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991.
992.
Serruya SJ Cecatti JG Lago Td 《Cadernos de saúde pública / Ministério da Saúde, Funda??o Oswaldo Cruz, Escola Nacional de Saúde Pública》2004,20(5):1281-1289
This article evaluates the implementation of the Brazilian Ministry of Health's Program for Humanization of Prenatal and Childbirth Care using data generated by the SISPRENATAL/DATASUS database from the Unified National Health System. From its beginning in June 2000 until December 2002, 3,983 municipalities joined the Program, and 71% of participating municipalities (3,183) reported their health care activities, constituting a database with 720,871 women. Nearly 20% of the women had six or more prenatal visits, and approximately half of them had the postpartum follow-up visit and required lab tests performed in 2002. In addition, 41% of the women had been vaccinated against tetanus. The number of HIV antibody tests was twice that of syphilis during the two-year period. Only a small percentage of women (2% in 2001 and 5% in 2002) received the entire set of prenatal and childbirth care services. The low percentages attest to the need for permanent evaluation aimed at improving quality of care and guaranteeing both high-quality maternal and perinatal results and the inalienable right of women to safe care and well-being during pregnancy and delivery. 相似文献
993.
GABA(A) receptors have structural and functional homology with a super-family of cys-loop ligand-gated ion channel receptors including the nicotinic acetylcholine receptors. Amino acid residues involved in ligand-binding pockets are homologous among super-family members, leading to the multiple-loop model of binding sites situated at subunit interfaces, validated by structural studies on the nicotinic acetylcholine receptor and water-soluble snail acetylcholine binding protein. This article will briefly review the literature on the agonist binding sites on the receptor super-family, and then describe the current situation for attempts to identify sites for allosteric modulators on the GABA(A) receptors. A combination of mutagenesis and photoaffinity labeling with anesthetic ligands has given some leads in this endeavor. Current work by others and ourselves focuses on three putative sites for modulators: (1) within the ion channel domain TM2, near the extracellular end; (2) the agonist binding sites and homologous pockets at other subunit interfaces of the pentameric receptor; and (3) on the linker region stretching from the agonist site loop C to the top of the TM1 region. It is likely that concrete structural information will be forthcoming soon. 相似文献
994.
Jacob C Szilagyi C Allen JM Bertrand C Lagente V 《British journal of pharmacology》2004,143(2):257-268
We investigated the generation of reactive oxygen species (ROS) from bronchoalveolar lavage (BAL) cells of either control or LPS-exposed rats and the effects of PDE4 inhibitors on ROS production. The PDE4 inhibitors, rolipram and Ariflo (cilomilast, SB 207499) dose-dependently (0.1-10 microm) inhibited fMLP-induced superoxide anion (O(2)(*-)) production (IC(50)s: 0.03 and 0.55 microm, respectively) in BAL cells of Wistar rats collected 3 h after an LPS-aerosol (200 micrograms ml(-1), 1 h). These BAL contained 85-95% neutrophils (BAL cells enriched in neutrophils). In contrast, BAL cells collected at the end of the challenge contained only macrophages and in these conditions, rolipram and Ariflo (0.1-10 microm) could only inhibit 25 and 45% of fMLP-induced O(2)(*-) release, respectively. We also observed that the inhibition of p44/42(MAPK) by PD98059 (1-10 microm) increased O(2)(*-) release by BAL cells enriched in neutrophils, but not by macrophages, and prevented the inhibition of O(2)(*-) production induced by PDE4 inhibitors. Western blot analysis showed that PDE4 inhibitors strongly activated p44/42(MAPK) in BAL cells enriched in neutrophils but not in macrophages. And in these cells, PDE4 and p44/42(MAPK) were co-immunoprecipitated by a polyclonal anti-PDE4 antibody. The following cell permeable-cAMP analogues, dbcAMP (10 microm-1 mm), 8-CPT-cAMP (1 mm) and 8-pMeOPT-2'-O-Me-cAMP (0.5 mm), could not reduce fMLP-induced O(2)(*-) production and both PKA inhibitors, PKA inhibitor 14-22 amide myristoylated (50 nm-1 microm) and H-89 (100 nm-1 microm), did not affect the decrease of O(2)(*-) release induced by PDE4 inhibitors in BAL cells enriched in neutrophils. These data suggest that PDE4 inhibitors decreased fMLP-induced O(2)(*-) release in BAL cells enriched in neutrophils but not in macrophages, through p44/42(MAPK) activation by a cAMP- and a PKA-independent mechanism. 相似文献
995.
Meng CQ Somers PK Hoong LK Zheng XS Ye Z Worsencroft KJ Simpson JE Hotema MR Weingarten MD MacDOnald ML Hill RR Marino EM Suen KL Luchoomun J Kunsch C Landers LK Stefanopoulos D Howard RB Sundell CL Saxena U Wasserman MA Sikorski JA 《Journal of medicinal chemistry》2004,47(25):6420-6432
Vascular cell adhesion molecule-1 (VCAM-1) mediates recruitment of leukocytes to endothelial cells and is implicated in many inflammatory conditions. Since part of the signal transduction pathway that regulates the activation of VCAM-1 expression is redox-sensitive, compounds with antioxidant properties may have inhibitory effects on VCAM-1 expression. Novel phenolic compounds have been designed and synthesized starting from probucol (1). Many of these compounds demonstrated potent inhibitory effects on cytokine-induced VCAM-1 expression and displayed potent antioxidant effects in vitro. Some of these derivatives (4o, 4p, 4w, and 4x) inhibited lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 from human peripheral blood mononuclear cells (hPBMCs) in a concentration-dependent manner in vitro and showed antiinflammatory effects in an animal model. Compounds 4ad and 4ae are currently in clinical trials for the treatment of rheumatoid arthritis (RA) and prevention of chronic organ transplant rejection, respectively. 相似文献
996.
997.
Association of the functional V158M catechol-O-methyl-transferase polymorphism with panic disorder in women 总被引:2,自引:0,他引:2
Domschke K Freitag CM Kuhlenbäumer G Schirmacher A Sand P Nyhuis P Jacob C Fritze J Franke P Rietschel M Garritsen HS Fimmers R Nöthen MM Lesch KP Stögbauer F Deckert J 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2004,7(2):183-188
Panic disorder is an anxiety disorder with an estimated heritability of up to 48%. Pharmacological and genetic studies suggest that genes coding for proteins involved in the catecholaminergic system might be relevant for the pathogenesis of the disease. In the present study, we genotyped a single nucleotide polymorphism (472G/A=V158M) in the coding region of the catechol-O-methyl-transferase (COMT) gene in 115 patients with panic disorder and age- and sex-matched controls. Association analysis revealed a significant excess of the more active COMT allele (472G=V158) in patients with panic disorder (p=0.04), particularly in female patients (p=0.01), but not in male patients (p=1.0). The assessment of a possible interaction of the COMT polymorphism with a previously reported functional 30-bp VNTR in the monoamine oxidase A promoter (MAOALPR) in female patients did not yield significant results. Our data support a role of the 472G/A (V158M) COMT polymorphism or a nearby locus in the pathogenesis of panic disorder in women. 相似文献
998.
