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Biomedical subjects

S Ghione

Publications and source records attributed to S Ghione.

At least 19 recordsLinked to original sources

Detection of digitalis compounds using a surface plasmon resonance-based biosensor.

An automated surface plasmon resonance-based biosensor system has been used to detect endogenous and exogenous digitalis-like factors (EDLF) in the pmolar range in real time. EDLF was purified from umbilical cord blood. EDLF has been suggested to play a role in hypertension and in perinatal adaptation. Highly specific polyclonal anti-ouabain antibodies showed a high affinity binding capacity for ouabain, ouabagenin and strophantidin with an IC50 value of 5 x 10(-10) M, 7.0 x 10(-10) M and 2 x 10(-8) M, respectively. EDLF cross-reacted with antibodies and its concentration in plasma at IC50 was around 50 pmol ouabain equivalent. This study shows the potential usefulness of the biosensor technology for biomolecular interaction analysis. The features of this technology (fully automated, measured in real time, sharpened response) offer several advantages compared with a traditional immunoassay like radioimmunoassay (RIA) in the detection of digitalis compounds in human fluids.

Antibodies

Ultrasonic myocardial texture in hypertensive mild-to-moderate left ventricular hypertrophy: a videodensitometric study.

Myocardial texture analysis of two-dimensional echocardiographic gray level distribution is abnormal in hypertensive patients with severe increase of left ventricular mass. The aim of this study was to investigate the behavior of this parameter in hypertensive patients with absent-to-moderate left ventricular hypertrophy, more representative of the overall hypertensive population. We compared male essential hypertensive patients, with absent or mild-to-moderate left ventricular hypertrophy, with normotensive sedentary healthy subjects as controls. The groups (n = 18 each) were age- (+/- 2 years) and sex-matched. All subjects performed ambulatory blood pressure measurements for the evaluation of 24 h mean systolic and diastolic blood pressure. Quantitative analysis of echocardiographic digitized imaging was performed through a calibrated 256 gray level digitization system to calculate midseptum and midposterior end-diastolic and end-systolic first and second order textural analysis. In particular were observed the mean gray level cyclic variations to deriving the cyclic variation index (CVI). The hypertensives showed a significantly lower CVI compared with controls both for septum (P < .001) and for posterior wall (P < .0001). No significant relationships were found between CVI and relative diastolic thickness both of septum and posterior wall. Conversely, a significant inverse relationship was found between systolic arterial pressure values and CVI both of septum and posterior wall. Abnormalities of two dimensional echocardiographic gray level distribution are present also in hypertensive patients with absent or with mild-to-moderate levels of left ventricular hypertrophy, but seem unrelated to the degree of echocardiographic hypertrophy as such. Changes in collagen network distribution or microcirculatory alterations, secondary to pressure-volume overload per se or to other complex humoral factors, could explain these abnormalities. Further work is needed to establish the clinical, therapeutic, and prognostic implications of these findings.

Adult

Do geomagnetic disturbances of solar origin affect arterial blood pressure?

OBJECTIVE: Episodic reports suggest that geomagnetic disturbances of solar origin are associated with biological and clinical events, including increased arterial blood pressure (BP). We reassessed this aspect by relating solar activity levels to ambulatory BP measured in our out-patient population. PATIENTS AND METHODS: The ambulatory BP measurements of 447 consecutive untreated patients attending a hypertension out-patient clinic who did a monitoring for diagnostic purposes over 5 years were retrieved. The mean daytime, night-time and 24-h BP and heart rate values were related to the temporally corresponding geomagnetic index k-sum obtained by the nearest observatory. K-sum is a local measurement of the irregular disturbances of the geomagnetic field caused by solar particle radiation. RESULTS: Significant to highly significant positive correlations were observed for k-sum with systolic (daytime and 24 h) and diastolic BP (daytime, night-time and 24 h), but not with heart rate. No correlations were found with the k-sum of 1 or 2 days before the monitorings. Multiple correlations which also included other potential confounding factors (date, age) confirmed a significant effect of k-sum on BP. Comparison made in season-matched subgroups of quiet and disturbed days (using three different criteria of definition), always showed significantly higher values in the disturbed days for all BP parameters except systolic night-time pressure. The difference between the quietest and the most disturbed days was of about 6 to 8 mm Hg for 24-h systolic and diastolic BP. CONCLUSION: These results are unlikely to be due to unrelated secular trends, but seem to reflect a real relation between magnetic field disturbances and BP.

Adult

Changes in pain perception and pain-related somatosensory evoked potentials in humans produced by exposure to oscillating magnetic fields.

