Iron Game
Veteran
Written by Dan Gwartney, MD
Most anabolic steroid (AAS) users are not extreme in their practices. While people find it interesting to discuss the cycles of professional athletes, amazed by the number and amount of drugs used to achieve elite levels of mass and power, the common user tends to plan cycles chosen for convenience and reliability. Though it is often passed over due to its familiarity, the classical cycle for decades was “Deca & D-bol,” referring to nandrolone decanoate and methandrostenolone (Deca-Durabolin and Dianabol). Dan Duchaine (deceased), renowned author of The Underground Steroid Handbook and former AAS guru to many top bodybuilders, once commented that if someone doesn’t grow on Deca and Dianabol, nothing will work.1
Deca and D-bol is considered a near-ideal cycle by many recreational AAS users, as it is convenient, inexpensive, effective and relatively free from side effects. [Note: methandrostenolone is no longer sold under the trade name Dianabol] D-bol (a term used generically to refer to all methandrostenolone products) provides rapid gains in strength and mass, though this is accompanied by a significant increase in body water and side effects (acne, irritability, hair loss) are common with higher dose use. D-bol use by women holds a very high risk of hirsute (masculinizing) side effects, including: facial hair, deepening voice and clitoral hypertrophy. It is also important to note that D-bol is a 17á-alkylated steroid, which means that it can cause liver damage at moderate dosages; rarely, cases of liver tumors, malignant cancers, or blood-filled cysts have been reported, posing serious, even fatal threats to a user’s health.2
Deca (again, a term used generically for many nandrolone products) is very nearly the opposite. It is slow to act, requiring two weeks or longer to generate noticeable gains, but the gains are usually of higher quality even though they are not as pronounced. Deca does not carry as high a risk of androgenic effects in males even though it binds tightly to the androgen receptor. In fact, Deca is actually converted into a less androgenic metabolite by the enzyme 5á-reductase (the enzyme that converts testosterone to DHT and thought to be responsible for hair loss and prostate enlargement). Impotence and loss of libido is infrequently associated with Deca; many AAS users combine Deca with an androgenic AAS such as D-bol to prevent these changes in sexual drive or function. The combination of Deca and D-bol is considered an ideal balance of two complementary drugs by most users.3
One side effect that is not uncommon in many AAS cycles, including the venerable Deca and D-bol cycle is gynecomastia (“bitch tits”).4 Gynecomastia is the growth of breast tissue in a male. This condition is relatively common during puberty and later in life; it is also seen in severe cases of obesity and with the use of certain drug therapies, including: antipsychotics, anti-androgens used during prostate cancer treatment and AAS excess. When gynecomastia occurs during a cycle that includes Deca, the condition is often blamed on other drugs in the cycle, as Deca is commonly believed to be resistant to aromatization. In the case of the prototypical Deca and D-bol cycle, this is reasonable, as one metabolic by-product of methandrostenolone (D-bol) is a potent estrogen, 17á-methylestradiol.2 However, the pristine reputation of nandrolone may be unwarranted and incorrect. Deca is rarely used in one-drug cycles, as it is fairly mild in regard to size or strength gains, particularly in comparison to most other AAS. When used without stacking with other AAS, Deca cycles are generally low to moderate in dose (200mg-600mg/week). It is rare for an adult male to report any significant side effects, with the possible exception of impotence and a reduction in libido (sex drive). This occurs because nandrolone interacts with the androgen receptor and progesterone receptors.5 Progesterone is a female sex hormone, much like estrogen. Many of the steroid-based contraceptives for men being developed within the pharmaceutical industry combine an androgen (such as a long-acting testosterone) along with a progestin.6 While high doses of androgens do lower sperm counts dramatically, to completely shut down sperm production, extremely high concentrations of testosterone are required and the effect is not uniform among all men. Additionally, the concentrations of androgen-only contraception required for effective contraception would result in significant side effects in many people. By combining an androgen and a progestin, researchers have found that fairly consistent contraceptive results can be achieved without introducing significant side effects. As nandrolone is capable of activating both androgen and progestin receptors, it is easy to see how fertility and sex drive could be affected when anabolic (supraphysiologic) doses are used. In fact, natural testosterone production is quickly suppressed and it may take several weeks to months after nandrolone use ends before normal testosterone production is restored. Thus, most experienced AAS users include post-cycle support at the end of a Deca-inclusive cycle, such as hCG and/or Clomid.3
Not only does nandrolone directly interact with androgen and progestin receptors, it also holds the potential of being converted into estradiol (the most potent natural estrogen, commonly a metabolite of testosterone). Herein lies a matter of much confusion. Only recently have the steps involved in the aromatase reaction been defined in sufficient detail to discuss and analyze.7 While testosterone and androstenedione are both natural substrates (starting blocks) for the aromatase reaction, nandrolone is not normally formed in human males in significant amounts.8 In fact, only recently has it been proven that metabolites of nandrolone may be present in athletes absent of the use of anabolic steroids, though again, only trace amounts were produced— below the limits allowed by most drug tests.8 Nandrolone appears to be a very minor by-product of the aromatase reaction that does not accumulate under normal physiologic conditions. Nowhere in the string of reactions involved in classic aromatization is 19-nortestosterone (nandrolone) formed. It is likely that the nandrolone metabolites detected in human males under hCG stimulation represent an overload of the aromatase system with nandrolone being a flawed product, similar to a factory reject.
