Kategoriarkiv: Forskning og artikler

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Understanding the rhythm of breathing: so near yet so far

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Nevner mange interessante prinsipper om pusten og hvordan dens rytmiske egenskaper regulerer kroppsfunksjoner.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671763/

Abstract
Understanding the mechanisms leading from DNA to molecules to neurons to networks to behavior is a major goal for neuroscience, but largely out of reach for many fundamental and interesting behaviors. The neural control of breathing may be a rare exception, presenting a unique opportunity to understand how the nervous system functions normally, how it balances inherent robustness with a highly regulated lability, how it adapts to rapidly and slowly changing conditions, and how particular dysfunctions result in disease. Why can we assert this? First and foremost, the functions of breathing are clearly definable, starting with its regulatory job of maintaining blood (and brain) O2, CO2 and pH; failure is not an option. Breathing is also an essential component of many vocal and emotive behaviors including, e.g., crying, laughing, singing, and sniffing, and must be coordinated with such vital behaviors as suckling and swallowing, even at birth. Second, the regulated variables, O2, CO2 and pH (and temperature in non-primate mammals), are continuous and are readily and precisely quantifiable, as is ventilation itself along with the underlying rhythmic motor activity, i.e., respiratory muscle EMGs. Third, we breathe all the time, except for short breaks as during breath-holding (which can be especially long in diving or hibernating mammals) or sleep apnea. Mammals (including humans) breathe in all behavioral states, e.g., sleep-wake, rest, exercise, panic, or fear, during anesthesia and even following decerebration. Moreover, essential aspects of the neural mechanisms driving breathing, including rhythmicity, are present at levels of reduction down to a medullary slice. Fourth, the relevant circuits exhibit a remarkable combination of extraordinary reliability, starting ex utero with the first air breath – intermittent breathing movements actually start in utero during the third trimester – and continuing for as many as ~109 breaths, as well as considerable lability, responding rapidly (in less than one second) and with considerable precision, over an order of magnitude in metabolic demand for O2 (~0.25 to ~5 liters of O2/min). Breathing does indeed persist! Finally, breathing is genetically determined to work at birth, with a well-defined developmental program underlying a neuroanatomical organization with apparent segregation of function, i.e., rhythmogenesis is separate from motor pattern (burst shape and coordination) generation. Importantly, single human gene mutations can affect breathing, and several neurodegenerative disorders compromise breathing by direct effects on brainstem respiratory circuits (See below).

 

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Evidence for surgery in degenerative lumbar spine disorders

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Nevner forskjellige kirurgiske inngrep og den svake effekten på korsryggsmerter.

Selbe Studien her: http://www.ncbi.nlm.nih.gov/pubmed/24315148

http://www.anatomy-physiotherapy.com/component/content/article/33-articles/systems/musculoskeletal/spine/lumbar/572-evidence-for-surgery-in-degenerative-lumbar-spine-disorders

Low Back Pain (LBP) has a high lifetime prevalence rate. This article reviews the available evidence on the effectiveness of surgical interventions for some conditions resulting in low back pain (LBP) or spine-related irradiating leg pain. The most important findings are presented below:

– The current evidence does not support surgery as effective treatment compared to high-intensity conservative interventions for the treatment of discogenic LBP without disc herniation or spinal stenosis.
– In patients with disc herniations surgery can lead to short-term benefits of leg pain, to a lesser extent for LBP. However, no difference between surgery and conservative treatment is present at the 1-year follow-up
– In spondylolisthesis (type II and III) surgery appears to lead to better clinical improvements compared to conservative treatment. Fusion appears to be superior to decompression techniques.
– In patients with degenerative spinal stenosis surgery resulting in better outcomes, both in leg pain and disability, compared to conservative interventions. However the evidence is not consistent and the quality of the studies was not all of high quality. > From: Jacobs et al., Beste Pract Res Clin Rheumatol 27 (2013) 673-84. All rights reserved to Elsevier Ltd.

