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[thewilman]

Effect of Oral Creatine Supplementation on Human Muscle GLUT4 Protein Content After Immobilization

B. Op 't Eijnde, B. Ursø, E.A. Richter, P.L. Greenhaff, and P. Hespel
From the Faculty of Physical Education and Physiotherapy (B.O.E., P.H.), Exercise Physiology and Biomechanics Laboratory, Katholieke Universiteit Leuven, Leuven, Belgium; the Department of Human Physiology (B.U., E.A.R.), Copenhagen Muscle Research Center, University of Copenhagen, Copenhagen, Denmark; and the School of Biomedical Sciences (P.L.G.), Queens Medical Center, University of Nottingham, Nottingham, U.K.

Address correspondence and reprint requests to Peter Hespel, PhD, Faculty of Physical Education and Physiotherapy, Exercise Physiology and Biomechanics Laboratory, Tervuursevest 101, B-3001 Leuven, Belgium. E-mail: [email protected] .


The purpose of this study was to investigate the effect of oral creatine supplementation on muscle GLUT4 protein content and total creatine and glycogen content during muscle disuse and subsequent training. A double-blind placebo-controlled trial was performed with 22 young healthy volunteers. The right leg of each subject was immobilized using a cast for 2 weeks, after which subjects participated in a 10-week heavy resistance training program involving the knee-extensor muscles (three sessions per week). Half of the subjects received creatine monohydrate supplements (20 g daily during the immobilization period and 15 and 5 g daily during the first 3 and the last 7 weeks of rehabilitation training, respectively), whereas the other 11 subjects ingested placebo (maltodextrine). Muscle GLUT4 protein content and glycogen and total creatine concentrations were assayed in needle biopsy samples from the vastus lateralis muscle before and after immobilization and after 3 and 10 weeks of training. Immobilization decreased GLUT4 in the placebo group (-20%, P < 0.05), but not in the creatine group (+9% NS). Glycogen and total creatine were unchanged in both groups during the immobilization period. In the placebo group, during training, GLUT4 was normalized, and glycogen and total creatine were stable. Conversely, in the creatine group, GLUT4 increased by 40% (P < 0.05) during rehabilitation. Muscle glycogen and total creatine levels were higher in the creatine group after 3 weeks of rehabilitation (P < 0.05), but not after 10 weeks of rehabilitation. We concluded that 1) oral creatine supplementation offsets the decline in muscle GLUT4 protein content that occurs during immobilization, and 2) oral creatine supplementation increases GLUT4 protein content during subsequent rehabilitation training in healthy subjects.

 

[marshbomb]

I love whoring.

 

[rafter]

The Positive Effects of Testosterone on the Heart
by Doug Kalman MS, RD


Steroids will cause your kidneys to implode, your heart to blow a ventricle, and your liver to squirt out of your arse, fly across the room, and knock the cat off the futon. We read it on the Internet and saw an after school special about it, so it must be true, right?

Actually, the more you learn about steroids, the more you come to realize that, like all drugs, there's a difference between their intelligent use and outright abuse. In this article, Doug Kalman takes a look at the effects of Testosterone on the heart. What he found may surprise you.


Over the years we've all heard the repeated mantra that anabolic steroids are bad for the heart. Some physicians will tell you that gear raises your risk of heart disease by lowering your good cholesterol (HDL) and raising your bad cholesterol (LDL). In fact, as some docs will tell you, steroids are known to even induce cardiac hypertrophy (enlargement of the heart). And since you can't flex your heart in an effort to woo women, who'd want that?

But, as in every story, there's more than one side. In fact, let it be said, the dangers of steroids are overstated and, hold onto your seats, may even be good for the heart. Let's examine some of the scientific studies on the positive effects of Testosterone on the heart.


What are the cardiovascular effects of steroids?

Cardiologists at the Royal Prince Alfred Hospital in Australia recruited both juicing and non-juicing bodybuilders for a study. Each bodybuilder had various aspects of the heart measured (carotid intima-media thickness, arterial reactivity, left ventricular dimensions, etc.). These measurements indicate whether bodybuilding, steroid usage or both affect the function, size, shape and activity of the heart.

The doctors found some obvious and not so obvious results. Predictably, those bodybuilders who used steroids were physically stronger than those who didn't. What was surprising was that the use of steroids was not found to cause any significant changes or abnormalities of arterial structure or function.

In essence, when the bodybuilders (both groups) were compared with sedentary controls, any changes in heart function were common to bodybuilders. The take home message from this study is that bodybuilding itself can alter (not impair) arterial structure/function and that steroids do not appear to impair cardiac function. (1)


Does MRFIT need a T boost?

A famous cardiac study was published about 10 years ago. It soon became on ongoing study known as the Multiple Risk Factor Intervention Trial (MRFIT). The present study examined changes in Testosterone over 13 years in 66 men aged 41 to 61 years. The researchers determined if changes in total Testosterone are related to cardiovascular disease risk factors.

The average Testosterone levels at the beginning of the study were 751 ng/dl and decreased by 41 ng/dl. Men who smoked or exhibited Type A behavior were found to have even greater decreases in T levels. The change in Testosterone was also associated with an increase in triglyceride levels and a decrease in the good cholesterol (HDL).

The authors concluded that decreases in Testosterone levels as observed in men over time are associated with unfavorable heart disease risk. (2) Sounds to me like a good reason to get T support/replacement therapy in the middle age years!

In a similar study, researchers in Poland examined if Testosterone replacement therapy in aging men positively effected heart disease risk factors. Twenty-two men with low T levels received 200 mg of Testosterone enanthate every other week for one year. Throughout treatment, Testosterone, estradiol, total cholesterol, HDL and LDL were measured.

The researchers determined that T replacement returned both Testosterone and estradiol levels back to normal and acceptable levels. They also found that T replacement lowered cholesterol and LDL (the bad cholesterol) without altering HDL (the good cholesterol). Furthermore, there was no change in prostate function or size.

The take home message from this study is that T replacement doesn't appear to raise heart disease risk and it may actually lower your risk. (3) It appears that more physicians should be prescribing low dose Testosterone to middle age and aging men for both libido, muscle tone and for cardiac reasons.


What about younger men?

It's been long established that men have a higher risk of heart disease. One of the risk factors implicated is Testosterone. Reportedly, the recreational use of Testosterone can alter lipoprotein levels and, in fact, case reports exist describing bodybuilders who've abused steroids and have experienced heart disease or even sudden death. But the question remains, is the causal association one of truth or just an association?

To answer this, researchers at the University of North Texas recruited twelve competitive bodybuilders for a comprehensive evaluation of the cardiovascular effects of steroids. Six heavyweight steroid-using bodybuilders were compared with six heavyweight drug-free bodybuilders.

As expected, the heavy steroid users had lower total cholesterol and HDL levels as compared to the drug-free athletes. What was unexpected was that the steroid users also had significantly lower LDL (the bad cholesterol) and triglyceride levels as compared to the non-steroid users. In addition, the juicers also had lower apolipoprotein B levels (a marker for heart disease risk). Thus, the authors concluded that androgens do not appear to raise the risk of cardiovascular disease. (4) The take home message from this study is that the negative cardiac side effects of steroids are most likely overstated.

In a little more progressive study, researchers at the Albert Einstein College of Medicine in the Boogie Down Bronx (the BDB to those in the know) examined Testosterone as a possible therapy for cardiovascular disease. (5) The researchers note that T can be given in oral, injectable, pellet and transdermal delivery forms. It's noted that injections of Testosterone (100 to 200 mg every two weeks) in men with low levels of T will decrease total cholesterol and LDL while raising the HDL.

In fact, Testosterone therapy has been found to have antianginal effects (reduces chest pain). Low levels of Testosterone are also correlated with high blood pressure, specifically high systolic pressure. The researchers determined that returning T levels back to normal and even high-normal levels have positive cardiovascular effects and should be considered as an adjunctive treatment for maintaining muscle mass when someone has congestive heart failure.


Putting it all together

Strong research demonstrates that the risks of negative cardiovascular effects of steroids are overstated. In fact, a recent paper published in the Canadian Journal of Applied Physiology questioned the whole risk of using steroids. (6) Joey Antonio, Ph.D. and Chris Street MS, CSCS published strong data showing that the risks of steroid use are largely exaggerated, much like scare tactics used by your parents while you were a kid. Of course, it goes unsaid that abuse of anything will lead to unwanted consequences.

We know that as we age, circulating Testosterone levels naturally decrease. For most people the Testosterone decrease goes from high-normal to mid to low normal. Data shows that there's an inverse relationship between T levels and blood pressure as well as abdominal obesity (that paunch we see on so many middle age males).

Testosterone replacement lowers abdominal obesity and restores Testosterone back to normal levels. Restored Testosterone is correlated with better mood, better muscle tone, stronger sex drive, lower cardiovascular disease risks, stronger bones and better memory. It's important to note that while conservative use gives a pronounced positive health benefit, higher doses may not necessarily lead to further health benefits.


What to do

If you see your body composition changing (your gut starts looking like your Uncle Lester's), your strength or muscle tone diminishing despite your hard training and good diet, and your sex drive not matching up to TC's columns, have your Testosterone levels checked. The acceptable normal range for Testosterone to physicians is 300 mg/dl to 1100 mg/dl. Yes, that's a pretty wide range.

In the clinic, we see people with the complaints consistent with "andropause" (a term for male menopause) and/or increased cardiovascular risk having Testosterone levels between 300 mg/dl and 550 mg/dl. Bringing it up to the mid to high-normal level is what gives the health and "youthful" benefits. Traditionally 200 mg/dl of supplemental Testosterone given every one to two weeks improves body composition, lowers total cholesterol and LDL, while raising HDL.

It appears that supplemental T is a healthier and safer way to go than many of the drugs used to treat poor lipid profiles. The data presented in this article applies for males over 35, not those who are 18. If you think that you can benefit from Testosterone therapy look for physicians who market themselves as "anti-aging" or "longevity physicians" as well as the more progressive endocrinologists or cardiologists.

Long story short, used intelligently, Testosterone is good medicine!


About the author: Douglas S. Kalman MS, RD is a Director for Miami Research Associates (MiamiResearch.com) a leading pharmaceutical and nutrition research organization in Miami, Florida. Doug is also a national spokesperson for the American College of Sports Medicine and according to his latest test has high T levels. Doug can be reached at [email protected].

References:

1) Sader MA, Griffiths KA, McCredie RJ, et al. Androgenic anabolic steroids and arterial structure and function in male bodybuilders. J Am Coll Cardiol 2001;37(1):224-230.

2) Zmuda JM, Cauley JA, Kriska A, et al. Longitudinal relation between endogenous testosterone and cardiovascular disease risk factors in middle aged men. A 13 year follow-up of former Multiple Risk Factor Intervention Trial participants. Am J Epidemiol 1997;146609-617.

3) Zgliczynski S, Ossowski M, Slowinska-Srednicka J, et al. Effect of testosterone replacement therapy on lipids and lipoproteins in hypogonadal and elderly men. Atherosclerosis 1996;121(1):35-43.

4) Diekerman RD, McConathy WJ, Zachariah NY. Testosterone, sex hormone-binding globulin, lipoproteins and vascular disease risk. J Cardiovasc Risk 1997;4(5-6):363-366.

5) Shapiro J, Christiana J, Frishman WH. Testosterone and other anabolic steroids as cardiovascular drugs. Am J Ther 1999;6(3):167-174.

6) Antonio J, Street C. Androgen use by athletes: A reevaluation of the health risks. Can J Appl Physiol 1996;21(6):421-440.

 

[powerhouse21]

Creatine Supplementation
Beth Lulinski, M.S., R.D.
Creatine is marketed as "nature's muscle builder" and "the most legitimate sports supplement around." Professional and amateur athletes alike are gobbling up this alleged ergogenic aid, hoping to increase their strength and performance. Creatine supplementation is claimed to increase muscle power by playing a role in the transfer of energy to help the muscle contract. Supplement labels state that "creatine is converted to phosphocreatine, which is important for short energy bursts such as sprinting and weight lifting" and that "depletion of phosphocreatine can result in muscle fatigue and fading muscle power." Claims are also made that supplementation increases muscle body mass.

Health-food stores sell creatine supplements in capsule, chewable, and powdered form, the most popular being the powder. One teaspoon of powder contains 5 grams (g) of creatine monohydrate. The recommended daily dose is 1-2 teaspoons dissolved in 8 ounces of water or sweetened beverage. Manufacturers and distributors suggest a five- to seven-day loading phase with intake of 10-20 g (2-4 scoops) daily to fill up the muscle. The maintenance phase of 5-10 g/day is recommended before and/or immediately following a workout. This protocol is claimed to increase creatine muscle stores by 20-50%.

