Increase In Plasma Corticosteroids Research Articles

What price smoking.

The alarming high mortality from lung cancer due to cigarette smoking might obscure awareness of the latter's other possible fateful implications. Authoritative statistical, clinical, autopsy and experimental studies attest to the excess incidence of coronary heart disease in cigarette smokers as compared with nonsmokers. Men of the former group have a threefold increase in the incidence of myocardial infarction. Men with angina pectoris who smoke develop myocardial infarction more frequently than persons with angina who don't smoke. Death from coronary heart disease is substantially higher in smokers than in nonsmokers. It is estimated that one-half of excess death rate is due to smoking. Spain et al (JAMA 224:1005, 1973) reported autopsy findings, noting that in women who died suddenly 62 percent of those who died of coronary heart disease were heavy smokers versus 28 percent of heavy smokers in the group in which the cause of sudden death was other than coronary heart disease. Several investigators ascertained that atherosclerotic changes are substantially greater in smokers than in nonsmokers. According to Auerbach et al (New England J Med 273:775, 1965) the incidence and severity of coronary atherosclerosis in autopsies paralleled the number of cigarettes smoked by the individual and the length of time of smoking. Deposition and accumulation of cholesterol-lipid, the essential feature of vascular atherosclerosis, are aided and accelerated by high serum levels of these compounds in smokers. Too, it is well documented that animals kept on atherogenic diet, when subjected to various types of stress, develop atherosclerosis at an accelerated rate. Nicotine exerts an identical influence. In volunteers as well as in experimental animals there was significant increase in plasma corticosteroids after cigarette smoking or intravenously given nicotine, with consequent vascular atherogenesis. Corticosteroids render myocardial cells more susceptible to the adverse influence of catecholamines. As stated by Lord (JAMA 191:249, 1965), ”heavy cigarette smoking may favor atherogenesis by at least four mechanisms, namely (1) tobacco hypersensitivity with the arterial wall as target organ, (2) by altering the clotting-fibrinolytic balance by shortening platelet survival, (3) by elevation of the free fatty acids in the serum, and (4) by lowering the lateral wall pressure associated with increased velocity of blood flow.” In subjects with coronary atherosclerosis the precise cybernetics and functional adaptability of the heart become restricted, with consequent oxygen deficit in areas supplied by atherosclerotic vessels. In subjects with coronary atherosclerosis, smoking reduces coronary blood flow. Nicotine in cigarette smoke exerts a positive inotropic influence with consequent enhanced contractile action of the myocardium. Thus systole becomes prolonged and diastole shortened, with consequent reduction of coronary blood flow and oxygen supply. The latter is aggravated by high carboxyhemoglobin levels in smokers and also by hydrogen cyanide in cigarette smoke, which interferes with the enzymatic utilization of oxygen. Norepinephrine released by the action of nicotine increases oxygen consumption by myocardial cells. Norepinephrine has great affinity to myocardial cells (cardiotropism). Nicotine induces an increased supply of norepinephrine. The latter, through enhancement of serum free fatty acids increases their deposition in myocardial cells. The inability of these cells to convert the free fatty acids into energy results in impairment of myocardial contractility. Confirmatory evidence of myocardial damage caused by smoking was recorded by Reece et al (Arch Environ Health 24:262, 1972). Dogs subjected to chamber exposure to cigarette smoke and treadmill exercise daily for about one year developed enlargement of both ventricles, decreased activity of enzymes: glutamic oxaloacetic transaminase, lactic dehydrogenase and creatine phosphokinase. It may be added that cardiac function may be weakened by nicotine-induced arrhythmias and conduction disturbances. It seems that the campaign against smoking is an enormous challenge as far as the community and the average individual are concerned. Alas, sometimes even sophisticated attitudes may give way to the urge of euphoria through smoking.

