Pub Date : 2010-10-01DOI: 10.1358/mf.2010.32.8.1507853
B J Wiskur, K Tyler, K Campbell-Dittmeyer, S R Chaplan, A D Wickenden, B Greenwood-Van Meerveld
This study examined the efficacy of a novel TRPV1 antagonist, JNJ-17203212, in two experimental rat models that exhibit a hypersensitive visceral motor response (VMR) to colorectal distension (CRD). In the first model, intraluminal administration of acetic acid (1% solution) into the distal colon produced an acute colonic hypersensitivity. In the second model, intraluminal administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) into the distal colon produced a chronic, post-inflammatory colonic hypersensitivity 30 days post-TNBS administration. Throughout this study, colonic sensitivity was assessed via quantification of VMR to CRD in rats following a single, oral administration of JNJ-17203212 (3, 10 or 30 mg/kg) or vehicle. Intraluminal administration of acetic acid and TNBS resulted in increased VMR to CRD when compared to controls. In both groups, VMR to CRD was significantly reduced by administration of JNJ-17203212 at 30 mg/kg. The results of this study show that the selective TRPV1 antagonist, JNJ-17203212, reduces sensitivity to luminal distension in both an acute, noninflammatory and a chronic, post-inflammatory rodent model of colonic hypersensitivity. These data indicate that TRPV1 is involved in the pathogenesis of visceral hypersensitivity and that JNJ-17203212 may be a potential therapeutic agent for functional bowel disorders characterized by abdominal hypersensitivity, such as irritable bowel syndrome.
{"title":"A novel TRPV1 receptor antagonist JNJ-17203212 attenuates colonic hypersensitivity in rats.","authors":"B J Wiskur, K Tyler, K Campbell-Dittmeyer, S R Chaplan, A D Wickenden, B Greenwood-Van Meerveld","doi":"10.1358/mf.2010.32.8.1507853","DOIUrl":"https://doi.org/10.1358/mf.2010.32.8.1507853","url":null,"abstract":"<p><p>This study examined the efficacy of a novel TRPV1 antagonist, JNJ-17203212, in two experimental rat models that exhibit a hypersensitive visceral motor response (VMR) to colorectal distension (CRD). In the first model, intraluminal administration of acetic acid (1% solution) into the distal colon produced an acute colonic hypersensitivity. In the second model, intraluminal administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) into the distal colon produced a chronic, post-inflammatory colonic hypersensitivity 30 days post-TNBS administration. Throughout this study, colonic sensitivity was assessed via quantification of VMR to CRD in rats following a single, oral administration of JNJ-17203212 (3, 10 or 30 mg/kg) or vehicle. Intraluminal administration of acetic acid and TNBS resulted in increased VMR to CRD when compared to controls. In both groups, VMR to CRD was significantly reduced by administration of JNJ-17203212 at 30 mg/kg. The results of this study show that the selective TRPV1 antagonist, JNJ-17203212, reduces sensitivity to luminal distension in both an acute, noninflammatory and a chronic, post-inflammatory rodent model of colonic hypersensitivity. These data indicate that TRPV1 is involved in the pathogenesis of visceral hypersensitivity and that JNJ-17203212 may be a potential therapeutic agent for functional bowel disorders characterized by abdominal hypersensitivity, such as irritable bowel syndrome.</p>","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29513427","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}
Pub Date : 2010-10-01DOI: 10.1358/mf.2010.32.8.1469897
W Sziegoleit, C Lautenschläger, C Walther, P Presek
The influences of both being in a supine position for a prolonged period and food intake on cardiovascular variables were studied under clinical-pharmacological test conditions. In a randomized crossover design study without drug or placebo administration, 6 healthy male volunteers received a light standard meal before and during test A and fasted in test B. In both tests, while they were continuously supine for more than 8 h, a synchronous recording of cardiovascular variables was done at 24, 26 and 28 min after starting the supine position (first recordings) and 25 times from 2 to 480 min after the first recordings. Using a multifactorial statistical analysis, each parameter was evaluated regarding the factors eating and time of supine recording. Eating led to a significant decrease in diastolic and mean blood pressure, PQ time and QS₂ time, a downward trend in systemic vascular resistance and an upward trend in systolic blood pressure and cardiac output. When the subjects remained in a supine position for prolonged periods, significant increases in systolic, diastolic, mean blood pressure and systemic vascular resistance were noted as well as significant decreases in cardiac output and QS₂ time. Thus, eating and remaining in a supine position for prolonged periods should be considered as sources of bias in clinical-pharmacological studies on cardiovascular drug effects and accompanying placebo controls.
