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  • 1
    ISSN: 0303-7207
    Keywords: Estrous cycle ; Gonadotropin-releasing hormone receptor ; LH ; Pituitary ; Sheep ; mRNA
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: aminophylline ; bronchitis ; chronic obstructive airways disease ; respiratory function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have assessed the value of the area under the MEFV curve (AUC) as an index of respiratory function in chronic bronchitis and compared it with PFR, FEV1, FVC, volume at 75% PFR (V75), V50, V25, F50 and F75. The reproducibility of these parameters was tested in 10 normal subjects and 10 patients with chronic bronchitis. The FVC was the most reproducible while the coefficient of variation for the AUC was the same as for the other MEFV curve indices. The sensitivity (percentage change on bronchodilatation after intravenous aminophylline) of the above measurements was also tested in a further nine patients with chronic bronchitis. The AUC was much more sensitive to bronchodilatation than any of the other measurements. Therefore although the AUC was less reproducible than simple spirometric indices, it was more sensitive to bronchodilatation by a greater factor. This probably outweights its poor reproducibility and AUC would therefore seem to be a useful new index of bronchodilatation in chronic bronchitis.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: atrial natriuretic factor (ANF) ; adrenocorticotrophic hormone (ACTH) ; aldosterone secretion ; cortisol ; angiotensin II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of human ANF 99-126 on the aldosterone and cortisol responses to ACTH infusion were studied in 8 normal volunteers. ACTH infusion caused a significant rise in aldosterone and cortisol on each study day. On the day that ANF was concomitantly infused the aldoster-one, but not the cortisol, response to ACTH was significantly attenuated. These results show that a pharmacological dose of ANF selectively inhibits ACTH mediated mineralocorticoid as opposed to glucocorticoid release in man. These results support in vitro and in vivo findings from animal experiments. These findings also compliment previous studies showing that ANF inhibits ANG II stimulated aldosterone release in normal subjects.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: Angiotensin II ; Noradrenaline release ; tyramine infusion ; arterial pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six normal volunteers were studied on four separate occasions. On each occasion they received two concomitant infusions which were either placebo/placebo, placebo/tyramine, angiotensin II/placebo or angiotensin II/tyramine. Angiotensin II infusion was given at a constant rate of 2ng/kg/min whereas the tyramine infusion consisted of 10 min increments at 1.25, 2.5, 3.75, 5, 7.5 and 10 μg·kg−1·min−1. Tyramine infusion caused a dose dependent increase in systolic blood pressure with increases in diastolic blood pressure and plasma noradrenaline only at the highest doses. These changes were not affected by concomitant angiotensin infusion. We have therefore found no evidence to support the enhancement of haemodynamic or plasma noradrenaline responses to tyramine infusion by low dose infusion of angiotensin II in man.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: α2-adrenoceptors ; antihypertensives ; β-receptors ; α-methyldopa ; β-Blockers ; catecholamines ; clonidine ; CNS ; noradrenaline ; opiates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Much of our knowledge about the CNS control of blood pressure is derived from animal studies using techniques such as intracerebroventricular administration of drugs, stereotactic ablation of specific brain nuclei, and biochemical analysis of these nuclei. These methods have identified numerous specific brain nuclei in the brain stem and a meshwork of interconnecting neurones involved in cardiovascular control. The main neurotransmitter involved is noradrenaline but recent interest has focused on several laterally situated nuclei which are capable of synthesizing adrenaline. Centrally acting antihypertensive drugs are thought to act by stimulating central α2-adrenoceptors either by the parent drug itself (clonidine) or via the formation of an active metabolite (α-methyldopa). This leads to decreased peripheral sympathetic activity and a hypotensive response but the latter is often attained at the expense of central side-effects such as drowsiness or dry mouth. The mechanism of the antihypertensive effect of β-Blockers remains uncertain although the balance of evidence is against a central effect. The central administration of propranolol causes decreased peripheral sympathetic activity in animals, but plasma catecholamine levels are little altered by β-Blockers in man. In equipotent antihypertensive doses, central α-agonists cause a much greater reduction in plasma noradrenaline than β-Blockers.
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  • 6
    ISSN: 1432-1041
    Keywords: renin ; aldosterone ; dopamine ; natriuretic hormone ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute natriuretic effect of human atrial natriuretic peptide (ANP) has been well described in man. We have now studied possible hormonal mediators of this effect. We studied six healthy volunteers on two occasions when they received either an infusion of ANP of 1.5 pmol·kg−1·min−1 for 30 min followed by 15 pmol·kg−1·min−1 for a further 30 min, or matching vehicle infusions in a randomized single-blind fashion. On the placebo day, plasma renin activity (PRA) rose from 1.26±0.08 to 1.57±0.14 ng A1·ml−1·h−1, while on the ANP study day PRA fell from 1.45±0.15 to 1.28±0.05 ng A1·ml−1·h−1 (p〈0.01). No significant changes were found in plasma aldosterone concentrations or in urinary dopamine excretion. These results provide evidence that ANP suppresses renin release in man.
