Role of PKC and CaV1.2 in Detrusor Overactivity in a Model of Obesity Associated with Insulin Resistance in Mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A kinetic model for the ultrasound catalyzed hydrolysis of solventless TEOS-water mixtures and the role of the initial additions of ethanol

The acid and ultrasound catalyzed hydrolysis of solventless TEOS-water mixtures are studied, as a function of the initial additions of ethanol to the mixtures, by means of flux calorimetry measurements. A device was specially designed for this purpose. Under acid conditions, our proposed method has been able to resolve hydrolysis from other condensation reactions, by detecting the exothermal hydrolysis reaction heat. The process has been explained by a dissolution and reaction mechanism. Ultrasound forces the dissolution process to start the reaction. The alcohol produced in the reaction helps the dissolution process to further enhance the hydrolysis. Initial amounts of pure ethanol added to the mixtures shorten the start time of the reaction, due to an additional effect of dissolution, and diminish the reaction rate, as a result of the solvent dilution effect. Our dissolution and reaction mechanism modeling describes the main points arising from the experimental data and yields k(H) = 0.24 M(-1) min(-1) for the second-order hydrolysis rate constant at 39 degrees C.

Ghost poles in the nucleon propagator in the linear sigma model approach and its role in pi N low-energy theorems

Complex mass poles, or ghost poles, are present in the Hartree-Fock solution of the Schwinger-Dyson equation for the nucleon propagator in renormalizable models with Yukawa-type meson-nucleon couplings, as shown many years ago by Brown, Puff and Wilets (BPW), These ghosts violate basic theorems of quantum field theory and their origin is related to the ultraviolet behavior of the model interactions, Recently, Krein et.al, proved that the ghosts disappear when vertex corrections are included in a self-consistent way, softening the interaction sufficiently in the ultraviolet region. In previous studies of pi N scattering using ''dressed'' nucleon propagator and bare vertices, did by Nutt and Wilets in the 70's (NW), it was found that if these poles are explicitly included, the value of the isospin-even amplitude A((+)) is satisfied within 20% at threshold. The absence of a theoretical explanation for the ghosts and the lack of chiral symmetry in these previous studies led us to re-investigate the subject using the approach of the linear sigma-model and study the interplay of low-energy theorems for pi N scattering and ghost poles. For bare interaction vertices we find that ghosts are present in this model as well and that the A((+)) value is badly described, As a first approach to remove these complex poles, we dress the vertices with phenomenological form factors and a reasonable agreement with experiment is achieved, In order to fix the two cutoff parameters, we use the A((+)) value for the chiral limit (m(pi) --> 0) and the experimental value of the isoscalar scattering length, Finally, we test our model by calculating the phase shifts for the S waves and we find a good agreement at threshold. (C) 1997 Elsevier B.V. B.V.

A structure based model for liposome disruption and the role of catalytic activity in myotoxic phospholipase A(2)S

Venom phospholipase A(2)s (PLA(2)s) display a wide spectrum of pharmacological activities and, based on the wealth of biochemical and structural data currently available for PLA(2)S, mechanistic models can now be inferred to account for some of these activities. A structural model is presented for the role played by the distribution of surface electrostatic potential in the ability of myotoxic D49/K49 PLA(2)s to disrupt multilamellar vesicles containing negatively charged natural and non-hydrolyzable phospholipids. Structural evidence is provided for the ability of K49 PLA(2)s to bind phospholipid analogues and for the existence of catalytic activity in K49 PLA(2)s. The importance of the existence of catalytic activity of D49 and K49 PLA(2)s in myotoxicity is presented. (C) 2003 Elsevier Ltd. All rights reserved.

