Trace analysis of benzophenone-type UV filters in water and their effects on human estrogen and androgen receptors.

To carry out risk assessments of benzophenone-type UV filters (BPs), fast and accurate analytical methods are crucial to determine and monitor levels in the environment. This study presents an LC-MS/MS method that requires minimal sample preparation and yet can identify 10 different BPs in environmental samples such as surface or wastewater resulting in a LOQ range from 2 to 1060 ng/L. The method suitability was tested through environmental monitoring, which showed that, BP-4 is the most abundant derivative found in the surface waters of Germany, India, South Africa and Vietnam.

Association of systemic antibody response against polyethylene terephthalate with inflammatory serum cytokine profile following implantation of differently coated vascular prostheses in a rat animal model.

Experimental studies demonstrated antibodies against matrix and coating of polyester-based vascular prostheses. Thus, this study examined associations of these antibodies with serum cytokines (IL-2, IL-4, and IL-10) and local inflammatory reactions. Rats (n = 8/group) intramuscularly received prosthesis segments [PET-C, PET-G, and PET-A groups: polyethylene terephthalate (PET)-based prostheses coated with bovine collagen and gelatin or human serum albumin, respectively; uncoated polytetrafluoroethylene-based (PTFE) prosthesis], with sham-operated controls.

[Robot-assisted surgery - Progress or expensive toy? : Matched-pair comparative analysis of robot-assisted cholecystectomy vs. laparoscopic cholecystectomy].

Aim And Methods: By means of a matched-pair analysis comparing data obtained from laparoscopic cholecystectomy (LC) and robot-assisted laparoscopic cholecystectomy (RAC), the value of both methods as well as the advantages and disadvantages of both approaches were elucidated. The consideration was carried out by evaluation of postoperative surgical results, a cost analysis and a subjective survey of the patients using a questionnaire. Thus, from the 35 consecutive RAC, 35 (parallel) retrospectively matched pairs were established.

A proteomic study using zebra mussels (D. polymorpha) exposed to benzo(α)pyrene: the role of gender and exposure concentrations.

It has recently been established that the use of proteomics can be a useful tool in the field of ecotoxicology. Despite the fact that the mussel Dreissena polymorpha is a valuable bioindicator for freshwater ecosystems, the application of a proteomic approach with this organism has not been deeply investigated. To this end, several zebra mussel specimens were subjected to a 7-day exposure of two different concentrations (0.

Brivanib, a novel dual VEGF-R2/bFGF-R inhibitor.

The process of neo-vascularisation from pre-existing blood vessels (angiogenesis) plays a critical role in both tumour growth and dissemination in multiple cancer types. Tumour angiogenesis is an attractive target for cancer treatment, and the VEGF/VEGF-R and FGF/FGF-R systems have been identified as key factors for neo-angiogenesis. Several active compounds have been developed so far and some of them are already widely used in clinical protocols.

[SRC kinases in tumor therapy].

The proto-oncogene src encodes a nonreceptor tyrosine kinase whose expression and activity are correlated with advanced malignancy and poor prognosis in a variety of human cancers. Nine additional enzymes with homology to src have been identified and collectively are referred to as src family kinases (SFKs). SFKs represent the largest family of nonreceptor tyrosine kinases and interact directly with receptor tyrosine kinases, G-protein-coupled receptors, steroid receptors, signal transducers and activators of transcription, and molecules involved in cell adhesion and migration.

Time course of fibronectin in the peri-implant tissue and neointima formation after functional implantation of polyester-based vascular prostheses with different porosity in pigs.

Intima hyperplasia, resulting from extracellular matrix (ECM) secretion, can lead to vascular prosthesis occlusion and is a major problem in vascular surgery. Fibronectin might contribute to ongoing ECM secretion. However, the exact role of fibronectin and its influence on neointima formation remains unclear.

Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations.

Noonan syndrome is a genetic condition characterized by congenital heart defects, short stature, and characteristic facial features. Familial or de novo mutations in PTPN11, RAF1, SOS1, KRAS, and NRAS are responsible for 60-75% of the cases, thus, additional genes are expected to be involved in the pathogenesis. In addition, the genotype-phenotype correlation has been hindered by the highly variable expressivity of the disease.

N-terminal interaction domain implicates PAK4 in translational regulation and reveals novel cellular localization signals.

The serine/threonine kinase PAK4 is a Rho GTPases effector protein implicated in many critical biological processes, including regulation of cell morphology and motility, embryonic development, cell survival, response to infection, and oncogenic transformation. Consistently with its pro-oncogenic features, PAK4 was found to be overexpressed in many cancer cell lines and tissues, and to be necessary to promote activation of survival pathways. PAK4, like other Paks, is now considered a promising target for specific therapy.

