Sustanon

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.

FUTURE DIRECTIONS

          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..

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.

Phenserine

    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).

Desferrioxamine

     Desferrioxamine

    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.

RNA TARGETS IN BIOLOGY AND MEDICINE

     

    

1 INFECTIOUS DISEASE   
HIV: DRUGS THAT SUPPRESS THE TAR STEMLOOP FROM INTERACTING WITH A TAT TRANS-ACTIVATOR. 

ANTIBIOTICS: i.e: BACTERIAL RIBOSOME PEPTIDAL TRANSFERASE IS BLOCKED BY ERYTHROMYCIN



2 ARTHRITIS/CANCER  (Message Pharmaceuticals)

CYTOKINE mRNAs: DRUGS THAT SUPPRESS AUF-1 BINDING TO THE 3'UTRS OF IL-1- AND TNF-mRNAs

     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.