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.

Ferromagnetic Resonance Assisted Optomechanical Magnetometer.

The resonant enhancement of mechanical and optical interaction in optomechanical cavities enables their use as extremely sensitive displacement and force detectors. In this Letter, we demonstrate a hybrid magnetometer that exploits the coupling between the resonant excitation of spin waves in a ferromagnetic insulator and the resonant excitation of the breathing mechanical modes of a glass microsphere deposited on top. The interaction is mediated by magnetostriction in the ferromagnetic material and the consequent mechanical driving of the microsphere. The magnetometer response thus relies on the spectral overlap between the ferromagnetic resonance and the mechanical modes of the sphere, leading to a peak sensitivity of 850 pT Hz^{-1/2} at 206 MHz when the overlap is maximized. By externally tuning the ferromagnetic resonance frequency with a static magnetic field, we demonstrate sensitivity values at resonance around a few nT Hz^{-1/2} up to the gigahertz range. Our results show that our hybrid system can be used to build a high-speed sensor of oscillating magnetic fields.

The iris signal: blue periphery, tan collaret and freckles pattern - strong indicators for epidermal skin cancer in South-Eastern Europe.

BACKGROUND: Eye and skin share the embryological origin. Both are established risk factors in epidermal skin cancer. There are few reports using iris colour classification scales, most of them analyse colour in general or are too complex to use in daily practice. OBJECTIVES: To investigate which iris colour pattern is associated with epidermal skin cancer in a S-E European Caucasian population. METHODS: A case-control study was conducted on 480 patients: 229 skin cancers patients and 251 controls (dermatological patients free of skin cancers) admitted in two medical clinics of Dermatology in Bucharest, between October 2011 and May 2014. High-resolution iris photographs were taken for each patient. Three parameters of the iris were analysed individually and in association patterns for each patient: periphery, collaret and freckles. RESULTS: The most frequent iris colour pattern associated with epidermal skin cancer was blue periphery with light brown collaret and freckles present. In terms of individual parameters, the strongest indicators for skin cancer patients were blue periphery and blue collaret. CONCLUSIONS: The results of this study sustain the hypothesis that blue periphery with light brown collaret and freckles iris pattern is a reliable phenotypic marker for epidermal skin cancer. The results of this study differ from previous reports in which skin cancer risk was associated with a homogeneous blue iris. We account these differences in the characteristics of the recruited patients (S-E European, skin type II and III). The assessment of iris colour patterns is an easy and inexpensive detection tool in skin cancer risk assessment.

Which is the Best Imaging Method in Pancreatic Adenocarcinoma Diagnosis and Staging - CT, MRI or EUS?

INTRODUCTION: Imaging has a decisive role in the diagnosis and staging of pancreatic cancer, the most used imaging methods being computed tomography, magnetic resonance imaging and endoscopic ultrasonography. MATERIAL AND METHOD: They were studied retrospectively over a 3 years period, 140 patients with pancreatic cancer. AIM OF THE STUDY: This study aims to determine the effectiveness of CT, MRI and EUS in diagnosis and staging of panceatic cancer. RESULTS: CT showed a diagnostic accuracy of 83.3%, with sensitivity and specificity of 81.4% and 43% respectively. MRI showed superior diagnostic accuracy compared to CT (89,1%). However, EUS demonstrated the best diagnostic value in PC (accuracy of 92,7%). Concerning the locoregional staging, the 3 diagnostic methods showed similar result. There were no significant differences concerning the diagnosis of intra-abdominal metastases. Differences have appeared in the case of extra-abdominal. Thus, there were 4 cases of lung metastases which have been identified only on CT and MRI. CONCLUSION: EUS is the most effective technique used in the diagnosis of pancreatic cancer, the present study demonstrating an accuracy of 92.7%. Moreover, EUS offers the possibility to collect samples for cytological examination by EUS guided fine needle aspiration. However, there are some limitations of EUS in identifying extra-abdominal metastases. Thus, the assessment of tumor extension must be completing by performing CT or MRI.

