Journal of pharmacological methods最新文献

{"title":"A new method for measuring auricular inflammation in the mouse","authors":"Armando Colorado,&nbsp;James T. Slama,&nbsp;William B. Stavinoha","doi":"10.1016/0160-5402(91)90056-B","DOIUrl":"10.1016/0160-5402(91)90056-B","url":null,"abstract":"<div><p>The croton oil ear test is widely used to identify prospective topical antiinflammatory drugs. Ear inflammation is produced by applying a 2% solution of croton oil on the ears of mice or rats. The effectiveness of the drug that is dissolved in the croton oil solution can be gauged by comparing the croton oil treated ears with the croton oil plus drug treated ears. The effect is measured following sacrifice of the animal by weighing either the excised ear (Tonelli et al., 1965; Glenn et al.,1978; Swingle et al., 1981; Soliman et al., 1983; Mantione and Rodriguez, 1990) or a plug taken from the ear (Tubaro et al., 1985; Davis et al., 1989a; Davis et at., 1989b). Use of this technique for the generation of a time-course evaluation of antiinflammatory activity requires a large amount of the chemical to be tested and the sacrifice of many animals. In other assays, ear thickness has been measured by caliper (Carlson et al., 1985; Maloff et al., 1989) or by dial micrometer (Griswold et al., 1987), which allow multiple measurements to be made, but the pressure on the ear was not reported. In a recent review of pharmacological methods, Chang and Lewis (1989) caution that using calipers to measure ear thickness is subject to operator error and bias. Furthermore, they emphasize care must be taken to not leave the calipers in contact with the ear too long, as it is possible to squeeze substantial amounts of edema fluid out of the ear tissue. To address these limitations, this report describes a device for evaluating inflammation by measuring the thickness of the ear while using only precisely reproducible light pressure that does not vary with the operator of the instrument. The device allows a time sequence of measurements on the same animal, thus substantially reducing the amount of material and number of animals required for evaluation.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 1","pages":"Pages 73-77"},"PeriodicalIF":0.0,"publicationDate":"1991-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90056-B","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13080010","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}

{"title":"Measurement of tachykinin-induced salivation in conscious rats","authors":"L.E. Wagner,&nbsp;B.E. Tomczuk,&nbsp;J.M. Yanni","doi":"10.1016/0160-5402(91)90055-A","DOIUrl":"10.1016/0160-5402(91)90055-A","url":null,"abstract":"<div><p>A method of quantitatively measuring tachykinin-induced salivation in conscious, male, Sprague-Dawley rats is described. Salivation is quantified by determining the weight of a preweighed, absorbant foam cube after it has been used to swab the oral cavity of a tachykinin challenged rat. Salivation is induced by intravenous (i.v.) injection of sialogogues (<em>μ</em>g/kg) via the lateral tail vein. Measurements are made immediately after injection. Substance P (Sub.P), Sar⁹, Met (O₂)¹¹Substance P (Sar⁹ Sub.P), a selective neurokinin (NK) 1 receptor agonist, Physalaemin and Eledoisin are equipotent sialogogues as determined by this method. Neurokinin A (NKA), the endogenous NK2 receptor agonist, is 0.27 (0.14–0.46) times as potent as Sub.P, while (Suc-[Asp⁶,MePhe⁸]Substance P(6–11), (senktide), a selective NK3 receptor agonist, only induced salivation at 300 <em>μ</em>g/kg. Acetylcholine (Ach) is only 0.006 (0.002–0.012) times as potent as Sub.P. Treatment with the neurokinin antagonist [D-Arg¹, D-Trp^7,9Leu¹¹]-Substance P (spantide) dose-dependently inhibits Sub.P stimulated salivation. Atropine dose-dependently inhibits Ach induced salivation but is inactive against Sub.P-induced salivation. These data are consistent with literature values and indicate that this method provides a simple, quantitative model, free of any possible anesthetic side effects, for the measurement of neurokinin stimulated salivation and the assessment of potential neurokinin antagonists in vivo.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 1","pages":"Pages 67-72"},"PeriodicalIF":0.0,"publicationDate":"1991-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90055-A","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12881433","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}

