Bioinspired silk fibroin nano-delivery systems protect against 5-FU induced gastrointestinal mucositis in a mouse model and display antitumor effects on HT-29 colorectal cancer cells in vitro.

Colorectal cancer (CRC), is the second cause of cancer-related deaths worldwide is one of the most prevalent types of cancers. Conventional treatment continues to rely on surgery, chemotherapy, and radiotherapy, but for advanced cases, adjuvant chemotherapy remains the main approach for improving surgical outcomes and lower the disease recurrence probability. Chemotherapy-induced gastrointestinal (GI) toxicity is the main dose-limiting factor for many chemotherapeutic regimens, including 5-FU, and one of the biggest oncological challenges. Up to 40% of the patients receiving 5-FU get mucositis, 10-15% of which develop severe symptoms. In this context, our study aimed to develop a bioinspired nanosized drug delivery system as a strategy to reduce 5-FU associated side effects, such as GI mucositis. To this end, SF-based nanoparticles were prepared and characterized in terms of size and morphology, as well as in terms of in vitro antitumoral activity on a biomimetic colorectal cancer model by investigation of apoptosis, DNA fragmentation, and release of reactive oxygen species. Additionally, the capacity of the SF-based nanocarriers to offer intestinal protection against 5-FU-induced GI mucositis was evaluated in vivo using a mouse model that mimics the chemotherapy-associated gut mucositis occurring in colorectal cancer. Our studies show that silk fibroin nanoparticles efficiently deliver 5-FU to tumor cells in vitro while protecting against drug-induced GI mucositis in a mouse model.

The effect of red blood cell transfusion on peripheral tissue oxygen delivery and consumption in septic patients.

OBJECTIVES: The impact of blood transfusion on tissue oxygen delivery (DO2) and tissue oxygen consumption (VO2) is a subject of current clinical studies. The primary objective of this observational study is to evaluate and measure the parameters involved in determining DO2 and VO2, in early phase of septic patients. A secondary objective of this study is to assess the potential benefit of blood transfusion on tissue metabolism by serial measurements of lactic acid (Ac. Lac.). MATERIAL AND METHODS: A group of 29 patients were studied, each patient received between one to three units of fresh packed red blood cells (pRBC). Clinical and paraclinical criteria for sepsis as well as the plasma value of haemoglobin (Hb) below 10g/dL represented the inclusion criteria in this study. We evaluated Hb, haematocrit (HCT), arterial blood oxigen saturation (SAO2), central venous oxygen saturation (SCVO2), parameters which are involved in determination of DO2 and VO2, before and after the transfusion of one unit of pRBC. Values of Ac. Lac. were also assessed in order to determine the type of metabolism (aerobic or anaerobic). SCVO2, SAO2, Hb, HCT and Ac. Lac. were determined using Epoc blood analyser. The cardiac output (CO) and systemic vascular resistance (SVR) were monitored during blood transfusion, using Vigileo monitor (Edward's Life Science, PreSep catheter kit). SAO2 was also monitored by pulse-oximetry. RESULTS: Changes in Hb, HCT and SCVO2 before and after pRBC transfusion (which further determine VO2) were statistically significant (P<0.001). A statistically significant increase (P<0.001) was obtained in Ac. Lac. values, before and after pRBC transfusion. SAO2 and CO directly involved in producing DO2, were clinically monitored during blood transfusion and the results remained constant. CONCLUSION: Results obtained in this clinical study show an increase in DO2 in critically ill septic patients and also an increase in oxygen tissue uptake which is similar to VO2, clearly pointing out the benefit of pRBC transfusion. The benefits of pRBC transfusion on tissue metabolism in critically ill septic patients remain elusive because of lactic acid values increase during and after transfusion. Based on our findings we recommend that Hb values used as a single trigger for pRBC transfusion should be further studied and that additional parameters such as SCVO2 and lactic acid should be considered as possible triggers for transfusion. Values of Hb and HCT should never be neglected.

Can a channelized Hotelling observer assess image quality in acquired mammographic images of an anthropomorphic breast phantom including image processing?

