Pág. 1 de 7 LIST-ADoP-001 Rev: 12/00 Lista de Substâncias e Métodos Proibidos Código Mundial Antidopagem 1 de Janeiro de 2012 (Data de Entrada em Vigor) Ratificada pela Conferência de Partes da Convenção Internacional contra a Dopagem no Desporto da UNESCO em 15/11/2011 e pelo Grupo de Monitorização da Convenção Contra a Dopagem do Conselho da Europa em 8/11/2011
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Nonpharmameds .docNon-pharma therapy for glaucoma and other
al. 1996; Ahlemeyer & Krieglstein 2003) GBE ocular diseases (Consensus document 2010)
protects against glutamate toxicity.
(Chandrasekaran et al. 2002; Chandrasekaran et Ginkgo biloba extract (GBE)
al. 2003) It can reduce glutamate-inducedelevation of calcium concentrations (Zhu et al.
Ginkgo biloba extract contains over 60 known 1997) and can reduce oxidative metabolism in bioactive compounds, about 30 of which are both resting and calcium-loaded neurons. (Oyama found nowhere else in nature. The standardized et al. 1994) Neurons in tissue culture are protected extract used most widely in clinical research, from a variety of toxic insults by GBE, which EGb 761 (Dr Willmar Schwabe GmbH & Co, inhibits apoptosis. (Ahlemeyer et al. 1999; Zhou & Zhu 2000; Guidetti et al. 2001; Lu et al. 2006) flavone glycosides (flavonoids), 6% terpenelactones (ginkgolides and bilobalide), GBE improves both peripheral and cerebral blood flow. It is effective in treating Raynaud’s disease, other, uncharacterized compounds. (De Feudis which is strongly associated with normal-tension glaucoma. (Muir et al. 2002; Choi et al. 2009) Ithas been reported to protect myocardium against GBE has been claimed effective in a variety of hypoxia and ischemia-reperfusion injury (Haramaki disorders associated with aging, including et al. 1994; Punkt et al. 1995) and to relax blood cerebrovascular disease, peripheral vascular vessel walls. (Satoh & Nishida 2004) GBE is a disease, dementia, tinnitus, bronchoconstriction, strong inhibitor of platelet activating factor. (Koch and sexual dysfunction. GBE appears to have 2005) There is mixed evidence for functional many properties applicable to the treatment of improvement in patients with Alzheimer’s-type and non-IOP-dependent risk factors for glaucomatous multi-infarct dementias. Preliminary data suggest damage. (Ritch 2000) GBE exerts significant that GBE may increase the probability of survival protective effects against free radical damage in the elderly population. (Dartigues et al. 2007) and lipid peroxidation in various tissues andexperimental systems. Its antioxidant potential is It has been suggested that alterations in systemic comparable to water soluble antioxidants such as NO and ET-1 activity (endothelial dysfunction) are ascorbic acid and glutathione and lipid soluble involved in vascular dysregulation in glaucoma.
ones such as alpha-tocopherol and retinol (Nicolela et al. 2003; Grieshaber & Flammer 2005; acetate. (Köse & Dogan 1995) The antioxidant Henry et al. 2006; Su et al. 2006) Ginkgo biloba properties of are due to its direct free radical extract reportedly attenuates endothelial scavenging activity. Proteasome inhibitory dysfunction (Zhou et al. 2006) and improvement of properties of anthocyanins may contribute to their peripheral circulation by GBE is at least partly attributable to its effects on the NO-pathway or neuroprotective activities, rationalizing their use endothelium-dependent vasodilation. (Chen et al.
in neurodegenerative disorders. (Dreiseitel et al.
1997; Wu & Zhu 1999) Further studies of GBE on the ocular circulation and progression of normal-tension glaucoma are warranted.
