Pub Date : 2000-05-01DOI: 10.1211/146080800128735890
Pulane Matlaba, S. Daya, T. Nyokong
Binding of aluminium to acetylcholine has important biological implications particularly in Alzheimer's disease. An electrochemical technique, adsorptive cathodic stripping voltammetry, has been employed in this study to investigate the in-situ formation of a complex between aluminium and acetylcholine. The stability of the resulting complex was compared with that of the in-situ complexes formed between acetylcholine and sodium or calcium. From the shifts in the reduction potential of the metals on addition of acetylcholine it is concluded that a strong complex is formed between acetylcholine and aluminium. Much weaker complexes are formed between calcium or sodium and acetylcholine. These results have important implications in the aetiology of Alzheimer's disease-in which brain aluminium concentrations are known to be high and brain cholinergic function is lower than normal.
{"title":"Interaction of the Neurotransmitter Acetylcholine with Aluminium, Calcium and Sodium","authors":"Pulane Matlaba, S. Daya, T. Nyokong","doi":"10.1211/146080800128735890","DOIUrl":"https://doi.org/10.1211/146080800128735890","url":null,"abstract":"Binding of aluminium to acetylcholine has important biological implications particularly in Alzheimer's disease. An electrochemical technique, adsorptive cathodic stripping voltammetry, has been employed in this study to investigate the in-situ formation of a complex between aluminium and acetylcholine. The stability of the resulting complex was compared with that of the in-situ complexes formed between acetylcholine and sodium or calcium. From the shifts in the reduction potential of the metals on addition of acetylcholine it is concluded that a strong complex is formed between acetylcholine and aluminium. Much weaker complexes are formed between calcium or sodium and acetylcholine. These results have important implications in the aetiology of Alzheimer's disease-in which brain aluminium concentrations are known to be high and brain cholinergic function is lower than normal.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88480521","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 : 2000-04-01DOI: 10.1211/146080800128735845
A. Dehpour, A. Mirsalehian, F. Nakhjavani, Daryoosh Davoodi Oskoei, A. Mani, S. Amanpour, Katayoun Fayaz Moghadam, Z. Ataei
Differences between the colonization sites of Helicobacter pylori might explain the different patterns of H. pylori-induced gastrointestinal pathology. The migration of H. pylori from the antrum to the gastric body and fundus during omeprazole monotherapy has been reported in H. pylori-infected subjects. The aim of this study was to determine the influence of pretreatment with omeprazole on later colonization by H. pylori, by use of the rapid urease test, culture, and the polymerase chain reaction on gastric samples obtained from the antrum and gastric body of non-germ-free immature rats. Pretreatment of rats with omeprazole did not significantly affect the incidence of H. pylori colonization during the four-week study. The preferred ecological niche of H. pylori in rats was the antrum rather than the gastric body. This difference was significant in animals not treated with omeprazole but not in treated groups, i.e. frequent injection of omeprazole led to the equal distribution of H. pylori in the antrum and gastric body. If clinical investigations confirm these results more precautions should be taken in omeprazole monotherapy because it is well known that H. pylori colonization of the gastric body is associated with multifocal gastric atrophy, an important risk factor in gastric adenocarcinoma.
