W H Sutherland, N J Lewis-Barned, M C Pratt, H C Tillman, R J Walker
The effect of acute hyperinsulinemia on plasma lipoprotein a [Lp(a)] concentration in 25 patients with non-insulin dependent diabetes mellitus (NIDDM) and in 10 healthy subjects was examined. Insulin was infused into the subjects for 2 hours while baseline plasma glucose concentrations were maintained. Plasma Lp(a) levels showed a small but significant mean (+/- SD) increase in NIDDM patients (12 +/- 26 U/l, p < 0.01) but did not vary significantly in healthy subjects (3 +/- 15 U/l) when insulin was infused. There was considerable individual variation (-35 to 98 U/l) in the response of Lp(a) to acute hyperinsulinemia and the response was correlated significantly with baseline Lp(a) levels (r = 0.399, p < 0.05). These data suggest that acute hyperinsulinemia at constant baseline glucose levels may raise plasma Lp(a) levels in NIDDM patients more particularly in those with high initial Lp(a) concentrations.
本文观察了25例非胰岛素依赖型糖尿病(NIDDM)患者和10例健康人急性高胰岛素血症对血浆脂蛋白a [Lp(a)]浓度的影响。受试者输注胰岛素2小时,同时维持基线血浆葡萄糖浓度。注射胰岛素后,NIDDM患者血浆Lp(a)水平平均(+/- SD)升高(12 +/- 26 U/l, p < 0.01),但差异不显著(3 +/- 15 U/l)。Lp(a)对急性高胰岛素血症的反应存在显著的个体差异(-35 ~ 98 U/l),且与基线水平有显著相关性(r = 0.399, p < 0.05)。这些数据表明,在恒定的基线血糖水平下,急性高胰岛素血症可能会升高NIDDM患者的血浆Lp(a)水平,尤其是那些初始Lp(a)浓度较高的患者。
{"title":"The response of plasma lipoprotein (a) concentration to acute hyperinsulinemia in patients with non-insulin dependent diabetes and in healthy subjects.","authors":"W H Sutherland, N J Lewis-Barned, M C Pratt, H C Tillman, R J Walker","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effect of acute hyperinsulinemia on plasma lipoprotein a [Lp(a)] concentration in 25 patients with non-insulin dependent diabetes mellitus (NIDDM) and in 10 healthy subjects was examined. Insulin was infused into the subjects for 2 hours while baseline plasma glucose concentrations were maintained. Plasma Lp(a) levels showed a small but significant mean (+/- SD) increase in NIDDM patients (12 +/- 26 U/l, p < 0.01) but did not vary significantly in healthy subjects (3 +/- 15 U/l) when insulin was infused. There was considerable individual variation (-35 to 98 U/l) in the response of Lp(a) to acute hyperinsulinemia and the response was correlated significantly with baseline Lp(a) levels (r = 0.399, p < 0.05). These data suggest that acute hyperinsulinemia at constant baseline glucose levels may raise plasma Lp(a) levels in NIDDM patients more particularly in those with high initial Lp(a) concentrations.</p>","PeriodicalId":21140,"journal":{"name":"Research communications in chemical pathology and pharmacology","volume":"83 1","pages":"77-86"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19155944","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}
Under normal circumstances, the body barriers effectively limit the entry and retention of dietary aluminum. However, both parathyroid hormone (PTH) and calcitriol (physiologically active hormonal form of vitamin D3) have been reported to produce elevation of serum aluminum in animals fed an aluminum-supplemented ration. To compare the effects of calcitriol with those of PTH with reference to their putative effect to enhance aluminum absorption, an experiment was designed wherein the serum levels of both PTH and calcitriol would be changing markedly during a short time-frame. To condition the rabbits used