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991.
J. Pallás C. Fari?as-Alvarez D. Prieto J. Llorca M. Delgado-Rodríguez 《Epidemiology and infection》1999,123(1):95-102
A cross-sectional study was conducted in prisons of Cantabria (northern Spain) from June 1992 to December 1994. Inmates were asked to participate in a survey on prevalence and risk factors for monoinfections and coinfections with HIV, HBV and HCV. Crude and multiple odds ratios of risk factors were calculated (by polychotomous logistic regression). Prevalence of coinfections was higher than that of monoinfections. IDU risk factors were the main independent variables associated with monoinfections and coinfections with these agents. The strength of association increased with the degree of coinfection for IDU risk factors and penal status, e.g. duration of injecting drug use for more than 5 years yielded an adjusted OR ranging from 1.3 (95% CI: 0.4-5.1) for HBV monoinfection to 180 (95% CI: 61.0-540.0) for HIV-HBV-HCV coinfection. In comparison, sexual behaviours were less important than IDU risk factors. 相似文献
992.
993.
Inhibition of rat corneal angiogenesis by 16-kDa prolactin and by endogenous prolactin-like molecules. 总被引:4,自引:0,他引:4
Z Due?as L Torner A M Corbacho A Ochoa G Gutiérrez-Ospina F López-Barrera F A Barrios P Berger G Martínez de la Escalera C Clapp 《Investigative ophthalmology & visual science》1999,40(11):2498-2505
PURPOSE: The cornea is an avascular organ, where induction of new blood vessels involves the turn-on of proangiogenic factors and/or the turn-off of antiangiogenic regulators. Prolactin (PRL) fragments of 14 kDa and 16 kDa bind to endothelial cell receptors and inhibit angiogenesis. This study was designed to determine whether antiangiogenic PRL-like molecules are involved in cornea avascularity. METHODS: Sixteen-kDa PRL and basic fibroblast growth factor (bFGF) or anti-PRL antibodies were placed into rat cornea micropockets and neovascularization evaluated by the optical density associated with capillaries stained by the peroxidase reaction and by the number of vessels growing into the implants. Prolactin receptors in corneal epithelium were investigated by immunocytochemistry. RESULTS: bFGF induced a dose-dependent stimulation of corneal neovascularization. This effect was inhibited by coadministration of 16-kDa PRL, as indicated by a 65% reduction in vessel density and a 50% decrement in the incidence of angiogenic responses. Corneal angiogenic reactions of different intensities were induced by implantation of polyclonal and monoclonal anti-PRL antibodies. Corneal epithelial cells were labeled by several anti-PRL receptor monoclonal antibodies. CONCLUSIONS: These findings show that exogenous 16-kDa PRL inhibits bFGF-induced corneal neovascularization and suggest that PRL-like molecules with antiangiogenic actions function in the cornea. PRL receptors in the corneal epithelium may imply that PRL in the cornea derives from lacrimal PRL internalized through an intracellular pathway. These observations are consistent with the notion that members of the PRL family are potential regulators of corneal angiogenesis. 相似文献
994.
New quinoxaline 1,4-di-N-oxides for treatment of tuberculosis 总被引:1,自引:0,他引:1
Sainz Y Montoya ME Martínez-Crespo FJ Ortega MA López de Ceráin A Monge A 《Arzneimittel-Forschung》1999,49(1):55-59
Some quinoxaline 1,4-di-N-oxides derivatives with very different substituents in 2, 3, 6 and 7 positions have been synthesized in order to obtain new hypoxia selective agents. Some of these products have been tested as antituberculosis agents and very interesting results have been obtained from the first screening. 相似文献
995.
