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22 avril 2012 7 22 /04 /avril /2012 12:12
The circadian clock and pathology of the ageing brain Anna A. Kondratova1 & Roman V. Kondratov2 About the authors top of page Abstract Ageing leads to a functional deterioration of many brain systems, including the circadian clock — an internal time-keeping system that generates ~24-hour rhythms in physiology and behaviour. Numerous clinical studies have established a direct correlation between abnormal circadian clock functions and the severity of neurodegenerative and sleep disorders. Latest data from experiments in model organisms, gene expression studies and clinical trials imply that dysfunctions of the circadian clock contribute to ageing and age-associated pathologies, thereby suggesting a functional link between the circadian clock and age-associated decline of brain functions. Potential molecular mechanisms underlying this link include the circadian control of physiological processes such as brain metabolism, reactive oxygen species homeostasis, hormone secretion, autophagy and stem cell proliferation.
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22 avril 2012 7 22 /04 /avril /2012 12:10
Nature Reviews Neuroscience 13, 293-307 (May 2012) | doi:10.1038/nrn3229 Impaired mitochondrial function in psychiatric disorders Husseini Manji1, Tadafumi Kato2, Nicholas A. Di Prospero1, Seth Ness1, M. Flint Beal3, Michael Krams1 & Guang Chen1 About the authors top of page Abstract Major psychiatric illnesses such as mood disorders and schizophrenia are chronic, recurrent mental illnesses that affect the lives of millions of individuals. Although these disorders have traditionally been viewed as 'neurochemical diseases', it is now clear that they are associated with impairments of synaptic plasticity and cellular resilience. Although most patients with these disorders do not have classic mitochondrial disorders, there is a growing body of evidence to suggest that impaired mitochondrial function may affect key cellular processes, thereby altering synaptic functioning and contributing to the atrophic changes that underlie the deteriorating long-term course of these illnesses. Enhancing mitochondrial function could represent an important avenue for the development of novel therapeutics and also presents an opportunity for a potentially more efficient drug-development process.
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22 avril 2012 7 22 /04 /avril /2012 12:03
Les indications de plus en plus nombreuses de l'utilisation du sang de cordon ont entraîné ces dernières années la constitution de multiples banques de stockage. Dans plusieurs pays étrangers, des institutions publiques coexistent avec des structures privées. Ces dernières proposent parfois aux familles de payer pour que soit conservé le sang de cordon de leur enfant en vue d'une possible utilisation ultérieure pour lui-même ou un de ses proches. Il existe également des banques privées à but non lucratif, souvent financées par des fondations, qui participent à la collecte nationale anonyme et solidaire. Enfin, se développent de plus en plus des organismes dont l'activité est mixte. Ces diverses options toujours été rejetées en France (qui connaît en nombre d'unités stockées un très important retard sur ses voisins européens). Cependant, pour la première fois, le Comité consultatif national d'éthique (CCNE) est revenu, de façon encore très restreinte, sur son opposition de principe aux banques privées depuis toujours martelée. Dans les familles où les enfants « sont exposées au risque d'hémopathies congénitales génétiquement transmises » (drépanocytose, thalassémie notamment), une conservation personnelle du sang de cordon au sein de biobanques privées « à caractère familial et solidaire » pourrait être réalisée, suggère le CCNE. « Les unités non utilisées par la famille seraient mises à disposition d'autrui », précise le Figaro qui évoque ce jeudi 19 avril dans ses colonnes la teneur de l'avis du CCNE. Par ailleurs, le CCNE se prononce pour la première fois en faveur de la création de biobanques privées à but non lucratif dont l'activité serait cependant restreinte à la collecte anonyme de sang de cordon (à visée allogénique). Concernant, la possibilité de stocker le sang du cordon de son enfant en vue d'une hypothétique utilisation pour lui-même ou pour un membre de sa famille, le CCNE demeure intransigeant : « Les autogreffes de sang placentaire comme substitut de la moelle osseuse gardent, encore aujourd'hui, des indications rarissimes sinon nulles, donc assez exceptionnelles pour effacer le bien fondé de biobanques créées à ce seul effet. Leur caractère privé à but lucratif les incite trop souvent à des publicités non fondées sur des faits scientifiques avérés, et partant, souvent mensongères », écrivent les sages. Le président du CCNE, Alain Grimfeld est même allé jusqu'à affirmer que prétendre que conserver pour soi son sang de cordon pourrait être utile, relève de « la science fiction ».
