Our webshop gets facelift & updates – www.superhumangear.com

We would like to announce that our webshop is getting a major update. New design, bug fixes (payment gateways), etc.

Currently accepted payment methods: Google checkout, Bank wire (EU), ACH (USA)  Paypal (in some cases only!) – future implementations will include Alertpay, Dotpay and Moneybookers.

You can still order via email at superhumangear@gmail.com if you wish to use any other payment method!

www.superhumangear.com

SOME OF OUR SPECIAL DEALS:

NEW ARRIVAL: TB500 thymosin beta-4 recovery protein with performance enhancing properties $60 /5 mg

NEW ARRIVAL: IGF-1 lr3 1000 mcg $60

CICACTRICURE anti-wrinkle cream with peptides: $39

LIPOSTABIL – BUY HERE

AICAR 1 g SALE – BUY HERE

HYACETAM hyaluronic acid 5 ml 5%

ACTOVEGIN 5×5 ml SALE

CEREBROLYSIN 10 ml ampoules

SERMORELIN (GEREF) 2 mg $35

WE MADE THE ULTIMATE MOVE – SUPERHUMANSTORE.COM SUPERHUMANSHOP.COM

We have moved! New site, new look, new products, new deals!

Bookmark: www.superhumanstore.com and www.superhumanshop.com

also working superhumangear.co and superhumangear.net

Important news: Superhumangear.com has moved to superhumangear.co

After weeks of struggle, we were still unable to recover our own domain. Long story short, our domain registrar called enom.com has PUT OUR DOMAIN ON HOLD because of a decision made by a site called legitscript.org who put our site in their list of so called “rogue pharmacies” due to some ridiculous claims (their site list 98 percent of any site related to health or beauty as rogue pharmacy). Our losses are huge. We have lost our great results is search engihnes and our daily visit has dropped hugely. Obviously, people think that we had to shut down the business. Well, fortunately, we only had to move to a different domain until we sort out things, so all you have to do is take out a letter at the end, instead of .com we are .co – WWW.SUPERHUMANGEAR.CO

We will be back with some special offers early july.

Thank you all for your support!

Can you buy AICAR and GW1516 cheap or at discounted price?

The short answer is: YES, you can, but be careful. Some  info below.

There are more and more far east providers of Aicar who offer the substance at fractions of huge worldwide chem manufacturers cost. Most of them has lower purity, check COA and HPLC results.

AICAR is a potent AMPK activator for research. Current price at Sigma-Aldrich for 98% purity Aicar is 300 USD for 25 milligrams!

AICAR ≥98% (HPLC), powder CAS no. 2627-69-2

5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside, Acadesine, N¹-(β-D-Ribofuranosyl)-5-aminoimidazole-4-carboxamide

So, how can you buy approximately 1 gram for the same price? – you buy from a smaller, non-worldwide, not so high rated raw chemical supplier THROUGH US.

1000 mg Aicar for $299  http://superhumangear.com/store_wp/shop/performance/aicar-acadesine-1000-mg-special-deal/

There are many peptide and body building sites that sell Aicar in 100 mg doses at around $100. Our price is half of that – but we don’t dilute it into liquid, you get the raw powder – and you can start experimenting with it.

100 mg Aicar for 59 dollars ONLY http://superhumangear.com/store_wp/shop/performance/aicar-100-mg-vial-lowest-price-blowout-deal/ 

Please note that 100 mg is barely enough for any research if done on mammals. It can be used as a sample or test project on cell cultures. The smallest recommended amount you can test mammals with is 1 gram.

 

NEW: BUY GW1516 GW501516 pparδ agonist endurance obesity AMPK $160 SALE

BUY CHEAP GW1516 research material

We are proud to announce that we carry GW1516

This substance drags a lot of attention and currently undergoes a lot of testing. It is a PPAR-β/δ agonist that acts synergistically with exercise to increase running endurance after 4 weeks.

$160 per gram so once again we will bring you the latest research materials at the most affordable prices! Product is shipped in a sealed foil bag.

Researchers at the Salk Institute have shown that agonists of both AMP-activated protein kinase (AMPK ) and a peroxisome proliferator-activated receptor (PPAR) can mimic some of the beneficial effects of exercise in mice. In a treadmill running test, the PPAR-β/δ agonist, GW 1516 (GW 501516), acted synergistically with exercise to increase running endurance after 4 weeks. The AMPK agonist, AICAR, surprisingly enhanced running endurance even in sedentary mice, also after 4 weeks dosing. PPAR-δ and AMPK agonists have the potential to treat diseases such as diabetes, where exercise has been shown to be beneficial and to offer protection against obesity, but also have the more controversial potential to increase endurance in athletes.

Like exercise, AICAR and GW1516 trigger a variety of changes that contribute improved endurance and the ability of muscle cells to burn fat. A phase II clinical trial of GW1516 for the potential treatment of dyslipidemia has been completed.

