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Biomedical subjects

G Marone

Publications and source records attributed to G Marone.

At least 55 records · Page 3Linked to original sources
PubMed1998

Alterations of cerebral blood flow and antiphospholipid antibodies in patients with systemic lupus erythematosus.

Twenty-two patients with systemic lupus erythematosus and 13 healthy controls were included in a cerebral blood flow study and underwent brain-dedicated single-photon emission computed tomography using 99m technetium-d, l-hexamethylpropylene amine oxime together with a brain computed tomography scan. Plasma levels of antiphospholipid antibodies (lupus anticoagulant and anticardiolipin IgM and IgG antibodies) were also determined. Brain computed tomography showed signs of focal cerebral ischemia in 4 patients (18%), whereas cerebral blood flow by single-photon emission computed tomography was abnormal in 13 of 22 patients (59%), who showed bilateral or monolateral hypoperfusion in the temporo-parietal regions. Patients with abnormal cerebral blood flow had a longer duration of disease than those with normal blood flow (8.9 +/- 1.9 years vs. 5.3 +/- 1.5 years, P < 0.05). Plasma antiphospholipid antibodies were present in 15 patients (68%), but the prevalence was similar in those with normal (6/9, 66%), or abnormal (9/13, 69%) cerebral blood flow. No statistically significant difference in lupus anticoagulant or anticardiolipin antibodies was observed between patients with and without cerebral blood flow abnormalities. Our study shows that patients with systemic lupus erythematosus frequently have cerebral blood flow abnormalities, which could precede those observed by computed tomography. Plasma lupus anticoagulant and anticardiolipin titers were not correlated with normal cerebral blood flow.

Adolescent↗
PubMed1998

Molecular basis for the lack of HERG K+ channel block-related cardiotoxicity by the H1 receptor blocker cetirizine compared with other second-generation antihistamines.

In the current study, the potential blocking ability of K+ channels encoded by the human ether-a-go-go related gene (HERG) by the piperazine H1 receptor antagonist cetirizine has been examined and compared with that of other second-generation antihistamines (astemizole, terfenadine, and loratadine). Cetirizine was completely devoid of any inhibitory action on HERG K+ channels heterologously expressed in Xenopus laevis oocytes in concentrations up to 30 microM. On the other hand, terfenadine and astemizole effectively blocked HERG K+ channels with nanomolar affinities (the estimated IC50 values were 330 and 480 nM, respectively), whereas loratadine was approximately 300-fold less potent (IC50 approximately 100 microM). In addition, in contrast to terfenadine, cetirizine did not show use-dependent blockade. In SH-SY5Y cells, a human neuroblastoma clone that constitutively expresses K+ currents carried by HERG channels (IHERG), as well as in human embryonic kidney 293 cells stably transfected with HERG cDNA, extracellular perfusion with 3 microM cetirizine did not exert any inhibitory action on IHERG. Astemizole (3 microM), on the other hand, was highly effective. Terfenadine (3 microM) caused a marked (approximately 80%) inhibition of IHERG in SH-SY5Y cells, whereas loratadine, at the same concentration, caused a 40% blockade. Furthermore, the application of cetirizine (3 microM) on the intracellular side of the membrane of HERG-transfected human embryonic kidney 293 cells did not affect IHERG, whereas the same intracellular concentration of astemizole caused a complete block. The results of the current study suggest that second-generation antihistamines display marked differences in their ability to block HERG K+ channels. Cetirizine in particular, which possesses more polar and smaller substituent groups attached to the tertiary amine compared with other antihistamines, lacks HERG-blocking properties, possibly explaining the absence of torsade de pointes ventricular arrhythmias associated with its therapeutical use.

Animals↗
PubMed1998

Deep Intubation of 6 French Guiding Catheters for Transradial Coronary Interventions.