 

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Evolution of Air Breathing: Oxygen Homeostasis and the Transitions from Water to Land and Sky

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Omfattende studie som beskriver hvordan vi har tilpasset oss høyere nivåer av oksygen. Bekrefter alle innspill jeg har hatt om oksygen sin destruktive effekt og at beskyttelsen mot oksygenets skadevirkninger er viktigere enn å få mer oksygen inn i kroppen. Lunger, sirkulasjonssystem, hemoglobin, antioksidantsystem og det at mitokondriene er godt gjemt inni en annen celle som er godt beskyttet av en tett cellevegg er forsvars- og reguleringsmekanismer mot det livsfarlige men også livsnødvendige oksygenet.

Nevner at den opprinnelige atmosfæren bestod av veldig lite O2(1-2% eller 2,4 mmHg) og mer enn dobbelt så mye CO2. Dette er miljøet mitokondriene ble utviklet i for 2,7 billioner år siden, og som de fortsatt lever i inni cellene våre. Om oksygennivået økes tilmer enn dette blir mitokondriene dårligere og mister sin funksjon.

Nevner også at forsvarsmekanismene mot oksygen var tilstede helt fra starten. Og hemoglobin (blodcelle i dyr) og klorofyll (i planter) tilfredstiller alle de nødvendige beskyttende egenskapene vi trenger mot oksygen.

Nevner at CO2 var den første antioksidanten i evolusjonen.

Beskriver også det som skjer i mitokondria, at hypoxi (lavere O2 tilgjengelighet) gir mindre ROS og økt mitochondrial uncoupling (produksjon av varme istedet for ATP). Vi kan se dette som om mitokondriene går på tomgang med lavt turtall, mens ATP produksjon er høyt turtall og dermed også mer slitasje.

Nevner også evolusjonen av diafragma som den primære pustemuskelen.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926130/

Abstract
Life originated in anoxia, but many organisms came to depend upon oxygen for survival, independently evolving diverse respiratory systems for acquiring oxygen from the environment. Ambient oxygen tension (PO2) fluctuated through the ages in correlation with biodiversity and body size, enabling organisms to migrate from water to land and air and sometimes in the opposite direction. Habitat expansion compels the use of different gas exchangers, for example, skin, gills, tracheae, lungs, and their intermediate stages, that may coexist within the same species; coexistence may be temporally disjunct (e.g., larval gills vs. adult lungs) or simultaneous (e.g., skin, gills, and lungs in some salamanders). Disparate systems exhibit similar directions of adaptation: toward larger diffusion interfaces, thinner barriers, finer dynamic regulation, and reduced cost of breathing. Efficient respiratory gas exchange, coupled to downstream convective and diffusive resistances, comprise the “oxygen cascade”—step-down of PO2 that balances supply against toxicity. Here, we review the origin of oxygen homeostasis, a primal selection factor for all respiratory systems, which in turn function as gatekeepers of the cascade. Within an organism’s lifespan, the respiratory apparatus adapts in various ways to upregulate oxygen uptake in hypoxia and restrict uptake in hyperoxia. In an evolutionary context, certain species also become adapted to environmental conditions or habitual organismic demands. We, therefore, survey the comparative anatomy and physiology of respiratory systems from invertebrates to vertebrates, water to air breathers, and terrestrial to aerial inhabitants. Through the evolutionary directions and variety of gas exchangers, their shared features and individual compromises may be appreciated.

Introduction

Oxygen, a vital gas and a lethal toxin, represents a trade-off with which all organisms have had a conflicted relationship. While aerobic respiration is essential for efficient metabolic energy production, a prerequisite for complex organisms, cumulative cellular oxygen stress has also made senescence and death inevitable. Harnessing the energy from oxidative phosphorylation while minimizing cellular stress and damage is an eternal struggle transcending specific organ systems or species, a conflict that shaped an assortment of gas-exchange systems.

