Gotowa bibliografia na temat „25 hydroxyl”

The oxysterol, 25-hydroxycholesterol (25-HC), is important for sterol metabolism and emerging evidence suggests that 25-HC plays a more critical role in immunity and infection. However, the precise antiviral mechanism and the target of 25- HC remains unclear. Here efforts were made to investigate the link between viral infection and the triggering of the 25-HC associated interferon (IFN) response, and how this dynamically alters the endogenous level of 3-hydroxy- 3-methylglutaryl-CoA reductase (HMGCR), a key enzyme that catalyses the production of the precursor of cholesterol and oxysterols. In this thesis I have sought to specifically explore the temporal changes and role of HMGCR in DNA virus (cytomegalovirus) and RNA (Influenza) virus infections. I hypothesise that HMGCR is a target for 25-HC associated IFN-mediated host defence against viral infection. To characterise HMGCR and test this hypothesis, the following objectives were defined: (1). To establish an experimental system to quantitatively study the endogenous HMGCR protein level; (2). To investigate the mechanism of the down-regulation of HMGCR involved in the IFN-mediated innate immune response; (3). To study the behaviour of HMGCR in the influenza virus induced 25-HC associated IFN-mediated innate immune response; (4). To study the behaviour of HMGCR in the cytomegalovirus induced 25-HC associated IFN-mediated innate immune response. Chapter 3, describes establishing an experimental system for the quantification of endogenous HMGCR levels. Different protein detection methods, including a modified western blot protocol and immunostaining, were tested. The results of RNA interference of HMGCR demonstrate that under lipid-deficient condition with the supplementation of mevastatin (an HMGCR inhibitor) the modified western blot protocol specifically detects endogenous HMGCR. This chapter lays the foundational work for the temporal analysis and testing the role of HMGCR in infection. In Chapter 4, the mechanism of the degradation of HMGCR following 25-HC and IFN treatments, in wild-type and Ch25h−/− mouse bone marrow derived macrophages (BMDMs), was investigated. Similar to 25-HC, IFN-γ treatment results in the drop of both the transcript and protein abundance of HMGCR in wild-type BMDMs. Differential temporal analysis of RNA and protein alterations and the use of proteasome inhibitors reveals that both 25-HC and IFN-γ lead to a marked reduction of HMGCR protein via a proteasomal degradation mechanism within early times of treatments. Further, the immediate reduction of HMGCR levels induced by IFN-γ was completely abrogated in Ch25h−/− BMDMs. Hence, the reduction of HMGCR following IFN-γ treatment is due to the de novo synthesis in macrophages of 25-HC. However, the decrease of Hmgcr gene expression was observed in not only wild-type but also Ch25h−/− BMDMs, suggesting additional mechanisms for regulating Hmgcr RNA levels. These results demonstrate the mechanism of the down-regulation of HMGCR resulted from the induction of IFN response during viral infection, is only partially due the de novo synthesis of 25-HC. In chapter 5, influenza A virus was used to investigate the role of HMGCR in the IFN-mediated innate immune response. The inhibition of HMGCR by RNA interference inhibited viral growth, suggesting the requirement of HMGCR for optimal intracellular viral growth. Viral infection in wild-type murine BMDMs reduced the endogenous HMGCR levels. However, the reduction of HMGCR at early times was prevented in Ch25h−/− BMDMs. Intriguingly, the decrease of HMGCR at late time points was still observed in Ch25h−/− BMDMs. These results indicate that the down-regulation of HMGCR with influenza virus infection in BMDMs at early times is completely due to the de novo synthesis of 25-HC; whereas at late times alternative pathways or mechanisms exist. Additionally, human epithelial A549 cells and A549/PIV5-V cells that are deficient in STAT1 were used to study the role of IFN pathway in the down-regulation of HMGCR at late times during viral infection. Results from these studies show that at late times the reduction of HMGCR is due to IFN-independent mechanisms. Chapter 6, extends these investigations to the herpes virus murine cytomegalovirus and infection of BMDMs. HMGCR is known to be essential for cytomegaloviral infections and 25-HC, statin and RNAi inhibition of HMGCR restrict viral growth. 25-HC is shown to reduce HMGCR at immediate early times of infection. However, most notably, the down-regulation of HMGCR was also observed in Ch25h−/− BMDMs at late times with murine cytomegalovirus infected BMDMs. These results confirm that alternative pathways or mechanisms exist, playing roles in the crosstalk between cholesterol metabolism and innate immune response. Collectively, this study characterises the role of HMGCR in the 25-HC associated IFN-mediated host defence against viral infection. Results indicate that, in addition to the IFN-mediated host response, alternative pathways or other mechanisms also result in the down-regulation of HMGCR during viral infection. HMGCR is at the crossroad of different pathways or mechanisms, and is therefore not only targeted by 25-HC. Hence, further questions can be addressed from these results: (1). What are the alternative pathways or mechanisms for the down-regulation of HMGCR? (2). How do these pathways or mechanisms work in hosts’ immune system? Answering these questions can contribute to refining the pathway map of innate immunity and understanding the precise role of HMGCR, or even the sterol biosynthesis pathway, in hosts’ immune response against pathogens.

