Functional antagonism of ß-arrestin isoforms balance IGF-1R expression and signalling with distinct cancer-related biological outcomes.

With very similar 3D structures, the widely expressed ß-arrestin isoforms 1 and 2 play at times identical, distinct or even opposing roles in regulating various aspects of G protein-coupled receptors (GPCR) expression and signalling. Recent evidence recognizes the ß-arrestin system as a key regulator of not only GPCRs, but also receptor tyrosine kinases, including the highly cancer relevant insulin-like growth factor type 1 receptor (IGF-1R). Binding of ß-arrestin1 to IGF-1R leads to ligand-dependent degradation of the receptor and generates additional MAPK/ERK signalling, protecting cancer cells against anti-IGF-1R therapy. Because the interplay between ß-arrestin isoforms governs the biological effects for most GPCRs, as yet unexplored for the IGF-1R, we sought to investigate specifically the regulatory roles of the ß-arrestin2 isoform on expression and function of the IGF-1R. Results from controlled expression of either ß-arrestin isoform demonstrate that ß-arrestin2 acts in an opposite manner to ß-arrestin1 by promoting degradation of an unstimulated IGF-1R, but protecting the receptor against agonist-induced degradation. Although both isoforms co-immunoprecipitate with IGF-1R, the ligand-occupied receptor has greater affinity for ß-arrestin1; this association lasts longer, sustains MAPK/ERK signalling and mitigates p53 activation. Conversely, ß-arrestin2 has greater affinity for the ligand-unoccupied receptor; this interaction is transient, triggers receptor ubiquitination and degradation without signalling activation, and leads to a lack of responsiveness to IGF-1, cell cycle arrest and decreased viability of cancer cells. This study reveals contrasting abilities of IGF-1R to interact with each ß-arrestin isoform, depending on the presence of the ligand and demonstrates the antagonism between the two ß-arrestin isoforms in controlling IGF-1R expression and function, which could be developed into a practical anti-IGF-1R strategy for cancer therapy.

Erectile dysfunction post-radical prostatectomy - a challenge for both patient and physician.

Post-radical prostatectomy erectile dysfunction (post RP ED) is a major postoperative complication with a great impact on the quality of life of the patients. Until present, no proper algorithm or guideline based on the clinical trials has been established for the management of post RP ED. According to literature, it is better to initiate a penile rehabilitation program as soon as possible after surgery than doing nothing, in order to prevent and limit the postoperative local hypoxygenation and fibrosis. The results of numerous clinical trials regarding the effectiveness of the phosphodiesterase 5 inhibitors therapy on post RP ED have made them the gold standard treatment. Encouraging results have been achieved in studies with vacuum erectile devices, intraurethral suppositories with alprostadil and intracavernosal injections, but due to their side effects, especially in the cases of intracavernosal injections and intraurethral suppositories, their clinical use was limited therefore making them a second line option for the post RP ED treatment. What should not be forgotten is that penile implant prosthesis has proven very effective, numerous studies confirming high rates of satisfaction for both patients and partners.

Reactor for in situ measurements of spatially resolved kinetic data in heterogeneous catalysis.

The present work describes a reactor that allows in situ measurements of spatially resolved kinetic data in heterogeneous catalysis. The reactor design allows measurements up to temperatures of 1300 degrees C and 45 bar pressure, i.e., conditions of industrial relevance. The reactor involves reactants flowing through a solid catalyst bed containing a sampling capillary with a side sampling orifice through which a small fraction of the reacting fluid (gas or liquid) is transferred into an analytical device (e.g., mass spectrometer, gas chromatograph, high pressure liquid chromatograph) for quantitative analysis. The sampling capillary can be moved with microm resolution in or against flow direction to measure species profiles through the catalyst bed. Rotation of the sampling capillary allows averaging over several scan lines. The position of the sampling orifice is such that the capillary channel through the catalyst bed remains always occupied by the capillary preventing flow disturbance and fluid bypassing. The second function of the sampling capillary is to provide a well which can accommodate temperature probes such as a thermocouple or a pyrometer fiber. If a thermocouple is inserted in the sampling capillary and aligned with the sampling orifice fluid temperature profiles can be measured. A pyrometer fiber can be used to measure the temperature profile of the solid catalyst bed. Spatial profile measurements are demonstrated for methane oxidation on Pt and methane oxidative coupling on Li/MgO, both catalysts supported on reticulated alpha-Al(2)O(3) foam supports.

Fatty acid-spermine conjugates as DNA carriers for nonviral in vivo gene delivery.