Nociception has been reported to be influenced by exposure to magnetic fields (MFs). The aim of this study was to investigate the effects of 2 h exposure to weak, oscillating MFs on pain perception thresholds and on pain-related somatosensory evoked potentials (SEPs). In 11 healthy volunteers, pain perception thresholds and pain-related SEPs were assessed by intracutaneous electrical stimulation. After sham treatment, pain thresholds significantly increased, whereas after MFs a slight non-significant decrease in thresholds was found. After both treatments pain-related SEP amplitude was reduced, but this decrease was more evident and statistically significant only after MF exposure. The increase found in thresholds after sham exposure may be due to stress-induced analgesia (SIA) and the contrasting behaviour recorded after MF exposure might indicate a suppression of SIA. The significant reduction in pain-related SEP amplitude observed after MF exposure provides the first evidence that human SEPs are influenced by MFs.

Adult

Further evidence for an endogenous digitalis-like compound in newborn and adult plasma detected by anti-ouabain antiserum.

It is widely but not unanimously accepted that one or more endogenous digitalis-like factors (EDLF) circulate in human plasma. In this paper we provide confirmatory evidence that newborn plasma contains a factor with immunological and biological properties similar to ouabain and demonstrate that this factor may be present also in the adult. In fact, we obtained in newborn and adult plasma extracts, identical HPLC elution profiles of ouabain-like immunoreactivity and 86Rb erythrocyte uptake inhibitory activity with a major peak corresponding to the retention time of ouabain. The fact that immunoreactivity and biological digitalis-like activity in the peak are due to an identical substance is strongly supported by the correlation between RIA and 86Rb uptake inhibitory values observed in the purified fractions. Finally, the strong correlation between immunoreactivity observed in plasma samples after simple SepPak C18 extraction and after additional HPLC suggests that less purified samples may be assayed for screening purposes. However, for a more quantitative assessment, this simple extraction method needs a subsequent HPLC purification for eliminating an overestimation of values due to cross-reacting impurities.

Adult

Hypertension-associated hypalgesia. Evidence in experimental animals and humans, pathophysiological mechanisms, and potential clinical consequences.

A behavioral hypalgesia (increased response threshold to noxious stimuli) has been consistently, although not invariably, reported in spontaneous and experimental acute and chronic hypertension in the rat. Studies in human hypertension have also demonstrated a diminished perception of pain, assessed as pain thresholds or ratings. The sensitivity to painful stimuli correlated inversely with blood pressure levels, and this relationship extended into the normotensive range. Evidence in humans and rats points to a role of the baroreflex system in modulating nociception. In the rat, blood pressure-related antinociception may be due to attenuated transmission of noxious stimuli at the spinal level secondary to descending inhibitory influences that are projected from brain stem sites involved in cardiovascular regulation and that may depend on baroreceptor activation and/ or on a central "drive." Both endorphinergic and noradrenergic central neurons (the latter acting through postsynaptic alpha 2-receptors) have been shown to be involved, and other mediators probably also play a role. Functionally, blood pressure-related antinociception may represent an aspect of a more-complex coordinated adaptive response of the body to "stressful" situations. It is still uncertain whether in human essential hypertension hypalgesia is secondary to elevated blood pressure or whether both depend on some common mechanism. Studies on the effect of hypotensive treatment are too few to allow conclusions. According to one hypothesis, the reduction in pain perception caused by baroreceptor activation secondary to blood pressure elevation may represent a rewarding mechanism that may be reinforced with repeated stress and may be involved in the development of hypertension in some individuals. Hypertension-associated hypalgesia may have clinically relevant consequences, especially in silent myocardial ischemia and unrecognized myocardial infarction, both of which are more prevalent in hypertensive individuals.

Animals

Exposure to oscillating magnetic fields influences sensitivity to electrical stimuli. I. Experiments on pigeons.

The comparison of two measurements of the pigeon threshold for electrical stimuli, performed 2 h apart, reveals stress-induced analgesia as a result of stressful manipulations between the two tests. When pigeons are exposed to a weak, oscillating magnetic field between the two measurements, the analgesic response is inhibited and a hyperalgesic effect is recorded. The present findings are in agreement with previous studies showing that magnetic treatments may alter pigeons' emotional state and some of their behavioral patterns.

Animals

Exposure to oscillating magnetic fields influences sensitivity to electrical stimuli. II. Experiments on humans.

