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Biomedical subjects

M Barbagallo

Publications and source records attributed to M Barbagallo.

At least 55 records · Page 3Linked to original sources
PubMed1993

Cellular ionic effects of insulin in normal human erythrocytes: a nuclear magnetic resonance study.

Elevated erythrocyte cytosolic free calcium, and suppressed free magnesium and pH values are associated with the hyperinsulinaemia and insulin resistance of hypertension, obesity, and Type 2 (non-insulin-dependent) diabetes mellitus. To determine the role of insulin in this process, we utilized 19F- and 31P-nuclear magnetic resonance spectroscopy to study the cellular ionic effects of insulin in vitro on normal human erythrocytes. Insulin elevated cytosolic free calcium levels in a dose- and time-dependent manner. The effect began at 10 microU/ml, peaked at 200 microU/ml, and continued at both the 500 microU/ml and 1000 microU/ml doses. At 200 microU/ml, free calcium levels rose from 24.6 +/- 2.5 nmol/l to a peak value at 120 min of 66.4 +/- 11 nmol/l (p < 0.05 vs basal), levels remaining elevated throughout the incubation (45.7 +/- 5.6 nmol/l at 60 min, and 47.9 +/- 9.1 nmol/l at 180 min, p < 0.05 vs basal, respectively). Similarly, insulin also increased intracellular free magnesium at all time points (basal: 177 +/- 11 mumol/l; 60 min: 209 +/- 19 mumol/l; 120 min: 206 +/- 22 mumol/l; and 180 min: 202 +/- 12 mumol/l; p < 0.05 vs basal at all times). No insulin-induced changes in pH were observed. We conclude: (i) that insulin in physiological concentrations may participate in regulating divalent cations in the mature human erythrocyte, (ii) that insulin per se cannot account for the previously described cellular ionic lesions of hypertension and diabetes, and (iii) that future clinical studies of cell ion metabolism should be conducted in the fasting state, be controlled for ambient circulating insulin levels, or both.

Calcium↗
PubMed1993

Independent effects of hyperinsulinemia and hyperglycemia on intracellular sodium in normal human red cells.

To study the contribution of glucose vis-à-vis insulin in the altered sodium homeostasis of diabetes mellitus, we utilized 23Na-NMR spectroscopy to noninvasively measure intracellular sodium (Nai) in red blood cells of non-diabetic, thin, normotensive subjects (n = 9), before and 60, 120, and 180 min after in vitro incubation with elevated glucose (15 mmol/L) and insulin (200 mumol/L) concentrations. Hyperglycemia caused a significant rise in Nai compared to basal values at 60 (9.1 +/- 0.8 to 9.7 +/- 0.8 mEq/L, P < .05), and 120 min (10.0 +/- 0.7 mEq/L, P < .05 v basal). Hyperinsulinemia induced a more pronounced and prolonged elevation of Nai. Significant elevations occurred at 60 (8.0 +/- 0.5 to 10.2 +/- 0.7 mEq/L, P < .05), 120 (10.5 +/- 1.1) mEq/L, P < .05 v basal), and 180 (9.1 +/- 0.5 mEq/L, P < .05 v basal) minutes. Thus, both hyperinsulinemia, and to a lesser extent, hyperglycemia cause intracellular sodium accumulation in normal human red cells. Since glucose transport in red cells is not insulin-dependent, insulin and glucose presumably exert their effects independently. Altogether, we suggest that these insulin- and glucose-mediated effects on cellular sodium, if present in other tissues as well, may underlie the increased total body sodium and the salt-dependent hypertension characteristic of chronic diabetic or hyperinsulinemic syndromes.

Erythrocytes↗
PubMed1993

Ionic basis of hypertension in diabetes mellitus. Role of hyperglycemia.

