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51.
Hans-Georg Eichler Robert Mader Brigitte Blöchl-Daum Günther Steger Hugo Rainer 《Cancer chemotherapy and pharmacology》1987,20(1):81-82
Summary Coupling of mitoxantrone, a new antitumor agent, to a macromolecular carrier system may improve the drug's selectivity of action and pharmacokinetic properties. We have studied in vitro binding of mitoxantrone to poly(I)·poly(C), a macromolecular, double-stranded homoribopolymer, by equilibrium dialysis and high-performance liquid chromatography (HPLC).Results showed high binding affinity for mitoxantrone to poly(I)·poly(C) (Kd=1.05·10-6
M), the calculated number of mitoxantrone-binding sites is 60 per molecule poly(I)·poly(C). In view of the good tolerance in clinical studies, poly(I)·poly(C) may thus be a useful drug carrier for mitoxantrone. A mitoxantrone:poly(I)·poly(C) ratio of 1:30 (w/w) is recommended for therapeutic studies.This study was supported by the Österreichischer Forschungsfonds 相似文献
52.
Ludwig Kappos Reinhard Heun Hans-Georg Mertens 《European archives of psychiatry and clinical neuroscience》1990,240(1):34-38
Summary In a retrospective matched-pairs study the efficacy of azathioprine treatment was compared with no treatment over a period of at least 10 years. Of 277 patients with clinically definite multiple sclerosis seen during the years 1973 and 1974, 42 pairs were selected by similarity in disability score, sex, age and disease duration. Only 3 patients were lost to follow-up, and in 2 cases the initial diagnosis could not be confirmed. At the end of the 10-year period the number of wheelchair-bound, bedridden or deceased patients was double in the untreated as compared with the azathioprine-treated group but the number of non- or only minimally handicapped patients was similar in each group. The mean disability score was significantly lower in the treated group. Although caution is warranted as in every retrospective study because of insufficiently controlled confounding variables, these results support a positive but weak long-term effect of azathioprine. 相似文献
53.
Thomas Pernerstorfer Bernd Jilma Hans-Georg Eichler Susanne Aull Sylvia Handler & Wolfgang Speiser 《British journal of haematology》1999,105(4):1127-1129
Based on heparin's antithrombin and anti-FXa activity and its in vitro inhibition of activated factor VII (FVIIa) activity, we hypothesized that unfractionated heparin (UFH) may decrease plasma levels of FVIIa in humans. Therefore, 10 healthy young male volunteers received an intravenous UFH infusion over 24 h. Heparin decreased FVIIa levels by 30% (95% CI 14-47%) at 12 h, which was sustained until 24 h. In contrast, neither the substrate pool (i.e. total factor VII) as measured by FVII antigen nor FVII activity were affected by UFH. These results may improve our understanding of the regulation of FVIIa levels and heparin's mode of action. 相似文献
54.
J. Plisiene MD A. Blumberg MD G. Haager Msc C. Knackstedt MD J. Latsch MD C. Norra MD M. Arndt MD S. Tuerk Msc N. Heussen Msc M. Kelm MD H. G. Predel MD P. Schauerte MD 《Clinical research in cardiology》2008,97(11):820-826
Aims This prospective pilot-study was performed to assess whether regular moderate physical activity elevates the parasympathetic
tone to the atrio-ventricular node and decreases VR during permanent AF.
Background Adequate ventricular rate (VR) control in patients with permanent atrial fibrillation (AF) is not easy to accomplish.
Methods 10 patients (mean age 59 ± 10 years) with permanent AF (duration: 10 ± 8 years) underwent moderate physical exercise adjusted
to their individual physical capability (45 min walking/jogging twice a week). To analyze VR control physical exercise tests
and Holter-ECG recordings were performed before and after 4 months. In addition, stepwise lactate tests and psycho-pathometric
examinations were obtained.
Results After 4 months of training, there was a trend toward a decrease of mean VR in 24 h Holter-ECGs by 12% from 76 ± 20 to 67 ± 12 bpm
(P = 0.05) while there was no significant decrease of the minimal VR (38 ± 8 vs. 36.3 ± 4.5 bpm, P = 0.54). At a lactate threshold of 2 mmol/l there was a trend towards an increase of the running speed from 105 ± 11 to 116 ± 12 m/min
(P = 0.05). A significant VR decrease of 8% (range 5–10%) was observed at almost all exercise levels during exercise treadmill
testing. Increases of exercise capacity and decreases of VR were accompanied by subjective improvements of health perception.
Conclusion Regular moderate physical activity decreases VR at rest and during exercise while increasing exercise capacity. Physical training
should be taken into account for ventricular rate control during AF.
The study was supported by the German Atrial Fibrillation Competence Network (AFCN) funded by the Fedral Ministry of Education
and Research (FMBI).
A. Blumberg and J. Plisiene contributed equally to this study. 相似文献
55.
