C4BQ0: a genetic marker of familial HCV-related liver cirrhosis.

Source Department of Medicine and Pneumology, V Cervello Hospital, Via Trabucco 180, 90146 Palermo, Italy. [email protected] Abstract BACKGROUND AND METHODS: Host may have a role in the evolution of chronic HCV liver disease. We performed two cross-sectional prospective studies to evaluate the prevalence of cirrhosis in first degree relatives of patients with cirrhosis and the role of two major histocompatibility complex class III alleles BF and C4 versus HCV as risk factors for familial clustering. FINDINGS: Ninety-three (18.6%) of 500 patients with cirrhosis had at least one cirrhotic first degree relative as compared to 13 (2.6%) of 500 controls, (OR 7.38; CI 4.21-12.9). C4BQ0 was significantly more frequent in the 93 cirrhotic patients than in 93 cirrhotic controls without familiarity (Hardy-Weinberg equilibrium: chi2 5.76, P = 0.016) and in 20 families with versus 20 without aggregation of HCV related cirrhosis (29.2% versus 11.3%, P = 0.001); the association C4BQ0-HCV was found almost only in cirrhotic patients with a family history of liver cirrhosis. CONCLUSIONS: Our studies support the value of C4BQ0 as a risk indicator of familial HCV related cirrhosis

Salinomycin and other ionophores as a new class of antimalarial drugs with transmission-blocking activity

The drug target profile proposed by the Medicines for Malaria Venture for a malaria elimination/eradication policy focuses on molecules active on both asexual and sexual stages of Plasmodium, thus with both curative and transmission-blocking activities. The aim of the present work was to investigate whether the class of monovalent ionophores, which includes drugs used in veterinary medicine and that were recently proposed as human anticancer agents, meets these requirements. The activity of salinomycin, monensin, and nigericin on Plasmodium falciparum asexual and sexual erythrocytic stages and on the development of the Plasmodium berghei and P. falciparum mosquito stages is reported here. Gametocytogenesis of the P. falciparum strain 3D7 was induced in vitro, and gametocytes at stage II and III or stage IV and V of development were treated for different lengths of time with the ionophores and their viability measured with the parasite lactate dehydrogenase (pLDH) assay. The monovalent ionophores efficiently killed both asexual parasites and gametocytes with a nanomolar 50% inhibitory concentration (IC50). Salinomycin showed a fast speed of kill compared to that of standard drugs, and the potency was higher on stage IV and V than on stage II and III gametocytes. The ionophores inhibited ookinete development and subsequent oocyst formation in the mosquito midgut, confirming their transmission-blocking activity. Potential toxicity due to hemolysis was excluded, since only infected and not normal erythrocytes were damaged by ionophores. Our data strongly support the downstream exploration of monovalent ionophores for repositioning as new antimalarial and transmission-blocking leads

The T.O.S.C.A. Project: Research, Education and Care

Despite recent and exponential improvements in diagnostic- therapeutic pathways, an existing “GAP” has been revealed between the “real world care” and the “optimal care” of patients with chronic heart failure (CHF). We present the T.O.S.CA. Project (Trattamento Ormonale dello Scompenso CArdiaco), an Italian multicenter initiative involving different health care professionals and services aiming to explore the CHF “metabolic pathophysiological model” and to improve the quality of care of HF patients through research and continuing medical education

Role of prothrombotic polymorphisms in successful or unsuccessful aging

The study of the genetic profile of centenarians aims to identify the genes and allelic variants which may influence a greater life expectancy and that can be considered as predisposing factors associated to the aging diseases, such as Alzheimer. Centenarians, that represent a cohort of selected survivors, show an hypercoagulability state characterised by striking signs of high coagulation enzyme activity, as directly assessed by the tested higher plasma level of some important factors involved in the haemostasis balance. Anyway, these individuals seem to have a reduced susceptibility to dementia, as well as to cardiovascular events. In this study we analyze the frequencies of Leiden Factor V polymorphism (G1691A), and G20210A of prothrombin (FII) in three cohorts of subjects: patients with Alzheimer\u2019s disease (unsuccessful aging), nonagenarians (successful aging) and young healthy controls, to assess whether allelic variants associated to the modification of haemostatic system function, may play a role in the protection or susceptibility to Alzheimer disease, as well as to reach a successful aging. No significant differences were observed in the frequencies of the three groups studied. These results indicate that the presence or absence of the gene variants examined did not influence the achievement of advanced age and are not risk factors for Alzheimer\u2019s disease. The state of hypercoagulability and the possession of these risk alleles appear to be compatible with the achievement of longevity and are not implied as risk factors in Alzheimer disease development

