Molecular Biology of Atherosclerotic Ischemic Strokes

Among the causes of global death and disability, ischemic stroke (also known as cerebral ischemia) plays a pivotal role, by determining the highest number of worldwide mortality, behind cardiomyopathies, affecting 30 million people. The etiopathogenetic burden of a cerebrovascular accident could be brain ischemia (~80%) or intracranial hemorrhage (~20%). The most common site when ischemia occurs is the one is perfused by middle cerebral arteries. Worse prognosis and disablement consequent to brain damage occur in elderly patients or affected by neurological impairment, hypertension, dyslipidemia, and diabetes. Since, in the coming years, estimates predict an exponential increase of people who have diabetes, the disease mentioned above constitutes together with stroke a severe social and economic burden. In diabetic patients after an ischemic stroke, an exorbitant activation of inflammatory molecular pathways and ongoing inflammation is responsible for more severe brain injury and impairment, promoting the advancement of ischemic stroke and diabetes. Considering that the ominous prognosis of ischemic brain damage could by partially clarified by way of already known risk factors the auspice would be modifying poor outcome in the post-stroke phase detecting novel biomolecules associated with poor prognosis and targeting them for revolutionary therapeutic strategies

β-amyloid wall deposit of temporal artery in subjects with spontaneous intracerebral haemorrhage.

Background: Cerebral Amyloid Angiopathy has been indicated as an important cause of spontaneous non-hypertensive intracerebral haemorrhage (ICH). Aims: to analyze the presence of β-amyloid deposit in the temporal artery of consecutive patients with ICH in comparison to control subjects and its relation to APO-E haplotype frequency. Methods: We enrolled consecutive patients admitted to Neurosurgery Ward of University Hospital "P. Giaccone" of Palermo with a diagnosis of spontaneous non hypertensive ICH and as control 12 subjects without brain haemorrhage. Biopsy of superficial temporal artery has been performed and β-amyloid deposit was quantified. Results: Among 25 subjects with ICH, 10 (40%) had APOE epsilon 2 allele and among these subjects 7 (70%) showed amyloid accumulation on temporal artery specimens, 8 (32%) subjects had APOE epsilon 3 allele and among these subjects only 2 (25%) showed amyloid accumulation on temporal artery specimens, whereas 7 (28%) had APOE epsilon 4 allele and of these, 7 (100%) showed amyloid accumulation on temporal artery specimens. At multivariable logistic regression analysis for the presence of amyloid, predictive factors for the presence of amyloid in temporal artery biopsies were: age, hypertension, intralobar site of haemorrhage, APOE epsilon 2 and APOE epsilon 4 alleles. Discussion: Our findings of a higher frequency of amyloid deposition in temporal artery specimens in subjects with spontaneous intracerebral haemorrhage indicate a possible role of temporal artery as a possible diagnostic site of biopsy in subjects at high risk to develop intracranial haemorrhage related to Cerebral Amyloid Angiopath

Inter-familial and intra-familial phenotypic variability in three Sicilian families with Anderson-Fabry disease.

Abstract BACKGROUND: Anderson-Fabry disease (AFD) is an inborn lysosomal enzymopathy resulting from the deficient or absent activity of the lysosomal exogalactohydrolase, α-galactosidase A. This deficiency, results in the altered metabolism of glycosphingolipids which leads to their accumulation in lysosomes, thus to cellular and vascular dysfunction. To date, numerous mutations (according to recent data more than 1000 mutations) have been reported in the GLA intronic and exonic mutations. Traditionally, clinical manifestations are more severe in affected hemizygous males than in females. Nevertheless, recent studies have described severe organ dysfunction in women. THE AIM OF THE STUDY: This study reports clinical, biochemical, and molecular findings of the members of three Sicilian families. The clinical history of these patients highlights a remarkable interfamilial and intrafamilial phenotypic variability which characterizes Fabry disease relative to target organs and severity of clinical manifestations. DISCUSSION: Our findings, in agreement with previous data, report a little genotype-phenotype correlation for the disease, suggesting that the wide phenotypic variability of Anderson-Fabry disease is not completely ascribable to different gene mutations but other factors and mechanisms seem to be involved in the pathogenesis and clinical expression of the disease. Moreover, this study emphasies the importance of pedigree analysis in the family of each proband for identifying other possibly affected relatives

The Software Architecture and development approach for the ASTRI Mini-Array gamma-ray air-Cherenkov experiment at the Observatorio del Teide

The ASTRI Mini-Array is an international collaboration led by the Italian National Institute for Astrophysics (INAF) and devoted to the imaging of atmospheric Cherenkov light for very-high gamma-ray astronomy. The project is deploying an array of 9 telescopes sensitive above 1 TeV. In this contribution, we present the architecture of the software that covers the entire life cycle of the observatory, from scheduling to remote operations and data dissemination. The high-speed networking connection available between the observatory site, at the Canary Islands, and the Data Center in Rome allows for ready data availability for stereo triggering and data processing

Feedback linearization control of wind turbine equipped with doubly fed induction generator

This paper focuses on several control techniques of a wind turbine of rated power of about 1 MW. In particular, a wind generator equipped with an asynchronous doubly-fed induction machine has been considered and its dynamic model in MATLAB/SIMULINK environment has been implemented. Starting from this model the feedback linearization control has been derived, and several simulations have been carried out, with the aim of compare its dynamic performances with the classical field oriented control, and with the V/f control. The results allow us to conclude that a DFIG controlled by a feedback linearization technique ensures better dynamic performance

