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The delegates have decided to accept the advice of the expert advisory committees that the current scheduling of preparations in Schedules 5 and 6 remains appropriate. The delegates noted the decision to retain listing of teeth whitening preparations containing up to 6 per cent hydrogen peroxide or 18 per cent carbamide peroxide in Schedule 5, or exempt when below 3 per cent and 9 per cent respectively, is to some extent also consistent with the evaluation of such products by the European Commission Scientific Committee on Cosmetics and Non Food Products intended for Consumers (SCCNFP).
Years ago, our group examined the cytoprotective effects exerted by the GHRP-6 preventive administration in the hepatic tissue subjected to I/R, as in other distal organs from the ischemic site (ie, lungs, kidneys, and small intestine). Histological and biochemical results allowed us to conclude that the pharmacological preconditioning induced by the GHRP-6 treatment attenuated I/R liver damage. Besides respiratory distress syndrome like pulmonary changes, intestinal transmural infarct and acute tubular necrosis in kidneys were significantly reduced. These results indicated for the first time a systemic cytoprotective effect for the GHRP-6, suggesting its potential efficacy to control the inflammatory response associated with acute I/R and shock, which eventually originated multiple organs damage (MOD). Cytoprotection induced by GHRP-6 treatment was also related to the attenuation in the generation of ROS and preservation of the antioxidant defense reserves. Histological analysis as the assessment of myeloperoxidase activity evidenced a clear anti-inflammatory GHRP-6-induced effect in the liver and remote organs. Moreover, the molecular mechanism mediating the action of GHRP-6 peptide was shown to involve the phosphatidylinositol 3-kinase/RAC-alpha serine/threonine-protein kinase (PI-3K/AKT1) pathway, as the induction of the hypoxia-inducible factor-1 alpha (HIF-1α) all committed in cellular survival.51 Subsequently, Granado et al52 examined the potential anti-inflammatory impact of GHRP-2 in lipopolysaccharide (LPS)-challenged rats. GHRP-2 administration attenuated the effects of LPS on the elevation of circulating levels of transaminases, nitrites/nitrates, and tumor necrosis factor-alpha (TNF-α), via direct interaction with liver nonparenchymal cells. Globally, the exogenous administration of these two synthetic GHRPs appeared to exert a potent hepatoprotective role by attenuating the inflammatory response orchestrated by liver-resident macrophages. Another line of evidences document the benefits of 15-daily injections of GHRP-2 (100 μg/kg) in arthritic rats, so that the treatment ameliorated the external symptoms of arthritis and decreased the circulating levels of interleukin 6 (IL-6) as the nitrite/nitrate release from peritoneal macrophages in vitro. This experiment extrapolated the counter-inflammatory properties of GHRP-2 to a nonepithelial organ and suggested again a direct interaction with ghrelin receptor of immune cells.53 Similarly, effects have been attributed to ghrelin by inhibiting the inflammatory response via AKT1-activated pathway with a concomitant reduction of myeloperoxidase activity, the rate of apoptosis, and oxidative stress.54 All these data suggest that GHRPs exert a mutually inclusive beneficial effect by directly protecting parenchymal organs epithelial cells, and simultaneously by modulating the magnitude of the inflammatory response by direct interaction with the effector immune cells. Supporting the protective effect of GHRP-6 on epithelial organs, a recent study has excellently described and dissected the mechanistic bases on how GHRP-6 prevented gastric mucosal damage induced by water immersion restraint (WRS) and other forms of stress. The data indicated that the protective effect of GHRP-6 on WRS-induced gastric mucosal injury is somehow mediated by peripherally suppressing the vagal efferent effect on the stomach, including gastric acid secretion. Although more studies are clearly demanded, the present findings open the possibility to use GHRP-6 in preventing Curling ulcers.55
In June 2011, the delegate considered a request to restrict the use of chloramphenicol (Schedule 3) to ophthalmic use for the treatment of bacterial conjunctivitis only. The delegate decided that a more restrictive wording of the Schedule 3 chloramphenicol entry would not result in further benefits concerning its ophthalmic use, therefore the wording of the entry remained unchanged.