The respiratory organ is the “gatekeeper” that determines the amount of oxygen available for distribution. Gas exchangers arose as simple air-blood diffusion interfaces that in active animals progressively gained in complexity in coordination with the cardiovascular system, leading to serial “step-downs” of oxygen tension to maintain homeostasis between uptake distribution and cellular protection.

While a comprehensive treatment of the evolutionary physiology of respiration is beyond the scope of any one article, here we focuses on the first step of the oxygen cascade—convection and diffusion in the gas-exchange organ—to provide an overview of the diversity of nature’s “solutions” to the dilemma of acquiring enough but not too much oxygen from the environment.

Ubiquity of Reactive Oxygen Species

As reviewed by Lane (407) and Maina (466), the primary atmosphere contained mainly nitrogen, carbon dioxide, and water vapor. Much of these were swept away by meteorite bombardment and replaced with a secondary atmosphere (416-418, 579, 590) consisting of hydrogen sulfide, cyanide, carbon monoxide, carbon doxide, methane, and more water vapor from volcanic eruptions. Only trace oxygen (<0.01% present atmospheric level) existed (418), originated from inorganic (photolysis and peroxy hydrolysis) (622) and organic (photosynthesis) sources.

Oxidative respiration is the reverse process as O2 accepts four electrons successively to form water. Many of these steps are catalyzed by transitional metal ions (e.g., iron, copper, and magnesium). Therefore, aerobic respiration, oxygen toxicity and radiation poisoning represent equivalent forms of oxidative stress (407).

Origin of Oxygen Sensing and Antioxidation—Metalloproteins

If oxidative stress was present from the beginning, early anaerobic organisms must have possessed effective antioxidant defenses, including mechanism(s) for controlled O2 sensing, storage, transport, and release as well as pathways for neutralizing ROS. The general class of compounds that fulfill these requirements is the metalloproteins that transfer electrons via transitional metals (766, 767), for example, heme proteins and chlorophyll (Fig. 2).

Hydrogen may have been the first electron donor and CO2 the first electron acceptor for synthesizing ATP by chemiosmosis (408).

Because of a high redox potential of O2 as the terminal electron acceptor in electron transport, aerobic respiration is far more efficient in energy production (36 moles of ATP per mole of glucose) than anaerobic respiration (~5 moles). Aerobic multicellular organisms arose approximately 1 Ga and more complex organisms such as marine molluscs thrived approximately 550 to 500 million years ago (Ma). Exposed to a still low O2 tension in the deep sea, these organisms uniformly possessed metalloprotein respiratory pigments with a characteristically high O2 affinity for efficient O2 storage and slow O2 release thereby avoiding flooding the cell with excessive ROS (783). Contemporary myoglobin continues to perform this regulatory function in muscle.

It is well recognized that embryos and undifferentiated cells grow better in a hypoxia (129, 153). A low O2 tension (1%-5%) is an important component of the embryonic and mesenchymal stem cell “niche” that maintains stem cell properties, minimizes oxidative stress, prevents chromosomal abnormalities, improves clonal survival, and perpetuates the undifferentiated characteristics (457). In addition, hypoxia stimulates endothelial cell proliferation, migration, tubulogenesis, and stress resistance (752, 850) as well as preferential growth and vascularization of many malignant tumor cells; the latter observation constitutes the basis for the use of adjuvant hyperoxia to enhance tumor killing during irradiation and chemotherapy (277,738). Collectively, these responses to O2 tension suggest that the pulmonary gas-exchange organs adapted in a direction toward controlled restriction of cellular exposure to O2.

Origin of the Oxygen Cascade

The oxygen cascade (Fig. 6) describes serial step-downs of O2 tension from ambient air through successive resistances across the pulmonary, cardiac, macrovascular and microvascular systems into the cell and mitochondria. These resistances adapt in a coordinated fashion in response to changes in ambient O2 availability or utilization (333). Traditional paradigm holds that the primary selection pressure in the evolution of O2 transport systems is the efficiency of O2 delivery to meet cellular metabolic demands. If this is the sole function of the cascade, why are there so many resistances? Once we accept the anaerobic origin of eukaryotes and their persistent preference for hypoxia, an alternative paradigm becomes plausible, namely, the entire oxygen cascade could be viewed as an elaborate gate-keeping mechanism the major function of which is to balance cellular O2 delivery against oxidative damage.