GBE preserves mitochondrial metabolism andATP production in various tissues and partially In the eye, GBE may have a protective effect prevents morphologic changes and indices of against the progression of diabetic retinopathy oxidative damage associated with mitochondrial (Droy-Lefaix et al. 1996) and reduces ischemia- aging. (Pierre et al. 1999; Janssens et al. 2000; reperfusion injury in rat retina. (Szabo et al. 1993) Sastre et al. 2002; Eckert et al. 2003; Eckert et GBE protects retinal photoreceptors against light- al. 2005) In contrast to other antioxidants, gingko induced damage by preventing oxidative stress in has the capacity to enter the inner mitochondrial the retina. (Ranchon et al. 1999; Xie et al. 2007) antioxidant at the mitochondrial level. (Hirooka et prevented by simultaneous treatment with GBE.
al. 2004) It can scavenge nitric oxide (Marcocci (Meyniel et al. 1992) In a rat model of central et al. 1994) and possibly inhibit its production.
retinal artery occlusion, GBE reduced edema and necrosis and blocked the reduction in b-waveamplitude. (Droy-Lefaix et al. 1993) Substantial experimental evidence exists tosupport the view that GBE has neuroprotective dexamethasone-induced IOP elevation in rabbits.
hypoxia/ischemia, seizure activity, cerebral (Jia et al. 2008) It reduced the dexamethasone- edema, and peripheral nerve damage. (Smith et associated accumulation of extracellular materials within the cribriform layers of the trabecular (EGb 761) in global brain ischemia and in excitotoxicity-induced neuronal death.
cellularity. In cultured human trabecular cells, Pharmacopsychiatry 36 Suppl 1: S89-94.
GBE substantially reduced dexamethasone-induced myocilin expression. (Jia et al. 2008) Ma Chen X, S Salwinski & TJF Lee (1997): Extracts et al investigated the dosage dependence of of Ginkgo biloba and ginsenosides exert cerebral intragastral GBE versus saline on RGC survival vasorelaxation via a nitric oxide pathway. Clin Exp in the rat optic nerve crush model. The mean survival rate increased significantly (P<0.001)from 58.4±9.0% in the saline group to 74.2±6.8% Choi WS, CJ Choi, KS Kim & et al (2009): To in the high-dosage GBE group. The same group compare the efficacy and safety of nifedipine found that intraperitoneal administration gave sustained release with Ginkgo biloba extract to treat patients with primary Raynaud's phenomenonin South Korea; Korean Raynaud study (KOARA GBE has been reported to improve automated visual field indices. (Raabe et al. 1991; Quarantaet al. 2003) In one clinical cross-over study of Chung HS, A Harris, JK Kristinsson, T Ciulla, C Kagemann & R Ritch (1999): Ginkgo biloba volunteers, GBE increased ophthalmic artery extract increases ocular blood flow velocity. J blood flow by a mean of 24%. (Chung et al.
Ocular Pharmacol Therap 15: 233-240.
1999) A more recent study, however, failed toconfirm these results. (Wimpissinger et al. 2007) Dartigues JF, L Carcaillon, C Helmer & et al(2007): Vasodilators and nootropics as predictors A systematic review of case reports concluded of dementia and mortality in the PAQUID cohort. J that the causality between ginkgo intake and bleeding is unlikely’’. (Ernst et al. 2005) Asystematic review of eight randomized controlled De Feudis FV (1991): Ginkgo biloba Extract (EGb trials concluded that the available evidence does 761): Pharmacological activities and clinical not demonstrate that GBE causes significant applications. Paris. Elsevier: Pages.
changes in blood coagulation parameters’’.
(Savovic´ et al. 2005) The idea that the Dreiseitel A, P Schreier, A Oehme & et al (2008): combination of ginkgo and anticoagulant or Inhibition of proteasome activity by anthocyanins antiplatelet drugs might represent a serious and anthocyanidins. Biochem Biophys Res Comm health risk is based on several case reports but not supported by clinical trials. (Izzo & Ernst2009) Droy-Lefaix MT, ME Szabo & MN Doly (1993):Ischaemia and reperfusion-induced injury in the spontaneously hypertensive rats: effects of free therapeutic use of Ginkgo biloba extract for radical scavengers. Int J Tissue React 15: 85-91.
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constituents. Eur J Pharmacol 367: 423-430.
Eckert A, U Keil, S Kressmann & et al (2003): Chandrasekaran K, Z Mehrabian, B Spinnewyn & Effects of EGb 761 Ginkgo biloba extract on et al (2002): Bilobalide, a component of the mitochondrial function and oxidative stress.
