Journal of pharmacological methods最新文献

{"title":"Enhanced detection of hyperactivity after drug withdrawal with a simple modification of the open-field apparatus","authors":"Helena M.T. Barros,&nbsp;Marcos A.L. Tannhauser,&nbsp;Semiramis L. Tannhauser,&nbsp;Mario Tannhauser","doi":"10.1016/0160-5402(91)90037-6","DOIUrl":"10.1016/0160-5402(91)90037-6","url":null,"abstract":"<div><p>The open-field apparatus has been used to study withdrawal reactions from chronic treatments with central nervous system depressant drugs. To study the behavior of the same animal after drug withdrawal, the rats are introduced into the open field on consecutive days. Because the open field is a novel environment, the repetition could lead to false-negative results with regard to drug withdrawal. To overcome this problem, we sought a modification of the open field, using different floor-painting patterns every time the animal is observed. The most frequently observed withdrawal manifestation was hyperactivity. We verified that long-term treatment withdrawal reactions from barbital, clonazepam, and ethanol were seen more often if the rats were introduced in the modified open field. In addition, fewer animals were used here than in other trials and hyperactivity was detected more frequently in the modified open field than was sound-induced convulsions. We propose that the modified open field is more useful than the classic one for screening of drug withdrawal reactions.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 4","pages":"Pages 269-275"},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90037-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12921149","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 method for maintaining and protecting chronic arterial and venous catheters in conscious rats","authors":"Stan Z. Kurowski,&nbsp;Kenneth J. Slavik,&nbsp;Julianna E. Szilagyi","doi":"10.1016/0160-5402(91)90035-4","DOIUrl":"10.1016/0160-5402(91)90035-4","url":null,"abstract":"<div><p>The ability to monitor arterial blood pressure and heart rate directly, as well as to sample venous blood, or inject pharmaceutical agents intravenously is important in pharmacological studies of the cardiovascular system. The rat is a frequently used and accepted animal model for cardiovascular investigations, especially those relating to hypertension. Even though the rat is a major model for these studies, the size of the rat has made it difficult to maintain catheters for a long period of time. Although there have been previous methods available, the authors report on an improved method to implant, maintain, and protect arterial and venous catheters in conscious rats for extended periods of time. A Silastic/Tygon catheter is implanted intraarterially and intravenously, exteriorized, and protected with a spring device. Catheters remained patent throughout a 5-week period during which time direct blood pressure recordings were obtained and baroreflexes were evaluated in conscious, unrestrained rats. The described design and methods provide an inexpensive means to maintain chronically implanted venous and arterial catheters in the conscious rat. Furthermore, rats may be gang housed.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 4","pages":"Pages 249-256"},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90035-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12920609","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":"Validation of a human atrial trabecular preparation for evaluation of inotropic substances","authors":"Rosalind S. Labow ,&nbsp;Suzanne Desjardins ,&nbsp;Wilbert J. Keon","doi":"10.1016/0160-5402(91)90036-5","DOIUrl":"10.1016/0160-5402(91)90036-5","url":null,"abstract":"<div><p>Assessment of cardioactive substances is usually performed using animal tissue, with the effects being extrapolated to humans, thereby potentially introducing errors due to species differences. In order to validate the use of human atrial tissue, known positive and negative inotropic agents were tested on trabeculae obtained from patients' atrial appendages at the time of cardiac surgery requiring cardiopulmonary bypass. Trabeculae were selected according to strict criteria: cross-sectional area &lt; 1.0 mm², resting force (RF) &lt; 0.7 g, and developed force (DF) &gt;0.8 g. Each trabecula received only one drug in a cumulative dose manner. Where necessary, the vehicle used to dissolve or stabilize the drug solution was also tested. In addition, the relative DF of “no-drug,” “time-only” controls were measured during the same time period. After adjusting for the effect of time on the preparation, relative DF was increased to 157% by dobutamine (1.5 × 10⁻⁵ M), to 136% by amrinone (5.6 × 10⁻⁴ M), and to 117% by ouabain (2 × 110⁻⁷ M). The relative DF decreased with nifedipine and propranolol, with 50% inhibition for both drugs being 1.5 × 10⁻⁷ M. Although human ventricular muscles might be more appropriate to use in order to determine the effects observed with the whole heart, they are extremely difficult to obtain on a regular basis. The results of this study show that the atrial trabecular preparation offers an acceptable alternative.