CARDIOPROTEZIONE ED ANESTESIA EPIDURA- LE TORACICA: UN CASO DI ISCHEMIA MIOCAR- DICA POSTOPERATORIA

Obiettivo. Analisi dell’effetto cardioprotettivo perioperatorio dell’anestesia peridurale toracica (TEA) in un paziente car- diopatico sottoposto a chirurgia non cardiaca. Materiali e metodi. Paziente di 59 anni affetto da patologia neoplastica, BPCO severa, insufficienza renale cronica e car- diopatia ipertensiva (ASA IV), viene sottoposto ad intervento chirurgico di cistectomia radicale e resezione duodeno-digiu- nale. In fase preoperatoria si posiziona un catetere epidurale (T10) e si somministra un bolo di Levobupivacaina (75 mg) e Fentanest (0,05 mg). Si procede a monitoraggio intraoperato- rio con CardioQ che evidenzia uno stato ipotensivo iniziale con bassa portata e basse resistenze. Trascorsi 150 minuti si somministra un bolo peridurale con Levobupivacaina (25 mg) e Fentanest (0,005 mg). Al termine della chirurgia si procede alla somministrazione mediante pompa infusionale di Levo- bupivacaina (1.25 mg/ml) e Morfina (0,05 mg/ml) alla veloci- ta di 5 ml/h; Il paziente si trasferisce in UTI dove si continua l’infusione peridurale per le successive 24h. Ridotta la velocitàdi infusione si sospende la stessa e dopo 4 h si assiste a com- parsa di dolore toracico con sottoslivellamento del tratto ST- T in sede antero-laterale e relativa diagnosi di angina instabi- le. Risultati. Dall’analisi del monitoraggio intraoperatorio e postoperatorio (Tabelle I, II) non si rileva alcuna alterazione dei parametri emodinamici ed elettrocardiografici suggestiva di un evento ischemico. I suddetti parametri si sono mantenu- ti nel range di valori fisiologici per tutta la durata dell’infusio- ne peridurale, e successivamente in seguito alla sospensione della stessa si è verificata la comparsa dell’evento ischemico, correlato all’aumento delle resistenze vascolari periferiche come documentato dal PRAM. Discussione. La TEA, attraverso il controllo del dolore perio- peratorio e della risposta simpatico-adrenergica, determina una vasodilatazione delle arterie coronarie stenotiche e una riduzione degli episodi di ischemia miocardica 1,2. Dall’analisi della letteratura 3 e dai dati obiettivi emersi si ipotizza che la sospensione del protocollo anestesiologico attraverso la TEA abbia indotto una riduzione della cardioprotezione e di con- seguenza un incremento del rischio potenziale di malattia coronarica acuta

Early high-dosage atorvastatin treatment improved serum immune-inflammatory markers and functional outcome in acute ischemic strokes classified as large artery atherosclerotic stroke: A randomized trial

Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-a, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile

Design of wave energy converter (WEC): A prototype installed in Sicily

The purpose of this work is to describe a possibility of installation of a wave converter in Sicily, in the Mediterranean Sea. In this paper we present the design of buoyant electrical generator, in particular, wave linear permanent magnet generator which can make wave energy converted to electrical energy

IgG4 Related Syndrome: Another Multiorgan Disease in the Interest Field of Internal Medicine.

BACKGROUND: IgG4-related disease is a rare, clinical and pathologic disease entity of unknown etiology. Its main features are increased serum concentrations of IgG4 > 1,35 g/l, lymphocyte and IgG4+plasma-cell infiltration within tissues, fibrosis or sclerosis. The classical presentation of IgG4-RSD is pancreatitis which is combined with the involvement of biliary ducts in 74 percent of patients. Extrapancreatic manifestations include: abdominal or mediastinal lymphadenopathy; the involvement of salivary glands and lacrimal glands, kidneys, lung, retroperitoneum. Since IgG4-related disease is a multiorgan lymphoproliferative syndrome, it requires a careful differential diagnosis from other distinct disorders (sarcoidosis, immune rheumatic diseases, hematologic diseases, malignancies). Another distinctive feature is a fairly fast response to steroids, that represents the first-choice therapy. Immunosuppressant drugs (azathioprine, mycophenolate mofetil, methotrexate) might be chosen as glucocorticoid-sparing medications or to maintain steroid-induced remission (Fig. 1). METHODS: We report the case of a 70-year-old man and we performed a brief review of loiterature. RESULTS: Our patient has a clinical history including bronchial asthma, aortic aneurysm, histologically confirmed retroperitoneal fibrosis causing hydroureteronephrosis, prostatitis, interstitial pulmonary fibrosis, sclerosing chronic pancreatitis (histologically documented), previous chronic cholecystitis (histologically confirmed), previous pericarditis, xeroftalmia, polyclonal hypergammaglobulinemia, eosinophilia. His serum IgG4 levels were significantly increased (5560 mg/dl). In regard to the above mentioned elements a systemic disease characterized by elevated serum levels of IgG4 and IgG4-positive lymphoplasmacytic infiltrative lesions in several tissues, was suspected. Immune-rheumatic diseases and infectious diseases were excluded. Steroid treatment was started achieving a significant swift response. CONCLUSION: Until now IgG4 related disease has been considered rare in the West and exclusive of Japanese and Korean countries, our case report leads us to reflect on the necessity to take into account this disease in patients with multisystemic involvement