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1.
2.
L. Marzio F. Di Felice V. Celiberti O. Pieramico L. Grossi M. DiGioacchino B. P. Imbimbo F. Cuccurullo 《European journal of clinical pharmacology》1990,39(4):369-372
Summary To evaluate the influence of the stomach and the cholinergic system on gallbladder contraction induced by physiological stimuli, the reduction in gallbladder volume in 7 healthy volunteers has been studied by real-time ultrasonography after the oral and intraduodenal administration of olive oil, preceded by pretreatment with cimetropium bromide or placebo. After an overnight fast, each subject swallowed 50 ml olive oil or it was administered through a naso-duodenal tube in the proximal duodenum. Cimetropium bromide 5 mg or placebo was given intravenously under double-blind control.After the placebo pretreatment, gallbladder contraction was greater and faster after intraduodenal oil than after oral oil. Cimetropium bromide decreased the extent, velocity and duration of gallbladder contraction induced by intraduodenal olive oil but it only reduced the velocity of the contraction induced by oil given orally.It is concluded that in normal human subjects the stomach modulates the extent and velocity of postprandial gallbladder contraction and that anticholinergic agents antagonize the gastric and duodenal phases of the response of the gallbladder to a meal. 相似文献
3.
RITA PEREGO LUIGIA GOZZINI EMANUELE ARLANDINI GIORGIO BOLIS ROBERTO DE CASTIGLIONE 《Chemical biology & drug design》1995,46(5):341-345
Endothelin-1 (ET), the most potent vasoconstrictor yet discovered, is a peptide containirig 21 amino acids with two intrachain disulfide bridges. With the aim of obtaining two-chain derivatives, Et was submitted to chemical and enzymatic treatments. Reaction of ET with CNBr in 70% HCOOH gave, in addition to the expected [Hse7 lactone]-7,8-seco-ET and unreacted material, a by-product whose molecular weight was 25 m.u. greater than that of ET. When the reaction mixture, after lyophilisation, was immediately quenched with NH3-saturated dry MeOH, two products could be recovered in a 5:1 ratio, both obtained by nucleophilic attack of the homoserine lactone: the expected [Hse7-NH2]-7,8-seco-ET and [Hse7]ET, resulting from competitive intramolecular reaction of the deprotonated α-amino group of the Asp8 residue. The Lys9-Glu10 bond turned out to be very resistant to enzymatic attack both by Lys-C-endopeptidase and trypsin. The 9,10-seco-ET derivative could be obtained by treatment with Lys-C-endopeptidase only by using a high enzyme/ET ratio and after a prolonged incubation time. Cleavage of the Lys9-Glu10 bond could not be achieved by treatment with trypsin, even with a high enzyme/substrate ratio. The main product was 13, 14-seco-ET, deriving from the action of chymotripsin (present as an impurity in the trypsin preparation) on Tyr13. The structure of these peptides was confirmed by amino-acid sequence analysis and fast atom bombardment mass spectrometry (FAB-MS). Nicking of the ET structure at different positions had different impact on the biological properties of the resulting derivatives. © Munksgaard 1995. 相似文献
4.
MOTOYOSHI NOMIZU YOSHIMASA INAGAKI TAKEYOSHI YAMASHITA AKO OHKUBO AKIRA OTAKA NOBUTAKA FUJII PETER P. ROLLER HARUAKI YAJIMA 《Chemical biology & drug design》1991,37(2):145-152
A new two-step deprotection/cleavage procedure for t-butoxycarbonyl (Boc) based solid phase peptide synthesis is reported. First the protective groups are removed from 4-(oxymethyl)-phenylacetamidomethyl (PAM) resin attached peptide with the weak hard acid, trimethylsilyl bromide-thioanisole/trifluoroacetic acid (TFA). In the second step, the peptide is cleaved from the resin with a stronger hard acid such as trimethylsilvl trifluoromethanesulfonate in TFA or with HF. The method is also shown to deformylate Nin-formyltryptophan moiety efficiently. The usefulness of this procedure for practical solid phase peptide synthesis is demonstrated by comparison with other deprotection methods in the synthesis of urotensin II and human endothelin. 相似文献
5.
