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101.
Malavia NK Zurakowski D Schroeder A Princiotto AM Laury AR Barash HE Sodroski J Langer R Madani N Kohane DS 《Biomaterials》2011,32(33):8663-8668
There are approximately 33.4 million adults living with HIV worldwide of which an estimated 15.7 million are women. Although there has been enormous progress in the therapy of HIV/AIDS, treatment is not curative. Prevention is therefore of paramount importance, but vaccine-based and microbicidal approaches are still in their infancy. Since women acquire the virus largely through sexual intercourse, we developed liposomal systems potentially suitable for intra-vaginal use to prevent HIV-1 infection. We formulated liposomes from a range of naturally-occurring and synthetic lipids with varying physicochemical properties, and tested their ability to inhibit infection of transformed cells that express receptors specific to the virus. We identified formulations with the most favorable balance between decreasing HIV infection and causing cytotoxicity (i.e. therapeutic index). The therapeutic index improved with increasing cardiolipin content, and degree of unsaturation. Tissue reaction to these formulations was benign after intra-vaginal instillation in an in vivo female mouse model. These results support the potential use of cardiolipin-based liposomes enriched with synthetic lipids as microbicides for the prevention of HIV infection in women. 相似文献
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103.
Snake venom contains a complex protein mixture belonging to a few well-characterized protein families: disintegrins, phospholipase A2, serine protease, l-amino acid oxidase, Zn-dependent metalloproteinase, natriuretic peptides, myotoxins, cysteine-rich secretory protein (CRISP) toxins, Kunitz-type protease inhibitors and C-type lectin-like. Despite their pharmacological importance, little is known about the exact composition of each protein family. We report here the cloning of 25 complete ORFs from Macrovipera lebetina transmediterranea venom gland that encodes several isoforms and novel C-type lectins (CTLs). 16 alpha and nine beta CTL chains were identified. Based on their sequence alignment, we categorized the 16 CTL alpha subunits into five groups and the nine CTL beta subunits into four groups to deduce the phylogenetic tree of M. lebetina transmediterranea CTLs. Sequence analysis revealed that they share a high degree of similarity with each other and with other snake venom CTLs. The M. lebetina transmediterranea CTL sequences described here contain a C-lectin carbohydrate recognition domain-like fold (C-lectin CRD-like) characterized by several conserved amino acid residues in their structure, especially the cysteine. Finally, based on the comparison of some Macrovipera CTL, we propose that some new CTL gene versions should have occurred through “domains shuffling” from former genes. 相似文献
104.
Intra-articular injections of hyaluronan are generally well tolerated; the most common adverse event associated with their use is an inflammatory reaction or a flare at the injection site. Naturally derived sodium hyaluronates have not been associated with pseudosepsis; we describe a case of severe arthritis mimicking acute septic arthritis after naturally hyaluronan. A 70-year-old woman had a medial femorotibial and patellofemoral compartment knee osteoarthritis. Hyaluronic acid injection was indicated because of the persistence of a pain while walking and restricted ability to walk 100 m, as well as the installation of a flessum. She was admitted for an evaluation of a joint effusion occurring within 48 h after the first hyaluronic acid intra-articular injection (first course), with no fever or chills. Joint fluid was found to be cloudy and contained 24,000 cells per mm(3). A knee aspiration was performed to evaluate the possibility of a joint infection. The examination of synovial fluid under phase contrast and polarizing microscopes showed no crystals, and culture on standard media was negative. Acute septic arthritis was considered to be the most likely diagnosis, and probabilistic antibiotic therapy was started. The result of the bacteriological examinations also returned negative. The absence of general signs, particularly fever and chills, with fast effusion regression in less than 4 days did not plead in favor of a septic origin. In front of this beam of arguments, antibiotic therapy was stopped after 4 days. The nonsteroidal anti-inflammatory drug (Nimésulide) was given. The clinical and laboratory test abnormalities were normalized within 2 weeks. Our case has the particularity to occur after using Curavisc, which is known as producing no allergenic reactions. Moreover, the described reaction occurred with the very first infiltration within the very first course. 相似文献
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107.