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22 avril 2012 7 22 /04 /avril /2012 12:00
Il est fréquent de retrouver des artères jambières calcifiées chez les diabétiques, les insuffisants rénaux, les sujets âgés, et plus généralement les coronariens et autres patients « vasculaires ». Ces calcifications pariétales se traduisent par une mauvaise compressibilité, voire une incompressibilité, des artères. Cliniquement, ce diagnostic se fait banalement à l'aide d'un doppler continu et d'un brassard à tension. Une équipe américaine a eu l'idée d'évaluer la mortalité des sujets présentant une mauvaise compressibilité des artères jambières et de la comparer à celle des sujets ayant un index de pressions systoliques (IPS) réduit et à celle des sujets normaux. Cette étude a été menée par la Mayo Clinic sur des patients explorés consécutivement entre 1998 et 2007. Quelque 16 000 sujets âgés en moyenne de 67,8 ± 13 ans (n : 16 493 ; 59 % d'hommes) ont été suivis pendant près de 6 ans en moyenne (5,8 ± 3,1 ans). Un quart d'entre eux sont décédés au cours de ce suivi (n : 4 365 ; 26 %). Un index de pressions systoliques (IPS) compris entre 1,00 et 1,3 était considéré comme normal tandis que l'artériopathie oblitérante des membres inférieurs (AOMI) était définie par un IPS <= 0,9. Les artères de jambes étaient dites « incompressibles» en cas d'IPS >= 1,4 et (ou) de pression artérielle systolique mesurée à la cheville > 255 mm Hg. Le taux de survie a été de 88 % chez les sujets ayant un IPS normal contre 70 % en cas d'AOMI et de 60 % en cas d'artères de jambes incompressibles. Après ajustement sur l'âge, le sexe, les habituels facteurs de risque cardiovasculaire, les comorbidités et les traitements, il est apparu que des artères de jambes incompressibles sont un marqueur de risque indépendant de décès, avec une mortalité doublée par rapport aux sujets normaux (hazard ratio [HR] : 2,0 ; intervalle de confiance à 95 % [IC] : 1,8-2,2) et une mortalité augmentée de 30 % par rapport aux sujets ayant une AOMI (HR : 1,3 ; IC : 1,2-1,4). Le sur risque a semblé particulièrement marqué chez les femmes. Il s'agit de la première étude concluant que l'incompressibilité des artères de jambe est associée à une mortalité supérieure à celle observée en cas de « banale » AOMI. Sujet certainement à creuser. Arain FA et coll. : Survival in patients with poorly compressible leg arteries. J Am Coll Cardiol 2012; 59: 400-7 20/04/12 (JIM) Docteur Olivier Meillard
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21 avril 2012 6 21 /04 /avril /2012 19:08
Integr Cancer Ther. 2009 Jun;8(2):164-7.
An alternative treatment for cervical intraepithelial neoplasia II, III.
Swanick S, Windstar-Hamlin K, Zwickey H.
Source
Natural Health Center, National College of Natural Medicine, Portland, Oregon 97210, USA.
Abstract
BACKGROUND:
This report describes a case of a woman with progressive and recurrent cervical dysplasia 4 years after cervical conization for severe dysplasia.
PATIENT AND METHODS:
A 20-year-old female was referred for colposcopy and biopsy following results of moderate to severe atypia of cervical cells on her Papanicolaou (Pap) test. Her colposcopy was satisfactory and her biopsy revealed cervical intraepithelial neoplasia (CIN) II, III. She refused the conventional recommendation of loop electrosurgical excision procedure (LEEP) and, as an alternative, elected to receive escharotic treatment at a frequency of 2 treatments per week for 5 weeks. In addition to the escharotic treatment she followed an oral vitamin and botanical protocol. She was followed for 5 years.
