20: EPO
50
time to exhaustion at 80% VO2max increased about ______%
Autologous doping
uses a person's own blood that was previously stored
Homologous doping
uses blood from a matched donor
hematocrit
using blood doping to alter the _____ also affects normal developmental processes for the blood, parameters like ratio of reticulocyte hemo to total hemo become altered
Biosimilar drugs
faster path to approval is possible for follow-on biologic drugs that are similar to approved ones, can be same drug company that makes variant like in altered pharmacokinetics
symptoms of anemia
fatigue, breathlessness, heart beating faster, paleness, increased sweatiness, palpitations, cardiac output
World Anti-doping agency
formed by international agreement in 1999 in response to scandals
causes of anemia
genetic disorders, autoimmunity, premature birth, iron deficiency, vitamin B12 deficiency, chemotherapy, renal disease
blood viscosity
greatly increases risk of clotting, heart attack, stroke, pulmonary embolism
120
lifespan of an RBC - ____ days
blood doping
many untimely deaths of endurance athletes are suspected to be the result of _____ ______
Old Approach
method: compare an athlete's blood/urine parameters to normal patterns for the healthy population
sickle cell disease
mutation in hemoglobin, premature birth, common among blacks
1970s
natural human EPO hormone was purified during the _______
power output
net oxygen uptake capacity is a major determinant of _____ _____ during aerobic physical activity
anemia
one cause is reduced EPO production by diseased kidneys
Biosimilar drugs
only medically available outside USA, but also used for doping. Epoeitin beta, delta, omega, zeta
transfusion
originally blood doping was done by ______...increase capacity of bloodstream, increase oxygen
peripheral tissues
oxygen is released by capillaries in _______ _________
Recombinant EPO
(epoetin alpha) is present in blood and urine of users
Epoetin alpha
(recombinant erythropoietin, procrit, epogen) FDA approved in 1989
Aerobic metabolism
(uses oxygen) - is 19X better at deriving useful cellular energy from food than anaerobic metabolism
Darbepoetin alpha
Aransep: sequence-modified, highly glycosylated EPO with increased half-life
glycoprotein
EPO is a __________ (protein + carb modifications), modifications not from bacteria
lowest possible dose
FDA black box warning suggests using ______ _____ ___ to achieve medical benefit
6 minutes
If oxygen is cut off completely, the brain will die in just ___ ________
Kidney
Natural source of erythropoietin, produced by special O2 sensing cells here
Peginesatide
Omontys: a chemically modified peptide that mimics Erythropoietin
seconds
Only good for competitions of endurance that the difference is a matter of ________
autologous doping
USA cycling team admitted to using ______ _______ in the 1984 Olympics
anemia
a diseased state caused by reduced blood hemoglobin concentration (several types)
Erythropoietin
a hormone that stimulates the formation of red blood cells
O2
absorbed in the lung capillary beds, released in the tissue capillary beds
STAT dimers
activate transcription of key genes in the erythroblast lineage
EpoR
activates the JAK/STAT signal transduction pathway
Carbohydrate modifications
added to rDNA-based EPO as it moves through endoplasmic reticulum and Golgi apparatus
bone marrow
all cell types in the blood come from a common stem cell present in the ____ ________
Epoetin
an rDNA derived version of the human hormone erythropoietin that treats certain types of anemia and can be used as a performance enhancing drug
30
average O2 diffusion distance in human muscle is _____ mega meters
exogenous EPO
can treat certain types of anemia, such as caused by chemotherapy that poisons blood cell lineages and renal disease that decreases natural EPO
arteries
carry blood away from the heart
veins
carry blood to the heart
Erythropoietin
circulates as an endocrine hormone
RBCs
contain special O2 binding protein called hemoglobin
New Approach
creates a biological passport for each athlete through serial in-competition and out-of-competition blood and urine tests
deviations
detect cheaters by finding unlikely ________ from an athlete's own historical patterns
RBCs
have lost most specialized organelles including nucleus
50,000
human body contains about ________ miles of capillaries
Erythropoietin
increased within hours of low blood O2 levels, trigger can be low atmospheric O2 levels or blood loss that reduces blood O2 density
blood viscosity
increases with hematocrit in a non-linear fashion
net oxygen uptake
influenced by ability of cardiovascular system to efficiently circulate blood
net oxygen uptake
influenced by ability of muscles to take in and use oxygen efficiently
net oxygen uptake
influenced by capacity of the blood to transport oxygen (blood oxygen density)
net oxygen uptake
influenced by training, which can improve both transport and utilization
RBCs
primary function is to transport O2
mammalian cell culture
rDNA based EPO must be manufactured using ______ ______ ______ for production
12
recombinant EPO increased VO2 max by about _____%
Blood doping
seeks to improve an endurance athlete's VO2max by increasing the oxygen carrying capacity of the blood - usually increases hematocrit
WADA code
set of rules regulating doping testing and punishment, does not apply to most US pro athletes
erythropoietin receptor
signaling by the __________ ___________ stimulates cell proliferation and differentiation in the erythroblast lineage
carbohydrate modifications
tests can identify recombinant EPO based on this difference in _____ ______
Hematocrit
the percent of the blood volume occupied by RBCs (aka erythrocytes)
anemia
will shift VO2 max down power curve, makes you less capable of doing aerobic work
recombinant EPO
with the availability of _________ ____, drug-based doping became a major problem in endurance sports