Natural Products from Antarctic Colonial Ascidians of the Genera Aplidium and Synoicum: Variability and Defensive Role

Ascidians have developed multiple defensive strategies mostly related to physical, nutritional or chemical properties of the tunic. One of such is chemical defense based on secondary metabolites. We analyzed a series of colonial Antarctic ascidians from deep-water collections belonging to the genera Aplidium and Synoicum to evaluate the incidence of organic deterrents and their variability. The ether fractions from 15 samples including specimens of the species A. falklandicum, A. fuegiense, A. meridianum, A. millari and S. adareanum were subjected to feeding assays towards two relevant sympatric predators: the starfish Odontaster validus, and the amphipod Cheirimedon femoratus. All samples revealed repellency. Nonetheless, some colonies concentrated defensive chemicals in internal body-regions rather than in the tunic. Four ascidian-derived meroterpenoids, rossinones B and the three derivatives 2,3-epoxy-rossinone B, 3-epi-rossinone B, 5,6-epoxy-rossinone B, and the indole alkaloids meridianins AG, along with other minoritary meridianin compounds were isolated from several samples. Some purified metabolites were tested in feeding assays exhibiting potent unpalatabilities, thus revealing their role in predation avoidance. Ascidian extracts and purified compound-fractions were further assessed in antibacterial tests against a marine Antarctic bacterium. Only the meridianins showed inhibition activity, demonstrating a multifunctional defensive role. According to their occurrence in nature and within our colonial specimens, the possible origin of both types of metabolites is discussed.

Study and modeling of the desintegration kinetics of coated paper

The disintegration of recovered paper is the first operation in the preparation of recycled pulp. It is known that the defibering process follows a first order kinetics from which it is possible to obtain the disintegration kinetic constant (KD) by means of different ways. The disintegration constant can be obtained from the Somerville index results (%lsv and from the dissipated energy per volume unit (Ss). The %slv is related to the quantity of non-defibrated paper, as a measure of the non-disintegrated fiber residual (percentage of flakes), which is expressed in disintegration time units. In this work, disintegration kinetics from recycled coated paper has been evaluated, working at 20 revise rotor speed and for different fiber consistency (6, 8, 10, 12 and 14%). The results showed that the values of experimental disintegration kinetic constant, Ko, through the analysis of Somerville index, as function of time. Increased, the disintegration time was drastically reduced. The calculation of the disintegration kinetic constant (modelled Ko), extracted from the Rayleigh’s dissipation function, showed a good correlation with the experimental values using the evolution of the Somerville index or with the dissipated energy

Study and modeling of the desintegration kinetics of coated paper

The disintegration of recovered paper is the first operation in the preparation of recycled pulp. It is known that the defibering process follows a first order kinetics from which it is possible to obtain the disintegration kinetic constant (KD) by means of different ways. The disintegration constant can be obtained from the Somerville index results (%lsv and from the dissipated energy per volume unit (Ss). The %slv is related to the quantity of non-defibrated paper, as a measure of the non-disintegrated fiber residual (percentage of flakes), which is expressed in disintegration time units. In this work, disintegration kinetics from recycled coated paper has been evaluated, working at 20 revise rotor speed and for different fiber consistency (6, 8, 10, 12 and 14%). The results showed that the values of experimental disintegration kinetic constant, Ko, through the analysis of Somerville index, as function of time. Increased, the disintegration time was drastically reduced. The calculation of the disintegration kinetic constant (modelled Ko), extracted from the Rayleigh’s dissipation function, showed a good correlation with the experimental values using the evolution of the Somerville index or with the dissipated energy

Natural Products from Antarctic Colonial Ascidians of the Genera Aplidium and Synoicum: Variability and Defensive Role