Mitochondria consume the majority of cellular O2, directly control intracellular O2 tension, and generate most of the cellular ROS (136). Intracellular O2 tension in turn regulates mitochondrial oxidative phosphorylation, ROS production, cell signaling, and gene expression. Via O2-dependent oxidative phosphorylation the mitochondria act as cellular O2 sensors in the regulation of diverse responses from local blood flow to electric activity (830). Earlier studies reported that hypoxia increases mitochondrial ROS generation (126, 782, 823) via several mechanisms: (i) O2 limitation at the terminal complex IV (cytochrome c oxidase) in the mitochondrial electron transport chain causes electrons to back up the chain with increased electron leak to form superoxide (•O2−). (ii) Hypoxia induces conformational changes in complex III (ubiquinol cytochrome c oxidoreductase) to enhance superoxide formation (88, 287). (iii) Oxidized cytochrome c scavenges superoxide (722). Hypoxia-induced O2 limitation at complex IV leads to cytochrome c reduction, limiting its ability to scavenge superoxide and enhancing mitochondrial ROS leakage. However, recent studies of isolated mitochondria show that hypoxia actually reduces mitochondrial ROS generation and causes mitochondrial uncoupling, suggesting extramitochondrial sources of ROS generation in hypoxia (330). These conflicting reports remain to be resolved. Nonetheless, moderate hypoxia rapidly and reversibly downregulates mitochondrial enzyme transcripts, in parallel with reductions in mitochondrial respiratory activity and O2 consumption (631).

As paleo-atmospheric O2 concentration increased and multicellular aerobic organisms arose, the endosymbiotic mitochondria-host relationship faced the challenge of balancing conflicting needs of aerobic energy generation for the host cell and anaerobic protection for its internal power generator. The host cell must finely control a constant supply of O2 to the mitochondria for oxidative phosphorylation while simultaneously protecting mitochondria against oxidative damage by maintaining a near-anoxic level of local O2 concentration. This trade-off may have led to the evolution of ever more elaborate physicochemical barriers that created and maintained successive O2 partial pressure gradients, by convection and diffusion in the lung, chemical binding to hemoglobin, distribution and release via cardiovascular delivery, dissociation from hemoglobin, and diffusion into peripheral cells with or without myoglobin facilitated transport. As a result, the primordial anoxic conditions of the Earth necessary for survival and optimal function of this proteobacterial remnant are preserved inside the host cell. In working human leg muscle O2 tension at the sarcoplasmic and mitochondrial boundaries has been estimated at approximately 2.4 mmHg (0.32 kPa) (835) and muscle mitochondrial O2 concentration at half-maximal metabolic rate 0.02 to 0.2 mmHg (834), that is, in the range of the ancient atmospheric level approximately 2 Ga. Raising O2 tension above these levels impairs mitochondrial activity (672). In this context, protection of mitochondria from O2 exposure likely constitutes a major selection factor in the evolution of complex aerobic life while the various forms of systemic O2 delivery systems are necessary but secondary functions that sustain the “gate-keeping” barrier apparatus to maintain adequate partial pressure gradients along the O2 transport cascade and preserve the near-anoxic intracellular conditions for the mitochondria. In parallel with physical barriers, cells also developed various biochemical scavenging and antioxidant pathways to counteract the toxic effects of ROS as ambient oxygenation increased.

