Survival of transplanted neural stem/progenitor cells (NSPC) is limited after spinal cord injury (SCI). This thesis tested whether ephrin-B3 could enhance the survival of spinal cord derived NSPC because ephrin-B3 enhanced the survival of endogenous NSPC in the mouse brain. Preclustered ephrin-B3-Fc was tested, and preclustered Fc fragments and phosphate-buffered saline (PBS) were used as controls. This study showed that spinal cord derived NSPC and normal and injured rat spinal cord expressed EphA4 receptors. In culture, ephrin-B3-Fc increased the survival of NSPC at 1µg/mL (p<0.05), but Fc fragments reduced NSPC survival dose-dependently. In the injured spinal cord, infusion of ephrin-B3-Fc increased the proliferation of endogenous ependymal cells compared with infusion of PBS (p<0.05). However, in the injured cord, infusion of either ephrin-B3-Fc or Fc fragments caused a 20-fold reduction in the survival of transplanted NSPC (p<0.001). Thus, after SCI, ephrin-B3-Fc and Fc fragments are toxic to transplanted NSPC.

Survival of transplanted neural stem/progenitor cells (NSPC) is limited after spinal cord injury (SCI). This thesis tested whether ephrin-B3 could enhance the survival of spinal cord derived NSPC because ephrin-B3 enhanced the survival of endogenous NSPC in the mouse brain. Preclustered ephrin-B3-Fc was tested, and preclustered Fc fragments and phosphate-buffered saline (PBS) were used as controls. This study showed that spinal cord derived NSPC and normal and injured rat spinal cord expressed EphA4 receptors. In culture, ephrin-B3-Fc increased the survival of NSPC at 1µg/mL (p<0.05), but Fc fragments reduced NSPC survival dose-dependently. In the injured spinal cord, infusion of ephrin-B3-Fc increased the proliferation of endogenous ependymal cells compared with infusion of PBS (p<0.05). However, in the injured cord, infusion of either ephrin-B3-Fc or Fc fragments caused a 20-fold reduction in the survival of transplanted NSPC (p<0.001). Thus, after SCI, ephrin-B3-Fc and Fc fragments are toxic to transplanted NSPC.

The aim of this thesis was to introduce the intrathecal baclofen delivery method and assessment of its efficacy on patients with severe spasticity. It is an invasive spasticity affecting method which uses an abdominally implanted programmable infusion pump connected with a catheter inserted in the spinal canal. The pump delivers baclofen to the cerebrospinal fluid (baclofen is the central myorelaxans). This method reduces adverse effects of the drug, however it is an invasive method, that can bring various complications. In the practical part, I evaluated one patient with spinal spasticity before and after the treatment initiation. The spasm frequency was decreased by 2 points. The muscular tone measured by the Ashworth scale was decreased by 0,5 point, by 0,7 according to the modified Ashworth scale. Powered by TCPDF (www.tcpdf.org)

Le projet porte sur l’étude de l’effet de l’eugénol, composant principal du clou de girofle, sur la douleur neuropathique. L’objectif principal du projet était de déterminer la contribution du système nerveux central dans l’effet analgésique de l’eugénol. Lors d’une étude préliminaire, la pénétrabilité de l’eugénol a été évaluée dans le système nerveux central du rat. Des échantillons de sang, de cerveau et de moelle épinière ont été prélevés et les concentrations d’eugénol dans ces différents tissus ont été analysées à l’aide d’un spectromètre de masse. Les résultats ont montré que l’eugénol pénètre bien le système nerveux central avec une distribution plus importante dans la moelle épinière. Après l’induction de la douleur neuropathique à des rats Sprague-Dawley par le modèle de ligatures du nerf sciatique, des injections intrathécales d’eugénol furent réalisées afin d’évaluer l’effet central de l’eugénol. La plus forte dose d’eugénol a atténué l’allodynie secondaire après 15min, 2h et 4h et a aussi amélioré l’hyperalgésie thermique après 2h et 4h. Ces résultats confirment l’hypothèse que l’eugénol atténue les deux aspects de la douleur neuropathique que sont l’allodynie et l’hyperalgésie. Les injections au niveau lombaire permettent de penser que l’eugénol, un agoniste/antagoniste des récepteurs vanilloïdes pourrait diminuer la douleur neuropathique en agissant notamment au niveau des récepteurs vanilloïdes situés dans la corne dorsale de la moelle épinière. / The project is based on the study of the effects of eugenol, the main component of clove oil, on neuropathic pain. The main objective was to determine the central effect of eugenol. In a preliminary study we evaluated the penetrability of eugenol in the central nervous system of rats. Blood, brain and spinal cord samples were collected and concentrations were determined by mass spectrometry. Brain-toplasma and spinal cord-to-plasma ratios suggest that eugenol penetrates the central nervous system of rats relatively well, with a preferential distribution in the spinal cord. Following the induction of neuropathic pain in male Sprague-Dawley rats using the sciatic nerve ligation model, intrathecal injections of eugenol were done to evaluate the central effect of eugenol. Treatment with the high dose of eugenol significantly decreased secondary mechanical allodynia measured by the Von Frey test after 15min, 2h and 4h and improved thermal hyperalgesia measured by the Hargreaves device after 2h and 4h. Results support the hypothesis that eugenol may alleviate neuropathic pain, both allodynia and hyperalgesia. Eugenol, a vanilloid agonist/antagonist may therefore reduce neuropathic pain by acting on vanilloid receptors at the level of the dorsal horn of the spinal cord.

