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71.
72.
Rolf W. Hartmann Martin Frotscher Dorothea Ledergerber Gerald A. Wchter Gertrud L. Grün Tom F. Sergejew 《Archiv der Pharmazie》1996,329(5):251-261
In search of potential drugs for the treatment of estrogen- and androgen-dependent cancer as well as the prophylaxis of metastases, tetralones, tetralins, and dihydronaphthalenes bearing a OCH3 substituent at the benzene nucleus and an imidazol-4-yl, imidazol-1-yl, or 1,2,4-triazol-1-yl substituent in 2-position were synthesized with and without C1-spacer between the rings (compounds 2 – 26 ). The compounds were tested in vitro for inhibition of the three target enzymes P450 arom (human placental microsomes), P450 17 (rat testicular microsomes), and P450 TxA2 (citrated human whole blood). To examine selectivity, some compounds were further tested in vitro for inhibition of P450 18 (bovine adrenal mitochondria), P450 see (bovine adrenal mitochondria) and corticoid formation (aldosterone, corticosterone; ACTH stimulated rat adrenal tissue). In vivo, selected compounds were examined in Sprague Dawley rats regarding P450 TxA2 inhibition, reduction of plasma testosterone concentration, antiuterotrophic activity (inhibition of the uterotrophic activity of androstenedione), reduction of plasma estradiol concentration (pregnant mares' serum gonadotropin-primed rats), and mammary tumor inhibiting activity (dimethylbenzanthracene-induced tumor; pre- and postmenopausal model). In the series of imidazol-4-yl compounds, which represent a novelty in the field of azole inhibitors of steroidogenic P450 enzymes, strong inhibitors of P450 arom and/or P450 17 were found: 7-OCH3-2-(imidazol-4-ylmethylene)-1-tetralone ( 4 ) and 7-OCH3-2-(imidazol-4-ylmethyl)-tetralin ( 12 ) are among the most potent inhibitors of P450 arom in vitro known so far. Compound 4 is a selective inhibitor, whereas 12 shows in addition strong inhibition of P450 17. In contrast to 12 , the 6-OCH3 derivative (compound 11 ) is a selective inhibitor of P450 17, being 50 times more potent than ketoconazole. Some imidazol-1-yl compounds show a marked inhibition of P450 TxA2: 2-(imidazol-1-ylmethyl)-1-tetralone ( 13 ) is a selective inhibitor of P450 TxA2, whereas 7-OCH3-2-(imidazol-1-ylmethyl)-tetralin ( 17 ) as well as 2-(imidazol-1-ylmethyl)-tetralin ( 16 ) and 7-OCH3-2-imidazol-1-yl-3,4-dihydronaphthalene ( 25 ) additionally show strong inhibition of P450 arom and P450 17. Regarding the other steroidogenic P450 enzymes as well as corticosterone formation, the compounds show only little inhibitory activity. Aldosterone formation, however, is inhibited at low concentrations. Nevertheless, 4 and 12 are more selective, i.e. inhibit aldosterone synthesis less than the well known inhibitor of P450 arom fadrozole. The compounds show activity in the aforementioned in vivo tests. 相似文献
73.
J. B. Payne R. A. Reinhardt M. P. Masada L. M. DuBois A. C. Allison 《Journal of periodontal research》1993,28(6):451-453
Gingival crevicular fluid (GCF) IL-8 and IL-1,1β levels were determined by sandwich enzyme-linked immunosorbent assays. Associations between IL-8 and IL-1β GCF levels, and between these cytokines and patient estrogen status were evaluated. IL-8 and IL-1β were detected more frequently and in higher amounts/30 s GCF sample in estrogen-deficient patients than in estrogensufficient patients. IL-8 and IL-1β GCF levels were significantly correlated. These lindings suggest that GCF IL-8 levels are associated with patient estrogen status and local IL-1β concentrations. 相似文献
74.
