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Biomedical subjects

M Condorelli

Publications and source records attributed to M Condorelli.

At least 91 records · Page 5Linked to original sources
PubMed1986

Possible role of calmodulin in the control of histamine release from human basophil leukocytes.

We investigated the possible role of calmodulin (CaM) in the control of histamine release from human basophil leukocytes using several CaM antagonists. Trifluoperazine (TFP) (10(-6)-2 X 10(-5) M), pimozide (10(-6)-1.5 X 10(-5) M), chlorpromazine (CPZ) (10(-5)-10(-4) M) and promethazine (PMZ) (2 X 10(-5)-10(-4) M) inhibited in vitro histamine secretion from human basophils induced by several immunological (antigen, anti-IgE, and formyl-L-methionyl-L-leucyl-L-phenylalanine: f-met peptide) and nonimmunological (Ca2+ ionophore A23187 and the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate: TPA) stimuli. Trifluoperazine sulfoxide (TFP-S) and chlorpromazine sulfoxide (CPZ-S), which have very low affinity to CaM, had practically no inhibitory effect on histamine release from human basophils. The inhibitory effect of TFP could be made irreversible by irradiating the cells with UV light. A sulfonamide derivative, the compound N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) (2.5 X 10(-5)-2 X 10(-4) M), which selectively binds to CaM, inhibited the release of histamine from basophils. In contrast, the chloride deficient analogue, W-5, which interacts only weakly with CaM, had practically no inhibiting effect. The IC50 for enzyme release by a series of eight CaM antagonists was closely correlated (r = 0.91; p less than 0.001) with the CaM specific binding, supporting the concept that these agents act by binding to CaM and thereby inhibiting histamine release. TFP and W-7 inhibited histamine release in the absence and in the presence of increasing concentrations of extracellular Ca2+. These results emphasize the possible role of CaM in the control of histamine secretion from human basophils.

Basophils↗
PubMed1986

Effect of nifedipine on dipyridamole thallium-201 myocardial scintigraphy.

The effect of a calcium antagonist drug, nifedipine, on dipyridamole thallium-201 images was assessed in 10 angina patients with positive dipyridamole test. Two dipyridamole thallium-201 tests were performed, the first in basal conditions, the second after administration of 20 mg nifedipine. After dipyridamole, heart rate and double product increased respectively from 68.0 +/- 8.2 to 94.7 +/- 11.5 beats/min (p less than 0.01) and from 9459.5 +/- 1800.2 to 12,770.0 +/- 1864.7 mmHg X beats/min (p less than 0.01). Dipyridamole when infused after nifedipine induced an increase in heart rate from 74.2 +/- 7.16 to 88.8 +/- 5.6 beats/min (p less than 0.01) and in double product from 9650.5 +/- 1348.0 to 11,399.0 +/- 1146 mmHg X beats/min (p less than 0.05). Systolic and diastolic blood pressures were unmodified during the two studies. Segment scores were comparable before and after nifedipine. Thus, nifedipine does not worsen thallium-201 myocardial images obtained during dipyridamole infusion, therefore, this test could provide an alternative to exercise thallium-201 in patients receiving calcium antagonist drugs.

Coronary Circulation↗
PubMed1986

Exercise-induced changes of left ventricular ejection time in noninvasive evaluation of chest pain.

Significance and clinical usefulness of exercise-induced changes of noninvasive left ventricular ejection time, recorded by mechanocardiography, in detecting coronary artery disease is still controversial. We investigated the changes of the left ventricular ejection time (LVET), corrected for heart rate as ETI (LVET/square root RR), after a standard 4-min exercise by bicycle ergometer (50 W/min for 2 min, increased by 20 W after 2 min) in 56 male volunteers. They were invasively studied for typical or atypical chest pain. Thirty-four had coronary artery disease (CAD) and the others served as controls. Immediately after exercise LVET shortened according to the rise in heart rate in both groups. ETI increased similarly. After 2 minutes from exercise ETI increased only in the CAD group, according to a longer LVET, in spite of the rise in heart rate. In contrast, ETI was unchanged in controls, according to a shortened LVET. Totally, 27/34 CAD patients and 9/22 controls had a greater ETI than at rest. Employing this delta ETI as a "marker" of CAD we found a predictive accuracy of 74%. We suggest postexercise ETI could be a simple and inexpensive support to electrocardiogram in basic evaluation of subjects with chest pain.

Angina Pectoris↗
PubMed1986

Physiological concentrations of zinc inhibit the release of histamine from human basophils and lung mast cells.