Gutiérrez-Salinas J Miranda-Garduño L Trejo-Izquierdo E Díaz-Muñoz M Vidrio S Morales-González JA Hernández-Muñoz R 《Biochemical pharmacology》1999,58(11):1831-1839
Ethanol metabolism can induce modifications in liver metabolic pathways that are tightly regulated through the availability of cellular energy and through the redox state. Since partial hepatectomy (PH)-induced liver proliferation requires an oversupply of energy for enhanced syntheses of DNA and proteins, the present study was aimed at evaluating the effect of acute ethanol administration on the PH-induced changes in cellular redox and energy potentials. Ethanol (5 g/kg body weight) was administered to control rats and to two-thirds hepatectomized rats. Quantitation of the liver content of lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, and adenine nucleotides led us to estimate the cytosolic and mitochondrial redox potentials and energy parameters. Specific activities in the liver of alcohol-metabolizing enzymes also were measured in these animals. Liver regeneration had no effect on cellular energy availability, but induced a more reduced cytosolic redox state accompanied by an oxidized mitochondrial redox state during the first 48 hr of treatment; the redox state normalized thereafter. Administration of ethanol did not modify energy parameters in PH rats, but this hepatotoxin readily blocked the PH-induced changes in the cellular redox state. In addition, proliferating liver promoted decreases in the activity of alcohol dehydrogenase (ADH) and of cytochrome P4502E1 (CYP2E1); ethanol treatment prevented the PH-induced diminution of ADH activity. In summary, our data suggest that ethanol could minimize the PH-promoted metabolic adjustments mediated by redox reactions, probably leading to an ineffective preparatory event that culminates in compensatory liver growth after PH in the rat. 相似文献
996.
García-Sáinz JA Gottfried-Blackmore A Vázquez-Prado J Romero-Avila MT 《European journal of pharmacology》1999,385(2-3):263-271
Human alpha(1b)-adrenoceptors stably expressed (B(max) approximately 800 fmol/mg membrane protein) in mouse fibroblasts were able to increase intracellular Ca(2+) and inositol phosphate production in response to noradrenaline. Activation of protein kinase C desensitized the alpha(1b)-adrenergic-mediated actions but did not block the ability of the cells to respond to lysophosphatidic acid. Inhibition or downregulation of protein kinase C also blocked the action of the tumor promoter on the adrenergic effects. Photolabeling experiments indicated that the receptor has an apparent molecular weight of approximately 80 kDa. The receptors were phosphorylated in the basal state and such phosphorylation was increased when the cells were incubated with phorbol myristate acetate or noradrenaline. Incubation of the cells with phorbol myristate acetate or noradrenaline blocked noradrenaline-promoted [35S]GTP-gamma-S binding to membranes, suggesting receptor-G protein uncoupling. The results indicate that activation of protein kinase C blocked/desensitized human alpha(1b)-adrenoceptors and that such effect was associated to receptor phosphorylation. 相似文献
997.
The effects of micro-, delta- and kappa-opioid receptor agonists, and orphanin FQ/nociceptin (Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-Arg-Lys-Leu-Ala-Asn-Gln), on K+-induced [Ca2+]i increase were examined in SK-N-SH cells. Exposure to K+ (50 mM) resulted in a [Ca2+]i rise, which was blocked (-85%) by furaldipine (1 microM) and increased (63%) by BayK 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethyl-pyridine-5 -carboxylate) (0.5 microM), indicating the involvement of L-type Ca2+ channels. The kappa-opioid receptor agonists 3,4-dichloro-N-Methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide (U-50488H) (1-50 microM) and 5,7,8-N-Methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4,5]dec-8-yl]benze neacetamide (U-69593) (25 microM), and the mu-opioid receptor agonist sufentanil (100 nM-3 microM) inhibited the amplitude of K+-induced [Ca2+]i increase. The agonist of the orphan opioid receptor, orphanin FQ/nociceptin (1 microM), induced dual excitatory and inhibitory effects on the depolarisation-induced Ca2+ influx. The effects of the opioid receptor agonists were not blocked by the kappa-opioid receptor antagonist nor-binaltorphimine (1 microM), only weakly prevented by naloxone (10-100 microM) and naltrexone (100 microM), and partially prevented by pertussis toxin (100 ng/ml, 24 h). The antagonist of the orphan opioid receptor, [Phe1psi(CH2-NH)Gly2]nociceptin(1-13)NH2 (1 microM), prevented the inhibitory effect of U-50488H, sufentanil and orphanin FQ. The present study provides pharmacological evidence for the presence of L-type Ca2+ channels in SK-N-SH cells, that are modulated by opioids through orphan opioid receptor activation. 相似文献
998.
