How do Medicines Work?

I've always taken medicines for granted, not knowing how they actually work.  I was just researching online because this came up in mind to me, how I never understood how medicines actually work.

Medicines work in a variety of different ways.  The more common ones we take are used to: relieve pain, fight infection, fight diseases, and supplement a deficiency.  But how exactly do the medicines do these jobs?

Well, it all starts off by knowing what happens to the medicine when it enters your body.  There are four main parts to how medicines are processed by your body.  These include administration, delivery, performance, and elimination.

In order for all medicines to work, the must be absorbed into the blood. The most common type of medicine, an oral pill, goes into the stomach and then reaches the small intestine.  These medicines are then absorbed in the small intestine into the blood stream.  So basically, almost all medicines get absorbed into the bloodstream from the small intestine, or they are just injected directly into the bloodstream.

The full article can be found here.

Popeye the Chemist?

Children and adults alike have always been told to eat their vegetables. It has long been known that vegetables contain many essential vitamins and proteins that are beneficial to our bodys. But does anyone truly know just how necessary these yucky green plants are to our bodys? If there are any people who understand the benefits of vegetables, Popeye the Sailor definitely falls under this category. For years, Popeye has been chugging down his cans of Spinach, which have never failed to provide him with all the strength and energy required to be the main character of a television series. But how realistic are the benefits of Popeye's eating habits?

A new study from engineering researchers at Rensselaer Polytechnic Institute shows, for the first time, the benefits of spinach and broccoli for our bones. In essence, this study reveals how the little-understood protein osteocalcin plays a significant role in the strength of our bones.

Diagram portraying role of osteocalcin in bone (showing origins of bone fractures):

The significance in this study lies in the fact that it is the first study to ever implicate the role of osteocalcin in giving bone the ability to resist fracture. Since osteocalcin is always the point of fracture, strengthening this protein could lead to the overall strengthening of the bone. However, osteocalcin is also associated with Type 2 Diabetes and problems in reproductive health as well.

Thus, this study is not only promising for the strengthening of bones, but also for a better means of treating Type 2 diabetes and reproductive health issues. The findings of this research study are very promising, and could lead to new strategies and therapeutics for fighting osteoporosis and lowering the risks and pain associated with bone fractures.

 - Sam Choi

New Optical Tweezers for Trapping Specimens Just Nanometers Across

A novel technique has been created by chemistry researchers of Stanford University that poses a great potential leap in the chemistry world. This microscale technique known as "Optical Trapping" uses beams of light as tweezers to hold and manipulate tiny psrticles. This method allows scientists to Trap particles that are smaller than 10 nanometers. Up to this point in time, it was impossible even for top tier scientists with access to the best of technology to manipulate particles of such a small size. This developmet of a new method of trspping particles opens up a myriad of potential uses. The design for this light particle tool is near completion, and researchers expect to develop a prototype by early 2013. Here's a link to the original article: http://www.sciencedaily.com/releases/2012/12/121204154418.htm Stay updated for new posts coming soon! - Sammy C

Medicinal chemists receive 20 million euro grant to optimize drug binding kinetics

 Medicinal chemists receive 20 million euro grant to optimize drug binding kinetics

 In order for newly developed drugs to be used for treating people, these drugs have to pass certain tests to prove their efficiency. Often, the drugs are tested in labs to see if they work in lab experiments; if they succeed, they move on to clinical trials. If they are very successful in treating patients in these trials, then the drugs have a good chance of becoming legal in medicine. However, many drugs that seem successful in lab experiments do not succeed in clinical studies due to lack of effectiveness. There is mounting evidence that binding kinetics - the time a drug remains bound to its pharmaceutically relevant protein target - may be of greater importance for its effect in the patient than its binding affinity. The K4DD consortium, including medicinal chemists Iwan de Esch, Chris de Graaf, Martine Smit, and Rob Leurs, started last week to tackle this problem.
K4DD
The K4DD consortium is financially supported by Europe’s Innovative Medicines Initiative (IMI) programme and major pharmaceutical companies. "The 20 partners are the key players in their fields: world-leaders in medicinal chemistry and molecular pharmacology, involved in the structural elucidation of drug targets, and at the forefront of computational modeling and bio-analytical techniques. This ensemble of technologies allows the study of the drug-target interaction from the very first picoseconds to the eventual times of treatment."

