Thursday, January 31, 2013


Sustanon - a very popular steroid which is highly valued benefit by bodybuilders, because in comparison to other testosterone products it has several advantages. Sustanon is a mixture of the four testosterones which,  have a synergistic effect because of certain structures. This feature results in two positive qualities that are of interest to athletes.

 On the basis of a specific interaction of existing chemicals Sustanon per milligram has better effect than Testosterone enanthate, cypionate, and propionate. Besides the effect of these chemicals is temporally one after another, so that Sustanon is effective quickly and at the same time remains for effective action in the body for several weeks, due to contained in Sustanon propionate. 
Sustanon having an impact on the body the next day, and continues to be active in it 3 - 4 weeks due to the additions of the decanoate. Sustanon has a distinct androgenic effect which is combined with a strong anabolic. Therefore it is well suited to build up strength and mass. Going strong gain physical strength while adding body weight.  

Athletes who use Sustanon tell of solid muscle gain, because it accumulates significantly less water and less strongly flavored as Testosterone.

Wednesday, January 30, 2013


          Our ultimate goal is to use newly discovered compounds directed to APP-mRNA 5'UTR to limit A(3-peptide output in cell culture systems, and subsequently to therapeutically test these compounds in transgenic mouse models for APP and A(3 over-expression. We have developed a collaboration with Dr. Steve Gullans (Director of Renal Division Research, Harvard Institutes of Medicine).
     During the course of this project, we have started a screen for APP 5'UTR-binding compounds from a unique library of 1,500 FDA preapproved drugs arranged in a convenient format for transferring to cells growing in 96 well plates. Using a new transfection-based assay, in which APP-5'UTR sequences drive the expression of luciferase and green fluorescent protein (GFP) reporter genes, our two laboratories are conducting a screen to identify new "hits" of therapeutic compounds that already have FDA approval.

     Single lead drugs, or more potent combinations, will be tested for their capacity to suppress APP translation by RNA targeting. In conducting these screens, great care has to be taken to ensure that lead compounds do not alter APLP-1 and APLP-2 and ferritin gene expression.
     This serves as a screening control designed to minimize side effects. New and powerful combinations of FDA-approved drugs will soon be available as therapy for AD patients to use at low doses. Their efficacy will be directed to suppress APP translation, an effect that subsequently would reduce neurotoxic production of A(3-peptide..

Tuesday, January 29, 2013

Phenserine improves cognitive performance

     Phenserine improves cognitive performance in rats and is undergoing phase II clinical trials as an acetylcholinesterase inhibitor.

     We found that phenserine imparts a double therapeutic action by targeting 5'UTR sequences in APP mRNA to suppress translation of the precursor, and reduces A(3-peptide secretion with a high degree of specificity. The finding that Df suppresses translational enhancement by 5'UTR sequences in APP mRNA is consistent with evidence for the presence of a modified IRE in the 5'UTR of APP mRNA.

    Neither Df or most anticholinesterases is considered to be completely desirable as agents for AD therapy. Desferrioxamine generates hypotension at high doses (Hallaway & Hedlund, 1992), and current anticholinesterases have been shown to be beneficial only for mild cases of AD over 1 year of usage with marked side effects to the liver .
       There is clearly a need to develop effective screens to generate more promising APP 5'UTR-directed drugs, such as phenserine, for future clinical us.

Monday, January 28, 2013


    Impairment of the cholinergic system is one of the most important clinical featured symptoms of AD. This process can be partially reversed by acetylcholinesterase inhibitors, including phenserine. Coincidentally, we have discovered that phenserine is a member of a class of preexisting medicinal compounds that also block APP translation by targeting the unique stemloop formed from 5'UTR sequences in APP mRNA.

       Indeed, studies of rats with forebrain cholinergic lesions have shown that phenserine decreases the level of APP production, unlike some other acetylcholinesterase inhibitors that increase the production of APP. Phenserine is an example of a small molecule (Mw = 487) that acts, at least in part, by blocking translation of APP mRNA through the regulation of the 5'UTR, to suppress APP synthesis, thus inhibiting A(3-peptide output (Dr. N. Greig, NIA, Baltimore, MD).