We have previously shown that physiological concentrations of zinc (congruent to 7 X 10(-6) M) inhibit the release of histamine from human basophil leukocytes (Marone et al., J. Pharmacol. Exp. Ther. 217: 292, 1981). In these experiments we compared the effect of zinc chloride on the release of chemical mediators from human basophils and mast cells isolated from human lung. Preincubation (5 min, 37 degrees C) of human basophils and lung mast cells with zinc chloride (10(-6)-3 X 10(-5) M) caused dose-related inhibition of histamine and peptide leukotriene C4 (LTC4) release induced by anti-IgE. Increase Ca2+ concentrations (0.3 to 6 mM) in the extracellular medium completely reversed the inhibitory effect of zinc on anti-IgE-mediated histamine secretion. Zinc chloride was a competitive antagonist of the action of Ca2+ in histamine secretion induced by anti-IgE with a dissociation constant (Kd) of about 10(-5) M in both the basophil and mast cell systems. Thus physiological concentrations of zinc inhibit the release of histamine from human basophils and lung mast cells, presumably by blocking Ca2+ uptake induced by anti-IgE activation.

Basophils↗
PubMed1986

IgE-mediated activation of human heart in vitro.

We used human cardiac tissue from the right atrial appendages of patients undergoing corrective heart surgery to study content and de novo synthesis of mediators in the human heart. Human heart tissue contained 1.7 +/- 0.1 micrograms/g wet weight of histamine (mean +/- S.E.M.) and spontaneously produced 6-keto-PGF1 alpha (38.4 ng/g wet weight/min), PGF1 alpha (1.9 ng/g wet weight/min), PGE (1.7 ng/g wet weight/min) and thromboxane B2 (TxB2) (1.7 ng/g wet weight/min). Spontaneous release of PGD2, leukotriene C4 and histamine was negligible. Rabbit anti-human IgE (1-10 micrograms/ml) dose-dependently induced the release of histamine (5 to 15% of the total histamine content) and of PGD2 (5 to 100 ng/g of wet tissue). The effect of anti-IgE was dose-related and reached a maximum after 30-45 min of incubation. A significant linear correlation (rs = 0.90; p less than 0.001) was found between de novo synthesis of PGD2 and the secretion of histamine induced by anti-IgE challenge of human heart. These results support the concept that PGI2 is the main, but not the sole, product of arachidonic acid metabolism synthesized by human heart in vitro. Additionally, anti-IgE challenge of human heart in vitro induces the release of histamine and PGD2. The local concentrations of these mediators appear high enough to play some role in the modulation of several cardiac functions in vivo.

Animals↗
PubMed1986

Human basophil releasability. I. Age-related changes in basophil releasability.

Releasability of human basophils (i.e., the response to a standard stimulus) is an important parameter in several pathophysiologic conditions. We studied the IgE (anti-IgE)- and non-IgE-mediated (f-met peptide and Ca2+ ionophore A23187) releasability of human basophils obtained from 63 normal donors whose ages ranged from 1 to 86 years. The maximum percent of histamine release induced by anti-IgE was significantly correlated (rs = 0.57; p less than 0.001) with the age of donors. The sensitivity to a standard concentration of anti-IgE (3 X 10(-2) mcg/ml) was also correlated with the age of cell donors (rs = 0.68; p less than 0.001). In the population of 63 donors tested, the maximum percent of histamine release and the cell sensitivity to anti-IgE appeared to be independent of the serum concentration of IgE. However, we found a positive correlation (rs = 0.55; p less than 0.05) between serum IgE level and anti-IgE-induced histamine release in the group less than 20 years of age. In contrast, a negative correlation (rs = -0.32; p less than 0.05) between serum IgE level and anti-IgE-induced histamine secretion was found in the group greater than 21 years of age. The maximum percent of histamine release induced by f-met peptide and Ca2+ ionophore A23187 appeared to be independent to both the age of the donors and the serum IgE level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

The Wiskott-Aldrich syndrome: studies of platelets, basophils and polymorphonuclear leucocytes.

Platelets, basophils and neutrophils from a patient with the Wiskott-Aldrich syndrome (WAS) were exposed to stimuli that activate specific membrane receptor or directly initiate biochemical events (e.g. the Ca2+ ionophore A23187 and ionomycin or arachidonic acid). Platelets from this patient did not aggregate in response to ADP, collagen, thrombin or adrenaline, which activate specific membrane receptors. Platelet aggregation, however, was normal in response to compound A23187, ionomycin or exogenous arachidonic acid. Histamine release from basophils of the WAS patient was normal in response to anti-IgE, a formylated peptide (f-met peptide), and to A23187. Similarly, the release of the lysosomal enzymes, beta-glucuronidase and lysozyme, from neutrophils of the WAS patient in response to serum treated zymosan (Zx), f-met peptide, and A23187 was not significantly different from that of his parents and 13 normal donors. These results suggest that the primary defect in WAS is selectively present in platelets and is located in a biochemical step between receptor activation and Ca2+ influx and/or initiation of arachidonate metabolism.

