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The nature of the response to both hGH and AOD9604 is not clearly understood. We hypothesized that both molecules may influence the expression of the β3-adrenergic receptors (β3-ARs), the major lipolytic receptor in fat tissue. Both AOD9604 and hGH can increase β3-AR mRNA expression, as well as protein levels and function, in mouse and human cell lines in vitro (11). This response was investigated at the level of RNA and protein expression and function. The results for each mode of analysis were consistent in that both hGH and AOD9604 acted in a dose- and time-dependent manner to modulate the β3-AR response.
Specifically, T α 1 has been shown to enhance the function of certain immune cells called T and dendritic cells. This is very important to anyone with a depressed immune system or suffering from an infection, as these white blood cells play pivotal roles in the body’s defense process. T cells, for example, come in two forms: killer and helper T cells. Killer T cells are responsible for hunting down and destroying our body’s own cells that are cancerous or infected with bacteria or viruses. Helper cells work with the other cells of the immune system to orchestrate and carry out appropriate immune responses.
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 [30]. 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 [34]. 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.
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In vitro and in vivo investigations revealed a specific region within the hormone molecule that is responsible for the molecular events associated with lipid metabolism [18, 24, 25]. AOD9604 is a peptide fragment of the C-terminus or lipolytic domain of hGH (hGH177-191), with an additional tyrosine residue at the N-terminal end for stabilization. In vitro and in vivo experiments have shown similar effects of AOD9604 and hGH on lipid metabolism when chronically applied to mice [20, 21]. Interestingly, AOD9604 mimics the effect of hGH on lipid metabolism, without having growth promoting or pro-diabetic effects. The safety and tolerability of AOD9604 has been studied in the human clinical trials described in this paper.
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