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991.
The synthesis of two series of 1-(but-2-ynyl)pyrazole containing a pyrrolidine or a diethylamine moiety, respectively, is described, together with their muscarinic receptor affinities. 相似文献
992.
Moreno Gálvez A García Mateo JV Martínez Calatayud J 《Journal of pharmaceutical and biomedical analysis》2002,27(6):1027-1036
This article deals with the simultaneous determination of dissolution profiles of two drugs with overlapped spectra, present in the same pharmaceutical formulation. The official procedure for the dissolution profile is adapted to the continuous-flow methodology; the dissolution vessel is connected to an FIA manifold, in which the sample aliquots from the dissolution vessel are treated in order to adjust to the suitable pH and dilution degree to be monitored. The resulting solution is injected into the carrier stream, an acetic acid–acetate buffer at pH 4.3 and forced to the flow-cell of the spectrophotometer. The simultaneous determination of both profiles is based on the first derivative spectra and the zero-crossing mathematical procedure. The empirical profile of the curve is adjusted by regression using different approaches; the three-parameter plot method is selected. The analytical errors, when the concentration of one drug is very low or very high, are also checked. A binary mixture in commercially available formulations of solid oral administration of sulphametoxazole and trimethoprim is presented. 相似文献
993.
BACKGROUND: Mediterranean diets are felt to be healthful diets linked with reduced mortality from diet-related noncommunicable diseases. OBJECTIVE: To examine trends in diet, activity, obesity and diet-related noncommunicable diseases for Spain and compare these with other European countries, particularly those from the Mediterranean area. DESIGN: A combination of large-scale primary and secondary nationally representative data analysis are used. DATA: Nationally representative data on household food consumption, physical activity, adult obesity, and cause of death are combined with regionally representative adolescent obesity data, obtained in the last four decades. Comparative diet and obesity data come from nationally representative comparable data, obtained during the same period. RESULTS: The Spanish diet has shifted toward a very high level of fat intake, high fruit and dairy intake and moderate vegetable intake. Dairy and fruit intakes were the highest in Europe, as was the proportion of energy from fat, when we compared with the available data. Adult overweight and obesity trends show a marked increase in the past decade to levels as high as Italy and far above France. Overweight for children aged 6-7 is above that of even the USA, while adolescent overweight levels are among the highest in the world. Cardiovascular disease mortality is low, as with Italy and France, and the cancer mortality rate is lower than Italy and France. CONCLUSIONS: We have observed that, in Spain, relatively high obesity prevalences and dairy intake levels are related to much lower levels of cardiovascular disease and cancer mortality than are found in other European countries. This unique Spanish dietary and obesity pattern should be further explored in order to clarify the causal links. SUPPORT: The National Institutes of Health (NIH; R01-HD30880 and R01-HD38700). 相似文献
994.
Saracíbar G Casado A Rodríguez VM Portillo MP Macarulla MT Abecia LC Echevarría E Casis L 《Nutritional neuroscience》2002,5(5):353-358
Nefazodone is an antidepressant drug that inhibits serotonin and noradrenaline reuptake. The aim of the present work was to study the effects of nefazodone on food intake, body weight, adiposity and hypothalamic NPY immunostaining in rats. For this purpose, male Sprague-Dawley rats (3-month-old) were administered with nefazodone (20 mg/kg; i.p) daily for two weeks. The control group was given 0.9% NaCl solution. Hypothalamic arcuate, paraventricular, periventricular, supraoptic and suprachiasmatic nuclei and the lateral hypothalamic area were immunostained for NPY. Chronic nefazodone administration in rats did not modify food intake, body weight and adipose depot size (subcutaneous, perirenal and epididymal white adipose tissues, and interscapular brown adipose tissue). However, a significant decrease in paraventricular NPY immunostaining was found in the nefazodone group compared with the control group. No changes in other hypothalamic regions such as arcuate, periventricular, supraoptic and suprachiasmatic nuclei, and lateral and medial preoptic areas were observed. Because nefazodone is an alpha1-adrenoceptor antagonist, it can be proposed that the expected decrease in food intake after nefazodone administration, due to its effects on NPY arcuate-paraventricular projection, could be masked by the opposite orexigenic effect of alpha1-adrenoceptor blockade. 相似文献
995.