GW-501516 (also known as GW-501,516, GW1516 or GSK-516) is a PPARδ modulator compound being investigated for drug use by GlaxoSmithKline.^[1][2] It activates the same pathways activated through exercise, including PPARδ and AMP-activated protein kinase. It is being investigated as a potential treatment for obesity, diabetes, dyslipidemia and cardiovascular disease.^[3][4] GW-501516 has a synergistic effect when combined with AICAR: the combination has been shown to significantly increase exercise endurance in animal studies more than either compound alone. ^[5][6]

GW-50156 regulates fat burning through a number of widespread mechanisms;^[7] it increases glucose uptake in skeletal muscle tissue and increases muscle gene expression, especially genes involved in preferential lipid utilization.^[8][9][10] This shift changes the body’s metabolism to favor burning fat for energy instead of carbohydrates or muscle protein, potentially allowing clinical application for obese patients to lose fat effectively without experiencing muscle catabolism or the effects and satiety issues associated with low blood sugar.^[11] GW-501516 also increases muscle mass, which improved glucose tolerance and reduced fat mass accumulation even in mice fed a very high fat diet, suggesting that GW-501516 may have a protective effect against obesity ^[12]

It has been demonstrated at oral doses of 5 mg a day to reverse metabolic abnormalities in obese men with pre-diabetic metabolic syndrome, most likely by stimulating fatty acid oxidation.^[13] Treatments with GW-501516 have been shown to increase HDL cholesterol by up to 79% in rhesus monkeys and the compound is now undergoing Phase II trials to improve HDL cholesterol in humans.^[14]

Concerns were raised prior to the 2008 Beijing Olympics that GW-501516 could be used by athletes as a performance enhancing drug which was not currently controlled by regulations or detected by standard tests. One of the main researchers from the study on enhanced endurance consequently developed a urine test to detect the drug, and made it available to the International Olympic Committee.^[15] The World Anti-Doping Agency has also begun work on a test for GW-501516 and other related PPARδ modulators,^[16] and they have been added to the prohibited list from 2009 onwards.^[17] The compound has yet to be named a controlled or prohibited substance by any nation’s drug enforcement or regulation agency. To date, no athlete is known to have tested positive for the substance, though the increase in endurance, muscle fiber performance, fat loss and metabolism suggests GW-501516 has the potential for ergogenic use and abuse.

 

beta-Thymosins, small acidic peptides with multiple functions

Abstract

The beta-thymosins are a family of highly conserved polar 5 kDa peptides originally thought to be thymic hormones. About 10 years ago, thymosin beta(4) as well as other members of this ubiquitous peptide family were identified as the main intracellular G-actin sequestering peptides, being present in high concentrations in almost every cell. beta-Thymosins bind monomeric actin in a 1:1 complex and act as actin buffers, preventing polymerization into actin filaments but supplying a pool of actin monomers when the cell needs filaments. Changes in the expression of beta-thymosins appear to be related to the differentiation of cells. Increased expression of beta-thymosins or even the synthesis of a beta-thymosin normally not expressed might promote metastasis possibly by increasing mobility of the cells. Thymosin beta(4) is detected outside of cells in blood plasma or in wound fluid. Several biological effects are attributed to thymosin beta(4), oxidized thymosin beta(4), or to the fragment, acSDKP, possibly generated from thymosin beta(4). Among the effects are induction of metallo-proteinases, chemotaxis, angiogenesis and inhibition of inflammation as well as the inhibition of bone marrow stem cell proliferation. However, nothing is known about the molecular mechanisms mediating the effects attributed to extracellular beta-thymosins.

PMID:

11311852

[PubMed – indexed for MEDLINE]

Thymosin beta 4 induces hair growth via stem cell migration and differentiation

BUY THYMOSIN BETA 4 HERE

Cell Biology Section, NIH, NIDCR, Building 30, Room 433, 30 Convent Dr. MSC 4370, Bethesda, MD 20892, USA.

Abstract

Thymosin beta 4 is a small 43-amino-acid molecule that has multiple biological activities, including promotion of cell migration angiogenesis, cell survival, protease production, and wound healing. We have found that thymosin beta 4 promotes hair growth in various rat and mice models including a transgenic thymosin beta 4 overexpressing mouse. We have also determined the mechanism by which thymosin beta 4 acts to promote hair growth by examining its effects on follicle stem cell growth, migration, differentiation, and protease production.

PMID:

17947589

[PubMed – indexed for MEDLINE]

Magnesium-L-threonate to fight neurodegenerative diseases

article taken from Lef.org

Aged people are in the midst of an escalating Alzheimer’s epidemic.1,2 It is now the sixth leading cause of death in the United States.3

The horrific progression of Alzheimer’s disease from dementia to personal extinction afflicts between 24-30 million people worldwide.4,5 Americans account for approximately one-fifth of those cases, which are expected to triple by 2050.3,6

While there is no cure for Alzheimer’s, there is new hope thanks to the work of a team of researchers at Massachusetts Institute of Technology (MIT.)7

These scientists have identified several correctable factors involved in Alzheimer’s onset—and a novel nutritional intervention that may effectively target them.

In this article, you will learn of the vital role that magnesium plays in protecting the aging brain’s structure and function and why conventional supplements don’t deliver enough magnesium into the brain.