First report of OXA-72 producing Acinetobacter baumannii in Romania.

This is the first report of an OXA-72-producing Acinetobacter baumannii strain in Romania, isolated from chronic leg ulcer samples. Identification of the strain was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Presence of carbapenem resistance genes was investigated by PCR and sequencing. Our data support the spread of the bla OXA-72 gene in Eastern Europe.

Electrochemical comparison and biological performance of a new CoCrNbMoZr alloy with commercial CoCrMo alloy.

A new CoCrNbMoZr alloy, with Nb and Zr content is characterized from the point of view of surface features, corrosion resistance and biological performance in order to be proposed as dental restorative material. Its properties are discussed in comparison with commercial Heraenium CE alloy based on Co, Cr and Mo as well. The microstructure of both alloys was revealed by scanning electron microscopy (SEM). The composition and thickness of the alloy native passive films were identified by X-ray photoelectron spectroscopy (XPS). The surface characteristics were analyzed by atomic force microscopy (AFM) and contact angle techniques. The quantity of ions released from alloys in artificial saliva was evaluated with inductively coupled plasma-mass spectroscopy (ICP-MS) measurements. The electrochemical stability was studied in artificial Carter-Brugirard saliva, performing open circuit potentials, polarization resistances and corrosion currents and rates. The biological performance of the new alloy was tested in vitro in terms of human adipose stem cells (hASCs) morphology, viability and proliferation status. The new alloy is very resistant to the attack of the aggressive ions from the artificial saliva. The surface properties, the roughness and wettabiliy sustain the cell behavior. The comparison of the new alloy behavior with that of existing commercial CoCrMo alloy showed the superior properties of the new metallic biomaterial.

Gelatin-poly(vinyl alcohol) porous biocomposites reinforced with graphene oxide as biomaterials.

The present work aims to develop new biocomposites based on gelatin (Gel) and poly(vinyl alcohol) (PVA) reinforced with graphene oxide (GO). On the one hand, the model is designed with consideration of the high performance of the aforementioned biopolymers as biomaterials; on the other hand, the original component of the system, GO, is expected to improve structural stability and boost mechanical strength. Porous Gel-PVA/GO materials with GO content ranging from 0.5 to 3 wt% are obtained by freeze-drying. Structural analysis by Fourier transform infrared spectrometry (FT-IR), X-ray diffraction (XRD) and transmission electron microscopy (TEM) revealed the ability of well-dispersed GO nanosheets to form interactions with the polymers, leading to a unique molecular structuration. 3D analysis by X-ray microtomography (microCT) and scanning electron microscopy (SEM) suggests that GO has an influence on pore adjustment. According to mechanical tests, GO undoubtedly exhibits a beneficial effect on the polymer resistance against compressive stress, improving their compressive strengths by 97-100% with the addition of 0.5-3 wt% GO. Moreover, biological assessment using the MC3T3-E1 preosteoblast murine cell line indicated the fabrication of a cytocompatible composite formula, with potential for further in vivo testing and tissue engineering applications.

VEGF Expression in Pancreatic Cancer and Other Malignancies: A Review of the Literature.

Angiogenesis is a crucial event for tumor growth and it is regulated predominantly by several different growth factors. Vascular endothelial growth factor protein family (VEGF) and its receptors are probably the most important tissue factors responsible for angioblast differentiation and tube formation. VEGF protein family currently comprises several members: VEGF (or VEGF-A), VEGF-B, VEGF-C and VEGF-D, VEGF-F, placental growth factor (PlGF), and their receptors VEGFR-1, VEGFR-2 and VEGFR-3. VEGF is a key angiogenic growth factor and its level of expression is a critical marker for detection of the angiogenic diseases. The potent role of VEGF in tumor angiogenesis has been widely described in the past decade, being expressed in most types of nondigestive and digestive cancers. VEGF family members play an important role in the development of pancreatic cancer (especially VEGF-A, VEGF-C, VEGF-D, VEGFR-1 and VEGFR-2). VEGF-A is the most specific and prominent angiogenic factor among all family members and VEGFR-2 is the most important receptor in evaluating the angiogenesis in pancreatic cancer. Thus, VEGF overexpression may be considered as a diagnostic marker and as a poor prognostic factor of the disease.

