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Background and objectives Interleukin 18 (IL-18) is a pleiotropic cytokine involved in rheumatoid arthritis (RA) pathogenesis. This study was carried out to evaluate the effi cacy of IL-18 binding protein (IL-18BP) gene therapy in the rat adjuvant- induced arthritis (AIA) model and to decipher the mechanisms by which IL-18BP delivery lessens bone destruction.Materials and methods Arthritis was induced in female Lewis rat by Mycobacterium butyricum and the mRNA expression of IL-18 and IL-18BP was determined in the joints. In a preventive study, rats were divided into an adenovirus producing IL-18BP-Fc (AdmIL-18BP-Fc) group (n=8) and an adenovirus producing green fl uorescent protein (AdGFP) group (n=7). On day 8 after AIA induction, adenoviruses were injected. Clinical parameters were assessed. At day 18, during maximal arthritis, the rats were euthanized, ankles were collected and x-rays were performed. mRNA and protein were extracted from joints for analysis by quantitative reverse transcriptase-PCR, multiplex, Western blot and zymography.Results The authors observed a decrease in the (IL-18BP/ IL-18) ratio from day 7 to 45. Administration of AdmIL-18BPd-Fc decreased clinical parameters and prevented bone and joint destruction compared to AdGFP administration. IL-18BP delivery reduced the (receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG)) ratio by 70%, the matrix metalloproteinase 9 (MMP9) level by 33% and the tartrate-resistant acid phosphatase (TRAP) level by 44% in the joint homogenates from AdmIL-18BPd-Fc compared to AdGFP treated rats.Conclusions In rat AIA, a decrease in the (IL-18BP/IL-18) ratio was observed. IL-18BP delivery prevented joint and bone destruction by downregulating MMP9, (RANKL/OPG) and TRAP, suggesting a potential benefi t of a similar therapy in RA.Abstract topics Towards novel therapeutic strategies.
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Abstract : The role of order effects has been widely shown and discussed in areas such as memory and social impression formation. This work focuses in a first half on order effects influencing the verdict chosen at the end of a criminal trial. Contrary to impression formation but according to trial's characteristics, it has been hypothesised that a recency effect would influence the verdict's choice. Three groups of students (N = 576) received a mock trial resume with a specific order stemming from the combination of three witnesses, one expert and two ocular witnesses. Results show a recency effect, the last testimony provoking significantly more acquittals if discriminating, and more condemnations if incriminating. The second half of this work starts from Gestalt and sociopsychological researches presenting numerous insights into cognitive organization of perceptions and opinions. It has been postulated that a witness probative value will change according to the emitted verdict, an incriminating witness or expert possessing a higher probative value in a condemning verdict than in an innocenting one, on the other hand a discriminating witness or expert having a higher probative value in an acquittal than in a condemnation. Results using a seven points scale measuring witnesses' probative value confirm this hypothesis. Argumentations written by the subjects to explain their verdict and refering to the accusing expert also show a congruency effect as categories of arguments are identical in case of condemnation or acquittal, the only difference between both types of verdicts residing in the frequency of these categories following the judgement, higher use of incriminating arguments in case of guiltiness and higher use of discriminating ones if the accused is found innocent. Rsum : L'intervention des effets sriels a fait l'objet de nombreuses recherches dans le domaine de la mmoire et de la formation d'impression en psychologie sociale. Ce travail s'intresse dans une premire partie aux effets d'ordre pouvant influencer le choix du verdict la fin d'un procs pnal. Contrairement aux rsultats obtenus en matire de formation d'impression, mais conformment aux caractristiques d'un procs, l'hypothse de l'intervention d'un effet de rcence a t formule, affirmant que les derniers tmoins influencent le plus le choix du verdict. Trois groupes d'tudiants (N = 576) ont lu le rsum d'un procs fictif prsentant trois tmoignages, deux tmoins visuels dcharge et un expert charge. Chaque groupe recevait un ordre spcifique de prsentation des tmoins de sorte que l'expert se trouvait en premire, deuxime ou troisime position. Les rsultats montrent un effet de rcence, le dernier tmoin provoquant davantage d'acquittements s'il est disculpant et davantage de condamnations s'il est inculpant. La seconde partie de ce travail mane des recherches effectues dans le domaine de la thorie de