Defense against the Dark Arts of Oxidation

To summarize, the evolution of life on Earth has adapted to a wide range of ambient O2 levels from 0% to 35%. Periods of relative hyperoxia promote biodiversity and gigantism but incur excess oxidative stress and mandating the upregulation of antioxidant defenses. Periods of relative hypoxia promote coordinated conservation of resources and downregulation of metabolic capacities to improve energy efficiency and channel some savings into compensatory growth of gas-exchange organs. The trajectory of early evolution is at least partly coupled to O2 content of the atmosphere and the deep ocean, and there is a plausible explanation for the coupling, namely, defense against the dark arts of oxidation. Oxygen is capable of giving and taking life. The anaerobic proteobacteria escaped the fate of annihilation by taking refuge inside another cell and in a brilliant evolutionary move coopted its own oxygen-detoxifying machinery to provide essential sustenance for the host cell in return for nourishment and physical protection from oxidation. As the threat of oxidation increased with rising environmental O2 concentration, selection pressure escalated for ever more sophisticated defense mechanisms against oxidative injury and in direct conflict with simultaneously escalating selection pressures to harness the energetic advantage of oxidative phosphorylation.

Trading off the above opposing demands shaped all known respiratory organs, from simple O2 diffusion across cell membranes to facilitated transport via O2 binding proteins to gas-exchange systems of varying complexity (skin, gills, tracheae, book lung, alveolar lung, and avian lung) (Sections 2-5). Concurrently evolving with a convective transport system, these increasingly elaborate respiratory organs not only increase O2 uptake but also maintain air-to-mitochondria O2 tension gradients and intracellular O2 fluxes at a hospitable ancestral level. This epic struggle began at the dawn of life and persisted to the present on a universal scale. The evolutionary trajectory of air breathing has continued contemporary significance to the understanding of oxygen-dependent metabolic homeostasis, especially in relation to maturation, senescence, and aging-related organ degeneration and disease.

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The role of hyperventilation – hypocapnia in the pathomechanism of panic disorder

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Her er en spennede studie som nevner at relasjonen mellom panikkanfall og hyperventillering kommer i utgangspunktet av metabolsk acidose, som er en kompensasjon for kronisk hyperventillering. Når CO2 synker øker nervesystemets sensitivitet til catacholaminer (stresshormoner som adrenalin og noradrenalin) og panikkanfallet kommer. I hyperkapnisk acidose (høy CO2) minker sensitiviteten til stresshormoner og kroppen beskyttes mot panikkanfall. Igjen en bekreftelse på at acidose fra CO2 er beskyttende, mens acidose fra andre ting er provoserende.

http://www.ncbi.nlm.nih.gov/pubmed/17713689

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462006005000048&lng=en&nrm=iso&tlng=en

OBJECTIVE: The authors present a profile of panic disorder based on and generalized from the effects of acute and chronic hyperventilation that are characteristic of the respiratory panic disorder subtype. The review presented attempts to integrate three premises: hyperventilation is a physiological response to hypercapnia; hyperventilation can induce panic attacks; chronic hyperventilation is a protective mechanism against panic attacks.
METHOD: A selective review of the literature was made using the Medline database. Reports of the interrelationships among panic disorder, hyperventilation, acidosis, and alkalosis, as well as catecholamine release and sensitivity, were selected. The findings were structured into an integrated model.
DISCUSSION: The panic attacks experienced by individuals with panic disorder develop on the basis of metabolic acidosis, which is a compensatory response to chronic hyperventilation. The attacks are triggered by a sudden increase in (pCO2) when the latent (metabolic) acidosis manifests as hypercapnic acidosis. The acidotic condition induces catecholamine release. Sympathicotonia cannot arise during the hypercapnic phase, since low pH decreases catecholamine sensitivity. Catecholamines can provoke panic when hyperventilation causes the hypercapnia to switch to hypocapnic alkalosis (overcompensation) and catecholamine sensitivity begins to increase.
CONCLUSION: Therapeutic approaches should address long-term regulation of the respiratory pattern and elimination of metabolic acidosis.

Chronic hyperventilation predisposes an individual to PD, since compensatory mechanisms (such as alterations in renal function and tissue buffer capacity) lead to chronic metabolic acidosis, which remains latent until it is activated by chronic hypocapnia.

Therefore, therapeutic approaches should address long-term regulation of respiratory patterns60 and elimination of metabolic acidosis.