Researchers have found that a new highly absorbable formof magnesium called magnesium-L-threonate concentrates more efficiently in the brain, rebuilds ruptured synapses, and restores the degraded neuronal connections observed in Alzheimer’s disease and other forms of memory loss.

In experimental models, magnesium-L-threonate induced improvements of 18% for short-term memory and 100% for long-term memory.8

Magnesium Deficiency: An Overlooked Cause of Neurologic Decay

Half of all aging individuals in the developed world are magnesium deficient, a nutritional deficit that worsens over time.

Confirmatory data show that Americans are no exception.9,10 For instance, American women consume just 68% of the recommended daily intake of magnesium.11

Magnesium has long been known as a key nutrient for optimal brain function. More recently, scientists have found it specifically promotes learning and memory as a result of its beneficial effect on synaptic plasticity and density.7,8,12

Magnesium works with calcium to modulate “ion channels” that open in response to nerve impulses, which in turn trigger neurotransmitter release. The most important of those channels is controlled by a complex called the NMDA receptor.13,14 NMDA receptors play an important role in promoting neural plasticity and synaptic density, the structural underpinnings of memory.15-17

Magnesium deficiency can cause symptoms ranging from apathy and psychosis to memory impairment.13,18 Insufficient magnesium slows brain recovery following injury from trauma19 and in laboratory studies accelerates cellular aging.20

Ominously, magnesium deficiency may produce no overt symptoms in its initial stages.21

Part of the problem is that it is difficult for the body to maintain sufficiently high concentrations of magnesium in the brain.8

For this reason, researchers have long sought ways that higher magnesium brain concentrations might be achieved and sustained.

A Breakthrough Form of Magnesium

Scientists have been challenged to find a way to raise magnesium levels in the brain.8 Even intravenous infusions cause only a modest elevation of magnesium levels in the central nervous system.22

An innovative team of researchers from the Massachusetts Institute of Technology (MIT) recently found a way to surmount this obstacle. They formulated a new magnesium compound called magnesium-L-threonate or MgT that in lab tests allows for oral administration while maximizing magnesium “loading” into the brain.7,8

Based on prior research, they meticulously documented that increased levels of magnesium in the brain promote synaptic density and plasticity in the hippocampus.14 Up until now, however, no widely available forms of magnesium met the criteria needed for rapid absorption and efficient transfer into the central nervous system.8

By contrast, MgT yielded compelling results.

MgT oral supplements increased magnesium levels in spinal fluid, an index of measurement in brain magnesium by about 15%, while none of the other magnesium compounds tested produced significant elevations.8 While a 15% increase may not sound like a lot, it induced a profound effect on neurological function.

To evaluate the effects of MgT on memory, the researchers tested it against currently available magnesium compounds. They used a simple assessment of learning and memory called the Novel Object Recognition Test or NORT. A high NORT score means that the animal is good at recognizing and identifying new objects, a skill that is critical in aging humans as well.8 NORT is a good test of function in the hippocampus, which is rich in the NMDA receptors so closely controlled by magnesium.23

The researchers put aged animals through the NORT test, supplementing them with MgT or one of the commercially available magnesium compounds. Only MgT significantly enhanced both short- and long-term memory, boosting scores by 15% for short-term memory and 54% for long-term memory compared to magnesium citrate.8

Better Function of Memory-Forming Synaptic Connections

Given the effect of MgT in increasing synaptic density and plasticity in experimental animals (rats), the research team asked the obvious next question, “Do those changes lead to an increase in the number of neurotransmitter release sites, and, subsequently, to enhanced signal transmission?”8 That, after all, is the hallmark of learning and memory.

Using high-tech microscopic measuring devices, the team demonstrated that the magnesium elevation in brain tissue observed in MgT supplementation increases the number of functioning neurotransmitter release sites.8 This effect could be likened to increasing the number of soldiers on the battlefield: when the call to action comes, a much larger force is prepared to perform.

The final question to be addressed in this series of studies was whether the increased density of synaptic connections directly correlated with the observed improvements in memory created by MgT supplementation.

The researchers systematically plotted out the time-course of the increase in synaptic density following MgT supplementation, and found that it directly paralleled the improvements in memory.8 They also found that when MgT supplementation was stopped, the density of synaptic connections dropped back to baseline, further confirming the correlation. They found that MgT supplementation boosted all of the animals’ performance, not just average performance.

Improvement in Spatial Short-Term Memory

Spatial working memory is an essential memory function, helping you remember where things are and where you are in relation to the world over the short term. It is working memory that enables you to find your car keys as you head out the door or return to the correct page in the magazine you were reading a few minutes ago.

The MIT researchers tested spatial working memory in experimental animals. Without treatment, both young and old animals forgot the correct choice about 30% of the time. After 24 days of MgT supplementation, however, both young and old animals had improved this measurement of memory performance by more than 17%.8

Even more impressive, by 30 days of supplementation, the older animals’ performance became equal to that of their younger counterparts. Since the older animals were more forgetful at baseline than the younger animals that meant that the older animals had a larger percentage memory improvement (nearly 19%) than the younger animals’ more modest 13%.8

When MgT supplementation was suspended, the memory-enhancing effects persisted in younger animals, but in older animals spatial working memory performance declined dramatically, returning to baseline within 12 days.8 When MgT supplementation to the older animals was resumed, however, their memory performance was restored in 12 days.