This class of peptides is used to enhance the insulin-like growth of muscles by bodybuilders. These compounds are great for targeting specific muscle groups. Also known as Somatomedic C, IGF-1 has become one of the more popular peptides used for muscle building in the last 10 years or so. Englishman Dorian Yates, who was named Mr. Olympian for six straight years in the 1990s, is thought to have been a prominent user. This contributed to make many professional bodybuilders to include it in their regimen as well. IGF-1 is also available in different variants.
In studies GHRP-6 has shown biological actions similar to the naturally occurring hunger stimulating peptide ghrelin. Its main use is to promote food intake by stimulating hunger and aid in energy metabolism. It can be used in the treatment of GH deficiency as well as cachexia, eating disorders and obesity. GHRP-6 is a synthetic met-enkephalin (a naturally occurring opioid growth factor) analog. GHRP-6 contains D-amino acids that are entirely synthetic, lacks opioid activity, and shares no sequence relation with GHRH. It has also been shown that GHRP-6 can lead to re-stimulation of the natural production of HGH.
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Then there’s colostrum. Colostrum is packed with growth factors, including IGF-1, that amplify lean muscle gains and increase the body’s ability to burn fat. In many studies, colostrum has been shown to restore IGF-1 and stimulate IGF-1 production. Colostrum is also a natural immunity drug, containing antibodies and antigens that knock out disease-causing agents such as bacteria, viruses, and fungi.
More than a decade ago, CD36 was identified as one of the GHRP-6 receptors . This is a scavenger receptor endowed with multiligand and multifunctional capabilities and is expressed by a broad constellation of mammalian cells . Granulation tissue neovascularization is perhaps the most renowned physiological role of CD36 in wound healing . Serendipitous observations of our laboratory indicated that CD36 mRNA transcript appeared abundantly represented in clinical samples of granulation tissue of either acute (deep burn injuries) or chronic (pressure ulcers) wounds, as in laboratory rat’s controlled full-thickness wounds. This finding incited us to speculate on the effects associated with CD36 agonistic stimulation beyond that of the angiostatic action via thrombospondin binding . Here we provide the first experimental evidence on the favorable impact of the topical administration of GHRP-6, as a candidate to qualitatively improve the healing process.
In July 1972, the DPSSC decided to include vitamin D in Schedule 4 when the recommended daily dose exceeded 25 micrograms. This decision was based on the Canadian restrictions on vitamins A and D that drugs containing more than 10,000 international units of vitamin A in a recommended daily dose were prescription only and that the same restriction would apply to drugs containing more than 1,000 units of vitamin D in a recommended daily dose.
Combined, the loss of muscle and bone mass, is a quick ticket to the grave. The lack of supporting muscle and bone tissue, means that falls are more likely to occur, lengthy hospital stays inevitable, and the immobility created from these sustained injuries, produce further reduction in muscle mass and bone mass. A vicious cycle, which can be stopped in its tracks through the use of peptides such as SARMs.
In no particular order of importance, here they are: I swallow colostrum capsules every morning, I drink raw animal milk such as camel milk and goat milk in moderation, and I use the equivalent of around 30 grams of grass-fed whey protein each day in a smoothie (if you’re vegan or if whey protein doesn’t agree with your stomach, you can combine digestive enzymes with a vegan protein such as brown rice protein, pea protein or hemp protein for an effect similar to whey protein).
The delegates' reasons for the final decision to exempt from the proposed Appendix C entries, teeth whitening preparations containing more than18 per cent of carbamide peroxide and more than 6 per cent of hydrogen peroxide manufactured for and supplied solely by registered dental practitioners as part of their dental practice, comprise of the following.
