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12-04-2008, 08:56 AM
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Igf-1
Just thoguht I start this IGF-1 discussion thread. Comments, analysis and experiences......post them up!
I found this somewhere on the net so it is not mine but interesting stuff. IGF1, also known as somatomedin C, is polypeptide hormone about the same size as insulin. It is produced predominantly in the liver in response to growth hormone (GH) release from the pituitary gland. Many of the growth promoting effects of GH are due to its ability to release IGF1 from the liver. The conversion ratio of GH to IGF1 varies greatly in different individuals but most external sources of GH convert around 4-6mcg of IGF per one I.U. of GH. IGF-1 acts on several different tissues to enhance growth. IGF1 belongs in the 'superfamily' of substances known as 'growth factors,' along with epidermal (skin), transforming; platelet derived fibroblast, nerve, and ciliary neurotrophic growth factors. None of the other factors have any bearing on exoskeletal tissue incidentally however These agents all have in common the ability to stimulate cell division, known as mitogenesis, and cell differentiation. Meaning That In the case of IGF1 which does act on muscle tissue it will initiate the growth of new muscle fibers, and subsequently new receptors for testosterone. Users have unanimously concluded that it enhances cycles of steroids significantly. They also seem to be adamant about its ability to reduce fat and improve vascularity a great deal. The IGF1 Hype There is a considerable amount of hype surrounding IGF1. Every one is blaming the distended bellies of modern Bodybuilders on it. Also the freaky proportions that old bodybuilders that have been around for years are starting to attain. Anti-aging proponents are touting it as the miracle cure for every thing from Parkinson's disease to Alzheimer's. And the medical community has published numerous articles on it for its ability to cause cancer, diabetes and gigantism. While at the same time performing documented experiments on thousands of patients of muscle wasting diseases. And reporting significant turnabouts in there conditions. So what is a guy to think about IGF1 as far as athletic enhancement is concerned? Well first of all you need to know that most experiments conducted with IGF1 do not list the type of IGF used. I have written Dr. Robert Saline of the Swedish rejuvenation institute on several occasions and we have had in-depth discussions on the subject of IGF1 for physical appearance enhancement. He feels it would be unethical to prescribe IGF1 to a bodybuilder to increase muscle mass simply due to the fact that IGF1 has valid applications in the medical community, (Like I could give a rats ass about "ethical"). He can not argue that it is extremely effective as a promoter of muscle growth far beyond what androgens (steroids) alone can offer. Well fortunately in America IGF1 is not a drug (yet) and the FDA has no control over it as of now. This will change in the very near future however, Im absolutely sure of it. How to use IGF1 Assuming that you have acquired legitimate IGF1 (R3) long chain, That's IGF1 with the binding protein added. You should take dosages ranging from 60mcg up to 120mcg per day in divided doses. One injection in the morning and again at bed time. Never exceed 120mcg in one day. IGF1 can cause serious gastrointestinal problems such as tumors intestinal swelling diarrhea and vomiting. Most IGF1 comes in a concentration of 1000mcg per ML or CC so it makes it easy to measure in an insulin syringe. 10 IU on the syringe is 100mcg. Do the math. IGF + Insulin If you plan on doing IGF1 with Insulin, listen closely IGF1 is not that expensive, sure you can get away with using less by including insulin in the stack, but IGF1 and Insulin together have a pro-insulin effect on your blood sugar balance. It can enhance the chances of a hypoglycemic episode ten fold. I would recommend against it for any one not ABSOLUTLY comfortable with insulin or IGF1. Here is how insulin and IGF1 work together. Igfbp3 is the binding protein, which allows IGF1 to remain active in the system for a long enough period of time to really work its magic. IGF1 by nature has a half-life of less than 10 minutes by its self. The molecule was so small it would escape the blood stream very rapidly. This was the reason IGF1 was so "underground". It took very frequent injections at high dosages to achieve even minimal results. Aside from this reconstituting the compound required a degree in biochemistry. This short acting version was the only IGF1 known until recently IGF1 would have been administered in 100 mcg dosages 4-6 times a day. That is a hell of a lot of IGF1. That explains a lot of the distended bellies. Now with R3 long chain IGF1 and the Binding protein IGFBP3 IGF1 will last up to 6 hours in the system. By binding IGF to the IGFBP3 you make the molecule larger and it gets trapped in the blood stream until the protein is broken down and the IGF molecule escapes. You can further its life by combining Insulin with it, although I here its very risky. Insulin prevents the breakdown of IGFBP3 and leaves the IGF1 molecule roaming free in the blood stream for longer periods of time up to 12 hours as insulin levels return to normal IGFBP3 will begin to break down and the IGF1 will escape from its bound protein IGFBP3 again having a half life of less than 10 minutes. Insulin should be taken at the normal dosage it is usually administered at minus 10% about 45 minutes prior to the IGF1 infusion. Again let me remind you this can be deadly if you don't know what you are doing. And of course do not use Insulin for the nighttime injection of IGF1 by taking it in the morning you prolong the IGF1's half life to 12 hours and then take a 6 hour injection, you should be fine. Hell if you want to eat a big bowl of rice and drink another 100g of simple carbs 45 minutes before the bed time IGF1 infusion you could spike insulin for at least a few hours of extended IGF1 activity. If your not going to be using insulin in the stack then go ahead and do the same in the morning. What users report Users of IGF1 have reported various results but all along the same lines, It does not appear to be dramatically less effective in any one individual (at least not to the best of my knowledge). I have a good friend who had to stop taking IGF1 due to stomach illness that was completely unrelated But he to experienced good gains from it for the 2 weeks he was on it, his dosage was 120mcg per day. One hour after the first injection he went to the gym and immediately told me about the uncontrollable pump he got from just one set. That would indicate to me that he was experiencing some form of cell volumization. The general consensus on IGF1 seems to be that its benefits are as fallow: Increased Pump Pumps are reported to be so severe that workouts are often cut short due to lack of ability to the muscle through the full range of motion...ouch Gains retention is increased if IGF is used in a cycle I am not sure why, but IGF1 seems to make gains on a cycle stick with virtually no post cycle loss. Every bodybuilder I've spoken with seems to think this for some reason. Most of them use drugs like Anadrol or Dianabol with it because of the amount of size attained with these drugs. The usual draw back to these drugs is that in most