Hans Jürgen Steinfelder Silke Schramm Hans-Georg Joost 《Naunyn-Schmiedeberg's archives of pharmacology》1987,336(1):105-110
Summary The inhibition of insulin-stimulated glucose transport by lipolytic agents was studied in isolated rat adipose cells. Two different mechanisms for the inhibition of glucose transport by lipolytic hormones and agents were distinguished by use of the antilipolytic agent prostaglandin E2 (PGE2). The inhibition of glucose transport induced by lipolytic hormones such as glucagon, catecholamines or ACTH in the presence of adenosine deaminase was antagonized by PGE2. In contrast, inhibition of hexose transport by alkylxanthines was only partially (20–30%) attenuated by PGE2, although the eicosanoid had antagonized cyclic AMP accumulation and stimulation of lipolysis in response to all tested lipolytic agents. The inhibition of glucose transport by IBMX was immediate, whereas the lipolytic hormones (isoprenaline and ACTH) exhibited a latency of 2–3 min. In addition, the inhibition induced by the lypolytic hormones disappeared after cooling of the cells to 22°C, at which temperature IBMX was still inhibitory. Thus, the PGE2-sensitive component of the effect of lipolytic agents on glucose transport appears to be mediated by adenylate cyclase or its subunits N
s/N
i. The PGE2-insensitive effect of alkylxanthines probably reflects a direct interaction of the agents with a regulatory site at the transporter or a related protein.
Send offprint requests to H. J. Steinfelder at the above address 相似文献
56.
H G Predel O Schulte-Vels K Gl?nzer H Meyer-Lehnert H J Kramer 《American journal of hypertension》1991,4(11):871-879
In six patients with essential hypertension (EH) and in six healthy volunteers (C) the effects of a 60-min intravenous (iv) infusion of human atrial natriuretic peptide (alpha-hANP) (24 ng/min/kg) on systemic and renal hemodynamics and renal excretory function were evaluated. Basal plasma ANP concentrations in patients with EH were higher (P less than .05) than in C (30.9 +/- 4.5 v14.0 +/- 1.7 pmol/L). Maximal effects of alpha-hANP infusion occurred after 30 to 60 min. Blood pressure (BP) declined from 154 +/- 5/109 +/- 4 to 139 +/- 7/94 +/- 4 in EH and from 117 +/- 1/72 +/- 2 to 106 +/- 1/65 +/- 3 mm Hg in C (P less than .05). Cardiac output (CO) increased transiently from 6.1 +/- 0.3 to 6.5 +/- 0.4 L/min in EH and from 6.8 +/- 0.3 to 7.2 +/- 0.5 L/min in C, whereas heart rate (HR) remained constant both in patients with EH and in C (69 +/- 3 to 72 +/- 5 and 60 +/- 3 to 63 +/- 3/min). The increases in urine flow and in urinary sodium excretion from 3.6 +/- 0.2 to 16.0 +/- 2.0 mL/min and from 230 +/- 33 to 1004 +/- 137 mumol/min, respectively, in EH were more pronounced than in C (from 3.9 +/- 1.0 to 8.4 +/- 0.8 mL/min and from 211 +/- 37 to 451 +/- 84 mumol/min); (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
57.
The neuropeptide calcitonin gene-related peptide (CGRP) binds to a subpopulation of dorsal root ganglion (DRG) neurons, elevates intracellular calcium, and causes inward currents in about 30% of lumbar DRG neurons. Using whole-cell patch clamp recordings, we found in the present study that application of CGRP to isolated and cultured DRG neurons from the adult rat enhances voltage-gated TTX-resistant (TTX-R) Na(+) inward currents in about 30% of small- to medium-sized DRG neurons. During CGRP, peak densities of Na(+) currents increased significantly. CGRP shifted the membrane conductance of the CGRP-responsive cells towards hyperpolarization without changing the slope of the peak conductance curve. The effect of CGRP was blocked by coadministration of CGRP8-37, an antagonist at the CGRP receptor. The effect of CGRP was also blocked after bath application of PKA14-22, a membrane-permeant blocker of protein kinase A, and PKC19-31, a PKC inhibitor, in the recording pipette. These data show pronounced facilitatory effects of CGRP on TTX-R Na(+) currents in DRG neurons which are mediated through CGRP receptors and intracellular pathways involving protein kinases A and C. Thus, in addition to prostaglandins, CGRP is another mediator that affects TTX-R Na(+) currents which are thought to occur mainly in nociceptive DRG neurons. 相似文献
58.
