Administration of Il-18bp by Gene Therapy Reduces Inflammation and Prevents Joint Destruction by Downregulation of Mmp9 In Rat Aia: Role ff Mmp9 In Bone and Joint Destruction in Arthritis

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.

Arlequin journaliste : comédie en un acte, en prose, mêlée de vaudevilles ([Reprod.]) / par les CC. D***, Em. Dupaty et Chazet

Collection : Les archives de la Révolution française ; 12.181

Insulin-like growth factor I (IGF I) stimulates DNA synthesis in fetal rat brain cell cultures.

Addition of insulin, IGF I or IGF II to serum-free cultures of fetal rat brain cells (gestation day 15/16) significantly stimulates DNA synthesis. The dose-response curves show that IGF I is more potent than insulin; half maximal stimulation of [3H]thymidine incorporation is obtained at about 0.4 nM IGF I and 14 nM insulin, respectively. Cultures initiated 2 days later (gestation day 17/18) showed a decreased responsiveness to both peptides. No additive effect was observed after combined addition of both peptides at near-maximal doses. Both peptides show a latency of action of about 12-18 h. In the presence of either IGF or insulin, neuronal as well as glial enzymes are increased, suggesting that neuronal and glial precursor cell division is influenced. IGF I and IGF II interact with a specific binding site for which insulin competes very weakly; however IGF I and IGF II bind with relatively high affinity to the insulin specific binding site. The present results support the hypothesis that both insulin and IGF stimulate mitotic activity by interacting with specific somatomedin receptors and suggest a physiological role of IGF in the developing brain.

Plan du fort et des environs de Kattiéh : Pour servir à la relation de la campagne de Syrie / J. F. S. Bailly del.

Échelle(s) : [ca 1:10 000], 1000 mètres [= 10 cm]

Plan d'El-Arych : Pour servir à la relation de la campagne de Syrie / J. F. S. Bailly del.

Échelle(s) : [ca 1:3 300], 100 mètres [= 3 cm]

A multicenter phase II study (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma

Introduction: Mantle cell lymphoma (MCL) accounts for 6% of all B-cell lymphomas and is in most cases an incurable disease. It is characterized by the translocation t(11;14) leading to Cyclin D1 over-expression. Cyclin D1 is downstream of the mammalian target of rapamycin (mTOR) threonine kinase and can be effectively blocked by mTOR inhibitors. We set out to define the single agent activity of the orally available mTOR inhibitor everolimus in a prospective, multicentre trial in patients with relapsed or refractory MCL (NCT00516412).Methods: Eligible patients with confirmed relapsed or refractory MCL received everolimus 10 mg for 28 days (one cycle) for a total of 6 cycles or until disease progression. The primary endpoint was the best objective response (OR) with adverse reactions, time to progression (TTP), time to treatment failure, response duration and molecular response as secondary endpoints.Results: A total of 36 patients with 35 evaluable patients at a median age of 69 years (range 40 to 85 years) from 19 centers were enrolled between August 2007 and January 2010. Treatment was generally well tolerated with anemia (11%), thrombocytopenia (11%), neutropenia (8%), diarrhea (3%) and fatigue (3%) being the most frequent complications of CTC grade 3 or higher. The OR rate was 20% (95% CI: 8-37%) with 2 complete remissions (CR) and 5 partial response (PR), stable disease (SD) 48% and progression disease (PD) 28%. At a median follow-up of 6 months, TTP was 5.45 months (95% CI: 2.8-8.2 months) for the entire population and 10.6 months for the 18 patients receiving 6 or more cycles of treatment. Three patients achieved a lasting complete molecular response when assessed in the peripheral blood.Conclusion: This study demonstrates that single agent everolimus is well tolerated and has anti-lymphoma activity including lasting molecular responses. Further studies of everolimus either in combination with chemotherapy or as single agent for maintenance treatment are warranted in MCL.