{"title":"Hemodynamic effects of eating and prolonged supine position in healthy subjects studied under clinical-pharmacological test conditions.","authors":"W Sziegoleit, C Lautenschläger, C Walther, P Presek","doi":"10.1358/mf.2010.32.8.1469897","DOIUrl":"https://doi.org/10.1358/mf.2010.32.8.1469897","url":null,"abstract":"<p><p>The influences of both being in a supine position for a prolonged period and food intake on cardiovascular variables were studied under clinical-pharmacological test conditions. In a randomized crossover design study without drug or placebo administration, 6 healthy male volunteers received a light standard meal before and during test A and fasted in test B. In both tests, while they were continuously supine for more than 8 h, a synchronous recording of cardiovascular variables was done at 24, 26 and 28 min after starting the supine position (first recordings) and 25 times from 2 to 480 min after the first recordings. Using a multifactorial statistical analysis, each parameter was evaluated regarding the factors eating and time of supine recording. Eating led to a significant decrease in diastolic and mean blood pressure, PQ time and QS₂ time, a downward trend in systemic vascular resistance and an upward trend in systolic blood pressure and cardiac output. When the subjects remained in a supine position for prolonged periods, significant increases in systolic, diastolic, mean blood pressure and systemic vascular resistance were noted as well as significant decreases in cardiac output and QS₂ time. Thus, eating and remaining in a supine position for prolonged periods should be considered as sources of bias in clinical-pharmacological studies on cardiovascular drug effects and accompanying placebo controls.</p>","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29513430","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}
Pub Date : 2010-10-01DOI: 10.1358/mf.2010.32.8.1561056
A Tomillero, M A Moral
{"title":"Gateways to clinical trials.","authors":"A Tomillero, M A Moral","doi":"10.1358/mf.2010.32.8.1561056","DOIUrl":"https://doi.org/10.1358/mf.2010.32.8.1561056","url":null,"abstract":"","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29513431","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}
Pub Date : 2010-10-01DOI: 10.1358/mf.2010.32.8.1464032
A Yenisehirli, O A Elalmis
We have shown that in isolated human atrial strips the β1-adrenoceptor agonist dobutamine can induce spontaneous, stable and durable rhythmic contractions. The amplitude and frequency of these contractions were regulated endogenously by the tissue. We tested whether the spontaneously contracted atrial strips could be used as an experimental assay model to determine inotropic and chronotropic effects of existing drugs and candidate chemicals directly on human heart muscle. The well-established inotropic and chronotropic effects of the calcium channel blocker (verapamil), the β-adrenoceptor blocker (propranolol), the phosphodiesterase inhibitor (theophylline) and the Na(+)/K(+)-ATPase inhibitor (ouabain) were tested on spontaneously contracting strips of human atrium. With demonstrative tracings, we showed the negative inotropic and chronotropic effects of verapamil and propranolol, the positive inotropic and chronotropic effects of theophylline and the transient inotropic and tachyarrhythmic effects of ouabain on dobutamine-pretreated human atrial strips. By using this method the undetermined inotropic and chronotropic effects of any candidate compound can be evaluated directly on spontaneously contracting human atrial muscle. Furthermore, we demonstrated the advantages of using dobutamine instead of conventional electrical field stimulation in order to obtain stable and durable contractions of the atrial strips. In conclusion, we describe a new, simple, reliable, convenient and ethical method for investigating the inotropic and chronotropic effects of candidate drugs directly on human atrium tissue without the need for human test subjects.