for this comparison, they were fed a vitamin D-free diet, which caused the level of calcitriol and its precursors to decline rapidly. The calcitriol deficit together with the ensuing lack of calcium absorption resulted in a state of secondary hyperparathyroidism. Vitamin D-depletion was shown to be complete by the high level of serum PTH and a low (unmeasurable) level of serum calcitriol. To enable comparison of PTH with calcitriol, exogenous calcitriol infusion (60 IU/day) was started by osmotic pump simultaneously with the beginning of an aluminum (aluminum lactate) supplemented diet. Aliquots were collected for both serum PTH and serum calcitriol at intervals during the 7 day study. A rising serum aluminum level was highly correlated with the rising serum calcitriol level in the rabbits (r = 0.903, p = 0.036) during the first 4 days of the infusion. The mean serum aluminum levels rose nearly 13 parts per billion (ppb) in the 7 day period. Declining serum PTH (due to feedback mechanisms of calcitriol suppressing PTH synthesis) showed a negative correlation of serum aluminum and serum PTH (r = -0.959, p = < 0.01) during the first 4 days of infusion. Control rabbits (vitamin-D depleted) fed aluminum-supplemented rations have shown only a minimal transient rise in serum aluminum level which returned to the pre-test level by the end of the week. To test for any effect of PTH on serum aluminum in the absence of calcitriol, five rabbits were implanted with osmotic pumps infusing PTH (mean 6.0 U/hr) and started on an aluminum supplemented diet. These rabbits, having previously been depleted of vitamin D were already in a state of nutritional secondary hyperparathyroidism as shown by their elevated pretest PTH levels. During the 7 day infusion, the serum aluminum rose only a mean of approximately 1 part per billion (ppb).(ABSTRACT TRUNCATED AT 400 WORDS)
在正常情况下,人体屏障有效地限制了膳食铝的进入和滞留。然而,据报道,甲状旁腺激素(PTH)和骨化三醇(维生素D3的生理活性激素形式)在饲喂补铝日粮的动物中引起血清铝的升高。为了比较骨化三醇和甲状旁腺激素对铝吸收的影响,我们设计了一项实验,其中甲状旁腺激素和骨化三醇的血清水平在短时间内会发生显著变化。为了使兔子适应这种比较,他们被喂食不含维生素d的食物,这导致骨化三醇及其前体的水平迅速下降。骨化三醇缺乏症和随后的钙吸收不足导致继发性甲状旁腺功能亢进。高水平的血清甲状腺激素和低水平(无法测量)的血清骨化三醇显示了维生素d的消耗。为了比较PTH与骨化三醇的差异,在开始添加铝(乳酸铝)的同时,通过渗透泵开始外源性骨化三醇输注(60 IU/天)。在7天的研究中,每隔一段时间收集一次血清甲状旁腺激素和骨化三醇的等量。在给药前4天,家兔血清铝水平升高与骨化三醇水平升高高度相关(r = 0.903, p = 0.036)。在7天期间,平均血清铝水平上升了近十亿分之十三(ppb)。注射前4天血清PTH下降(由于骨化三醇抑制PTH合成的反馈机制),血清铝与血清PTH呈负相关(r = -0.959, p = < 0.01)。对照组(缺乏维生素d)饲喂补铝口粮,血清铝水平只有短暂的微小上升,到一周结束时又恢复到试验前的水平。为了检测在骨化三醇不存在的情况下甲状旁腺激素对血清铝的影响,5只家兔被植入注入甲状旁腺激素的渗透泵(平均6.0 U/hr),并开始补铝饮食。这些兔子,先前已经耗尽了维生素D,已经处于营养性继发性甲状旁腺功能亢进的状态,从它们的PTH水平升高可以看出。在7天的输注期间,血清铝仅平均上升约1十亿分之一(ppb)。(摘要删节为400字)
{"title":"Comparative effects of calcitriol and parathyroid hormone on serum aluminum in vitamin D-depleted rabbits fed an aluminum-supplemented diet.","authors":"J F Long, L A Nagode, C L Steinmeyer, G Renkes","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Under normal circumstances, the body barriers effectively limit the entry and retention of dietary aluminum. However, both parathyroid hormone (PTH) and calcitriol (physiologically active hormonal form of vitamin D3) have been reported to produce elevation of serum aluminum in animals fed an aluminum-supplemented ration. To compare the effects of calcitriol with those of PTH with reference to their putative effect to enhance aluminum absorption, an experiment was designed wherein the serum levels of both PTH and