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M Triggiani

Publications and source records attributed to M Triggiani.

At least 37 records · Page 2Linked to original sources
PubMed1999

Role of arachidonyl triglycerides within lipid bodies in eicosanoid formation by human polymorphonuclear cells.

Increasing evidence suggests that the subcellular and glycerolipid localization of esterified arachidonic acid (AA) is a key factor in regulating its availability to lipases. The goal of the current study was to determine the potential of AA stored in triglycerides (TG) to serve as a substrate for lipases and 5-lipoxygenase during neutrophil (polymorphonuclear leukocytes, PMN) activation. PMN containing high concentrations of AA in TG were generated by culturing PMN in vitro with high concentrations of exogenous AA (eAA) for 12 h. Cellular AA increased 2- and 4-fold in PMNs incubated with 5 and 20 microM AA, respectively, and this increase was almost exclusively observed in neutral lipids (NL). Further analysis revealed that 88% of the AA in the NL fraction was associated with TG. Subsequent experiments were designed to determine whether this AA in TG could be mobilized and metabolized to eicosanoids during cell activation. TG pools of AA were increased as previously described and then PMN were stimulated with ionophore, A23187. In contrast to the 43-fold increase in TG AA after eAA loading (20 microM), free AA increased by only 1.9-fold after cell stimulation. Similarly, leukotriene (LT)B(4) production increased only 2-fold after loading TG with large quantities of AA. The magnitude of increase in free AA released and in LTB(4) formation was similar to the magnitude of increase in AA mass in phospholipase (PL), suggesting that PL, and not TG, served as the source of released AA and subsequent product generation. To confirm that AA in TG did not serve as a source for eicosanoid production, cellular pools of AA were differentially labeled with [(14)C]AA and [(3)H]AA, and the [(3)H]AA-to-[(14)C]AA ratio of LTB(4) and 20-hydroxyl LTB(4) produced during cell stimulation was measured. The [(3)H]AA/[(14)C]AA ratios of LTs were markedly different from the ratios in TG, thus providing further evidence that AA pools in TG are not a major source of AA for LT generation.

Arachidonic Acids↗
PubMed1999

Refractory angina despite patent coronary artery bypass grafts: treatment with transmyocardial laser revascularization and scintigraphic evidence of improved myocardial perfusion.

Progression of coronary artery disease that causes recurrent angina in patients who have already undergone coronary artery bypass grafting (CABG) is a challenge to cardiac surgeons. The presence of myocardial ischemia that is not due to bypass grafts occlusion, but to the quality of the coronary vessels characterized by diffuse atherosclerotic peripheral disease, makes the situation even more difficult, since it is not possible to perform myocardial revascularization either by percutaneous transluminal angioplasty (PTCA) or by means of new grafts. We report the case of a patient who, 4 years after triple CABG, developed refractory angina despite patency of bypass grafts (to left anterior descending artery, obtuse marginal branch and posterior descending) and maximally tolerated conventional medical treatment. Native coronary arteries were occluded. Because of the exiguous caliber of the distal portion of epicardial vessels and poor run-off, a redo CABG was judged to be unfeasible. Transmyocardial laser revascularization (TMLR) was performed through left anterior thoracotomy, minimizing the risk of damage to the grafts. Clinical improvement (from CCS class IV to 0) and scintiscan showing improved myocardial perfusion to the laser-treated regions confirm the effectiveness of TMLR in otherwise inoperable coronary artery disease.

Angina Pectoris↗
PubMed1998

Immunopharmacology of human mast cells and basophils.

Human mast cells and basophils play a key role in the pathogenesis of several immunological and inflammatory disorders, not only by producing inflammatory and fibrogenic mediators, but also by directly (CD40 ligand) and indirectly secreting various cytokines and chemokines. Studies carried out to evaluate the effects of drugs that modulate the release of mediators and cytokines from these cells have contributed to clarifying the biochemical mechanism by which immunological and non-immunological stimuli activate these cells. Significant differences have been documented between human mast cells and basophils as regard the pharmacological agents that modulate the release of mediators, between mast cells isolated from different anatomical sites, and between compounds of the same class of drugs. Efforts to gain insight into the biochemical events occurring during immunological activation of mast cells and basophils could lead to the identification of new biochemical targets for therapeutic interventions in several immunological disorders.