Role In Muscle Contraction
To meet the demands of a high-intensity exercise, such as a sprint, muscles derive their energy from a series of reactions involving adenosine triphosphate (ATP), phosphocreatine (PCr), adenosine diphosphate (ADP), and creatine. ATP, the amount of which is relatively constant, provides energy when it releases a phosphate molecule and becomes ADP. ATP is regenerated when PCr donates a phosphate molecule that combines with ADP. Stored PCr can fuel the first 4-5 seconds of a sprint, but another fuel source must provide the energy to sustain the activity. Creatine supplements increase the storage of PCr, thus making more ATP available to fuel the working muscles and enable them to work harder before becoming fatigued [1].

Sources
The body's pool of creatine can be replenished either from food (or supplements) or through synthesis from precursor amino acids. Dietary sources include beef, tuna, cod, salmon, herring, and pork [2]. The normal dietary intake of creatine is 1-2 g/day, although vegetarians may consume less [3,4]. Dietary creatine is absorbed from the intestines into the bloodstream. If the dietary supply is limited, creatine can be synthesized from the body stores of the amino acids glycine, arginine, and methionine. The kidneys use glycine and arginine to make guanidinoacetate, which the liver methylates to form creatine [1], which is transported to the muscle cells for storage. It is also stored in the kidneys, sperm cells, and brain tissue [5].

The maximum amount of creatine the body can store is about 0.3 gram per kilogram of body weight [6]. The creatine content of skeletal (voluntary) muscles averages 125 millimoles per kilogram of dry matter (mmol/kg/dm) and ranges from about 60 to 160 mmol/kg/dm. Approximately 60% of muscle creatine is in the form of PCr. Human muscle seems to have an upper limit of creatine storage of 150 to 160 mmol/kg/dm. Athletes with high creatine stores don't appear to benefit from supplementation, whereas individuals with the lowest levels, such as vegetarians, have the most pronounced increases following supplementation. Without supplementation, the body can replenish muscle creatine at the rate of about 2 g/day [7].

Although creatine is a natural component of food, the amount of food required to supersaturate the muscle with PCr may not be feasible. For example, it could require 22 pounds of meat daily [8]. If creatine monohydrate is proven to be a safe and effective ergogenic aid, creatine supplementation may be the simplest way to increasing muscle stores. It may be beneficial to avoid caffeine if taking creatine supplements. One study showed that caffeine diminished strength gains seen with creatine use [9].

Evidence Supporting Use
Several studies support the use of creatine supplementation for enhancing activities that require short periods of high-intensity power and strength. These include weightlifting, sprinting, and rowing.

One study demonstrated that daily supplementation with 5 g of creatine monohydrate increased the intracellular creatine and PCr content of quadriceps muscle in 17 human subjects. Those with the lowest initial total creatine content had the greatest increase. In addition, exercise enhanced creatine uptake in muscle. No adverse effects were reported [5].
Another study found that one week of creatine supplementation at 25 g/day enhanced muscular performance during repeated sets of bench press and jump squat exercise. Creatine supplementation appeared to allow the subjects to complete their workouts at a higher intensity. The researchers concluded that, over time, working at higher intensities may provide a more intense training stimulus and improved muscular adaptations [10].
Another study demonstrated that females receiving 4 days of high-dose creatine intake (20 g/day) followed by low-dose creatine intake (5 g/day) during 10 weeks of resistance training (3hours/week) increased muscle PCr concentrations by 6%. Also, maximal strength of the muscle groups trained increased by 20-25%, maximal intermittent exercise capacity of the arm flexors increased by 10-25% and fat-free mass increased by 60% [11].
A double-blind study provided 20 g/day of creatine monohydrate for 5 days to qualified sprinters and jumpers who performed 45 seconds of continuous jumping and 60 seconds of continuous treadmill running. Supplementation enhanced performance in the jumping test by 7% for the first 15 seconds and 12% for the next 15 seconds, but there was no difference for the final 15 seconds. There was a 13% improvement in the time of intensive running to exhaustion [12].
Another double-blind study supplemented with 18.75 g/day of creatine monohydrate for 5 days prior to high-intensity intermittent work to exhaustion, and then 2.25 g/day during testing. The workouts consisted of cycling to exhaustion using several protocols: (a) nonstop, (b) 60 seconds work/120 seconds rest, (c) 20 seconds work/40 seconds rest, and (d) 10 seconds work/20 seconds rest. Creatine supplementation significantly increased the total work time for all four protocols [13].
Another study tested male subjects performing two bouts of 30 second isokinetic cycling before and after ingesting 20 g creatine monohydrate daily for 5 days. Work production improved about 4%. Cumulative increases in both peak and total work production over the two exercise bouts were positively correlated with the increase in muscle creatine [14].
A 12-week placebo-controlled study of 19 weightlifters in their mid-twenties found that the creatine group could lift more weight and had greater increases in fat-free mass and muscle-fiber size than did the placebo group. The researchers thought that the creatine let the athletes who used it train harder [15].
Three additional studies suggest that creatine supplementation may not be beneficial for running velocity, sprint swimming performance, or a maximal cycling effort [7]. Short bouts of repeated anaerobic activity have shown some potential benefits with creatine supplementation use in a laboratory setting. However, creatine supplementation has not been shown to enhance single-event performance such as stationary cycling [16-19]. Taken together, these studies do not support creatine supplementation to enhance aerobic activities such as distance running.
Other areas of research include therapeutic uses of creatine to help patients with muscle wasting caused by disease states such as muscular dystrophy and amyotrophic lateral sclerosis (ALS). Small-scale preliminary studies show some gains in strength may be possible for these patients, which could improve their quality of life. One study of 81 patients with various neurologic diseases found that giving 10 g/day of creatine for five days, followed by 5 grams for another week, increases their muscle strength by about 10% [20]. Large-scale studies should be done before recommendations are made to such patients.

Adverse Effects
Creatine supplementation often causes weight gain that can be mistaken for increase in muscle mass. Increasing intracellular creatine may cause an osmotic influx of water into the cell because creatine is an osmotically active substance [10]. It is possible that the weight gained is water retention and not increased muscle. The retention of water may be connected to reports of muscle cramps, dehydration, and heat intolerance when taking creatine supplements. It would be prudent to encourage proper hydration for creatine users. Further research is needed to investigate these and other possible side effects.

Creatine is classified as a "dietary supplement" under the 1994 Dietary Supplement Health and Education Act and is available without a prescription. Creatine is not subjected to FDA testing, and the purity and hygienic condition of commercial creatine products may be questionable [21]. A 1998 FDA report lists 32 adverse creatine-associated events that had been reported to FDA. These include seizure, vomiting, diarrhea, anxiety, myopathy, cardiac arrhythmia, deep vein thromboses and death. However, there is no certainty that a reported adverse event can be attributed to a particular product [22]. A recent survey of 28 male baseball players and 24 male football players, ages 18 to 23, found that 16 (31%) experienced diarrhea, 13 (25%) experienced muscle cramps, 7 (13%) reported unwanted weight gain, 7 (13%) reported dehydration, and 12 reported various other adverse effects [23].

Caution Urged
There appears to be some potential for creatine supplementation. However, many questions remain. Are there any long-term harmful effects from supplementation? Is there a point where enhanced performance levels off from long-term supplement usage? What effect does "stacking" or taking two ergogenic aids simultaneously have on the body? What happens if you immediately stop taking the creatine supplement? Is the enhanced performance great enough to warrant the expense of the supplement? Until further research answers these questions, creatine is not recommended for the average athlete.

For Additional Information
Jenkins, MA. Creatine supplementation in athletes: Review
Creatine is the object of intensive research. To keep current, use the links below to visit the abstracts on PubMed and click on "Related Articles" when you arrive.
References
Murray RK and others. Harper's Biochemistry, 24th Edition. Stamford, CT: Appleton & Lange, 1996.
Sahelian R, Tutle D. Creatine: Nature's Muscle Builder. Garden City, NY: Avery Publishing Group, 1997.
Toler S. Creatine is an ergogen for anaerobic exercise. Nutrition Reviews 55:21-25, 1997.
Maughan R. Creatine supplementation and exercise performance. International Journal of Sport Nutrition 5:94-101, 1995.
Harris RC, Soderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clinical Science 83:367-374, 1992.
Haff GG, Potteiger JA. Creatine supplementation for the strength/power athlete. Strength and Conditioning 19(6):72-74, 1997.
Coleman E. Creatine monohydrate: a sprint performance enhancer? HCRC Web site.
Modica P. Creatine supplements show some sports benefit. Medical Tribune News Service. July 10, 1997.
Vandenberghe K and others. Caffeine counteracts the ergogenic action of muscle creatine loading. Journal of Applied Physiology 80:452-457, 1996.
Volek JS and others. Creatine supplementation enhances muscular performance during high-intensity resistance exercise. Journal of American Dietetic Association 97:765-770, 1997.
Vandenberghe K and others. Long-term creatine intake is beneficial to muscle performance during resistance training. Journal of Applied Physiology 83:2055-2063, 1997.
Bosco C and others. Effect of oral creatine supplementation on jumping and running performance. International Journal of Sports Medicine 18:369-372, 1997.
Prevost MC, Nelson AG, Morris GS. Creatine supplementation enhances intermittent work performance. Research Quarterly for Exercise and Sport 68:233-240, 1997.
Casey A and others. Creatine ingestion favorably affects performance and muscle metabolism during maximal exercise in humans. American Journal of Physiology 271(1):E31-E37, 1996.
Volek JS and others. Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Medicine and Science in Sports and Exercise 31:1147-1156, 1999.
Dawson B and others. Effects of oral creatine loading on single and repeated maximal short sprints. Australian Journal of Science and Medicine in Sport 27(3):56-61, 1995.
Cooke WH, Grandjean PW, Barnes WS. Effect of oral creatine supplementation on power output and fatigue during bicycle ergometry. Journal of Applied Physiology 78:670-673, 1995.
Odland LM and others. Effect of oral creatine supplementation on muscle [Pcr] and short-term maximum power output. Medicine and Science in Sports and Exercise 29:216-219, 1997.
Snow RJ and others. Effect of creatine supplementation on sprint exercise performance and muscle metabolism Journal of Applied Physiology 84:1667-1673, 1998.
Tarnopolsky M. Creatine monohydrate increases strength in patients with neuromuscular diseases. Neurology 52:854-857, 1999.
Sorgen C. Creatine supplementation: The quest for power performance. Today's Dietitian (1)3:26-29, 1999.
FDA Special Nutritionals Adverse Event Monitoring System. Accessed June 7, 1999.
Juhn MS and others. Oral creatine supplementation in male collegiate athletes: A survey of dosing habits and side effects. Journal of the American Dietetic Association 99:593-594, 1999.

 

[xjsynx]

Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities.

* Xin ZC,
* Kim EK,
* Lin CS,
* Liu WJ,
* Tian L,
* Yuan YM,
* Fu J.

Department of Urology, the 1st Hospital, Peking University, 8 Xishiku Street, Xicheng District, Beijing 100034, China. [email protected]

AIM: To clarify the mechanism of the therapeutic action of icariin on erectile dysfunction (ED). METHODS: PDE5 was isolated from the human platelet and PDE4 from the rat liver tissue using the FPLC system (Pharmacia, Milton Keynes, UK) and the Mono Q column. The inhibitory effects of icariin on PDE5 and PDE4 activities were investigated by the two-step radioisotope procedure with [(3)H]-cGMP/[(3)H]-cAMP. Papaverine served as the control drug. RESULTS: Icariin and papaverine showed dose-dependent inhibitory effects on PDE5 and PDE4 activities. The IC(50) of Icariin and papaverine on PDE5 were 0.432 micromol/L and 0.680 micromol/L, respectively and those on PDE4, 73.50 micromol/L and 3.07 micromol/L, respectively. The potencies of selectivity of icariin and papaverine on PDE5 (PDE4/PDE5 of IC(50)) were 167.67 times and 4.54 times, respectively. CONCLUSION: Icariin is a cGMP-specific PDE5 inhibitor that may be developed into an oral effective agent for the treatment of ED.

PMID: 12646997 [PubMed - indexed for MEDLINE]

 

[jasonschaffin]

Wow my computer has slowed down. Where are we at??? By now this could be 2500......

 

[TheMyth]

The testosterone mimetic properties of icariin.Zhang ZB, Yang QT.
Department of Urology, Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, China. [email protected]

AIM: To evaluate the testosterone mimetic properties of icariin. METHODS: Forty-eight healthy male Sprague-Dawley rats at the age of 15 months were randomly divided into four groups with 12 rats each: the control group (C), the model group (M), the icariin group (ICA) and the testosterone group (T). The reproductive system was damaged by cyclophosphamide (intraperitoneal injection, 20 mg/kg x day) for 5 consecutive days for groups M, ICA and T, at the sixth day, ICA (gastric gavage, 200 mg/kg x day) for the ICA group and sterandryl (subcutaneous injection, 5 mg/rat . day) for the T group for 7 consecutive days, respectively. The levels of serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), serum bone Gla-protein (BGP) and tartrate-resistant acid phosphatase activity in serum (StrACP) were determined. The histological changes of the testis and the penis were observed by microscope with hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase biotin-dUTP-X nick end labeling (TUNEL), respectively. RESULTS: (1) Icariin improved the condition of reproductive organs and increased the circulating levels of testosterone. (2) Icariin treatment also improved the steady-state serum BGP and might have promoted bone formation. At the same time, it decreased the serum levels of StrACP and might have reduced the bone resorption. (3) Icarrin suppressed the extent of apoptosis of penile cavernosal smooth muscle cells. CONCLUSION: Icariin has testosterone mimetic properties and has therapeutic potential in the management of hypoandrogenism.