L'objectif de ce travail est d'acquerir des donnees thermodynamiques sur les especes hydrolysees et les complexes organiques des terre rares (tr), en vue de mieux comprendre leur comportement dans les eaux naturelles. Des mesures de solubilite d'hydroxydes solides de la et de gd, realisees dans une large gamme de ph(5-11) et de temperature (40-150\c), montrent que les especes hydrolysees intermediaires tr(oh) 2 +, tr(oh) 2 + et tr(oh) 3 o sont toujours negligeables par rapport aux ions tr 3 + et tr(oh) 4 -. Les constantes de dissociation ks 0 et ks 4 correspondantes sont determinees et extrapolees a 25\c. Ces donnees montrent la large predominance de l'espece tr 3 + dans toute la gamme de ph rencontres dans la plupart des milieux naturels (4-8) et permettent de calculer les proprietes thermodynamiques des ions trivalents la 3 +, gd 3 + et, pour la premiere fois, celles de la(oh) 4 - et gd(oh) 4 -. Ces resultats montrent que les valeurs de la premiere constante d'hydrolyse k 1 1, proposees dans la litterature sont largement surestimees. La stchiometrie et les constantes de stabilite des complexes formes par la 3 +, gd 3 + et yb 3 + avec les anions organiques carboxyliques acetate, malonate, o-phtalate et salicylate ont ete determinees entre 25 et 80\c par mesure potentiometrique. Parallelement, des mesures de solubilite d'hydroxydes de la et gd en presence d'acetate ont permis de valider les constantes deduites des mesures potentiometriques. Dans tous les cas, deux complexes permettent de modeliser les resultats experimentaux. Nos donnees, comparees a celles obtenues pour d'autres metaux et d'autres ligands, mettent en evidence le comportement chimique specifique des especes mono et dicarboxyliques. Enfin, une revue bibliographique des teneurs en tr dans les eaux de rivieres mondiales, nous permet de proposer un controle des teneurs en tr 3 + par la solubilite d'un phosphate solide et celui de la concentration totale en tr par leur adsorption sur la fraction colloidale (<0,2m) inorganique.

