5 MB 27/05/13 II Jornada Analítica
Transcrição
5 MB 27/05/13 II Jornada Analítica
Dr. Efraim Olszewer Pituitary Gland and Hypothalamus Where nervous and endocrine systems interact Hypothalamus regulates secretions of anterior pituitary Posterior pituitary is an extension of the hypothalamus Anterior pituitary produces nine major hormones that Regulate body functions Regulate the secretions of other endocrine glands Pituitary Gland Structure • Posterior pituitary (neurohypophysis): extension of the nervous system via the infundibulum – Secretes neurohormones • Anterior pituitary (adenohypophysis) – Consists of three areas with indistinct boundaries: pars distalis, pars intermedia, pars tuberalis Hypothalamus, Anterior Pituitary, and Target Tissues Releasing and Inhibiting Hormones • • • Tropins or tropic hormones: hormones that regulate the hormone secretions of target endocrine tissues. All anterior pituitary hormones are tropins. Releasing hormones secreted by the hypothalamus: – GHRH. Growth hormone-releasing hormone. Causes the anterior pituitary to release growth hormone. – TRH. Thyroid-releasing hormone. Causes the anterior pituitary to release thyroid-stimulating hormone (TSH). – CRH. Corticotropin-releasing hormone. Causes anterior pituitary to produce adrenocorticotropic hormone (ACTH) – GnRH. Gonadotropin-releasing hormone. Causes anterior pituitary to produce FSH (follicle stimulating hormone) and LH (luteinizing hormone). – PRH. Prolactin-releasing hormone. Causes the anterior pituitary to release prolactin. Inhibiting hormones: – GHIH. Growth hormone-inhibiting hormone, somatostatin. Causes the anterior pituitary to decrease release of growth hormone. – PIH. Prolactin-inhibiting hormone. Causes the anterior pituitary to decrease release of prolactin. Hypothalamus, Posterior Pituitary and Target Tissues • Hypothalamic neurons syntheisze ADH and oxytocin. • Latter hormones travel to post. pituitary via axons of hypothalamic neurons. • ADH and oxytocin enter circulation in post. pituitary. Hormones of Posterior Pituitary: ADH Antidiuretic hormone (ADH). Also called vasopressin. A. Osmoreceptors (specialized neurons of hypothalamus monitor changes in intercellular osmolality (relative concentrations of electrolytes and water). If the concentration of electrolytes increases or if the concentration of water decreases, then ADH secretion is stimulated. B. Baroreceptors (specialized neurons found in walls of atria of heart, large veins, carotid arteries, aortic arch) sense changes in blood pressure (BP). If BP decreases, then ADH secretion is stimulated. Control of ADH Secretion Control of Oxytocin Secretion Anterior Pituitary Hormones • • • • • • • • • Growth hormone (GH) or somatotropin Thyroid-stimulating hormone (TSH) Adrenocorticotropic hormone (ACTH) Melanocyte-stimulating hormone (MSH) Beta endorphins Lipotropins Luteinizing hormone (LH) Follicle-stimulating hormone (FSH) Prolactin Growth Hormone (GH or somatotropin) • Stimulates uptake of amino acids; protein synthesis; growth in most tissues. • Stimulates breakdown of fats to be used as an energy source but stimulates synthesis of glycogen: glucose sparing • Promotes bone and cartilage growth • Regulates blood levels of nutrients after a meal and during periods of fasting • Stimulates glucose synthesis by liver Metabolic Action of Growth Hormone Figure 16.6 Growth Hormone Stimulation: functions in regulating growth, tissue maintenance, metabolism GHRH from hypothalamus causes release of… Growth hormone from anterior pituitary effects… Target tissues: most tissues of the body • Direct effect: GH binds to receptors on cells and causes changes within the cells. Increased lipolysis and decreased use of glucose for energy • Indirect effect: causes liver and skeletal muscle to produce somatomedins; e.g., insulinlike growth factors (IGF’s) – Insulinlike growth factors: bind to receptors on membranes of target cells. Stimulate growth in cartilage, bone; increased synthesis of proteins in skeletal muscle. Regulation of GH Secretion 1. Stress and decreased glucose levels increase release of GHRH and decrease release of GHIH. 2. GHRH and GHIN travel via thehypothalamohypophyseal portal system to ant. pituitary 3. Increased GHRH and reduced GHIH act on AP and result in increased GH secretion. 4. GH acts on target tissues. 5. Increasing GH levels have neg feedback effect on hypothala. Growth Hormone: Inhibition • Hypothalamus produces growth hormone inhibiting hormone (GHIH = somatostatin) • Inhibits production of GH by anterior pituitary. • GHRH secretion in response to low blood glucose, stress, increase in certain a.a. • GHIH secretions in response to high blood glucose. • Peak GH levels during deep sleep; levels lower at other times of day. • Hyposecretion of GH may result in dwarfism • Hypersecretion may result in giantism or acromegaly depending on ossification of epiphyseal plates TSH and Thyroid Hormones • TRH from hypothalamus causes the release of TSH from anterior pituitary which causes secretion and storage of hormones T3 and T4 from and within the thyroid gland • TSH increases activity of phospholipase that opens Ca2+ channels, increasing Ca2+ concentration in cells of the thyroid gland • T3 and T4 inhibit TRH and TSH secretion Adrenocorticotrophic Hormone (ACTH) • CRH from hypothalamus causes release of ACTH from anterior pituitary which – Causes cortisol secretion from the adrenal cortex (a glucocorticoid from the zona fasciculata) – Causes aldosterone secretion from the adrenal cortex (a mineralocorticoid from the zona glomerulosa) – Binds directly to melanocytes of the skin; causes increase in production of melanin. Melanocyte Stimulating Hormone, Endorphins, and Lipotropins • ACTH, MSH, endorphins and lipotropins all derived from the same large precursor molecule when stimulated by CRH • MSH causes melanocytes to produce more melanin • Endorphins act as an analgesic; produced during times of stress. • Lipotropins cause adipose cells to catabolize fat LH, FSH, Prolactin • Gonadotrophs: glycoprotein hormones that promote growth and function of the gonads • LH and FSH – Both hormones regulate production of gametes and reproductive hormones • Testosterone in males • Estrogen and progesterone in females • GnRH from hypothalamus stimulates LH and FSH secretion • Prolactin: role in milk production – Regulation of secretion: prolactin-releasing hormone (PRH) and prolactin-inhibiting hormones (PIH) Thyroid Gland • • • One of largest endocrine glands; Highly vascular. Iodine