Kategoriarkiv: Forskning og artikler

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HIF-1α and HIF-2α induce angiogenesis and improve muscle energy recovery.

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HIF er et signalmolekyl som aktiverer angiogenese, altså produksjonen av nye blodkar. Ved lave oksygennivåer økes HIF. Dette kan komme fra trening, men også fra øvelser med å holde pusten.

http://www.ncbi.nlm.nih.gov/pubmed/25208310

Abstract

BACKGROUND:

Cardiovascular patients suffer from reduced blood flow leading to ischemia and impaired tissue metabolism. Unfortunately, an increasing group of elderly patients cannot be treated with current revascularization methods. Thus, new treatment strategies are urgently needed. Hypoxia inducible factors (HIFs) upregulate the expression of angiogenic mediators together with genes involved in energy metabolism and recovery of ischemic tissues. Especially, HIF-2α is a novel factor and only limited information is available about its therapeutic potential.

METHODS:

Gene transfers with adenoviral HIF-1α and HIF-2α were done into the mouse heart and rabbit ischemic hindlimbs. Angiogenesis was evaluated by histology. Left ventricle function was analysed with echocardiography. Perfusion in rabbit skeletal muscles and energy recovery after electrical stimulation-induced exercise were measured with ultrasound and 31 P-magnetic resonance spectroscopy (31 P-MRS), respectively.

RESULTS:

HIF-1α and HIF-2α gene transfers increased capillary size up to 5-fold in myocardium and ischemic skeletal muscles. Perfusion in skeletal muscles was increased by 4-fold without edema. Especially AdHIF-1α enhanced the recovery of ischemic muscles from electrical stimulation-induced energy depletion. Special characteristic of HIF-2α gene transfer was a strong capillary growth in muscle connective tissue and that HIF-2α gene transfer maintained left ventricle function.

CONCLUSIONS:

We conclude that both AdHIF-1α and AdHIF-2α gene transfers induced beneficial angiogenesis in vivo. Transient moderate increases in angiogesis improved energy recovery after exercise in ischemic muscles. This study shows for the first time that a moderate increase in angiogenesis is enough to improve tissue energy metabolism which is potentially a very useful feature for cardiovascular gene therapy.

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Postural function of the diaphragm in persons with and without chronic low back pain.

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Denen Studien beskriver på en svært god måte hvordan diafragmas posisjon og bevegelse kan relateres til ryggplager. Når diafragm får lite bevegelse, spesielt i de fremre og mitre delene, blir vinkelen diafragma står i kroppen brattere. Dette kobles til ryggsmerter. Jo brattere vinkelen er, jo større sjangse for ryggsmerter. Bildene viser hvordan diafragma beveger seg mindre og står høyere opp i kroppen hos det med kroniske ryggsmerter. Den viser også hvordan største delen av bevegelsen i diafragma skjer på bakre del, ikke fremre eller midtre, men ved korsryggplager blir det minst bevegelse i fremre og midtre del, mens bakre del har lige god bevegelse. Spesielt interessant å legge merke til er at den viser ingen forskjell mellom Control og Patients diafragma bevegelse under Tidal Breathing (abdominal pust). Dette viser at for å øke styrke og bevegelse i diafragma må man ta i mer. Abdominal pust er ikke diafragma trening.

http://www.ncbi.nlm.nih.gov/pubmed/22236541/

Hele her: http://www.rehabps.cz/data/JOSPT.pdf

Abstract

STUDY DESIGN:

A case-control study.

OBJECTIVES:

To examine the function of the diaphragm during postural limb activities in patients with chronic low back pain and healthy controls.

BACKGROUND:

Abnormal stabilizing function of the diaphragm may be an etiological factor in spinal disorders. However, a study designed specifically to test the dynamics of the diaphragm in chronic spinal disorders is lacking.

METHODS:

Eighteen patients with chronic low back pain due to chronic overloading, as ascertained via clinical assessment and magnetic resonance imaging, and 29 healthy subjects were examined. Both groups presented with normal pulmonary function test results. A dynamic magnetic resonance imaging system and specialized spirometric readings were used with subjects in the supine position. Measurements during tidal breathing (TB) and isometric flexion of the upper and lower extremities against external resistance with TB were performed. Standard pulmonary function tests, including respiratory muscle drive (PI(max) and PE(max)), were also assessed.