Arachidonic Acid↗
PubMed1986

Reversal of left ventricular hypertrophy following treatment with beta-blockers: experience with tertatolol.

Hypertrophy in response to increasing blood pressure in primary hypertension leads to important functional consequences for the left ventricle. In fact, the progression of hypertensive heart disease, from an adaptive left ventricular hypertrophy with compensated ventricular function to severe hypertrophy with left ventricular failure, has been long thought to be related to the severity and duration of hypertension. Antihypertensive treatment seems to prevent or minimize the occurrence of left ventricular hypertrophy, but questions arise as to whether this therapy is also able to restore normal hemodynamic conditions, or at least to minimize the hemodynamic abnormalities. This review aims at summarizing current knowledge on the effects of the antihypertensive treatment with beta-blockers, including tertatolol, on hypertension-induced left ventricular hypertrophy. The pathogenetic mechanisms underlying the cardiovascular changes associated with hypertension are discussed. A decrease in left ventricular wall thickness as well as in left ventricular mass has been reported in most of the studies performed with different types of beta-adrenergic blocking agents. The extent of this reduction seems to be related not only to the fall in systemic blood pressure, but also to a decrease in sympathetic stimulation. With regard to the functional consequences of hypertension, the reversal of left ventricular hypertrophy following antihypertensive treatment with beta-blockers is usually associated with an improvement in left ventricular performance. This phenomenon can hardly be ascribed to the direct effects of beta-blocking agents. It is more likely to be related to the concomitant reduction in the afterload and to the improved left ventricular compliance, associated with a decrease in left ventricular wall thickness.

Adrenergic beta-Antagonists↗
PubMed1986

Impaired responsiveness of the ventricular sensory receptor in hypertensive patients with left ventricular hypertrophy.

We studied the control of forearm vascular resistance (FVR) by cardiopulmonary receptors in seven patients with hypertension and left ventricular hypertrophy (LVH) and in seven normotensive control subjects. Increasing levels of lower body negative pressure (LBNP) (-10 and -40 mm Hg) induced a progressive decrease in central venous pressure (CVP) and an increase in FVR. The changes in these two variables were correlated both in normal subjects and patients with hypertension (slope for normal subjects = -29.9, for patients with hypertension = -40.3, NS). After propranolol, there was a significant reduction in the increase in FVR induced by -40 mm Hg LBNP in normal subjects (+107 +/- 5 vs +129 +/- 15 mm Hg/ml/sec, p less than .05) but not in patients with hypertension. Consequently, the slope of the delta CVP/delta FVR regression was reduced in normal subjects (-20.6, p less than .01) but not in patients with hypertension. In another seven normal subjects and seven patients with hypertension and LVH we assessed the effects of -10 and -40 mm Hg LBNP on left ventricular filling pressure (LVFP). LBNP induced similar changes in CVP, LVFP, and total peripheral resistance both in normal subjects and in patients with hypertension. Propranolol failed to modify the effects of LBNP on CVP and LVFP in both groups and reduced the response of total peripheral resistance to -40 mm Hg LBNP only in normal subjects. Propranolol did not reduce the response of FVR to the cold pressor test and sustained handgrip or the arterial baroreflex response to the injection of phenylephrine and increased neck tissue pressure. Thus, hypertension-induced LVH seems to be associated with a selective impairment of the left ventricular sensory receptors.

Adult↗
PubMed1986

Relation between QT and QS2 intervals during exercise and recovery. Response in patient with coronary artery disease and age-matched control subjects.