{"title":"A quantitative method for measuring labeled compounds with whole-body autoradiography in tissue sections","authors":"Eeva-Liisa Sainio ,&nbsp;Pertti Sainio","doi":"10.1016/0160-5402(91)90053-8","DOIUrl":"10.1016/0160-5402(91)90053-8","url":null,"abstract":"<div><p>Whole-body autoradiography is an effective method for localizing labeled compounds in various organs. However, the technique is limited in its ability to quantify such material.</p><p>Using tissue sections, this study investigated certain parameters involved in the quantitative estimation of labeled compounds by whole-body autoradiography. These included correlation between thickness of the section and radioactivity counted, the precision of such measurements, and the reproducibility of the autoradiographic films as tested by image analysis transmission. The precision of radioactivity measurements using tapes with a tissue section or a “punch biopsy” (punching off a piece of tissue from the section) was compared.</p><p>The results revealed excellent linearity between the thickness of the section and the radioactivity counted (<em>r</em> = 0.97) when section thickness was 10–30 μm. The measurement precision using tapes was better than with the “punch specimen” method. The reproducibility of photographic films was good when transmission was measured by image analysis.</p><p>It was concluded that a thickness of 30 μm is ideal for use in whole-body autoradiographic studies. It appeared that radioactivity measurement of tissue sections on tapes was superior to direct measurement from organs. Image analysis was employed and statistically evaluated for the first time in this study, and the promising findings suggest that it is likely to become the method of choice for future studies of this type.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 1","pages":"Pages 53-59"},"PeriodicalIF":0.0,"publicationDate":"1991-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90053-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13080007","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}

{"title":"Assessment with potential mapping of the cardiac protective effect of a drug. Example of trimetazidine","authors":"P. d'Alché ,&nbsp;P. Clauser ,&nbsp;M. Morel ,&nbsp;V. Gauthier","doi":"10.1016/0160-5402(91)90052-7","DOIUrl":"10.1016/0160-5402(91)90052-7","url":null,"abstract":"<div><p>SATAPEC is a computerized system built in the Laboratory for recording over 256 multiplexed channels and for automatic processing of cardiac electrical potentials. The results are printed out in the form of maps (either in black and white or in color) showing potential distributions, depolarization, repolarization, duration of activation, or various other analog-digital data.</p><p>The cardioprotective ability of a drug may be assessed with SATAPEC. As an example, the effect of trimetazidine (TMZ) is examined using 2 groups of 12 rabbits (one group serving as a control and the second group pretreated with TMZ). An elastomer mesh with 240 regularly spaced chlorided silver wire electrodes is placed around the ventricles following thoracotomy. A ligature is made starting from the anterior interventricular artery (AIV). Recordings are taken from the 240 unipolar epicardial electrograms (reference potential taken at Wilson terminal) 1 min before ligation and then every min for 8 min following ligation. Once the electrograms are plotted and any aberrant tracings eliminated, ST variation is calculated automatically. Files containing ST variations at different instants are stored in the computer memory and the mean ΣST/240 curves of the two groups of rabbits are plotted versus time. Mean electric potential maps, obtained by aligning all of the individual maps, are then printed. With these maps the location and extent of the epicardial injured area can be visualized. Pretreatment with TMZ (2.5 mg/kg) has shown a beneficial effect on ischemia injury.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 1","pages":"Pages 43-51"},"PeriodicalIF":0.0,"publicationDate":"1991-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90052-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13080006","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}

{"title":"Comparison of a fluorimetric and a colorimetric method for the determination of hydrogen peroxide production by rat pleural macrophages","authors":"Claudia Von Rein,&nbsp;Rolf Hirschelmann","doi":"10.1016/0160-5402(91)90054-9","DOIUrl":"10.1016/0160-5402(91)90054-9","url":null,"abstract":"<div><p>A fluorimetric and a colorimetric method for the determination of hydrogen peroxide (H₂O₂) production by isolated cells were compared. Despite a higher sensitivity of the fluorimetric assay, using homovanillic acid (HVA) as reagent, a significantly lower H₂O₂ production by rat pleural macrophages was measured in comparison to the colorimetric phenol red method. A negative influence of HVA on H₂O₂ production was detected in the colorimetric assay. These results suggest that the fluorimetric assay with HVA is unsuitable for determining H₂O₂ formation by isolated cells.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 1","pages":"Pages 61-65"},"PeriodicalIF":0.0,"publicationDate":"1991-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90054-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13080008","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}