Ascidians have developed multiple defensive strategies mostly related to physical, nutritional or chemical properties of the tunic. One of such is chemical defense based on secondary metabolites. We analyzed a series of colonial Antarctic ascidians from deep-water collections belonging to the genera Aplidium and Synoicum to evaluate the incidence of organic deterrents and their variability. The ether fractions from 15 samples including specimens of the species A. falklandicum, A. fuegiense, A. meridianum, A. millari and S. adareanum were subjected to feeding assays towards two relevant sympatric predators: the starfish Odontaster validus, and the amphipod Cheirimedon femoratus. All samples revealed repellency. Nonetheless, some colonies concentrated defensive chemicals in internal body-regions rather than in the tunic. Four ascidian-derived meroterpenoids, rossinones B and the three derivatives 2,3-epoxy-rossinone B, 3-epi-rossinone B, 5,6-epoxy-rossinone B, and the indole alkaloids meridianins AG, along with other minoritary meridianin compounds were isolated from several samples. Some purified metabolites were tested in feeding assays exhibiting potent unpalatabilities, thus revealing their role in predation avoidance. Ascidian extracts and purified compound-fractions were further assessed in antibacterial tests against a marine Antarctic bacterium. Only the meridianins showed inhibition activity, demonstrating a multifunctional defensive role. According to their occurrence in nature and within our colonial specimens, the possible origin of both types of metabolites is discussed.

Fly Ash Soil Stabilization for Non-Uniform Subgrade Soils, Volume II: Influence of Subgrade Non-Uniformity on PCC Pavement Performance, TR-461, 2005

To provide insight into subgrade non-uniformity and its effects on pavement performance, this study investigated the influence of non-uniform subgrade support on pavement responses (stress and deflection) that affect pavement performance. Several reconstructed PCC pavement projects in Iowa were studied to document and evaluate the influence of subgrade/subbase non-uniformity on pavement performance. In situ field tests were performed at 12 sites to determine the subgrade/subbase engineering properties and develop a database of engineering parameter values for statistical and numerical analysis. Results of stiffness, moisture and density, strength, and soil classification were used to determine the spatial variability of a given property. Natural subgrade soils, fly ash-stabilized subgrade, reclaimed hydrated fly ash subbase, and granular subbase were studied. The influence of the spatial variability of subgrade/subbase on pavement performance was then evaluated by modeling the elastic properties of the pavement and subgrade using the ISLAB2000 finite element analysis program. A major conclusion from this study is that non-uniform subgrade/subbase stiffness increases localized deflections and causes principal stress concentrations in the pavement, which can lead to fatigue cracking and other types of pavement distresses. Field data show that hydrated fly ash, self-cementing fly ash-stabilized subgrade, and granular subbases exhibit lower variability than natural subgrade soils. Pavement life should be increased through the use of more uniform subgrade support. Subgrade/subbase construction in the future should consider uniformity as a key to long-term pavement performance.

Strategy selection: An introduction to the modeling challenge

Modeling the mechanisms that determine how humans and other agents choose among different behavioral and cognitive processes-be they strategies, routines, actions, or operators-represents a paramount theoretical stumbling block across disciplines, ranging from the cognitive and decision sciences to economics, biology, and machine learning. By using the cognitive and decision sciences as a case study, we provide an introduction to what is also known as the strategy selection problem. First, we explain why many researchers assume humans and other animals to come equipped with a repertoire of behavioral and cognitive processes. Second, we expose three descriptive, predictive, and prescriptive challenges that are common to all disciplines which aim to model the choice among these processes. Third, we give an overview of different approaches to strategy selection. These include cost‐benefit, ecological, learning, memory, unified, connectionist, sequential sampling, and maximization approaches. We conclude by pointing to opportunities for future research and by stressing that the selection problem is far from being resolved.

Modeling and control of electromechanical systems

The material presented in the these notes covers the sessions Modelling of electromechanical systems, Passive control theory I and Passive control theory II of the II EURON/GEOPLEX Summer School on Modelling and Control of Complex Dynamical Systems.We start with a general description of what an electromechanical system is from a network modelling point of view. Next, a general formulation in terms of PHDS is introduced, and some of the previous electromechanical systems are rewritten in this formalism. Power converters, which are variable structure systems (VSS), can also be given a PHDS form.We conclude the modelling part of these lectures with a rather complex example, showing the interconnection of subsystems from several domains, namely an arrangement to temporally store the surplus energy in a section of a metropolitan transportation system based on dc motor vehicles, using either arrays of supercapacitors or an electric poweredflywheel. The second part of the lectures addresses control of PHD systems. We first present the idea of control as power connection of a plant and a controller. Next we discuss how to circumvent this obstacle and present the basic ideas of Interconnection and Damping Assignment (IDA) passivity-based control of PHD systems.