Confusion prevails regarding the aromatization of nandrolone associated with steroid use. It has been reported by many sources, including respected researchers in prestigious scientific journals, that nandrolone is a non-aromatizable steroid.9 A close examination of related research reveals possible sources for the confusion and provides a concrete answer to the question.
The aromatase reaction is a complex, multi-step pathway involving a number of enzymatic reactions.7 It is present in many different tissue types (brain, ovary, adipose, placenta, etc.) and across many different species (human, horse, pig, etc.).10-13 In fact, even certain bacteria are capable of aromatizing androgens.7 In part, solving the hypothesis regarding any possible interaction of nandrolone with the aromatase reaction has been muddied by studying the enzyme system using vastly different sources. It is known that the aromatase enzyme (cytochrome p450arom) varies greatly. Bacterial aromatase has little similarity to mammalian aromatase. Among animals, there are distinct differences between pigs, horses and man that make translating results from one species to the others difficult.7,10,11,14 Further, it has been shown that even within a single species, there are different promoters (signals that “turn on” enzyme production) in different tissues.12 Conditions that may promote aromatization in the testes are different from those of fat cells.
In mammals, the aromatase reaction involves two separate enzymes that are jointly involved in converting androgens into estrogens.7,12 The first, the hemoprotein CYParom encoded by the CYP19 gene (for those of you who need that kind of information), is the catalyst. It attacks the 19-carbon in two steps and the nearby 1-carbon by oxidizing the androgen molecule at those points. The resulting response and actions of the second enzyme (NADPH-cytochrome P450 reductase) cause the loss of the 19-carbon and the simultaneous generation of a phenolic A-ring (a defining feature of an estrogen). In the absence of a 19-carbon, such as in nandrolone, the reaction would be much less efficient if it was even able to function.
Many medico-scientific journals have noted nandrolone to be a non-aromatizable AAS. Studies using brain cells have shown nandrolone to be more neurotoxic (damaging to nerve cells) because it is not aromatized. It is true that nandrolone is not a candidate for classic aromatization, as the 19-carbon that is missing from nandrolone is the starting point for the entire aromatase reaction. Interestingly, nandrolone stimulates aromatase in rat models, even though it does not participate in the reaction. This would accelerate the conversion of other androgens (testosterone, D-bol, etc).
Yet, the results of a recent study published in the Climacteric prove that nandrolone and other 19-nortestosterone-derived steroids can be converted into estrogenic steroids through a series of enzymatic reactions that take place in the human liver.15 The [?_from=R40&_trksid=p5197.m570.catalytic"]catalytic[/URL] (accelerating) first enzyme, CYP 450arom, is not present in the adult human liver, though CYP 450arom is present in certain liver diseases and tumors. However, another enzyme called CYP 450 monooxygenase is able to attack the 2-carbon of the nandrolone and begin the generation of the phenolic A-ring…the definitive step in converting an androgen (or 19-norandrogen in this case) into an estrogen.