users there is a post cycle "crash" that occurs, so the reasoning is to toss IGF1 into the stack and grow larger faster with out the post cycle crash blues. Reverses testicular atrophy Testicles if shrunken will return to "full swing" so to speak even in the middle of a cycle. If not shrunken they will not shrink during the cycle. This may explain partially why gains are kept after the cycle. Fatigue Users report feeling drained and tired all day. This seems to be one of the negative side effects to IGF1, it will make you sleep longer and you will require more sleep at night to feel rested for the morning. This is common with high doses of HGH and exhibited in children, whose IGF1 levels are extraordinarily high. A child needs 4 hours more sleep than an adult on average does. This may be directly or indirectly related to IGF1 levels. Stiffness An almost arthritic feeling is commonly associated with high levels of HGH, well IGF1 has the exact same property. IGF1 will cause your hands, fingers and knuckles to ache this is one way you can be sure you got real IGF1. IGF-1's Side effects Every thing has a down side. To bake a cake ya gotta brake an egg. IGF1 is no exception. The drug used in larger quantity around the 100mcg+ range will cause headaches, occasional nausea and can contribute to low blood sugar or hypoglycemia in some users. Although I have never heard of this first hand I'm sure its true. IGF1 will attach its self to the lining of the intestine and cause atrophy of the gut. Every thing IGF1 touches will grow and you have a lot of receptors on the lining of the large intestine and inner wall of the abdominal well. This is what causes the GH gut look. You can easily avoid this by limiting your dosages and cycle lengths. IGF1 cycles should be kept to 4-6 weeks with 4-6 weeks off in-between. IGF-1 is considerably more powerful than HGH and you need to think of it along those lines as far as dosing goes. We all know what to much HGH can do over prolonged periods of usage. The Neanderthal look is definitely not going to win any shows this year. I would recommend 80 mcg a day for 4 weeks at a time you should get good results from that for a while. I don't know if you will need to up the dosage at any point, but I would think in the case of IGF1 it wouldn't matter. If 80mcg doesn't do it for ya, then bump it up to 100 You should definitely feel it at this point If not suspect the IGF1 as being fake. Beyond 120 mcg per day your asking for trouble, This compound demands as much respect as its sister amino Insulin. Clinical Facts about IGF-1 IGF-1 is a polypeptide of 70 amino acids (7650 daltons), and is one of a number of related insulin-like growth factors present in the circulation. The molecule shows approximately 50% sequence homology with proinsulin and has a number of biological activities similar to insulin. IGF-1 is a mediator of longitudinal growth in humans or how tall you are capable of becoming. Serum IGF-1 concentrations are altered by age, nutritional status, body composition, and growth hormone secretion. A single basal IGF-1 level is useful in the assessment of short stature in children and in nutritional support studies of acutely ill patients. For the diagnosis of acromegaly, a single IGF-1 concentration is more reliable than a random hGH measurement (Oppizi, et al., 1986). IGF-1 can be used for the assessment of disease activity in acromegaly (Barkan, et al., 198. Almost all (>95%) of serum IGF-1 circulates bound to specific IGF binding proteins (IGFBPs), of which six classes (IGFBPs 1-6) have been identified (Rudd, 1991). BP3 is thought to be the major binding protein of IGF-1. __________________
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"all i know is, when im at the beach, chicks dont ask how much i bench, they just want to know how big my arms are."  classic
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12-04-2008, 08:57 AM
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IGF-1 Once Again Proves to be One of the Most Powerful Mediators of Muscle Growth
As we approach the new millennium we find the science of building muscle progressing faster than ever before. Long gone are the days of simple trial and error when it comes to building muscle. The modern bodybuilder demands more than just "hear say" if they are to adopt a new training routine or nutritional supplement. This column was created to keep today?s bodybuilder on the cutting edge of scientific research that might benefit them in their quest for body perfection. Not since the travels of Juan Ponce de Leon has the fountain of youth seemed so close! Title: Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function Researchers: Elisabeth R. Barton-Davis*, Daria I. Shoturma*, Antonio Musaro, Nadia Rosenthal, and H. Lee Sweeney*, * Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA and Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA Source: Proc Natl Acad Sci U S A 1998 Dec 22;95(26):15603-7 Summary: Although the mechanisms underlying age associated muscle loss are not entirely understood, researchers attempted to moderate the loss by increasing the regenerative capacity of muscle. This involved the injection of a recombinant adeno-associated virus directing overexpression of insulin-like growth factor I (IGF-I) in differentiated muscle fibers. They demonstrated that the IGF-I expression promotes an average increase of 15% in muscle mass and a 14% increase in strength in young adult mice (Figure 1), and remarkably, prevents aging-related muscle changes in old adult mice, resulting in a 27% increase in strength as compared with uninjected old muscles (Figure 2). Muscle mass and fiber type distributions were maintained at levels similar to those in young adults. These results suggest that gene transfer of IGF-I into muscle could form the basis of a human gene therapy for preventing the loss of muscle function associated with aging and may be of benefit in diseases where the rate of damage to skeletal muscle is accelerated. Discussion: I?m not sure where to begin. This study has the potential to completely change the way we age. In this experiment, a recombinant adeno-associated virus, directing overexpression of insulin-like growth factor I (IGF-I) in mature muscle fibers, was injected into the muscles of mice. The DNA that was originally in the virus was removed along with markers that stimulate immune response. DNA coding for IGF-1 was then put into the virus along with a promoter gene to ensure high rates of transcription. The results, as you can see by figures 1 & 2, were dramatic. IGF-1 plays a crucial role in muscle regeneration. IGF-1 stimulates both proliferation and differentiation of stem cells in an autocrine-paracrine manner, although it induces differentiation to a much greater degree. IGF-1, when injected locally, increases satellite cell activity, muscle DNA, muscle protein content, muscle weight and muscle cross sectional area. The importance of IGF-1 lies in the fact that all of its apparent functions act to induce muscle growth with or without overload although it really shines as a growth promoter when combined with physical loading of the muscle. IGF-1 also acts as an endocrine growth factor having an anabolic effect on distant tissues once released into the blood stream by the liver. IGF-1 possesses the insulin-like property of inhibiting degradation, but in addition can stimulate protein synthesis. The