Deep intubation of coronary guides may improve the backup support required to deliver interventional materials through 6 French catheters. Eighteen patients (17 male, 1 female) with 20 lesions were selected for transradial angioplasty and stenting using the Cordis Long Brite Tip¨ guide. Patients with an evolving acute myocardial infarction and those with an abnormal Allen test were excluded. All patients were pretreated with aspirin, ticlopidine, and heparin. The mean age was 55 (range 34Ð81). The target vessel was the right coronary in 6 of 20 (30%), the circumflex artery in 6 of 20 (30%), left anterior descending in 4 of 20 (20%), vein grafts in 3 of 20 (15%), and ramus intermedius in one case (5%). Seventeen lesions were treated with stents, and 3 with PTCA alone. Three lesions received 2 stents. Procedural success (less than 20% residual stenosis) was obtained in 19/20 cases. No dissections were seen as a result of deep intubation. Dampening of pressure and ischemia occurred in only 2 patients. Deep intubation with this guide may be safely used to obtain support when performing 6 French angioplasty and stenting using the transradial approach.

Journal Article↗
PubMed1998

[Echo-guided radiofrequency percutaneous ablation of hepatocellular carcinoma in cirrhosis using a cooled needle].

INTRODUCTION: Radiofrequency hyperthermia using the newly-developed "cooled-tip" needle is one of the latest US-guided percutaneous treatments of hepatocellular carcinoma arising in cirrhosis. The continuous cooling of the needle tip allows tissue heating and necrosis far from the electrode without tissue charring, which was the major drawback of the old monopolar technique. Herein we report our preliminary results on feasibility and effectiveness of the thermoablation of mono- or paucifocal hepatocellular carcinoma with the cooled-tip needle. MATERIAL AND METHODS: November, 1996, to January, 1998, we treated thirteen cirrhotic patients (mean age 69.5 yrs, 10 men, 12 HCV-positive; 11 in Child's Class A and 2 in Class B) with 19 hepatocellular carcinoma nodules (mean diameter: 27 mm; range: 10-41 mm; 6 with diameter > 3 cm). None of the patients had portal thrombosis and/or extrahepatic spread. We used a radiofrequency generator (100 W power) connected to an 18 G perfusion electrode needle with an exposed tip of 2-3 cm. The circuit is closed through a dispersive electrode positioned under the patient's thighs. A peristaltic pump infuses a chilled (2-5 degrees C) saline solution to guarantee the continuous cooling of the needle tip. The needle was placed into target lesions under US guidance. The interventional procedure was carried out under general anesthesia using Propofol without intubation. Dynamic CT (more recently with the helical technique) was carried out 15-20 days after thermoablation to assess treatment efficacy. RESULTS: In all, 31 thermal injuries (at 1000-1200 mA for 10-15 minutes) were caused in 21 sessions in the 19 hepatocellular carcinoma nodules (mean: 1.5 lesions per nodule and 1.6 sessions per patient). Complete necrosis as assessed at dynamic CT (no enhancement during the arteriographic phase) was achieved in 16 of 19 nodules (84%). No side-effects occurred. During the follow-up (median: 11 months) no death occurred and five patients had recurrent hepatocellular carcinoma appearing either as single nodule or as multinodular liver involvement. CONCLUSIONS: In our experience radiofrequency hyperthermia with the cooled-tip needle permits effective and safe percutaneous ablation of HCC in cirrhosis. In addition, treatment time is short and lesions > 3 cm can be treated. Further experience is needed to better define the role of percutaneous thermoablation in the treatment strategy of hepatocellular carcinoma.

Aged↗
PubMed1997

Relapsing neoplastic seeding after percutaneous ethanol injection for hepatocellular carcinoma. Clinical and ultrasonographic findings in a cirrhotic patient.

