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18 avril 2011 1 18 /04 /avril /2011 11:08

Neuroimmunomodulation.2006;13(5-6):337-46. Epub 2007 Aug 6.

Stress and wound healing.

Christian LM, Graham JE, Padgett DA, Glaser R, Kiecolt-Glaser JK.

Department of Molecular Virology, Immunology, and Medical Genetics, Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA. christian.109@osu.edu


Over the past decade it has become clear that stress can significantly slow wound healing:

stressors ranging in magnitude and duration impair healing in humans and animals.

For example, in humans, the chronic stress of caregiving as well as the relatively brief stress of academic examinations impedes healing.

Similarly, restraint stress slows healing in mice.

The interactive effects of glucocorticoids (e.g. cortisol and corticosterone) and proinflammatory cytokines [e.g. interleukin-1beta (IL-1beta), IL-1alpha, IL-6, IL-8, and tumor necrosis factor-alpha] are primary physiological mechanisms underlying the stress and healing connection.

The effects of stress on healing have important implications in the context of surgery and naturally occurring wounds, particularly among at-risk and chronically ill populations.

In research with clinical populations, greater attention to measurement of health behaviors is needed to better separate behavioral versus direct physiological effects of stress on healing.

Recent evidence suggests that interventions designed to reduce stress and its concomitants (e.g., exercise, social support) can prevent stress-induced impairments in healing.

Moreover, specific physiological mechanisms are associated with certain types of interventions. In future research, an increased focus on mechanisms will help to more clearly elucidate pathways linking stress and healing processes.


Copyright (c) 2006 S. Karger AG, Basel.

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18 avril 2011 1 18 /04 /avril /2011 10:21

Psychosom Med. 2007 Apr;69(3):217-24. Epub 2007 Mar 30.

Depressive symptoms, omega-6:omega-3 fatty acids, and inflammation in older adults.

Kiecolt-Glaser JK, Belury MA, Porter K, Beversdorf DQ, Lemeshow S, Glaser R.

Department of Psychiatry, Ohio State University College of Medicine, 1670 Upham Drive, Columbus, OH 43210, USA. Kiecolt-Glaser.1@osu.edu

OBJECTIVE: To address how interactions between polyunsaturated fatty acid (PUFA) levels and depressive symptoms were related to proinflammatory cytokine synthesis. Depression and stress promote proinflammatory cytokine production. Dietary intakes of omega-3 (n-3) and omega-6 (n-6) PUFAs also influence inflammation; high n-6:n-3 ratios enhance proinflammatory cytokine production, although n-3 has anti-inflammatory properties.

METHODS: Blood samples from 43 older adults (mean age = 66.67 years, SD = 10.09) provided data on PUFAs and tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-6 soluble receptor (sIL-6r). Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale.

RESULTS: Depressive symptoms and n-6:n-3 ratios worked together to enhance proinflammatory cytokines beyond the contribution provided by either variable alone, with substantial variance explained by their interaction: 13% for IL-6 and 31% for TNF-alpha, whereas full models accounted for 18% and 40%, respectively. Although predicted cytokine levels were consistent across n-6:n-3 ratios with low depressive symptoms, higher n-6:n-3 ratios were associated with progressively elevated TNF-alpha and IL-6 levels as depressive symptoms increased. Higher levels of sIL-6r were associated with higher n-6:n-3 ratios. Six individuals who met the criteria for major depressive disorder had higher n-6:n-3 ratios and TNF-alpha, IL-6, and sIL-6r levels than those who did not meet the criteria; excluding these six individuals reduced the variance explained by the depressive symptoms and n-6:n-3 ratio interaction.

CONCLUSIONS: Diets with high n-6:n-3 PUFA ratios may enhance the risk for both depression and inflammatory diseases.




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18 avril 2011 1 18 /04 /avril /2011 10:18

Brain Behav Immun. 2008 Feb;22(2):215-23. Epub 2007 Sep 12.

Epstein-Barr virus-encoded dUTPase enhances proinflammatory cytokine production by macrophages in contact with endothelial cells: evidence for depression-induced atherosclerotic risk.

Waldman WJ, Williams MV Jr, Lemeshow S, Binkley P, Guttridge D, Kiecolt-Glaser JK, Knight DA, Ladner KJ, Glaser R.

Department of Pathology, The Ohio State University Medical Center, Columbus, OH 43210, USA.


Increased levels of proinflammatory cytokines, TNF-alpha and IL-6, predict mortality and morbidity. In cardiovascular disease patients, they are observed in atherosclerotic lesions and serum.


