{"title":"Transitory models of experimentally induced intraocular pressure changes in the rabbit","authors":"C. Hariton, D. Marce, C. Debon","doi":"10.1016/0160-5402(90)90019-H","DOIUrl":"10.1016/0160-5402(90)90019-H","url":null,"abstract":"<div><p>The purpose of this study was to evaluate the relationship between inducer dosage, animal weight, and kinetics in intraocular pressure (IOP) changes in three transitory-induced models for antiglaucoma drugs screening: oral water-loading, 5% glucose intravenous administration, and 20% NaCl infusion. For these models, a dose-dependent elevation of IOP was observed in three weight groups of rabbits (1, 2.2, and 3.8 kg). Dose-effect relationships were established, considering for each weight group two relevant parameters: maximal IOP changes and areas under or upper the kinetic curves of IOP changes. Among the three models studied, our results led us to consider water-loading as a weight-independent model, allowing us to compare results obtained by this model in New Zealand rabbits with different ages (40–150 days) or weights (0.9–3.8 kg).</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 2","pages":"Pages 79-88"},"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)90019-H","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13384373","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":"Methamphetamine- and apomorphine-induced changes in spontaneous motor activity using a new system to detect and analyze motor activity in mice","authors":"Kinzo Matsumoto , Cai Bing , Kazuo Sasaki , Hiroshi Watanabe","doi":"10.1016/0160-5402(90)90022-D","DOIUrl":"10.1016/0160-5402(90)90022-D","url":null,"abstract":"<div><p>A new system was devised to detect animal spontaneous motor activity in more detail, and methamphetamine- and apomorphine-induced changes in spontaneous motor activity were analyzed using this system.</p><p>The system consists of a doughnut-shaped cage with 36 units of detectors. Scanning of each detector unit was three-dimensionally carried out, and then scanning data were fed into a personal computer. These steps were completed within 0.1 sec and repeated. Spontaneous motor activity was analyzed as changes in parameters, such as total activity, locomotor activity, vertical activity (the number of rearings and the rearing time), motion time, and average speed.</p><p>Regarding dependence on the dosages of methamphetamine and apomorphine, the time courses of changes in total activity and locomotor activity markedly differed from those for changes in vertical activity. Changes in the numbers of rearings and rearing time induced by 2 <span><math><mtext>mg</mtext><mtext>kg</mtext></math></span> methamphetamine peaked 40–80 min after administration, whereas those in other parameters did so 15–25 min after. Three <span><math><mtext>mg</mtext><mtext>kg</mtext></math></span> apomorphine-induced changes in total activity and locomotor activity showed two peaks 10–15 and 40–50 min after administration, respectively. At the same dosage, apomorphine markedly increased rearing time with slight but not significant effects on the number of rearings. These effects peaked 20–30 min after administration.</p><p>These results indicate this system to be quite useful to detect and analyze drug-induced changes in spontaneous motor activity.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 2","pages":"Pages 111-119"},"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)90022-D","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13384371","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 the β2 adrenoceptor and Ca2+ channel-blocking activity of drugs with the rat portal vein","authors":"Sheila A. Doggrell","doi":"10.1016/0160-5402(90)90025-G","DOIUrl":"10.1016/0160-5402(90)90025-G","url":null,"abstract":"<div><p>The rat portal vein has spontaneous mechanical activity. The effects of β-adrenoceptor agonists and antagonists and verapamil alone and together on this mechanical activity have been determined. Isoprenaline, but not dobutamine, attenuated the contractile activity. Three successive challenges to isoprenaline produced identical attenuation curves. The responses to isoprenaline were antagonized by propranolol, metoprolol, and ICI 118,551, and the pA<sub>2</sub> values, derived by Schild analysis, were 9.12, 6.78, and 9.33, respectively. Thus, the rat portal vein contains predominantly β<sub>2</sub>-adrenoceptors. Verapamil attenuated the contractile activity of the rat portal vein, and this attenuation was not altered by the presence of propranolol at 10<sup>−5</sup> M. The potencies of isoprenaline and propranolol were not altered by the presence of a 30% attentuation of the contractile activity with verapamil at 10<sup>−7</sup> M. Thus, the rat portal vein may be used to determine the potencies of drugs as β<sub>2</sub>-adrenoceptor antagonists and as voltage dependent calcium channel blockers. In addition, the potency of drugs as β<sub>2</sub>-adrenoceptor antagonists on the rat portal vein may be determined in the presence of some voltage dependent calcium channel blockade.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 2","pages":"Pages 145-156"},"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)90025-G","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13326394","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}
Arturo Lopez-Anaya, Jashvant D. Unadkat, Louise A. Schumann
