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1.
Transfer of clonidine and dexmedetomidine across the isolated perfused human placenta 总被引:4,自引:0,他引:4
T. I. ALA-KOKKO P. PIENIMÄKI E. LAMPELA A. I. HOLLMÉN O. PELKONEN K. VÄHÄKANGAS 《Acta anaesthesiologica Scandinavica》1997,41(2):313-319
Background: The placental transfer of the a2 receptor agonist clonidine, earlier used as an adjuvant in obstetric epidural analgesia, was compared with the transfer of the newer and more %-selective agonist dexmedetomidine.
Methods: Term placentas were obtained immediately after delivery with maternal consent and a 2-hour recycling perfusion of a single placental cotyledon was performed. Disappearance from the maternal circulation, accumulation in placental tissue and appearance in the fetal circulation of clonidine or dexmedetomidine with the reference compound antipyrine were followed in 4 experiments for both drugs.
Results: At 2 hours the percent dexmedetomidine found in the fetal circulation was 12.5 (SD 5.1)%, while 48.1 (SD 20.3)% was found in the perfused placental cotyledon. A higher mean clonidine than dexmedetomidine concentration was achieved in the fetal circulation (1.90 vs. 0.56 nmol/l, P <0.05). At 2 hours the percent clonidine found in the fetal circulation was 22.1 (SD 2.4)% ( P <0.05), while 11.3 (SD 3.3)% ( P <0.05) was re tained in the perfused placental cotyledon. The transfer indexes, describing maternal-to-fetal transfer of dexmedetomidine and clonidine normalized with the transfer of antipyrine, were 0.88 (SD 0.07) and 1.04 (SD 0.08) respectively ( P <0.05).
Conclusions: Dexmedetomidine disappeared faster than clonidine from the maternal circulation, while even less dexmedetomidine was transported into the fetal circulation. This was due to its greater placental tissue retention, the basis for which probably is the higher lipophilicity of dexmedetomidine. 相似文献
Methods: Term placentas were obtained immediately after delivery with maternal consent and a 2-hour recycling perfusion of a single placental cotyledon was performed. Disappearance from the maternal circulation, accumulation in placental tissue and appearance in the fetal circulation of clonidine or dexmedetomidine with the reference compound antipyrine were followed in 4 experiments for both drugs.
Results: At 2 hours the percent dexmedetomidine found in the fetal circulation was 12.5 (SD 5.1)%, while 48.1 (SD 20.3)% was found in the perfused placental cotyledon. A higher mean clonidine than dexmedetomidine concentration was achieved in the fetal circulation (1.90 vs. 0.56 nmol/l, P <0.05). At 2 hours the percent clonidine found in the fetal circulation was 22.1 (SD 2.4)% ( P <0.05), while 11.3 (SD 3.3)% ( P <0.05) was re tained in the perfused placental cotyledon. The transfer indexes, describing maternal-to-fetal transfer of dexmedetomidine and clonidine normalized with the transfer of antipyrine, were 0.88 (SD 0.07) and 1.04 (SD 0.08) respectively ( P <0.05).
Conclusions: Dexmedetomidine disappeared faster than clonidine from the maternal circulation, while even less dexmedetomidine was transported into the fetal circulation. This was due to its greater placental tissue retention, the basis for which probably is the higher lipophilicity of dexmedetomidine. 相似文献
2.
3.
Rupprecht Matthaei 《Pflügers Archiv : European journal of physiology》1924,202(1):88-111
Zusammenfassung Während die Argumente für einen peripheren Ursprung der Nachbewegung (Nb.) der Kritik nicht standhalten, läßt sich die Erscheinung auf das Überdauern einer zentralen (subkortikalen) Erregung, die von der längeren Willküranstrengung herstammt, zurückführen. Die Nb. bietet weitgehende Ähnlichkeit mit der auf einem Bestehen unterschwelliger Dauererregungen beruhenden Zunahme der Reflextätigkeit des Froschrückenmarkes nach funktioneller Beanspruchung. Der rhythmische Verlauf der Nb., ihr Umschlag in ein Schwererwerden der angestrengten Extremität, sowie eine Reihe von Summationserscheinungen und die willkürliche Hemmbarkeit, endlich die Tatsache der Beeinflussung entsprechender nicht angespannter Muskeln der andern Körperhälfte stützen den Beweis. Die subjektive Seite der Nb. ist, wie der Novocainversuch zeigt, im wesentlichen peripher bedingt zu denken. 相似文献
4.
