+), or with flap surgery (RBF). Results: All treatment modalities resulted in statistically significant clinical improvements after 1 year. Defects treated with GTR alone presented a probing attachment level (PAL) gain of 2.9 mm, a residual PPD (PPD12) of 4.9 mm, a radiographic bone level (RBL) gain of 3.1 mm, and a residual IC (IC12) of 2.7 mm. GTR combined with Bio-Oss® did not improve the healing outcome (PAL gain: 2.5 mm; PPD12: 4.9 mm; RBL gain: 2.8 mm; IC12: 3.3 mm). Impregnation of the Bio-Oss® with gentamicin 2% mg/ml resulted in clinical improvements (PAL gain: 3.8 mm; PPD12: 4.2 mm; RBL gain: 4.7 mm; IC12: 2.1 mm), superior to those of the other treatment modalities, but the difference was not statistically significant. Defects treated with only flap surgery showed the most inferior clinical response (PAL gain: 1.5 mm; PPD12: 5.1 mm; RBL gain: 1.2 mm; IC12: 4.2 mm) of all groups. Conclusion: The results failed to demonstrate an added effect of Bio-Oss® implantation in combination with GTR on the healing of deep interproximal 1- or 2-wall, or combined 1- and 2-wall intrabony defects compared with GTR alone. Local application of gentamicin, on the other hand, improved the treatment outcome but not to an extent that it was statistically significant. Zusammenfassung Von Proteinen befreiter boviner Knochen und Gentamycin als Adjuvans der GTR bei der Behandlung von infraalveolären Knochentaschen. Eine randomisierte kontrollierte klinische Studie. Ziele: Die Evaluation ob, Bio-Oss® welches als Adjuvans zur GTR verwendet wird, die Heilung von 1- oder 2-wandigen Knochentaschen im Vergleich zu alleiniger GTR verbessert. Sowie die Untersuchung, ob die Imprägnierung von Bio-Oss® mit Gentamycin einen zusätzlichen Effekt haben könnte. Material und Methoden: 60 mit wenigstens einer approximalen Knochentasche mit Sondierungstiefe (PPD) ,7 mm und röntgenologischem Nachweis einer infraalveolären Komponente (IC) von ,4 mm, wurden randomisiert entweder mit einer resorbierbaren Membran (GTR), einer resorbierbaren Membran in Kombination mit Bio-Oss® welche mit Kochsalzlösung imprägniert war (DBB-), einer resorbierbaren Membran in Kombination mit Bio-Oss® welche mit Gentamycin imprägniert war (DBB+) oder mit Lappen-OP (RPF) behandelt. Ergebnisse: Nach einem Jahr hatten alle Behandlungsweisen eine statistisch signifikante klinische Verbesserung zum Ergebnis. Defekte, die mit alleiniger GTR behandelt wurden zeigten einen Gewinn an klinischem Attachmentniveau (PAL) von 2,9 mm, einer PPD (PPD12) von 4,9 mm, einem Gewinn an röntgenologischem Knochenniveau (RBL) von 3,1 mm und einer IC (IC12) von 2,7 mm. GTR in Kombination mit Bio-Oss® verbesserte das Ergebnis der Heilung nicht (PAL Gewinn: 2,5 mm; PPD12: 4,9; RBL Gewinn: 2,8 mm; IC12: 3,3 mm). Die Imprägnierung von Bio-Oss® mit Gentamycin 2% mg/ml hatte klinische Verbesserungen zum Ergebnis (PAL Gewinn: 3,8 mm; PPD12: 4,2 mm; RBL Gewinn: 4,7 mm; IC12: 2,1 mm), die größer waren als die der anderen Behandlungsweisen, jedoch waren die Unterschiede nicht statistisch signifikant. Defekte, die nur mit Lappen-OP behandelt wurden zeigten das schlechteste klinische Ergebnis von allen Gruppen (PAL Gewinn: 1,5 mm; PPD12: 5,1 mm; RBL Gewinn: 1,2 mm; IC12: 4,2 mm). Schlussfolgerung: Die Ergebnisse konnten im Vergleich mit alleiniger GTR keinen zusätzlichen Effekt der Bio-Oss®-Implantation in Kombination mit GTR hinsichtlich der Heilung von tiefen approximalen 1- oder 2-wandigen oder kombinierten 1- oder 2-wandigen Knochentaschen aufzeigen. Auf der anderen Seite verbessert die lokale Applikation von Gentamycin das Behandlungsergebnis, jedoch war das Ausmaß nicht statistisch signifikant. Résumé Os bovin déprotéiné et gentamicine comme adjuvant à la RTG pour le traitement des lésions intra-osseuses. Une étude clinique contrôlée et randomisée. Objectifs: Evaluer si Bio-Oss® utilisé comme adjuvant de la RTG améliore la cicatrisation des lésions intra-osseuses par rapport à la RTG seule et examiner si l'imprégnation de Bio-Oss® avec de la gentamicine pourrait avoir un effet supplémentaire. Matériels et Méthodes: 60 patients, présentant au moins une lésion intra-osseuse interproximale avec une profondeur de poche au sondage (PPD) ,7 mm et la présence avérée radiologiquement d'une composante intra-osseuse (IC) ,4 mm, ont été traités au hasard avec soit une membrane résorbable (GTR), une membrane résorbable en combinaison avec du Bio-Oss® imprégné de solution saline (DBB-), une membrane résorbable en combinaison avec du Bio-Oss® imprégné de gentamicine (DBB+), ou par chirurgie à lambeau (RBF). Résultats: Toutes les modalités de traitement entraînaient des améliorations cliniques significatives statistiquement après un an. Les lésions traitées par RTG seule présentaient un gain d'attache de 2.9 mm, une PPD résiduelle (PPD12) de 4.9 mm, un gain de niveau osseux radiographique (RBL) de 3.1 mm, et un IC résiduel (IC12) de 2.7 mm. La RTG combinée avec le Bio-Oss® n'améliorait pas le devenir de la cicatrisation. (gain de PAL: 2.5 mm; PPD12: 4.9; gain de RBL: 2.8 mm; IC12: 3.3 mm). L'imprégnation du Bio-Oss®avec la gentamicine (2% mg/ml) apportait des améliorations cliniques (gain de PAL: 3.8 mm; PPD12: 4.2 mm; gain de RBL: 4.7 mm; IC12: 2.1 mm), supérieurs à ceux des autres modalités de traitement, mais la différence n'était pas significative. Le traitement des lésions par lambeaux seulement entraînait la réponse clinique la moins bonne (gain de PAL: 1.5 mm; PPD12: 5.1 mm; gain de RBL: 1.2 mm; IC12: 4.2 mm). Conclusion: Ces résultats ne pouvaient démontrer un effet supplémentaire, sur la cicatrisation de lésions profondes interproximales avec une ou deux parois, de l'implantation de Bio-Oss® en combinaison avec la RTG par rapport à la RTG seule. L'application locale de gentamicine, par contre, améliorait le devenir du traitement mais pas suffisamment pour être statistiquement significatif. [source] Local application of n,3 or n,6 polyunsaturated fatty acids in the treatment of human experimental gingivitisJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 4 2002Jörg Eberhard Abstract Background: Polyunsaturated fatty acids have the potential to attenuate inflammation by the synthesis of mediators of the 15-lipoxygenase pathways, which show opposite effects to the pro-inflammatory arachidonic acid metabolites such as leukotriene B4 (LTB4). Aims: The aim of this clinical study was to evaluate the effects of topical application of n,6 or n,6 polyunsaturated fatty acids in patients with experimental gingivitis. Methods: In each subject, similar teeth served as experimental and control over a 21-day non-hygiene phase and a 9-day resolving phase. Efficacy assessment was based on the bleeding on probing frequency (BOP) and the gingivocrevicular fluid volume (GCF). GCF was determined by