Sabe-se que a cada ano cerca de dois bilhões de pessoas consomem bebidas alcoólicas, e no Brasil há uma estimativa de que aproximadamente 11,2% da população é dependente de álcool, o que representa mais de cinco milhões de pessoas. Básicamente se pode dizer que todos os órgãos são afetados pela exposição crônica e aguda, mas as miopatias alcoólicas atingem de 1/3 a 2/3 dos alcoólatras e são as das doenças musculares mais frequentes. A literatura apresenta vários suplementos nutricionais que prometem melhora na performance de atividade físicas promovendo conservação ou hipertrofia das fibras musculares, mas estudos mais profundos tem demonstrado que apenas as suplementações de creatina e &#x3B2;- hidroxi-&#x3B2;-metilbutirato (HMB) demonstraram efeitos sobre a otimização dos ganhos de força e massa muscular, Os trabalhos com HMB afirmam que esta substância diminui a degradação proteica muscular e estimula a síntese proteica, entre outras atividades. Considerando os prejuízos causados pelo álcool no tecido muscular e os benefícios produzidos pelo HMB no mesmo tecido pensou-se na realização de um trabalho associando as duas substâncias para responder as seguintes perguntas: a-) o álcool e o HMB alteram do peso dos animais, atuando individualmente e em conjunto? b-) o álcool e o HMB alteram a área das fibras musculares do EDL e do sóleo, atuando individualmente e em conjunto? c-) se as alterações ocorrerem elas são semelhantes nos músculos EDL e sóleo? Para isso foram utilizados 25 ratos (Rattus novergicus), machos, adultos (com aproximadamente 90 dias de idade (407g) divididos em 4 grupos: Grupo Controle Placebo, Grupo Experimental Álcool (25%), Grupo &#x3B2;-Hidroxi &#x3B2;-Metilbutirato (0,3g/Kg) e Grupo Álcool + &#x3B2;-Hidroxi &#x3B2;- Metilbutirato. Foram retiradas amostras dos músculos sóleo e extensor longo dos dedos e submetidas a coloração de HE. Foi realizado a morfometria de duzentas fibras de cada músculo de cada animal. Estas fibras tiveram as suas áreas calculadas. Os dados obtidos foram submetidos ao tratamento estatístico. Os dados encontrados nesta pesquisa permitiram concluir que: : a-) o álcool alterou, de maneira negativa o peso dos animais, mas o HMB não, mesmo quando atuou em conjunto com o álcool, ou seja, o HMB não conseguiu anular o efeito negativo do álcool; b-) o álcool alterou, de maneira negativa a área das fibras dos músculos EDL e sóleo, e o HMB não, mas quando ele atuou em conjunto, conseguiu anular o efeito negativo do álcool; c-) as alterações produzidas pela ação do álcool e HMB, individualmente ou em conjunto foram semelhantes nos músculos EDL e sóleo.<br>It is known that every year about two billion people consume alcoholic beverages, and in Brazil there is an estimate that approximately 11.2% of the population is dependent on alcohol, which is more than five million people. Basically you can say that all organs are affected by chronic and acute exposure, but alcoholic myopathy reach 1/3 to 2/3 of alcoholics, and are the most frequent muscular diseases. The literature contains several nutritional supplements that promise improvement in physical activity performance promoting conservation or hypertrophy of muscle fibers, but further study has shown that only creatine supplementation and &#x3B2;-hydroxy-&#x3B2;-methylbutyrate (HMB) have shown effects on optimization the strength gains and muscle mass, works with HMB claim that this substance decreases muscle protein degradation and stimulates protein synthesis, among other activities. Considering the damage caused by alcohol in muscle tissue and the benefits produced by the HMB in the same fabric was thought in achieving a work combining the two substances to answer the following questions: a-) alcohol and HMB alter the weight of the animals, acting individually and together? b-) alcohol and HMB alter the area of the muscle fibers of the soleus and EDL individually and jointly acting? c) if changes occur they are similar in EDL and soleus muscles? For this we used 25 rats (Rattus norvegicus), adult male (approximately 90 days old (407 g) divided in 4 groups: Control Group Placebo Experiment Group Alcohol (25%), Group &#x3B2;-hydroxy &#x3B2;-methylbutyrate (0.3g / kg), and Group Alcohol + &#x3B2;-hydroxy &#x3B2;-methylbutyrate. soleus and samples were taken long extensor muscles of the fingers and subjected to HE staining. morphometry was performed two hundred fibers of each muscle of each animal. These fibers had calculated their areas the data were subjected to statistical analysis the data found in this study showed that: a-) alcohol changed in a negative way the weight of the animals, but the HMB not even when he served in together with the alcohol, i.e., HMB could not nullify the negative effects of alcohol; b) alcohol changed in a negative way the area of the fibers of the EDL and soleus muscles, and HMB not, but when he acted together, could nullify the negative effect of alcohol; c) the changes produced by the action of alcohol and HMB, individually or together were similar in EDL and soleus muscles.