enters follicular cells by active transport. Only gland that stores hormone. Histology – Composed of follicles: follicular cells surrounding thyroglobulin/thyroid hormones – Parafollicular cells: between follicles Physiology – Follicular cells secrete thyroglobulin into lumen of follicle. Iodine and a.a. tyrosine necessary for production of T3 and T4. Hormones stored here attached to the thyroglobulin then absorbed into follicular cells; hormones disattached from thyroglobulin and released into circulation. – Parafollicular cells. Secrete calcitonin which reduces [Ca2+] in body fluids when Ca levels are elevated. Biosynthesis of Thyroid Hormones Thyroid Hormones • Produced by follicular cells • Triiodothyronine or T3 -less produced • Tetraiodothyronine or T4 or thyroxine-more – 99.6% of thyroxine in the blood is bound to thyroxine-binding globulin (TBG) from the liver. Rest is free. – TBG has a higher affinity for T4 than for T3; amt of free unbound T3 in plasma is 10x’s greater than free T4. – Only free thyroxine and T3 can enter cells; boundthyroxine serves as a reservoir of this hormone – 33-40% of T4 converted to T3 in cells: T3 more potent – Bind with intracellular receptor molecules and initiate new protein synthesis – Increase rate of glucose, fat, protein metabolism in many tissues thus increasing body temperature – Normal growth of many tissues dependent on presence of thyroid hormones. Effects of T3 and T4 1. Maintain normal rate of metabolism. 2. Increase the rate at which glucose, fat, and protein are metabolized. 3. Increase the activity of Na+-K+ pump which increases body temperature. 4. Can alter the number and activity of mitochondria resulting in greater ATP synthesis and heat production. 5. Normal growth and maturation of bone, hair, teeth, c.t., and nervous tissue require thyroid hormone. 6. Both T3 and T4 play a permissive role for GH and GH does not have its normal effect on tissues if T3 and T4 are lacking. 7. See Table 18.4 for effects of hypo- and hypersecretion Regulation of T3 and T4 Secretion Regulation of Calcitonin Secretion • Produced by parafollicular cells • Secretion triggered by high Ca2+ concentration in blood; acts to decrease Ca2+ concentration • Primary target tissue: bone. Decreases osteoclast activity, lengthens life span of osteoblasts. Parathyroid Glands • • • Embedded in thyroid Two glands on each side Secrete PTH: target tissues are bone, kidneys and intestines. – Increases blood calcium and phosphate levels – Stimulates osteoclasts – Promotes calcium reabsorption by kidneys and PO4 excretion – Increases synthesis of vitamin D which, in turn, increases absorption of Ca and PO4 by intestines. Net loss of PO4 under influence of PTH. • Regulation depends on calcium levels. Effects of Parathyroid Hormone Figure 16.11 Adrenal Glands • Near superior poles of kidneys; retroperitoneal • Inner medulla; outer cortex • Medulla: formed from neural crest; sympathetic. Secretes epinephrine and norepinephrine • Cortex: three zones from superficial to deep – Zona glomerulosa – Zona fasciculata – Zona reticularis Adrenal Medulla • • • • • • • Secretory products are neurohormones: epinephrine and norepinephrine Combine with adrenergic membrane-bound receptors All function through G protein mechanisms Secretion of hormones prepares body for physical activity Effects are short-lived; hormones rapidly metabolized Epinephrine – Increases blood levels of glucose – Increases fat breakdown in adipose tissue – Causes dilation of blood vessels in skeletal muscles and cardiac muscles. Epinephrine and norepinephrine increase heart rate and force of contraction; cause blood vessels to constrict in skin, kidneys, gastrointestinal tract, and other viscera Hormones of Adrenal Cortex • Mineralocorticoids: Zona glomerulosa – Aldosterone produced in greatest amounts. Increases rate of sodium reabsorption by kidneys increasing sodium blood levels • Glucocorticoids: Zona fasciculata – Cortisol is major hormone. Increases fat and protein breakdown, increases glucose synthesis, decreases inflammatory response • Androgens: Zona reticularis – Weak androgens secreted then converted to testosterone by peripheral tissues. Stimulate pubic and axillary hair growth and sexual drive in females Regulation of Cortisol Secretion Glucocorticoids (Cortisol) • Help the body resist stress by: – Keeping blood sugar levels relatively constant – Maintaining blood volume and preventing water shift into tissue • Cortisol provokes: – Gluconeogenesis (formation of glucose from noncarbohydrates) – Rises in blood glucose, fatty acids, and amino acids Stress and the Adrenal Gland Figure 16.15 Pancreas • • Located along small intestine and stomach; retroperitoneal Exocrine gland – Produces pancreatic digestive juices • Endocrine gland – Consists of pancreatic islets – Composed of • Alpha cells; secrete glucagon • Beta cells; secrete insulin • Delta cells; secrete somatostatin Glucagon • A 29-amino-acid polypeptide hormone that is a potent hyperglycemic agent • Its major target is the liver, where it promotes: – Glycogenolysis – the breakdown of glycogen to glucose – Gluconeogenesis – synthesis of glucose from lactic acid and noncarbohydrates – Release of glucose to the blood from liver cells Insulin • Target tissue is the liver, adipose tissue, muscle, and satiety center of hypothalamus • A 51-amino-acid protein consisting of two amino acid chains linked by disulfide bonds • Synthesized as part of proinsulin and then excised by enzymes, releasing functional insulin • Insulin: – Lowers blood glucose levels – Enhances transport of glucose into body cells – Counters metabolic activity that would enhance blood glucose levels Regulation of Blood Glucose Levels • The hyperglycemic effects of glucagon and the hypoglycemic effects of insulin Figure 16.17 Diabetes Mellitus (DM) • Results from hyposecretion or hypoactivity of insulin • The three cardinal signs of DM are: – Polyuria – huge urine output – Polydipsia – excessive thirst – Polyphagia – excessive hunger and food consumption • Hyperinsulinism – excessive insulin secretion, resulting in hypoglycemia Diabetes Mellitus (DM) Figure 16.18 Regulation of Insulin Secretion Regulation of Blood Nutrient Levels Regulation of Blood Nutrient Levels During Exercise Hormones of the Reproductive System Male: Testes • Testosterone – Regulates production of sperm cells and development and maintenance of male reproductive organs and secondary sex characteristics • Inhibin – Inhibits FSH secretion Female: Ovaries • Estrogen and Progesterone – Uterine and mammary gland development and function, external genitalia structure, secondary sex characteristics, menstrual cycle • Inhibin – Inhibits FSH secretion • Relaxin – Increases flexibility of symphysis pubis Pineal Body • In epithalamus; produces melatonin and arginine vasotocin Thymus Gland, GI Tract, Kidneys • Thymosin. Development of the immune system. • GI tract: several hormones regulate digestion and enzyme secretion. Studied with digestive system. • Kidneys – secrete erythropoietin, which signals the production of red blood cells • Adipose tissue – releases leptin, which is involved in the sensation of satiety, and stimulates increased energy expenditure Hormone-like Substances • Autocrines: chemical signals released by a cell and the substance affects that same cell. – Chemical mediators of inflammation which are modified fatty acids: eicosanoids such as prostaglandins, thromboxanes, prostacyclins, and leukotrienes • Paracrines: chemical signals released into intercellular fluid and affecting nearby cells. – Endorphins and enkephalins modulate sensation of pain – Several growth factors Effects of Aging on Endocrine System • Gradual decrease in secretory activity of some glands – – – – GH as people age except in people who exercise regularly Melatonin Thyroid hormones Kidneys secrete less renin • Familial tendency to develop type II diabetes EXERCICIO DANO CELULAR RECUPERAÇÃO ÁPICE DA PERFORMANCE HUMANA ELEVADOS NÍVEIS DE HORMÔNIOS ANABOLIZANTES HGH Testosterona (H) DHEA T3 e T4 Estrogênios (M) Progesterona (M) Melatonina Pregnenolona PREMISSAS 1. MECANISMOS DE AÇÃO HORMONAL 2. NUTRIÇÃO CELULAR ADEQUADA VOLTADA PARA O BOM DESEMPENHO HORMONAL 3. RESPOSTAS ENDOCRINAS E IMUNES DO EXERCICIO NUTRIÇÃO X HORMÔNIOS X RENDIMENTO POR QUE ESTUDAR? TROCA/COMUNICAÇÃO INTERCELULAR SÍNTESE DE MOLÉCULAS VARIAÇÃO DA ENERGIA LIVRE MINERAIS ENVOLVIDOS COM A MODULAÇÃO HORMONAL ZINCO SELENIO IODO CROMO VANADIO BORO COMPLEXO B Nutrição • Recomendações específicas da DIRETRIZ DA SOCIEDADE BRASILEIRA DE MEDICINA DO ESPORTE • ACSM - Medicine & Science in Sports & Exercise: March 2009 - Volume 41 - Issue 3 - pp 709-731 SPECIAL COMMUNICATIONS: Position Stands Proteínas Gorduras Carboidratos Vitaminas Minerais Nutracêuticos Fitoquímicos Água Desbiose Detoxificação Administração Tabletes Cápsulas Soft gels Líquidos Pós e barras . Carboidratos CARBOIDRATOS - ANTES 3A6 HORAS 5 MINUTOS 30 A 60 MINUTOS Décombaz J, et al. Fructose and galactose enhance postexercise human liver glycogen synthesis. Med Sci Sports Exerc. 2011 Oct;43(10):1964-71. CARBOIDRATOS - DURANTE INTENSIDADE DURAÇÃO DIETA/ OFERTA AMBIENTE Atenua respostas imunossupressoras de citocinas e hormônios (Gleeson, Venkatraman, Pendergast, Nieman, Pendersen: 1998-2012) EQUILÍBRIO E PROPORÇÃO • CHO de 40 a 70 % do valor energético total • GORDURAS não mais que 30 % do VET Planejamento • Dia a dia do Atleta – ELITE X AMADORES • Dia da Competição • Semana de Competição • Erros mais comuns PONTOS-CHAVE * Ao longo do TREINAMENTO: • Manter balanço energético para : – Evitar overreaching e overtraining – Evitar desequilíbrios hormonais – Infecções oportunistas PONTOS-CHAVE * COMPETIÇÃO: • Iniciar a prova corretamente hidratado – Evitar : – Desidratação; – Complicações Gastro-intestinais; – Fadiga e Cãibras; Hopkins M, et al. The relationship between substrate metabolism, exercise and appetite control: does glycogen availability influence the motivation to eat, energy intake or food choice? Sports Med. 2011 Jun 1;41(6):507-21. Erros mais comuns: • Entender a real necessidade do atleta • Açúcares simples • Ingestão de sódio – De 800 a 1200 mg para 1600 a 2500 mg • Ingestão de estimulantes como cafeína – Náuseas, dores de cabeça e desidratação • Gorduras e fibras CARBOIDRATOS • • • • • Reposição de glicogênio Manutenção da glicemia Retardo da fadiga Relação Insulina/Cortisol Constituem mais de 50% do valor energético total da alimentação • Podem chegar até 75% da ingestão diária Desempenho 1) Carboidratos de alto índice glicêmico 2) Recomendação – Esforço – 0,7 gr de cho/kg PC/hr 3) 8 mg Na por gr/CHO Oxidação exógena de CHO Asker E. Jeukendrup (2011): Nutrition for endurance sports: Marathon, triathlon, and road cycling, Journal of Sports Sciences, 29:sup1, S91-S99 Esvaziamento Gástrico e a Liberação de Fluidos • A combinação de glicose e frutose esvazia mais rapidamente que apenas a glicose. • Acúmulo no plasma ainda é mais rápido. • Isto sugere que a hidratação e aporte de fluidos seja facilitada. Pfeiffer B, et al. Nutritional intake and gastrointestinal problems during competitive endurance events. Med Sci Sports Exerc. 2012 Feb;44(2):344-51. Sintomas Gastrointestinais • Comum em corredores de endurance • Sintomas associados com a ingestão de fibras, proteínas, gorduras e bebidas com alta concentração de carboidratos • Glicose com frutose – melhor tolerabilidade em função da maior taxa de esvaziamento, aparecimento no plasma e oxidação – Currell K, et al. Plasma deuterium oxide accumulation following ingestion of different carbohydrate beverages. Appl Physiol Nutr Metab. 2008. Dec; 33(6):1067-72. – Jeukendrup AE, et al. Effect of beverage glucose and sodium content on fluid delivery. Nutr Metab (Lond). 2009 Feb 20;6:9. Conclusão – Glicose + Frutose • Juntos conferem maior oxidação que quando comparada a glicose isoladamente • Aumenta a eficiência oxidativa • Aumenta a biodisponibilidade de fluidos • Parece reduzir a fadiga em exercício de muito longa duração • Melhora a performance quando comparada a glicose isoladamente Burke LM, et al. Carbohydrates for training and competition. J Sports Sci. 2011;29 Suppl 1:S17-27. Gorduras Gorduras • Dieta normal: Triglicerídeos, Colesterol e Fosfolipídios • Ácidos Graxos: Saturados, Monoinsaturados, Poliinsaturados • Esvaziamento Gástrico Lento • Dietas Hiperlipídicas demoram a digerir Jeukendrup AE. Nutrition for endurance sports: marathon, triathlon, and road cycling. J Sports Sci. 2011;29 Suppl 1:S91-9. Gorduras FAT LOADING? ESTRATEGIA PARA MELHORAR O DESEMPENHO EM ATIVIDADES DE LONGA DURAÇÃO? Jeukendrup AE, Randell R. Fat burners: nutrition supplements that increase fat metabolism. Obes Rev. 2011 Oct;12(10):841-51. Jeukendrup AE, Saris WH, Brouns F, Halliday D, Wagenmakers JM. Effects of carbohydrate (CHO) and fat supplementation on CHO metabolism during prolonged exercise. Metabolism. 1996 Jul;45(7):915-21. Jeukendrup AE, Saris WH, Schrauwen P, Brouns F, Wagenmakers AJ. Metabolic availability of medium-chain triglycerides coingested with carbohydrates during prolonged exercise. J Appl Physiol. 