A dissertation presented in partial compliance with the requirements for the Master's Degree in Technology: Chiropractic, Technikon Natal, 2000. / The literature shows neck pain, including cervical facet syndrome, to be a common problem. It also provides evidence that inflammation plays a role in cervical facet pathology. Prescription of nonsteroidal anti-inflammatory drugs (NSAIDs) is the first line treatment of allopathic physicians for neck pain. Traumeel S is a complex of homoeopathic remedies indicated in a variety of anti-inflammatory, traumatic and degenerative disorders. It has been clinically shown that Traumeel S is effective in the treatment of inflammation. There is a paucity of clinical research into the treatment of acute neck pain, including cervical facet syndrome, with antiinflammatory agents. The aim of this study was to compare the relative effectiveness of piroxicam, an NSAID, with Traumeel S in the treatment of acute cervical facet syndrome. The study was a double-blind, comparative, clinical trial. Fifty consecutive patients complying with all inclusion criteria were randomly assigned to either the Traumeel S group or the piroxicam group. Each patient in the NSAID group received 40 mg of piroxicam per day for the first two days and 20 mg per day for the following 5 days. The Traumeel S group received the same dosage of placebo piroxicam capsules and 3 Traumeel S tablets in crushed form, per day. Placebo Traumeel Stablets, also in crushed form, were taken 3 times a day by the NSAID group to facilitate blinding. III Patients were assessed on days 1, 3 and 7 of the trial. Subjective assessment involved two questionnaires: the CMCC Neck Disability Index, and the NRS-101 / M

A dissertation submitted to the Faculty of Health in partial compliance with the requirements for a Master's Degree in Technology: Chiropractic,Technikon Natal, 2001. / The purpose of this study was to evaluate Piroxicam versus Protease administration, in terms of subjective and objective clinical findings, in order to determine the effectiveness of each approach in the treatment of grade 1 and 2 acute ankle inversion sprains. The study was a prospective, randomized, double blinded, controlled study. The study involved 30 subjects, 15 in each group which were selected from the general population. One group received Protease and strapping while the other group two received Piroxicam and strapping. Patients received 3 treatments over a period of one week. Patients in the Protease group received 1200mg (3 x 400mg) of Protease daily before meals for seven days. Patients in the Piroxicam group received 40mg (2 x 20mg) of Piroxicam for the first two days, and then 20mg (1 x 20mg) for the following five days, administered with meals. All patients were taught how to apply an elastic crepe bandage to the ankle, which was to be used at all times, except during bathing for the duration of the study / M

This study investigated the expression and activity of tissue transglutaminase (tTG) in human umbilical vein endothelial cells (HUVEC) and vessel wall. tTG was located in the SMC and sub-endothelium of normal vessels. Cross-linking activity was also in this area. Vessels with atherosclerotic plaque showed increased staining for tTG and cross-links. Positive staining for tTG was located in the SMC, neointima, macrophages and the fibrous cap. Most cross-linking activity was observed in the fibrous cap, and cross-linking was observed around macrophages and smooth muscle cells. Cross-linking activity was also observed with incorporation of a labelled cross-linking substrate into vessel sections. Free tTG could be extracted from the vessel wall. HUVEC expressed 10 g tTG/mg total protein. tTG was detected in cell lysate and extracellular matrix, but not in the culture supernatant. Thrombin up-regulated tTG expression at both the mRNA and protein level. Optimal up-regulation was at a thrombin concentration of 1 U/ml The up-regulation by thrombin was dependent on thrombin activity, and was mediated through the thrombin receptor, protease-activated receptor 1 (PAR-1). Cross-linking activity was also increased after thrombin treatment, measured with a microtitre plate assay and an in situ assay. The specific activity of tTG increased after thrombin treatment. Thrombin treatment increased the level of tTG in the HUVEC ECM. Treatment of HUVEC with PMA reduced the expression of tTG mRNA, reduced the level of tTG protein, but increased the tTG cross-linking activity compared to untreated cells.

No description available.