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  • 7
    ISSN: 1432-1041
    Keywords: atrial natriuretic factor (ANF) ; frusemide ; renin-angiotensin system ; sympathetic nervous system ; sodium balance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effects of atrial natriuretic factor (ANF) 15 pmol/kg/min on renal function were studied in 7 normal male volunteers during maximal water diuresis. Subjects were studied in neutral salt balance either before, or after, seven days treatment with 40 mg oral frusemide. The post-frusemide state was associated with activation of the renin-angiotensin system (RAAS) and generally higher noradrenaline levels; this state was also associated with sodium retention, mainly due to enhanced distal nephron reabsorption. Without diuretic pretreatment ANF produced a natriuresis and diuresis associated with inhibition of both proximal and distal nephron sodium reabsorption. In contrast, after frusemide pretreatment, ANF caused an increase in water excretion (urinary flow rate) but no change in sodium excretion. In the post-diuretic condition ANF did not affect renal tubular handling of sodium. The enhanced tubular reabsorption of sodium post-frusemide, and the failure of ANF to suppress this, could be due to activation of the RAAS and SNS.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1041
    Keywords: salbutamol ; sublingual ; oral ; inhaled ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Administration of drugs by the sublingual route provides rapid systemic absorption and avoids first-pass metabolism. The purpose of the present study was to assess the pharmacokinetics, efficacy and adverse effects of standard salbutamol tablets given by this route to patients with asthma. Seven asthmatic patients were given either sublingual salbutamol tablet 2 mg (SL), swallowed tablet 2 mg (O), metered dose inhaler 200 µg (MDI) or placebo (PL), in a randomized single-blind cross-over design. Airways responses (FEV1, FVC, PEFR), finger tremor (Tr), heart rate (HR), plasma potassium (K) and plasma salbutamol were measured over a 6 h period following drug administration. There were highly significant changes in FEV1 with MDI, O and SL routes compared with PL, although the response to MDI was greater and more rapid than with O or SL. There were similar findings for FVC and PEFR responses. There were no adverse effects with MDI, whereas both 0 and SL produced significant tremor responses. There were no differences between O and SL for any of the pharmacodynamic parameters. In addition, pharmacokinetic profiles for O and SL were also similar apart from an initial delay in absorption with SL. There were however, no significant differences in any of the pharmacokinetic parameters, between O and SL. This suggests that buccal absorption of salbutamol was negligible, and that systemic absorption occurred after swallowing of the dissolved sublingual tablet. These results show that sublingual administration of salbutamol tablet has no clinical benefit over the oral route.
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  • 9
    ISSN: 1432-1041
    Keywords: Atrial natriuretic factor (ANF) ; platelet aggregation ; aldosterone ; whole blood ; ex-vivo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Atrial natriuretic factor (ANF) binding sites have been shown to be present on human platelet membranes. We investigated the effect of an infusion of ANF 5 pmol·kg−1.min−1 on platelet aggregation in whole blood ex-vivo in 8 normal volunteers. Spontaneous platelet aggregation, collagen (0.6–2 μg·ml−1)-induced or ADP (0.5–2.0 μM)-induced aggregation was not affected by ANF. Plasma aldosterone was however significantly attenuated by ANF. These results show that a pharmacological dose of ANF does not affect platelet aggregation in man. These results suggest that the high plasma levels of ANF normally achieved in chronic heart failure or acute myocardial infarction are unlikely to contribute to the platelet hyperreactivity, often observed in these conditions.
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  • 10
    ISSN: 1432-1041
    Keywords: Atrial natriuretic factor ; Cyclosporin A ; heart transplantation ; renal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The mechanism(s) causing high levels of plasma atrial natriuretic factor (ANF) in cardiac allograft recipients is(are) unclear. The kidney is important for the clearance of ANF and renal function may decline with cyclosporin A therapy in these patients. The relationship between plasma ANF level and renal function and also the pharmacokinetics of a continuous infusion of ANF (15.5 ng·kg−1·min−1 for 60 min) was examined in 6 cardiac allograft recipients on cyclosporin A therapy. Resting plasma ANF levels were significantly higher in these patients than in 8 healthy subjects (71 vs. 21 ng·l−1). Both effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were significantly lower in these patients than in healthy subjects (215 vs. 617 ml·min−1 and 55 vs. 102 ml·min−1 respectively). There was a significant inverse correlation between plasma ANF and ERPF (r=-0.86) and between plasma ANF and GFR (r=-0.81). During the period of ANF infusion, steady state plasma ANF levels were significantly higher in cardiac allograft recipients. Total body clearance of ANF was marginally lower in these patients than in healthy subjects (60 vs. 10.0 l·min−1) although this difference did not reach statistical significance. Derived endogenous secretion rate of ANF was threefold higher in patients when compared to healthy subjects (633 vs. 208 ng·min−1). We have therefore shown that cardiac allograft recipients on cyclosporin A have elevated plasma ANF levels and also decreased renal function. Pharmacokinetic analysis have shown that this increase in plasma ANF levels is due more to increased ANF secretion than to decreased ANF clearance in these patients.
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