Youth and social cohesion in Ibero-America: a model in the making. Summary

Includes bibliography

The role of clouds in improving the regression model for hourly values of diffuse solar radiation

The study introduces a new regression model developed to estimate the hourly values of diffuse solar radiation at the surface. The model is based on the clearness index and diffuse fraction relationship, and includes the effects of cloud (cloudiness and cloud type), traditional meteorological variables (air temperature, relative humidity and atmospheric pressure observed at the surface) and air pollution (concentration of particulate matter observed at the surface). The new model is capable of predicting hourly values of diffuse solar radiation better than the previously developed ones (R-2 = 0.93 and RMSE = 0.085). A simple version with a large applicability is proposed that takes into consideration cloud effects only (cloudiness and cloud height) and shows a R-2 = 0.92. (C) 2011 Elsevier Ltd. All rights reserved.

Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: Role for the adenosine A(2A) receptor

Acute lung injury is an inflammatory condition for which treatment is mainly supportive because effective therapies have not been developed. Cannabidiol, a non-psychotropic cannabinoid component of marijuana (Cannabis sativa), has potent immunosuppressive and anti-inflammatory properties. Therefore, we investigated the possible anti-inflammatory effect of cannabidiol in a murine model of acute lung injury. Analysis of total inflammatory cells and differential in bronchoalveolar lavage fluid was used to characterize leukocyte migration into the lungs; myeloperoxidase activity of lung tissue and albumin concentration in the bronchoalveolar lavage fluid were analyzed by colorimetric assays; cytokine/chemokine production in the bronchoalveolar lavage fluid was also analyzed by Cytometric Bead Arrays and Enzyme-Linked Immunosorbent Assay (ELISA). A single dose of cannabidiol (20 mg/kg) administered prior to the induction of LPS (lipopolysaccharide)-induced acute lung injury decreases leukocyte (specifically neutrophil) migration into the lungs, albumin concentration in the bronchoalveolar lavage fluid, myeloperoxidase activity in the lung tissue, and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) 1, 2, and 4 days after the induction of LPS-induced acute lung injury. Additionally, adenosine A(2A) receptor is involved in the anti-inflammatory effects of cannabidiol on LPS-induced acute lung injury because ZM241385 (4-(2[7-Amino-2-(2-furyl)[1,2,4] triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl) phenol) (a highly selective antagonist of adenosine A(2A) receptor) abrogated all of the anti-inflammatory effects of cannabidiol previously described. Thus, we show that cannabidiol has anti-inflammatory effects in a murine model of acute lung injury and that this effect is most likely associated with an increase in the extracellular adenosine offer and signaling through adenosine A(2A) receptor. (C) 2012 Elsevier B. V. All rights reserved.

The role of the C-terminal region of pulchellin A-chain in the interaction with membrane model systems

Pulchellin is a Ribosome Inactivating Protein containing an A-chain (PAC), whose toxic activity requires crossing the endoplasmic reticulum (ER) membrane. In this paper, we investigate the interaction between recombinant PAC (rPAC) and Langmuir monolayers of dipalmitoyl phosphatidyl glycerol (DPPG), which served as membrane model. Three catalytically active, truncated PACs with increasing deletion of the C-terminal region, possessing 244,239 and 236 residues (rPAC(244), rPAC(239) and rPAC(236)), were studied. rPAC had the strongest interaction with the DPPG monolayer, inducing a large expansion in its surface pressure-area isotherm. The affinity to DPPG decreased with increased deletion of the C-terminal region. When the C-terminal region was deleted completely (rPAC(236)), the interaction was recovered, probably because other hydrophobic regions were exposed to the membrane. Using Polarization Modulated-Infrared Reflection Absorption Spectroscopy (PM-IRRAS) we observed that at a bare air/water interface rPAC comprised mainly alpha-helix structures, the C-terminal region had unordered structures when interacting with DPPG. For rPAC(236) the alpha-helices were preserved even in the presence of DPPG. These results confirm the importance of the C-terminal region for PAC-ER membrane interaction. The partial unfolding only with preserved C-terminal appears a key step for the protein to reach the cytosol and develop its toxic activity. (C) 2011 Elsevier B.V. All rights reserved.