Anne d'Autriche et la Fronde : d'après les Mémoires de madame de Motteville / texte établi par Henry Chapoy

Collection : Petits mémoires sur l'histoire de France ; VI

Resposta do coqueiro à adubação com uréia, superfosfato simples e cloreto de potássio em dois solos do nordeste do Brasil

Foram realizados dois experimentos axiais no período de 1987 a 1992, visando estudar a resposta do coqueiro à adubação com uréia, superfosfato simples e cloreto de potássio em dois solos do nordeste do Brasil. Na Areia Quartzosa, houve resposta ao nitrogênio, para número de frutos. O nível crítico do nutriente na folha 14, de 17,18 g kg-1, foi atingido com a aplicação de 1,538 kg/plantaano-1 de N. No mesmo solo, o fósforo não influenciou a produção de frutos, enquanto o potássio a influenciou linearmente. No Podzólico Amarelo, foi observado efeito da uréia, superfosfato simples e cloreto de potássio no número de frutos. O efeito da uréia no teor de nitrogênio na folha foi linear, não permitindo a obtenção do nível crítico. O nível crítico de fósforo na folha 14, de 1,21 g kg-1, foi obtido com a aplicação de 2,01 kg/planta ano-1 de superfosfato simples. O efeito do cloreto de potássio no teor de potássio na folha não foi significativo, o que não ocorreu para o cloro, cujo nível crítico na folha 14 foi de 6,07 g kg-1, obtido com aplicação de 2,06 kg/plantaano-1 de cloreto de potássio.

Avaliação de fatores edafoclimáticos e do manejo na produção de cafeeiros (Coffea arabica L.) no Oeste Paulista

Atributos do clima, solo e manejo foram caracterizados em 10 lavouras comerciais de café, estabelecidas na região oeste do estado de São Paulo, nos municípios de Sagres, Pompéia, Iacri, Bastos, Herculândia, Marília, Vera Cruz, Garça e Gália. Os objetivos foram identificar os principais fatores limitantes à cultura e estabelecer um modelo multivariado simples para explicar as produções observadas entre 1984 e 1989. Foram analisados, por correlação simples, mais de 2.000 atributos em relação às produções finais. Os atributos que apresentaram significância a 5% de probalidade pelo teste t de Student foram combinados em sucessivas análises de regressão múltipla. Três equações, com quatorze, cinco e seis variáveis preditoras, foram selecionadas, com graus de explicação da produção observada da ordem de 77, 73 e 75%, respectivamente. Quatro variáveis foram comuns aos três modelos: produção do ano anterior, idade da lavoura, temperatura mínima absoluta média na época do abotoamento e florescimento e soma dos teores de silte e argila nos horizontes subsuperficiais. Outras variáveis selecionadas foram: precipitação na época do abotoamento e florescimento; precipitação na época da maturação e colheita; densidade do solo e água disponível junto à cova (camada de 20-40 cm); macroporosidade na rodagem de máquinas (camada de 0-20 cm); adubação nitrogenada; pH em água e fósforo, ambos na área adubada (camada de 20-40 cm); teor de cálcio trocável e relação Mg:K trocáveis, ambos na área adubada (camada de 0-20 cm). A análise dos dados de produção no período de seis anos mostrou que as lavouras encontravam-se em processo de depauperamento, com declínio da produtividade da ordem de 400 kg ha-1 ano-1. As áreas necessitavam de melhoria da calagem, fosfatagem em profundidade, restabelecimento dos níveis de magnésio no solo e adubação mineral equilibrada. Também ficou evidenciada a necessidade de ser evitada a instalação da lavoura em áreas de acúmulo de ar frio no inverno ou solos com acentuado gradiente textural.

Higher CNS penetration-effectiveness of long-term combination antiretroviral therapy is associated with better HIV-1 viral suppression in cerebrospinal fluid.