Ginkgo biloba extract (EGb 761), protects Pharmacopsychiatry 36 Suppl 1: S15-23.
against neuronal death in global brain ischemiaand in glutamate-induced excitotoxicity. Cell Mol Eckert A, U Keil, I Scherping & et al (2005): Stabilization of mitochondrial membrane potentialand improvement of neuronal energy metabolism Chandrasekaran K, Z Mehrabian, B Spinnewyn & by Ginkgo biloba extract EGb 761. Ann NY Acad.
bilobalide, a component of Ginkgo biloba extract Ernst E, PH Canter & JT Coon (2005): Does of Ginkgo biloba extracts. Phytomedicine 12: 10- Ginkgo biloba increase the risk of bleeding’ A systemic review of case reports. Perfusion 18:52-6.
Köse K & P Dogan (1995): Lipoperoxidationinduced by hydrogen peroxide in human Grieshaber MC & J Flammer (2005): Blood flow erythrocyte membranes. 2. Comparison of the in glaucoma. Curr Opin Ophthalmol 16: 79-83.
antioxidant effect of Ginkgo biloba extract (EGb761) with those of water-soluble and lipid-soluble Guidetti C, S Paracchini, S Lucchini & et al antioxidants. J Int Med Res 23: 9-18.
(2001): Prevention of neuronal cell damageinduced by oxidative stress in vitro: effect of Lu G, Y Wu, YT Mak & et al (2006): Molecular different Ginkgo biloba extracts. J Pharmacy evidence of the neuroprotective effect of Ginkgo biloba (EGb761) using bax/bcl-2 ratio after brainischemia in senescence-accelerated mice, strain- Haramaki N, S Aggarwal, T Kawabata, MT Droy- Lefaix & L Packer (1994): Effects of naturalantioxidant Ginkgo biloba extract (EGb 761). On Ma K, L Xu, H Zha & et al (2009): Dosage myocardial ischemia-reperfusion injury. Free dependence of the effect of Ginkgo biloba on the rat retinal ganglion cell survival after optic nervecrush. Eye 23: 1598-1604.
Henry E, DE Newby, DJ Webb, PW Hadoke & CJO'Brien (2006): Altered endothelin-1 Ma K, L Xu, H Zhang & et al (2009): The effect of vasoreactivity in patients with untreated normal- ginkgo biloba on the rat retinal ganglion cell pressure glaucoma. Invest Ophthalmol Vis Sci survival in the optic nerve crush model. Acta Hirooka K, M Tokuda, O Miyamoto & et al Marcocci L, JJ Maguire, MT Droy-Lefaix & L (2004): The Ginkgo biloba extract (EGb 761) Packer (1994): The nitric oxide-scavenging provides neuroprotective effect on retinal properties of Ginkgo biloba extract (EGb 761).
ganglion cells in a rat model of chronic glaucoma.
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Meyniel G, M Doly, M Millerin & P Braquet (1992): Izzo AA & E Ernst (2009): Interaction between Involvement of PAF (Platelet-Activating Factor) in herbal medicines and prescribed drugs. An chloroquine-induced retinopathy. C R Acad Sci III updated systematic review. Drugs 69: 1777- Muir AH, R Robb, M McLaren, F Daly & JJ Belch Janssens D, E Delaive, J Remacle & C Michiels (2002): The use of Ginkgo biloba in Raynaud's (2000): Protection by bilobalide of the ischaemia- disease: a double-blind placebo-controlled trial.
respiratory activity. Fundam Clin Pharmacol 14:193-201.
Nicolela MT, SN Ferrier, CA Morrison & et al(2003): Effects of cold-induced vasospasm in Jia LY, L Sun, DS Fan & et al (2008): Effect of glaucoma: the role of endothelin-1. Invest topical Ginkgo biloba extract on steroid-induced changes in the trabecular meshwork andintraocular pressure. Arch Ophthalmol 126: 1700- Oyama Y, PA Fuchs, N Katayama & K Noda (1994): Myricetin and quercetin, the flavonoidconstituents of Ginkgo biloba extract, greatly Kobuchi H, MT Droy-Lefaix, Y Christen & L reduce oxidative metabolism in both resting and Packer (1997): Ginkgo biloba extract (EGb Ca (2+)-loaded brain neurons. Brain Res 635:125- 761): Inhibitory effect on nitric oxide production in the macrophage cell line RAW 264.7. BiochemPharmacol 53: 897-904.
