SIMPLE METHOD TURNS HUMAN SKIN CELLS IN TO IMMUNE STRENGTHENING WHITE BLOOD CELLS

For the first time, scientists have turned human skin cells into transplantable white blood cells, soldiers of the immune system that fight infections and invaders. The work, done at the Salk Institute, could let researchers create therapies that introduce into the body new white blood cells capable of attacking diseased or cancerous cells or augmenting immune responses against other disorders

The work, as detailed in the journal Stem Cells, shows that only a bit of creative manipulation is needed to turn skin cells into human white blood cells.

"The process is quick and safe in mice," says senior author Juan Carlos Izpisua Belmonte, holder of Salk's Roger Guillemin Chair. "It circumvents long-standing obstacles that have plagued the reprogramming of human cells for therapeutic and regenerative purposes."

Those problems includes the long time -- at least two months -- and tedious laboratory work it takes to produce, characterize and differentiate induced pluripotent stem (iPS) cells, a method commonly used to grow new types of cells. Blood cells derived from iPS cells also have other obstacles: an inability to engraft into organs or bone marrow and a likelihood of developing tumors.

The new method takes just two weeks, does not produce tumors, and engrafts well.

"We tell skin cells to forget what they are and become what we tell them to be -- in this case, white blood cells," says one of the first authors and Salk researcher Ignacio Sancho-Martinez. "Only two biological molecules are needed to induce such cellular memory loss and to direct a new cell fate."

Belmonte's team developed the faster technique (called indirect lineage conversion) and previously demonstrated that these approaches could be used to produce human vascular cells, the ones that line blood vessels. Rather than reversing cells all the way back to a stem cell state before prompting them to turn into something else, such as in the case of iPS cells, the researchers "rewind" skin cells just enough to instruct them to form the more than 200 cell types that constitute the human body.

The technique demonstrated in this study uses a molecule called SOX2 to become somewhat plastic -- the stage of losing their "memory" of being a specific cell type. Then, researchers use a genetic factor called miRNA125b that tells the cells that they are actually white blood cells.

The researchers are now conducting toxicology studies and cell transplantation proof-of-concept studies in advance of potential preclinical and clinical studies.

"It is fair to say that the promise of stem cell transplantation is now closer to realization," Sancho-Martinez says.

Study co-authors include investigators from the Center of Regenerative Medicine in Barcelona, Spain, and the Centro de Investigacion Biomedica en Red de Enfermedades Raras in Madrid, Spain.

A Simple Description Of Neuropathy

Today's post from holisticlifestylecommunityblog.blogspot.com (see link below) is a comprehensive yet simply explained description of neuropathy in all its forms. You should be able to find your own form of neuropathy here, plus a simple explanation of how it differs from others. Well worth a read for both people new to the disease and people who already have some knowledge. The live links and references have been left in because a) they are very useful for your further research and b) they give verification to the post. Absolutely one of the best descriptions of the condition to be found on this blog.

Peripheral Neuropathy

Posted by Holistic Lifestyle Community Blog THURSDAY, FEBRUARY 2, 2012

Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness.

The four cardinal patterns of peripheral neuropathy are polyneuropathy, mononeuropathy, mononeuritis multiplex and autonomic neuropathy. The most common form is (symmetrical) peripheral polyneuropathy, which mainly affects the feet and legs. The form of neuropathy may be further broken down by cause, or the size of predominant fiber involvement, i.e., large fiber or small fiber peripheral neuropathy. Frequently the cause of a neuropathy cannot be identified and it is designated idiopathic.

Neuropathy may be associated with varying combinations of weakness, autonomic changes, and sensory changes. Loss of muscle bulk or fasciculations, a particular fine twitching of muscle, may be seen. Sensory symptoms encompass loss of sensation and "positive" phenomena including pain. Symptoms depend on the type of nerves affected (motor, sensory, or autonomic) and where the nerves are located in the body. One or more types of nerves may be affected. Common symptoms associated with damage to the motor nerve are muscle weakness, cramps, and spasms. Loss of balance and coordination may also occur. Damage to the sensory nerve can produce tingling, numbness, and pain. Pain associated with this nerve is described in various ways such as the following: sensation of wearing an invisible "glove" or "sock", burning, freezing, or electric-like, extreme sensitivity to touch. The autonomic nerve damage causes problems with involuntary functions leading to symptoms such as abnormal blood pressure and heart rate, reduced ability to perspire, constipation, bladder dysfunction (e.g., incontinence), and sexual dysfunction.

Classification

Peripheral neuropathy may be classified according to the number of nerves affected or the type of nerve cell affected (motor, sensory, autonomic), or the process affecting the nerves (e.g. inflammation in neuritis).