Alterations of cell ion content have been reported acutely after oral glucose ingestion, and chronically in subjects with hypertension and noninsulin dependent diabetes mellitus (NIDDM). We have hypothesized that these ionic abnormalities, elevated cytosolic free calcium (Cai), and suppressed intracellular pH (pHi) and free magnesium (Mgi), common to both of these syndromes, may explain their frequent clinical coincidence. To investigate the potential role of glucose in this process, we utilized 19F- and 31P-NMR spectroscopy to measure Cai, Mgi, and pHi in normal human red blood cells before and 60, 120, and 180 min after in vitro incubation with glucose (15 mmol/L) and equimolar concentrations of the glucose analogs, L-glucose, 2-deoxyglucose, and 3-O-methylglucose. At each point in time (from t = 0 to t = 60, 120, 180 min), glucose induced significant (P < .05) elevations in Cai (27.2 +/- 2.2 to 68.3 +/- 7.2, 70.7 +/- 10.5, 59.8 +/- 10.1 nmol/L), while suppressing pHi (7.28 +/- 0.02 to 7.22 +/- 0.03, 7.23 +/- 0.03, 7.22 +/- 0.03), and Mgi (206 +/- 10 to 151 +/- 7, 131 +/- 7, 143 +/- 5 mumol/L). This glucose induced ionic effect was dose dependent, significant elevations in Cai being observed at 10 and 15 mmol/L, but not at the other concentrations tested. It was also specific, no changes in Cai being observed with any of the glucose analogs tested. Thus, hyperglycemia per se elevates Cai and suppresses Mgi and pHi in normal human red cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1993

Sex hormones and hemostatic risk factors for coronary heart disease in men with hypertension.

OBJECTIVE AND DESIGN: It has been hypothesized that risk factors for coronary heart disease in men are linked and that the underlying factor linking them may be an alteration in the sex hormone milieu. As a test of this hypothesis, sex hormones and fibrinogen, factor VII and plasminogen activator inhibitor (PAI-1), hemostatic factors recently shown to be risk factors for myocardial infarction, were measured in men with hypertension and in healthy control subjects. RESULTS: The fasting serum testosterone and free testosterone levels were decreased and the plasma factor VII and PAI-1 levels increased in the men with hypertension. CONCLUSION: These findings are consistent with the stated hypothesis.

Blood Coagulation Factors↗
PubMed1993

[Silent myocardial ischemia: prevalence, prognostic significance, diagnosis].

Silent myocardial ischemia (SMI) has been demonstrated in 2 to 5% of subjects in totally asymptomatic population, in 30% of patients with history of previous myocardial infarction and in 60 to 100% of patients with stable or unstable angina pectoris. In these patients, 60 to 80% of transient episodes of ischemia are silent and SMI is induced by daily activities and so can be registered during continuous ECG monitoring. The finding of SMI during an exercise testing or during ambulatory monitoring has an unfavourable prognostic significance both in apparently asymptomatic subjects and in patients suffering from stable or unstable angina pectoris or survivors to a myocardial infarction. Stress testing and Holter monitoring are the most used non invasive tests to detect SMI. The sensitivity and specificity of ergometer test can be improved by 201-Tl myocardial scintigraphy. Moreover, the ergometer test can be used as a provocative test to induce changes in regional wall kinesis and so these alterations can be evaluated by using echocardiogram and radioisotopic or contrast ventriculography. The echocardiogram allows to evaluate the presence of kinesis changes induced by stress test or by pharmacological stimulation with dipyridamole or dobutamine. SMI can be also detected through the study of metabolic alterations during cardiac catheterism.

Angina Pectoris↗
PubMed1993

Diabetes, hypertension and atherosclerosis: pathophysiological role of intracellular ions.