Made available in DSpace on 2014-12-17T15:38:52Z (GMT). No. of bitstreams: 1 EdianaROG_DISSERT.pdf: 2182777 bytes, checksum: a6c802e96d340606dfb3cbb335b79787 (MD5) Previous issue date: 2011-04-01 / The present work investigated the cognitive operation of children diagnosed with acute lymphoblastic leukaemia (ALL), accompanied at pediatric oncologic institutions at the city of Natal/RN. Had participated in this study twenty children, of both sexes, between six and twelve years old, with the ALL diagnostic, who were in treatment (n=10) and out of treatment for at least one year (n=10) and were submitted exclusively to chemotherapy as CNS prophylaxis. The utilized protocol of neuropsychological evaluation covered the following cognitive abilities: intellective capability, attentional and memory systems, and executive functions. Data was analyzed through descriptive and inferential measures, with the support of the Mann-Whitney U Test and T-test, considering the influence of the variables sex, age at diagnostic and the past time since the beginning of the treatment over children s performance. The intellective capability evaluation showed low score to the out-of-treatment groups, female and children under five years old to the diagnostic. In concern of attentional systems, groups showed the expected performance. In a relevant way, in the evaluation of executive functions, were found reduced scores within all groups, especially inside the in-treatment group. Memory evaluation pointed to reduced performance in items concerning to learning evolution and spontaneous evocation after interference to the several groups. It can be concluded, reffer to the occurrence of transitory and permanent impact associated to the intrusion of chemotherapic components during the maturational course of the CNS. It s expected that the present investigation and the development of similar studies enable major comprehension about the mode, extension and repercussion of these damages subsidizing the development of strategies which may minimize them and provide better xxiii life quality to this clinical subgroup / O presente trabalho investigou o funcionamento cognitivo de crian?as diagnosticadas com Leucemia Linf?ide Aguda (LLA) acompanhadas por institui??es oncol?gicas pedi?tricas no munic?pio de Natal/RN. Participaram deste estudo 20 crian?as diagnosticadas com LLA, de ambos os sexos, com idades entre seis e doze anos, que estavam em tratamento (n=10) e fora de tratamento h? pelo menos 1 ano (n=10), submetidas exclusivamente ? quimioterapia como profilaxia do SNC. O protocolo de avalia??o neuropsicol?gica utilizado contemplou as seguintes habilidades cognitivas: capacidade intelectiva, sistemas atencionais e de mem?ria e fun??es executivas. Os dados foram analisados atrav?s de medidas descritivas e inferenciais com o aux?lio do Teste U de Mann-Whitney e do Teste t, considerando-se a influ?ncia das vari?veis sexo, idade ao diagn?stico e tempo decorrido desde o in?cio do tratamento sobre o desempenho das crian?as. A avalia??o da capacidade intelectiva revelou baixas pontua??es para os grupos fora de tratamento, sexo feminino e crian?as menores de cinco anos ao diagn?stico. Quanto aos sistemas atencionais os grupos apresentaram desempenho dentro do esperado. De forma relevante, na avalia??o das fun??es executivas foram encontradas pontua??es reduzidas em todos os grupos, com destaque para o grupo em tratamento. A avalia??o da mem?ria indicou desempenho rebaixado em itens concernentes ? evolu??o da aprendizagem e evoca??o espont?nea ap?s interfer?ncia para os diversos grupos. Conclui-se que estas informa??es aludem ? ocorr?ncia de impactos transit?rios e permanentes associados ? intrus?o de componentes quimioter?picos no curso maturacional do SNC. Espera-se que a presente investiga??o e o desenvolvimento de estudos semelhantes possibilitem maior compreens?o acerca da modalidade, extens?o e repercuss?o de tais preju?zos, subsidiando o desenvolvimento de xxi estrat?gias que possam minimiz?-los e proporcionar maior qualidade de vida para este subgrupo cl?nico