Hepatoprotective effects of a self-micro emulsifying drug delivery system containing Silybum marianum native seed oil against experimentally induced liver injury.

The main purpose of this study was to certify the effect of native silymarin oil (SM-oil) formulated in a self-microemulsifying drug delivery system (SMEDDS). The optimal formulation was 25% of SM-oil, 33.3 % of Cremophor RH40, 20% of Transcutol HP, 16.6% of Labrasol and 5% of Capryol 90. In this novel formulation the SM-oil was the active substance and the lipid part. The in vivo study examined the preventive effects of SMEDDS containing SM native seeds oil against carbon tetrachloride (CC14) induced hepatotoxicity in mice. Determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels and also liver histology investigations have been done. The liver antioxidant status was determined with the concentrations of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), and glutathione (GSH) hepatic lipid peroxidation was examined and expressed in terms of malondialdehyde (MDA) content. The plasma levels of AST and ALT significantly diminished by pre-treatment with 500 mg/kg and 1000 mg/kg SMEDDS. The pre-treatment with 500 mg/kg and 1000 mg/kg SMEDDS increased GSH level by about 6% respectively 24% compared to the CC14 group. Due to preventive administration of 500 mg/kg and 1000 mg/kg of SMEDDS in the intoxicated animals, MDA levels were reduced by 22% respectively 58%. Also, an insignificant rise by almost 17% and 19% in the animals treated with the both doses of SMEDDS could be noticed. It can be concluded that hepatotoxicity may be avoided by the oral application of our formulation.

Esophagectomy in esophageal cancer - is there an optimal approach?

INTRODUCTION: Esophageal cancer is a public health problem,with increasing incidence and postoperative morbidity over the past recent years. Although a number of new surgical techniques, including minimally invasive surgery, have been developed, mortality and morbidity have remained elevated.The element that seems to influence the early postoperative morbidity and mortality is the method of approach. MATERIAL AND METHODS: retrospective observational study which is carried out in the period 2003-2012 including esophageal neoplasm patients operated in the First Surgical Clinic -Hospital "Sf. Spiridon", Iasi. 140 patients were included, of which only 33 have received surgery with curative aim. SURGICAL TECHNIQUE: we consider 2 techniques in our study:transhiatal (TH) technique (without opening the chest)followed by esophagoplasty with cervical anastomosis and transthoracic esophagectomy (TT) with intrathoracic or cervical anastomosis. RESULTS: We performed 57.58 % (n = 19) of interventions by TT versus 42.42% (n = 14) by TH. The overall rate of postoperative morbidity rate was 78.8% (n = 26). Overall early postoperative mortality rate was 15.5% (n = 5) caused by pleuropulmonary sepsis (2 cases), lung emboli (1 case) and sepsis caused by anastomotic leak (2 cases). CONCLUSION: TT and TH esophagectomy have precise indications in esophageal surgery for malignancies, the mortality and morbidity rate being strongly influenced by the surgical approach.

Comparative study of leptin and leptin receptor gene expression in different swine breeds.