To assess the effect of a magnetic treatment on pain perception, we compared the sensory threshold in 18 healthy volunteers. We determined the threshold by noninvasive electrical stimulation of the tooth pulp and skin before and after exposure to an altered magnetic field of low intensity and to a sham treatment. Five different parameters were recorded: the sensory and pain thresholds for the tooth and the sensory, pain, and tolerance thresholds for the skin. Two hours of exposure to a weak, oscillating magnetic fields induced a significant decrease in three parameters (dental sensory and cutaneous pain and tolerance thresholds), whereas the other two parameters showed a similar tendency. When the same subjects were exposed to a sham treatment, only marginal, nonsignificant variations in all parameters were observed. These results represent the first piece of evidence that weak alterations of the magnetic field may induce hyperalgesia in humans.

Adult

Evidence for an endogenous ouabain-like immunoreactive factor in human newborn plasma coeluted with ouabain on HPLC.

The identification in human plasma of ouabain as an endogenous digitalis-like factor (EDLF) claimed by Hamlyn et al. has recently been contradicted by two studies which failed to demonstrate endogenous ouabain-like immunoreactivity in HPLC fractions in which exogenous ouabain was eluted. In this paper we report the results obtained on the cross-reactivity with antiouabain antibodies of an EDLF purified by us from human newborn cord plasma. We found that this EDLF coeluted with ouabain on HPLC and cross-reacted both with rabbit anti-ouabain antiserum and with the purified antibodies, which excluded possible interferences due to antibodies directed against non-ouabain portions of the immunogen. Similar but not identical slopes of the ouabain and EDLF displacements curves were observed in all competition ELISA experiments. The inhibitory effect of EDLF on erythrocyte 86Rb uptake was reversed by antiouabain antiserum and antibodies. The concentration of EDLF in newborn plasma, in the four different purifications studied ranged from 30 to 380 pM ouabain equivalents (o.e.) by ELISA and from 100 to 300 pM o.e. by 86Rb uptake. Our data thus support the existence, in human newborn plasma, of a factor with both biological and immunological ouabain-like properties, although not necessarily identical to ouabain.

Chromatography, High Pressure Liquid

The stimulatory effect on human erythrocyte rubidium-86 uptake by anti-cardiac-glycoside antibodies.

Considerable, but as yet still controversial evidence indicates the presence, in mammalian tissues of endogenous digitalis-like factors (EDLFs) which inhibit cell membrane Na+, K(+)-adenosine triphosphatase (Na+, K(+)-ATPase) and which may cross-react with anti-digitalis antibodies. The aim of this study was to evaluate the effect of antibodies against cardiac glycosides on Na+, K(+)-ATPase in human erythrocytes. For this purpose, we measured the effect of antibodies against two different cardiac glycosides (anti-ouabain rabbit antiserum and anti-digoxin Fab fragments) on the activity of the Na+, K(+)-ATPase, as measured by erythrocyte rubidium-86 (86Rb) uptake, in subjects who had never come into contact with exogenous cardiac glycosides, and compared these results with the effect of two control rabbit sera: a normal serum and an antiserum to a non-related antigen. Anti-ouabain rabbit antiserum and anti-digoxin Fab fragments induced a significantly greater percentage change in 86Rb uptake in the erythrocytes than the two control sera (ANOVA followed by multiple comparison by the Games-Howell test). The average percentage change was +11.8 +/- 16.3% (n = 19) (mean +/- SD) for anti-ouabain antiserum +10.8 +/- 15.6% (n = 23) for anti-digoxin Fab fragments, -1.68 +/- 11.2% (n = 11) for anti-rhGM-CSF antiserum, and -5.8 +/- 11.7 (n = 10) for normal control serum. In a subgroup of ten subjects in whom the 3 antisera were tested simultaneously, the stimulation of erythrocyte 86Rb uptake induced by the two antidigitalis antibodies correlated significantly (r = 0.906, p = 0.001, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Diastolic function in the different patterns of left ventricular adaptation to essential hypertension.

Recent reports have shown that four distinct left ventricular anatomical patterns, with different hypertension severity and hemodynamic features, are associated with sustained arterial hypertension (normal anatomy, concentric remodeling, concentric hypertrophy and eccentric hypertrophy). The aim of this study was to evaluate left ventricular diastolic function in these different left ventricular anatomic patterns. To achieve this aim, 94 borderline-to-severe essential hypertensive patients (60 never treated before, 34 off treatment for at least 3 weeks before the study) underwent an echo-Doppler study; left ventricular thickness, dimension and mass index were obtained. Early (E) and late (A) transmitral flow velocity, their ratio (A/E) and the early filling fraction (EFF) were obtained by pulsed-wave Doppler and used as left ventricular diastolic function indexes. Differences between groups were evaluated by one-way ANOVA followed by Scheffe F-test. A normal left ventricular anatomy was found in 41 (44%), concentric remodeling in 17 (18%), concentric hypertrophy in 21 (22%) and eccentric hypertrophy in 15 (16%) patients. Early filling fraction and A/E ratio which resulted were significantly different for the groups (P < 0.001 and P < 0.002, respectively). As compared with the group with normal left ventricle, patients with concentric hypertrophy had significantly EFF and those with eccentric hypertrophy had significantly lower EFF and higher A/E ratio. Our results thus confirm the presence of distinct anatomical left ventricular adaptation patterns in arterial hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological

Echo Doppler diastolic function and exercise tolerance.