Proteome profile in Myotonic Dystrophy type 2 myotubes reveals dysfunction in protein processing and mitochondrial pathways.

Myotonic Dystrophy type 2 (DM2) is caused by a DNA microsatellite expansion within the Zinc Finger Protein 9 gene leading to an abnormal splicing pattern largely responsible for the pathological condition. To better define the functional changes occurring in human DM2 myotubes we performed a quantitative proteome comparison between myotubes of DM2 and control patients using two-dimensional gel electrophoresis followed by mass spectrometry. Our results indicate that the proteins, altered in DM2 cultures, belong to two major functional categories: i) mitochondrial components, with a reduction of EFTu, HSP60, GRP75 and Dienoyl-CoA-Isomerase, an enzyme involved in fatty acids degradation; ii) the ubiquitin proteasome system with increase of the 26S proteasome regulatory subunit 13 and a reduction of Proteasome subunit Alfa6 and of Rad23B homolog.

Mutant Huntingtin induces activation of the Bcl-2/adenovirus E1B 19-kDa interacting protein (BNip3).

Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive neuronal death in the basal ganglia and cortex. Although increasing evidence supports a pivotal role of mitochondrial dysfunction in the death of patients' neurons, the molecular bases for mitochondrial impairment have not been elucidated. We provide the first evidence of an abnormal activation of the Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNip3) in cells expressing mutant Huntingtin.

Identification of novel RasGRF1 interacting partners by large-scale proteomic analysis.

The brain-specific Ras guanine nucleotide exchange factor RasGRF1 is a protein harbouring a complex array of structural motifs. It contains a pleckstrin homology (PH1) domain, a coiled coil region (CC) and an ilimaquinone (IQ) one in addition to the catalytic Ras and Rac exchange factor domains. In this study, we used the recombinant N-terminal PH1, CC and IQ region (PHCCIQ) fused to the chitin-binding domain to isolate interacting proteins from mouse brain extracts.

Transcriptomic and proteomic analyses of mouse cerebellum reveals alterations in RasGRF1 expression following in vivo chronic treatment with delta 9-tetrahydrocannabinol.

We have applied transcriptomic and proteomic techniques to identify changes in the RNA and the protein levels in the mouse cerebellum after chronic treatment with Delta(9)-tetrahydrocannabinol (THC). Among approximately 14,000 transcripts in a mouse cDNA microarray library, we found 11 genes with altered expression. RasGRF1, a neuron-specific Ras guanine nucleotide exchange factor, showed a reduction both at the RNA and protein levels with a specific decrease of the protein pool associated to cell membranes.

Local tissue reaction and differentiation of the prosthesis-specific antibody response following functional implantation of vascular grafts in pigs.

The study was aimed at investigating the local tissue reactions through a histological examination of beta-1-integrin expression and neointima formation, and humoral immune responses by detection of prosthesis-specific antibodies, after functional implantation of vascular prostheses. In three groups of pigs, the infrarenal aorta was replaced with segments of collagen-impregnated Dacron-prostheses: M-prosthesis--medium primary porosity, double velour layer, crimping; C-prosthesis--low primary porosity, no velour, crimping; T-prosthesis--high primary porosity, no velour, no crimping. For each prosthesis type, one series with four animals was used for examining the tissue reactions, and a second series with eight animals was used to study the antibody response, both until 116 days postoperative.

Immune response against polyester implants is influenced by the coating substances.

The aim of this study was to evaluate the influence of the coating of polymer implants upon the individual humoral immune response to the polymer matrix. Intramuscular implantation and explantation of samples from three different polyester vascular prostheses coated with collagen, gelatin, or human serum albumin was performed in LEW.1A rats and subsequently compared to sham operated control animals.

SCLIP, a microtubule-destabilizing factor, interacts with RasGRF1 and inhibits its ability to promote Rac activation and neurite outgrowth.

RasGRF1 is a neuron-specific guanine nucleotide exchange factor for the small GTPases Ras and Rac. It is implicated in the regulation of memory formation and in the development of tolerance to drug abuse, although the mechanisms have been elucidated only in part. Here we report the isolation, by the yeast two-hybrid screen, of the microtubule-destabilizing factor SCLIP (SCG10-like protein) as a novel RasGRF1-interacting protein.

Digital image analysis for morphometric evaluation of tissue response after implanting alloplastic vascular prostheses.