inserting a filter paper strip for 30 s and measurements were performed on a Periotron 8000. The LTB4 concentration was analyzed by reversed-phase high-pressure liquid chromatography. Results: After 21 days of plaque growth, the BOP, GCF and LTB4 levels were significantly increased in all groups, with no differences between the control and experimental side. Rinsing of an area with established gingivitis for a 9-day period significantly reduced the GCF in the n,6 group (71.9 (18.7) versus 47.4 (11.4) Periotron Units, median (inter quartile range)). Conclusion: The topical application of n,6 or n,6 fatty acids failed to inhibit the development of experimental gingivitis. Rinsing with n,6 fatty acids could reduce the level of GCF in established experimental gingivitis. Zusammenfassung Hintergrund: Vielfach ungesättigte Fettsäuren haben das Potential, die Entzündung durch die Synthese von Mediatoren des 15-Lipoxygenaseweges zu behindern. Dies zeigt Gegeneffekte zu den pro-inflammatorischen Arachnoidonsäuremetaboliten wie Leukotrien B4 (LTB4). Ziele: Das Ziel dieser klinischen Studie war die Überprüfung des Effektes einer topischen Applikation von n,3 oder n,6 vielfach ungesättigten Fettsäuren bie Patienten mit experimenteller Gingivitis. Methoden: Bei jeder Person dienten ähnliche Zähne als Experiment und Kontrollen über eine 21tägige Nichthygiene-Phase und einer 9tägigen Erholungsphase. Wirksamkeitsmessungen basierten auf der Häufigkeit von Provokationsblutung (BOP) und dem Volumen der gingivalen krevikulären Flüssigkeit (GCF). GCF wurde durch Einbringen von Filterpapierstreifen für 30 Sekunden bestimmt. Die Messungen wurden mit einen Periotron 8000 durchgeführt. Die LTB4 Konzentration wurde mit der Umkehrphasen-Hochdruck-Flüssigkeitschromatographie analysiert. Ergebnisse: Nach 21 Tagen des Plaquewachstums waren die Level für BOP, GCF und LTB4 in allen Gruppen signifikant erhöht, ohne Differenzen zwischen den Kontrollen und den experimentellen Flächen. Die Spülung eines Gebietes mit etablierter Gingivitis für eine 9tägige Periode reduzierte die GCF in der n,6 Gruppe signifikant (71.9 (18.7) versus 47.4 (11.4) Peritron-Einheiten, Median (Zwischenquartilstreuung)). Zusammenfassung: Die topische Applikation von n,3 oder n,6 Fettsäuren verhindert die Entwicklung einer experimentellen Gingivitis nicht. Die Spülung mit n,6 Fettsäure konnte den Level der GCF bei einer bestehenden experimentellen Gingivitis reduzieren. Résumé Origine: Les acides gras poly-insaturés ont le potentiel d'atténuer l'inflammation en synthétisant des médiateurs des voies de la lipoxygénase 15 qui montrent des effets opposés aux métabolites de l'acide arachidonique pro-inflammatoire comme la leucotriène B4 (LTB4). But: Le but de cette étude clinique a été d'évaluer les effets de l'application topique d'acide gras poly-insaturés n,3 ou n,6 chez des patients effectuant d'une gingivite expérimentale. Méthodes: Chez chaque sujet, des dents semblables ont servi de sites tests et contrôles durant une phase sans hygiène buccale de 21 jours et une phase de retour à la normale de 9 jours. L'efficacité a été mesurée sur base de la fréquence du saignement au sondage (BOP) et le volume de fluide gingivale (GCF). Le GCF a été déterminé en insérant des papiers filtres pendant 30 s et les mesures ont été lues à l'aide du Périotron 8000. La concentration de LTB4 a été analysée par chromotographie liquide à haute pression à phrase arrière. Résultats: Après 21 jours d'accumulation de plaque dentaire les niveaux de BOP, GCF et LTB4 ont augmenté significativement dans tous les groupes sans aucune différence entre les sites tests et contrôles. Le rinçage d'une zone avec gingivite établie durant une période de 9 journées diminuait les GCF dans le groupe n,6 (unités du Péritron 72 (médian 19) versus 47 (11)). Conclusion: L'application topique d'acide gras n,3 ou n,6 ne permettait pas d'inhiber le développement de la gingivite expérimentale. Le rinçage avec des acides gras n,6 pouvait réduire le niveau de GCF dans la gingivite expérimentale établie. [source] 5-HT1B Receptor-Mediated Regulation of Serotonin Clearance in Rat Hippocampus In VivoJOURNAL OF NEUROCHEMISTRY, Issue 5 2000Lynette C. Daws Abstract: The 5-hydroxytryptamine (5-HT; serotonin) transporter (5-HTT) is important in terminating serotonergic neurotransmission and is a primary target for many psychotherapeutic drugs. Study of the regulation of 5-HTT activity is therefore important in understanding the control of serotonergic neurotransmission. Using high-speed chronoamperometry, we have demonstrated that local application of 5-HT1B antagonists into the CA3 region of the hippocampus prolongs the clearance of 5-HT from extracellular fluid (ECF). In the present study, we demonstrate that the 5-HT1B antagonist cyanopindolol does not produce this effect by increasing release of endogenous 5-HT or by directly binding to the 5-HTT. Dose-response studies showed that the potency of cyanopindolol to inhibit clearance of 5-HT was equivalent to that of the selective 5-HT reuptake inhibitor fluvoxamine. Local application of the 5-HT1A antagonist WAY 100635 did not alter 5-HT clearance, suggesting that the effect of cyanopindolol to prolong clearance is not via a mechanism involving 5-HT1A receptors. Finally, the effect of low doses of cyanopindolol and fluvoxamine to inhibit clearance of 5-HT from ECF was additive. These data are consistent with the hypothesis that activation of terminal 5-HT1B autoreceptors increases 5-HTT activity. [source] Recombinant human platelet-derived growth factor BB (rhPDGF-BB) and beta-tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat modelJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 8 2009Loay Al-Zube Abstract Diabetes mellitus is a common systemic disease that has been associated with poor fracture healing outcomes. The mechanism through which diabetes impairs bone regeneration is unknown. One possible mechanism may be related to either decreased or uncoordinated release of local growth factors at the fracture site. Indeed, previous studies have found reduced platelet-derived growth factor (PDGF) levels in the fracture callus of diabetic rats, suggesting that local application of PDGF may overcome the negative effects of diabetes and promote fracture healing. To test this hypothesis, low (22 µg) and high (75 ug) doses of recombinant human PDGF-BB (rhPDGF-BB) were applied directly to femur fracture sites in BB Wistar diabetic rats that were then compared to untreated or vehicle-treated animals. rhPDGF-BB treatment significantly increased early callus cell proliferation compared to that in control specimens. Low dose rhPDGF-BB treatment significantly increased callus peak torque values (p,<,0.05) at 8 weeks after fracture as compared to controls. High dose rhPDGF-BB treatment increased callus bone area at 12 weeks postfracture. These data indicate that rhPDGF-BB treatment ameliorates the effects of diabetes on fracture healing by promoting early cellular proliferation that ultimately leads to more bone formation. Local application of rhPDGF-BB may be a new therapeutic approach to treat diabetes-impaired fracture healing. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 1074,1081, 2009 [source] Immunization for Protection of the Reproductive Tract: A ReviewAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2002MICHAEL W. RUSSELL PROBLEM: Local application of non-replicating antigens to the female reproductive tract is ineffective in stimulating the common mucosal immune system, and induces only weak genital antibody responses. Studies of immune responses to genital infections such as gonorrhea also support the concept that, lacking mucosal immune inductive sites, the reproductive tract is ill-equipped to mount effective immune responses. METHOD OF STUDY: Intranasal (i.n.) and intravaginal (i.vag.) routes of immunization of mice with a protein antigen coupled to cholera toxin (CT) B subunit, or genetically engineered as chimeric proteins with the A2/B sunbunits of CT or type II heat-labile enterotoxin, were compared for their ability to induce specific antibody responses in vaginal fluids, saliva, and serum. RESULTS: Mice immunized i.n. developed substantially stronger vaginal immunoglobulin A (IgA) and immunoglobulin G (IgG) and serum IgG and IgA antibodies, than those immunized i.vag. which also failed to develop salivary antibodies. Vaginal antibody responses induced i.n. persisted for at least 1 year, and were recallable by booster immunization after a prolonged period. CONCLUSIONS: Such alternative strategies for inducing potent genital antibody responses offer the prospect of prophylactic immunization against genital infections. Further studies are required to evaluate their applicability to humans, and to comprehend the cellular and molecular mechanisms involved in delivering effective immune responses to the reproductive tracts. [source] Corneal and conjunctival findings after mitomycin C application in pterygium surgery: an in-vivo confocal microscopy studyACTA OPHTHALMOLOGICA, Issue 2 2009Andrey Zhivov Abstract. Purpose:, To perform a qualitative assessment of the topical side-effects of mitomycin C on cornea after pterygium surgery. Methods:,In-vivo confocal microscopy (Heidelberg Retina Tomograph II in combination with the Rostock Cornea Module) was performed in 10 patients with unilateral primary pterygium. Mitomycin C 0.02% was applied topically to seven eyes for 5 min intraoperatively and twice daily for 5 days postoperatively. Three eyes underwent surgery without application of cytostatic agent. Patient follow-up was 1 month. Results:, After application of mitomycin C, complete epithelialization of the operated zone was found 2 weeks after surgery. In-vivo confocal microscopy revealed signs of superficial punctate keratitis for 2 weeks in the central cornea only after application of mitomycin C. The presence of epithelial and stromal oedema in this group was noted for up to 2 weeks in the central cornea and for up to 4 weeks in the operated zone. In the control group, complete epithelialization was found after 1 week; there were no signs of oedema after 1 week in the central cornea or after 2 weeks in the operated zone. Leucocyte infiltration and increased Langerhans cell density were noted in both groups in the operated and central zones. Analysis of the conjunctiva revealed a decrease in goblet cell density following cytostatic application. Conclusion:, Local application of mitomycin C delays corneal epithelialization, and prolongs postoperative epithelial and stromal oedema in both the centre and periphery. Moreover, signs of punctate keratitis were noted 2 weeks after surgery in central intact cornea. Nevertheless, in-vivo confocal microscopy shows that these changes are reversible 4 weeks after application of mitomycin C 0.02%. [source] Local Applications of GM-CSF Induce the Recruitment of Immune Cells in Cervical Low-Grade Squamous Intraepithelial LesionsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2010Pascale Hubert Citation Hubert P, Doyen J, Capelle X, Arafa M, Renoux V, Bisig B, Seidel L, Evrard B, Bousarghin L, Gerday C, Boniver J, Foidart J-M, Delvenne P, Jacobs N. Local applications of GM-CSF induce the recruitment of immune cells in cervical low-grade squamous intraepithelial lesions. Am J Reprod Immunol 2010; 64: 126,136 Problem, Quantitative alterations of antigen-presenting cells (APC) in (pre)neoplastic lesions of the uterine cervix associated with human papillomavirus (HPV) infection suggest a diminished capacity to capture viral antigens and to induce a protective immune response. Method of study, To test whether a cervical application of GM-CSF could restore an immune response against HPV in women with cervical low-grade squamous intraepithelial lesions (LSIL), we performed two clinical trials with 11 healthy women and 15 patients with LSIL. Results, GM-CSF applications were well tolerated in all enrolled women, and no difference in toxicity between the treated and placebo groups was observed during the follow-up (until 30 months). Interestingly, in the GM-CSF treated group, a significant increase of APC and cytotoxic T-lymphocyte infiltration was observed in the cervical biopsies with no change in regulatory T cell numbers. All the HPV16+ patients exhibited an immune response against HPV16 after GM-CSF applications, as shown by NK and/or T cells producing IFN-, whereas no cellular immune response was observed before the treatment. Moreover, the anti-virus-like particles antibody titers also increased after the treatment. Conclusion, These encouraging results obtained from a limited number of subjects justify further study on the therapeutic effect of APC in cervical (pre)neoplastic lesions. [source] Delivery of small interfering RNA with a synthetic collagen poly(Pro-Hyp-Gly) for gene silencing in vitro and in vivoDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 8 2010Taro Adachi Silencing gene expression by small interfering RNAs (siRNAs) has become a powerful tool for the genetic analysis of many animals. However, the rapid degradation of siRNA and the limited duration of its action in vivo have called for an efficient delivery technology. Here, we describe that siRNA complexed with a synthetic collagen poly(Pro-Hyp-Gly) (SYCOL) is resistant to nucleases and is efficiently transferred into cells in vitro and in vivo, thereby allowing long-term gene silencing in vivo. We found that the SYCOL-mediated local application of siRNA targeting myostatin, coding a negative regulator of skeletal