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41.
Mariusz Świąder Izabela Zakrocka Katarzyna Świąder Andrzej Zawadzki Jarogniew J. Łuszczki Stanisław J. Czuczwar Darin Munir 《Pharmacological reports : PR》2019,71(3):466-472
Backgroundβ2-Adrenergic receptor agonists are widely used agents in the treatment of asthma or preterm labor. Since prevalence of asthma was shown to be higher in patients with epilepsy and modulation of noradrenergic system activity may modify epilepsy course, the aim of the present study was to examine the effect of salbutamol (SALB), one of the most commonly used β2-adrenergic receptor agonist on the anticonvulsant potency of four classical antiepileptic drugs (AEDs): valproate (VPA), carbamazepine (CBZ), phenytoin (DPH) and phenobarbital (PB) in mice subjected to the maximal electroshock (MES)-induced seizures.MethodsSeizures were caused by a current delivered through ear-clip electrodes. The influence of AEDs and SALB on animals’ motor coordination and memory processes was also evaluated.ResultsSingle SALB injection did not change, whereas 7 days SALB administration decreased seizure threshold in the MES-induced seizures in mice. Moreover, SALB injected ip for 1 day and for 7 days lowered the antiepileptic activity of PB in the MES-induced seizures in mice, but did not change the effect of other analyzed AEDs: VPA, CBZ or DPH. Butoxamine, a selective β2-adrenergic receptor antagonist, reversed SALB influence on the activity of PB. SALB given alone or in combination with the tested AEDs did not affect animals’ motor performance and memory after both single and 7 days administration.ConclusionsPresented results show that SALB may decrease the antiepileptic efficacy of PB. A special caution is advised to patients with epilepsy receiving β2-adrenergic receptors agonists in the pharmacotherapy of pulmonary and obstetrical disorders. 相似文献
42.
Karin A.M. Janssens Albertine J. OldehinkelIrma J. Bonvanie Judith G.M. Rosmalen 《Journal of psychosomatic research》2014
Objective
An inactive lifestyle has been associated with functional somatic symptoms (FSS), but findings are contradictory. Moreover, mediating factors in this relationship are unclear. We examined whether low physical activity was related to FSS in adolescents, and whether this association was mediated by low physical fitness.Methods
This study was part of the Dutch longitudinal cohort study TRAILS, in which 1816 adolescents (mean age 16.3 years, SD 0.7) participated during the third (T3) and 1881 (mean age 19.1 years, SD 0.6) during the fourth (T4) assessment waves. Adolescents' exercise and sedentary behavior levels and the number of FSS were assessed by questionnaires at T3 and T4. Physical fitness (VO2Max) was determined for 687 adolescents by a shuttle run test at T3. The association between physical activity and FSS was examined with bootstrapped linear regression analyses, adjusted for smoking and gender. In addition, bootstrapped mediation analyses were performed.Results
A lack of exercise (b = 0.05, bootstrap 95%-CI: 0.01 to 0.09) and high sedentary behavior (b = 0.10, bootstrap 95%-CI: 0.06 to 0.14) at T3 were positively associated with FSS at T3. Since no longitudinal effects were found, shared associations were tested instead of mediation. The associations between a lack of exercise and FSS, and sedentary behavior and FSS were shared with physical fitness (b = 0.01, bootstrap 95%-CI: 0.010.02. and b = 0.03, bootstrap 95%-CI: 0.010.05).Conclusion
An inactive lifestyle is associated with increased FSS in adolescents. Only part of this association is shared with low physical fitness. 相似文献43.
Setor K. Kunutsor Timo H. Mäkikallio Claudio G. S. Araújo Sae Young Jae Sudhir Kurl Jari A. Laukkanen 《Scandinavian cardiovascular journal : SCJ》2013,47(5):255-258
AbstractObjectives. The inverse and independent association between cardiorespiratory fitness (CRF) and arterial thrombotic disease is well established. However, the potential association between CRF and venous thromboembolism (VTE) is not well known. We aimed to assess the prospective association of CRF with the risk of VTE. Design. Cardiorespiratory fitness, as measured by maximal oxygen uptake (VO2max), was assessed using a respiratory gas exchange analyser in 2,249 men aged 42–61 years without a history of VTE at baseline in the Kuopio Ischemic Heart Disease prospective cohort. Cox-regression models were used to calculate hazard ratios (HR) with 95% confidence interval (CI) for VTE. We corrected for within-person variability in CRF levels using data from repeat measurements taken several years apart. Results. There were 144 (6.4%) incident VTE events recorded during a median follow-up of 25.2 years. The age-adjusted regression dilution ratio of CRF was 0.58 (95% CI: 0.53–0.64). The risk of VTE did not significantly decrease per 1 standard deviation increase in CRF in age-adjusted analysis (HR 0.90; 95% CI 0.75–1.08). The association remained consistent in analyses adjusted for several established and emerging risk factors (HR 0.90; 95% CI 0.73–1.12). The corresponding adjusted HRs were 0.80 (95% CI: 0.52–1.23) and 0.82 (95% CI: 0.51–1.32) respectively, when comparing the extreme tertiles of CRF levels. Conclusions. In a middle-aged Caucasian male population, CRF was not associated with future risk of VTE. Further studies are required to confirm and to generalize these findings, particulary in women and other age groups. 相似文献
44.
