Journal of pharmacological methods最新文献

{"title":"An isometric method to study respiratory smooth muscle responses in mice","authors":"J. Garssen ,&nbsp;H. Van Loveren ,&nbsp;H. Van Der Vliet ,&nbsp;F.P. Nijkamp","doi":"10.1016/0160-5402(90)90031-F","DOIUrl":"10.1016/0160-5402(90)90031-F","url":null,"abstract":"<div><p>An isometric method to measure the smooth muscle tone of murine tracheas in vitro was developed. Nine trachea rings from just beneath the larynx were prepared free of excess tissue with the help of a binocular microscope. These trachea parts were slipped onto supports in an organ bath containing Krebs' solution. Isometric tension was measured with a force displacement transducer connected to the upper-trachea support, and is expressed as changes in grams force.</p><p>The cholinergic agonist carbachol contracted isolated tracheas. Serotonin also induced contractions, but was less potent than carbachol. Histamine induced tracheal contractions only at very high concentrations.</p><p>Sympathomimetic β adrenergic agonists relaxed carbachol-precontracted tracheas with the following order of potency: isoprenaline (β₁ and β₂ adrenoceptor agonist) &gt; salbutamol (β₂ adrenoceptor agonist) &gt; prenalterol (β₁ adrenoceptor agonist). Adrenaline and noradrenaline relaxed carbachol-precontracted tracheas, with adrenaline being the more potent relaxant.</p><p>For the study of airway reactivity, this mouse trachea model has several advantages over immunopharmacologic models: The immune system of the mouse has been characterized extensively, and many reagents are available to study the immune system and, thus, possible interactions of this system with pharmacological mechanisms. Other animal models used in pharmacology are generally less well defined immunologically.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 3","pages":"Pages 209-217"},"PeriodicalIF":0.0,"publicationDate":"1990-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(90)90031-F","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13139516","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":"Intragastric inulin as a measure of mucosal damage caused by aspirin","authors":"Lorentz E. Wittmers Jr. ,&nbsp;Lee A. Anderson ,&nbsp;Mary M. Fall ,&nbsp;Agnes A. Auch","doi":"10.1016/0160-5402(90)90033-H","DOIUrl":"10.1016/0160-5402(90)90033-H","url":null,"abstract":"<div><p>In an attempt to find a method of gastric mucosal damage assessment that yields consistent results, the experiments presented here employed the measurement of the movement of inulin out of the gastric contents into the stomach wall and vascular compartment as an estimate of mucosal damage. Anesthetized male Sprague-Dawley rats were functionally nephrectomized and were administered a control or test solution containing ³H-inulin. The test solutions contained one of three doses of aspirin. Blood samples were taken at 15-min intervals over a 90-min exposure period. The stomach was removed from the animal and full-thickness tissue samples taken for measurement of ³H-inulin content. When the gastric mucosa was exposed to the test agents, there was a significantly greater accumulation of inulin in the body and antrum as well as in the plasma when compared to controls. We conclude that intragastric inulin can be employed to estimate gastric mucosal damage.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 3","pages":"Pages 229-239"},"PeriodicalIF":0.0,"publicationDate":"1990-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(90)90033-H","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13230595","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":"Biostatistical modeling of the effect of intravenous histamine-infusion on the rat gastric acid secretion","authors":"A.Tanju Özçelikay ,&nbsp;Orhan Altinkurt ,&nbsp;Yusuf Öztürk ,&nbsp;Nuray Yildizoǧlu-Ari ,&nbsp;V.Melih Altan","doi":"10.1016/0160-5402(90)90034-I","DOIUrl":"10.1016/0160-5402(90)90034-I","url":null,"abstract":"<div><p>In this study, a variety of linear and nonlinear biostatistical models of regression were tested to evaluate the histamine-induced gastric acid secretion using the lumen-perfusion model in the rat. Among the linear, parabolic, and polynomial models tested, 3rd- and 4th-order polynomial models of regression exerted best correlations between the time and histamine-induced gastric acid secretion. In order to avoid undulatory behaviors in the regression curves, we conducted the polynomial regression analysis up to 5th order.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 3","pages":"Pages 241-250"},"PeriodicalIF":0.0,"publicationDate":"1990-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(90)90034-I","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13230596","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":"Computer-assisted quantification and image processing of whole-body autoradiograms","authors":"Roland d'Argy ,&nbsp;Göran O. Sperber ,&nbsp;Bengt S. Larsson ,&nbsp;Sven Ullberg","doi":"10.1016/0160-5402(90)90027-I","DOIUrl":"10.1016/0160-5402(90)90027-I","url":null,"abstract":"<div><p>A computerized image-processing system especially adapted for analysis of whole-body autoradiograms has been developed. It consists of commercially available standard components, including a black-and-white video camera, a microcomputer, and graphics equipment. The lower performance of the hardware has been compensated for by more flexible software. When the system was calibrated, special attention was paid to local variations in the measuring system in different parts of the picture.