Mononeuropathy

Mononeuropathy is a type of neuropathy that only affects a single nerve. It is diagnostically useful to distinguish them from polyneuropathies, because the limitation in scope makes it more likely that the cause is a localized trauma or infection. The most common cause of mononeuropathy is by physical compression of the nerve, known as compression neuropathy. Carpal tunnel syndrome is one example of this. The "pins-and-needles" sensation of one's "foot falling asleep" (paresthesia) is caused by a compression mononeuropathy, albeit a temporary one which can be resolved merely by moving around and adjusting to a more appropriate position. Direct injury to a nerve, interruption of its blood supply (ischemia), or inflammation can also cause mononeuropathy.

Mononeuritis multiplex

Mononeuritis multiplex is simultaneous or sequential involvement of individual noncontiguous nerve trunks, either partially or completely, evolving over days to years and typically presents with acute or subacute loss of sensory and motor function of individual nerves. The pattern of involvement is asymmetric, however, as the disease progresses, deficit(s) becomes more confluent and symmetrical, making it difficult to differentiate from polyneuropathy. Therefore, attention to the pattern of early symptoms is important. Mononeuritis multiplex may also cause pain, which is characterized as deep, aching pain that is worse at night, is frequently in the lower back, hip, or leg. In people with diabetes mellitus, mononeuritis multiplex is typically encountered as acute, unilateral, severe thigh pain followed by anterior muscle weakness and loss of knee reflex.

Electrodiagnostic studies will show multifocal sensory motor axonal neuropathy. It is caused by, or associated with, several medical conditions:

diabetes mellitus.
vasculitides: polyarteritis nodosa, Wegener granulomatosis, and Churg-Strauss syndrome.
immune-mediated diseases like rheumatoid arthritis, lupus erythematosus (SLE), and sarcoidosis.
infections: leprosy, lyme disease, HIV.
amyloidosis.
cryoglobulinemia.
chemical agents, including trichloroethylene and dapsone.
rarely, the sting of certain jellyfish, such as the sea nettle.
Polyneuropathy

Polyneuropathy is a pattern of nerve damage which is quite different from mononeuropathy. The term "peripheral neuropathy" is sometimes used loosely to refer to polyneuropathy. In a polyneuropathy, many nerve cells in different parts of the body are affected, without regard to the nerve through which they pass. Not all nerve cells are affected in any particular case. In distal axonopathy, one common pattern, the cell bodies of neurons remain intact, but the axons are affected in proportion to their length. Diabetic neuropathy is the most common cause of this pattern. In demyelinating polyneuropathies, the myelin sheath around axons is damaged, which affects the ability of the axons to conduct electrical impulses. The third and least common pattern affects the cell bodies of neurones directly. This usually picks out either the motor neurones (known as motor neurone disease) or the sensory neurones (known as sensory neuronopathy or dorsal root ganglionopathy).

The effect of this is to cause symptoms in more than one part of the body, often on left and right sides symmetrically. As for any neuropathy, the chief symptoms include weakness or clumsiness of movement (motor); unusual or unpleasant sensations such as tingling or burning; reduction in the ability to feel texture, temperature, etc.; and impaired balance when standing or walking (sensory). In many polyneuropathies, these symptoms occur first and most severely in the feet. Autonomic symptoms may also occur, such as dizziness on standing up, erectile dysfunction and difficulty controlling urination.

Polyneuropathies are usually caused by processes that affect the body as a whole. Diabetes and impaired glucose tolerance are the most common causes. Other causes relate to the particular type of polyneuropathy, and there are many different causes of each type, including inflammatory diseases such as lyme disease, vitamin deficiencies, blood disorders, and toxins (including alcohol and certain prescribed drugs). Most types of polyneuropathy progress fairly slowly, over months or years, but rapidly progressive polyneuropathy also occurs. It is important to recognize that glucose levels in the blood can spike to nerve-damaging levels after eating even though fasting blood sugar levels and average blood glucose levels can still remain below normal levels (currently typically considered below 100 for fasting blood plasma and 6.0 for HGBA1c, the test commonly used to measure average blood glucose levels over an extended period). Studies have shown that many of the cases of peripheral small fiber neuropathy with typical symptoms of tingling, pain and loss of sensation in the feet and hands are due to glucose intolerance before a diagnosis of diabetes or pre-diabetes. Such damage is often reversible, particularly in the early stages, with diet, exercise and weight loss. The treatment of polyneuropathies is aimed firstly at eliminating or controlling the cause, secondly at maintaining muscle strength and physical function, and thirdly at controlling symptoms such as neuropathic pain.

Autonomic neuropathy

Autonomic neuropathy is a form of polyneuropathy which affects the non-voluntary, non-sensory nervous system (i.e., the autonomic nervous system) affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Autonomic nerve fibers form large collections in the thorax, abdomen and pelvis outside spinal cord, however they have connections with the spinal cord and ultimately the brain. Most commonly autonomic neuropathy is seen in persons with long-standing diabetes mellitus type 1 and 2. In most but not all cases, autonomic neuropathy occurs alongside other forms of neuropathy, such as sensory neuropathy. Autonomic neuropathy is one cause of malfunction of the autonomic nervous system, but not the only one; some conditions affecting the brain or spinal cord can also cause autonomic dysfunction, such as multiple system atrophy, and therefore cause similar symptoms to autonomic neuropathy.