Adenylyl Cyclases↗
PubMed1998

Surgery of cavo-atrial renal carcinoma employing circulatory arrest: immediate and mid-term results.

From 1990 to 1995, 12 patients with cavo-atrial renal cell carcinoma underwent resection of the tumor. Circulatory arrest was employed in 11/12 cases. The neoplasm extended to the inferior vena cava in two patients and to the intrahepatic veins or right atrium in five cases. Two severely cardiac compromised patients died perioperatively. Of five patients who showed preoperative suspicion of isolated metastases, 3 patients died postoperatively because of relapsing disease after a mean period of 10.8 months. Five patients are alive and doing well after a mean follow-up of 14.8 months. In our experience myocardial dysfunction determined poor immediate survival. Mid-term survival was influenced by preoperative metastases and lymph-node involvement, but not by intracaval extension. Circulatory arrest appears to be a relatively safe technique to remove renal carcinoma with cavo-atrial extension and should be indicated whenever there are no metastases.

Adult↗
PubMed1998

Inferior epigastric artery as a conduit for myocardial revascularization: a two-year clinical and angiographic follow-up.

The inferior epigastric artery has been proposed as a suitable conduit for myocardial revascularization but its mid-term patency rate has not been assessed. A prospective clinical and angiographic study on the use of the inferior epigastric artery as an additional arterial conduit together with bilateral internal thoracic artery grafting was conducted in 38 patients. No deaths or major postoperative complications occurred. Twenty-three patients underwent repeat angiography after an average of 21.2 months. The left and right internal thoracic artery grafts patency rate was 95.6% (44/46), while inferior epigastric artery patency rate was 52.2% (12/23). By relating patency to the grafted coronary branch, the following results were obtained: 100% for the left anterior descending (3/3), right coronary (1/1) and ramus medianus (1/1); 40% (4/10) and 37.5% (3/8) for diagonals and obtuse marginals respectively. The low patency rates observed when the inferior epigastric artery is used on diagonals and obtuse marginals indicate that this vessel cannot be considered a suitable conduit for extensive application of arterial revascularization. We suggest that the inferior epigastric artery should only be used in patients presenting with contraindications to bilateral internal thoracic artery or right gastroepiploic artery grafting, or exhibiting unsuitable saphenous veins.

Coronary Angiography↗
PubMed1997

Glycosylation enhances oxygen radical-induced modifications and decreases acetylhydrolase activity of human low density lipoprotein.