RESULTS:
The patient's 4-month and 10-month follow-up Pap smears revealed negative cervical cytology for intraepithelial lesion or malignancy. Her 10-month colposcopy was satisfactory and no lesions were noted on the colposcopic exam. Liquid based Pap results continued to remain normal for 5 years after the initiation of treatment.
DISCUSSION:
Escharotic treatment of high-grade cervical neoplasias with satisfactory colposcopy holds promise as an effective and low-risk alternative therapy to LEEP and other excisional procedures.
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21 avril 2012 6 21 /04 /avril /2012 19:02
Cell Mol Life Sci. 2001 Aug;58(9):1234-45.
Bromelain: biochemistry, pharmacology and medical use.
Maurer HR.
Source
Department of Biochemistry, Molecular Biology and Biotechnology, Institute of Pharmacy, Freie Universität Berlin, Germany. hrmaurer@zedat.fu-berlin.de
Abstract
Bromelain is a crude extract from the pineapple that contains, among other components, various closely related proteinases, demonstrating, in vitro and in vivo, antiedematous, antiinflammatory, antithrombotic and fibrinolytic activities. The active factors involved are biochemically characterized only in part. Due to its efficacy after oral administration, its safety and lack of undesired side effects, bromelain has earned growing acceptance and compliance among patients as a phytotherapeutical drug. A wide range of therapeutic benefits has been claimed for bromelain, such as reversible inhibition of platelet aggregation, angina pectoris, bronchitis, sinusitis, surgical traumas, thrombophlebitis, pyelonephritis and enhanced absorption of drugs, particularly of antibiotics. Biochemical experiments indicate that these pharmacological properties depend on the proteolytic activity only partly, suggesting the presence of nonprotein factors in bromelain. Recent results from preclinical and pharmacological studies recommend bromelain as an orally given drug for complementary tumor therapy: bromelain acts as an immunomodulator by raising the impaired immunocytotoxicity of monocytes against tumor cells from patients and by inducing the production of distinct cytokines such as tumor necrosis factor-a, interleukin (Il)-1beta, Il-6, and Il-8. In a recent clinical study with mammary tumor patients, these findings could be partially confirmed. Especially promising are reports on animal experiments claiming an antimetastatic efficacy and inhibition of metastasis-associated platelet aggregation as well as inhibition of growth and invasiveness of tumor cells. Apparently, the antiinvasive activity does not depend on the proteolytic activity. This is also true for bromelain effects on the modulation of immune functions, its potential to eliminate burn debris and to accelerate wound healing. Whether bromelain will gain wide acceptance as a drug that inhibits platelet aggregation, is antimetastatic and facilitates skin debridement, among other indications, will be determined by further clinical trials. The claim that bromelain cannot be effective after oral administration is definitely refuted at this time.
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21 avril 2012 6 21 /04 /avril /2012 18:57
Clin Exp Rheumatol. 2006 Jan-Feb;24(1):25-30.
Efficacy and tolerance of an oral enzyme combination in painful osteoarthritis of the hip. A double-blind, randomised study comparing oral enzymes with non-steroidal anti-inflammatory drugs.
Klein G, Kullich W, Schnitker J, Schwann H.
Source
Rehabilitation Centre for Cardiovascular and Rheumatic Diseases, Saalfelden, Germany.
Abstract
OBJECTIVE:
The objective of this study was to establish the non-inferiority of an oral enzyme therapy (Phlogenzym-(PE)) as compared to the non-steroidal anti-inflammatory drug (NSAID) diclofenac (DC) in patients with osteoarthritis (OA) of the hip.