       We have tested the capacity of the lead compound phenserine (and other related RNA-targeting compounds) to block APP gene expression through 5'UTR sequences in APP mRNA. The iron chelator, Df, was used as a positive control, representing a small molecule that markedly suppressed APP mRNA translation via 5'UTR sequences (Molecular weight of Df = 656.8).

Friday, January 25, 2013



    Autopsy samples from AD patients reveal elevated levels of iron, particularly in the neurons of the basal ganglia Iron is relevant to neurodegenerative pathogenesis in the brains of AD patients, as evidenced by their disrupted brain-iron distribution. Since we had discovered that the APP 5'UTR is a modified ironresponsive element, we decided to test whether iron chelation by Df can suppress translation conferred to a luciferase reporter by APP mRNA 5'UTR sequences. In the first step, a Luciferase-reporter construct, MS121, was prepared by inserting a PCR-generated APP-mRNA 5'UTR fragment.

    Neuroblastoma cells (SY5Y) were transfected with this APP-5'UTR-specific construct and cells were then exposed to Df (5uM), before preparation aof cell lysates and use of a luciferase assay to determine levels of reporter gene activity. As a negative control, neuroblastoma cells were transfected with a parental pGL-3 reporter plasmid. The results showed that the APP 5'UTR was clearly a target for the action of Df to suppress APP-5'UTR translational regulation.

     Desferrioxine was shown to be beneficial for Alzheimer's patients in one study. However, the use of this iron chelator is currently restricted to the treatment of patients with sickle cell disease, thalassemias, arid to counteract iron poisoning. We reasoned that Df would be a strong positive control to screen for new compounds, including anticholinesterase derivatives (phenserine), which might suppress APP mRNA translation without chelating intracellular iron.

Thursday, January 24, 2013






2 ARTHRITIS/CANCER  (Message Pharmaceuticals)


Wednesday, January 23, 2013

     Oxandrolone contributes to a strong increase in strength. This is due to the fact that the synthesis of creatin phosphate is raised in the muscle cell and does not accumulate fluid. Weightlifters and security forces that do not want to move to a higher category use this as drug gives them a chance to get stronger, not adding to their own weight. Good results are obtained simultaneous reception of Oxandrolone and 120 - 140mg Clenbuterol per day.  

      This is due to the fact that it contributes to a strong increase in strength., and significantly enhances the effect of many steroids on the body, especially combined with Deca-Durabolin, Dianabol and a variety of testosterone, as arises when taking Oxandrolone strength gains while Deca-Durabolin, Dianabol or testosterone that accumulate fluid and contribute to strong growth in tissue, the result is an additional muscle mass.  

     The combination of 200 mg Deca per week, 500 mg of testosterone enanthate per week and 25 mg Oxandrolone day causes most athletes a good gain in strength and muscle mass. Deca-Durabolin has a distinct anabolic effect and stimulates the synthesis of proteins, oxandrolone increases strength, and testosterone makes the athlete more aggressive during the workout and accelerates regeneration.

Tuesday, January 22, 2013

Oxandrolone does not have any side effects

    Oxandrolone in reasonable doses does not have any side effects. This is understandable, since drug originally designed for women and children. This is one of the few steroids which does not cause a delay premature physical development of children, as it does not promote closure epofizez  compounds, and the drug is primarily used in children to stimulate growth of the body and women - in osteoporosis. The drug causes (if any is) very weak virilization.  

  This quality makes it a favorite means of athletes as at a dose of 10-15 mg a day they rarely observed outward manifestations of masculinity. Oxandrolone love bodybuilding and powerlifting athletes.

Monday, January 21, 2013


    Oxandrolone appeared in the U.S. in 1964. Anavar called the company "Searle." Over two decades, was very popular until July 1, 1986 did not stop the production of Anavar. Today, the drug is still produced under different names.  

    Oxandrolone SPA company "SPA Milano" from Italy is one of the few in Europe anabolic steroid containing the substance (oxandrolone).

Friday, January 18, 2013

The dosage of testosterone

      Not all that rare, as among bodybuilders and powerlifters in the environment, are the dosages of testosterone enanthate 2000 mg per day. It was a day, not a week. As ordinary user to such doses do not go up, it can be limited to the same two grams of the drug, but in a week. A normal return on testosterone enanthate starts with 500 mg per week, although this is, nevertheless, the dosage for beginners in the "steroids."
     Injections of testosterone enanthate can be done once in 5-7 days, but I would recommend more frequent injections.

