Saporin-S6: A Useful Tool in Cancer Therapy

Thirty years ago, the type 1 ribosome-inactivating protein (RIP) saporin-S6 (also known as saporin) was isolated from Saponaria officinalis L. seeds. Since then, the properties and mechanisms of action of saporin-S6 have been well characterized, and it has been widely employed in the construction of conjugates and immunotoxins for different purposes. These immunotoxins have shown many interesting results when used in cancer therapy, particularly in hematological tumors. The high enzymatic activity, stability and resistance to conjugation procedures and blood proteases make saporin-S6 a very useful tool in cancer therapy. High efficacy has been reported in clinical trials with saporin-S6-containing immunotoxins, at dosages that induced only mild and transient side effects, which were mainly fever, myalgias, hepatotoxicity, thrombocytopenia and vascular leak syndrome. Moreover, saporin-S6 triggers multiple cell death pathways, rendering impossible the selection of RIP-resistant mutants. In this review, some aspects of saporin-S6, such as the chemico-physical characteristics, the structural properties, its endocytosis, its intracellular routing and the pathogenetic mechanisms of the cell damage, are reported. In addition, the recent progress and developments of saporin-S6-containing immunotoxins in cancer immunotherapy are summarized, including in vitro and in vivo pre-clinical studies and clinical trials.     

Self-reported influenza vaccination uptake in people with chronic diseases: data from Progressi delle Aziende Sanitarie per la Salute in Italia (PASSI)

BackgroundInfluenza is an important public health problem, with potential severe consequences among people with chronic diseases. The aim of this study was to obtain reliable measures of seasonal influenza vaccine uptake in this population, otherwise not available in Italy.MethodsProgressi delle Aziende Sanitarie per la Salute in Italia (PASSI) is a nationwide surveillance system of health-related behaviours and acceptance of preventive interventions (including influenza immunisation) offered by the Italian National Health Service. Data are collected with telephone interviews at local health unit level for supporting local activities. The survey sample is randomly selected from local health unit lists of adult residents. The trend of annual vaccine coverage since 2008 was estimated for people aged 18–64 years who reported having at least one chronic disease. To obtain a sufficient sample size in subgroups, we analysed the characteristics of vaccinated people in the 2010–13 cumulative dataset. Univariate, multivariate, and logistic regression analyses were undertaken.FindingsIn 2008–13, 13 659 individuals with at least one chronic disease were interviewed. Vaccination coverage fell significantly from 29·7% (95% CI 27·2–32·4) in 2007–08 to 19·9% (18·0–22·1) in 2012–13. During 2010–13, the overall proportion of vaccinated people with a chronic disease was 25·6% (24·5–26·7). Vaccine coverage of people with diabetes (34·3%, 31·7–36·9) or cardiovascular diseases (31·8%, 29·6–34·2) was greater than that of people affected by renal failure, respiratory diseases, tumours, or chronic liver diseases (26·5% [22·5–30·7], 24·9% [23·2–26·7], 22·2% [20·0–24·6], and 20·6% [17·5–24·6], respectively). Vaccination coverage increased with age (from 13·1% [11·0–15·5] in the 18–34 year age group to 33·4% [31·9–35·1] in people aged 50–64 years); it was higher among people with a low educational level than among those with a high educational level, higher in those having economic difficulties than in those with no economic difficulties, and higher among Italian citizens than among non-citizens.InterpretationIn the past few years, prevalence of influenza vaccination in Italian adults with at least one chronic disease was well below the Ministry of Health's goal (75% minimum) and showed a downward trend. A major reason of this evolution is probably the changing public perception of the benefits and risks of vaccines. PASSI is a source of useful data not otherwise available for public health intervention.FundingItalian Ministry of Health.     

Microenvironment and tumor cell plasticity: An easy way out

Cancer cells undergo genetic changes allowing their adaptation to environmental changes, thereby obtaining an advantage during the long metastatic route, disseminated of several changes in the surrounding environment. In particular, plasticity in cell motility, mainly due to epigenetic regulation of cancer cells by environmental insults, engage adaptive strategies aimed essentially to survive in hostile milieu, thereby escaping adverse sites. This review is focused on tumor microenvironment as a collection of structural and cellular elements promoting plasticity and adaptive programs. We analyze the role of extracellular matrix stiffness, hypoxia, nutrient deprivation, acidity, as well as different cell populations of tumor microenvironment.     

Biocide activity of microfiber mops with and without silver after contamination

ObjectiveThe purpose of the present research was to compare the residual microbial load in Solo System microfiber mops with silver and in normal microfiber mops without silver to see whether those with the silver prevent bacterial proliferation and spread more effectively during normal cleaning operations.MethodsMops with and without silver were experimentally contaminated with suspension of Staphylococcus aureus ATCC 6538. The bioburden was evaluated by a filtering procedure according to UNI EN 1174 after contamination, after washing and after different times of impregnation in an alcohol-base detergent.Results and discussionThe results obtained lead to the conclusion that silver microfiber mop was significantly more effective in reducing bacterial load despite initial high level contamination (10⁶-10⁷ CFU/50 cm²). Indeed, after low temperature washing, the bacterial load was already completely eliminated while the mop without silver still presented relatively high levels of the microorganism (approximately 10² CFU/50 cm²) even after being soaked for 8 hours in a detergent/disinfectant.     

Role of Thrombolestagrophy in Monitoring Perioperative Coagulation Status and Effect of Thromboprophylaxis in Bariatric Surgery

Background  

Thromboelastography is a technique that surveys the properties of viscoelastic blood clot. The purpose of this paper was to evaluate the hypercoagulability state and the effect of antithrombotic prophylaxis on thromboelastogram (TEG) results in bariatric surgery.     

Clinical impact of direct referral to primary percutaneous coronary intervention following pre-hospital diagnosis of ST-elevation myocardial infarction.

AIMS: Treatment delay is a powerful predictor of survival in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). We investigated effectiveness of pre-hospital diagnosis of STEMI with direct referral to PCI, alongside more conventional referral strategies. METHODS AND RESULTS: From January 2003 to December 2004, 658 STEMI patients were referred for primary PCI at our intervention laboratory. Three predefined referral routes were compared: (1) for patients within 90 min drive of the PCI centre, pre-hospital diagnosis and direct transportation (n=166), (2) diagnosis at the interventional hospital emergency department (n=316), (3) diagnosis at local hospitals before transportation (n = 176). Pre-hospital diagnosis was associated with more than 45 min reduction in treatment delay (P = 0.001). No significant difference in in-hospital mortality was apparent in the overall study population. In the cardiogenic shock subgroup (n = 80), pre-hospital diagnosis was associated with a two-thirds reduction in in-hospital mortality (P = 0.019); mortality was only 6.2% in shock patients who underwent PCI in < 2 h. CONCLUSION: This study shows that pre-hospital diagnosis can provide a reduction in primary PCI treatment delay, and suggests the hypothesis that this referral strategy might provide survival benefits to patients with cardiogenic shock.