Pore-scale modeling of two-phase flow instabilities in porous media

Les problèmes d'écoulements multiphasiques en média poreux sont d'un grand intérêt pour de nombreuses applications scientifiques et techniques ; comme la séquestration de C02, l'extraction de pétrole et la dépollution des aquifères. La complexité intrinsèque des systèmes multiphasiques et l'hétérogénéité des formations géologiques sur des échelles multiples représentent un challenge majeur pour comprendre et modéliser les déplacements immiscibles dans les milieux poreux. Les descriptions à l'échelle supérieure basées sur la généralisation de l'équation de Darcy sont largement utilisées, mais ces méthodes sont sujettes à limitations pour les écoulements présentant de l'hystérèse. Les avancées récentes en terme de performances computationnelles et le développement de méthodes précises pour caractériser l'espace interstitiel ainsi que la distribution des phases ont favorisé l'utilisation de modèles qui permettent une résolution fine à l'échelle du pore. Ces modèles offrent un aperçu des caractéristiques de l'écoulement qui ne peuvent pas être facilement observées en laboratoire et peuvent être utilisé pour expliquer la différence entre les processus physiques et les modèles à l'échelle macroscopique existants. L'objet premier de la thèse se porte sur la simulation numérique directe : les équations de Navier-Stokes sont résolues dans l'espace interstitiel et la méthode du volume de fluide (VOF) est employée pour suivre l'évolution de l'interface. Dans VOF, la distribution des phases est décrite par une fonction fluide pour l'ensemble du domaine et des conditions aux bords particulières permettent la prise en compte des propriétés de mouillage du milieu poreux. Dans la première partie de la thèse, nous simulons le drainage dans une cellule Hele-Shaw 2D avec des obstacles cylindriques. Nous montrons que l'approche proposée est applicable même pour des ratios de densité et de viscosité très importants et permet de modéliser la transition entre déplacement stable et digitation visqueuse. Nous intéressons ensuite à l'interprétation de la pression capillaire à l'échelle macroscopique. Nous montrons que les techniques basées sur la moyenne spatiale de la pression présentent plusieurs limitations et sont imprécises en présence d'effets visqueux et de piégeage. Au contraire, une définition basée sur l'énergie permet de séparer les contributions capillaires des effets visqueux. La seconde partie de la thèse est consacrée à l'investigation des effets d'inertie associés aux reconfigurations irréversibles du ménisque causé par l'interface des instabilités. Comme prototype pour ces phénomènes, nous étudions d'abord la dynamique d'un ménisque dans un pore angulaire. Nous montrons que, dans un réseau de pores cubiques, les sauts et reconfigurations sont si fréquents que les effets d'inertie mènent à différentes configurations des fluides. A cause de la non-linéarité du problème, la distribution des fluides influence le travail des forces de pression, qui, à son tour, provoque une chute de pression dans la loi de Darcy. Cela suggère que ces phénomènes devraient être pris en compte lorsque que l'on décrit l'écoulement multiphasique en média poreux à l'échelle macroscopique. La dernière partie de la thèse s'attache à démontrer la validité de notre approche par une comparaison avec des expériences en laboratoire : un drainage instable dans un milieu poreux quasi 2D (une cellule Hele-Shaw avec des obstacles cylindriques). Plusieurs simulations sont tournées sous différentes conditions aux bords et en utilisant différents modèles (modèle intégré 2D et modèle 3D) afin de comparer certaines quantités macroscopiques avec les observations au laboratoire correspondantes. Malgré le challenge de modéliser des déplacements instables, où, par définition, de petites perturbations peuvent grandir sans fin, notre approche numérique apporte de résultats satisfaisants pour tous les cas étudiés. - Problems involving multiphase flow in porous media are of great interest in many scientific and engineering applications including Carbon Capture and Storage, oil recovery and groundwater remediation. The intrinsic complexity of multiphase systems and the multi scale heterogeneity of geological formations represent the major challenges to understand and model immiscible displacement in porous media. Upscaled descriptions based on generalization of Darcy's law are widely used, but they are subject to several limitations for flow that exhibit hysteric and history- dependent behaviors. Recent advances in high performance computing and the development of accurate methods to characterize pore space and phase distribution have fostered the use of models that allow sub-pore resolution. These models provide an insight on flow characteristics that cannot be easily achieved by laboratory experiments and can be used to explain the gap between physical processes and existing macro-scale models. We focus on direct numerical simulations: we solve the Navier-Stokes equations for mass and momentum conservation in the pore space and employ the Volume Of Fluid (VOF) method to track the evolution of the interface. In the VOF the distribution of the phases is described by a fluid function (whole-domain formulation) and special boundary conditions account for the wetting properties of the porous medium. In the first part of this thesis we simulate drainage in a 2-D Hele-Shaw cell filled with cylindrical obstacles. We show that the proposed approach can handle very large density and viscosity ratios and it is able to model the transition from stable displacement to viscous fingering. We then focus on the interpretation of the macroscopic capillary pressure showing that pressure average techniques are subject to several limitations and they are not accurate in presence of viscous effects and trapping. On the contrary an energy-based definition allows separating viscous and capillary contributions. In the second part of the thesis we investigate inertia effects associated with abrupt and irreversible reconfigurations of the menisci caused by interface instabilities. As a prototype of these phenomena we first consider the dynamics of a meniscus in an angular pore. We show that in a network of cubic pores, jumps and reconfigurations are so frequent that inertia effects lead to different fluid configurations. Due to the non-linearity of the problem, the distribution of the fluids influences the work done by pressure forces, which is in turn related to the pressure drop in Darcy's law. This suggests that these phenomena should be taken into account when upscaling multiphase flow in porous media. The last part of the thesis is devoted to proving the accuracy of the numerical approach by validation with experiments of unstable primary drainage in a quasi-2D porous medium (i.e., Hele-Shaw cell filled with cylindrical obstacles). We perform simulations under different boundary conditions and using different models (2-D integrated and full 3-D) and we compare several macroscopic quantities with the corresponding experiment. Despite the intrinsic challenges of modeling unstable displacement, where by definition small perturbations can grow without bounds, the numerical method gives satisfactory results for all the cases studied.