The clinical coincidence of hypertension, obesity and non insulin diabetes mellitus (NIDDM) has long been recognized. Increasing interest has also been recently focused on the possible role of insulin and insulin resistance in mediating this association. There is also evidence that hyperglycemia per se may have a role in the pathogenesis of hypertension and atherosclerosis in NIDDM patients. Glucose is a determinant to cellular ion homeostasis, promoting an increase of intracellular calcium and suppressing intracellular free magnesium and pH. Moreover, hyperglycemia promotes glycosilation of proteins and the consequent accumulation of advanced glycosilation end products in tissues. It has recently been suggested that iter is a cellular ionic basis for the clinical and epidemiological linkage of hypertension, left ventricular hypertrophy (LVH), obesity and non insulin dependent diabetes mellitus (NIDDM). These clinical conditions may be different expressions of a common underlying defect in ion handling, displayed by elevated cytosolic free calcium and suppressed free magnesium levels. Therapeutically, reversal of this excess free calcium accumulation and/or free magnesium deficit with ion specific agents, such as calcium channel blocker drugs, may thus ameliorate not only the elevated blood pressure of hypertension but also the concurrent cardiac, vascular and metabolic aspects of the hypertensive states.

Arteriosclerosis↗
PubMed1992

Renal divalent cation excretion in secondary hypertension.

1. To determine whether abnormal renal calcium excretion is unique to primary genetic hypertension, blood pressure and 24 h urinary excretion of calcium, magnesium, sodium and creatinine were measured in deoxycorticosterone-saline and two-kidney, one-clip Goldblatt hypertensive rats and in their respective controls on low (0.2%) and high (1.8%) dietary calcium intakes. 2. Calcium supplementation lowered blood pressure (P < 0.05) in deoxycorticosterone-saline rats and in control saline-loaded rats, raised blood pressure in two-kidney, one clip rats, and had no effect in sham-operated control rats. 3. On both diets, calcium excretion was higher in hypertensive than in normotensive rats. The high calcium diet increased urinary calcium excretion in all rats, but the changes in urinary calcium excretion closely paralleled the diet-induced changes in blood pressure. Thus, urinary calcium excretion in deoxycorticosterone-saline animals, in whom calcium lowered blood pressure the most, rose the least (107%). Urinary calcium excretion rose the most in two-kidney, one-clip animals (1113%), whose blood pressure also rose the most. 4. Urinary magnesium excretion was also abnormal in hypertensive rats compared with normotensive rats, falling on the high compared with the low calcium diet in normotensive rats, but not in either hypertensive strain. Furthermore, urinary magnesium excretion was closely linked to urinary calcium excretion in saline-loaded control rats (r = 0.78; P = 0.008), but was dissociated from urinary calcium excretion in deoxycorticosterone-saline rats (r = 0.02; not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Lipids and serum apoproteins in subjects with slight or mild coronary atherosclerosis evaluated with angiography].

In this study 126 subjects (91 males and 35 females, range of age 43-65 years) were studied by coronary angiography. We considered positive for coronary atherosclerosis also patients showing mild or moderate stenosis (> or = 25%). In all subjects we have evaluated serum lipid and apoprotein A-I, B, C-II, C-III and E levels; therefore also cholesterol concentrations in all lipoprotein fractions, separated by sequential ultracentrifugation (VLDL d < 1.006, LDL d 1.006-1.063, HDL d > 1.063 g/ml) and apoprotein B in LDL have been measured. Subjects with coronary atherosclerosis have shown significantly higher levels of total cholesterol, LDL-cholesterol, total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios than controls. Therefore, a lower apo A-I/apo B ratio in males and a higher LDL-apo B levels in females has been found in subjects with coronary atherosclerosis in comparison with controls. The stepwise multiple analysis has demonstrated that LDL-cholesterol levels is the parameter that best correlates with the presence of coronary atherosclerosis. These data confirm the importance of the reduction of LDL-cholesterol levels in primary and secondary prevention of coronary heart disease.

Apolipoproteins↗
PubMed1991

Intermittent treatment with intravenous 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHBuBP) in the therapy of postmenopausal osteoporosis.