OBJECTIVES: To determine HIV-1 RNA in cerebrospinal fluid (CSF) of successfully treated patients and to evaluate if combination antiretroviral treatments with higher central nervous system penetration-effectiveness (CPE) achieve better CSF viral suppression. METHODS: Viral loads (VLs) and drug concentrations of lopinavir, atazanavir, and efavirenz were measured in plasma and CSF. The CPE was calculated using 2 different methods. RESULTS: The authors analyzed 87 CSF samples of 60 patients. In 4 CSF samples, HIV-1 RNA was detectable with 43-82 copies per milliliter. Median CPE in patients with detectable CSF VL was significantly lower compared with individuals with undetectable VL: CPE of 1.0 (range, 1.0-1.5) versus 2.3 (range, 1.0-3.5) using the method of 2008 (P = 0.011) and CPE of 6 (range, 6-8) versus 8 (range, 5-12) using the method of 2010 (P = 0.022). The extrapolated CSF trough levels for atazanavir (n = 12) were clearly above the 50% inhibitory concentration (IC50) in only 25% of samples; both patients on atazanavir/ritonavir with detectable CSF HIV-1 RNA had trough levels in the range of the presumed IC50. The extrapolated CSF trough level for lopinavir (n = 42) and efavirenz (n = 18) were above the IC50 in 98% and 78%, respectively, of samples, including the patients with detectable CSF HIV-1 RNA. CONCLUSIONS: This study suggests that treatment regimens with high intracerebral efficacy reflected by a high CPE score are essential to achieve CSF HIV-1 RNA suppression. The CPE score including all drug components was a better predictor for treatment failure in the CSF than the sole concentrations of protease inhibitor or nonnucleoside reverse transcriptase inhibitor in plasma or CSF.

TESTAMENTS. — Pièces diverses. — POESIES françaises et latines.

Contient : Lettre de M. Le Camus, avocat au Parlement (Rouen, 22 août 1628) ; Lettres écrites à Mathieu Molé, procureur général, par un de ses cousins (s. d.) ; Testament de Hugues, comte de Rodez (8 octobre 1176) ; Charte de Hugues, comte de Rodez, extraite du cartulaire de l'abbaye de Conques (1195) ; Note de Madame de la Reynie, annonçant à Baluze l'envoi de la pièce suivante (22 avril 1711) ; Testament de Jean de Pins, évêque de Rieux (27 avril 1537) ; Testament de Gabriel de Chazeron, gentilhomme ordinaire de la chambre du roi (31 mars 1624) ; Testament d'Anne-Marie-Louise d'Orléans, duchesse de Montpensier (27 février 1685) ; Testament de Charlotte-Marguerite de Montmorency, princesse douairière de Condé (9 août 1659) ; Testament de Guillaume de Lamoignon (20 octobre 1676) ; Testament de Perrot d'Ablancourt (5 octobre 1664) ; Testament de Henri de Sponde, évêque de Pamiers (11 mai 1643) ; Testament du P. Maimbourg (28 décembre 1685), accompagné d'une note autographe du même (8 février [1686]) ; Accord entre Charles, comte de Ventadour, et les seigneurs de Soudeille (31 octobre 1429) ; Extrait de l'inventaire des titres de Ventadour ; Note sur la fondation d'une vicairie dans l'église de Saint-Exupery en 1442 ; Lettre de Dupuy, archiprêtre de Saint-Exupery, à Baluze (28 juillet 1692), et copie d'une lettre du curé dudit lieu ; « Les Muses françoises à la Reyne, » recueil de huit sonnets anonymes ; « Prière aux Muses en faveur de Monsieur l'abbé de Saint-Vincent » [de Senlis, J.-P. Berthier], sonnet, par G. Colletet (26 août 1658) ; autographe ; Recueil de pièces de vers latins en l'honneur du même J.-P. Berthier (1er janvier 1664) ; Anagrammes latines sur le même nom, signées T. Billon ; Extrait d'un arrêt de 1655 relatif aux droits des curés sur les dîmes inféodées ; « Carta de parabien a los señalados señores de la esplendida Camara de Justicia, » par le sieur Lagravete, suivie de la liste et de l'éloge des membres du Parlement, par le même ; Vie de l'impératrice Adelaïde, par saint Odilon de Cluny (Migne, Patr. lat., t. CXLII, col. 967) ; Lettre du P. L. Frizon à Baluze (Bordeaux, 18 septembre 1680), et distiques sur le Louvre, envoyés par le même à Colbert (Cf. Sommervogel, Biblioth. de la Compagnie de Jésus, t. III, col. 1012)