In other words, magnesium-L-threonate improved memory in both old and young animals, but had a substantially greater effect on aged individuals—the very ones most in need of memory enhancements.

Novel Magnesium Compound Halts Neurologic Decay

Levels of Alzheimer’s disease and associated memory loss among aging Americans are reaching epidemic levels. The neurodegenerative processes involved in memory loss results from deterioration of connectivity between brain cells but are not a “natural function” of aging. Low magnesium status can accelerate brain cell aging and memory loss. Standard magnesium offers limited protection to brain cells. Magnesium-L-threonate is a new form of magnesium that dramatically boosts levels of magnesium in the brain. Boosting brain magnesium with magnesium-L-threonate enhances synaptic density and plasticity, the structural basis of learning and memory. In numerous experimental models, supplementation with magnesium-L- threonate has been shown to enhance memory and cognitive performance in multiple tests.

Enhanced Spatial Long-Term Memory

Long-term spatial memory is crucial for older individuals. It’s how you remember where you live or how to get to the grocery store. Loss of spatial long-term memory is one of the main reasons that older people with dementia get lost running even simple errands.

To test spatial long-term memory in MgT-supplemented animals, the researchers used a maze that required the animal to swim and find a submerged platform on which to rest. Again, both old and young animals supplemented with magnesium-L-threonate learned significantly faster than untreated animals during the training sessions.8

One hour after the training period, the researchers removed the submerged platform, causing the animals to have to search for its last location. Both young and old supplemented and unsupplemented animals remembered where the platform had been over the short term and were searching for it in the correct quadrant of the maze.

But after 24 hours, a remarkable difference was observed. Untreated animals, both young and old, completely forgot where the platform had been hidden, randomly searching in all quadrants of the maze. Supplemented animals, on the other hand, continued to search in the correct part of the maze more than twice as long as they looked in incorrect areas.8 That translated into improvements in spatial long-term memoryof 122% in younger supplemented animals, and nearly 100% in older supplemented animals.

In short, MgT supplementation doubled the accuracy of long-term spatial memory in older animals, and more than doubled it in younger animals.

Better Recall

One critical memory function is the ability to bring up an important memory based on only partial information, a function called pattern completion.8 You use pattern completion memory to find your way around a familiar neighborhood after dark or following a heavy snowstorm. In both cases, some familiar cues are gone, but a healthy brain will fill in the missing details by completing a recognizable pattern.

As decsribed on the previous page, when researchers removed some of the external visual cues from the water maze, younger animals had no particular difficulty finding their way to the hidden platform during the first 24-hour period. Older animals, on the other hand, demonstrated substantial impairment when familiar cues were missing, spending more than twice as much time searching for the missing platform. When given MgT for 30 days, however, older animals performed as well as the younger ones, quickly finding the platform even when many of the external cues were unavailable.8

In human terms, this kind of improvement could mean the difference between a routine trip to the grocery store at dusk versus getting lost in the dark.

Having successfully demonstrated that magnesium-L-threonate (MgT) improves multiple forms of learning and memory in living animals, the research team sought to explore the cellular and molecular basis of that improvement. They wanted to understand in a detailed fashion just what changes the MgT was producing in the brains of older animals that helped them form stronger, more stable memories.

What they determined was compelling.

Increased Brain Cell Signaling

The first step was to determine the effects of MgT supplementation on signaling between brain cells mediated by what are known as NMDA receptors. These receptors operate through varying concentrations of calcium and magnesium in brain tissue, making them a logical point of observation.

The first finding was that MgT treatment in animals resulted in stronger signaling at essential brain cell synapses.8 This increase in signaling was accomplished by a 60% increase in production of new NMDA receptors and by increases of up to 92% in related proteins that play essential supporting roles in brain signal transmission.8

Higher Memory- Forming Synaptic Plasticity and Density

Synaptic plasticity, or the ability to rapidly change the number and strength of brain cell synapses, is critical to the brain’s ability to form, retain, and retrieve memories. The research team compared synaptic plasticity in the brains of MgT-supplemented animals versus controls.8

They found that production of a very special subunit of the NMDA receptor, one closely associated with synaptic plasticity, was selectively enhanced by MgT supplementation.8 This molecular change is known to cause potent long-term increases in synaptic strength, and hence a greater capacity for information storage and memory.8,24-26

The result of these increases in NMDA receptor numbers was a 52% enhancement in long-term potentiation,8 which is the cellular equivalent of memory formation in the brain tissues of MgT-supplemented animals.27,28

Memory depends not only on synaptic plasticity, but also on the healthy physical structure of synapses between brain cells. Unfortunately, synaptic connections in the memory-rich hippocampus region of the brain decline with aging, which directly correlates with memory loss.8,29,30,31

