Effects of aflatoxin B1 on pregnant inbred Sprague-Dawley rats and their F1 generation. A contribution to transplacental carcinogenesis.
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Biomedical subjects
Publications and source records attributed to B Hesse.
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Regional venous plasma aldosterone concentrations were determined and assessed against concurrent arterial levels in 16 patients with primary aldosteronism. The results obtained by sampling from the left adrenal vein or the left renal vein allowed correct side prediction of the presupposed adenoma in each patient. The problems caused by intermittent secretion of aldosterone by the tumour and the importance of correct positioning of the catheter are emphasized. Repeated sampling and continuing reference to systemic, arterial aldosterone levels proved valuable.
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The significance of changes in sodium balance and urinary sodium excretion for renal PG excretion was studied in normal man. In protocol B a strongly negative sodium balance was produced in 5 healthy young subjects by a low sodium diet given for 7 days (lo mmol Na/day) with 80 mg furosemide p.o. added on the last two days. 24 hour urinary PGE2 excretion remained constant, while plasma renin increased. In protocol A the effect of i.v. furosemide (1 mg/kg bwt) on urinary PGE2 and PGF2 alpha excretion rates was examined in 5 healthy young subjects. Rapid but short-lasting increases in PG excretion rates ran in parallel with the changes in urine flow rate. The study suggests that PGE2 is not of importance for the sodium homeostasis in normal man. Renal prostaglandins may play a modifying role for the renal response to loop diuretics but are hardly instrumental for the diuretic effect.
1. Urinary prostaglandin (PG) E2 excretion and plasma renin were measured in five healthy volunteer subjects for 2 h after intravenous injection of frusemid (protocol A) and during salt restriction for 7 days with frusemide added on the 2 last days (protocol B). 2 In protocol A, peak values in PGE2 and urine flow were reached in 10-20 min, after which the values rapidly subsided. Plasma renin increased twofold in 60 min. 3. In protocol B, even during severe antinatriuresis (day 5) and during maximal negative sodium balance (day 7), no change in urinary PGE2 excretion was observed. Plasma renin increased twofold on day 5 and increased tenfold on day 7. 4. The result of protocol B does not suggest any essential role of renal PGE2 for sodium excretion or sodium homeostasis in man. The result of protocol A may point to a role of renal prostaglandins for the diuretic action of frusemide.
Two patients, one with Bartter's syndrome and one with severe abuse of diuretics, were investigated before and after indomethacin treatment. Before indomethacin the two patients showed a similar pattern of hypokalaemic alcalosis, secondary hyperaldosteronism, and increased urinary excretion of PGE2 and kallikrein. After a few days on peroral indomethacin medication the hypokalaemia was significantly improved, the plasma renin activity, and the urinary excretion of aldosterone, PGE2 and kallikrein were normalized in both patients. It is concluded that the beneficial effect of indomethacin cannot be used as a proof of prostaglandin overproduction as the primary defect in Bartter's syndrome.
In a modified two-stage carcinogenesis experiment, the effectiveness of the initiator 7,12-dimethylbenz(a)anthracene (DMBA) and the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) in the epithelium of the forestomach of the mouse has been investigated. Fifty mice were treated intragastrically with a single dose of DMBA (50 mg/kg body weight), followed by repeated intragastric administration of TPA (10 mg/kg body weight) over a period of 35 weeks. In comparison with the corresponding control groups (no treatment, DMBA initiation only, and TPA treatment only), the initiated and promoted group clearly showed the highest tumor incidence in the target organ (45 tumor-bearing animals of 50 animals). No tumors of the forestomach were found in the untreated control group and the TPA-treated group, whereas in the DMBA-initiated group, ten animals had developed tumors of the forestomach. In addition to the mouse skin model for two-stage carcinogenesis, the mouse forestomach appears to respond to DMBA initiation-TPA promotion. This organ provides an additional tissue with which to investigate tumor promotion and further to ascertain specific parameters of the promotion step.
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1. Hepatic elimination of renin was measured in 10 well-compensated cardiac patients with normal liver function during a control period and during a period of reduced hepatic plasma flow, induced by physical exercise (seven patients) or intravenous infusion of lysine vasopressin (three patients). 2. Hepatic renin elimination rate (hepatic plasma flow x arterial-hepatic vein difference of plasma renin activity) was found to be linearly correlated with arterial plasma renin activity (r = 0.986, P less than 0.001). 3. When hepatic plasma flow fell by 45% the hepatic extraction ratio of renin (arterial-hepatic vein plasma renin activity difference/arterial plasma renin activity) increased by 75%. Hepatic renin clearance (hepatic plasma flow x extraction ratio) remained constant. 4. The results indicate that changes in the hepatic elimination rate of renin do not contribute to changes in plasma renin activity during these events.
The effect of an acute 10% blood volume reduction on plasma renin activity (PRA) was examined in seven patients with minor heart diseases during haemodynamic investigation and in five healthy subjects after 3 days furosemide administration. PRA was not significantly changed. Blood pressure remained constant, atrial pressures decreased. The effect on PRA of an acute 10% blood volume expansion with albumin infusion was studied in thirteen patients with liver or heart diseases. A slight reduction of PRA after albumin did not exceed the expected decrease due to plasma dilution. Blood pressure was unchanged, atrial pressures increased. Renal blood flow increased after albumin in all of the five patients investigated. The effect of PRA of an acute 10% blood volume expansion with whole blood flow increased after albumin in all of the five patients investigated. The effect on PRA of an acute 10% blood volume expansion with whole blood was then investigated in five healthy subjects, pretreated with furosemide for 3 days. A significant decrease in PRA was found. Blood pressure remained constant. It is concluded that an acute blood loss of 10% and an acute blood volume expansion of 10% with albumin have little influence on PRA in supine man, whereas an acute blood volume expansion of 10% with whole blood induces a significant PRA suppression.
