Haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure

AM5 (adrenomedullin 5), a newly described member of the CGRP (calcitonin gene-related peptide) family, is reported to play a role in normal cardiovascular physiology. The effects of AM5 in HF (heart failure), however, have not been investigated. In the present study, we intravenously infused two incremental doses of AM5 (10 and 100 ng/min per kg of body weight each for 90 min) into eight sheep with pacing-induced HF. Compared with time-matched vehicle control infusions, AM5 produced progressive and dose-dependent increases in left ventricular dP/dt(max) [LD (low dose), +56 mmHg/s and HD (high dose), +152 mmHg/s] and cardiac output (+0.83 l/min and +1.81 l/min), together with decrements in calculated total peripheral resistance (−9.4 mmHg/min per litre and −14.7 mmHg/min per litre), mean arterial pressure (−2.8 mmHg and −8.4 mmHg) and LAP (left atrial pressure; −2.6 mmHg and −5.6 mmHg) (all P<0.001). HD AM5 significantly raised PRA (plasma renin activity) (3.5-fold increment, P<0.001), whereas plasma aldosterone levels were unchanged over the intra-infusion period and actually fell in the post-infusion period (70% decrement, P<0.01), resulting in a marked decrease in the aldosterone/PRA ratio (P<0.01). Despite falls in LAP, plasma atrial natriuretic peptide and B-type natriuretic peptide concentrations were maintained relative to controls. AM5 infusion also induced significant increases in urine volume (HD 2-fold increment, P<0.05) and urine sodium (2.7-fold increment, P<0.01), potassium (1.7-fold increment, P<0.05) and creatinine (1.4-fold increment, P<0.05) excretion and creatinine clearance (60% increment, P<0.05). In conclusion, AM5 has significant haemodynamic, endocrine and renal actions in experimental HF likely to be protective and compensatory in this setting. These results suggest that AM5 may have potential as a therapeutic agent in human HF

Characterization and quantification of postharvest losses of apple fruit stored under commercial conditions.

The objectives of this study were to characterize and quantify postharvest losses of apples under commercial conditions in Santa Catarina state, Brazil. Two experiments were conducted using ?Gala? and ?Fuji? apples. The first experiment was to characterize and quantify the most important causes of loss of fruit treated or not treated with 1-methylcyclopropene (1-MCP) then held in controlled atmosphere (CA) storage. This experiment was conducted in commercial storage facilities from 2007 to 2010. In each year, 10 samples of &#8776;380 kg each for ?Gala? and 400 kg each for ?Fuji? were collected from bins of commercially harvested fruit from each of 15 ?Gala? and 17 ?Fuji? orchards. Half of the samples from each orchard were treated with 1-MCP at harvest. Fruit were stored in CA, at 0.7 °C, for 150 to 300 days. After storage, one subsample of 100 disorder-free apples were selected from each sample and held at 22 °C for 7 days to simulate shelf-life conditions. The fruit were analyzed after CA storage and shelf life for the incidence of disorders. The second experiment was conducted in 2011 to identify the main fungi causing decay during storage. In this study, apples were stored in 10 commercial CA storage rooms at 0.7 °C for 180 to 240 days. After storage, fruit with decay symptoms were collected at the commercial sorting line. A total of 10 samples of 100 decayed apples were taken throughout the sorting period for each cultivar and storage room. The fungal decays were identified by visual symptoms on each fruit. Total apple losses during storage varied from 3.9% to 12.1% for ?Gala? and 6.6% to 8.4% for ?Fuji?, depending on the year and 1-MCP treatment. During storage, deterioration caused by fungal decay was &#8776;60% and 80% of total losses for ?Gala? and ?Fuji?, respectively. During shelf life, additional losses caused by fungal decay ranged from 8.4% to 17.6% for ?Gala? and 12.4% to 27.2% for ?Fuji?, depending on the year. Senescent breakdown and superficial scald were the major physiological disorders. 1-MCP treatment had no effect on losses due to decay. Bull?s-eye rot, blue mold, gray mold, and alternaria rot were the most prevalent fungal decay symptoms, accounting for 52%, 27%, 9% and 10% of ?Gala? losses and 42%, 25%, 18% and 5% of ?Fuji? losses, respectively. Sources of variability for losses among years and orchards is discussed