{"title":"Simple and effective procedure for complete urine collection from infant macaques (Macaca nemestrina)","authors":"Arturo Lopez-Anaya, Jashvant D. Unadkat, Louise A. Schumann","doi":"10.1016/0160-5402(90)90021-C","DOIUrl":"10.1016/0160-5402(90)90021-C","url":null,"abstract":"<div><p>A diaper method, used in pediatric medicine, has been adapted and validated for total urine collection from infant macaques (<em>Macaca nemestrina</em>). The device consists of cellulose sponges and polyethylene sheets. The method proposed is non-invasive, simple, and does not significantly hinder the movement of the infant. The method should be useful when one is conducting pharmacokinetic studies in which total urine collection is required.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 2","pages":"Pages 105-109"},"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)90021-C","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13384370","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}
Walter E. Colbert, Billie F. Wilson, Patricia D. Williams
{"title":"Effects of temperature on the experimental reliability of the isolated rat phrenic nerve/diaphragm preparation","authors":"Walter E. Colbert, Billie F. Wilson, Patricia D. Williams","doi":"10.1016/0160-5402(90)90049-Q","DOIUrl":"10.1016/0160-5402(90)90049-Q","url":null,"abstract":"","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 1","pages":"Pages 53-57"},"PeriodicalIF":0.0,"publicationDate":"1990-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(90)90049-Q","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13323706","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":"Radioisotopic model for investigating thromboembolism in the rabbit","authors":"G.R. May , C.M. Herd , K.D. Butler , C.P. Page","doi":"10.1016/0160-5402(90)90046-N","DOIUrl":"10.1016/0160-5402(90)90046-N","url":null,"abstract":"<div><p><sup>111</sup>Indium (<sup>111</sup>In)-oxine labeled platelets have been used in a variety of species to assess platelet behavior in vivo. We have shown that <sup>111</sup>in-oxine is a suitable label for rabbit platelets and, using a noninvasive technique for the automated, continuous, external imaging of these radiolabeled platelets, we have shown that intravenous adenosine disphosphate (ADP), collagen, platelet activating factor (PAF), and thrombin all elicit dose-related accumulation of platelet-(but not erythrocyte-)associated radioactivity in the thoracic region and a concomitant fall in both the cranial and hindlimb regions of the anesthetized rabbit. Intracarotid (i.c.) ADP, collagen, PAF, and thrombin also produce dose-related increases in platelet-associated radioactivity in the thoracic and decreases in the cranial and hindlimb regions. However, the initial fall in cranial counts induced by i.c. thrombin was followed by a marked increase that was sustained for up to 3 hr.</p><p>These results suggest this may be a useful model for investigating the mechanisms of platelet activation in the arterial and venous circulations in vivo and may provide a novel model for investigating thromboembolic events in the cerebral circulation.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 1","pages":"Pages 19-35"},"PeriodicalIF":0.0,"publicationDate":"1990-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(90)90046-N","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13275550","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":"Screening procedure for assessment of ototoxicity in the common marmoset","authors":"Ryta A. Kuzel, Jan M. Smith, Paul N. Trennery","doi":"10.1016/0160-5402(90)90045-M","DOIUrl":"10.1016/0160-5402(90)90045-M","url":null,"abstract":"<div><p>Detection of drug-induced Ototoxicity in safety evaluation studies of novel chemical entities is rarely attempted. Where such examinations are included, they usually rely on reflex testing. The Brainstem Auditory Evoked Response can be measured with the use of externally positioned electrodes, and it monitors electrophysiologic responses to sound from the cochlear nerve and associated structures of the 8th cranial nerve. These responses have been reproducibly measured in sedated marmosets and the method shown to be a sensitive detector of hearing loss caused by loop diuretics or aminoglycoside antibiotics. Additionally, where hearing damage is reversible, recovery can also be monitored. It is proposed that where a sensitive marker for Ototoxicity is considered necessary as part of a multifaceted study investigating in vivo drug safety, this procedure may prove advantageous over existing methods.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 1","pages":"Pages 9-18"},"PeriodicalIF":0.0,"publicationDate":"1990-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(90)90045-M","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13368872","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}
Joseph D. Fondacaro , David C. Kolpak, Daniel B. Burnham, Gerald P. McCafferty
