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Sánchez-Criado JE de Las Mulas JM Bellido C Aguilar R Garrido-Gracia JC 《The Journal of endocrinology》2005,184(1):59-68
The selective oestrogen receptor modulator (SERM) tamoxifen (TX) has agonist/antagonist actions on LH secretion in the rat. Whereas in the absence of oestrogens TX elicits progesterone receptor (PR)-dependent GnRH self-priming, it antagonizes oestrogen-stimulatory action on LH secretion. The aim of these experiments was to explore whether TX treatment-induced differential expression of oestrogen receptor (ER)alpha and ERbeta in the gonadotrope may determine its agonist effect on LH secretion. In the first experiment, basal LH secretion, GnRH-stimulated LH secretion and PR-dependent GnRH self-priming were determined in incubated pituitaries from ovariectomized (OVX) rats treated with oestradiol benzoate (EB), TX or raloxifene (RX). Cycling rats in metoestrus or pro-oestrus were used as basic controls. As in pro-oestrus, pituitaries from OVX rats treated with EB exhibited GnRH-stimulated LH secretion, immunohistochemical PR expression and GnRH self-priming. While RX had no effect on these parameters, TX induced PR expression and GnRH self-priming. GnRH self-priming was absent in pituitaries incubated with the antiprogestin ZK299. In the second experiment, we evaluated the immunohistochemical expression of ERalpha and ERbeta in gonadotropes of cycling rats and OVX rats treated with EB, TX or RX. We found that while ERalpha expression was similar in all six groups, ERalpha expression was oestrous cycle dependent. Moreover, ERalpha expression in gonadotropes of TX-treated rats was as high as that found in pro-oestrus, while ERalpha expression in the gonadotropes of RX-treated rats was lower than in metoestrous or pro-oestrous pituitaries. These results suggest that, in the absence of the cognate ligand, TX, unlike RX, may regulate LH secretion through the ERalpha subtype in gonadotropes. 相似文献
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Alvarez-Soria MA Herrero-Beaumont G Sánchez-Pernaute O Bellido M Largo R 《Rheumatology (Oxford, England)》2008,47(5):627-633
Objectives. Synoviocytes play a crucial role in the inflammatoryresponse leading to structural damage in OA. Our aim was toassess the effects of diacerein and NSAIDs on cellular responsesof synoviocytes associated with inflammation and structuralintegrity of cartilage in OA. Methods. The effects of diacerein, celecoxib, diclofenac, meloxicamand indomethacin on prostaglandin (PG) E2 production, cyclo-oxygenase-2(COX-2) protein expression, nitrite levels, presence of MMP-1and -13, and activation of nuclear factor-B (NF-B) were studiedon stimulated OA synoviocytes and chondrocytes. Results. Diacerein and NSAIDs inhibited IL-1β-stimulatedNF-B activation in synoviocytes and chondrocytes except indomethacinin synoviocytes. Diacerein further increased COX-2 protein expressionand PGE2 synthesis in synoviocytes stimulated with IL-1β,while no effect was observed on stimulated chondrocytes. NSAIDsdiminished until almost basal levels PGE2 release in both cellsand, surprisingly, these drugs also diminished COX-2 proteinexpression both in synoviocytes and chondrocytes. With regardto structural mediators, diacerein decreased MMP-13 levels insynoviocytes but did not modify MMP-1 presence. NSAIDs induceda significant increase in MMP-1 levels in both cell types andin MMP-13 levels in chondrocytes. Conclusions. Diacerein does not seem to reduce but rather increaseinflammatory mediators in synoviocytes, while it does not overallaffect chondrocyte inflammatory profile. KEY WORDS: Osteoarthritis, Cytokines and inflammatory mediators, Extracellular matrix, Synovium, Non-steroidal anti-inflammatory drugs
Submitted 2 November 2007; revised version accepted 15 February 2008. 相似文献
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Ohne Zusammenfassung 相似文献
57.