Pierre S, I Jamme, MT Droy-Lefaix & et al (1999):Ginkgo biloba extract (EGb 761) protects NaK- Koch E (2005): Inhibition of platelet activating ATPase activity during cerebral ischemia in mice.
factor (PAF)-induced aggregation of human thrombocytes by ginkgolides: considerations onpossible bleeding complications after oral intake Punkt K, K Welt & L Schaffranietz (1995): induced ion shifts (Na+, K+, Ca2+ and Mg2+ by free radical scavengers in the rat retina.
myocardium caused by experimental hypoxia with and without ginkgo biloba extract EGb 761pretreatment. A cytophotometrical study. Acta Wimpissinger B, F Berisha, G Garhoefer & et al (2007): Influence of Gingko biloba on ocular bloodflow. Acta Ophthalmol Scand 85: 445-9.
Quaranta L, S Bettelli, MG Uva & et al (2003):Effect of Ginkgo biloba extract on pre-existing Wu WR & XZ Zhu (1999): Involvement of visual field damage in normal tension glaucoma.
monoamine oxidase inhibition in neuroprotective and neurorestorative effects of Ginkgo bilobaextract against MPTP-induced nigrostriatal Raabe A, M Raabe & P Ihm (1991): Therapeutic dopaminergic toxicity in C57 mice. Life Sci 65: follow-up using automatic perimetry in chronic cerebroretinal ischemia in elderly patients.
Prospective double-blind study with graduated dose Ginkgo biloba treatment. Klin Monatsbl Intraperitoneal injection of Ginkgo biloba extract enhances antioxidation ability of retina andprotects photoreceptors after light-induced retinal Ranchon I, JM Gorrand, J Cluzel, MT Droy-Lefaix damage in rats. Curr Eye Res 32: 471-9.
& M Doly (1999): Functional protection ofphotoreceptors from light-induced damage by Zhou LJ & XZ Zhu (2000): Reactive oxygen dimethylthiourea and Ginkgo biloba extract.
species-induced apoptosis in PC12 cells and Invest Ophthalmol Vis Sci 40: 1191-1199.
protective effect of bilobalide. J Pharmacol ExpTher 293: 982-988.
Ritch R (2000): A potential role for Ginkgo bilobaextract in the treatment of glaucoma. Medical Zhou W, H Chai, A Courson & et al (2006): Ginkgolide A attenuates homocysteine-inducedendothelial dysfunction in porcine coronary Sastre J, A Lloret, C Borras & et al (2002): GBE EGb 761 protects against mitochondrial aging inthe brain and in the liver. Cell Mol Biol 48: 685- Zhu L, J Wu, H Liao, J Gao, XN Zhao & ZX Zhang (1997): Antagonistic effects of extract from leavesof Ginkgo biloba on glutamate neurotoxicity. Acta Electropharmacological actions of Ginkgo bilobaextract on vascular smooth and heart muscles.
Grape seed extract
Grape seed proanthocyanidins have a broad Savovic´ J, B Wider & E Ernst (2005): Effects of spectrum of pharmacological and medicinal Ginkgo biloba on blood coagulation parameters: properties against oxidative stress. Grape seed a systematic review of randomised clinical trials.
proanthocyanidin extract (GSE) provides excellent Evid Based Integrative Med 2: 167-76.
protection against free radicals in both in vitro andin vivo models. (Bagchi et al. 2002) GSE-induced Smith PF, K Maclennan & CL Darlington (1996): improvement in myocardial ischemia-reperfusion The neuroprotective properties of the Ginkgo injury in vitro has been reported. (Pataki et al.
