摘要:

Abstract:Dibutyryl cyclic AMP, and α‐ and β‐adrenoceptor stimulators are all able to elicit inotropic effects, α‐ and β‐Adrenoceptor stimulation are known to change each myocardial contraction‐relaxation cycle differently. In order to elucidate the myocardial function of cyclic AMP the effects of dibutyryl cyclic AMP on the contraction‐relaxation cycle of isolated rat heart papillary muscle were examined and compared to the effects of α‐ and β‐adrenoceptor stimulation, respectively. Dibutyryl cyclic AMP (in the presence of propranolol) increased developed tension (Tmax) by 18%, rate of tension rise (T′max) by 46%, rate of tension fall (T′min) by 62% and onset‐rate of relaxation (T″min) by 136%. These changes in the contraction‐relaxation cycle were strikingly similar to those produced by isoprenaline (β‐adrenoceptor stimulation). The response to dibutyryl cyclic AMP, however, developed much slowlier than did the response to isoprenaline. The latter effect was associated with cyclic AMP elevation in a way indicating a trigger function for cyclic AMP. The α‐adrenoceptor stimulation (by phenylephrine combined with propranolol), however, increased measures both for contraction and for relaxation by about the same degree, and the effects occurred without changes of cyclic AMP contents. Phenylephrine alone (combined α‐ and β‐adrenoceptor stimulation) elicited a substantial cyclic AMP elevation but gave mechanical effects only slightly different from the pure α‐adrenergic response. Thus cyclic AMP effects did not seem to be fully expressed in this case. As a whole, the results indicate that the effects of both dibutyryl cyclic AMP and of isoprenaline are mediated by the cyclic AMP‐system while α

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00874.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The splake, a popular game fish, is a crossbreed which must be reared in nurseries. The fish are marked under anaesthesia for later study. We analyzed the effect of a common anaesthetic, tricaine (MS‐222), on the metabolism of foreign compounds in the liver and duodenum of the splake. In the liver and to some extent in the duodenum, aryl hydrocarbon hydroxylase and epoxide hydrase activities were reduced during treatments. The ethoxycoumarin O‐deethylase activities were not affected in either the liver or duodenum. Tricaine significantly decreased the hepatic UDP‐glucuronosyltransferase activity. The decrease was greater when the aglycone used was p‐nitrophenol than with methylumbelliferone. A similar effect was also found after trypsin treatment of the microsomes. No significant decrease in the UDP‐glucuronosyltransferase activity was detected in the duodenal mucosa. This was the case when both p‐nitrophenol and methylumbelliferone were used a

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00875.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The effect of digoxin on both the negative inotropic action and the myocardial uptake of a new anthracycline antibiotic violamycin B1 has been studied in isolated guinea pig atria. In concentrations upto 2.0×10−7M/l digoxin did not prevent the negative inotropic effect of violamycin B1 caused by the concentrations of 0.7 and 5.0×10−4M/l. Corresponding to these findings, the uptake of violamycin B1 into the atrial tissue was not influenced by digoxin. However, violamycin B1 in the cardiotoxic concentration of 5.0×10−4M/l decreased the atrial uptake of digoxin. It is suggested that no competition seems to exist in myocardial uptake of anthracycline antibiotics and cardiac gl

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00876.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Primary suspensions of isolated liver cells, prepared from rat livers perfused with Ca++free buffer and 0.05% collagenase, were used for studies of sulfadimidine and sulfanilamide uptake and metabolism at various temperatures (29°–41°) and pH (6.4–7.8). The intracellular: extracellular ratio for sulfanilamide was found to be insensitive to both temperature and pH variations, while the corresponding ratio for sulfadimidine was pH dependent but insensitive to temperature variation. Decreasing pH increased the cell content of sulfadimidine. Sulfanilamide was metabolized by acetylation only, while sulfadimidine gave rise to several metabolites. The rate of sulfanilamide acetylation in primary cell suspensions was of the same order of magnitude as the acetylation rate of sulfanilamide published previously for the intact organ. Sulfanilamide was acetylated at the highest rate in the pH‐region from 7.0 to 7.5, while sulfadimidine was metabolized most rapidly between pH 6.7 and 7.3. At pH 7.5 sulfadimidine was metabolized at a rate only 35% of the rate at pH 7.3. The acetylation rate of both drugs increased with increasing temperature, approximately 5% per degree celcius, and exhibited a Q1

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00877.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Theophylline and the surface active agents specified below were instilled into the jejunum of anaesthetized rats, and the cAMP levels in the mucosal tissue determined after 7 1/2 and 15 min. incubationin vivo.Most experiments were done in rats prepared with two tied intestinal loops; one of these served as the control loop and the other as the stimulated loop. The surfactants (mmol/l) included dodecylsulphate (17), dioctylsulphosuccinate (5.6), cetrimonium bromide (4.1), deoxycholic acid (2.4 and 3.6) and Lubrol WX (0.5% w/v). Theophylline (10 mmol/l) caused a substantial increase in cAMP (110%±17, n=7 and 60%±8.9, n=10, respectively) and dodecylsulphate a minor and transitory increase (28.1%±3.8, n=10 and 11.7%±4.9, n=8). The other agents were without stimulatory effect on cAMP, allthough like dodecylsulphate they may significantly affect normal intestinal cation and glucose transport under these conditions. The results, therefore, do not suggest that stimulation of cAMP and intestinal secretion induced thereby is any significant phenomenon in the overall hydragogue effect of these agents, at least not in short term jejunal experime

