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排序方式: 共有691条查询结果,搜索用时 15 毫秒
1.
Henry Havel Gregory Finch Pamela Strode Marc Wolfgang Stephen Zale Iulian Bobe Hagop Youssoufian Matthew Peterson Maggie Liu 《The AAPS journal》2016,18(6):1373-1378
Advancing nanomedicines from concept to clinic requires integration of new science with traditional pharmaceutical development. The medical and commercial success of nanomedicines is greatly facilitated when those charged with developing nanomedicines are cognizant of the unique opportunities and technical challenges that these products present. These individuals must also be knowledgeable about the processes of clinical and product development, including regulatory considerations, to maximize the odds for successful product registration. This article outlines these topics with a goal to accelerate the combination of academic innovation with collaborative industrial scientists who understand pharmaceutical development and regulatory approval requirements—only together can they realize the full potential of nanomedicines for patients. 相似文献
2.
M Havel H Teufelsbauer P Kn?bl R Dalmatiner P Jaksch W Zw?lfer M Müller T Vukovich 《The Journal of thoracic and cardiovascular surgery》1991,101(6):968-972
To study the hemostyptic effect of aprotinin (Trasylol) in patients undergoing extracorporeal circulation for coronary artery bypass operations, we randomized 12 of 24 patients to receive aprotinin in high dosage (about 800 mg) during extracorporeal circulation. From the resulting two groups each, one patient was excluded from the study because of postoperative myocardial infarction (control group) and surgical hemorrhage (aprotinin group) leading to a second operation. Although heparin was used for anticoagulation in all 22 patients, all had a marked increase in plasma levels of thrombin-antithrombin III complexes during extracorporeal circulation, indicating an intravasal activation of coagulation. By monitoring the plasma levels of fibrin degradation products in patients without aprotinin therapy, we recorded a concomitant hyperfibrinolysis significantly less pronounced in patients receiving aprotinin (p less than 0.005). The mean total postoperative blood loss was lower in patients receiving aprotinin (620 ml) than in control patients (1000 ml; p less than 0.03). The results confirm previous reports of a hemostyptic effect of aprotinin in cardiac operations. This effect is probably due to a prevention of hyperfibrinolysis. 相似文献
3.
Aprotinin increases release of von Willebrand factor in cultured human umbilical vein endothelial cells. 总被引:1,自引:0,他引:1
M P Havel A Griesmacher G Weigel A Owen P Simon H Teufelsbauer T Vukovich E Wolner 《Surgery》1992,112(3):573-577
Through the perioperative administration of the proteinase inhibitor aprotinin, hemostasis can be improved and postoperative bleeding reduced after cardiac operations. The mechanism of action has been only partially clarified. The goal of our study was to investigate the influence of aprotinin on the synthesis of von Willebrand factor (vWF) in human endothelial cells. Human umbilical vein endothelial cells (HUVEC) were cultivated in vitro and incubated with different aprotinin concentrations (55, 100, and 215 mol/L). With all investigated aprotinin concentrations, there was an increase in vWF synthesis compared with basal secretion (p less than 0.001). When the HUVEC were preincubated with aprotinin and stimulated with thrombin, there was a further significant increase in vWF synthesis. HUVEC that, were first incubated with aprotinin and then stimulated with thrombin demonstrated a significant increase in vWF synthesis compared with basal secretion in nonincubated cells (p less than 0.0001). Also, compared with the cells that had received thrombin stimulation alone, the combination of aprotinin incubation and thrombin stimulation led to a significantly higher vWF concentration (p less than 0.05). Because vWF is necessary for the interaction with platelet factor glycoprotein Ib and platelet adhesion, the demonstrated increase in vWF synthesis could be one of the mechanisms of action of aprotinin leading to its blood-sparing effect. 相似文献
4.
Dodd Steven W. Havel Henry A. Kovach Paul M. Lakshminarayan Chitra Redmon Martin P. Sargeant Charlene M. Sullivan Gary R. Beals John M. 《Pharmaceutical research》1995,12(1):60-68
Mixing pharmaceutical preparations of soluble neutral regular insulin solution (NRI) and neutral protamine Hagedorn (NPH) crystalline insulin suspension leads to a reduction in the measurable amount of soluble insulin in the formulation supernatant. However in spite of the loss in soluble insulin, the time-actions of these components have been shown, in clinical trials, to be unaffected. The interaction between these different physical forms of insulin has been studied using reversed-phase HPLC, isothermal titrating calorimetry, and Doppler electrophoretic light scattering analysis. Sorbent surface and solution perturbation studies revealed that the NRI adsorbs to the surface of the NPH crystal with an equilibrium constant ranging from 104 M–1 to 107 M–!, depending on the protamine concentration, pH, ionic strength, and temperature. This adsorption behavior suggests that the binding is mediated by electrostatic interactions arising between the positively-charged NPH crystal and the negatively-charged NRI hexamer. Doppler electrophoretic light scattering results, used to probe the pH-dependent surface charge of NPH and soluble insulin hexamer, support the conclusion that electrostatic interactions mediate the adsorption process. Adsorption studies under physiological conditions indicate that the elevated temperature and ionic strength, in a subcutaneous depot, are sufficient to lead to the dissociation of the NRI/NPH complex that exists in these NPH mixture formulations. 相似文献
5.
