Interaction between cholinergic and nitrergic vasodilation: a novel mechanism of blood pressure control

Objective: Cholinergic vasodilation has been thought to play little if any role in the regulation of blood pressure in humans. Autonomic denervation potentiates the vasoconstriction evoked by nitric oxide synthase inhibition in humans, but the mechanism is unclear. We hypothesized that this may be related to loss of neuronal, non-nitric-oxide-dependent vasodilation. Methods: To test this hypothesis, we examined effects of cholinergic blockade on blood pressure, heart rate and peripheral vascular responses to systemic infusion of the nitric-oxide-dependent vasoconstrictor l-NMMA (0.5 mg/kg/min over 15 min) in eight normal subjects. Results: The l-NMMA-induced increase in mean (±S.E.) arterial pressure was roughly three times larger (P=0.002) in the presence than in the absence of cholinergic blockade (38±6 vs. 13±2 mmHg). Similarly, the increase in systemic and calf vascular resistance was more than twofold larger during l-NMMA-atropine. This potentiation was specific for nitric-oxide-dependent vasoconstriction, because atropine did not alter the responses to phenylephrine infusion. Cholinergic blockade also altered (P=0.004) the heart rate response to nitric oxide synthase inhibition; during l-NMMA alone heart rate decreased by 10±2 beats/min, whereas during l-NMMA-atropine infusion it increased by 14±4 beats/min. Conclusion: Cholinergic mechanisms play an important hitherto unrecognized role in offsetting the hypertension and cardiac sympathetic activation caused by nitric oxide synthase inhibition in humans. Decreased parasympathetic activity and impaired nitric oxide synthesis characterize several cardiovascular disease states, as well as normal aging. The conjunction of these two defects could trigger sudden death and contribute to the hypertension of the elderl

Sympathectomy potentiates the vasoconstrictor response to nitric oxide synthase inhibition in humans

Objective: Nitric oxide exerts its cardiovascular actions at least in part by modulation of the sympathetic vasoconstrictor tone. There is increasing evidence that nitric oxide inhibits central neural sympathetic outflow, and preliminary evidence suggests that it may also modulate peripheral sympathetic vasoconstrictor tone. Methods: To test this latter concept, in six subjects having undergone thoracic sympathectomy for hyperhydrosis, we compared the vascular responses to systemic l-NMMA infusion (1mg/kg/min over 10 min) in the innervated and the denervated limb. We also studied vascular responses to the infusion of the non-nitric-oxide-dependent vasoconstrictor phenylephrine. Results: l-NMMA infusion evoked a roughly 3-fold larger increase in vascular resistance in the denervated forearm than in the innervated calf. In the denervated forearm, vascular resistance increased by 58±10 percent (X±SE), whereas in the innervated calf it increased only by 21±6 percent (P<0.01, forearm vs. calf). This augmented vasoconstrictor response was specific for l-NMMA, and not related to augmented non-specific vasoconstrictor responsiveness secondary to sympathectomy, because phenylephrine infusion increased vascular resistance similarly in the denervated forearm and the innervated calf (by 24±7, and 29±8 percent, respectively). The augmented vasoconstrictor response was related specifically to denervation, because in control subjects, the vasoconstrictor responses to l-NMMA were comparable in the forearm and the calf. Conclusions: These findings indicate that in the absence of sympathetic innervation, the vasoconstrictor responses to nitric oxide synthase inhibition are augmente

An Integrated Approach to Strategic Asset Management

This paper focuses on identifying and analysing the elements of Strategic Management for infrastructure and engineering assets. These elements are contended to involve an understanding of governance, corporate policy, corporate objectives, corporate strategy and interagency collaboration and will in turn, allow the ability determine a broader and more comprehensive framework for engineering asset management, ie a ‘staged approach’ to understanding how assets are managed within organisations. While the assets themselves have often been the sole concern for good management practices, other social and contextual elements have come into the mix in order to promote strategic asset management. The development of an integrated approach to asset management is at the base of the research question. What are the considerations and implications for adopting and implementing an integrated strategic asset management (ISAM) framework? While operational matters have been given prominence, a subset of corporate governance, Asset Governance, details the policies and processes needed to acquire, utilise, maintain and account for an organisation’s assets. Asset governance stems from the organisation’s overarching corporate governance principles; as a result it defines the management context in which engineering asset management is implemented. This aspect will be examined to determine the appropriate relationship between organisational strategic management and strategic asset management to further the theoretical engagement with the maturity of strategy,policy and governance for infrastructure and engineered assets. Asset governance stems from the organisation’s overarching corporate governance principles; as a result it defines the management context in which engineering asset management is implemented. The research proceeds by a document analysis of corporate reports and policy recommendations in terms of infrastructure and engineered assets. The paper concludes that incorporating an integrated asset management framework can promote a more robust conceptualisation of public assets and how they combine to provide a comprehensive system of service outcomes

