"Approaching the drug to the cell" could improve both the treatment and in the PrEP
A combination of particle formulations of drugs atazanavir and ritonavir plusan immune buffer designed to induce drug certain cells with the aim of keeping the drug for longer in the body, produced declining 100 times the number of T CD4 cells in mouse lymph nodes infected with HIV and still greater reduction in the amount new viruses produced by the cells. Pretreatment with the drug also causes infections produced with significantly lower viral loads, it is suggested, from this concept, which might be used for pre-exposure prophylaxis (PrEP) as well as in the treatment of HIV infection or AIDS. The drug combination has largely prevented the adsorption of HIV on T lymphocyte cells and thus has a considerable potential to prevent or suppress the long-term infection.
Editor's note: I understand the last sentence a modest but clear of a call to attention for a possible "cure" a treatment medium or long term or a "functional cure" with fewer visits to the hospital, improving even more the quality of life of PLWHA
The discovery of potential drug combination was taken almost nearly hoc basis. The damping experimental immune drug, URMC-099 was being investigated as a possible treatment for suppressing inflammation caused by HIV brain and nervous system, the long and chronic process of HIV infection. It works by suppressing the quinasse B, a family of proteins that act as switches for inflammatory genes (aspirin is also a suppressor quinasse).
From Wikipedia, the free encyclopedia. (Redirected fromkinase) Inbiochemistry, ankinase orkinaseIt is a type ofenzymetransferringphosphate groupsdonors high-energy molecules (such asATP) To specific target molecules (substrates). The process is calledphosphorylation.  The target molecule can be activated or inactivated by means of phosphorylation. All kinases require aionas the divalent metalMg2+orMn2+to transfer the phosphate group. These enzymes are activated bycyclic AMPWhich catalyzes the phosphorylation of certain proteins. A protein kinase catalyzes the addition of phosphate reaction of this grouping and this reaction is unidirectional, with the ATP being broken for producing the energy needed for the reaction. A protein phosphatase, does exactly the reverse reaction of kinases, it removes a phosphate grouping, ie does dephosphorylation. The cells contain several proteins kinases and protein phosphatases each being responsible for acting in a specific group or a specific protein. The protein kinases belong to a large family of enzymes that share a sequence of amino acids 290. Some specific amino acid sequences that allow specific kinases recognizing groups on the protein to be phosphorylated. Source: Widepedia. To read the full article, click here
The same team also researching a new drug delivery method body for the protease inhibitor atazanavir drug, boosted by ritonavir. Both of these drugs have been formulated as nanoparticles - thousands of drug particles small enough to pass into cells and even cellular components. These nanoparticles were then linked to folic acid, a common micronutrient, whose molecules are also used by cells of the immune system, with the result that, arriving in lymph nodes, the drug was developed proactively in T cells
Adding the nano formulated URMC-099 driven by atazanavir (nano ATV) induced the cells in mice - which have been genetically adapted to have human immune systems - maintain the intracellular drug levels for a longer time, up to ten days in a single dose especially in places where the cells in HIV viral particles are built.
This resulted first in a considerable decline in CD4 cells infected with HIV. In untreated mice, the CD4 count, expressed as the percentage of T lymphocytes that were CD4 cells decreased from the 75 40% - as seen in the majority of courses of infection by HIV. Using nano ATV, the percentage of CD4 was maintained at 60% -within the range of uninfected mice.
However nano ATV achieved this feat by itself, probably due to his distinctive feature that had not been noticed before (always remember d history of penicillin). The URMC-099, though without producing any effect on its own structure produced a reduction considerávemente higher than expected and beyond the effect of atazanavir when dosed as nano ATV. The viral load in treated mice was about 100.000 copies / ml; in mice treated with improved potency atazanavir was 1600 copies / ml and was URMC-099 284 copies / ml. The effect persisted shortly after the withdrawal of the dose. Mice were first infected and not treated for nine weeks; nanoATV was then injected once a week and URMC-099 administered daily in this way for three weeks. CD4 counts remained stable when measured one week later.
What was unprecedented, however, was that the addition to URMC-099 atazanavir have produced significantly greater decline in the number of HIV-infected cells, both T-lymphocyte cells and macrophages in the spleen and lymph nodes and especially the actual viral production infected cells.