insulin-like effects are probably due to the similarity of the signaling pathways between insulin and IGF-1 following ligand binding at the receptors. The ability of IGF-I to stimulate protein synthesis resembles the action of GH, which was shown in separate studies on volunteers to stimulate protein synthesis without affecting protein degradation. Although it is often believed that the effects of GH are mediated through IGF-1, this cannot be the case entirely. First, the effects of the two hormones are different, in that GH does not change protein degradation. Second, the effect of GH is observed with little or no change in systemic IGF-1 concentrations. Age related muscle loss has been prevented with GH injections, however it is believed that this is accomplished through IGF-1. The results of this study are similar to other studies where IGF-1 was injected directly into muscle tissue, resulting in increases in size and strength of experimental animals. Using a virus as a genetic vehicle has an advantage over simply injecting the growth factor. The effects of a single viral treatment last significantly longer (months if not years) because the muscle cell itself is constantly overproducing its own IGF-1 from injected DNA. The fact that the IGF-1 produced by the muscle of these mice did not reach the blood stream is interesting. Systemic injections of IGF-1 have not been successful in inducing this kind of anabolic effect in humans. In addition, IGF-1 produced by the liver is genetically different than that produced by muscle tissue. It could be that providing additional DNA for the muscle to produce it?s own IGF-1 is the key to achieving anabolic and rejuvenative effects specifically in skeletal muscle. In this study there was a preferential preservation of type IIb muscle fibers in aging mice. These are the fibers most sensitive to muscle hypertrophy from training and they are also the first fibers to disappear with aging. In the mice receiving the engineered virus, there was also a preservation of the motor neuron, leading to an increase in functional capacity. It is speculated that age related muscle loss is secondary to the loss of neuronal activation of type-II fibers. By preventing the degeneration of typ-II motor units, functional capacity could be maintained into old age. This technique may also serve useful in the prevention of osteoporosis. Further study is necessary to determine wether IGF-1 is having an effect only on muscle fibers or on nervous tissues as well. Finally, it was also exciting to see muscle growth in the young mice who received the injection (15% increase in muscle mass). This means that the injection provided levels of IGF-1 far and above what the muscle normally has access to and not simply a preservation of normal levels. Remember that this was not combined with exercise. The growth of the injected muscles happened even without an extreme mechanical stimulus. The mice were simply allowed to run around as they usually do. Because of these dramatic results, the authors expressed concern about the use of this technique to enhance performance or cosmetic appearance. Research Update is not my personal soap box so I won?t go off on the gender centered hypocrisy of cosmetic enhancement in our society. All we can hope for is that this technique will be used to treat more important diseases such as muscular dystrophy and thereby become somewhat available for other uses as well. Mutations of the Myostatin Gene I know that we have all heard of the unlimited growth potential that we can accomplish through suppression of the Myostatin Gene. Yes it is very scary the possible side effects in the future, but there is an anti-myostatin antibody readily available in three month therapy dosages that can permanently, yes permanently suppress your Myostatin gene and allow you to have permanent unlimited muscle growth. Along with Myostatin suppression your body produces a totally different chain of growth factors. In studies, one "elite" individual who was tested and had a obvious mutation of his myostatin gene, showed to produce a different strain of IGF-1, had abnormal testosterone production, higher levels of GH, and upon administration of anabolic/androgenic factors grew with a much less dosage, and responded more aggessively to these compounds. Myostatin research is an amazing field in which I am absolutely intrigued by. When I worked for a bioscience company on the study of the TGF ? family of growth factors, the research doctors there found that administration of Long R3 IGF-1 actualy had a distinct effect on AR growth, cellular hyperplasia, cellular hypertrophy, and certain MYOSTATIN activity which bordered along the lines of total suppression. They were unsure if Long R3 actualy mutated the myostatin gene, but it does have a distinct effect on your bodies TGF ? growth factors (Transforming Growth Factor family, of which myostatin is a member of). The effects are unsure, but are definitely in a positive direction. After three years after my Long R3 usage my "natural" body weight is 236 at around eight percent BF. Sometimes I eat once a day and haven't been able to train but four times this month due to my job. After going through Special Forces Assesment and Selection I weighed 220 after traveling a great deal on foot with a hundred pound pack and eating sometimes once every two days. In high school my natural bodyweight was 185. When I turned twenty I was using in excess of 100mcgs daily of Long R3 IGF-1, which was unheard of. Now, clean, if I eat more than three meals daily and up my protein to as little as 230 grams daily, with the addition of training for an hour a day, I balloon. My arms are still 19 1/2 inches and I dont train them now due to my job. Long R3 enhanced my genetics to a new level, and to this day, I firmly believe, and the doctors that I worked with, believe that I in some way tweaked my myostatin gene. I just thought this might be interesting to some that ever used Long R3, and Im sure few went to doses of 100mcg's + daily! If you ever decide to Myostatin therapy (which is available out of the Czech Republic) or Long R3, be smart and research first. Just a little anabolic food for thought for Elite, and good luck. DISCLAIMER: THIS POST IS FOR INFORMATIONAL PURPOSES ONLY!!! Good luck and godspeed Sean Bishop Myostatin (GDF- is expressed uniquely in human skeletal muscle as a 12 kDa mature glycoprotein consisting of 113 amino acid residues and secreted into plasma. Myostatin is a member of the transforming growth factor ? superfamily of secreted growth and differentiation factors that is essential for proper regulation of skeletal muscle mass. Studies have shown that myostatin could play an important role in cardiac development and physiology. References McPherron A.C. and Lee S.J.: Double muscling in cattle due to mutations in the myostatin gene. Proc. Natl. Acad. Sci. USA 94, 12457-12461 (1997) Sharma M. et al.: Myostatin, a transforming growth factor ? superfamily member, is expressed in heart muscle and is upregulated in cardiomyocytes after infarct. Journal of Cellular Physiology 180:1-9 (1999) Gonzalez-Cadavid N.F., Taylor W.E. et al.: Organization of the human myostatin gene and expression in heathy men and HIV-infected men with muscle wasting. Proc. Natl. Acad. Sci. USA 95, 14938-14943 (199 Department of Medicine/Endocrinology, University of New Mexico School of Medicine, Albuquerque 87131-5271, USA.