Memories of the world of the mountains

This paper describes a particular book called Souvenirs du monde des montagnes, which draws its iconography from the history of a Swiss mountain family from 1910 to 1930. By simply dipping into the first few pages, the reader will be lost between real and virtual universes, wonder about the evolution of the images' meanings, and question an object's true content. This setup, developed using state-of-the-art computer vision technology, offers unprecedented freedom: we can make technological references disappear to place the user in fruitful turmoil between visible and hidden meanings. The shadow of a bird flies over the pages, foxes' lanterns light up the text, paper mountains emerge. Once the last page has been turned, the reader will never look at books in the same way again

A Comparison of Professional Traders and Psychopaths in a Simulated Non-Zero Sum Game

In a prior study psychopathic individuals showed a diminished level of cooperativeness but realized higher individual rewards in a prisoner’s dilemma game, compared with community controls. The present study replicated this finding with professional bank traders, who exhibited less cooperative behavior than both of the aforermentioned groups (community controls and psychopathic patients). While the bank traders did not obtain a higher gain than the psychopathic individuals at an absolute level, they maximized the discrepancy between their own profit and the yield of their anonymous computerized gaming partner. The bank traders were more prone than psychopathic patients to rely on strategies that considerably harmed the profit of their gaming partners without necessarily optimizing their own total profit. The community controls achieved the same overall gain as traders and psychopaths. Unlike traders and psychopathic patients, the normal controls balanced overall gains of themselves and their game opponent, which led to the highest overall profit, whereas the traders achieved the lowest overall profit

Recommendations for the application and follow-up of quality controls in medical laboratories

This is a translation of the paper “Recommendations for the application and follow-up of quality controls in medical biology laboratories” published in French in the journal Annales de Biologie Clinique (Recommandations pour la mise en place et le suivi des contrôles de qualité dans les laboratoires de biologie médicale. Ann Biol Clin (Paris). 2019;77:577-97.). The recommendations proposed in this document are the result of work conducted jointly by the Network of Accredited Medical Laboratories (LABAC), the French Society of Medical Biology (SFBC) and the Federation of Associations for External Quality Assessment (FAEEQ). The different steps of the implementation of quality controls, based on a risk analysis, are described. The changes of reagent or internal quality control (IQC) materials batches, the action to be taken in case of non-conform IQC results, the choice of external quality assessment (EQA) scheme and interpretation of their results as well as the new issue of analyses performed on several automatic systems available in the same laboratory are discussed. Finally, the concept of measurement uncertainty, the robustness of the methods as well as the specificities of near-patient testing and rapid tests are described. These recommendations cannot apply for all cases we can find in medical laboratories. The implementation of an objective alternative strategy, supported with documented evidence, might be equally considered

Ribonuclease inhibitor 1 regulates erythropoiesis by controlling GATA1 translation.

Ribosomal proteins (RP) regulate specific gene expression by selectively translating subsets of mRNAs. Indeed, in Diamond-Blackfan anemia and 5q- syndrome, mutations in RP genes lead to a specific defect in erythroid gene translation and cause anemia. Little is known about the molecular mechanisms of selective mRNA translation and involvement of ribosomal-associated factors in this process. Ribonuclease inhibitor 1 (RNH1) is a ubiquitously expressed protein that binds to and inhibits pancreatic-type ribonucleases. Here, we report that RNH1 binds to ribosomes and regulates erythropoiesis by controlling translation of the erythroid transcription factor GATA1. Rnh1-deficient mice die between embryonic days E8.5 and E10 due to impaired production of mature erythroid cells from progenitor cells. In Rnh1-deficient embryos, mRNA levels of Gata1 are normal, but GATA1 protein levels are decreased. At the molecular level, we found that RNH1 binds to the 40S subunit of ribosomes and facilitates polysome formation on Gata1 mRNA to confer transcript-specific translation. Further, RNH1 knockdown in human CD34+ progenitor cells decreased erythroid differentiation without affecting myelopoiesis. Our results reveal an unsuspected role for RNH1 in the control of GATA1 mRNA translation and erythropoiesis