Scope and Mechanistic Study of the Coupling Reaction of α,β-Unsaturated Carbonyl Compounds with Alkenes: Uncovering Electronic Effects on Alkene Insertion vs Oxidative Coupling Pathways

The cationic ruthenium-hydride complex [(C6H6)(PCy3)(CO)RuH]+BF4– (1) was found to be a highly effective catalyst for the intermolecular conjugate addition of simple alkenes to α,β-unsaturated carbonyl compounds to give (Z)-selective tetrasubstituted olefin products. The analogous coupling reaction of cinnamides with electron-deficient olefins led to the oxidative coupling of two olefinic C–H bonds in forming (E)-selective diene products. The intramolecular version of the coupling reaction efficiently produced indene and bicyclic fulvene derivatives. The empirical rate law for the coupling reaction of ethyl cinnamate with propene was determined as follows: rate = k[1]1[propene]0[cinnamate]−1. A negligible deuterium kinetic isotope effect (kH/kD = 1.1 ± 0.1) was measured from both (E)-C6H5CH═C(CH3)CONHCH3 and (E)-C6H5CD═C(CH3)CONHCH3 with styrene. In contrast, a significant normal isotope effect (kH/kD = 1.7 ± 0.1) was observed from the reaction of (E)-C6H5CH═C(CH3)CONHCH3 with styrene and styrene-d8. A pronounced carbon isotope effect was measured from the coupling reaction of (E)-C6H5CH═CHCO2Et with propene (13C(recovered)/13C(virgin) at Cβ = 1.019(6)), while a negligible carbon isotope effect (13C(recovered)/13C(virgin) at Cβ = 0.999(4)) was obtained from the reaction of (E)-C6H5CH═C(CH3)CONHCH3 with styrene. Hammett plots from the correlation of para-substituted p-X-C6H4CH═CHCO2Et (X = OCH3, CH3, H, F, Cl, CO2Me, CF3) with propene and from the treatment of (E)-C6H5CH═CHCO2Et with a series of para-substituted styrenes p-Y-C6H4CH═CH2 (Y = OCH3, CH3, H, F, Cl, CF3) gave the positive slopes for both cases (ρ = +1.1 ± 0.1 and +1.5 ± 0.1, respectively). Eyring analysis of the coupling reaction led to the thermodynamic parameters, ΔH⧧ = 20 ± 2 kcal mol–1 and ΔS⧧ = −42 ± 5 eu. Two separate mechanistic pathways for the coupling reaction have been proposed on the basis of these kinetic and spectroscopic studies

Storability of 'SCS417 Monalisa' apple as affected by harvest maturity, 1-methylcyclopropene treatment, and storage atmosphere.

The objective of this work was to determine the storability of 'SCS417 Monalisa' apple fruit in response to harvest maturity, 1-methylcyclopropene (1-MCP) treatment, and storage atmospheres. Fruit quality was evaluated after two, four, six, and eight months plus one day or seven days in shelf life at 22°C. The controlled atmosphere (CA) and 1-MCP (1.0 ?L L-1) treatments reduce fruit ethylene production and respiration, prevent rapid softening, and inhibit the incidence of scald-like symptoms, flesh browning, cracking, and fungal decay, in comparison with air storage . The combination of 1-MCP and CA provides additive benefits in firmness retention and in the reduction of the incidence of physiological disorders. CA and/or 1-MCP increase the risk of fruit developing wrinkly skin disorder. The loss of flesh firmness and acidity and the development of all physiological disorders and decay are higher in late-harvested fruit. The storage life of 'SCS417 Monalisa' apple is about two months in cold air and from six to eight months in cold CA, considering the time necessary to reach a flesh firmness of 53 N. The limiting factor for the long-term storage of 'SCS417 Monalisa' apple fruit under CA without 1-MCP is the development of physiological disorders and fungal decay