The aim of this study was to examine the suitability of digital image analysis, using the KS400 software system, for the morphometric evaluation of the tissue response after prosthesis implantation in an animal model. Twenty-four female pigs aged 10 weeks were implanted with infrarenal Dacron(R) prostheses for 14, 21, 28, and 116 days. Following the explantation and investigation of the neointima region, the expression of beta-1-integrin, the proliferation rate by means of Ki-67 positive cells, and the intima thickness were evaluated as exemplary parameters of the tissue response after implantation.

Changes in the expression of G protein-coupled receptor kinases and beta-arrestins in mouse brain during cannabinoid tolerance: a role for RAS-ERK cascade.

The focus of our study was to determine the role of G protein-coupled receptor kinases (GRKs) and beta-arrestins in agonist-induced CB1 receptor modulation during cannabinoid tolerance and their dependence from the extracellular signal-regulated kinase (ERK) cascade. In wild-type mice, chronic Delta9-tetrahydrocannabinol (THC) exposure significantly activated specific GRK and beta- arrestin subunits in all the considered brain areas (striatum, cerebellum, hippocampus, and prefrontal cortex), suggesting their involvement in the adaptive processes underlying CB1 receptor downregulation and desensitization. These events were ERK-dependent in the striatum and cerebellum, because they were prevented in the genetic (Ras-GRF1 knockout mice) and pharmacological (SL327-pretreated mice) models of ERK activation inhibition, whereas in the hippocampus and prefrontal cortex, they appeared to be mostly ERK-independent.

ERK-dependent modulation of cerebellar synaptic plasticity after chronic Delta9-tetrahydrocannabinol exposure.

Chronic exposure to Delta9-tetrahydrocannabinol (THC) induces tolerance to cannabinoid-induced locomotor effects, which are mediated by cannabinoid receptors (CB1Rs) located in motor control regions, including the cerebellum. There is substantial evidence of cerebellar CB1R molecular adaptation and modifications in receptor signaling after prolonged cannabinoid exposure. However, very little is known about the effects of chronic cannabinoid administration on cerebellar synaptic plasticity, which may contribute to the development of cannabinoid behavioral tolerance.

The guanine nucleotide exchange factor RasGRF1 directly binds microtubules via DHPH2-mediated interaction.

RasGRF is a family of guanine nucleotide exchange factors with dual specificity for both Ras and Rac GTPases. In this study, using mouse brain extracts, we show that both RasGRF1 and RasGRF2 interact with microtubules in an in vitro microtubule assembly system and this binding is very tight. To characterize this association, recombinant purified proteins containing different regions of RasGRF1 were tested for their ability to bind microtubules preassembled from pure tubulin.

Vascular graft infections: in vitro and in vivo investigations of a new vascular graft with long-term protection.

We investigated a polyester vascular prosthesis (PET) coated with elemental silver (SC). Measurement of silver release over a period of 52 weeks by means of inductively coupled plasma atomic emission spectrometry of PET with (PET-G) and without (PET-N) gelatine impregnation revealed a silver release on the first day of 1.2 +/- 0.

Ras/ERK signalling in cannabinoid tolerance: from behaviour to cellular aspects.

We investigated the role of the Ras/extracellular-regulated kinase (ERK) pathway in the development of tolerance to Delta(9)-tetrahydrocannabinol (THC)-induced reduction in spontaneous locomotor activity by a genetic (Ras-specific guanine nucleotide exchange factor (Ras-GRF1) knock-out mice) and pharmacological approach. Pre-treatment of wild-type mice with SL327 (50 mg/kg i.p.

Healing characteristics of a new silver-coated, gelatine impregnated vascular prosthesis in the porcine model.

Objectives: To investigate the intraluminal and extraluminal healing behaviour of a new metallic silver coated, gelatine impregnated vascular graft.

Design: Comparative animal experimental investigation with randomisation of the animals to control and experimental groups.

Material And Methods: 24 pigs were assigned to two control and two experimental groups.

Antibody response to collagen after functional implantation of different polyester vascular prostheses in pigs.

Besides inflammation, specific immune responses are seen also after implantation of biomaterials. The aim was to investigate the humoral response to bovine collagen type I following implantation of various polyester (Dacron) prostheses into pigs. In 24 randomized pigs, the infrarenal aorta was replaced with a segment of collagen-impregnated, woven polyester prosthesis of low, medium, or high porosity.

Characteristics of titanium-coated polyester prostheses in the animal model.

Commercially available polyester vascular prostheses (n = 6) in the control group (CG) and titanium-coated vascular prostheses (TP; n = 7) were interposed within the infrarenal aorta of pigs. The respective healing characteristics and patency rates were compared after 3 months. For evaluation purposes, macroscopic, histological, and immunohistochemical criteria were applied.