Les Maladies Inflammatoires Chroniques de l’Intestin (MICI) comprennent la maladie de Crohn (MC) et la rectocolite hémorragique (RCH). Ce sont des inflammations chroniques du tube digestif dont les causes sont inconnues. Une meilleure connaissance de leur épidémiologie pourrait orienter vers des pistes étiologiques. Jusqu’à la création du Registre EPIMAD en 1988, il n’existait en France aucune donnée d’incidence. Nous avons créé en 1988 une étude prospective d’incidence des MICI, reconnu «Registre» par l’Inserm et l’InVS en 1992. Le territoire couvert par Epimad comporte le Nord, le Pas-de-Calais, la Somme et la Seine-Maritime avec près de 6 millions d’habitants soit 9,3% de la population française. La collection des cas repose sur une collaboration multidisciplinaire incluant les gastroentérologues (GE) (libéraux, hospitaliers, adultes et pédiatres; n=262), les services d’Epidémiologie de Lille et Rouen, la plateforme d’aide méthodologique en Biostatistiques du CHRU de Lille et les Centres Hospitalo-Universitaires de Lille, Amiens et Rouen. Neuf enquêteurs se déplacent sur les lieux de consultation des GE et recueillent les informations nécessaires à la validation des diagnostics. Deux GE experts revoient chaque dossier indépendamment et posent le diagnostic final de MC ou RCH certaine, probable ou possible, de colite indéterminée, de colite aiguë ou de colite inclassée. Pour les cas atypiques et non classés, un suivi systématique est effectué pour le classement définitif (MICI ou non MICI). Un croisement des bases du Registre et des bases hospitalières est effectué une fois par an pour mesurer l’exhaustivité. 80% des cas incidents sont diagnostiqués par les GE libéraux, 13% par les GE des hôpitaux généraux et 7% par les GE universitaires. Entre 1988 et 2008, l’incidence moyenne des MICI était de 11,3/105 habitants (6,4 pour la MC, 4,4 pour la RCH et 0,5 pour IBDU). Pendant cette période, l’incidence de la MC a augmenté de 30% (100% chez l’adolescent) alors que celle de la RCH est restée stable. Le délai diagnostique médian était de 3 mois dans la MC et de 2 mois dans la RCH. Le pourcentage de patients ayant un diagnostic posé plus de 9 mois après l’apparition des symptômes a diminué avec le temps. La validité diagnostique dans les cas non classant d’emblée a été assurée par un suivi de 2 ans et a montré que seul l’âge < 40 ans était prédictif d’une évolution vers une MICI chez un patient présentant une colite aiguë. Nous avons aussi mis en évidence des présentations cliniques différentes en fonction de l’âge. Ainsi, chez l’adulte jeune, la MC est plus étendue que chez les sujets > 60 ans au diagnostic. Grâce à un nombre élevé de cas incidents, une hétérogénéité spatiale de l’incidence des MICI a été montrée dans les zones agricoles et suburbaines sans lien avec le niveau social des populations. En utilisant la méthode des statistiques de scan rajoutant la dimension temporelle à l’analyse spatiale, nous avons trouvé plusieurs clusters de sur et sous incidence constants dans le temps. Nos perspectives sont: 1) Poursuivre l’enregistrement des cas incidents et établir des données de prévalence; 2) Etudier les facteurs de risque environnementaux par des études d’épidémiologie analytique (corrélations écologiques, études cas témoins, études exposés-non exposés); 3) Etudier les facteurs de risque génétiques (fréquence des variants NOD2) dans la population du Registre; 4) Créer une étude prospective sur les paramètres prédictifs (profil génétique, profil métagénomique du microbiote intestinal, profil sérologique) de développer une MC dans une population de sujets à haut risque (sujets indemnes de MC âgés de 10 à 35 ans et appartenant à une famille multiplexe, à la descendance de formes conjugales ou à une paire de jumeaux discordants). Conclusions: EPIMAD est le plus gros Registre mondial sur les MICI en population générale, reconnu pour la qualité de ses travaux, rendu possible par la création d’un réseau-ville-hôpital unique. / Inflammatory Bowel Disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) are among the most serious and perplexing of digestive diseases. Their pathophysiology remains poorly understood. Geographic variations in the incidence of IBD could offer new clues about environmental risk factors. There were no data concerning the incidence of IBD in France. We created the first French prospective study on IBD incidence in 1988. This study became “Registre” recognized by Inserm and InVS in 1992. This prospective study was performed through all gastroenterologists (GE) (n=262) of the region of Nord, Pas-de-Calais, Somme and Seine-Maritime including near of 6 million of inhabitants corresponding to 9.3% of the whole French population. Collection of new cases is based on a close multidisciplinary collaboration including GE (whatever their practice), Epidemiology Unit of Hospital and University of Lille and Rouen, Biostatistics Unit of Lille Hospital and University and Academic Hospitals of Amiens, Lille and Rouen. Each GE referred patients consulting for the first time with clinical symptoms compatible with IBD. Data are collected by 9 interviewer practitioners present at the GE’s consulting room. Two independent experts GE assessed each case independently and made a final diagnosis of definite, probable, possible CD, UC or ulcerative proctitis (UP); Inflammatory Bowel Disease unclassifiable (IBDU); acute colitis or unspecified colitis. Possible cases of IBD, acute colitis and unspecified colitis are systematically followed-up and when a new event is recorded the chart is reviewed by the experts and a new final diagnosis is made. A control of the completeness collection is made each year by crossing data from Hospital Health databases. 80% of incident cases have been reported by private GE, 13% by general hospitals and 7% by academic centres. From 1988 to 2008 the mean annual incidence was 11.3/105 inhabitants for IBD including 6.4 for CD, 4.4 for UC and 0.5 for IBDU with a ratio CD/UC of 1.45. During this period CD incidence increased by 30% (100% in young adults) while that of UC remained stable. Valuable clinical information has been obtained; median time between onset of symptoms and diagnosis was 3 months in CD and 2 months in UC. The number of patients with a diagnosis delay > 9 months decreased over time. Age < 40 years at diagnosis was the only clinical predictor for subsequent IBD in patients with an initial diagnosis of acute colitis. Clinical presentation according to age at diagnosis may influence clinical course of IBD. In younger patients IBD had a more disabling course than in the elderly-onset IBD patients. Thanks to the large number of incident cases, we assessed spatial IBD incidence variation at the canton level and analyzed its association with a deprivation index. A spatial heterogeneity was found with a noteworthy predominance of CD in agricultural areas but no significant link with deprivation. We completed the spatial analysis using spatial scan statistics methods allowing revealing several time-constant (since 1988) clusters and other time-varying clusters. Perspectives: 1) To continue to record incident cases and establish prevalence data of IBD; 2) To study environmental risk factors using epidemiological analytic studies; 3) To study genetic risk factors establishing a geographic map of NOD2 variants in the EPIMAD’s area and 4) To assess the predictiveness of patient microbiota and host factors in a prospective, longitudinal study enrolling yet-healthy subjects at risk to develop CD (healthy patients aged 10-35 years and belonging to discordant twins, to offspring of IBD affected couples and to IBD multiplex families). In conclusion, since 1988, the EPIMAD registry has been recognized as a valuable tool for studies on genetic and environmental risk factors. It has also made it possible to reinforce networking between private practices, general and university hospitals at a regional level.

