Health and Medical News and Resources

General interest items edited by Janice Flahiff

[Research article summary] First major analysis of Human Protein Atlas published, could explain many drug side effects

From the 23 January 2015 KTH article

A research article published today in Science presents the first major analysis based on the Human Protein Atlas, including a detailed picture of the proteins that are linked to cancer, the number of proteins present in the bloodstream, and the targets for all approved drugs on the market.

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The Human Protein Atlas, a major multinational research project supported by the Knut and Alice Wallenberg Foundation, recently launched (November 6, 2014) an open source tissue-based interactive map of the human protein. Based on 13 million annotated images, the database maps the distribution of proteins in all major tissues and organs in the human body, showing both proteins restricted to certain tissues, such as the brain, heart, or liver, and those present in all. As an open access resource, it is expected to help drive the development of new diagnostics and drugs, but also to provide basic insights in normal human biology.

The analysis shows that almost half of the protein-coding genes are expressed in a ubiquitous manner and thus found in all analysed tissues.

The analysis suggests that approximately 3,000 proteins are secreted from the cells and an additional 5,500 proteins are located to the membrane systems of the cells.

“This is important information for the pharmaceutical industry. We show that 70% of the current targets for approved pharmaceutical drugs are either secreted or membrane-bound proteins,” Uhlén says. “Interestingly, 30% of these protein targets are found in all analysed tissues and organs. This could help explain some side effects of drugs and thus might have consequences for future drug development.”

The analysis also contains a study of the metabolic reactions occurring in different parts of the human body. The most specialised organ is the liver with a large number of chemical reactions not found in other parts of the human body.
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The study has been carried out by researchers in Sweden at KTH Royal Institute of Technology, Uppsala University, Karolinska Institute, Chalmers University of Technology, Lund University, and Stockholm University.

 

 

January 28, 2015 Posted by | Medical and Health Research News | , , , , , | Leave a comment

Aspirin to Zoloft: Ways Medicines Work

From the 8 August 2013  US National Library of Medicine article

Most medicines work by binding to and modifying the actions of proteins, tiny molecular machines that perform important cellular tasks. Details about protein structure and function help scientists develop medicines that block proteins or otherwise interact with them. But even when a drug is designed to target a specific protein, it can sometimes impact others, causing side effects. The way medicines work also can be influenced by how a person’s body absorbs and processes them.

Findings from research funded by the National Institutes of Health have shed light on how some common medicines work.

HIV protease with saquinavir.

HIV protease with saquinavir.
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Antibiotics, Antivirals

Antibiotics and antiviral drugs attack proteins that are only found in the targeted bacterium or virus and that are crucial for the pathogen’s survival or multiplication. In many cases, the targets are enzymes, which are proteins that speed up chemical reactions. The antibiotic penicillin, for example, hones in on an enzyme that builds bacterial cell walls, causing infecting bacteria to burst and die. Protease inhibitors like saquinavir shut down an enzyme that would otherwise help HIV spread in the body.

Anticancer Agents

Tubulin with taxol.

Tubulin with taxol.
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Many anticancer drugs act by killing cells that divide rapidly, but they can also affect healthy dividing cells. For example, paclitaxel (Taxol), which is prescribed for breast, ovarian and other cancers, works by binding to the tubulin protein, inhibiting the formation of structures called microtubules that are needed for cell division. Newer anticancer drugs are more discriminating, often targeting important proteins that are abnormally active in certain cancers. One such drug, imatinib mesylate (Gleevec), halts a cell-communication pathway that is always “on” in a cancer of the blood called chronic myelogenous leukemia. Gleevec’s target is a protein called a kinase, and the drug’s design is based on years of experiments on the basic biology of how cancer cells grow.

Antihistamines, Antidepressants, Aspirin

Adrenergic receptor with carazolol, a beta-blocker.

Adrenergic receptor with carazolol, a beta-blocker. View larger image.

Some of the most widely prescribed drugs function by blocking proteins called G protein-coupled receptors, which play key roles in transmitting the signals that allow a cell to respond to its environment. The drug loratadine (Claritin) relieves allergies by blocking the histamine receptor; antidepressant medications (such as Prozac, Paxil and Zoloft) affect the serotonin receptor; and beta-blockers treat heart disease by interfering with the adrenergic receptor. Signaling can also be stopped by targeting the enzymes that create a molecule involved in the process. This is how aspirin works—it inhibits the enzyme cyclooxygenase, which makes pain-signaling molecules called prostaglandins.

Weight Loss, Cholesterol Blockers

Pancreatic lipase with an inhibitor similar to orlistat.

Pancreatic lipase with an inhibitor similar to orlistat.
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Medicines taken to control weight or cholesterol also work by interacting with specific proteins. The weight-loss drug orlistat (Xenical or Alli) blocks the action of pancreatic lipase, reducing the amount of fat that is absorbed from food. Cholesterol-lowering medications, such as atorvastatin (Lipitor) and simvastatin (Zocor), block the action of HMG-CoA reductase, an enzyme involved in making cholesterol.

Future Directions

With a better understanding of the specific relationships between a drug and its target (and off-target) proteins, researchers are using a variety of existing data to identify and test FDA-approved drugs for new uses and to predict potential side effects. This could reduce the time and cost of bringing drugs to market. Scientists are also learning more about how a person’s genes may influence the effectiveness and safety of certain drugs. Another area of active research involves developing new ways to deliver drugs to specific organs or disease sites, also improving therapeutic benefits and reducing side effects.

Content adapted from the poster “How Do Drugs Work?” available from the RCSB Protein Data Bank. Images courtesy of David S. Goodsell, The Scripps Research Institute.

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This Inside Life Science article also appears on LiveScience Link to external Web site.

 

August 25, 2013 Posted by | Educational Resources (High School/Early College(, Health Education (General Public) | , , , , , , , , , , , , | Leave a comment

Internet search data and unreported side effects of drugs

Public Health--Research & Library News

A very interesting use of crowdsourcing for medical research.

Using data drawn from queries entered into Google, Microsoft and Yahoo search engines, scientists at Microsoft, Stanford and Columbia University have for the first time been able to detect evidence of unreported prescription drug side effects before they were found by the Food and Drug Administration’s warning system.

Using automated software tools to examine queries by six million Internet users taken from Web search logs in 2010, the researchers looked for searches relating to an antidepressant, paroxetine, and a cholesterol lowering drug, pravastatin. They were able to find evidence that the combination of the two drugs caused high blood sugar.

The study, which was reported in the Journal of the American Medical Informatics Association [White, R.W. et al. Web-scale pharmacovigilance: listening to signals from the crowd. J Am Med Inform Assoc doi:10.1136/amiajnl-2012-001482] on Wednesday, is based on data-mining techniques similar to those…

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March 22, 2013 Posted by | Consumer Health | , , , , , , | Leave a comment

   

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