Mutagenic investigation of peppermint oil in the Salmonella/mammalian-microsome test.
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Animals↗
Biomedical subjects
P H Andersen
Publications and source records attributed to P H Andersen.
Characterization of the beta-adrenergic receptor on the human platelet: a beta 2-subtype.
The human platelet beta-adrenergic receptor was characterized by using the ability of different drugs to stimulate the adenylate cyclase activity and the effects of various beta-antagonists to block the isoprenaline-stimulated adenylate cyclase activity. Isoprenaline was found 10 times more potent than adrenaline and 1000 times more potent than noradrenaline in stimulating the adenylate cyclase activity in these cells. Isoprenaline-stimulated activity was blocked by the non-selective beta-antagonists propranolol and alprenolol and by the beta 2-selective antagonist IPS 339 and prenalterol. Metoprolol, a beta 1-selective blocker, was without effect on the isoprenaline-stimulated adenylate cyclase activity. We conclude from our findings that the beta-adrenergic receptor type on the human platelet is mainly of the beta 2-subtype.
Adenylyl Cyclases↗
No change in rat cerebral cortex calmodulin content following chronic treatment with lithium, reserpine, imipramine, and lithium combined with reserpine or imipramine.
Rats were treated 2-3 weeks with lithium, reserpine, imipramine, and combinations of lithium with reserpine or imipramine. Lithium was given in the diet, while the other drugs were dissolved in 0.9% saline and given intraperitoneally twice daily. The control and lithium groups received only vehicle injections. Twenty-four hours after the last injection the rats were decapitated and the cerebral cortex dissected. The tissue was sliced and the noradrenaline-stimulated cyclic AMP accumulation determined or the tissue was homogenized and centrifuged at 10,000 X g for 30 min. and the calmodulin content determined in the pellet and the supernatant. Reserpine treatment was found to cause an 50% increase in the noradrenaline-stimulated cyclic AMP accumulation, while treatment with imipramine and the combination lithium-imipramine decreased the noradrenaline-stimulated cyclic AMP accumulation by 40%. The tissue content of calmodulin was, however, found unaltered by all treatments.
Animals↗
Forskolin-stimulated adenylate cyclase activity in rat cerebral cortex following chronic treatment with psychotropic drugs.
Rats were treated with lithium, imipramine, reserpine, and lithium combined with imipramine or reserpine. Lithium was given in the diet (40 mmol/kg) resulting in a serum-Li+ level of 0.5-0.6 mmol/l. Other drugs were dissolved in 0.9% saline and given intraperitoneally once or twice daily. After 3 weeks of treatment, forskolin-stimulated adenylate cyclase activity was measured in cerebral cortex homogenates. Reserpine did not affect the forskolin stimulation, while both imipramine and lithium caused a decrease in this activity. The combined treatments lithium-imipramine and lithium-reserpine also exhibited a clear decrease in forskolin stimulation, but the effect of concomitant lithium and imipramine treatment did not differ from the effect seen after any of the treatments alone. The unstimulated activity was unaltered by all treatments. The inhibition of lithium and imipramine on the forskolin stimulation indicates an interference of these two drugs with the forskolin-mediated activation of the adenylate cyclase.
Adenylyl Cyclases↗
Lithium inhibition of forskolin-stimulated adenylate cyclase.
The lithium sensitivity of forskolin- and fluoride-stimulated adenylate cyclase activity was investigated in rat brain homogenates in vivo and in vitro. The unstimulated and fluoride-stimulated activity was not affected by lithium, while the forskolin stimulation exhibited a pronounced inhibition by this cation. Furthermore, if Mn2+ was substituted for Mg2+ in the assay media, the forskolin-stimulated activity was even more sensitive to lithium. The results indicate an action of lithium mainly on the catalytic moiety in the adenylate cyclase system. However, the effect cannot be direct on this protein, since the unstimulated activity was unaffected. The action is rather on the microenvironment surrounding this protein, thereby interfering with a possible conformational change of the adenylate cyclase of importance for the activation of this enzyme.
Adenylyl Cyclase Inhibitors↗
Characterization of and drug influence on a calmodulinsensitive phosphodiesterase purified from bovine brain.
A calmodulin-sensitive phosphodiesterase was purified from bovine brain. The purification procedure involved ammonium sulphate fractionation, two chromatographic steps on DEAE-cellulose, gel-filtration on Sephadex G-200, and finally one DEAE-cellulose run, and gave a 2300-fold purification. The purified phosphodiesterase had a Vmax for cyclic AMP of 126 mumol/mg protein X min. and was activated 8-fold by addition of calmodulin and calcium. According to SDS-electrophoresis the purified enzyme contained one major peptide of 59,000 daltons, but the preparation was not homogeneous. The enzyme was characterized kinetically and with regard to the effect of cations, pH temperature, and nucleotides. Furthermore, the influence in vitro on enzyme activity of several classes of drugs, e.g. antidepressants, neuroleptics, antiallergics, platelet inhibitors, and some "reference phosphodiesterase inhibitors" was investigated.