Lipoprotein(a) and other lipoproteins in hypothyroid patients before and after thyroid replacement therapy 总被引:4,自引:0,他引:4
Becerra A Bellido D Luengo A Piédrola G De Luis DA 《Clinical nutrition (Edinburgh, Scotland)》1999,18(5):319-322
AIMS: To analyse the influence of thyroid hormones on serum lipoprotein(a) (Lp(a)) concentration and other lipid parameters, and hence potentially on coronary artery disease (CAD) risk. METHODS: Thirty-six patients with hypothyroidism and 165 age-matched control euthyroid subjects were evaluated in a cross- sectional study, determining thyroid function tests and fasting serum lipids and lipoproteins. In a follow-up study for those hypothyroid patients the same determinations were repeated after normalization of thyroid state by levothyroxine (L-T(4)) replacement therapy. Patients needing other treatments were excluded. At baseline, patients with hypothyroidism had significantly higher levels of Lp(a), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo) A-I and apo B, and a higher TC/high-density lipoprotein cholesterol (HDL-C) ratio than control subjects. RESULTS: Severity of the hypothyroid state, expressed by serum thyroid-stimulating hormone, was correlated with serum levels of Lp(a), LDL-C, and TC (r= 0.64, 0.52, 0.49, P= 0.005, P= 0.033, P= 0. 048, respectively). The pretreatment Lp(a) levels were also correlated with those of posttreatment Lp(a)(r= 0.68, P= 0.002). All patients, who presented basal Lp(a) levels higher than 30 mg/dl, showed a decrease in Lp(a) concentrations by L-T(4)therapy, and these normalized in eight cases (22.2%). Euthyroid state gave rise to a significant reduction of serum Lp(a) by 32.3%, of LDL-C by 22. 8%, of TC by 17%, of apo A-I by 9.6%, and of apo B by 9.3%. After L-T(4)therapy, CAD risk, expressed as TC/HDL-C ratio, decreased by 19.9%. CONCLUSIONS: These results show that hypothyroidism is associated not only with elevated serum levels of LDL-C but also with elevated serum Lp(a) concentrations. Lp(a) levels may be at least partially modulated by thyroid hormone-dependent mechanisms, thus increasing the risk of developing premature atherosclerosis in hypothyroid state, that might be reduced by L-T(4)therapy. 相似文献
58.
A Arnedo Pe?a F González Morán J Bellido Blasco J V Martí Canos L Safont Adsuara C Calvo Mas 《Gaceta sanitaria / S.E.S.P.A.S》1991,5(25):169-173
In May 1989, a foodborne outbreak of acute gastroenteritis was identified in a state school in Adzaneta, Castellón. A dtudy was undertaken to describe it, investigate its causes, and recommend adequate control measures. Sixteen children and 2 teachers were affected (attack rate: 28.57%). Kaplan and cols clinical and epidemiological criteria for Norwalk-like virus as the responsible agent were present. The probable origin of the outbreak was a foodhandler who was already ill beforehand. The examination of stools of the foodhandler and a patient showed small round structures similar to the Norwalk virus. In Spain, the number of foodborne outbreaks without known causal agent has steadily increased in recent years. It may be that this microorganism is responsible for some of these outbreaks in which, for several reasons, the causal agent cannot be identified. 相似文献
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J P de la Cruz I Bellido S Camara F Martos F Sanchez de la Cuesta 《Scandinavian journal of haematology》1986,36(4):394-397
We have used the impedance aggregometer to study the in vitro effect of acetylsalicylic acid (ASA) in whole blood (WB) versus platelet-rich plasma (PRP) using blood samples from 24 male and 24 female healthy volunteers. IC50 was calculated from dose-response curves of ADP-, adrenaline-, collagen- and arachidonic acid-induced aggregation. ASA inhibited platelet aggregation in WB with a lower IC50 than PRP in male and female samples; the greater differences between WB and PRP inhibitory effect of ASA were in collagen- and archidonic acid-induced aggregation. A higher ASA concentration was needed in order to produce half maximal inhibition of platelet aggregation in female than in male samples with both WB and PRP method, except when ADP was used as the aggregating agent in PRP. 相似文献