Since data on the efficacy of 4-amino-2-hydroxybutylidene-1,1-bisphosphonate (AHBuBP) in the therapy of osteoporosis are not yet available, we have examined in an open, randomized study, the effects of an intravenous intermittent treatment with this drug on the vertebral and radial bone mass in postmenopausal osteoporosis. Forty postmenopausal osteoporotic women were randomly assigned to one of two groups, one treated with AHBuBP (5 mg/day on two consecutive days every 3 months for one year; n = 20), the other with oral calcium (n = 20). The bone mineral density (BMD) of the spine increased significantly in women receiving AHBuBP, whereas it tended to decrease in patients given calcium. The differences in the vertebral BMD changes between groups was highly significant (P less than 0.01). Radial BMD tended to increase in patients treated with AHBuBP, and to decrease in patients receiving calcium. The difference in the linear trends was statistically significant (P less than 0.05). The side effects of AHBuBP (a transient acute phase reaction in 3 out of 20 subjects) were slight and well-tolerated. A good effect of AHBuBP was observed also on back pain (P less than 0.05). We conclude that intermittent treatment with AHBuBP is capable of increasing spinal BMD and conserving radial BMD in postmenopausal osteoporosis and may represent a convenient therapeutic choice in this condition.

Aged↗
PubMed1991

Increased plasminogen activator inhibitor antigen levels in diabetic patients with stable angina.

PAI-1 antigen, tPA antigen and thrombin - antithrombin III complexes (TAT) levels were measured in 10 males with stable angina and type-II diabetes mellitus and in 16 males with stable angina without diabetes or other risk factors (hyperfibrinogenaemia, hyperlipidaemia, diabetes, hypertension, smoking and obesity) known to increase PAI levels. Ten healthy men of equivalent age served as controls. Because only diabetics with coronary artery disease (CAD) showed a decreased fibrinolytic capacity, a second study was performed on the 16 non-diabetic CAD patients to determine whether submaximal workload induces significant changes of tPA and PAI levels. TAT levels were increased in CAD, and significantly so in the diabetic group. tPA levels were increased only in the CAD patients without diabetes. PAI levels were significantly increased in diabetic CAD patients (5.26 +/- 1.96 ng/ml) but not in the stable angina patients without diabetes (2.97 +/- 1.44 ng/ml). Immunologically-reactive tPA released after exercise was higher in the 16 CAD patients without diabetes than in controls. Our data could indicate that in stable angina without diabetes there is no chronic latent activation of the clotting system, with no impairment of fibrinolytic activity. On the other hand, the presence of diabetes mellitus seems to influence the fibrinolytic capacity in CAD, particularly increasing PAI levels.

Adult↗
PubMed1991

[Arterio-jugular difference of oxygen and intracranial pressure in comatose, head injured patients. I. Technical aspects and complications].

The monitoring of the comatose head injured patients is based on the recording of several data; the intracranial pressure measurements (ICP), associated with the arterial pressure recording, gives a good estimate of the cerebral perfusion pressure (CPP) but further information about the cerebral perfusion are needed. Based on the assumption that the cerebral metabolic rate is kept constant strong relationships exist between the cerebral blood flow (CBF) and the arterovenous difference of oxygen (AVDO2). In order to obtain samples of cerebral venous blood a catheter must be inserted in the internal jugular vein (IJ) with the tip of the cannula reaching the superior jugular bulb. In 224 patients we measured the ICP trough ventricular or subdural catheters; invasive measurement of the arterial pressure was also carried on in all the patients. In 45 patients we measured the AVDO2 and we tested the safety and the reliability of the jugular vein cannulation. During the insertion of the jugular catheters a slight increase of ICP, without any clinical significance, was recorded; in two cases (on a total of 45) accidental carotid puncture occurred. In 9 cases we tested the concordance of the oxygen content between the two IJs; looking at the mean values no statistical difference is detected between the two sides but in some cases relevant differences are recorded. In two cases we inserted the catheters more cranially, reaching a sinus of the cranial basis; the blood collected from these points carries less oxygen that the blood collected in the neck. The rate of infection in this series of ICP monitoring is very low (1.78%) and we had no bleeding at the moment of the insertion of the catheters. Since no significant complications related to the IJ cannulation were recorded we conclude that these techniques are safe and can be easily performed in the clinical setting. Further studies are required in order to investigate the clinical meaning of the differences in the IJs content of oxygen.

