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991.
Desipramine (DMI, 15 mg/kg, s.c.) decreased [3H]CGP-12177-labelled cortical β-adrenoceptor density (Bmax) by 30% upon chronic (14 day) treatment. However, even a single dose (in mg/kg) of DMI (15) or the β-adrenoceptor agonist, clenbuterol (20), induced a rapid (24 hour) and significant reduction of β-adrenoceptor Bmax (−15%; p<0.01). Acute treatment with amitryptiline (10), clorgyline (1), fluoxetine (10), nomifensine (10) or maprotiline (20) had no significant effect on [3H]CGP-12177-labelled β-adrenoceptors, suggesting that rapid down-regulation may not be a general property of antidepressant drugs. None of the antidepressants altered the Bmax of [3H]ketanserin-labelled 5-HT2A receptors on acute treatment. These results show that β-adrenoceptor down-regulation by clenbuterol and DMI is not dependent on chronic treatment and may, therefore, be a poor correlate of the gradual onset of therapeutic efficacy seen clinically with antidepressant drugs. 相似文献
992.
In an attempt to establish an in vitro/in situ correlation of intestinal permeability data, the permeability coefficients (P
app) for a series of model peptides, which were determined using an in situ perfused rat ileum model, were compared to the permeability coefficients (P
mono) determined using an in vitro cell culture model (Caco-2). The model peptides, which were all blocked on the N-terminal (acetyl, Ac) and the C-terminal (amide, NH2) ends, consisted of D-phenylalanine (F) residues (e.g., AcFNH2, AcFFNH2, AcFFFNH2). To alter the degree of hydrogen bonding potential, the nitrogens of the amide bonds were sequentially methylated [e.g., AcFF(Me)FNH2, AcF(Me)F(Me)FNH2, Ac(Me)F(Me)F(Me)FNH2, Ac-(Me)F(Me)F(Me)FNH(Me)]. These peptides were shown not to be metabolized in the in situ perfused rat ileum system. The results of the transport experiments showed that there were poor correlations between the apparent permeability coefficients (P
app) determined in an in situ perfused rat ileum model and the octanol–water partition coefficients (r = 0.60) or the hydrogen bonding numbers (r = 0.63) of these peptides. However, good correlations were observed between the in situ
P
app values for these peptides and their partition coefficients in heptane–ethylene glycol (r = 0.96) and the differences in their partition coefficients between octanol–water and isooctane–water (r = 0.86). These results suggest that lipophilicity may not be the major factor in determining the intestinal permeability of these peptides and that hydrogen bonding potential may be a major contributing factor. A good correlation (r = 0.94) was also observed between the P
app values determined for these peptides in the in situ perfused ileum model and those P
mono values determined in the in vitro cell culture model (Caco-2) (Conradi et al., Pharm. Res. 8:1453–1460, 1991). These results suggest that the permeability values determined in the Caco-2 cell culture model may be a good predictor of the intestinal permeability of peptides. 相似文献
993.
氯菊酯可明显抑制Ca~(2+)—ATP酶活性,其抑制作用是可逆的,底物动力学分析表明为非竞争性抑制,介质的酸度可影响其抑制效应;氯氰菊酯对该酶活性无明显影响.氯菊酯和氯氰菊酯均能可逆性地抑制Ca~(2+),Mg~(2+)—ATP酶活性,但氯菊酯为反竞争性抑制.且有一定的pH依赖性,而氯氰菊酯为非竞争性抑制,其抑制率基本不受pH的影响,表明这两种杀虫剂在Ca~(2+) ,Mg~(2+)—ATP酶上有不同的结合位点. 相似文献
994.
M. M. Moens A. V. Mertens L. S. De Clerck H. P. Van Bever C. H. Bridts W. J. Stevens 《Pediatric allergy and immunology》1993,4(2):89-92
In patients with allergic asthma and rhinitis high numbers of hypodense eosinophils (HE) have been demonstrated. In a previous study we reported that asthmatic and healthy children had more HE than their adult counterparts. We assumed that this might, in part, he due to the presence of immature eosinophils in children. To distinguish between immature and activated eosinophils, determination of eosinophil cationic protein (ECP) might be interesting as it is known that high serum levels of ECP are associated with increased activation of eosinophiis. In this study we determined (he levels of ECP in scrum in asthmatic and healthy children and adults trying to distinguish activated from immature eosinophils. We found that ECP levels were not increased in children (healthy and asthmatic) compared to adults (healthy and asthmatic). This supports the hypothesis that increased numbers of HE in childhood are, at least in part, immature eosinophils. Nevertheless, we could confirm that inflammation was present in children because soluble interleukin-2-receptor (slL-2R), a marker of lymphocyte activation, was higher in asthmatic children as compared to healthy children. IL-6, a marker of macrophage/monocyte activation, was not different in the different patient groups. We conclude that although signs of inflammation are present in childhood asthma, the increased numbers of HE in children are in part due to the presence of immature eosinophils. 相似文献
995.
