County Summits Convene and Pharmacies Use RX Bags w/
Don’t Share Message This Month
Data indicate social access (sharing) is a major contributor to the misuse of prescription drugs. According to the National Survey on Drug Use and Health, most prescription drug abusers obtain their drugs from family and friends. In WV, 64% of nonmedical users of pain relievers reported getting the most recently used drug from a friend or relative for free, and another 7.6% reported buying them from a friend or relative.
Take Care WV, a statewide prescription drug abuse prevention campaign, continues this month through county summits and online pharmacy viagra distribution of RX bags with the “Don’t share RX medication.” message.
“This campaign is aimed at changing social/culture norms about sharing prescription drugs,” said Dr. Andy Whisman, Senior Evaluation Specialist with the WV Prevention Resource Center. “West Virginians are a caring people who want to help one another out when the can. Sharing prescriptions, however, is illegal and can be dangerous.”
COMMUNITY DISCUSSIONS/ COUNTY-WIDE SUMMITS: Three dozen (36) counties have partnered with the WV Prevention Resource Center and WV Center for Civic Life to convene multiple discussions and county-wide summits about what communities can do about prescription drug abuse. The community discussions took place across the state this summer, and the summits are set for this month. Additional information about these events (including dates/times/locations/forum participant booklets/forum starter video) is available at www.prevnet.org/communityforums.aspx.
RX BAGS FOR PHARMACIES: All of WV’s 55 counties are participating in statewide use of pharmacy bags with the Take Care WV logo/website/message. Earlier this summer, county partners received large quantities of RX bags (the white paper ones you get your prescriptions in) to distribute to local pharmacies willing to participate. Most pharmacies,
including many individual stores and major chains such as Rite Aid, Walmart/Sam’s Club, Kroger, Fruth, are participating in this effort to make sure all West Virginian’s know it is illegal to share prescription medication, and RX misuse and abuse can be just as dangerous and deadly as illicit drug use. The bags also include the statement: Only take prescription medication as advised by your doctor.
PUBLIC SERVICE ANNOUNCEMENTS / WEBSITE: In addition to the forums/summits and RX bags, the Take Care WV campaign includes public service announcements (PSAs) and a website. Television, radio, and print ads were developed and are available to download online. During a five-week paid media placement earlier this summer the television PSAs aired more than 3,000 times on cable and broadcast stations across WV. The PSAs are also being distributed by local prevention and media partners. The website links to all PSAs, RX drug facts/statistics, information about proper RX storage and disposal, and a link to the WV Prescription Drug Abuse Quitline.
The Take Care WV Campaign, developed and implemented by the WV Partnership to Promote Community Well-Being and the WV Prevention Resource Center, has been supported with funding from the following grants: 2009 Drug Free WV Grant, WV’s federal Strategic Prevention Framework State Incentive Grant (SPF SIG), and WV’s federal Projects of Regional & National Significance (PRNS) Grant.
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Erectile Dysfunction—Urgent Care for Men in NYC
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In years past it was called impotence, but things have changed. In the past men who suffered from this malady—and their wives—would have to suffer through it in silence and sometimes shame. Medical advances have taken a turn for the best when it comes to husbands and wives and their most intimate of moments.
There is no denying that a healthy sex life is paramount to a positive marital experience. With that fact stated, it is (pardon the pun) hard to understand why any man would allow this issue to separate a himself from his beloved.
Many things can cause erectile order cialis (ED) in a seemingly healthy man. These things include--but are not limited to--injury to the affected area, and the taking of prescription drugs for other issues altogether. Many pharmaceuticals come with the warning that the users’ libido may be affected to some degree. Diabetes is another major cause of ED. In fact, some reports list the percentage of men with diabetes--who at some point in their treatment suffer from ED--as high as 75%. Kidney disease is another cause of this particular illness, because of it affects nerve function and circulation. Hardening of the arteries and hypertension also routinely affects a man’s ability to achieve a viable erection.
The medical establishment has grown tremendously when it comes to their approaches toward righting this wrong. Long ago was the day that men were advised to eat a dozen oysters before they attempted to enjoy their amorous attentions. Today there are several highly effective methods to negate the negative impact of ED. Viagra happens to be the most publicized of the bunch and it also garnered so much attention due the fact that it was the first of its kind to hit the market.
A doctor can assess your overall medical condition and prescribe the best ED medication for you. One of the best places to receive such a diagnosis is Urgent Care of NYC located on Madison Avenue in the heart of Manhattan. This center is one of a kind and offers such services as a guaranteed personal one-on-one with a board certified doctor, not a nurse practioner, as in many other places. They are clean, neat and up-to-date with all their approaches and equipment, and deliver the kind of personal care that is sorely lacking in the medical field these days. NYC Urgent Care accepts most insurance and also offers an affordable walk-in fee of just ninety-nine dollars if you happen to be uncovered at this time.