{"title":"Dobutamine-induced spontaneous rhythmic contractions of human isolated atrial strips mimic physiological responses of intact human heart.","authors":"A Yenisehirli, O A Elalmis","doi":"10.1358/mf.2010.32.8.1464032","DOIUrl":"https://doi.org/10.1358/mf.2010.32.8.1464032","url":null,"abstract":"<p><p>We have shown that in isolated human atrial strips the β1-adrenoceptor agonist dobutamine can induce spontaneous, stable and durable rhythmic contractions. The amplitude and frequency of these contractions were regulated endogenously by the tissue. We tested whether the spontaneously contracted atrial strips could be used as an experimental assay model to determine inotropic and chronotropic effects of existing drugs and candidate chemicals directly on human heart muscle. The well-established inotropic and chronotropic effects of the calcium channel blocker (verapamil), the β-adrenoceptor blocker (propranolol), the phosphodiesterase inhibitor (theophylline) and the Na(+)/K(+)-ATPase inhibitor (ouabain) were tested on spontaneously contracting strips of human atrium. With demonstrative tracings, we showed the negative inotropic and chronotropic effects of verapamil and propranolol, the positive inotropic and chronotropic effects of theophylline and the transient inotropic and tachyarrhythmic effects of ouabain on dobutamine-pretreated human atrial strips. By using this method the undetermined inotropic and chronotropic effects of any candidate compound can be evaluated directly on spontaneously contracting human atrial muscle. Furthermore, we demonstrated the advantages of using dobutamine instead of conventional electrical field stimulation in order to obtain stable and durable contractions of the atrial strips. In conclusion, we describe a new, simple, reliable, convenient and ethical method for investigating the inotropic and chronotropic effects of candidate drugs directly on human atrium tissue without the need for human test subjects.</p>","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29513428","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}
Pub Date : 2010-10-01DOI: 10.1358/mf.2010.32.8.1440747
O J Owolabi, Z A M Nworgu, K Odushu
Nauclea latifolia (Rubiaceae) is a medicinal plant used in Nigeria folk medicine for the treatment of gastrointestinal disorders. The root bark of the plant was extracted with 70% ethanol and the extract screened for antidiarrheal activity by investigating castor oil-induced diarrhea and small intestinal motility in mice. The effects of the extract on isolated rat ileum were also investigated. The extract (125, 250 and 500 mg/kg) caused a significant decrease in the frequency of diarrhea and conferred protection following castor oil administration (P < 0.05). It also significantly (P < 0.0001) inhibited small intestinal motility in mice at the same doses. Its activity was dose-dependent and when compared to atropine, its antidiarrheal effects at 500 mg/kg were 179% and 165% respectively, in castor oil-induced diarrhea and small intestinal motility experiments. Extract effects on rat ileum revealed a significant (P < 0.0001) inhibition of acetylcholine-induced contractions at 0.2 and 2 mg/mL final bath concentrations used. These findings confirm the antidiarrheal activity of the root bark extract of N. latifolia.