OBJECTIVE: To investigate the possible association between Doppler left ventricular filling pattern and exercise capacity in a group of normotensives to severe hypertensive patients. BACKGROUND: Invasive left ventricular filling indexes evaluated at rest are reported to be related to exercise capacity in heart failure. Whether exercise capacity is limited by abnormalities of left ventricular filling also in other less severe conditions is however unclear. METHODS: Fifty-one subjects with normal to severely elevated blood pressure underwent a standard exercise test on cycle ergometer, negative for myocardial ischemia, and a complete echo Doppler evaluation showing a basal systolic function within normal limits. RESULTS: Basal systolic function indexes were not significantly related to exercise duration. On the contrary, exercise duration was highly significantly correlated to the relative atrial contribution to left ventricular filling (0.001 < P < 0.05), in both the overall group and the two subgroups in whom exercise was interrupted because of fatigue (n = 30) or because of attaining target heart rate (n = 21). Significant correlations were also observed between exercise time and resting blood pressure, whereas no association with resting heart rate, age and body surface area was found. Exercise time also correlated to left ventricular mass and mass index but not to left ventricular volume. Multiple regression analysis showed that exercise tolerance was significantly related to diastolic blood pressure and left ventricular filling. Echo Doppler indexes of left ventricular filling are associated with exercise duration; left ventricular diastole could thus influence effort tolerance, not only in patients with cardiac insufficiency, but also in subjects with normal to elevated blood pressure levels and normal systolic function at rest.

Blood Pressure

Insulin resistance and vasodilation in essential hypertension. Studies with adenosine.

Insulin-mediated vasodilation has been proposed as a determinant of in vivo insulin sensitivity. We tested whether sustained vasodilation with adenosine could overcome the muscle insulin resistance present in mildly overweight patients with essential hypertension. Using the forearm technique, we measured the response to a 40-min local intraarterial infusion of adenosine given under fasting conditions (n = 6) or superimposed on a euglycemic insulin clamp (n = 8). In the fasting state, adenosine-induced vasodilation (forearm blood flow from 2.6 +/- 0.6 to 6.0 +/- 1.2 ml min-1dl-1, P < 0.001) was associated with a 45% rise in muscle oxygen consumption (5.9 +/- 1.0 vs 8.6 +/- 1.7 mumol min-1dl-1, P < 0.05), and a doubling of forearm glucose uptake (0.47 +/- 0.15 to 1.01 +/- 0.28 mumol min-1dl-1, P < 0.05). The latter effect remained significant also when expressed as a ratio to concomitant oxygen balance (0.08 +/- 0.03 vs 0.13 +/- 0.04 mumol mumol-1, P < 0.05), whereas for all other metabolites (lactate, pyruvate, FFA, glycerol, citrate, and beta-hydroxybutyrate) this ratio remained unchanged. During euglycemic hyperinsulinemia, whole-body glucose disposal was stimulated (to 19 +/- 3 mumol min-1kg-1), but forearm blood flow did not increase significantly above baseline (2.9 +/- 0.2 vs 3.1 +/- 0.2 ml min-1dl-1, P = NS). Forearm oxygen balance increased (by 30%, P < 0.05) and forearm glucose uptake rose fourfold (from 0.5 to 2.3 mumol min-1dl-1, P < 0.05). Superimposing an adenosine infusion into one forearm resulted in a 100% increase in blood flow (from 2.9 +/- 0.2 to 6.1 +/- 0.9 ml min-1dl-1, P < 0.001); there was, however, no further stimulation of oxygen or glucose uptake compared with the control forearm. During the clamp, the ratio of glucose to oxygen uptake was similar in the control and in the infused forearms (0.27 +/- 0.11 and 0.23 +/- 0.09, respectively), and was not altered by adenosine (0.31 +/- 0.9 and 0.29 +/- 0.10). We conclude that in insulin-re15-76sistant patients with hypertension, adenosine-induced vasodilation recruits oxidative muscle tissues and exerts a modest, direct metabolic effect to promote muscle glucose uptake in the fasting state. Despite these effects, however, adenosine does not overcome muscle insulin resistance.

Adenosine