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"all i know is, when im at the beach, chicks dont ask how much i bench, they just want to know how big my arms are." classic
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12-04-2008, 08:59 AM
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OBJECTIVE: To increase lean body mass and improve health status in patients with wasting
associated with the acquired immunodeficiency syndrome (AIDS) by treatment with recombinant human growth hormone (rhGH), recombinant human insulin-like growth factor 1 (rhIGF-1), or both. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: University of New Mexico Clinical Research Center and University of Texas Southwestern Medical Center. PATIENTS: 60 patients with AIDS and wasting as defined by the Centers for Disease Control and Prevention. Patients were divided into four groups of 15 patients each. INTERVENTION: Group 1 received 1.4 mg of rhGH once daily plus placebo twice daily; group 2 received 5 mg of rhIGF-1 twice daily plus placebo once daily; group 3 received 5 mg of rhIGF-1 twice daily plus 1.4 mg of rhGH once daily; and group 4 received placebo three times daily. MEASUREMENTS: Body weight, body composition, muscle strength, protein catabolism, quality of life, and immune status were assessed at baseline, and changes in these variables were measured at 6 and 12 weeks. RESULTS: At 6 weeks, lean body mass had increased and total fat mass had decreased in the groups receiving rhGH, rhIGF-1, or both. Group 3 had the greatest changes in lean body mass (mean +/- SE, 3.2 +/- 0.59 kg; P < 0.001); only in this group were changes in body mass maintained at 12 weeks. Only patients in group 1 had improvement in muscular strength of the knees and upper body (P = 0.04) and quality of life (P = 0.01). Immunologic function did not improve in any group. CONCLUSIONS: Growth factor therapy had significantly increased lean body mass and decreased fat mass by 6 weeks, but these improvements persisted for 12 weeks only in group 3. Growth factor therapy at the dosages used in this study is not recommended because the magnitude of weight gain was modest and improvements in quality-of-life measures varied. Publication Types: Clinical trial Multicenter study Randomized controlled trial It sounds to me that the IGF when taken by itself stops exerting anabolic effects after 6 weeks and the hGH and IGF together were the only ones to continue yielding positive effects after this time. Also they are talking about the dose around 5mg twice a day for a total daily dose of 10mg/day but the email Mr. N had forwarded to me from you had said that the dose you were recommending was in the area of 50-100mcg's/day. Can you clarify for me the difference. Also I had some questions on the effects when taken with insulin. Is IGF going to increase my chance of hyperglycemia and therefore cause an increased risk if taken with insulin? If so how can this be controlled. Note, that's because it wasn't the long r3 version that they had to use so much. Different effects of IGF-I on insulin-stimulated glucose uptake in adipose tissue and skeletal muscle Fredrik Frick1, Jan Oscarsson1, Kerstin Vikman-Adolfsson1, Malin Ottosson2, Noriko Yoshida2, and Staffan Ed?n1 1 Department of Physiology and Pharmacology and 2 Wallenberg Laboratory, G?teborg University, S-405 30 Goteborg, Sweden The effect of insulin-like growth factor I (IGF-I) on insulin-stimulated glucose uptake was studied in adipose and muscle tissues of hypophysectomized female rats. IGF-I was given as a subcutaneous infusion via osmotic minipumps for 6 or 20 days. All hypophysectomized rats received L-thyroxine and cortisol replacement therapy. IGF-I treatment increased body weight gain but had no effect on serum glucose or free fatty acid levels. Serum insulin and C-peptide concentrations decreased. Basal and insulin-stimulated glucose incorporation into lipids was reduced in adipose tissue segments and isolated adipocytes from the IGF-I-treated rats. In contrast, insulin treatment of hypophysectomized rats for 7 days increased basal and insulin-stimulated glucose incorporation into lipids in isolated adipocytes. Pretreatment of isolated adipocytes in vitro with IGF-I increased basal and insulin-stimulated glucose incorporation into lipids. These results indicate that the effect of IGF-I on lipogenesis in adipose tissue is not direct but via decreased serum insulin levels, which reduce the capacity of adipocytes to metabolize glucose. Isoproterenol-stimulated lipolysis, but not basal lipolysis, was enhanced in adipocytes from IGF-I-treated animals. In the soleus muscle, the glycogen content and insulin-stimulated glucose incorporation into glycogen were increased in IGF-I-treated rats. In summary, IGF-I has opposite effects on glucose uptake in adipose tissue and skeletal muscle, findings which at least partly explain previous reports of reduced body fat mass, increased body cell mass, and increased insulin responsiveness after IGF-I treatment. insulin-like growth factor I; soleus muscle; glycogen; triglyceride; lipid; free fatty acids; C-peptide; L-thyroxine; cortisol Title: Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function Researchers: Elisabeth R. Barton-Davis*, Daria I. Shoturma*, Antonio Musaro, Nadia Rosenthal, and H. Lee Sweeney*, * Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA and Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, MA Source: Proc Natl Acad Sci U S A 1998 Dec 22;95(26):15603-7 Summary: Although the mechanisms underlying age associated muscle loss are not entirely understood, researchers attempted to moderate the loss by increasing the regenerative capacity of muscle. This involved the injection of a recombinant adeno-associated virus directing overexpression of insulin-like growth factor I (IGF-I) in differentiated muscle fibers. They demonstrated that the IGF-I expression promotes an average increase of 15% in muscle mass and a 14% increase in strength in young adult mice (Figure 1), and remarkably, prevents aging-related muscle changes in old adult mice, resulting in a 27% increase in strength as compared with uninjected old muscles (Figure 2). Muscle mass and fiber type distributions were maintained at levels similar to those in young adults. These results suggest that gene transfer of IGF-I into muscle could form the basis of a human gene therapy for preventing the loss of muscle function associated with aging and may be of benefit in diseases where the rate of damage to skeletal muscle is accelerated. Discussion: I?m not sure where to begin. This study has the potential to completely change the way we age. In this experiment, a recombinant adeno-associated virus, directing overexpression of insulin-like growth factor I (IGF-I) in mature muscle fibers, was injected into the muscles of mice. The DNA that was originally in the virus was removed along with markers that stimulate immune response. DNA coding for IGF-1 was then put into the virus along with a promoter gene to ensure high rates of transcription. The results, as you can see by figures 1 & 2, were dramatic. IGF-1 plays a crucial role in muscle regeneration. IGF-1 stimulates both proliferation and differentiation of stem cells in an autocrine-paracrine manner, although it induces differentiation to a much greater degree. IGF-1, when injected locally, increases satellite cell activity, muscle DNA, muscle protein content, muscle weight and muscle cross sectional area. The importance of IGF-1 lies in the fact that all of its apparent functions act to induce muscle growth with or without overload although it really shines as a growth promoter when combined with physical loading of the muscle.