It is understood how important intimacy is to couples. Intimacy produces the emotional fulfillment that is so important between a man and a woman. ED should not come in the way of an otherwise loving and close relationship. ED is treatable in any number of simple ways, and any man quietly suffering through it should contact Urgent Care of New York immediately to get their love life back on track. Just call 212-696-5900 or log on to Walk-in-Clinic-NY.com to quickly book a same day appointment--and get back what you’ve been missing.
Drugs disrupt DHFR dynamics
One of the most-studied cases of the relationship between dynamics and catalysis is the bacterial dihydrofolate reductase (DHFR). DHFR catalyzes the reduction of dihydrofolate to tetrahydrofolate while oxidizing the cofactor nicotinamide adenine dinucleotide phosphate (NADPH). As part of this catalytic process, a region of the protein called the "Met 20 loop" switches from a "closed" state that shields the active site from solvent to an "occluded" state that separates the substrate from the cofactor. NMR studies of DHFR structural dynamics have correlated the protein motions with the chemical changes. In a recent study appearing in Structure, researchers from the University of North Carolina show that the binding of inhibitors such as methotrexate (MTX) and trimethoprim (TMP) appears to uniquely disrupt the dynamic networks of DHFR.
Previously, seminal work from the lab of Peter Wright surveyed the dynamics of DHFR in every step of its reaction pathway. Boehr et al. determined that structural fluctuations in each complex represented motions towards the next step in the reaction. The conformational exchange rates they obtained from their relaxation-dispersion experiments closely resembled the rate constants that had been independently determined for the chemical steps. In almost every complex the conformational exchange was widespread, affecting residues in both the substrate and cofactor binding sites, as well as important distal locations such as the Met 20 loop.
Because the existing work from the Wright lab hewed as close to the natural substrates and products as possible, Mauldin et al. chose to examine the dynamic effects of cheap cialis binding to DHFR. Like Wright's group, they used relaxation-dispersion experiments to identify conformational changes taking place on the μs-ms timescale. In the NADPH:DHFR complex the motions are widespread, encompassing the substrate binding site, the Met 20 loop, and distal locations. Binding of either cialis eliminates about half of this dynamic network and dramatically reduces the fluctuation rates of those residues for which conformational exchange continues to occur.
Based on their fits of the exchange rates, Mauldin et al. conclude that the substrate binding pocket moves in a way that mimics the enzyme's normal motions in the transition from its closed state to its occluded state. The long-range conformational changes that actually complete this transition, however, have been completely quenched. With the inhibitors bound, DHFR is like a car that's turning over but won't start. Part of the enzyme is still moving in exactly the right way to proceed along the reaction coordinate, but for some reason this motion doesn't catch on throughout the protein.
In order to gain a more complete understanding of the dynamic effects, Mauldin et al. performed experiments to identify the motion of the protein on the ps-ns timescale. Analyzing the dynamics of methyl and amide resonances using the Lipari-Szabo model-free formalism, the authors realized that inhibitor binding did cause long-range changes in dynamics, just in a faster regime. Where the natural substrate complexes have motions that occur hundreds or thousands of times per second, the inhibitor-bound forms have (smaller) motions that occur millions of times per second. Because these altered motions encompass the Met 20 loop and surrounding residues, the authors argue that they reflect abortive attempts by the protein to transition into the occluded state.
Although these inhibitors do not appear to change the protein's overall conformation, they produce long-range dynamic effects on short timescales and quench distal motions on intermediate timescales. The binding pocket appears to still be experiencing fluctuations related to the transition between the closed and occluded conformational states, but the mechanism that couples the binding site dynamics to the motion of the loop that defines these two states appears to be broken.
The million-dollar question is this: do drugs alter DHFR dynamics because they inhibit the chemistry, or do these drugs inhibit the chemistry because they alter DHFR dynamics? Quenching dynamics costs energy in the form of conformational entropy, and it may be possible to tune a drug for improved efficiency by blocking the binding site without altering the dynamics. This is only true, however, if the dynamics don't matter to successful inhibition. On the other hand, if blocking the conformational switching of the Met 20 loop inhibits the enzyme, then drugs can be designed for that angle of attack as well. In the case of a protein like DHFR, where the bacterial enzyme has similar activity but a very different structure from its human equivalent, drugs that target regions other than the active site may significantly reduce side-effects. As a result, protein targets that were previously off-limits due to shared chemistry may become tractable due to divergent dynamics and structure.
Mauldin, R., Carroll, M., & Lee, A. (2009). Dynamic Dysfunction in Dihydrofolate Reductase Results from Antifolate Drug Binding: Modulation of Dynamics within a Structural State Structure, 17 (3), 386-394 DOI: 10.1016/j.str.2009.01.005
Boehr, D., McElheny, D., Dyson, H., & Wright, P. (2006). The Dynamic Energy Landscape of Dihydrofolate Reductase Catalysis Science, 313 (5793), 1638-1642 DOI: 10.1126/science.1130258
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