Bartolomé-Nebreda JM Gómez-Monterrey I García-López MT González-Muñiz R Martín-Martínez M Ballaz S Cenarruzabeitia E LaTorre M Del Río J Herranz R 《Journal of medicinal chemistry》1999,42(22):4659-4668
Analogues of the previously reported potent and highly selective CCK(1) receptor antagonist (4aS, 5R)-2-benzyl-5-(N-Boc-tryptophyl)amino-1,3-dioxoperhydropyrido-[1, 2-c]pyrimidine (2a) were prepared to explore the structural requirements at the Boc-tryptophan domain for CCK(1) receptor affinity. Structural modifications of 2a involved the Trp side chain, its conformational freedom, the Boc group, and the carboxamide bond. Results of the CCK binding and in vitro functional activity evaluation showed three highly strict structural requirements: the type and orientation of the Trp side chain, the H-bonding acceptor carbonyl group of the carboxamide bond, and the presence of the Trp amino protection Boc. Replacement of this acid-labile group with 3, 3-dimethylbutyryl or tert-butylaminocarbonyl conferred acid stability to analogues 14a and 15a, which retained a high potency and selectivity in binding to CCK(1) receptors, as well as an in vivo antagonist activity against the acute pancreatitis induced by caerulein in rats. Oral administration of compounds 14a and 15a also produced a lasting antagonism to the hypomotility induced by CCK-8 in mice, suggesting a good bioavailability and metabolic stability. 相似文献
999.
We present data demonstrating that the cytotoxic compound [Pt2Cl4(diminazene aceturate)2]Cl4.4H2O (Pt-berenil) circumvents cisplatin resistance in ovarian carcinoma cells. The analysis of the interaction of Pt-berenil with linear and supercoiled DNA indicates that this compound induces the formation of a large number of covalent interstrand cross-links on DNA and that this number is significantly higher than that produced by cis-diamminedichloroplatinum(II) (cis-DDP). Renaturation experiments, interstrand cross-link assays, and electron microscopy indicate that the kinetics of DNA interstrand cross-link formation caused by Pt-berenil binding is faster than that caused by cis-DDP at similar levels of platinum bound to DNA. Furthermore, the number of DNA interstrand cross-links in Pt-berenil-DNA complexes is influenced by supercoiling. Circular dichroism experiments show that Pt-berenil strongly inhibits the B-DNA-to-Z-DNA transition of poly(dG-m5 dC). poly(dG-m5dC) at salt concentrations (3 mM MgCl2) at which the native methylated polynucleotide readily adopts the Z-DNA conformation, which suggests that the induction of interstrand cross-links by Pt-berenil inhibits the Z-DNA transition. On the basis of these results, we propose that bis(platinum) compounds with structure similar to Pt-berenil may act as blockers of DNA conformational changes and may also display activity in cisplatin-resistant cells. 相似文献
1000.
J. Knapp P. Bokník M.C. Deng S. Huke I. Lüss O. Klein-Wiele B. Linck H. Lüss F.U. Müller P. Nacke H.H. Scheld W. Schmitz U. Vahlensieck J. Neumann 《Naunyn-Schmiedeberg's archives of pharmacology》1999,360(4):464-472
It is unknown whether protein phosphatases types 1 and 2A are present in and can regulate the tone of human vascular tissue. The expression and possible function of serine/threonine protein phosphatases (PP) type 1 (PP1) and type 2A (PP2A) were studied in isolated human coronary arteries. Catalytic subunits of PPI and PP2A were identified by means of phosphatase activity measurement in tissue homogenates, by separation of enriched extracts through affinity column chromatography, by immunoblotting with specific antibodies, by hybridization of mRNA with specific DNA probes and PCR of reverse transcribed mRNA. Based on these methods, the catalytic subunits of PP1(alpha,beta,gamma) and PP2A(alpha,beta) were identified. Appropriately, cantharidin, an inhibitor of PP1 and PP2A, increased basal tone of human isolated coronary artery rings with an EC50 of about 16 micromol/l by increasing the phosphorylation state of the regulatory light chains of myosin. In summary, PP1 and PP2A are expressed in human coronary arteries and they can alter vascular tone. 相似文献