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Tissue Oxygenation Response to Mild Hypercapnia during Cardiopulmonary Bypass with Constant Pump Output

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Nevner at oksygenering av vev ikke er pga CO2 sin vasodilerende effekt, men fra økt pumping av blod og høyre-skift av oksygendissassosiasjonskurven. Denne studien ga ikke økt oksygenering av vev når hjertets pumpeevne ble holdt konstant. Den påpeker at blodtrykk og hjerterytme ikke ble endret ved hyperkapni, selv om hjertets pumpeevne øker.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1464052/

It is well established that mild hypercapnia improves peripheral perfusion and increases tissue PO2. Our main question was whether peripheral vasodilation is a direct effect of the CO2 or a secondary result of increased cardiac output and related central autonomic homeostatic responses. We found that mild hypercapnia did not increase subcutaneous tissue oxygenation when systemic blood flow and mean arterial pressure remained constant during cardiopulmonary bypass. Increased tissue oxygenation during mild hypercapnia thus most likely results from a hyperdynamic circulatory response and shifting oxyhaemoglobin dissociation curve rather than direct peripheral vasodilation.

Hypercapnia increases both sympathetic and cardiac vagus nerve activity in anaesthetized dogs. Such co-activation of vagus and sympathetic systems, which can be initiated reflexively or by action on higher centres, has been shown to be of distinct physiological benefit in controlling reactions that relate cardiac function to body need. Since the sympathetic and parasympathetic systems are co-activated during systemic hypercapnia, blood pressure and heart rate response depends on the functional balance between these two systems. We were unable to evaluate heart rate during bypass, but have previously shown that both mean arterial blood pressure and heart rate remained essentially unchanged during hypercapnia even though cardiac output increases 25%.11

Thus, the vasodilator effect of CO2 is particularly marked in the cerebral circulation where a CO2 concentration of 7 to 10% nearly doubles cerebral blood flow (CBF) in humans,39 while mild hypercapnia (PaCO2 ~ 50 mmHg) impairs autoregulation of CBF and is associated with an overall increase in cerebral oxygenation.11, 40 A similar cerebrovascular response during cardiopulmonary bypass leads to an increase in CBF41 that is associated with a reduction in cerebral oxygen consumption.42 On the other hand, peripheral vasomotor tone during hypercapnia is essentially the result of a balance between the direct effects of CO2 and the level of sympathetic activity.38

The mechanism by which CO2 exerts its direct effects on the cerebral vasculature seems to involve nitric oxide (NO), ATP-sensitive potassium channels, and cyclooxygenase-dependent pathways. The CO2-NO axis is considered a cardinal pathway for CBF regulation in humans. Thus, although ATP-sensitive and Ca2+-activated potassium channels are also major systems that respond to hypercapnic acidosis, their response is incomplete in the absence of NO donors. In both animals43 and humans,44 hypercapnic vasodilatation is mediated by inhibition of nitric oxide synthase — the enzyme responsible for nitric oxide synthesis. It is probable that the vasodilation to hypercapnic acidosis is mediated either by increased synthesis of NO or increased sensitivity to NO.

However, 20 to 30 minutes is sufficient to obtain stable tissue oxygen values with tonometric systems that accommodate tissue oxygen probes.

 

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Breath-holding and its breakpoint

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Alt om hva som gjør at vi ikke greier å holde pusten lenge.

http://ep.physoc.org/content/91/1/1.long

This article reviews the basic properties of breath-holding in humans and the possible causes of the breath at breakpoint. The simplest objective measure of breath-holding is its duration, but even this is highly variable. Breath-holding is a voluntary act, but normal subjects appear unable to breath-hold to unconsciousness. A powerful involuntary mechanism normally overrides voluntary breath-holding and causes the breath that defines the breakpoint. The occurrence of the breakpoint breath does not appear to be caused solely by a mechanism involving lung or chest shrinkage, partial pressures of blood gases or the carotid arterial chemoreceptors. This is despite the well-known properties of breath-hold duration being prolonged by large lung inflations, hyperoxia and hypocapnia and being shortened by the converse manoeuvres and by increased metabolic rate.