Factors behind the increased levels of these cytokines are multifaceted and may include latent herpesviruses, such as Epstein-Barr virus (EBV) that can be reactivated by stress.


Previously, we showed that the EBV-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTPase), a protein synthesized in the early phase of virus replication, can induce human monocytes/macrophages to produce TNF-alpha and IL-6. In this study, we modeled the interactions that take place between macrophages and endothelial cells in vivo using human umbilical vein endothelial cells (HUVEC).


HUVEC were stimulated by soluble factors induced by EBV dUTPase-treated monocyte-derived macrophages (MDM) that resulted in the upregulation of VCAM-1 and ICAM-1.

These changes were related to MDM production of TNF-alpha following the activation of NF-kappaB.

In a previous study, chronically stressed dementia caregivers had elevations in plasma IL-6 levels, a risk for cardiovascular disease.

We found a relationship between plasma IL-6 levels and neutralizing antibody titers to EBV dUTPase suggesting that one source of the plasma IL-6 observed in our previous study could be related to the effect of EBV-encoded dUTPase on macrophages.


The results suggest that EBV-encoded dUTPase can enhance production of proinflammatory cytokines by monocytes/macrophages in contact with endothelial cells of blood vessels, and may play a role in cardiovascular pathology and chronic inflammation.

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18 avril 2011 1 18 /04 /avril /2011 10:07

Health Psychol. 2009 Sep;28(5):621-30.

Cognitive word use during marital conflict and increases in proinflammatory cytokines.

Graham JEGlaser RLoving TJMalarkey WBStowell JRKiecolt-Glaser JK.

Department of Biobehavioral Health, 315 East Health and Human Development Building, The Pennsylvania State University, University Park, PA 16802, USA. jeg32@psu.edu

OBJECTIVE: To examine whether greater cognitive engagement during a marital conflict discussion, as evidenced by use of words that suggest thinking and meaning-making, results in attenuated proinflammatory cytokine increases to stress and wounding.

DESIGN: Husbands and wives (N = 84 individuals) were observed during two separate 24-hr visits: each visit included a wounding procedure, which was followed by a nonconflictive marital discussion (first visit) and a conflictive marital discussion (second visit).

MAIN OUTCOME MEASURES: Serum proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha).

RESULTS: Individuals who used more cognitive processing words during the conflict discussion (but not the nonconflictive discussion) showed smaller increases in serum IL-6 and TNF-alpha over 24 hours; they also had lower levels of both cytokines 24 hours after baseline controlling for demographics, hostility, depressed mood, positive and negative interactions, and marital quality.

Effects of word use were not mediated by ruminative thoughts after conflict. Although both men and women benefited from their own cognitive engagement, only husbands' IL-6 patterns were affected by spouses' engagement.

CONCLUSION: In accord with research demonstrating the value of cognitive processing in emotional disclosure, this research suggests that productive communication patterns may help mitigate the adverse effects of relationship conflict on inflammatory dysregulation.

PMID: 19751089 [PubMed - indexed for MEDLINE]

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18 avril 2011 1 18 /04 /avril /2011 10:02

Psychosom Med. 2010 May;72(4):365-9. Epub 2010 Apr 21.

Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge.

Kiecolt-Glaser JK.

Department of Psychiatry, The Ohio State Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, Columbus, Ohio 43210-1228, USA. Janice.Kiecolt-Glaser@osumc.edu

Inflammation is the common link among the leading causes of death.


Mechanistic studies have shown how various dietary components can modulate key pathways to inflammation,

including sympathetic activity,

oxidative stress,

transcription factor nuclear factor-kappaB activation,

and proinflammatory cytokine production.


Behavioral studies have demonstrated that stressful events and depression can also influence inflammation through these same processes.


If the joint contributions of diet and behavior to inflammation were simply additive, they would be important.


However, several far more intriguing interactive possibilities are discussed:

stress influences food choices;

stress can enhance maladaptive metabolic responses to unhealthy meals;

and diet can affect mood as well as proinflammatory responses to stressors.


Furthermore, because the vagus nerve innervates tissues involved in the digestion, absorption, and metabolism of nutrients, vagal activation can directly and profoundly influence metabolic responses to food, as well as inflammation;

in turn, both depression and stress have well-documented negative effects on vagal activation, contributing to the lively interplay between the brain and the gut.