T. Shioya M. Kagaya M. Sano M. Itaba T. Shindo M. Miura 《European journal of clinical pharmacology》1996,50(5):375-380
Objective:
We studied the bronchodilatory effect of tiquizium bromide [3-(di-2-thienylmethylene)-5-methyl-trans-quinolizidinium bromide; TQZ], an antimuscarinic agent, on airway smooth muscle in vitro, and also in patients with chronic
obstructive pulmonary disease (COPD).
Methods:
In the first experiment, canine tracheal smooth muscle was used to measure the pA2 of TQZ in vitro. The selectivity of TQZ
for muscarinic receptor subtypes was also examined with a radioligand binding assay.
Results:
The pA2 value of TQZ was 8.75. The pK
i values of TQZ for M1, M2, and M3 were 8.70, 8.94, and 9.11, respectively. In an open pilot experiment, the effects of TQZ
inhalation were studied in seven patients with COPD (seven men, mean age 68.5 years). TQZ significantly increased forced vital
capacity (FVC) and forced expiratory volume in 1 s (FEV1) in a dose-dependent manner. The mean maximum increases in FVC and FEV1 caused by inhaled TQZ (2.0 mg) were 24% and 29%, respectively, and they were measured 1 h after the drug had been inhaled.
The FVC and FEV1 were still significantly higher than the control values even 8 h after the drug had been inhaled. No adverse effects were
observed after inhalation of TQZ.
Conclusion:
These data suggest that TQZ is an effective antimuscarinic agent, and that it causes significant bronchodilation in patients
with COPD.
Received: 3 April 1995/Accepted in revised form: 27 November 1995 相似文献
6.
目的 探究格隆溴铵对高氧诱导幼鼠急性肺损伤(ALI)的影响及作用机制。方法 从30只SD幼鼠中随机选取10只为对照组,其余幼鼠成功复制高氧诱导的ALI模型,随机分为ALI组、格隆溴铵组,每组10只。格隆溴铵组雾化吸入0.8 mg/(kg·d)格隆溴铵,ALI组、对照组吸入等体积生理盐水,连续给药7 d后,测量幼鼠肺组织湿/干重比值(W/D)、肺指数,检测白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)及肿瘤坏死因子-α(TNF-α)水平及血清活性氧基团(ROS)、超氧化物歧化酶(SOD)水平,比较肺组织病理学变化及Toll样受体4/髓分化因子88(TLR4/MyD88)通路蛋白的表达。结果 与对照组比较,ALI组W/D及肺指数升高(P <0.05),血清IL-1β、IL-6、TNF-α、SOD水平升高(P <0.05),ROS水平降低(P <0.05),TLR4、MyD88蛋白相对表达量上调(P <0.05);与ALI组比较,格隆溴铵组W/D及肺指数降低(P <0.05),血清IL-1β、IL-6、TNF-α、SOD水平降低(P <0.05),ROS水平升高(P <0.05),TLR4、MyD88蛋白相对表达量下调(P <0.05)。结论 格隆溴铵能改善血清炎症指标及氧化应激指标,降低高氧诱导的ALI,其作用机制可能与TLR4/MyD88通路有关。 相似文献
7.
Dendrites and spines undergo dynamic changes in physiological and pathological conditions. Dendritic outgrowth has been observed in surviving neurons months after ischemia, which is associated with the functional compensation. It remains unclear how dendrites in surviving neurons are altered shortly after ischemia, which might reveal the mechanisms underlying neuronal survival. Using primary cortical cultures, we monitored the dendritic changes in individual neurons after oxygen-glucose deprivation (OGD). Two to four hours of OGD induced approximately 30–50% cell death in 24 h. However, the total dendritic length in surviving neurons was significantly increased after OGD with a peak at 6 h after re-oxygenation. The increase of dendritic length after OGD was mainly due to the sprouting rather than the extension of the dendrites. The dendritic outgrowth after 2 h of OGD was greater than that after 4 h of OGD. Application of NMDA receptor blocker MK-801 abolished OGD-induced dendritic outgrowth, whereas application of AMPA receptor antagonist CNQX had no significant effects. These results demonstrate a NMDA receptor-dependent dendritic plasticity shortly after OGD, which provides insights into the early response of surviving neurons after ischemia. 相似文献
8.