Introduction: La prévalence de l'hypovitaminose D peut atteindre 90% chez les patients après une chirurgie bariatrique type dérivation bilio-pancréatique (DBP) malgré la supplémentation avec des méga-doses de vitamine D. Notre hypothèse est que la méthode de dosage immuno-compétitive courante de Roche pourrait ne pas reconnaître de façon équimolaire les deux formes de la 25-OH vitamine D (25-OH-D2 et 25-OH-D3), surestimant ainsi la prévalence du déficit en vitamine D et exposant ces patients, et plus particulièrement ceux supplémentés en D2, à un risque de toxicité à la vitamine D. Objectif: Notre objectif était de comparer deux méthodes de dosage sérique de la vitamine 25-OH-D totale : la méthode ECLIA de Roche et la méthode LC-MS/MS chez la population ayant eu une chirurgie bariatrique. Méthode: Il s’agit d’une étude transversale et corrélationnelle avec dosage sérique de la 25-OH-D dans trois groupes : un groupe contrôle de 48 sujets apparemment sains choisis aléatoirement au laboratoire de biochimie clinique et deux groupes de patients post-dérivation bilio-pancréatique un supplémenté en vitamine D3 (n=44) et l’autre en vitamine D2 (n=30). Les patients ont été recrutés au cours de leur visite de suivi à la clinique de l'obésité au CHUS et à l’IUCPQ. Le nombre d'échantillons par groupe a été établi selon les recommandations du Clinical and Laboratory Standard Institute (EPO9-A2-IR). L'étude comparative (régression linéaire, régression de Deming et le graphique des différences de Bland-Altman) a été réalisée en utilisant le logiciel Analyse-it en considérant p <0,05 comme statistiquement significatif. Résultats: La corrélation entre les deux méthodes était acceptable dans le groupe contrôle de sujets apparemment sains et dans le groupe post-DBP supplémenté en vitamine D3 avec des biais moyens respectifs de -1.7% et -9.2%. Cependant, cette corrélation était inacceptable dans le groupe post-DBP supplémenté en vitamine D2 avec un biais moyen de -45.3%. La méthode LC-MS/MS nous a permis de détecter quatre patients (13%) avec excès ou intoxication en vitamine D dans le groupe post-DBP supplémenté en D2, pour lesquels il était nécessaire d'arrêter la supplémentation en vitamine D. Conclusion : Malgré la bonne corrélation apparente entre la méthode Roche et la méthode LC-MS/MS dans le groupe contrôle de sujets apparemment sains et dans le groupe de patients post-DBP supplémenté en vitamine D3, un biais considérable semble exister, en particulier en présence de la 25-OH-D2. La méthode Roche sous-estime la 25-OH-D totale sérique jusqu’à 95.7% et la spectrométrie de masse a conduit à un ajustement posologique pour plus d’un patient sur quatre. La méthode LC-MS/MS est donc la méthode la plus appropriée pour le suivi sécuritaire de la population bariatrique post-DBP supplémentée en vitamine D2. Il est à noter que nos résultats pourraient être généralisés à tous les types de chirurgie bariatrique et autres patients tels que les insuffisants rénaux. Ils permettraient également la mise à jour des recommandations du suivi post-chirurgie bariatrique et le changement des pratiques en optimisant le choix de suppléments en vitamine D (D2 vs D3) en fonction de la méthode de dosage disponible et d’orienter les laboratoires pour le choix de méthodes de dosage dépendamment de la clientèle servie.