PMID: 16751992 [PubMed - indexed for MEDLINE]

 

[rafter]

Nurtition more Important Than Training
Written by Tom Venuto


Legendary bodybuilding trainer Vince, "The Iron Guru" Gironda was famous for saying, "Bodybuilding is 80% nutrition!" But is this really true or is it just another fitness and bodybuilding myth passed down like gospel without ever being questioned?

Which is really more important, nutrition or training? This IS an interesting question and I believe there is a definite answer:

The first thing I would say is that you cannot separate nutrition and training. The two work together synergistically and regardless of your goals - gaining muscle, losing fat, athletic conditioning, whatever. You will get less than-optimal or even non-existent results without paying attention paid to both.

In fact, I like to look at gaining muscle or losing fat in three parts - weight training, cardio training and nutrition - with each part like a leg of a three legged stool. pull ANY one of the legs off the stool, and guess what happens?

In reality, it's impossible to put a specific percentage on which is more important - how could we possibly know such a number to the digit?

Nutrition and training are both important, but at certain stages of your training progress, I do believe placing more attention on one component over the other can create larger improvements. Let me explain:

If you're a beginner and you don't posses nutritional knowledge, then mastering nutrition is far more important than training and should become your number one priority. I say this because improving a poor diet can create rapid, quantum leaps in fat loss and muscle building progress.

For example, if you've been skipping meals and only eating 2 times per day, jumping your meal frequency up to 5 or 6 smaller meals a day will transform your physique very rapidly.

If you're still eating lots of processed fats and refined sugars, cutting them out and replacing them with good fats like the omega threes found in fish and unrefined foods like fruits, vegetables and whole grains will make an enormous and noticeable difference in your physique very quickly.

If your diet is low in protein, simply adding a complete protein food like chicken breast, fish or egg whites at each meal will muscle you up fast.

No matter how hard you train or what type of training routine you're on, it's all in vain if you don't provide yourself with the right nutritional support.

In beginners (or in advanced trainees who are still eating poorly), these changes in diet are more likely to result in great improvements than a change in training.

The muscular and nervous systems of a beginner are unaccustomed to exercise. Therefore, just about any training program can cause muscle growth and strength development to occur because it's all a "shock" to the untrained body.

You can almost always find ways to tweak your nutrition to higher and higher levels, but once you’ve mastered all the nutritional basics, then further improvements in your diet don't have as great of an impact as those initial important changes...

Eating more than six meals will have minimal effect. Eating more protein ad infinitum won't help. Once you're eating low fat, going to zero fat won't help more - it will probably hurt. If you're eating a wide variety of foods and taking a good multi vitamin/mineral, then more supplements probably wont help much either. If you're already eating natural complex carbs and lean proteins every three hours, there's not too much more you can do other than continue to be consistent day after day...

At this point, as an intermediate or advanced trainee who has the nutrition in place, changes in your training become much more important, relatively speaking. Your training must become downright scientific.

Except for the changes that need to be made between an "off season" muscle growth diet and a "precontest" cutting diet, the diet won't and can't change much - it will remain fairly constant.

But you can continue to pump up the intensity of your training and improve the efficiency of your workouts almost without limit. In fact, the more advanced you become, the more crucial training progression and variation becomes because the well-trained body adapts so quickly.

According to powerlifter Dave Tate, an advanced lifter may adapt to a routine within 1-2 weeks. That's why elite lifters rotate exercises constantly and use as many as 300 different variations on exercises.

Strength coach Ian King says that unless you're a beginner, you'll adapt to any training routine within 3-4 weeks. Coach Charles Poliquin says that you'll adapt within 5-6 workouts.

So, to answer the question, while nutrition is ALWAYS critically important, it's more important to emphasize for the beginner (or the person whose diet is still a "mess"), while training is more important for the advanced person... (in my opinion).

It's not that nutrition ever ceases to be important, the point is, further improvements in nutrition won't have as much impact once you already have all the fundamentals in place.

Once you've mastered nutrition, then it's all about keeping that nutrition consistent and progressively increasing the efficiency and intensity of your workouts, and mastering the art of planned workout variation, which is also known as "periodization."

The bottom line: There's a saying among strength coaches and personal trainers...

 

[powerhouse21]

Anabolic Pump Training
by Dave Barr


Like Feeling Pumped?

Good. Because stimulating a pump can be a powerful trigger for muscle growth. This increase in blood flow delivers more nutrients to the working muscle, which is known as activating the anabolic pump.

In this article we'll discuss how to train to achieve maximal blood flow and the biggest pumps, while greatly stimulating muscle growth. Specifically, we'll look at:

1) Ramp Contractions

2) Taper Training

3) The Mechanical Muscle Pump


How To Get Pumped

Ask the average person about getting pumped and they'll tell you about how an AC/DC song makes them feel or the experience when their favorite team scores a goal. Occasionally you'll even get someone who'll share his secret for "male enhancement."

But for most of us, a muscle pump is one of the best feelings in the world. It can be a great motivator because not only does it look and feel great, but it actually helps us optimize our gym efforts. Best of all, we know we've earned it. If we understand how the pump works, we're better able to improve this sought-after reward.



"Male Enhancement"?

The main stimulators of blood flow are metabolic by-products (a.k.a. metabolites) that build up during the course of muscle contraction. Substances like potassium and adenosine "leak" out of the muscle during intense contraction, and are the important mediators of the desired hyperemia (a.k.a. increased blood flow). These metabolites are signals for a number of metabolic processes, the most noticeable of which is the blood flow stimulation that's used to clear them away.

You probably aren't concerned with the details of the process, so let's just say that even if you don't care about metabolite clearance from the muscle, the elevated blood flow also brings nutrients to keep the muscle strong and stimulate growth. Essentially, it feeds our muscle. Perhaps even better is the fact that the metabolite buildup also hinders muscle contraction, and the improved clearance serves to increase muscle strength by removing this inhibition.

Based on what you've just read, it might be obvious that the best way to stimulate the muscle pump is to cause as much metabolite accretion as possible. This is accomplished through one of two ways, both of which can be combined to maximize the anabolic pump.




The Pulsatile Pump

During the normal course of a normal set, muscles contract and relax (somewhat), which actually helps to pump blood around, just like a mini-heart. When we contract maximally, we occlude blood flow and allow metabolites to build up. As we relax the muscle during the eccentric (negative) part of the movement, we allow more blood to reach the working muscle. Whether you knew it or not, every set you've ever done has had this rhythmic effect on blood flow, and if we manipulate it just right we can greatly enhance the effect.

One of the best ways to induce a muscle pump is to perform isometric (static) contractions. This is because the metabolites produced during normal contractions aren't cleared away with each rep, as would normally occur during dynamic or moving contractions.

Stated differently, the cyclic contraction pattern of preventing blood flow and then allowing flow to proceed, is disrupted during static contraction training. By allowing metabolites to build up and reach a critical point, we induce a tremendously powerful stimulus to activate the anabolic pump.


Case Study: Isometric Barr

My first lesson in the power of isometric contractions was during a lab experiment in which I was the subject. I was having my arterial blood flow measured (by Doppler Ultrasound) during a bunch of different muscle contractions in order to demonstrate the different effect of each.

In order to add to the impact of what occurred, a visual display of blood flow traced across a computer monitor (much like an ECG), while the swishing wave sound of blood was amplified through a set of speakers.



As the blood flowed through my artery, everything seemed normal as indicated by the rhythmic waves on the monitor and resulting wave-like sounds. When I lightly contracted my biceps, the blood flow decreased in amplitude. Not only did the size of the waves on the monitor diminish, but the sound became less audible. But when I relaxed the muscle, the blood flow waves didn't just return to normal, they came back much larger than before. This is due to the slight metabolite buildup that had happened.



What really stood out to me occurred when I maximally contracted my biceps: the wave became a flatline and the sound stopped. This flatline had essentially indicated the (temporary) death of blood flow.

I was instructed to hold this for 25 seconds and then relax. When I finally did, the normal wave pattern had become a huge surge of blood -- the visual representation of which filled up the entire screen. The sound was like an enormous wave was crashing overhead. This is exactly what we're trying to achieve with ramp contractions.


Ramp Contractions

The idea behind ramp contractions is simple, but the conceptualization might not be. The idea is that we gradually increase the tension on the muscle during an isometric contraction, essentially ramping up contraction strength until we're maximally contracting against the unmovable object. As indicated earlier, this temporarily restricts muscle blood flow, resulting in a huge anabolic surge once the tension is released.

Ideally, different muscle lengths will be used for the ramp contractions to ensure that all muscle fibers are reached equally. For example, if we're using ramp contractions for our biceps, we'd use sets in which our elbows were largely straight, those with elbows bent at 90 degrees, and those with a peak contraction. The latter of which will yield the greatest blood flow occlusion, so most people find it easiest to end their sets of ramp contractions with them. If they're performed too early in the set, fatigue will build up that would hinder subsequent contraction strength.


Ramp Contractions: In Practice

In order to perform ramp contractions, we of course need to ensure that we have the desired contraction angle for the immovable object. If we use the example of biceps training again, this is easiest accomplished through either power rack pins or very heavy weight. If we're using a power rack, just set the pins to where you want the contraction to be held and pull the empty bar up into them.

Alternatively, if we don't have access to a power rack with movable pins, ramp contractions can be performed by setting the bar on a squat rack (or any bench) at the desired height. If we use excessive weight, such that it can't be moved, we can pull up as hard as we want to achieve an isometric contraction.

Ramp contractions are usually performed in conjunction with a traditional training routine, following the completion of the normal static sets. The ramping up of contraction intensity takes 5 seconds to go from 0% to maximal contraction. It seems as though the ramping process isn't only preferred by most people, but the progressive buildup of tension allows the body to contract harder for longer. Although they're isometric, make no mistake that these contractions are intense.

Key Point: Just because ramp contractions are isometric doesn't mean they should be treated as such. In order to achieve the greatest contraction, it should be your intent to actually move the bar, even though this is clearly impossible. Studies suggest that it's this intent to move the bar that yields the greatest results.

Details:

Total Sets: 3-5
Reps: 1 (naturally)
Duration: 10 Seconds
Rest: 1-2 Minutes


Taper Training

Another key to activating the anabolic pump is to employ a method called taper training. Once again we focus on the metabolite-induced stimulation of blood flow to trigger muscle growth, but this time we combine high reps with our normal training routine in order to achieve the desired effect. In fact, taper training is best thought of as an adjunct to normal training rather than a system of its own.




Extreme Taper

The way in which it serves to optimize blood flow for the anabolic pump is by using the fatigue and stimulation of the preceding sets for maximal effect. Once all heavy work on a muscle is completed, lighter sets are performed with higher reps. Because the muscle is already stressed by the first part of the workout, it's primed to receive the extra nutritive blood flow that the high reps will induce.

For example, if we perform 6 sets of chest work with a 6-10 rep range, we will have already stimulated muscle growth. But by tapering down the weight for more sets, we'll be able to feed the anabolic drive though elevated blood flow. Low reps create the need while the high reps activate the feed.


Taper Training: In Practice

It's best to use taper training within ten minutes of the last set to ensure that the muscle isn't completely fatigued, but still in the receptive state for blood flow. Using chest training again, we'd begin tapering down the weight five minutes after the last heavy work set. Sets of the first chest exercise are used again, but this time, the weight is adjusted such that 15 reps can be performed.

Following this set, you'd wait one minute before doing the same exercise with a weight with which 20 reps can be performed. Don't let the high reps fool you; you're going to feel a serious burn. From here it's best to move on to sets of subsequent chest exercises.

Key Point: By the time you get to even the second tapered set, the weight may be so low that it seems inconsequential. But remember that the key here it to stimulate metabolite buildup, which is exactly how the anabolic pump is activated.

Details:

Total Sets: 3-6
Reps: 15-25
Rest: 1-2 minutes


Case Study: Stagnant Space Blood

When I was working with NASA at the Johnson Space Center in Houston, I had the opportunity to have my leg blood flow examined via Doppler Ultrasound, the same measurement technique described under Ramp Contractions. (The reason that this is studied in astronauts is because zero gravity screws with the way our blood flow works, and if we have any hope of long term space flight, this is one problem that needs to be solved.)

When the probe was applied to my upper calf I was happy to see that most of the blood traveled though the vein in a smooth motion. But what surprised me was an area behind the valve (much like an inward-opening gate) where the blood just swirled around in a circle and didn't flow at all.

This is analogous to having a small room filled with people and only a single door. If the door is opened inwards, most of the people could leave except for those who were trapped behind the door as it opened. Interestingly, it's this localized inhibition of blood flow that's often responsible for blood clots.



