In vivo performance of antibiotic embedded electrospun PCL membranes for prevention of abdominal adhesions

The aim of this study was to prepare nonwoven materials from poly(-caprolactone) (PCL) and their antibiotic containing forms by electrospinning, so as to prevent postsurgery induced abdominal adhesions in rats. -Caprolactone was first polymerized by ring-opening polymerization, and then it was processed into matrices composed of nanofibers by electrospinning. A model antibiotic (Biteral®) was embedded within a group of PCL membranes. In the rat model, defects on the abdominal walls in the peritoneum were made to induce adhesion. The plain or antibiotic embedded PCL membranes were implanted on the right side of the abdominal wall. No membrane implantation was made on the left side of the abdominal wall that served as control. Macroscopical and histological evaluations showed that using these barriers reduces the extent, type, and tenacity of adhesion. The antibiotic embedded membranes significantly eliminated postsurgery abdominal adhesions, and also improved healing

Understanding The Endothelial to Hematopoietic Transition In Mouse Development

The endothelial to hematopoietic transition (EHT) is a key developmental event leading to the formation of blood stem and progenitor cells during embryogenesis. A small subset of cells called hemogenic endothelial cells (HE) undergoes the EHT by becoming pre-hematopoietic stem and progenitor cells (Pre-HSPC). Eventually after losing all their endothelial characteristics they become HSPC. Despite extensive studies on this process, there are several questions remaining: What are the differences between hemogenic and non hemogenic endothelial cells? How different is the EHT process in the aorta-gonad-mesonephros (AGM) generating mostly blood stem cells (self-renewing and generating all cell types) and the yolk sac (YS) producing mostly blood progenitors (non self-renewing and generating only a few cell types)? To address these questions, I used single cell transcriptomics because of the scarcity of the HE and the Pre-HSPC within the endothelial population in the AGM and YS. I examined the cells isolated at E9.0, E10.5 and E11.0 mouse embryos. I showed that the major endothelial population of AGM and YS is different from each other, which might be linked with their distinct hematopoietic program. I showed that the pre-HSPC in AGM and YS are transcriptionally alike suggesting that the different hematopoietic program between AGM and YS could be due to the microenvironment. Additionally, I identified a new population detected only in YS at E10.5 co-expressing endothelial and erythroid genes. The molecular mechanism of the EHT is still not understood. Since the TGFβ signaling triggers a similar event during heart development called endothelial to mesenchymal transition (EndMT), we hypothesized that TGFβ activity may play a similar role in EHT. When I activated the TGFβ signaling by adding TGFβ2 during in vitro EHT differentiation, I observed surprisingly a complete block of the hematopoiesis. When I inhibited it by adding the Tgfbr1 inhibitor, it enhanced blood development. Additionally, the mRNA profile of the treated cells confirmed that inhibition of Alk5 is promoting the EHT, while the TGFβ activation results in cells with a phenotype closer to cardiac and mesenchymal cells. Consequently, despite the fact that both EndMT and EHT lead to a loss of endothelial cell identity and the generation of mobile cells, our study suggests that the signaling events initiating both processes are different

In vitro and in vivo degradation of non-woven materials made of poly(e-caprolactone) nanofibers prepared by electrospinning at different conditions

The aim of this study was to prepare non-woven materials from a biodegradable polymer, poly(ε-caprolactone) (PCL) by electrospinning. PCL was synthesized by ring-opening polymerization of ε-caprolactone in bulk using stannous octoate as the catalyst under nitrogen atmosphere. PCL was then processed into non-woven matrices composed of nanofibers by electrospinning of the polymer from its solution using a high voltage power supply. The effects of PCL concentration, composition of the solvent (a mixture of chloroform and DMF with different DMF content), applied voltage and tip–collector distance on fiber diameter and morphology were investigated. The diameter of fibers increased with the increase in the polymer concentration and decrease in the DMF content significantly. Applied voltage and tip–collector distance were found critical to control 'bead' formation. Elongation-at-break, ultimate strength and Young's modulus were obtained from the mechanical tests, which were all increased by increasing fiber diameter. The fiber diameter significantly influenced both in vitro degradation (performed in Ringer solution) and in vivo biodegradation (conducted in rats) rates. In vivo degradation was found to be faster than in vitro. Electrospun membranes were more hydrophobic than PCL solvent-casted ones; therefore, their degradation was a much slower process