calcitriol would be changing markedly during a short time-frame. To condition the rabbits used for this comparison, they were fed a vitamin D-free diet, which caused the level of calcitriol and its precursors to decline rapidly. The calcitriol deficit together with the ensuing lack of calcium absorption resulted in a state of secondary hyperparathyroidism. Vitamin D-depletion was shown to be complete by the high level of serum PTH and a low (unmeasurable) level of serum calcitriol. To enable comparison of PTH with calcitriol, exogenous calcitriol infusion (60 IU/day) was started by osmotic pump simultaneously with the beginning of an aluminum (aluminum lactate) supplemented diet. Aliquots were collected for both serum PTH and serum calcitriol at intervals during the 7 day study. A rising serum aluminum level was highly correlated with the rising serum calcitriol level in the rabbits (r = 0.903, p = 0.036) during the first 4 days of the infusion. The mean serum aluminum levels rose nearly 13 parts per billion (ppb) in the 7 day period. Declining serum PTH (due to feedback mechanisms of calcitriol suppressing PTH synthesis) showed a negative correlation of serum aluminum and serum PTH (r = -0.959, p = < 0.01) during the first 4 days of infusion. Control rabbits (vitamin-D depleted) fed aluminum-supplemented rations have shown only a minimal transient rise in serum aluminum level which returned to the pre-test level by the end of the week. To test for any effect of PTH on serum aluminum in the absence of calcitriol, five rabbits were implanted with osmotic pumps infusing PTH (mean 6.0 U/hr) and started on an aluminum supplemented diet. These rabbits, having previously been depleted of vitamin D were already in a state of nutritional secondary hyperparathyroidism as shown by their elevated pretest PTH levels. During the 7 day infusion, the serum aluminum rose only a mean of approximately 1 part per billion (ppb).(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":21140,"journal":{"name":"Research communications in chemical pathology and pharmacology","volume":"83 1","pages":"3-14"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19155940","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}
T Fujita, T Nakajima, T Matsuma, H Nishida, S Sakuma, Y Fujimoto
The effect of 13-hydroperoxyoctadecadienoic acid (13-HPODE) on the synthesis of prostaglandins (PGs) was examined in rabbit kidney medulla microsomes. Medulla microsomes were incubated with arachidonic acid in 0.1 M-Tris/HCl buffer (pH 8.0) containing reduced glutathione and hydroquinone and the PGE2, PGF2a and PGD2 formed were measured by high-pressure liquid chromatography using 9-anthryldiazomethane for derivatization. Under our incubation conditions rabbit kidney medulla was found to produce mainly PGE2. The addition of 13-HPODE inhibited the production of all three PGs to a similar extent. 13-Hydroxyoctadecadienoic acid did not suppress the formation of PGs, indicating the requirement of the hydroperoxy moiety for the inhibitory effect of 13-HPODE on PG formation. Experiments utilizing the native fatty acid linoleic acid and tert-butyl hydroperoxide suggested the importance of the fatty acid-derived hydroperoxide in PG synthesis by kidney medulla. We conclude that 13-HPODE is an inhibitor of renomedullary cyclooxygenase and may have functional effects within the kidney.