Plasma renin activity (PRA), plasma noradrenaline concentration, heart rate, blood pressure, and clearances of para-aminohippurate and inulin were measured in twelve normal subjects (clearances in only three subjects) before and after 40 min of 60 degrees upright tilting. The tilting experiments were repeated after inflation of an anti-gravity suit to 60 mmHg on the lower extremities. Inflation of the anti-gravity suit caused an abolition of the postural PRA increase, a marked reduction of the postural increases in plasma noradrenaline and heart rate, and elimination of the decreases in pulse pressure, inulin and para-aminohippurate clearances and sodium excretion. The results suggest a decisive role of the sympathetic nervous system for postural renin increase, probably mainly activated by stretch receptors in the low-pressure cardiopulmoanry area.
Arterial and coronary sinus noradrenaline (NA) and adrenaline (A) concentrations, cardiac output, pulmonary artery oxygen saturation (PAO2), coronary sinus oxygen saturation, left ventricular end-diastolic pressure (LVEDP), and arterial pressure were examined in 21 patients with ischaemic heart disease at rest and during exercise before and after intravenous propranolol. The heart had a net uptake of A and a net release of NA. It can be estimated that at least 50% of NA in the coronary sinus derived from the heart. NA in the coronary sinus and in the arterial blood originated therefore, at least partially, in different tissues. The NA concentration showed close correlation with PAO2, but not with cardiac index or arterial blood pressure. Multiple regression analysis also revealed a relationship between LVEDP and arterial and coronary sinus NA independent of PAO2. A very close correlation between arterial and coronary sinus NA (r = 0.93, P less than 0.001) indicates that they are largely controlled by the same factors.
Plasma renin activity in the brachial artery and in the renal vein together with arterial noradrenaline concentration were determined repeatedly during and after 10 min of dynamic exercise in eight cardiac patients. Arterial renin increased slightly during exercise and gradually returned to control level after exercise. Renal vein renin increased markedly during exercise and returned to the resting value immediately after exercise, similarly to the changes in plasma noradrenaline and heart rate. A close temporal relationship between the changes in the renal veno-arterial renin difference, plasma noradrenaline and heart rate strongly suggests that the sympathetic nervous system is a major determinant of renin release in man during exercise.
The changes in plasma renin activity (PRA) during short-term salt depletion (and peroral furosemide on the first day) and after bolus injection of propranolol were compared to the change during long-term treatment with diuretic and with propranolol in 19 patients with benign primary hypertension. A highly significant correlation was found between PRA on short-term and long-term salt depletion (r=0.02). A highly significant correlation was likewise found between initial PRA and decrement of PRA after bolus injection of or long-term treatment with propranolol. Only a weak inverse correlation was found between PRA reached during short-term salt depletion or long-term diuretic treatment and the fall in diastolic BP during long-term treatment (r=0.60). No significant correlation was found between decrease in PRA on propranolol (bolus/long-term) and diastolic BP reduction. It is concluded that the short-term PRA response to salt depletion and propranolol in the individual patient gives a good prediction of the PRA level on long-term diuretic or propranolol treatment, but is of no value in predicting the BP reduction during treatment.
To study the mechanisms by which acute beta-adrenergic blockade may change the activity of the sympathetic nervous system we have measured haemodynamic responses including splanchnic blood flow in twenty-three patients with ischaemic heart disease at rest and during supine exercise before and after i.v. injection of 0.039 mmol (10 mg) dl-propranolol. After propranolol both at rest and on exercise blood pressure, cardiac output and heart rate decreased, while splanchnic vascular resistance increased; mixed venous oxygen saturation decreased whilst arterial oxygen saturation and oxygen uptake were unchanged. Plasma noradrenaline increased after propranolol, values correlating with mixed venous oxygen saturation and splanchnic vascular resistance, both at rest and during exercise before and after propranolol, only at rest was there any correlation with arterial blood pressure. The increase in sympathetic nervous activity after propranolol may be due to a reduction in cardiac output and thereby alteration of the metabolic state (oxygen or related factors) in tissues. Afferent neural signals from the tissues may play a significant role in the regulation of sympathetic nervous activity.
1. Ten patients on maintenance diuretic treatment received an intravenous infusion of antidiuretic hormone at a low rate for 1 hr. 2. A gradual reduction in mean plasma renin activity was observed and this was significant at 60 min. 3. There was a significant correlation between the initial value and the extent of the fall in plasma renin activity. There was no consistent change in blood pressure, heart rate and blood volume. 4. The results point to an intrarenal site of action of antidiuretic hormone.
In eleven patients with chronic heart failure forearm blood flow (FBF) was measured by plethysmography with a mercury-in-silastic strain gauge and splanchnic blood flow (SBF) with indocyanine green (ICG) infusion clearance at rest during right heart catheterization. The measurements were repeated during 8 min supine exercise on a bicycle ergometer, SBF during exercise being calculated from the changes of the brachial artery to hepatic vein oxygen differences and the ICG values at rest. Close correlations were found between cardiac output and FBF, and cardiac output and SBF at rest. During exercise forearm and splanchnic vascular resistances were both closely correlated with the brachial to pulmonary artery oxygen difference. It is concluded that in patients with heart failure vasoconstriction occurs during exercise in resting limbs and visceral organs, both closely related to the circulatory strain.