What's worse is that they applied the probe to my chest and found that I have a slightly leaky heart valve (mitral valve regurg), which they assured me was quite normal. After finding these issues with me it was decided that I should no longer be a subject, if for no other reason than my own sense of well being. Awesome.

Conclusion: Beware of scientists with probes. You never know where they'll stick them or what they might find.


The Mechanical Muscle Pump

No, this isn't a weak new supplement specially formulated to get you "jacked" and "swole" (and make girls like you). The muscle pump is a fundamental physical process in which we assist our natural blood flow by contracting our muscles.

If you've ever performed vigorous physical activity and were told not to lie down afterwards, this is why. Walking around occurs by contracting our muscles which squeezes our blood vessels and subsequently forces (or pumps) the blood around our body. Hence the muscle pump.

If we didn't have such a mechanism, our blood could pool in our legs as we stand (due to gravity), which would reduce blood supply to our tissues, including our brains. Once this happens, we pass out.

You may have heard such stories from military personnel who are forced to stand at attention for long periods of time. If they don't periodically contract their calf and thigh muscles, without making it appear as though they're moving, then there's a chance that their blood will remain in their legs and down they go.




Now you're probably not passing out during training, but we can use this muscle pump to improve strength by simply getting off of our asses after a set. By walking around, we're preventing any gravity-induced pooling, and assisting blood flow to the muscles being trained.

This helps inter-set recovery, especially during leg training, but is recommended following every set. After all, if we're just sitting there waiting for our next set then we're not experiencing ideal metabolite clearance, and our strength on subsequent sets will be impeded.


Frequently Asked Questions

Q: You're wrong! I know that doing high reps doesn't cause good muscle growth!

A: I agree that if you're performing high reps exclusively then a good pump doesn't mean much at all. It's the combination of low-moderate rep training with taper training that activates the anabolic pump. Remember that the former causes the need while the latter feeds.

Q: You say that metabolites are good for blood flow, but then walking around is good because it clears metabolites (via the muscle pump). What gives?

A: Good question. The metabolite buildup is initially required to activate the anabolic pump, but remember that it also reduces muscle strength. This is why it's desirable to achieve the buildup later in the workout. But the enhanced pumping blood flow caused by walking around is used to clear away metabolites during earlier sets, when muscle strength is critical. Remember that the anabolic pump is only activated after the need is induced by lower rep training.


Conclusion

Wanna get pumped? Try ramp contractions and taper training, and utilize the mechanical muscle pump during this week's workouts!

Special thanks to Sabrina and my forensic botanist, David Lounsbury.

 

[TheMyth]

I win! I hit it on the nail!

 

[xjsynx]

Goal. We all have them. But what truly is a goal. Webster dictionary defines goal as:
1. The end toward which effort is directed
2. The terminal point of a race.
When we think of our goals we think of how quickly can we accomplish them. Whether your goal is losing a few pounds, increasing performance, or bursting through a new plateau, we all want to race to the finish line. Unfortunately, we all have lives and sometimes life gets in the way and knocks us out of the race. We seek out products that make claims that will help us reach our goals and reach them quickly. However, we find only once again we have lost our hard earned dollars and have become no closer to the finish line. Well, not anymore!

Applied Nutriceuticals has the answer to putting you back in the drivers seat and racing towards your goal at speeds you never thought possible! Finally there is a product that makes every day…..Race Day! That product is RPM from Applied Nutriceuticals. What is RPM? Rpm is an exclusive formula that provides explosive energy, crisp uncanny mental focus, noticeable strength increases, all while giving you insane pumps, suppressed estrogen, increased testosterone, while incinerating fat!!!! RPM is instant gratification from the very first dose! RPM is in its own race class!

Lets look under the hood at this super-charged formula………………

RPM’s formula is so unique it requires it’s own class. RPM, the supplement world’s first Anabolic-Cognitive Energy System Enhancer (A-CESE), where anabolics meet cognitive psy-stimulants!
How do A-CESEs differ from other product categories on the market? An A-CESE is a product that contains testosterone-like, anti-catabolic, and aromatase-inhibiting properties, while at the same time delivering optimal mind/muscle connection/contraction through unique peripheral vasostimulatory perfusion and increased cognitive psycho-motor control. RPM combines P-SARM Synthase AI- a unique blend of research-grade icariin, Arginine , Naringenin, and oligomeric proanthocyanidins (OPC’s), and Methyl-AMP Complex, a powerful blend of methyl-xanthine caffeine and chocamine.


AN uses the highest quality ingredients in scientifically-proven doses to achieve maximal results!! In the product constituent P-SARM Synthase AI, RPM utilizes pharmaceutical-grade Icariin, a potent vasodilator with anabolic and anti-catabolic effects, that can also yield stronger, more forceful muscle contractions!! Icariin works through several different mechanisms: by increasing nitric oxide (NO) through PDE5 inhibition, by acting as a potent anti-catabolic agent that increases the testosterone to cortisol ratio, by increasing muscle contractility by deactivating AchE (Acetycholinesterase), and by boosting endogenous testosterone levels through increasing cAMP and luteinizing hormone and decreasing prolactin. It also is considered a Phytochemical Selective Androgen Receptor Modulator or P-SARM. A P-SARM is a phytochemical (plant-derived) compound that mimics the effects of androgens on muscle mass, strength, bone growth, drive, and sexual function, while at the same time not negatively effecting blood lipids or blood pressure. P-SARMs provide an excellent alternative to other “enhancement” products on the market, including oral bioavailability, flexible biochemical structure, and lack of steroid-related side-effects!!!


As mentioned before, Icariin has potent anti-catabolic effects, along with testosterone-mimicking and muscle-contraction-enhancing benefits - several studies have shown that it actually competes with glucocorticoids for receptor sites in a manner similar to testosterone, while at the same time improving the testosterone to cortisol ratio. This is caused by two different mechanisms of action: the aforementioned competition with glucocorticoids, and also increased testosterone production, through increased cAMP (cyclic AMP, a second messenger important in hormone signaling) levels, luteininzing hormone (LH) levels, the actual mimicry of testosterone in spermatogenesis, and decreased prolactin levels. Icariin seems to block glucorticoids from binding to cortisol receptors, thus blocking the action of cortisol. This alone will cause an anabolic effect by positively skewing the T:C ratio, which is a trigger for greater protein synthesis, increased aggression towards the iron, and insane muscle contractions!!

RPM also reduces aromatase and estradiol, allowing for the greater production of T as a substrate for aromatase activity- as users of RPM report huge rises in strength, physique hardness, and positive aggression while using this compound, an effect that can be at least partially attributed to the androgen-mimicking qualities of Icariin. RPM also has a dopaminergic effect, allowing for increased dopamine levels and decreased prolactin levels, both of which are triggers for increased testosterone. Also, icariin can enhance muscle contraction by decreasing the effects of acetylcholinesterase (AChE). Acetylcholine (Ach) is a neurotransmitter necessary for muscle contraction, and AChE is responsible for disabling ACh at the neuromuscular junction. Icarin actually blocks this disabling action, allowing for ACh to stay at the synapse, and better exert its effects, for a longer period of time- allowing for harder and stronger muscle contractions!!!

Icariin is a selective inhibitor of cyclic guanosine monophosphate (cGMP)- specific phosphodiasterase type 5 (PDE5 for the purposes of this article). This is important, because PDE5 hydrolyze cGMP into an inactive molecule. cGMP is important because nitric oxide (NO) requires cGMP to moderate vascular control and vasodilation. So, essentially, no cGMP, no vasodilation (the “PUMP”), because NO requires cGMP to work. The more cGMP, the more NO-induced vasodilation- therefore greater pumps!! Icariin stops PDE5 from disabling cGMP and allowing cGMP to extend its activity, which exerting the effects of NO in skeletal muscle, allowing for a stronger muscle contraction and pump. Viagra is probably the most well known PDE5 inhibitor on the market- but how does Icariin compare? In scientific studies, pure icariin has been found to have roughly one-tenth the PDE5 inhibitory activity and nitric oxide productivity of Viagra- and in P-SARM Synthase AI, the dosage is tailored appropriately to reflect these findings!! In short, the PDE5 inhibition displayed by icariin puts RPM in a class above all other NO enhancers- the effects can actually be viewed as “pharmaceutical-like!!!!”


The inclusion of oligomeric proanthocyanidins (OPCs) are also essential in the creation of any good A-CESE, because OPCs contain their own combination of unique and effective constituents, which allows P-SARM Synthase AI to exert potent anti-aromatase (AI), anti-oxidant, and vasodilatory effects. OPCs have been shown in numerous studies to have the ability to block the conversion of androgens to estrogens, with a potency comparable to several widely marketed pharmaceutical AI inhibitors (Arimidex). RPM reduces aromatase activity and estradiol as well, allowing for more testosterone (T) to be produced!!

Compounds exhibiting AI characteristics also reduce SHBG (steroid hormone binding globulin) as well. This is important, because this allows for a drastic increase in free testosterone (T). When this occurs, coupled with T levels that are already high from decreased aromatization of estrogen, WATCH OUT!!!! Look for longer, harder more intense workouts, rapid strength increases with personal records on all your lifts, greater protein synthesis, quicker recovery, while also allowing for increased lipolysis (fat burning)!! This, coupled with the androgen-mimicking qualities of the P-SARM Icariin, gives the product a unique “hardness” enhancing quality, giving the user of the product an “eye” popping type of physique that looks to be cut from stone!!!

OPCs also protect against free radicals and subsequent DNA and oxidative damage, qualities that are extremely important to the hard-training athlete. Oxidative damage is a common occurrence during stress and hard training, and it can stop lean body mass gains in their tracks!! Less oxidative damage, better recovery, giving you the ability to train longer and harder!!! The nitric oxide-enhancing, vasodilatory properties of OPCs have also been documented in countless studies. The flavonoids contained in OPCs actually increase levels of Nitric Oxide Synthase (NOS), the enzyme that allows for the conversion of arginine to nitric oxide. This is very important, as nitric oxide synthase competes with arginase for the utilization of the amino acid L-arginine. Arginase converts L-arginine into ornthine, and increased arginase and ornthine activity, are counteractive to the nitric oxide production pathway. By increasing NOS, the flavonoids in OPCs “crowd out” arginase, allowing for more arginine to be processed into NO. The result is higher NO levels, even greater vasodilation, and gigantic pumps and a physique hard as nails!!

Naringin, and its novel component Naringenin, also exert extensive effects within the P-SARM Synthase AI complex. Naringin (and Naringenin) exhibit remarkable aromatase and estrogen-inhibiting properties by decreasing the cytochrome P450arom isoform, an enzyme that also allows for the oxidative metabolism for chemical modification and degradation of oral medications. This can have very positive effects on the T:E ratio, and the combination of OPCs and Naringenin can be potentially additive or synergistic in eliminating estrogen, and allowing for more circulating free testosterone and all of its benefits!!! Naringin and Naringenin have also been shown to have profound effects on the metabolism of caffeine and PDE5 inhibitors such as Icariin, allowing for these compounds to be much more effective on a per dose basis- by up to 35%!!!

L-Arginine is also an essential component of the P-SARM Synthase AI matrix. L-Arginine is an amino acid that is necessary for cell division, the healing of wounds, displacing ammonia from the body, the release of hormones, and immune function. Most importantly, L-arginine is necessary for the production of Nitric Oxide (NO, as mentioned above), a messenger gas responsible for the promotion of blood vessel relaxation (“pump”), and the regulation of vascular tone. NO is derived from arginine and oxygen via Nitric Oxide synthase (NOS), and, as mentioned above, NO exerts its effects on tissue through cGMP. The inclusion of Arginine in the P-SARM Synthase AI complex allows for a steady, continuous supply of L-arginine for conversion to NO, allowing for a more effective product. Numerous research studies document the positive effects of L-Arginine and NO on increasing lean body mass, and possibly even mediating greater growth hormone response!!

As you can see, the P-SARM Synthase AI decoction offers an extremely potent blend of testosterone-optimizing, estrogen eliminating, and NO-enhancing effects. The “other” synergistic component blend of RPM, Methyl-AMP Complex, makes this A-CESE unmatched as a mind/muscle connector/contractor through unique peripheral vasostimulatory perfusion and increased cognitive psycho-motor control!!

Methyl-Xanthine Anhydrous Caffeine (MXAC), the first component of the Methyl-AMP Complex, is a metabolic stimulant that heightens mental alertness and focus and improves muscle contraction and coordination. MXAC exerts very strong effects on vasodilation- a process that begins with the activation of Norepinephrine (NE) by MXAC, and the deactivation of cAMP-PDE, an enzyme that breaks down cAMP When MXAC acts on a cell, cAMP-PDE can no longer turn cAMP into AMP, so the action of cAMP is prolonged within the cell. Sound like boring biochemistry? Let’s take a look at the overall effect on the body- when cAMP levels are increased due to cAMP-PDE inactivation, the blood vessels in skeletal muscle tend to relax- the result? More rapid blood flow into the muscle, resulting in bulging vascularity and massive pumps!! MXAC also contains significant amounts of theobromine, a vasodilator that ups the amount of nutrients and oxygen into the brain and skeletal muscle. This greater blood flow to the brain contributes to the cognitive enhancement capabilities of MXAC, by blocking adenosine uptake without activating adenosine receptors- resulting in an increase in dopamine and serotonin levels, causing a positive influence on mood, allowing the user to maintain an optimal training environment.