Differential expression patterns of metastasis suppressor proteins in basal cell carcinoma

Background: Basal cell carcinomas (BCCs) are common malignant skin tumors. Despite having a significant invasion capacity, they metastasize only rarely. Our aim in this study was to detect the expression patterns of the NM23-H1, NDRG1, E-cadherin, RHOGDI2, CD82/KAI1, MKK4, and AKAP12 metastasis suppressor proteins in BCCs. Methods: A total of 96 BCC and 10 normal skin samples were included for the immunohistochemical study. Eleven frozen BCC samples were also studied by quantitative real time polymerase chain reaction (qRT-PCR) to detect the gene expression profile. Results: NM23-H1 was strongly and diffusely expressed in all types of BCC. Significant cytoplasmic expression of NDRG1 and E-cadherin was also detected. However, AKAP12 and CD82/KAI1 expression was significantly decreased. The expressions of the other proteins were somewhere between the two extremes. Similarly, qRT-PCR analysis showed down-regulation of AKAP12 and up-regulation of NM23-H1 and NDRG1 in BCC. Morphologically aggressive BCCs showed significantly higher cytoplasmic NDRG1 expression scores and lower CD82/KAI1 scores than non-aggressive BCCs. Conclusion: The relatively preserved levels of NM23-H1, NDRG1, and E-cadherin proteins may have a positive effect on the non-metastasizing features of these tumors. © 2014 The International Society of Dermatology

Radiofrequency-induced thermotherapy of nasopharyngeal angiofibroma and immunohistochemical analysis of vessel proliferation: a case report

<p>Abstract</p> <p>Introduction</p> <p>Nasopharyngeal angiofibroma presents with symptoms of nasal obstruction and epistaxis. The treatment of choice is embolization followed by surgery.</p> <p>Case presentation</p> <p>A 52-year-old man underwent surgery for nasopharyngeal angiofibroma after adjuvant radiofrequency-induced thermotherapy. To the best of the authors' knowledge, this is the first case of angiofibroma with clinical follow-up after thermocoagulation therapy supported by quantitative, double immunohistochemistry. We found this case of angiofibroma to be of interest owing to the presentation of symptoms leading to biopsy, the pathohistological observations obtained with synchronous Ki67/cluster of differentiation 34 and Ki67/smooth muscle actin immunohistochemistry and high pericyte proliferation.</p> <p>Conclusion</p> <p>Coagulation of angiofibroma vessels followed by acquisition of a thick mantle of pericytes in a patient with a nasopharyngeal growth suggests that radiofrequency-induced thermotherapy could be a useful, palliative therapy for bleeding nasopharyngeal angiofibroma, supporting vessel maturation prior to surgical tumor removal.</p

Obsessive- compulsive disorder in the parkinson disease

Purpose: Obsessive disorder assessment using Leyton Obsessional Inventory was done in patients with idiopathic Parkinson's Disease. Materials and Methods: Fifty patients diagnosed with Parkinson's disease according to United Kingdom Parkinson's Disease Society Brain Bank (UK-PDSBB) criteria and 37 healty individuals were included in the study.All subjects were assesed by the same psychiatrist using the Leyton obsessional inventory. Results: The Leyton obssesional scores were higher in the Parkinson's disease group than in the control group (p<0,001). In addition, correlation was found between the severity of disease and degree of obsession (p:0,771). Conclusion: Parkinson's disease is a neurodejenerative disorder with predominant motor symptoms but with progression , nonmotor symptoms also emerge. The patient's qualty of life may be much affected by these nonmotor symptoms. Diagnosis and treatment of the pyschiatric symptoms in Parkinson's disease may help improve life quality

Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition.