A case of neoplastic implant after percutaneous ethanol injection (PEI) therapy for hepatocellular carcinoma (HCC) occurring in two steps is described. A 74-year-old male cirrhotic patient underwent PEI for a 5-cm HCC nodule. To obtain complete tumoral necrosis, 80 ml were injected under sonographic guidance in four sessions. Ten months after the completion of PEI a subcutaneous nodule was palpated in the abdominal wall within the area of needle punctures. Histologic examination of the excised nodule confirmed the sonographic and Power Doppler diagnosis of metastatic HCC. At the US exam scheduled three months later a non-palpable subcutaneous nodule of 16 mm was appreciated near the surgical wound. Once again metastatic HCC was demonstrated at pathological examination. Copyright 1997 Elsevier Science Ireland Ltd.

Journal Article↗
PubMed1997

Human synovial mast cells. II. Heterogeneity of the pharmacologic effects of antiinflammatory and immunosuppressive drugs.

OBJECTIVE: To evaluate the in vitro effects of 4 antiinflammatory and 5 immunosuppressive agents on the release of preformed and de novo-synthesized mediators from human synovial mast cells (HSyMC) activated by immunologic and nonimmunologic stimuli. METHODS: The effects of antiinflammatory and immunosuppressive agents were evaluated on the in vitro release of histamine and tryptase and the de novo synthesis of prostaglandin D2 (PGD2) and leukotriene C4 (LTC4) by HSyMC challenged with anti-IgE and substance P. RESULTS: Nimesulide, a sulfonanilide nonsteroidal antiinflammatory drug (NSAID) chemically unrelated to other acidic NSAIDs (such as acetylsalicylic acid [ASA], diclofenac, and piroxicam) inhibited in a concentration-dependent manner the release of preformed (histamine and tryptase) mediators from HSyMC challenged with anti-IgE. In contrast, diclofenac and piroxicam had little or no effect on HSyMC activated by anti-IgE. ASA, diclofenac, piroxicam, and nimesulide caused a concentration-dependent inhibition of IgE-mediated PGD2 release from HSyMC. Nimesulide, but not diclofenac or piroxicam, also inhibited the de novo synthesis of LTC4 by HSyMC challenged with anti-IgE. Nimesulide, diclofenac, and piroxicam had no effect on HSyMC activated by substance P. Cyclosporin A (CSA) inhibited histamine release from HSyMC challenged with anti-IgE, whereas cyclosporin H (CSH) had no effect. FK-506 also inhibited histamine release from HSyMC activated by anti-IgE, whereas rapamycin had no effect. Neither CSA, CSH, FK-506, nor rapamycin inhibited the release of histamine from HSyMC induced by substance P. Methotrexate had no effect on the release of mediators from these cells, whereas adenosine (R-phenylisopropyl adenosine and 5'-N-ethylcarboxamide adenosine) enhanced histamine release from immunologically activated HSyMC in a concentration-dependent manner. CONCLUSION: Mast cells isolated from human synovia display 4 levels of pharmacologic heterogeneity with regard to 1) the inhibitory effects of 4 antiinflammatory drugs; 2) the capacity of different immunosuppressive drugs to exert antiinflammatory activity; 3) the inhibition of the release of different mediators; and 4) the capacity of antiinflammatory and immunosuppressive drugs to modulate HSyMC activated by different stimuli. This complexity of pharmacologic modulation of HSyMC in vitro might help explain the different activity of the compounds used to treat various pathophysiologic aspects of the inflammatory arthritides.

Adenosine↗
PubMed1997

Metabolic and hemodynamic effects of peptide leukotriene C4 and D4 in man.