Shao Zezhi Li Yuping Krishnamoorthy Ramesh Chermak Todd Mitra Ashim K. 《Pharmaceutical research》1993,10(2):243-251
Various surfactants were investigated to compare their effects on insulin dissociation, -chymotryptic degradation, and rat enteral absorption. With a circular dichroism technique, sodium dodecyl sulfate (SDS) at a 5 mM concentration was found to completely dissociate procine-zinc insulin hexamers (0.5 mg/ml) into monomers. The catalytic activity of -chymotrypsin (0.5 µM) was also abolished by 5 mM SDS. When insulin was injected into the distal jejunum/ proximal ileum segment of the rat, 5 mM SDS greatly enhanced its pharmacological availability, from a negligible value to 2.8%. Being a cationic surfactant, hexadecyl trimethylammonium bromide (CTAB) also efficiently dissociated insulin hexamers at concentrations of 1–5 mM. However, extensive charge–charge interaction was observed below a CTAB concentration of 0.6 mM, leading to insulin precipitation at a molar CTAB:insulin ratio of 1:1 to 2:1. An -chymotryptic degradation study also revealed near-complete dissociation of insulin hexamers at 1 mM CTAB. Above 1 mM, however, CTAB acted as an enzyme inhibitor, most likely by means of charge repulsion. Enteral absorption studies showed a much lower pharmacological availability, only 0.29%. Nonionic surfactants such as Tween 80 and polyoxyethylene 9 lauryl ether were ineffective in dissociating insulin hexamers. Tween 80, at 5 mM, neither significantly altered the -chymotryptic degradation pattern nor enhanced the enteral absorption of insulin. The relative effectiveness of different species of bile salts on insulin hexamer dissociation appeared to be similar. Sodium glycocholate at a 30 mM concentration also significantly increased insulin pharmacological availability, to 2.3%. A morphological study did not reveal any significant alteration of the rat intestinal mucosal integrity after exposure to 5 mM SDS for 30 min. The results further emphasize the importance of the degree of insulin aggregation on its enteral transport. 相似文献
9.
溴化异丙托品对稳定期COPD患者肺功能及运动耐受性的影响 总被引:1,自引:0,他引:1
目的 观察不同剂量的溴化异丙托品(IPB)短时及长期应用,对稳定期慢性阻塞性肺疾病(COPD)患者的肺功能及运动耐受性的影响。方法 37例稳定期COPD患者,随机分3组,分别吸人IPB160μg/次、80μg/次、40μg/次。用药前后行肺功能及自行车功量仪极量运动负荷法运动试验测验。结果 吸入IPB160μg/次、80μg/次组与安慰剂对照组相比,通气及运动指标均明显改善(P〈0.01、P〈0. 相似文献
10.
Bouritius H Bajnath RB Groot JA 《Pflügers Archiv : European journal of physiology》1999,437(4):589-595
Activation of the basolateral receptor for adenosine in HT-29cl.19A cells, by 100 μM adenosine, increased the equivalent
short-circuit current (ΔI
sc= 24±2 μA/cm2), depolarized the intracellular potential (ΔV
a= 26±2 mV) and decreased the fractional apical membrane resistance (ΔfR
a=–0.48). The changes in all parameters reached their peak values simultaneously. This suggests that the primary action of
the adenosine-activated pathway is on only one membrane. Bumetanide inhibited the transepithelial response and repolarized
the cell potential. After preincubation with 100 μM forskolin, application of 300 μM adenosine caused a significant further
change in V
a, I
sc, the transepithelial potential (V
t) and fR
a. Together with the results from ion-replacement studies, the observations indicate that adenosine activates channels other
than the cystic fibrosis transmembrane conductance regulator (CFTR). The rank order of potencies of adenosine and adenosine
analogues implies that the receptor is of the A2 subtype. Preincubation with 4-bromophenacyl bromide (4-BPB) inhibited the effect of an adenosine analogue by 50%, indicating
that activation of phospholipase A2 may be involved in the adenosine-induced response.
Received: 5 August 1998 / Received after revision: 12 October 1998 / Accepted: 5 November 1998 相似文献