biloba leaf: a review of the possible relationshiop 2002; Bagchi et al. 2003; Shao et al. 2003) Activin, a new generation antioxidant derived from grape seed proanthocyanidins, reduces plasma levels ofoxidative stress and adhesion molecules (ICAM-1, Su WW, ST Cheng, TS Hsu & WJ Ho (2006): VCAM-1 and E-selectin) in patients with systemic Abnormal flow-mediated vasodilation in normal- sclerosis. (Kalin et al. 2002) Supplementation of a meal with GSE minimizes postprandial oxidative stress by increasing the antioxidant levels in dysfunction. Invest Ophthalmol Vis Sci 47: 3390- plasma, and, as a consequence, enhancing the resistance to oxidative modification of low densitylipoproteins. (Natella et al. 2002) Grape seed Szabo ME, MT Droy-Lefaix, M Doly & P Braquet proanthocyanidins have also been reported to (1993): Modification of ischemia/reperfusion- have activity against HIV-1 entry into cells. (Nair et al. 2002) Grape seed extract has recently been Shigematsu et al. 2003) It inhibits lipid shown to inhibit the growth of prostate cancer peroxidation of low-density lipoprotein (LDL), cells in mice. (Raina et al. 2007) In the eye, GSE prevents the cytotoxicity ofoxidized LDL, and inhibits key components of cataractogenesis by protects cells against lipid peroxidation.
reducing oxidative stress within lens epithelial (Chanvitayapongs et al. 1997) Resveratrol cells. (Barden et al. 2008) and significantly protects against the degeneration of neurons prevents and postpones development of cataract afteraxotomy. (Araki et al. 2004) A single infusion formation in rats with hereditary cataracts.
of resveratrol can elicit neuroprotective effects on cerebral ischemia-induced neuron damagethrough free radical scavenging and cerebral blood Resveratrol
elevation due to nitric oxide release. (Lu et al.
2006) Its antiapoptotic activity has led to the Resveratrol (3,5,40-trihydroxystilbene), a suggestion that resveratrol may make a useful powerful polyphenolic antioxidant, is found dietary supplement for minimizing oxidative injury largely in the skins of red grapes and berries and in immune-perturbed states and human chronic came to scientific attention as a possible explanation for the low incidence of heart diseaseamong the French, who eat a relatively high-fat Levels of intracellular heme (iron-protoporphyrin diet (the French paradox). Many studies suggest IX), a pro-oxidant, increase after stroke. In that consuming alcohol (especially red wine) neuronal cell cultures, resveratrol induces heme may reduce the incidence of coronary heart oxygenase 1, suggesting that increased heme disease (CHD). Grape juice, which is not a oxygenase activity is a unique pathway by which fermented beverage, is not a significant source of resveratrol can exert its neuroprotective actions.
resveratrol. A large number of studies in the past few years suggests its benefit in vitro and in vivoin a variety of human disease models, including Resveratrol directly inhibits CYP1B1. The cardioprotection, neuroprotection, immune versatility of RSV lies in its diverse targeting of regulation, and cancer chemoprevention. For an membrane and intracellular receptors, signaling extensive review, see (Pervaiz & Holme 2009).
Substantial data show that actions of resveratrol include inhibition of lipid peroxidation and platelet transcription factors, and it can activate or repress aggregation, metal chelating (primarilycopper), a number of signal-transducing pathways found free radical’scavenging activity, antiinflammatory throughout the cell (Pervaiz & Holme 2009) activity, modulation of lipid metabolism,antifungal properties, and anticancer and There appears to be an association between aging estrogen-like activity. (Pervaiz & Holme 2009) and neurodegenerative diseases, such asAlzheimer’s, and that modulation by both caloric Resveratrol increases the lifespan of the yeast, restriction and drugs which mimic caloric restriction, such as resveratrol, can ameliorate Caenorhabditis elegans, and the fruitfly, these diseases. (Liu et al. 2007) Resveratrol Drosophila melanogaster. It was later shown to reduces the levels of secreted and intracellular extend the lifespan of the short-lived fish, amyloid-ß peptides by proteosomal degradation.