The time course of the effects of intravenous or intracoronary administration of peptide leukotrienes on metabolic parameters and on systemic and coronary hemodynamics was evaluated in 15 patients with normal coronary arteries. Peptide leukotriene C4 (2 nmol given as a bolus intravenous injection) induced an early fall (at 2 min) in mean arterial pressure (P < 0.02) associated with a rise in heart rate (P < 0.001) and in plasma levels of epinephrine (P < 0.05) and norepinephrine (P < 0.005), but without significant changes in coronary blood flow or coronary vascular resistance. Mean arterial pressure, heart rate, norepinephrine, and epinephrine returned to baseline values 10 min after leukotriene C4 administration. In contrast, at 10 min post leukotriene C4, with coronary blood flow and myocardial oxygen consumption unchanged, an increase in coronary vascular resistance (P < 0.05) and in myocardial oxygen extraction (P < 0.01) was observed, which returned to baseline values at 20 min post leukotriene C4. Peptide leukotriene D4 (3 nmol, given in the left coronary artery) induced an early (20 s) and transient fall in mean arterial pressure (P < 0.001) paralleled by a rise in heart rate and plasma levels of epinephrine and norepinephrine, all of which returned to baseline at 10 min. Coronary vascular resistance increased at 10 and 15 min (P < 0.02 and P < 0.05, respectively) and myocardial oxygen extraction at 15 min (P < 0.02). These results suggest that small doses of peptide leukotrienes induce both an early and transient fall in mean arterial pressure associated with secondary sympathoadrenergic activation, and a late increase in small coronary arteriolar resistance.

Adult↗
PubMed1997

Loratadine and desethoxylcarbonyl-loratadine inhibit the immunological release of mediators from human Fc epsilon RI+ cells.

BACKGROUND: Loratadine, a novel histamine H1-receptor antagonist, is effective in the treatment of patients with seasonal and perennial rhinitis and some allergic skin disorders. Histamine and other chemical mediators are synthesized and immunologically released by human peripheral blood basophils and tissue mast cells (Fc epsilon RI+ cells). OBJECTIVE: To evaluate the effects of loratadine and its main metabolite, desethoxylcarbonyl-loratadine (des-loratadine), on the immunological release of preformed (histamine and tryptase) and de novo synthesized mediators (leukotriene C4: LTC4 and prostaglandin D2:PGD2) from human Fc epsilon RI+ cells. METHODS: Human Fc epsilon RI+ cells purified from peripheral blood and from skin (HSMC) and lung tissue (HLMC) were preincubated with loratadine and des-loratadine before immunological challenge with Der p 1 antigen or anti-Fc epsilon RI. The release of preformed mediators (histamine and tryptase) and de novo synthesized eicosanoids was evaluated in the supernatants of human Fc epsilon RI+ cells. RESULTS: Preincubation (15 min, 37 degrees C) of purified (36-74%) basophils with loratadine (3 x 10(-6)-10(-4)M) and des-loratadine before Der p 1 antigen or anti-Fc epsilon RI challenge concentration-dependently (5-40%) inhibited the release of histamine and LTC4. Loratadine (3 x 10(-6)-10(-4)M) and des-loratadine also inhibited (10-40%) histamine, LTC4, and PGD2 release from purified HLMC (16-68%) activated by anti-Fc epsilon RI. Loratadine (3 x 10(-6)-10(-4)M) and des-loratadine caused concentration-dependent inhibition (10-40%) of histamine, tryptase, LTC4, and PGD2 release from purified HSMC (24-72%) immunologically challenged with anti-Fc epsilon RI. CONCLUSION: These results indicate that loratadine and its main metabolite have anti-inflammatory activity by inhibiting the release of preformed and de novo synthesized mediators from human Fc epsilon RI+ cells.

Adult↗
PubMed1997

Heterogeneous effects of protamine on human mast cells and basophils.