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"all i know is, when im at the beach, chicks dont ask how much i bench, they just want to know how big my arms are." classic
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12-04-2008, 09:00 AM
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IGF-1 also acts as an endocrine growth factor having an anabolic effect on distant tissues once released into the blood stream by the liver. IGF-1 possesses the insulin-like property of inhibiting degradation, but in addition can stimulate protein synthesis. The insulin-like effects are probably due to the similarity of the signaling pathways between insulin and IGF-1 following ligand binding at the receptors.
The ability of IGF-I to stimulate protein synthesis resembles the action of GH, which was shown in separate studies on volunteers to stimulate protein synthesis without affecting protein degradation. Although it is often believed that the effects of GH are mediated through IGF-1, this cannot be the case entirely. First, the effects of the two hormones are different, in that GH does not change protein degradation. Second, the effect of GH is observed with little or no change in systemic IGF-1 concentrations. Age related muscle loss has been prevented with GH injections, however it is believed that this is accomplished through IGF-1. The results of this study are similar to other studies where IGF-1 was injected directly into muscle tissue, resulting in increases in size and strength of experimental animals. Using a virus as a genetic vehicle has an advantage over simply injecting the growth factor. The effects of a single viral treatment last significantly longer (months if not years) because the muscle cell itself is constantly overproducing its own IGF-1 from injected DNA. The fact that the IGF-1 produced by the muscle of these mice did not reach the blood stream is interesting. Systemic injections of IGF-1 have not been successful in inducing this kind of anabolic effect in humans. In addition, IGF-1 produced by the liver is genetically different than that produced by muscle tissue. It could be that providing additional DNA for the muscle to produce it?s own IGF-1 is the key to achieving anabolic and rejuvenative effects specifically in skeletal muscle. In this study there was a preferential preservation of type IIb muscle fibers in aging mice. These are the fibers most sensitive to muscle hypertrophy from training and they are also the first fibers to disappear with aging. In the mice receiving the engineered virus, there was also a preservation of the motor neuron, leading to an increase in functional capacity. It is speculated that age related muscle loss is secondary to the loss of neuronal activation of type-II fibers. By preventing the degeneration of typ-II motor units, functional capacity could be maintained into old age. This technique may also serve useful in the prevention of osteoporosis. Further study is necessary to determine wether IGF-1 is having an effect only on muscle fibers or on nervous tissues as well. Finally, it was also exciting to see muscle growth in the young mice who received the injection (15% increase in muscle mass). This means that the injection provided levels of IGF-1 far and above what the muscle normally has access to and not simply a preservation of normal levels. Remember that this was not combined with exercise. The growth of the injected muscles happened even without an extreme mechanical stimulus. The mice were simply allowed to run around as they usually do. Because of these dramatic results, the authors expressed concern about the use of this technique to enhance performance or cosmetic appearance. Research Update is not my personal soap box so I won?t go off on the gender centered hypocrisy of cosmetic enhancement in our society. All we can hope for is that this technique will be used to treat more important diseases such as muscular dystrophy and thereby become somewhat available for other uses as well. Title: Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats. Researchers: Gregory R. Adams & Samuel A. McCue Department of Physiology and Biophysics, University of California, Irvine, Ca. Source: Journal of Applied Physiology 84(5): 1716-1722, 1998 Summary: The present study was undertaken to test the hypothesis that direct IGF-I infusion would result in an increase in muscle DNA as well as in various measurements of muscle size. Either 0.9% saline or nonsystemic doses of recombinant human IGF-I (rhIGF-1) were infused directly into a non-weight-bearing muscle of rats, the tibialis anterior (TA), via a fenestrated catheter attached to a subcutaneous miniosmotic pump. Saline infusion had no effect on the mass, protein content, or DNA content of TA muscles. Local IGF-I infusion had no effect on body or heart weight. The absolute weight of the infused TA muscles was ~9% greater (P < 0.05) than that of the contra-lateral TA muscles. IGF-I infusion resulted in significant increases in the total protein and DNA content of TA muscles (P < 0.05). As a result of these coordinated changes, the DNA-to-protein ratio of the hypertrophied TA was similar to that of the contra-lateral muscles. These results suggest that IGF-I may be acting to directly stimulate processes such as protein synthesis and satellite cell proliferation, which result in skeletal muscle hypertrophy. Discussion: The details of the mechanisms and pathways by which mechanical stress stimulates localized muscle fiber hypertrophy are still being elucidated. It is clear however, that growth hormone (GH), fibroblast growth factors (FGF) and insulin-like growth factors (IGF) play a central role in this process. Insulin-like growth factor I (IGF-I) peptide levels have been shown to increase in overloaded skeletal muscles (G. R. Adams and F. Haddad. J. Appl. Physiol. 81: 2509-2516, 1996). In that study, there was an increase in IGF-1 content before measurable increases in muscle protein and was correlated with an increase in muscle DNA content. Several other studies have shown that muscle fibers undergoing hypertrophy, due to mechanical stress, express elevated levels of IGF-I prior to hypertrophy. IGF-1 appears to be an important regulator of the nuclear to cytoplasmic ratio. Studies have show that a muscle will only undergo hypertrophy if it can maintain the ratio of the cell?s volume to the number of nuclei within a finite limit. In the study above, a relatively "unloaded" muscle, the anterior tibialis, was injection with 0.9 - 1.9 micrograms/kg/day of rhIGF-1 which then mimicked the effects of physically loading the muscle. There was an increase in protein content, cross sectional area and DNA content. The increase in muscle DNA is presumed to be a result of increased proliferation and differentiation of satellite cells which donate their nuclei upon fusion with damaged or hypertrophying muscle cells. Take note that the quantities of IGF-1 used in the injections were extremely small, much smaller than studies that have shown relatively poor results from administering IGF-1 systemically which range from 1.0 to 6.9 milligrams/kg/day. All of the attention and discussion of half-hazzardly injecting fat into muscles to increase the girth of a limb is only a symptom of the obsessive nature of bodybuilding. I would imagine that locally injecting minute amounts (micrograms) of rhIGF-1 to actually increase the growth of individual muscles would be a far better alternative to injecting fat, Esiclene or even getting silicone implants. Those bodybuilders at the national or professional level with lagging calves would be wise to consider the results of this study should they stumble across a bottle of Genentech?s rhIGF-1!