The effect of workplace smoking bans on heart rate variability and pulse wave velocity of non-smoking hospitality workers

OBJECTIVES: To investigate the effect of a change in second-hand smoke (SHS) exposure on heart rate variability (HRV) and pulse wave velocity (PWV), this study utilized a quasi-experimental setting when a smoking ban was introduced. METHODS: HRV, a quantitative marker of autonomic activity of the nervous system, and PWV, a marker of arterial stiffness, were measured in 55 non-smoking hospitality workers before and 3-12 months after a smoking ban and compared to a control group that did not experience an exposure change. SHS exposure was determined with a nicotine-specific badge and expressed as inhaled cigarette equivalents per day (CE/d). RESULTS: PWV and HRV parameters significantly changed in a dose-dependent manner in the intervention group as compared to the control group. A one CE/d decrease was associated with a 2.3 % (95 % CI 0.2-4.4; p = 0.031) higher root mean square of successive differences (RMSSD), a 5.7 % (95 % CI 0.9-10.2; p = 0.02) higher high-frequency component and a 0.72 % (95 % CI 0.40-1.05; p < 0.001) lower PWV. CONCLUSIONS: PWV and HRV significantly improved after introducing smoke-free workplaces indicating a decreased cardiovascular risk.

Pharmacokinetic and pharmacodynamic assessment of valganciclovir in solid organ transplant recipients