</p><p>Utility programs for the manipulation of contrast, pseudocoloring, and image enhancement, etc., are available. Some programs have been especially designed to comply with specific problems and demands related to different autoradiographic applications. A program displaying the density histogram for an area of interest is particularly useful for the quantitation of whole-body autoradiograms. It allows the operator to select interactively a range of densities. Image elements (pixels) corresponding to the densities in this range are shown in red on the monitor, and their average true density is calculated. This procedure permits the marking and analysis of delicate structures on autoradiograms. Other programs allow a picture, stored in memory, to be rotated or translated, and two pictures to be superimposed for comparison. Various applications of using image analyses in whole-body autoradiography are presented and illustrated.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 3","pages":"Pages 165-181"},"PeriodicalIF":0.0,"publicationDate":"1990-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(90)90027-I","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13230790","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 simple method for the separation and quantitation of radiolabeled thyroid hormones in thyroxine clearance studies","authors":"Scott J. Grossman","doi":"10.1016/0160-5402(90)90028-J","DOIUrl":"10.1016/0160-5402(90)90028-J","url":null,"abstract":"<div><p>A method was developed to facilitate the separation and quantitation of radiolabeled thyroxine in plasma for thyroxine clearance studies. Following intravenous injection of radioactive thyroxine, the radiolabeled thyroid hormones were isolated from plasma protein and polar metabolites by solid phase extraction on a C₁₈ sorbent bed. The individual thyroid hormones were then separated by ionpair reversed phase chromatography and sequentially eluted through a UV detector and radiochromatographic detector. The radioactivity of individual radiolabeled thyroid hormones was corrected for recovery of carrier as determined from UV absorbance. The recoveries of thyroxine and 3,5,3'-triiodothyronine (T₃) were 96% and 101%, respectively.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 3","pages":"Pages 183-188"},"PeriodicalIF":0.0,"publicationDate":"1990-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(90)90028-J","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13230591","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 sampling of blood, bile, and urine in rats for pharmacokinetic studies","authors":"Zhi-Xin Xu,&nbsp;Srikumaran Melethil","doi":"10.1016/0160-5402(90)90030-O","DOIUrl":"10.1016/0160-5402(90)90030-O","url":null,"abstract":"<div><p>A method for simultaneous serial sampling of blood, bile, and urine from rats is described. Techniques for cannulation of jugular and femoral veins, bile duct, and bladder are described that make serial sampling of these three fluids possible. A saline infusion regimen was developed that prevents dehydration and maintains constant hematocrit values throughout the experiment. Accuracy of timed-samples can be easily controlled along with complete collection of voided urine. This method also allows for economy in terms of cost (number of animals used) and time in pharmacokinetic investigations involving the rat where extensive sampling of blood, bile, and urine are needed. In addition, interanimal variability, which can be quite high in such studies, is avoided by sampling all these three fluids in a single rat. While the kinetic parameters of blood aluminum obtained from this anesthetized animal model compare well with those in unanesthetized rats reported from this laboratory, this method is most useful for comparative studies.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 3","pages":"Pages 203-208"},"PeriodicalIF":0.0,"publicationDate":"1990-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(90)90030-O","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13230593","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":"Cannulation and continuous cross-sectional area measurement of small blood vessels","authors":"Ed Vanbavel,&nbsp;Trudi Mooij,&nbsp;Maurice J.M.M. Giezeman,&nbsp;Jos A.E. Spaan","doi":"10.1016/0160-5402(90)90032-G","DOIUrl":"10.1016/0160-5402(90)90032-G","url":null,"abstract":"<div><p>Techniques have been developed for the study of isolated small arteries. To pressurize and perfuse segments of these vessels, a cannula with a low resistance to flow was developed. This cannula consisted of two concentric micropipettes. The end of a vessel segment was sucked into the inner pipette and clamped by applying subatmospheric pressure on the outer pipette. Subsequently, the vessel was pressurized via the inner pipette. To enable perfusion, the segment was cannulated at both ends.</p><p>Mean cross-sectional area (CSA) of the cannulated segments was continuously measured using a fluorescence technique. The emission of light by fluorescein isothiocyanate (FITC) labeled dextran in the vessel lumen was measured using a photomultiplier tube (PMT). PMT current was linearly related to the vessel CSA.</p><p>Twenty-nine rat mesenteric vessels with inside diameters ranging from 110 to 350 μm (mean 226 μm) when maximally dilated at 80 mm Hg were cannulated. CSA was monitored during variations in perfusion pressure and addition of vasoactive agents.