To investigate the mechanisms of anaphylactoid reactions to protamine, we have examined the in vitro effects of increasing concentrations of protamine (10(-6)-3 x 10(-4) mol litre-1) on the release of preformed (histamine and tryptase) and de novo synthesized (peptide leukotriene C4 (LTC4) or prostaglandin D2 (PGD2)) mediators from human basophils and mast cells isolated from lung parenchyma, heart, skin and synovial tissues. Protamine 10(-6)-3 x 10(-4) mol litre-1 induced release of histamine, but not de novo synthesis of LTC4 from basophils. At concentrations from 10(-5) to 3 x 10(-4) mol litre-1 it induced histamine release from human heart (mean 6.5 (SEM 1.5)%), skin (17.7 (4.1)%) and to a lesser extent from synovial mast cells, but not from lung mast cells. Protamine also caused the release of tryptase from heart mast cells (12.8 (3.2) micrograms/10(7) cells), but did not induce de novo synthesis of LTC4 and PGD2 from lung and skin mast cells. In these experiments cross-linking of IgE by anti-IgE caused release of LTC4 or PGD2 from human basophils or mast cells. These results demonstrate that protamine acted as an incomplete secretagogue, causing the release of preformed mediators from human basophils and mast cells.

Adult↗
PubMed1997

Milestones in the biology and pharmacology of H1-receptor antagonists.

Daniele Bovet's pioneering discovery that a series of compounds possessing anti-histamine activity reduced the symptoms of anaphylaxis provided the proof that histamine plays a pivotal role as a mediator of allergic reactions. Basophils and mast cells are the major sources of histamine in man and they are thus one of the primary effector cells of allergic inflammation. Some H1-receptor antagonists possess a variety of antiinflammatory activity to H1 antagonism in vitro and in vivo. This promising area should be explored further and much remains to be done in the evaluation of the immunomodulatory effects of anti-histamines.

Histamine↗
PubMed1997

Molecular and cellular biology of mast cells and basophils.

In all mammalian species investigated so far, mast cells and basophils are the only cells that synthesize histamine and express plasma membrane receptors that bind IgE with high affinity (Fc epsilonRI). Human basophils and mast cells derive from distinct precursors that originate in the bone marrow and fetal liver and probably circulate in peripheral blood. There is extensive evidence that mast cells and basophils and their mediators are primary effectors of allergic inflammation. Immunologically activated human basophils release two cytokines: IL-4 and IL-13. Expression of several cytokines has been documented in a number of experimental models of human and rodent mast cells. However, to date few studies have analyzed the mechanisms of gene expression in human Fc epsilonRI+ cells. Some of these studies imply a role for NFAT and GATA family members in the IgE-mediated activation of cytokine gene transcription in basophils and mast cells. Studies of human basophils and mast cells isolated from different anatomic sites have established the different profiles of eicosanoids released by these cells. Recently, the characterization of arachidonic acid pools and the identification of novel enzymes involved in arachidonate remodeling and mobilization clarified in part how eicosanoid productions is regulated in mast cells and basophils. In addition to histamine, human mast cell secretory granules contain the neutral proteases tryptase, chymase and carboxypeptidase that possess several biochemical properties. In particular, tryptase may play a role as a fibrogenic factor and chymase might convert angiotensin I to angiotensin II. Mast cells are present in human heart and in human coronary arteries raising the possibility that local activation of cardiac mast cells might contribute to certain cardiovascular diseases. Recent evidence also suggests that mast cells and basophils can play a role during viral and bacterial infections. It is now evident that in man these two cells not only participate in inflammation associated with allergic disease, but also in chronic and fibrotic disorders affecting several organs and in host defense against bacterial and viral infections.

Animals↗
PubMed1997

Characterization of platelet-activating factor acetylhydrolase in human bronchoalveolar lavage.