1995 Sep;79(3):756-62. LIPÍDEOS: Ácidos Graxos N-3 “ A suplementação de ácidos graxos poliinsaturados ômega 3 Influencia o equilíbrio das respostas imunes no atleta por influenciar a síntese de citocinas e mediadores inflamatórios” Andrade, PMM. Dietary Long Chain n-3 Fatty Acids and Anti-Inflammatory Action:Potential Application in the field of Physical Exercise. Nutrition, 20:243,2004. Metabolismo dos AGE Ácidos Graxos N-6 Linoléico C 18:2 Enzima Ácidos Graxos N-3 Alfa-linolênico C18:3 6-desaturase Gama-linolênico C 18:3 C18:4 Elongase Dihomo-Gama-linolênico C 18:3 Prostaglandinas Série 1 C 20:4 5-desaturase Araquidônico C 20:4 Prostaglandinas Série 2 Tromboxanos Eicosapentanóico C 20:5 Leucotrienos Série 4 Prostaglandinas Série 3 Tromboxanos Leucotrienos Série 5 Elongase Docosapentaenóico C 22:5 Elongase 6-desaturase Beta-oxidação Docosahexaenóico C 22:6 CONCENTRAÇÃO PLASMATICA DE ACIDOS GRAXOS RESPOSTA IMUNO-INFLAMATORIA APÓS A SUPLEMENTAÇÃO DE AG N3 RESPOSTA HORMONAL APÓS SUPLEMENTAÇÃO DE N3 Exposição Tóxica e Destoxificação em atletas • Inalaçao de toxinas ambientais • Deposição e absorção cutânea de pesticidas nos treinos ao ar livre (o que é potencializado pela sudorese) • Ingestão elevada de frutas e cereais cultivados com agrotóxicos • Suplementos com corantes, flavolizantes, conservantes e outros ativos químicos “O processo de detoxificação de xenobioticos no organismo pode representar significativa utilização de nutrientes essenciais, não somente para a manutenção das funções vitais como também para o atendimento das exigencias fisilógicas e metabolicas associadas ao esforço físico.” ÁGUA Principal recurso ergogênico!!!! – A taxa normal de transpiração nos atletas varia de 0.5 a 2.0 L/h !!! – Depende da temperatura, humidade, intensidade do esforço !!! Maughan RJ, Noakes TD: Fluid replacement and exercise stress. A brief review of studies on fluid replacement and some guidelines for the athlete. Sports Med 1991, 12(1):16-31. REPOSIÇÃO HÍDRICA • Antes do exercício - 600 a 800 ml de líquido 2 horas antes da atividade • Durante o exercício - 500 a 1000 ml/h (125 –250 ml a cada 15 minutos) • Após o exercício - 150% de líquidos considerando o que foi perdido • Água e Eletrólitos Curr Sports Med Rep. 2004 Aug;3 (4):219-23. GSSI,2002. Água Alcalina • Combate os radicais livres – (ORP negativo) • Equilíbrio funcional • pH > 7 • Por que usar? – Dietas modernas são ácidas; – Suplementos esportivos são ácidos; – Plástico aquecido libera xenoestrógenos; Conclusão • Adequar o balanço nitrogenado • Adequar a ingestão de vitaminas do metabolismo energético e do complexo B • Compostos atioxidantes • Proteínas de alto valor biológico • Lipídios monoinsaturados • Omega 3 AFINAL….. “Não adianta ter uma Ferrari e por gasolina de terceira no tanque.” Como o exercício de força altera o metabolismo da fibra muscular? Estrutura do Músculo Esquelético Membrana celular: Sarcolema: retirada de cargas e produtos e condução de excitação elétrica para fibra muscular. Invaginação do Sarcolema: Tubulos T: transmissão do potencial para dentro do músculo Retículo sarcoplasmático (RS): crescimento, reparo e substituição muscular Miofibrilas: Milhares de filamento proteicos organizados – 2 tipos • Filamentos finos: – Actina – Tropomiosina – Troponina Banda I p/ A • Filamentos grossos: – Miosina Estende-se toda Banda A • Zona H: região na qual os filamentos grossos não são sobrepostos pelos finos Suprimento sanguíneo do Músculo esquelético • Vasos sanguíneos orientados em paralelo • N capilares - contraem e dilatam de acordo com controle Nervoso, hormonal e local Atividades aeróbias (corrida,natação,ciclismo): fluxo sanguíneo (até 100x) e superfície efetiva para permuta de gases e nutrientes entre sangue e fibras musculares (VASODILATAÇÃO) Atividade de força muscular: fluxo sanguíneo durante contração (> pressão intramuscular) – Fte energética p/ esforço muscular: reações anaeróbias glicolíticas e Cr fosfato. fluxo sanguíneo e vasodilatação durante o relaxamento Óxido nítrico • Neurotransmissores, estesse de cisalhamento e distensão dos vasos Liberação de NO pelas células do endotélio vascular • VASODILATADOR: – > Fluxo sanguíneo – > Aporte muscular de nutrientes, oxigênio e mensageiros químicos, – Rápida eliminação das substâncias tóxicas acumuladas (ácido láctico, amónia, etc) – músculos conseguem produzir energia durante mais tempo, e, uma vez que estão bem oxigenados, evitar o processo de anaerobiose provocado pela falta de oxigénio. • Precursor: L-arginina Distribuição das fibras musculares nas diferentes categorias atléticas Categoria atlética % fibras vermelhas % de fibras rápidas Corredores de maratona 82 18 Nadadores 74 26 Atleta masculino nível médio 45 55 Halterofilistas 45 55 *Corredores de velocidade e Saltadores 37 63 Guyton;1985. Síntese Proteica Após repetidas lesões das fibras musculares: Miofibrilas das células Aumentam número Sofrem espessamento quantidade de proteínas contrateis nas fibras treinadas significativo ATP intramuscular, PCr e glicogênio muscular reserva de energia anaeróbica – Ritmo + rápido de transferência de energia p/ treinamento de força Hipertrofia do tec conjuntivo – Proteção p/ as articulações e músculos de possíveis lesões. Hormônios sinalizadores • Insulina (Pâncreas) • IGF (Fígado) • GH ( Hipófise anterior) • Testosterona Hormônios são reconhecidos e captados por receptor específico: Membrana celular (tempo resposta: min ou seg) Dentro do núcleo - Interage com DNA (tempo resposta: min, hs ou dias) Glicose Aminoácidos Arginina, Lisina Insulina Transporte glicose (músculo e cels adiposas Estimula síntese proteica Inibe proteólise transporte de aa através membrana plasmática níveis celulares de RNA formação de proteínas pelos ribossomos Substrato energético (Glicose, AGL) Jejum Refeição rica em PTN Exercício Mistura de AA (arginina) Stress GH Captação de Glicose pelos tecidos Estimula produção (fígado) IGF (I e II) Estágio IV sono Estimula síntese proteica Lipólise transporte de aa através membrana plasmática níveis celulares de RNA formação de proteínas pelos ribossomos • Liberação: durante o sono • Importante repouso e treinamento adequado Testosterona • Efeito direto sobre a síntese de tecido muscular • Afeta indiretamente o conteúdo proteico das fibras – promove liberação de GH • Migra para nucleo celular (interage com receptores) que iniciam a síntese proteica • Mulheres: [ testosterona] 1/10 : aumenta com exercícío. Nutrição - alternativa para “ativar” mecanismos anabólicos? Suplementos de aminoácidos – reforçam a produção natural dos hormônios anabólicos? • • • • • • Arginina Ornitina Lisina Tirosina Leucina outros aminoácidos. Doses muito elevadas e perigosas p/ aumentar liberação GH Leucina • Qdo combinada com Insulina – efeitos anabólicos no músculo. • Mecanismos ainda não esclarecidos. • AA não serve apenas como substrato para síntese. • translação do mRNA p70S6K • Insulina e leucina ativam a p70S6K através de mecanismo distintos no músculo esquelético humano. • Evidência de que a leucina degradação protéica Mecanismos sinalizadores da insulina e de AA Arginina Estímulo para a liberação do GH Lisina Estímulo para a liberação do GH Estímulo para liberação de Insulina Arginina e Lisina • Objetivo: – Verificar efeito da ingestão dos AA arginina e Lisina na [GH] • Protocolo: – Placebo, 1,5mg de L-arginina e 1,5mg L-Lisina , Placebo sem exercício de força, AA sem exercícíos de força. • Resultados: – [ ] GH > 30, 60 e 90 min com exercícío – Ingestão dos aa não induziu mudanças [GH]. Metz e col, 1997. Proteínas • Não existe mecanismo de armazenamento Excesso PTN é oxidado e N excretado • Estão sempre sendo renavadas - Turnover proteico • Ritmo de renovação de 3 a 5g/kg/dia • A maioria das PTN e enzimas estruturais são sintetizadas e degradas a altas taxas (≠ meia vida) • Ruptura das PTN em AA – enzimas hidrolíticas (mecanismos influenciados pela insulina) Proteínas Gde parte dos AA liberados por proteólise são reciclados p/ síntese PTN ~ 50g são degradados (0,8g/kg/dia) – AA liberados - Renovação contínua PTN – Catabolizados diretamente p/obtenção de energia – Transformados em gordura (PTN em excesso) – Transformados em carboidrato Neoglicogênese Falta de PTN ou energia: aceleração do catabolismo proteico AA podem entrar na rota da gliconeogênese Catabolismo proteico • PTN degradada em seus AA componentes • Degradação dos AA Liberação de Amônia Incorporada às moléculas de Glutamina e Alanina Transportadas para o Fígado Detoxificação Uréia (metabolicamente inerte) Excreção Rim Taxa de conversão de aminoácidos derivados da amônia ate uréia é limitado Contra- indicações – dieta rica em PTN • Função renal excreção de Nitrogênio sobrecarga renal perda de água Desidratação • Perda de Cálcio Dietas ricas em PTN excreção urinária de Cálcio. 20 mg de Ca/1 g de PTN. ♀ EUA: 9/1. • Aterogênese Ptn de origem animal – ricas em gordura. Dietas hiperproteicas (< 2g/kg/dia)- Não associada ao surgimento e/ou indução de patologias hepáticas e renais Atenção: Indivíduos com histórico familiar de problemas renais Balanço do Nitrogênio INDIVÍDUO SAUDÁVEL + Nitrogênio ingerido DIETA BALANCEADA Nitrogênio excretado 90 % urina 10 % fezes EQUILÍBRIO NITROGENADO • Equilíbrio Nitrogenado Ingesta = Excreção • Balanço Nitrogenado Positivo Ingesta > Excreção - Crescimento (infância e adolescência) - Gestação e lactação - Treinamento resistido Nitrogênio ingerido • Balanço Nitrogenado Negativo Ingesta < Excreção - Jejum prolongado - Dietas pobres em proteína - Infecções, queimaduras, cirurgias -Ingestão adequada de PTN e CHO (organismo cataboliza PTNenergia (MM) Nitrogênio excretado Nitrogênio excretado Nitrogênio ingerido Nitrogênio ingerido Nitrogênio excretado Digestão Proteínas da dieta Lúmen Intestinal Aminoácidos 40% Capilares aa + Dipeptídios Tripeptídios 60% Enterócito Aminoácidos aa Dipeptidases Tripeptidase •Somente fetos e recém-nascidos são capazes de captar algumas PTN sem digestão prévia (Imunoglobulinas do colostro do leite). •Velocidade de transporte dos peptídeos ultrapassa a velocidade de transporte de aa. •Após fracionamento das PTN pelas enzimas pancreáticas e peptidases da borda em escova, os di e tripeptídeos produzidos são transportados através da membrana da borda em escova Dose de proteína ingerida Como avaliar a ingestão de proteína? • Consumo absoluto em gramas • % de contribuição para o VCT • Quantidade consumida por kg peso /dia Níveis excessivos e perigosos • Consumo absoluto por gramas: >165g/dia • % de contribuição do VCT: > 35% • Quantidade consumida por kg peso /dia: >2,7g/kg/dia (em indivíduo de 80kg) * hiperaminoacemia, hiperamonemia, hyperinsulinemia, nausea, diarréia e até a morte Recomendação prática • Consumo absoluto por gramas: <118g/dia • % de contribuição do VCT: < 25% • Quantidade consumida por kg peso /dia: >1,5 2,0 g/kg/dia • Aumento de ptn – Não deve ser alta em gordura total e saturada • Aumento de ptn – cuidado com deficiência nutricional Bodybilders (200- 400g) RDA • Consumo absoluto por gramas: >118g/dia • % de contribuição do VCT: > 15-20% de • Quantidade consumida por kg peso /dia: >0,8g/kg/dia • Indivíduos que praticam atividade física intensa - 1,2g a 1,7g/dia. Recomendações Situação Recomendação Atletas recreacionais (4x/sem por 0,8 a 1,0 g/Kg/dia 30 min) Treinamento de resistência 1,2 a 1,6 g/Kg/dia aeróbia 1,2 g/Kg/dia Intensidade moderada 1,6 g/Kg/dia Volume extremo (tour de ciclismo) Treinamento de força Novatos Regulares 1,2 a 1,7 g/Kg/dia 1,5 a 1,7 g/Kg/dia 1,0 a 1,2 g/Kg/dia Atletas adolescentes durante o 1,5 g/Kg/dia pico de crescimento Maughan, 2004 Disponibilidade de CHO • Fadiga precoce • Diminuição da performance • Catabolismo muscular • Ingestão adequada de CHO previne: – Gliconeogenese muscular – Preservação da massa muscular • Quantidade de CHO mínima: 120g/dia –150g/dia Disponibilidade de CHO • > Secreção de Insulina: anabólico captação de aa pelo músculo. • Se 1g CHO/ Kg é ingerido na 1a hora após, há quebra de proteína muscular e um Balanço Positivo. Velocidade de absorção de AA Whey protein – Rápida Abs: PTN soluvel – subito AA, por curto período Caseína - Lenta absorção Fixa estômago - atrasa esvaziamento gástrico Moderado AA, por prolongado período Síntese Proteica: Estimulada 68% após refeição WP e 31% após refeição CAS Catabolismo muscular: inibido 34% por 7h CAS Será que uma rápida absorção resulta em uma maior síntese protéica? Ergogenic Aid - Defined Substance or device that enhances energy production, use, or recovery and provides an athlete with a competitive advantage. Ergogenic Aid - Examples Mechanical (shoes) Psychological (hypnosis) Physiologic (blood doping) Nutritional (creatine) Pharmacologic (anabolic steroids) Why do athletes use supplements? • • • • Provide more convenient form of nutrient Prevent a perceived deficiency Provide direct ergogenic effect Belief that every top athlete is taking it; they can’t afford to lag behind Many athletes will do whatever it takes to win… • In 