Another added benefit of MXAC is the ability to stimulate the central nervous system, which may help the athlete feel better and more alert, allowing for enhanced focus and clear-headedness. It also stimulates the neural system to fire muscles into action more effectively via norepinephrine stimulation, and also by producing changes in calcium activity, thus stimulating ion transport of potassium into non-contracting tissues. This is important because ion transport helps reduce the increase in blood potassium concentrations during exercise, helping maintain the excitability of the muscle fiber, allowing for a stronger, longer muscle contraction!!

 

[rafter]

Wow my computer has slowed down. Where are we at??? By now this could be 2500......

its gettin close

 

[xjsynx]

Chocamine, the other component of the Methyl-AMP Complex, is a specially standardized cocoa extract comprised of several different important constituents that enhance mood, cognitive awareness, and muscle contraction. PEA, tyramine, and L-Tyrosine are the most prevalent constituents of chocamine, and have the biggest impact on the positive effects of the compound. The amino acid tyrosine has profound psycho-stimulant effects for maximal cognitive enhancement- Tyrosine is a precursor to the neurotransmitter dopamine, and in human subjects tyrosine (and Chocamine) supplementation causes increased dopamine and norepinephrine levels, which can be helpful for increasing athletic ability and cognitive function. Tyrosine has the ability to ward off exercise-related fatigue by creating a favorable dopamine to serotonin ratio, which can alter the psychological profile of fatigue for the user. A simple shift in amino acid ratio can create a large difference in perception and concentration, and higher dopamine levels are highly correlated with increased focus and mental connection, along with some mood enhancement/anti-depressant activities. Tyrosine has been shown to reduce or prevent stress-related cognitive impairment, along with preventing the oversecretion of glucocorticoids.

Phenylethylalanine (PEA) and tyramine are two more important constituents of Chocamine. PEA is a biogenic amine derived from the amino acid phenylalanine, and it has some effects very similar to amphetamine. It has strong mood-enhancing qualities, along with the ability to increase focus and offset lack of sleep. Tyramine is another biogenic amine found in Chocamine- it is responsible for the increased release of NE in the neurons, creating an excitatory effect on the CNS. It has also been shown to increase dopamine levels and increase the generation of cAMP, and also to aid in lipolysis (another added bonus of this product). Chocamine also contains significant amounts of caffeine and theobromine, both of which also add a psycho-motor stimulatory effect, thus resulting in increased peripheral vasodilation, muscle contractility, and the mind/muscle stimulatory link!!!

Conclusion.
Ready to rev up your workout? RPM takes the guesswork out of your supplementation. Finally there is 1 product that will make selecting your supplements easy. RPM does it all and does it effectively. You feel it from the very first dose. RPM is backed by proven scientific research that will have you reaching your goals in no time. With RPM….. everyday is race day!


References
Tian L, Xin ZC, Yuan YM, Fu J, Liu WJ, Wang LL. Zhonghua Yi Xue Za Zhi. 2004 Jun 2;84(11):954-7. Effects of icariin on the erectile function and expression of nitrogen oxide synthase isoforms in corpus cavernosum of arterigenic erectile dysfunction rat model

Xin ZC, Kim EK, Lin CS, Liu WJ, Tian L, Yuan YM, Fu J. Asian J Androl. 2003 Mar;5(1):15-8. Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities.

Tian L, Xin ZC, Yuan YM, Fu J, Liu WJ, Wang LL. Zhonghua Yi Xue Za Zhi. 2004 Jan 17;84(2):142-5. [Article in Chinese] Effects of icariin on intracavernosal pressure and systematic arterial blood pressure of rat

Hull EM, Muschamp JW, Sato S. Dopamine and serotonin: influences on male sexual behavior. Physiol Behav. 2004 Nov 15;83(2):291-307

Pavone C, Curto F, Anello G, Serretta V, Almasio PL, Pavone-Macaluso M. J Urol. 2004 Dec;172(6 Pt 1):2347-9. Prospective, crossover comparison of sublingual apomorphine (3mg) with oral sildenafil (50mg) for male erectile dysfunction.

Kruger TH, Haake P, Hartmann U, Schedlowski M, Exton MS. Orgasm-induced prolactin secretion: feedback control of sexual drive? Neurosci Biobehav Rev. 2002 Jan;26(1):31-44.

Chen J, Wollman Y, Chernichovsky T, Iaina A, Sofer M, Matzkin H. BJU Int. 1999 Feb;83(3):269-73. Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo-controlled study.

Klotz T, Mathers MJ, Braun M, Bloch W, Engelmann U. Effectiveness of oral L-arginine in first-line treatment of erectile dysfunction in a controlled crossover study. Urol Int. 1999;63(4):220-3. PMID: 10743698

Stanislavov R, Nikolova V. Treatment of erectile dysfunction with pycnogenol and L-arginine. J Sex Marital Ther. 2003 May-Jun;29(3):207-13. PMID: 12851125

Kim NN, Christianson DW, Traish AM. Role of arginase in the male and female sexual arousal response. J Nutr. 2004 Oct;134(10 Suppl):2873S-2879S; discussion 2895S. Review. PMID: 15465804

Ying, Pan, Wei-Yun Zhang, Xing Xia, and Ling-Dong Kong, “Effects of Icariin on Hypothalamic-Pituitary-Adrenal Axis Action and Cytokine Levels in Stressed Sprague-Dawley Rats” Biol. Pharm. Bull., Vol. 29, 2399-2403.

Aghdasi B, Reid MB, and Hamilton SL. (1997) Nitric oxide protects the skeletal muscle Ca2+ release channel from oxidation induced activation. J Biol Chem 272:25462-25467

Balon TW, Nadler JL. (1997)Evidence that nitric oxide increases glucose transport in skeletal muscle. J Appl Physiol. 1997 Jan;82(1):359-63.

Etgen GJ Jr, Fryburg DA, Gibbs EM. (1997) Nitric oxide stimulates skeletal muscle glucose transport through a calcium/contraction- and phosphatidylinositol-3-kinase-independent pathway. Diabetes Nov;46(11):1915-9.

McAllister RM, Hirai T, Musch TI. (1995) Contribution of endothelium-derived nitric oxide (EDNO) to the skeletal muscle blood flow response to exercise. Med Sci Sports Exerc. Aug;27(8):1145-51

Wilson, JR and Kapoor S. (1993) Contribution of endothelium-derived relaxing factor to exercise-induced vasodilation in humans. J. Appl. Physiol. 75:2740-2744.
12. Young ME, Leighton B.(1998) Evidence for altered sensitivity of the nitric oxide/cGMP signalling cascade in insulin-resistant skeletal muscle. Biochem J. Jan 1;329 ( Pt 1):73-9

Liu, HJ et al. [The effect of icariin and astragalosid I on the proliferation and differentiation of bone marrow stromal cells] Zhong Yao Cai. 2006 Oct;29(10):1062-5. Chinese.
PMID: 17326409 [PubMed - in process]

Ning, H et al. Effects of icariin on phosphodiesterase-5 activity in vitro and cyclic guanosine monophosphate level in cavernous smooth muscle cells. Urology. 2006 Dec;68(6):1350-4.
PMID: 17169663 [PubMed - indexed for MEDLINE]

Jiang, Z. et al Effects of icariin on hypothalamic-pituitary-adrenal axis action and cytokine levels in stressed Sprague-Dawley rats. Biol Pharm Bull. 2006 Dec;29(12):2399-403.
PMID: 17142971 [PubMed - indexed for MEDLINE]

Zhang, Z. et al The testosterone mimetic properties of icariin. Asian J Androl. 2006 Sep;8(5):601-5. Epub 2006 Jun 5.
PMID: 16751992 [PubMed - indexed for MEDLINE]

Liu, W. Effects of icariin on erectile function and expression of nitric oxide synthase isoforms in castrated rats. Asian J Androl. 2005 Dec;7(4):381-8.
PMID: 16281085 [PubMed - indexed for MEDLINE]

Xin, ZC Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities. Asian J Androl. 2003 Mar;5(1):15-8.
PMID: 12646997 [PubMed - indexed for MEDLINE]

Stanislavov, R. and Nikolova. 2003. Treatment of Erectile Dysfunction with Pycnogenol and L-arginine. Journal of Sex and Marital Therapy, 29(3): 207 – 213.

Alba-Roth J, Müller O, Schopohl J, von Werder K (1988). "Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion". J Clin Endocrinol Metab 67 (6): 1186-9.

Barbul A. Arginine: biochemistry, physiology, and therapeutic implications. JPEN. 1986; 10:227-238.
Adams MR, McCredie R, Jessup W, et al. Oral L-arginine improves endothelium-dependent dilatation and reduces monocyte adhesion to endothelial cells in young men with coronary artery disease. Atherosclerosis. 1997; 129:261-269.
Andres A, Morales JM, Praga M, et al. L-arginine reverses the antinatriuretic effect of cyclosporin in renal transplant patients. Nephrol Dial Transplant. 1997; 12:1437-1440.
Bode-Boger SM, Boger RH, Galland A, et al. L-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship. Br J Clin Pharmacol. 1998; 46:489-497.
Isidori A, Lo Monaco A, Cappa M. A study of growth hormone release in man after oral administration of amino acids. Current Med Res Opinion. 1981; 7:475-481.
Wascher TC, Posch K, Wallner S, et al. Vascular effects of L-arginine: anything beyond a substrate for the NO-synthase? Biochem Biophys Res Commun. 1997; 234:35-38.
Kijuma, I. et al Grape seed extract is an aromatase inhibitor and a suppressor of aromatase expression. Cancer Res. 2006 Jun 1;66(11):5960-7.
Sano, T. et al Anti-thrombotic effect of proanthocyanidin, a purified ingredient of grape seed. Thromb Res. 2005;115(1-2):115-21.
Eng, ET et al Suppression of estrogen biosynthesis by procyanidin dimers in red wine and grape seeds. Cancer Res. 2003 Dec 1;63(23):8516-22.
Fitzpatrick, DF et al Vasodilating procyanidins derived from grape seeds. Ann N Y Acad Sci. 2002 May;957:78-89.
Yu, H et al [Study of anti-atherosclerosic effect of grape seed extract and its mechanism] Wei Sheng Yan Jiu. 2002 Aug;31(4):263-5. Chinese.
Dell’Agli, H et al n vitro inhibition of human cGMP-specific phosphodiesterase-5 by polyphenols from red grapes.J Agric Food Chem. 2005 Mar 23;53(6):1960-5.
Sen, SK et al. Oxygen, oxidants, and antioxidants in wound healing: an emerging paradigm. Ann N Y Acad Sci. 2002 May;957:239-49. Review.

LeBail, JC et al Chalcones are potent inhibitors of aromatase and 17beta-hydroxysteroid dehydrogenase activities.Life Sci. 2001 Jan 5;68(7):751-61.

LeBail, JC et al Effects of phytoestrogens on aromatase, 3beta and 17beta-hydroxysteroid dehydrogenase activities and human breast cancer cells.
Life Sci. 2000 Feb 25;66(14):1281-91.

LeBail, JC et al Aromatase and 17beta-hydroxysteroid dehydrogenase inhibition by flavonoids. .Cancer Lett. 1998 Nov 13;133(1):101-6.

LeLain, L et al Inhibitors of human and rat testes microsomal 17beta-hydroxysteroid dehydrogenase (17beta-HSD) as potential agents for prostatic cancer.

Arayne, LS. Et al Grape fruit juice-drug interactions.Pak J Pharm Sci. 2005 Oct;18(4):45-57. Review.

Ho, PC et al. Inhibition of human CYP3A4 activity by grapefruit flavonoids, furanocoumarins and related compounds.
J Pharm Pharm Sci. 2001 Sep-Dec;4(3):217-27.

Fuhr, U Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man.
Br J Clin Pharmacol. 1993 Apr;35(4):431-6.

Jetter, A. et al Effects of grapefruit juice on the pharmacokinetics of sildenafil. Clin Pharmacol Ther. 2002 Jan;71(1):21-9.

Nehlig, A; Daval JL, Debry G (1992 May-Aug). "Caffeine and the central nervous system: Mechanisms of action, biochemical, metabolic, and psychostimulant effects". Brain Res Brain Res Rev 17 (2):

Bolton, Ph.D., Sanford; Gary Null, M.S. (1981). Caffeine: Psychology, Use, and Abuse. Orthomolecular Psychiatry 10 (3): 202-211.

Newton, R; Broughton LJ, Lind MJ, Morrison PJ, Rogers HJ, Bradbrook ID (1981). "Plasma and salivary pharmacokinetics of caffeine in man". European Journal of Clinical Pharmacology 21 (1): 45-52.

