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Biomedical subjects

G Johansson

Publications and source records attributed to G Johansson.

At least 325 records · Page 18Linked to original sources

DSP4-induced two-way active avoidance impairment in rats: involvement of central and not peripheral noradrenaline depletion.

N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4) (50 mg/kg IP), a new selective noradrenaline (NA) neurotoxin, was found to cause a severe impairment of the acquisition of a two-way active avoidance task 1 week following administration, an effect that was blocked by the selective NA uptake inhibitor desipramine. In a second experiment, systemically injected 6-OHDA (2 x 30 mg/kg IP) was not found to cause any avoidance impairment, although its effects upon peripheral NA were still evident 21 days after administration: The peripheral NA depletion caused by DSP4 almost disappeared 14 days after injection. In a third experiment, the avoidance impairment induced by DSP4 was produced even 10 weeks after treatment. Data from both the shuttlebox experiment and an activity box experiment suggest that the acquisition impairment is not readily explained on the basis of some deficit in spontaneous behavior or an altered perception of pain. The present data suggest that the effect of DSP4 upon active avoidance acquisition is mediated via central, and not peripheral NA neurons.

Amines↗

Paracetamol plus supplementary doses of codeine. An analgesic study of repeated doses.

A double-blind, multicentre analgesic trial was carried out in patients suffering from pain after removal of an impacted lower wisdom tooth. 266 patients were evaluated after random allocation to treatment with paracetamol 500 mg, paracetamol 500 mg plus codeine 20 mg, paracetamol 500 mg plus codeine 30 mg, or paracetamol 500 mg plus codeine 40 mg. On the day of surgery the patients assessed their own pain intensity hourly on a visual analogue scale. The analysis of the results was carried out according to the method which considered repeated dose intake. A statiscally significant dose-response relationship was obtained between the supplementary doses of codeine and analgesic efficacy. In the comparison of side effects, their frequency increased with increasing amounts of codeine. In clinical practice codeine 30 mg appeared to be the optimal supplement for paracetamol 500 mg.

Acetaminophen↗

Reoperation for primary hyperparathyroidism.

The reasons for failure of the initial exploration and the results of reoperation were analyzed in 53 patients with a diagnosis of primary hyperparathyroidism, 29 of whom were referred after initial operations elsewhere. Seventy-nine reoperations were performed. Sternotomy was used in 15 patients, and in retrospect was necessary in only 5. There was no operative mortality. The reasons for initial failure were incorrect diagnosis in 6 patients, true recurrence in 4 and persistent disease in 43. Persistence was caused by surgical failure in two thirds and pathology failure in one third. Of 47 patients reoperated on for hyperparathyroidism, 39 (83 percent) were cured, a rate warranting this type of surgery. Analysis of a long-term series of initial operations demonstrates a persistence rate of 5 percent (24 of 461) and a recurrence rate of 1 percent (4 of 461) in this disease. The need for reoperation was les than 1 percent over the recent 5 year period.

Female↗

Urinary excretion of urate in renal calcium stone disease and in renal tubular acidification disturbances.

The 24-hour urinary excretion of urate was investigated in 467 consecutive stone formers - 350 males and 117 females - and 89 apparently healthy controls with no history of stone disease. Males had a higher urinary excretion of urate than females but there was no difference between stone formers and controls. Urinary urate decreased with advancing age. Patients with a proximal tubular acidification defect had a lower urate clearance than patients with a normal acidification of the urine. Patients with hyperuricosuria presented a higher frequency of stone operations but a lower stone episode rate than matched normouricosuric stone formers. Hyperuricosuria in combination with renal acidification defects was associated with the highest frequency of stone operations. Hyperuricosuric patients also had a higher excretion of calcium than normouricosuric patients. Hyperuricosuria is not a common feature of calcium stone disease but when present is associated with a more severe stone disease in terms of stone operations.

Acidosis, Renal Tubular↗

Effects of bendroflumethiazide on urate metabolism during treatment of patients with renal stones.

Treatment with bendroflumethiazide (2.5 mg, twice daily with potassium supplements) in 63 patients with calcium-containing renal stones for a minimum period of 1 year (average duration of treatment 2.6 years) increased the serum urate values in all patients with an average of 90 mumol./l. (conversion factor: 1 mmol. urate = 183 mg.). Despite this the mean urinary urate excretion was unchanged. In the individual patient a systematic effect of therapy was evident since in patients with low pretreatment values the thiazide increased the urate output while in those with the highest levels before therapy it caused a reduction. In most patients there was a reduction of the urate clearance during therapy, which was most evident in those with the highest pretreatment clearance values. In patients with incomplete types of renal acidification defects the same effects were seen on urate metabolism during thiazide treatment as in the other, idiopathic, stone formers. Although the possible role of urate in calcium stone formation has not been definitely settled this study shows that thiazides do not cause hyperuricosuria and hence their beneficial effects on calcium excretion are not counteracted.