Mathematical Modeling to Investigate Antiarrhythmic Drug Side Effects: Rate-Dependence Role in Ionic Currents and Action Potentials Shape in the O’Hara Model

Sudden cardiac death due to ventricular arrhythmia is one of the leading causes of mortality in the world. In the last decades, it has proven that anti-arrhythmic drugs, which prolong the refractory period by means of prolongation of the cardiac action potential duration (APD), play a good role in preventing of relevant human arrhythmias. However, it has long been observed that the “class III antiarrhythmic effect” diminish at faster heart rates and that this phenomenon represent a big weakness, since it is the precise situation when arrhythmias are most prone to occur. It is well known that mathematical modeling is a useful tool for investigating cardiac cell behavior. In the last 60 years, a multitude of cardiac models has been created; from the pioneering work of Hodgkin and Huxley (1952), who first described the ionic currents of the squid giant axon quantitatively, mathematical modeling has made great strides. The O’Hara model, that I employed in this research work, is one of the modern computational models of ventricular myocyte, a new generation began in 1991 with ventricular cell model by Noble et al. Successful of these models is that you can generate novel predictions, suggest experiments and provide a quantitative understanding of underlying mechanism. Obviously, the drawback is that they remain simple models, they don’t represent the real system. The overall goal of this research is to give an additional tool, through mathematical modeling, to understand the behavior of the main ionic currents involved during the action potential (AP), especially underlining the differences between slower and faster heart rates. In particular to evaluate the rate-dependence role on the action potential duration, to implement a new method for interpreting ionic currents behavior after a perturbation effect and to verify the validity of the work proposed by Antonio Zaza using an injected current as a perturbing effect.

The role of EBI-3 in a murine model of lung metastases of melanoma

In dieser Arbeit wurde die Rolle des Epstein-Barr Virus induzierten Gens 3 in einem Mausmodel des durch B16-F10 Zellen hervorgerufenen metastasierenden Melanoms untersucht. Das von aktivierten antigenpräsentierenden Zellen exprimierte EBI-3 gehört zur Familie der löslichen Typ 1 Zytokinrezeptoren, weist eine hohe Homologie zur p40 Untereinheit des IL-12 auf und bildet zusammen mit p28 das IL-27. Die intravenöse Injektion der B16-F10 Zelllinie führte zu einer signifikanten Erniedrigung der Tumormetastasen in den EBI-3 defizienten Lungen sowie zu einer höheren Lebenserwartung dieser Mäuse im Vergleich zu den B6 Wildtypen. Darüber hinaus habe ich in den EBI-3 defizienten Mäusen eine verminderte VCAM-1 Expression auf den Endothelzellen der Lunge gefunden während Änderungen in der VEGF Expression nicht detektiert wurden. Der immunologische Hintergrund, der diesen therapeutischen Effekt hervorrief, konnte durch die T-Zellaktivierung durch die kürzlich neu beschriebene DC Population, welche Interferon-produzierende Killer Dendritische Zellen genannt werden (IK-DC), die zusätzlich von aktivierten und maturierten klassischen DCs unterstützt wurden, erklärt werden. IK-DCs von EBI-3 defizienten Mäusen produzierten höhere Mengen an IFN-g während die klassischen DCs MHC und co-stimulatorische Moleküle exprimierten, welche die Sekretion von IL-12 initiierten. Das Zusammenspiel der genannten Faktoren induzierte eine verstärkte CD4 und CD8 T-Zellantwort in den Lungen dieser Mäuse. Dies wiederum resultierte im TNF- und TRAIL abhängigen programmierten Zelltod der B16-F10 Melanomzellen in den Lungen der EBI-3 defizienten Mäuse, wohingegen sowohl weitere anti-apoptotische Mechanismen als auch T regulatorische Zellen keinen Einfluss auf die in den EBI-3 defizienten Mäusen beobachtete Tumorabwehr zu spielen scheint. Schlussendlich konnten EBI-3 defiziente CD8+ T-Zellen, welche zuvor mit Tumorantigen geprimed wurden, adoptiv in B6 Wildtypmäuse transferiert werden, was zeigte, dass diese Zellen in der Lage sind, die Tumormasse in den Empfängermäusen signifikant zu verringern. Zusammengefasst, demonstrieren diese Daten, dass das Blockieren von EBI-3 im metastasierenden Melanom ein vielversprechender Angriffspunkt in der Tumortherapie darstellt.