As one example, omega-3 fatty acid intake can boost mood and vagal tone, dampen nuclear factor-kappaB activation and responses to endotoxin, and modulate the magnitude of inflammatory responses to stressors.


A better understanding of how stressors, negative emotions, and unhealthy meals work together to enhance inflammation will benefit behavioral and nutritional research, as well as the broader biomedical community.


PMID: 20410248 [PubMed - indexed for MEDLINE]PMCID: PMC2868080 [Available on 2011/5/1]

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18 avril 2011 1 18 /04 /avril /2011 09:58

Psychoneuroendocrinology. 2011 Mar 7. 

Sympathetic and parasympathetic activity in cancer-related fatigue: More evidence for a physiological substrate in cancer survivors.

Fagundes CPMurray DMHwang BSGouin JPThayer JFSollers JJ 3rdShapiro CLMalarkey WBKiecolt-Glaser JK.

Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, The Ohio State University, Columbus, OH, USA.

Fatigue is a notable clinical problem in cancer survivors, and understanding its pathophysiology is important.

This study evaluated relationships between fatigue and both sympathetic and parasympathetic nervous system activity in breast cancer survivors. Norepinephrine and heart rate variability (HRV) were evaluated at rest, as well as during and after a standardized laboratory speech and mental arithmetic stressor.

The participants, 109 women who had completed treatment for stage 0-IIIA breast cancer within the past two years, were at least two months post surgery, radiation or chemotherapy, whichever occurred last.

Women who reported more fatigue had significantly higher norepinephrine and lower HRV before and after the stressor than their less fatigued counterparts.

Fatigue was not related to treatment or disease variables including treatment type, cancer stage, time since diagnosis, and time since treatment.

Importantly, the relationship between HRV and cancer-related fatigue was sizeable. Based on research that has demonstrated characteristic age-related HRV decrements, our findings suggest a 20-year difference between fatigued and non-fatigued cancer survivors, raising the possibility that fatigue may signify accelerated aging.

Furthermore, lower HRV and elevated norepinephrine have been associated with a number of adverse health outcomes; accordingly, fatigue may also signal the need for increased vigilance to other health threats.

PMID: 21388744 [PubMed - as supplied by publisher]

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17 avril 2011 7 17 /04 /avril /2011 22:26


Référence: Myers, L. et Bouic, P.J.D. L'analyse par cytométrie en flux des changements du rapport TH1-TH2 chez des personnes allergiques utilisant ModucareMD (stérol et stéroline) (Flow cytometric analysis of the TH1-TH2 shift in allergic individuals using ModucareMD (sterols/sterolins)). Proceedings of the 26th Annual Congress of the Physiology Society of South Africa, 1998;

Étude: Un essai pilote comparatif et à l'insu, a été effectué sur 24 individus atopiques (affichant surtout une sensibilité au pollen) sur une période de 12 semaines. Pour déterminer si l'équilibre entre les TH1 et les TH2 des T4 était différent chez les individus allergiques et non allergiques, plusieurs marqueurs cliniques et de laboratoire de l'activité ont été mesurés. Quatre groupes ont été suivis : les personnes allergiques ont reçu soit un placebo, soit des capsules actives de ModucareMD et leur profil de lymphokines fut établi au départ, puis 4 semaines plus tard. Un groupe de personnes non allergiques servant de groupe témoin fut formé de la même façon. Les lymphocytes sanguins ont été analysés par cytométrie en flux.

Résultats: Il a été démontré que les personnes allergiques affichaient au début de l'essai une augmentation significative du décompte de lymphocytes T4+ contenant de l'interleukine-4 (IL-4), comparativement aux personnes non allergiques du groupe témoin. L'absorption de ModucareMD a provoqué une diminution significative des taux d'IL-4 tant chez les personnes allergiques que chez les sujets des groupes témoins. Il fut intéressant d'observer que, contrairement aux personnes allergiques, les sujets non allergiques recevant les capsules de stérol et stéroline ont vu le taux d'interféron gamma des lymphocytes T4+ augmenter après 4 semaines de thérapie.

Des changements statistiquement significatifs sont survenus chez les individus allergiques dans les secteurs suivants : moins de rhinorrée, mois d'hypertrophie du cornet nasal, moins de symptômes de rhinopharyngite, diminution du taux plasmatique d'IgE et augmentation du nombre de cellules produisant des TH1. Des améliorations subjectives ont été rapportées par les patients eux-mêmes lorsque nous avons utilisé un questionnaire international pour consigner les symptômes des patients.