2',3'-Cyclic-Nucleotide Phosphodiesterases↗
Cyclic AMP phosphodiesterase activity in rat brain following chronic treatment with lithium, imipramine, reserpine, and combinations of lithium with imipramine or reserpine.
The adaptability of the cyclic AMP phosphodiesterase (PDE) following chronic treatment (4-6 weeks) with lithium, reserpine, imipramine, and combinations of lithium with imipramine or reserpine has been studied in rat brain tissue. All drugs, except lithium, were given intraperitoneally once a day. Control animals received only vehicle. Lithium was given in the diet in a concentration yielding a plasma level of 0.5-0.6 mmol/l. The PDE activity was measured in homogenates from cerebral cortex and "limbic" forebrain. These two brain areas were both found to contain three types of PDE activity. One was mainly associated with the pellet after a 10,000 X g centrifugation for 10 min. This enzyme hydrolyzed both cyclic AMP and cyclic GMP with a Km value of 130 +/- 48 microM for cyclic AMP, but was insensitive to calcium and calmodulin. Two types were mainly found in the supernatant after the centrifugation with Km values cyclic AMP of 300 +/- 108 microM and 4 +/- 3 microM, respectively. The former hydrolyzed both cyclic AMP and cyclic GMP and was stimulated 7-fold by calcium and calmodulin, while the latter only hydrolyzed cyclic AMP and was insensitive to calcium and calmodulin. None of the treatments affected the "pellet" enzyme or the low affinity enzyme from the supernatant. However, lithium treatment, even combined with reserpine or imipramine, increased the high affinity enzyme. This increase was also apparent in the DEAE-ion exchange chromatographic profile of the PDE enzymes.
3',5'-Cyclic-AMP Phosphodiesterases↗
Hepatic adenoma. Observations after estrogen withdrawal.
A case of ruptured, benign hepatic adenoma occurred in a young woman taking oral contraceptives. Our observation of this patient after biopsy and control of hemorrhage is the subject of this report. We support the concept that these tumors may regress or remain dormant after estrogen withdrawal, and question the need for routine resection of benign hepatic adenomas. Further observations of growth patterns after estrogen withdrawal are needed.
Adult↗
Gastrostomy. An evaluation of the Dragstedt method.
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Adolescent↗
Mutagenic investigation of flavourings: dimethyl succinate, ethyl pyruvate and aconitic acid are negative in the Salmonella/mammalian-microsome test.
Three flavourings: dimethyl succinate, ethyl pyruvate and aconitic acid, commonly used in candy, beverages, and baked goods, were tested in the Salmonella/mammalian-microsome test. Tester strains were TA 1535, TA 100, TA 1537 and TA 98 and doses were 32, 160, 800, 4000 and 20 000 micrograms per plate. All tests were performed with and without the S9 fraction from Aroclor induced rat liver. None of the flavourings showed mutagenic potential. These results support the classification made by the Council of Europe, List I (1981).
Aconitic Acid↗
Effects of captopril on ambulatory blood pressure, renal and cardiac function in microalbuminuric type 1 diabetic patients.
OBJECTIVE: To study the effect of Captopril on ambulatory blood pressure, renal and cardiac function and extracellular volume in microalbuminuric Type 1 diabetic patients. DESIGN: Randomized, double blind placebo controlled study of two years duration. SETTING: University clinic. PATIENTS: Twenty-two patients without hypertension. INTERVENTION: Patients received 50 mg Captopril or placebo twice a day. MEASUREMENTS: Ambulatory blood pressure, renal function, extracellular volume, and echocardiographic indices of cardiac function and dimensions were assessed annually. Clinic blood pressure and urinary albumin excretion were measured every 3 months. RESULTS: Twenty-four hour mean arterial blood pressure was unchanged in the Captopril group (mean +/- SD) (baseline 93 +/- 4 and follow up 91 +/- 8 mmHg) and in the placebo group (96 +/- 7 and 97 +/- 10 mmHg, NS). Night/day ratio of blood pressure was unaffected. Glomerular filtration rate was unchanged and renal plasma flow increased in the Captopril (557 +/- 97 and 600 +/- 112 ml min-1) versus the placebo group (574 +/- 85 and 535 ml min-1, p = 0.05). Filtration fraction was reduced in the Captopril versus the placebo group (p < 0.05). Extracellular volume and echocardiographically derived parameters were unaffected. The relative change in day time mean arterial blood pressure in the Captopril group correlated with changes in urinary albumin excretion (Spearmans r = 0.85, p < 0.05) unlike clinic mean arterial blood pressure (r = 0.33, p = 0.35). CONCLUSION: Diurnal rhythm of blood pressure was unaffected by long term administration of Captopril. Renal plasma flow was increased and filtration fraction reduced. A significant association between changes in urinary albumin excretion and blood pressure after Captopril was revealed only by the implementation of ambulatory blood pressure measurements.
Adult↗