The K4DD research consortium is funded by the Innovative Medicines Initiative (IMI), a joint undertaking between the European Union and the pharmaceutical industry association EFPIA.
Division of Medicinal Chemistry
Within the Division of Medicinal Chemistry of the Amsterdam Institute for Molecules, Medicines and Systems, funding of 825.000 euro will allow the development of new techniques to measure binding kinetics, as well as better understanding them. With this new understanding, scientists believe that K4DD will be able to create new drugs with "improved kinetic profiles," thus allowing the drugs to be more effective in clinical trials, allowing them to become official medicines.
For more information, visit  http://www.aimms.vu.nl/en/news-events/news-archive/2012/20-million-euro-grant-to-optimize-drug-binding-kinetics.asp

BioMAP screening = New Antibiotics

A really interesting article was posted recently on a scientific research news website. The article gave a summary of the work that researchers at University of California, Santa Cruz have undergone. The focus of their studies is BioMAP screening.

This novel screening procedure allows for new antibiotics to be discovered from natural sources, and in this case, especially marine natural products.

What makes this method of screening even more impressive is that it allows completely new types of antibiotics to be created. It's been a known issue in the field of medicine for bacteria and diseases to become resistant to antibiotics. Thus, by creating completely new types of antibiotics, the bacteria that is already used to conventional drugs will face much more difficulty in remaining resistant to drugs, or remaining alive for that matter.

If you guys have been updating yourselves regularly on our blog, you'll see that one of our latest posts was actually about the issue of how a bacteria gains resistance to drugs. If you've read that post, and understand the ideas behind it, you'll be able to understand how significant this method of BioMAP screening really is. Truly Amazing, and it seems to be very promising for the future creation of drugs!

'till next time,

peace, love, SammyC

(Choi)


P.S. here's the full article in case you guys want to see all the deets.

http://www.sciencedaily.com/releases/2012/11/121126131337.htm

The Chemistry of Pain Relievers

4-hydroxyacetanalide, or acetominophen is commonly used in pain relievers such as Tylenol.

The structure of acetominophen

 Acetominophen works as a pain reliever by inhibiting the creation of prostaglandins, which are chemical messengers that transmit pain signals.  Acetominophen blocks the signaling of these prostaglandins, bot does not block some other characteristics of them.  An example of this is that prostaglandins promote the inflammation of body tissues during injury, and acetominophen does not inhibit the swelling.
You can find more information at : http://www.chemistryexplained.com/A-Ar/Acetaminophen.html#b

Students Develop Molecule that Inhibits Influenza Virus

Faculty-directed undergraduate student researchers at Alma College have managed to develope a molecule that can inhibit certain strains of the influenza virus, three years after receiving a $150,000 National Science Foundation grant. By receiving the grant, the researchers managed to fund the project of synthesizing neuraminidase inhibitors that could guide the future development of antiviral drugs, according to principal investigator Jeff Turk.

 (Picture of Jeff Turk and his students researching medicinal drugs.)

According to Turk,“The influenza virus spreads in the body by an enzyme-mediated pathway. The neuraminidase enzyme found on the surface of the influenza virus is responsible, in part, for the spread of the virus. If we can create a molecule that inhibits the neuraminidase protein, we can slow or even halt the spread of the virus.”

Initially, Turk designed a computer model of small molecules with the potential to bind inside the neuraminidase protein, inhibiting the influenza infection. Over the course of the NSF grant, Turk and his students synthesized, evaluated and modified the molecules.

With his discovery, Turk intends to seek additional grant funding so as to be able to apply his research to the creation of medicinal drugs, while at the same time receiving endorsements from  James Stevens, a scientist and team lead in the Virology Surveillance and Diagnosis Branch of the Influenza Division at the Centers for Disease Control and Prevention, who intends to assist Turk in his research.