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"all i know is, when im at the beach, chicks dont ask how much i bench, they just want to know how big my arms are." classic
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12-06-2008, 04:19 PM
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My Experience with using
Genentech rhIGF-1 who has improved on the original growth factor with the long R3, has been looked upon as the miracle growth factor drug for several years now, I have personal used direct from the US, the long r-3 version $2,200 usd per 1mg. 10, 100mcg vials, (I used 50mcg daily for 12 weeks) with little success, you will see that many companies in China claim to carry this same version that Genentech who holds the original research patent for this product, and has stopped all US distribution due to legal pressures of the US Government several years ago (this product still to this day is only a research product) you will see prices like 200 usd for the same version of IGF "wrong" In a nut shell, the hype or hope you may say, that this product is the same and safe way to combine insulin with GH, and will stimulate the same ultimate anabolic power that combining these two growth factors will, without the risk of insulin shock. this is what IGF Long R-3 is basically. the fact is it's not! and will not give you the same results that you will get by physically combining Growth Hormone with synthetic Insulin. I have heard many miracle stories from others that say they have had tremendous success by using the Long r-3 "not the Media grade" the highest grade available, this is the product that sales for $2,200.00 per 1mg, still today direct from Genentech. I personally believe the theories behind this drug,
but genetics plays the whole role in witch it will effect you in a anabolic factor. This goes for GH as well, and the same reasons apply for not being able to produce synthetic stem cell (this would be the worlds next miracle growth factor ) the problem with any growth factors other then the physical combining of GH & Insulin, is the body quickly responses to these drugs as a virus, and it is neutralized by the bodies immune system immediately "basically destroyed" That is trying to make a long story short. And this same debate will go on for years, just like GH. The bottom line is, that to date, the physical combination of GH and insulin is still the most powerful anabolic to man. It also has the highest risk of death or completely disabling you for life, if you are not 100% perfect when using. I personally seen a man go into insulin shock and die from the use. “Rick Gaspero” is also another example of how risky this use is “I may have spelled the last name” But he was one of the biggest up and coming super stars that lost it all from GH and slin use. I think there is more Hype then IGF deserves to get. I still make better gains myself with good IE Lily Humitrope GH, combined with T-3, But then again we are not talking IGF. SO IN SHORT MY EXPERIENCE WITH IGF WAS NEGATIVE Peace
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12-08-2008, 07:34 PM
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IGF is a sort of new compound but in my opinion the stuff needs to be given close attention. From my research IGF originates or is the left over of broken down GH in our system. Right or wrong that's my understanding
The problem I have with GH is that you get that weird numbness of your fingers among other things. I personally like IGF because of lack of numbness and I;ve seen it work. Most of the sides are basically like GH, minus a few here and there. I was a little tired while on it and wanted to sleep all the time...lol but I was getting crazy pumps much like anadrol in the gym. Also, it is not going to give you huge gains, at least at 40mcg ED but at 100-120mcg ED things change. My friend has used it at 40mcg with little result.....I mean it wasnt little, he was getting cut put on few lbs and got decent pumps. But then he started to do 120mcg ED and gained 15lbs. Now it is also possible that he created hyperplasia(sp?) while at 40mcg then when he hit is with a heavier dose of juice he said that he kept growing. Now this dude is on year round training for years who wants to compete so for him to gain major size is harder than a newb. Now, I did 40mcg ED and didnt blow up but I can see some changes in my body. Gained a few lbs while bf stayed the same or decreased a little at the end but I def felt it. I might try 60mcg ED next and maybe 100down the road If Im going to do 100mcg ED Im def hiting specific muscle areas since if this IGF is injected locally it stays in that muscle for the most part.
__________________
"all i know is, when im at the beach, chicks dont ask how much i bench, they just want to know how big my arms are." classic
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12-08-2008, 07:40 PM
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__________________
"all i know is, when im at the beach, chicks dont ask how much i bench, they just want to know how big my arms are." classic
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12-08-2008, 07:42 PM
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__________________
"all i know is, when im at the beach, chicks dont ask how much i bench, they just want to know how big my arms are." classic
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12-09-2008, 04:00 PM
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Hey Vass, I purchased direct From Gen.T like i said, it came 10, 100mcg vials, 1mg (NOT THE MEDIA GRADE) It came as a Re-Combinate, 1 vial of 1ml HCL solution per 1 vial, 10, 100mcg vials of IGF-L-R-3. One big question for you partner, GH, you can't us BA water to Mix, only HCL, GH and BA water is a no-no!!! well just like IGF and GH we all know you can use Distilled water in Both, the only draw back is, it will only stay good for 12 hours. But BA water **can't** be used with GH, can it be used with IGF? What form my man did you use? and was it a R-Com. it seems to have the same effects as GH, I get the swelling in wrist, and will get and insulin crash if my Carb. timing is not on with GH. IGF the real deal was **** for me my man. not even the same side effects, is it possible you had GH instead of Igf? How good to you feel about your source? Peace Brother Last edited by lisan; 12-09-2008 at 04:46 PM.
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12-10-2008, 12:37 AM
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I dont think I had GH. My fingers never went numb but I was tired a lot which is pretty normal with IGF. The bigest change was that I was able to eat without geting fat....I mean I ate clean but ate ever 2-3 hours around the clock minus the sleep of course. I got the same results my buddy got at that dosage so I think it was real. I stopped taking it for 2 weeks now and I still get insane pumps in the gym and I'm not geting any smaller either even though I cut my juice down to just about HRT dosage. In the past when I did that I was flat but now is different....so who knows Did you use all 10 bottles? If you did you crazy...lol j/k What sucked about it bro? Just curious....did you see a difference? What dosage did you use?