{"title":"Effect of Pretreatment with Omeprazole on the Frequency of Helicobacter pylori Colonization in the Antrum and Gastric Body of Non-germ-free Immature Rats","authors":"A. Dehpour, A. Mirsalehian, F. Nakhjavani, Daryoosh Davoodi Oskoei, A. Mani, S. Amanpour, Katayoun Fayaz Moghadam, Z. Ataei","doi":"10.1211/146080800128735845","DOIUrl":"https://doi.org/10.1211/146080800128735845","url":null,"abstract":"Differences between the colonization sites of Helicobacter pylori might explain the different patterns of H. pylori-induced gastrointestinal pathology. The migration of H. pylori from the antrum to the gastric body and fundus during omeprazole monotherapy has been reported in H. pylori-infected subjects. The aim of this study was to determine the influence of pretreatment with omeprazole on later colonization by H. pylori, by use of the rapid urease test, culture, and the polymerase chain reaction on gastric samples obtained from the antrum and gastric body of non-germ-free immature rats. \u0000 \u0000 \u0000 \u0000Pretreatment of rats with omeprazole did not significantly affect the incidence of H. pylori colonization during the four-week study. The preferred ecological niche of H. pylori in rats was the antrum rather than the gastric body. This difference was significant in animals not treated with omeprazole but not in treated groups, i.e. frequent injection of omeprazole led to the equal distribution of H. pylori in the antrum and gastric body. \u0000 \u0000 \u0000 \u0000If clinical investigations confirm these results more precautions should be taken in omeprazole monotherapy because it is well known that H. pylori colonization of the gastric body is associated with multifocal gastric atrophy, an important risk factor in gastric adenocarcinoma.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90517075","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 : 2000-04-01DOI: 10.1211/146080800128735836
K. Takara, Y. Tanigawara, F. Komada, K. Nishiguchi, T. Sakaeda, K. Okumura
The inhibitory effects of nicardipine, nifedipine and itraconazole on P-glycoprotein-mediated transport of [3H]digoxin were examined using LLC-PK1 and LLC-GA5-COL150 cells, a porcine kidney epithelial LLC-PK1 cell line transformed with MDRI cDNA from man which results in overexpression of P-glycoprotein on the apical membrane. Basal-to-apical transport of [3H]digoxin in LLC-GA5-COL150 cells was higher than in LLC-PK1 cells; apical-to-basal transport was markedly lower in LLC-PK1 cells and even lower in LLC-GA5-COL150 cells. This is consistent with the possibility that [3H]digoxin is transported by P-glycoprotein. Co-administration of nicardipine or itraconazole markedly inhibited the basal-to-apical transport of [3H]digoxin in LLC-GA5-COL150 cells, and apical-to-basal transport also increased. The effect of nifedipine was less marked than that of nicardipine or itraconazole. Intracellular accumulation of [3H]digoxin after apical application in LLC-GA5-COL150 cells was 2.3 times less than in LLC-PK1 cells, and was increased by the addition of nicardipine or itraconazole, consistent with their inhibitory effects on transcellular transport. Following basal application of [3H]digoxin, its intracellular accumulation in LLC-GA5-COL150 cells was, unexpectedly, comparable with that in LLC-PK1 cells, and was hardly affected by the addition of nicardipine or itraconazole. In conclusion, it has been shown that nicardipine and itraconazole inhibited transport of digoxin, which is presumably mediated by P-glycoprotein. This explains their effects observed in clinical use.