Recall that the CYP 450arom played a &_nkw=catalytic"]catalytic[/URL] role, speeding up the classic aromatase reaction. CYP 450 monooxygenase is much slower and less efficient. This accounts for the comments that nandrolone aromatizes at a rate of 20 percent of testosterone or androstenediol.3 In fact, the rate may be much less. Realizing that Deca is injected intra-muscularly and disperses slowly, and the enzyme system discussed in the Climacteric article was specific to the liver, it is unlikely that standard nandrolone-containing cycles would see a major contribution to feminizing effects from nandrolone being aromatized. However, oral norandrogen-precursors were prominently marketed during the prohormone glory days and an oral norandrogen (7á-methylnortestosterone) is being developed as a potential male contraceptive. It is possible, especially at abusive doses, that such oral norandrogens may elevate estrogen levels sufficiently to cause gynecomastia or other estrogen-related problems. In women provided with oral norandrogens for menopause, researchers speculate that the drugs may hold the potential of increasing estrogen and thus, risk for blood-clotting problems or estrogen-sensitive cancers.15
Nandrolone is considered a relatively safe AAS and has been used extensively by recreational bodybuilders and power athletes. It has rarely been considered to increase the risk of estrogen-related problems, as steroids missing the 19-carbon are not substrates for the classic aromatization reaction. However, in addition to its capacity to stimulate progesterone receptors (a related group of feminizing sex steroid hormones), nandrolone may also increase estrogen levels via a secondary aromatase reaction, promoting the development of gynecomastia and prolonging the delay in restoring natural testosterone production post-cycle. Classic aromatization of testosterone or other androgens may also be accelerated by nandrolone. Oral forms of nandrolone, including prohormones, likely have a much higher estrogenic index and a higher risk of estrogenic side effects due to hepatic (liver) first pass clearance.
References:
1. Personal communication with Dan Duchaine, Columbus, OH;1996.
2. Llewellyn W. Dianabol (methandrostenolone). Anabolics 2005. Body of Science Press, Jupiter, FL;2005:114-8.
3. Llewellyn W. Deca-durabolin (nandrolone decanoate). Anabolics 2005. Body of Science Press, Jupiter, FL;2005:109-12.
4. Babigian A, Silverman RT. Management of gynecomastia due to use of anabolic steroids in bodybuilders. Plast Reconstr Surg, 2001;107:240-2.
5. Markiewicz L, Gurpide E. Estrogenic and progestagenic activities of physiologic and synthetic androgens, as measured by in vitro bioassays. Methods Find Exp Clin Pharmacol, 1997;19:215-22.
6. Walton MJ, Kumar N, et al. 7alpha-methyl-19-nortestosterone (MENT) vs testosterone in combination with etonogestrel implants for spermatogenic suppression in healthy men. J Androl, 2007;28:679-88.
7. Auvray P, Nativelle C, et al. Study of substr,ate specificity of human aromatase by site directed mutagenesis. Eur J Biochem, 2002;269:1393-1405.
8. Reznik Y, Dehennin L, et al. Urinary nandrolone metabolites of endogenous origin in man: a confirmation by output regulation under human chorionic gonadotropin stimulation. J Clin Endocrinol Metab, 2001;86:146-50.
9. Hobbs CJ, Jones RE, et al. Nandrolone, a 19-nortestosterone, enhances insulin-independent glucose uptake in normal men. J Clin Endocrinol Metab, 1996;81:1582-5.
10. Dintinger T, Gaillard JL, et al. Androgen and 19-norandrogen aromatization by equine and human placental microsomes. J Steroid Biochem, 1989 Nov;33(5):949-54.
11. Moslemi S, Auvray P, et al. Structure-function relationships for equine and human aromatases. A comparative study. Ann NY Acad Sci, 1998;839:576-7.
12. Simpson ER, Davis SR. Minireview: aromatase and the regulation of estrogen biosynthesis— some new perspectives. Endocrinology, 2001;142(11):4589-94.
13. Gaillard JL, Silberzahn P. Aromatization of 19-norandrogens by equine testicular microsomes. J [/w/ih/2900077329685"]Biol Chem[/URL], 1987 Apr 25;262(12):5717-22.
14. Roselli CE. The effect of anabolic-androgenic steroids on aromatase activity and androgen receptor binding in the rat preoptic area. Brain Res, 1998 May 11;792(2):271-6.
15. Kuhl H, Wiegratz I. Can 19-nortestosterone derivatives be aromatized in the liver of adult humans? Are there clinical implications? Climacteric, 2007;10:344-53.
