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991.
Relapses of multiple sclerosis (MS) are considered to be the clinical expression of acute T-cell-mediated inflammatory demyelinating lesions disseminated in the CNS, whereas disease progression seems to result from widespread axonal degeneration. The pathophysiology of both disease components is incompletely understood. Astrocytes in MS lack beta(2)-adrenoceptors, which via cAMP-mediated processes inhibit the expression of major histocompatibility (MHC) class II molecules and stimulate glycogenolysis in normal conditions. In a pro-inflammatory CNS environment this beta(2)-adrenoceptor defect might allow astrocytes to transform into facultative antigen-presenting cells that can initiate the inflammatory cascade. The same receptor defect might impair astrocytic glycogenolysis, which normally generates lactate that is transported to axons as an energy source. Failure of axonal energy metabolism might result in axonal degeneration through mechanisms that involve intra-axonal accumulation of Ca(2+) ions and mitochondrial dysfunction. If this hypothesis is correct, therapies designed to elevate cAMP levels in astrocytes should reduce or prevent both relapses and progression of MS. 相似文献
992.
Therapeutic drug monitoring of lopinavir/ritonavir given alone or with a non-nucleoside reverse transcriptase inhibitor 下载免费PDF全文
993.
Le Mire J Arnulf L Guibert P 《Clinics in occupational and environmental medicine》2004,4(1):143-65, viii
Malaria caused by Plasmodium falciparum continues to be the principal medical threat to travelers in tropical zones. Eighty percent of malaria cases occur in sub-Saharan Africa. Prevention capacity nears 100%. In the event of infection, early diagnosis and bitherapy (treatment that includes two different active molecules) provide a nonfatal outcome. The greatest risk occurs in the weeks after returning home. The history of malaria has shown that it is important to anticipate the evolving nature of the disease and to be able to respond to it in a timely fashion. The efficiency of preventive treatments should lead toward the goal of zero malaria cases when dealing with travelers; however, virtually all empiric experience indicates that this goal rarely is reached. 相似文献
994.
995.
Welters MJ Filippov DV van den Eeden SJ Franken KL Nouta J Valentijn AR van der Marel GA Overkleeft HS Lipford G Offringa R Melief CJ van Boom JH van der Burg SH Drijfhout JW 《Vaccine》2004,23(3):305-311
Many successful candidate vaccines capable of combating tumours in animal models come to an untimely end because of the costs associated with the approval and production of the GMP-grade materials, which are usually of biological origin, for use in humans. We have used a GMP-compatible method to chemically synthesize a pure synthetic E7 protein of the human papillomavirus type 16 (HPV16-E7). This oncogen-derived protein is constitutively expressed in cervical cancer and its precursors and is thus considered as an excellent target for tumour-specific immunity. Injection of a mixture of the synthetic HPV16-E7 protein and the synthetic adjuvant CpG in mice resulted in strong functional HPV16-specific cytotoxic T-lymphocyte responses as measured by CD8+ MHC class I-tetramer staining, the detection of antigen-specific intracellular IFNgamma production and the ability to protect mice against a challenge with HPV16-E7+ TC-1 tumour cells in both prophylactic and therapeutic vaccination regimens. Our results demonstrate the potential use of pure synthetic vaccines that can be efficiently produced under GMP at low cost, which will stimulate the translation of new vaccination strategies into phase I/II clinical trials. 相似文献
996.
Mallet E Belohradsky BH Lagos R Gothefors L Camier P Carrière JP Kanra G Hoffenbach A Langue J Undreiner F Roussel F Reinert P Flodmark CE Stojanov S Liese J Levine MM Muñoz A Schödel F Hessel L;Hexavalent Vaccine Trial Study Group 《Vaccine》2004,22(11-12):1343-1357
To reduce the number of injections needed to comply with paediatric vaccination requirements, a liquid, hexavalent vaccine (DTaP-IPV-PRP-T-HBs; Hexavac; Aventis Pasteur MSD) has been developed for primary and booster vaccination of infants and toddlers. In extensive clinical studies, Hexavac has been shown to be highly immunogenic. Seroconversion or seroprotective titres of antibodies against all antigens were achieved in the majority of infants following a primary series of three doses administered at 1-2-month intervals from 2 months of age. Hexavac also induced immunologic memory, as evidenced by the anamnestic response to booster vaccination at 12-18 months of age. These responses were comparable with those seen following concomitant administration of Pentavac (DTaP-IPV//PRP-T) and monovalent hepatitis B vaccine (H-B-Vax II), and were also within the ranges observed for other relevant licensed vaccines. Clinical studies comparing the immunogenicity of Hexavac administered at either 2, 3 and 4 months or 2, 4 and 6 months demonstrated that it can be used by either vaccination schedule. A further study also supported the use of primary doses of Hexavac at 3 and 5 months with a booster at 12 months of age. Hexavac demonstrated a good reactogenicity and tolerability profile. The most frequently reported adverse events after both primary and booster doses were local reactions of redness and swelling/induration and a systemic response of mild fever, irrespective of the vaccine used for priming. Hexavac provided immunity against six important childhood diseases with a single injection at each visit. 相似文献
997.