{"title":"Antidiarrheal evaluation of the ethanol extract of Nauclea latifolia root bark.","authors":"O J Owolabi, Z A M Nworgu, K Odushu","doi":"10.1358/mf.2010.32.8.1440747","DOIUrl":"https://doi.org/10.1358/mf.2010.32.8.1440747","url":null,"abstract":"<p><p>Nauclea latifolia (Rubiaceae) is a medicinal plant used in Nigeria folk medicine for the treatment of gastrointestinal disorders. The root bark of the plant was extracted with 70% ethanol and the extract screened for antidiarrheal activity by investigating castor oil-induced diarrhea and small intestinal motility in mice. The effects of the extract on isolated rat ileum were also investigated. The extract (125, 250 and 500 mg/kg) caused a significant decrease in the frequency of diarrhea and conferred protection following castor oil administration (P < 0.05). It also significantly (P < 0.0001) inhibited small intestinal motility in mice at the same doses. Its activity was dose-dependent and when compared to atropine, its antidiarrheal effects at 500 mg/kg were 179% and 165% respectively, in castor oil-induced diarrhea and small intestinal motility experiments. Extract effects on rat ileum revealed a significant (P < 0.0001) inhibition of acetylcholine-induced contractions at 0.2 and 2 mg/mL final bath concentrations used. These findings confirm the antidiarrheal activity of the root bark extract of N. latifolia.</p>","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29514098","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}
Pub Date : 2010-10-01DOI: 10.1358/mf.2010.32.8.1501437
Z Mandic, K Novak-Lauš, L Bojic, S Popovic-Suic, V Maricic-Došen, G Pelcic, D Dobutovic, D Biuk, Z Kovacic, J Pavan
The purpose of this study was to assess both the benefits of a 3-month travoprost 0.004%/timolol 0.5%fixed combination (trav/tim) regimen in comparison with previous medications for the control of intraocular pressure (IOP) and the tolerability of these drug regimens in glaucoma patients. An observational, non-interventional, open-label study of 406 eyes with primary open angle glaucoma and ocular hypertension was thus undertaken. One drop of trav/tim fixed combination was administered in the evening for 3 months. Patients were divided into five groups according to previous drug regimens: timolol 0.5% monotherapy; betaxolol 0.5% monotherapy; latanoprost 0.005% monotherapy; travoprost 0.004% monotherapy; and dorzolamide 2%/timolol 0.5% fixed combination. Upon medication substitution, the trav/tim fixed combination provided better IOP control and tolerability in all five patient groups. At the 3-month follow up, the mean IOP changes from previous therapy were as follows: 5.2 ± 2.7 mmHg (20.8% change) in timolol 0.5% group; 5.7 ± 2.2 mmHg (22.5% change) in betaxolol 0.5% group; 3.8 ± 2.6 mmHg (24.5% change) in latanoprost 0.005% group; 4.4 ± 2.8 mmHg (20% change) in travoprost 0.004% group; and 3.4 ± 4.1 mmHg (14.5% change) in dorzolamide 2%/timolol 0.5% fixed combination group. The difference between baseline and trav/tim combination patient satisfaction at the 3-month follow-up was significant. Thus, the trav/tim fixed combination provided better IOP control and tolerability than previous mono- or polytherapies.
{"title":"Observational study of patients switched to the fixed travoprost 0.004%/timolol 0.5% combination in Croatia.","authors":"Z Mandic, K Novak-Lauš, L Bojic, S Popovic-Suic, V Maricic-Došen, G Pelcic, D Dobutovic, D Biuk, Z Kovacic, J Pavan","doi":"10.1358/mf.2010.32.8.1501437","DOIUrl":"https://doi.org/10.1358/mf.2010.32.8.1501437","url":null,"abstract":"<p><p>The purpose of this study was to assess both the benefits of a 3-month travoprost 0.004%/timolol 0.5%fixed combination (trav/tim) regimen in comparison with previous medications for the control of intraocular pressure (IOP) and the tolerability of these drug regimens in glaucoma patients. An observational, non-interventional, open-label study of 406 eyes with primary open angle glaucoma and ocular hypertension was thus undertaken. One drop of trav/tim fixed combination was administered in the evening for 3 months. Patients were divided into five groups according to previous drug regimens: timolol 0.5% monotherapy; betaxolol 0.5% monotherapy; latanoprost 0.005% monotherapy; travoprost 0.004% monotherapy; and dorzolamide 2%/timolol 0.5% fixed combination. Upon medication substitution, the trav/tim fixed combination provided better IOP control and tolerability in all five patient groups. At the 3-month follow up, the mean IOP changes from previous therapy were as follows: 5.2 ± 2.7 mmHg (20.8% change) in timolol 0.5% group; 5.7 ± 2.2 mmHg (22.5% change) in betaxolol 0.5% group; 3.8 ± 2.6 mmHg (24.5% change) in latanoprost 0.005% group; 4.4 ± 2.8 mmHg (20% change) in travoprost 0.004% group; and 3.4 ± 4.1 mmHg (14.5% change) in dorzolamide 2%/timolol 0.5% fixed combination group. The difference between baseline and trav/tim combination patient satisfaction at the 3-month follow-up was significant. Thus, the trav/tim fixed combination provided better IOP control and tolerability than previous mono- or polytherapies.</p>","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29513432","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}