Adolescent↗
PubMed1991

[Arterio-jugular difference of oxygen and intracranial pressure in comatose, head injured patients. II. Clinical correlations].

The ICP monitoring is currently used in the treatment of the head injured patients in order to avoid dangerous increases of the pressure and critical reduction of cerebral perfusion pressure (CPP). The cerebral blood flow is dependent on the CPP and is kept constant, under normal circumstances, by autoregulation. When autoregulation is impaired or overwhelmed oxygen delivery becomes uncoupled to the metabolic needs of cerebral tissue: in such a condition the rate of oxygen extraction changes and the artero-jugular difference for O2 (AVDO2) reflects this change. The AVDO2 can be used as an estimate of the CBF and can detect a situation of hyperemia (low AVDO2) or ischemia (high AVDO2). In 224 comatose head injured patients the ICP was measured using ventricular or subarachnoid catheters: the CPP was continuously assessed and the outcome was evaluated six months after the trauma. In 45 patients the AVDO2 was studied and the data were corrected for a PaCO2 of 40 mmHg and investigated. The severity of the ICP is decisive for the prognosis and, accordingly, the number of times the CPP is below 60 mmHg plays a major role in the outcome. The mortality rate was 21% for the patients without ICP greater than 20 mmHg and 54% for the patients with severe increases in ICP. The mean values of AVDO2 were low, ranging around 4.6 vol%; only 4 patients showed some temporary evidence of ischemia, as assessed by an AVDO2 greater than 8 vol%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

[Vascular damage in arterial hypertension: its noninvasive assessment].

Arterial hypertension is a definite risk factor for the atherosclerotic disease and thus has a primary role in the genesis of cardiovascular diseases, but it acts also though a direct structural damage of great and small arteries and arterioles. Up to date, clinical research and technological advancements have made possible the development of instruments and methods for the evaluation of the vascular damage. Ultrasonographic methods are now the better non invasive tools for the study of arterial diseases, allowing a definition power comparable to angiography, and giving useful data on characters and composition of plaques, also minimal, at the level of the arterial district of lower limbs, epiaortic, renal, and abdominal vessels. These methods allow the study of the vascular lesion under the hemodynamic (CW or pulsed Doppler with spectral signal analysis) and the morphological profile (high resolution echotomography) or both echo-Doppler duplex scanning or color flow imaging). Arterial compliance of great vessels can be studied through the Doppler evaluation of pulsed wave velocity along the arterial tree. Other useful parameters are the aortic distensibility (ratio between % change in arterial volume and blood pressure), the elastic module, the index of arterial rigidity and the aortic index (ratio between pulse pressure and stroke volume). By using this latter parameter we demonstrated a significant decrease of arterial compliance that is proportional to the severity of blood pressure values. Small vessels may be studied through strain-gauge plethysmography, that allows to obtain the regional blood flows at the hand and forearm (skin circulation) and the calf (muscular circulation) both in basal conditions and after ischaemic stimulus. From the ratio between mean arterial pressure and post-ischemic blood flow it is possible to obtain minimal vascular resistances, expression of the maximal vasodilatation capacity in the arteriolar bed. With this method we showed that minimal vascular resistances increase proportionally with the increase of blood pressure in borderline hypertensives, in mild, moderate and severe stable arterial hypertension and in hypertension of the aged. The cutaneous microcirculation may be studied also by laser Doppler and capillaroscopy, that show a reduced capillary perfusion in hypertension. Clinically, these diagnostic tools are also extremely useful for studying the effects of antihypertensive treatment on structure and function of arterial vessels, as it seems that some drugs are able to counteract the structural alterations related to hypertension.

