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51.
Abraham Nudelman Yitschak Binnes Naomi Shmueli-Broide Yael Odessa J. Paul Hieble Anthony C. Sulpizio 《Archiv der Pharmazie》1996,329(3):125-132
Vinylogous (Groups III and V ) and acetylenologous (Group IV ) analogs of the classical β-adrenergic agents — stimulants and blockers — were prepared in order to evaluate the effect of degree of saturation, position of unsaturation and rigidity of the chain linking the aromatic ring and the amino containing functional group on biological activity. Derivatives from Group III , which represent 4-aryl-3-butenyl-2-ol-amine analogs of Group II , retained β1-adrenoceptor antagonist activity albeit substantially less potent (50–200-fold) than that possessed by their aryloxy counterparts. Consistent with the SAR for Group II compounds, substitution at position 2 of the aromatic ring yielded the most potent antagonists ( 5a, 5d, 5g ), with KB's ranging from 73–93 nM while 3,4-dichloro substitution ( 5e ) markedly reduced antagonist potency (KB = 2,400 nM). Agonist activity was also noted for 5b and 5d , suggesting that these compounds may be best classified as partial agonists. Representatives from Groups IV and V were inactive as antagonists at the β1-adrenoceptor confirming the importance of the spatial relationship between the hydroxyl and the amino nitrogen. 相似文献
52.
提要本研究是在大鼠VD_3+Nicotine引起的心血管钙超载模型上观察心钠素(ANF)治疗(10ug ·kg~-1/d),对钙超载的影响。结果发现,钙超载组动物主动脉、心肌组织钙含量较对照组分别增高24倍(54.4±2.2vs 2.3±0.04fumol/gww)和9倍(16.9±2.1vs1.8±0.1umol/gww)。ANF治疗能显著抑制钙超载的发生,主动脉和心肌组织钙含量较钙超载组分别降低92%(3.8±0.4 umol/gww)和66%(5.6±0.6umol/gww)。离体滋流的钙超载血管环较对照组对去甲肾上腺素收缩反应增强;对乙酰胆碱舒张反应减弱,对硝普钠舒张反应无影响。ANF能显著改善钙超载所致的血管反应性障碍。实验结果表明,ANF具有显著的防治心血管钙超载的作用。 相似文献
53.
P. A. Milligan P. E. McGill C. W. Howden A. W. Kelman B. Whiting 《European journal of clinical pharmacology》1993,45(6):507-512
Summary A randomised crossover study was performed in subjects with rheumatoid arthritis (or other arthropathies) to investigate if any alteration in the steady pharmacokinetics of the NSAID piroxicam (a drug which is extensively metabolised via cytochrome P450) or its major metabolites occurred as a result of coadministering either cimetidine or nizatidine.Twelve females and 2 males with mean age, weight, and albumin concentrations of 58 years, 61 kg, and 40 g·L–1 respectively, completed the study. Comparisons were made between the following parameters: plasma piroxicam AUCs [AUC0-24(P)], plasma 5-hydroxypiroxicam AUCs [AUC0-24(5-OHP)], the ratio of these i.e. AUC0-24(5-OHP):AUC0-24(p), the % piroxicam daily dose excreted in urine as 5-hydroxypiroxicam (before and after glucuronidase incubation); and the mean of the steady state trough piroxicam, and 5-hydroxypiroxicam concentrations (obtained during each study phase in addition to the wash-out period).A statistically significant difference as a result of initiating either cimetidine or nizatidine was obtained only for the ratio AUC0-23(5-OHP):AUC0-24(P). This was indicative of a weak potential to inhibit piroxicam hydroxylation.No clinically significant alteration in the steady state pharmacokinetics of piroxicam occurred in these subjects as a result of cimetidine or nizatidine coadministration. Consequently it is unlikely that any adverse events would arise from these combinations. 相似文献
54.
中国汉坦病毒H82O5株G2糖蛋白基因的克隆及在真核细胞中的瞬时表达 总被引:2,自引:1,他引:1
从感染病毒乳鼠脑组织提取总RNA,采用RT-PCR和分子克隆技术将扩增到的G2糖蛋白基因插入含CMV启动子的pcDNA3.1/His质粒载体中,通过脂质体介导转染COS-7细胞,用SDS-PAGE、Western-blot及IFIA方法分别测定表达产物的相对分子量及特异性。结果证明获得正向插入的G2-pcDNA3.1/His重组表达质粒,表达产物的相对分子量为56ku,与理论预期大小一致,并且可与汉坦病毒H8205株的腹水抗体起特异反应。表明构建的G2-pcDNA3.1/His重组质粒所表达的蛋白为中国汉坦病毒株特有,能在哺乳动物细胞中表达并具有抗原性,重组质粒可应用于汉坦病毒的DNA疫苗研究。 相似文献
55.