The lack of efficient in vivo gene delivery is a well-known shortcoming of nonviral delivery vectors, in particular of chemical vectors. We developed a series of novel nonviral carriers for plasmid-based in vivo gene delivery. This new transport device is based on the assembly of DNA plasmids with synthetic derivatives of naturally occurring molecules-fatty acid-spermine conjugates (or lipospermines). We tested the ability of these fatty acid conjugates to interact with plasmid DNA (pDNA) and found that they formed DNA nanocomplexes, which are protected from DNase I degradation. This protection was shown to directly correlate with the length of the aliphatic component. However, this increase in the length of the hydrocarbon chain resulted in increased toxicity. The cationic lipids used for transfection typically have a C(16) and C(18) hydrocarbon chain. Interestingly, toxicity studies, together with further characterization studies, suggested that the two most suitable candidates for in vivo delivery are those with the shortest hydrocarbon chain, butanoyl- and decanoylspermine. Morphological characterization of DNA nanocomplexes resulting from these lipospermines showed the formation of a homogenous population, with the diameter ranging approximately from 40 to 200 nm. Butanoylspermine was found to be the most promising carrier from this series, resulting in a significantly increased gene expression, in relation to naked plasmid, in both tissues herein targeted (dermis and M. tibialis anterior). Thus, we established a correlation between the in vitro properties of the ensuing DNA nanocarriers and their efficient in vivo gene expression.

Multivariate comparison of elemental concentrations in human teeth.

R-mode factor analysis was applied to characterize the chemical composition of human teeth investigated by particle induced X-ray emission (PIXE), Rutherford backscattering spectrometry (RBS) and X-ray fluorescence (XRF) techniques. The approach developed in this study enabled the separation between essential mineral teeth components and the pollutants deposited in teeth tissues during the human life. The three independent sources of metals incorporated in human teeth were found. The first source, representing about 43% of the variance of the concentration data, was characterized by pollutant elements of power industry emissions. The second factor was loaded with toxic elements of general urban pollution. The third factor represented the tooth source as it contained mainly large fractions of the mineral components of the tooth tissue as Ca and K.

Diagnosis of spatiotemporal chaos in wave envelopes of a nematic electroconvection pattern.

In this paper we report and analyze complex spatiotemporal dynamics recorded in electroconvection in the nematic liquid crystal I52, driven by an ac voltage slightly above the onset value. The instability mechanism creating the pattern is an oscillatory (Hopf) instability, giving rise to two pairs of counterpropagating rolls traveling in oblique directions relative to the unperturbed director axis. If a system of nonlinear partial differential equations shows the same set of unstable modes, the pattern above the onset is represented in a weakly nonlinear analysis as a superposition of the traveling rolls in terms of wave envelopes varying slowly in space and time. Motivated by this procedure, we extract slowly varying envelopes from the space-time data of the pattern, using a four-wave demodulation based on Fourier analysis. In order to characterize the spatiotemporal dynamics, we apply a variety of diagnostic methods to the envelopes, including the calculation of mean intensities and correlation lengths, global and local Karhunen-Loève decompositions in Fourier space and physical space, the location of holes, the identification of coherent vertical structures, and estimates of Lyapunov exponents. The results of this analysis provide strong evidence that our pattern exhibits extensive spatiotemporal chaos. One of its main characteristics is the presence of coherent structures of low and high intensities extended in the vertical (parallel to the director) direction.

[Androgen-secreting tumor in an adrenal tumor discovered by accident after amenorrhea caused by a meningeal hemorrhage]. / Tumeur androgènosecrétante de la surrénale découverte par hasard après une aménorrhée installée brutalement suite a une hémorragie méningée.

Androgen-secreting tumors are uncommon among adrenal secreting tumors. The case reported here concerns an adrenal tumor secreting androgens, unexpectedly found after a sudden amenorrhea caused by a meningeal haemorrhage, with positive outcome after adrenalectomy. The indication of increased secretion of oestrogens and androgens, should suggest the presence of adrenal androgen-secreting tumor.

[Recto-vesical and recto-vesico-vaginal fistulae caused by radiotherapy for carcinoma of the uterine cervix. Surgical treatment]. / Fistulele recto-vezicale si recto-vezico-vaginale postradice dupa neoplasm al colului uterin. Tratament chirurgical.

The authors present a study based on 4 cases of fistulous communication between the terminal digestive tube and the genitourinary tract, which appeared after surgery and radiation therapy for carcinoma of the uterine cervix. The diagnosis criteria (symptoms, clinical and imagistic findings), the objectives of the surgical treatment (external digestive derivation, treatment of the fistula and reconstruction of the digestive tube), the steps of the operation and the early and late postoperative evolution are pointed out. The conclusions are shown at the end.

[Gastrojejunocolic fistula after transmesocolic gastrojejunostomy for stenotic duodenal ulcer]. / Fistula gastro-jejuno-colica dupa gastro-jejunostomie transmezocolica pentru ulcer bulbar stenozant.

The authors are presenting the case of a 53 year-old patient, suffering from type II diabetes mellitus and ankylosing spondylitis, admitted in our clinic in July 1997 for gastrojejunocolic fistula, 5 years after a transmesocolic gastrojejunostomy for obstructive chronic duodenal ulcer. The severe metabolic disorders and the radiologic aspects which led to the diagnosis, as well as the morphopathologic lesions found and the ways to approach the fistula, the stenotic duodenal ulcer and the reconstruction of the digestive continuity in a single surgical procedure are further discussed. The conclusions are shown at the end.