{"title":"Nicardipine and Itraconazole Inhibited Transcellular Transport of Digoxin","authors":"K. Takara, Y. Tanigawara, F. Komada, K. Nishiguchi, T. Sakaeda, K. Okumura","doi":"10.1211/146080800128735836","DOIUrl":"https://doi.org/10.1211/146080800128735836","url":null,"abstract":"The inhibitory effects of nicardipine, nifedipine and itraconazole on P-glycoprotein-mediated transport of [3H]digoxin were examined using LLC-PK1 and LLC-GA5-COL150 cells, a porcine kidney epithelial LLC-PK1 cell line transformed with MDRI cDNA from man which results in overexpression of P-glycoprotein on the apical membrane. \u0000 \u0000 \u0000 \u0000Basal-to-apical transport of [3H]digoxin in LLC-GA5-COL150 cells was higher than in LLC-PK1 cells; apical-to-basal transport was markedly lower in LLC-PK1 cells and even lower in LLC-GA5-COL150 cells. This is consistent with the possibility that [3H]digoxin is transported by P-glycoprotein. Co-administration of nicardipine or itraconazole markedly inhibited the basal-to-apical transport of [3H]digoxin in LLC-GA5-COL150 cells, and apical-to-basal transport also increased. The effect of nifedipine was less marked than that of nicardipine or itraconazole. Intracellular accumulation of [3H]digoxin after apical application in LLC-GA5-COL150 cells was 2.3 times less than in LLC-PK1 cells, and was increased by the addition of nicardipine or itraconazole, consistent with their inhibitory effects on transcellular transport. Following basal application of [3H]digoxin, its intracellular accumulation in LLC-GA5-COL150 cells was, unexpectedly, comparable with that in LLC-PK1 cells, and was hardly affected by the addition of nicardipine or itraconazole. \u0000 \u0000 \u0000 \u0000In conclusion, it has been shown that nicardipine and itraconazole inhibited transport of digoxin, which is presumably mediated by P-glycoprotein. This explains their effects observed in clinical use.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80540618","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 : 2000-04-01DOI: 10.1211/146080800128735854
S. Naito, M. Nishimura, H. Nogawa, H. Yoshitsugu, Yumi Tamao, Satoru Asano, Y. Nomura
Detailed sex differences in the disposition and metabolism of BOF-4272, a newly developed xanthine oxidase/xanthine dehydrogenase inhibitor, are described on the basis of in-vivo studies in rats. In both male and female rats, at all times after oral administration of 14C-labelled BOF-4272, the highest level of radioactivity (except for radioactivity in the gastrointestinal tract) was observed in the liver, then in the kidney. Little radioactivity was detected in other tissues. After oral administration the total 14C concentration profiles in the plasma and kidney were almost identical in male and female rats whereas total 14C concentrations in the liver to 24h were higher in female rats than in males. Levels of BOF-4269 (the sulphide metabolite of BOF-4272) in the contents of the large intestine to 24h after the oral administration of BOF-4272 were higher in female rats than in males. BOF-4269 was the main metabolite found in the plasma in female rats after intravenous or oral administration. The area under the plasma concentration-time curve (AUC0-t) for BOF-4272 after oral administration was almost identical in female and male rats, whereas that for BOF-4269 was 2.8 times higher in female rats than in males. These findings suggest that differences between the disposition of 14C-labelled BOF-4272 in rats of different sexes are mainly because of differences between the metabolism of BOF-4272 to BOF-4269 by the intestinal flora, the elimination of BOF-4269 by the liver, or both.
