Phosphodiesterase-4 inhibition improves corticosteroid insensitivity in pulmonary endothelial cells under oxidative stress.

Several clinical studies have shown that smoking in asthmatics and chronic obstructive pulmonary disease patients is closely associated with corticosteroid refractoriness. In this work, we have analyzed glucocorticoid insensitivity in human pulmonary artery endothelial cells (HPAECs) under cigarette smoke extract (CSE) exposure as well as the possible additive effects of the combination therapy with a phosphodiesterase (PDE)-4 inhibitor. Interleukin (IL)-8 was measured in cell supernatants by ELISA. Histone deacetylase (HDAC), histone acetylase (HAT), and intracellular cAMP levels were measured by colorimetric assays and enzyme immunoassay, respectively. PDE4 isotypes and glucocorticoid rec…

Description of a new species: Dorylaimus parasiticus , a parasite of amphibians in the Iberian Peninsula (Nematoda: Dorylaimida)

Dorylaimus parasiticussp. nov. (Nematoda: Dorylaimidae) si described from the digestive tract and general body cavity of Salamandra salamandra, Rana perezi, and Bufo bufo, amphibians of the Iberian Peninsula (Spain). This is the first record of a member of the Order Dorylaimida size, a thick transversely striated body cuticle with 20 to 26 longitudinal ridges.

Helminth fauna of the invasive American red-eared sliderTrachemys scriptain eastern Spain: potential implications for the conservation of native terrapins

AbstractIn this study we report on the helminth fauna of the invasive American red-eared slider Trachemys scripta in five localities from eastern Spain where this species co-occurs with two native, endangered freshwater turtles, i.e. Emys orbicularis and Mauremys leprosa. In total, 46 individuals of T. scripta were analysed for parasites. Adult individuals of three helminth species were found: the monogenean Neopolystoma orbiculare, the digenean Telorchis solivagus and the nematode Serpinema microcephalus. Telorchis solivagus and S. microcephalus are trophically transmitted parasites of native turtles that probably infected T. scripta through shared infected prey. Neopolystoma orbiculare in…

The component helminth community in six sympatric species of Ardeidae.

We studied the helminth communities in 6 sympatric species of Ardeidae (Ixobrychus minutus (Linnaeus, 1766), Nycticorax nycticorax (Linnaeus, 1758), Bubulcus ibis (Linnaeus, 1758), Egretta garzetta (Linnaeus, 1766), Ardea cinerea (Linnaeus, 1758), and Ardea purpurea (Linnaeus, 1766)) from "La Albufera de Valencia," Spain. The survey revealed 13 species of helminth parasites: 5 digeneans, 2 cestodes, and 6 nematodes. The component helminth communities of the Ardeidae examined are depauperate and conform to the pattern typically found in isolationist communities, probably because of their high trophic dependence on a few prey species. Evenness was positively correlated with richness and abund…

Paracrobeles psammophilus sp. nov. (Nematoda: Cephalobidae) from El Saler, Valencia (Spain)

Paracrobeles psammophilus sp. nov. (Nematoda: Cephalobidae) is described from soil of the Dehesa de El Saler (province of Valencia, Spain). This is the second record of a species of the genus Paracrobeles Heyns, 1968. The new species is characterized by rounded cheilorhabdions and the large spicules and gubernaculum of males.

Roflumilast N-oxide reverses corticosteroid resistance in neutrophils from patients with chronic obstructive pulmonary disease

Background Glucocorticoid functions are markedly impaired in patients with chronic obstructive pulmonary disease (COPD). The phosphodiesterase 4 inhibitor roflumilast N-oxide (RNO) is the active metabolite of roflumilast approved as a treatment to reduce the risk of exacerbations in patients with severe COPD. Objective We sought to characterize the differential effects of RNO versus corticosteroids and their potential additive/synergistic effect in neutrophils from patients with COPD, thus providing scientific rationale for the combination of roflumilast with corticosteroids in the clinic. Methods Peripheral blood neutrophils were isolated from patients with COPD (n = 32), smokers (n = 7), …

Oxidative stress-induced glucocorticoid resistance is prevented by dual PDE3/PDE4 inhibition in human alveolar macrophages

Summary Background Oxidative stress is present in airway diseases such as severe asthma or Chronic Obstructive Pulmonary Disease and contributes to the low response to glucocorticoids through the down-regulation of histone deacetylase (HDAC) activity. Objective To study the effects of the phosphodiesterase (PDE)-3 and 4 inhibitors and their combination vs. glucocorticoids in a model of lipopolysaccharide (LPS)-induced cytokine release in alveolar macrophages under oxidative stress conditions. Methods Differentiated U937 or human alveolar macrophages were stimulated with H2O2 (10–1000 μm) or cigarette smoke extract (CSE, 0–15%) for 4 h before LPS (0.5 μg/mL, 24 h) addition. In other experime…

Role of dopamine and glutamate receptors in cocaine-induced social effects in isolated and grouped male OF1 mice.

Cocaine administration in paired male mice decreases social contacts as well as increases avoidance and flee elements. As dopamine (DA) and glutamate seem to be involved in some of cocaine's effects, an attempt was made to assess whether a range of associated receptors influenced the social impacts of this drug of abuse. The NMDA antagonist memantine (10 and 40 mg/kg); the AMPA antagonist CNQX (1 and 20 mg/kg); the DA release inhibitor CGS 10746b (2 and 8 mg/kg): the DA D1 antagonist SCH 23390 (0.05 and 0.5 mg/kg); and the DA D2/D3 antagonist raclopride (0.03 and 0.3 mg/kg) were administered prior to 25 mg/kg of cocaine and behaviour was evaluated during an encounter between an experimental…

Cocaine exposure during adolescence affects anxiety in adult mice.

Psychostimulant drugs such as cocaine have profound and long-lasting neurobiological effects, which may affect anxiety or social behaviors. These actions could be greater when cocaine is administered during a developmental period such as adolescence. The present work attempts to further clarify the long-lasting effects of cocaine administration on mice, examining three major variables: age; pattern of drug administration; and housing conditions. Adolescent (postnatal day 26) or early adult mice (postnatal day 46) were exposed to a daily or binge cocaine administration and 15 days later their behavior was evaluated, the mice being housed either in isolation or in groups during this stage. Af…

Multilocus and morphological analysis of south‐eastern Iberian Wall lizards (Squamata,Podarcis)

The phylogenetic relationships among the wall lizards of the Podarcis hispanicus complex that inhabit the south-east (SE) of the Iberian Peninsula and other lineages of the complex remain unclear. In this study, four mitochondrial and two nuclear markers were used to study genetic relationships within this complex. The phylogenetic analyses based on mtDNA gene trees constructed with ML and BI, and a species tree using *BEAST support three divergent clades in this region: the Valencia, Galera and Albacete/Murcia lineages. These three lineages were also corroborated in species delimitation analyses based on mtDNA using bPTP, mPTP, GMYC, ABGD and BAPS. Bayesian inference species delimitation m…

Anti-Inflammatory Effect Of Roflumilast N-Oxide In Glucocorticoid Insensitive Human Neutrophils From Chronic Obstructive Pulmonary Disease Patients