 Over the course of the NSF grant, 12 students have participated in the project, and 11 students have presented research findings at local and national American Chemical Society meetings. With the help of these students, Turk manages to get reinforcement on his research and enlighten their minds so that they may be able to achieve medical breakthroughs in the future.

“We have made significant progress on our research because of the efforts of our undergraduates students,” says Turk. “This is a culmination of only three summers of work, and the progress they have made is very commendable.”

With the introduction of undergraduate students into his research, and with additional funding, Turk believes that his research will manage to create a drug that suppresses several strains of the influenza virus better than other drugs for the virus.

For more information, visit the website: http://www.alma.edu/news/releases/archives/2012/11/16/drug_discovery

Found a cool article on how scientists use nanoparticles to fight off a virus!

       Many sexually transmitted diseases spread by bacteria, like syphilis and chlamydia, can be controlled and cured with antibiotics. By comparison, cheap and effective treatments for viral STDs have largely remained elusive. Researchers in Mark Saltzman’s lab are working to change that, developing nanoparticles to prevent infection by a widespread viral STD: herpes simplex virus type 2.
HSV-2 is unfortunately common in the United States. About one of every six people between the ages of 14 and 49 years has a genital herpes infection, and while the infection can be managed with treatment, it can’t be cured. Worse, HSV-2 leaves individuals more vulnerable to additional infections, including HIV.

        Saltzman, the Goizueta Foundation Professor of Biomedical Engineering, and the Chemical & Environmental Engineering & Physiology, has developed nanoparticles that deliver molecules to the potential infection site with the hope of preventing and treating HSV-2 infection.
In a paper in the Journal of Controlled Release, Saltzman and colleagues demonstrate that topical administration of their nanoparticles can improve survival after HSV-2 infection in mice. The nanoparticles carry short interfering RNA (siRNA) molecules that have been shown to interfere with nectin-1, a protein involved in HSV-2 infection and cell-to-cell transmission. In their experiments, the researchers showed that their nanoparticles can both prevent lethal infection with HSV-2 in mice and increase survival time when administered in 3 applications, before and after infection.

       “This work provides proof-of-concept that these siRNA delivery vehicles are promising options for topical, localized therapeutics for sexually transmitted infections,” says Jill Steinbach, a postdoctoral researcher in Saltzman’s group and the lead author of the paper. “We are excited to see such encouraging results of decreased symptoms associated with infection, and enhanced survival out to an unprecedented duration of 28 days.”

        Critically, the nanoparticles also improved survival time without causing inflammation at the administration site, which can leave patients vulnerable to additional infections and has been a problem with previous experimental efforts.

         Further, the researchers’ nanoparticles, made from polylactic-co-glycolic acid (PLGA), use materials that have already been approved by the FDA, which could facilitate faster approval of treatments for humans down the road, whether they are to be used against HSV-2 or additional pathogens.

        “We are encouraged in the potential of these tunable PLGA nanoparticles to provide a safe, durable, and non-toxic alternative to other microbicides that have been shown to promote infection through inflammation of the intravaginal tract,” says Steinbach. “Currently, we seek to enhance nanoparticle delivery by using a variety of surface modifications that enable increased cell penetration, while obtaining a better understanding of how the delivery vehicles interact with the cell to exert their effect. We are hopeful to further improve delivery of these materials and apply them to a wide range of pathologies in global health.”

Here is a picture showing an siRNA complex at work:


More info can be found from http://seas.yale.edu/news-events/news/biomedical-engineers-develop-nanoparticles-fight-persistent-viral-infections

Making us Stronger from the Inside

      Most traditional antivirals target the virus themselves by partially inhibiting their methods of reproducing.  However, a new study has found a way to help boost our natural immunity, boosting the protective capabilities of our cells.  Researchers at the Washington University School of Medicine were able to find a drug that is capable of boosting our natural immunity through an automated screening technique capable of screening large quantities at the same time.  The researchers screened 2,240 compounds and found 64 that helps to enhance our natural response to viral infections.  These drugs do this by enhancing cells' interferon system.  Out of these drugs, the most notable one found was idarubicin, a drug normally used to treat for cancer by preventing cells from dividing.  I think that this discovery is amazing, as it allows for a more broader view for finding antivirals, that not only target the viruses, but our own cells and so that we can be more protected and ready against viral invasions.