Trevor C. Chen Tsung‐Jen Yang Min‐Jyue Huang Ho‐Seng Wang Kuo‐Wei Tseng Hsin‐Lian Chen Kazunori Nosaka 《Scandinavian journal of medicine & science in sports》2019,29(5):725-735
This study compared nine resistance eccentric exercises targeting arm, leg, and trunk muscles in one session for changes in maximal voluntary isometric contraction strength (MVC), delayed onset muscle soreness (DOMS), plasma creatine kinase (CK) activity, and myoglobin (Mb) concentration after the first and second bouts. Fifteen sedentary men (20‐25 years) performed 5 sets of 10 eccentric contractions with 80% of MVC load for the elbow flexors (EF), elbow extensors (EE), pectoralis, knee extensors (KE), knee flexors (KF), plantar flexors (PF), latissimus, abdominis, and erector spinae (ES) in a randomized order and repeated the same exercises 2 weeks later. MVC decreased at 1 (16%‐57%) to 4 (13%‐49%) days, DOMS developed (peak: 43‐70 mm), and CK activity (peak: 23 238‐207 304 IU/L) and Mb concentration showed large increases after the first bout. The magnitude of decrease in MVC was greater (P < 0.05) for EF, EE, and PEC than others and for KF than KE, PF, and ES. DOMS was greater (P < 0.05) for EF, EE, and ES than others. Changes in all measures were smaller (P < 0.05) after the second than the first bout, and the magnitude of the repeated bout effect was similar among the muscles. Plasma CK activity and Mb concentration did not increase significantly after the second exercise bout. It was concluded that muscle damage was greater for arm than leg muscles, and muscle proteins in the blood increased to a critical level after unaccustomed whole‐body resistance exercises, but the magnitude of damage was largely attenuated for all muscles similarly after the second bout. 相似文献
45.
目的:分析我国重点短缺药品品种,探讨供应保障措施,为缓解药品短缺和实施相关政策提供参考。方法:检索我国政府网站,收集整理短缺药品监测报告,从监测哨点角度、省级监测平台角度和短缺药品来源角度,总结归纳出我国重点短缺药品品种,分析其短缺原因,提出措施建议。结果与结论:我国短缺药品中,国产药品、化学药品占比较高,抗肿瘤药短缺问题突出,基本药物目录、医保目录内品种占比高。为做好短缺药品综合供应保障,应在落实已有政策的基础上,学习国外管理经验,着力解决重点短缺药品、完善监测平台、发挥政策引导作用,加强企业社会责任意识,做好数据挖掘和信息公开,多举措保障药品的可及性。 相似文献
46.
美国食品药品管理局(FDA)于2018年5月发布了“考虑列入OTC专论的外用药活性成分的最大用量试验:研究要点和考虑的因素供企业用的指导原则”。最大用量试验(MUsT)是评估外用药体内生物利用度的标准方法,该指导原则对MUsT许多研究要点提出了具体的建议。详细介绍该指导原则的主要内容,期待对我国这方面的研究和监管有益。 相似文献
47.
Elvia Mena-Avila Ricardo Márquez-Gómez Guillermo Aquino-Miranda Gustavo Nieto-Alamilla José-Antonio Arias-Montaño 《Pharmacological reports : PR》2018,70(1):146-155
Background
Clobenpropit, a potent antagonist/inverse agonist at the histamine H3 receptor (H3R), reduced the cytotoxic action of 6-hydroxydopamine (6-OHDA) in neuroblastoma SH-SY5Y cells transfected with the human H3R. We therefore set out to study whether this effect involved a receptor-independent action on dopamine transport.Methods
The uptake of [3H]-dopamine was assayed in SH-SY5Y cells and rat striatal or cerebro-cortical isolated nerve terminals (synaptosomes). Clobenpropit binding to the human norepinephrine (NET) and dopamine (DAT) transporters was analyzed by molecular modeling.Results
In SH-SY5Y cells, [3H]-dopamine uptake was inhibited by desipramine (selective NET inhibitor), GBR-12909 (selective DAT inhibitor), and fluoxetine (selective inhibitor of the serotonin transporter, SERT) with IC50 values 37, 537, and 2800 nM, respectively. The potency rank order indicates that [3H]-dopamine uptake is primarily performed by NET. Clobenpropit inhibited [3H]-dopamine uptake (maximum inhibition 82.7 ± 2.8%, IC50 490 nM), and the effect was reproduced by the H3R antagonist/inverse agonist iodophenpropit, but not by the agonists R-α-methylhistamine and immepip or the antagonists/inverse agonists ciproxifan and A-331440. Clobenpropit also inhibited [3H]-dopamine uptake by rat striatal and cerebro-cortical synaptosomes (?54.6 ± 11.3% and ?46.3 ± 9.6%, respectively, at 10 μM). Modeling of the human NET and DAT obtained by homology from the crystal of Drosophila melanogaster DAT showed that clobenpropit can bind to a site also recognized in both transporters by nisoxetine, a potent NET inhibitor.Conclusion
These data indicate a direct inhibitory effect of clobenpropit on catecholamine transport. 相似文献48.