Increasing evidence highlights that term labour is an inflammatory event associated with increased production of pro-­‐inflammatory mediators and leukocyte influx into the intrauterine tissues. Preterm labour (PTL), defined as labour before 37 weeks gestation, is a major clinical problem, and preterm birth is the leading cause of neonatal mortality and morbidity worldwide. The causes of PTL are poorly understood, but intrauterine infection and inflammation have been shown to be important factors. Therefore, there is growing interest in the hypothesis that preterm labour may occur as a result of the premature activation of the inflammatory pathways normally initiated with labour at term, either idiopathically, or in response to a pathological intrauterine infection. The aim of this thesis was to use a mouse model of infection-­induced PTL to: characterise the local inflammatory and immune response to an intrauterine infection; investigate the potential of anti‐inflammatory agents to delay delivery of pups and to improve their survival; and to investigate the role of specific immune cell populations in infection-­induced preterm labour. To characterise the inflammatory and immune response to intrauterine infection, CD1 mice received an intrauterine injection of PBS vehicle or increasing doses of bacterial-­derived lipopolysaccharide (LPS) on day 17 of gestation. Time to delivery, and the number of live born pups were determined. Intrauterine administration of increasing doses of LPS dose-­dependently induced preterm labour and reduced the proportion of live born pups. Analysis of tissues harvested six hours post-­surgery demonstrated that in response to intrauterine LPS administration, there was increased expression of inflammatory cytokines and chemokines within the utero-­placental tissues, amniotic fluid and maternal serum; and an influx of neutrophils into the decidua, compared to mice receiving PBS. Given these results, the potential of anti‐inflammatory agents to delay LPS-­induced preterm delivery and improve pup survival was then investigated using the same mouse model. Prior to intrauterine LPS administration, mice were pre-­‐treated with epi-­lipoxin, BML-­111 (a stable lipoxin analogue), or IL-­10. Time to delivery was unaffected by pre-­treatment with the anti-­inflammatory agents, however epi-­lipoxin significantly increased the proportion of live born pups in mice delivering preterm, compared to mice receiving only LPS. To further investigate the role of immune cells in infection-­induced PTL, antibody-­based depletion strategies were used to selectively deplete specific immune cell populations to determine whether they played a causative role in LPS­‐induced preterm delivery. Despite successful depletion of macrophages or neutrophils, it was not found to significantly affect LPS-­induced preterm delivery, suggesting these immune cells are not required for the induction of preterm labour in response to intrauterine infection. However, it is likely that they contribute to the intrauterine inflammatory response as depletion resulted in altered inflammatory signalling within the intrauterine tissues. Collectively, this work has demonstrated that the presence of intrauterine bacterial LPS, as a surrogate model of infection, induces a robust inflammatory and immune response within the utero‐placental tissues that involves the increased production of inflammatory mediators and the influx of immune cells into the decidua, which ultimately leads to PTL. Whilst the anti-­inflammatory treatments tested here did not delay LPS-­induced PTL, epi-­lipoxin attenuated LPS-­induced mortality in pups born preterm, suggesting this anti‐inflammatory agent may be useful in protecting the fetus from the adverse effects of infection-­induced preterm birth. Using models such as the one described here, are vital to improving our understanding of the events regulating the induction of PTL and will ultimately aid the search for novel therapeutic options for the treatment of PTL.