{"title":"Effect of 13-hydroperoxyoctadecadienoic acid on prostaglandin synthesis in rabbit kidney medulla microsomes.","authors":"T Fujita, T Nakajima, T Matsuma, H Nishida, S Sakuma, Y Fujimoto","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effect of 13-hydroperoxyoctadecadienoic acid (13-HPODE) on the synthesis of prostaglandins (PGs) was examined in rabbit kidney medulla microsomes. Medulla microsomes were incubated with arachidonic acid in 0.1 M-Tris/HCl buffer (pH 8.0) containing reduced glutathione and hydroquinone and the PGE2, PGF2a and PGD2 formed were measured by high-pressure liquid chromatography using 9-anthryldiazomethane for derivatization. Under our incubation conditions rabbit kidney medulla was found to produce mainly PGE2. The addition of 13-HPODE inhibited the production of all three PGs to a similar extent. 13-Hydroxyoctadecadienoic acid did not suppress the formation of PGs, indicating the requirement of the hydroperoxy moiety for the inhibitory effect of 13-HPODE on PG formation. Experiments utilizing the native fatty acid linoleic acid and tert-butyl hydroperoxide suggested the importance of the fatty acid-derived hydroperoxide in PG synthesis by kidney medulla. We conclude that 13-HPODE is an inhibitor of renomedullary cyclooxygenase and may have functional effects within the kidney.</p>","PeriodicalId":21140,"journal":{"name":"Research communications in chemical pathology and pharmacology","volume":"83 1","pages":"51-60"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19155942","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}
The teratogenicity of 13-cis-retinoic acid (RA) either administered alone or following pretreatment with phenobarbital sodium (PB), was assessed. Groups of gravid CF-1 mice were administered dosages of either 10, 100, 200, or 400 mg/kg of RA orally on either days 11, 12 or 13 of gestation, in order to determine structural alterations. In addition, separate groups of mice were orally pretreated with 80 mg/kg/day of PB on days 7 through 10 of gestation prior to the administration of RA. Skeletal alterations attributed to maternal administration of either 100, 200 or 400 mg/kg of RA on days 11-13 included delayed ossification of the limbs and supraoccipital bone, the presence of extra ribs, and various sternebral defects. Soft tissue alterations included cleft palate and dilation of the renal pelves which occurred following maternal exposure on days 11 and 12-13, respectively. Significant decreases in the incidence of cleft palate and delayed ossification of the limbs were observed in those dams administered RA on days 11 or 12, respectively, following prior treatment with PB. These data suggest that administration of PB, a prototypical hepatic microsomal enzyme inducer, may partially antagonize the teratogenicity of RA.
{"title":"Teratogenicity of 13-cis retinoic acid and phenobarbital sodium in CF-1 mice.","authors":"M M Yuschak, R F Gautieri","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The teratogenicity of 13-cis-retinoic acid (RA) either administered alone or following pretreatment with phenobarbital sodium (PB), was assessed. Groups of gravid CF-1 mice were administered dosages of either 10, 100, 200, or 400 mg/kg of RA orally on either days 11, 12 or 13 of gestation, in order to determine structural alterations. In addition, separate groups of mice were orally pretreated with 80 mg/kg/day of PB on days 7 through 10 of gestation prior to the administration of RA. Skeletal alterations attributed to maternal administration of either 100, 200 or 400 mg/kg of RA on days 11-13 included delayed ossification of the limbs and supraoccipital bone, the presence of extra ribs, and various sternebral defects. Soft tissue alterations included cleft palate and dilation of the renal pelves which occurred following maternal exposure on days 11 and 12-13, respectively. Significant decreases in the incidence of cleft palate and delayed ossification of the limbs were observed in those dams administered RA on days 11 or 12, respectively, following prior treatment with PB. These data suggest that administration of PB, a prototypical hepatic microsomal enzyme inducer, may partially antagonize the teratogenicity of RA.</p>","PeriodicalId":21140,"journal":{"name":"Research communications in chemical pathology and pharmacology","volume":"82 3","pages":"259-78"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19114434","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}
This study investigates the use of the buccal route of administration in the delivery of human insulin in rats. Streptozocin-induced diabetic female Wistar rats were used in this study. Insulin (100 U) either free (i.e., insulin solution) or associated with a carrier, namely erythrocyte-ghosts (EG) and liposomes-vesicles (LEV), was administered buccally. Blood samples were collected from the tail over a period of 5 hr. These results indicate that insulin absorption occurred, as evidenced from a decrease in blood glucose concentration, and in the case of free insulin and erythrocyte-ghosts-insulin (EG-INS). The magnitude of the blood glucose level decline was at its maximum of 39.53 mg/dl (at 2 hr) and 26.23 mg/dl (at 4 hr) for free insulin and EG-INS, respectively. No significant difference in the blood glucose level profile was observed after either LEV or liposomes-vesicles-insulin (LEV-INS). This study demonstrates the ability of human insulin to be absorbed from the mouth cavity when it is instilled in the form of a simple solution or EG-INS suspension. This absorption resulted in a definite pharmacological effect but not a significant therapeutic effect.
