Serotonin and Noradrenaline Reuptake Inhibitors Improve Micturition Control in Mice

Poor micturition control may cause profound distress, because proper voiding is mandatory for an active social life. Micturition results from the subtle interplay of central and peripheral components. It involves the coordination of autonomic and neuromuscular activity at the brainstem level, under the executive control of the prefrontal cortex. We tested the hypothe- sis that administration of molecules acting as reuptake inhibitors of serotonin, noradrenaline or both may exert a strong effect on the control of urine release, in a mouse model of overac- tive bladder. Mice were injected with cyclophosphamide (40 mg/kg), to increase micturition acts. Mice were then given one of four molecules: the serotonin reuptake inhibitor imipra- mine, its metabolite desipramine that acts on noradrenaline reuptake, the serotonin and nor- adrenaline reuptake inhibitor duloxetine or its active metabolite 4-hydroxy-duloxetine. Cyclophosphamide increased urine release without inducing overt toxicity or inflammation, except for increase in urothelium thickness. All the antidepressants were able to decrease the cyclophosphamide effects, as apparent from longer latency to the first micturition act, decreased number of urine spots and volume of released urine. These results suggest that serotonin and noradrenaline reuptake inhibitors exert a strong and effective modulatory ef- fect on the control of urine release and prompt to additional studies on their central effects on brain areas involved in the social and behavioral control of micturition

Fabrication of 3D cell-laden hydrogel microstructures through photo-mold patterning

Native tissues are characterized by spatially organized three-dimensional (3D) microscaled units which functionally define cells–cells and cells–extracellular matrix interactions. The ability to engineer biomimetic constructs mimicking these 3D microarchitectures is subject to the control over cell distribution and organization. In the present study we introduce a novel protocol to generate 3D cell laden hydrogel micropatterns with defined size and shape. The method, named photo-mold patterning (PMP), combines hydrogel micromolding within polydimethylsiloxane (PDMS) stamps and photopolymerization through a recently introduced biocompatible ultraviolet (UVA) activated photoinitiator (VA-086). Exploiting PDMS micromolds as geometrical constraints for two methacrylated prepolymers (polyethylene glycol diacrylate and gelatin methacrylate), micrometrically resolved structures were obtained within a 3 min exposure to a low cost and commercially available UVA LED. The PMP was validated both on a continuous cell line (human umbilical vein endothelial cells expressing green fluorescent protein, HUVEC GFP) and on primary human bone marrow stromal cells (BMSCs). HUVEC GFP and BMSCs were exposed to 1.5% w/v VA-086 and UVA light (1 W, 385 nm, distance from sample = 5 cm). Photocrosslinking conditions applied during the PMP did not negatively affect cells viability or specific metabolic activity. Quantitative analyses demonstrated the potentiality of PMP to uniformly embed viable cells within 3D microgels, creating biocompatible and favorable environments for cell proliferation and spreading during a seven days' culture. PMP can thus be considered as a promising and cost effective tool for designing spatially accurate in vitro models and, in perspective, functional constructs

Lab-on-Chip for testing myelotoxic effect of drugs and chemicals

In the last 20 years, one of the main goals in the drug discovery field has been the development of reliable in vitro models. In particular, in 2006 the European Centre for the Validation of Alternative Methods has approved the colony-forming unit granulocytes–macrophages test, which is the first and currently unique test applied to evaluate the myelotoxicity of xenobiotics in vitro. The present work aimed at miniaturizing this in vitro assay by developing and validating a Lab-on-Chip platform consisting of a high number of bioreactor chambers with screening capabilities in a high-throughput regime

Estimating the probability of piping-induced breaching of flood embankments

Flood Defenc

Microfabricated Physiological Models for In Vitro Drug Screening Applications

Microfluidics and microfabrication have recently been established as promising tools for developing a new generation of in vitro cell culture microdevices. The reduced amounts of reagents employed within cell culture microdevices make them particularly appealing to drug screening processes. In addition, latest advancements in recreating physiologically relevant cell culture conditions within microfabricated devices encourage the idea of using such advanced biological models in improving the screening of drug candidates prior to in vivo testing. In this review, we discuss microfluidics-based models employed for chemical/drug screening and the strategies to mimic various physiological conditions: fine control of 3D extra-cellular matrix environment, physical and chemical cues provided to cells and organization of co-cultures. We also envision future directions for achieving multi-organ microfluidic devices

A priori estimates and large population limits for some nonsymmetric Nash systems with semimonotonicity

We address the problem of regularity of solutions $u^i(t, x^1, \ldots, x^N)$ to a family of semilinear parabolic systems of $N$ equations, which describe closed-loop equilibria of some $N$-player differential games with quadratic Lagrangian in the velocity, running costs $f^i(x)$ and final costs $g^i(x)$. By global (semi)monotonicity assumptions on the data $f,g$, and assuming that derivatives of $f^i, g^i$ in directions $x_j$ are of order $1/N$ for $j \neq i$, we prove that derivatives of $u^i$ enjoy the same property. The estimates are uniform in the number of players $N$. Such behaviour of the derivatives of $f^i, g^i$ arise in the theory of Mean Field Games, though here we do not make any symmetry assumption on the data. Then, by the estimates obtained we address the convergence problem $N \to \infty$ in a ``heterogeneous'' Mean Field framework, where players all observe the empirical measure of the whole population, but may react differently from one another.Comment: 65 page

Consolidación y fragmentación de la investigación de la comunicación en México, 1987-1997

Este artículo expone de una manera breve y general las conclusiones del trabajo de investigación sobre los procesos de estructuración del campo de la investigación académica de la comunicación en México de 1987 a 1997. El acercamiento empírico exploratorio de este trabajo supone el acopio y la sistematización de datos sobre la producción mexicana de conocimiento sobre la comunicación y sus condiciones contextuales; sobre sus productores, tanto individuales como institucionales; y sobre sus productos objetivos, especialmente las publicaciones académicas. A partir de los resultados del análisis de toda esta información, se construyó un modelo heurístico de las determinaciones socioculturales de la estructuración del campo desde la década de 1960 hasta la de 1990, que permite formular la "doble disyuntiva" que se enfrentó en los años noventa para alcanzar la legitimación académica y social