5.
Density of γ/δ+ T cells in the jejunal epithelium of patients with coeliac disease and dermatitis herpetiformis is increased with age 下载免费PDF全文
E SAVILAHTI T
RML A ARATO G HACSEK K HOLM T KLEMOLA A NEMETH M MKI T REUNALA 《Clinical and experimental immunology》1997,109(3):464-467
Increased density of γ/δ T cell receptor (TCR)+ intraepithelial lymphocytes is the only characteristic in the jejunum of patients with coeliac disease and dermatitis herpetiformis which is not normalized on a gluten-free diet. We explored the age-dependent changes in intraepithelial γ/δ and α/β TCR+ cells from 137 biopsies from patients with coeliac disease and dermatitis herpetiformis and from controls. Biopsy specimens from 100 patients with coeliac disease and dermatitis herpetiformis and from 37 controls were studied with an immunohistochemical method using MoAbs to T cell receptors and peroxidase staining. An increase in the density of intraepithelial γ/δ T cells above the mean +2 s.d. of the density in controls was present in 97 of 100 specimens from patients with coeliac disease and dermatitis herpetiformis. The density of γ/δ+ cells of patients with coeliac disease and dermatitis herpetiformis on a normal gluten-containing diet showed a positive correlation with age (r = 0.45, P< 0.0001). In controls, the density of γ/δ+ cells remained low throughout the age-range studies, from age 0.6–57 years. In controls, α/β+ cells increased with age (r = 0.57, P< 0.001). The increase in density of intraepithelial lymphocytes with age is in agreement with their thymus-independent character and local proliferation. 相似文献
6.
In an effort to assess the effect of ambient temperature on the gross efficiency (Effg) of step exercise 12 subjects performed a modified step test either at —15 °C or 21°C ascending to three different heights (corresponding to light, moderate and heavy work), for 20 min each with a frequency of 18 steps min-1. Heart rate (HR), rectal temperature, skin temperatures and heat flux from skin were continuously measured. Oxygen consumption was measured during the last 5 min of each step height and perceptions of thermal sensation were recorded. The results indicate that, while using conventional clothing adequate in these temperatures, Effg is altered in a contradictory manner. At —15°C Effg increased with increasing work load, whereas at 21°C it decreased when the work load increased. The highest Effg (heavy work at —15°C and light work at 21°C) values are reflected as rather similar rectal temperatures (37.4–37.7°C) and identical mean skin temperatures (32.8 °C) as well as the same (slightly warm) thermal sensation of the legs. At — 15 °C the lowest Effg in light work was probably hue to the need to warm up the muscles. At 21°C, on the contrary, the activation of heat dissipation systems was probably responsible for the lowest Effg in heavy work. 相似文献
7.
P.
Kp T. JAHNUKAINEN J.
GR
NLUND M.
RAUTANEN L.
HALKOLA I.
VLIMKI 《Acta physiologica (Oxford, England)》1997,160(3):283-289
To investigate the pulmonary haemodynamic effects of meconium aspiration and subsequent adenosine triphosphate (ATP) treatment, 12 anaesthetized and ventilated pigs (wt 24-28 kg) received either ATP or an equal volume of saline into the right heart in doses of 0.02 to 0.80 lmol kg-1 min?1 after intratracheal administration of 2 mL kg?1 of human meconium. Meconium instillation induced significant increases in pulmonary vascular pressures and total and postarterial resistances calculated from pulmonary artery occlusion studies, but did not affect the systemic haemodynamics, except for a fall in heart rate and increase in central venous pressure. Infusion of ATP at the lowest doses (0.02 and 0.08 µmol kg?1 min?1) selectively decreased the pulmonary arterial pressure and vascular resistance and at 0.32 and 0.80 µmol kg?1 min?1 reduced both the pulmonary and systemic resistances. In the lung circulation the increasing doses of ATP reduced preferably the arterial, but also the postarterial resistance. Withdrawal of ATP infusion led to a significant rebound effect especially in the postarterial segment of the lung circulation. Meconium aspiration thus induces an acute, predominantly postarterial obstruction in the lung circulation and infusion of ATP at low doses selectively dilates the pulmonary vascular bed and may help to preclude elevation of capillary pressures in meconium aspiration-induced pulmonary hypertension. 相似文献
8.