__________________
"all i know is, when im at the beach, chicks dont ask how much i bench, they just want to know how big my arms are." classic
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12-10-2008, 04:24 PM
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when i say BA i Mean Ba water .9 ba water Bact sterile. HCL the same used in GH. Vass are you saying in a nutshell that IGF is better then GH? for you? I had no gains that i am willing to say i am impressed with my friend, when i used the real IGF, I have had more gains with GH! But this may be mate! I do know this! I had the real deal with IGF Lr 3 sorry to say i can't tell you i had a positive experience my man! I also never had a pre-mixed IGF also my man! I also have heard many fellows make the same statements you have about the use of IGF. I still wonder if we are not talking GH? I NEVER HAD A PRE-MIX BROTHER! i HAD TO MIX BEFORE USE, AND TRIED USING SEVERAL RE-COMBINES TO SEE IF I MAY HAVE SCREWED UP! Sorry Vass Peace
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12-14-2008, 12:45 PM
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I was doing 50 mcg daily for 12 weeks, and it does come in dry form i have to mix the HCL prior, it will last 21 days when refrigerated. also word to the wise, and this goes for GH as well, NEVER EXPOSE THESE PRODUCT TO SUNLIGHT "UV" IT WILL DESTROY THE PRODUCT IN LESS THEN 1 to 2 HOURS OF BEING EXPOSED DIRECT, EQ IS ALSO A PRODUCT THAT MUST STAY OUT OF UV LIGHT. ALL ANABOLICS FALL UNDER THIS STANDARD, THESE JUST HAPPEN TO BE THE WORST. Another practice that will damage the potency of your gear is the repeated heating and cooling. A properly produced hormone will never separate within the vial in the first place. Just store at room temp in a dark place and your product will last years past the expiration date. this practice started when many kitchen children home brewing High dose products soon seen that the crystal would separate from the suspension, many then started using higher amounts of solvents to help prevent this from happening, not understanding the damage this will do to the muscle area at the injection site, not to mention the crappy feeling you get when you use! "sorry got off the subject a bit" Peace
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12-24-2008, 11:26 PM
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Got you man,
I think that doing it 12 weeks straight was not optimum and if you really want to big gains you def need to go to 100mcg. WIth that being said, my experience with this stuff was kind of interesting..... First off I did it at the end of a cycle of EQ/Primo/Test. I only used 40 mcg (sub-q) for 4 weeks which did not make me gain much weight on the scale. I felt that I gained 2-3lbs and lost that much fat. It was kind of constant. At first, I did not get the pumps everybody talks about. But about 2 weeks in I started to recover at an accelerated pace. I would literally blast a body part and be recovered within a day or so which noramlly would take 3-4. I could easily do one body part 2x a week. Week 3 the pumps started to appear slow at first. Week 4 I was like a machine.....my appetite was through the roof, pumps were crazy and recovery was incredible. Now that I'm about 3-weeks off I can def see that my arms, shoulders which I was working on more than others are bigger and are staying bigger than before. I'm still geting the pumps, not as bad but still strong. Weight is about the same give or take a lb AND the most noticeable change is the food intake.....I eat like crazy! I mean I do watch my bf so it doesnt get out of control but it seems to me that I def need to eat more. Soon I need to get the cardio back to 2-3x a week and Im not sure what Im going to do. I already eat every 3 hours 5-6 meals/day....lol, One of my biggest issues form time to time is that I eat too clean and not have enough fat. THis maybe a good cause of why I didnt gain more weight but I def see differences in my body nonetheless. Im overall a lot harder than I was in the past coming off a cycle. My next run I will prob will do it at the begining of the cycle and see what happenes....maybe run 60mcg this time ...not sure if sub-q or IM
__________________
"all i know is, when im at the beach, chicks dont ask how much i bench, they just want to know how big my arms are." classic
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12-26-2008, 03:12 PM
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Ya Vass, I have a good friend that says exactly the same thing you do as far as gains, I Personally just did not get anything, and you are 100 right about the 100mcg daily on the Media grade. I may try again just to see and make a few changes in Diet and timing. Thanks my man good info Peace
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12-26-2008, 03:18 PM
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May be good news
Tercica Announces Agreement With Genentech for Worldwide Growth Hormone and IGF-1 Combination Product Development and Commercialization
Posted on: Tuesday, 10 July 2007, 18:22 CDT Tercica, Inc. (Nasdaq:TRCA) today announced an agreement with Genentech, Inc. for the development, manufacture and worldwide commercialization of two products containing Genentech's recombinant human growth hormone Nutropin AQ® [somatropin (rDNA origin)] and Tercica's recombinant insulin-like growth factor-1 Increlex® (mecasermin [rDNA origin] injection) for the treatment of short stature, adult growth hormone deficiency (AGHD), and potentially other metabolic disorders. Nutropin AQ® and Increlex® were originally designed and formulated so that the therapies could be combined and potentially given as a single, daily injection. Pending U.S. Food and Drug Administration guidance and timely IND acceptance, Tercica plans to initiate Phase II clinical development in 2008 of one combination product for patients with low IGF-1 levels and short stature not associated with growth hormone deficiency; and a second combination product for patients with AGHD. "This collaboration allows us to embark on two new and exciting development programs that each have scientific merit," said John A. Scarlett, M.D., Tercica's President and Chief Executive Officer. "With demonstrated synergies in pre-clinical studies, the combination of rhGH and rhIGF-1 could have the potential for several important therapeutic benefits compared to either rhGH or rhIGF-1 monotherapy alone for the treatment of patients with short stature and AGHD and potentially other adult metabolic disorders. With our current cash position, equity sales associated with this agreement and possible collaboration for both programs through sublicensing of Tercica's ex-U.S. rights, Tercica continues to have profitability in 2010 as a goal without additional equity financing unless needed to support additional new initiatives or strategic opportunities." Terms of Agreement Under the terms of the collaboration, Tercica may be eligible to receive a total of up to $53 million in equity payments, opt-in payments, research and development cost reimbursement, and milestone payments. In connection with the transaction, Genentech will purchase 708,591 shares of Tercica's common stock for $4 million. Tercica will fund and lead initial development efforts for both combination products. Genentech has certain rights to opt-in to the development programs for both products. The opt-in rights remain open until completion of a Phase II clinical study for each product that is sufficient to enable a pivotal trial. Upon exercise of any opt-in by Genentech, Genentech shall reimburse certain incurred research and development costs. Following such exercise by Genentech, a cost and profit share structure will take effect for all future