Role of the gap junctions in the contractile response to agonists in pulmonary artery from two rat models of pulmonary hypertension

International audienceBackground: Pulmonary hypertension (PH) is characterized by arterial vascular remodelling and alteration in vascular reactivity. Since gap junctions are formed with proteins named connexins (Cx) and contribute to vasoreactivity, we investigated both expression and role of Cx in the pulmonary arterial vasoreactivity in two rat models of PH. Methods: Intrapulmonary arteries (IPA) were isolated from normoxic rats (N), rats exposed to chronic hypoxia (CH) or treated with monocrotaline (MCT). RT-PCR, Western Blot and immunofluorescent labelling were used to study the Cx expression. The role of Cx in arterial reactivity was assessed by using isometric contraction and specific gap junction blockers. Contractile responses were induced by agonists already known to be involved in PH, namely serotonin, endothelin-1 and phenylephrine. Results: Cx 37, 40 and 43 were expressed in all rat models and Cx43 was increased in CH rats. In IPA from N rats only, the contraction to serotonin was decreased after treatment with 37-43Gap27, a specific Cx-mimetic peptide blocker of Cx 37 and 43. The contraction to endothelin-1 was unchanged after incubation with 40Gap27 (a specific blocker of Cx 40) or 37-43Gap27 in N, CH and MCT rats. In contrast, the contraction to phenylephrine was decreased by 40Gap27 or 37-43Gap27 in CH and MCT rats. Moreover, the contractile sensitivity to high potassium solutions was increased in CH rats and this hypersensitivity was reversed following 37-43Gap27 incubation. Conclusion: Altogether, Cx 37, 40 and 43 are differently expressed and involved in the vasoreactivity to various stimuli in IPA from different rat models. These data may help to understand alterations of pulmonary arterial reactivity observed in PH and to improve the development of innovative therapies according to PH aetiology

Direct characterization of circulating DNA in blood plasma using μLAS technology

Circulating cell-free DNA (cfDNA) is a powerful cancer biomarker for establishing targeted therapies or monitoring patients' treatment. However, current cfDNA characterization is severely limited by its low concentration, requiring the extensive use of amplification techniques. Here we report that the μLAS technology allows us to quantitatively characterize the size distribution of purified cfDNA in a few minutes, even when its concentration is as low as 1 pg/μL. Moreover, we show that DNA profiles can be directly measured in blood plasma with a minimal conditioning process to speed up considerably speed up the cfDNA analytical chain

Primary cilia disappear in rat podocytes during glomerular development

Most tubular epithelial cell types express primary cilia, and mutations of primary-cilium-associated proteins are well known to cause several kinds of cystic renal disease. However, until now, it has been unclear whether mammalian podocytes express primary cilia in vivo. In this study, we determined whether primary cilia are present in the podocytes of rat immature and mature glomeruli by means of transmission electron microscopy of serial ultrathin sections. In immature glomeruli of fetal rats, podocytes express the primary cilia with high percentages at the S-shaped body (88 ± 5%, n = 3), capillary loop (95 ± 4%, n =  4), and maturing glomerulus (76 ± 13%, n = 5) stages. The percentage of ciliated podocytes was significantly lower at the maturing glomerulus stage than at the former two stages. In mature glomeruli of adult rats, ciliated podocytes were not found at all (0 ± 0%, n = 11). These findings indicate that the primary cilia gradually disappear in rat podocytes during glomerular development. Since glomerular filtration rate increases during development, the primary cilia on the podocytes are subjected to a stronger bending force. Thus, the disappearance of the primary cilia presumably prevents the entry of excessive calcium-ions via the cilium-associated polycystin complexes and the disturbance of intracellular signaling cascades in mature podocytes

Killer immunoglobulin-like receptor and human leukocyte antigen-C genotypes in rheumatoid arthritis primary responders and non-responders to anti-TNF-α therapy

The identification of patients who will respond to anti-tumor necrosis factor alpha (anti-TNF-α) therapy will improve the efficacy, safety, and economic impact of these agents. We investigated whether killer cell immunoglobulin-like receptor (KIR) genes are related to response to anti-TNF-α therapy in patients with rheumatoid arthritis (RA). Sixty-four RA patients and 100 healthy controls were genotyped for 16 KIR genes and human leukocyte antigen-C (HLA-C) group 1/2 using polymerase chain reaction sequence-specific oligonucleotide probes (PCR-SSOP). Each patient received anti-TNF-α therapy (adalimumab, etanercept, or infliximab), and clinical responses were evaluated after 3 months using the disease activity score in 28 joints (DAS28). We investigated the correlations between the carriership of KIR genes, HLA-C group 1/2 genes, and clinical data with response to therapy. Patients responding to therapy showed a significantly higher frequency of KIR2DS2/KIR2DL2 (67.7% R vs. 33.3% NR; P = 0.012). A positive clinical outcome was associated with an activating KIR–HLA genotype; KIR2DS2(+)HLA-C group 1/2 homozygous. Inversely, non-response was associated with the relatively inhibitory KIR2DS2(–)HLA-C group 1/2 heterozygous genotype. The KIR and HLA-C genotype of an RA patient may provide predictive information for response to anti-TNF-α therapy

Effects of cyclopiazonic acid and dexamethasone on serotonin-induced calcium responses in vascular smooth muscle cells

We previously observed that sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA) blockade by cyclopiazonic acid (CPA) significantly potentiates serotonin (5-hydroxytryptamine (5-HT))-induced vascular contractions. Furthermore, 5-HT receptor antagonist methysergide partially inhibited CPA-potentiated 5-HT contractions. In the present study, we further investigated whether SERCA inhibition potentiates 5-HT-induced Ca(2+) responses along with attenuating the receptor antagonism by store-operated Ca(2+) (SOC) entry and protein kinase C (PKC)-mediated mechanisms. The effects of dexamethasone that was previously shown to induce SOC entry and enhance 5-HT responses were also tested. For this purpose, intracellular Ca(2+) levels were monitored in A7r5 embryonic rat vascular smooth muscle cells by spectrofluorometry using the fluorescent indicator fura-2. The results showed that CPA, although not dexamethasone, significantly potentiated 5-HT-induced Ca(2+) elevations. Ketanserin partially decreased 5-HT-induced and CPA-potentiated Ca(2+) elevations whereas both PKC inhibitor D-sphingosine and SOC entry blocker 2-aminoethoxydiphenyl borate (2-APB) abolished the remaining responses. The data suggests that diminished antagonistic effect on 5-HT-induced Ca(2+) elevations in the presence of SERCA inhibition is induced by SOC entry and PKC activation

Coproduction of Hydrogen and Carbon Black from Natural Gas Cracking under Concentrated Solar Radiation

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Heat transfer model and scale-up of an entrained-flow solar reactor for the thermal decomposition of methane

International audienceEnergy Methane Hydrogen Carbon Reactor model a b s t r a c t The solar thermochemical decomposition of CH 4 is carried out in a solar reactor consisting of a cavity-receiver containing an array of tubular absorbers, through which CH 4 flows and thermally decomposes to H 2 and carbon particles. A reactor model is formulated by coupling radiation/convection/conduction heat transfer and chemical kinetics for a two-phase solid-gas reacting flow. Experimental validation is accomplished by comparing measured and simulated absorber temperatures and H 2 concentrations for a 10 kW prototype reactor tested in a solar furnace. The model is applied to optimize the design and simulate the performance of a 10 MW commercial-scale reactor mounted on a solar tower system configuration. Complete conversion is predicted for a maximum CH 4 mass flow rate of 0.70 kg s À1 and a desired outlet temperature of 1870 K, yielding a solar-to-chemical energy conversion efficiency of 42% and a solar-to-thermal energy conversion efficiency of 75%

Dynamic Simulations of Fresnel Solar Power Plants

AbstractAs solar energy is a variable power source, solar power plants are facing transients that are not experienced in conventional power plants such as nuclear or fossil ones. It is thus of primary importance to be able to simulate the dynamic behavior of the solar plants for their design and operation. The regulation modes have to be decided and the operation strategy has to be optimized. Using concentrated solar energy enables to convert solar power into heat before running thermodynamic cycles. Thermal inertia of the systems along with possible heat thermal storages help to smooth solar variations provided that these systems can be managed dynamically. Two solar power plants (with oil or water/steam as heat transfer fluid) are simulated with Dymola using Modelica code. The solar power plant using oil as heat transfer fluid is already running and preliminary results are compared with simulated data. Concerning the solar steam power plant, the model is run to investigate the regulation scheme of the plant that will be commissioned at the end of 2013. For both plant a DNI perturbation is tested and results are discussed concerning the system response and possible improvements