{"title":"A rapid screening method for the assessment of benzodiazepine receptor-related physical dependence in mice","authors":"P.F. VonVoigtlander,&nbsp;R.A. Lewis","doi":"10.1016/0160-5402(91)90049-B","DOIUrl":"10.1016/0160-5402(91)90049-B","url":null,"abstract":"<div><p>We have developed a model of benzodiazepine-type physical dependence in which mice were injected subcutaneously with the test compound on a fixed schedule (0800 and 1600 for 3 days, the <span>pm</span> dose = <span>am</span> dose × 2). If tolerated, then a starting dose of 150 mg/kg/day was generally used initially and the dose was lowered to 15 and 1.5 mg/kg/day in subsequent assays if the higher doses were active in the test. Twenty-four hours after the last dose, the mice received an intravenous injection of flumazenil (2.5 mg/kg), and 5 min later they were tested for electroshock seizure thresholds by an up-down titration method. Flumazenil-precipitated withdrawal was manifested by a lowering of the mA seizure threshold. We have found that compounds with benzodiazepine agonist properties significantly lower these thresholds in a dose-related fashion. For example, the following compounds (lowest effective mg/kg/day dose) were active in this regard, chlordiazepoxide (150), diazepam (15), flurazepam (15), alprazolam (15), triazolam (15), midazolam (15), zopiclone (150), Ro 16-6028 (150), and Ro 17-1812 (150). In contrast, zolpidem (150), tracazolate (15), and CL 218872 (15) did not cause physical dependence by this criterion. This rapid and simple screening test may be readily used to predict the physical-dependence-inducing properties of compounds that act at the benzodiazepine receptor.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 1","pages":"Pages 1-5"},"PeriodicalIF":0.0,"publicationDate":"1991-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90049-B","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12846089","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}

{"title":"Assessment of antinociceptive drug effects in the presence of impaired motor performance","authors":"John L. Plummer,&nbsp;Patricia L. Cmielewski,&nbsp;Geoffrey K. Gourlay,&nbsp;Harry Owen,&nbsp;Michael J. Cousins","doi":"10.1016/0160-5402(91)90057-C","DOIUrl":"10.1016/0160-5402(91)90057-C","url":null,"abstract":"<div><p>The hot-plate (HP) and tail-flick (TF) tests are widely used to assess analgesic activity of drugs. These tests do not directly measure the intensity of the noxious stimulus perceived by the animal, but only the animal's response to it, and so may be affected by non-analgesic drugs. Sedatives and muscle relaxants, for example, may impair the ability to respond and hence be wrongly considered to have analgesic activity. We examined response of rats in the HP (55°C, cutoff time 25 sec) and TF (cutoff time 5 sec) tests following administration of pentobarbitone, diazepam or pancuronium. These drugs all impaired motor performance as assessed by reduction in mean rotarod performance times to 6–32% of predrug values. However, HP and TF latencies were not appreciably prolonged. We also found that pancuronium did not alter effects of morphine on HP or TF latencies, despite reduction in rotarod performance to 38% of predrug values. Our results support the validity of HP and TF tests as analgesic assays even in the presence of substantial impairment of motor performance.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 1","pages":"Pages 79-87"},"PeriodicalIF":0.0,"publicationDate":"1991-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90057-C","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13080011","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}

