Pro/Anti-inflammatory cytokine imbalance in postischemic left ventricular remodeling.

OBJECTIVES: Cytokines play an important role in left ventricular remodeling consequent to myocardial ischemia. The aim of this study was to correlate cytokine production and lymphocyte apoptosis to post-ischemic left ventricular remodeling in patients affected by acute myocardial infarction (AMI) undergoing primary cutaneous angioplasty (PCI). METHODS: In 40 patients, affected by AMI and undergoing PCI, we evaluated peripheral blood mononuclear cells (PBMCs), tumor necrosis factor-alpha (TNF-alpha) and interleukin 10 (IL10) production and apoptosis on day 1, day 3, day 7, 1 month and 6 months after PCI. Patients were divided into two subgroups of remodeling or not remodeling by echocardiographic criteria. RESULTS: In the subgroup of remodeling patients, at each timepoint TNF-alpha production was increased significantly in comparison with the subgroup of not remodeling patients. IL10 production was statistically lower in remodeling subjects than in not remodeling ones 1 and 6 months after reperfusion. There were no differences between the two groups as regards lymphomonocyte apoptosis. CONCLUSIONS: We found an increased production of pro-inflammatory cytokine TNF-alpha and a corresponding decrease of anti-inflammatory/regulatory cytokine IL10 in remodeling patients and we concluded that this cytokine imbalance resulted in pro-inflammatory effects which might contribute to the progression of left ventricular remodeling.

Takayasu's arteritis: a review of the literature.

Takayasu's arteritis is a rare, idiopathic, chronic inflammatory disease with cell-mediated inflammation, involving mainly the aorta and its major branches. It leads to stenosis, occlusion or aneurysmal degeneration of large arteries. The clinical presentation is characterised by an acute phase with constitutional symptoms, followed, months or years later, by a chronic phase in which symptoms relate to fibrosis or occlusion of vessels. Angiography is the gold standard for diagnosis and for topographical classification and it correlates with symptoms and prognosis. Here we focus on the pathophysiology, clinical and angiographical classification, diagnostic assessment and therapeutic approach of Takayasu's arteritis.

[Hypogammaglobulinemia and thymoma (Good's syndrome): a case report and a literature review]. / Ipogammaglobulinemia associata a timoma (sindrome di Good): descrizione di un caso clinico e revisione della letteratura.

Good's syndrome is a rare adult-onset immunodeficiency disease characterized by hypogammaglobulinemia and thymoma. A 61-year-old male patient was diagnosed with Good's syndrome after a 2-year history of recurrent respiratory infections. Chest X-ray and chest computed tomography scan showed a mediastinal mass which was surgically removed. Histology revealed a thymoma. Following surgery he presented with recurrent respiratory and urinary tract infections and with esophageal candidiasis, even though his overall conditions dramatically improved after starting treatment with an appropriate dosage of intravenous immunoglobulins. Laboratory tests showed hypogammaglobulinemia, mild neutropenia, lymphopenia with no B cells, decreased CD4+ lymphocytes with an inverted CD4/CD8 ratio and increased interleukin-4-producing CD4+ lymphocytes, suggestive of an excessive Th2 response.

Takayasu's arteritis: case report of a patient with recurrent subclavian steal syndrome.

Takayasu's arteritis is a chronic inflammatory disease of unknown origin in which cell-mediated inflammation involves large arteries progressing from the adventitia to the intima, until the lumen of the vessel is narrowed. Here we report a case of a 48-year-old female patient who was diagnosed with Takayasu's arteritis 6 years ago. At that time, because of severe involvement of both the right and left carotid arteries, she underwent application of a Hemashield vascular prosthesis, including the ascending aorta, left common carotid artery, and right common carotid artery. Due to the fact that there were also bilateral subclavian artery stenoses, the application of the prosthesis induced bilateral subclavian steal syndrome. This year she developed stenosis of the prosthesis and the bilateral subclavian steal syndrome disappeared until she underwent percutaneous transluminal angioplasty, which restored cerebral flow through the carotid arteries after which the subclavian steal syndrome reappeared.

[Lymphocyte apoptosis in non-ST segment elevation acute myocardial infarction ]. / L'apoptosi linfocitaria nell'infarto miocardico acuto senza sopraelevazione del tratto ST.

It is well known that lymphocytes play a major role in coronary plaque destabilization in acute coronary syndromes. The aim of this study was to evaluate circulating lymphocyte apoptosis in patients with non-ST elevation myocardial infarction (NSTEMI) in comparison with subjects with stable angina and with healthy controls. We considered spontaneous lymphomonocyte apoptosis (evaluated by ELISA), interleukin (IL)-2 production (evaluated by ELISA), Fas expression on T cells (evaluated by flow cytometry) and Fas ligand mRNA (evaluated by reverse transcriptase polymerase chain reaction), as well as Fas functionality. To evaluate T-cell activation, we also investigated T-cell subpopulations (CD4/CD8 ratio), T-cell surface HLA-DR and CD69 expression (evaluated by flow cytometry) in blood taken within 6 hours from onset of NSTEMI. Spontaneous apoptosis was significantly increased in NSTEMI patients in comparison with the two control groups and it was associated with an increased expression of Fas, an increased susceptibility to the Fas agonist (CH-11) and a normal production of IL-2 in cell cultures. We also found a significant increase of HLA-DR+ CD3+ and CD69+ CD4+ cells in NSTEMI patients. These data suggest that the enhanced apoptosis is due to a mechanism of "active" antigen-driven death, induced by the expression of death cytokines and not by the failure of cell growth factors. We conclude that in case of NSTEMI peripheral lymphocytes are activated and undergo an enhanced programmed cell death due to activation mechanisms. It is likely that lymphocyte activation occurs before the onset of acute ischemia and contributes to the plaque rupture and to the myocardial ischemic insult.

Platelet hyperactivity after statin treatment discontinuation.

Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular events by cholesterol lowering as well as by non-lipid related actions. Among them, the modulation of platelet activity could play a relevant role in vascular protection. Furthermore withdrawal of statins has been associated with increased cardiovascular event rate. The aim of our study was to evaluate platelet activity after cerivastatin discontinuation in eighteen subjects that did not accept other drugs and in sixteen subjects continuing treatment with simvastatin. Fourteen subjects at the end of the discontinuation period decided to receive other drugs (simvastatin) and they were evaluted six weeks later. We measured complete lipid profile by the chromogenic method (LDL-C was calculated); oxidized-LDL (ox-LDL; ELISA), platelet P-selectin (P-sel) expression (flow cytometry detection), platelet aggregation (% change of transmitted light), intracellular citrullin production (iCit; HPLC) as an indicator of intracellular NO synthase activity at baseline and 7, 14, 28, 60 days after statin discontinuation. P-sel expression and platelet aggregation were increased at 14 days (p < 0.001 and p < 0.05) in association with raised ox-LDL (r = 0.30, p < 0.05) and decreased iCit (r = 0.53, p < 0.01). Increased LDL-C was related to P-sel and platelet aggregation at 28 days (r = 0.30, p < 0.05). Subjects continuing statin treatment had no significant changes of P-sel at 28 (p = 0.221) and 60 days (p = 0.238). Subjects treated with simvastatin after 60 days of diet showed a significant reduction of P-sel and platelet aggregation after six weeks of treatment (p < 0.01). Our data suggest a platelet hyperactivation state in the second week after statin discontinuation which is partially related to raised LDL-C. Such a finding could participate in the increased cardiovascular event rate after statin discontinuation.