BACKGROUND: Posttranslational nonenzymatic glycosylation of native low-density lipoprotein (n-LDL) occurs both in vitro and in vivo in diabetic patients. Glycosylated LDL (glc-LDL) behave similarly to oxidized LDL in some respects. In fact, unlike n-LDL, uptake the glc-LDL can occur in part by the "scavenger" receptor(s), as also demonstrated for oxidized LDL. The enzyme acetylhydrolase, carried by LDL, catabolizes platelet activating factor (PAF). This enzymatic activity is inhibited in oxidized LDL. However, it is unknown whether glc-LDL have reduced acetylhydrolase activity. OBJECTIVE: The first aim of the study was to investigate whether glc-LDL were more susceptible than n-LDL to oxidative modification, and which different oxygen radical species were involved in the phenomenon. Moreover, in order to investigate whether glycosylation may affect acetylhydrolase, we also measured this enzymatic activity in both n- and glc-LDL. METHODS: In vitro glc-LDL and n-LDL were exposed to the oxidants xanthine/xanthine oxidase (X/XO; 2 mM and 100 mU/ml, respectively), or CuSO4 (10 microM) for 18 hs at 37 degrees C. Parallel experiments were done in the presence of the superoxide radical scavenger superoxide dismutase (SOD; 330 U/ml), the hydrogen peroxide scavenger catalase (1000 U/ml), or the hydroxyl radical scavenger dimethylthiourea (10 mM) or dimethylsulfoxide (1 mM). Standards of PAF and lyso-PAF were visualized with iodine vapors after separation by thin layer chromatography. The distribution of label was determined by an imaging scanner. Labeled products were then isolated from the chromatography plate, and the amount of 3H-lyso-PAF formed was determined by liquid scintillation counting. RESULTS: Glc-LDL were more susceptible than n-LDL to lipid peroxidation (n-LDL 22.9 +/- 3.4 vs 34.8 +/- 4.2* nmoles/MDA/mg of protein in glc-LDL oxidized by X/XO and n-LDL 28.9 +/- 4.2 vs 40.4 +/- 4.1* in glc-LDL oxidized by CuSO4, *p < 0.05 vs n-LDL). SOD, but not other scavengers, prevented peroxidation, indicating an obligatory role for superoxide radicals. Oxidation of glc-LDL also induced a higher degree of apolipoprotein-B100 modifications than n-LDL, with increased electrophoresis mobility and decreased TNBS reactivity. These effects were similarly prevented by SOD. Finally, acetylhydrolase activity was significantly lower in glc-LDL than in n-LDL. CONCLUSION: Glycosylation increases LDL oxidation due to superoxide radicals, and also reduces acetylhydrolase activity. These phenomenona may contribute to enhance and/or accelerate the progression of atherosclerosis in diabetic patients.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1997

Surgical treatment for life-threatening acute myocardial infarction: a prospective protocol.

OBJECTIVE: In this paper we describe the preliminary results of a prospective operative protocol designed in order to define the role of emergent myocardial revascularization in extensive acute myocardial infarction and in post-infarction cardiogenic shock. METHODS: Entry criteria are: age < 75 years; anterior acute myocardial infarction with ST segment elevation > 4 leads, infero-postero-lateral or inferior and right ventricular within 6 h from onset of chest pain; post-infarction cardiogenic shock within 3 h from onset of shock. From November 1994 to July 1995, after emergency coronary arteriography, 23 patients were treated by coronary artery bypass grafting. Fifteen were operated for extensive acute myocardial infarction (group A, mean age 54.1 +/- 9.4 years) and eight for post-infarction cardiogenic shock (group B mean age 65.0 +/- 8.7 years). Mean time from onset was 4.4 +/- 1.3 h in group A and 2.2 +/- 0.8 h in group B. Mean left ventricular ejection fraction was 39.3 +/- 12.7% in group A and 22.6 +/- 3.5% in group B. Six out of eight group B patients needed intraaortic balloon counterpulsation preoperatively, and 2/8 cardiopulmonary resuscitation. RESULTS: Myocardial revascularization consisted in 3.4 +/- 1.1 grafts in group A (vein grafts, except for 8 patients who also received a left internal thoracic artery graft) and 3.3 +/- 1.1 vein grafts in group B. All patients in group B and 3/15 (20%) in group A underwent intraaortic balloon counterpulsation. In-hospital death occurred in 1/15 (6.7%) patients of group A and in 4/8 (50%) patients of group B. At a mean follow-up of 4.1 +/- 3.4 months for group A and 3.9 +/- 2.2 months for group B left ventricular ejection fraction was 43.4 +/- 9.0% in group A and 35.7 +/- 13.1% in group B. CONCLUSIONS: Experience of 9 months with this prospective protocol showed its effectiveness in the management of critically ill patients with acute coronary occlusion leading to low mortality rate in acute myocardial infarction and improved survival rate in post-infarction cardiogenic shock.

Aged↗
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↗
PubMed1997

Six-and-half years' experience with the St. Jude BioImplant porcine prosthesis.