Traumatic spinal cord injury (SCI) is a devastating condition for which there is no effective clinical treatment. Neuroprotective molecules that minimize tissue loss have shown promising results; however systemic delivery may limit in vivo benefits due to short systemic half-life and minimal passage across the blood-spinal cord barrier. To overcome these limitations, an injectable intrathecal delivery vehicle comprised of hyaluronan and methylcellulose (HAMC) was developed, and previously demonstrated to be safe and biocompatible intrathecally. Here, HAMC was determined to persist in the intrathecal space for between 4-7 d in vivo, indicating it as an optimal delivery system for neuroprotective agents to reduce tissue degeneration after SCI. HAMC was then investigated as an in vivo delivery system for two neuroprotective proteins: erythropoietin (EPO) and fibroblast growth factor 2 (FGF2). Both proteins demonstrated a diffusive release profile in vitro and maintained significant bioactivity during release. When EPO was delivered intrathecally with HAMC to the injured spinal cord, reduced cavitation in the tissue and significantly improved neuron counts were observed relative to the conventional delivery strategies of intraperitoneal and intrathecal bolus. When FGF2 was delivered intrathecally from HAMC, therapeutic concentrations penetrated into the injured spinal cord tissue for up to 6 h. Poly(ethylene glycol) modification of FGF2 significantly increased the amount of protein that diffused into the tissue when delivered similarly. Because FGF2 is a known angiogenic agent, dynamic computed tomography was developed for small animal serial assessment of spinal cord hemodynamics. Following SCI and treatment with FGF2 from HAMC, moderate improvement of spinal cord blood flow and a reduction in permeability were observed up to 7 d post-injury, suggesting that early delivery of neuroprotective agents can have lasting effects on tissue recovery. Importantly, the entirety of this work demonstrates that HAMC is an effective short-term delivery system for neuroprotective agents by improving tissue outcomes following traumatic SCI.

Traumatic spinal cord injury (SCI) is a devastating condition for which there is no effective clinical treatment. Neuroprotective molecules that minimize tissue loss have shown promising results; however systemic delivery may limit in vivo benefits due to short systemic half-life and minimal passage across the blood-spinal cord barrier. To overcome these limitations, an injectable intrathecal delivery vehicle comprised of hyaluronan and methylcellulose (HAMC) was developed, and previously demonstrated to be safe and biocompatible intrathecally. Here, HAMC was determined to persist in the intrathecal space for between 4-7 d in vivo, indicating it as an optimal delivery system for neuroprotective agents to reduce tissue degeneration after SCI. HAMC was then investigated as an in vivo delivery system for two neuroprotective proteins: erythropoietin (EPO) and fibroblast growth factor 2 (FGF2). Both proteins demonstrated a diffusive release profile in vitro and maintained significant bioactivity during release. When EPO was delivered intrathecally with HAMC to the injured spinal cord, reduced cavitation in the tissue and significantly improved neuron counts were observed relative to the conventional delivery strategies of intraperitoneal and intrathecal bolus. When FGF2 was delivered intrathecally from HAMC, therapeutic concentrations penetrated into the injured spinal cord tissue for up to 6 h. Poly(ethylene glycol) modification of FGF2 significantly increased the amount of protein that diffused into the tissue when delivered similarly. Because FGF2 is a known angiogenic agent, dynamic computed tomography was developed for small animal serial assessment of spinal cord hemodynamics. Following SCI and treatment with FGF2 from HAMC, moderate improvement of spinal cord blood flow and a reduction in permeability were observed up to 7 d post-injury, suggesting that early delivery of neuroprotective agents can have lasting effects on tissue recovery. Importantly, the entirety of this work demonstrates that HAMC is an effective short-term delivery system for neuroprotective agents by improving tissue outcomes following traumatic SCI.

No description available.