1995, 198 Olympic-level power athletes were given this scenario: – You are offered a banned substance with 2 guarantees: • You will not be caught • By taking the substance you will win Only 3 declined! …at any cost The same 198 athletes were offered a banned substance with 2 additional guarantees: You will win every event for the next 5 years You will die at the end of those 5 years 50% still said they would use it! Prevalence 1996-1999 10,449 boys and girls age 12-18 surveyed: – 4.7% of boys and 1.6% of girls used protein powder or shake, creatine, amino acids/HMB, DHEA, growth hormone, or anabolic steroids at least weekly to improve appearance or strength Placebo effect in athletes Athletes are HIGHLY suggestible – 97% believe placebo effect works – 73% said they had experienced it – Beedie CJ. J Sports Sci Med 2007 • “Expectancy Effect” is significant – Belief in efficacy performance improvement • Pill Colors red/orange/yellow stimulant • Injection > pill • Expensive > cheap Nocebo effect in athletes Belief that a substance negatively affects performance 1.57% slower 3x30sec sprints from nocebo – Beedie et al. Ergogenic Aid # 1 Anabolic Steroids Analogs of testosterone More than 100 types Forms: Oral Injection Topical (gels, creams) Prevalence 2009 Jr high: 2% 12th grade: 5% (males 7%, >females 2%) Anabolic Steroids – Proven Effects • • • • • Increase in fat-free mass Increase in body weight Increase in arm girth Increase in leg girth Increase in bench press and squat scores • Increase in libido Anabolic Steroids—Disproven Effects • No effect on endurance exercise – Males on treadmill • Eur J Appl Physiol 2006 – VO2max in rats • Med Sci Sports Exer 2004 Anabolic Steroids - Side Effects Hepatocellular damage Cardiovascular disease (stroke, MI) Psychological disturbance Effects can sometimes be permanent! “Side effects of anabolic androgenic steroids abuse” Followed body builders for 2 years • • • • Decr LH, FSH, SHBG Decr sperm count and fertility index Decr HDL (57 42) No change liver/prostate US, hematological indices More side effects… Men – – – – – – – – Acne Premature baldness Prostatic hypertrophy Prostatitis *Injection complications Testicular atrophy *Impotence *Gynecomastia More side effects… Adolescents Premature closure of physes Decreased libido Depression More side effects… Women – – – – – – Clitoral enlargement Menstrual dysfunction Male-pattern baldness *Masculinization Deepening of voice *Hirsutism Side effects that can be PERMANENT Premature growth plate closure Testicular atrophy Gynecomastia Male pattern baldness Female masculinization Excessive hair growth Deepening voice Clitoral enlargement Anabolic Steroid regulation Illegal except by prescription Banned by the USADA, NCAA, NFL, NBA, and MLB Prohormones Precursors of testosterone Androstenedione Dehydroepiandrosterone Androstenediol Prohormones – the evidence No improvement in strength or lean body mass *Causes positive urine test for steroids Prohormones - Side Effects • May be similar to anabolic steroids, but probably less frequent. Prohormone regulation • Anabolic Steroid Control Act of 2004 – prohormones classified as controlled substances • Banned – USADA, NCAA, NFL, NHL, NBA, MLS Stimulants Stimulants Caffeine Amphetamines Cocaine Sympathomimetics Ephedrine Pseudoephedrine Phenylephrine Phenylpropanolamine (PPA) Modafinil (Provigil) Stimulant Use Prevalence • Ephedrine: – 3.5% in NCAA athletes • Clin J Sports Med 2001 – 12% of HS boys/26% of girls have tried • Med Sci Sports Exer 2002 • Caffeine – 33% of British club track/field athletes – 60% of British club cyclists • Chester N, Int J Sports Med 2008 Caffeine’s Proven Effects – Increased time to fatigue (”capacity”) in wide range of lab protocols • Prolonged submaximal (> 90 min) • Sustained high-intensity (20-60 min) • Short-duration supra-max (1-5 min) – Likely beneficial in endurance and “stop-n-go” sports – No clear benefit in strength/power events Caffeine in Endurance Running • • • • • • 4.2-sec faster 1.5-km 1-3% faster 5-km 24-sec faster 8-km 50-sec faster 10-km military pack march No change in 21-km race Improved treadmill time-to-exhaustion in marathoners Caffeine in Other Sports • Rowing: 1-3% faster 2000m race • Swimming: 24-sec faster 1500m race – About 21 min • Cycling: 3.5% higher mean power in 40km race Caffeine Dosing • Doses 2-9 mg/kg in studies • 2-5 mg/kg usually effective • 250-500 mg – – – – – Cola: 40 mg Coffee: 100 mg Tea: 20-100 mg Red Bull: 115 mg Vivarin: 200 mg • No difference in fx between “users” and “nonusers” Caffeinated Sports Drinks No proven performance benefit – 18-km run times – Pl vs carb drink vs carb+150mg caffeine – consumed 4x in race – Int J Sports Med 2005 Ephedrine 78-sec faster 10-km run (with backpack & helmet) vs placebo – 30-sec faster than caffeine -0.8 mg/kg – No benefit when added to caffeine Modafinil Cycling at 85% VO2max – 22% longer time to exhaustion vs Placebo 18.3 min vs 15.6 – Central mechanism: decreased RPE – Dose 4 mg/kg – No side-efx seen Stimulant Mechanisms of Action Not conclusively known Likely: CNS-regulated decreased perceived exertion Stimulants - Side Effects • • • • • • Anxiety* Dysrhythmias* Hypertension* Hallucinations Addiction Death Stimulant regulation Many prohibited by WADA & NCAA Most ADHD meds Some still allowed (cold meds) Pseudephedrine, PPA Caffeine WADA: no longer monitored NCAA < 15 mcg/ml 1 cup coffee = 100mg = 1.5 mcg/ml in urine Blood Doping Increasing the number of red blood cells in the body to increase the oxygen carried to muscle Administration of blood, red blood cells, or related blood products Erythropoietin Stimulates bone marrow to produce red blood cells Blood Doping – proven effects • Increased Endurance – 7% increase in Hgb – 5% increase in VO2 max – 34% increase in time to exhaustion at 95% VO2 max – 44 second improvement in 5 mile treadmill run time (Williams and Branch summarized study findings) Blood Doping - Side Effects Infections with transfusions Increased viscosity of blood Stroke, MI, PE Blood Doping - regulation Erythropoietin only by prescription Doping prohibited by WADA, NCAA Blood tested for antigens Ceiling on allowable Hct level at 50 Beta-2-Agonists Physiology – Bronchodilation, tachycardia – Examples: albuterol, terbutaline, salmeterol Beta-2-Agonists – proven effects Clear benefit in asthma and EIB – No increase in ventilation of performance in studies of NON-asthmatic athletes Clenbuterol: anabolic (25% as effective as anabolic steroids) Side effects: tremor, tachycardia