Pub Date : 2010-09-01DOI: 10.1358/mf.2010.32.7.1507854
A D Knapton, J Zhang, F D Sistare, J P Hanig
Exposure of the vasculature to vasodilators, pharmaceuticals and industrial chemicals may lead to injury of the blood vessel wall in animals. Vascular injury may begin with changes in the permeability of vascular endothelial cell and vessels, resulting in possible hemorrhage and edema leading subsequently to immune cell infiltration. The present study was undertaken to determine if the direct exposure of the Sprague Dawley rat mesenteric vasculature through the perfusion of aminophylline, fenoldopam, compound 48/80, histamine or serotonin has any such effects on the blood vessels, and if the two vital dyes Monastral blue B and Evans blue can be used to enhance the visualization of the vascular damage. Microscopic visualization was enhanced by the use of dyes and a variety of alterations of the perfused mesenteric vessels were detected, including varying degrees of mast cell degranulation, microvascular vasodilatation and increased vascular permeability. Macroscopic evidence of vascular damage was minimal. This study demonstrates that in situ perfusion of the rat mesentery is a simple and useful method to eliminate the influence of a variety of physiologic influences or homeostatic responses and can be used to further investigate drug-induced vascular damage.
{"title":"The use of in situ perfusion of the rat mesentery as a model to investigate vascular injury directly induced by drugs.","authors":"A D Knapton, J Zhang, F D Sistare, J P Hanig","doi":"10.1358/mf.2010.32.7.1507854","DOIUrl":"https://doi.org/10.1358/mf.2010.32.7.1507854","url":null,"abstract":"<p><p>Exposure of the vasculature to vasodilators, pharmaceuticals and industrial chemicals may lead to injury of the blood vessel wall in animals. Vascular injury may begin with changes in the permeability of vascular endothelial cell and vessels, resulting in possible hemorrhage and edema leading subsequently to immune cell infiltration. The present study was undertaken to determine if the direct exposure of the Sprague Dawley rat mesenteric vasculature through the perfusion of aminophylline, fenoldopam, compound 48/80, histamine or serotonin has any such effects on the blood vessels, and if the two vital dyes Monastral blue B and Evans blue can be used to enhance the visualization of the vascular damage. Microscopic visualization was enhanced by the use of dyes and a variety of alterations of the perfused mesenteric vessels were detected, including varying degrees of mast cell degranulation, microvascular vasodilatation and increased vascular permeability. Macroscopic evidence of vascular damage was minimal. This study demonstrates that in situ perfusion of the rat mesentery is a simple and useful method to eliminate the influence of a variety of physiologic influences or homeostatic responses and can be used to further investigate drug-induced vascular damage.</p>","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29462477","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}
Pub Date : 2010-09-01DOI: 10.1358/mf.2010.32.7.1487085
A Saberivand, I Karimi, L A Becker, A Moghaddam, S Azizi-Mahmoodjigh, M Yousefi, S Zavareh
Cannabis sativa L. has been used for the treatment of various gynecological diseases in traditional medicine. The potential of this plant to protect against complications of menopause has been raised but rarely studied. Twenty female rats were divided into five groups: sham-operated (sham), ovariectomized (OVX) and three other ovariectomized groups: HST1%, HST2% and HST10% which received 1%, 2% and 10% hempseed, respectively, in their diet for 3 weeks. The effects of hempseed on plasma lipid and lipoprotein profiles, estradiol and calcium levels were evaluated. Rats were tested for behavioral changes using the forced swimming test. The results showed that ovariectomy, independent of the type of diet, caused elevation of plasma calcium, total cholesterol and HDL-cholesterol levels, while hempseed modified this effect. Plasma estradiol levels were significantly lower in the OVX group compared to other groups. The swimming times for the OVX and sham groups were significantly shorter than that of the HSD10% group. All hempseed-treated groups were less anxious and showed significant declines in fecal boli compared to the sham group. The exploratory diving percent decreased in the HST10% group compared with other groups. These results suggest that hempseed may improve post-ovariectomy complications in rats.