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 4","pages":"Pages 257-268"},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90036-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12921148","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":"Relative potencies of 5-lipoxygenase inhibitors on antigeninduced contractions of guinea pig tracheal strips","authors":"Hwei Ling Cho,&nbsp;Peter P.K. Ho,&nbsp;Edward D. Mihelich,&nbsp;David W. Snyder","doi":"10.1016/0160-5402(91)90038-7","DOIUrl":"10.1016/0160-5402(91)90038-7","url":null,"abstract":"<div><p>A quantitative method to assess relative potencies (IC₅₀) of 5-lipoxygenase (5-LO) enzyme inhibitors was established in antigen-induced contractions of tracheas isolated from actively sensitized guinea pigs (Schultz-Dale model). The relative potencies of four purported 5-LO inhibitors determined in this tissue assay were compared with those from a crude enzyme preparation isolated from guinea pig neutrophils. All compounds suppressed ovalbumin (OA)-induced tracheal contractions in a concentration-related manner in the presence of indomethacin and pyrilamine. IC₅₀ Values, determined from the percent inhibition values obtained from responses at 30 ng/mL OA of these compounds ranged from 0.56–15 μM. A similar rank order of potency for inhibition of 5-HETE formation from a crude enzyme preparation was observed. This suggested that these agents had a common mechanism of action in the two assay systems and further validated the IC₅₀ values determined in trachea assay. LY171883, an LTD₄/LTE₄ receptor antagonist, also suppressed OA-induced contractions concentration dependently with an IC₅₀ of 4.9 μM determined by this method. LTD₄ concentration-response curves were not altered by any of the four 5-LO inhibitors, ruling out the possibility that these agents were acting as LT receptor antagonists. Results of this study demonstrated that relative potencies of 5-LO inhibitors can be quantitatively assessed using this airway tissue model, which helps in identifying potential therapeutic agents for asthma.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 4","pages":"Pages 277-287"},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90038-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12827515","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":"Quantitation of urinary α2u-globulin and albumin by reverse-phase high performance liquid chromatography","authors":"Lois D. Lehman-McKeeman,&nbsp;Douglas Caudill","doi":"10.1016/0160-5402(91)90034-3","DOIUrl":"10.1016/0160-5402(91)90034-3","url":null,"abstract":"<div><p>A rapid, reproducible, and sensitive high-performance liquid chromatography (HPLC) method for the quantitation of α2u-globulin, the major urinary protein excreted by adult male rats, and albumin has been developed. Total urinary proteins, isolated by a simple Sephadex G-25 gel filtration step, are separated and quantitated by reverse-phase HPLC on a C₄ Macrosphere 300 column. The proteins are separated and eluted with a two-step gradient of acetonitrile in aqueous trifluoroacetic acid. Detection limits of 9 and 25 μg/mL of urine were established for albumin and α2u-globulin, respectively. Quantitation of urinary excretion of the two proteins in young adult male and female rats and aging male rats showed that values obtained with this method compared favorably with values from previously developed immunological techniques. To quantitate total urinary protein excretion, we modified the Bradford protein assay to use rat urinary protein as standard. Given the established importance of α2u-globulin in the development of male rat-specific nephrotoxicity and nephrocarcinogenicity, these methods should be useful for studying the renal handling of this protein under normal and nephrotoxic conditions.