Nothobranchius furzeri, (Valenzano & Cellerino 2006) and has now been shown to significantlyincrease the health and survival of mice on a In the eye, resveratrol suppresses selenite- high-calorie diet, pointing to a new approach to induced oxidative stress and cataract formation in treating diseases of aging. (Baur et al. 2006) rats. (Doganay et al. 2006) The authors suggested Among its multiple functions, resveratrol that the presence of oxidative stress in selenite activates sirtuins (silent information regulator cataract development and its prevention by proteins), a family of proteins that play an resveratrol support the possibility that high natural important role in DNA repair, gene silencing, consumption of resveratrol in food can help chromosomal stability and longevity. (Michan & prevent human senile cataract. Resveratrol also induces dilation of retinal arterioles, suggesting apotential benefit for this compound in the treatment The physiologic effects of resveratrol appear to of retinal vascular disease. (Nagaoka et al. 2007) be related to its ability to regulate nutrition and Sirtuin-1 activators (such as resveratrol) longevity genes. (Pervaiz & Holme 2009) demonstrate neuroprotective properties in mouse Resveratrol is an effective antioxidant. (Frankel models of optic neuritis and multiple sclerosis.
et al. 1993; Chanvitayapongs et al. 1997; radical scavenging and cerebral blood flow Araki T, Y Sasaki & J Milbrandt (2004): elevation. J Agric Food Chem 54: 3126-31.
Increased nuclear NAD biosynthesis and SIRT1activation prevent axonal degeneration. Science Marambaud P, H Zhao & P Davies (2005): Resveratrol promotes clearance of Alzheimer’sdisease amyloid-beta peptides. J Biol Chem 280: Bagchi D, M Bagchi, S Stohs & et al (2002): Cellular protection with proanthocyanidinsderived from grape seeds. Ann N Y Acad Sci Michan S & D Sinclair (2007): Sirtuins in mammals: Insights into their biological function.
Biochem J 404: 1’13.
Bagchi D, CK Sen, SD Ray & et al (2003):Molecular mechanisms of cardioprotection by a Nagaoka T, TW Hein, A Yoshida & et al (2007): novel grape seed proanthocyanidin extract. Mutat Resveratrol, a component of red wine, elicits dilation of isolated porcine retinal arterioles: role ofnitric oxide and potassium channels. Invest Barden CA, HL Chandler, P Lu & et al (2008): Effect of grape polyphenols on oxidative stress incanine lens epithelial cells. Am J Vet Res 69: 94- Nair MP, C Kandaswami, S Mahajan & et al (2002): Grape seed extract proanthocyanidinsdownregulate HIV-1 entry coreceptors, CCR2b, Baur JA, KJ Pearson, NL Price & et al (2006): Resveratrol improves health and survival of mice peripheral blood mononuclear cells. Biol Res 35: on a high-calorie diet. Nature 444: 337-342.
Chanvitayapongs S, B Draczynska-Lusiak & AY Natella F, F Belelli, V Gentili & et al (2002): Grape Sun (1997): Amelioration of oxidative stress by antioxidants and resveratrol in PC12 cells.
postprandial oxidative stress in humans. J Agric Doganay S, M Borazan, M Iraz & Y Cigremis Pataki T, I Bak, P Kovacs & et al (2002): Grape (2006): The effect of resveratrol in experimental cataract model formed by sodium selenite. Curr recovery during reperfusion after ischemia in isolated rat hearts. Am J Clin Nutrition 75: 894-899.
Frankel EN, AL Waterhouse & JE Kinsella(1993): Inhibition of human LDL oxidation by Pervaiz S & AL Holme (2009): Resveratrol: Its Biologic Targets and Functional Activity.
Antioxidants Redox Signaling 11: 2851-2897.
Kalin R, A Righi, A Del Rosso & et al (2002):Activin, a grape seed-derived proanthocyanidin Raina K, RP Singh, R Agarwal & C Agarwal extract, reduces plasma levels of oxidative stress (2007): Oral grape seed extract inhibits prostate and adhesion molecules (ICAM-1, VCAM-1 and tumor growth and progression in TRAMP mice.