Leptin is an important regulator of appetite, energy metabolism, and reproduction and is mainly synthesized in the adipocytes and then secreted into the bloodstream. The leptin receptor was classified as type I cytokine receptor due to its structural homology with IL-6 receptors and the signaling pathways in which they are both involved. The aim of our study is to comparatively assess the gene expression levels of leptin (lep) and leptin receptor (lepr) in different swine breeds specialized either in meat production (Duroc, Belgian Landrace, Large White, Synthetic Lines LS-345, and LSP-2000) or fat production (Mangalitsa) in order to correlate them with morphological and productivity characteristics. Additionally, lepr pattern of expression was evaluated comparatively between different tissue types in the Mangalitsa breed. Our results revealed high expression of the lep gene in Mangalitsa compared to those of all the other breeds, while for the lepr gene, average/medium levels were registered in Mangalitsa and increased pattern of expression was found in the synthetic lines LS-345 and LSP-2000. Regarding the comparative analysis of lepr gene expression in various tissues in the Mangalitsa breed, elevated levels were found in the liver and kidney, while the lowest expression was identified in the brain and muscles. Our results suggest that the Mangalitsa population exhibits leptin resistance, which might be correlated with atypical morpho-productive characteristics for this breed, such as below-average prolificacy and a strong tendency to accumulate fat.

Clinical, Histopathological and Therapeutical Analysis of Inferior Eyelid Basal Cell Carcinomas.

RATIONALE: Eyelids are very susceptible area for non-melanoma skin cancers; among that, basal cell carcinoma has the highest incidence (almost 90% of malignant eyelid tumors) and 50-60% of eyelid basal cell carcinomas appear on inferior eyelid. OBJECTIVE: To analyze clinical features of inferior eyelid basal cell carcinoma and to determine the efficacy of surgical treatment with frozen sectioncontrolled margins and methods of primary reconstruction of defects. METHODS: A review of medical records of cases with primary inferior eyelid basal cell carcinoma treated by surgical excision with urgent histopathology controlled margins by FS technique, doubled by paraffin examination from October 2011 to October 2014. After histopathology confirmation of tumor free margins, proper inferior eyelid reconstruction was performed. RESULTS: The review resulted in 36 patients with 36 lesions analyzed by clinical, histopatological and therapeuticalaspectswith a mean follow-up of 20 months. All lesions were primary BCC affecting inferior eyelid. There were no recurrence in the follow-up period. Inferior eyelid reconstruction techniques were direct closure for small defects and complex techniques for defects more than one third of eyelid length. DISCUSSION: Appropriate eyelid examination is mandatory in any routine ophthalmic check-up. Clinical signs suggestive of BCC should be familiar to ophthalmologist in order to have an early diagnosis and treatment for these tumors. Surgical treatment with FS controlled excision followed by eyelid reconstruction is an efficient treatment for inferior eyelid BCC. ABBREVIATIONS: basal cell carcinoma (BCC); frozen section (FS);Mohs micrographic surgery (MMS).

Peritoneal fibrinolytic activity and adhesiogenesis.

INTRODUCTION: Postoperative adhesions after abdominal or pelvic surgery remain an important clinical problem causing infertility, pain and bowel obstruction. Their prevention and treatment remains poorly understood and inadequate. The formation of adhesions is caused by the organization of a fibrin matrix, an organization that takes place during the coagulation process when there is suppression of fibrinolysis. METHODS: In this study peritoneal tissue and peritoneal fluid from two groups of patients were sampled and analysed. The first group comprised of 12 patients undergoing abdominal surgery for an acute abdomen during which known peritoneal factors of aggression (trauma, chemical, bacterial) were present which are known to increase the propensity for peritoneal adhesion formation. A second group consisting of 6 patients undergoing surgery in the absence of these peritoneal aggression factors acted as a reference control group. Each patient had peritoneal tissue sampled at the time of surgery and analysed for levels of gene expression of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1). Patients also had peritoneal drain fluid collected postoperatively and analysed for quantities of fibrin degradation products (FDPs) and fibrinogen. RESULTS: The aim of this study was to evaluate the role of PAI-1 and tPA genes at peritoneal tissue level. Peritoneal tissue was obtained during surgery and the variation of expression of PAI-1 and tPA genes was quantified. The obtained results highlighted an increase of expression in PAI-1 gene and decrease of expression in tPA gene in patients with increased factors of peritoneal aggression compared to patients without, indicating a decreased fibrinolytic potential in patients with increased peritoneal adhesion propensity. Increased factors of peritoneal aggression also resulted in increased levels of FDPs and fibrinogen in peritoneal exudates.