Laetitia Dahan Amine Sadok Jean-Louis Formento Jean Fran?ois Seitz Hervé Kovacic 《British journal of pharmacology》2009,158(2):610-620
Background and purpose:
Oxaliplatin is the first platinum-based compound effective in the treatment of colorectal cancer. Oxaliplatin combined with cetuximab for metastatic colorectal cancer is under evaluation. The preliminary results seem controversial, particularly for the use of cetuximab in K-Ras mutated patients. K-Ras mutation is known to affect redox homeostasis. Here we evaluated how the efficacy of oxaliplatin alone or combined with cetuximab varied according to the Ras mutation and redox status in a panel of colorectal tumour cell lines.Experimental approach:
Viability was evaluated by methylthiazoletetrazolium assay, reactive oxygen species production by DCFDA and lucigenin on HT29-D4, Caco-2, SW480 and SW620 cell lines.Key results:
Combination of oxaliplatin and cetuximab was less cytotoxic than oxaliplatin alone in colorectal cells harbouring wild-type Ras and membrane expression of receptors for epidermal growth factor receptor (EGFR), such as HT29-D4 and Caco-2 cells. In contrast, cetuximab did not affect oxaliplatin efficiency in cells harbouring K-RasV12 mutation, irrespective of membrane EGFR expression (SW620 and SW480 cells). Transfection of HT29-D4 with K-RasV12 decreased oxaliplatin IC50 and impaired cetuximab sensitivity, without affecting expression of membrane EGFR compared with HT29-D4 control. Oxaliplatin efficacy relies on endogenous production of H2O2. Cetuximab inhibits H2O2 production inhibiting the EGFR/Nox1 NADPH oxidase pathway. Oxaliplatin efficacy was impaired by short hairpin RNA for Nox1 and by catalase (H2O2 scavenger).Conclusions and implications:
Cetuximab limited oxaliplatin efficiency by affecting the redox status of cancer cells through Nox1. Such combined therapy might be improved by controlling H2O2 elimination. 相似文献108.
109.
Cocaine and many other psychostimulants strongly induce urokinase-type plasminogen activator (uPA) expression in the mesolimbic dopaminergic pathway, which plays a major role in drug-mediated behavioral plasticity [Bahi A, Boyer F, Gumy C, Kafri T, Dreyer JL. In vivo gene delivery of urokinase-type plasminogen activator with regulatable lentivirus induces behavioral changes in chronic cocaine administration. Eur J Neurosci 2004;20:3473-88; Bahi A, Boyer F, Kafri T, Dreyer JL. Silencing urokinase in the ventral tegmental area in vivo induces changes in cocaine-induced hyperlocomotion. J Neurochem 2006;98:1619-31; Bahi A, Dreyer JL. Overexpression of plasminogen activators in the nucleus accumbens enhances cocaine-, amphetamine- and morphine-induced reward and behavioral sensitization. Genes Brain Behav 2007]. In this study, the role of mesolimbic dopamine (DA) pathways in the development of cocaine reward was examined by conditioned-place preference in rats with bilateral intra-accumbens injections of uPA-expressing lentiviral vectors. We show that overexpression of uPA in the Nac significantly augments cocaine-induced place preference. Furthermore, while this did not affect the ability of preference to be extinguished, reinstatement with a low dose of cocaine produced significantly greater preference to the cocaine-associated context. Once CPP had been established, and the preference extinguished, reinstatement induced by a priming dose of cocaine was facilitated by uPA. Inhibition of this serine protease expression using doxycycline abolished the augmented acquisition produced by overexpression of uPA but not the expression of the cocaine-induced CPP. When uPA is inhibited during the acquisition phase, animals no longer demonstrate place preference for the environment previously paired with cocaine. B428, a specific uPA inhibitor does not affect drug reinstatement after extinction if uPA has been activated during acquisition, a clear indication that uPA is involved in the acquisition phase of conditioned-place preference. Our results suggest that that increased uPA expression with repeated drug exposure produces conditions for enhanced acquisition of cocaine-induced CPP, indicating that cocaine-induced CPP and reinstatement may be dependent on active extracellular uPA. 相似文献
110.
Rouprêt M Hupertan V Yates DR Comperat E Catto JW Meuth M Lackmichi A Ricci S Lacave R Gattegno B Richard F Hamdy FC Cussenot O 《BJU international》2008,101(11):1448-1453