{"title":"In‐vivo Sex Differences in Disposition and Metabolism of Sulphoxide‐containing Drug BOF‐4272 in Rats","authors":"S. Naito, M. Nishimura, H. Nogawa, H. Yoshitsugu, Yumi Tamao, Satoru Asano, Y. Nomura","doi":"10.1211/146080800128735854","DOIUrl":"https://doi.org/10.1211/146080800128735854","url":null,"abstract":"Detailed sex differences in the disposition and metabolism of BOF-4272, a newly developed xanthine oxidase/xanthine dehydrogenase inhibitor, are described on the basis of in-vivo studies in rats. \u0000 \u0000 \u0000 \u0000In both male and female rats, at all times after oral administration of 14C-labelled BOF-4272, the highest level of radioactivity (except for radioactivity in the gastrointestinal tract) was observed in the liver, then in the kidney. Little radioactivity was detected in other tissues. After oral administration the total 14C concentration profiles in the plasma and kidney were almost identical in male and female rats whereas total 14C concentrations in the liver to 24h were higher in female rats than in males. Levels of BOF-4269 (the sulphide metabolite of BOF-4272) in the contents of the large intestine to 24h after the oral administration of BOF-4272 were higher in female rats than in males. BOF-4269 was the main metabolite found in the plasma in female rats after intravenous or oral administration. The area under the plasma concentration-time curve (AUC0-t) for BOF-4272 after oral administration was almost identical in female and male rats, whereas that for BOF-4269 was 2.8 times higher in female rats than in males. \u0000 \u0000 \u0000 \u0000These findings suggest that differences between the disposition of 14C-labelled BOF-4272 in rats of different sexes are mainly because of differences between the metabolism of BOF-4272 to BOF-4269 by the intestinal flora, the elimination of BOF-4269 by the liver, or both.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91024580","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 : 2000-04-01DOI: 10.1211/146080800128735809
P. Giunchedi, P. Chetoni, U. Conte, M. Saettone
This investigation deals with the preparation, in-vitro characterization and preliminary in-vivo evaluation of albumin microspheres containing piroxicam. The albumin-piroxicam microspheres, designed for ocular administration, were prepared by a spray-drying technique. The morphological and dimensional characteristics of the particles were studied by scanning-electron microscopy and particle-size analysis. Their in-vitro release behaviour was investigated in pH 7-0 USP23 buffer by use of a flow-through apparatus. Piroxicam in the albumin microspheres dissolved more quickly in-vitro than did piroxicam powder. The pharmacokinetic profile of piroxicam in aqueous humour was investigated in albino rabbits. The albumin-piroxicam microspheres resulted in greater bioavailability of piroxicam than commercial piroxicam eyedrops.
{"title":"Albumin Microspheres for Ocular Delivery of Piroxicam","authors":"P. Giunchedi, P. Chetoni, U. Conte, M. Saettone","doi":"10.1211/146080800128735809","DOIUrl":"https://doi.org/10.1211/146080800128735809","url":null,"abstract":"This investigation deals with the preparation, in-vitro characterization and preliminary in-vivo evaluation of albumin microspheres containing piroxicam. The albumin-piroxicam microspheres, designed for ocular administration, were prepared by a spray-drying technique. The morphological and dimensional characteristics of the particles were studied by scanning-electron microscopy and particle-size analysis. Their in-vitro release behaviour was investigated in pH 7-0 USP23 buffer by use of a flow-through apparatus. \u0000 \u0000 \u0000 \u0000Piroxicam in the albumin microspheres dissolved more quickly in-vitro than did piroxicam powder. The pharmacokinetic profile of piroxicam in aqueous humour was investigated in albino rabbits. The albumin-piroxicam microspheres resulted in greater bioavailability of piroxicam than commercial piroxicam eyedrops.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72652435","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 : 2000-04-01DOI: 10.1211/146080800128735863
M. Rasool, L. M. Latha, P. Varalakshmi
The effect of Withania somnifera Linn. Dunal (Solanaceae) on adjuvant arthritic rats was studied and compared with that of indomethacin. These results indicate that Withania somnifera has promising anti-arthritic activity as a result of its stabilizing action on lysosomal enzyme activity. The anti-inflammatory activity of Withania somnifera was assessed by measuring paw swelling and lysosomal enzyme activity in control and experimental rats. Increased paw diameter and lysosomal enzyme activity in the arthritic animals were significantly suppressed to near normal levels in rats treated with 1000 mg kg−1Withania somnifera root powder and 3 mg kg−1 indomethacin.
