Methods and findings in experimental and clinical pharmacology最新文献_第8页

Evaluation of calcium dobesilate for its anti-cataract potential in experimental animal models. 多贝酸钙抗白内障潜能的实验动物模型评价。

Methods and findings in experimental and clinical pharmacology Pub Date : 2010-04-01 DOI: 10.1358/mf.2010.32.3.1423888

T Velpandian, J Nirmal, P Gupta, A R Vijayakumar, S Ghose

引用次数: 10

A controlled clinical trial to evaluate the effect of GanedenBC(30) on immunological markers. 一项评估GanedenBC(30)对免疫标志物影响的对照临床试验。

Methods and findings in experimental and clinical pharmacology Pub Date : 2010-03-01 DOI: 10.1358/mf.2010.32.2.1423881

M Kimmel, D Keller, S Farmer, D E Warrino

{"title":"A controlled clinical trial to evaluate the effect of GanedenBC(30) on immunological markers.","authors":"M Kimmel, D Keller, S Farmer, D E Warrino","doi":"10.1358/mf.2010.32.2.1423881","DOIUrl":"https://doi.org/10.1358/mf.2010.32.2.1423881","url":null,"abstract":"GanedenBC(30), a probiotic, has been shown to significantly increase T-cell production of TNF-alpha after ex vivo exposure to a strain of adenovirus (AdenoVI) or influenza A (H3N2 Texas strain [FluTex]). The current controlled study was designed to further evaluate the effect of GanedenBC(30) on immunological marker levels following viral exposure. Ten healthy subjects' baseline immunological marker levels were analyzed. Subjects consumed 1 capsule/day of GanedenBC(30) for 28 days and returned for post-treatment immunological marker evaluation. Subjects' baseline measurements served as their own control. All subjects completed the study with no adverse events; however, one subject was excluded from the final analysis based on a reasonable consideration as an outlier. CD3+CD69+ cells, IL-6, IL-8, interferon-gamma (IFN-gamma) and TNF-alpha levels were increased after exposure to AdenoVI and FluTex. IL-1beta levels also increased after exposure to AdenoVI but were decreased after ex vivo exposure to FluTex. CD3+CD69+ cells increased significantly (P = 0.023) after exposure to both viral strains. Differences in IL-8 levels after FluTex exposure achieved statistical significance (P = 0.039) as did IFN-gamma levels after AdenoVI exposure (P = 0.039). A regimen of one capsule per day containing 500 million CFU of GanedenBC30 may be a safe and effective option for enhancing the immunological response to common viral respiratory tract infections.","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28931834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 33

The contractile effects of endothelins on isolated isthmic segment of human oviduct at the luteal phase of the menstrual cycle. 内皮素对月经周期黄体期离体人输卵管峡段的收缩作用。

Methods and findings in experimental and clinical pharmacology Pub Date : 2010-03-01 DOI: 10.1358/mf.2010.32.2.1428740

S M Jankovic, S V Jankovic, G Lukic, D Canovic, M Folic

引用次数: 8

Acemetacin antinociceptive mechanism is not related to NO or K+ channel pathways. 阿西美辛抗感知机制与NO或K+通道途径无关。

Methods and findings in experimental and clinical pharmacology Pub Date : 2010-03-01 DOI: 10.1358/mf.2010.32.2.1423883

M Gil-Flores, M I Ortiz, G Castañeda-Hernández, A E Chávez-Piña

{"title":"Acemetacin antinociceptive mechanism is not related to NO or K+ channel pathways.","authors":"M Gil-Flores, M I Ortiz, G Castañeda-Hernández, A E Chávez-Piña","doi":"10.1358/mf.2010.32.2.1423883","DOIUrl":"https://doi.org/10.1358/mf.2010.32.2.1423883","url":null,"abstract":"Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) used for the treatment of acute gout and inflammation. However, its use is limited due to side effects. Acemetacin is a prodrug of indomethacin that exhibits better gastric tolerability in preclinical and clinical trials. The aim of this study was to examine if the systemic administration of acemetacin involved the sequential participation of nitric oxide (NO) or K+ channel pathways to confer its antinociceptive effect, as compared to indomethacin. The antinociceptive effect of both drugs was studied with the formalin test. Equimolar doses of acemetacin or indomethacin were administered orally. The intraplantar administration of either L-NAME, glibenclamide, apamin or charybdotoxin plus indomethacin or acemetacin was studied using the formalin test and the anti-inflammatory and antihyperalgesic effects were measured. The antinociceptive effect of acemetacin or indomethacin was not significantly different when pretreatment with L-NAME, glibenclamide, apamin or charybdotoxin was done. The antihyperalgesic and antiinflammatory effects were also similar for both indomethacin and acemetacin. Our results suggest that the antinociceptive effect of indomethacin or acemetacin is not mediated by NO or K+ channel activation.","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28931830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Mitochondrial pores modulate the protective effect of acetylcholine on ventricular myocytes during ischemia/reperfusion injury. 线粒体孔调节乙酰胆碱对心肌细胞缺血再灌注损伤的保护作用。