PURPOSE: To study the feasibility of a channelized Hotelling observer (CHO) to predict human observer performance in detecting calcification-like signals in mammography images of an anthropomorphic breast phantom, as part of a quality control (QC) framework. METHODS: A prototype anthropomorphic breast phantom with inserted gold disks of 0.25 mm diameter was imaged with two different digital mammography x-ray systems at four different dose levels. Regions of interest (ROIs) were extracted from the acquired processed and unprocessed images, signal-present and signal-absent. The ROIs were evaluated by a CHO using four different formulations of the difference of Gaussian (DoG) channel sets. Three human observers scored the ROIs in a two-alternative forced-choice experiment. We compared the human and the CHO performance on the simple task to detect calcification-like disks in ROIs with and without postprocessing. The proportion of correct responses of the human reader (PCH ) and the CHO (PCCHO ) was calculated and the correlation between the two was analyzed using a mixed-effect regression model. To address the signal location uncertainty, the impact of shifting the DoG channel sets in all directions up to two pixels was evaluated. Correlation results including the goodness of fit (r2 ) of PCH and PCCHO for all different parameters were evaluated. RESULTS: Subanalysis by system yielded strong correlations between PCH and PCCHO , with r2 between PCH and PCCHO was found to be between 0.926 and 0.958 for the unshifted and between 0.759 and 0.938 for the shifted channel sets, respectively. However, the linear fit suggested a slight system dependence. PCCHO with shifted channel sets increased CHO performance but the correlation with humans was decreased. These correlations were not considerably affected by of the DoG channel set used. CONCLUSIONS: There is potential for the CHO to be used in QC for the evaluation of detectability of calcification-like signals. The CHO can predict the PC of humans in images of calcification-like signals of two different systems. However, a global model to be used for all systems requires further investigation.

Acute cardiotoxicity induced by doxorubicin in right ventricle is associated with increase of oxidative stress and apoptosis in rats.

Doxorubicin (DOX) is one of the most effective chemotherapeutic agents, but its efficiency is seriously limited by the risk of developing cardiomyopathy. The most recognized cardiotoxic effect is left ventricular (LF) dysfunction, but MRI and echocardiography data demonstrated significant right ventricle (RV) function impairment. In order to clarify this aspect, the present study investigated the potential of DOX to induce acute RV cardiotoxicity at the same time as LV impairment. Rats were intraperitoneally (i.p.) injected with a single dose of 15 mg/kg DOX. DOX-treated rats were characterized by decreased body and heart weights, elevated levels of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) activities compared to controls. Biochemical analyses on RV tissue revealed that the level of malondialdehyde (MDA) was significant increased (p<0.05) and activities of catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPX) antioxidant enzymes were decreased by 13%, 27% and 18%, respectively, compared to control. Histopathogical and electron microscopic studies revealed DOX-induced damage in both ventricles and an increase of interstitial collagen fibers compared to controls (p<0.001), whereas immunohistochemical analysis showed weak and irregular desmin expression. Furthermore, mitochondrion-induced apoptotic pathways were also activated in both ventricles, as reflected by the up-regulation of Bax/Bcl-2 mRNA expression ratio (p<0.001) and increase of Bax and caspase-3 protein expression, as well as by the significant elevation of TUNEL positive nuclei, compared to controls (p<0.001). The results showed that DOX exerted RV toxic effects at the same time as those reported in the LV, which might be mediated through the mitochondrial-dependent apoptosis.

Chrysin attenuates cardiomyocyte apoptosis and loss of intermediate filaments in a mouse model of mitoxantrone cardiotoxicity.