Most anabolic steroid (AAS) users are not extreme in their practices. While people find it interesting to discuss the cycles of professional athletes, amazed by the number and amount of drugs used to achieve elite levels of mass and power, the common user tends to plan cycles chosen for convenience and reliability. Though it is often passed over due to its familiarity, the classical cycle for decades was “Deca & D-bol,” referring to nandrolone decanoate and methandrostenolone (Deca-Durabolin and Dianabol). Dan Duchaine (deceased), renowned author of The Underground Steroid Handbook and former AAS guru to many top bodybuilders, once commented that if someone doesn’t grow on Deca and Dianabol, nothing will work.1
Deca and D-bol is considered a near-ideal cycle by many recreational AAS users, as it is convenient, inexpensive, effective and relatively free from side effects. [Note: methandrostenolone is no longer sold under the trade name Dianabol] D-bol (a term used generically to refer to all methandrostenolone products) provides rapid gains in strength and mass, though this is accompanied by a significant increase in body water and side effects (acne, irritability, hair loss) are common with higher dose use. D-bol use by women holds a very high risk of hirsute (masculinizing) side effects, including: facial hair, deepening voice and clitoral hypertrophy. It is also important to note that D-bol is a 17á-alkylated steroid, which means that it can cause liver damage at moderate dosages; rarely, cases of liver tumors, malignant cancers, or blood-filled cysts have been reported, posing serious, even fatal threats to a user’s health.2
Deca (again, a term used generically for many nandrolone products) is very nearly the opposite. It is slow to act, requiring two weeks or longer to generate noticeable gains, but the gains are usually of higher quality even though they are not as pronounced. Deca does not carry as high a risk of androgenic effects in males even though it binds tightly to the androgen receptor. In fact, Deca is actually converted into a less androgenic metabolite by the enzyme 5á-reductase (the enzyme that converts testosterone to DHT and thought to be responsible for hair loss and prostate enlargement). Impotence and loss of libido is infrequently associated with Deca; many AAS users combine Deca with an androgenic AAS such as D-bol to prevent these changes in sexual drive or function. The combination of Deca and D-bol is considered an ideal balance of two complementary drugs by most users.3
One side effect that is not uncommon in many AAS cycles, including the venerable Deca and D-bol cycle is gynecomastia (“bitch tits”).4 Gynecomastia is the growth of breast tissue in a male. This condition is relatively common during puberty and later in life; it is also seen in severe cases of obesity and with the use of certain drug therapies, including: antipsychotics, anti-androgens used during prostate cancer treatment and AAS excess. When gynecomastia occurs during a cycle that includes Deca, the condition is often blamed on other drugs in the cycle, as Deca is commonly believed to be resistant to aromatization. In the case of the prototypical Deca and D-bol cycle, this is reasonable, as one metabolic by-product of methandrostenolone (D-bol) is a potent estrogen, 17á-methylestradiol.2 However, the pristine reputation of nandrolone may be unwarranted and incorrect. Deca is rarely used in one-drug cycles, as it is fairly mild in regard to size or strength gains, particularly in comparison to most other AAS. When used without stacking with other AAS, Deca cycles are generally low to moderate in dose (200mg-600mg/week). It is rare for an adult male to report any significant side effects, with the possible exception of impotence and a reduction in libido (sex drive). This occurs because nandrolone interacts with the androgen receptor and progesterone receptors.5 Progesterone is a female sex hormone, much like estrogen. Many of the steroid-based contraceptives for men being developed within the pharmaceutical industry combine an androgen (such as a long-acting testosterone) along with a progestin.6 While high doses of androgens do lower sperm counts dramatically, to completely shut down sperm production, extremely high concentrations of testosterone are required and the effect is not uniform among all men. Additionally, the concentrations of androgen-only contraception required for effective contraception would result in significant side effects in many people. By combining an androgen and a progestin, researchers have found that fairly consistent contraceptive results can be achieved without introducing significant side effects. As nandrolone is capable of activating both androgen and progestin receptors, it is easy to see how fertility and sex drive could be affected when anabolic (supraphysiologic) doses are used. In fact, natural testosterone production is quickly suppressed and it may take several weeks to months after nandrolone use ends before normal testosterone production is restored. Thus, most experienced AAS users include post-cycle support at the end of a Deca-inclusive cycle, such as hCG and/or Clomid.3
Not only does nandrolone directly interact with androgen and progestin receptors, it also holds the potential of being converted into estradiol (the most potent natural estrogen, commonly a metabolite of testosterone). Herein lies a matter of much confusion. Only recently have the steps involved in the aromatase reaction been defined in sufficient detail to discuss and analyze.7 While testosterone and androstenedione are both natural substrates (starting blocks) for the aromatase reaction, nandrolone is not normally formed in human males in significant amounts.8 In fact, only recently has it been proven that metabolites of nandrolone may be present in athletes absent of the use of anabolic steroids, though again, only trace amounts were produced— below the limits allowed by most drug tests.8 Nandrolone appears to be a very minor by-product of the aromatase reaction that does not accumulate under normal physiologic conditions. Nowhere in the string of reactions involved in classic aromatization is 19-nortestosterone (nandrolone) formed. It is likely that the nandrolone metabolites detected in human males under hCG stimulation represent an overload of the aromatase system with nandrolone being a flawed product, similar to a factory reject.