{"title":"Buccal administration of human insulin in streptozocin-diabetic rats.","authors":"A al-Achi, R Greenwood","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This study investigates the use of the buccal route of administration in the delivery of human insulin in rats. Streptozocin-induced diabetic female Wistar rats were used in this study. Insulin (100 U) either free (i.e., insulin solution) or associated with a carrier, namely erythrocyte-ghosts (EG) and liposomes-vesicles (LEV), was administered buccally. Blood samples were collected from the tail over a period of 5 hr. These results indicate that insulin absorption occurred, as evidenced from a decrease in blood glucose concentration, and in the case of free insulin and erythrocyte-ghosts-insulin (EG-INS). The magnitude of the blood glucose level decline was at its maximum of 39.53 mg/dl (at 2 hr) and 26.23 mg/dl (at 4 hr) for free insulin and EG-INS, respectively. No significant difference in the blood glucose level profile was observed after either LEV or liposomes-vesicles-insulin (LEV-INS). This study demonstrates the ability of human insulin to be absorbed from the mouth cavity when it is instilled in the form of a simple solution or EG-INS suspension. This absorption resulted in a definite pharmacological effect but not a significant therapeutic effect.</p>","PeriodicalId":21140,"journal":{"name":"Research communications in chemical pathology and pharmacology","volume":"82 3","pages":"297-306"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19114437","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}
We investigated the hypothesis that one mechanism underlying fatty acid toxicity is the selective inhibition of rate-limiting and/or regulated tricarboxylic acid cycle and related enzymes by fatty acyl coenzyme A (CoA) derivatives by examining the effects of several fatty acyl CoAs on purified citrate synthase (CS) and glutamate dehydrogenase (GDH). The results indicate that, at pathophysiological levels, palmitoyl CoA, a long-chain acyl CoA, is a potent inhibitor of CS and GDH with IC50 values of 3-15 microM. At much higher levels (in the pathological and toxicological range), octanoyl and decanoyl CoA (medium-chain acyl CoAs) inhibited both enzymes with IC50 values of 0.4-1.6 mM. Butyryl CoA, a short-chain acyl CoA, inhibited CS (IC50 = 0.9 mM) at toxicological levels but inhibited GDH poorly. These results suggest that the long-chain fatty acyl CoA inhibition of CS and GDH may assume some pathophysiological importance in fatty acid toxicity and in metabolic encephalopathies in which organic acidemia is persistent. The findings also provide additional support for the original hypothesis.