Ortweiler, W; Simon HU, Splinter FK, Peiker G, Siegert C, Traeger A. (1985). "Determination of caffeine and metamizole elimination in pregnancy and after delivery as an in vivo method for characterization of various cytochrome p-450 dependent biotransformation reactions". Biomed Biochim Acta. 44 (7-8): 1189-99

Graham T, Rush J, van Soeren M (1994). "Caffeine and exercise: metabolism and performance.". Can J Appl Physiol 19 (2): 111-38.

Fredholm B, Bättig K, Holmén J, Nehlig A, Zvartau E (1999). "Actions of caffeine in the brain with special reference to factors that contribute to its widespread use.". Pharmacol Rev 51 (1): 83-133

Verkhratsky A. (2005). "Physiology and Pathophysiology of the Calcium Store in the Endoplasmic Reticulum of Neurons". Physiol. Rev. 85 (1): 201-279.

Dews, P.B. (1984). Caffeine: Perspectives from Recent Research. Berlin: Springer-Valerag.

Ivy, JL; Costill DL, Fink WJ, Lower RW (1979 Spring). "Influence of caffeine and carbohydrate feedings on endurance performance". Med Sci Sports 11 (1): 6-11.

Graham, TE; Spriet, LL (1991 Dec). "Performance and metabolic responses to a high caffeine dose during prolonged exercise". J Appl Physiol 71 (6): 2292-8.

Trice, I; Haymes, EM (Mar 1995). "Effects of caffeine ingestion on exercise-induced changes during high-intensity, intermittent exercise". Int J Sport Nutr 5 (1): 37-44

Lieberman, HR, Corkin S, Spring BJ, Wurtman RJ, and Growden JH. The effects of dietary neurotransmitter precursors on human behavior. Am J Clin Nutr 42: 366-370, 1985.

Banderet, LE, and Lieberman HR. Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Brain Res Bull 22: 759-762, 1989.

Gelenberg AJ, Gibson CJ, Wojcik JD. Neurotransmitter precursors for the treatment of depression. Psychopharmacol Bull 1982;18:7-18.

Wurtman, RJ, and Lewis MC. Exercise, plasma composition and neurotransmission. In: Advances in Nutrition and Top Sport, edited by Brouns F.. Basel: Karger, 1991, vol. 32, p. 94-109.

Romanowski, W, and Grabiec S. The role of serotonin in the mechanism of central fatigue. Acta Physiol Pol 25: 127-134, 1974.

David L. Nelson, Michael M. Cox (2005). Lehninger Principles of Biochemistry. W.H. Freeman and Company, 435–439.

Sir Ghillean Prance, Mark Nesbitt (2004). The Cultural History of Plants. New York: Routledge.

William Gervase Clarence-Smith (2000). Cocoa and Chocolate, 1765-1914. London: Routledge, 10, 31.

Usmani O; Belvisi M, Patel H, Crispino N, Birrell M, Korbonits M, Korbonits D, Barnes P (2005). "Theobromine inhibits sensory nerve activation and cough.". FASEB J 19 (2): 231-3.

Serafini, M., Bugianesi, R., Maiani, G., Valtuena, S., De Santis, S. & Crozier, A. 2003. Plasma antioxidants from chocolate. Nature 424, 1013.

Kondo K, Hirano R, Matsumoto A, Igarashi O, Itakura H., Inhibition of LDL oxidation by cocoa, Lancet, November 1996; 348(2):1514.

MATISSEK R., Evaluation of xanthine derivatives in chocolate: nutritional and chemical aspects.

Smit HJ, Gaffan EA, Rogers PJ. (2004) Methylxanthines are the psycho-pharmacologically active constituents of chocolate. Psychopharmacology Nov;176(3-4):412-9.

Bitter Chocolate: Investigating the Dark Side of the World's Most Seductive Sweet, by Carol Off, Random House, 2006.

Chocolate, by the editors of Fine Cooking magazine, 2006.

The True History of Chocolate, by Sophie D. Coe & Michael D. Coe, Thames & Hudson, 1996.

Naked Chocolate, by David Wolfe and Shazzie, Rawcreation, 2005.

The Great Book of Chocolate, by David Lebovitz, Ten Speed Press, 2004.

The Chocolate Connoisseur, by Chloe Doutre-Roussel, Piatkus, 2005.

Green & Black's Chocolate Recipes, by Kyle Cathie Limited, 2003.

 

[jasonschaffin]

The testosterone mimetic properties of icariin.Zhang ZB, Yang QT.
Department of Urology, Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, China. [email protected]

AIM: To evaluate the testosterone mimetic properties of icariin. METHODS: Forty-eight healthy male Sprague-Dawley rats at the age of 15 months were randomly divided into four groups with 12 rats each: the control group (C), the model group (M), the icariin group (ICA) and the testosterone group (T). The reproductive system was damaged by cyclophosphamide (intraperitoneal injection, 20 mg/kg x day) for 5 consecutive days for groups M, ICA and T, at the sixth day, ICA (gastric gavage, 200 mg/kg x day) for the ICA group and sterandryl (subcutaneous injection, 5 mg/rat . day) for the T group for 7 consecutive days, respectively. The levels of serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), serum bone Gla-protein (BGP) and tartrate-resistant acid phosphatase activity in serum (StrACP) were determined. The histological changes of the testis and the penis were observed by microscope with hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase biotin-dUTP-X nick end labeling (TUNEL), respectively. RESULTS: (1) Icariin improved the condition of reproductive organs and increased the circulating levels of testosterone. (2) Icariin treatment also improved the steady-state serum BGP and might have promoted bone formation. At the same time, it decreased the serum levels of StrACP and might have reduced the bone resorption. (3) Icarrin suppressed the extent of apoptosis of penile cavernosal smooth muscle cells. CONCLUSION: Icariin has testosterone mimetic properties and has therapeutic potential in the management of hypoandrogenism.

PMID: 16751992 [PubMed - indexed for MEDLINE]

If my reproductive system is ever sabotaged AN will be getting all my money

 

[TheMyth]

me too!

 

[xjsynx]

Wow my computer has slowed down. Where are we at??? By now this could be 2500......

We have about 1k more to go, so come back in a hour, and we should be close

 

[powerhouse21]

AIM: Obesity is generally linked to complications in lipid metabolism and oxidative stress. The aim of this study was to compare the effect of a proprietary extract of Cissus quadrangularis (CQR-300) to that of a proprietary formulation containing CQR-300 (CORE) on weight, blood lipids, and oxidative stress in overweight and obese people. METHODS: The first part of the study investigated the in vitro antioxidant properties of CQR-300 and CORE using 3 different methods, while the second part of the study was a double-blind placebo controlled design, involving initially 168 overweight and obese persons (38.7% males; 61.3% females; ages 19-54), of whom 153 completed the study. All participants received two daily doses of CQR-300, CORE, or placebo and were encouraged to maintain their normal levels of physical activity. Anthropometric measurements and blood sampling were done at the beginning and end of the study period. RESULTS: CQR-300 as well as CORE exhibited antioxidant properties in vitro. They also acted as in vivo antioxidants, bringing about significant (p < 0.001) reductions in plasma TBARS and carbonyls. Both CQR-300 and CORE also brought about significant reductions in weight, body fat, total cholesterol, LDL-cholesterol, triglycerides, and fasting blood glucose levels over the respective study periods. These changes were accompanied by a significant increase in HDL-cholesterol levels, plasma 5-HT, and creatinine. CONCLUSION: CQR-300 (300 mg daily) and CORE (1028 mg daily) brought about significant reductions in weight and blood glucose levels, while decreasing serum lipids thus improving cardiovascular risk factors. The increase in plasma 5-HT and creatinine for both groups hypothesizes a mechanism of controlling appetite and promoting the increase of lean muscle mass by Cissus quadrangularis, thereby supporting the clinical data for weight loss and improving cardiovascular health.

PMID: 17274828 [PubMed - indexed for MEDLINE]

 

[thewilman]

Hello...just a whore post

 

[TheMyth]

We have about 1k more to go, so come back in a hour, and we should be close

your evil. I like your style

 

[thewilman]

Sequestration of cAMP response element-binding proteins by transcription factor decoys causes collateral elaboration of regenerating Aplysia motor neuron axons

Pramod K. Dash*, Lian-Ming Tian, and Anthony N. Moore
Department of Neurobiology and Anatomy, University of Texas-Houston Health Science Center, Houston, TX 77225

Communicated by Eric R. Kandel, Columbia University College of Physicians, New York, NY, May 13, 1998 (received for review August 26, 1997)

Axonal injury increases intracellular Ca2+ and cAMP and has been shown to induce gene expression, which is thought to be a key event for regeneration. Increases in intracellular Ca2+ and/or cAMP can alter gene expression via activation of a family of transcription factors that bind to and modulate the expression of CRE (Ca2+/cAMP response element) sequence-containing genes. We have used Aplysia motor neurons to examine the role of CRE-binding proteins in axonal regeneration after injury. We report that axonal injury increases the binding of proteins to a CRE sequence-containing probe. In addition, Western blot analysis revealed that the level of ApCREB2, a CRE sequence-binding repressor, was enhanced as a result of axonal injury. The sequestration of CRE-binding proteins by microinjection of CRE sequence-containing plasmids enhanced axon collateral formation (both number and length) as compared with control plasmid injections. These findings show that Ca2+/cAMP-mediated gene expression via CRE-binding transcription factors participates in the regeneration of motor neuron axons.

 

[buffhunk29]

These are great guys!! :frustrate :frustrate I cant keep caught up!!!!

 

[thewilman]

Did you hit it Myth???

 

[TheMyth]

he who has the most post by 2500 shoudl win something, or the top 3!

 

[Manu20]

We have about 1k more to go, so come back in a hour, and we should be close

Hhaha:rofl:

 

[marshbomb]

whore

 

[thewilman]

Top 5

 

[Manu20]

I say the top 3

 

[TheMyth]

Icarin and direct corrolation to testosterone, how could anyone get better than that?

 

[thewilman]

That's I roll...ho fo' shizzle, my nizzle

 

[powerhouse21]

Aim

Once considered a problem of developed countries, obesity and obesity-related complications (such as metabolic syndrome) are rapidly spreading around the globe. The purpose of the present study was to investigate the use of a Cissus quadrangularis formulation in the management of metabolic syndrome, particularly weight loss and central obesity.

Methods

The study was a randomized, double-blind, placebo-controlled design involving 123 overweight and obese persons (47.2% male; 52.8% female; ages 19–50). The 92 obese (BMI >30) participants were randomized into three groups; placebo, formulation/no diet, and formulation/diet (2100–2200 calories/day). The 31 overweight participants (BMI = 25–29) formed a fourth (no diet) treatment group. All participants received two daily doses of the formulation or placebo and remained on a normal or calorie-controlled diet for 8 weeks.

Results

At the end of the trial period, statistically significant net reductions in weight and central obesity, as well as in fasting blood glucose, total cholesterol, LDL-cholesterol, triglycerides, and C-reactive protein were observed in participants who received the formulation, regardless of diet.

Conclusion

Cissus quadrangularis formulation appears to be useful in the management of weight loss and metabolic syndrome.



Although still defined in diverse terms, metabolic syndrome is a common disorder arising as a result of the increased prevalence of obesity throughout the world [1]. Metabolic syndrome, also known as insulin resistance syndrome and Syndrome X, has 3 main potential etiologic categories: obesity and disorders of adipose tissue; insulin resistance; and a constellation of independent factors (e.g., molecules of hepatic, vascular, and immunologic origin) that mediate specific components of the metabolic syndrome [2].

In the United States, over 60% of the adult population is now overweight or obese [3] and 47 million people have metabolic syndrome, which will soon overtake cigarette smoking as the number one risk factor for heart disease [4,5]. Globally, the disorder has become a major public health challenge. (In Cameroon, approximately 25% of the population is now considered obese.)

Since it has been determined that abdominal fat poses a greater health risk than fat stored in the lower half of the body [11], waist circumference has become a major factor in body-fat assessment [12,13]. A large waist circumference (>88 cm in women and 102 cm in men) is associated with an increased risk for type 2 diabetes, dyslipidemia, hypertension and CVD in patients with a body mass index (BMI) 25–34 [8]. Moreover, for obese patients with metabolic complications, changes in waist circumference are useful predictors of CVD risk factors [13,14]. Thus, in addition to weight (kg), fat (%) and BMI, changes in waist measurement (cm) was one of the primary endpoints in this study.

Because of its links with obesity, it is difficult to identify a unique role for insulin resistance in patients with metabolic syndrome. Although insulin resistance generally rises with increasing body fat content, one finds a broad range of insulin sensitivities at all levels [6]. Although most people with BMI ≥ 30 have postprandial hyperinsulinemia and relatively low insulin sensitivity, there is variation in insulin sensitivity even within the obese population [6,7]. Overweight persons (BMI 25–29) also exhibit a spectrum of insulin sensitivities, which seems to suggest an inherited component to insulin resistance.