Regulation – WADA: most prohibited – NCAA: inhalation permitted Beta blockers Physiology – Decreased heart rate, reduced tremor, lower BP Examples – Atenolol – Metoprolol – Propranolol Efficacy in sports – Proven improved scores in shooting sports Beta blockers • Side effects – Hypotension, bronchospasm, bradycardia • Regulation – NCAA: banned in Rifle sports – WADA: banned in… • Aeronautic, archery, autos, billiards, bobsled, boules, bridge, curling, golf, gymnastics, motorcycling, modern pentathlon, powerboating, bowling, sailing, shooting, skiing, snowboarding, wrestling – Alcohol banned for same reason Creatine Most popular nutritional supplement In 2000, >$300 million in sales in the US Creatine Replenishes ATP in anaerobic exercise Made in liver, kidneys, and pancreas Dietary sources: meat, fish Stored in skeletal muscle Excreted as creatinine in urine Creatine – disproven effects • Meta-analysis 2002: – NO overall benefit on anaerobic performance (weight lifting, sprint cycling, spring running, sprint swimming, kayaking, arm cranking, or jumping/kicking) – 29 quality studies • 35% were statistically significant between Cr and Placebo • 65% NON statistically significant Creatine – disproven effects • Meta-analysis 2003: – No significant difference in field-based athletic performance (e.g. running, swimming) X X X Branch JD. Int J Sports Nutr Exerc Metab June 2003 Creatine – proven effects • 2003 meta-analysis of strength efx: – 8% increase in 1RM strength vs placebo (20% vs 12%) – 14% increase in # of reps – Highly variable response • Body Composition – Increase in weight and lean body mass by 1-2 kg over short term Rawson, Volek. J Strength Cond Res 2003. Creatine Mechanisms of Action Increases PCr energy availability – ->Increased effort in resistance training • Increased satellite cell and myonuclei • Increased gene expression for contractile proteins – ? Due to more available energy • Increased contractile protein synthesis Creatine Mechanisms of Action Creatine - Side Effects Studies of 2-10 weeks: no side efx Long term: Creatine - regulation Not banned anywhere Surveys suggest ~ 50% of male college athletes and 1/3 of all NFL players are on creatine β-Hydroxy-Methylbutyrate (HMB) • Physiology – A metabolite of the essential amino acid leucine – Produced in small amounts endogenously – Regulates protein metabolism • Less catabolism, more anabolism • ? Increased muscle mass HMB – proven effects • Meta-analysis 2003: – Small increase in lean mass and 25% greater strength vs placebo • Greater effect in untrained persons – Less muscle breakdown – Some utility in muscle wasting • Side-efx: none reported in 3 studies • Non-regulated Nissen, Sharp. J Appl Physiol 2003 Buffering Agents: proven • Mitigate metabolic acidosis after strenuous exercise – Bicarbonate, citrate • NaHCO3: Proven ergogenic efx in high-intensity exercise – – – – – – 100m & 200m swim 400 & 800 m run Repeated sprints Repeated judo throws 30 min high-intensity running 60 min max-effort cycle ergometry • Citrate less effective in studies Bicarbonate Dose: 0.2 - 0.3 mg/kg GI side effects common β-Alanine Supplementation results in higher skeletal muscle CARNOSINE, an intracellular buffer Proven effective in high-intensity anaerobic performance – >1 to <5 min duratio n Acidosis most prominent – Delays onset of neuromusc fatigue – Increased time to exhaustion – (no change in VO2max or max strength) β-Alanine • Dose – 3.2 – 6.4 gm/day – Effective after 4 week supplementation – 800 mg qid or 1600 mg slow-release qid • Side-efx: paresthesias at doses higher than above – No others reported • Not regulated or prohibited Nitric Oxide-releasing agents • Physiology – Arginine is a precursor of NO – NO regulates BP and blood flow to organs – Most supplements: Arginine αketoglutarate • Claims – Improves “pump” and blood flow to muscles – Increases strength and size – Speeds recovery Nitric Oxide-releasing agents: the evidence Several studies in performance – Endurance exercise: No benefit in endurance athletes Limited evidence of benefit in debilitated pts – Strength exercise: mixed results, no benefit proven, more studies needed Nitric Oxide-releasing agents Side effects – Diarrhea, nausea, migraines Regulation: none Peptide Hormones & Analogues Adreno-corticotripon (ACTH) Growth hormone (hGH) Chorionic gonadotropin (hCG) Insulin-like growth factor (ILGF-1) Leutenizing hormine (LH) Erythropoietin (EPO) etc. Diuretics & Urine Manipulators • Can be used to mask urine tests • Examples – Acetazolamide (altitude sickness) – Furosemide (Lasix) – Spironolactone (acne, HF) – Hctz (Htn) Anti-Estrogens Often used to counteract side-efx of anabolic steroids – Tamoxifen (breast cancer) – clomiphene (infertility) Other Substances • NO proven ergogenic effects from: – – – – – – – – – – Citrulline, Carnitine, Coenzyme Q, Colostrum Asparagine, Arginine, Pyruvate, Ribose Choline, Chromium picolinate Antioxidants, Bee pollen, Boron Folate, Gamma-hydroxy-butyrate Inosine, leucine Yohimbine Vitamins and Minerals Branched chain amino acids • Inconsistent effects in Overtraining Syndrome Supplements, Herbals, Energy Drinks • ‘TAKE AT YOUR OWN RISK’ – Be VERY cautious to recommend any • Not tested by the FDA – Often contain traces of banned substances – May not contain what label says • No such thing as “side-effect free!” • Some supplement ingredients are discussed on USADA at http://www.usantidoping.org.dro/ Contamination facts 2001 IOC international study; – 634 non-hormonal supplements, – 15% contained undeclared steroids 2007 study of 58 USA supplements – 25% contaminated w/ prohib steroids – 11% contaminated w/ prohib stimulants 2008 UK study of 152 supplements – 10% contaminated w/ steroids/stim Drugs in Elite Athletes 2010-11 NCAA Banned Drugs The NCAA bans the following classes of drugs: a. Stimulants a. Phenylephrine and pseudoephedrine OK b. Anabolic Agents c. Alcohol and Beta Blockers (banned for rifle only) d. Diuretics and Other Masking Agents e. Street Drugs f. Peptide Hormones and Analogues g. Anti-estrogens h. Beta-2 Agonists Anti Doping in Elite Amateur Competition • WADA rules apply – Testing will be done in accordance with WADA/USADA • Permitted/Prohibited? http://www.usantidoping.org.dro 1-800-233-0393 2010 WADA Prohibited Substances Anabolic androgenic steroids Other anabolic agents – Clenbuterol, selective androgen receptor modulators (SERM) Erythropoiesis-stimulating agents Growth hormone and growth factors Chorionic gonadotropins, LH Insulins Platelet-rich plasma (IM