Thursday, January 17, 2013

Side effects of testosterone

     Since testosterone is easily aromatized, its use in high doses can cause side effects such as water retention, acne, deposition of fat on the female type. But for most athletes, the problem begins with high doses of the drug - from grams per week and up, with both doses of testosterone are advised to take antiestrogens at least the same tamoxifen. With doses of 500-600 mg of testosterone enanthate per week, the person who uses testosterone, can not notice any "side effects"The conversion of testosterone to DHT means a risk of side effects such as hair loss and prostate enlargement. Again, this only applies to high dosages of the drug and is characteristic only for those people who have in the skin of the head and the prostate has been an increased level of the enzyme 5Reductase. 
    The use of testosterone, even at doses of more than two grams a week did not infringe either the liver or other organs. And the restoration of natural testosterone production after such a shock, "course" is very successful, without delay.

Wednesday, January 16, 2013

The use of testosterone

    When people talk about testosterone, primarily mean those in which the active substance is testosterone enanthate. This broadcast we will look at in the first place.

    The only purpose of testosterone enanthate - help in the set weight. And the task he handles a hundred percent. Increased tendency to flavor here for the benefit of the drug, since estradiol has provided substantial assistance in the collection of mass. In the case of high-dose testosterone enanthate muscle mass may be the result of the formation of new fibers (hyperplasia of the muscles). Testosterone enanthate has the influence and the power of the athlete, of course, in the direction of improvement. The uniqueness of testosterone is that it has an equally strong impact on both beginners and veterans in the "steroid front."

Tuesday, January 15, 2013

High doses of testosterone increases the number of androgen receptors in muscle fibers

   What is a molecule of testosterone, you know, once again we are on the characteristics of its structure will not stop. Just recall that by virtue of these features easily aromatize testosterone, that is, converted to estradiol. Besides estrogen testosterone by the enzyme.  Reductase is easily converted to dihydrotestosterone (DHT), which means the strengthening of its androgenic properties (action on the prostate body hair and scalp, sebaceous glands, as well as increased libido), but the erosion of the cells of skeletal muscles.

   According to studies, the use of high doses of testosterone increases the number (upregulation) of androgen receptors in muscle fibers. Results from another study also deserve to play them here in full. Here they are: "anabolic steroids in combination with strength training provokes an increase in muscle size as a result of their hypertrophy, and due to the formation of new muscle fibers. The key to this, obviously, must be regarded as the activation of satellite cells, which significantly increases with high doses of steroids. " Furthermore, it was also established experimentally that the use of testosterone enanthate at a dose of only 3 mg per kg of body weight per week raises the level of growth hormone in the blood by 22% and insulin-like growth factor by 21%.

Monday, January 14, 2013

Testosterone Enanthate

       "We were the first and still the best" - this motto is the best suited drugs such as Testosterone Enanthate that are effective in the matter are different esters of testosterone. It is unlikely that today there is at least one bodybuilder, based pre-season which is not testosterone.  

     On the impact of testosterone is one of the best preparations for a set of mass, and the ratio of price / quality, and it does not equal.  

   What can I say: the king - even in Africa the king!

Friday, January 11, 2013

RNA Targets Therapeutic for the Alzheimer's Disease Amyloid Precursor Protein

 Our goal to suppress Alzheimer's APP gene expression at the translational level has the advantage that the APP 5'UTR RNA target is unique, thus affording a higher degree of selectivity.

    There are regulatory sites in the 3'UTR of APP mRNA that can be utilized as targets to suppress APP gene expression. However, our finding that the 5'UTR of APP mRNA is a powerful, translational enhancer element makes this RNA structure a very attractive target for regulating APP gene expression as a therapeutic strategy to slow AD progression.

      The vaccination strategy to target and suppress steady-state levels of A(3 peptide has been successfully developed by Elan Pharmaceuticals, who reduced later stage formation of (3-amyloid plaques, neuritic dystrophy, and astrogliosis, and other "Alzheimer's disease-like pathology" in the PDAPP transgenic mouse. RNA targeting and vaccination approaches may ultimately be complementary approaches as therapeutic strategies to help AD patients.

   Werstuck and Green  demonstrated a model system for the selection of RNA-binding compounds to inhibit translation of reporter proteins under the control of specific upstream RNA stemloops.