Chemistry For a Healthier World

An article on drugs, and their intended method of treating symptoms/diseases. I found it interesting how the article breaks down all aspects of a drugs use, how a drug is made, and how a drug functions in terms of chemistry. One of the most interesting things mentioned in the article are about resistance. When illnesses/diseases are treated with drugs, the weaker strains of bacteria are killed, but the stronger ones remain. This poses a huge problem since the stronger strains quickly multiply to form a large group of strains only made of the drug resistant bacteria. Chemists are learning to prevent this from occurring, and have already solved this problem in many aspects of drug use. The question is, when will chemists be able to solve this problem for all drugs being used?

Here is a picture of some drug-resistant bacteria:



This article really ties together the key ideas of our blog, so go on and check this article out y'all!
You can find it in the link below:

http://publications.nigms.nih.gov/chemhealth/med.htm


keep yourselves updated, and check back soon for my next blog post

'till next time,

peace, love, sammywhammy

A new field of chemistry has arrived to the medical scene - bioorthogonal chemistry - in which the medicines are made inside of a patient.  Carolyn Bertozzi, founded this field of chemistry around ten years ago at the 243rd National Meeting and Exposition of the American Chemical Society.  Bertozzi explains that the advantage of this new field of chemistry is that it allows medicines to be produced inside the patient, allowing proper dosage of drugs.  She gives the example in which bioorthogonal chemistry would solve the problem of various drugs that do not reach targeted tissues in high enough concentrations.  Not only would bioorthogonal chemistry help solve dosage problems, but it would also help fight viruses as well.  Bertozzi states that this new field allows us to create proteins, fats, and sugars without harming the actual cells.  Since viruses invade cells through glycans, one could prevent the infection of viruses using bioorthogonal chemistry

Here is a picture of Bertozzi explaining bioorthogonal chemistry:



I think that this new development is amazing.  First of all, just thinking of the medicine forming in your body just sounds so futuristic.  Secondly, this development will help solve problems that one would not be able to fix today such as the drug dosage issue Bertozzi raised and preventing the invasion of viruses.

Here's a neat article:

Results of a new study demonstrate the feasibility of a novel strategy in drug discovery: screening large numbers of existing drugs — often already approved for other uses — to see which ones activate genes that boost natural immunity.

Using an automated, high-volume screening technique, researchers at Washington University School of Medicine in St. Louis have identified a cancer drug that enhances an important natural response to viral infection in human cells.

“Over many years of research, we have developed a good understanding of the human body’s own mechanisms to fight viruses,” says the study’s first author Dhara Patel, PhD, a postdoctoral research scholar at Washington University. “Instead of targeting the virus itself, which most current antiviral drugs do, we have designed a strategy to look for chemical compounds that will enhance this innate antiviral system.”

The results of the study, led by Michael J. Holtzman, MD, the Selma and Herman Seldin Professor of Medicine, appear May 4 in PLoS ONE.

Of the 2,240 compounds the researchers tested, 64 showed increased activity in the cells’ interferon signaling pathway, an important player in the body’s response to viruses. The 64 compounds included many different classes of drugs treating conditions as diverse as depression, high blood pressure and ulcers. But the one that stood out is idarubicin, a cancer drug commonly prescribed to treat leukemia, lymphoma and breast cancer. Even at low doses, idarubicin significantly ramps up the interferon signaling system.

In treating cancer, idarubicin stops cells from dividing by blocking a protein that unwinds DNA. As long as DNA remains tightly packed, it can’t be copied. And if DNA can’t be copied, a cell can’t divide. Interestingly, though, the researchers showed that idarubicin’s antiviral effects are totally unrelated to what makes it a good cancer drug.

Like many cancer drugs, idarubicin has toxic side effects, so it is unlikely to ever be prescribed for patients fighting viral infections. But, its identification demonstrates that the new strategy works.“We tested other cancer drugs that work the same way as idarubicin but have very different structures,” Patel says. “Although they act the same way that idarubicin does in cancer cells, they had no effect on the interferon system.”