The increased chance of CVD and type 2 diabetes require therapeutic consideration for the vast numbers of overweight/obese persons now at high risk for these diseases [1]. The current International Diabetes Foundation recommendations for preventing or delaying the development of diabetes include both primary and secondary interventions. The former emphasizes lifestyle changes such as calorie restriction and increased physical activity, and the latter (for people at high risk for CVD) uses pharmacological agents [15] that specifically target individual components of metabolic syndrome [15-20]. When used by obese patients in combination with dietary regimes, these agents can produce some weight loss and some reversal of accompanying complications. The role of pharmacotherapy, however, has been compromised by safety issues leading to the withdrawal of some medications from the market [21,22]. The combination of safety concerns and high costs have forced many populations to continue to rely on traditional healing methods using the indigenous pharmacopoeia.

Cissus quadrangularis, for example, is used by common folk in India to hasten the fracture healing process [23-28]. In Cameroon, the whole plant is used in oral re-hydration, while in Africa and Asia the leaf, stem, and root extracts are utilized in the management of various ailments [29-33]. Phytochemical analyses of Cissus quadrangularis reveal a high content of ascorbic acid, carotene, phytosterol substances and calcium [34,35], and there have also been reports of the presence of β-sitosterol, δ-amyrin and δ-amyrone [36]. All these components have potentially different metabolic and physiologic effects [37,38]. Although researchers have investigated several uses of Cissus quadrangularis, its potential application against metabolic syndrome has not yet been reported.

Several other dietary supplements (green tea, soy, chromium, selenium, B-vitamins) have only marginal effects in treating obesity but they address other metabolic syndrome symptoms and thus were included in the formulation. Green tea (Camellia sinensis) extracts contain high concentrations of epigallocatchin gallate and may work with other chemicals to increase levels of fat oxidation and thermogenesis [39,40]. Numerous studies on soy (Glycine max) protein show it is associated with a reduction in serum cholesterol and triglyceride levels and suggest it may protect against the development of coronary heart disease [41]. Chromium helps insulin metabolize fat, turn protein into muscle, and convert sugar into energy [42]; thus, chromium supplementation can favorably influence glucose/insulin metabolism, reduce levels of harmful LDL cholesterol, and increase HDL cholesterol [43]. Both humans and animals require selenium for the optimal functioning of the selenoproteins, which reduce the risk of CVD by decreasing lipid peroxidation and influencing the metabolism of the cell-signaling prostaglandins [44]. Lastly, B-vitamins (B-6, B-12 and folic acid) regulate energy metabolism [45], which plays a critical role in obesity management; they also maintain lower homocysteine levels [46], which are closely associated with cardiovascular health benefits.

The purpose of the present study was to examine the efficacy of a Cissus quadrangularis formulation (Cylaris™) containing the above agents in the management of obesity and metabolic syndrome.

Table 1
Baseline (week 0) characteristics of study participants



The study was a prospective, randomized, double blind, placebo-controlled design conducted by the Laboratory for Nutrition and Nutritional Biochemistry at the University of Yaoundé I, Cameroon, Africa. The Cameroon National Ethics Committee approved the protocol. Applicants were advised of the study's purpose, nature, and potential risks, and all gave their written informed consent before participation. The study was conducted in accordance with the Helsinki Declaration (1983 version).

Participants

Eligibility criteria included meeting the minimal standards for overweight (i.e., a BMI >25 and a waist circumference >85.5 cm.) and a willingness to participate in an 8-week trial. Exclusion criteria (confirmed via an initial interview and physical examination) included pregnancy/lactatation, use of any form of weight-reducing medication, participation in intense exercise programs, medical conditions known to affect serum lipids, and a history of drug or alcohol abuse. For the 123 eligible participants, BMIs ranged from 25.5 to 45.6; waist circumferences from 85.5 cm to 125 cm; and weight from 62.6 kg to 142 kg. (See Table 1 for other baseline characteristics.) Ninety-two persons qualified as obese (BMI >30), and 31 as overweight (BMI = 25–29). The age range was 19 to 50; males = 47.2%; females = 52.8%.

Intervention

The 92 obese persons were randomized to a placebo or one of two treatment groups; the 31 overweight persons formed a fourth group. One obese treatment group was prescribed a calorie-controlled (2100–2200 calories/day) diet; none of the groups was prescribed an exercise regimen. Apart from the expected lower anthropomorphic and serological characteristics of the overweight group, none of the baseline differences between the groups was clinically significant.

The overweight group was used for general comparison with the obese groups, thus the results were expressed in percentages rather than absolute values. The formulation/diet group was used to determine if a short-term, calorie-controlled diet would significantly increase anthropomorphic and serological outcomes compared to the formulation/non-diet group.

Materials

The Cissus quadrangularis formula, Cylaris™, contains a Cissus quadrangularis extract (supplied by Gateway Health Alliances, Inc, Fairfield, California, USA), standardized to contain a minimum of 2.5% phytosterols and a minimum of 15% soluble plant fiber. The formula also consists of a soy albumin extract (supplied by Gateway Health Alliances, Inc, Fairfield, California, USA); a green tea extract standardized to 22% EGCG and 40% caffeine; niacin bound chromium (ChromeMate™ supplied by InterHealth Nutraceuticals, Inc, Benicia, California, USA); selenium standardized to 0.5% l-Selenomethionine; vitamin B6 (as pyridoxine hydrochloride); vitamin B12 (as cyanocobalamin); and folic acid (supplied by Protein Research, Inc, Livermore, California, USA). All active and placebo capsules were manufactured and bottled by Protein Research, Inc.

Participants received two daily doses (514 mg each) of the Cissus formulation or placebo for 8 weeks. Each capsule was taken with 8–12 oz of water immediately prior to meals (preferably breakfast and dinner). In keeping with the experimental design, the capsules were identical in shape, color and appearance, and neither the participants nor researchers knew which capsule was administered. Side effects were noted on each visit.

Body weight and percentage of body fat were determined in the 12-hour- fasted participants with a Tanita™ BC-418 Segmental Body Composition Analyzer/Scale that uses bio-electrical impedance analysis for body composition analysis. Height was measured with a Harpended™ stadiometer, which measures the length of curved line staffage to the nearest 0.5 cm.

Blood (5 ml) samples were collected after an overnight fast at the start and end of the 8 week trial period. The blood was collected into vacutainer tubes, and the serum was separated (via centrifugation) and stored (200 μl aliquots) at -20°C until needed for analyses. The concentrations of total cholesterol, triacylglycerol, HDL-cholesterol, LDL-cholesterol, and glucose were measured using commercial diagnostic kits (cholesterol Infinity, triglyceride Infinity, EZ HDL™ cholesterol, EZ LDL™ cholesterol, Glucose Trinder) from SIGMA Diagnostics. C-reactive protein was measured using an ELISA method (BioCheck™ hsC-Reactive Protein ELISA kit, Foster City, CA USA).

Statistical analyses

The data for each parameter was summarized via n, mean, and standard deviation for Week 0 and Week 8 and the percent difference (Week 8 – Week 0/week 0). The percent change from baseline was tested for differences using analysis of variance. Contrasts were used for testing pair-wise differences.



Tables

Table 2
Effectiveness of Cissus quadrangularis formulation on anthropomorphic characteristics: Percent difference in means from Week 0 to Week 8


Table 3
Effectiveness of Cissus quadrangularis formulation on serological characteristics: Percent difference in means from Week 0 to Week 8



Anthropomorphic characteristics

Waist circumference is an extremely important determinant in the diagnosis of obesity and metabolic syndrome. As shown in Table 2, the significant reduction in this variable across all treatment groups was paralleled by significant reductions in weight and BMI for the two obese treatment groups.

To translate the percentage loss over 8 weeks into actual measurements, the mean change in weight (kg) for the 3 obese (BMI >30) groups was 95.6 to 93.3 (placebo); 95.8 to 89.2 (formulation/no diet); and 95.3 to 87.2 (formulation/diet). The mean change for the overweight (BMI 25 – 29) group was 76.3 to 72.6 kg (formulation/no diet).

Thus, over a period of 8 weeks, the placebo group lost 2.3 kg; the overweight group lost 3.7 kg and the two obese groups lost 6.6 kg and 8.1 kg, respectively.

Serological characteristics

As shown in Table 3, there was a significant improvement in virtually every measurement for the three treatment groups vs. placebo. Eight-week use of the Cissus formulation significantly reduced plasma total cholesterol and LDL cholesterol in the three treatment groups and increased HDL cholesterol in the two obese groups by 50.5 % and 43.0% The increase in the concentration of circulating HDL-cholesterol in the three treatment groups shows a large reduction in the ratio of total cholesterol to HDL-cholesterol ratios as well as LDL-cholesterol to HDL-cholesterol ratios. All three treatment groups also demonstrated a significant decrease in triglycerides, C- reactive protein, and fasting blood glucose levels.

To translate the percentage loss over 8 weeks into actual measurements, the mean change in Total cholesterol (mg/dl) for the 3 obese (BMI >30) groups was 160.8 to 155.8 (placebo); 159.1 to 116.1 (formulation/no diet); and 171.0 to 126.5 (formulation/diet. The mean change for the overweight (BMI 25 – 29) group was 152.6 to 123.9.

Thus, over a period of 8 weeks, Total cholesterol declined 5.0 mg/dl for the placebo group; 28.7 mg/dl for the overweight group; and 43.0 mg/dl and 44.5 mg/dl for the two obese groups.

Adverse events

Adverse events with an incidence >5 included headache (12), gas (11), dry mouth (7), diarrhea (7), and insomnia (6). Since the incidence of all reported side effects was always higher in the placebo group than in any of the treatment groups, it is probably safe to conclude that the Cissus formulation had few, if any, negative side effects.





Our results support the hypothesis that the use of a Cissus quadrangularis formulation has efficacy in the management of weight loss and metabolic syndrome, particularly for central obesity. The use of the formulation (which also contains green tea, soy, chromium, selenium, and B-vitamins) over an 8-week period brought about a significant reduction in many of the anthropomorphic measures: weight, % body fat, BMI and, especially, waist circumference of obese and overweight patients, regardless of calorie-controlled diet (see Table 2).

Waist circumference is a particularly important factor in weight and body-fat assessment since fat distribution, rather than total body fat, is currently the key indicator of weight-related health problems. The dramatic reduction in waist circumference that accompanied the 8-week use of the Cissus quadrangularis formulation for both the diet and no diet groups is particularly important because waist circumference is a major criterion in the diagnosis of obesity and metabolic syndrome [2] and is generally considered a surrogate measure for abdominal visceral fat [12,13]. Moreover, not only does the risk of type 2 diabetes increase with the degree and duration of obesity it, too, is associated with central obesity [6,7].

The reduction in the primary anthropomorphic measurements can be attributed to the synergistic effects of Cylaris™, Glycine max extract, Camellia sinensis extract and ChromeMate™ ingredients in the formula, all of which have previously been shown to affect weight loss activity [32,35,39,41,42].

Cissus quadrangularis phytosterols and fiber extracts have been shown to have anti-lipase, and anorexiant properties that reduce the absorption of dietary fats and enhance satiation by increasing serum serotonin levels [47]. In 1999, Swiss researchers found that men who were given a combination of caffeine and green tea catechin extract burned more calories than those given only caffeine or a placebo. It was postulated that the catechins and caffeine combination sustained the effect of norepinephrine on thermogenesis longer than caffeine alone [39]. Numerous studies on chromium supplementation have also demonstrated weight loss in overweight and obese people [48,49]. Grant et al. (1997) reported that chromium with a moderate diet and exercise regimen influences weight loss and body composition [50].

The modification of certain serological characteristics (blood parameters) (see Table 3) by Cissus formulation may or may not be dependent on weight loss. Only the reduction of LDL-cholesterol followed a similar pattern to weight loss over the 8-week trial period. The circulating concentration of total cholesterol and triglycerides, though reduced by the formulation, could be independent of weight loss since all treatment groups (diet/no diet) showed significant cholesterol reduction. The increase in the concentration of circulating HDL-cholesterol in the treatment groups shows a reduction in the ratio of total cholesterol to HDL-cholesterol as well as LDL-cholesterol to HDL-cholesterol. This reduced ratio also implies a reduction in the risk of atherosclerosis and coronary heart disease [51].

Although the exact mechanisms for the formulation's cholesterol-lowering ability needs further study, the various ingredients might interact in a manner similar to statins, fibrates, probucol, nicotinic acid or cholesterol absorption inhibitors. Green tea catechins have a number of antioxidant activities related to cholesterol regulation. For example, the inhibition of the oxidation of low-density lipoproteins and the antithrombotic activity both aid in lowering total cholesterol/LDL-cholesterol and increasing HDL-cholesterol levels [52,53]. Also, the phytochemical constituents (phytosterols, β-sitosterol, δ-amyrin and δ-amyrone), in Cissus quadrangularis may have activity similar to other plant sterols. The molecular structure of phytosterols, for example, is practically identical to that of cholesterol.

