Pde

Currently available antipsychotic medications work primarily by antagonizing D 2 dopamine receptors, thus raising intracellular cAMP levels. We hypothesized that intracellular stimulation of cAMP levels in the CNS would have similar effects to treatment with antipsychotic medication. To test this hypothesis, we studied the effect of an acute treatment of rolipram, an inhibitor of type 4 phosphodiesterases that degrade cAMP, on acoustic startle and prepulse inhibition (PPI) of the acoustic startle response in C57BL/6J mice known to exhibit poor PPI. PPI is disrupted in schizophrenia patients, and the ability of a drug to increase PPI in mice is predictive of antipsychotic efficacy. We show here that acute treatment with rolipram significantly increases PPI at doses that do not alter the acoustic startle response (lowest effective dose 0.66 mg/kg). In addition, rolipram (0.66 mg/kg) blocks the disruptive effects of amphetamine (10 mg/kg) on PPI. At a slightly higher dose (1.0 mg/kg), rolipram also induces catalepsy. Thus, phosphodiesterase-4 (PDE 4 ) inhibition has many of the same behavioral effects as traditional antipsychotic medications. In contrast to traditional antipsychotics, these effects are achieved through alteration of an intracellular second messenger system rather than antagonism of neurotransmitter receptors. Given previous reports showing rolipram improves cognition, we conclude that PDE 4 represents an important novel target for further antipsychotic drug development.

Psoriasis is a common inflammatory skin condition, affecting 2–4% of the worldwide population. Psoriasis remains an important public health challenge because there are many clinical forms of psoriasis in particular sites, probably related to the dysregulation of different cytokines. Therefore, there is a continuous need to improve treatment options with mechanisms of action different from those of the currently known therapies. Advances in knowledge of the molecular bases of pathogenesis lead to a better understanding of the disease, thus influencing the development and management of effective treatments. Moreover, data from recent published work indicate that psoriasis coexists with cardiovascular diseases, metabolic syndrome, diabetes mellitus and psychiatric disorders. We present results from our 52‐week open‐label trial in a cohort of psoriatic and psoriatic arthritis patients treated with daily p.o. doses of apremilast 60 mg. We confirmed the efficacy and safety of the drug in ...

Objective: To investigate the effect of chronic use of sildenafil and intracavernous injection (ICI) with trimix in men not responding to on-demand monotherapy with sildenafil or ICI with prostaglandin-E1 (PGE1). Patients and methods: The study included 40 patients with erectile dysfunction (ED), with a mean (SD) age of 50.7 (11.3) years and unresponsive to on-demand sildenafil or ICI with PGE1 as monotherapy. They were assessed using the Sexual Health in Men (SHIM)-5 score for ED severity, penile colour Doppler ultrasonography (CDUS) for peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI) with an ICI test using 0.25 mL of trimix of papaverine, PGE1 and phentolamine. Testosterone, prolactin and cholesterol levels were assessed. Patients received 25 mg sildenafil daily for 8 weeks, combined with twice weekly ICI with 0.25 mL of trimix. After treatment, the Erection Hardness Score (EHS), penile CDUS with ICI and ED Inventory of Treatment Satisfaction were assessed. Results: The mean (SD) SHIM-5 score before treatment was 8.3 (0.5) in 15 of the 40 men and 6.3 (0.4) in 25. Penile haemodynamics were normal in five (13%), showed arterial insufficiency in five (13%), venous occlusive disease in 26 (65%) and mixed vascular in four (10%). There was an improved SHIM-5 score in 28 (70%) patients, as shown by their haemodynamic values, duration of erection and EHS with therapy, and 66% satisfaction with treatment. Adverse effects (penile pain, headache, facial flushing, dyspepsia, nasal congestion, dizziness) were reported in 17 patients (43%). Conclusion: Chronic use of trimix plus daily low-dose sildenafil improved penile haemodynamics in these patients with ED not responding to on-demand phosphodiesterase-5 inhibitors or ICI with PGE1 monotherapy.