One of the most vital structures to be found at brain cell synapses is the synaptic bouton, from the French word for button. When an electrical impulse reaches a pre-synaptic bouton, and ample calcium and magnesium are present, neurotransmitters are released to transmit the impulse to the next neuron in line. The greater the number and density of synaptic boutons, the stronger the electrochemical signal that the synapse can produce, and the more sustained the memory that is created.32

When the researchers examined the brains of control and MgT-supplemented animals under a high-power microscope, they readily detected much greater densities of synaptic bouton proteins in tissues from the supplemented animals. Those proteins are essential for neurotransmitter release in the several regions of the hippocampus vital for memory formation and retrieval.8 Remarkably, the density of the synaptic boutons was closely correlated with the memory performance of each individual animal on the novel object recognition test.

Mechanisms of Brain Aging and Memory Loss

Every memory you have, even those you’ve lost, produces physical changes in your brain. Memories form and are stored in multiple brain regions, but the most active and essential area is the hippocampus, a small, sea horse-shaped structure deep in the center of your brain. Hippocampal memory enables you to recognize and distinguish between old friends and new acquaintances, or to find your way around a well-known floor plan. It is also used to comprehend and navigate new experiences based on old ones. This puts the hippocampus squarely at the center of your ability to assimilate new information and integrate it with what you already know. As you learn and experience new events, cells in your memory centers tighten and enhance their neuronal connections, known as synapses.35 The ability of brain cells to quickly form new synapses and remove old ones is referred to as neurologic plasticity. Large numbers of synapses, and a high density of specialized synaptic structures called boutons, promote rapid retrieval and processing of the information stored by connected cells.36 In essence, neuronal plasticity is the physical equivalent of learning, while synaptic density is roughly the equivalent of memory. Young brains exhibit high levels of neurologic plasticity that produce large numbers of interconnected synapses. That’s why young people learn quickly and have strong memories. With aging, however, the numbers of synapses, and the ability to rapidly form new ones, steadily declines.37 And that’s just in “normal” aging.29 People with Alzheimer’s disease, or its precursor, mild cognitive impairment (MCI) experience more rapid loss of both plasticity and synaptic number.30,38-40 And that’s when memories begin to fade, or worse, to be lost entirely. Since time immemorial, people have suspected that specific nutrients can positively affect cognitive functions such as learning and memory.41 It’s now known that many nutrients can actually modify aging brain function, in part by increasing formation of brain synapses.42 Magnesium has been established as having a positive impact on both neural plasticity and synaptic density.7,8,12

Near-Term Research

The MIT team is rapidly putting in place two human studies of MgT on memory function, with results expected in the near future. Meanwhile, they have recently discovered several new roles for MgT in managing memory, in this case unwanted memories of the kind associated with post-traumatic stress disorder (PTSD).

Fear memories are expressed in response to objects or events previously linked with a potential danger. Over time, fearful reactions can dissipate when the triggering event is experienced in a safe environment.

Animal studies reveal that MgT enhances this process, so that events which previously caused an emotional response no longer trigger fear.33,34 MgT helps the pre-frontal region of the brain block the return of old fear memories.33,34

Research reveals that MgT works by enhancing neural plasticity in the hippocampus and prefrontal cortex.34 These findings led the researchers to recommend that elevating brain magnesium with MgT be used to dampen traumatic memories and treat PTSD, anxiety, and depression.33,34

PRP treatment: Platelets are a rich source of growth factors that can be applied to facial aesthetics

Platelets are a rich source of growth factors that can be applied to facial aesthetics

The use of platelet-rich plasma for rejuvenation and augmentation is discussed by Dr Sabine Zenker

