Papers by Giuseppe Sagnella
KINCALCby S. W. Orchard, Elsevier-BIOSOFT, 1984. $30.00/�18.00
Trends Biochem Sci, 1985
Trends in Biochemical Sciences, 1985
Model fitting and mathematical models are becoming increasingly important in the. biochemical sci... more Model fitting and mathematical models are becoming increasingly important in the. biochemical sciences. Here the statistical procedures of linear and non-linear regression for parameter estimation and goodness-of-fit analysis are examined. The mechanics of non-linear regression are described for the Gauss-Newton method, with particular reference to the Michaelis--Menten model. Suitable computer software is suggested to entice those who wish to familiarize themselves with these powerful tools.
Fitting linear models to structure-activity data
Trends in Pharmacological Sciences, 1985
Journal of Clinical Investigation, 1982
A B S T R A C T Cardiovascular responses to intravenous administration of norepinephrine and the ... more A B S T R A C T Cardiovascular responses to intravenous administration of norepinephrine and the properties of alpha receptors on platelets were compared in normal human subjects and subjects with multiple system atrophy (MSA) and sympathetic degeneration. All the subjects with MSA had low plasma norepinephrine concentrations (in the supine position) (0.42±0.09 nM, normal 3.47±0.58 nM), which did not increase on tilt. The pressor sensitivity of subjects with MSA to norepinephrine infusion was increased 10to 20-fold, demonstrating denervation supersensitivity to adrenergic agonists. Analysis of alpha receptors was by binding of [3H]dihydroergocryptine to platelets. Results are shown as mean±standard error of the mean. In the MSA subjects, the number of alpha receptors (1,712±699 fmol/108 platelets) was about sevenfold greater than in normal subjects (224±21 fmol/108 platelets), and the affinity, as measured by the equilibrium dissociation constant (Kd), was similar in both groups (MSA subjects, 9.6±4.3 nM; normal subjects, 4±0.5 nM).
Glucocorticoid receptor restriction fragment length polymorphisms and blood pressure
European Journal of Internal Medicine
Subcellular distribution of multiple forms of acid p-nitrophenyl phosphatase in rat kidney
International Journal of Biochemistry, 1980
ABSTRACT 1.1. Two forms of acid p-nitrophenyl phosphatase activity are present in rat kidney sepa... more ABSTRACT 1.1. Two forms of acid p-nitrophenyl phosphatase activity are present in rat kidney separable from subcellular fractions of renal cortical homogenates by gel filtration on Sephadex G-100.2.2. The lysosomal and the microsomal enzymes had molecular weight (mol. wt) of greater than 100,000 and had similar kinetic and inhibitory properties.3.3. In contrast, the soluble fraction contained not only this high molecular weight form but also a lower molecular weight form (mol. wt 20,000).4.4. This latter form differed in its response to inhibitors, had different Km value but had the same acid pH optimum.
Vasopeptidase inhibitors
Journal of the renin-angiotensin-aldosterone system : JRAAS, 2002
Vasopeptidase inhibitors are a new class of drugs that have dual inhibitory effects on two key en... more Vasopeptidase inhibitors are a new class of drugs that have dual inhibitory effects on two key enzymes involved in the metabolism of vasoactive peptides. Essentially, they inhibit angiotensin-converting enzyme (ACE), thereby blocking the generation of angiotensin II (Ang II); at the same time they prevent the breakdown of natriuretic peptides by the enzyme neutral endopeptidase. The combination of reduction of Ang II on a background of increased natriuretic peptide activity has several potential advantages for the treatment of cardiovascular and renal disease and in particular, hypertension and congestive heart failure (CHF). Several vasopeptidase inhibitors, such as sampatrilat, fasidotril, gemopatrilat and omapatrilat (Vanlev, the most clinically developed vasopeptidase inhibitor to date) are under intensive clinical investigation. Recent clinical trials have demonstrated effective antihypertensive activity in hypertension, independent of age, renin and salt status or ethnic origin, and have also highlighted the potential for vasopeptidase inhibition as a new therapeutic modality for the treatment of CHF. Moreover, ongoing research suggests that this new class of drugs may be an important approach, not only for the treatment of hypertension and of conditions associated with overt volume overload but also for ischaemic heart disease.
