233 research outputs found

    Outcomes in the emergency endovascular repair of blunt thoracic aortic injuries

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    Abstract Thoracic aorta blunt injury (BAI) is a highly lethal lesion. A large number of victims die before obtaining emergency care. Thoracic endovascular aneurysm repair (TEVAR) is a less invasive method compared with open surgery and may change protocols for BAI treatment. This retrospective study was developed to evaluate the potential issues about thoracic endografting in the management of these patients. Twenty-seven patients with a BAI underwent aortic stent grafting. Intervention was preceded by the treatment of more urgent associated lesions in nine cases. In-hospital mortality was 7.4%. No paraplegia or ischemic complications developed because of the coverage of the left subclavian artery. In one case (3.2%), a type I endoleak was detected, proximal endograft infolding in two cases (7.4%) and endograft distal migration in further two cases were detected during follow-up (6-110 months). Thoracic endovascular aneurysm repair of BAI showed encouraging results in terms of perioperative mortality and morbidity. Concerns still remain about the potential mid- and long-term complications in younger patients

    Management of Symptomatic Venous Aneurysm

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    Venous aneurysms (VAs) have been described in quite of all the major veins. They represent uncommon events but often life-threatening because of pulmonary or paradoxical embolism. We describe our twelve patients' series with acute pulmonary emboli due to venous aneurysm thrombosis. Our experience underlines the importance of a multilevel case-by-case approach and the immediate venous lower limbs duplex scan evaluation in pulmonary embolism events. Our data confirm that anticoagulant alone is not effective in preventing pulmonary embolism. We believe that all the VAs of the deep venous system of the extremities should be treated with surgery as well as symptomatic superficial venous aneurysm. A simple excision can significantly improve symptoms and prevent pulmonary embolism

    Mid- and Long-Term Results of Endovascular Treatment in Thoracic Aorta Blunt Trauma

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    Study Aim. Evaluation of results in blunt injury of the thoracic aorta (BAI) endovascular treatment. Materials and Methods. Sixteen patients were treated for BAI. Thirteen patients had associated polytrauma, 4 of these had a serious hypotensive status and 4 had an hemothorax. In the remaining 3, two had a post-traumatic false aneurysm of the isthmus and 1 had a segmental dissection. In those 13 patients a periaortic hematoma was associated to hemothorax in 4. All patients were submitted to an endovascular treatment, in two cases the subclavian artery ostium was intentionally covered. Results. One patient died for disseminated intravascular coagulation. No paraplegia was recorded. No ischemic complications were observed. A type I endoleak was treated by an adjunctive cuff. During the followup (1–9 years) 3 patients were lost. A good patency and no endoleaks were observed in all cases. One infolding and 1 migration of the endografts were corrected by an adjunctive cuff. Conclusion. The medium and long term results of the endovascular treatment of BAI are encouraging with a low incidence rate of mortality and complications. More suitable endo-suite and endografts could be a crucial point for the further improvement of these results

    Anticancer Ruthenium(III) Complexes and Ru(III)-Containing Nanoformulations: An Update on the Mechanism of Action and Biological Activity

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    The great advances in the studies on metal complexes for the treatment of different cancer forms, starting from the pioneering works on platinum derivatives, have fostered an increasingly growing interest in their properties and biomedical applications. Among the various metal-containing drugs investigated thus far, ruthenium(III) complexes have emerged for their selective cytotoxic activity in vitro and promising anticancer properties in vivo, also leading to a few candidates in advanced clinical trials. Aiming at addressing the solubility, stability and cellular uptake issues of low molecular weight Ru(III)-based compounds, some research groups have proposed the development of suitable drug delivery systems (e.g., taking advantage of nanoparticles, liposomes, etc.) able to enhance their activity compared to the naked drugs. This review highlights the unique role of Ru(III) complexes in the current panorama of anticancer agents, with particular emphasis on Ru-containing nanoformulations based on the incorporation of the Ru(III) complexes into suitable nanocarriers in order to enhance their bioavailability and pharmacokinetic properties. Preclinical evaluation of these nanoaggregates is discussed with a special focus on the investigation of their mechanism of action at a molecular level, highlighting their pharmacological potential in tumour disease models and value for biomedical applications

    Localization of lipopolysaccharide from Escherichia Coli into human atherosclerotic plaque

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    Experimental studies showed that gut-derived lipopolysaccharide (LPS) is pro-atherogenic, however, its relationship with human atherosclerosis is still to be defined. We investigate if gut-derived LPS from Escherichia Coli localizes in human carotid plaque and its potential role as pro-inflammatory molecule in the atherosclerotic lesion. LPS from Escherichia Coli and Toll-like receptor 4 (TLR4) were studied in specimens from carotid and thyroid arteries of 10 patients undergoing endarterectomy and 15 controls matched for demographic and clinical characteristics. Blood LPS were significantly higher in patients compared to controls. Immunochemistry analysis revealed positivity for antibodies against LPS and TLR4 coincidentally with positivity for CD68 only in the atherosclerotic plaque of carotid arteries but not in thyroid arteries; the positivity for LPS and TLR4 was greater in the area with activated macrophages. LPS concentration similar to that detected in atherosclerotic plaque resulted in a dose-dependent TLR4-mediated Nox2 up-regulation by human monocytes. These data provide the first evidence that LPS from Escherichia Coli localizes in human plaque and may contribute to atherosclerotic damage via TLR4-mediated oxidative stress

    perspectives and potential applications of ruthenium based nanocarriers for cancer therapy