{"title":"A new model of myocardial infarction in yucatan minipigs","authors":"Steven A. Hamburger,&nbsp;Linda J. Kopaciewicz,&nbsp;Richard E. Valocik","doi":"10.1016/0160-5402(91)90029-5","DOIUrl":"10.1016/0160-5402(91)90029-5","url":null,"abstract":"<div><p>Myocardial infarction studies in pigs have been complicated by the use of antiarrhythmic drugs or the high incidence of ventricular fibrillation. We report on a new model of experimental myocardial infarction in thiamylal-anesthetized Yucatan minipigs. These studies were performed in the absence of intravenous antiarrhythmic drugs. No animals required resuscitation during either surgery or reperfusion and only 19% were resuscitated during occlusion. Extensive systemic hemodynamic, regional contractility and coronary blood flow measurements were continuously obtained during left anterior descending coronary artery (LAD) occlusion (45 min) and reperfusion (240 min). Mean arterial blood pressure and left ventricular + dP/dt decreased during occlusion, and both declined further upon reperfusion. Persistent dysfunction (segmental shortening from 24.8 ± 1.3 to 3.9 ± 0.9% (<em>p</em> &lt; 0.001); pre-occlusion and 5 min post-occlusion, respectively) occurred immediately after occlusion in the myocardium perfused by the LAD, while late declines in segmental shortening (19.6 ± 0.9 to 17.2 ± 1.2%; pre-occlusion and 240 min post-reperfusion, respectively) were observed in myocardium perfused by the left circumflex coronary artery. While heart rate did not change during occlusion, tachycardia occurred at the onset of reperfusion. Although initial reactive hyperemia following reperfusion was manually inhibited, high LAD blood flow following reperfusion occured early (0 to 60 min) but returned below pre-occlusion values late (180 to 240 min). The area at risk represented23.1 ± 0.9% (<em>n</em> = 34) of the left ventricle and 39.0 ± 3.2% of this area was infarcted. Therefore, 9.2 ± 0.9% of the left ventricle was infarcted. These data suggest that myocardical infarction in anesthetized minipigs can be achieved without the aid of intravenous antiarrhythmic drugs and reduced cardioversion. Therefore, this new model can be utilized in the evaluation of therapeutic compounds focused on altering the detrimental consequences of myocardical infarction.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"25 4","pages":"Pages 291-301"},"PeriodicalIF":0.0,"publicationDate":"1991-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90029-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13046601","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}

{"title":"Placental transfer of theophylline during in situ perfusion in the rabbit","authors":"Daniela Omarini ,&nbsp;Maria Monica Barzaco ,&nbsp;Angela Bortolotti ,&nbsp;José Aramayona ,&nbsp;Maurizio Bonati","doi":"10.1016/0160-5402(91)90026-2","DOIUrl":"10.1016/0160-5402(91)90026-2","url":null,"abstract":"<div><p>Many physiological changes take place during pregnancy, and the disposition profile of endogenous and exogenous compounds may change, too. Thus knowledge of the disposition pattern of a compound may be useful in relation to its therapeutic effect(s) and its potential toxicity on the fetus and the newborn. Because the amount of a compound received by the fetus is a product of placental transfer rate, and available maternal amount, and because it is difficult to control and evaluate the factors that may affect such a transfer in women, we set up an <em>in situ</em> perfused placental model in the rabbit. The reliability of the model was borne out by comparing the placental transfer of theophylline with antipyrine, a commonly used marker of placental exchange, at steady state after a two-step infusion at mean arterial plasma concentrations of 8 and 5 <span><math><mtext>mg</mtext><mtext>L</mtext></math></span>, respectively for theophylline and antipyrine. The rabbit placenta was perfused <em>in situ</em> with a modified Earle's buffer at a 1-<span><math><mtext>mL</mtext><mtext>min</mtext></math></span> flow rate. During perfusion, maternal plasma, placental perfusate, biochemical parameters, gas exchange, body temperature, and electrocardiogram were carefully monitored. The maternal plasma and perfusate drug concentrations over time were fitted by appropriate models and kinetic parameters were calculated. Umbilical vein/maternal artery concentration ratios reached equilibrium soon after the loading infusion was stopped for both drugs. Placental clearance averaged 0.62 and 0.77 <span><math><mtext>mL</mtext><mtext>min</mtext></math></span> for theophylline and antipyrine, respectively, and the clearance index of theophylline was 0.81 ± 0.07. Although human and rabbit placentas are structurally dissimilar, the rabbit placenta perfused <em>in situ</em> appears to be a useful preparation for measuring the transfer processes and the related and governing factors, of different compounds.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"25 4","pages":"Pages 263-273"},"PeriodicalIF":0.0,"publicationDate":"1991-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90026-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13046599","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}

{"title":"Maintenance of cns tissues in vitro for subsequent pharmacologie evaluation: A simple and inexpensive superfusion chamber","authors":"Erick W. Black,&nbsp;Joan M. Lakoski","doi":"10.1016/0160-5402(91)90028-4","DOIUrl":"10.1016/0160-5402(91)90028-4","url":null,"abstract":"<div><p>A new simple, inexpensive holding chamber is described for maintaining brain slices in a viable condition for long periods of time. The advantages of its superfusion-type operation and application of this chamber to in vitro electrophysiologic studies of the pharmacologie action of serotonin in the midbrain dorsal raphe nucleus are discussed.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"25 4","pages":"Pages 285-289"},"PeriodicalIF":0.0,"publicationDate":"1991-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90028-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13046600","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}