Arteriosclerosis↗
PubMed1991

Histological evidence of increased turnover in bone from spontaneously hypertensive rats.

24 weeks-old spontaneously hypertensive male rats and normotensive genetic controls were subjected to: histomorphometry of the proximal tibiae, assay of mineral density of the femurs by dual photon absorptiometry, and measurement of the calcium content of the femoral bone ash by atomic absorption spectophotometry. Compared with the controls, the hypertensive rats showed osteopenia and increased bone turnover; their osteoid volumes and the surface area of both osteoclasts and osteoblasts were all increased. The data suggest that, during aging, spontaneously hypertensive rats both lose bone mass more rapidly and also have an increased skeletal metabolic rate with respect to the controls.

Animals↗
PubMed1991

Effect of obesity on left ventricular function studied by radionuclide angiocardiography.

Several studies have shown a significant association of obesity with cardiovascular morbidity and mortality. The present study was carried out to investigate central and systemic haemodynamics in overweight and moderate obese, but otherwise healthy subjects, and in a lean control group to determine whether obesity can influence left ventricular performance per se. In this study an attempt has been made to eliminate misleading factors, such as diabetes, lipid abnormalities and hypertension. A total of 67 subjects, 44 with overweight or moderate obesity and 23 lean healthy subjects, were included. Patients were divided into three groups according to BMI levels and Garrow's criteria as follows: lean control group (BMI less than 25 kg/m2); overweight (BMI from 25 to 30 kg/m2); moderate obese (BMI greater than 30 less than 40 kg/m2). Overweight and moderate obese subjects were further subgrouped according to duration of obesity (DO) in subgroup A (DO less than 98 months) and in subgroup B (DO greater than 98 months). Haemodynamic assessment was performed using first pass radionuclide angiocardiography. When compared with lean subjects, overweight and moderate obese subjects were characterized by a significant increase in cardiac output (CO), stroke volume (SV), end diastolic volume (EDV), end systolic volume (ESV), total blood volume (TBV) and total plasma volume (TPV) and by a significant decrease in left ventricular ejection fraction (EF); some of these changes appeared to be related to the degree of obesity. In overweight and moderate obese subjects, total peripheral resistance (TPR) was lower than in lean controls, but this difference was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Alterations of calcium metabolism in spontaneously hypertensive rats.

We have examined the femurs of eight male spontaneously hypertensive rats and eight male Wistar Kyoto rats, aged 24 weeks. The mineral density of the bones was determined at the mid-point of the femurs by dual photon absorptiometry and the calcium content was estimated on bone ash by atomic absorption spectrophotometry. The data show that spontaneously hypertensive rats have lower bone density and calcium content than do age-matched Wistar Kyoto rats.

Absorptiometry, Photon↗
PubMed1990

Cardiac arrhythmias as correlated with the circadian rhythm of arterial pressure in hypertensive subjects with and without left ventricular hypertrophy.

To evaluate the relationship among supraventricular and ventricular arrhythmias with blood pressure and heart rate (HR) values, we studied 2 groups of 20 hypertensive men with (group I) and without (group II) left ventricular hypertrophy. Ambulatory electrocardiographic tracings were recorded continuously, together with ambulatory arterial pressure. Systolic (SBP) and diastolic (DBP) blood pressure values measured over 24 h showed no difference between the two groups, but we found greater variability in SBP in group I. The incidence of ventricular and supraventricular arrhythmias was significantly higher in patients of group I; moreover, we found a strong correlation between the incidence of ventricular extrasystoles (VPCs) and SBP, DBP, and HR values in group I, whereas in group II the incidence of supraventricular extrasystoles (APCs) was higher during peaks of SBP and HR values. The relationship between APCs and SBP observed in group II may be attributable to the pressure stimulus on a normal atrium, and the significant correlation between VPCs and SBP, DBP, and HR values may be due to episodes of subendocardial ischemia or to the influence of adrenergic stimulation on previously compromised myocardial tissue.

Arrhythmias, Cardiac↗