muscle growth, in mouse skeletal muscles, caused a marked increase in the muscle mass within a few weeks after application. Furthermore, in vivo administration of an anti-luciferase siRNA/SYCOL complex partially reduced luciferase expression in xenografted tumors in vivo. These results indicate a SYCOL-based non-viral delivery method could be a reliable simple approach to knockdown gene expression by RNAi in vivo as well as in vitro. [source] Density Functional Study of the Complexation Reaction of Sn(CH3)3X (X = F, Cl, Br and I) with Halide AnionsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 20 2003Frank De Proft Abstract The Lewis acid-base reaction between Sn(CH3)3X and Y, (with X, Y = F, Cl, Br and I) has been studied using quantum chemical calculations. Complexation energies were calculated at the Density Functional Theory (DFT) level and rationalized on the basis of a local application of the hard and soft acids and bases principle. It was observed that smaller differences in the local softness of the interacting sites in the Lewis acid and base correspond to stronger interactions. Moreover, the calculated sequences in complexation energies can be reproduced using equations containing chemical concepts introduced within the framework of conceptual density functional theory and rooted in the hard and soft acids and bases principle and referring only to the reactants. A method of treating the electronegativity and softness of the halide anions is presented based on a Taylor expansion of the electronegativity of the neutral halogens and the softness-polarizability proportionality. Experimental evidence for the calculated sequences was gathered from measured 117Sn chemical shifts and 1J (13C- 119/117Sn) coupling constant changes upon complexation. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Negative cross-talk between presynaptic adenosine and acetylcholine receptorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2006A. V. Shakirzyanova Abstract Functional interactions between presynaptic adenosine and acetylcholine (ACh) autoreceptors were studied at the frog neuromuscular junction by recording miniature end-plate potentials (MEPPs) during bath or local application of agonists. The frequency of MEPPs was reduced by adenosine acting on presynaptic adenosine A1 receptors (EC50 = 1.1 µm) or by carbachol acting on muscarinic M2 receptors (EC50 = 1.8 µm). However, carbachol did not produce the depressant effect when it was applied after the action of adenosine had reached its maximum. This phenomenon implied that the negative cross-talk (occlusion) had occurred between A1 and M2 receptors. Moreover, the occlusion was receptor-specific as ATP applied in the presence of adenosine continued to depress MEPP frequency. Muscarinic antagonists [atropine or 1-[[2-[(diethylamino)methyl)-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido [2,3-b][1,4]benzodiazepine-6-one) (AFDX-116)] had no effect on the inhibitory action of adenosine and adenosine antagonists [8-(p -sulfophenyl)theophylline (8-SPT) or 1,3-dipropyl-8-cyclopentylxanthine (DPCPX)] had no effect on the action of carbachol. These data suggested that membrane,delimited interactions did not occur between A1 and M2 receptors. Both carbachol and adenosine similarly inhibited quantal release triggered by high potassium, ionomycin or sucrose. These results indicated a convergence of intracellular pathways activated by M2 and A1 receptors to a common presynaptic effector located downstream of Ca2+ influx. We propose that the negative cross-talk between two major autoreceptors could take place during intense synaptic activity and thereby attenuate the presynaptic inhibitory effects of ACh and adenosine. [source] Electrophysiological and behavioural evidence for an antagonistic modulatory role of adenosine A2A receptors in dopamine D2 receptor regulation in the rat dopamine-denervated striatumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2000Ingrid Strömberg Abstract It has been shown that striatal adenosine A2A receptors can antagonistically interact with dopamine D2 receptors at the membrane level leading to a decrease in the affinity and efficacy of D2 receptors. Extracellular recordings and rotational behaviour were employed to obtain a correlate to these findings in an animal model of Parkinson's disease (PD). The recordings were performed in rats with unilateral 6-hydroxydopamine (6-OHDA)-induced catecholamine depletion. While recording in the dopamine-depleted striatum, local applications of the dopamine D2 agonist quinpirole reduced neuronal activity. However, when the adenosine A2A antagonist MSX-3 was applied simultaneously with quinpirole, the inhibition of neuronal firing seen after quinpirole alone was significantly potentiated (P < 0.001, n = 11). In contrast, local application of CGS 21680 attenuated the effect of quinpirole. The doses of MSX-3 and CGS 21680 used to achieve the modulation of quinpirole action had no effect per se on striatal neuronal firing. Furthermore, rotational behaviour revealed that MSX-3 dose-dependently increased the number of turns when administrated together with a threshold dose of quinpirole while no enhancement was achieved when MSX-3 was combined with SKF 38393. MSX-3 alone did not induce rotational behaviour. In conclusion, this study shows that low ineffective doses of MSX-3 enhance the effect of quinpirole on striatal firing rate, while the A2A agonist exerts the opposite action. This mechanism gives a therapeutic potential to A2A antagonists in the treatment of PD by enhancing D2 receptor function. [source] Experimental and computational investigation of three-dimensional mixed-mode fatigueFATIGUE & FRACTURE OF ENGINEERING MATERIALS AND STRUCTURES, Issue 1 2002S. C. Forth Experimental and computational methods were developed to model three-dimensional (3-D) mixed-mode crack growth under fatigue loading with the objective of evaluating proposed 3-D fracture criteria. The experiments utilized 7075-T73 aluminium forgings cut into modified ASTM E740 surface crack specimens with pre-cracks orientated at angles of 30, 45 and 60° in separate tests. The progress of the evolving fatigue crack was monitored in real time using an automated visualization system. In addition, the amplitude of the loading was increased at prescribed intervals to mark the location of the 3-D crack front for post-test inspection. In order to evaluate proposed crack growth equations, computer simulations of the experiments were conducted using a 3-D fracture model based on the surface integral method. An automatic mesher advanced the crack front by adding a ring of elements consistent with local application of fracture criteria governing rate and direction of growth. Comparisons of the computational and