Methods and findings in experimental and clinical pharmacology Pub Date : 2010-03-01 DOI: 10.1358/mf.2010.32.2.1428738

Guo-Quan Sun, Jue Wang, Qing Li, Zhi-Guo Ye, Qiang Xia

{"title":"Mitochondrial pores modulate the protective effect of acetylcholine on ventricular myocytes during ischemia/reperfusion injury.","authors":"Guo-Quan Sun, Jue Wang, Qing Li, Zhi-Guo Ye, Qiang Xia","doi":"10.1358/mf.2010.32.2.1428738","DOIUrl":"https://doi.org/10.1358/mf.2010.32.2.1428738","url":null,"abstract":"In this study, we investigated the cardioprotective effect of acetylcholine (ACh) via modulation of mitochondrial permeability transition pore (MPTP) opening through the mitochondrial ATP-sensitive potassium channel (mitoK(ATP) channel). In isolated ventricular myocytes from male Sprague-Dawley rats, 0.1 micromol/L ACh was administered for 6 min, before 30 min of simulated ischemia and 30 min of reperfusion (I/R). A mitoK(ATP) inhibitor (5-hydroxydecanoate, 5-HD) and an MPTP opener (atractyloside, Atr) were used to analyze the underlying mechanisms. Myocyte contractile function, myocyte viability, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) and mitochondrial membrane potential were assayed. During reperfusion, the amplitudes of contraction, +/-dL/dt(max), and end-diastolic length of myocytes were decreased, which were markedly improved by pretreatment with ACh. However, such effects of ACh were reversed by 100 micromol/L 5-HD for 20 min before ischemia, or 20 micromol/L Atr for 20 min at the beginning of reperfusion. Pretreatment with ACh markedly reduced I/R-induced cell death, LDH release, ROS signals and mitochondrial membrane potential dissipation, all of which were reversed by 5-HD or Atr. In conclusion, ACh may protect ventricular myocytes from I/R injury by inhibiting MPTP opening and stabilizing the mitochondrial membrane potential through activating the mitoK(ATP) channel.","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28931831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

The effect of the NMDA receptor antagonist dizocilpine on behavioral manifestations of serotonin and adrenergic antidepressants in rats. NMDA受体拮抗剂二唑西平对大鼠血清素和肾上腺素能抗抑郁药行为表现的影响。

Methods and findings in experimental and clinical pharmacology Pub Date : 2010-03-01 DOI: 10.1358/mf.2010.32.2.1481727

K Pruus, R Rudissaar, L Allikmets, J Harro

{"title":"The effect of the NMDA receptor antagonist dizocilpine on behavioral manifestations of serotonin and adrenergic antidepressants in rats.","authors":"K Pruus, R Rudissaar, L Allikmets, J Harro","doi":"10.1358/mf.2010.32.2.1481727","DOIUrl":"https://doi.org/10.1358/mf.2010.32.2.1481727","url":null,"abstract":"Glutamatergic neurotransmission has been implicated in affective disorders, possibly through the modulation of monoaminergic mechanisms. The aim of this study was to investigate the effect of coadministration of the noncompetitive NMDA antagonist dizocilpine (MK-801) with different, primarily noradrenergic and serotonergic antidepressants on forced swimming test (FST) and open-field behavior in rats. Acute administration of dizocilpine at doses of 0.02- 0.1 mg/kg did not show any effect in the open-field test or FST. Acute administration of citalopram (5 mg/kg), fluoxetine (20 mg/kg), desipramine (20 mg/kg) and maprotiline (20 mg/kg) did not influence FST, although coadministration of dizocilpine with serotonergic but not noradrenergic antidepressants caused a significant reduction of immobility. In the open-field test, fluoxetine had no effect on horizontal activity but significantly reduced the number of rearings. The coadministration of dizocilpine with fluoxetine elicited significant horizontal locomotor activation and attenuated the effect of fluoxetine on vertical activity. The combined administration of other antidepressants with dizocilpine tended to increase horizontal activity similar to that recorded with fluoxetine plus dizocilpine, but these effects were not statistically significant. Thus, the present results indicated that the coadministration of serotonergic antidepressants with NMDA receptor antagonists may induce faster and more pronounced antidepressant activity when compared to treatment with antidepressants alone. In contrast, the NMDA antagonists did not potentiate the antidepressant-like effects of noradrenergic antidepressants.","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28931833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

Inhibition of isolated human myometrium contractility by minoxidil and reversal by glibenclamide. 米诺地尔对离体人肌层收缩力的抑制和格列苯脲的逆转。

Methods and findings in experimental and clinical pharmacology Pub Date : 2010-03-01 DOI: 10.1358/mf.2010.32.2.1434163