{"title":"Differential effects of fatty acyl coenzyme A derivatives on citrate synthase and glutamate dehydrogenase.","authors":"J C Lai, B B Liang, E J Jarvi, A J Cooper, D R Lu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We investigated the hypothesis that one mechanism underlying fatty acid toxicity is the selective inhibition of rate-limiting and/or regulated tricarboxylic acid cycle and related enzymes by fatty acyl coenzyme A (CoA) derivatives by examining the effects of several fatty acyl CoAs on purified citrate synthase (CS) and glutamate dehydrogenase (GDH). The results indicate that, at pathophysiological levels, palmitoyl CoA, a long-chain acyl CoA, is a potent inhibitor of CS and GDH with IC50 values of 3-15 microM. At much higher levels (in the pathological and toxicological range), octanoyl and decanoyl CoA (medium-chain acyl CoAs) inhibited both enzymes with IC50 values of 0.4-1.6 mM. Butyryl CoA, a short-chain acyl CoA, inhibited CS (IC50 = 0.9 mM) at toxicological levels but inhibited GDH poorly. These results suggest that the long-chain fatty acyl CoA inhibition of CS and GDH may assume some pathophysiological importance in fatty acid toxicity and in metabolic encephalopathies in which organic acidemia is persistent. The findings also provide additional support for the original hypothesis.</p>","PeriodicalId":21140,"journal":{"name":"Research communications in chemical pathology and pharmacology","volume":"82 3","pages":"331-8"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19114440","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}
A variety of drugs, known to induce acute attacks in porphyric patients has been found to inhibit the glyoxalase pathway. Glyoxalase I is competitively inhibited by sulphadimidine, oxytetracycline, chloramphenicol, etc. Allylisopropyl acetamide (AIA) seems to inhibit glyoxalase II. This inhibition could play a contributing role in the overproduction of porphyrins in porphyria and thus help explain the mechanism of induction of porphyric attacks. The results indicate, that the Heme pathway and the glyoxalase cycle are closely connected.
{"title":"The influence of porphyrogenic drugs on the glyoxalase enzymes.","authors":"R Van Brummelen, S Myburgh, S H Bissbort","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A variety of drugs, known to induce acute attacks in porphyric patients has been found to inhibit the glyoxalase pathway. Glyoxalase I is competitively inhibited by sulphadimidine, oxytetracycline, chloramphenicol, etc. Allylisopropyl acetamide (AIA) seems to inhibit glyoxalase II. This inhibition could play a contributing role in the overproduction of porphyrins in porphyria and thus help explain the mechanism of induction of porphyric attacks. The results indicate, that the Heme pathway and the glyoxalase cycle are closely connected.</p>","PeriodicalId":21140,"journal":{"name":"Research communications in chemical pathology and pharmacology","volume":"82 3","pages":"339-49"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19115082","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}
H Watanabe, S Yamada, N Yoshikawa, J Kasanuki, S Yoshida, A Tokunaga
Rats that were given an intraperitoneal injection of gold thioglucose (GTG, 0.3 mg/g) developed hemorrhagic lesions in the gastric mucosa 24 hours after the injection. The gastric juice volume and the generation of acid and pepsin were significantly increased 24 hours after the GTG injection (p < 0.01). Simultaneous administration of famotidine (3 mg/kg) with GTG significantly reduced gastric juice secretion and the generation of acid and pepsin (all p < 0.01), as well as suppressing the development of hemorrhagic lesions. These results indicate that there is a relationship between the hemorrhagic lesions induced by GTG and increased acid and pepsin generation. Rats treated with GTG seem to be a useful new animal model for the investigation of pepsin secretion.
{"title":"Effect of famotidine on gastric mucosal lesions induced by gold thioglucose in rats.","authors":"H Watanabe, S Yamada, N Yoshikawa, J Kasanuki, S Yoshida, A Tokunaga","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Rats that were given an intraperitoneal injection of gold thioglucose (GTG, 0.3 mg/g) developed hemorrhagic lesions in the gastric mucosa 24 hours after the injection. The gastric juice volume and the generation of acid and pepsin were significantly increased 24 hours after the GTG injection (p < 0.01). Simultaneous administration of famotidine (3 mg/kg) with GTG significantly reduced gastric juice secretion and the generation of acid and pepsin (all p < 0.01), as well as suppressing the development of hemorrhagic lesions. These results indicate that there is a relationship between the hemorrhagic lesions induced by GTG and increased acid and pepsin generation. Rats treated with GTG seem to be a useful new animal model for the investigation of pepsin secretion.</p>","PeriodicalId":21140,"journal":{"name":"Research communications in chemical pathology and pharmacology","volume":"82 3","pages":"287-95"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19114436","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}
Y Fujita, H I el Belbasi, K S Min, S Onosaka, Y Okada, Y Matsumoto, N Mutoh, K Tanaka
The fate cadmium(Cd) bound to phytochelatin [PC, (gamma-Glu-Cys)n-Gly)] was studied in rats using synthesized 109Cd-PC. Less Cd was absorbed through the digestive tracts than CdCl2, but the ratio of renal Cd to hepatic Cd was higher. After parenteral administration of Cd-PC, Cd was distributed mainly in the liver, kidney, small intestine and pancreas. More Cd was found in the kidney than the liver after Cd-PC (n = 5) administration. Most of the Cd was bound to the high molecular weight fraction in the hepatic cytosol 0.5 hr after administration and moved to the metallothionein fraction at 6 hr. The tissue distribution of Cd was not affected even when free PC (n = 5) was administered 3 hr after or before Cd injection. The distribution in the kidney increased only in the case of the simultaneous administration of Cd with PC. These findings show that the absorbance of Cd bound to PC from the alimentary tract is lower than that of CdCl2 although absorbed Cd is distributed to the kidney more than CdCl2, and Cd is liberated from PC soon after uptake by the cells.