E-selectin) in systemic sclerosis. Free Radical Shao ZH, LB Becker, TL Vanden Hoek & et al Liu Q, F Xie, R Rolston & et al (2007): (2003): Grape seed proanthocyanidin extract Prevention and treatment of Alzheimer disease attenuates oxidant injury in cardiomyocytes.
and aging: antioxidants. Mini Rev Med Chem 7: Shigematsu S, S Ishida, M Hara & et al (2003): Resveratrol, a red wine constituent polyphenol, prevents superoxide-dependent inflammatory mononuclear cells. Eur J Clin Invest 33: 818-823.
responses induced by ischemia/reperfusion,platelet-activating factor, or oxidants. Free Radic Lu KT, RY Chiou, LG Chen & et al (2006): Neuroprotective effects of resveratrol on cerebralischemia-induced neuron loss mediated by free Shindler KS, E Verntura, TS Rex & et al (2007):SIRT1 activation confers neuroprotection in experimental optic neuritis. Invest Ophthalmol Vis attention deficit hyperactivity disorder in children.
Valenzano DR & A Cellerino (2006): Resveratrol After oral administration of pycnogenol, plasma and the pharmacology of aging: a new vertebrate samples significantly inhibited NFkB activation and model to validate an old molecule. Cell Cycle 5: MMP-9 release from human monocytes, indicating that it exerts anti-inflammatory effects by inhibitingproinflammatory gene expression. (Grimm et al.
Yamakoshi J, M Saito, S Kataoka & S Tokutake 2006) Glutamate inhibits cyclo-oxygenases 1 and (2002): Procyanidin-rich extract from grape 2. (Schafer et al. 2006) This cytotoxicity was seeds prevents cataract formation in hereditary inhibited by both GBE and pycnogenol.
cataractous (ICR/f) rats. J Agric Food Chem 50: (Kobayashi et al. 2000) Pycnogenol not only suppresses the generation of reactive oxygenspecies, but also attenuates caspase-3 activation Zhuang H, YS Kim, RC Koehler & S Dore and DNA fragmentation, suggesting protection against Aß-induced apoptosis. (Peng et al. 2002) resveratrol, a red wine constituent, protectsneurons. Ann N Y Acad Sci 993: 276-286.
Pycnogenol has also been reported to inhibitangiotensin-converting enzyme and to enhance Pycnogenol
the microcirculation by increasing capillarypermeability. (Packer et al. 1999) It inhibits Pycnogenol, an extract of French maritime pine progression of preproliferative diabetic retinopathy bark (Pinus pinaster), is primarily composed of (Schonlau & Rohdewald 2001) and may reduce procyanidins and phenolic acids and is a potent the risk of formation of both diabetic retinopathy antioxidant with strong free radical-scavenging and cataract. (Kamuren et al. 2006) More recently, activity against reactive oxygen and nitrogen in patients with mild to moderate retinal edema, pycnogenol treatment significantly improved both catechin and epicatechin subunits, which are the edema and retinal thickness as measured by important in human nutrition. (Rohdewald 2002) high resolution ultrasound. (Steigerwalt et al.
2009) Laser Doppler flow velocity measurements Pycnogenol is effective in patients with venous at the central retinal artery showed a statistically microangiopathy (Cesarone et al. 2006)and significant increase from 34 to 44 cm/s in the accelerates healing in leg ulcerations from chronic venous insufficiency (Belcaro et al. 2005) effects in the control group. (Steigerwalt et al.
and diabetes. (Belcaro et al. 2006) In chronic venous insufficiency, pycnogenol reduced lowerleg circumference and symptoms of pain, Steigerwalt et al (Steigerwalt et al. 2008) evaluated the effects of the food supplement ‘heaviness", and reddening of the skin. (Koch Mirtogenol (Mirtoselect and Pycnogenol) on IOP and ocular blood flow in 20 subjects versus 18 endothelial cells from Aß-induced injury. (Liu et controls. After three months of treatment, the IOP was lowered compared to that of untreated creatinine, BUN, LDH, IL-1beta, IL-6, and TNF- controls from a baseline of 25.2 mmHg to 22.0 alpha levels in ischemia reperfusion injury in mmHg (p<0.05). Ocular blood flow (central unilaterally nephrectomized rats. (Ozer Sehirli et retinal, ophthalmic, and posterior ciliary arteries) improved both in the systolic and diastoliccomponents as measured by Color Doppler Pretreatment with pycnogenol reduces smoke- induced platelet aggregation. (Araghi-Niknam etal. 2000) Pycnogenol significantly reduces LDL- cholesterol levels. (Devaraj et al. 2002; Koch Rohdewald & RR Watson (2000): Pine bark 2002) A randomized controlled trial reported it extract reduces platelet aggregation. Integrative effective for erectile dysfunction. (Stanislavov et al. 2007) It has also been reported to improvesymptoms of jetlag. (Belcaro et al. 2008) It Belcaro G, MR Cesarone, BM Errichi & et al inhibits not only HIV-1 binding to host cells, but also its replication after entry in susceptible cells improvement and faster healing with local use of in vitro. (Feng et al. 2008) It has been reported to increase urinary catecholamines and ameliorate Belcaro G, MR Cesarone, BM Errichi & et al Koch R (2002): Comparative study of Venostasin (2006): Diabetic ulcers: microcirculatory and Pycnogenol in chronic venous insufficiency.