Adult↗

Metabolic and hormonal response to physical exercise during beta 1-selective and non-selective beta-blockade.

The effects of a beta 1-selective (metoprolol, 150 mg per day) and a non-selective beta-blocking agent (propranolol, 120 mg per day) on metabolic and hormonal responses to physical exercise (a 30 min bicycle ergometer test) were investigated against placebo in seven healthy male volunteers with a double blind cross-over design. The blood glucose level remained unchanged during placebo, it tended to increase during metoprolol, whereas it decreased during propranolol. Both metoprolol and propranolol counteracted the exercise-induced increase in plasma free fatty acids and caused a slight decrease in muscle glycogenolysis. The increase in blood lactate concentration during exercise was not influenced by beta-blockade. The secretion of glucagon and cortisol was not modified significantly by beta-blockade, whereas the growth hormone response to exercise was promoted equally by both beta-blocking agents. It has been assumed previously that, during treatment with beta-blocking agents, diminished hepatic gluconeogenesis, caused by the lack of lactate or free fatty acids, may result in a decline in blood glucose levels. The present results indicate that an inhibition of beta 2-mediated hepatic glycogenolysis by propranolol may also influence blood glucose homeostasis during exercise.

Adrenergic beta-Antagonists↗

The TCDD receptor in rat intestinal mucosa and its possible dietary ligands.

Induction of aryl hydrocarbon hydroxylase (AHH) by polycyclic aromatic hydrocarbons and other inducers such as 2,3,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to occur following binding of the inducer to a soluble receptor protein similar to steroid hormone receptors. This receptor is usually called the TCDD receptor, since TCDD has the highest affinity of all known ligands for the receptor. In the present paper a receptor for TCDD in cytosol from rat intestinal mucosa has been studied, using isoelectric focusing in polyacrylamide gel. This receptor's biochemical properties were found to be similar to those of the TCDD-receptor in rat liver cytosol. The dissociation constant (Kd) of the 3H-TCDD-receptor complex in rat intestinal mucosa was 0.7-3.1 nM, and it was present at a concentration of 70-80 fmol/mg protein. Starvation did not significantly increase the receptor level. The affinities of some potential dietary ligands for the TCDD receptor in rat intestinal mucosa were also studied. Indole-3-carbinol had 1/2,600 of the affinity of TCDD for the receptor protein. Butylated hydroxyanisole (BHA), transstilbene oxide and quercetinpentamethylether competed even more weakly with 3H-TCDD for binding to the receptor. The biological significance of the occurrence of low-affinity ligands of dietary origin for the TCDD receptor is uncertain at the present time.

Animals↗

Effects of magnesium hydroxide in renal stone disease.

Magnesium is a known inhibitor of the formation of calcium oxalate crystals in the urine and was proposed for prophylactic treatment in renal stone disease as early as the 17th and 18th centuries. We have treated 55 patients with recurrent renal calcium stone disease without signs of magnesium deficiency (normal serum magnesium, urinary magnesium, intracellular magnesium in muscle biopsies, gastrointestinal absorption of 28Mg, and magnesium loading test) from our outpatient stone clinic for up to four years with 500 mg Mg2+, in the form of Mg(OH)2, daily. The mean stone episode rate before therapy was 0.8 stones/year/patient. Forty-three recurrent renal calcium stone-formers without medical therapy served as controls. Serum magnesium increased initially but after one year returned to the pretreatment level. Urinary magnesium excretion increased promptly and remained elevated during the follow-up period. The urinary calcium excretion remained unchanged. The magnesium/calcium ratio in the urine increased and approached a value earlier found in healthy subjects without stone disease. Urinary citrate increased on therapy when analysed after three years of treatment. The mean stone episode rate decreased from 0.8 to 0.08 stones/year on treatment and 85% of the patients remained free of recurrence during follow-up, whereas 59% of the patients in the control group continued their stone formation. Side effects were few. Magnesium treatment in renal calcium stone disease is effective with few side effects. No clinical signs of magnesium excess were observed.

Adult↗

The alcoholic patient and surgical stress.

In order to find out how the response to operative trauma is influenced by chronic alcohol consumption, 53 patients (28 alcoholics and 25 non-alcoholics) were investigated. The chronic alcoholic was defined as a person having a regular, daily alcohol consumption of over 70 g pure alcohol for at least 3 years. The mean annual consumption in the patients studied was 52 litres pure alcohol (143 ml/day). The investigation was also designed to determine whether the pre-operative infusion of alcohol could prevent the withdrawal syndrome and in that way alter the stress response. The results clearly showed a diminished adrenocortical response to surgical stress in alcoholic patients. While it was possible to suppress some catecholamine-mediated withdrawal symptoms by pre-operative alcohol infusion this did not influence the stress response in any way. It is concluded that complications under anaesthesia and in convalescence in alcoholic patients are not only the consequence of the withdrawal but rather of the general toxic effects of alcohol especially on the endocrine and metabolic functions.