BACKGROUND AND AIMS OF THE STUDY: In this study, we reviewed our experience in heart valve replacement with the St. Jude BioImplant heart valve, which is a low-profile, low-pressure glutaraldehyde-fixed porcine prosthesis mounted on a flexible Delrin stent. METHODS: During the period May 1989-January 1996, 117 patients were implanted with 132 BioImplant prostheses; three patients were lost to follow up and excluded from the series. Mean age was 67.5 +/- 9.8 years (range: 19 to 82 years); myocardial revascularization was performed in 22 (19.3%) patients. In-hospital mortality rate was 6% (7/117 patients). By January 1996, 114 patients (53 males, 61 females), in whom 59 aortic, 35 mitral, 15 mitro-aortic and five tricuspid prostheses had been implanted, were eligible for the analysis. Mean follow up was 40.4 +/- 21.7 months (range: 1 to 76 months). RESULTS: The survival probability of survivors was 72.1 +/- 6.5 at 77 months. Seventeen patients died during follow-up. The mean NYHA class improved from 3.1 +/- 0.6 preoperatively to 1.4 +/- 0.6 postoperatively. The freedom probabilities were respectively 89.5 +/- 5.3% from thromboembolism, 93.2 +/- 3.7% from infective endocarditis, 84.5 +/- 10.3% from structural dysfunction, 99.1 +/- 0.9% from non-structural dysfunction, and 80.1 +/- 10.2% from reoperation. The freedom probability for valve-related events was respectively 75.3 +/- 12.3%, 98.0 +/- 1.9% and 67.2 +/- 17.2% for patients who underwent mitral, aortic and mitro-aortic heart valve replacement (p = 0.05 comparing only patients who underwent mitral or aortic replacement); moreover the freedom probability from valve-related events was 71.6 +/- 11.2% in patients aged < or = 65 years and 90.2 +/- 6.6% in patients aged > 65 years (p = 0.006). CONCLUSIONS: The BioImplant heart valve, in our experience, seems to be a valuable device which shows a mid-term performance similar to that of other porcine prostheses.

Adult↗
PubMed1997

[Transmyocardial laser revascularization in patients with peripheral coronary atherosclerosis. Indications and preliminary results].

BACKGROUND: Surgical intervention for coronary artery disease (CAD) is determined by the viability of coronary artery branches. When peripheral coronary artery disease is present, conventional bypass grafting is not suitable. Research has recently been done on alternative methods such as transmyocardial laser revascularization (TMLR). TMLR works through the vascular connections that are present between the cardiac chambers and the myocardial muscle in the human heart. The creation of 1-mm transmural cardiotomies through a CO2 laser should improve myocardial perfusion. METHODS: From February to June of 1996, twelve patients (9 males and 3 females with a mean age of 67.8 +/- 4.6) with CAD (mean n0 of diseased vessels 2.7), angina (mean CCS class 3.5 +/- 0.5), mean ejection fraction 47.8% and viable ischemic myocardium on scintiscan in segments without graftable coronary branches, underwent TMLR at our institute. Nine of the 12 patients also underwent associated CABG (mean number of anastomoses per patient: 2.5). Cardiopulmonary bypass was never used, since coronary anastomoses and laser cardiotomies were performed on the beating heart. RESULTS: Perioperative mortality was 2/12 (16.6%). Postoperative inotropic support and diuretic therapy was required in most cases. At a mean follow-up period of 4.2 months, all remaining patients are still alive: 5/10 are angina-free (CCS 0), 4/10 are in CCS class 1 and 1/10 is in CCS class 2 (mean 0.6 +/- 0.7). CONCLUSIONS: We believe that TMLR could be considered an effective mean to treat symptomatic myocardial ischemic disease in which coronary bypass grafting is not suitable. During the immediate postoperative period, contractile myocardial dysfunction occurs in a high percentage of patients treated using TMLR and consequently it would be worthwhile to invest in further research.

Aged↗
PubMed1997

Timing for surgical treatment in native infective endocarditis. A seven-year experience.