Le projet porte sur l’étude de l’effet de l’eugénol, composant principal du clou de girofle, sur la douleur neuropathique. L’objectif principal du projet était de déterminer la contribution du système nerveux central dans l’effet analgésique de l’eugénol. Lors d’une étude préliminaire, la pénétrabilité de l’eugénol a été évaluée dans le système nerveux central du rat. Des échantillons de sang, de cerveau et de moelle épinière ont été prélevés et les concentrations d’eugénol dans ces différents tissus ont été analysées à l’aide d’un spectromètre de masse. Les résultats ont montré que l’eugénol pénètre bien le système nerveux central avec une distribution plus importante dans la moelle épinière. Après l’induction de la douleur neuropathique à des rats Sprague-Dawley par le modèle de ligatures du nerf sciatique, des injections intrathécales d’eugénol furent réalisées afin d’évaluer l’effet central de l’eugénol. La plus forte dose d’eugénol a atténué l’allodynie secondaire après 15min, 2h et 4h et a aussi amélioré l’hyperalgésie thermique après 2h et 4h. Ces résultats confirment l’hypothèse que l’eugénol atténue les deux aspects de la douleur neuropathique que sont l’allodynie et l’hyperalgésie. Les injections au niveau lombaire permettent de penser que l’eugénol, un agoniste/antagoniste des récepteurs vanilloïdes pourrait diminuer la douleur neuropathique en agissant notamment au niveau des récepteurs vanilloïdes situés dans la corne dorsale de la moelle épinière. / The project is based on the study of the effects of eugenol, the main component of clove oil, on neuropathic pain. The main objective was to determine the central effect of eugenol. In a preliminary study we evaluated the penetrability of eugenol in the central nervous system of rats. Blood, brain and spinal cord samples were collected and concentrations were determined by mass spectrometry. Brain-toplasma and spinal cord-to-plasma ratios suggest that eugenol penetrates the central nervous system of rats relatively well, with a preferential distribution in the spinal cord. Following the induction of neuropathic pain in male Sprague-Dawley rats using the sciatic nerve ligation model, intrathecal injections of eugenol were done to evaluate the central effect of eugenol. Treatment with the high dose of eugenol significantly decreased secondary mechanical allodynia measured by the Von Frey test after 15min, 2h and 4h and improved thermal hyperalgesia measured by the Hargreaves device after 2h and 4h. Results support the hypothesis that eugenol may alleviate neuropathic pain, both allodynia and hyperalgesia. Eugenol, a vanilloid agonist/antagonist may therefore reduce neuropathic pain by acting on vanilloid receptors at the level of the dorsal horn of the spinal cord.

Introduction: Hysterectomy is the most common major gynecological operation in the Western World and approximately 5000 benign hysterectomies are performed in Sweden every year. Consequently it is a surgical procedure that affects many women. The procedure comprises challenges concerning perioperative health care, perceived postoperative symptoms, quality of life aspects and health economics. The concept of fast track is a multimodal strategy to reduce hormonal surgical stress response and achieve an enhanced postoperative recovery and is today considered to be evidence based in relation to colorectal surgery. Spinal anesthesia, as an important part of fast track, provides benefits of extended effect on analgesia and reduced postoperative morbidity. It is reasonable to believe that employing the strategies of fast track including spinal anesthesia could also provide substantial benefits for women requiring surgical removal of the uterus. Aims: To determine whether duration of hospital stay, presence and intensity of postoperative symptoms, duration of sick leave and cost-effectiveness differ between women undergoing benign fast track abdominal hysterectomy in spinal anesthesia with intrathecal morphine (SA) and in standard general anesthesia (GA). Material &amp; Methods: 180 women participated in this open randomized multicenter study with five participating hospitals in the southeast region of Sweden. One hundred and sixty two completed the study; 82 women were randomized to SA and 80 to GA. A fast track model comprising premedication without sedatives, intravenous fluid regulation, analgesics based on non-opioids, pre-emptive antiemetic therapy, early enteral nutrition and mobilization and standard criteria for discharge were used. End points were duration of hospital stay, use of analgesics, perceived postoperative symptoms, occurrence of postoperative complications, duration of sick leave and health economic evaluations. Results: Duration of hospital stay did not differ between the two modes of anesthesia. Vomiting and pruritus occurred significantly more often after SA. Complication rates did not differ between groups. Women with SA experienced less overall discomfort and had a reduced need for opioids postoperatively. Abdominal pain, drowsiness and fatigue occurred less often and with lower intensity among the women in the SA group. Health related quality of life improved faster and the duration of sick leave was shorter in women after SA. Total costs (hospital costs plus costs for productivity loss) were lower for the SA group. Within the first 29 days after hysterectomy the women in the SA group gained more QALYs than women in the GA group. Conclusions: The duration of hospitalisation after fast track abdominal hysterectomy was less than 50 hours and mode of anesthesia did not influence this. SA displayed considerable advantages regarding postoperative symptoms and recovery. SA was considered cost-effective in comparison with GA due to lower total costs and more QALYs gained. Our study indicates that SA should be recommended as the first choice of anesthesia in benign abdominal hysterectomy.