Breath-holding has, however, two much less well-known but important properties. First, the central respiratory rhythm appears to continue throughout breath-holding. Humans cannot therefore stop their central respiratory rhythm voluntarily. Instead, they merely suppress expression of their central respiratory rhythm and voluntarily ‘hold’ the chest at a chosen volume, possibly assisted by some tonic diaphragm activity. Second, breath-hold duration is prolonged by bilateral paralysis of the phrenic or vagus nerves. Possibly the contribution to the breakpoint from stimulation of diaphragm muscle chemoreceptors is greater than has previously been considered. At present there is no simple explanation for the breakpoint that encompasses all these properties.

At breakpoint from maximum inflation in air, the Pa/etO2 is typically 62 ± 4 mmHg and the PetCO2 is typically 54 ± 2 mmHg (n = 5; Lin et al. 1974), and the longer the breath-hold the more they change.

Nunn (1987) estimates that consciousness in normal adults is lost at PaO2 levels below ∼27 mmHg and PaCO2 levels between 90 and 120 mmHg.

This is because the rhythmic EMG and negative pressure waves occur simultaneously, because their frequency and amplitude are within the respiratory range and because they increase as CO2 levels rise towards the end of the breath-hold. This CO2 rise would stimulate the central respiratory rhythm.

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Rapid changes in histone deacetylases and inflammatory gene expression in expert meditators.

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Om hvordan 1 hel dag med meditasjon endrer genene som styrer betennelser.

http://www.ncbi.nlm.nih.gov/pubmed/24485481/

Abstract

BACKGROUND:

A growing body of research shows that mindfulness meditation can alter neural, behavioral and biochemical processes. However, the mechanisms responsible for such clinically relevant effects remain elusive.

METHODS:

Here we explored the impact of a day of intensive practice of mindfulness meditation in experienced subjects (n=19) on the expression of circadian, chromatin modulatory and inflammatory genes in peripheral blood mononuclear cells (PBMC). In parallel, we analyzed a control group of subjects with no meditation experience who engaged in leisure activities in the same environment (n=21). PBMC from all participants were obtained before (t1) and after (t2) the intervention (t2-t1=8h) and gene expression was analyzed using custom pathway focused quantitative-real time PCR assays. Both groups were also presented with the Trier Social Stress Test (TSST).

RESULTS:

Core clock gene expression at baseline (t1) was similar between groups and their rhythmicity was not influenced in meditators by the intensive day of practice. Similarly, we found that all the epigenetic regulatory enzymes and inflammatory genes analyzed exhibited similar basal expression levels in the two groups. In contrast, after the brief intervention we detected reduced expression of histone deacetylase genes (HDAC 2, 3 and 9), alterations in global modification of histones (H4ac; H3K4me3) and decreased expression of pro-inflammatory genes (RIPK2 and COX2) in meditators compared with controls. We found that the expression of RIPK2 and HDAC2 genes was associated with a faster cortisol recovery to the TSST in both groups.

CONCLUSIONS:

The regulation of HDACs and inflammatory pathways may represent some of the mechanisms underlying the therapeutic potential of mindfulness-based interventions. Our findings set the foundation for future studies to further assess meditation strategies for the treatment of chronic inflammatory conditions.

 

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Cytokine Dysregulation, Inflammation and Well-Being

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Om hvordan cytokiner kobler nervesystem og immunsystem med betennelser. Den forteller at betennelser er utgangspunktet for de fleste livsstilsykdommer og smertetilstander som følge av autoimmunesykdommer.