Thursday, January 10, 2013


       Like the use of protease inhibitors to limit APP cleavage, drug-induced down-regulation of APP-gene transcriptional control has the intrinsic problem that DNA motifs are shared with several other genes. Certainly targeting the DNA promoter sites in front of the APP gene as a therapeutic strategy for AD has the disadvantage that several genes share the common enhancer sequences that control APP gene expression. As an example, NFkB is a well-characterized transcription enhancer that controls immunoglobulin gene expression, in addition to APP gene expression, in response to inflammatory signals.

    AP-1 sites are palindromes in front of the APP gene, which bind the cJun/cFos proto-oncogenes during stress, but the presence of this site in the enhancers of several other stress-responsive genes precludes the use of this site as a therapeutic target for AD. These considerations imply that new DNA-targeting drugs will not only suppress the gene of interest (e.g., APP for AD), but will also interfere with the expression of related and essential housekeeping genes, resulting in unwanted metabolic side effects. Despite these difficulties, companies such as Abbott Laboratories  and Hoechst Marion Roussel (Ringheim et al., 1998) have explored the potential
to modulate APP gene transcription.

Wednesday, January 9, 2013


       RNA Targets in HIV, Infectious Disease, and Cytokines RNA structure has become the focus for developing therapeutic strategies to regulate the expression of many disease-associated genes because any given RNA structure is unique to the gene from which it is expressed. However, the concept that RNA-directed compounds can confer a therapeutic impact is not new. For decades, antibiotics, like erythromycin, have been characterized to be bactericidal based on their capacity to bind to unique ribosomal RNA sequences in the bacterial 23S ribosome subunit. The B component of streptogramins inhibits peptide elongation in vivo during the early rounds of protein synthesis in a manner similar to that of the smaller microlides, including erythromycin. Ribotargets (Cambridge, UK) is a company that seeks to inhibit the essential TAT-Tar interaction to prevent HIV infection and AIDS.

     In this case, the TAT transactivating protein binds to the TAR stemloop at the viral LTR to promote viral growth. Blocking this interaction with selected compounds will interfere with the viral life cycle and be of therapeutic benefit. Scriptgen Inc. has a drug-discovery program directed to a single RNA target, the replication origin of hepatitis C virus. Message Pharmaceuticals (Malvern, PA), is the only company interested in diseaseassociated RNA targets of endogenously expressed genes . A major project in their program is to modulate cytokine expression as a therapeutic strategy for arthritis and cancer. Tumor necrosis factor (TNF) and interleukin-1 (IL-1) gene expression is up-regulated in the joints aof arthritis patients. Low molecular weight RNA-binding compounds can be screened for their capacity to inhibit binding of the AUF-1 to the AU-rich sequences in the 3'UTR of these cytokine mRNAs.

    Another class of drugs (CSAIDS) were previously shown to interfere with a kinase that phosphorylates the 3'UTR AUF-1, which controls cytokine mRNA stability in response to cellular signaling.

Friday, January 4, 2013


      Many existing drugs are designed to bind to the active sites and then suppress protein activities that promote the development of disease progress. For example, cocktails of protease inhibitors are used to therapeutically block hepatitis C virus infections (Fattori et al., 2000) by inactivating the viral NS3 protease (Barbato et al., 2000). Statins are low molecular-weight compounds that suppress HMG-CoA reductase activity and, thus, cholesterol synthesis, to therapeutically assist patients at risk for coronary heart disease (Penzak, Chuck, & Stajich, 2000). RNA aptmers are also used as protease inhibitors .

     There are some drawbacks to the use of viral-associated protein targets for drug selection. In the case of HIV-associated diseases, rapid genetic drift in protein sequences makes viral targets immunoevasive. Therefore, these protein sequences are less attractive targets for long-term therapeutic strategies.