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 4","pages":"Pages 239-247"},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90034-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12885956","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 novel technique for the administration of bronchodilator drugs formulated as dry powders to the anaesthetized guinea pig","authors":"Stephen L. Underwood,&nbsp;Debbie Lingham,&nbsp;Julita Pearson,&nbsp;David Raeburn","doi":"10.1016/0160-5402(91)90044-6","DOIUrl":"10.1016/0160-5402(91)90044-6","url":null,"abstract":"<div><p>A technique is described for the administration of dry powder formulations of bronchodilator drugs to the anaesthetized guinea pig. The technique has been evaluated by comparing the efficacy of several bronchodilator drugs administered either as dry powders coformulated with a lactose carrier or as nebulized solutions. In each case, the dry powder formulation had comparable bronchodilator activity and duration of action to an equivalent dose administered as a nebulized solution. This technique offers a simple and inexpensive method for the rapid screening of bronchodilator drugs without the problems associated with aerosol administration.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 3","pages":"Pages 203-210"},"PeriodicalIF":0.0,"publicationDate":"1991-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90044-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12917366","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 novel method for the evaluation of bronchoactive agents in the conscious guinea pig","authors":"D.I. Ball ,&nbsp;R.A. Coleman ,&nbsp;R.W. Hartley ,&nbsp;A. Newberry","doi":"10.1016/0160-5402(91)90043-5","DOIUrl":"10.1016/0160-5402(91)90043-5","url":null,"abstract":"<div><p>We describe a simple, noninvasive, nontraumatic and reproducible method in which the activities of bronchoactive agents may be recorded in six conscious guinea pigs simultaneously. The method involves the use of “head out” whole body plethysmographs from which respiratory rate can be recorded, by monitoring respiration-related changes in pressure within the body chamber. Exposure of a guinea pig to an aerosolised bronchoconstrictor agent causes an increase in respiratory rate, which is quantified by measuring the area under the respiratory rate curve using a purpose-built respiratory computer. This can be carried out for six animals simultaneously and independently. When exposed to a standard bronchoconstrictor aerosol challenge at intervals over a 6 hr period, the areas under the respiratory rate curves for each animal are highly reproducible. Inhalation of nebulized solutions of acetylcholine (ACh), histamine (Hist), 5-hydroxytryptamine, bradykinin, leukotriene D₄ and the thromboxane A₂-mimetic, U-46619, but not prostaglandin F_2α (PGF_2α) caused dose-related bronchoconstriction observed as increases in respiratory rate. In addition, salbutamol, clenbuterol, N-ethylcarboxamide adenosine (NECA) and PGE₂ all inhibited ACh (1 mg mL⁻¹) and Hist (1 mg mL⁻¹)-induced increases in respiratory rate in a dose-related fashion. The method described, which is both noninvasive and nontraumatic, may therefore be used to quantify in the conscious guinea pig, both bronchoconstrictor and bronchodilator agents.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 3","pages":"Pages 187-202"},"PeriodicalIF":0.0,"publicationDate":"1991-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90043-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12917365","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 method for rapid and frequent blood collection from the rat tail vein","authors":"Patricia Frank ,&nbsp;Grant L. Schoenhard ,&nbsp;Earl Burton","doi":"10.1016/0160-5402(91)90047-9","DOIUrl":"10.1016/0160-5402(91)90047-9","url":null,"abstract":"<div><p>A technique is described for the collection of blood samples after dilation of rat tail veins using a controlled temperature device. Frequent blood samples of seven or eight per rat were collected during a 6-hr period. Further samples were taken from the same vein after recannulation during the next 5 days. This technique was also used to administer drugs intravenously through one vein and to collect blood samples from the contralateral vein. kw]Blood collection; Rat; Tail vein</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 3","pages":"Pages 233-238"},"PeriodicalIF":0.0,"publicationDate":"1991-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90047-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12916472","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":"Simultaneous recording of vesical and urethral pressure in urethane-anesthetized rats: Effect of neuromuscular blocking agents on the activity of the external urethral sphincter","authors":"B. Conte ,&nbsp;C.A. Maggi ,&nbsp;M. Parlani,&nbsp;G. Lopez ,&nbsp;S. Manzini,&nbsp;A. Giachetti","doi":"10.1016/0160-5402(91)90041-3","DOIUrl":"10.1016/0160-5402(91)90041-3","url":null,"abstract":"<div><p>In urethane-anesthetized rats we made a disconnection of the urinary bladder from the urethra and performed a simultaneous recording of the vesical and external urethral sphincter (EUS) pressures.