la forme et de la psychologie sociale ayant un intrt marqu pour l'organisation cognitive de nos perceptions et de nos opinions. L'hypothse que nous avons pose souligne le lien entretenu entre l'valuation de la force probante d'un tmoin et le verdict mis : un tmoignage discriminant possdera plus de poids en cas d'acquittement qu'en cas de condamnation, inversement un tmoignage incriminant aura plus de poids en cas de condamnation qu'en cas d'acquittement. L'utilisation d'une chelle en sept points mesurant la force probante des deux types de tmoins confirme cette hypothse, l'estimation de la valeur accorde un mme tmoin variant selon le type de verdict choisi. Les argumentations de chaque verdict ont galement montr que les catgories d'arguments se rfrant l'expert taient identiques en cas de condamnation ou d'acquittement de l'inculp, par contre les frquences de ces catgories entretiennent un lien congruent avec le verdict, celles inculpantes tant majoritairement utilises pour asseoir la culpabilit mais peu reprsentes en cas d'acquittement, inversement celles disculpantes apparaissant bien plus lorsqu'il s'agit d'innocenter l'inculp que pour le condamner.
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From my experience with public administration in my country, Cape Verde, and through readings in the area of development administration, I have found that a distinctive role and specific societal goals are usually ascribed to public administration in developing country. In studying American public administration approaches and operation, I was stuck by the fact that the definition of roles and societal goals for public administration seems not to be a forefront concern in the field. How to do things and achieve efficiency, in a managerial and rational perspective, seemed to draw much more attention than the purpose of doing things. Somehow, the contrast with the concept of development administration seemed too sharp, and I became curious about the reasons for such disparate approaches. Historical, cultural, and environmental differences would probably not be the only explanation for that since the concept of development administration was shaped, in the late 50s and 60s, by American authors and institutional aid agencies, and then offered to developing countries. At the same time, looking to poor results of the successive prescriptions of the development administration movement, I was no sure that such a concept and the framework it establishes was worthwhile. What practical answers and arrangement did they bring to the needs and challenges of public administrations in developing countries?
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OBJECTIVES: We developed a population model that describes the ocular penetration and pharmacokinetics of penciclovir in human aqueous humour and plasma after oral administration of famciclovir. METHODS: Fifty-three patients undergoing cataract surgery received a single oral dose of 500 mg of famciclovir prior to surgery. Concentrations of penciclovir in both plasma and aqueous humour were measured by HPLC with fluorescence detection. Concentrations in plasma and aqueous humour were fitted using a two-compartment model (NONMEM software). Inter-individual and intra-individual variabilities were quantified and the influence of demographics and physiopathological and environmental variables on penciclovir pharmacokinetics was explored. RESULTS: Drug concentrations were fitted using a two-compartment, open model with first-order transfer rates between plasma and aqueous humour compartments. Among tested covariates, creatinine clearance, co-intake of angiotensin-converting enzyme inhibitors and body weight significantly influenced penciclovir pharmacokinetics. Plasma clearance was 22.8  9.1 L/h and clearance from the aqueous humour was 8.2  10(-5) L/h. AUCs were 25.4  10.2 and 6.6  1.8 μg  h/mL in plasma and aqueous humour, respectively, yielding a penetration ratio of 0.28  0.06. Simulated concentrations in the aqueous humour after administration of 500 mg of famciclovir three times daily were in the range of values required for 50% growth inhibition of non-resistant strains of the herpes zoster virus family. CONCLUSIONS: Plasma and aqueous penciclovir concentrations showed significant variability that could only be partially explained by renal function, body weight and comedication. Concentrations in the aqueous humour were much lower than in plasma, suggesting that factors in the blood-aqueous humour barrier might prevent its ocular penetration or that redistribution occurs in other ocular compartments.
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Report on a review of selected general and application controls over the Iowa Public Employees Retirement System (IPERS) Benefits Administration System for the period April 23, 2007 through May 16, 2007
