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    Thread: PEPTIDES: descriptions, theories & some good articles

    1. #1
      JerkKILLER's Avatar
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      Default PEPTIDES: descriptions, theories & some good articles

      Hey ES brothers and sisters-

      Over the next month (possibly longer) I'm going to be doing my best to post up some good information on the various peptide products out there right now. These would include: IGF-1, CJC-1295, GHRP-2, GHRP-6, MGF, PegMGF, Melanotan II, and even some others which you may have -or not have- heard of yet.

      I promise there's going to be some good stuff here so lets get started.

    2. #2
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      ** IGF-1 **

      More Muscle: Why Do Workouts Work?

      By Patrick L. Barry, Science.NASA.gov


      posted: 30 December, 2004


      Most machines don't improve with use. Old pickup trucks don't gradually become Ferraris just by driving them fast, and a pocket calculator won't change into a supercomputer by crunching lots of numbers.

      The human body is different. As weightlifters know, the more that people use their muscles, the stronger they become. And unused muscles do not remain preserved; neglect causes them to waste away, or atrophy.

      It's a remarkable response, one that scientists don't fully understand. Somehow, muscle cells "sense" how they're being used and then remodel themselves to better fit the task. How does this happen? And what exactly is it about exercise that triggers the changes?

      NASA needs to know the answers. Astronauts in space exercise furiously to keep fit. Even so, their muscles tend to weaken.

      Normally, people's muscles do a lot of work that they're hardly aware of--lifting their bodies and maintaining posture against gravity. In space, that constant muscular work is removed. There's a danger of atrophy," explains Kenneth Baldwin, a professor in the Department of Physiology and Biophysics at the University of California, Irvine.

      With NASA support, Baldwin is researching the inner workings of muscles and plumbing the fundamental mystery: Why do workouts work?

      NASA has a special interest in isometric exercises--i.e., non-moving exercises where an astronaut pushes hard against a fixed surface. Motionless exercises allow for simple lightweight equipment less expensive to launch and less prone to break during a mission. But are they effective?

      To find out, Baldwin's group gave laboratory rats a workout by activating the rodents' leg muscles with painless electrical stimulation. They tested three types of exercise: muscle contraction, muscle lengthening, and isometric, where the muscle exerts a force while remaining the same length. (Just think of doing push-ups: muscle contraction occurs in the "up" part of a push-up, muscle lengthening during the "down" part, and isometric while holding a push-up midway.)

      After the sessions, the scientists performed tests to see how the rats' muscles responded. "What we found," says Baldwin, "was that after 12 sessions, all three types of workout tended to provide about the same amount of muscle growth," even the isometric exercises that involved no motion.

      This was nothing new. Other scientists had come to the same conclusions before. But Baldwin's group took their analysis a step further:

      In addition to measuring overall muscle mass--how "buff" were the rats?--they also measured the amount of contractile proteins within the muscle cells. Contractile proteins are what actually cause a muscle to contract. They are what give a muscle its strength.

      To their surprise, Baldwin's team found that while isometric exercises did prevent leg muscles from withering, they did not stop a decline in the amount of contractile proteins in those muscles. The muscle was actually degrading on the molecular level.


      No one knows why this is so, but one thing seems clear: Isometric exercise might not be the best way to maintain astronaut muscles. Baldwin plans to investigate further with just-renewed funding from NASA.

      A more unconventional possibility is that astronauts could stave off muscle atrophy by taking a pill. Anti-atrophy pills are only speculative right now, Baldwin says, but there are reasons to believe that they might be possible. That's because when atrophy sets in, the muscle isn't just withering away passively -- it's actively breaking itself down!

      A complex network of enzymes within the muscle's cells disassembles muscle proteins molecule by molecule. "In order to chop those proteins up, you use a lot of energy," notes Baldwin. If scientists could pinpoint a key "lynchpin" enzyme in this network, they may be able to design a drug to block its action, thus slowing the breakdown of the muscle.

      This active breakdown of muscle protein is going on all the time in everybody's muscles, as is the constant assembly of new proteins. Whether a muscle grows, shrinks, or stays the same size depends on the balance between these rates of destruction and construction, a bit like the water level in a bathtub that's both filling and draining at the same time.