Alcalá B Arreaza L Salcedo C Uría MJ De La Fuente L Vázquez JA 《Emerging infectious diseases》2002,8(12):1512-1514
A mass immunization campaign for 18-month to 19-year-olds was undertaken in Spain in 1996-1997 because of an epidemic of serogroup C meningococcal disease associated with a C:2b:P1.2,5 strain belonging to the A4 lineage. Surveillance for the "capsule-switching" phenomenon producing B:2b:P1.2,5 isolates was undertaken. Of 2,975 meningococci characterized, B:2b:P1.2,5 and B:2b:P1.2 antigenic combinations were found in 18 isolates; 15 meningococci were defined as serogroup B belonging to the A4 lineage. 相似文献
996.
Zudaire I Pío R Martín-Subero I Lozano MD Blanco D García López JJ Odero de Dios MD Rey N Zulueta J Siebert R Calazanz MJ Montuenga L 《Anales del sistema sanitario de Navarra》2002,25(3):305-315
Lung cancer is one of the most frequent causes of cancer death in Western countries. Overall 5-year survival rate is lower than 15% mainly due to the late diagnosis of the disease. Primary prevention (reduction of tobacco consumption) and more effective methods for early detection are needed. Some studies have recently shown that low-dose spiral computed tomography (CT) is a useful technique to the detection of pulmonary malignant nodules in early stages. Studies are developing to evaluate its efficacy in series of high-risk patients. A new cytogenetic technique has been developed: the FICTION technique (Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasms). This technique allows the simultaneous study of immunophenotypic markers and genetic abnormalities present in tumour cells. The goal of our project is optimise this technique in sputum and bronchoalveolar lavage specimens from lung cancer patients. The overall goal of this project is evaluate the usefulness of this technique, together with the new radiological techniques, in early detection programs of lung cancer in high-risk patients. In the present study we review the cytogenetic studies on lung cancer carried out in the recent years. We also introduce the basic methodological aspects that will be developed in our project. 相似文献
997.
Silvestre Busto C Gost Garde J Astier Peña P Ezpeleta Iturralde P 《Revista espa?ola de salud pública》2002,76(5):605-612
BACKGROUND: The objective of this study is to explore the perception that participants in a clinical trial have about the information disclosured by the physician, during patient recruitment and along the study as a preliminary stage for drafting a questionnaire. METHODS: Qualitative study by means of quasi-structure interviews to subjects of different features taken from a patients list obtained by randomized selection of participants in clinical trials approved within the 1998-1999 period. For conducting the interviews, a guide was prepared based on the recommendations of the Helsinki Declaration. RESULTS: Six (6) interviews were held with 7 individuals, as one married couple was interviewed. Most of the categories encountered belonged to the Helsinki Declaration. In addition, others being related to the fulfillment of expectations and to the balance of the risks/benefits done by the individuals for deciding to take part in the study. CONCLUSIONS: The patients were acceptably informed of the most points dealt with under the Helsinki Declaration. The existence of lacking areas having a major impact on the fulfillment of their expectations however having been revealed. 相似文献
998.
Superoxide anions mediate veratridine-induced cytochrome c release and caspase activity in bovine chromaffin cells 下载免费PDF全文
Jordán J Galindo MF Tornero D Benavides A González C Agapito MT González-García C Ceña V 《British journal of pharmacology》2002,137(7):993-1000
1. Mitochondrial mechanisms involved in veratridine-induced chromaffin cell death have been explored. 2. Exposure to veratridine (30 micro M, 1 h) produces cytochrome c release to the cytoplasm that seems to be mediated by superoxide anions and that is blocked by cyclosporin A (10 micro M), MnTBAP (10 nM), catalase (100 IU ml(-1)) and vitamin E (50 micro M). 3. Following veratridine treatment, there is an increase in caspase-like activity, blocked by vitamin E (50 micro M) and the mitochondrial permeability transition pore blocker cyclosporin A (10 micro M). 4. Superoxide anions open the mitochondrial permeability transition pore in isolated mitochondria, an effect that is blocked by vitamin E (50 micro M) and cyclosporin A (10 micro M), but not by the Ca2+ uniporter blocker ruthenium red (5 micro M). 5. These results strongly suggest that under the stress situation caused by veratridine, superoxide anions become important regulators of mitochondrial function in chromaffin cells. 6. Exposure of isolated bovine chromaffin mitochondria to Ca2+ results in mitochondrial swelling. This effect was prevented by ruthenium red (5 micro M) and cyclosporin A (10 micro M), while it was not modified by vitamin E (50 micro M). 7. Veratridine (30 micro M, 1 h) markedly decreased total glutathione and GSH content in bovine chromaffin cells. 8. In conclusion, superoxide anions seem to mediate veratridine-induced cytochrome c release, decrease in total glutathione, caspase activation and cell death in bovine chromaffin cells. 相似文献
999.