RESUME : Valganciclovir (Valcyte®) is an orally administered ester prodrug of the standard anticytomegalovirus (CMV) drug ganciclovir. This drug enabled an important reduction of the burden of CMV morbidity and mortality in solid organ transplant recipients. Prevention of CMV infection and treatment of CMV disease requires drug administration during many weeks. Oral drug administration is therefore convenient. Valganciclovir has been developed to overcome the poor oral availability of ganciclovir, which limits its concentration exposure after oral administration and thus its efficacy. This prodrug crosses efficiently the intestinal barrier, is then hydrolyzed into ganciclovir, providing exposure similar to intravenous ganciclovir. Valganciclovir is now preferred for the prophylaxis and treatment of CMV infection in solid organ transplant recipients. Nevertheless, adequate dosage adjustment is necessary to optimize its use, avoiding either insufficient or exaggerate exposure related to differences in its pharmacokinetic profile between patients. The main goal of this thesis was to better describe the pharmacokinetic and pharmacodynamic profile of valganciclovir in solid organ transplant recipients, to assess their reproducibility and their predictability, and thus to evaluate the current recommendations for valganciclovir dosage adjustment and the potential contribution of routine therapeutic drug monitoring (TDM) to patients' management. A total of 437 ganciclovir plasma concentration data from 65 transplant patients (41 kidney, 12 lung, 10 heart and 2 liver recipients, 58 under oral valganciclovir prophylaxis, 8 under oral valganciclovir treatment and 2 under intravenous ganciclovir) were measured using a validated chromatographic method (HPLC) developed for this study. The results were analyzed by non-linear mixed effect modeling (NONMEM). A two-compartment model with first-order absorption appropriately described the data. Systemic clearance was markedly influenced by GFR, with further differences between graft types and sex (CL/GFR = 1.7 in kidney, 0.9 in heart and 1.2 in lung and liver recipients) with interpatient variability (CV%) of 26% and interoccasion variability of 12%. Body weight and sex influenced central volume of distribution (V1 = 0.34 l/kg in males and 0.27 l/kg in females) with an interpatient variability of 20%. Residual intrapatient variability was 21 %. No significant drug interaction influenced GCV disposition. VGC prophylactic efficacy and tolerability were good, without detectable dependence on GCV profile. In conclusion, this analysis highlights the importance of thorough adjustment of VGC dosage to renal function and body weight. Considering the good predictability and reproducibility of GCV profile after oral VGC in solid organ transplant recipients, routine TDM does not appear to be clinically indicated. However, GCV plasma measurement may still be helpful in specific clinical situations such as documentation of appropriate exposure in patients with potentially compromised absorption, or lack of response to CMV disease treatment, or under renal replacement therapy. RESUME : Le valganciclovir (Valcyte®) est un promédicament oral du ganciclovir qui est un anti-infectieux de référence contre les infections à cytomegalovirus (CMV). Cet antiviral a permis de réduire les effets délétères de cette infection jusqu'ici responsable d'une importante morbidité et mortalité chez les transplantés d'organe. La prévention et le traitement de l'infection à CMV sont donc nécessaires mais requièrent l'administration d'un agent antiviral sur une longue période. Un médicament administré par voie orale représente donc un avantage évident. Le valganciclovir a été développé dans le but d'améliorer la faible absorption orale du ganciclovir, et donc son efficacité. Cet ester valylique du ganciclovir traverse plus facilement la barrière gastro-intestinale, puis est hydrolysé en ganciclovir dans la circulation sanguine, produisant une exposition comparable à celle d'une perfusion intraveineuse de ganciclovir. De ce fait, le valganciclovir est devenu largement utilisé pour la prophylaxie mais aussi le traitement de l'infection à CMV. Néanmoins une utilisation optimale de ce nouveau médicament nécessite de bonnes connaissances sur son profil pharmacocinétique afin d'établir un schéma de dose adapté pour éviter tant une surexposition qu'une sous-exposition résultant des différences d'élimination entre les patients. Le but de cette thèse a été d'étudier le profil pharmacocinétique et pharmacodynamique du valganciclovir chez les transplantés d'organe ainsi que sa reproductibilité et sa prédictibilité. Il s'agissait d'apprécier de manière critique le schéma actuellement recommandé pour l'adaptation des doses de valganciclovir, mais aussi la contribution éventuelle d'un suivi des concentrations sanguines en routine. Un total de 437 taux sanguins de ganciclovir ont été mesurés, provenant de 65 patients transplantés d'organe (41 rénaux, 12 pulmonaires, 10 cardiaques et 2 hépatiques, 58 sous une prophylaxie orale de valganciclovir, 8 sous un traitement de valganciclovir et 2 sous