      Baldwin is taking a look at the mechanisms behind the "construction" half of this balance. In particular, his group is focusing on a hormone called Insulin-like Growth Factor 1 (IGF-1). Muscles produce IGF-1 in response to strenuous exercise, and this hormone in turn activates enzymes in the muscle cells that cause the cells to grow. Indeed, Baldwin found that levels of IGF-1 in the rats' muscles were higher just after exercising.

      "Some people think that it's the mechanical stress that turns the gene (for IGF-1) on, but we really don't understand that process yet. What we do know is that IGF-1 triggers muscle growth," Baldwin explains.

      Might supplements of IGF-1 be used to ensure that construction of muscle proteins keeps pace with protein destruction in astronauts? Baldwin says they're entertaining the idea and are already discussing ways in which that might be done.

      If they're successful, it will be good news for more than just astronauts. After all, we're all owners of that incredible, self-adapting machine called the human body.

    3. #3
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      ** IGF-1 **

      Exercise Improves Kids' Academics

      By Dan Peterson, LS's Sports Columnist


      posted: 29 December 2008


      The end of 2008 brings some discouraging news about our kids' brains and brawn. Recent results from an international math and science test show United States students are performing near the middle of the pack compared to other countries, while their levels of obesity continue to climb.

      Historically, these two trends were studied independently with plans of action developed for each. However, several researchers and a new book have been making the case for linking these two problems by showing the effects of aerobic exercise not only on a student's fitness level but also on their test scores.

      Earlier this month, the latest (2007) TIMSS (Trends in International Mathematics and Science Study) scores were released. They compare fourth grade students from 36 countries and eighth grade students from 48 countries. They were tested on subjects that were common to all of the countries, including algebra, geometry, chemistry and physics. Overall, 425,000 students participated in the test, which is administered every four years.

      In math, American fourth graders came in at 11th place of the 36 countries while eighth graders scored ninth out of 48. Hong Kong and Taiwan ranked first for fourth grade and eighth grade, respectively. In science, Singapore topped the list for both fourth grade and eighth grade, with U.S. science students taking eighth place and 11th place.

      While the American math scores have improved slightly, the science scores have dropped. In 2003, U.S. fourth graders were in sixth place in the world and eighth graders were in ninth place. Only 6 percent of U.S. eighth-grade students reached the TIMSS "advanced" level in math, compared to 45 percent of students in Chinese Taipei, 40 percent in Korea, 40 percent in Singapore, 31 percent in Hong Kong, 26 percent in Japan and 10 percent in Hungary.

      Regarding student fitness, the most recent figures from the Centers for Disease Control and Prevention report that the percentage of overweight or obese 6- to 11-year-olds has tripled since 1980, with more than 125 million children at unhealthy levels.

      Leaping backward

      Ironically, one of the solutions proposed for raising test scores, the federal No Child Left Behind program, encourages schools to focus more of the school day on the core academic subjects while reducing class time in peripheral subjects, like art, music, and physical education. In fact, only 6 percent of American high schools offer a daily gym class. Yet a 2002 Virginia Tech study showed no relationship between reduced class time in those subjects and higher overall standardized tests.

      In his latest book, "Spark: The Revolutionary New Science of Exercise and the Brain" (2008, Little, Brown), John Ratey, a Harvard clinical associate professor of psychiatry, argues for more physical fitness for students as a cure for not only their obesity but also their academic performance.

      "I cannot underestimate how important regular exercise is in improving the function and performance of the brain." Ratey writes. "Exercise stimulates our gray matter to produce Miracle-Gro for the brain." That "Miracle-Gro" is a brain chemical called brain-derived neurotropic factor, or BDNF. When we exercise, our working muscles send chemicals into our bloodstream, including a protein known as IGF-1.

      Once in the brain, IGF-1 orders the production of more BDNF. The additional BDNF helps new neurons and their connections grow. In addition, levels of other neurotransmitters are increased after a strenuous exercise session.


      "Dopamine, serotonin, norepinephrine — all of these are elevated after exercise," says Ratey. "So having a workout will help focus, calming down, and impulsivity — it's like taking a little bit of Prozac and a little bit of Ritalin."

      Evidence mounts

      Research showing a link between fitness and academics is growing.