We investigated the relationship between QT interval and QS2 (electromechanical systole) during exercise and recovery in patients with coronary artery disease (CAD) and exercise-induced myocardial ischemia (n = 12), and in age-matched controls (n = 20). Upright bicycle exercise was performed (50 watts/min + 20 watts/min every 2 min), recording electrocardiographic lead 2 (100 mm/sec) for QT and QS2 measurement at rest, at each step of uninterrupted exercise and every 60 sec during a 3-min recovery period. Resting data showed a QT less than QS2 finding in both groups; during exercise, QT and QS2 decreased. The values of QT and QS2, collected at each step of exercise and plotted against heart rate (HR) separately for both groups, showed a significant correlation coefficient. Comparing the regression lines of HR-QT and HR-QS2 separately for both groups, we found that both intervals decreased in parallel and the mean QT remained shorter than QS2 in both groups during exercise. The QT/QS2 ratio remained unchanged significantly during exercise and recovery in CAD. In control subjects, the ratio remained unchanged during exercise and the first min of recovery, while a significant change was detected in late (2,3 min) recovery from an adrenergic-induced effect. The mean exercise-induced response of QT-QS2 relationship includes a QT less than QS2 pattern in both groups. In CAD patients, an abnormal pattern was found in two patients during recovery by a relative prolongation of QT, suggesting the possibility of a risk factor for dangerous arrhythmias or sudden death.

Blood Pressure↗
PubMed1986

Effects of prostaglandin synthesis inhibition on sympathetic-and parasympathetic-mediated coronary hemodynamic responses.

In chloralose-anesthetized dogs with the left circumflex coronary artery perfused at constant flow, the effects of indomethacin or naproxen on coronary and systemic responses to sympathetic and parasympathetic stimulation were evaluated. Sympathetic stimulation was evoked either by 1-min carotid artery occlusion or by epinephrine (5 micrograms) or norepinephrine (5 micrograms) intracoronary administration. Reflex or direct parasympathetic stimulation was produced by ouabain (40 micrograms) or acetylcholine (2.5 micrograms) injection, respectively, in the perfused coronary artery. The administration of indomethacin or naproxen reduced the integrated areas of coronary vasodilatation induced by epinephrine and norepinephrine. The extent of this reduction was dose-dependent with both indomethacin (epinephrine: r = 0.774, n = 35, P less than .001; norepinephrine: r = 0.766, n = 35, P less than .001; norepinephrine: r = 0.799, n = 35, P less than .001) up to 1.5 and 7 mg/kg, respectively. Further increase in dosage of both prostaglandin synthesis inhibitors failed to induce further reduction of integrated areas of coronary vasodilatation. In contrast, the maximum fall in coronary perfusion pressure, induced by both catecholamines, remained unmodified after inhibition of prostaglandin synthesis, whereas a faster return of the perfusion pressure to base line was observed. The extent of cyclooxygenase activity inhibition induced by indomethacin or naproxen, assessed through the radioimmunoassay of thromboxane B2, showed a consistent dose-dependent increase until complete inhibition was attained with 1.5 mg/kg of indomethacin and 7 mg/kg of naproxen. No significant change in the coronary and systemic hemodynamic response induced by carotid occlusion and by ouabain or acetylcholine intracoronary administration was observed. Furthermore, complete cyclooxygenase inhibition, induced by either indomethacin or naproxen, was able to reduce the coronary vasodilatation induced by isoproterenol (5 micrograms) intracoronary injection but failed to modify the coronary vasoconstriction elicited by both epinephrine and norepinephrine in propranolol-treated dogs. These data indicate that the prostaglandin system is involved in the coronary vasodilatation induced by humoral sympathetic stimulation, whereas coronary hemodynamic responses to both neural sympathetic or parasympathetic stimulation are not influenced by the administration of prostaglandin synthesis inhibitors.

Acetylcholine↗
PubMed1986

Noninvasive techniques in clinical pharmacology. Time intervals in assessment of vasodilators in coronary artery disease.

We enrolled 15 male volunteers with angiographic evidence of coronary artery disease (CAD) to investigate the effects of sublingual administration, on different days, at random, of placebo and three drugs with different action such as isosorbide dinitrate, nifedipine and molsidomine. We recorded simultaneously electrocardiogram, phonocardiogram and carotid pulse at paper speed of 100 mm/s; blood pressure was measured by auscultatory method. We calculated the systolic time intervals (STI) being noninvasive indices of left ventricular function and the ratio of diastolic time to heart rate (%D), well related to coronary blood flow in patients with severe obstructive lesions. Placebo decreased heart rate (HR) without effects on STI or %D. Isosorbide dinitrate induced a prolonged pre-ejection period (PEP) (by decreasing preload), tachycardia and a significantly decreased %D, suggesting a fall in coronary blood flow time. Nifedipine decreased diastolic blood pressure and values of PEP (by decreasing afterload) without effects on %D. Finally, molsidomine prolonged PEP (by decreasing preload) without reflex induced tachycardia and changes of %D. In conclusion, mechanocardiography can be useful in noninvasive assessment of vasodilators in CAD patients.

Blood Pressure↗