</p><p>Throughout the collecting phase, the EUS pressure was higher than that recorded into the bladder. Gallamine (10 <span><math><mtext>mg</mtext><mtext>kg</mtext></math></span> i.v.) or d-tubocurarine (100 <span><math><mtext>μg</mtext><mtext>kg</mtext></math></span> i.v.), did not alter the value of intraurethral pressure.</p><p>When a reflex bladder contraction occurred in response to filling (expulsion phase) the intravesical pressure exceeded the urethral pressure and at the top of the vesical contraction a series of rapid intraluminal pressure high frequency oscillations (IPHFO) were recorded at the urethral recording site, which were abolished by neuromuscular blocking agents as well as after acute sectioning of pudendal nerves. IPHFO was still present in rats in which the periurethral muscles (pelvic floor), have been precedently dissected.</p><p>To get further information about the physiological consequence of the EUS functional impairment induced by neuromuscular blocking agents, we used the non-stop transvesical cystometrogram.</p><p>In these conditions, blockade of the EUS did not produce passive urine dripping during the filling phase, but absence of the rhythmic striated urethral activity during the vesical expulsion phase produced a significant increase of the residual volume from 35% (control) to 75%.</p><p>We present an original pharmacological method in a species whose small dimensions create technical problems for recording pressure signals from the lower urinary tract. Moreover, we have gained information on the origin of the IPHFOs and about the role of the EUS during the collecting and the expulsion phase of the voiding cycle in urethane anesthetized rats.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 3","pages":"Pages 161-171"},"PeriodicalIF":0.0,"publicationDate":"1991-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90041-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12917364","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":"Development of a near anesthetic-free isolated canine hindlimb model","authors":"John A. Reitan,&nbsp;Nguyen D. Kien,&nbsp;Richard W. Martucci,&nbsp;Steven J. Thorup,&nbsp;Paul J. Dennis","doi":"10.1016/0160-5402(91)90046-8","DOIUrl":"10.1016/0160-5402(91)90046-8","url":null,"abstract":"<div><p>A denervated, isolated canine hindlimb (HL) model was developed to minimize residual anesthetic contamination. To test the preparation, we determined the peripheral arterial vascular effects of atropine sulfate and the effect of the basal anesthetic on arterial resistance. In four dogs that were under halothane and oxygen anesthesia, the HL was prepared to allow either vascular isolation of the limb or continuity with the systemic circulation. During isolation the HL was perfused by roller pump at a preset flow rate through an infant oxygenator. Inspired gas fed to the oxygenator contained either 0%, 1.25%, or 2.5% halothane to determine that anesthetic's effect on HL arterial vascular resistance. No halothane (0%) was used in the oxygenator inflow during the atropine measurements. Vascular resistance was calculated from HL arterial pressure at constant flow. Halothane caused a significant stepwise fall in vascular resistance, with a decrease of 68% at 2.5% inspired concentration (<em>p</em> &lt; 0.01). Atropine produced a progressive attenuation of resistance that decreased by 18% after the 2.5 <span><math><mtext>mg</mtext><mtext>kg</mtext></math></span> dose (<em>p</em>&lt; 0.01). The model proved stable over time and demonstrated an apparent direct, dose-dependent vasodilating effect of both atropine and halothane in the canine HL muscle arterial bed.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"26 3","pages":"Pages 223-232"},"PeriodicalIF":0.0,"publicationDate":"1991-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(91)90046-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12917368","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}