As biologic therapies become first line treatments for many inflammatory disorders, it becomes increasingly important for the practicing physician to be familiar with how these drugs function at the molecular level. This information is useful in making therapeutic decisions and helping patients understand their treatment options. It is critical to patient safety and clinical response that the molecular differences between these drugs inform prescribing practices. To this end, we present and analyze the available structural biology information about the biologics used in the treatment of psoriasis including inhibitors of tumor necrosis factor alpha (TNFα), interleukin-17 (IL-17), and interleukin-23 (IL-23). We describe and analyze the molecular surface character of known binding epitopes for medications in these classes, showing that significant differences exist in epitope location, hydrophobicity, and charge. Some of these differences can be correlated with clinical data, but our analysis ultimately points to the need for more structural information to allow for a better understanding of the structure-function relationship of biologic therapies.

Physical activity has the potential to offset age-related impairments in the regulation of blood flow and O2 delivery to the exercising muscles; however, the mechanisms underlying this effect of physical activity remain poorly understood. The present study examined the role of cGMP in training-induced adaptations in the regulation of skeletal muscle blood flow and oxidative metabolism during exercise in aging humans. We measured leg hemodynamics and oxidative metabolism during exercise engaging the knee extensor muscles in young [ n = 15, 25 ± 1 (SE) yr] and older ( n = 15, 72 ± 1 yr) subjects before and after a period of aerobic high-intensity exercise training. To determine the role of cGMP signaling, pharmacological inhibition of phosphodiesterase 5 (PDE5) was performed. Before training, inhibition of PDE5 increased ( P < 0.05) skeletal muscle blood flow and O2 uptake during moderate-intensity exercise in the older group; however, these effects of PDE5 inhibition were not dete...

In this paper, we consider the problem of enhancing the stability of a coupled transport-diffusion system related to parallel-flow heat exchange process. It is shown that the degree of stability can be enhanced by using a residual mode filter (RMF)-based controller which is of finite-dimension.

it was assumed that this represented retrograde ejaculation, but elegant studies of men taking selective a blockers have consistently found that the failure is not of ejection (ie, antegrade expulsion of semen) but emission (ie, deposition of semen in the posterior urethra). Five-a reductase inhibitors are also effective for management of BPH symptoms and progression but may also cause ejaculation disturbance; in these cases, it is likely atrophy of the glandular elements and their ability to produce seminal fluid that disrupts ejaculation.

The gut microbiota, mainly located in the colon, is engaged in a complex dialogue with the large intestinal epithelium through which important regulatory processes for the health and well-being of the host take place. Imbalances of the microbial populations, called dysbiosis, are related to several pathological status, emphasizing the importance of understanding the gut bacterial ecology. Among the ecological drivers of the microbiota, the spatial structure of the colon is of special interest: spatio-temporal mechanisms can lead to the constitution of spatial interactions among the bacterial populations and of environmental niches that impact the overall colonization of the colon. In the present study, we introduce a mathematical model of the colon microbiota in its fluid environment, based on the explicit coupling of a population dynamics model of microbial populations involved in fibre degradation with a fluid dynamics model of the luminal content. This modeling framework is used to study the main drivers of the spatial structure of the microbiota, specially focusing on the dietary fibre inflow, the epithelial motility, the microbial active swimming and viscosity gradients in the digestive track. We found 1) that the viscosity gradients allow the creation of favorable niches in the vicinity of the mucus layer; 2) that very low microbial active swimming in the radial direction is enough to promote bacterial growth, which sheds a new light on microbial motility in the colon and 3) that dietary fibres are the main driver of the spatial structure of the microbiota in the distal bowel whereas epithelial motility is preponderant for the colonization of the proximal colon; in the transverse colon, fibre levels and chemotaxis have the strongest impact on the distribution of the microbial communities.

Multiframe image super-resolution is a technique to obtain a high-resolution image by fusing a sequence of low-resolution ones. This paper deals with a new approach to robust super resolution based on regularization framework. Since registration is an important step that ensures the success of super resolution algorithms, must choose the most suitable method. We suggest a new algorithm specified at low resolution images with small deformations using fourth-order partial differential equations (PDE) regularization in the last step of super resolution. The deformations are not parametric and differs from one image to another. We use a curvature registration specially because image are slightly deformed. Experimental results show the robustness of the proposed method compared to classical super resolution methods.

The paper presents the approximate analytical solution for the partial differential equation (PDE) describing heat transfer in human tooth. The equation governing the phenomenon is solved analytically using variational iteration method (VIM). The results obtained are presented graphically and discussed. It is observed from the results obtained that the temperature was significantly influenced by the parameters.

Modern physics has become so vast and so complicated that a deep connection between empirical technologically-oriented physics and the realm of basic theory becomes more and more a rare exercise in crossdisciplinary cooperation. This paper will give an overview of many important developments both on the empirical side and the theoretical side, well known to both but not to each other, and give the specifics of a way to connect them more effectively. After the initial review, it provides a three-step program for reorganizing and simplifying our fundamental assumptions about the laws of physics, starting by linking recent progress in areas like backwards time physics, coherence phenomena in quantum optics and cavity QED to the retrieval of an updated form of Einstein's vision of a universe of mathematically elegant and rigorous continuous fields, addressing empirical and theoretical questions which are still open in the study of nuclear interactions and in the mathematical study of solitons, including the Higgs boson and faster than light (FTL) effects and the origin of mass. If there is any hope of humans ever achieving faster than light travel, it will depend on resolving the issues raised here.

It is well known that classical systems governed by ODE or PDE can have extremely complex emergent properties. Many researchers have asked: is it possible that the statistical correlations which emerge over time in classical systems would allow effects as complex as those generated by quantum field theory (QFT)? For example, could parallel computation based on classical statistical correlations in systems based on continuous variables, distributed over space, possibly be as powerful as quantum computing based on entanglement? This paper proves that the answer to this question is essentially "yes," with certain caveats. More precisely, the paper shows that the statistics of many classical ODE and PDE systems obey dynamics remarkably similar to the Heisenberg dynamics of the corresponding quantum field theory (QFT). It supports Einstein's conjecture that much of quantum mechanics may be derived as a statistical formalism describing the dynamics of classical systems. Pred...

Image Inpainting is technique in which mainly used to filling the region which are damaged and want to recover from unwanted object by collecting the information from the neighbouring pixels. Image inpainting technique has been widely used for reconstructing damaged old photographs and removing unwanted objects from images. In this paper, we present an improved Exemplar based Structure tensor inpainting method based on the exemplar-based image inpainting technique by modifying the distance function. The method proved to be effective in removing large objects from an image, ensuring accurate propagation of linear structures, and eliminating the drawback of “garbage growing ” which is a common problem in other methods. Experimental results show that our method improves the quality of image inpainting compared with the conventional exemplar-based image completion algorithms.

Image inpainting was historically done manually by painters for removing defect from paintings and photographs. Fill the region of missing information from a signal using surrounding information and re-form signal is the basic work of inpainting algorithms. Here in this paper we have studied and reviewed many different algorithms present for doing image inpainting and explain their approach. We have briefly explain some algorithms for video inpainting applications. This paper contain work done in the field of image inpainting and guide newcomers who are willing to work in image inpainting field.

Materiales y métodos Corazones aislados de ratas Wistar macho de 6 meses de edad fueron perfundidos por el sistema de Langendorff y sometidos a 30 min de isquemia global (IG), seguidos de 60 min de reperfusión (R) [grupo CI]. Otros corazones fueron tratados 10 min antes de la IG y durante los primeros 10 min de la R con 30 μg/ml de G CP en ausencia ó en presencia de L -nitro-L-arginina metil éster [L-NAME, inhibidor de la enzima óxido nítrico sintasa (NOS)]. Al final de R se midió el tamaño del infarto (TI), mediante la tinción con sales de tetrazolio. Las funciones sistólica y diastólica fueron determinadas a través de la presión desarrollada del ventrículo izquierdo (PD) y la presión diastólica final (PDF), respectivamente. El estrés oxidativo fue evaluado a través del contenido de glutatión reducido (GSH) y de la concentración de sustancias reactivas al ácido tiobarbitúrico (TBARS). En mitocondrias aisladas se determinó la apertura del poro de 2+ permeabilidad transitoria inducid...

Introducción La insuficiencia cardíaca (IC) es un síndrome caracterizado por la imposibilidad del corazón de bombear sangre en los volúmenes adecuados para satisfacer las necesidades metabólicas de los tejidos. Numerosas observaciones relacionan el aumento de actividad de la CaMKII con el desarrollo de insuficiencia cardíaca (IC), pero no hay estudios longitudinales que describan el estado de fosforilación de esta proteína (PCaMKII) como indicador de su actividad durante la evolución de la hipertrofia a la IC.

Introduction. The three effective, commercially available drugs for the treatment of erectile dysfunction-sildenafil, vardenafil, and tadalafil-inhibit the same substrate, the erectolytic enzyme phosphodiesterase type 5 (PDE5). Although there are pharmacological differences between these three compounds, few comparative studies have been conducted to date. Aim. The aim of this study was to determine the efficacy of sildenafil, tadalafil, and vardenafil in a randomly assigned 8-week fixed regimen. Methods. This was a spontaneous, open-label, randomized, multicenter, crossover study where the patients were randomized to receive sildenafil 50 mg, sildenafil 100 mg, tadalafil 20 mg, or vardenafil 20 mg. Main Outcome Measures. The primary outcome included the posttreatment analysis of erectile function domains of the abridged International Index of Erectile Function (IIEF5+1). The secondary objectives included the analysis of peak-systolic velocities (PSVs), end-diastolic velocities (EDVs), and resistive index (RI), and the estimate of the percentage of men with normal penile hemodynamic parameters after each treatment. Results. In all groups of patients taking sildenafil 50 mg, sildenafil 100 mg, tadalafil 20 mg, and vardenafil 20 mg at a frequency reflecting the common treatment regimens in real life, there was a statistically significant baseline-to-end point improvement in subjective perception of erectile function measured by IIEF5+1. When the four groups were compared, the treatments were not different in modifying IIEF5+1 and penile flow parameters. However, the within-group analysis showed that PSV improved in the sildenafil 50 mg group and that PSV together with RI

The aim of this article is to show the opportunities for penetration of new renewable energy sources into the Brazilian energy mix, enabling it to continue generating a high quantity of clean energy compared to the world average. Different scenarios for the evolution of such sources in Brazil and in the world were analyzed within the 2010-2030 horizon. The study showed not only the benefits brought by these sources in terms of GHG emission avoidance but also the impact in terms of employment creation and the public investment necessary to obtain such benefits.

In solving the wave equation for a given set of boundary and initial conditions, separation of variables can be used to find the solution provided that the boundary conditions are homogeneous. If they are not, it becomes very difficult to solve the wave equation but thanks to the integral transform technique which can be used to solve the wave equation no matter the circumstance of the boundary and initial conditions and regardless of the nature of the wave equation, whether it is linear or nonlinear. The only prerequisite in using the integral transform is that you first have to derive the wave profile that satisfies the boundary or initial conditions and then go ahead and solve.

In this paper, we study the growth of gradients of solutions of elliptic equations, including the Dirichlet eigenfunction solutions on bounded plane convex domain. Several results related to Bi-Lipschicity of quasiconformal harmonic (qch) mappings with respect to quasi-hyperbolic and euclidean metrics, are proved. In connection with the subject, we announce a few results concerning the so called interior estimate, including Proposition 1.1. In addition, a short review of the subject is given.

Suppose that h is a harmonic mapping of the unit disc onto a C 1, α domain D. Then h is q.c. if and only if it is bi-Lipschitz. In particular, we consider sufficient and necessary conditions in terms of boundary function that h is q.c. We give a review of recent related results including the case when domain is the upper half plane. We also consider harmonic mapping with respect to ρ metric on codomain.

The aim of this paper is to review of six recent symmetric mapping functions. The mapping function can be largely used for GPS meteorological measurements, InSAR atmospheric corrections and precise measurements of very long baseline interferometry (VLBI). These spacebased techniques use radio signal that propagate through the Earth's atmosphere. The electrically-neutral region, predominantly the troposphere, affects the speed and direction of travel of radio waves leading to existence of excess path. The mapping function models the elevation angle dependence of the delay. Within the past decade, significant improvements have been achieved in order to use of Numerical Weather Models (NWM) for geodetic positioning. Ray-tracing algorithms have been performed through refractivity shells retrieved from NWMs in order to relate zenith delays to slant delays. Therefore, there seems to be a real need for deep review of recent developments in the mapping function domain. This paper propos...

Background— Right ventricular failure from increased pulmonary vascular loading is a major cause of morbidity and mortality, yet its modulation by disease remains poorly understood. We tested the hypotheses that, unlike the systemic circulation, pulmonary vascular resistance (R PA ) and compliance (C PA ) are consistently and inversely related regardless of age, pulmonary hypertension, or interstitial fibrosis and that this relation may be changed by elevated pulmonary capillary wedge pressure, augmenting right ventricular pulsatile load. Methods and Results— Several large clinical databases with right heart/pulmonary catheterization data were analyzed to determine the R PA -C PA relationship with pulmonary hypertension, pulmonary fibrosis, patient age, and varying pulmonary capillary wedge pressure. Patients with suspected or documented pulmonary hypertension (n=1009) and normal pulmonary capillary wedge pressure displayed a consistent R PA -C PA hyperbolic (inverse) dependence, C ...

The performance of hexa methylene tetra amine (HMTA) (C6H12N4) as a corrosion inhibitor for mild steel in
simulated CO2-saturated brine solution was investigated in the absence and presence of inhibitor at various HMTA
concentrations, temperatures, and velocities using weight loss technique. Doehlert Experimental Design (DED) was used
for designing of experiments. A second order polynomial equation with main, quadratic and interactive influences was
suggested and optimized. Nonlinear regression statistical analysis was used for estimation of polynomial coefficients
based on Quasi-Newton & Rosenbrock method. Inhibitor concentration showed a high positive impact in reducing the
corrosion rate, while temperature and mixing velocity showed the negative effect. The optimum (minimum) corrosion
rate was 18.714 gmd at 35.69 °C brine temperature, 74.47 ppm HMTA concentration, and 163.12 rpm mixing velocity.
At these optimum conditions a 92% inhibition efficiency was obtained.

Psoriasis Vulgaris is a complex multifactorial dermatological disease, with various genetic and environmental factors implicated in the onset and progression of the disease and comorbidities. Cardiovascular disease (CVD) and metabolic syndrome are essential psoriasis comorbidities that suggest a potential hypercoagulable background of the disease. To better understand the link between psoriasis, hypercoagulation and comorbidities, we investigated the prothrombotic polymorphism rs5918T > C in integrin B3 (ITGB3) in 102 patients diagnosed with psoriasis and 97 healthy controls, all Caucasian. The patients, carriers of rs5918T > C polymorphism, were compared with non-carriers for metabolic risk factors related to metabolic syndrome and CV disease. Our results revealed that the incidence of ITGB3rs5918(C) allele carriage was only slightly increased in psoriatic patients compared to healthy controls (20.6% vs 18.6%), and psoriatic patients with the polymorphism showed an increased incidence of metabolic risk factors. Dyslipidemia, high triglycerides (42.9% vs 27.5%), high cholesterol (66.7% vs 45.5%) and low High Density Lipoprotein (HDL) (47.6% vs 32.8%) were significantly more prevalent (p = .019) among psoriatic carriers of the rs5918(C) polymorphism compared to psoriatic non-carriers. The incidence of metabolic syndrome was significantly higher among polymorphism carriers (52.4%) compared to non-carriers (20.5%) within the psoriatic patient group (p = .014), whereas CVD incidence was higher but non-significantly. The carriage of ITGB3rs5918(C) polymorphism in patients with psoriasis was associated with a higher risk of metabolic syndrome and dyslipidaemias and a higher but non-significant prevalence of CVD compared to non-carriers. However, the frequency of this polymorphism was similar in psoriasis patients and healthy controls.

Apoptosis is a biological process of death or cellular suicide present in all the cells of the metazoans. It maintains the balance between the regeneration of pluripotential cells -or stem cells- and the elimination of cells that have already served their function, of cells that have reproduced in excess, or have been genetically damaged beyond repair. Apoptosis activation in cardiomyocytes is a common problem in a large variety of cardiomyopathies; it has been suggested that it is an important contributor ventricular hypertrophy and to the increase of the infarct size in patients with cardiac failure and cardiovascular disease. Clinical diagnosis of apoptosis is a reality in the medical science, its application in different aspects of cardiology includes from coronary cardiopathy to rhythm alterations. In this sense, the use of the non-invasive imaging, can be very useful for the in vivo detection of this type of cellular death in patients with myocardial necrosis, acute myocardial infarct, acute rejection of cardiac transplantation, myocarditis, intracardial malignant tumours, as well as in cardiotoxicity cases and other cardiomyopathies. Particularly, binding of Tc99m-labeled Annexin V, produces gammagraphic images that allow the identification of apoptotic cells in vivo in SPECT and SestaMiBi systems. In summary, the use of these techniques will be invaluable in the near future for anti-apoptosis therapy and intervention in the routine of the daily Cardiology practice.

Purpose Erectile dysfunction (ED) is one of the most prevalent male sexual dysfunctions. ED has been in the past mistakenly considered a purely psycho-sexological symptom by patients and doctors. However, an ever-growing body of evidence supporting the role of several organic factors in the pathophysiological mechanisms underlying ED has been recognized. Methods The Italian Society of Andrology and Sexual Medicine (SIAMS) commissioned an expert task force involving several other National Societies to provide an updated guideline on the diagnosis and management of ED. Derived recommendations were based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Results Several evidence-based statements were released providing the necessary up-to-date guidance in the context of ED with organic and psychosexual comorbidities. Many of them were related to incorrect lifestyle habits suggesting how to associate pharmacotherapies and counseling, in a couple-centered approach. Having the oral therapy with phosphodiesterase type 5 inhibitors as the gold standard along with several other medical and surgical therapies, new therapeutic or controversial options were also discussed. Conclusions These are the first guidelines based on a multidisciplinary approach that involves the most important Societies related to the field of sexual medicine. This fruitful discussion allowed for a general agreement on several recommendations and suggestions to be reached, which can support all stakeholders in improving couple sexual satisfaction and overall general health.

Magnetic resonance imaging (MRI) intensity inhomogeneities can be attributed to imperfections in the RF coils or some problems associated with the acquisition sequences. The result is a slowly varying shading artifact over the image that can produce errors with conventional intensity-based classification. The removal of the spatial intensity inhomogeneities from MR images is difficult because the inhomogeneities could change with different MRI acquisition parameters from patient to patient and from slice to slice. We propose a shape-based classification technique to overcome this problem using the level set approach. A signed distance function is dedicated to describe the model of the tissue of interest. Then, a partial differential equation (PDE) is derived to describe the evolution of an observed structure. At each iteration, the observed structure is registered with the prior shape model. The algorithm is used at different levels of noise and intensity inhomogeneities showing a good accuracy.

Compartmentalisation of cAMP and PKA activity in cardiac muscle cells plays a key role in maintaining basal and enhanced contractility stimulated by sympathetic nerve activity. In cardiomyocytes, activation of adrenergic receptor increases cAMP production, which is countered by the hydrolytic activity of selective phosphodiesterases (PDEs). The intracellular regional dynamics of cAMP production and hydrolysis modulate downstream signals resulting in different biological responses. The interplay between beta receptors (βARs) signalling and phosphodiesterase 5 (PDE5) activity remains to be addressed. Using combined strategies with pharmacological inhibitors and genetic deletion of PDEs and βAR isoforms, we revealed a specific pool of cAMP that is under dual regulation by PDE2 and, indirectly, PDE5 activity. Inhibition of PDE5 with sildenafil produces a cGMP-dependent activation of PDE2 that attenuates cAMP generation induced by βAR agonists, with concomitant modulation of stimulated c...

Most men older than 60 years experience some degree of erectile dysfunction (ED). The physiology of erections is complex, with contributions from hormonal, vascular, psychological, neurologic, and cellular components. ED is strongly associated with cardiovascular risk factors, and this fact plays a major role in the prevention and treatment of ED. In this article, we review the evaluation of ED in terms of history, physical examination, and common laboratory studies. Additionally, we review major considerations when prescribing phosphodiesterase type 5 inhibitors and other medical treatments, including intraurethral alprostadil, penile injection therapy, and testosterone replacement.

interstitial cells and the nerve fibres of the outer muscle layers of lateral wall, indicating the presence of PDE2 activity. Discussion and conclusion Our study is the first to show the distribution of PDE2 in the bladder which was shown to be present in the urothelium, mainly umbrella cells, the interstitial cells of the suburothelium and the outer muscle, as well as in nerve fibres.

The formation of vegetation patterns has been widely studied and discussed over the years and it has been related to two different mechanisms: depletion of water in the center of vegetation patches and production of toxicity by the decomposition of plant residues in soil. In this work we present a spatially explicit model that combines these two processes showing that negative plant-soil feedbacks can explain the development of different vegetation patterns also when water is not a limiting factor. This also demonstrates that the toxicity effects may change the stability properties of the vegetation patterns.

Myocardial NO signaling appears elevated in heart failure (HF). Whether this results from increased NO production, induction of the high-output NO synthase (NOS)2 isoform, or changes in NOS regulatory pathways (such as caveolae) remains controversial. We tested the hypothesis that increased abundance of caveolin-3 and/or sarcolemmal caveolae contribute to increased NO signaling in pacing-induced HF. Abundance of caveolin-3 (0.59Ϯ0.08 versus 0.29Ϯ0.08 arbitrary units, Pϭ0.01) but not caveolin-1 was increased in HF compared with control conditions, assessed by Western blot. Additionally, transmission electron microscopy revealed increased caveolae (2.7Ϯ0.4 versus 1.3Ϯ0.3 per micrometer myocyte membrane, PϽ0.005). The association between caveolin-3 and NOS3 at the sarcolemma and T tubules was unchanged in HF compared with control myocytes. The impact of NOS inhibition with L-N G-methylarginine hydrochloride (L-NMMA) on ␤-adrenergic inotropy was assessed in conscious dogs before and after HF. In control dogs, dobutamine (5 g ⅐ kg Ϫ1 ⅐ min Ϫ1) increased ϩdP/dt by 36Ϯ7%, and this was augmented to 66Ϯ24% by 20 mg/kg L-NMMA (Pϭ0.04 versus without L-NMMA, nϭ8) but not affected by 10 mg/kg L-NMMA (34Ϯ10%, PϭNS; nϭ8). In HF, dobutamine ϩdP/dt response was depressed (PϽ0.001 versus control), and increased concentrations were required to match control inotropic responses (10 to 15 g ⅐ kg Ϫ1 ⅐ min Ϫ1 , 48Ϯ7%). L-NMMA enhanced ϩdP/dt responses similarly at 10 mg/kg (61Ϯ17%, Pϭ0.02; nϭ4) and 20 mg/kg (54Ϯ7%, Pϭ0.04; nϭ7). Caveolin-3 abundance positively correlated with L-NMMA augmentation of dobutamine inotropic responses in HF (rϭ0.9, Pϭ0.03; nϭ4). Thus, in canine pacing-induced HF, expression of caveolin-3 and of sarcolemmal caveolae is increased. This increase is associated with augmented agonist-stimulated NO signaling, likely via a compartmentation effect. (Circ Res. 2000;86:1085-1092.

The aim of the present study was to obtain evidence for the possible modulatory effect of leptin on glucosensing capacity in hypothalamus and hindbrain of rainbow trout. In a first experiment, trout were injected ICV with saline alone or containing increased doses of leptin (0.3-30 g l −1). Leptin induced in general in both hypothalamus and hindbrain dose-dependent changes in parameters related to glucosensing (increased glycogenic and glycolytic potentials together with increased GK activity, and increased mRNA levels of genes involved in glucosensing response) compatible with those occurring under hyperglycemic conditions, a situation that is known to produce anorexia. The anorectic action of leptin in our experimental conditions was observed in a second experiment. The specificity of leptin action was tested in a third experiment in which trout were injected ICV with saline, or leptin alone, or leptin plus agents known to inhibit leptin signaling pathways in mammals. The results obtained suggest that the central action of leptin on glucosensing system can be related to the JAK/STAT and IRS-PI(3)K pathways. Finally, we also provide evidence for a peripheral effect of central leptin treatment (increased liver glycogenolytic potential), which could be associated with increased sympathetic activity.