The two peptides CJC 1295 Ipamorelin, are often used in conjunction for better results. Known individually as CJC 1295 and Ipamorelin, these peptides have similar roles, which we will look at later. But for now, the CJC 1295 and Ipamorelin combination, is chiefly used together because the production of growth hormone secretion is 10 times more effective than using them individually. This makes it convenient for most users, to guarantee quicker results. Above all, it is popular among athletes, bodybuilders and weightlifters in need of building strength or speeding up the recovery of an injury.
TO-2 hamster model of DCM was characterized by progressive LV dilation, LV wall thinning, LV systolic dysfunction, and reduced life span; both GHRP-2 and GHRP-6 ameliorated all the dysfunctional ventricular parameters and reduced the progression of the DCM.34 We also examined the potential impact of GHRP-6 in a rat model of DCM/heart failure induced by doxorubicin (DX). The concurrent administration of GHRP-6 was undertaken with the purpose to study the potential prophylactic impact before the cardiac function demise. As part of the prolonged treatment with DX, the concurrent administration of GHRP-6 completely prevented failure of cardiac function, which was evaluated as the percentage of ejection fraction by echocardiography (Figure 2, prevention). This effect significantly increased the survival of animals. Similar results were obtained in the therapeutic administration schedule, with functional recovery of cardiac muscle to physiological levels (Figure 2, regression), also attenuating systemic damages and, consequently, decreasing the mortality rates of rats. In the experimental model of DX-induced cardiac and systemic damage, GHRP-6 additionally attenuated various extracardiac damages observed in the renal tubular and bronchoalveolar epithelial structures as in the hepatic parenchyma.35
IGF-1 is the only natural hormone that can stimulate lean muscle mass gains and help the body choose to burn stored fat over simple glucose for fuel, meaning, you will burn off more fat. Studies demonstrate that only colostrum supplements containing lactoferrin can produce lean muscle gains that complement IGF-1 supplementation. That’s because it is actually the lactoferrin in some brands of colostrum that work to increase muscle mass and to burn adipose tissue. In fact, in a recent 2013 study, participants who supplemented with lactoferrin over a period of eight weeks experienced increased weight loss, reduced visceral and subcutaneous fat, reduced waist circumference, and reduced hip circumference.
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In more recent years, these data were further substantiated using again the TO-2 hamster DCM biomodel in which GHRP-2 reduced the progression of LV remodeling, dysfunction, and the ensued myocardial fibrosis by an antioxidant mechanism.36 The abovementioned myocardial fibrotic process amelioration reveals an additional potential use for GHRP in an unmet medical need. Chronic treatment with hexarelin in spontaneously hypertensive rats, in addition to decreasing ventricular hypertrophy, diastolic dysfunction, and high blood pressure, significantly reduced cardiac fibrosis by decreasing interstitial and perivascular myocardial collagen deposition and myocardial hydroxyproline content. Mechanistically, hexarelin treatment increased matrix metalloproteinase (MMP)-2 and MMP-9 activities and decreased myocardial mRNA expression of tissue inhibitor of metalloproteinase (TIMP)-1.37
Since GHRP-6 influences natural GH release, rules for its administration are similar to those when administering GH itself, i.e. do not have the dose within a 2 hour window after a meal, and/or wait 30 minutes till eating after dosing, due to any endogenous insulin release from the meal possibly stunting the release of natural GH and its uptake by the relevant cells.
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In June 2011, the delegate decided to reschedule from Schedule 2 to Schedule 3, combination ibuprofen+paracetamol preparations (up to 200 mg of ibuprofen and 500 mg of paracetamol) when in packs of 30 dosage units or less. The delegate also decided that combination ibuprofen+paracetamol preparations in packs of more than 30 dosage units are to be captured by Schedule 4.