S S Prabhakaran, K R Dhanasekar, E Thomas, R Jose, J Peedicayil, P Samuel

{"title":"Inhibition of isolated human myometrium contractility by minoxidil and reversal by glibenclamide.","authors":"S S Prabhakaran, K R Dhanasekar, E Thomas, R Jose, J Peedicayil, P Samuel","doi":"10.1358/mf.2010.32.2.1434163","DOIUrl":"https://doi.org/10.1358/mf.2010.32.2.1434163","url":null,"abstract":"This study investigated the ability of the antihypertensive drug minoxidil to inhibit potassium chloride (KCl)-induced contractility of the isolated human myometrium. Twelve strips of myometrium obtained from 12 patients who underwent hysterectomy were triggered to contract with 55 mM KCl before and after incubation with 3 concentrations (1, 3 and 10 microM) of minoxidil. The percent inhibition by minoxidil on the extent of contraction, and the area under the contractile curve of KCl-induced contraction of the myometrial strips was determined. Furthermore, the effect of 10 microM glibenclamide on the inhibition generated by 3 microM minoxidil on KCl-induced contractility was studied. It was found that minoxidil produced a concentration-dependent inhibition of KCl-induced contractility of the myometrium and that glibenclamide reversed this inhibitory effect. These results suggest that the inhibitory effect of minoxidil on isolated human myometrium contractility may prove useful in clinical conditions requiring relaxation of the myometrium.","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28931829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Assessing anxiolytic-like effects of selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors using the elevated plus maze in mice. 在小鼠中使用升高正迷宫评估选择性5 -羟色胺再摄取抑制剂和5 -羟色胺-去甲肾上腺素再摄取抑制剂的焦虑样作用。

Methods and findings in experimental and clinical pharmacology Pub Date : 2010-03-01 DOI: 10.1358/mf.2010.32.2.1428741

T Takeuchi, T Owa, T Nishino, C Kamei

{"title":"Assessing anxiolytic-like effects of selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors using the elevated plus maze in mice.","authors":"T Takeuchi, T Owa, T Nishino, C Kamei","doi":"10.1358/mf.2010.32.2.1428741","DOIUrl":"https://doi.org/10.1358/mf.2010.32.2.1428741","url":null,"abstract":"The anxiolytic-like effects of selective serotonin reuptake inhibitors (SSRIs; paroxetine, fluvoxamine) and serotonin-noradrenaline reuptake inhibitors (SNRIs; milnacipran, venlafaxine) were compared with those of benzodiazepines (diazepam, chlordiazepoxide) and tricyclic antidepressants (imipramine, amitriptyline) using the elevated plus maze in mice. Paroxetine and fluvoxamine had no significant effects on the time spent in open arms and the number of open arm entries, even at a dose of 20 mg/kg p.o. On the other hand, milnacipran and venlafaxine showed a dose-dependent increase in the time spent in open arms and the number of open-arm entries. Significant effects were observed at doses of 10 and 20 mg/kg p.o. for both drugs. Diazepam and chlordiazepoxide showed potent anxiolytic-like effects, whereas imipramine and amitriptyline caused no anxiolytic-like effects. Like diazepam and chlordiazepoxide, milnacipran and venlafaxine increased the distance moved in open arms at the same dose levels showing anxiolytic-like effects. From these results, it may be concluded that SNRIs caused anxiolyic-like effects similar to benzodiazepines.","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28931832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Gateways to clinical trials. 通往临床试验的大门。

Methods and findings in experimental and clinical pharmacology Pub Date : 2010-03-01

A Tomillero, M A Moral

引用次数: 0

In vitro and in vivo characterization of tapentadol metabolites. 他他多体内外代谢产物的表征。

Methods and findings in experimental and clinical pharmacology Pub Date : 2010-01-01 DOI: 10.1358/mf.2010.32.1.1434165

R Terlinden, B Y Kogel, W Englberger, T M Tzschentke

{"title":"In vitro and in vivo characterization of tapentadol metabolites.","authors":"R Terlinden, B Y Kogel, W Englberger, T M Tzschentke","doi":"10.1358/mf.2010.32.1.1434165","DOIUrl":"https://doi.org/10.1358/mf.2010.32.1.1434165","url":null,"abstract":"Tapentadol is a novel, centrally acting analgesic combining micro-opioid receptor (MOR) agonism and noradrenaline (NA) reuptake inhibition in a single molecule. Many classic opioids form active metabolites that contribute to analgesia and/or side effects, and the involved cytochrome P450 enzyme complex can give rise to pharmacokinetic drug-drug interactions and variability in drug efficacy due to enzyme polymorphisms. Here we report on the relevance of tapentadol metabolites. Nine metabolites, including the major metabolite tapentadol-O-glucuronide, had no analgesic effects in the tail-flick test in mice. In the phenylquinone writhing test in mice, only 5 of these metabolites showed analgesic effects. The absence or presence of analgesia correlated with moderate activity (0.5 microM < K(i) < 1.1 microM) at the NA transporter or MOR. However, the systemic exposure for these metabolites found in humans after therapeutic oral doses of tapentadol was far below their respective K(i) values at these binding sites (by a factor of > 45). Thus, it is highly unlikely that tapentadol forms metabolites that contribute in any relevant degree to its analgesic activity.","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28914726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 72