Molecular and functional interactions between tumor necrosis factor-alpha receptors and the glutamatergic system in the mouse hippocampus : implications for seizure susceptibility

Tumor necrosis factor (TNF)-alpha is a proinflammatory cytokine acting on two distinct receptor subtypes, namely p55 and p75 receptors. TNF-alpha p55 and p75 receptor knockout mice were previously shown to display a decreased or enhanced susceptibility to seizures, respectively, suggesting intrinsic modifications in neuronal excitability. We investigated whether alterations in glutamate system function occur in these naive knockout mice with perturbed cytokine signaling that could explain their different propensity to develop seizures. Using Western blot analysis of hippocampal homogenates, we found that p55(-/-) mice have decreased levels of membrane GluR3 and NR1 glutamate receptor subunits while GluR1, GluR2, GluR6/7 and NR2A/B were unchanged as compared to wild-type mice. In p75(-/-) mice, GluR2, GluR3, GluR6/7 and NR2A/B glutamate receptor subunits were increased in the hippocampus while GluR1 and NR1 did not change. Extracellular single-cell recordings of the electrical activity of hippocampal neurons were carried out in anesthetized mice by standard electrophysiological techniques. Microiontophoretic application of glutamate increased the basal firing rate of hippocampal neurons in p75(-/-) mice versus wild-type mice, and this effect was blocked by 2-amino-5-phosphopentanoic acid and 6-nitro-7-sulfamoyl-benzo(f)quinoxaline-2,3-dione denoting the involvement of N-methyl-D-aspartic acid and AMPA receptors. In p55(-/-) mice, hippocampal neurons responses to glutamate were similar to wild-type mice. Spontaneous glutamate release measured by in vivo hippocampal microdialysis was significantly decreased only in p55(-/-) mice. No changes were observed in KCl-induced glutamate release in both receptor knockout mice strains versus wild-type mice. These findings highlight specific molecular and functional interactions between p55 and p75 receptor-mediated signaling and the glutamate system. These interactions may be relevant for controlling neuronal excitability in physiological and pathological conditions.peer-reviewe

O2-Filled Swimbladder Employs Monocarboxylate Transporters for the Generation of O2 by Lactate-Induced Root Effect Hemoglobin

The swimbladder volume is regulated by O2 transfer between the luminal space and the blood In the swimbladder, lactic acid generation by anaerobic glycolysis in the gas gland epithelial cells and its recycling through the rete mirabile bundles of countercurrent capillaries are essential for local blood acidification and oxygen liberation from hemoglobin by the “Root effect.” While O2 generation is critical for fish flotation, the molecular mechanism of the secretion and recycling of lactic acid in this critical process is not clear. To clarify molecules that are involved in the blood acidification and visualize the route of lactic acid movement, we analyzed the expression of 17 members of the H+/monocarboxylate transporter (MCT) family in the fugu genome and found that only MCT1b and MCT4b are highly expressed in the fugu swimbladder. Electrophysiological analyses demonstrated that MCT1b is a high-affinity lactate transporter whereas MCT4b is a low-affinity/high-conductance lactate transporter. Immunohistochemistry demonstrated that (i) MCT4b expresses in gas gland cells together with the glycolytic enzyme GAPDH at high level and mediate lactic acid secretion by gas gland cells, and (ii) MCT1b expresses in arterial, but not venous, capillary endothelial cells in rete mirabile and mediates recycling of lactic acid in the rete mirabile by solute-specific transcellular transport. These results clarified the mechanism of the blood acidification in the swimbladder by spatially organized two lactic acid transporters MCT4b and MCT1b