Recent studies show that metabolic syndrome causes an inflammatory process in the blood vessels that leads to arteriosclerosis. This inflammatory process can be gauged by blood levels of C-reactive protein [54] and, as our results showed, Cissus formulation significantly reduced the circulating concentrations of CRP thereby inhibiting the inflammatory process and possibly reducing individual components of metabolic syndrome [54]. In metabolic syndrome, the body becomes resistant to insulin, and high levels of glucose remain trapped in the blood. In response, the pancreas produces more insulin. The extra insulin temporarily allows glucose to enter the cells and also increases cholesterol and triglyceride levels.

In sum, Cissus formulation administered twice daily to obese and overweight persons with symptoms of metabolic syndrome results in both weight reduction and an improvement in the symptoms associated with metabolic syndrome. It has also shown efficacy in the control and lowering of triglyceride concentrations, total cholesterol, LDL-cholesterol, and fasting blood glucose. The formulation may also have applications in other metabolic diseases, such as diabetes mellitus.

 

[TheMyth]

send my bottle of Lipo to.....

 

[jasonschaffin]

Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo
Sue C. Bodine1, Trevor N. Stitt1, Michael Gonzalez1, William O. Kline1, Gretchen L. Stover1, Roy Bauerlein1, Elizabeth Zlotchenko1, Angus Scrimgeour2, John C. Lawrence2, David J. Glass1 & George D. Yancopoulos1

1 Regeneron Pharmaceuticals, Inc. 777 Old Saw Mill River Road, Tarrytown, New York 10591-6707, USA

2 Departments of Pharmacology and Medicine, University of Virginia, Charlottesville, Virginia, 22908, USA
Correspondence should be addressed to Sue C. Bodine [email protected] or George D. Yancopoulos [email protected]ublished 10 October 2001
Skeletal muscles adapt to changes in their workload by regulating fibre size by unknown mechanisms1, 2. The roles of two signalling pathways implicated in muscle hypertrophy on the basis of findings in vitro 3, 4, 5, 6, Akt/mTOR (mammalian target of rapamycin) and calcineurin/NFAT (nuclear factor of activated T cells), were investigated in several models of skeletal muscle hypertrophy and atrophy in vivo. The Akt/mTOR pathway was upregulated during hypertrophy and downregulated during muscle atrophy. Furthermore, rapamycin, a selective blocker of mTOR7, blocked hypertrophy in all models tested, without causing atrophy in control muscles. In contrast, the calcineurin pathway was not activated during hypertrophy in vivo, and inhibitors of calcineurin, cyclosporin A and FK506 did not blunt hypertrophy. Finally, genetic activation of the Akt/mTOR pathway was sufficient to cause hypertrophy and prevent atrophy in vivo, whereas genetic blockade of this pathway blocked hypertrophy in vivo. We conclude that the activation of the Akt/mTOR pathway and its downstream targets, p70S6K and PHAS-1/4E-BP1, is requisitely involved in regulating skeletal muscle fibre size, and that activation of the Akt/mTOR pathway can oppose muscle atrophy induced by disuse.

 

[Manu20]

Come on guys almost there

 

[thewilman]

I say the top 3

Go back to work!!! :whip:

 

[rafter]

whoring only gets your STDs.

 

[powerhouse21]

he who has the most post by 2500 shoudl win something, or the top 3!

YES I AGREE

 

[xjsynx]

Hello...just a whore post

:welcome:

 

[TheMyth]

what number are we on?

 

[Manu20]

Damn so close to the info being released

 

[marshbomb]

less than 100

 

[powerhouse21]

I think having to endure hundreds of mouse clicks in the past 24 hours and the onset of carpal tunnel is worth something?

 

[thewilman]

whoring only gets your STDs.

Pennicillin

 

[Manu20]

Go back to work!!! :whip:

Haha after we hit 2500

 

[TheMyth]

repn is always good for a post count. That is one RIPPED MOFO, man, Imagine when he starts taking RPN, it will be unfair to the rest of the people!

 

[marshbomb]

keep it goin

 

[Manu20]

whoring only gets your STDs.

Its a good thing i work in a doctors office then

 

[rafter]

Pennicillin

true, it gets you a good supply of that too.

 

[TheMyth]

Must truck on, pick a winner for the study already! Jeez! lol

 

[jasonschaffin]

Skeletal Muscle Hypertrophy

Work overload

Chronic disease, disuse and aging are all causes of muscle atrophy. This fact directly impacts an individual�s ability to maintain an independent life-style. In contrast, stretching and work overload of skeletal muscle induces hypertrophy of skeletal muscle and myotubes in vivo and in vitro, respectively. Compensatory growth in response to an imposed load is an important and well-known biological adaptation of skeletal muscle. However, little is known about the systemic changes in hypertrophying muscle at the molecular level.

In 1967, A.L. Goldberg made the seminal observation that if workload on a muscle is increased suddenly by tenotomy of a synergistic muscle; its wet and dry weight may increase by 30-50% within 6-d. Hypertrophic growth was evident within 24-h and reached maximum levels by 5-d. Furthermore, the rate and extent of skeletal muscle hypertrophy was similar in hypophysectomized and normal animals. On the basis of these studies, it was concluded that increased workload stimulated skeletal muscle growth and that pituitary growth hormone, which is required for normal muscle growth, and thyroid hormones were not essential for skeletal muscle hypertrophy to occur (Goldberg, 1967). As a direct result, many researchers have investigated the biological mechanisms responsible for work overload induced skeletal muscle hypertrophy. This was followed by the additional conclusions that skeletal muscle hypertrophy was independent of insulin, which is required for normal postnatal growth of skeletal muscle (Goldberg, 1968). Skeletal muscle hypertrophy is indistinguishable in male and female rats (Mackova and Hnik, 1972) and it can occur in fasting animals (Goldberg, 1971). In addition, skeletal muscle hypertrophy results in increased amino acid transport (Arvil, 1967), increased satellite cell proliferation (Schiaffino et. al., 1972), increased protein synthesis, decreased protein degradation (Goldberg, 1969), and involves fiber-type switching (Booth and Baldwin, 1996). Whether induced by stretch-overload or stimulation, hypertrophy is accompanied by an increase in total RNA content, which was evident within six hours after tenotomy of a synergistic muscle (Goldberg, 1971). Maximal RNA synthesis was observed three days after the initiation of work overload. De novo synthesis of RNA in response to work overload appears to play an essential role, because treatment of tenotomized animals with actinomycin D, an inhibitor of DNA-dependent RNA synthesis, prevented skeletal muscle hypertrophy (Goldberg and Goodman, 1969), which may be a result of the associated increases in RNA polymerase activities and the rate of RNA synthesis (Carson, 1997).

The hypertrophic signal is intrinsic, as it is primarily the exercised muscle that undergoes hypertrophy and not all the muscles of the limb or the whole body. It appears the hypertrophying skeletal muscle produces autocrine growth factors and that the morphological basis of the mechanism involves the cytoskeleton and the extracellular matrix. The stretching of skeletal muscle results in the activation of intracellular signaling molecules. While there is a body of knowledge that suggests integrins and autocrine growth factors are involved in mechanotransduction (i.e., conversion of a mechanical force into a chemical signal), it is still unclear what the global changes in gene expression pattern are and what intracellular signaling pathways are involved (Figure 1).
he cellular mechanisms contributing to an increase in skeletal muscle mass, a desired output of the livestock industry, include increased cell size as a result of increased muscle protein accretion, satellite cell proliferation and subsequent fusion of the satellite cells to existing myofibers. Recently, the targeted inactivation of myostatin demonstrated the utility of model organisms in defining a genetic mechanism controlling skeletal muscle growth in livestock (McPherron et al., 1997; McPherron and Lee, 1997; Grobet et al., 1997; Kambadur et al., 1997). There is a body of knowledge that suggests that myostatin inhibits skeletal muscle growth (McPherron et al., 1997; Zhu et al., 2000). In addition, myostatin expression in skeletal muscle increases during muscle atrophy and decreases during the regeneration of skeletal muscle (Carlson et al., 1999; Wehling et al., 2000; Sakuma et al., 2000; Lalani et al., 2000; Gonzalez-Cadavid et al., 1998; Kirk et al., 2000). This correlation suggests that myostatin expression is inversely correlated with the rate of skeletal muscle growth. In contrast to Transforming Growth Factor-b (TGF-b ), which in the presence of serum causes myoblast to become post mitotic (Olson et al., 1986), myostatin inhibits myoblast proliferation and protein synthesis in an autocrine/paracrine manner (Thomas et al.; 2000; Taylor et al.; 2001). However, it is still unclear at a molecular level how myostatin and TGF-b differ in this respect, as they are both members of the TGF super family. Lack of such knowledge is a critical problem, because, until this information becomes available, it will not be possible to develop and effectively evaluate new genetic or therapeutic strategies to specifically inhibit myostatin activity and thereby enhance skeletal muscle growth. Furthermore, myostatin is known to interact with other genes (Casas et al., 2000) to control growth and carcass traits in cattle. However, these interacting genes have not been identified. Thus, we need to define the molecular mechanisms repressing skeletal muscle growth at the molecular level to insure that improvements in the efficiency of lean tissue deposition are made in the future.
Ractopamine

There is an increase in skeletal muscle mass and a decrease in body fat in livestock in response to the oral administration of several b -adrenergic agonists (b -AA; for review see Bergen and Merkel, 1991; Mersmann, 1998). While these effects are beneficial to the livestock industry, administration of b -AA can also result in cardiac muscle hypertrophy, which is undesirable. The mode of action of b -AA on gene expression in adipose tissue and cardiac muscle are well documented. In contrast, very little is known about the b -AA activated intracellular signaling pathways in skeletal muscle. Identification of a skeletal muscle specific response to b -AA that was beneficial to lean tissue deposition and not detrimental to cardiac muscle would provide information that is necessary for the development of future growth promotants, which may also have human applications as well.

In cell culture, b -AA increase protein accumulation in skeletal myotubes (Anderson et. al., 1990) and decrease lipid accumulation in adipogenic cells. In growing pigs, oral administration of b -AA results in parallel increases in skeletal muscle mass, protein and RNA content, increased RNA/DNA and protein DNA ratios (Bergen et. al., 1989), increased protein synthesis and decreased protein degradation (Kim and Sainz, 1992), all of which are indicative of skeletal muscle hypertrophy.

Upon binding of an bJM Reecy, Figure 4, Intracellular Signaling Pathways -AA to the b -adrenergic receptor on adipose cells, the Gs protein ® adenylyl cyclase ® cAMP ® PKA ® CREB intracellular signaling pathway is activated. Thereby regulating adipose-specific gene expression. However, in cardiac muscle, the cAMP ® PKA ® CREB portion of this pathway is incapable of regulating skeletal a -actin gene expression, which is up-regulated in response to b -AA administration (Bishopric et. al., 1992). It has been suggested that b -AA activated intracellular signaling may involve Ca2+ release, MAPK or PI3-kinase activation (Bishopric et. al., 1992; Izevbigie and Bergen, 2000; Morisco et. al., 2000). Although the work cited previously provides convincing evidence that administration of b -AA can alter gene expression, the precise mechanism by which this occurs in skeletal muscle is largely unknown. In addition, because a number of intracellular signaling pathways are activated by b -AA, it is likely that altered intracellular signaling regulates skeletal a -actin gene expression. However, this cannot be established without determining the molecular mechanism whereby b -AA alter the level of gene expression during skeletal muscle hypertrophy. This will require that the specific changes in promoter activity are determined, so the molecular mechanisms of skeletal muscle hypertrophy can be resolved.

Significance

It has been estimated that the world population will increase from 6 billion to 8 billion by 2025 (Dyson, 2000). This fact will place a great strain on the world�s food supply. Thus, there is a pressing need to improve the efficiency of food production.

In approximately 30 years, more than 70 million Americans will be over 65 years old, and the 85+ group will be the fastest growing segment of the population. By 60 � 70 years of age, muscle mass of human beings decreases by 25 � 30% (Edstrom and Larsson, 1987). Falling is a serious problem for the elderly, especially for those 85 years and older. Approximately 30% of 65+ year olds sustain a fall, with about half of them falling multiple times. Approximately 10-15% of the time a fall results in serious injuries (Province et. al., 1995) and many of these falls contribute significantly to morbidity and mortality (Robbins et. al., 1989). Buchner et al. (1997) reported that exercise designed to maintain skeletal muscle mass delayed the onset of the first fall, and sped the recovery from fall-related injuries. There are numerous conditions that either result in skeletal muscle atrophy or are the consequence of skeletal muscle atrophy. An example for the latter case is bed-ridden elderly in nursing homes whom develop decubitus ulcers. The cost of skeletal muscle atrophy � medical and emotional � is enormous; not to mention the impact that it has on relatives. In addition, the enlargement of skeletal muscles is of interest to many Americans attempting to improve their athletic ability or physical appearance.

 

[powerhouse21]

just more senseless whoring