“While idarubicin is not something you would give to a patient who has the flu, we are continuing to screen more drugs,” Patel says. “We’re starting to find compounds from different drug classes that are not so toxic and that have similar properties in enhancing interferon signaling. We’re still validating them, but we’re very excited about what we’re finding.”

Traditionally, techniques for drug discovery involve trying to enhance or inhibit a very specific interaction. To treat a particular disease, scientists might try to disable a harmful protein, or replace a missing one, for example. But such approaches assume that altering a specific interaction of interest will result in the desired effect.

“I think our technique accepts the fact that we don’t understand everything that’s going on in the cell,” Patel says. “Instead of looking at one particular interaction, we measure the downstream effects.”

She compares it to driving a car and trying to make it go faster.

“Traditionally, we would pick a specific part — a part of the car that we think is responsible for speed — and then test compounds that alter the part in a way that we think will make the car go faster,” she says. “With our approach, we don’t assume we know what is responsible for speed. Instead, we take entire cars, treat them with many different compounds, and just see which ones go faster.”

Patel says this screening technique is unusual because it can identify drugs that enhance the body’s own immune response to a broad range of viruses, unlike a vaccine, which only protects against a specific virus.

The method has also shed light on how some compounds with known antiviral properties actually fight viruses. In addition to cancer drugs, antidepressants and blood pressure medications, the initial 64 drugs they identified with increased interferon activity included some known antiviral drugs.

“We already knew some of these compounds had antiviral properties, we just didn’t know why,” Patel says. “Now we’re starting to find out how they actually work.”

---

Patel DA, Patel AC, Nolan WC, Zhang Y, Holtzman, MJ. High throughput screening for small molecule enhancers of the interferon signaling pathway to drive next generation antiviral drug discovery. PLoS ONE. May 4, 2012.

The full text will be available after 5 p.m. EDT Friday, May 4, 2012, at

‪http://dx.plos.org/10.1371/journal.pone.0036594‬.

This work was supported by grants from the National Institutes of Health (NIH), including the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Disease (NIAID), and the Martin Schaeffer Fund.

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

This is a cool article Sam Choi found:

ScienceDaily (Mar. 26, 2012) — The traditional way of making medicines from ingredients mixed together in a factory may be joined by a new approach in which doctors administer the ingredients for a medicine separately to patients, and the ingredients combine to produce the medicine inside patients' bodies.

That's one promise from an emerging new field of chemistry, according to the scientist who founded it barely a decade ago. Carolyn Bertozzi, Ph.D., spoke on the topic -- bioorthogonal chemistry -- in San Diego on March 27 in delivering the latest Kavli Foundation Innovations in Chemistry Lecture at the 243rd National Meeting & Exposition of the American Chemical Society (ACS).

Bertozzi explained that the techniques of bioorthogonal chemistry may fundamentally change the nature of drug development and diagnosis of disease, so that the active ingredients for medicines and substances to image diseased tissue are produced inside patients.

"Suppose a drug doesn't reach diseased tissue in concentrations high enough to work," Bertozzi said, citing one example of the potential of the new chemistry. "Maybe it is an oral drug that doesn't get absorbed very well into the blood through the stomach. You can imagine a scenario in which doctors administer two parts of the molecule that makes up the drug. The two units reach diseased tissue in large amounts or get absorbed through the stomach just fine. Then they recombine, producing the actual drug in the patient's body. Bioorthogonal chemistry is chemistry for life…literally!"

Bertozzi explained that bioorthogonal chemistry opens the door to creating new proteins, fats and sugars directly inside living cells without harming them. The field emerged from her frustration in the late 1990s with the lack of tools available to see sugars on the surfaces of living cells. Chains of these sugars, called glycans, sit on the surfaces of cells in the body and control the doorways through which different molecules enter. When a disease-causing virus enters and infects a cell, for instance, proteins on the virus's surface attach to certain glycans.