Practical implications of current natriuretic peptide research
Journal of the renin-angiotensin-aldosterone system : JRAAS, 2000
Since the original discovery of atrial natriuretic peptide (ANP) nearly 20 years ago and the subs... more Since the original discovery of atrial natriuretic peptide (ANP) nearly 20 years ago and the subsequent realisation of the existence of a family of natriuretic peptides, there has been considerable progress in the elucidation of the physiological and pathophysiological significance of these peptides. This review has examined two potentially important practical aspects arising from natriuretic peptide research - the significance of measurement of plasma levels of ANP and of brain natriuretic peptide BNP for cardiovascular disease and the therapeutic potential of targeting the natriuretic peptide system. Several situations where the measurement of plasma ANP and BNP may be of benefit in the overall assessment and prognosis of cardiac disease have been discussed. The measurement of plasma levels of these peptides appears to have limited value as a specific diagnostic tool and is unlikely to replace well-established procedures to assess cardiac function. Nevertheless, given the strong negative predictive value, the value of the measurement of plasma natriuretic peptides particularly BNPs, in people with suspected heart disease, rests on the evidence that a normal value indicates a low risk of cardiac impairment. Moreover, a consistently elevated plasma level of BNP after myocardial infarction is associated with a distinctly poor prognosis. In turn, this may help to select those with high plasma levels for subsequent detailed investigation of cardiac dysfunction. This may be an important option, especially where the facilities for the more invasive cardiological procedures are not available. Intriguingly, recent research also suggests the possibility that plasma levels of natriuretic peptides may have an important role in guiding more effective therapy for heart failure. The potent cardiovascular and renal effects of ANP and BNP provide an important therapeutic potential for hypertension and for conditions associated with volume overload. A number of approaches which have been used to enhance endogenous activity of these peptides have been highlighted. The use of the native peptides ANP and BNP may well be valuable in some circumstances, such as in critically ill individuals with congestive heart failure or renal failure. However, the limitations of the use of peptides, especially for long-term treatment, are obvious. In view of this, considerable effort has been devoted to the development of orally active agents to enhance endogenous natriuretic peptides by inhibition of breakdown by neutral endopeptidase. This research has led to the development of vasopeptidase inhibitors - dual inhibitors of both endopeptidase and angiotensin-converting enzyme - to enhance endogenous natriuretic peptide function on a background of reduced angiotensin II activity. The broad spectrum of action and the potentially important target-organ protection of these inhibitors offer potential benefits which may well go beyond existing treatment of hypertension and of conditions associated with overt volume overload.
Distribution of β-endorphin in normal and schizophrenic human brains
European Journal of Clinical Investigation, 1979
Abstract. β-Endorphin was measured by radioimmunoassay in post-mortem human brains. Samples of br... more Abstract. β-Endorphin was measured by radioimmunoassay in post-mortem human brains. Samples of brain were taken from five discrete areas, both from control brains and brains of schizophrenic patients. No difference in β-endorphin levels was found in these two groups ...
EFFECTS OF CHANGES IN DIETARY SODIUM INTAKE AND SALINE INFUSION ON IMMUNOREACTIVE ATRIAL NATRIURETIC PEPTIDE IN HUMAN PLASMA
Lancet, 1985
Plasma levels of immunoreactive atrial natriuretic peptide (IrANP) were measured in healthy normo... more Plasma levels of immunoreactive atrial natriuretic peptide (IrANP) were measured in healthy normotensive subjects before and after saline infusion and changes in dietary salt intakes. When 2 litres of 0.9% saline (308 mmol Na+) were infused over 1 h, plasma levels (mean +/- SD) of IrANP increased from 5.8 +/- 2.8 pg/ml to 15.8 +/- 12.5 pg/ml. Plasma levels on the fifth day of a low sodium diet (10 mmol/day) were 3.8 +/- 2.4 pg/ml, a normal sodium intake (150 mmol/day) 6.4 +/- 2.9 pg/ml, and a high salt intake (350 mmol/day) 12.7 +/- 6 pg/ml. These results suggest that atrial natriuretic peptides could be important hormones in the control of sodium balance in normal man.
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Papers by Giuseppe Sagnella