These studies on human subjects were paralleled by contemporary experimental progresses in basic science, which demonstrated that hexarelin enhanced H9c2 cardiomyocyte proliferation in a dose-dependent manner. Since these were in vitro experiments, they completely excluded a potential intervention of the GH axis and clearly indicated a direct GHRP binding to cardiac cells membranes.32 Weekers et al33 demonstrated that 14 days of pretreatment with GHRP-2, but not GH, selectively protected against the postischemic diastolic dysfunction and myocardial stunning of excised hearts submitted to ischemia/reperfusion in isolated, perfused rabbit hearts.
In October 2005, the NDPSC decided to amend the Schedule 5 entry for thyme oil to include the wording "in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels".
GHRP-6 and all GHRP’s are mimetics of ghrelin, a hormone produced by cells of the stomach in response to a fasted condition, including brief fasts. Ghrelin and ghrelin mimetics work by activating the ghrelin receptor, also called the growth hormone secretagogue receptor (GHS-R1a). Elevated ghrelin levels act towards increasing GH levels by stimulation of ghrelin receptors in the pituitary.
Placebo-treated wounds appeared hypertrophied and proved a firm consistency by day 17 onward. For the three experiments, day 30 following injury established a clear definition on the wounds evolution. The most remarkable effect of GHRP-6 intervention can be ascribed to HTS prevention. As shown in Table 3, GHRP-6 administration aborted the debut of HTS in 90.5% of the treated wounds. These wounds were also negative to palpation. On the contrary, 87.5% of the wounds receiving the jelly CMC solution evolved to HTS with nipple-like, reddish appearance and a firm consistency nodule at palpation (Figures 5(a) and 5(b)).
CJC-1295 is a fast-acting Growth Hormone Releasing Hormone designed to enhance the body’s natural production and release of human growth hormone and Insulin-like Growth Factor 1 (IGF-1). In doing so, CJC-1295 reverses the age-related decline, generates new muscle cells and increases fat loss. Another great trait of CJC-1295 is its ability to promote slow wave sleep, a deep sleep responsible for the highest levels of cell regeneration, muscle growth and memory retention.
There is no “one right way”, to use Ipamorelin. For example, if you are using 500 to 1000 mcg doses daily, twice a day, your cycle might run for an 8 week period. If on the other hand, you are an athlete training for a competition, you might be on 3 injections per day, at 300-500 mcg, and will stay on for a 12 week period. For new users, you might find a 300 mcg injection is too high, and you will cut back to 200 mcg until your body gets used to it, for an 8-week cycle.
"In circumstances where a medicine is widely known to be used in connection with modifying a physiological process in persons (as appears to be the case with some SARMs and other peptide products), that medicine is likely to satisfy the definition of a therapeutic good despite any disclaimer to the effect that it is for research purposes only and/or not for human use."
Author Contributions: Conceived and designed the experiments: JBA, AAC, DGBH, YMM, ARU, AGO, VFC, FHB, GGN. Analyzed the data: JBA, AAC, DGBH, YMM, ARU, AGO, VFC, FHB. Wrote the first draft of the manuscript: JBA. Contributed to the writing of the manuscript: JBA, AGO, YMM. Agree with manuscript results and conclusions: JBA, AAC, DGBH, YMM, ARU, AGO, VFC, FHB, QB, GGN. Jointly developed the structure and arguments for the paper: JBA, AGO, GGN. Made critical revisions and approved final version: QB, GGN. All authors reviewed and approved of the final manuscript.
The goal of this review is to offer a summary of the most relevant achievements of the pharmacological knowledge with synthetic GHRP (GHRP-6, GHRP-2, and hexarelin) in a historical perspective line. General cyto- and cardioprotection fields are specially focused, since all these agents have contributed to the discovery of novel functions and mechanisms involved in cellular survival, senescence, and death. We deem that cardiologists, clinicians, and basic and clinical pharmacologists would receive some benefit from this text, in correspondence to the futuristic pharmacological opportunities offered by these agents. To date, cytoprotection remains as an orphan niche in contemporary medical armamentarium.