"To do that, we had to come up with a chemical reaction that would be really selective, only targeting the sugar of interest and the fluorescent probes that we delivered to it," said Bertozzi. The chemicals also couldn't stick to other biomolecules that the researchers didn't want to see.

That turned out to be a tall order, indeed. "We pulled all of our big textbooks off the shelves and flipped through them to see if there was something out there that fit our criteria," she said. Those criteria were essentially the conditions inside a living cell or living organism such as a mouse -- a reaction that could occur in water at pH 7 and at 98.6 degrees Fahrenheit. The reaction also couldn't interfere with all the other biomolecules in a cell or organism that keep it alive.

"It was a pretty restrictive set of conditions that a traditionally trained organic chemist like me never had to work within," she explained. That's because these types of reactions are usually performed in very clean, dry test tubes and flasks under conditions that the chemist can control. A living cell or organism, with all its water, proteins, fats, sugars and metabolites is very messy and uncontrollable by comparison.

Bertozzi and her team at the University of California, Berkeley, went on to develop a slew of reactions that can add fluorescent labels to biomolecules.

Now, the field is exploding, with her group and others reporting new bioorthogonal chemical reactions every year that help researchers see sugars, fats, proteins, and even DNA and RNA, that can't be seen using conventional methods. Researchers currently use the reactions not only to see where a biomolecule is within a living cell or organism, but also to determine when a biomolecule is made and what it binds to. Researchers also are using the methods to add things besides labels, like drugs, to various biomolecules. Some of the chemicals used for the reactions are currently available separately or in kits.

Several of Bertozzi's reactions are patented, and some are licensed to companies, including Redwood Bioscience, a company she co-founded with David Rabuka, Ph.D. The company is focused on bringing this technology to the clinic.

The scientists acknowledged funding from the National Institutes of Health and the Howard Hughes Medical Institute.

Take a look at this neat article I found:

US scientists have developed a method to deliver probes into cells to track the cells. Therapies such as those based on stem cells that require whole body tracking using non-invasive imaging, for example magnetic resonance imaging (MRI), would benefit from the probes.

Current nanoparticle-based tracking systems rely on probes entering cells passively, which is inefficient because the probes often get sequestered in endosomes (compartments in cells that sort molecules for degradation or recycling back to the cell membrane). Now, a team from the Lawrence Berkeley National Laboratory led by Brett Helms has avoided this problem by coating a nanocrystal probe with a polymer vector colloid and attaching guanidine and amine groups to the polymer so that the whole thing mimics a virus.

'In this manner, we would be able to recapitulate a virus' ability to quickly enter cells - in our case, with nanocrystal imaging probes as cargo,' explains Helms. Nanocrystal probes are desirable because they can be tailored for specific imaging techniques such as MRI or whole-body fluorescence imaging.

The team also found that as well as providing an exceptionally fast cell-entry trajectory, the coating prevented the nanocrystal cargo from having a negative impact on long-term cell health. 'We hypothesised that this is related to the shorter residence time of the vector-bound nanocrystals in endosomes, where they can degrade in the acidic microenvironment into toxic ions,' explains Helms, 'and the ability of the vector to keep the nanocrystals from diffusing widely in the cell's interior, where they can be expected to disrupt cellular processes.'

'The colloidal polymer vectors will make a significant difference in the field of cancer biology, as they present an unique opportunity to track different cell types in vivo for analysis,' says Eva Harth, an expert in developing vectors for imaging reagents at Vanderbilt University, US. 'The combination of nanocrystal confinement in the colloidal vector, rapid uptake and a high overall nanocrystal concentration in intact cells makes the luminescence of the localisation pattern in the cystosol [the liquid inside cells] much more intense. With this, an entire new arena of in vivo cell tracking and analysis is possible and can be further developed for other imaging devices with greater tissue depth.' 

Helms' team now plans to implant and image probes in mice to prove that they are ready to be used for cell tracking.

Making Drugs Inside Patients

A very interesting article on new research being done through chemistry. A new field of chemistry can potentially be used to create drugs inside patients.

http://www.sciencedaily.com/releases/2012/03/120327091055.htm