RESULTS:

Using multivariate analysis of covariance, smaller diaphragm excursions and higher diaphragm position were found in the patient group (P<.05) during the upper extremity TB and lower extremity TB conditions. Maximum changes were found in costal and middle points of the diaphragm. A 1-way analysis of covariance showed a steeper slope in the middle-posterior diaphragm in the patient group both in the upper extremity TB and lower extremity TB conditions (P<.05).

CONCLUSION:

Patients with chronic low back pain appear to have both abnormal position and a steeper slope of the diaphragm, which may contribute to the etiology of the disorder.

 

Perhaps the most clinically important finding of this study concerns the ab- normal coordination of the diaphragm in the patient group during inspiration with postural tasks. This impairment was demonstrated by reduced move- ment of the diaphragm in the anterior and middle portion, while the posterior (crural) part moved in the same manner as in the control group. This pattern of diaphragmatic recruitment resulted in a steeper angle in the middle-posterior part of the diaphragm (FIGURE 4), which may exacerbate the symptomology of chronic low back pain by increasing the anterior shear forces on the ventral region of the spinal column.

Poor coordination of particular di- aphragmatic parts in the patients (points B and C) resulted in an asymmetric dia- phragmatic activation during inspiration, as demonstrated by a steeper slope of the crural part of the diaphragm. Evidently, limited motion of the costal part may result in a more domed inspiratory diaphragmatic position.

In healthy subjects, the diaphragm is able to perform the dual task (trunk stability and respiration) when trunk stability is challenged.19 Generally, dur- ing any body movement, with activation of the extremities during weight-bearing or weight-lifting activities and transi- tional movements, there is simultaneous spinal bracing and transdiaphragmatic pressure elevation.11,22 Intra-abdominal pressure increases, with a simultaneous decrease of intrapleural pressure, during a contraction of both the posterior (cru- ral) and anterior (costal) portions of the diaphragm.7 This coordination may be compromised in patients with chronic low back pain.

CONCLUSION

We found reduced diaphragm movement when isometric flexion against resistance of the up- per or lower extremities was applied. The combined, more cranial position in the anterior and middle portions of the diaphragm and, particularly, the steeper slope between the middle and crural por- tions of the diaphragm in patients with chronic low back pain may contribute to low back pain symptoms. However, given that the results are based on cross- sectional analysis, we cannot exclude the possibility of reverse causation. Still, the results support the theory that patients with low back pain complaints present with compromised diaphragm function, which may play an important role in pos- tural stability.

KEY POINTS

FINDINGS: We found reduced diaphragm movement in patients with chronic low back pain compared to healthy controls when isometric flexion against resis- tance of the upper or lower extremity was applied, mainly in the anterior

and middle portions. This pattern of diaphragmatic recruitment resulted in
a steeper angle in the middle-posterior part of the diaphragm and likely a great- er strain during activity on the ventral region of the spinal column. IMPLICATIONS: Abnormal postural activa- tion of the diaphragm during the pos- tural task of isometric resistance to the extremities may serve as 1 underlying mechanism of chronic low back pain. CAUTION: Only an isolated analysis of the diaphragm excursion was performed, due to the limited field of view. In ad- dition, the diaphragm excursion alone may not be sufficient to understand all mechanical actions of the rib cage and related musculature. We used a con- venience sample in which the patient and control groups differed in size and certain demographic characteristics. Because our study was cross-sectional in nature, we cannot exclude the possibil- ity that low back pain symptoms may be indicative of an initial pathogenic insult resulting in secondary quantitative as well as qualitative adaptive changes in diaphragmatic function.

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Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans

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Denne viser hvordan selv de uten diabetes får økt cytokinverdi (betennelse) i blodet i 1-2 timer etter blodsukkerstigning. I denne studien var det snakk om blodsukker over 15 mmol/L. De sier at blodsukker økninger påvirker cytokinnivået mer enn et stabilt høyt blodsukker.

http://circ.ahajournals.org/content/106/16/2067.full

Control Subjects:

Plasma IL-6 levels rose from a basal value of 2.0±0.7 pg/mL to a peak of 3.1±0.9 pg/mL at 1 hour (P<0.01) and returned to basal level at 3 hours (Figure 2).

Fasting plasma TNF-α levels were 3.3±1.2 pg/mL; they peaked at 1 hour (4.9±1.4 pg/mL, P<0.01), and returned to baseline at 3 hours.