苦参的药效研究。研究了茄科杜纳尔对佐剂性关节炎大鼠的作用，并与吲哚美辛进行了比较。这些结果表明，苦参对溶酶体酶活性具有稳定作用，具有良好的抗关节炎活性。通过测定对照组大鼠和实验大鼠的足跖肿胀和溶酶体酶活性来评价苦参的抗炎活性。用1000 mg kg - 1苦参根粉和3 mg kg - 1吲哚美辛处理后，关节炎动物的足径增加和溶酶体酶活性明显被抑制到接近正常水平。
{"title":"Effect of Withania somnifera on Lysosomal Acid Hydrolases in Adjuvant‐induced Arthritis in Rats","authors":"M. Rasool, L. M. Latha, P. Varalakshmi","doi":"10.1211/146080800128735863","DOIUrl":"https://doi.org/10.1211/146080800128735863","url":null,"abstract":"The effect of Withania somnifera Linn. Dunal (Solanaceae) on adjuvant arthritic rats was studied and compared with that of indomethacin. \u0000 \u0000 \u0000 \u0000These results indicate that Withania somnifera has promising anti-arthritic activity as a result of its stabilizing action on lysosomal enzyme activity. \u0000 \u0000 \u0000 \u0000The anti-inflammatory activity of Withania somnifera was assessed by measuring paw swelling and lysosomal enzyme activity in control and experimental rats. Increased paw diameter and lysosomal enzyme activity in the arthritic animals were significantly suppressed to near normal levels in rats treated with 1000 mg kg−1Withania somnifera root powder and 3 mg kg−1 indomethacin.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76532532","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 : 2000-04-01DOI: 10.1211/146080800128735827
T. Ogihara, I. Tamai, A. Tsuji
This study was designed to characterize the structural requirements for stereoselective transport of substrates by the monocarboxylate transporters (proton cotransporter and anion antiporter) of Caco-2 cells by examining the inhibitory effect of the optical isomers of chiral monocarboxylic acids and the transcellular transport of two Chiral monocarboxylic acids and the transcellular transport of two Chiral monocarboxylic acids. In the presence of a proton gradient the transport of a trace concentration (1 μM) of l-lactic acid in Caco-2 cells was inhibited stereoselectively by 2-hydroxy- and 2-methoxymonocarboxylic acids, for example S- and R-mandelic and S- and R-2-methoxypropionic acids. Similar results were obtained in the presence of a bicarbonate ion gradient. Transport was also inhibited non-stereoselectively by several other monocarboxylic acids, for example S- and R-2-phenylpropionic acids. Transport of both S- and R-mandelic acids apparently involved saturable and non-saturable processes. For the saturable process affinity was higher and capacity lower for S-mandelic acid than for the R isomer, whereas no stereoselectivity was observed for transport of S- and R-2-phenylpropionic acids. It is suggested that a 2-hydroxyl or 2-methoxy group is important for specific stereoselective carrier-mediated transport of monocarboxylic acids across intestinal epithelial cells.
{"title":"Structural Requirements of Substrates for Stereoselective Monocarboxylate Transport in Caco‐2 Cells","authors":"T. Ogihara, I. Tamai, A. Tsuji","doi":"10.1211/146080800128735827","DOIUrl":"https://doi.org/10.1211/146080800128735827","url":null,"abstract":"This study was designed to characterize the structural requirements for stereoselective transport of substrates by the monocarboxylate transporters (proton cotransporter and anion antiporter) of Caco-2 cells by examining the inhibitory effect of the optical isomers of chiral monocarboxylic acids and the transcellular transport of two Chiral monocarboxylic acids and the transcellular transport of two Chiral monocarboxylic acids. In the presence of a proton gradient the transport of a trace concentration (1 μM) of l-lactic acid in Caco-2 cells was inhibited stereoselectively by 2-hydroxy- and 2-methoxymonocarboxylic acids, for example S- and R-mandelic and S- and R-2-methoxypropionic acids. Similar results were obtained in the presence of a bicarbonate ion gradient. Transport was also inhibited non-stereoselectively by several other monocarboxylic acids, for example S- and R-2-phenylpropionic acids. Transport of both S- and R-mandelic acids apparently involved saturable and non-saturable processes. For the saturable process affinity was higher and capacity lower for S-mandelic acid than for the R isomer, whereas no stereoselectivity was observed for transport of S- and R-2-phenylpropionic acids. It is suggested that a 2-hydroxyl or 2-methoxy group is important for specific stereoselective carrier-mediated transport of monocarboxylic acids across intestinal epithelial cells.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89199665","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 : 2000-04-01DOI: 10.1211/146080800128735818
S. Tomasi, M. Roch, J. Renault, J. Corbel, P. Uriac
Many problems are encountered in the synthesis of polyamines, natural compounds of biological interest. We describe here the rapid optimization of experimental conditions for the synthesis of orthogonally substituted triamines starting from simple building blocks-diamines and bromoalkylphthalimides. For this purpose we have adapted Bergeron's liquid-phase method (N-alkylation of sulphonamides) to solid-phase organic synthesis. The solid support was Multipin crowns enabling rapid optimization of the key-step-deprotonation of the sulphonamide. The combination of different building-blocks could lead to wide diversity.