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    Perspectives and Potential Applications of Ruthenium-Based Nanocarriers for Cancer Therapy Rita Santamaria*1 , Carlo Irace1, Gerardino D'Errico 2, Daniela Montesarchio2 and Luigi Paduano2 1Department of Pharmacy, University of Napoli "Federico II", via D. Montesano 49, I-80131, Napoli, Italy 2Department of Chemical Sciences, University of Napoli "Federico II", Complesso Universitario di Monte Sant'Angelo, via Cintia 21, I-80126, Napoli, Italy *Corresponding author: Rita Santamaria, Associate Professor, Department of Pharmacy, University of Napoli "Federico II", via D. Montesano 49, I-80131, Napoli, Italy, Fax: 0039081678403, Tel: 0039 081678421, E-Mail: [email protected] Citation: Rita Santamaria, Carlo Irace, Gerardino D'Errico, Daniela Montesarchio, Luigi Paduano (2013) Perspectives and Potential Applications of Ruthenium-Based Nanocarriers for Cancer Therapy. J Pharm Drug Devel 1(2): e201. doi: 10.15744/2348-9782.1.e201 Received Date: September 30, 2013 Accepted Date: October 15, 2013 Published Date: October 23, 2013 Editorial Open Acces

    Breast cancer chemotherapeutic options: a general overview on the preclinical validation of a multi-target ruthenium(III) complex lodged in nucleolipid nanosystems

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    In this review we have showcased the preclinical development of original amphiphilic nanomaterials designed for ruthenium‐based anticancer treatments, to be placed within the current metallodrugs approach leading over the past decade to advanced multitarget agents endowed with limited toxicity and resistance. This strategy could allow for new options for breast cancer (BC) interventions, including the triple‐negative subtype (TNBC) with poor therapeutic alternatives. BC is currently the second most widespread cancer and the primary cause of cancer death in women. Hence, the availability of novel chemotherapeutic weapons is a basic requirement to fight BC subtypes. Anticancer drugs based on ruthenium are among the most explored and advanced nextgeneration metallotherapeutics, with NAMI‐A and KP1019 as two iconic ruthenium complexes having undergone clinical trials. In addition, many nanomaterial Ru complexes have been recently conceived and developed into anticancer drugs demonstrating attractive properties. In this field, we focused on the evaluation of a Ru(III) complex—named AziRu—incorporated into a suite of both zwitterionic and cationic nucleolipid nanosystems, which proved to be very effective for the in vivo targeting of breast cancer cells (BBC). Mechanisms of action have been widely explored in the context of preclinical evaluations in vitro, highlighting a multitarget action on cell death pathways which are typically deregulated in neoplasms onset and progression. Moreover, being AziRu inspired by the well‐known NAMI‐A complex, information on non‐nanostructured Ru‐based anticancer agents have been included in a precise manner

    Site-specific replacement of the thymine methyl group by fluorine in thrombin binding aptamer significantly improves structural stability and anticoagulant activity

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    Here we report investigations, based on circular dichroism, nuclear magnetic resonance spectroscopy, molecular modelling, differential scanning calorimetry and prothrombin time assay, on analogues of the thrombin binding aptamer (TBA) in which individual thymidines were replaced by 5-fluoro-2'-deoxyuridine residues. The whole of the data clearly indicate that all derivatives are able to fold in a G-quadruplex structure very similar to the 'chair-like' conformation typical of the TBA. However, only ODNs TBA-F4: and TBA-F13: have shown a remarkable improvement both in the melting temperature (ΔTm ≈ +10) and in the anticoagulant activity in comparison with the original TBA. These findings are unusual, particularly considering previously reported studies in which modifications of T4 and T13 residues in TBA sequence have clearly proven to be always detrimental for the structural stability and biological activity of the aptamer. Our results strongly suggest the possibility to enhance TBA properties through tiny straightforward modifications

    Role of continuous glucose monitoring in diabetic patients at high cardiovascular risk. an expert-based multidisciplinary delphi consensus

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    Background: Continuous glucose monitoring (CGM) shows in more detail the glycaemic pattern of diabetic subjects and provides several new parameters (“glucometrics”) to assess patients’ glycaemia and consensually guide treatment. A better control of glucose levels might result in improvement of clinical outcome and reduce disease complications. This study aimed to gather an expert consensus on the clinical and prognostic use of CGM in diabetic patients at high cardiovascular risk or with heart disease. Methods: A list of 22 statements concerning type of patients who can benefit from CGM, prognostic impact of CGM in diabetic patients with heart disease, CGM use during acute cardiovascular events and educational issues of CGM were developed. Using a two-round Delphi methodology, the survey was distributed online to 42 Italian experts (21 diabetologists and 21 cardiologists) who rated their level of agreement with each statement on a 5-point Likert scale. Consensus was predefined as more than 66% of the panel agreeing/disagreeing with any given statement. Results: Forty experts (95%) answered the survey. Every statement achieved a positive consensus. In particular, the panel expressed the feeling that CGM can be prognostically relevant for every diabetic patient (70%) and that is clinically useful also in the management of those with type 2 diabetes not treated with insulin (87.5%). The assessment of time in range (TIR), glycaemic variability (GV) and hypoglycaemic/hyperglycaemic episodes were considered relevant in the management of diabetic patients with heart disease (92.5% for TIR, 95% for GV, 97.5% for time spent in hypoglycaemia) and can improve the prognosis of those with ischaemic heart disease (100% for hypoglycaemia, 90% for hyperglycaemia) or with heart failure (87.5% for hypoglycaemia, 85% for TIR, 87.5% for GV). The experts retained that CGM can be used and can impact the short- and long-term prognosis during an acute cardiovascular event. Lastly, CGM has a recognized educational role for diabetic subjects. Conclusions: According to this Delphi consensus, the clinical and prognostic use of CGM in diabetic patients at high cardiovascular risk is promising and deserves dedicated studies to confirm the experts’ feeling
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