Confusion prevails regarding the aromatization of nandrolone associated with steroid use. It has been reported by many sources, including respected researchers in prestigious scientific journals, that nandrolone is a non-aromatizable steroid.9 A close examination of related research reveals possible sources for the confusion and provides a concrete answer to the question.
The aromatase reaction is a complex, multi-step pathway involving a number of enzymatic reactions.7 It is present in many different tissue types (brain, ovary, adipose, placenta, etc.) and across many different species (human, horse, pig, etc.).10-13 In fact, even certain bacteria are capable of aromatizing androgens.7 In part, solving the hypothesis regarding any possible interaction of nandrolone with the aromatase reaction has been muddied by studying the enzyme system using vastly different sources. It is known that the aromatase enzyme (cytochrome p450arom) varies greatly. Bacterial aromatase has little similarity to mammalian aromatase. Among animals, there are distinct differences between pigs, horses and man that make translating results from one species to the others difficult.7,10,11,14 Further, it has been shown that even within a single species, there are different promoters (signals that “turn on” enzyme production) in different tissues.12 Conditions that may promote aromatization in the testes are different from those of fat cells.
In mammals, the aromatase reaction involves two separate enzymes that are jointly involved in converting androgens into estrogens.7,12 The first, the hemoprotein CYParom encoded by the CYP19 gene (for those of you who need that kind of information), is the catalyst. It attacks the 19-carbon in two steps and the nearby 1-carbon by oxidizing the androgen molecule at those points. The resulting response and actions of the second enzyme (NADPH-cytochrome P450 reductase) cause the loss of the 19-carbon and the simultaneous generation of a phenolic A-ring (a defining feature of an estrogen). In the absence of a 19-carbon, such as in nandrolone, the reaction would be much less efficient if it was even able to function.
Many medico-scientific journals have noted nandrolone to be a non-aromatizable AAS. Studies using brain cells have shown nandrolone to be more neurotoxic (damaging to nerve cells) because it is not aromatized. It is true that nandrolone is not a candidate for classic aromatization, as the 19-carbon that is missing from nandrolone is the starting point for the entire aromatase reaction. Interestingly, nandrolone stimulates aromatase in rat models, even though it does not participate in the reaction. This would accelerate the conversion of other androgens (testosterone, D-bol, etc).
Yet, the results of a recent study published in the Climacteric prove that nandrolone and other 19-nortestosterone-derived steroids can be converted into estrogenic steroids through a series of enzymatic reactions that take place in the human liver.15 The [?_from=R40&_trksid=p5197.m570.catalytic"]catalytic[/URL] (accelerating) first enzyme, CYP 450arom, is not present in the adult human liver, though CYP 450arom is present in certain liver diseases and tumors. However, another enzyme called CYP 450 monooxygenase is able to attack the 2-carbon of the nandrolone and begin the generation of the phenolic A-ring…the definitive step in converting an androgen (or 19-norandrogen in this case) into an estrogen.