Platelet-activating factor (PAF) is a mediator produced in human airways during acute and chronic inflammatory lung diseases. The levels of PAF are regulated by acetylhydrolase (AH), the enzyme that converts PAF to lyso-PAF. To determine whether AH was present in human bronchoalveolar lavage (BAL) fluid, BAL was obtained from normal donors (n = 18) and from adult patients with mild bronchial asthma (n = 15) or with lung fibrosis (n = 15). AH activity was consistently found in the cell-free BAL fluid. BAL-AH is an enzyme different from secretory phospholipase A2 and from plasma AH and erythrocyte AH. Furthermore, BAL-AH is inhibited as much as 95% by exposure to an oxygen radical-generating system (xanthine/xanthine oxidase). BAL-AH is significantly correlated with the number of BAL macrophages (rs = 0.63; p < 0.02). In addition, BAL macrophages release AH both spontaneously and after stimulation with tumor necrosis factor-alpha (TNF-alpha) (100 ng/ml). BAL-AH activity in patients with bronchial asthma (1.32 +/- 0.18 pmol of PAF converted to lyso-PAF/min) is significantly lower than that in normal donors (2.25 +/- 0.26 pmol/min; p < 0.001). In contrast, BAL-AH activity in patients with lung fibrosis (6.13 +/- 0.81 pmol/min) is higher than that found in normal donors (p < 0.01). The variations in BAL-AH activity in patients with bronchial asthma or lung fibrosis are due to a reduction and to an increase, respectively, in the number of active molecules rather than to changes in enzyme affinity. These data demonstrate that human BAL fluid contains an extracellular AH activity that inactivates PAF released in the airways. BAL-AH is secreted by alveolar macrophages and is highly sensitive to oxygen radical-induced damage. The secretion and inactivation of BAL-AH may influence the levels of this enzyme in BAL fluid during acute and chronic inflammatory lung diseases and, ultimately, regulate the proinflammatory activities of PAF in these disorders.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1996

Eosinophil granule proteins activate human heart mast cells.

Eosinophilia in humans is often associated with heart disease and cardiac localization of eosinophil granule proteins, and several results suggest that granule proteins mediate endomyocardial damage. Here we investigated the in vitro effects of the four principal eosinophil granule proteins (eosinophil cationic protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin, and eosinophil peroxidase (EPO)) on the activation of effector cells of inflammation (mast cells) isolated from human heart tissue (HHMC). ECP and, to a lesser extent, MBP (0.3-3 microM), but not eosinophil-derived neurotoxin and eosinophil peroxidase stimulated the release of preformed (histamine and tryptase) and the de novo synthesis of vasoactive and proinflammatory mediators (PGD2) from HHMC. Activation of HHMC by ECP and MBP was Ca2+- and temperature-dependent and was abolished by preincubation (15 min, 37 degrees C) with 2-deoxy-D-glucose (10 mM) and antimycin A (1 microM). There was a significant correlation between the maximal percentage of histamine release induced by ECP and anti-IgE from HHMC (rs = 0.73; p < 0.005), by MBP and anti-IgE (rs = 0.79; p < 0.001), and by ECP and MBP (rs = 0.65; p < 0.005). A positive correlation was also found between histamine and tryptase secretion (rs = 0.71; p < 0.001) and between histamine and PGD2 release induced by ECP from HHMC (rs = 0.85; p < 0.001). This is the first demonstration that some eosinophil cationic proteins, namely ECP and MBP, found at the site of heart damage in patients with eosinophilia, act as complete secretagogues on HHMC. This observation indicates another mechanism by which infiltrating eosinophils and their metabolic products cause inflammatory reactions and thus endomyocardial lesions in patients with eosinophilia.

Blood Proteins↗
PubMed1996

Human synovial mast cells. I. Ultrastructural in situ and in vitro immunologic characterization.