 Most AD patients are currently treated with acetylcholinesterase inhibitors, which act as cognitive enhancers. Acetylcholinesterase inhibitors (e.g., Aricept, Eisai Co Ltd, Tokyo, Japan; Pfizer Inc., New York, NY) are proteintargeted inhibitors of the esterase that cleaves acetylcholine, the cholinergic neurotransmitter. These drugs slow down the rate of cognitive decline by increasing acetylcholine neurotransmitter levels in the brain (al-Jafari, Kamal, Greig, Alhomida, & Perry, 1998). The anticholinesterases provide limited improvement of cognitive performance in AD patients, and thus are of only partial benefit to AD patients early in disease progression. One problem associated with the use of anticholinesterases is that they have not been shown to confer any therapeutic action on the neuropathological events that might cause AD (i.e., amyloid, apolipoprotein E, alpha-1 antichymotrypsin, heparan sulfate proteoglycans, and the microtubule-associated protein, tau). We will discuss our discovery that a new anticholinesterase, phenserine, directly suppresses APP mRNA translation through the 5'UTR, thus imparting a therapeutic impact on A(3-peptide buildup, in addition to being an anticholinesterase (Shaw, Utsuki, Rogers, Yu, Lahiri, & Grieg, 2001). Current protein-based therapeutic approaches for AD aim to arrest the accumulation of the major amyloid plaque-associated protein, the A(3 peptide. The exact mechanism by which amyloid becomes toxic is unknown, but the presence of copper and iron and oxidative stress is a critical event (Huang et al., 1999; Bush et al., 2000). At the same time, neurotoxic protofibrils deposit in the neuritic amyloid plaques as Ap peptide is converted from an open-coil structure into a beta-sheet conformation (Kimberly, Xia, Rahmati, Wolfe, & Selkoe, 2000; Teplow, 1998; Walsh et al., 1999). Haass et al. (1992) first showed that Ap peptide is secreted from all cells in the body after being cleaved from the transmembrane APP. The elegant work of Wolfe et al. (1999) demonstrated that two transmembrane aspartates in presenilin-1 constitute the endoproteolytic peptidase conferring y-secretase activity. Thus, PS-1 mutations cause familial AD (Levy- Lahad, 1995; Scheuner et al., 1996), and PS-1 appears to function as the y-secretase that catalyzes the final cleavage of APP to Ap (Wolfe et al., 1999).

    Companies, including Bristol-Myers Squibb, have programs to screen, from large combinatorial libraries, for small molecules that can suppress the secretases (PS-1 and PS-2) that cleave APP to the 40-42 amino acid Ap peptide. One drawback of developing drugs that inhibit both (3 and y-secretase activity (and hence the generation of A(3 peptide) is that these secretases have other cellular targets. For example, the transcription factor notch is cleaved by PS-1, and it remains to be seen whether drug-induced inhibition of y-secretase will generate cytotoxic side effects associated with the disappearance of an essential downstream transcriptionally activated protein (Song et al., 1999). This concern was addressed by recent work showing that transfectants bearing PS-1 and PS-2 mutations maintain nuclear translocation of notch to the nucleus with relative preservation of notch-1 signaling (Berezovska et al., 2000). However, new protease inhibitors directed toward (3- and y-secretases may also affect other unrelated cellular targets, although this subject remains open to the development of a drug that proves the concept

Thursday, January 3, 2013

Targeting an RNA Structure in the Amyloid Precursor Protein Gene as a New Therapeutic Strategy for Alzheimer's Disease

     Recently, the possibility of developing drugs that knock out the unwanted genetic function associated with unique RNA structures has led laboratories in industry and academia to screen for medicinal compounds directed to disease-associated RNA targets.

    Small molecules that influence RNA  directed activity are to be screened from large combinatorial libraries of compounds. To date, most accumulated knowledge in this field centers around the development of drugs that offer therapies against infectious diseases. For example, drug discovery related to hepatitis C virus infection targets a unique translation control signal, the internal ribosome initiation site (IRES), which is essential for the viral life cycle (Anwar, Ali, Tanveer, & Siddiqui, 2000).

   We will discuss the RNA structure formed by the 5' untranslated region (5'UTR) of the endogenous amyloid precursor protein (APP) gene (APP 5'UTR) as a therapeutic drug target for Alzheimer's disease (AD) (Figure 11.1) (Rogers et al., 1999). Interleukin-1 and iron regulate APP gene expression at the translational level through the APP 5'UTR, similar to the iron-storage protein, ferritin (Rogers, 1996, 1999). This finding is consistent with the fact that the secreted ectodomain of the precursor (APPs) binds (and probably sequesters) the neurotoxic metals, copper, and iron.