Plasmatic coagulation parameters were studied in patients on parenteral cephalosporins with different hepatic pharmacokinetics. Sixty patients received either cefotaxime (4 g/day), ceftriaxone (2 g/day) or latamoxef (4 g/day) pre- and postoperatively for at least 5 days at random. They received parenteral nutrition without vitamin K supply and had no oral intake. A significant drop (p less than 0.05) in vitamin-K-dependent coagulation factors was recorded in patients treated with latamoxef, while patients receiving ceftriaxone and cefotaxime did not exhibit a significant change in their plasmatic coagulation parameters. Interference of some cephalosporins with the vitamin-K-dependent hepatic metabolism of clotting factors seems to be likely, rather than a suppression of intestinal vitamin K production by the intestinal microflora. 相似文献
6.
Libor Velíek† Jana Velíková Yael Ptachewich Shlomo Shinnar‡ Solomon L. Mosh醇 《Epilepsia》1995,36(2):179-185
Summary We determined the effects of the N-methyl-Daspartate (NMDA) receptor blocker MK-801 (0.05, 0.1, and 0.5 mg/kg intraperitoneally, i.p.) and phenytoin (PHT, 5, 10, and 20 mg/kg i.p.) on flurothyl-induced clonic and tonic-clonic seizures in 9-, 1 5, 30-, and 60-day-old male rats. Both agents had seizure-, age-, and dose-specific effects. The highest dose of MK-801 was anticonvulsant against clonic flurothyl-induced seizures only in 9- and 60-day-old rats, but suppressed tonic-clonic seizures in all ages. The lowest dose of MK-801 (0.05 mg/kg) produced significant anticonvulsant effects only in 15 day old rats. PHT did not have any effect on clonic seizures throughout development. Both doses of PHT (10 and 20 mg/kg) were anticonvulsant against tonic-clonic seizures in adult rats but not in any other age group. The results indicate that NMDA receptors play an important role in tonic-clonic flurothyl-induced seizures throughout development (especially in 15-day-old rats) and that the anticonvulsant effects of PHT may vary at different stages of brain development. 相似文献
7.
Age-Specific Effects of Baclofen on Pentylenetetrazol-Induced Seizures in Developing Rats 总被引:1,自引:0,他引:1
Summary: Purpose : To determine whether seizures have age-specific features, we studied the role of γ-aminobutyric acid, (GABAB) transmission in rats of various ages (9, 15, 30, and 60 postnatal days). Methods: We used a GABA, receptor agonist baclofen (2 or 5 mg/kg intraperitoneally, i.p.) and a GABAB receptor antagonist CGP 35348 (100 or 600 mg/kg i.p.) in the pentylenetetrazol (PTZ)-induced model of clonic and tonic-clonic seizures (100 mg/kg subcutaneously, s.c.).
Results : Whereas baclofen was anticonvulsant and CGP 35348 proconvulsant in most animals, there were distinct age-related differences in the effectiveness of these drugs and the antagonist had some anticonvulsant activity in adults. Furthermore, the two drugs acting at GABAB receptors had a different profile of action in clonic seizures as compared with tonic-clonic seizures.
Conclusions : The differences in the age-specific action of the GABAB agonist and antagonist suggest that different GABAB receptor subsets may mediate the drug effects. The results indicate that putative antiepileptic drugs (AEDs) must be tested during development because it may not be possible to extrapolate age-specific anticonvulsant effects from studies in adult animals. 相似文献
Results : Whereas baclofen was anticonvulsant and CGP 35348 proconvulsant in most animals, there were distinct age-related differences in the effectiveness of these drugs and the antagonist had some anticonvulsant activity in adults. Furthermore, the two drugs acting at GABA
Conclusions : The differences in the age-specific action of the GABA
8.
Krásná E Kolesár L Slavcev A Valhová S Kronosová B Jaresová M Stríz I 《Inflammation》2005,29(1):33-37
IL-18 is a multifunctional cytokine that augments both innate and acquired immunity and potentiates Th1 and Th2 reactions.
We studied the expression of IL-18 receptor (IL-18R) on renal and respiratory epithelial cell lines. Both cell lines upregulated
IL-18R mRNA and IL-18R membrane expression in response to TNF alpha and other proinflammatory cytokines. The function of IL-18R
was confirmed by induction of IL-8 release from epithelial cells in response to recombinant IL-18. Epithelial cells may represent
an important target for IL-18, mainly under inflammatory conditions associated with TNF alpha release. 相似文献
9.
Cytogenetic observations in a human gastric leiomyosarcoma 总被引:1,自引:0,他引:1
The chromosomes of a human gastric leiomyosarcoma were studied in preparations from short-term cultures. The tumor had a triploid-near-triploid modal population characterized by extensive numerical and structural changes. Of these deviations, del(1)(p12-13), monosomy 14, and underrepresentation of chromosomes 18 and 22 were abnormalities in common with two of the three previously studied leiomyosarcomas of the small bowel. 相似文献
10.
Electrical stimulation of the parasympathetic auriculo-temporal nerve (40 Hz, 30 min), in the anaesthetized rat under - and -adrenoceptor blockade, increased [3H]thymidine and [3H]leucine uptake into the parotid glands by 80 and 263 %, respectively. The increase in response to parasympathetic stimulation was almost the same ([3H]thymidine 82 % and [3H]leucine 283 %) when atropine (2 mg kg-1 I.P. or I.V.) was included in the pretreatment. Neither intravenous infusion of vasoactive intestinal peptide (0.5-20 mg kg-1 min-1, 30 min) nor of bethanechol (10 mg kg-1 min-1, 30 min), under adrenoceptor blockade, increased the uptake of [3H]thymidine into the glands. However, these drugs increased [3H]leucine uptake, and in combination they interacted positively. Whereas vasoactive intestinal peptide is likely to be involved in the parasympathetic nerve-evoked protein synthesis, the nature of the non-adrenergic, non-cholinergic component(s) involved in the mitogenic response is presently unknown. 相似文献