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W A Ritschel A Sabouni A S Hussain 《Methods and findings in experimental and clinical pharmacology》1989,11(10):643-646
The objective of this study was to investigate the role of the transfollicular pathway in the diffusion process of chemicals through excised human skin in vitro. Skin was obtained from 5 cadavers (3 males, 3 females) within 24 h of death. The age of the subjects varied between 18-77 years. Three radiolabelled drugs, namely 14C-coumarin, 3H-propranolol and 3H-griseofulvin, were studied. The permeation parameters such as flux, lag time, diffusion coefficient and permeability constant were determined across scalp and abdominal skin using the Thomas Diffusion Cell. For all tested substances the flux through scalp skin was higher than across abdominal skin and the lag time was decreased. The differences were statistically significant at p less than 0.05 for coumarin and propranolol. These data suggest that the transfollicular pathway in permeation might have a significant impact on the diffusion parameters for some drugs. Also, in the case of coumarin, permeability seems to be epidermis/dermis-controlled, whereas for griseofulvin and propranolol the Stratum corneum apparently is the permeability limiting barrier. 相似文献
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Previously we have described the properties of store-operated channel currents (SOCs) in freshly dispersed rabbit portal vein smooth muscle cells. In addition to Ca2+ store depletion these SOCs could also be activated by α-adrenoceptor stimulation and diacylglycerol (DAG) via a protein kinase C (PKC)-dependent mechanism. In the present study we have investigated the effect of β-adrenoceptor stimulation on SOCs in rabbit portal vein myocytes. With whole-cell recording the selective β-adrenoceptor agonist isoprenaline reduced the current evoked by cyclopiazonic acid (CPA, sarcoplasmic/endoplasmic reticulum ATPase inhibitor) by over 85%. With cell-attached patch recording, bath application of isoprenaline produced a pronounced inhibition of SOC activity evoked by either CPA or the acetoxymethyl ester form of BAPTA (BAPTA-AM). SOC activity evoked by CPA, the DAG analogue, 1-oleoyl-acetyl- sn -glycerol (OAG) or the phorbol ester, phorbol-12,13-dibutyrate (PDBu) was also markedly inhibited by the adenylate cyclase activator, forskolin, and the cell-permeable non-hydrolysable analogue of cyclic adenosine monophosphate (cAMP), 8-Br-cAMP. With inside-out patches, bath application of PDBu evoked channel currents with similar properties to SOCs which were inhibited by over 90% by a catalytic subunit of protein kinase A (PKA) and by 8-Br-cAMP. Moreover bath application of PKA inhibitors, H-89, KT5720 and an inhibitory peptide to quiescent cell-attached or inside-out patches, activated channel currents with similar properties to SOCs. These data suggest that in rabbit portal vein myocytes, stimulation of β-adrenoceptors inhibits SOC activity via a cAMP-dependent protein kinase signal transduction cascade. In addition it is concluded that constitutive PKA activity has a profound inhibitory effect on SOC activity in this vascular preparation. 相似文献
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目的:观察应用凌晨3:00皮下注射短效胰岛素治疗2型糖尿病黎明现象的疗效。方法:对40例有黎明现象的2型糖尿病患者,使用短效胰岛素凌晨3:00注射4~6U。抽取肘静脉血测定空腹血糖(FPG)及早餐后2h血糖(2hPG),免疫比浊法测定糖化血红蛋白(HbA1c),比较治疗前后上述指标变化。结果:本组患者FPG从治疗前(9.5±1.6)mmol/L下降至(6.0±0.4)mmol/L,治疗2个月后仍保持为(5.6±0.4)mmol/L;2hPG从治疗前(13.8±0.8)mmol/L下降至(7.4±0.4)mmol/L,在治疗2个月后保持为(7.9±0.3)mmol/L;FPG和2hPG与治疗前比较,均具有显著性差异(P<0.01)。治疗2个月后,HbA1c从治疗前(8.3±0.6)%下降至(6.5±0.3)%,与治疗前比较,有显著性差异(P<0.01)。结论:短效胰岛素强化治疗黎明现象具有快速稳定的降血糖和降糖化血红蛋白作用。 相似文献
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目的探讨硫酸锌对高脂喂养载脂蛋白E(ApoE)基因敲除小鼠血脂和氧化低密度脂蛋白(oxLDL)水平,及主动脉中基质金属蛋白酶9(MMP-9)和细胞分化抗原40(CD40)mRNA表达的影响。方法 AopE基因敲除小鼠连续14周喂饲高脂饲料,同时分别给予小鼠浓度为2.5、25 mmol/L硫酸锌水溶液作为低剂量组和高剂量组。测定小鼠血脂和oxLDL水平,并测定主动脉中MMP-9和CD40 mRNA表达水平。结果低剂量组和高剂量组小鼠血清中甘油三酯和oxLDL水平明显低于动脉粥样硬化(AS)模型组(P〈0.01)。低剂量组和高剂量组小鼠主动脉MMP-9 mRNA和CD40 mRNA水平与AS模型组没有差异。结论补充硫酸锌降低了AS模型动物的甘油三酯和oxLDL水平,具有潜在的抗AS作用,但对主动脉MMP-9和CD40 mRNA表达无影响。 相似文献