Infected untreated mice had cells by 40 1000 in its producing spleen HIV and actively by 50,3 1000 in their lymph nodes. With nanoATV alone, which was reduced to 4,0 and 10,8 1000 to spleen and lymph node, respectively, and less than and less than 0,1 2.3, respectively, when URMC-099 was added.
The researchers also conducted a series of experiments in which they infected mice with HIV after nanoATV and URMC-099 treatment, or as a way to prepare the therapeutic modulation. They first dosed mice with atazanavir alone nanoATV ordinary alone or this plus URMC-099. Then after drug withdrawal, they mice infected with HIV.
Drugs not actually present at the time of HIV infection do not prevent infection: but they reduced the number of cells with built-DNA HIV after infection starting copies of DNA 11,471 by 1000 cells with atazanavir (not ordinary best than no treatment) to 74 copies / 1000 cells nanoATV alone and 33 / 1000 with URMC-099. Not integrated into the viral RNA in cells decreased from 1100 1000 copies per cell with atazanavir 100 the ordinary copies / 1000células on nanoATV alone 19 copies / 1000 cells with added URMC-099.
Pre-infection treatment with the two drugs produced also has profound breaks the number of cells producing new virus. Only NanoATV produced 90,8, 94,2 and 95,7% decrease in active viral expression by cells depending on the dose (1, 10 and 100 micromoles of nanoATV respectively). Adding the URMC-099 produced further decreases in patients HIV expression by 63,8, 81,7, 97,8 and 91,3% respectively to four doses of URMC-099 (0,1, 1,0. 10 and 100 nanograms / ml respectively). This means that production after viral infection was reduced by 94,1% when the two lower doses of nanoATV and URMC-099 were used 99,6% when the two higher doses were used and 99,3% when the next two higher doses were used .
Since both drugs apodem dye this effect? As we said above, combining nano atazanavir formulated a folic acid molecule enabled the penetration of effective drug in cells; the nanoparticles are small enough even to get into organelles (cell components) where the cells and viral proteins are removed, copied and reassembled, but would not be eliminated quickly, as they would be if the drug molecules themselves would be if they were in context
organelle From Wikipedia, the free encyclopedia. (Redirected fromorganelles) Incell biology, organelles, organelles, or yetorganelles( "Small bodies") are bounded by membrane compartments have specific roles to play in the overall function of a cell. Organelles work in an integrated way, each taking one or more cellular functions. The name "organelle" comes from the idea that these structures are the parts of the cell, as the organs are to the body (hence the nameorganelle,the suffix-shebeing onediminutive). Organelles are identified bymicroscopyand can also be purified bycell fractionation. There are many types of organelles, particularly cellseukaryotic. whileprokaryoteslack organellesper seSome contain the basic microcompartimentosproteinsWhich are supposed to serve as primitive organelles.  Fonte Wikepedia. Pata learn more, click here.
Adding URMC-099 interrupted the process from the cells by pressing their "self-destruct button," when stimulated by inflammatory HIV proteins, and lived longer. The drugs suppressed joints specific cellular proteins which act as activators of immune response genes to treat HIV infection, making possible viral replication.
The measurements of the amount of the enzyme reverse transcriptase (RT) of HIV into cells has shown that with the two higher doses of URMC-099, activity was still repressed this process | RT | for five days after the last dose!
"This is the first formulation known to date (09 / 02 / 2016) of combinations capable to reach the lymph nodes of infected animals and reduce by more than 90%, the number of infectious viral particles," the researchers say. They aim to improve the directivity of the nanoATV fixing the protein components of HIV protective envelope to conduct further experiments in human cells.
Published: 05 2016 February
A note mine. Although to always be careful when I use that word to dream of 4 letters, I, the skeptic, I begin to see hope ****.
That's the most I can say
Translated and revised by Claudio Souza in the day dawn 09 February 2016 the original Combination nanotherapy angiograms drastically the amount of HIV produced by cells in mice
Tip Carlos jackson
Zhang G et al.The mixed lineage kinase-inhibitor URMC 3-099 Improves therapeutic outcomes for long-acting antiretroviral therapy. Nanomedicine 12, 109-122. 2016