Chrysin (CHR) is a natural flavonoid and is present in high concentration in honey, propolis and many plant extracts. The aim of the present study was to evaluate the effects of CHR to reduce cardiomyocyte apoptosis and loss of intermediate filaments in a mouse model of mitoxantrone cardiotoxicity. Morphology of the cardiomyocytes was determined by optic and transmission electron microscopy and biochemistry methods. The expression of Bcl-2, Bax and Caspase-3 were assessed by immunofluorecence. Tunel assay was used to assess apoptosis in cardiomyocytes. In addition, the distribution of desmin protein was evaluated using immunohistochemistry. Our results show that MTX treatment significantly increased serum levels of creatine kinase isoenzyme (CK-MB), indicator of cardiac injury and withdrawn under CHR protection. Expression levels of Bcl-2 decreased, while those of Bax and caspase-3 increased following MTX treatment. 50 mg/kg of daily CHR intake reduced Bax and caspase-3 immunopositivity and restored Bcl-2 levels to a value comparable to the control. TUNEL (+) cardiomyocyte nuclei of MTX group showed typical signs of apoptosis which almost completely disappeared in response to 50 mg/kg CHR treatment. In parallel, an irregular distribution and a weak expression of desmin is associated with MTX induced cardiotoxic effects which was also restored by CHR treatment. In conclusion chrysin inhibits MTX-triggered cardiomyocyte apoptosis via multiple pathways, including decrease of the Bax/Bcl-2 ratio and caspase-3 expression along with preservation of the desmin disarray.

Pandemic influenza A vs seasonal influenza A in hospitalized children in Athens.

BACKGROUND: Data on pandemic H1N1 influenza (pH1N1) virus infection in hospitalised children are limited. AIMS AND OBJECTIVES: To examine the epidemiological and clinical characteristics of children hospitalised with pH1N1 at a large tertiary-care centre in Athens and compare them with those of children hospitalised with seasonal influenza A in previous years. METHODS: All children (n = 146) admitted with confirmed pH1N1 between October 2009 to February 2010 and January 2011 to May 2011 were included. Data on children ≧ 6 months of age (n = 109) were compared with those of 138 children admitted with seasonal influenza A who were examined during two previous influenza seasons (2002-2003 and 2004-2005). RESULTS: The age distribution was similar between seasonal and pandemic H1N1. Bronchial asthma was significantly more common in the seasonal influenza group but the clinical presentation was similar in the two groups, except that fever was more common in patients with pH1N1. Children admitted with seasonal influenza were more likely to develop acute otitis media. There were no significant differences between the two groups for severe outcomes (admission to the ICU, mechanical ventilation or death). Only one child with seasonal influenza (0.6%) and three with pH1N1 influenza (2%) required admission to the ICU. Mean length of hospitalisation was longer in the seasonal influenza group. CONCLUSION: Clinical manifestations were similar between pH1N1 and seasonal influenza, and the pandemic virus did not appear to cause more severe disease in hospitalised children.

Diabetic gangrene: medical and surgical causes and consequences.

Diabetic gangrene is the chronic complication which involves many medical, economic and social problems. In this study we have analyzed the medical and surgical causes and consequences of diabetic gangrene on three groups of patients: 120 patients (96 males and 24 females; aged (X +/- SD) 57 +/- 14 years hospitalised in the Clinic of Diabetes, Nutrition and Metabolic Diseases of the "N. Paulescu" Institute, 72 patients (59 males and 13 females; mean age 60 +/- 10 years) hospitalised in the Surgical Clinic of Cantacuzino Hospital; 29 patients (23 males and 6 females; mean age 58 +/- 11 years) hospitalised in the Cardiovascular Department of Fundeni Hospital. The analyses of data obtained showed: in 77% of cases the initial lesions might have been avoided by an appropriate education programme of the patients; in 66% of cases the progression of lesion from medical to surgical stage was caused by tardily coming of patient to physician; average duration of hospitalization was 27 days in the Clinic of Diabetes, Nutrition and Metabolic Diseases, 33 days in the Clinic of Surgery of "Cantacuzino" Hospital and 25 days in Cardiovascular Department of Fundeni Hospital; the surgical mortality was 8%; 47% operated patients were cured and 53% were incompletely cured and required more out patient care; 35% were thigh amputations, that shows the high invalidity potential of diabetic gangrene; the cost of medical and/or surgical care of diabetic gangrene is higher than the cost of hospitalisation for other patients; the diabetic gangrene predominantly neuropathic was better cured and the arteriopathic component breaks the medical curing and impose high amputations; diabetic gangrene is more frequent with older people, but with young people it is a cause of early retiring and psycho-social concern.