Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

"This book reviews the pathophysiology of functional pain disorders, including irritable bowel syndrome, fibromyalgia, vulvodynia, and interstitial cystitis, and considers the relationship of these disorders with one another and with anxiety, depression, post-traumatic stress disorder, and chronic fatigue syndrome. The authors also describe treatment options, including antidepressants and psychological therapies"--Provided by publisher.

Chronic pain

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

Renal insufficiency, chronic --- Epidemiology

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

Chronic pain affects nearly one in every four adults worldwide, with pain one of the most common symptoms resulting in medical consultation. The increasing focus on chronic pain presents difficulties for the busy practitioner. Patients typically describe a complex pattern of discomfort, disability, and distress, with pain affecting physical, social, and psychological functioning. Clinicians must efficiently condense widely varied symptomatic descriptions into characteristic patterns to permit accurate diagnosis and implement effective treatment. This atlas serves as a useful educational resour

Chronic Disease -- Atlases. --- Chronic pain -- Atlases. --- Pain -- Atlases.

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

Chronic kidney disease (CKD) is rapidly becoming a global healthcare problem, with an estimated 10% of the general population affected. As a result, it is becoming increasingly important that primary care physicians and general physicians as well as aspiring nephrologists, have a firm understanding of CKD as well as access to the key information.Practical and highly-accessible, this book provides a comprehensive guide to the understanding and management of patients with CKD. It offers both primary care physicians and non-nephrology specialists an introduction to and insights into the disease.

Chronic renal failure. --- Chronic renal failure --- Chronic kidney failure --- Chronic renal insufficiency --- End-stage kidney disease --- End-stage renal disease --- ESRD (Disease) --- Kidney failure, Chronic --- Renal failure, Chronic --- Renal insufficiency --- Renal insufficiency, Chronic --- Diseases --- Kidneys --- Treatment.