Tyrosine-derived polycarbonate-silica xerogel nanocomposites for controlled drug delivery.

Biodegradable polymer-ceramic composites offer significant potential advantages in biomedical applications where the properties of either polymers or ceramics alone are insufficient to meet performance requirements. Here we demonstrate the highly tunable mechanical and controlled drug delivery properties accessible with novel biodegradable nanocomposites prepared by non-covalent binding of silica xerogels and co-polymers of tyrosine-poly(ethylene glycol)-derived poly(ether carbonate). The Young's moduli of the nanocomposites exceed by factors of 5-20 times those of the co-polymers or of composites made with micron scale silica particles. Increasing the fraction of xerogel in the nanocomposites increases the glass transition temperature and the mechanical strength, but decreases the equilibrium water content, which are all indicative of strong non-covalent interfacial interactions between the co-polymers and the silica nanoparticles. Sustained, tunable controlled release of both hydrophilic and hydrophobic therapeutic agents from the nanocomposites is demonstrated with two clinically significant drugs, rifampicin and bupivacaine. Bupivacaine exhibits an initial small burst release followed by slow release over the 7 day test period. Rifampicin release fits the diffusion-controlled Higuchi model and the amount released exceeds the dosage required for treatment of clinically challenging infections. These nanocomposites are thus attractive biomaterials for applications such as wound dressings, tissue engineering substrates and stents.

Downregulation of hsp22 gene expression in Drosophila melanogaster from sites located near chemical plants.

A common physiological response of organisms to environmental conditions is variation in gene expression, especially true for genes encoding for heat shock proteins. In insects, this process has been examined for induced heat or cold stress. The putative long-term imprinted/acquired heat shock protein response due to unfriendly environmental conditions has been far less studied. The Drosophila melanogaster hsp22 gene, which has been extensively reviewed as being sensitive to different changing life conditions, was examined by qRT-PCR, using carboxy-X-rhodamine. In the present study, we focused on the detection of hsp22 level of transcription in three D. melanogaster isolates, collected from sites located near different chemical plants in Romania and subjected to one-year adaptation to laboratory conditions. In all isolates, the hsp22 gene expression was determined using the housekeeping genes Gapdh1 and UbcD10 as internal controls. According to our experimental results, the D. melanogaster hsp22 gene was significantly downregulated compared to the same gene in w(1118)iso, used as a calibrator. We showed that hsp22 could play an important role in relation to stress resistance and adaptation. This study highlights the importance of in vivo studies to demonstrate genome plasticity to overcome different damages induced by any presumed source of stress.

Phylogenetic relationships of the Hucul horse from Romania inferred from mitochondrial D-loop variation.

The existence of the Hucul horse on Romanian territory has been documented from the very distant past; today Hucul is a unique breed that is part of the FAO Program for the Preservation of Animal Genetic Resources. We compared Hucul with several primitive European and Asiatic breeds in order to elucidate the origin of these horses. We analyzed a 683-bp mitochondrial DNA (mtDNA) D-loop fragment in a population of Hucul horses and compared the polymorphic sites with sequences from other primitive breeds, including Exmoor, Icelandic Pony, Sorraia, Przewalski Horse, Mongolian Wild Horse, Konik, and Shetland Pony, as well as with Arabian, Akhal Teke and Caspian Pony. The sequences were truncated to 247 bp to accommodate short sequence data for the other species. Eighty horses were analyzed; 35 polymorphic sites representing 33 haplotypes were observed. The mean percentage of polymorphic sites was 14.2% for this mtDNA fragment. A neighbor-joining phylogenetic tree was constructed based on Kimura two-parameter distances and the Network 3.111 software was used for phylogenetic analysis. The Hucul horse was classified separately from all other primitive breeds. It is possible that the Hucul horse is not part of the pony class, as it segregated apart from all primitive pony breeds. We found multiple origins in the maternal lineage of domestic horse breeds and demonstrated the uniqueness of the Hucul breed; its origins remain unclear.