Recall that the CYP 450arom played a &_nkw=catalytic"]catalytic[/URL] role, speeding up the classic aromatase reaction. CYP 450 monooxygenase is much slower and less efficient. This accounts for the comments that nandrolone aromatizes at a rate of 20 percent of testosterone or androstenediol.3 In fact, the rate may be much less. Realizing that Deca is injected intra-muscularly and disperses slowly, and the enzyme system discussed in the Climacteric article was specific to the liver, it is unlikely that standard nandrolone-containing cycles would see a major contribution to feminizing effects from nandrolone being aromatized. However, oral norandrogen-precursors were prominently marketed during the prohormone glory days and an oral norandrogen (7á-methylnortestosterone) is being developed as a potential male contraceptive. It is possible, especially at abusive doses, that such oral norandrogens may elevate estrogen levels sufficiently to cause gynecomastia or other estrogen-related problems. In women provided with oral norandrogens for menopause, researchers speculate that the drugs may hold the potential of increasing estrogen and thus, risk for blood-clotting problems or estrogen-sensitive cancers.15
Nandrolone is considered a relatively safe AAS and has been used extensively by recreational bodybuilders and power athletes. It has rarely been considered to increase the risk of estrogen-related problems, as steroids missing the 19-carbon are not substrates for the classic aromatization reaction. However, in addition to its capacity to stimulate progesterone receptors (a related group of feminizing sex steroid hormones), nandrolone may also increase estrogen levels via a secondary aromatase reaction, promoting the development of gynecomastia and prolonging the delay in restoring natural testosterone production post-cycle. Classic aromatization of testosterone or other androgens may also be accelerated by nandrolone. Oral forms of nandrolone, including prohormones, likely have a much higher estrogenic index and a higher risk of estrogenic side effects due to hepatic (liver) first pass clearance.
References:
1. Personal communication with Dan Duchaine, Columbus, OH;1996.
2. Llewellyn W. Dianabol (methandrostenolone). Anabolics 2005. Body of Science Press, Jupiter, FL;2005:114-8.
3. Llewellyn W. Deca-durabolin (nandrolone decanoate). Anabolics 2005. Body of Science Press, Jupiter, FL;2005:109-12.
4. Babigian A, Silverman RT. Management of gynecomastia due to use of anabolic steroids in bodybuilders. Plast Reconstr Surg, 2001;107:240-2.
5. Markiewicz L, Gurpide E. Estrogenic and progestagenic activities of physiologic and synthetic androgens, as measured by in vitro bioassays. Methods Find Exp Clin Pharmacol, 1997;19:215-22.
6. Walton MJ, Kumar N, et al. 7alpha-methyl-19-nortestosterone (MENT) vs testosterone in combination with etonogestrel implants for spermatogenic suppression in healthy men. J Androl, 2007;28:679-88.
7. Auvray P, Nativelle C, et al. Study of substr,ate specificity of human aromatase by site directed mutagenesis. Eur J Biochem, 2002;269:1393-1405.
8. Reznik Y, Dehennin L, et al. Urinary nandrolone metabolites of endogenous origin in man: a confirmation by output regulation under human chorionic gonadotropin stimulation. J Clin Endocrinol Metab, 2001;86:146-50.
9. Hobbs CJ, Jones RE, et al. Nandrolone, a 19-nortestosterone, enhances insulin-independent glucose uptake in normal men. J Clin Endocrinol Metab, 1996;81:1582-5.
10. Dintinger T, Gaillard JL, et al. Androgen and 19-norandrogen aromatization by equine and human placental microsomes. J Steroid Biochem, 1989 Nov;33(5):949-54.
11. Moslemi S, Auvray P, et al. Structure-function relationships for equine and human aromatases. A comparative study. Ann NY Acad Sci, 1998;839:576-7.
12. Simpson ER, Davis SR. Minireview: aromatase and the regulation of estrogen biosynthesis— some new perspectives. Endocrinology, 2001;142(11):4589-94.
13. Gaillard JL, Silberzahn P. Aromatization of 19-norandrogens by equine testicular microsomes. J [/w/ih/2900077329685"]Biol Chem[/URL], 1987 Apr 25;262(12):5717-22.
14. Roselli CE. The effect of anabolic-androgenic steroids on aromatase activity and androgen receptor binding in the rat preoptic area. Brain Res, 1998 May 11;792(2):271-6.
15. Kuhl H, Wiegratz I. Can 19-nortestosterone derivatives be aromatized in the liver of adult humans? Are there clinical implications? Climacteric, 2007;10:344-53.
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