{"title":"N-alkylation of N1-mesitylenesulphonylputrescine with N-(4-bromobutyl)phthalimide: A Parallel Approach Using Multipin Solid-phase Synthesis","authors":"S. Tomasi, M. Roch, J. Renault, J. Corbel, P. Uriac","doi":"10.1211/146080800128735818","DOIUrl":"https://doi.org/10.1211/146080800128735818","url":null,"abstract":"Many problems are encountered in the synthesis of polyamines, natural compounds of biological interest. We describe here the rapid optimization of experimental conditions for the synthesis of orthogonally substituted triamines starting from simple building blocks-diamines and bromoalkylphthalimides. For this purpose we have adapted Bergeron's liquid-phase method (N-alkylation of sulphonamides) to solid-phase organic synthesis. The solid support was Multipin crowns enabling rapid optimization of the key-step-deprotonation of the sulphonamide. The combination of different building-blocks could lead to wide diversity.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81014368","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 : 2000-03-01DOI: 10.1211/146080800128735773
M. Baradaran, M. Mojtahedzadeh, F. Roshanzamir, M. Ganji, A. Mohaghegh, R. Malekzadeh
The relationship between histamine H2-antagonist pharmacokinetic behaviour and the response of intragastric pH to physiological stress, and vital support measurements, have been prospectively evaluated in ten critically ill patients of mean (± s.d.) age 61 ± 16 years, mean weight 60 ± 9.7 kg, and APACHE (acute physiology and chronic health evaluation) II score 10 ± 6. In this double-blind, cross-over study patients received either a continuous ranitidine infusion made locally by Chimi-Darou, Iran (study drug) or Zantac (control drug). Subjects were randomized to receive 6.25 mg h−1 of the study drug for 24 h during the initial phase, after which drugs were switched for the next 24 h. The two phases of the study were separated by a wash-out period of 16 h. Intragastric pH was measured for 72 h with an antimony pH probe catheter. Concentrations of ranitidine in plasma and gastric juice were determined by HPLC. Mean ± s.e.m. gastric pH was 4.47 ± 0.65 for patients receiving the locally made study drug and 4.25 ± 0.69 for those receiving Zantac (P=0.5351). There was good correlation between intragastric pH and plasma ranitidine concentration (r=0.97, P=0.0055 and r=0.94, P=0.169 for study and control drugs, respectively). Ranitidine was also present in significant quantities in the gastric juice. There was no correlation between intragastric pH and gastric concentration of ranitidine (r=0.37, P=0.6142) for the control drug nor between the concentrations of the drug in the gastric juice and plasma (r=0.055, P=0.9292). There was no correlation between median pH and APACHE II score or Glasgow coma scale (GCS) score (P=0.557 and P=0.541, respectively).