BACKGROUND: Early surgical intervention in infective endocarditis is performed only when there is persistence of sepsis, hemodynamic instability or when arterial embolism has occurred, otherwise a 4-week antibiotic therapy before surgery is considered necessary. Our 7-year experience in the surgical treatment of native endocarditis in 28 patients, is here revised focusing on the timing of surgery. METHODS: Patients were retrospectively divided into group A (n. 16) with blood cultures that became negative before surgery and group B (n. 11) with blood cultures positive at the time of urgent surgery. One patient with constantly negative blood cultures was not assigned to any group. In group A antibiotic therapy was administered until 3 consecutive blood cultures became negative and the patients were then operated on the basis of echocardiographic findings after a mean duration of antibiotic therapy of 17.4 +/- 6.3 days. RESULTS: Twenty-six patients out of 28 underwent replacement of the infected valve (mechanical bileaflets in 16 patients, porcine stented in 7 and porcine stentless in 3). Valve repair was performed in 2 patients. Overall operative mortality was) 7.1% (2/28); death occurred in 2 patients of group B, operated on for cardiogenic shock. Two/26 patients died (1 acute renal failure and 1 stroke) at a mean follow-up of 32.5 +/- 24.8 (range 3-95) months. CONCLUSIONS: Patients who underwent surgery for infective endocarditis after blood culture negativization showed no mortality and no recurrence of disease even if a 4 weeks antibiotic course was not completed. This experience suggests that earlier operations can be performed safely, lowering the incidence of hemodynamic impairment and arterial embolism.

Endocarditis, Bacterial↗
PubMed1996

Antigen-induced generation of lyso-phospholipids in human airways.

The goal of the current study was to examine the formation of phospholipids, 1-radyl-2-lysosn-glycero-phospholipids (lyso-PL) and 2-acetylated phospholipids (such as PAF) as well as mechanisms responsible for generating these phospholipids in bronchoalveolar lavage fluid (BAI.F) from allergic subjects challenged with antigen. Bronchoalveolar lavage was performed in normal and allergic subjects before, 5-30 min, 6 h, and 20 h after segmental antigen challenge via a wedged bronchoscope. Levels of 1-hexadecyl-2-lyso-phospholipids and 1-hexadecyl-2-acetyl-phospholipids were initially determined by negative ion chemical ionization gas chromatography/mass spectrometry (NICI-GC/MS). Antigen dramatically elevated quantities of 1-hexadecyl-2-lyso-phospholipids in allergic subjects 20 h after challenge when compared to non-allergic controls. In contrast, there was not a significant increase in levels of 1-hexadecyl-2-acetyl-phospholipids after antigen challenge. Closer examination of 1-radyl-2-lyso-sn-glycero-3-phosphocholine (GPC) revealed that 1-palmitoyl-2-lyso-GPC, 1-myristoyl-2-lyso-GPC and 1-hexadecyl-2-lyso-GPC were three major molecular species produced after antigen challenge. 1-palmitoyl-2-lyso-GPC increased sevenfold to levels of 222 +/- 75 ng/ml of BALF 20 h after antigen challenge. The elevated levels of lyso-PL correlated with levels of albumin used to assess plasma exudation induced by allergen challenge. In contrast, the time course of prostaglandin D2 (PGD2) or 9 alpha, 11 beta PGF2 (11 beta PGF2) formation did not correlate with lyso-PL generation. To examine the mechanism leading to lyso-phospholipid formation in antigen-challenged allergic subjects, secretory phospholipase A2 (PI.A2) and acetyl hydrolase activities were measured. There was a significant increase in PLA2 activity found in BALF of allergic subjects challenged with antigen when compared to saline controls. This activity was neutralized by an antibody directed against low molecular mass, (14 kD) human synovial PLA2 and dithiothreitol. Acetyl hydrolase activity also markedly increased in BALF obtained after antigen challenge. This study indicates that high levels of lyso-PLs are present in airways of allergic subjects challenged with antigen and provides evidence for two distinct mechanisms that could induce lyso-PL formation. Future studies will be necessary to determine the ramifications of these high levels of lyso-phospholipids on airway function.

Adult↗