Résumé clinique: La réponse TH1-TH2 chez les individus allergiques semble perturbée lorsqu'on la compare à celle des témoins sains, non allergiques. ModucareMD semble diminuer la synthèse d'IL-4 chez les personnes allergiques aussi bien que chez les témoins sains.


Reference: Myers, L and Bouic, PJD. Flow cytometric analysis of the TH1-TH2 shift in allergic individuals using Moducare® (sterols/sterolins). Proc. 26th Annu Cong Physiol Soc S. Afr. 1998

Study: A placebo-controlled blinded pilot study was performed on 24 atopic individuals (mainly pollen sensitivity) over a 12-week period. To determine whether the balance between TH1 and TH2 CD4 cells differs between allergic and non-allergic individuals, several laboratory and clinical markers of activity were measured. Four groups were followed: allergic persons were given either placebo or active Moducare® capsules and the lymphokine profile was determined at baseline and again 4 weeks later. A group of non-allergic persons serving as controls was similarly formed. Blood lymphocytes were analysed using flow cytometry.

Results: It was shown that allergic persons exhibited significantly raised IL4 containing CD4+ cells at the start of the study when compared to the non-allergic control group. The intake of Moducare® induced a significant decrease in IL4 in both allergic as well as in the control groups. It was interesting to note that, unlike the allergic persons, the non-allergic controls receiving the sterols/sterolins capsules increased their IFN-y CD4+ cells after 4 weeks of therapy.

Statistically significant changes occurred with the allergic individuals in the following: less rhinorea, less turbinate hypertrophy, less post nasal drip symptoms, lower IgE plasma levels and higher TH1 producing cells. Subjective improvements were reported by the patients themselves when use of an international questionnaire was made to record patient symptoms.

Clinical Summary: The TH1-TH2 response in allergic individuals appears perturbed when compared to that of healthy, non-allergic controls. Moducare® appears to decrease the synthesis of IL4 in allergic persons as well as in healthy controls.


Video : 



Dr. Daniel Crisafi talks about RxBalance Moducare



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17 avril 2011 7 17 /04 /avril /2011 07:27

Biofactors. 2004;21(1-4):375-7.

Assessment system for dioxin absorption in the small intestine and prevention of its absorption by food factors.

Natsume YSatsu HKitamura KOkamoto NShimizu M.

Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.


It has been reported that 90% of the amount of dioxin in the whole body is absorbed orally with food.


However, a concise and simple system to assess dioxin absorption in the small intestine has not yet been established.

The present study reports a new in vitro assessment system for this purpose. A stable dioxin-responsive cell line was established by introducing a plasmid that incorporates a xenobiotic-responsive element upstream of the luciferase gene into human hepatic HepG2 genomic DNA.

Dioxin was added to the apical side of differentiated human intestinal epithelial Caco-2 cell monolayers that had been cultured on a semipermeable membrane, and the basal medium was recovered after an appropriate incubation time.

To the recovered medium was added dioxin-responsive HepG2, and a luciferase assay was performed.

The established stable cell line clearly showed dose-and time-dependent response to dioxin.

When a food factor such as chlorophyll, which has been reported to increase dioxin excretion in in vivo studies, was added with dioxin, a significant decrease in dioxin permeability to the Caco-2 monolayer was observed.


This assessment system would be useful to search for those food factors that could prevent dioxin absorption in the small intestine.


PMID: 15630229 [PubMed - indexed for MEDLINE]

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17 avril 2011 7 17 /04 /avril /2011 07:18

Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):717-25.

Heme and chlorophyll intake and risk of colorectal cancer in the Netherlands cohort study.

Balder HFVogel JJansen MCWeijenberg MPvan den Brandt PAWestenbrink Svan der Meer RGoldbohm RA.

Department Food and Chemical Risk Analysis, TNO Quality of Life, Zeist, the Netherlands. balder@voeding.tno.nl


BACKGROUND: The evidence for red meat as a determinant of colorectal cancer remains equivocal, which might be explained by differences in heme content. Heme is the pro-oxidant, iron-containing porphyrin pigment of meat and its content depends on the type of meat. Chlorophyll from green vegetables might modify this association.

METHODS: The Netherlands Cohort Study was initiated in 1986 when a self-administered questionnaire on risk factors for cancer was completed by 120,852 subjects ages 55 to 69 years.