METHODS:
Ninety patients presenting with painful episodes of OA of the hip were treated for 6 weeks in one study centre in a phase III, randomised, double blind, parallel group trial. Altogether, 45 patients were treated in the PE group and 45 patients were treated in the DC group. Primary efficacy criteria were: WOMAC dimensions pain, joint stiffness and function, and Lequesne index as multiple endpoint according to O'Brien. The efficacy criteria were analysed applying the test of non-inferiority with regard to mean changes and frequencies, t-test, U test, ANCOVA and descriptive methods.
RESULTS:
Within the 6 weeks observation period, the adjusted changes from baseline to endpoint of the target parameters worked out as follows (adjusted differences, mean +/- SEM): WOMAC subscale pain (PE -10.3 +/- 1.2, DC -9.5 +/- 1.2), WOMAC subscale joint stiffness (PE -3.9 +/- 0.5, DC -3.6 +/- 0.5), WOMAC subscale physical function (PE -31.7 +/- 3.5, DC -29.7 +/- 3.5), Lequesne's index (PE -2.89 +/- 0.47, DC -2.27 +/- 0.47). Non-inferiority of PE as compared to DC with regard to the O'Brien's global sum of the standardised adjusted changes from baseline to endpoint in pain, stiffness, physical function, and Lequesne's index was established with p = 0.0025. PE was simultaneously non-inferior as compared to DC with regard to the 4 single endpoints: WOMAC subscale pain (p = 0.0033), WOMAC subscale joint stiffness (p = 0.0061), WOMAC subscale physical function (p = 0.0039), Lequesne's index (p = 0.0008) (closed test procedure). The equivalence tests remained insignificant due to comparatively lower effects of DC. For 71.1% of the PE patients and for 61.4% of the DC patients rates of good or very good global investigator assessments of efficacy were calculated (test of non-inferiority: p = 0.0011). In the majority of patients, tolerability was judged in both drug groups as very good or good.
CONCLUSION:
This trial showed significant non-inferiority from 6 weeks treatment with PE in patients with OA of the hip with regard to the WOMAC dimensions pain, stiffness and physical function, to Lequesne's index, to the investigator and patients assessments of efficacy, and to the responder rates based on pain, physical function, and patient assessment of efficacy. With regard to drug tolerability some tendencies in favour of PE were detected. However, in this study there was no real difference between PE and DC 100 mg/day, implying an equal benefit-risk relation between the substances. PE may well be recommended for the treatment of patients with osteoarthritis of the hip with signs of inflammation as indicated by a high pain level.
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21 avril 2012 6 21 /04 /avril /2012 18:54
Clin Immunol. 2008 Mar;126(3):345-52. Epub 2007 Dec 21.
Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro.
Onken JE, Greer PK, Calingaert B, Hale LP.
Source
Department of Medicine, Division of Gastroenterology, Duke University Medical Center, Durham, NC 27710, USA.
Abstract
Oral bromelain has been anecdotally reported to decrease inflammation in ulcerative colitis (UC). Proteolytically active bromelain is known to decrease expression of mRNAs encoding pro-inflammatory cytokines by human leukocytes in vitro. To assess the effect of bromelain on mucosal secretion of cytokines in inflammatory bowel disease (IBD), endoscopic colon biopsies from patients with UC, Crohn's disease (CD), and non-IBD controls were treated in vitro with bromelain or media, then cultured. Secretion of pro-inflammatory cytokines and chemokines was measured. Significant increases in granulocyte colony-stimulating factor (G-CSF), interferon (IFN)-gamma, interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF) were detected in the media from actively inflamed areas in UC and CD as compared with non-inflamed IBD tissue and non-IBD controls. In vitro bromelain treatment decreased secretion of G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-gamma, CCL4/macrophage inhibitory protein (MIP)-1beta, and TNF by inflamed tissue in IBD. Bromelain may be a novel therapy for IBD.
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21 avril 2012 6 21 /04 /avril /2012 18:51
Clin Immunol. 2008 Jul;128(1):66-74. Epub 2008 May 14.
Bromelain treatment decreases neutrophil migration to sites of inflammation.