Dermal stimulation and augmentation continues to grow within the facial aesthetics industry. A bioresorbable material such as hyaluronic acid (HA) is
commonly used. Many exogenous fillers rely on an autologous fibrotic response for volume augmentation—but disadvantages include the transient effects of temporary, resorbable
fillers and foreign body reactions such as persistent erythema and swelling and encapsulation, granuloma formation and chronic or delayed infections. An autologous source for soft tissue augmentation is therefore a desirable alternative.
Human growth factors (GFs) have been extensively investigated, but there are now clinical applications of individual GFs: keratinocyte growth factor (Kepivance, Sweden) for oral
mucositis; and platelet derived growth factor (Regranex, UK) for non-healing diabetic wounds. But applied outside their normal environment, these exogenous GFs may have untoward effects— for example, the FDA introduced a black box warning on becaplermin in 2008 for increased cancer mortality. The safety of palifermin has so far not been established.
Platelets
Platelets are an excellent source of GFs in their naturally-occurring and biologically determined ratio, and are successful in acute wound healing. The application of platelet-rich plasma (PRP) has been proven to enhance early wound healing and
healing in diabetic ulcers. Concentrated platelet preparations have been used clinically since the 1990s to simulate the native wound healing environment compared with that after isolated growth factor application. There is also substantial clinical proof
of PRP in other areas of medicine—platelet gel is widely used inorthopaedics and oromaxillofacial surgery.
Platelet recovery systems have been developed where erythrocytes are separated from white cells and platelets in distinct fractions. Platelet pellets are resuspended in recovered plasma, usually with 6–7 times the normal concentration of platelets in peripheral blood. This concentration is an autologous source of growth factors. After injection into the dermis and subcutaneous layers, the platelets are activated endogeneously by the
body’s own coagulation factors such as thrombine and collagen.
This leads to platelet degranulation, releasing platelet GFs such as PGDF, ILGF, EGF and TGF-beta. Activated platelets also release proteins such as the adhesive glycoproteins fibrin, fibronectin and vitronectin. These proteins and GFs interact with cells
in the subcutaneous tissues, such as fibroblasts, endothelial cells and stem cells and after binding to their cellular receptors, they activate intracellular signaling events—mediating cell proliferation,migration, survival and production of extracellular matrix proteins. This results in tissue rejuvenation. For the enhancement of skin texture, glow and hydration,
PRP is applied via superficial dermal injection using a mesotherapy technique. When used as a filler, PRP is injected dermally or subdermally to volumise and reshape the skin. The autologous character of this agent means there are minimal side effects, but these usually take form of mild bruising, swelling or, theoretically, infection. Contraindications include pregnancy, breast feeding, autoimmune or blood disease and cancer.
There are several kits for PRP harvesting, including MyCells, Selphyl and Regen. The MyCells kit is designed for autologous PRP re-injection and has been approved by the FDA, the Medical Device Committee of the European Union and by the Israeli
health ministry. PRP for facial rejuvenation is currently injected in three countries: Japan, England and Israel.

Studies
There is poor clinical data available to prove the safety and efficacy of PRP injections. An initial pilot study of 10 women showed that PRP injections for facial rejuvenation is an effective way to address some of the more difficult areas on the face, around the eyes and the neck.
MyCells performed a clinical investigation in Japan, the UK and Israel with over 400 patients. In this study, the clinical effects and potential side effects of MyCells PRP skin rejuvenation were evaluated. The patients were facially injected with the MyCells PRP skin rejuvenation kit. Follow up was performed three to six months after primary injections. Treatment was performed for the following indications and techniques:
• Layer specific transplant
• “Tenting” of the skin
• “Cul-de-sac” and needle bevel up
• Over-correction up to 50%
• Serial treatments, providing an accumulative effect
• Minimal-trauma technique using a long needle

Patients were treated with intradermal injection using long 30G needles, injected in deep folds or wrinkles using the linear threading technique, and with superficial injection using the mesotherapy technique. Following injection, Auriderm XO gel (vitamin K) was applied.
Patients were reviewed at three-monthly intervals. Results were age-dependent. Younger patients less than 35 years were found to respond quickly with the main indication being skin rejuvenation and prevention—treatment every 12-24 months should suffice.
Patients up to 45 years required a second treatment 9-12 months later and annual booster injections. Patients aged 50–60 years required a second treatment at six months, a third at one year and three months, with a touch up two years after the first treatment. Patients over 60 needed a second treatment at three months, a third at nine months and a fourth treatment 1.5 years later. Over-corrections were performed on 30-50% of patients.
My clinical experience with PRP has shown that this modality may be an alternative or adjunctive therapy for tissue regeneration to any of the existing therapies. Its application for superficial or deep dermal stimulation leads to skin rejuvenation and global facial volumisation.
This biostimulation is safe, creates an immediate and long lasting volumetric effect and a natural result. It is easy to perform and the procedure has virtually no side-effects and high levels of patients satisfaction.