After 9.3 years of follow-up through the Cancer Registry, 1,535 incident colorectal cancer cases (869 men and 666 women) were available. Nineteen of the 150 items in the validated dietary questionnaire related to consumption of specific types of fresh and processed meat.

Heme iron content was calculated as a type-specific percentage of the total iron content and chlorophyll content of vegetables was derived from the literature.

RESULTS: Multivariate rate ratios for quintiles of heme iron intake and colon cancer were 1.00, 0.98, 1.04, 1.13, and 1.29 (P(trend) = 0.10) among men and 1.00, 1.31, 1.44, 1.18, and 1.20 (P(trend) = 0.56) among women, respectively.

No consistent associations were observed for rectal cancer.

Rate ratios for colon cancer increased across successive quintiles of the ratio of heme/chlorophyll among men only (1.00, 1.08, 1.01, 1.32, and 1.43; P(trend) = 0.01).

No associations were observed between fresh meat and colorectal cancer.

CONCLUSION: Our data suggest an elevated risk of colon cancer in men with increasing intake of heme iron and decreasing intake of chlorophyll. Further research is needed to confirm these results.

PMID: 16614114 [PubMed - indexed for MEDLINE]


J Nutr. 2005 Aug;135(8):1995-2000.

Natural chlorophyll but not chlorophyllin prevents heme-induced cytotoxic and hyperproliferative effects in rat colon.

de Vogel JJonker-Termont DSKatan MBvan der Meer R.

Wageningen Centre for Food Sciences (WCFS), Nutrition and Health Programme, The Netherlands.

Diets high in red meat and low in green vegetables are associated with an increased risk of colon cancer.

In rats, dietary heme, mimicking red meat, increases colonic cytotoxicity and proliferation of the colonocytes, whereas addition of chlorophyll from green vegetables inhibits these heme-induced effects.

Chlorophyllin is a water-soluble hydrolysis product of chlorophyll that inhibits the toxicity of many planar aromatic compounds.

The present study investigated whether chlorophyllins could inhibit the heme-induced luminal cytotoxicity and colonic hyperproliferation as natural chlorophyll does.

Rats were fed a purified control diet, the control diet supplemented with heme, or a heme diet with 1.2 mmol/kg diet of chlorophyllin, copper chlorophyllin, or natural chlorophyll for 14 d (n = 8/group).

The cytotoxicity of fecal water was determined with an erythrocyte bioassay and colonic epithelial cell proliferation was quantified in vivo by [methyl-(3)H]thymidine incorporation into newly synthesized DNA.

Exfoliation of colonocytes was measured as the amount of rat DNA in feces using quantitative PCR analysis. Heme caused a >50-fold increase in the cytotoxicity of the fecal water, a nearly 100% increase in proliferation, and almost total inhibition of exfoliation of the colonocytes.

Furthermore, the addition of heme increased TBARS in fecal water.

Chlorophyll, but not the chlorophyllins, completely prevented these heme-induced effects.


In conclusion, inhibition of the heme-induced colonic cytotoxicity and epithelial cell turnover is specific for natural chlorophyll and cannot be mimicked by water-soluble chlorophyllins.


PMID: 16046728 [PubMed - indexed for MEDLINE]

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17 avril 2011 7 17 /04 /avril /2011 07:14

Acta Biomed. 2006 Aug;77(2):118-23.

Diet and cancer.

Divisi DDi Tommaso SSalvemini SGarramone MCrisci R.

Department of Thoracic Surgery, University of L'Aquila, G. Mazzini Hospital, Teramo, Italy. duilio.divisi@virgilio.it


The aim of our study is to evaluate the relationship between diet and cancer development. It has been estimated that 30-40% of all kinds of cancer can be prevented with a healthy lifestyle and dietary measures.

A low use of fibres, the intake of red meat and an imbalance of Omega-3 and Omega-6 fats may contribute to increase the risk of cancer.

On the other hand, the assumption of lots of fruit and vegetables may lower the risk of cancer. Protective elements in a cancer-preventive diet include selenium, folic acid, vitamin B12, vitamin D, chlorophyll and antioxidants such as carotenoids (alpha-carotene, beta-carotene, lycopene, lutein, cryptoxanthin).

Ascorbic acid has limited benefits if taken orally, but it effective through intravenous injection.

A supplementary use of oral digestive enzymes and probiotics is also an anticancer dietary measure.

A diet drawn up according to the proposed guidelines could decrease the incidence of breast, colon-rectal, prostate and bronchogenic cancer.


PMID: 17172193 [PubMed - indexed for MEDLIN

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