      The California Department of Education (CDE) looked for a correlation between fitness scores and test scores. They found that kids who were deemed fit (by a standard test of aerobic capacity, BMI, abdominal strength, trunk strength, upper body strength and overall flexibility) scored twice as well on academic tests as those that were unfit. In the second year of the study, socio-economic status was taken into account, to possibly eliminate that variable as an explanation. As expected, those in the upper-income brackets scored better overall on the academic tests, but within the lower-income set of students, the same results were observed — kids who were more fit performed better academically.

      Charles Hillman, associate professor of kinesiology at the University of Illinois, was able to duplicate these findings with 259 third and fifth-grade Illinois students. His team also noticed that two of the tests, BMI and aerobic capacity, were significantly more influential to higher academic scores than the other four fitness factors. Digging deeper, he isolated two groups of 20 students, one fit and the other unfit. They were given cognitive tests of attention, working memory and processing speed while their brain's electrical activity was being measured by an electroencephalogram (EEG) test.

      The fit kids' brains showed more activity in the prefrontal cortex, known for its executive function and control over other brain processes.

      So, just send the kids on a fast jog and they will ace all of their tests? Not quite.

      “The exercise itself doesn't make you smarter, but it puts the brain of the learners in the optimal position for them to learn,” Ratey said. “There's no way to say for sure that improves learning capacity for kids, but it certainly seems to correlate to that."

    4. #4
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      Good read there Jerk. I really enjoy reading articles like this.

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      Great post bro!
      [SIZE="5"]Florida got the Oranges, I got the JUICE!!!

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      Thanks guys! Wasnt sure you'd like the kids academics one but I took a shot

      Have a great weekend and I'll post some more up next week.

    7. #7
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      ** CJC-1295 **



      CJC-1295 is a synthetic modification of growth hormone releasing factor (GRF) with D-Ala, Gln, Ala, and Leu substitutions at positions 2, 8, 15, and 27 respectively. These substitutions create a much more stable peptide with the substitution at position 2 to prevent DPP-IV cleavage, position 8 to reduce asparagine rearrangement or amide hydrolysis to aspartic acid, position 15 to enhance bioactivity, and position 27 to prevent methionine oxidation. By applying the Drug Affinity Complex (DAC) technology to GRF, the peptide selectively and covalently binds to circulating albumin after subcutaneous (SC) administration, thus prolonging its half-life. These substitutions are key in increasing the overall half life of CJC-1295 but there lies an even greater reason as to why the half life has been extended from ~7 minutes to greater than 7 days. Bioconjugation takes a reactive group and attaches it to a peptide, which in turn reacts with a nucleophilic (usually a partially negative molecule) entity found in the blood to form a more stable bond. Albumin, one of the most abundant substances in the human body is chosen as the nucelophile by this particular peptide thanks to a Cys34 thiol group that attracts it. By combining the tetrasubstituted GHRH analogue with maleimodoproprionic acid using a Lys linker, you create a GHRH peptide with a high binding affinity for albumin.

      So how effective is bioconjugation? How long will CJC-1295 stay in ones system? How will CJC-1295 impact IGF-1 levels? This is the exact question researchers asked and a study was conducted to determine the efficacy of CJC-1295. The objective of this study was to examine the pharmacokinetic profile, pharmacodynamic effects, and safety of CJC-1295, a long-acting GHRH analog. The study design was two randomized, placebo-controlled, double-blind, ascending dose trials with durations of 28 and 49 days. Healthy subjects, ages 21-61 years old were studied. After a single injection of CJC-1295, there were dose-dependent increases in mean plasma GH concentrations by 2- to 10-fold for 6 days or more and in mean plasma IGF-I concentrations by 1.5- to 3-fold for 9-11 days. The estimated half-life of CJC-1295 was 5.8-8.1 days. After multiple CJC-1295 doses, mean IGF-I levels remained above baseline for up to 28 days. No serious adverse reactions were reported.

      Sam L. Teichman, Ann Neale, Betty Lawrence, Catherine Gagnon, Jean-Paul Castaigne and Lawrence A. Frohman (2006). What was the research dose used in the study? A particularly important question, the dosage was 30-60 micrograms per kilogram of bodyweight.