{"title":"The effects of Cannabis sativa L. seed (hempseed) in the ovariectomized rat model of menopause.","authors":"A Saberivand, I Karimi, L A Becker, A Moghaddam, S Azizi-Mahmoodjigh, M Yousefi, S Zavareh","doi":"10.1358/mf.2010.32.7.1487085","DOIUrl":"https://doi.org/10.1358/mf.2010.32.7.1487085","url":null,"abstract":"<p><p>Cannabis sativa L. has been used for the treatment of various gynecological diseases in traditional medicine. The potential of this plant to protect against complications of menopause has been raised but rarely studied. Twenty female rats were divided into five groups: sham-operated (sham), ovariectomized (OVX) and three other ovariectomized groups: HST1%, HST2% and HST10% which received 1%, 2% and 10% hempseed, respectively, in their diet for 3 weeks. The effects of hempseed on plasma lipid and lipoprotein profiles, estradiol and calcium levels were evaluated. Rats were tested for behavioral changes using the forced swimming test. The results showed that ovariectomy, independent of the type of diet, caused elevation of plasma calcium, total cholesterol and HDL-cholesterol levels, while hempseed modified this effect. Plasma estradiol levels were significantly lower in the OVX group compared to other groups. The swimming times for the OVX and sham groups were significantly shorter than that of the HSD10% group. All hempseed-treated groups were less anxious and showed significant declines in fecal boli compared to the sham group. The exploratory diving percent decreased in the HST10% group compared with other groups. These results suggest that hempseed may improve post-ovariectomy complications in rats.</p>","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29462474","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}
Pub Date : 2010-09-01DOI: 10.1358/mf.2010.32.7.1501438
H Kawazoe, Y Motoki, Y Takechi, Y Shishino, K Ido, K Suemaru, H Araki
A retrospective study was carried out to compare the preventive effects of single and repeat treatment with dexamethasone (DEX) on delayed nausea and emesis in patients who had received carboplatin (CBDCA)-based combination chemotherapy. Sixty-four patients were evaluated. Efficacy was assessed using the nausea and emesis score, food intake score and the requirement for antiemetic medication. These forward scores were categorized as three-grade during the first 5 days after chemotherapy. Acute nausea and emesis were well controlled in both groups on day 1. Mean values of the nausea and emesis score on day 3 evening and the food intake score on day 4 morning in the repeat-treatment group was 1.31 ± 0.93 and 3.46 ± 1.03, respectively, which were significantly better when compared with the single-treatment group (2.00 ± 1.52; P = 0.028 and 2.79 ± 1.12; P = 0.018, respectively). Multivariate logistic regression analysis revealed that less frequent dispensing of antiemetic medication was significantly associated with the repeat-treatment group (adjusted odds ratio, 0.153; 95% confidence interval, 0.026-0.734; P = 0.018). These results suggest that repeat-dose DEX may be more effective than single-dose DEX for the prevention of delayed nausea and emesis after CBDCA-based combination chemotherapy.