Plasma IL-18 levels rose from a basal value of 116±28 pg/mL to a peak of 140±31 pg/mL at 2 hours (P<0.01) and returned to basal levels at 3 hours (110±26 pg/mL).

The novel findings of the present study were that (1) acute hyperglycemia in control and in IGT subjects induces an increase in plasma IL-6, TNF-α, and IL-18 concentrations; (2) the effect of sustained hyperglycemia is reproduced by transient oscillations in plasma glucose and is amplified by the IGT status; and (3) the antioxidant glutathione completely prevents the rise in plasma cytokines induced by hyperglycemia. These results indicate that hyperglycemic spikes affect cytokine concentrations more than continuous hyperglycemia, at least in the short term, and suggest that an oxidative mechanism mediates the effect of hyperglycemia.

Another finding of the present study was that glutathione, a powerful antioxidant, completely prevented cytokine increase induced by oscillatory hyperglycemia in healthy humans. Hyperglycemia-induced oxidative stress, 32 along with soluble advanced glycation end products and products of lipid peroxidation, possibly serves as a key activator of upstream kinases, leading to induction of inflammatory gene expression.33

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Inflammation-induced hyperalgesia: Effects of timing, dosage, and negative affect on somatic pain sensitivity in human experimental endotoxemia.

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En studie til som bekrefter at lav-grads betennelse gir hyperalgesi, altså økt smerteopplevelse.

http://www.ncbi.nlm.nih.gov/pubmed/24814500

Abstract

BACKGROUND:

Inflammation-induced pain amplification and hypersensitivity play a role in the pathophysiology of numerous clinical conditions. Experimental endotoxemia has recently been implemented as model to analyze immune-mediated processes in human pain. In this study, we aimed to analyze dose- and time-dependent effects of lipopolysaccharide (LPS) on clinically-relevant pain models for musculoskeletal and neuropathic pain as well as the interaction among LPS-induced changes in inflammatory markers, pain sensitivity and negative affect.

METHODS:

In this randomized, double-blind, placebo-controlled study, healthy male subjects received an intravenous injection of either a moderate dose of LPS (0.8ng/kg Escherichiacoli), low-dose LPS (0.4ng/kg), or saline (placebo control group). Pressure pain thresholds (PPT), mechanical pain sensitivity (MPS), and cold pain sensitivity (CP) were assessed before and 1, 3, and 6h post injection to assess time-dependent LPS effects on pain sensitivity. Plasma cytokines (TNF-α, IL-6, IL-8, IL-10) and state anxiety were repeatedly measured before, and 1, 2, 3, 4, and 6h after injection of LPS or placebo.

RESULTS:

LPS administration induced a systemic immune activation, reflected by significant increases in cytokine levels, body temperature, and negative mood with pronounced effects to the higher LPS dose. Significant decreases of PPTs were observed only 3h after injection of the moderate dose of LPS (0.8ng/kg). MPS and CP were not affected by LPS-induced immune activation. Correlation analyses revealed that decreased PPTs were associated with peak IL-6 increases and negative mood.

CONCLUSIONS:

Our results revealed widespread increases in musculoskeletal pain sensitivity in response to a moderate dose of LPS (0.8ng/kg), which correlate both with changes in IL-6 and negative mood. These data extend and refine existing knowledge about immune mechanisms mediating hyperalgesia with implications for the pathophysiology of chronic pain and neuropsychiatric conditions.

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Systemic Inflammation Decreases Pain Threshold in Humans In Vivo

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Denne viser hvordan systemisk betennelse, til og med lav-grads systemisk betennelse (som kommer fra kosthold), bidrar til å øke smertesensitivitet.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866228/

In conclusion, this study shows that systemic inflammation elicited by the administration of endotoxin to humans, results in lowering of the pain threshold measured by 3 quantitative sensory testing techniques. The current work provides additional evidence that systemic inflammation is accompanied by changes in pain perception.

Inflammation leads to a broad constellation of adaptive changes, called the ‘sickness response’. Features of this response include fever, increased sleep, decreased locomotion, decreased food and water intake, and hormonal changes [1]. Furthermore, the pain threshold for painful stimuli is lowered, resulting in hyperalgesia, and normally non-painful stimuli can become painful (allodynia).

Systemic inflammation has previously been shown to alter pain perception in animals and humans. Recently, Benson and colleagues reported altered pain perception after the administration of a very low dose of endotoxin (0.4 ng/kg) to healthy volunteers, mimicking low grade systemic inflammation [26].