Pasapera AM Gutiérrez-Sagal R Herrera J Galicia-Canales N García de la Mora G Ulloa-Aguirre A 《European journal of pharmacology》2002,452(3):347-355
In the present study, we used [3H]norethisterone to explore the bioconversion of this compound to A-ring reduced metabolites in African Green Monkey Kidney CV-1 cells and breast cancer T-47D cells. Additionally, we analyzed the capability of each norethisterone tetrahydro-reduced compound to bind the human oestrogen receptors alpha and beta and transactivate an oestrogen-sensitive reporter gene. The results showed that norethisterone is mainly metabolized to 3 alpha,5 alpha-norethisterone (>85% of total [3H]norethisterone added) by CV-1 and T-47D cells, and that both A-ring tetrahydro-reduced metabolites exhibit different capabilities to displace [3H]17beta-oestradiol from the oestrogen receptor alpha and beta, being 3 alpha,5 alpha-norethisterone the weakest competitor. We also found that 3 alpha,5 alpha-norethisterone and 3beta,5 alpha-norethisterone activate both oestrogen receptors at nanomolar concentrations and that the transactivation induced by the oestrogen receptor alpha was generally higher (1.7- to 4.0-fold) than that provoked by the beta receptor isoform. In oestrogen receptor alpha-transfected CV-1 and T-47 D cells, the oestrogenic-like potency of the 3beta,5 alpha-tetrahydro-reduced form was similar to that exhibited by 17beta-oestradiol and 2.5- to 4.0-fold higher than that shown by the 3 alpha,5 alpha-reduced compound; conversely, in the oestrogen receptor beta system the potency of the natural ligand was higher than that presented by the 3beta,5 alpha-tetrahydro-reduced metabolite. In CV-1 cells expressing the oestrogen receptor beta, the transactivation potency of 3beta,5 alpha-norethisterone was approximately 2-fold higher than that exhibited by its 3 alpha,5 alpha-tetrahydro-reduced isomer, whereas in T-47D cells the potency of the 3 alpha,5 alpha-tetrahydro-reduced compound was slightly higher than that shown by the 3beta,5 alpha A-ring reduced norethisterone metabolite. These results demonstrate that CV-1 and T-47D cells possess the enzymatic machinery to bioconvert norethisterone into the 5 alpha-reduced, 3 alpha-hydroxylated form and that neither 3 alpha,5 alpha- or 3beta,5 alpha-norethisterone exhibit preference or selectivity towards a particular oestrogen receptor isoform to induce a particular oestrogenic effect in these cell lines. 相似文献
1000.
Braña MF Cacho M García MA de Pascual-Teresa B Ramos A Acero N Llinares F Muñoz-Mingarro D Abradelo C Rey-Stolle MF Yuste M 《Journal of medicinal chemistry》2002,45(26):5813-5816
A series of mono and bisintercalators based on the 5,8-dihydrobenz[de]imidazo[4,5-g]isoquinoline-4,6-dione system were synthesized and evaluated for growth inhibitory properties in several human cell lines. All target compounds showed activity in the micromolar range. Representative compounds were evaluated using UV--vis spectroscopy and viscosimetric determinations, showing that they behave as DNA intercalators. Molecular modeling techniques were used in order to rationalize the moderate activity observed for bisnaphthalimides. 相似文献