The effects of conditioned behaviour and environmental factors on plasma corticosteroid levels in pigs

Young pigs have been subjected to various conditioning procedures or environmental factors and the changes in plasma corticosteroid levels measured. Pigs in an escape avoidance situation soon learned to avoid most of the shocks. It was possible to demonstrate conditioned suppression of food reinforced operant behaviour. However, neither the escape avoidance conditioning nor the conditioned suppression technique resulted in large increases in plasma corticosteroids compared with those elicited by administration of ACTH. Exposure of pigs to cold, or chasing them, resulted in larger increases of plasma corticosteroids than the conditioning procedures. A marked 24 hr rhythm in plasma corticosteroid levels was demonstrated.

PLASMA CORTICOSTEROID RESPONSE TO METYRAPONE

Abstract An oral metyrapone test has been carried out in 25 patients without endocrine disease. Metyrapone was administered in divided doses over 24 hours. For the assessment of the response a method for the determination of plasma corticosteroids, including Cortisol and 11‐deoxycortisol, has been established. The method is based upon the competitive protein binding principle. The results have been compared with those obtained by measurement of urinary excretion of 17‐hydroxycorticosteroids (17‐OHCS). The average increase in plasma corticosteroids was about 100% from the morning before the start of metyrapone administration till the next morning. With normal pituitary and adrenal function an increase in plasma corticosteroids of at least 5 μg/100 ml can be expected, and the plasma level on the morning after metyrapone should be at least 19 μg/100 ml. The response in urinary 17‐OHCS excretion was greater, an average increase of 200% was observed. It may therefore be expected that determination of 17‐OHCS in 24‐hour urine gives a better discrimination between the normals and those with reduced pituitary reserve than evaluation of the corticosteroid response from a plasma sample. The latter method is, however, easier to carry out, since it does not require urine collections, and can therefore be used in out‐patients.

Adrenocortical function in rats subjected to nutritional deprivation in early life.

SUMMARY Rats were undernourished during the foetal and suckling periods by limiting maternal food intake. Animals were weaned to an unrestricted diet at 25 days of age. Before weaning, the mean plasma corticosteroid concentration in undernourished animals was 39 μg/100 ml compared with 21 μg/100 ml in well-fed controls. At 15–17 weeks of age previously undernourished and control animals did not differ in basal plasma corticosteroid concentration. After stressful stimulation, however, levels were lower in animals subjected to early undernutrition than in controls. It is suggested that nutritional deprivation in infancy resulting in increased plasma corticosteroid levels at that time, permanently modifies the adrenocortical response to stress.

Radiation-induced intestinal damage and the second corticosteroid increase.

SummaryThe magnitude of the ‘second corticosteroid increase’ was determined in x-irradiated rats. Exposures of only the intestine initiated and sustained an increase in plasma corticosteroids from 1–5 days after 1000 R. At 3 days after irradiation, adrenal and plasma levels were dose-dependent.Resection before whole-body x-irradiation, regardless of size of resection or time between resection and irradiation, did not modify corticosteroid responses unless 80 per cent of the small intestine was removed.

Plasma corticosteroids in normal individuals with reference to the circadian rhythm, ACTH test, insulin test, and dexamethasone suppression test.

Fluorimetrically determined plasma corticosteroids were studied in normal individuals. In female subjects the 7 a.m. mean baseline values were significantly higher than those in the male subjects. The adrenal response during the 4-hour ACTH test was significantly higher in female controls than in the male. During insulin test (0.10 i.u./kg) the maximum increase in plasma corticosteroids was 10.7 (3.7-22.8) μg/100 ml (mean and range). No difference in response was observed between male and female controls. During the 1 mg dexamethasone test plasma corticosteroids were suppressed to 2.7 (1.4-4.4) μg/100 ml (mean and range); serum corticotrophin was also significantly suppressed.

Steroid responses to ACTH-like polypeptides.