 

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Hyperglycemia enhances the cytokine production and oxidative responses to a low but not high dose of endotoxin in rats.

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Denne beskriver hvordan hyperglycemi (regnes som blodsukker over 7 mmol/L i lengre perioder, eller fastende blodsukker over 7) gir økt cytokin-aktivitet i flere timer etter en stressende episode. Om man spiser en snickers går blodsukkeret opp til over 10, og om man kontinuerlig spiser mat som øker blodsukkeret er det en stor sjangse for at man har en kronisk betennelsesreaskjon med økt cytokin aktivitet.

Kobler vi det med denne, som nevner at cytokiner tilført fra utenfor muskelen kan gi hyperalgesi, så begynner bildet å bli klarere: «One mechanism of action, the immune-to-brain communication through activation of brain and spinal cord glial cells was reviewed by Wieseler-Frank et al. (2005). Activation of CNS glia and subsequent production of inflammatory cytokines can lead to hyperalgesia.» http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1552097/

Abstract

OBJECTIVE:

The aim of this study was to investigate whether hyperglycemia enhances the systemic inflammatory response and oxidative stress induced by endotoxin.

DESIGN:

Laboratory investigation.

SETTING:

University medical school.

SUBJECTS:

Forty-one male Sprague-Dawley rats.

INTERVENTIONS:

A hyperglycemic condition was produced in rats by glucose clamp for 3 hrs. Immediately on stopping the glucose infusion, animals received different doses of endotoxin injection (0, 0.2, or 1 mg/kg), and then blood glucose concentration was monitored over the ensuing 2 hrs. At the end of 2 hrs, levels of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, corticosterone, and alpha-1 acid glycoprotein were determined in serum, and malondialdehyde and total glutathione content were determined in the liver.

MEASUREMENTS AND MAIN RESULTS:

Over the 2-hr period, blood glucose concentrations returned to normal in initially hyperglycemic rats. However, the levels of cytokines, corticosterone, and alpha-1 acid glycoprotein were significantly higher in these animals compared with nonhyperglycemic controls, demonstrating an extended effect of prior hyperglycemia on markers of systemic inflammation. With low-dose (0.2 mg/kg) but not high-dose (1 mg/kg) endotoxin administration, hyperglycemic animals had significantly higher levels of cytokines compared with controls, indicating that prior hyperglycemia can enhance the systemic inflammatory response to a moderate endotoxin dose, but that the maximum effects of endotoxin on production of inflammatory cytokines are not altered by transient high glucose exposure.

CONCLUSIONS:

Systemic inflammation persists for a period following hyperglycemia, and this can enhance the systemic inflammatory response to a subsequent moderate stress.

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Noen studier om hvordan Substans P forholder seg til mat

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Denne nevner at en 10% reduksjon av anbefalt daglig magnesium inntakt øker sjangsen for osteoporose og Substans P

Bone Loss Induced by Dietary Magnesium Reduction to 10% of the Nutrient Requirement in Rats Is Associated with Increased Release of Substance P and Tumor Necrosis Factor-α1 

http://jn.nutrition.org/content/134/1/79.long

These data demonstrated that a Mg intake of 10% of NR in rats causes bone loss that may be secondary to the increased release of substance P and TNF-α.

Denne nevner hvordan tiltak som reduserer SP bidrar til å redusere de negative virkningene av magnesiummangel.

Neurogenic Inflammation and Cardiac Dysfunction due to Hypomagnesemia.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753099/

Significant protection against most of these MgD-mediated events has been observed with interventions that modulate neuronal SP release or its bioactivity, and with several antioxidants (vitamin E, probucol, epicaptopril, d-propranolol). In view of the clinical prevalence of hypomagnesemia, new treatments, beyond magnesium repletion, may be needed to diminish deleterious neurogenic and prooxidative components described in this article.

Denne nevner hvordan SP er involvert i insulin regulering og diabetes.

Role of Substance P in the Regulation of Glucose Metabolism via Insulin Signaling-Associated Pathways

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230056/

Our results demonstrate an important role for SP in adipose tissue responses and obesity-associated pathologies. These novel SP effects on molecules that enhance insulin resistance at the adipocyte level may reflect an important role for this peptide in the pathophysiology of type 2 diabetes.