Jalil Tavakkol AFSHARI Zahra REZAIEYAZDI Farnaz SHOJA‐TAHERI Majid SADEGHIZADEH 《International journal of rheumatic diseases》2007,10(3):209-213
Aim: Rheumatoid arthritis (RA) is the most common chronic inflammatory erosive joint disease with the worldwide distribution of approximately 0.5–1.0%. Etiology of RA is not exactly known but immunologic and genetic factors play an important role in the pathogenesis of the disease. Genetic factors such as human leukocyte antigens (HLA) are responsible for many autoimmune diseases; therefore we decided to look for a correlation between RA and the presence of HLA‐DQβ1 alleles as possible genetic markers. Methods: Genomic DNA from the whole blood samples of 25 patients with RA and 86 normal individuals as control group were extracted by salting out method. The genomic DNA was amplified by polymerase chain reaction‐sequence specific primer (PCR‐SSP) technique. HLA‐typing was done by this method after optimizing the PCR reaction for each allele. In this procedure seven serological subclasses of HLA‐DQβ1 can be detected. Results: Comparing the results between the patients and controls show a significant increase in the frequency of HLA‐DQ8 (*0302, *0305) alleles in RA patients. The P‐values were 0.007 and the relative risk for these alleles was evaluated higher than 1. Conclusions: The results suggest that DQ8 is the dominant HLA‐DQβ1 allele that is associated with susceptibility to RA in north‐eastern Iran. 相似文献
75.
目的 :应用SSP PCR(Sequencespecialprime polymerasechainreaction)基因检定技术对急性前葡萄膜炎 (a cuteanterioruveitis ,AAU)患者HLA B2 7基因进行检测 ,并且对HLA B2 7阳性与阴性患者临床特征加以分析。方法 :采用SSP PCR基因检定技术检测 98例AAU患者及 82例正常人样本的HLA B2 7基因。并对HLA B2 7阳性与阴性患者临床特征进行观察。结果 :98例AAU患者样本中有 5 7例样本呈HLA B2 7阳性 ,82例正常人样本有 4例样本呈HLA B2 7阳性 ,阳性率分别为 5 8.2 %和 4 .9%。经 χ2 检验 ,χ2 =4 1.33,P <0 .0 0 5 ,二组间有显著差异。HLA B2 7阳性患者多见于男性 ,单眼多见 ,粉尘状KP ,发病时视力下降明显 ,易于复发 ,且并发症少为其特征 ,激素治疗效果佳。结论 :采用SSP PCR基因检定技术测定HLA B2 7快速、简单、准确性高、客观性强 ,值得推广和应用。HLA B2 7与急性前葡萄膜炎有着高度相关性。HLA B2 7阳性患者与阴性患者在临床特征上有着一定程度的差异。 相似文献
76.
目的探讨CD11b在肺纤维化患者外周血中性粒细胞上的表达及红霉素对它的影响.方法肺纤维化患者(A组,n=13)13例经红霉素治疗3个月,收集治疗前后及健康对照组(B组,n=13)13例的外周血中性粒细胞涂片,用桥联酶免疫法测定CD11b表达阳性的中性粒细胞百分率.结果A组治疗前后,患者外周血中性粒细胞CD11b的表达阳性率均显著高于健康对照组(P<0.01);A组治疗前,患者外周血中性粒细胞CD11b的表达阳性率显著高于治疗后(P<0.01).结论肺纤维化患者外周血中性粒细胞CD11b的表达阳性率显著高于健康对照组;红霉素能抑制肺纤维化患者外用血中性粒细胞CD11b的表达. 相似文献
77.
SK&F 86466, 6-chloro-3-methyl-2,3,4,5-tetrahydro-1-H-3-benzazepine, is a potent and selective antagonist of the α2-adrenoceptor in vitro. This compound produced a small pressor response accompanied by a marked bradycardia when administered i.v. to the pithed normotensive rat. The pressor response was not affected by reserpine treatment, pretreatment with α- or β-adrenoceptor antagonists, atropine, or hexamethonium. The bradycardia was markedly reduced by bilateral vagotomy and pretreatment with atropine and attenuated by hexamethonium. The negative chronotropic action of SK&F 86466 was abolished by a combination of vagotomy and atropine. Mediation of the bradycardia by a baroreceptor reflex was ruled out by the observations that a lack of change in heart rate was associated with the vasopressor response to phenylephrine in the pithed rat pretreated with propranolol. It is concluded that the negative chronotropic action of SK&F 86466 in the pithed rat is mediated indirectly by activation of the cholinergic innervation of the heart. 相似文献
78.