{"title":"Comparison of antiemetic efficacy between single and repeat treatment with dexamethasone in patients receiving carboplatin-based combination chemotherapy.","authors":"H Kawazoe, Y Motoki, Y Takechi, Y Shishino, K Ido, K Suemaru, H Araki","doi":"10.1358/mf.2010.32.7.1501438","DOIUrl":"https://doi.org/10.1358/mf.2010.32.7.1501438","url":null,"abstract":"<p><p>A retrospective study was carried out to compare the preventive effects of single and repeat treatment with dexamethasone (DEX) on delayed nausea and emesis in patients who had received carboplatin (CBDCA)-based combination chemotherapy. Sixty-four patients were evaluated. Efficacy was assessed using the nausea and emesis score, food intake score and the requirement for antiemetic medication. These forward scores were categorized as three-grade during the first 5 days after chemotherapy. Acute nausea and emesis were well controlled in both groups on day 1. Mean values of the nausea and emesis score on day 3 evening and the food intake score on day 4 morning in the repeat-treatment group was 1.31 ± 0.93 and 3.46 ± 1.03, respectively, which were significantly better when compared with the single-treatment group (2.00 ± 1.52; P = 0.028 and 2.79 ± 1.12; P = 0.018, respectively). Multivariate logistic regression analysis revealed that less frequent dispensing of antiemetic medication was significantly associated with the repeat-treatment group (adjusted odds ratio, 0.153; 95% confidence interval, 0.026-0.734; P = 0.018). These results suggest that repeat-dose DEX may be more effective than single-dose DEX for the prevention of delayed nausea and emesis after CBDCA-based combination chemotherapy.</p>","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29462478","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}
Pub Date : 2010-09-01DOI: 10.1358/mf.2010.32.7.1440737
M Yoneko, Y Katayama, T Igarashi, T Mori, N Moro, Y Kondo, J Kamei, J Kojima
Cerebral salt wasting (CSW) frequently occurs concomitantly with an aneurysmal subarachnoid hemorrhage (SAH). CSW induces excessive natriuresis and osmotic diuresis, and reduces the total volume of blood. We previously reported that a rat model with SAH induced by endovascular puncture (EP) exhibited CSW. Therefore, we investigated the relationship between the spread of bleeding in the subarachnoid space and the intensity of CSW. We also investigated the development of CSW in different SAH models. SAH was induced by EP or by 0.3 mL of blood injection (BI) into the cisterna magna. To evaluate the occurrence of CSW, urine was cumulatively collected at the onset of SAH to 6 h later and analyzed for sodium (Na) excretion. SAH was classified from grade 1 (no bleeding) to grade 4 (severe bleeding) based on the spread of bleeding in the subarachnoid space. In the EP model (SAH grade > 2) as the SAH grade increased, the volume of urine and Na excretion also significantly increased. Although the BI model rats exhibited SAH of grade 4, the volume of urine and Na excretion did not change. Therefore, our conclusion is that the spread of bleeding in the subarachnoid space may not cause CSW.
{"title":"Characterization of cerebral salt wasting after subarachnoid hemorrhage model induced by endovascular puncture.","authors":"M Yoneko, Y Katayama, T Igarashi, T Mori, N Moro, Y Kondo, J Kamei, J Kojima","doi":"10.1358/mf.2010.32.7.1440737","DOIUrl":"https://doi.org/10.1358/mf.2010.32.7.1440737","url":null,"abstract":"<p><p>Cerebral salt wasting (CSW) frequently occurs concomitantly with an aneurysmal subarachnoid hemorrhage (SAH). CSW induces excessive natriuresis and osmotic diuresis, and reduces the total volume of blood. We previously reported that a rat model with SAH induced by endovascular puncture (EP) exhibited CSW. Therefore, we investigated the relationship between the spread of bleeding in the subarachnoid space and the intensity of CSW. We also investigated the development of CSW in different SAH models. SAH was induced by EP or by 0.3 mL of blood injection (BI) into the cisterna magna. To evaluate the occurrence of CSW, urine was cumulatively collected at the onset of SAH to 6 h later and analyzed for sodium (Na) excretion. SAH was classified from grade 1 (no bleeding) to grade 4 (severe bleeding) based on the spread of bleeding in the subarachnoid space. In the EP model (SAH grade > 2) as the SAH grade increased, the volume of urine and Na excretion also significantly increased. Although the BI model rats exhibited SAH of grade 4, the volume of urine and Na excretion did not change. Therefore, our conclusion is that the spread of bleeding in the subarachnoid space may not cause CSW.</p>","PeriodicalId":18443,"journal":{"name":"Methods and findings in experimental and clinical pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2010-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29462475","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}