Second messenger systems underlying amine and peptide actions on cardiac muscle in the horseshoe crab, Limulus polyphemus

The biochemical mechanisms by which octopamine, catecholamines and the peptide proctolin exert their actions on Limulus cardiac muscle were investigated. Amines produced long-lasting increases in the amplitude of contractions evoked by electrical stimulation. At 10(−5) mol l-1, the apparent order of potency for amine-induced increases in evoked contraction amplitude was dopamine approximately equal to octopamine greater than norepinephrine approximately equal to epinephrine. At this dose, amines produced long-lasting increases in the levels of cyclic AMP (octopamine greater than dopamine approximately equal to norepinephrine approximately equal to epinephrine), but not of cyclic GMP, in Limulus cardiac muscle. Like the amines, the adenylate cyclase activator forskolin enhanced cardiac muscle contractility and increased levels of cyclic AMP, but not of cyclic GMP. The phosphodiesterase inhibitor IBMX produced a transient increase in cardiac muscle contractility, but typically produced long-lasting negative inotropy. This agent increased levels of both cyclic AMP and cyclic GMP in Limulus cardiac muscle. Proctolin and the protein kinase C activator phorbol dB increased the contraction amplitude of the intact heart and the electrically stimulated myocardium. These compounds, as well as dopamine, elicited sustained contractures and rhythmic contractions when applied to deganglionated Limulus cardiac muscle rings. Unlike the amines, proctolin and phorbol dB did not increase cardiac muscle cyclic AMP levels. These results suggest that several second-messenger systems may be utilized by amines and peptides to produce excitatory actions on cardiac muscle fibers of the Limulus heart. Cyclic AMP appears to be an important second messenger underlying the effects of amines to enhance cardiac muscle contractility. Pharmacological data suggest that proctolin may alter cardiac muscle contractility and excitability by a mechanism which involves the phosphatidylinositol pathway. Dopamine, unlike the other amines, produces a number of proctolin-like effects and may activate both the cyclic AMP and the phosphatidylinositol systems in Limulus cardiac muscle

Leche tenemos, pero ¿cómo vivir de ella?

Las últimas y controvertidas decisiones de la Unión Europea, que dejan el mercado de la leche totalmente desregulado, están provocando que el precio que paga la industria que recoge y procesa la leche a quien la produce esté en caída libre, muy por debajo de los costes de producción. En este contexto, las organizaciones de La Vía Campesina están llevando a cabo movilizaciones en toda Europa contra estas políticas. Este texto reflexiona sobre la importancia de transitar hacia modelos de pequeñas producciones, sostenibles y conectadas con la población

Social capital and the social economy in a sub-national island jurisdiction

This paper begins with an explanation of social capital and its manifestation in structures and institutes of the social economy. It then describes how Prince Edward Island (PEl) is using social capital in the pursuit of economic sustainability. Next, the paper explores case studies of other sub-national island jurisdictions (SNIJs) and highlights how PEl could learn from the successes and failures of these other islands. Finally, it generates suggestions on how to more effectively invest in, and use, social capital in public policy measures. While the paper concentrates on PEl and other semi-autonomous islands, the recommendations may have wider implications in, and for, other jurisdictions.peer-reviewe

Involvement of cyclic AMP in multiple, excitatory actions of biogenic amines on the cardiac ganglion of the horseshoe crab Limulus polyphemus

Cyclic AMP appears to be involved in several excitatory actions of amines on neurones of the Limulus cardiac ganglion. Amines selectively increase levels of cardiac ganglion cyclic AMP with a magnitude and time course similar to that observed for amine-induced excitation of cardiac ganglion burst rate. With respect to either the physiological or biochemical effect, the apparent order of potency is octoparnine\u3eepinephrine==dopamine\u3enorepinephrine. Elevation of cardiac ganglion cyclic AMP levels by octopamine or dopamine is dose-dependent and is potentiated by the phosphodiesterase inhibitor 3-isobutyl 1-methylxanthine (IBMX). Several pharmacological agents which influence cyclic nucleotide metabolism, including forskolin, IBMX and 8-substituted cyclic AMP analogues, have amine-like effects on the Limulus cardiac ganglion. These effects include increased burst rate of the isolated cardiac ganglion and decreased burst duration, interburst interval and number of spikes per burst in follower neurones. Forskolin and IBMX increase levels of cardiac ganglion cyclic AMP, and IBMX also increases cyclic GMP levels in this tissue. Amines, forskolin and IBMX have direct effects on follower neurones pharmacologically isolated from pacemaker cell input. Octopamine, forskolin and IBMX depolarize follower neurones, while dopamine hyperpolarizes these cells. Amines, forskolin and IBMX elicit burst-like potentials in follower neurones, and increase the size of evoked, unitary junction potentials recorded in cardiac muscle fibres. These pharmacological and biochemical data suggest that multiple, excitatory effects of biogenic amines on the Limulus cardiac ganglion are mediated by simultaneous increases in cyclic AMP at several loci within this neural network

Nivolumab and immune-mediated colitis

Nivolumab is associated with a number of immune-regulated adverse events, including immune-mediated colitis and may present following the discontinuation of treatment. Current guidance suggests lower doses of methylprednisolone; however, we described faster resolution of the patient's symptoms compared to previous reported cases, using higher dosing, thereby minimizing hospitalization.</p

The onset of classical QCD dynamics in relativistic heavy ion collisions

The experimental results on hadron production obtained recently at RHIC offer a new prospective on the energy dependence of the nuclear collision dynamics. In particular, it is possible that parton saturation -- the phenomenon likely providing initial conditions for the multi--particle production at RHIC energies -- may have started to set in central heavy ion collisions already around the highest SPS energy. We examine this scenario, and make predictions based on high density QCD for the forthcoming 22 GeV run at RHIC.Comment: 4 pages, 2 figures, revte

Laser aiming simulation /LASIM/ Final report, Feb. 1967 - May 1968

Laser aiming simulation models for synchronous satellite optical communication system

How random is your heart beat?

We measure the content of random uncorrelated noise in heart rate variability using a general method of noise level estimation using a coarse grained entropy. We show that usually - except for atrial fibrillation - the level of such noise is within 5 - 15% of the variance of the data and that the variability due to the linearly correlated processes is dominant in all cases analysed but atrial fibrillation. The nonlinear deterministic content of heart rate variability remains significant and may not be ignored.Comment: see http://urbanowicz.org.p

American college of radiology appropriateness criteria ® treatment of stage I T1 glottic cancer

Background Controversy surrounds the appropriate therapy for T1 glottic cancer. Both transoral endolaryngeal resection and radiation offer excellent local control and voice quality; some lesions are best addressed with resection and others with radiation. Methods The American College of Radiology (ACR) Appropriateness Criteria are evidence‐based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guideline development includes an analysis of current literature from peer reviewed journals and the well‐established “modified Delphi” consensus methodology to rate the appropriateness of treatment. Where evidence is not definitive, expert opinion informed recommendations. Results The ACR Expert Panel on Radiation Oncology – Head and Neck Cancer developed consensus recommendations for treatment of T1 glottic cancer. Treatment planning is complex and decisions nuanced. Conclusion Best treatment for a particular cancer cannot be defined without consideration of the lesion's location, extent, depth of invasion, and quality of surgical exposure during direct laryngoscopy. © 2013 American College of Radiology. Head & Neck © 2013 Wiley Periodicals, Inc. Head Neck 36 : 3–8, 2014Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102052/1/hed23381.pd