Mallet E Matisse N Mathieu N Langue J Boisnard F Soubeyrand B;Pentavac Study Group 《Vaccine》2004,22(11-12):1415-1422
The main objective of this study was to assess in 5-6-year-old French children (n=234) the persistence of antibodies induced by a primary series vaccination (at 2-4 months of age) and a first booster (at 12-16 months of age) with a pentavalent two-component acellular pertussis combined vaccine (DTacP-IPV-Hib; Pentavac). The second objective was to evaluate in these 5-6-year-old French children the safety and the immunogenicity of a tetravalent acellular pertussis combined vaccine (DTacP-IPV; Tetravac) given as second booster. RESULTS: Seroprotective antibody levels against diphtheria, tetanus, types 1-3 poliomyelitis and PRP were maintained 4-5 years after primary-vaccination and first booster with Pentavac. As expected, anti-PT antibodies levels were low, suggesting that children were not colonised by Bordetella pertussis. The second booster with Tetravac was well tolerated and elicited a strong booster response for all antigens. CONCLUSION: acellular pertussis combined vaccine, used in primary-vaccination, could be considered as having the same priming effect and the same efficacy as whole cell pertussis vaccine. 相似文献
998.
Orvain J Xerri B Matillon Y 《International journal of technology assessment in health care》2004,20(1):25-34
Health technology assessment (HTA) in France covers a variety of activities performed for different customers (e.g., health professionals in the field and policy makers in government) for the benefit of patients. To promote the improvement of quality in health care, France has set up a series of distinct agencies that report to the Ministry of Health but are also accountable to their other customers. We place particular emphasis on ANAES (National Agency for Accreditation and Evaluation in Health) whose main remit is HTA. We show how the diversity of HTA activities and their decentralization suggests tight collaboration among all the different bodies which perform HTA or are closely involved with HTA, and we provide examples of such collaboration. 相似文献
999.
Introduction: The model organism Caenorhabditis elegans is widely used for genetic studies as well as a living biomonitor in ecotoxicology. In this study, we investigated whether C. elegans may represent a suitable model for rapid preliminary toxicity studies of pharmaceutical compounds. Methods: For this purpose, we used the EGFR kinase inhibitors BIBU1361, BIBX1382, and an inactive chemical analogue BIBU1476. As a first parameter to score for toxicity, we determined lethality of the wild-type C. elegans strain N2 (Bristol) in the presence of the compounds. The transgenic C. elegans strain PC72 (lacZ, heat shock protein-16 [hsp-16] construct) was used as a report organism for toxic effects. PC72 expresses β-Galactosidase which is induced by hsp-16 in direct response when exposed to toxic compounds. The expression of β-Galactosidase in cells was subsequently visualized by histochemical staining with X-Gal. Results: A rank order of potency with respect to lethality was established: BIBU1361>BIBX1382>>BIB1476. The induction of β-Galactosidase was concentration-dependent for each compound and demonstrated the same order of potency as observed for lethality. Furthermore, these compounds showed the same order for lethality in rodents, the first requirement of validation. Discussion: These results indicate that wild-type C. elegans and the transgenic strain PC72 are both suitable models to determine the toxicity of pharmaceutical compounds. This approach allows for an easy and fast ranking of compound toxicity, which may lead to a more rational choice for further in vivo tests. 相似文献
1000.
Guillot B Dalac S Delaunay M Baccard M Chevrant-Breton J Dereure O Machet L Sassolas B Zeller J Bernard P Bedane C Wolkenstein P;French Group of Cutaneous Oncology 《Melanoma research》2004,14(2):159-163
Neurofibromatosis 1 (NF1) is a genetically transmitted disease occurring approximately once in 3000 live births and resulting from mutations of the NF1 gene that encodes a protein named neurofibromin, a negative regulator of the ras-dependent pathway. An excess of neoplasia especially tumours of neuroectodermal origin is classically observed. The occurrence of malignant melanoma in patients with NF1 has already been described in scattered clinical reports but little is known as to the characteristics of melanoma arising in NF1 patients. A multicentric retrospective study was conducted on a panel of French referring centres for a period of 13 years to identify patients with both melanoma and NF1. Patients with mucosal or ocular melanoma were excluded. The diagnosis of malignant melanoma was based on specific histology whereas NF1 was identified according to the criteria proposed by the NIH Consensus Conference. All patient fulfilling criteria for both melanoma and NF1 were investigated using a common procedure recording clinical and histological data along with prognostic factors for the two diseases. Eleven patients were identified with both diseases. The clinical pattern of NF1 was quite similar to the classical form of the disease, but some unusual features were present as regards to the melanoma: a sex-ratio of 10 women for one man and an average age lower than expected (median age=33 years) for melanoma occurrence. Among prognostic factors, median thickness was high compared to large series of melanoma in the literature (3.20 versus 1.5 mm). Another neoplasia occurred in three patients. An increase in melanoma incidence in patients with NF1 remains hypothetical but our small series of malignant melanoma arising in NF1 patients displays a large female preponderance, a higher thickness than expected and a frequent association with a second neoplasia. The peculiar female proneness for cancer whatever its localization and the risk of multiple neoplasias have already been reported in NF1 patients and could be true for malignant melanoma as well. 相似文献