[Distal pancreatectomy with spleen preservation in a pseudopapillary pancreatic tumor case]. / Pancreatectomia corporeocaudala cu prezervarea splinei intr-un caz de tumora solida pseudopapilara de pancreas.

Pseudopapillary pancreatic tumors represent about 1-2% of all exocrine pancreatic tumors, studies in the literature about this type of tumor is limited. We present a female patient of 18 years hospitalized for nonspecific abdominal symptoms, diagnosed with corporeal pancreatic tumor approximately 3-4 cm. It takes practice surgical distal pancreatectomy with spleen preservation, pathological examination revealing a pseudopapillary pancreatic tumor. Postoperative evolution was favorable. Distal pancreatectomy with spleen preservation was indicated due to patient age.

[Radical neck dissection in advanced thyroid cancer]. / Disectia radicala a gâtului in cancerul tiroidian avansat.

We try to ascertain whether total thyroidectomy with radical neck dissection offers a survival and recurrency advantage for thyroid cancer. Between January 2000 and September 2009 in the 3rd Surgical Unit of the "Sf. Spiridon" Hospital of Iasi 189 operations were performed for malign thyroid disorders, 164 (86,77%) of which were performed for the papillary or foliculary cancer. The diagnosis was confirmed by hystopathological examination. The patients had a medium age of 51,48 (extremes 19 - 81 years). Women had a greater proportion, as expected (sex ratio F:M = 2,85:1). 59 total thyroidectomy with radical or modified radical neck dissection were performed. There were immediate (6 bleedings which needed reoperation for haemostasis, 7 unilateral recurrent laryngeal nerve injury) and late complications (8 cases of recurrency in the first 2 years). Total thyroidectomy with radical neck dissection became the ellective method for advanced thyroid cancer (the best results were for papillary cancer, female and age over 55).

Tuberculosis diagnosed after major hepatectomy for suspected malignancy.

A patient with a history of surgery and adjuvant chemotherapy 2 1/2 years previously for Dukes C colonic adenocarcinoma was diagnosed with a focal liver lesion on follow-up examinations. Ultrasound and computed tomography scan revealed a 3.8 cm soft tissue mass. Positron emission tomography scan showed intense uptake, corroborating the diagnosis of a colonic liver metastasis. Major hepatectomy was performed but pathology revealed that the lesion was in fact a benign tuberculosis pseudo-tumour. In developed countries liver tuberculosis remains extremely rare, particularly the macronodular form. The diagnosis is often made only after hepatectomy for suspected malignancy. The increasing use of potent anticancer chemotherapy may favour the reactivation of quiescent tuberculosis, posing a difficult differential diagnosis with liver metastases.

In vitro cytotoxicity and antioxidant activities of five medicinal plants of Malvaceae family from Cameroon.

The potential antiproliferative and antioxidant activities of extracts from five medicinal plants from Cameroon were evaluated in vitro on HepG-2 cells. The results showed the significant decrease of the viability of the cells in a concentration-dependent manner. According to the IC(50) obtained, the extracts of S. acuta (461.53±0.23) and U. lobata (454.93±0.12) showed significant antiproliferative activity. At fixed concentration (250µgmL(-1)), extracts demonstrated higher antiproliferative activity (67.05%; 65.42%), (52.62%; 56.64%) and (32.98%; 36.85%) respectively during 24, 48 and 72h. Extracts of S. cordifolia and V. album demonstrated significant antiproliferative property after 48h while S. rhombifolia exhibited weak cytotoxicity. The results of the antioxidant properties showed that theses extracts induced significantly increase of SOD, CAT and GsT activity after 48h. Taken together, the results extracts showed that of S. acuta and U. lobata may be a promising alternative to synthetic substances as natural compound with high antiproliferative and antioxidant activities.