development and commercial activities of both combination products, and Genentech will have certain commercialization rights, including the right to co-promote both combination products upon regulatory approval. If Genentech does not exercise any of its opt-in rights, then Tercica will have full development and commercialization rights to the combination products, and will owe Genentech royalties on worldwide sales. Development of GH/IGF-1 Combination Product About Increlex®(mecasermin [rDNA origin] injection): The active ingredient of Increlex® is recombinant human insulin-like growth factor-1 (IGF-1). IGF-1 is the direct mediator of growth hormone's (GH) effect on statural growth, and must be present for normal growth of bones and cartilage in children. In Primary IGFD, children's serum IGF-1 levels are low, despite the presence of a normal or elevated GH level. Without adequate IGF-1, children cannot achieve normal height. In children with this disorder, low IGF-1 levels are due to growth hormone resistance associated with mutations in GH receptors, post-GH receptor signaling pathways, or to defects in IGF-1 gene expression. Increlex® has been marketed in the United States by Tercica since early 2006. Exclusive rights to develop and commercialize Increlex® were licensed to Ipsen in October 2006 for all regions of the world except the United States, Japan, Canada, Taiwan and certain countries of the Middle East and North Africa. About Nutropin AQ® [somatropin (rDNA origin)]: Nutropin AQ® [somatropin (rDNA origin) injection] is produced using recombinant DNA technology and has the same amino acid sequence as human growth hormone produced naturally in the human body. It is marketed as Nutropin AQ® in Austria, Denmark, Finland, France, Germany, Ireland, the Netherlands, Norway, Sweden, Portugal, Spain and the United Kingdom. Other regulatory reviews are underway in Europe and worldwide, excluding North America and Japan. Nutropin AQ® is supplied as 10 mg of sterile liquid somatropin per cartridge for exclusive use with the Nutropin AQ® Pen, a simple, convenient, easy-to-use device for subcutaneous injection. Nutropin AQ® is approved for the treatment of GHD in children and adults, for the long-term treatment of short stature in children with Turner syndrome, the treatment of growth failure in chronic renal insufficiency patients prior to transplantation and the long-term treatment of children with idiopathic (of unknown origin) short stature (ISS). Potential of GH/IGF-1 Combination Product for Short Stature: One combination product will initially be studied in patients with low IGF-1 levels and short stature not associated with growth hormone deficiency, for example ISS. A potential cause of short stature in this group of patients could be a suboptimal IGF-1 secretion in response to growth hormone stimulation alone. Pre-clinical studies suggest that co-administration of GH and IGF-1 may increase specific growth responses greater than either therapy alone. Therefore, Tercica believes that treatment with a combination of both GH and IGF-1 may be superior to monotherapy of either component alone in a subpopulation of children with low IGF-1 and short stature not associated with growth hormone deficiency. Potential of GH/IGF-1 Combination Product for AGHD: A second combination product will initially be studied in the AGHD population. These patients have abnormalities in body composition (e.g., increased body fat and reduced lean muscle mass). Preclinical studies have suggested that co-administration of GH and IGF-1 result in synergistic effects on these parameters. Tercica also believes that delivered together as a combination product, some of the negative effects of each individual component could potentially be mitigated by the positive effects of the other, especially their effects on glucose metabolism. Upon review of the clinical data in AGHD, Tercica and Genentech will evaluate the attractiveness of this combination product in treating other metabolic disorders. Conference Call and Webcast Information Tercica's senior management team will host an investment community conference call tomorrow to discuss the collaboration with Genentech beginning at 9:00 a.m. EDT. To access the live teleconference, please dial (888) 803-8296 (U.S.) or (706) 634-1250 (international) and reference the conference ID# 6557103. To access the webcast, please go to the Events page on the Investors section of the Company's Web site at www.tercica.com. A telephone replay will be available approximately two hours after the call for 48 hours by dialing (800) 642-1687 from the U.S., or (706) 645-9291 for international callers and entering reservation number 6557103. A replay of the webcast will be available on the Company's Web site for 21 days at www.tercica.com. About Tercica Tercica is a biopharmaceutical company committed to improving endocrine health by partnering with the endocrine community to develop and commercialize new therapeutics for short stature and other metabolic disorders. For further information on Tercica, please visit www.tercica.com. Safe Harbor Statement Except for the historical statements contained herein, this press release contains forward-looking statements concerning Tercica's prospects and expectations, including without limitation, that Tercica: (A) may receive from Genentech up to $53 million in equity, opt-in and milestone payments and research and development cost reimbursement; (B) plans to initiate Phase II clinical development of the combination products in 2008 for both short stature and AGHD; (C) believes that treatment with a combination of both GH and IGF-1 may offer several important therapeutic benefits when compared with, and be superior to monotherapy in a subpopulation of children with low IGF-1 and short stature not associated with growth hormone deficiency, and for patients with AGHD; (D) believes that for patients with AGHD, delivered together as a combination product, some of the negative effects of each individual component could potentially be mitigated by the positive effects of the other, especially their effects on glucose metabolism; and (E) continues to have profitability as a goal in 2010 without the need for additional equity financing. Because Tercica's forward-looking statements are subject to risks and uncertainties, there are important factors that could cause actual results to differ materially from those in the forward-looking statements. These factors include, without limitation, risks and uncertainties related to the following: (i) for (A) (C) (D) and (E) above, data from Tercica's clinical trials of the combination products may not demonstrate sufficient efficacy or safety for either clinical development or commercial purposes or to enable Tercica to receive any financial remuneration, and Genentech may never opt-in; (ii) for (B) above, the FDA may have concerns or requirements that impede Tercica from beginning the Phase II clinical trials in 2008 or cause Tercica to stop all clinical development of the combination products; (iii) also for (E) above, Tercica's internal projections for revenues and costs through 2010 may be incorrect or not actually achieved, Tercica may be unable to sublicense its ex-U.S. rights on financial terms that it projects, or at all, and Tercica may undertake new and costly initiatives or strategic opportunities; and (iv) for (A) -- (E) above, the risks and uncertainties of drug development and others risks and uncertainties disclosed from time-to-time in reports filed by Tercica, including most recently Tercica's Form 10-Q for the quarter ending March 31, 2007 filed with the SEC on May 4, 2007. Tercica disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release. Peace
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