Sherry X. Yan Olivier G. Maisonet Carmen A. Perez Nelly Huppert Christine J. Hitchen Indra J. Das Naamit K. Gerber 《The breast journal》2020,26(5):897-903
Two commonly used whole breast irradiation (WBI) techniques, deep inspiration breath hold (DIBH) and prone positioning, are compared with regard to dosimetry and estimated late cardiac morbidity and secondary lung cancer mortality using published models. Forty patients with left‐sided DCIS or breast cancer who underwent lumpectomy and required adjuvant WBI were enrolled on a prospective trial comparing supine DIBH (S‐DIBH) with prone free breathing (P‐FB) planning. Patients underwent CT simulation in both positions; two plans were generated for each patient. Comparative dosimetry was available for 34 patients. Mean cardiac and lung doses were calculated. Risk of death from ischemic heart disease (IHD), risk of at least one acute coronary event (ACE), and lung cancer mortality were estimated from published data. Difference between S‐DIBH and P‐FB plans was compared using paired two‐tailed t test. Estimated mean risk of death from IHD by age 80 was 0.1% (range 0.0%‐0.2%) for both plans (P = 1.0). Mean risk of at least one ACE was 0.3% (range 0.1%‐0.6%) for both plans (P = .6). Mean lung cancer mortality risk was 1.4% (range 0.5%‐15.4%) for S‐DIBH and 1.0% (range 0.4%‐9.8%) for P‐FB (P = .008). Excess lung cancer mortality due to radiation was 0.5% (range 0.1%‐6.0%) with S‐DIBH and 0.0% (range 0.0%‐0.4%) with P‐FB (P = .008). Both S‐DIBH and P‐FB provide excellent cardiac sparing. Prone positioning results in lower lung dose than S‐DIBH and leads to an absolute decrease of 0.5% in excess lung cancer mortality for patients receiving WBI. 相似文献
49.
Glomerular podocytes play a key role in maintaining the integrity of the glomerular filtration barrier. This function may be regulated by angiotensin II (Ang II) through activation of cell-surface receptors. Although studies suggest that podocytes express receptors for Ang II, the Ang II binding site has not been characterized with radioligand binding techniques. We therefore used iodine 125-labeled Ang II to monitor Ang II-receptor density during differentiation of a mouse podocyte cell line. Scatchard analyses of equilibrium binding data revealed a single class of high-affinity binding sites (dissociation constant approximately 3 nmol/L) in both differentiated and nondifferentiated cells. During differentiation, the density of Ang II-receptor sites increased roughly 15-fold in differentiated podocytes (maximal density of specific binding sites 881 fmol/mg protein) compared with that in nondifferentiated cells (52 fmol/mg protein; P<.005). Glomerular podocytes expressed messenger RNA for AT1A, AT1B, and AT2 receptor subtypes, and competitive binding studies found that differentiated podocytes expressed mostly AT1 receptors (approximately 75%) with lesser amounts of AT2 (approximately 25%). Up-regulation of Ang II-receptor number was associated with increased Ang II-receptor responsiveness, as evidenced by enhanced Ang II-stimulated inositol phosphate (IP) generation and incorporation of tritiated thymidine. Both [3H]thymidine incorporation and IP generation were mediated by AT1-receptor activation. These data suggest that glomerular podocytes express a high-affinity binding site for Ang II with pharmacologic characteristics of both AT1 and AT2 receptors. This receptor site is up-regulated during podocyte differentiation, and receptor activation induces both IP generation and DNA synthesis by AT1-dependent mechanisms. We speculate that activation of podocyte Ang II receptors contributes to glomerular damage in disease states. 相似文献
50.
目的设计合成一系列4-(4-烷氧基苯基)-3-乙基-1H-1,2,4-三唑-5(4H)-酮类化合物,并评价其抗惊厥活性和神经毒性。方法以对乙酰氨基酚为起始原料,经烷基化、水解、环合等反应合成1,2,4-三唑-5(4H)-酮类化合物。通过最大电惊厥实验(MES)和神经毒性实验(NT),分别测定目标化合物的抗惊厥活性和神经毒性。结果与结论合成了20个新化合物,其结构经IR、1H-NMR和ESI-MS确证。药理学实验结果表明,所有化合物在不同剂量下都显示出抗惊厥活性。其中,3-乙基-4-(4-戊氧基苯基)-1H-1,2,4-三唑-5(4H)-酮(4e)的活性最强,其半数有效量ED50值为26.9 mg·kg-1,保护指数(PI)为11.0,虽然该化合物的活性低于阳性对照药卡马西平,但其保护指数优于卡马西平(PI=6.4);3-乙基-4-(4-(3-氟苄氧基)苯基)-1H-1,2,4-三唑-5(4H)-酮(4n)的ED50值为61.1 mg·kg-1,但其PI大于17.0,明显优于卡马西平,具有进一步研究的价值。 相似文献