{"title":"Cecectomized rat","authors":"Joseph D. Fondacaro , David C. Kolpak, Daniel B. Burnham, Gerald P. McCafferty","doi":"10.1016/0160-5402(90)90050-U","DOIUrl":"10.1016/0160-5402(90)90050-U","url":null,"abstract":"<div><p>Evaluation of antisecretory antidiarrheal agents in animal models is limited primarily to extrapolations of efficacy from enteropooling studies in vivo, isolated intestinal loops in situ, and Ussing flux chamber preparations in vitro. While these standard techniques are useful, they do not mimic secretory diarrhea. Our studies indicate that in rats, the cecum may serve a “reservoir” function in response to secretagogue administration. Thus, diarrhea is not observed consistently and reliably in this species to allow valid evaluation of potential antidiarrheal agents. Therefore, we have developed a reproducible model of secretory diarrhea utilizing conscious cecectomized rats by surgical resection of the cecum, without compromising ileocecal patency, and by the use of potent intestinal secretagogues. Animals quickly recover and maintain normal growth and other physiologic parameters for as long as 60 days. After 48 hr on standard chow, secretory diarrhea can be induced by oral administration of standard intestinal secretagogues (dimethyl prostaglandin E<sub>2</sub>, cholera toxin, or carbachol). Dimethyl prostaglandin E<sub>2</sub> (300 μg/kg, p.o.) induces diarrhea within 1 hr that continues for approximately 3.5 hr. Oral administration of known antidiarrheal agents chlorpromazine (10 mg/kg), clonidine (1 mg/kg), or morphine (10 mg/kg) all significantly reduce fecal output within 30–60 min following administration. These studies indicate that in the rat, the cecum may serve as a fluid reservoir during periods of small intestinal hypersecretion and that the cecectomized rat serves as a useful, accurate, and reliable tool for evaluating new compounds with proposed antidiarrheal activity</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 1","pages":"Pages 59-71"},"PeriodicalIF":0.0,"publicationDate":"1990-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(90)90050-U","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13368870","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}
Antonio Guglietta, Teresa Hervada, Ronald V. Nardi
{"title":"Computer-based quantitative morphometric analysis of the dynamic characteristics of indomethacin and ethanol-induced gastric lesions in the rat","authors":"Antonio Guglietta, Teresa Hervada, Ronald V. Nardi","doi":"10.1016/0160-5402(90)90051-L","DOIUrl":"10.1016/0160-5402(90)90051-L","url":null,"abstract":"<div><p>A computerized morphometric analysis was used to measure the gastric lesions in rats induced by oral administration of 2 mL of 100% EtOH or indomethacin 80 mg/kg. In both cases, the lesions were followed over a period of several days to determine their time course characteristics. Indomethacin lesions were present 1 hr after the administration of the drug and reached a peak after 6 hr. Ethanol lesions appeared as early as 1 min after administration and were fully expressed after 1 hr. Recovery of the gastric mucosa was observed after 2 and 6 days, respectively. The use of this computerized systems allows precise measurements of gastric lesions and facilitates the evaluation of the effect of drugs in the gastrointestinal tract.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 1","pages":"Pages 73-78"},"PeriodicalIF":0.0,"publicationDate":"1990-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(90)90051-L","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13368871","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}
Brian J. Day , Gary P. Carlson , Dennis B. DeNicola
{"title":"γ-Glutamyltranspeptidase in rat bronchoalveolar lavage fluid as a probe of 4-lpomeanol and α-naphthylthiourea-induced pneumotoxicity","authors":"Brian J. Day , Gary P. Carlson , Dennis B. DeNicola","doi":"10.1016/0160-5402(90)90044-L","DOIUrl":"10.1016/0160-5402(90)90044-L","url":null,"abstract":"<div><p>Bronchoalveolar lavage fluid analysis has gained popularity as a rapid in vivo screen to evaluate the toxicity of both systemic and inhaled pneumotoxicants and is used in addition to the more commonly evaluated pathologic changes. This study evaluated γ-glutamyltranspeptidase (GGT) in the bronchoalveolar lavage fluid (BALF) along with the more commonly measured enzyme, lactate dehydrogenase (LDH), as a useful indicator of acute lung injury from systematically administered pneumotoxicants. Adult male rats were injected ip with 2, 3, or 3.5 mg/kg body weight of α-naphthylthiourea (ANTU) or 5, 10, or 20 mg/kg of 4-ipomeanol, and measurements were made 8 or 24 hr postdose, respectively. ANTU, which selectively damages pulmonary endothelial cells, caused extensive pleural effusions with striking increases in BALF protein and white blood cell (WBC) content. 4-Ipomeanol, which selectively damages nonciliated bronchiolar Clara cells, caused dose dependent increases in both GGT and LDH activities in the BALF with GGT being increased at all doses tested. BALF protein content was also increased in the 4-ipomeanol-treated groups, but this change was not dose dependent. Analysis of GGT in BALF was a sensitive method to assess cytotoxicity associated with 4-ipomeanol-induced injury but was less useful in monitoring pulmonary endothelial cell damage induced by ANTU. Measurements of BALF protein and WBC content proved to be better in assessing injury by agents such as ANTU that primarily affect vascular permeability.</p></div>","PeriodicalId":16819,"journal":{"name":"Journal of pharmacological methods","volume":"24 1","pages":"Pages 1-8"},"PeriodicalIF":0.0,"publicationDate":"1990-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0160-5402(90)90044-L","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13135329","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}