improvement and faster healing with pycnogenol.
Liu F, BH Lau, Q Peng & V Shah (2000): Belcaro G, MR Cesarone, RJ Steigerwalt & et al Pycnogenol protects vascular endothelial cells (2008): Jet-lag: prevention with Pycnogenol.
from beta-amyloid-induced injury. Biol Pharm Bull Preliminary report: evaluation in healthy individuals and in hypertensive patients. MinervaCardioangiol 56 (5 Suppl): 3-9.
Ozer Sehirli A, G Sener & F Ercan (2009):Protective effects of pycnogenol against ischemia Cesarone MR, G Belcaro, P Rohdewald & et al reperfusion-induced oxidative renal injury in rats.
(2006): Improvement of diabetic microangiopathy with pycnogenol: A prospective, controlled study.
Angiology 57: 431-6.
Packer L, G Rimbach & F Virgili (1999):Antioxidant activity and biologic properties of a Cesarone MR, G Belcaro, P Rohdewald & et al procyanidin-rich extract from pine (Pinus (2006): Rapid relief of signs/symptoms in chronic maritima) bark, pycnogenol. Free Radic Biol Med venous microangiopathy with pycnogenol: a prospective, controlled study. Angiology 57: 569-76.
Peng QL, AR Buz'Zard & BH Lau (2002):Pycnogenol ( (R)) protects neurons from amyloid- beta peptide-induced apoptosis. Brain Res Mol Rohdewald & I Jialal (2002): Supplementation with a pine bark extract rich in polyphenolsincreases plasma antioxidant capacity and alters Rohdewald P (2002): A review of the French the plasma lipoprotein profile. Lipids 37: 931-934.
maritime pine bark extract (Pycnogenol), a herbalmedication with a diverse clinical pharmacology.
Dvoráková M, D Jezová, P Blazícek & et al Int J Clin Pharmacol Ther 40: 158-68.
(2007): Urinary catecholamines in children withattention deficit hyperactivity disorder (ADHD): Schafer A, Z Chovanova, J Muchova & et a modulation by a polyphenolic extract from pine (2006): Inhibition of COX-1 and COX-2 activity by bark (pycnogenol). Nutr Neurosci 10: 151-7.
plasma of human volunteers after ingestion ofFrench maritime pine bark extract (Pycnogenol).
Feng WY, R Tanaka, Y Inagaki & et al (2008): Pycnogenol, a procyanidin-rich extract fromFrench maritime pine, inhibits intracellular Schonlau F & P Rohdewald (2001): Pycnogenol replication of HIV-1 as well as its binding to host for diabetic retinopathy. A review. Int Ophthalmol Grimm T, Z Chovanova, J Muchova & et al Stanislavov R, V Nikolova & P Rohdewald (2007): (2006): Inhibition of NF-kappaB activation and Improvement of erectile function with Prelox: a MMP-9 secretion by plasma of human volunteers randomized, double-blind, placebo-controlled, after ingestion of maritime pine bark extract crossover trial. Int J Impot Res Aug 16; [Epub (Pycnogenol). J Inflamm (Lond) 27: 1.
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General Certificate of EducationAdvanced Subsidiary ExaminationJune 2011 Unit 2 The Concept of Liability Wednesday 25 May 2011 1.30 pm to 3.00 pm For this paper you must have: z an AQA 12-page answer book. Time allowed z 1 hour 30 minutes Instructions z Use black ink or black ball-point pen. z Write the information required on the front of your answer book. The Examining Body for