Fitzhugh DJ, Shan S, Dewhirst MW, Hale LP.
Source
Department of Pathology, DUMC 3712, Duke University Medical Center, Durham, NC 27710, USA.
Abstract
Bromelain, a mixture of proteases derived from pineapple stem, has been reported to have therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease. The purpose of this work was to understand potential mechanisms for this anti-inflammatory activity. Exposure to bromelain in vitro has been shown to remove a number of cell surface molecules that are vital to leukocyte trafficking, including CD128a/CXCR1 and CD128b/CXCR2 that serve as receptors for the neutrophil chemoattractant IL-8 and its murine homologues. We hypothesized that specific proteolytic removal of CD128 molecules by bromelain would inhibit neutrophil migration to IL-8 and thus decrease acute responses to inflammatory stimuli. Using an in vitro chemotaxis assay, we demonstrated a 40% reduction in migration of bromelain- vs. sham-treated human neutrophils in response to rhIL-8. Migration to the bacterial peptide analog fMLP was unaffected, indicating that bromelain does not induce a global defect in leukocyte migration. In vivo bromelain treatment generated a 50-85% reduction in neutrophil migration in 3 different murine models of leukocyte migration into the inflamed peritoneal cavity. Intravital microscopy demonstrated that although in vivo bromelain treatment transiently decreased leukocyte rolling, its primary long-term effect was abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion were correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128 over the time period studied. Taken together, these studies demonstrate that bromelain can effectively decrease neutrophil migration to sites of acute inflammation and support the specific removal of the CD128 chemokine receptor as a potential mechanism of action.
PMID: 18482869 [PubMed - indexed for MEDLINE] PMCID: PMC2516972 Free PMC Article
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21 avril 2012 6 21 /04 /avril /2012 18:48
Abstract
Protease supplementation has been purported to reduce the damaging effects of eccentric exercise and accelerate recovery of muscle function, possibly by regulating inflammation.
PURPOSE:
To determine the effectiveness of protease supplementation in attenuating eccentric exercise-induced skeletal muscle damage and inflammation.
METHODS:
After standard physical and hemodynamic assessment and fasting venous blood samples, subjects performed isokinetic extension/flexion of the quadriceps group on a Biodex isokinetic dynamometer at 60°·s(-1), followed by VO2max testing. Subjects were randomly assigned to consume 5.83 g daily of either a cellulose placebo (N = 15; 22.27 ± 3.33 yr, 71.17 ± 2.91 inches, 179.4 ± 24.05 lb, 50.55 ± 5.66 mL·kg(-1)·min(-1)) or a proteolytic supplement containing fungal proteases, bromelain, and papain (N = 14; 22.85 ± 5.9 yr, 70.0 ± 2.67 inches, 173.11 ± 29.94 lb, 49.69 ± 6.15 mL·kg(-1)·min(-1)) for a period of 21 d. After the supplementation period, subjects donated blood samples before performing a 45-min downhill (-17.5%) treadmill protocol at 60% of VO2max. An additional four blood draws and three muscle function tests were performed during the next 48 h. Blood was analyzed using standard hematology and clinical chemistry, enzyme-linked immunosorbent assay, and bead array. Blood data were analyzed using multivariate analysis of variance (MANOVA) with repeated measures, whereas Biodex data were analyzed using a MANOVA on %Δ values.
RESULTS:
Significant group differences (T1-T3, P = 0.033; T1-T4, P = 0.043) and another strong trend (T1-3 h, P = 0.055) were observed for flexion (peak torque %Δ at 60°·s(-1)) indicating higher force production in the protease group. Significant group × time interactions (P < 0.05) were observed, including elevations in circulating eosinophils and basophils in the protease group coinciding with lower levels of serum cyclooxygenase 2, interleukin 6, and interleukin 12 in this group.
CONCLUSIONS:
Protease supplementation seems to attenuate muscle strength losses after eccentric exercise by regulating leukocyte activity and inflammation.
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