      This bears repetition, Growth Hormone remained elevated for up to six days! IGF-1 concentrations were up 1.5 to 3 fold for 9-11 days! And the estimated half-life of CJC-1295 is 5.8-8.1 days! IGF-1 levels were elevated up to 28 days! At a dosage of 30-60 micrograms per kilogram of bodyweight, with no significant side effects. Excuse all he emphasis but this is a truly remarkable research product, its ability for efficacy is self-evident.

      So in short, what is CJC-1295? CJC-1295 is a long-acting analog of GH-releasing hormone. CJC-1295 exhibits the same effects of Human Growth Hormone, it has the ability to promote muscle mass, increase bone density, improve protein synthesis, increase IGF-1 levels potently, strengthen immune systems, stimulate the production of bone marrow cells that produce red blood cells, and of course reduce excess body fat, especially abdominal fat. (The reduction of abdominal fat is the single most profound effect of HGH replacement.)

      ** note from Jerkkiller **

      It appears the common dose for a 200lb test subject would be around 100mcg, 2-3x per week. But obviously, this would depend on your: finances (how much CJC-1295 u can afford), genetics, age, diet, workout regimine, goals, and other biological or environmental factors.

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      Default Re: PEPTIDES: descriptions, theories & some good articles

      Good read, JK! I have experimented with a few peptides in the past, so it's good to read about them, especially with the new peptides that are out now...looking forward to reading about those!

    9. #9
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      ** CJC-1295 **

      (here's the official Title + conclusion from the research article listed above)

      Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295,
      a long-acting analog of GH-releasing hormone, in healthy adults.

      J Clin Endocrinol Metab. 2006 Mar;91(3):799-805. Epub 2005 Dec 13.


      CONCLUSIONS: Subcutaneous administration of CJC-1295 resulted in sustained, dose-dependent increases in GH and IGF-I levels in healthy adults and was safe and relatively well tolerated, particularly at doses of 30 or 60 microg/kg. There was evidence of a cumulative effect after multiple doses. These data support the potential utility of CJC-1295 as a therapeutic agent.
      Last edited by JerkKILLER; 01-07-2010 at 02:18 AM.

    10. #10
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      ** CJC-1295 **

      (here's another one about how it affects natural GH pulsation)




      Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006 Dec;91(12):4792-7. Epub 2006 Oct 3.

      Ionescu M, Frohman LA.

      Section of Endocrinology, Metabolism, and Diabetes, University of Illinois at Chicago, 1747 West Roosevelt Road, Room 517, Chicago, Illinois 60608, USA.

      CONTEXT:
      Pulsatile GH secretion is considered important for many of the hormone's physiological effects. Short-term GHRH infusions enhance GH pulsatility and increase IGF-I, but the short GHRH half-life limits its therapeutic use. A synthetic GHRH analog (CJC-1295) that binds permanently to endogenous albumin after injection (half-life = 8 d) stimulates GH and IGF-I secretion in several animal species and in normal human subjects and enhances growth in rats.

      OBJECTIVE:
      Our objective was to assess GH pulsatility after a single injection of CJC-1295 and determine which GH secretion parameters correlated to the increase in IGF-I production.

      METHODS:
      GH pulsatility was assessed by 20-min blood sampling during an overnight 12-h period in healthy 20- to 40-yr-old men before and 1 wk after injection of either 60 or 90 microg/kg CJC-1295.

      RESULTS:
      GH secretion was increased after CJC-1295 administration with preserved pulsatility. The frequency and magnitude of GH secretory pulses were unaltered. However, basal (trough) GH levels were markedly increased (7.5-fold; P < 0.0001) and contributed to an overall increase in GH secretion (mean GH levels, 46%; P < 0.01) and IGF-I levels (45%; P < 0.001). No significant differences were observed between the responses to the two drug doses. The IGF-I increases did not correlate with any parameters of GH secretion.

      CONCLUSIONS: CJC-1295 increased trough and mean GH secretion and IGF-I production with preserved GH pulsatility. The marked enhancement of trough GH levels by continuous GHRH stimulation implicates the importance of this effect on increasing IGF-I. Long-acting GHRH preparations may have clinical utility in patients with intact pituitary GH secretory capability.

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