<br>Abstract : Introduction: The prevalence of hypovitaminosis D may reach 90 % in patients after BPD despite supplementation with mega doses of vitamin D. Although LC-MS/MS is the gold standard for vitamin D measurements, it is not routinely use in clinical practice. Our hypothesis is that methods of assays currently used in laboratories of Medical Biochemistry for evaluation of serum 25-hydroxyvitamin D may not recognize equimolarly the two forms of 25-OH-D (D2 and D3) thus overestimating the prevalence of vitamin D deficiency supplemented with D2 and exposing patients to the risk of toxicity. Objective: Our objective was to compare the ECLIA from Roche versus the LC-MS/MS method for quantitation of serum 25-hydroxy-vitamin D in patients who have undergone bariatric surgery. Design and methods: Cross-sectional and correlational study was performed on three different groups for the 25-OH-D levels quantitated by both methods. The control group of apparently healthy subjects (n=48) was randomly selected in a clinical chemistry laboratory. Test groups were patients who had undergone bilio-pancreatic diversion (BPD) and were supplemented either with vitamin D2 (n=30) or with vitamin D3 (n=44). Patients were recruited during their follow-up visit to the obesity clinics at the CHUS and at the IUCPQ. The number of samples per group was established according to the Clinical and Laboratory Standard Institute recommendation protocol (EPO9-A2-IR). The study comparing methods (linear regression, Deming and Bland-Altman bias) was performed using the Analyse-it software program considering p < 0.05 as statistically significant. Results: The agreement of LC-MS/MS with the Roche method was acceptable in the apparently healthy subjects group and in the post-BPD D3-supplemented group with an average bias of -1.7% and -9.2%, respectively. However, this agreement was unacceptable in the post-BPD D2-supplemented group with an average bias of -45.3%. The LC-MS/MS enabled us to detect four patients (13%) who had excess vitamin D or intoxication with vitamin D for which it was necessary to stop the supplementation with vitamin D in the D2 -supplemented group. Conclusion: Despite the apparent good agreement between the Roche method and LCMS/MS in the healthy subjects group and in the post-DBP D3-supplemented patient group, a considerable bias seems to exist, particularly in the presence of D2. Results showed that the routine method underestimated total vitamin D ad 95.7% in patients post BPD supplemented with D2. The LC-MS/MS method is therefore the most accurate method to follow the vitamin D2-supplemented bariatric population. This study could generalize the results to all types of bariatric surgeries and other patients such as renal impairment. The study could also update the recommendations of the postbariatric surgery monitoring, and suggest making changes to the clinical practices so as to optimize the choices of vitamin D supplements (D2 vs D3) depending on the assay method available. It could also guide laboratories in choosing methods depending on dosage of clients served.

Basische Magnesiumsalz-Hydrate, insbesondere die Chloride, stellen die Bindemittelphasen des Magnesiabaustoffs (auch Sorelbaustoff genannt) dar. Eine besondere Anwendung findet dieser Baustoff aufgrund seiner empirisch bekannten Beständigkeit gegenüber Salz bzw. salzhaltigen Lösungen zur Errichtung geotechnischer Barrieren in tiefen geologischen Formationen des Salinars. Die Bewertung der Langzeitbeständigkeit von Sorel-basierten Baustoffen in salinarer Umgebung erfordert Kenntnisse zu den Löslichkeitsgleichgewichten ausgehend vom ternären Grundsystem Mg(OH)2-MgCl2-H2O bis hin zu komplexeren Systemen bei NaCl-Sättigung und Anwesenheit von Sulfaten. Zielstellung dieser Arbeit war daher die experimentelle Bestimmung von Löslichkeitsdaten basischer Magnesiumchlorid- und Magnesiumsulfat-Hydrate im Temperaturbereich von 25 °C bis 120 °C. Der Einfluss von NaCl-Sättigung auf die Löslichkeit der basischen Magnesiumchlorid-Hydrate wurde im quaternären System Na+, Mg2+ / Cl-, OH- // H2O bei 25 °C untersucht. Anhand dieser Ergebnisse wurden PITZER-Parameter angepasst und erstellt, um thermodynamische Modellierungen auf Basis des Aktivitätskoeffizientenmodells nach PITZER für diese Systeme durchführen zu können.