ABSTRACT The intravenous administration in 6 hr of 75 U of purified porcine ACTH, or of commercial ACTH or of 0.75 mg of a synthetic ACTH-like polypeptide representing, from the N-terminus, amino acid residues 1-24, 1-23, or 1-20 of this hormone produced comparable increases in plasma 11-(OH) corticosteroids. Hence, full corticotropin activity as reflected by increases in plasma corticosteroids was manifested by synthetic molecules about ½ the size of the natural product. Moreover, 0.25 mg of the polypeptide composed of 24 amino acid residues proved to be equal to 75 U of purified porcine ACTH in raising plasma steroids during a prolonged 6-hr intravenous infusion, establishing that ACTH and the shorter synthetic molecule are at least equipotent on a molar basis. A synthetic MSH-type molecule, representing the first 13 amino acid residues of ACTH, did not have this property in man. The 0.75 mg dosage of the polypeptide representing amino acid residues 1–24 yielded the same increase in plasma 11-(OH) corti...

DER INSULINHYPOGLYKÄMIE-TEST ALS FUNKTIONSPRÜFUNG DES HYPOTHALAMUS-HYPOPHYSEN-NEBENNIERENRINDEN-SYSTEMS.

ABSTRACT In 22 subjects determinations of blood sugar and plasma corticosteroids (11-OHCS) were carried out before and during insulin-induced hypoglycaemia. In 17 of these patients (free from endocrine disorders) whose blood sugar fell below 45 mg/100 ml a distinct increase in plasma concentrations of 11-OHCS was noted. The mean maximal increase was found to be 13.1 ±3.7 μg/100 ml (range: 6.4–19.6 μg/100 ml). At sixty minutes p. i. the mean value of 11-OHCS was 25.3 ± 4.3 μg/100 ml. Of another 5 patients (2 with diabetes mellitus) where the blood sugar did not fall below 50 mg/100 ml 4 showed no increase in plasma corticosteroids. In order to effect an increase, in healthy subjects an insulin dose of 0.15 U/kg body weight is recommended. The increase of corticosteroid levels in plasma during hypoglycaemia is considered to be the consequence of stress-induced stimulation of the hypothalamo-pituitary-adrenal axis. This mechanism provides the base of the test in the detection of hypothalamic or pituitary disturbances (hypoglycaemia-test). The pathophysiological significance of this test is compared with that of the metopiron-test and its advantages over the pyrogen-test discussed.

HAEMODYNAMIC CHANGES AND ADRENAL FUNCTION IN MAN DURING INDUCED HYPOGLYCAEMIA.

ABSTRACT Observations were made on healthy volunteers during insulin induced hypoglycaemia (10 cases) and infusion of adrenaline (3 cases) or cortisol (1 case). In all cases a rise in the cardiac output was registered during insulin hypoglycaemia. The mean arterial blood pressure was relatively unchanged and the calculated peripheral vascular resistance decreased in all cases. A temporary rise in plasma corticosteroids was observed. After infusion of adrenaline similar circulatory changes were observed but no rise in plasma corticosteroids was found. Infusion of cortisol caused an increased plasma corticosteroid level but no circulatory changes. It is concluded that liberation of catechol amines and increased adrenocortical activity following hypoglycaemia are not necessarily interdependent.

THE EFFECT OF INTRAVENOUSLY INJECTED CORTICOTROPHIN IN MAN.

ABSTRACT A single intravenous injection of 10 U. S. P. units of a purified ACTH preparation in man produced a maximal effect for at least 4 hours, and the effect was still significant 8 hours after the injection. The biological half life of this preparation was calculated and found to be about 1 hour. When given as an infusion over 8 hours this preparation was calculated to give a maximally active plasma ACTH level for 9½ hours. A significantly increased plasma corticosteroid level was present 12 hours after the beginning of the infusion, and a comparable response was obtained by the same amount of ACTH twice injected intravenously with 4 hours interval. A maximal adrenocortical activity was obtained with 50 U. S. P. units of the same ACTH injected intramuscularly and this persisted for at least 8 hours. The result of this investigation is not consistent with the view often held that the biological half life of exogenous ACTH is short and this discrepancy may be explained by the purified ACTH preparation used here. The relation between different methods of ACTH administration and their significance in clinical therapy is discussed.