experimental results showed that the best correlation was obtained when KII and KIII were incorporated in the growth rate equations. [source] Successful treatment of keratoacanthoma centrifugum marginatum with local application of imiquimod creamINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2007Kiriaki Aroni MD No abstract is available for this article. [source] Cell proliferation and differentiation during fracture healing are influenced by locally applied IGF-I and TGF-,1: Comparison of two proliferation markers, PCNA and BrdUJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2003B. Wildemann Abstract Growth factors IGF-I and TGF-,1 are known to stimulate fracture healing. The purpose of this study was to investigate the role of locally applied IGF-I and TGF-,1 during the early phase of fracture healing (Days 5, 10, and 15 after fracture) on cellular processes like proliferation and differentiation in a rat model. Two different immunohistochemical markers were used to analyze cell proliferation: (1) injection of the thymidine analogue BrdU and subsequent immunohistochemical staining for BrdU-positive nuclei, and (2) the antibody against the "proliferating cell nuclear antigen" (PCNA). In comparison, both methods revealed similar results concerning the types of proliferating cells at the different time points and the two groups. Labeling indices of both methods showed very good correlation (e.g., rs: 0.887 and p < 0.001 at day 10 in the control group without growth factors). Comparison of the callus morphology and the proliferation rate showed differences during fracture healing due to the local application of IGF-I and TGF-,1 from coated implants. At Day 5 the callus of the group treated with growth factors displayed an earlier appearance of cartilage compared to the control group. This was accompanied by an onset of cell proliferation in chondrocytes. Likewise, at the later time points an enhanced maturation of the callus tissue and the proliferation pattern were detectable in the growth-factor group. These results indicate that local application of IGF-I and TGF-,1 accelerates early cellular processes during fracture healing. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 65B: 150,156, 2003 [source] Gentamicin used as an adjunct to GTRJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 5 2003An experimental study in rats Abstract Objectives: To evaluate in a discriminating "capsule" model whether local application of gentamicin may have an added effect on bone formation produced by Bio-Oss® and guide tissue regeneration (GTR). Material and Methods: Thirty male 3-month-old Wistar rats were used. After elevation of muscle-periosteal flaps, a rigid hemispherical Teflon capsule, loosely packed with 0.025 g of Bio-Oss® impregnated with 2 mg/ml gentamicin sulfate (Garamycin®), was placed with its open part facing the lateral bone surface of the mandibular ramus (test) in one side of the jaw. A capsule filled only with Bio-Oss® (control) was placed on the contralateral side of the jaw. After healing periods of 1, 2 and 4 months, groups of 10 animals were sacrificed and the specimens were processed for histological examination. The volumes of (1) the space created by the capsule, (2) newly formed bone, (3) Bio-Oss® particles, (4) loose connective tissue, and (5) acellular space in the capsule were estimated by a point-counting technique in three to four histological sections of each specimen, taken by uniformly random sampling. Results: The histological evaluation showed limited but increasing bone fill in the capsules from 1 to 4 months in both the test and control sides. After 4 months, the newly formed bone occupied 11.9% (CV: 0.39) of the space created by the capsules at the test sides versus 13.2% (CV: 0.41) at the control sides. There was no statistical significant difference between test and control specimens at any observation time (p>0.05). Conclusion: It is concluded that local application of gentamicin has no added effect on bone formation when combined with Bio-Oss® and GTR. Zussamenfassung Gentamycin als Adjunktiv zur GTR genutzt. Eine experimentelle Studie bei Ratten Ziele:Überprüfung in einem "unterscheidenden" Kapselmodell, ob die lokale Applikation von Gentamycin einen zusätzlichen Effekt bei der Knochenbildung, die durch Bio-Oss® bei der GTR hervorgerufen wurde, hat. Material und Methoden: 30 männliche 3monatige Wistar-Ratten wurden genutzt. Nach der Elevation von Muskel-Periost-Lappen wurde eine rigide halbsphärische Teflonkapsel, die locker mit 0,025 g von Bio-Oss®, was mit Gentamycinsulfat 2mg/ml (Garamycin®) imprägniert war, auf einer Seite des Unterkieferramus (Test) so platziert, dass der offene Teil zur lateralen Knochenoberfläche gerichtet war. Eine Kapsel, die nur mit Bio-Oss gefüllt war (Kontrolle), wurde auf der kontralateralen Seite des Kiefers platziert. Nach der Heilungsperiode von 1, 2 und 4 Monaten wurden Gruppen von 10 Tieren getötet und die Proben für die histologische Überprüfung aufbereitet. Das Volumen von 1) dem Spalt, der durch die Kapsel geschaffen wurde, 2) dem neu gebildeten Knochen, 3) den Bio-Oss Partikeln, 4) dem lockeren Bindegewebe und 5) dem azellulären Spalt in der Kapsel wurden mit einer Punktzähltechnik in 3 bis 4 histologischen Schnitten von jeder Probe unter Nutzung einer allgemeinen Zufallsauswahl bestimmt. Ergebnisse: Die histologische Überprüfung zeigte eine limitierte aber zunehmende Knochenfüllung in der Kapsel vom 1. zum 4. Monat sowohl in der Test- als auch der Kontrollseite. Nach 4 Monaten besetzte der neu gebildete Knochen 11,9% (cv: 0,39) des von der Kapsel geschaffenen Spaltes bei den Testseiten verglichen mit 13,2% (cv: 0,41) bei den Kontrollseiten. Es gab keine statistisch signifikante Differenz zwischen Test- und Kontrollproben zu irgendeiner Beobachtungszeit (p>0,05). Schlussfolgerung: Es wird geschlossen, dass die lokale Applikation von Gentamycin keinen zusätzlichen Effekt auf die Knochenbildung hat, wenn eine Kombination mit Bio-Oss und der GTR erfolgt. Résumé La gentamycine utilisée en association à la GTR. Une étude expérimentale chez le rat Le but de cette étude a été d'évaluer si l'application locale de gentamycine dans un modèle de capsule discriminatoire pouvait avoir un effet additionnel bénéfique sur la formation osseuse produite par le Bio-Oss® et la GTR. Cette étude a eu recours à trente rats Wistar mâles de trois mois. Après l'élévation de lambeaux muscle-périoste, une capsule en téflon hémisphérique rigide, remplie de manière lâche avec 0,025 g de Bio-Oss® imprégnée avec 2mg/ml de sulfate de gentamycine (Garamycin®) a été placée avec sa face ouverte en regard de la surface osseuse latérale de la branche mandibulaire (test) d'un côté de la mâchoire. Une capsule remplie uniquement de