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

B-cell chronic lymphocytic leukemia (B-CLL) is the most common form of adult leukemia on the Western world. B-CLL is characterized by the accumulation of mature B lymphocytes, which is explained mainly by a decreased cell mortality due to defect(s) in apoptotic cell death. Therapeutics approaches include corticosteroids, alkylating agents, nucleoside analogues or monoclonal antibodies, alone or in combination. Although these treatments are active, B-CLL remains an incurable disease, because of emergence of resistance. The laboratory where I performed my suited is particularly interested in the mechanisms of action of nucleoside analogues, aiming at improving their clinical efficacy.
My work has been initiated by the observation of a member of the team, L. Bastin-Coyette. He demonstrated that the lymphotoxicity of 2-chloroadenosine (an agonist of adenosine, not used in therapy) was due, at least partly, to a decrease in intracellular ATP. As the nucleoside analogues used to treat B-CLL, 2-chlorordeoxyadenosine (CdA) and fludarabine, have no significant effect on ATP concentration, we wondered whether their efficacy could be enhanced by combining them with compounds that induce a depletion in ATP. Hence, we tested the effect of glycolysis inhibitors: 2-deoxyclucose (2DG), 2-fluorodeoxyglucose (2FG) and 3-bromopyruvate (3BrPA). We have shown that these three inhibitors were able to inhibit (by more than 80%) glycolysis in leukemic cells. However, ATP reduction and cytotoxicity varied according to the inhibitor.
Next, we combined the different glycolysis inhibitors with CdA or fludarabine and we analyzed the cytotoxicity induced by these combinations. The combination of 2DG, and in a lesser extent, of 3BrPA with nucleoside analogues induced synergic cytotoxicity, suggesting that combination of these compounds with CdA or fludarabine could interesting to treat B-CLL. Conversely, 2FG, yet the most specific glycolysis inhibitor, tended to antagonize the cytotoxicity of nucleoside analogues. This last result suggests that glycolysis inhibition alone cannot explain the synergy observed with 2DG and 3BrPA. Probably other targets have been reached by 2DG and 3BrPA, which allow improving efficacy of nucleoside analogues.
Finally, we investigated the mechanisms of cytotoxicity of glycolysis inhibitors in leukemic cells. We examined whether they induced apoptosis (activation of caspace-3, clivage PARP) and searched whether their cytotoxicity could be counteracted by some means ‘addition of mannose, antioxydants, …). It appeared that the mechanisms of cytotoxicity are different for the three inhibitors, and that their cytotoxicity is not only due to glycolysis inhibition La leucémie lymphoïde chronique de type B (LLC-B) est la plus fréquente des leucémies de l’adulte en Occident. Elle est caractérisée par une accumulation de lymphocytes B matures quiescents qui s’explique principalement par leur résistance à l mort par apoptose. Le traitement consiste en l’administration de cortico-stéroïdes, d’agents alkylants, d’analogues de nucléosides ou d’anticorps monoclonaux, seuls ou en association. Malgré leur efficacité, ces traitements ne peuvent cependant pas guérir les malades. Des résistances apparaissent, soit d’emblée, soit au fil des traitements. Mon laboratoire d’accueil s’intéresse particulièrement au mode d’action des analogues de nucléosides et recherche des stratégies qui permettraient de renforcer leur efficacité.
Mon travail résulte de l’observation d’un chercher de l’équipe, L. Bastin-Coyette, qui a démontré que la lymphotoxicité de la 2-chloroadénosine (un agoniste de l’adénosine non utilisé en clinique) était due en partie à la chute d’ATP qu’il induisait. Comme les analogues de nucléosides utilisés en clinique, la 2-chlorodésocyadénosine (CdA) et la fludarabine, n’ont pas ou peu d’effet sur la concentration d’ATP, nous nous sommes demandé s’il serait possible de renforcer leur efficacité thérapeutique en les combinant à des agents qui font baisser l’ATP. Dans ce but, nous avons testé l’effet d’inhibiteurs de la glycolyse : le 2-désoxyglucose (2DG), le 2-fluorodésoxyglucose (2FG), et le 3-bromopyruvate (3BrPA). Nous avons pu démontrer que ces trois composés inhibaient effectivement la glycolyse dans les cellules leucémiques, mais que la chute d’ATP ainsi que la cytotoxicité qu’ils induisaient variait selon l’inhibiteur utilisé.
Dans une seconde étape, nous avons combiné ces trois inhibiteurs de la glycolyse avec la CdA ou à la fludarabine et analysé la cytotoxicité de ces combinaisons. L’association du 2DG, et dans une moindre mesure du 3BrPA, aux analogues de nucléosides produisait une cytotoxicité synergique dans les cellules de type LLC-B, suggérant que la combinaison de ces inhibiteurs de la glycolyse avec la fludarabine our la CdA pourrait être une thérapie avantageuse pour lutter contre la LLC-B. Au contraire, le 2FG, qui était l’inhibiteur le plus spécifique de la glycolyse, avait plutôt tendance à antagoniser leurs effets. Ce dernier résultat suggère que ce n’est pas l’inhibition de la glycolyse qui potentialise les effets des analogues de nucléosides et que les effets bénéfiques observés en présence de 2DG et 3BrPA résulteraient de l’atteinte d’autres cibles.
Finalement, nous avons investigué les mécanismes de cytotoxicité des inhibiteurs de la glycolyse dans les cellules leucémiques. Nous avons examiné s’ils induisaient de l’apoptose (activation de la caspace-3, clivagede PARP) et recherché s’il existait des moyens de contrecarrer leur cytotoxicité ‘addition de mannose, d’antioxydants, …). Il est apparu que ces trois inhibiteurs agissaient de façon différents, indiquant que leur cytotoxicité n’est pas seulement due à leur capacité d’inhiber la glycolyse

Glycolysis --- Nucleosides --- Leukemia, Lymphocytic, Chronic, B-Cell