{"title":"Gastric pH, Concentrations of Ranitidine in Gastric Juice and Plasma, and the Pharmacokinetics of Infused Ranitidine in Critically Ill Patients","authors":"M. Baradaran, M. Mojtahedzadeh, F. Roshanzamir, M. Ganji, A. Mohaghegh, R. Malekzadeh","doi":"10.1211/146080800128735773","DOIUrl":"https://doi.org/10.1211/146080800128735773","url":null,"abstract":"The relationship between histamine H2-antagonist pharmacokinetic behaviour and the response of intragastric pH to physiological stress, and vital support measurements, have been prospectively evaluated in ten critically ill patients of mean (± s.d.) age 61 ± 16 years, mean weight 60 ± 9.7 kg, and APACHE (acute physiology and chronic health evaluation) II score 10 ± 6. In this double-blind, cross-over study patients received either a continuous ranitidine infusion made locally by Chimi-Darou, Iran (study drug) or Zantac (control drug). Subjects were randomized to receive 6.25 mg h−1 of the study drug for 24 h during the initial phase, after which drugs were switched for the next 24 h. The two phases of the study were separated by a wash-out period of 16 h. Intragastric pH was measured for 72 h with an antimony pH probe catheter. Concentrations of ranitidine in plasma and gastric juice were determined by HPLC. \u0000 \u0000 \u0000 \u0000Mean ± s.e.m. gastric pH was 4.47 ± 0.65 for patients receiving the locally made study drug and 4.25 ± 0.69 for those receiving Zantac (P=0.5351). There was good correlation between intragastric pH and plasma ranitidine concentration (r=0.97, P=0.0055 and r=0.94, P=0.169 for study and control drugs, respectively). Ranitidine was also present in significant quantities in the gastric juice. There was no correlation between intragastric pH and gastric concentration of ranitidine (r=0.37, P=0.6142) for the control drug nor between the concentrations of the drug in the gastric juice and plasma (r=0.055, P=0.9292). There was no correlation between median pH and APACHE II score or Glasgow coma scale (GCS) score (P=0.557 and P=0.541, respectively).","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87916367","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 : 2000-03-01DOI: 10.1211/146080800128735764
S. Furusawa, H. Shibata, Hiromi Nishimura, S. Nemoto, M. Takayanagi, Y. Takayanagi, K. Sasaki
The apoptosis and cell cycle effect of doxorubicin were evaluated in the presence and absence of ivermectin in mouse doxorubicin-resistant P388 leukaemia cells. Ivermectin (2 μM) increased the sensitivity to doxorubicin of multidrug resistant (MDR) mouse leukemic P388 cells and significantly enhanced the apoptosis and intracellular accumulation of doxorubicin in resistant cells, but had no effect on parent cells. Using the fluorescent potential probe, 3,3′-dihexyl-oxacarbocyanine, we found that ivermectin induced a plasma membrane potential increase in resistant cells. Ivermectin also enhanced doxorubicin-induced G2/M blockade of the cell cycle in resistant cells. It is possible that ivermectin could reverse resistance by direct interaction with the P-glycoprotein or other components of the altered MDR cell membrane.
{"title":"Potentiation of Doxorubicin-Induced Apoptosis of Resistant Mouse Leukaemia Cells by Ivermectin","authors":"S. Furusawa, H. Shibata, Hiromi Nishimura, S. Nemoto, M. Takayanagi, Y. Takayanagi, K. Sasaki","doi":"10.1211/146080800128735764","DOIUrl":"https://doi.org/10.1211/146080800128735764","url":null,"abstract":"The apoptosis and cell cycle effect of doxorubicin were evaluated in the presence and absence of ivermectin in mouse doxorubicin-resistant P388 leukaemia cells. \u0000 \u0000Ivermectin (2 μM) increased the sensitivity to doxorubicin of multidrug resistant (MDR) mouse leukemic P388 cells and significantly enhanced the apoptosis and intracellular accumulation of doxorubicin in resistant cells, but had no effect on parent cells. Using the fluorescent potential probe, 3,3′-dihexyl-oxacarbocyanine, we found that ivermectin induced a plasma membrane potential increase in resistant cells. Ivermectin also enhanced doxorubicin-induced G2/M blockade of the cell cycle in resistant cells. It is possible that ivermectin could reverse resistance by direct interaction with the P-glycoprotein or other components of the altered MDR cell membrane.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90846655","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}
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