Последовательность действий при визуализации кровоизлияний/гематом мягких тканей у пожилых больных, инфицированных SARS-CoV-2

Aim. To determine ultrasound, computed tomography and angiographic image characteristics for soft tissue hemorrhages/hematomas, the sequence of using imaging methods in patients infected with SARS-CoV-2, to study the morphology of changes in soft tissues, to determine the essence of the concept and to develop treatment tactics for this complication of COVID-19.Material and methods. During 4 months of treatment of elderly patients (+60) infected with SARS-CoV-2, 40 patients were identified with soft tissue hemorrhages/hematomas, of which 26 (65%) patients with large hematomas (>10 cm in size and > 1000 ml in volume). The analysis of clinical and laboratory parameters, methods of instrumental diagnostics (ultrasound – 26 patients, CT – 10 patients, angiography – 9 patients, punctures – 6 patients) was carried out; autopsy material was studied in 11 cases.Results. Image characteristics of hemorrhages/hematomas of soft tissue density were obtained using modern instrumental methods, and the sequence of application of visualization methods was determined. A tactic for managing a patient with stopped and ongoing bleeding has been developed. The morphological substrate of hemorrhagic complications in a new viral infection was studied. All patients were treated with conservative and minimally invasive procedures (embolization, puncture with pressure bandage). 15 patients (57.7%) recovered, 11 patients (42.3%) died from the progression of COVID-19 complications.Conclusion. Comprehensive clinical and laboratory sequential instrumental diagnosis of soft tissue hemorrhages in COVID-19. Treatment should be conservative and significantly invasive. The use of the term “soft tissue hematoma” in SARS-CoV-2 infected patients is not a natural quality of the normal pathological process and should not be observed from our point of view.Цель исследования: определить визуальные ультразвуковые, компьютерно-томографические и ангиографические критерии мягкотканных кровоизлияний/гематом, последовательность использования методов визуализации у больных, инфицированных SARS-CoV-2, изучить морфологию изменений в мягких тканях, определить суть понятия и выработать лечебную тактику при таком осложнении COVID-19.Материал и методы. За 4 мес лечения пожилых больных (+60), инфицированных SARS-CoV-2, выявлено 40 пациентов с мягкотканными кровоизлияниями/гематомами, из них 26 (65%) пациентов с большими гематомами (размер >10 см и объем> 1000 мл). Проведен анализ клинико-лабораторных показателей, методов инструментальной диагностики (УЗИ – 26 пациентов, КТ – 10 пациентов, ангиография – 9 больных, пункции – 6 пациентов), в 11 случаях изучен материал аутопсии.Результаты. Современными инструментальными методами получена визуальная характеристика крово излияний/гематом мягкотканной плотности, определена последовательность применения методов визуализации. Разработана тактика ведения пациента при остановившемся и продолжающемся кровотечении. Изучен морфологический субстрат геморрагического осложнения при новой вирусной инфекции. Все больные пролечены консервативными и минимально инвазивными процедурами (эмболизация, пункция с давящей повязкой). Выздоровели 15 (57,7%) пациентов, умерли от прогрессирования осложнений COVID-19 11 (42,3%) больных.Заключение. Комплексная клинико-лабораторная последовательная инструментальная диагностика мягкотканных кровоизлияний при COVID-19-инфекции позволяет своевременно установить топический диагноз, оценить тяжесть кровопотери, ее остановку или продолжение кровотечения. Лечение должно носить консервативный и минимально инвазивный характер. Использование термина “гематома” мягких тканей у инфицированных SARS-CoV-2 больных не отражает суть происходящего патологического процесса и, с нашей точки зрения, не должно использоваться

Effect of oxygen loaded nanodroplets on human endothelial cells and macrophages cultured in normoxic versus hypoxic conditions

Policies and practices of contemporary confinement ENS de Lyon, 20 and 21 June 2016 Our programme (EN) More information: click ici

Aminobisphosphonate-activated gamma delta T cells in immunotherapy of cancer: doubts no more

Background: Activated V gamma V iota 2 T cells are able to kill most tumour cells because of recognition by T cell receptor and natural killer receptors. Objective: We discuss the possibility that the intentional activation of gamma delta T cells in vivo by aminobisphosphonates may represent a promising target for the design of novel and highly innovative immunotherapy in cancer patients. Methods: The antitumoural effects of gamma delta T cells both in vitro and in vivo have been demonstrated suggesting a new therapeutic approach for translation into the clinical setting. Results/conclusion: V gamma 9V delta 2 T lymphocytes represent a particularly interesting target for immunotherapeutic protocols based on N-aminobisphosphonate administration and several Phase I-II trials are ongoing investigating the activity of zoledronic acid plus IL-2 in solid tumours