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 3","pages":"Pages 219-227"},"PeriodicalIF":0.0,"publicationDate":"1990-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(90)90032-G","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13230594","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":"Identification of cardiotonic sodium channel activators by potassium depolarization in isolated guinea-pig atria","authors":"Heiner Berthold,&nbsp;Günter Scholtysik,&nbsp;Andreas Schaad","doi":"10.1016/0160-5402(90)90023-E","DOIUrl":"10.1016/0160-5402(90)90023-E","url":null,"abstract":"<div><p>The inotropic actions of various drugs known to increase force of contraction in isolated mammalian cardiac muscle were investigated in electrically driven (1 Hz) guinea-pig left atria under both normal [K⁺]_o (4.7 mM) and high [K⁺]_o (22 mM). Under normal [K⁺]_o a concentration-dependent increase in force of contraction could be confirmed with the β-adrenoceptor agonist, isoprenaline, the cyclase activator, forskolin, the inhibitors of the cyclic AMP-phosphodiesterase (PDE), amrinone, IBMX, and OPC 8212, the Na⁺ channel activators, DPI 201−106, SDZ 210−921, veratridine, and ATX II, the Na⁺-ionophore monensin, the inhibitor of <span><math><mtext>Na</mtext><msup><mi></mi><mn>+</mn></msup><mtext>K</mtext><msup><mi></mi><mn>+</mn></msup></math></span>-ATPase, ouabain, and the Ca²⁺ channel activators, Bay K 8644, CGP 28 H 392, and SDZ 202−791. Partial depolarization of the muscle preparations by increasing [K⁺]_o in the organ bath to 22 mM completely abolished the positive inotropic action of the Na⁺ channel-activating drugs. In contrast, the effects of the other compounds were still present, although changes in the maximal force development were observed. The efficacy of the PDE inhibitors amrinone and IBMX were slightly increased; the maximal effects of isoprenaline, monensin, forskolin, and OPC 8212 were unchanged; the effect of ouabain decreased to about half maximal values; while the efficacy of the Ca²⁺ channel activators were either unchanged (CGP 28 392) or decreased (Bay K 8644 and SDZ 202−791). The results suggest that inactivation of cardiac fast Na⁺ channels by partially depolarizing isolated, electrically driven atria is a suitable model to distinguish between cardiotonic agents acting through activation of Na⁺ channels and those with other mechanisms of action.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 2","pages":"Pages 121-135"},"PeriodicalIF":0.0,"publicationDate":"1990-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(90)90023-E","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12864671","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":"Extraction of physostigmine from biologic fluids and analysis by liquid chromatography with electrochemical detection","authors":"Glen D. Lawrence,&nbsp;Noraini Yatim","doi":"10.1016/0160-5402(90)90024-F","DOIUrl":"10.1016/0160-5402(90)90024-F","url":null,"abstract":"<div><p>A rapid and simple method is described for the extraction of physostigmine (Phy) and its hydrolysis product, eseroline, from plasma, whole blood, and cerebrospinal fluid (CSF) and their subsequent quantitation by high-performance liquid chromatography (HPLC) with dual electrode electrochemical detection. Phy and eseroline were extracted from biologic fluids with cyano-phase columns eluted with 0.1 M citrate buffer, pH 4 containing 20% acetonitrile. Phy recovery from citrate buffer and CSF was nearly 100%. Phy recovery from plasma was 82% when methanol was used to precipitate proteins and 62% when HCIO₄ was used to precipitate proteins. Phy recovery from whole blood was only 17%. These results are discussed in the context of attempting to measure Phy in fluids of patients receiving this drug in clinical trials for the treatment of Alzheimer's disease.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 2","pages":"Pages 137-143"},"PeriodicalIF":0.0,"publicationDate":"1990-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(90)90024-F","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13384372","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":"Isolated perfused rat kidney as a tool in the investigation of renal handling and effects of nonsteroidal antiinflammatory drugs","authors":"Peter G.F. Cox ,&nbsp;Miek M. Moons ,&nbsp;Jan F.G. Slegers ,&nbsp;Frans G.M. Russel ,&nbsp;Cees A.M. Van Ginneken","doi":"10.1016/0160-5402(90)90020-L","DOIUrl":"10.1016/0160-5402(90)90020-L","url":null,"abstract":"<div><p>An isolated perfused rat kidney (IPK) preparation is described in which renal perfusion flow, perfusion pressure, urinary flow, urinary pH, and glomerular filtration rate (GFR) are recorded continuously during the perfusion experiment. The usefulness of this IPK system in studying the renal handling and the effects of non-steroidal antiinflammatory drugs (NSAIDs) is shown using salicyluric acid (SU), salicylic acid (SA), and naproxen (NA). Excretion of SU involves glomerular filtration, active secretion, and passive reabsorption. The excretion rates of SA and NA were both much lower than their filtration rate, indicating extensive reabsorption. All three drugs accumulate in the 1PK but at different levels. SU accumulates much more than either SA or NA. The effects on renal function were different for the three drugs studied. SU had no effect on kidney function. SA perfusate concentrations greater than 100 <span><math><mtext>μg</mtext><mtext>mL</mtext></math></span> caused diuresis and natriuresis, while SA concentrations less than 100 <span><math><mtext>μg</mtext><mtext>mL</mtext></math></span> did not influence kidney function. NA perfusate concentrations ranging from 0.16 to 25 <span><math><mtext>μg</mtext><mtext>mL</mtext></math></span> caused a decrease in urinary flow and sodium excretion. Very high NA concentrations (⪢500 <span><math><mtext>μg</mtext><mtext>mL</mtext></math></span>) caused an increase in urinary flow and sodium excretion. We conclude that the IPK is a suitable preparation for characterizing and comparing renal handling and effects of NSAIDs.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 2","pages":"Pages 89-103"},"PeriodicalIF":0.0,"publicationDate":"1990-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(90)90020-L","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13384374","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}