The endothelial to haematopoietic transition (EHT) is the process whereby haemogenic endothelium differentiates into haematopoietic stem and progenitor cells (HSPCs). The intermediary steps of this process are unclear, in particular the identity of endothelial cells that give rise to HSPCs is unknown. Using single-cell transcriptome analysis and antibody screening, we identify CD44 as a marker of EHT enabling us to isolate robustly the different stages of EHT in the aorta-gonad-mesonephros (AGM) region. This allows us to provide a detailed phenotypical and transcriptional profile of CD44-positive arterial endothelial cells from which HSPCs emerge. They are characterized with high expression of genes related to Notch signalling, TGFbeta/BMP antagonists, a downregulation of genes related to glycolysis and the TCA cycle, and a lower rate of cell cycle. Moreover, we demonstrate that by inhibiting the interaction between CD44 and its ligand hyaluronan, we can block EHT, identifying an additional regulator of HSPC development

Skewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the FRMD7 gene

Aims: This study aimed to identify the underlying genetic defect of a large Turkish X linked nystagmus (NYS) family. Methods: Both Xp11 and Xq26 loci were tested by linkage analysis. The 12 exons and intron-exon junctions of the FRMD7 gene were screened by direct sequencing. X chromosome inactivation analysis was performed by enzymatic predigestion of DNA with a methylation-sensitive enzyme, followed by PCR of the polymorphic CAG repeat of the androgen receptor gene. Results: The family contained 162 individuals, among whom 28 had NYS. Linkage analysis confirmed the Xq26 locus. A novel missense c.686C>G mutation, which causes the substitution of a conserved arginine at amino acid position 229 by glycine (p.R229G) in exon 8 of the FRMD7 gene, was observed. This change was not documented in 120 control individuals. The clinical findings in a female who was homozygous for the mutation were not different from those of affected heterozygous females. Skewed X inactivation was remarkable in the affected females of the family. Conclusions: A novel p.R229G mutation in the FRMD7 gene causes the NYS phenotype, and skewed X inactivation influences the manifestation of the disease in X linked NYS females

Activation of the TGFβ pathway impairs endothelial to haematopoietic transition.

The endothelial to haematopoietic transition (EHT) is a key developmental process where a drastic change of endothelial cell morphology leads to the formation of blood stem and progenitor cells during embryogenesis. As TGFβ signalling triggers a similar event during embryonic development called epithelial to mesenchymal transition (EMT), we hypothesised that TGFβ activity could play a similar role in EHT as well. We used the mouse embryonic stem cell differentiation system for in vitro recapitulation of EHT and performed gain and loss of function analyses of the TGFβ pathway. Quantitative proteomics analysis showed that TGFβ treatment during EHT increased the secretion of several proteins linked to the vascular lineage. Live cell imaging showed that TGFβ blocked the formation of round blood cells. Using gene expression profiling we demonstrated that the TGFβ signalling activation decreased haematopoietic genes expression and increased the transcription of endothelial and extracellular matrix genes as well as EMT markers. Finally we found that the expression of the transcription factor Sox17 was up-regulated upon TGFβ signalling activation and showed that its overexpression was enough to block blood cell formation. In conclusion we showed that triggering the TGFβ pathway does not enhance EHT as we hypothesised but instead impairs it

Influence of composition, bonding characteristics and microstructure on the electrochemical and optical stability of AlOxNy thin films

Thin films of AlOxNy were deposited by magnetron sputtering in a wide composition range. Different structures and morphologies were observed, depending on the composition and bonding states, which opened the possibility to tailor the properties of this oxynitride system between those of pure Al and those of nitride and oxide films. In a wide range of stoichiometries, one can report the formation of nanocomposite porous films, where Al nanoparticles are dispersed in an amorphous matrix of AlOxNy. The electrochemical behaviour of the films was studied in isotonic NaCl solution. It was observed that the pitting 2 potential characteristic of aluminium disappears with the incorporation of oxygen and nitrogen in the films, being replaced by a smooth current increase. Electrochemical impedance spectroscopy performed during 35 days showed that the corrosion resistance of the films steadily increases. The unusual optical reflectance profile of some films is maintained after immersion for several months.Fundação para a Ciência e a TecnologiaPrograma Pessoa 2010/2011, Cooperação Portugal/França, Proc.º 441.00, Project“COLOURCLUSTER”