References:
Bhanot S, Alex JC. “Current applications of platelet gels in facial
plastic surgery.” Facial Plast Surg. 2002 Feb;18(1):27-33.
Choukroun et al. “Influence of Platelet Rich Fibrin (PRF) on proliferation
of human preadipocytes and tympanic keratinocytes: A
new opportunity in facial lipostructure (Coleman`s technique) and
tympanoplasty?”
Dougherty EJ. “An evidence-based model comparing the costeffectiveness
of platelet-rich plasma gel to alternative therapies for
patients with non-healing diabetic foot ulcers.” Adv Skin Wound
Care. 2008 Dec;21(12):568-75.
Ebisawa K, Kato R, Okada M, Kamei Y, Mazlyzam AL, Narita Y,
Kagami H, Ueda M. “Cell therapy for facial anti-aging.” Med J
Malaysia. 2008 Jul; 63 Suppl A:41.
Epply BL, Pietrzak WS, Blanton M. “Platelet-rich plasma: a review
of biology and applications in plastic surgery.” Plast Reconstr Surg.
2006 Nov;118(6):147e-159e.
Hom DB, Linzie BM, Huang TC. “The healing effects of autologous
platelet gel on acute skin wounds.” Arch Facial Plast Surg 2007;
9:174- 183.
Kim JH, Park C, Park HM. “Curative effect of autologous plateletrich
plasma on a large cutaneous lesion in a dog.” Vet Dermatol.
2009 Jan 21 [Epub ahead of print].
Martínez-Zapata MJ, Martí-Carvajal A, Solà I, Bolibar I, Angel
Expósito J, Rodriguez L, García J. “Efficacy and safety of the use
of autologous plasma rich in platelets for tissue regeneration: A
systematic review.” Transfusion. 2009 Jan;49(1):44-56. Epub 2008
Oct 14. Review.
Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE,
Georgeff KR. “Platelet-rich plasma: Growth factor enhancement
for bone grafts.” Oral Surg Oral Med Oral Pathol Oral Radiol Endod
1998;85:638-646)
Mazzucco L, Balbo V, Cattana E, Borzini P. “Platelet-rich plasma and
platelet gel preparation using Plateltex.” Blood Transfusion Centre
and Biotechnology Laboratory, Ospedale SS Antonio e Biagio, Alessandria,
Italy, Vox SanguinisVox Sanguinis (2008) ORIGINAL PAPER
©2008 The Author(s) Journal compilation ©2008 Blackwell Publishing
Ltd. DOI: 10.1111/j.1423-0410.2007.01027.x
Mishra A, Woodland J et al. “Treatment of tendon and muscle using
platelet-rich plasma.” Clin Sports Med 28 (2009) 113-115
Mishra A, Tummala P, King A, Lee B, Kraus M, Tse V, Jacobs CR.
“Buffered platelet-rich plasma enhances mesenchymal stem cell
proliferation and chondrogenic differentiation.” Tissue Eng Part C
Methods. 2009 Feb 13. [Epub ahead of print]
Mojalla A, Foyatier J-L. “The effects of different factors on the
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New treatments for anemia – non-EPO blood booster: sotatercept (ACE-011)

Sotatercept (formerly called ACE-011) is an investigational protein therapeutic that increases red blood cell (RBC) levels by targeting molecules in the TGF-β superfamily. Acceleron is developing sotatercept in collaboration with Celgene Corporation for the treatment of anemia caused by chemotherapy and chronic kidney disease.

Mechanism of Action

Sotatercept, the first in a novel class of anemia therapies, is a soluble fusion protein consisting of the extracellular domain of activin receptor type IIA (ActRIIA) linked to the Fc protein of human IgG1. Sotatercept binds with high affinity to activin A and other proteins in the TGF-β superfamily and inhibits signaling through the ActRIIA receptor.

Sotatercept increases hemoglobin levels and RBCs by a novel mechanism: it is not an erythropoietin (EPO)-based product or EPO-mimetic, does not bind the EPO receptor, but rather targets a pathway that is fundamentally distinct from EPO.  In preclinical studies, administration of sotatercept or a mouse version of the molecule to mice and cynomolgus monkeys was associated with increases in erythropoiesis and total red cell mass.  The precise actions of sotatercept underlying the promotion of erythropoiesis are under investigation.

Sotatercept also affects bone formation.  One of the functions of activin A is to inhibit bone growth.   Activin A signaling through ActRIIA suppresses activity of cells responsible for building bone (osteoblasts) and stimulates cells responsible for breaking down bone (osteoclasts). By blocking signaling through ActRIIA, sotatercept stimulates bone formation. In numerous animal models of diseases involving bone loss, sotatercept significantly increased bone mineral density, improved bone architecture, and increased bone formation rate and bone mechanical strength.  Similar effects were observed in experimental models of cancer-related bone loss (multiple myeloma and breast carcinoma) where treatment with a mouse form of sotatercept resulted in a significant reduction in tumor-induced osteolytic lesions. In the myeloma model, restoration of bone remodeling had a significant indirect effect on tumor burden and increased survival.

Acceleron and Celgene are developing sotatercept in anemia indications where the product’s unique pharmacology could potentially provide an innovative and differentiated alternative to existing anemia therapies.

Disease Overview

Anemia, a deficiency of healthy RBCs, is a debilitating condition that often accompanies chemotherapy or chronic kidney disease.  Patients with anemia typically experience fatigue and weakness, which impairs their quality of life and may limit their ability to receive optimal care.

Treatments for anemia include iron repletion, blood transfusion, and recombinant growth factors called erythropoietin stimulating agents (ESAs).  ESAs are currently the only approved drugs that stimulate the production of RBCs.

Clinical Need

ESAs have been used extensively to treat anemia. Recent studies of ESAs have shown an increased risk of mortality arising from exposure to high levels of recombinant erythropoietin and its derivatives, which may stimulate tumor progression, cause premature mortality, and increase the occurrence of thromboembolic events.  The safety concerns with ESAs have prompted substantial restrictions to their approved uses for the management of patients with cancer and kidney disease.

Sotatercept represents a new approach to anemia treatment.   Clinical trials in patients with CIA and CKD are currently underway to study its potential as a safe, effective treatment for anemia.

Clinical Trials

Acceleron is developing sotatercept together with Celgene Corporation for patients who suffer from anemia.  Sotatercept is currently being studied as a treatment for chemotherapy-induced anemia (CIA) and chronic kidney disease-related (CKD) anemia.

Phase 2/ 3 Study for Chemotherapy-Induced Anemia in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC).   For information on this trial, please click here.