Benson J Hahn F March T McDonald J Sopori M Seagrave J Gomez A Bourdelais A Naar J Zaias J Bossart G Baden D 《Journal of toxicology and environmental health. Part A》2004,67(18):1443-1456
Brevetoxins are potent neurotoxins produced by the marine dinoflagellate Karenia brevis. Exposure to brevetoxins may occur during a K. brevis red tide when the compounds become aerosolized by wind and surf. This study assesses possible adverse health effects associated with short-term inhalation exposure to brevetoxin 3. Male F344/Crl/Br rats were exposed to 500 microg brevetoxin 3/m3 by nose-only inhalation for 0.5 or 2 h/d for 5 consecutive days. Control rats were sham exposed for 2 h to vehicle. Calculated deposited brevetoxin doses were 8.3 and 33 microg/kg/d for the low- and high-dose groups, respectively. At the termination of exposures, only body weights of the high-dose group (Group B) were significantly below control values. By immunohistochemistry (IHC), small numbers of splenic and peribronchiolar lymphoid tissue macrophages stained positive for brevetoxin, while nasal mucosa, liver, and brain were IHC negative for brevetoxin. No gross or microscopic lesions were observed in any tissue examined. There was no biochemical evidence of cytotoxicity or inflammation in bronchoalveolar lavage fluid. Alveolar macrophages showed some evidence of activation following brevetoxin exposure. Humoral-mediated immunity was suppressed in brevetoxin-exposed rats as indicated by a >70% reduction in splenic plaque-forming cells in brevetoxin-exposed animals compared to controls. Results suggest that the immune system may be a target of toxicity following brevetoxin inhalation. Future studies will focus on identification of a no-effect level and mechanisms underlying brevetoxin-induced immune suppression. 相似文献
999.
Kanunfre CC da Silva Freitas JJ Pompéia C Gonçalves de Almeida DC Cury-Boaventura MF Verlengia R Curi R 《International immunopharmacology》2004,4(9):1171-1185
Several studies have shown that PPARgamma agonists play a role in the regulation of lymphocytes function and apoptosis. However, the molecular mechanism(s) underlying the immunomodulatory effects of PPARgamma agonists are not defined yet. In this study, the effects of PPARgamma (15d PGJ2 and ciglitizone) ligands on proliferation, cytokine production and apoptosis of Jurkat and Raji cells (human T and B lymphocytes, respectively) were examined. Ciglitizone and 15d PGJ2 presented antiproliferative and cytotoxic effects on Jurkat and Raji cells as shown by [14C]-thymidine incorporation and cell viability assay. In addition, 15d PGJ2 inhibited cytokine production (IL-2 in Jurkat cells and IL-10 in Raji cells). The mechanism whereby PPARgamma agonists induced cytotoxicity is via apoptosis as shown by DNA fragmentation, nuclear condensation and phosphatidylserine externalization. The induction of apoptosis by ciglitizone and 15d PGJ2 on Jurkat and Raji cells may explain the suppression of cytokine production and the decrease in proliferation observed in both cell types. The apoptotic process was associated with a decrease in mitochondrial membrane potential and a marked down-regulation of the c-myc expression. These findings might play a key role in the apoptosis of T and B lymphocytes induced by PPARgamma agonists. 相似文献
1000.
The incidence of the major clonal myeloid diseases, clonal cytopenias, acute, subacute (oligoblastic), and chronic myelogenous leukemia, polycythemia vera, thrombocythemia, and idiopathic myelofibrosis increases in a log-linear manner from young adulthood through advanced age. In older patients, diseases requiring cytotoxic treatment are more difficult and less successful to manage because comorbid conditions and poor performance status are more prevalent, decreasing the tolerance to therapy and increasing the frequency of side effects. This age effect is highlighted by the dramatically less favorable outcome in older than younger patients with acute myeloid leukemia with similar "favorable" cytogenetic changes. In addition, in acute and subacute myeloid leukemia in older patients, the disease is intrinsically more resistant to therapy. Overexpression of drug resistance genes and unfavorable genetic mutations are more prevalent in older patients and provide evidence that acute myeloid leukemia is often qualitatively different in these patients. The gradient of age effects is continuous; the frequency of poor outcome increasing by decade (or less). The decline in survival becomes especially steep as quinquagenarians (50-year-olds) age to nonagenarians (90-year-olds). Although improved drug schedules have led to significant improvements in event-free survival in younger patients, these improvements have been far less evident in older patients. New approaches, especially the development of drugs aimed at new targets, will be required to obtain a high frequency of long-term remissions in older patients. Agents that reverse inherent cellular drug resistance, farnesyltransferase inhibitors, BCL-2 inhibitors, and FLT3 inhibitors are early examples of such approaches. 相似文献