injection) – Other locations require Declaration 2010 WADA Prohibited Substances • Hormone antagonists and modulators – DHT blockers (finasteride, dutasteride) – They mask anabolic steroid use • Diuretics and masking agents – Acetazolamide, hctz, spironolactone – Plasma expanders; glycerol, IV albumin, etc. 2010 WADA Prohibited METHODS • Enhancement of Oxygen Transfer – Blood doping (transfusions, etc.) • Gene doping – Gene transfers – Substances than alter gene expression • Chemical or mechanical manipulation – IV infusions, except if hospitalized – Sample tampering 2010 WADA Prohibited in COMPETITION Stimulants, e.g. ADHD meds – Exceptions: Caffeine OK Phenylephrine and PPA OK Ephedrine < 10 mcg/ml Pseudoephedrine < 150 mcg/ml Narcotics Cannabinoids 2010 WADA Prohibited in COMPETITION • Glucocorticoids by oral, IV, IM, rectal – Declaration required for inhalation and other injection sides – Topicals OK 2010 WADA Prohibited in PARTICULAR SPORTS • Alcohol – Aeronautic, archery, auto, karate, shooting, motorcycle, bowling, powerboating • Beta-blockers – Aeronautic, archery, autos, billiards, bobsled, boules, bridge, curling, golf, gymnastics, motorcycling, modern pentathlon, powerboating, bowling, sailing, shooting, skiing, snowboarding, wrestling What if prohibited med is required to treat illness or injury? Declarations and Therapeutic Use Exemptions Declaration required for: – Non-systemic corticosteroid injections – Inhaled albuterol, salmeterol, glucocorticoids TUE required for – All other prohibited substances – Doc fills out, send to USADA, along with supporting documents – Process takes 1-2 months to approve – Variable duration Testing During Competition • Commonly tested substances: • Stimulants • Narcotics • Cannabinoids • Glucocorticosteroids • Anabolic Agents • Hormones and Related Substances • Diuretics and other Masking Agents • Beta-2 Agonists • Anti-Estrogenics • Prohibited methods, such as blood doping If a prohibited substance or method is detected in your sample – even if it was unintentional – it will result in a doping violation. Athletes’ Rights During Testing Having an Athlete Representative and/or Language Specialist present Doping Control Officer (DCO) explain any part of the testing process that you do not understand. A copy of all forms used to document the processing of your sample. Providing feedback to improve testing policies or procedures. Note: If any portion of the test does not seem right to you, document that on the doping control paperwork. Athlete’s Responsibilities During Testing • Comply with the doping control procedures. • Bringing a photo ID to the Doping Control Station. • Report to the Doping Control Station within 60 minutes of being notified for testing. • Stay within view of the DCO (or Chaperone) from the time you are notified until the sample collection procedures are complete. • Ensure that all paperwork is completely accurate A2 Biology Topic 7 Performance enhancing drugs Banned substances and practices Anabolic steroids Stimulants Hormones and releasing factors Beta-2 agonists Narcotics Beta blockers Hormone agonists Diuretics Blood doping Gene doping Is it an infringement of athletes human rights to be required to give blood and urine samples? Page reference: 178-179 Edexcel A2 Biology (concept) textbook Steroid hormones Pass through the plasma membrane and stimulate protein synthesis Steroid hormones Other steroid molecules Mechanism of action of steroid hormones: steroid hormone cell surface membrane Hormone enters cell and binds with receptor Complex binds to DNA and acts as a transcription factor receptor nuclear membrane enters nucleus hormone-receptor complex Switches on a gene for synthesis of a protein Testosterone Stimulates protein synthesis Results in bigger and stronger muscles Anabolic steroids Natural testosterone is quickly broken down. testosterone Testosterone is modified to produce drugs that remain for longer in the body These synthetic anabolic steroids are illegal. nandrolone Side-effects of using anabolic steroids Infertility due to disruption of normal hormone production: - disrupted menstrual cycle - reduced sperm production -impotence In addition: - liver damage - high blood pressure - heart attacks - increased aggression 21 year old body builder: A and B Severe acne conglobata C After 8 weeks off steroids and with antibiotics Peptide hormones Peptide hormones do not enter the cell. They bind to receptors on the cell surface membrane. They also act to switch genes on or off. Human erythropoietin Mechanism of action of peptide hormones: peptide hormone receptor cell surface membrane Inactive secondary messenger eg. cAMP Secondary messenger activated: initiates a protein kinase cascade acts as a transcription factor which switches on gene for a specific protein Erythropoietin Erythropoietin is synthesised in the kidneys Causes the synthesis of enzymes required for synthesis of red blood cells (erythrocytes) in bone marrow. Useful for treating anaemia. Use of erythropoeitin Increases number of blood cells and therefore enhances oxygen supply to muscles. Improvement of 10% in aerobic performance Use is popular with endurance athletes and cyclists Side-effects of overuse of erythropoietin Excess of red blood cells can lead to strokes and heart attacks . Attacks most common at night due to low heart rate. Thought to have caused the unexpected deaths of 18 european cyclists between 1987 1991 . Abuse difficult to prove as it is naturally occurring. Ethics of performance-enhancing drugs Problems with deciding on what is illegal: Ethical questions: Creatine is not banned: Classed as a nutritional supplement Can cause kidney damage and high blood pressure Is everything acceptable in the pursuit of sporting excellence? Erythropoietin is banned: Is a naturally occurring hormone Can cause strokes and heart attacks Isn´t it the choice of the athlete to risk using drugs or not? Blood doping banned: Donating, storing and transfusing own blood before competition Do use of performanceenhancing drugs improve or ruin competition? High altitude training not banned: Increases number of red blood cells. Caused by natural increase in erythropoietin production. Are there circumstances when drug use is acceptable? Essay Read pages 182 – 183 (of concept approach textbook) and answer question 2 on page 183: Describe an absolutist and a relativist ethical position on the proposal to set a maximum total red blood cell count for athlete rather than measure erythropoietin levels.