Phase 2 Study for Anemia in Patients with End-stage Renal Disease on Dialysis.   For information on this trial, please click here

In Phase 1 clinical studies in healthy volunteers, sotatercept was generally well tolerated, and, consistent with observations in preclinical studies, increased levels of hemoglobin and hematocrit, biomarkers of bone formation, and bone mineral density. The most common clinically significant adverse events observed included increased hemoglobin and increased hematocrit, which were pharmacologic effects of the drug, and also headache, all of which were manageable and reversible.

Scientists successfully test first gene therapy against aging-associated decline

A number of studies have shown that it is possible to lengthen the average life of individuals of many species, including mammals, by acting on specific genes. To date, however, this has meant altering the animals’ genes permanently from the embryonic stage – an approach impracticable in humans. Researchers at the Spanish National Cancer Research Centre (CNIO), led by its director María Blasco, have proved that mouse lifespan can be extended by the application in adult life of a single treatment acting directly on the animal’s genes. And they have done so using gene therapy, a strategy never before employed to combat ageing. The therapy has been found to be safe and effective in mice.

The results are published today in the journal EMBO Molecular Medicine. The CNIO team, in collaboration with Eduard Ayuso and Fátima Bosch of the Centre of Animal Biotechnology and Gene Therapy at the Universitat Autònoma de Barcelona (UAB), treated adult (one-year-old) and aged (two-year-old) mice, with the gene therapy delivering a “rejuvenating” effect in both cases, according to the authors.

Mice treated at the age of one lived longer by 24% on average, and those treated at the age of two, by 13%. The therapy, furthermore, produced an appreciable improvement in the animals’ health, delaying the onset of age-related diseases – like osteoporosis and insulin resistance – and achieving improved readings on ageing indicators like neuromuscular coordination.

The gene therapy utilised consisted of treating the animals with a DNA-modified virus, the viral genes having been replaced by those of the telomerase enzyme, with a key role in ageing. Telomerase repairs the extremes of chromosomes, known as telomeres, and in doing so slows the cell’s and therefore the body’s biological clock. When the animal is infected, the virus acts as a vehicle depositing the telomerase gene in the cells.

This study “shows that it is possible to develop a telomerase-based anti-ageing gene therapy without increasing the incidence of cancer”, the authors affirm. “Aged organisms accumulate damage in their DNA due to telomere shortening, [this study] finds that a gene therapy based on telomerase production can repair or delay this kind of damage”, they add.

‘Resetting’ the biological clock

Telomeres are the caps that protect the end of chromosomes, but they cannot do so indefinitely: each time the cell divides the telomeres get shorter, until they are so short that they lose all functionality. The cell, as a result, stops dividing and ages or dies. Telomerase gets round this by preventing telomeres from shortening or even rebuilding them. What it does, in essence, is stop or reset the cell’s biological clock.

But in most cells the telomerase gene is only active before birth; the cells of an adult organism, with few exceptions, have no telomerase. The exceptions in question are adult stem cells and cancer cells, which divide limitlessly and are therefore immortal – in fact several studies have shown that telomerase expression is the key to the immortality of tumour cells.

It is precisely this risk of promoting tumour development that has set back the investigation of telomerase-based anti-ageing therapies.

In 2007, Blasco’s group proved that it was feasible to prolong the lives of transgenic mice, whose genome had been permanently altered at the embryonic stage, by causing their cells to express telomerase and, also, extra copies of cancer-resistant genes. These animals live 40% longer than is normal and do not develop cancer.

The mice subjected to the gene therapy now under test are likewise free of cancer. Researchers believe this is because the therapy begins when the animals are adult so do not have time to accumulate sufficient number of aberrant divisions for tumours to appear.

Also important is the kind of virus employed to carry the telomerase gene to the cells. The authors selected demonstrably safe viruses that have been successfully used in gene therapy treatment of haemophilia and eye disease. Specifically, they are non-replicating viruses derived from others that are non-pathogenic in humans.

This study is viewed primarily as “a proof-of-principle that telomerase gene therapy is a feasible and generally safe approach to improve healthspan and treat disorders associated with short telomeres”, state Virginia Boccardi (Second University of Naples) and Utz Herbig (New Jersey Medical School-University Hospital Cancer Centre) in a commentary published in the same journal.

Although this therapy may not find application as an anti-ageing treatment in humans, in the short term at least, it could open up a new treatment option for ailments linked with the presence in tissue of abnormally short telomeres, as in some cases of human pulmonary fibrosis.

More healthy years

As Blasco says, “ageing is not currently regarded as a disease, but researchers tend increasingly to view it as the common origin of conditions like insulin resistance or cardiovascular disease, whose incidence rises with age. In treating cell ageing, we could prevent these diseases”.

With regard to the therapy under testing, Bosch explains: “Because the vector we use expresses the target gene (telomerase) over a long period, we were able to apply a single treatment. This might be the only practical solution for an anti-ageing therapy, since other strategies would require the drug to be administered over the patient’s lifetime, multiplying the risk of adverse effects”.

Provided by Centro Nacional de Investigaciones Oncologicas (CNIO)