Expression of p27 and p53: comparative analysis of uterine carcinosarcoma and endometrial carcinoma 总被引:1,自引:0,他引:1
A. Abargel I. Avinoach† V. Kravtsov† M. Boaz‡ M. Glezerman‡ & J. Menczer‡ 《International journal of gynecological cancer》2004,14(2):354-359
The aim of the study was to assess both p27 and p53 expression in the stromal and epithelial component of carcinosarcoma and to assess if their expression in the latter is different than in endometrial carcinoma. Immunohistochemical staining for p27 and p53 was performed on paraffin-embedded tissue blocks of 18 uterine specimens with carcinosarcoma and their expression assessed. Their expression in the epithelial element was also compared to that in 35 paraffin-embedded tissue blocks of endometrial endometrioid carcinoma. Reduced p27 expression was observed in a similarly high proportion of the stromal (77.8%) as well as of the epithelial component (66.7%) of carcinosarcoma. Although statistically not significant, the proportion of reduced p27 expression in endometrial carcinoma (85.7%) was higher than in the epithelial element of carcinosarcoma. The percentage of p53 overexpression in both elements of carcinosarcomas and in endometrial carcinomas was low and also similar (27.8 and 20.0%, respectively). Our results indicate that reduced p27 expression is common and p53 overexpression is infrequent in carcinosarcoma. Their similar rates of expression in the stromal and epithelial elements of the tumor support the contention of a monoclonal origin of carcinosarcoma. Unexpectedly, reduced p27 expression is more common in endometrial carcinoma than in the epithelial element of carcinosarcoma, in spite of the less favorable prognosticators and outcome in the latter. Further studies of p27 expression in carcinosarcoma are indicated to establish its clinical value in this aggressive malignancy. 相似文献
79.
AIMS: Diabetic ketoacidosis (DKA), a life-threatening acute complication of Type 1 diabetes, may be preventable with frequent monitoring of glycaemia and ketosis along with timely supplemental insulin. This prospective, two-centre study assessed sick day management using blood 3-hydroxybutyrate (3-OHB) monitoring compared with traditional urine ketone testing, aimed at averting emergency assessment and hospitalization. METHODS: One hundred and twenty-three children, adolescents and young adults, aged 3-22 years, and their families received sick day education. Participants were randomized to receive either a blood glucose monitor that also measures blood 3-OHB (blood ketone group, n = 62) or a monitor plus urine ketone strips (urine ketone group, n = 61). All were encouraged to check glucose levels > or = 3 times daily and to check ketones during acute illness or stress, when glucose levels were consistently elevated (> or = 13.9 mmol/l on two consecutive readings), or when symptoms of DKA were present. Frequency of sick days, hyperglycaemia, ketosis, and hospitalization/emergency assessment were ascertained prospectively for 6 months. RESULTS: There were 578 sick days during 21,548 days of follow-up. Participants in the blood ketone group checked ketones significantly more during sick days (276 of 304 episodes, 90.8%) than participants in the urine ketone group (168 of 274 episodes, 61.3%) (P < 0.001). The incidence of hospitalization/emergency assessment was significantly lower in the blood ketone group (38/100 patient-years) compared with the urine ketone group (75/100 patient-years) (P = 0.05). CONCLUSIONS: Blood ketone monitoring during sick days appears acceptable to and preferred by young people with Type 1 diabetes. Routine implementation of blood 3-OHB monitoring for the management of sick days and impending DKA can potentially reduce hospitalization/emergency assessment compared with urine ketone testing and offers potential cost savings. 相似文献
80.
CD44v6、P27蛋白在乳腺癌组织中的表达及意义 总被引:3,自引:0,他引:3
目的 探讨乳腺癌中CD44v6、p27蛋白表达的意义。方法 应用免疫组化S-P法检测65例乳腺癌中CD44v6、p27蛋白表达。结果 65例乳腺癌中CD44v6、p27蛋白表达总阳性率分别为58.4%、38.4%。CD44v6蛋白阳性表达率与乳腺癌组织学类型、腋淋巴结转移呈正相关(P<0.05,P<0.01),与预后呈负相关(P<0.01),与组织学分级无明显相关性(P>0.05);p27蛋白阳性表达与乳腺癌组织学类型、组织学分级及腋淋巴结转移呈负相关(P<0.05),与预后呈正相关(P<0.05)。结论 CD44v6、p27蛋白表达与乳腺癌浸润、转移及预后显著相关,检测乳腺癌中CD44v6、p27蛋白表达水平,对判断乳腺癌恶性程度、复发转移潜能,评估患者预后及术后选择合理治疗方案有一定参考价值。 相似文献