http://www.karger.com/Article/Abstract/87104

Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis, health, and well-being. Like the stress response, the inflammatory reaction is crucial for survival and is meant to be tailored to the stimulus and time. A full-fledged systemic inflammatory reaction results in stimulation of four major programs: the acute-phase reaction, the sickness syndrome, the pain program, and the stress response, mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Common human diseases such as atopy/allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro- versus anti-inflammatory and T helper (Th)1versus Th2 cytokine balance. Recent evidence also indicates the involvement of pro-inflammatory cytokines in the pathogenesis of atherosclerosis and major depression, and conditions such as visceral-type obesity, metabolic syndrome and sleep disturbances. During inflammation, the activation of the stress system, through induction of a Th2 shift, protects the organism from systemic ‘overshooting’ with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-α and C-reactive protein production and through activation of the corticotropin-releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the ‘systemic anti-inflammatory feedback’ and/or ‘hyperactivity’ of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health. These hypotheses require further investigation, but the answers should provide critical insights into mechanisms underlying a variety of common human immune-related diseases.

 

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Free oxygen radicals in whole blood correlate strongly with high-sensitivity C-reactive protein.

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Nevner at mengden ROS (Reactive Oxygen Species) i blod korresponderer direkte til CRP, en betenneslsesmarkør.

http://www.ncbi.nlm.nih.gov/pubmed/21291700

BACKGROUND:

Increased concentrations of reactive oxygen molecules are believed to be a driving force in inflammation. Although evident in tissue culture and animal models, it has been difficult to link reactive oxygen species (ROS) and inflammatory markers in humans. In patients recruited to represent a broad spectrum of risk factors, we investigated the relationship between the plasma concentration of oxygen radicals and high-sensitivity C-reactive protein (hs-CRP), utilizing a new chemistry with an easily oxidized chromophore.

METHODS:

ROS and hs-CRP were measured in blood from 59 fasting subjects selected to have variable risk predicted by classical risk factors. ROS were determined using the free oxygen radical monitor, which is an indirect colorimetric assay for the concentration of hydroperoxides in whole blood.

RESULTS:

Using log transformation, the correlation between ROS and hs-CRP was r = 0.505 (P < 0.0001). This relationship between ROS and hs-CRP was comparable (r = 0.527, P = 0.001) in the subgroup not currently on statin therapy (n = 39). ROS were not correlated with Framingham risk, r = -0.027 (P = 0.84).

CONCLUSION:

ROS directly measured in human blood correlates strongly with hs-CRP.

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You May Need a Nerve to Treat Pain: The Neurobiological Rationale for Vagal Nerve Activation in Pain Management.

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Alt om hvordan vagus nerven demper smerte gjennom 5 mekanismer samtidig: dempe betennelser, dempe sympaticus aktivitet (fight-or-flight), redusere oksidativt stress, aktivere smertedempende områder i hjernen og utløse smertedempende opioider og cannabinoider i kroppen. Den bekrefter også at pusten stimulerer vagusnerven, spesielt når man puster med HRV-synkron pust slik vi gjør i Verkstedet Breathing System Autonom Pust.

http://www.ncbi.nlm.nih.gov/pubmed/24451632

Mer fra Studien her.

Abstract

Pain is a complex common health problem, with important implications for quality of life and with huge economic consequences. Pain can be elicited due to tissue damage, as well as other multiple factors such as inflammation and oxidative stress. Can there be one therapeutic pathway which may target multiple etiologic factors in pain? In the present article, we review evidence for the relationships between vagal nerve activity and pain, and between vagal nerve activity and five factors which are etiologic to or protective in pain. Specifically, vagal nerve activity inhibits inflammation, oxidative stress and sympathetic activity, activates brain regions that can oppose the brain «pain matrix», and finally it might influence the analgesic effects of opioids. Together, these can explain the anti-nociceptive effects of vagal nerve activation or of acetylcholine, the principal vagal nerve neurotransmitter. These findings form an evidence-based neurobiological rationale for testing and possibly implementing different vagal nerve activating treatments in pain conditions. Perspective: In this article, we show evidence for the relationships between vagal nerve activity and pain, and between vagal nerve activity and five factors which are etiologic to pain. Given the evidence and effects of the vagus nerve activation in pain, people involved in pain therapy may need to seriously consider activation of this nerve.