The benefits of fish oil supplementation for inflammation based disorders has been well-documented,[1] prompting investigations into the pathways through which these benefits are achieved. This led Serhan et al. to the discovery of a new class of pro-resolution lipid mediators, termed resolvins .[2][3] There has subsequently been much research into their being a potential treatment for chronic inflammatory diseases such as asthma,[4] diabetes,[5] and arthritis.[6] The aim of this research was to study the bioactivity of resolvin E1 (RvE1) and its analogues; to do this a flexible and versatile route towards the chemical synthesis of RvE1 had to be developed, which would allow for easy modification of the stereochemistry of the C-C double bonds and hydroxyl groups, as well as producing fragments containing key functional groups. The first proposed route synthesised RvE1 from two key fragments termed the lactone and epoxide fragments. RvE1 contains three stereogenic hydroxyl groups, one with S configuration and two with R configuration. The epoxide fragment was to be converted into two adjacent sections of the RvE1 chain. The S-stereocentre was introduced via hydrolytic kinetic resolution using a Jacobsen s catalyst.[7] The two R-stereocentres were introduced via the chiral pool originating from 1,2:5,6-di-O-isopropylidene-D-mannitol. Unfortunately, problems were encountered late on in the synthesis of both fragments and therefore a new synthetic route had to be devised. The second proposed route synthesised RvE1 from two key fragments termed the alkyne and halide fragments. The S-stereocentre and one R-stereocentre were proposed to be introduced via asymmetric reduction of a ketone group. The other R-stereocentre was proposed to be synthesised with the use of chiral additives during an indium-mediated coupling reaction.[8] As work progressed on the halide fragment, the Lewis acid catalysed thermodynamic conversion of a branched chain homoallylic alcohol to its linear counterpart was trialled in order to obtain one of the conjugated diene system in RvE1. Using literature conditions for a similar system[9] this reaction was unsuccessful. The reaction mechanism was studied and a hypothesis was put forward that adding a catalytic amount of the aldehyde that the branched chain homoallylic alcohol was synthesised from to the reaction mixture would promote the thermodynamic conversion to the linear chain. These conditions were trialled on a number of different starting materials, leading to either an improvement in yield for the thermodynamic conversion, or the success of a previously unsuccessful conversion.