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00878.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Distribution of radioactivity in rats, serum levels in human volunteers and rats and elimination of radioactivity in volunteers, rats, and mice following oral administration of14C‐labelled THIP have been investigated. Peak values of radioactivity in the organs and in serum were seen half an hour after administration, indicating a rapid absorption. Highest concentrations of radioactivity were found in the kidneys, but radioactivity was seen in all investigated tissues including the brain. The radioactivity was mainly excreted with urine (84–93%). Thin‐layer chromatography of urine from volunteers, rats, and mice showed that most of the excreted radioactivity corresponds to unchanged THIP. Three metabolites were found in urine from rats each in amounts of 2–7% of the total dose given. Two of these metabolites were also found in urine from the volunteers in amounts of 30–35% and<2%, respectively, and in urine from mice in amounts of 21% and 6% of the total dose, respectively. No radioactivity corresponding to unchanged THIP was found in faeces indicating complete absorption of THIP following oral administration. One of the metabolites, the main one in man and mouse, seemed to be a glucuronic acid conjugate of THIP, but the chemical structure of the metabolites has not yet been es

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00879.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The effect of ethanol on RNA and protein synthesis was studied in regenerating rat liver. Partial hepatectomy stimulated the activity of ornithine decarboxylase (ODC) and that of tyrosine aminotransferase (TAT) as well as the synthesis of RNA. The intubation of ethanol (3 g/kg) 1 hr before the operation inhibited the stimulation of ODC and TAT when measured 4 hrs after the operation. Ethanol administration also inhibited RNA synthesis. By using inhibitors of alcohol dehydrogenase and aldehyde dehydrogenase it was shown that the inhibition of RNA synthesis (and also that of protein synthesis) was most probably a direct effect of ethanol itself. When RNA synthesis was measuredin vitroin purified nuclei, ethanol inhibited the incorporation of nucleotides to RNA. It is suggested that ethanol inhibits protein synthesis in regenerating rat liver at the transcriptional level by interfering in nuclei with the synthesis of RNA.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00880.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Metronidazole was given to rats with experimentally induced inflammation to evaluate whether the drug has any antiinflammatory effect. Inflammation was caused by injection of Freund's complete adjuvant into a paw. The oedema of the paw measured on the 4th day was not influenced after metronidazole 20 mg/kg/day or 160 mg/kg/day, whereas phenylbutazone 80 mg/kg/day significantly decreased the volume of the paw. The concentration of orosomucoid did not differ in the group of rats given metronidazole 20 mg/kg/day as compared to the control group. However, the orosomucoid concentration was lower in the group given metronidazole 160 mg/kg/day, as was the case in the phenylbutazone group. In groups of rats with polyarthritis studied on the 14th and 21st day there was no difference of arthritic index, volume of paw or orosomucoid concentration in neither low nor high dose metronidazole as compared to the control groups. The phenylbutazone groups, however, showed a lower arthritic index, lower volume of paw and lower orosomucoid concentration.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00881.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Rat liver parenchymal cells were isolated and incubated for 80 min. in buffered salt solutions.14C‐valine incorporation in the presence of a high concentration of unlabelled valine (4.2 mM) was taken as a measure of protein synthesis. The pH dependence of the synthesis of cell and medium proteins was studied at pH values varying from 6.6 to 7.9. The results showed that maximum protein synthesis occurred close to the physiological pH value. Protein synthesis was reduced at both lower and higher pH‐values. Protein synthesis was inhibited by the addition of ethanol (30 mM). The relative inhibition caused by ethanol got more pronounced as the pH of the hepatocyte suspensions was lowered. The metabolism of ethanol resulted in lowering of the pH in cell suspensions. It is suggested that the depression of protein synthesis by ethanol could be mediated by the fall in pH due to ethanol metabol

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00882.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Several drugs, mainly polycyclic amines, are accumulated in melanin‐containing tissues. They are bound to preformed melanin (bothin vivoandin vitro). Thiouracil is accumulated into melanin according to another principle: It is incorporated as a false precursor during melanin formation. It is thus taken up only in growing melanin, e.g. in the eye of pigmented mouse foetuses or in melanomas. The acceptance of a foreign substance during the formation of a foetal tissue seems theoretically important. We are also interested in the practical viewpoint of using false melanin precursors as selective melanoma seekers. Some related substances are therefore compared with respect to incorporation into growing melanin. The thiouracil uptake in the ocular melanin of a 5 day old mouse was 276 times higher than that of a 3 month old mouse based on weight units of melanin. Thiourea is incorporated in growing melanin as well but also binds slightly to preformed melanin. Uracil and fluorouracil showed no specific uptake into growing melanin. It thus seems as if the sulfur is essential for the incorporation into the melanin polymer.35S‐thiouracil and 2‐thio(2‐14C)uracil showed the same high uptake, indicating that at least part of the uracil moiety is incorporated together with the sulfur. There seems to be a relation between the property to be incorporated into melanin and the thyrostatic activity. Both in the formation of melanin and thyroid hormones, tyrosine is the physiological precursor and both reactions are catalyzed by oxidizing enzymes. Properly labelled thiouracil derivatives seem to be promising melanoma seekers for diagnostic and radiotherapeutic p

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb00883.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY