Urotensin II-Induced Increase in Myocardial Distensibility Is Modulated by Angiotensin II and Endothelin-1

Endogenous regulators, such as angiotensin-II (AngII), endothelin-1 (ET-1) and urotensin-II (U-II) are released from various cell types and their plasma levels are elevated in several cardiovascular diseases. The present study evaluated a potential crosstalk between these systems by investigating if the myocardial effects of U-II are modulated by AngII or ET-1. Effects of U-II (10(-8), 10(-7), 10(-6) M) were tested in rabbit papillary muscles in the absence and in the presence of losartan (selective AT, receptor antagonist), PD-145065 (nonselective ET-1 receptors antagonist), losartan plus PD-145065, AngII or ET-1. U-II promoted concentration-dependent negative inotropic and lusitropic effects that were abolished in all experimental conditions. Also, U-II increased resting muscle length up to 1.008 +/- 0.002 L/L(max). Correcting it to its initial value resulted in a 19.5 +/- 3.5 % decrease of resting tension, indicating increased muscle distensibility. This effect on muscle length was completely abolished in the presence of losartan and significantly attenuated by PD-145065 or losartan plus PD-145065. This effect was increased in the presence of AngII, resulting in a 27.5 +/- 3.9 % decrease of resting tension, but was unaffected by the presence of ET-1. This study demonstrated an interaction of the U-II system with the AngII and ET-1 systems in terms of regulation of systolic and diastolic function

Feohifomicosis Producida por Alternaria Infectoria con Presentación Clínica de Múltiples Lesiones Vegetantes en un Paciente Sometido a un Trasplante Renal

The genus Alternaria is one of the most common black moulds and appears to be increasing as a causative agent of subcutaneous phaeohyphomycosis, particularly among immunosuppressed patients. A 53-year-old patient who had received a kidney transplant presented with multiple verrucous lesions on the distal extremities. Positive histopathology and cultures, in addition to rDNA ITS region sequencing, identified the fungal isolate as Alternaria infectoria. Oral itraconazole was administered for 10 months. A follow-up at 15 months demonstrated no signs of infection. Clinical manifestations of cutaneous alternariosis vary significantly and only a few cases have been described in the literature. Although optimal treatment options remain controversial, this case of phaeohyphomycosis was successfully treated with itraconazole monotherapy

Heterotic domain wall solutions and SU(3) structure manifolds

We examine compactifications of heterotic string theory on manifolds with SU(3) structure. In particular, we study N = 1/2 domain wall solutions which correspond to the perturbative vacua of the 4D, N =1 supersymmetric theories associated to these compactifications. We extend work which has appeared previously in the literature in two important regards. Firstly, we include two additional fluxes which have been, heretofore, omitted in the general analysis of this situation. This allows for solutions with more general torsion classes than have previously been found. Secondly, we provide explicit solutions for the fluxes as a function of the torsion classes. These solutions are particularly useful in deciding whether equations such as the Bianchi identities can be solved, in addition to the Killing spinor equations themselves. Our work can be used to straightforwardly decide whether any given SU(3) structure on a six-dimensional manifold is associated with a solution to heterotic string theory. To illustrate how to use these results, we discuss a number of examples taken from the literature.Comment: 34 pages, minor corrections in second versio

An Introduction to EEG Source Analysis with an illustration of a study on Error-Related Potentials

International audienceOver the last twenty years blind source separation (BSS) has become a fundamental signal processing tool in the study of human electroencephalography (EEG), other biological data, as well as in many other signal processing domains such as speech, images, geophysics and wireless communication (Comon and Jutten, 2010). Without relying on head modeling BSS aims at estimating both the waveform and the scalp spatial pattern of the intracranial dipolar current responsible of the observed EEG, increasing the sensitivity and specificity of the signal received from the electrodes on the scalp. This chapter begins with a short review of brain volume conduction theory, demonstrating that BSS modeling is grounded on current physiological knowledge. We then illustrate a general BSS scheme requiring the estimation of second-order statistics (SOS) only. A simple and efficient implementation based on the approximate joint diagonalization of covariance matrices (AJDC) is described. The method operates in the same way in the time or frequency domain (or both at the same time) and is capable of modeling explicitly physiological and experimental source of variations with remarkable flexibility. Finally, we provide a specific example illustrating the analysis of a new experimental study on error-related potentials

Disseminated Well-Differentiated Gastro-Entero-Pancreatic Tumors Are Associated with Metabolic Syndrome

The association of well-differentiated gastro-entero-pancreatic neuroendocrine tumors (WD GEP-NETs) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. The aim of this study was to evaluate whether the presence of MetS or any MetS individual component was also influenced by GEP-NET characteristics at diagnosis. A cohort of patients with WD GEP-NETs (n = 134), classified according to primary tumor location (gastrointestinal or pancreatic), pathological grading (G1 (Ki67 ≤ 2%) and G2 (>3 ≤ 20%) (WHO 2010), disease extension (localized, loco-regional, and metastatic), and presence of hormonal secretion syndrome (functioning/non-functioning), was evaluated for the presence of MetS criteria. After adjustment for age and gender, the odds of having MetS was significantly higher for patients with WD GEP-NET grade G1 (OR 4.35 95%CI 1.30–14.53) and disseminated disease (OR 4.52 95%CI 1.44–14.15). GEP-NET primary tumor location or secretory syndrome did not influence the risk for MetS. None of the tumor characteristics evaluated were associated with body mass index, fasting plasma glucose category, or any of the individual MetS components. Patients with GEP-NET and MetS depicted a higher risk of presenting a lower tumor grade and disseminated disease. The positive association between MetS and GEP-NET characteristics further highlights the potential link between the two conditions.This work did not receive any funding either from public, commercial, or nonprofit agencies

Benign follicular tumors

Benign follicular tumors comprise a large and heterogeneous group of neoplasms that share a common histogenesis and display morphological features resembling one or several portions of the normal hair follicle, or recapitulate part of its embryological development. Most cases present it as clinically nondescript single lesions and essentially of dermatological relevance. Occasionally, however, these lesions be multiple and represent a cutaneous marker of complex syndromes associated with an increased risk of visceral neoplasms. In this article, the authors present the microscopic structure of the normal hair follicle as a basis to understand the type and level of differentiation of the various follicular tumors. The main clinicopathological features and differential diagnosis of benign follicular tumors are then discussed, including dilated pore of Winer, pilar sheath acanthoma, trichoadenoma, trichilemmoma, infundibuloma, proliferating trichilemmal cyst/tumor, trichoblastoma and its variants, pilomatricoma, trichodiscoma/fibrofolliculoma, neurofollicular hamartoma and trichofolliculoma. In addition, the main syndromes presenting with multiple follicular tumors are also discussed, namely Cowden, Birt-Hogg-Dubé, Rombo and Bazex-Dupré-Christol syndromes, as well as multiple tumors of follicular infundibulum (infundibulomatosis) and multiple trichoepitheliomas. Although the diagnosis of follicular tumors relies on histological examination, we highlight the importance of their knowledge for the clinician, especially when in presence of patients with multiple lesions that may be the cutaneous marker of a cancer-prone syndrome. The dermatologist is therefore in a privileged position to recognize these lesions, which is extremely important to provide further propedeutic, appropriate referral and genetic counseling for these patients.info:eu-repo/semantics/publishedVersio

Intricate macrophage-colorectal cancer cell communication in response to radiation

Both cancer and tumour-associated host cells are exposed to ionizing radiation when a tumour is subjected to radiotherapy. Macrophages frequently constitute the most abundant tumour-associated immune population, playing a role in tumour progression and response to therapy. The present work aimed to evaluate the importance of macrophage-cancer cell communication in the cellular response to radiation. To address this question, we established monocultures and indirect co-cultures of human monocyte-derived macrophages with RKO or SW1463 colorectal cancer cells, which exhibit higher and lower radiation sensitivity, respectively. Mono- and co-cultures were then irradiated with 5 cumulative doses, in a similar fractionated scheme to that used during cancer patients' treatment (2 Gy/fraction/day). Our results demonstrated that macrophages sensitize RKO to radiation-induced apoptosis, while protecting SW1463 cells. Additionally, the co-culture with macrophages increased the mRNA expression of metabolism- and survival-related genes more in SW1463 than in RKO. The presence of macrophages also upregulated glucose transporter 1 expression in irradiated SW1463, but not in RKO cells. In addition, the influence of cancer cells on the expression of pro- and anti-inflammatory macrophage markers, upon radiation exposure, was also evaluated. In the presence of RKO or SW1463, irradiated macrophages exhibit higher levels of pro-inflammatory TNF, IL6, CCL2 and CCR7, and of anti-inflammatory CCL18. However, RKO cells induce an increase of macrophage pro-inflammatory IL1B, while SW1463 cells promote higher pro-inflammatory CXCL8 and CD80, and also anti-inflammatory VCAN and IL10 levels. Thus, our data demonstrated that macrophages and cancer cells mutually influence their response to radiation. Notably, conditioned medium from irradiated co-cultures increased non-irradiated RKO cell migration and invasion and did not impact on angiogenesis in a chicken embryo chorioallantoic membrane assay. Overall, the establishment of primary human macrophage-cancer cell co-cultures revealed an intricate cell communication in response to ionizing radiation, which should be considered when developing therapies adjuvant to radiotherapy

Randomised short-term trial of high-span versus low-span APAP for treating sleep apnoea

PURPOSE: Auto-titrating continuous positive airway pressure (APAP) devices were developed to improve treatment efficacy and compliance in patients with obstructive sleep apnoea syndrome (OSAS). Since there are insufficient data on the optimal pressure range setting, we aimed to compare the adherence, efficacy and tolerability of treatment with high-span versus low-span APAP. METHODS: Seventy-six newly diagnosed OSAS patients fulfilling the treatment criteria were randomised to receive high-span (HS, range 4-15cmH2O, n?=?38) or low-span (LS, range 8-12cmH2O, n?=?38) APAP. Patients were assessed at 1 and 3 months. RESULTS: Median Epworth sleepiness scale (ESS) was 13 (IQR, 6-16) and median apnoea-hypopnoea index (AHI) was 35.9 (IQR, 27.6-56.3). There were no significant differences in baseline demographic and clinical characteristics between groups. Overall, no significant differences were found at the first month assessment. After 3 months of therapy, we found again no differences in residual AHI or ESS. However, the group HS proved less adherent than group LS, respectively, with median 87 % (IQR, 60.5-97.5) versus 94 % (IQR, 80.0-98.3) of the nights using =4 h (P?=?0.014) and mean (±SD) usage 5.7?±?1.6 versus 6.4?±?1.2 h/night (P?=?0.049). The group HS reported more frequently nasal congestion, excessive oronasal dryness and nocturnal awakenings of at least moderate intensity, the latter with statistical significance (P?=?0.005). CONCLUSIONS: Both pressure ranges appear to be equally effective to correct AHI and to improve symptoms. Though, patients with high-span APAP were less compliant to treatment, raising issues about the tolerability of wide pressure range settings of these devices.T Pinto has received financial support from Linde and Vitalaire (Healthcare Providers) for attending symposia and honoraria for speaking at symposia from Philips. After the conclusion of the study, JC Winck has started working in a global position for Linde. The remaining authors declare that they have no conflict of interest

Detection of antibodies to Toxoplasma gondii in neotropical primates from São Paulo state, Brazil

ΔΕΝ ΔΙΑΤΙΘΕΤΑΙ ΠΕΡΙΛΗΨΗToxoplasmosis is a life-threatening disease in neotropical primates. The aim of the present study was to determine the frequency of antibodies to Toxoplasma gondii in neotropical primates from São Paulo state (SP), Brazil. The modified agglutination test (MAT, cut-off: 25) was used in 49 neotropical primates upon or after their admission to Associação Mata Ciliar (Jundiaí, SP, Brazil). Eight of the 49 animals (16.3%) were seropositive. The genus Sapajus had the highest antibody titer (12,800), followed by the genus Callithrix (3,200). No association (p> 0.05) was found between seroprevalence and genera (Alouatta, Callicebus, Callithrix, and Sapajus), sex or age. The three positive primates of the genera Allouataand the one of the genera Callithrix died, whereas the two seropositive Sapajus were alive. Further studies on the epidemiology of T. gondii infection are necessary in a larger sample size of captive and wild neotropical primates