Webb DC Mahalingam S Cai Y Matthaei KI Donaldson DD Foster PS 《European journal of immunology》2003,33(12):3377-3385
The pathogenesis of human asthma and the development of key features of pulmonary allergy in mouse models has been critically linked to IL-13. Analyses of the receptor components employed by IL-13 have shown that delivery of this cytokine to the airways of naive IL-4Ralpha gene targeted (IL-4Ralpha(-/-)) mice fails to induce disease, suggesting that this membrane protein is critical for transducing IL-13-mediated responses. The current study demonstrates that, in contrast to naive mice, T helper 2 bias, airways hyperreactivity (AHR) and tissue eosinophilia develop in Ovalbumin-sensitized IL-4Ralpha(-/-) mice and that these responses can be inhibited by the IL-13 antagonist sIL-13Ralpha2Fc. Therefore, antigen stimulation induces an IL-13-regulated response that is independent of IL-4Ralpha. To determine the role of IL-5 and eosinophils in the development of disease in antigen-exposed IL-4Ralpha(-/-) mice, pulmonary allergy was examined in mice deficient in both factors. IL-4Ralpha/IL-5(-/-) mice were significantly defective in their ability to produce IL-13 and failed to develop AHR, suggesting that IL-5 indirectly regulates AHR in allergic IL-4Ralpha(-/-) mice by an IL-13-dependent mechanism. Collectively, these results demonstrate that IL-13-dependent processes regulating the development of AHR and T helper bias persist in the in the lungs of allergic IL-4Ralpha(-/-) mice. 相似文献
9.
Klaus I. Matthaei 《The Journal of physiology》2007,582(2):481-488
Although genetic manipulations in mice have provided a powerful tool for investigating gene function in vivo , recent studies have uncovered a number of developmental phenomena that complicate the attribution of phenotype to the specific genetic change. A more realistic approach has been to modulate gene expression and function in a temporal and tissue-specific manner. The most common of these methods, the Cre LoxP and tetracycline response systems, are surveyed here and their recently identified shortcomings discussed, along with a less well known system based on the E. coli lac operon and modified for use in mammals. The potential for further complications in interpretation due to hitherto unexpected epigenetic effects involving transfer of RNA or protein in oocytes or sperm is also explored. Given these problems we reiterate the necessity for the use of completely reversible methods that will allow each experimental group of animals to act as their own control. Using these methods with a number of specific modifications to eliminate non-specific effects from random insertion sites and inducer molecules, the full potential of genetic manipulation studies should be realized. 相似文献
10.
Type 2 cytokines in the pathogenesis of sustained airway dysfunction and airway remodeling in mice 总被引:10,自引:0,他引:10
Leigh R Ellis R Wattie JN Hirota JA Matthaei KI Foster PS O'Byrne PM Inman MD 《American journal of respiratory and critical care medicine》2004,169(7):860-867
The mechanisms underlying airway hyperresponsiveness remain unclear, although airway inflammation and remodeling likely play important roles. We have observed sustained airway hyperreactivity and airway remodeling occurring in mice after chronic allergen exposure and persisting beyond resolution of allergen-induced inflammation. The aim of this study was to delineate mechanisms involved in allergen-induced airway hyperreactivity and airway remodeling and to examine evidence for a causal association between airway remodeling and sustained airway hyperreactivity. Wild-type (WT) and interleukin (IL)-4-, IL-5-, and IL-13-deficient (-/-) mice were sensitized and studied 4 weeks after chronic allergen exposure. By measuring airway responsiveness and airway morphometry, we demonstrated that WT mice developed sustained airway hyperreactivity and aspects of airway remodeling after chronic allergen exposure. Both IL-4(-/-) and IL-13(-/-) mice were protected from developing sustained airway hyperreactivity and aspects of airway remodeling. In contrast, IL-5(-/-) mice developed sustained airway hyperreactivity and aspects of airway remodeling similar to that seen in WT mice. Our results confirm that IL-4 and IL-13, but not IL-5, are critical for the development of sustained airway hyperreactivity and airway remodeling after allergen exposure. 相似文献