{"title":"Fate of cadmium bound to phytochelatin in rats.","authors":"Y Fujita, H I el Belbasi, K S Min, S Onosaka, Y Okada, Y Matsumoto, N Mutoh, K Tanaka","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The fate cadmium(Cd) bound to phytochelatin [PC, (gamma-Glu-Cys)n-Gly)] was studied in rats using synthesized 109Cd-PC. Less Cd was absorbed through the digestive tracts than CdCl2, but the ratio of renal Cd to hepatic Cd was higher. After parenteral administration of Cd-PC, Cd was distributed mainly in the liver, kidney, small intestine and pancreas. More Cd was found in the kidney than the liver after Cd-PC (n = 5) administration. Most of the Cd was bound to the high molecular weight fraction in the hepatic cytosol 0.5 hr after administration and moved to the metallothionein fraction at 6 hr. The tissue distribution of Cd was not affected even when free PC (n = 5) was administered 3 hr after or before Cd injection. The distribution in the kidney increased only in the case of the simultaneous administration of Cd with PC. These findings show that the absorbance of Cd bound to PC from the alimentary tract is lower than that of CdCl2 although absorbed Cd is distributed to the kidney more than CdCl2, and Cd is liberated from PC soon after uptake by the cells.</p>","PeriodicalId":21140,"journal":{"name":"Research communications in chemical pathology and pharmacology","volume":"82 3","pages":"357-65"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19115084","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}
The nonselective beta adrenergic agonist isoproterenol, the beta-2 selective agonist clenbuterol and, to a lesser extent, the beta-1 selective agonists dobutamine and prenalterol reduced locomotor activity of rats in a dose-dependent manner. These effects were antagonized by the beta adrenergic antagonist propranolol, suggesting mediation by beta adrenergic receptors. The hydrophilic beta adrenergic antagonist CGP-12177, which crosses the blood-brain barrier poorly, also blocked the effect of clenbuterol on locomotor activity with a potency similar to propranolol, suggesting that stimulation of peripheral beta adrenergic receptors is sufficient for reducing locomotor activity.
{"title":"Reduced locomotor activity of rats mediated by peripheral beta adrenergic receptors.","authors":"J M O'Donnell","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The nonselective beta adrenergic agonist isoproterenol, the beta-2 selective agonist clenbuterol and, to a lesser extent, the beta-1 selective agonists dobutamine and prenalterol reduced locomotor activity of rats in a dose-dependent manner. These effects were antagonized by the beta adrenergic antagonist propranolol, suggesting mediation by beta adrenergic receptors. The hydrophilic beta adrenergic antagonist CGP-12177, which crosses the blood-brain barrier poorly, also blocked the effect of clenbuterol on locomotor activity with a potency similar to propranolol, suggesting that stimulation of peripheral beta adrenergic receptors is sufficient for reducing locomotor activity.</p>","PeriodicalId":21140,"journal":{"name":"Research communications in chemical pathology and pharmacology","volume":"82 3","pages":"375-8"},"PeriodicalIF":0.0,"publicationDate":"1993-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18903819","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}