OBJECTIVE: To examine the ultrastructure of human synovial mast cells in situ, to identify immunologic and nonimmunologic stimuli that activate these cells in vitro, and to quantify a number of preformed and de novo-synthesized mediators. METHODS: We conducted an ultrastructural study of synovial mast cells in situ and performed immunoelectron microscopy localization of tryptase and chymase. Isolated synovial mast cells were analyzed biochemically, immunologically, and functionally in vitro and compared with cells from human lung, heart, and skin. RESULTS: Ultrastructural study of synovial tissue revealed mast cells with homogeneously dense, scrolled, crystal, and mixed granules, and lipid bodies in the cytoplasm. A small percentage of mast cells showed evidence of degranulation. Immunoelectron microscopy demonstrated the subcellular localization of tryptase and chymase over granules of > 90% of the mast cells, which were of the MCTC subtype. Isolated synovial mast cells released histamine in response to immunologic (anti-IgE and anti-Fc epsilon receptor I [anti-Fc epsilon RI]) and nonimmunologic (substance P, recombinant human stem cell factor, and 48/80) stimuli, but did not respond to recombinant human C5a in vitro. Synovial mast cells differed from those isolated from other human tissues, in a variety of immunologic and biochemical features. There was a linear correlation between the percentage of histamine secretion and tryptase release (r = 0.79, P < 0.001) induced by cross-linking of Fc epsilon RI. Cross-linking of IgE with anti-IgE on synovial mast cells induced de novo synthesis of prostaglandin D2 (mean +/- SEM 87.5 +/- 4.9 ng/10(6) cells) and of leukotriene C4 (57.6 +/- 17.8 ng/10(6) cells). CONCLUSION: Mast cells ultrastructurally characterized in situ in synovial tissue were seen to differ from mast cells previously isolated from other human tissues. This raises the possibility that the local microenviroment influences their phenotype. Isolation of mast cells from human synovia can be useful for studying their role and their mediators in patients with arthritis.

Adult↗
PubMed1996

Giardiasis as a cause of hypokalemic myopathy in congenital immunodeficiency.

Hypokalemic myopathy may occur in several infections. We report a case of severe and transient myopathy secondary to hypokalemia induced by chronic intestinal infection with Giardia lamblia in a patient with common variable hypogammaglobulinemia. Hypokalemic myopathy is documented by serum enzymes, electromyography (reduction in the number of voluntarily activated motor unit action potentials and an increase in polyphasic motor unit action potentials, and pathological changes (hematoxylin-eosin, ATPase staining). The case reported involves hypokalemic myopathy induced by giardiasis in a patient with primary immunodeficiency; the histopathological changes observed in a skin/muscle biopsy from this patient are described for the first time.

Agammaglobulinemia↗
PubMed1996

Contrast media are incomplete secretagogues acting on human basophils and mast cells isolated from heart and lung, but not skin tissue.

To investigate the mechanisms of anaphylactoid reactions to radiocontrast media, in vitro mediator release induced by three iodinated contrast agents was examined using peripheral blood basophils and mast cells purified from human lung parenchyma, heart, and skin tissues. Three iodinated contrast agents, sodium and meglumine salts of ioxaglic acid, sodium and meglumine salts of ioxithalamic acid, and ioversol, were incubated with basophils purified from peripheral blood and human mast cells isolated and purified from different anatomical sites. Release of preformed (histamine and tryptase) and de novo synthesized mediators (prostaglandin D2 and leukotriene C4) into the supernatans was determined at various contrast medium concentrations after incubation for 60 min. Ioxaglate (0.2-0.3 M), ioxithalamate (0.3-0.5 M), and to a lesser extent ioversol (0.3-0.5 M) induced histamine release from basophils in a concentration-dependent manner. All three induced the release of preformed mediators (histamine and tryptase) from human lung, but not from skin mast cells. They also induced histamine and tryptase release from human heart mast cells. However, they did not induce the de novo synthesis of leukotriene C1 or prostaglandin D2 from human basophils or any type of mast cell examined. Cross-linking of IgE by anti-IgE induced the release of leukotriene C4 or prostaglandin D2 from human basophils or mast cells. Mannitol, an osmotic stimulus, induced the release of histamine from human basophils, but to a lesser extent from mast cells. These results show that different contrast media can differ in their ability to release mediators from enriched preparations of human basophils and mast cells. The three contrast agents examined act on basophils and mast cells as incomplete secretagogues, causing the release of preformed mediators, but not these novo synthesis of chemical mediators. It may be useful to measure plasma tryptase levels to detect adverse reactions caused by iodinated radiographic contrast materials.

Adult↗