Alcoholism↗

Effect of propranolol on myocardial cell necroses and blood levels of catecholamines in pigs subjected to stress.

The degree of myocardial cell necroses in pigs exposed to stress induced by a myorelaxant (succinylcholine) for about 12 min. was investigated. The Beta-adrenoceptor block propranolol was given in varying doses prior to the induced stress. The degree of necroses in these pigs was evaluated according to a point scale, ranging from 0 to 6 points, and compared with the changes found in untreated controls following stress. The blood levels of noradrenaline and adrenaline were assayed before, during an immediately after the period of stress. No protective effect of propranolol on the cardiac lesions was found when the drug was administered intravenously in a single dose of either 1 mg or 3 mg per kg. During the period of stress the blood levels of noradrenaline were high, indicating a high degree of activity in the sympatho-adrenal system. Propranolol in a single dose of 10 mg per kg intravenously reduced the number and size of heart lesions, while the blood levels of the catecholamines were lower under stress than after administration of 1 and 3 mg propranolol. After oral treatment with propranolol, 120 mg three times a day for 6 or 7 days, an almost complete absence of heart cell necrosis after the stress was obtained. The activity of the sympatho-adrenal system was elevated, as reflected by the high blood levels of catecholamines. The results indicate that stress-induced heart cell necrosis is mediated via the activity of the sympatho-adrenal system. The difference between a single and repeated doses of propranolol in protecting the heart suggests a complex of the adrenergic Beta-receptor blocker.

Animals↗

Renal handling of urate in patients with calcium stone disease.

The renal handling of urate was investigated in 28 recurrent calcium stone formers and 12 healthy controls. 12 patients were hyperuricosuric and 16 patients had incomplete proximal or distal acidification defects. Measurements of the glomerular filtration and the tubular reabsorption of filtered urate were made through the pyrazinamide (PZA)-suppression test of urate secretion. Hyperuricosuria could not be explained by defects in the renal handling of urate. Patients with proximal acidification defects had a higher tubular reabsorption of filtered urate than the other subjects. Tubular reabsorption of filtered urate was inversely correlated, and filtered urate escaping reabsorption positively correlated to the 24-hour excretion of urate. In contrast, the PZA-suppressible fraction of urate excretion, which is the net effect of tubular secretion and post-secretory reabsorption and thought to be the main regulator of urate excretion, was not correlated to the 24-hour excretion of urate. It is concluded that the renal handling of urate is basically normal in calcium stone disease, whereas minor deviations may co-exist with renal tubular acidification dysfunction.

Calcium↗

Modification of the metabolic and hormonal response to physical exercise by beta-blocking agents.

Beta-blockade is known to induce muscle fatigue and tendency to hypoglycaemia during prolonged exercise. In addition, beta-blocking agents influence the secretion of many hormones, which regulate glucose. We have investigated the effects of a beta 1-selective (metoprolol) and a non-selective (propranolol) beta-blocking agent on muscle glycogenolysis, blood glucose and lactate levels, plasma levels of free fatty acids and on secretion of insulin, growth hormone, glucagon and cortisol during physical exercise in a double blind cross-over study in seven healthy male volunteers. They participated in three bicycle ergometer tests each lasting for 30 minutes under treatment of placebo (C), metoprolol (M) or propranolol (P). A biopsy was obtained from the vastus lateralis muscle before and immediately after the exercise for muscle glycogen assay. The glycogen concentration after exercise tended to be lower in C than in M or P experiment. The blood glucose level decreased during P and at 30 min there was a significant difference between P and C. The blood lactate was significantly lower before exercise during P than C or M. The increase of blood lactate during exercise, however, was not inhibited by P. Both beta-blocking agents counteracted the increase of FFA during exercise. There was a marked increase of growth hormone secretion during beta-blockade. The secretion of glucagon and cortisol were slightly increased by P and M, but the plasma insulin level was not affected by beta-blockade.

Adult↗

Effect of stress on myocardial cells and blood levels of catecholamines in normal and amygdalectomized pigs.

The effects of restraint stress on heart activity, blood catecholamines and the development of myocardial necrosis were studied in five unoperated and five unsuccessfully amygdalectomized (sham-operated) pigs and compared with six bilaterally amygdalectomized pigs. In the sham-operated and the nonoperated animals, restraint stress often provoked intense tachycardia, as well as considerable elevations of blood catecholamines, particularly noradrenaline, associated with more or less widespread foci of myocardial necrosis. In contrast, the same restraint produced only minor heart rate increase in the six completely amygdalectomized animals; their blood noradrenaline levels were significantly lower and no myocardial necrosis could be detected, either macro- or microscopically. The results indicate that the amygdaloid part of the limbic system and the sympathoadrenal system are of importance in the induction of myocardial necrosis often noted in pigs when exposed to situations of severe mental stress.

Amygdala↗