Bio-Oss® (contrôle) a été placée dans le site contralatéral. Après des périodes de guérison de un, deux et quatre mois, des groupes de dix animaux ont été tués et les spécimens analysés histologiquement. Les volumes de 1) l'espace créé par la capsule, 2) l'os néoformé, 3) les particules de Bio-Oss®, 4) le tissu conjonctif lâche et 5) l'espace acellulaire dans la capsule ont été estimés par la technique de comptage par points dans trois à quatre coupes histologiques de chaque échantillon, pris de manière uniformément et randomisée. L'évaluation histologique a montré une augmentation limitée d'os dans les caspsules de un à quatre mois tant dans les sites tests que contrôles. Après quatre mois l'os néoformé occupait 11,9% (cv : 0,39) de l'espace créé par les capsules au niveau des sites tests vs 13,2% (cv : 0,41) au niveau des contrôles. Il n'y avait aucune différence statistique entre les échantillons tests et contrôles à aucun des temps d'observation (p>0,05). L'application locale de gentamycine n'aurait donc aucun effet sur la formation osseuse lorsqu'elle est placée avec le Bio-Oss® en association avec la GTR. [source] The intra-oral translocation of periodontopathogens jeopardises the outcome of periodontal therapyJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2001A review of the literature Abstract Background: Although periodontitis has a multi-factorial aetiology, the success of its therapy mainly focuses on the eradication/reduction of the exogenous/endogenous periodontopathogens. Most of the species colonise several niches within the oral cavity (e.g. the mucosae, the tongue, the saliva, the periodontal pockets and all intra-oral hard surfaces) and even in the oro-pharyngeal area (e.g., the sinus and the tonsils). Methods: This review article discusses the intra-oral transmission of periodontopathogens between these niches and analyses clinical studies that support the idea and importance of such an intra-oral translocation. Results and conclusions: Based on the literature, the oro-pharyngeal area should indeed be considered as a microbiological entity. Because untreated pockets jeopardise the healing of recently instrumented sites, the treatment of periodontitis should involve "a one stage approach" of all pathologic pockets (1-stage full-mouth disinfection) or should at least consider the use of antiseptics during the intervals between consecutive instrumentations, in order to prevent a microbial translocation of periodontopathogens during the healing period. For the same reason, regeneration procedures or the local application of antibiotics should be postponed until a maximal improvement has been obtained in the remaining dentition. This more global approach offers significant additional clinical and microbiological benefits. Zusammenfassung Grundlagen: Obwohl die Parodontitis eine multifaktorielle Ätiologie hat, konzentriert sich der Erfolg ihrer Therapie hauptsächlich auf die Eliminierung/Reduktion der exogenen/endogenen Parodontalpathogene. Die meisten dieser Spezies kolonisieren verschiedene Nischen innerhalb der Mundhöhle (z.B. die Schleimhäute, die Zunge, den Speichel, die parodontalen Taschen und alle intraoralen Hartgewebe) und sogar den oro-pharyngealen Bereich (z.B. die Nebenhöhlen und die Tonsillen). Methoden: Dieser Übersichtartikel diskutiert die intraorale Übertragung von Parodontalpathogenen zwischen diesen Nischen und analysiert klinische Studien, die die Idee und Wichtigkeit dieser intraoralen Übertragung unterstützen. Ergebnisse und Schlussfolgerung: Auf der Grundlage der Literatur sollte der oro-pharyngeale Bereich in der Tat als eine mikrobiologische Einheit angesehen werden. Weil unbehandelte Taschen die Heilung von kürzlich instrumentierten Stellen gefährden, sollte die Behandlung der Parodontitis ein einzeitiges Vorgehen bei allen pathogenen Taschen beinhalten (einzeitige vollständige Mundhöhlen-Desinfektion). Oder es sollten wenigsten die Verwendung von antiseptischen Mitteln während der Intervalle zwischen aufeinanderfolgenden Instrumentierungen erwogen werden, um die mikrobielle Übertragung von Parodontalpathogenen während der Heilungsphase zu verhindern. Aus dem gleichen Grunde sollten regenerative Maßnahmen oder die lokale Applikation von Antibiotika so lange verschoben werden, bis eine maximale Verbesserung im restlichen Gebiss erzielt wurde. Dieser globalere Ansatz liefert zusätzliche signifikante klinische und mikrobiologische Vorteile. Résumé Origine: Bien que la parodontite ait une étiologie multifactorielle, le succès de son traitement repose principalement sur l'éradication/réduction des bactéries parodontopathogènes exogènes/endogènes. La plupart des espèces colonisent plusieurs niches au sein de la cavité buccale (par exemple, les muqueuses, la langue la salive, les poches parodontales et toutes les surfaces dures intraorales), et même dans la zone oro-pharyngée (par example, les sinus et les amygdales). Méthodes: Cette revue critique discute la transmission intra-buccale des pathogènes parodontaux entre ces niches et analyse les études clinique qui soutiennent l'idée et l'importance d'une telle translocation intra-buccale. Résultats et conclusions: D'après la littérature, la zone oro-pharyngée peut vraiment être considérée comme une entité microbiologique. Puisque les poches non traitées compromettent la cicatrisation des sites récemment instrumentés, le traitement de la parodontite devrait impliquer une approche en une étape de toutes les poches pathologiques (désinfection de toute la bouche en une étape) ou devrait au moins considérer l'utilisation d'antiseptiques pendant les intervals entre deux instrumentations successives, de façon à prévenir une translocation bactérienne des pathogènes parodontaux pendant la période de cicatrisation. Pour la même raison, les procédures de régénération ou les applications locales d'antibiotiques devraient être remises jusqu'à ce qu'une amélioration maximale ait été obtenue sur le reste de la denture. Cette approche plus globale donne des bénéfices cliniques et microbiologiques supplémentaires significatifs. [source] Thrombin attenuation is neuroprotective in the injured rat optic nerveJOURNAL OF NEUROCHEMISTRY, Issue 3 2001Igor Friedmann The functional loss that often follows injury of the mammalian CNS has been attributed not only to the immediate neural loss, but also to secondary neuronal degeneration caused by toxic biochemical mediators in the environment of the injured nerve. We report here that a high thrombin content, produced as a result of injury-induced activation of prothrombin, appears to be an important mediator of secondary damage. Measurement of post-traumatic neuronal survival in vivo revealed that post-traumatic local application of the thrombin inhibitor N -,-(2-naphthylsulphonylglycyl)-4-(d,l)-amidinophenylalanine