un traitement intraveineux). Une méthode de chromatographie liquide à haute performance a été développée et validée pour cette étude. Les résultats ont été ensuite analysés par modélisation non linéaire à effets mixtes (NONMEM). Un modèle à deux compartiments avec absorption de premier ordre a permis de décrire les données. La clairance systémique était principalement influencée par le débit de filtration glomérulaire (GFR), avec une différence entre les types de greffe et les sexes (CL/GFR = 1.7 chez les greffés rénaux, 0.9 pour les greffés cardiaques et 1.2 pour le groupe des greffés pulmonaires et hépatiques) avec un variabilité inter-individuelle de 26% (CV%) et une variabilité inter-occasion de 12%. Le poids corporel ainsi que le sexe avaient une influence sur le volume central de distribution (V1 = 0.34 l/kg chez les hommes et 0.27 l/kg chez les femmes) avec une variabilité inter-individuelle de 20%. La variabilité intra-individuelle résiduelle était de 21 %. Aucune interaction médicamenteuse n'a montré d'influence sur le profil du ganciclovir. La prophylaxie avec le valganciclovir s'est révélée efficace et bien tolérée. En conclusion, cette analyse souligne l'importance d'une adaptation de la dose du valganciclovir à la fonction rénale et au poids du patient. Au vu de la bonne reproductibilité et prédictibilité du profil pharmacocinétique du ganciclovir chez les patients transplantés recevant du valganciclovir, un suivi des concentrations sanguines en routine ne semble pas cliniquement indiqué. Néanmoins, la mesure des taux plasmatiques de ganciclovir peut être utile dans certaines situations particulières, comme la vérification d'une exposition appropriée chez des patients susceptibles d'absorption insuffisante, ou ne répondant pas au traitement d'une infection à CMV ou encore sous épuration extra-rénale. RESUME LARGE PUBLIC : Le valganciclovir est un précurseur capable de libérer du ganciclovir, récemment développé pour améliorer la faible absorption orale de ce dernier. Une fois le valganciclovir absorbé, le ganciclovir libéré dans la circulation sanguine devient efficace contre les infections à cytomégalovirus. Ce virus largement répandu est responsable de maladies insidieuses et parfois graves chez les personnes présentant une baisse des défenses immunitaires, comme les greffés d'organe recevant un traitement anti-rejet. Le ganciclovir est administré pendant plusieurs mois consécutifs soit pour prévenir une infection après la transplantation, soit pour traiter une infection déclarée. La facilité d'administration du valganciclovir par voie orale représente un avantage sur une administration du ganciclovir par perfusion, qui nécessite une hospitalisation. Toutefois, la voie orale peut être une source supplémentaire de variabilité chez les patients, avec un impact potentiel sur l'efficacité ou la toxicité du médicament. Le but de cette étude a été - de décrire le devenir de ce médicament dans le corps humain (dont l'étude relève de la discipline de la pharmacocinétique) - de définir les facteurs cliniques pouvant expliquer les différences de concentration sanguine observées entre les patients sous une posologie donnée - d'explorer les relations entre les concentrations du médicament dans le sang et son efficacité ou la survenue d'effets indésirables (dont l'étude relève de la discipline de la pharmacodynamie). Cette étude a nécessité le développement et la validation, d'une méthode d'analyse pour mesurer la concentration sanguine du ganciclovir, puis son application à 437 échantillons provenant de 65 patients transplantés d'organe solide (41 rénaux, 12 pulmonaires, 10 cardiaques et 2 hépatiques) recevant du valganciclovir. Les résultats des mesures effectuées ont été analysés à l'aide d'un outil mathématique afin d'élaborer un modèle du devenir du médicament dans le sang chez chaque patient et à chaque occasion. Cette étude a permis d'évaluer chez des patients recevant le valganciclovir, la vitesse à laquelle l'organisme absorbe, distribue, puis élimine le médicament. La vitesse d'élimination dépendait étroitement de la fonction rénale, du type de greffe et du sexe alors que la distribution dépendait du poids et du sexe du patient. La variabilité non expliquée par ces facteurs cliniques était modérée et vraisemblablement sans conséquence clinique évidente soit sur l'efficacité ou la tolérance, qui se révèlent très satisfaisantes chez les patients de l'étude. Les observations n'ont pas révélé de relation entre les concentrations de médicament et l'efficacité thérapeutique ou la survenue d'effets indésirables, confirmant que les doses relativement faibles utilisées dans notre collectif de patients suffisaient à produire une exposition reproductible à des concentrations adéquates. En conclusion, le profil (et par conséquent l'absorption) du valganciclovir chez les patients transplantés semble bien prédictible après une adaptation de la dose à la fonction rénale et au poids du patient. Un contrôle systématique des concentrations sanguines n'est probablement pas indiqué en routine, mais cette mesure peut présenter un intérêt dans certaines conditions particulières.