The central melanocortin system directly controls peripheral lipid metabolism 总被引:4,自引:0,他引:4 下载免费PDF全文
Nogueiras R Wiedmer P Perez-Tilve D Veyrat-Durebex C Keogh JM Sutton GM Pfluger PT Castaneda TR Neschen S Hofmann SM Howles PN Morgan DA Benoit SC Szanto I Schrott B Schürmann A Joost HG Hammond C Hui DY Woods SC Rahmouni K Butler AA Farooqi IS O'Rahilly S Rohner-Jeanrenaud F Tschöp MH 《The Journal of clinical investigation》2007,117(11):3475-3488
Disruptions of the melanocortin signaling system have been linked to obesity. We investigated a possible role of the central nervous melanocortin system (CNS-Mcr) in the control of adiposity through effects on nutrient partitioning and cellular lipid metabolism independent of nutrient intake. We report that pharmacological inhibition of melanocortin receptors (Mcr) in rats and genetic disruption of Mc4r in mice directly and potently promoted lipid uptake, triglyceride synthesis, and fat accumulation in white adipose tissue (WAT), while increased CNS-Mcr signaling triggered lipid mobilization. These effects were independent of food intake and preceded changes in adiposity. In addition, decreased CNS-Mcr signaling promoted increased insulin sensitivity and glucose uptake in WAT while decreasing glucose utilization in muscle and brown adipose tissue. Such CNS control of peripheral nutrient partitioning depended on sympathetic nervous system function and was enhanced by synergistic effects on liver triglyceride synthesis. Our findings offer an explanation for enhanced adiposity resulting from decreased melanocortin signaling, even in the absence of hyperphagia, and are consistent with feeding-independent changes in substrate utilization as reflected by respiratory quotient, which is increased with chronic Mcr blockade in rodents and in humans with loss-of-function mutations in MC4R. We also reveal molecular underpinnings for direct control of the CNS-Mcr over lipid metabolism. These results suggest ways to design more efficient pharmacological methods for controlling adiposity. 相似文献
59.
Terlipressin dose response in healthy and endotoxemic sheep: impact on cardiopulmonary performance and global oxygen transport 总被引:8,自引:0,他引:8
Westphal M Stubbe H Sielenkämper AW Borgulya R Van Aken H Ball C Bone HG 《Intensive care medicine》2003,29(2):301-308
OBJECTIVE: To determine whether a goal-directed terlipressin infusion increases mean arterial pressure without causing a pulmonary vasopressive effect and whether this response impacts on key parameters of oxygen transport in healthy and endotoxemic sheep. DESIGN AND SETTING: Prospective controlled trial in a university research laboratory. ANIMALS AND INTERVENTIONS: Six conscious adult ewes instrumented for chronic study received terlipressin as titrated infusion started with 10 microg x kg(-1) x h(-1) and increased by 5 microg x kg(-1) x h(-1) every 15 min, either until mean arterial pressure was increased by 15 mmHg from baseline, or a maximum of 40 microg x kg(-1) x h(-1) was given. Following 24 h of recovery sepsis was induced and maintained in the same ewes by a continuous infusion of endotoxin ( Salmonella typhosa, 10 ng x kg(-1) min(-1)). After 16 h of endotoxemia the sheep were again treated with terlipressin. MEASUREMENTS AND RESULTS: Systemic oxygen delivery and consumption were calculated before and after the titration period; hemodynamic parameters were measured every 15 min. The increase in mean arterial pressure was greater during endotoxemia than in healthy controls. In both states terlipressin administration decreased cardiac index and diminished oxygen delivery and consumption. While mean pulmonary arterial pressure remained constant, terlipressin increased the pulmonary vascular resistance index in endotoxemic sheep. CONCLUSIONS: During ovine endotoxemia titrated terlipressin reversed hypotension but impaired the pulmonary circulation. The observed decrease in oxygen delivery may carry the risk of tissue hypoxia especially in sepsis, where oxygen demand is typically increased. 相似文献
60.
The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis 总被引:30,自引:0,他引:30 下载免费PDF全文
Schneider A Krüger C Steigleder T Weber D Pitzer C Laage R Aronowski J Maurer MH Gassler N Mier W Hasselblatt M Kollmar R Schwab S Sommer C Bach A Kuhn HG Schäbitz WR 《The Journal of clinical investigation》2005,115(8):2083-2098
G-CSF is a potent hematopoietic factor that enhances survival and drives differentiation of myeloid lineage cells, resulting in the generation of neutrophilic granulocytes. Here, we show that G-CSF passes the intact blood-brain barrier and reduces infarct volume in 2 different rat models of acute stroke. G-CSF displays strong anti-apoptotic activity in mature neurons and activates multiple cell survival pathways. Both G-CSF and its receptor are widely expressed by neurons in the CNS, and their expression is induced by ischemia, which suggests an autocrine protective signaling mechanism. Surprisingly, the G-CSF receptor was also expressed by adult neural stem cells, and G-CSF induced neuronal differentiation in vitro. G-CSF markedly improved long-term behavioral outcome after cortical ischemia, while stimulating neural progenitor response in vivo, providing a link to functional recovery. Thus, G-CSF is an endogenous ligand in the CNS that has a dual activity beneficial both in counteracting acute neuronal degeneration and contributing to long-term plasticity after cerebral ischemia. We therefore propose G-CSF as a potential new drug for stroke and neurodegenerative diseases. 相似文献