piperidide acetate in the rat optic nerve subjected to mild partial crush injury left twice as many retinal ganglion cells with functioning axons as in controls. Thus, by readjusting thrombin activity, thereby possibly obtaining a moderate post-traumatic increase and thus gaining the benefit of thrombin without its toxic effects, it may be possible to create an environment that is more favourable towards post-traumatic survival. [source] 5-HT1B Receptor-Mediated Regulation of Serotonin Clearance in Rat Hippocampus In VivoJOURNAL OF NEUROCHEMISTRY, Issue 5 2000Lynette C. Daws Abstract: The 5-hydroxytryptamine (5-HT; serotonin) transporter (5-HTT) is important in terminating serotonergic neurotransmission and is a primary target for many psychotherapeutic drugs. Study of the regulation of 5-HTT activity is therefore important in understanding the control of serotonergic neurotransmission. Using high-speed chronoamperometry, we have demonstrated that local application of 5-HT1B antagonists into the CA3 region of the hippocampus prolongs the clearance of 5-HT from extracellular fluid (ECF). In the present study, we demonstrate that the 5-HT1B antagonist cyanopindolol does not produce this effect by increasing release of endogenous 5-HT or by directly binding to the 5-HTT. Dose-response studies showed that the potency of cyanopindolol to inhibit clearance of 5-HT was equivalent to that of the selective 5-HT reuptake inhibitor fluvoxamine. Local application of the 5-HT1A antagonist WAY 100635 did not alter 5-HT clearance, suggesting that the effect of cyanopindolol to prolong clearance is not via a mechanism involving 5-HT1A receptors. Finally, the effect of low doses of cyanopindolol and fluvoxamine to inhibit clearance of 5-HT from ECF was additive. These data are consistent with the hypothesis that activation of terminal 5-HT1B autoreceptors increases 5-HTT activity. [source] Recombinant human platelet-derived growth factor BB (rhPDGF-BB) and beta-tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat modelJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 8 2009Loay Al-Zube Abstract Diabetes mellitus is a common systemic disease that has been associated with poor fracture healing outcomes. The mechanism through which diabetes impairs bone regeneration is unknown. One possible mechanism may be related to either decreased or uncoordinated release of local growth factors at the fracture site. Indeed, previous studies have found reduced platelet-derived growth factor (PDGF) levels in the fracture callus of diabetic rats, suggesting that local application of PDGF may overcome the negative effects of diabetes and promote fracture healing. To test this hypothesis, low (22 µg) and high (75 ug) doses of recombinant human PDGF-BB (rhPDGF-BB) were applied directly to femur fracture sites in BB Wistar diabetic rats that were then compared to untreated or vehicle-treated animals. rhPDGF-BB treatment significantly increased early callus cell proliferation compared to that in control specimens. Low dose rhPDGF-BB treatment significantly increased callus peak torque values (p,<,0.05) at 8 weeks after fracture as compared to controls. High dose rhPDGF-BB treatment increased callus bone area at 12 weeks postfracture. These data indicate that rhPDGF-BB treatment ameliorates the effects of diabetes on fracture healing by promoting early cellular proliferation that ultimately leads to more bone formation. Local application of rhPDGF-BB may be a new therapeutic approach to treat diabetes-impaired fracture healing. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 1074,1081, 2009 [source] Glycine Receptors Involved in Acamprosate's Modulation of Accumbal Dopamine Levels: An In Vivo Microdialysis StudyALCOHOLISM, Issue 1 2010PeiPei Chau Background:, Glycine receptors (GlyRs) in the nucleus accumbens (nAc) and nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area (VTA) have been suggested to be involved in the positive reinforcing and dopamine elevating effects of ethanol. Recent studies have also shown that ethanol high-preferring rats substantially decrease their ethanol intake when treated with a glycine transporter 1 inhibitor (ORG 25935). Acamprosate, a drug used for relapse prevention in treatment of alcohol dependence, has also been demonstrated to elevate extracellular dopamine levels in the nAc. However, the underlying mechanism of action of acamprosate is not fully understood. Here we investigated whether acamprosate interferes with a neuronal circuitry that previously has been demonstrated to be involved in the dopamine elevating effects of ethanol and taurine. Methods:, In vivo microdialysis in freely moving rats was used to assess accumbal dopamine levels before and during local (nAc) or systemic administration of acamprosate. Results:, Perfusion of 0.5 mM acamprosate in the nAc significantly increased dopamine levels. Pretreatment either with 10 ,M strychnine in the nAc or 100 ,M mecamylamine in the VTA, completely antagonized the acamprosate-induced elevation of accumbal dopamine levels. Also, systemic acamprosate administration elevated accumbal dopamine output, an effect that was abolished by local (nAc) pretreatment with 10 ,M strychnine. Conclusions:, These results suggest that both systemic and local application of acamprosate elevate extracellular dopamine levels in the nAc by activating accumbal GlyRs, and, secondarily, tegmental nAChRs. [source] Effect of local application of cold or heat for relief of pricking painNURSING & HEALTH SCIENCES, Issue 3 2002Yuka Saeki RN, phdArticle first published online: 17 SEP 200 Abstract The present study was designed to determine the effect of the application of cold or heat on the sensation of pricking pain based on autonomic responses. Electrical stimulation was applied to the antebrachium or brachium of subjects as an artificial pricking pain, and skin blood flow (BF) and skin conductance level (SCL) at the fingertip were measured. Pain sensation was evaluated using the visual analog scale. Pain stimulation produced a significant increase in SCL and a significant decrease in BF at both the antebrachium and brachium. Application of cold to the stimulation site using an ice-water pack reduced BF and SCL responses and pain sensation. Application of heat using a hot water bottle caused a significant increase in pain sensation and enhancement of BF and SCL responses. These results suggest that application of cold promotes relief of pricking pain sensation and suppression of autonomic responses, and that application of heat has no such effect. It is important that nurses ascertain the type of pain or source of pain and take proper measures for its relief. [source] Role of photodynamic therapy in psoriasis: a brief reviewPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 5 2008Yasmeen K. Tandon Background and purpose: Photodynamic therapy (PDT) is a light treatment modality which involves either systemic or local application of a photosensitizing compound, which preferentially deposits in the target cells, and is then followed by selective illumination of the lesion with visible light. The purpose of this study was to review the literature to examine the success, side effects, and different protocols used thus far to treat psoriasis using PDT. Methods: A thorough review of the literature was performed and analyzed. Results and conclusions: After a thorough review of the literature, PDT remains a potential treatment for psoriasis. Clinical improvement has been observed in most studies. The major limiting factor seen in many of the studies was the side effect of pain and burning sensations associated with PDT. This highlights the need for other photosensitizers with better tolerability profiles. [source] Retroviral-based gene therapy with cyclooxygenase-2 promotes the union of bony callus tissues and accelerates fracture healing in the ratTHE JOURNAL OF GENE MEDICINE, Issue 3 2008Charles H. Rundle Abstract Background An in vivo gene therapy strategy was developed to accelerate bone fracture repair. Methods Direct injection of a murine leukemia virus-based vector targeted transgene expression to the proliferating periosteal cells arising shortly after fracture. Cyclooxygenase-2 (Cox-2) was selected because the transgene for its prostaglandin products that promote angiogenesis, bone formation and bone resorption, are all required for fracture healing. The human (h) Cox-2 transgene was modified to remove AU-rich elements in the 3,-untranslated region and to improve protein translation. Results In vitro studies revealed robust and sustained Cox-2 protein expression, prostaglandin E2 and alkaline phosphatase production in rat bone marrow stromal cells and osteoblasts transgenic for the hCox-2 gene. In vivo studies in the rat femur fracture revealed that Cox-2 transgene expression produced bony union of the fracture by 21 days post-fracture, a time when cartilage persisted within the fracture tissues of control animals and approximately 1 week earlier than the healing normally observed in this model. None of the ectopic bone formation associated with bone morphogenetic protein gene therapy was observed. Conclusions This study represents the first demonstration that a single local application of a retroviral vector expressing a single osteoinductive transgene consistently accelerated fracture repair. Copyright © 2007 John Wiley & Sons, Ltd. [source] Concentration Gradient Along the Scala Tympani After Local Application of Gentamicin to the Round Window Membrane,THE LARYNGOSCOPE, Issue 7 2007Stefan K. Plontke MD Abstract Objectives: The distribution of gentamicin along the fluid spaces of the cochlea after local applications has never previously been demonstrated. Computer simulations have predicted that significant basal-apical concentration gradients might be expected, and histologic studies indicate that hair cell damage is greater at the base than at the apex after local gentamicin application. In the present study, gradients of gentamicin along the cochlea were measured. Methods: A recently developed method of sampling perilymph from the cochlear apex of guinea pigs was used in which the samples represent fluid originating from different regions along the scala tympani. Gentamicin concentration was determined in sequential apical samples that were taken after up to 3 hours of local application to the round window niche. Results: Substantial gradients of gentamicin along the length of the scala tympani were demonstrated and quantified, averaging more than 4,000 times greater concentration at the base compared with the apex at the time of sampling. Peak concentrations and gradients for gentamicin varied considerably between animals, likely resulting from variations in round window membrane permeability and rates of perilymph flow. Conclusions: The large gradients for gentamicin demonstrated here in guinea pigs account for how it is possible to suppress vestibular function in some patients with a local application of gentamicin without damaging auditory function. Variations in round window membrane permeability and in perilymph flow could account for why hearing losses are observed in some patients. [source] Benchmarking habitat quality: observations using River Habitat Survey on near-natural streams and rivers in northern and western EuropeAQUATIC CONSERVATION: MARINE AND FRESHWATER ECOSYSTEMS, Issue S1 2010Paul J. Raven Abstract 1.Some ecological effects of physically modifying rivers are still unclear, partly due to scale factors, but also because the character of high quality habitat is poorly understood. 2.Surveys at 278 sites on 141 near-natural streams and rivers in northern and western Europe were carried out between 1994 and 2009 to benchmark the habitat quality assessment system used for River Habitat Survey (RHS). 3.The objectives were to establish if RHS was suitable outside the UK, investigate if 500 m was still valid as the survey length, suggest a benchmarking strategy and recommend improvements to habitat quality assessment protocols. 4.Some modifications to RHS are needed to take account of differences in hydrological conditions, land-use and, most importantly, riparian habitat structure found in mainland Europe. 5.On average, 82,87% of channel attributes and 87,98% of channel and bank features were recorded within the first of consecutive RHS sites, confirming that 500 m is an effective sample length for characterizing small rivers. 6.Stream-flow character appeared to influence the distribution of several in-channel features, with greater diversity and between-site variation associated with rivers of mixed flow-types. To account for local variation and for effective use of survey time, it is recommended that two or more consecutive RHS sites are used for benchmarking purposes. 7.A suite of assessment protocols with agreed criteria and analytical rules, linked to specific objectives (e.g. nature conservation, geomorphic condition), is needed to establish the character and habitat quality of rivers in a consistent fashion. 8.A multi-discipline benchmarking programme using hydro-ecological regions in Europe would build on existing knowledge and help to improve both the inter-calibration and local application of quality assessment protocols. Data-sharing by hydrologists, river ecologists and fluvial geomorphologists would improve the basis for managing rivers in support of the European Water Framework Directive and Habitats Directive. Copyright © 2010 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||