The gut microbiota, mainly located in the colon, is engaged in a complex dialogue with the large intestinal epithelium through which important regulatory processes for the health and well-being of the host take place. Imbalances of the microbial populations, called dysbiosis, are related to several pathological status, emphasizing the importance of understanding the gut bacterial ecology. Among the ecological drivers of the microbiota, the spatial structure of the colon is of special interest: spatio-temporal mechanisms can lead to the constitution of spatial interactions among the bacterial populations and of environmental niches that impact the overall colonization of the colon. In the present study, we introduce a mathematical model of the colon microbiota in its fluid environment, based on the explicit coupling of a population dynamics model of microbial populations involved in fibre degradation with a fluid dynamics model of the luminal content. This modeling framework is used to study the main drivers of the spatial structure of the microbiota, specially focusing on the dietary fibre inflow, the epithelial motility, the microbial active swimming and viscosity gradients in the digestive track. We found 1) that the viscosity gradients allow the creation of favorable niches in the vicinity of the mucus layer; 2) that very low microbial active swimming in the radial direction is enough to promote bacterial growth, which sheds a new light on microbial motility in the colon and 3) that dietary fibres are the main driver of the spatial structure of the microbiota in the distal bowel whereas epithelial motility is preponderant for the colonization of the proximal colon; in the transverse colon, fibre levels and chemotaxis have the strongest impact on the distribution of the microbial communities.

In this paper, we employ the logistic map and the cubic map to locate the relaxation and the convergence to the periodic xed point of a system, speci cally, the period-1 xed point. e study has shown that the period-1 xed point of a logistic map as a recurrence has its convergence at a transcritical bifurcation having its power-law t with exponent β − 1 when α 1 and μ 0. e cubic map shows its convergence to the xed point at a pitchfork bifurcation decaying at a power law with exponent β − (1/2) α 1 and μ 0. However, the system shows their relaxation time at the same power law with exponents and z − 1.

Although originally characterised as a reproductive hormone, relaxin has emerged as a multi-functional endocrine and paracrine factor that plays a number of important roles in several organs, including the normal and diseased cardiovascular system. The recent discovery of the H3/ relaxin-3 gene, and the elusive receptors for relaxin (Relaxin family peptide receptor; RXFP1) and relaxin-3 (RXFP3/RXFP4) have led to the reclassification of a distinct relaxin peptide/receptor family. Additionally, the identification of relaxin and RXFP1 mRNA and/or relaxin binding sites in the heart and blood vessels has confirmed that the cardiovascular system is a target for relaxin peptides. While evidence for the production of relaxins within the cardiovascular system is limited, several studies have established that the relaxin genes are upregulated in the diseased human and rodent heart where they likely act as cardioprotective agents. The ability of relaxin to protect the heart is most likely mediated via its antifibrotic, anti-hypertrophic, anti-inflammatory and vasodilatory actions, but it may also directly stimulate myocardial regeneration and repair. This review describes relaxin and its primary receptor (RXFP1) in relation to the roles and effects of relaxin in the normal and pathological cardiovascular system. It is becoming increasingly clear that relaxin has a number of diverse physiological and pathological roles in the cardiovascular system that may have important therapeutic and clinical implications.

Introduction. The three effective, commercially available drugs for the treatment of erectile dysfunction-sildenafil, vardenafil, and tadalafil-inhibit the same substrate, the erectolytic enzyme phosphodiesterase type 5 (PDE5). Although there are pharmacological differences between these three compounds, few comparative studies have been conducted to date. Aim. The aim of this study was to determine the efficacy of sildenafil, tadalafil, and vardenafil in a randomly assigned 8-week fixed regimen. Methods. This was a spontaneous, open-label, randomized, multicenter, crossover study where the patients were randomized to receive sildenafil 50 mg, sildenafil 100 mg, tadalafil 20 mg, or vardenafil 20 mg. Main Outcome Measures. The primary outcome included the posttreatment analysis of erectile function domains of the abridged International Index of Erectile Function (IIEF5+1). The secondary objectives included the analysis of peak-systolic velocities (PSVs), end-diastolic velocities (EDVs), and resistive index (RI), and the estimate of the percentage of men with normal penile hemodynamic parameters after each treatment. Results. In all groups of patients taking sildenafil 50 mg, sildenafil 100 mg, tadalafil 20 mg, and vardenafil 20 mg at a frequency reflecting the common treatment regimens in real life, there was a statistically significant baseline-to-end point improvement in subjective perception of erectile function measured by IIEF5+1. When the four groups were compared, the treatments were not different in modifying IIEF5+1 and penile flow parameters. However, the within-group analysis showed that PSV improved in the sildenafil 50 mg group and that PSV together with RI