Acromegaly is characterized by an excessive amount of articular cartilage in joints caused by excess GH secretion . The tremendously thick articular cartilage in acromegaly can be explained by the local production of IGF-1 in cartilage cells through GH receptors [9,18]. Long-term treatment with GH might induce hypertrophy of the cartilage and changes in the joint geometry because of altered subchondral bone structures. Long-term treatment with GH by local injections may also be associated with various risks, including glucose intolerance, insulin resistance, diabetes, cancer, edema, and hypertension [26–29]. AOD9604 is not an agonist with a high affinity to the GH receptor and does not stimulate the production of IGF-1. Therefore, AOD9604 may be safer than human recombinant GH for the long-term treatment of OA.
When the AFL Peptides scandal hit, Calzada was forced to clarify the facts about AOD9604, and put out a cleverly worded press statement aimed at potential investors, concentrating on the fact that AOD9604 had been proven safe in large scale clinical trials (neglecting to mention a lack of effectiveness) and spoke of the success of AOD9604 on stimulating bone growth, and on cartilage and muscle cell repair in in-vitro trials (2,4). The black market uses for this peptide in muscle repair and treatment of obesity were also mentioned in the release, and it is clear through media reports on this scandal that Calzada gained traction from the profile boost (8).
From this study it appears that the β3-AR is an important contributor to the effects observed on body weight in obese mice treated with AOD9604 and hGH. To determine whether theβ 3-AR is partly responsible for this effect, we examined the effects of AOD9604 and hGH in theβ 3-KO mouse. The β3-KO mouse is not grossly obese, but female mice have increased fat depots (21) and the mice do develop late-onset obesity (Summers, R. J., personal communication). AOD9604 and hGH increased body mass and decreased BAT mass in the WT strain but had no effect in the KO animals. In WT mice, plasma glycerol was increased in response to AOD9604 and hGH treatment (4 wk). However, in the KO mice, only hGH resulted in increased levels of glycerol in the KO mice, and this effect was significantly less than that observed in the WT mice. This suggests that the regulation of the β3-AR is essential in the ability of AOD9604 and hGH to mediate chronic effects on lipolysis and fat mass reduction.
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The medicines delegate referred the proposal to upschedule paracetamol/ibuprofen from Schedule 2 to Schedule 3 to the Advisory Committee on Medicines Scheduling (ACMS) in early 2011. The proposal was submitted by the Advisory Committee on Non-Prescription Medicines (ACNM) as they were currently assessing a product in which the sponsor did not satisfactorily establish the efficacy and safety of the product and that public health concerns raised during the assessment of the product could be addressed by access to a pharmacist. AFT Pharmaceuticals had submitted a product application with the TGA at the time of this item being considered by the delegate and ACMS.
Results: AOD9604 had no effect on serum IGF-1 levels, which confirms the hypothesis that AOD9604 does not act via IGF-1. Results of oral glucose tolerance test demonstrated that, in contrast with hGH, AOD9604 has no negative effect on carbohydrate metabolism. There were no anti-AOD9604 antibodies detected in any of the patients selected for antibody assay. In none of the studies did a withdrawal or serious adverse event occur related to intake of AOD9604.
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Advanced Obesity Drug 9604 (AOD9604), targets fat metabolism directly by enhancing the breakdown of stored fats and inhibiting the synthesis of new fats. It is a peptide drug derived from the fat-reducing activity of human growth hormone (hGH). hGH has been shown to cause fat reduction, but is not suitable as an anti-obesity drug as it also causes an increase in muscle, organ and bone mass as well as causing diabetes to develop. The effectiveness of hGH declines in older people, correlating with the tendency to put on weight as one gets older. In support of this, the clinical trials so far have shown a greater effect of AOD9604 in the older population.
For GH to exhibit its fat burning effects, insulin must NOT be present. Insulin release in the body is caused mainly by consuming carbohydrates, although all types of macronutrients (carbs, fat and protein) still cause the release of insulin to some extent. Since HGH Frag works by causing the body to break down and release stored fat for use as energy, if you have recently consumed calories (food or beverage) your body will just use that for energy instead and little extra fat will be burnt. If however there is no food present for the body to use as energy, it will use the stored fat which the HGH Frag has caused to be released and you will notice reductions in body fat over the ensuing weeks.
These peptides are inhibitors of a protein called myostatin. Myostatin is secreted by muscle cells and acts to essentially block the development of new muscle fibers and, thus, the development of lean muscle mass. In fact, individuals who have mutations in the gene coding for this protein have significantly more muscle mass and enhanced strength. The administration of follastatin peptides can generate enhanced muscle mass and strength, and has been found especially useful in patients suffering from muscle-wasting diseases or who have difficulty gaining muscle.
Meanwhile, more Phase II clinical studies are planned for the next 12 months including a study examining the efficacy of oral administration, which has been shown to be effective in laboratory animals. This will be followed by a weight loss study. Confirmation of the age-effect will also be sought. Metabolic aims to start a two-year Phase III studies program in 2003, which would not place final FDA approval before 2005.
Both human GH (hGH) and a lipolytic fragment (AOD9604) synthesized from its C-terminus are capable of inducing weight loss and increasing lipolytic sensitivity following long-term treatment in mice. One mechanism by which this may occur is through an interaction with the beta-adrenergic pathway, particularly with the beta(3)-adrenergic receptors (beta(3)-AR). Here we describe how hGH and AOD9604 can reduce body weight and body fat in obese mice following 14 d of chronic ip administration. These results correlate with increases in the level of expression of beta(3)-AR RNA, the major lipolytic receptor found in fat cells. Importantly, both hGH and AOD9604 are capable of increasing the repressed levels of beta(3)-AR RNA in obese mice to levels comparable with those in lean mice. The importance of beta(3)-AR was verified when long-term treatment with hGH and AOD9604 in beta(3)-AR knock-out mice failed to produce the change in body weight and increase in lipolysis that was observed in wild-type control mice. However, in an acute experiment, AOD9604 was capable of increasing energy expenditure and fat oxidation in the beta(3)-AR knock-out mice. In conclusion, this study demonstrates that the lipolytic actions of both hGH and AOD9604 are not mediated directly through the beta(3)-AR although both compounds increase beta(3)-AR expression, which may subsequently contribute to enhanced lipolytic sensitivity.
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In our study, the rapid recovery from lameness (11 days) in the group that received AOD9604 and HA injection suggests that an early anti-inflammatory and pain-relieving effect could be induced before the tissue repair observed at the end of the treatment period (35 days). This result may be explained by the pain-relieving effects of GH . The intra-articular injection to the human knee using ultrasound guidance notably enhances the accuracy compared with injection using anatomical guidance [31–33]. Until recently, intra-articular injections to the rabbit knee using ultrasound guidance have rarely been reported . In our study, intra-articular injections were performed using ultrasound guidance to identify the correct trajectory for needle placement in the knee joint, as the rabbit knee joint is smaller than that of humans.
The secret to health and wellness has been revealed. Recent scientific developments and studies have confirmed that the use of peptide supplements under the careful supervision of hormone doctors, will help to deliver your body to a state of youthful proportion and function. Through peptide supplementation, you enable the body to regenerate, enhance and perform to its optimal level.