The role of proactive coping strategies and perceived health status for Social well-being and life-project in old age.

The latter part of the 20th century was a period characterized by a fundamental demographic transition of western society. This substantial and structural demographic change proposes several challenges to contemporary society and fosters the emergence of new issues and challenges. Among these, none is more crucial than the comprehension of the mechanisms and the processes that lead people to positive aging. Rowe and Kahn’s model of successful aging highlights the interplay between social engagement with life, health, and functioning for a positive aging experience. Other systemic models of successful aging (Kahana et al., 1996; 2003; Stevernik et al., 2006) emphasize the role of internal and external resources for attaining positive aging. Among these, the proactive coping strategies are indicated as important active strategies for avoiding the depletion of resources, counterbalancing the declines and maintaining social and civic involvement. The study has analyzed the role of proactive coping strategies for two facets of positive aging, the experience of a high social well-being and the presence of personal projects in fundamental life domains. As expected, the proactive coping strategies, referred to as the active management of the environment, the accumulation of resources and the actualization of human potentials are confirmed as positive predictors of high level of social well-being and of many personal projects focused on family, culture, leisure time, civic and social participation. Perceived health status give a significant contribution only to the possession of many personal projects. Gender and level of school education give also a significant contribution to these two dimensions of positive aging, highlighting how positive aging is rooted not only in the possession of personal resources, but also in historical models of education and in positive longitudinal chains related to early development.

The relationship between eating behavior and psychological distress among overweight and obese people: is there a role for mindfulness?

This research based on 3 indipendent studies, sought to explore the nature of the relationship between overweight/obesity, eating behaviors and psychological distress; the construct of Mindful eating trough the validation of the Italian adaptation of the Mindful Eating Questionnaire (MEQ); the role of mindfulnessand mindful eating as respectively potential mediator and moderator between overeating behavior (binge eating and emotional overeating) and negative outcomes (psychological distress, body dissatisfaction). All the samples were divided in normal weight, overweight and obese according to BMI categories. STUDY1: In a sample of 691 subjects (69.6% female, mean aged 39.26 years) was found that BMI was not associated with psychological distress, whereas binge eating increases the psychopathological level. BMI and male gender represent negative predictors of psychological distress, but certain types of overeating (i.e., NES/grazing, overeating during or out of meals, and guilt/restraint) result as positive predictors.. STUDY 2 : A sample of 1067 subjects (61.4% female, mean aged 34 years) was analized. The Italian MEQ resulted in a 26-item 4-factor model measuring Disinhibition, Awareness, Distraction, and Emotional response. Internal consistency and test-retest reliability were acceptable MEQ correlated positively with mindfulness (FMI) and it was associated with sociodemographic variables, BMI, meditation. type of exercise and diet. STUDY 3, based on a sample of 502 subjects (68.8% female, mean aged 39.42 years) showed that MEQ and FMI negatively correlated with BES, EOQ, SCL-90-R, and BIAQ. Obese people showed lower level of mindful eating and higher levels of binge eating, emotional overeating, and body dissatisfaction, compared to the other groups Mindfulness resulted to partially mediates the relationship between a) binge eating and psychological distress, b) emotional overeating and psychological distress, c) binge eating and mental well-being, d) emotional overeating and menal well-being. Mindful eating was a moderator only in the relationship between emotional overeating and body dissatisfaction.

Posttraumatic growth in cancer patients and partners--effects of role, gender and the dyad on couples' posttraumatic growth experience

Little is known about factors influencing positive effects in couples facing a cancer diagnosis.