The study was initiated to examine magnesium intake, supplementation and their relation to inflammation. Magnesium is the second most abundant extracellular ion following potassium. Outside the cell, magnesium can be found in bone tissue, cardiac muscle tissue, other tissues and in the blood. Magnesium form compounds which operate in several essential metabolic processes in the body. Magnesium deficiency may have an impact on insulin resistance and endothelial dysfunction, which may result in an increased level of inflammation. Increased inflammation over a longer period has been seen to increase the risk of common lifestyle induced diseases such as diabetes type II and coronary heart diseases. The study of magnesium and its influence on inflammation is thereby becoming important and interesting for all societies and in their effort to find solutions to maintain and increase the well-being of its individuals. The study is a literature study based on searches made in One Search and Pub Med databases. A total of ten studies were included, five for magnesium intake and five for supplementation. The majority of the studies showed a significant correlation between increased magnesium intake, dietary and supplementary, with decreased levels of inflammatory biomarkers and hints that magnesium might have a role in the inflammation process. What needs to be taken into account is that fiber intake in two studies attenuated magnesium’s inverse relation to inflammation. In addition of a decrease in inflammatory biomarker levels the risk for developing diabetes type II seemed to decrease as well with an increased intake of magnesium in one of the studies. Further studies need to be executed in order to establish the role of magnesium in inflammation and optimal dosage for prevention of metabolic and cardiovascular diseases. / Studien undersöker magnesiumintag och supplementering med magnesium samt dess inverkan på inflammation. Magnesium är den vanligast förekommande jonen intracellulärt efter kalium.  Extracellulärt magnesium förekommer i benvävnad, hjärtmuskelvävnad och i blodet. Magnesium bildar ämnen som medverkar i flera viktiga metabola processer i kroppen. Magnesiumbrist kan ha en inverkan på insulin resistans och endotel dysfunktion som följaktligen skulle kunna resultera i en ökad nivå av inflammation. Ökad inflammation under en längre tid har visat sig öka risken för vanliga livsstilssjukdomar som diabetes typ II och hjärt- och kärlsjukdomar. Forskning om magnesium och dess effekt på inflammation blir därmed viktig och intressant för samhällen i deras strävan att hitta lösningar till att bibehålla och öka välmåendet hos populationen. Studien är en litteraturstudie och är grundad på sökningar via databaserna One Search och Pub Med. Totalt tio studier inkluderades i arbetet, fem som undersökte magnesiumintag och inflammation samt fem som undersökte supplementering av magnesium och inflammation. Majoriteten av studierna visade på en signifikant korrelation mellan ett ökat magnesiumintag, via kosten och kosttillskott, och minskade nivåer av biomarkörer för inflammation. Det antyder att magnesium kan ha en roll i inflammationsprocessen. I de två studier som mätte fiberintaget var relationen mellan magnesiumintag och inflammation försvagad. Utöver en minskning av biomarkörer för inflammation sågs en minskad risk för att utveckla diabetes typ II vid ett ökat magnesiumintag i en av studierna. Fler studier krävs för att fastställa magnesiums betydelse vid inflammation samt den optimala doseringen för prevention av metabola och kardiovaskulära sjukdomar.

University of Macau / Institute of Chinese Medical Sciences

BACKGROUND: Inflammatory bowel disease (IBD) is a group of conditions characterized by chronic inflammation of the gastrointestinal (GI) tract. A new diagnosis of IBD in children and adolescents can have significant psychosocial effects on both the patient and the family. Child and parental coping strategies play a crucial role in the adjustment to IBD, especially within the first year of the diagnosis. AIMS: The primary aim of the study was to assess the stability of coping measures over time in children and parents following a new pediatric IBD diagnosis. The study also aimed to assess the impact of parental coping on parental healthcare resource utilization for children with newly diagnosed IBD, as well as the impact of parental coping on anxiety, depression, and quality of life in children with newly diagnosed IBD. METHODS: This was a prospective, longitudinal cohort study at Boston Children’s Hospital (BCH) that focused on children and adolescents with newly diagnosed IBD, as well as their parents. Patients and their parents were approached at the time they enrolled in the study and then again about 12 months later as part of a one-year follow-up. At both time points, they were asked to fill out various questionnaires about psychological functioning and answer other questions about medical care. RESULTS: The study identified and encountered 465 IBD patients, of which 126 were eligible for recruitment. There were 70 patients and families who signed a consent form for enrollment, 55 who fully or partially completed the questionnaires at baseline, and only 5 who also completed the questionnaires at follow-up. Due to the limited number of participants who completed the questionnaires at follow-up, no definitive conclusions could be drawn about the stability of coping measures over time. Parental anxiety, parental depression, frequent parental stress, and difficult parental stress were all found to be positively correlated with healthcare utilization and negatively correlated with the child’s quality of life. Parental anxiety, frequent parental stress, and difficult parental stress were all found to be positively correlated with the child’s anxiety. Parental depression, frequent parental stress, and difficult parental stress were all found to be positively correlated with the child’s depression. CONCLUSION: Preliminary findings suggest that poor parental coping leads to decreased child quality of life and increased healthcare utilization, child anxiety, and child depression. A larger sample size is needed to accurately evaluate the stability of coping measures over time. The next steps for this study involve further examination of the impact of parental coping and enrollment of more patients and families.