W. Nörenberg Ernst Schöffel Bela Szabo Klaus Starke 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(2):159-165
The aim of the study was to subclassify the soma-dendritic α2-autoreceptors in the locus coeruleus (LC) of the rat by means of antagonists. To this end, the frequency of spontaneous action
potentials was recorded extracellularly from single LC neurones in brain slices. The neurones fired spontaneously at an average
rate of 1 Hz. The selective α2-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) and noradrenaline decreased the action potential
discharge with IC50 values of 5 and 510 nM, respectively. The concentration-inhibition curves of UK 14,304 and noradrenaline were shifted to the
right by phentolamine (0.15 μM) and rauwolscine (0.15 μM) but not by prazosin (1 μM). Apparent K
d values of phentolamine were 17 nM (against UK 14,304) and 20 nM (against noradrenaline). Apparent K
d values of rauwolscine were 47 nM (against UK 14,304) and 70 nM (against noradrenaline). (+)-Oxaprotiline (1 μM) suppressed
the firing of the neurones within 10 to 33 min. In the continued presence of oxaprotiline, phentolamine and rauwolscine restored
firing with EC50 values of 120 and 250 nM, respectively. Prazosin (1 μM) again was ineffective. All three antagonist affinity estimates –
against UK 14,304, exogenous noradrenaline and endogenous noradrenaline (that accumulates in the extracellular space in the
presence of oxaprotiline) – yield an affinity order phentolamine > rauwolscine >> prazosin, prazosin being ineffective even
at a concentration of 1 μM. These findings identify the soma-dendritic α2-autoreceptors of the LC as the rat variant of the α2A/D-adrenoceptor, i.e. α2D. Not only presynaptic but also soma-dendritic α2-autoreceptors may at least predominantly be α2A/D throughout the nervous system.
Received: 3 March 1997 / Accepted: 21 April 1997 相似文献
56.
Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT1 ) receptors in rabbit aorta and human recombinant AT1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'2 = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [125 I]AII binding to rabbit aortic membranes (AT, receptors) and [125 I][Sar1 , Ile8 ]AII binding to human recombinant AT1 receptors in a concentration-dependent manner with IC50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [125 I)AII binding to bovine cerebellum membranes (ÀT2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [125 I]AII binding assay and insurmountable AT1 receptor antagonism in the functional study. 相似文献
57.
J. Viac C. Goujon L. Misery V. Staniek M. Faure D. Schmitt A. Claudy 《Photodermatology, photoimmunology & photomedicine》1997,13(3):103-108
Ultraviolet radiation B (UVB) on the skin induces erythema, inflammation and modifications of the immune system. These changes have been reported after excessive short-term or long-term exposure to broad spectrum UVB. In this study, we examined the effects of local repetitive UVB irradiation of 311 nm wavelength on the skin of seven young volunteers. Skin biopsies were taken before and after UVB irradiation, and we immunohistochemically analyzed the expression of CD1a and HLA-DR antigens of Langerhans cells (LC), the possible infiltration of dermis/epidermis by CD11b macrophages, the modifications or the induction of intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) involved in the binding of leukocytes to the endothelial surface and the development of perivascular infiltrates of LFA-1+ mononuclear cells. We also determined the expression of substance P receptors (SPR) using biotinylated substance P (SPB). Exposure of UVB 311 nm induced a drastic reduction of CD1a+ cells and a moderate increase of HLA-DR+ dendritic cells in the epidermis without infiltration by CD11b macrophages. An increase of the binding of SPB to upper layer epidermal cells was noted in five of seven biopsies. In the dermis, vessel-associated ICAM-1 expression increased and an induction of E-selectin occurred on nearly 20 to 40% of endothelial cells, but VCAM-1 expression remained undetectable. The percentage of LFA-1+ cells did not change significantly after irradiation. These observations may be compatible with a selective role of UVB 311 nm on the skin immune response. 相似文献
58.
对13例体外循环病人进行了观察,发现体外循环后TXB2/6-keto-PGF1α显著增高,表明体外循环使血小板受损,而血小板受损是体外循环后失血的主要原因之一。 相似文献
59.
60.
Acoustic rhinometry was performed in 35 normal nose-breathing children between 3 and 6 years. The average cross-sectional areas at the nasal valve, at the anterior end of the turbinates, and in the nasopharynx were 0.34±0.06 cm2, 0.35±0.08 cm2 and 1.37±0.48 cm2 respectively. The average minimal cross-sectional area was 0.29±0.06 cm2. The minimal cross-sectional area was located at the nasal valve in 14 and at the anterior end of nasal tubinates in 21 of the 35 children. As would be expected, the cross-sectional areas at different sites of the nasal cavity increased with increasing age of the children. But, whereas the minimal cross-sectional area increased by 0.024 cm2 per year, the nasopharyngeal cross-sectional area increased by 0.20 cm2 per year. No significant differences were found between boys and girls. Measurements of the posterior nasal and nasopharyngeal cross-sectional areas were unreliable, whenever the minimal cross-sectional area was less than 0.2 cm2. Furthermore, assessment of the nasopharynx may be difficult because of involuntary movements of the soft palate. 相似文献