Variabilité des concentrations plasmatiques de l'angiotensinogène et risque d'hypertension artérielle chez le rat transgénique [Variability of plasma angiotensinogen levels and risk of hypertension in a transgenic rat model].

AIM: Genetic polymorphisms of the human angiotensinogen gene are frequent and may induce up to 30% increase of plasma angiotensinogen concentrations with a blood pressure increase of up to 5mmHg. Their role for the pathogenesis of human arterial hypertension remains unclear. High plasma angiotensinogen levels could increase the sensitivity to other blood pressure stressors. METHODS: Male transgenic rats with a 9-fold increase of plasma angiotensinogen concentrations and male non-transgenic rats aged 10 weeks were treated or not with NG-Nitro-L-arginine-methyl ester for 3 weeks in their drinking water (n=3/group). Systolic blood pressure and body weight were measured at baseline and at the end of the study when left ventricular weight and ventricular expression of angiotensin I-converting enzyme and procollagen Iα1 were determined (polymerase chain reaction). RESULTS: At baseline, transgenic rats had +18mmHg higher bood pressure and -8% lower body weight compared to non-transgenic rats (P<0.05) without significant changes for the vehicle groups throughout the study (P>0.05). NG-Nitro-L-arginine-methyl ester increased blood pressure, left ventricular weight and left ventricular weight indexed for body weight by +41%, +17.6% and +18.6% (P<0.05) in transgenic and +25%, +5.3% and +6.7% (P>0.05) in non-transgenic rats compared to untreated animals, respectively. Cardiac gene expression showed no differences between groups (P>0.05). CONCLUSION: Increased plasma angiotensinogen levels may sensitize to additional blood pressure stressors. Our preliminary results point towards an independent role of angiotensinogen in the pathogenesis of human hypertension and associated end-organ damage.

Genetic variability of Brazilian rice landraces determined by SSR markers

The objective of this study was to evaluate the genetic variability of rice (Oryza sativa) landraces collected in Brazilian small farms. Twelve simple sequence repeat (SSR) markers characterized 417 landraces collected in 1986, 1987 and 2003, in the state of Goiás, Brazil. The number of landraces with long and thin grain type increased in the evaluated period, probably due to market demand. Based on the molecular data, the genetic variability increased during this period and, as per to the factorial correspondence analysis, most of the accessions were grouped according to the year of collection. The incorporation of modern rice cultivars in landrace cultivation areas and the selection carried out by small farmers are the most probable factors responsible for increasing landrace genetic variability, during the evaluated period. Genotype exchange between farmers, selection practice and local environmental adaptation are able to generate novel adapted allele combinations, which can be used by breeding programs, to reinitiate the process.