J. W. Constantine W. S. Lebel H. A. Woody 《Naunyn-Schmiedeberg's archives of pharmacology》1990,342(6):722-724
Summary Neurokinin A, neurokinin B and substance P caused concentration-related contractions of rabbit isolated aorta with pD2 values of 8.1, 6.9 and 6.0, respectively. [D-Pro2, D-Trp7,9]-substance P, a competitive tachykinin antagonist, had pA2 values of 5.3 against neurokinin A, 5.1 against neurokinin B and 5.2 against substance P indicating that tachykinin receptors
mediated responses to the agonists. [pGIu5,MePhe8,-McGly9]-substance P 5–11 (DiMe-C7), senktide and septide did not contract the aorta. It is concluded that of the known tachykinin
receptors smooth muscle of the rabbit isolated aorta contains only the NK-2 type.
Send offprint requests to J. W. Constantine at the above address 相似文献
996.
Three predominant proteins secreted by the human prostate gland 总被引:3,自引:0,他引:3
Analyses of the proteins of azoospermic ejaculates from subjects with defective seminal vesicles demonstrated that three prostatic-secreted proteins were predominant. Prostatic acid phosphatase (PAP), prostate-specific antigen (PSA; or gamma-seminoprotein), and beta-microseminoprotein (beta-MSP; or beta-inhibin), were identified as the three predominant proteins secreted by the normal human prostate gland. Immunohistochemical localization of these proteins, in the epithelium of normal prostatic acini and ducts, with the avidin-biotin complex procedure demonstrated that each PAP-immunoreactive cell was invariably immunoreactive both with PSA-and beta-MSP-monospecific antisera as well. 相似文献
997.
Psychophysical experiments indicate that the first stage of the reward pathway in medial forebrain bundle self-stimulation consists of small myelinated descending axons. Pharmacological experiments show that neuroleptics attenuate or abolish the rewarding effect. This had led to the hypothesis that the descending myelinated axons synapse on an ascending dopaminergic second stage projection. 2-Deoxy-[14C]glucose autoradiography in self-stimulating animals or animals receiving automatically administered rewarding stimulation after treatment with reward-blocking doses of pimozide reveals activation of a descending myelinated system but no stimulation-produced activation of an ascending dopaminergic projection system, even though the autoradiographic method reveals the mild elevations and depressions of activity in dopaminergic terminal fields consequent upon injections of neuroleptics and amphetamine, respectively, and the strong activation of the nigrostriatal projection produced by stimulating directly in the substantia nigra. When the effects of neuroleptics and clonidine are measured by the psychophysical method (that is, by lateral shifts in the rate-frequency function), it is found that both drugs produce only gradual and rather small attenuations of rewarding efficacy up to doses at which it is no longer possible to measure their effects. It is suggested that, for neuroleptics at least, the rewarding effect abruptly fails at these doses. It is further suggested that these drugs do not act on the rewarding pathway itself, but on the process by which the rewarding signal is converted to an enduring rewarding effect. 相似文献
998.
bcl-2反义寡核苷酸对膀胱癌BIU87细胞株的影响 总被引:2,自引:0,他引:2
目的:探讨bcl-2反义寡核苷酸对培养的膀胱癌BIU87细胞株的影响.方法:采用bcl-2基因第1外显子的反义寡核苷酸,以硫代磷酸修饰(PS-ASON),序列为5′-TCTCCCAGCGTGCGCCAT-3′,与膀胱癌细胞株BIU87共同孵育作为实验组.加入正义的bcl-2寡核苷酸,序列为5′-TACCGCGTGCGACCCTCT-3′(PS-SON)作为对照组,用流式细胞仪检测细胞凋亡和坏死率,电镜观察细胞形态变化.结果:与对照组相比,实验组的细胞坏死率明显上调,电镜下细胞形态呈坏死改变.结论:bcl-2的反义寡核苷酸引起膀胱癌细胞大量坏死,可能成为膀胱癌的治疗方法之一. 相似文献
999.
原癌基因蛋白质C-erbB-2在乳腺良恶性病变中表达的意义 总被引:3,自引:1,他引:2
目的:检测原癌基因蛋白质C-erbB-2在乳腺良恶性病变中的表达及意义.方法:对111例乳腺良恶性病变的石蜡切片标本进行免疫组织化学染色.结果:乳腺良恶性病变中乳腺导管内乳头状瘤病的C-erbB-2阳性率为31.3%,与乳腺纤维腺病和纤维腺瘤比较差异有显著性(P<0.01),乳腺癌C-erbB-2的阳性率为74.3%,与良性病变比较差异有显著性(P<0.01);乳腺癌C-erbB-2表达与肿瘤大小和组织学分级呈正比(P<0.05),与激素受体(ER、PR)水平及5年生存期呈反比(P<0.05),与淋巴结是否转移无关.结论:C-erbB-2表达的乳腺导管内乳头状瘤病容易癌变,C-erbB-2过度表达的乳腺癌组织分化差、生存期短、预后不好.C-erbB-2 可作为判定乳腺导管内乳头状瘤病早期癌变及乳腺癌预后的有效指标. 相似文献
1000.
The distribution of the specific radioactivity and the incorporation into protein of [3H]-tryptophan and [3H]valine at varying layers from surface to centre were measured in incubated slices of cerebral cortices from infant and adult rats. Specific radioactivity in free amino acids was in both age groups highest in the intact surface layer. Incorporation of tryptophan into protein was even in slices from adult rats but much less than the average in the surface layers in slices from infant rats. Incorporation of valine exhibited similar heterogeneity in both age groups. The results suggest in brain slice preparations a zonal compartmentation of amino acid and protein metabolism which varies for different amino acids. 相似文献