The signs and symptoms of autonomic neuropathy include the following:

urinary bladder conditions: bladder incontinence or urine retention.gastrointestinal tract: dysphagia, abdominal pain, nausea, vomiting, malabsorption, fecal incontinence, gastroparesis, diarrhea, constipation.
cardiovascular system: disturbances of heart rate (tachycardia, bradycardia), orthostatic hypotension, inadequate increase of heart rate on exertion.
other: hypoglycemia unawareness, genital impotence, sweat disturbances.
Neuritis

Neuritis is a general term for inflammation of a nerve or the general inflammation of the peripheral nervous system. Symptoms depend on the nerves involved, but may include pain, paresthesia (pins and needles), paresis (weakness), hypoesthesia (numbness), anesthesia, paralysis, wasting, and disappearance of the reflexes. Causes include:

Physical injury: One common cause of neuritis and subsequent inflammation of the nerves to the toes is the wearing of high-heeled shoes or ill-fitting shoes that bind the toes painfully. This can cause temporary numbness and pain in the affected toes for several days.

Infection: Herpes simplex, Shingles, Leprosy, Guillain-Barre syndrome, Lyme Disease, Chemical injury, Radiation.

Underlying conditions causing localized neuritis (affecting a single nerve): Diphtheria, Localized injury, Diabetes.

Underlying conditions causing polyneuritis (affecting multiple nerves): Beriberi, Vitamin B12 deficiency, Vitamin B6 excess, Metabolic diseases, Diabetes, Herpes zoster, Hypothyroidism, Porphyria, Infections (bacterial and/or viral), Autoimmune disease, especially Multiple Sclerosis, Cancer, Alcoholism, Wartenbergs migratory sensory neuropathy.

Types of neuritis include: Polyneuritis or Multiple neuritis (not to be confused with multiple sclerosis), Brachial neuritis, Optic neuritis, Vestibular neuritis, Cranial neuritis, often representing as Bell's Palsy, Arsenic neuritis.

Signs and Symptoms

Those with diseases or dysfunctions of their nerves can present with problems in any of the normal nerve functions. In terms of sensory function, there are commonly loss of function (negative) symptoms, which include numbness, tremor, and gait abnormality. Gain of function (positive) symptoms include tingling, pain, itching, crawling, and pins and needles. Pain can become intense enough to require use of opioid (narcotic) drugs (i.e., morphine, oxycodone). Skin can become so hypersensitive that patients are prohibited from having anything touch certain parts of their body, especially the feet. People with this degree of sensitivity cannot have a bedsheet touch their feet or wear socks or shoes, and eventually become housebound.

Motor symptoms include loss of function (negative) symptoms of weakness, tiredness, heaviness, and gait abnormalities; and gain of function (positive) symptoms of cramps, tremor, and muscle twitch (fasciculations). There is also pain in the muscles (myalgia), cramps, etc., and there may also be autonomic dysfunction.

During physical examination, specifically a neurological examination, those with generalized peripheral neuropathies most commonly have distal sensory or motor and sensory loss, though those with a pathology (problem) of the nerves may be perfectly normal; may show proximal weakness, as in some inflammatory neuropathies like Guillain–Barré syndrome; or may show focal sensory disturbance or weakness, such as in mononeuropathies. Ankle jerk reflex is classically absent in peripheral neuropathy.

Causes

The causes are broadly grouped as follows:

Genetic diseases: Friedreich's ataxia, Charcot-Marie-Tooth syndrome, Hereditary neuropathy with liability to pressure palsy.
Metabolic/Endocrine: diabetes mellitus, chronic renal failure, porphyria, amyloidosis, liver failure, hypothyroidism.
Toxic causes: Drugs (vincristine, metronidazole, phenytoin, nitrofurantoin, isoniazid, ethyl alcohol), organic metals, heavy metals, excess intake of vitamin B6 (pyridoxine).
Fluoroquinolone toxicity: Irreversible neuropathy is a serious adverse reaction of fluoroquinolone drugs. Inflammatory diseases: Guillain-Barré syndrome, systemic lupus erythematosis, leprosy, Sjögren's syndrome, Lyme Disease, sarcoidosis.
Vitamin deficiency states: Vitamin B12 (cyanocobalamin), vitamin A, vitamin E, vitamin B1 (thiamin).
Physical trauma: compression, pinching, cutting, projectile injuries (i.e. gunshot wound), strokes including prolonged occlusion of blood flow, electric discharge, including lightning strikes.
Others: shingles, malignant disease, HIV, radiation, chemotherapy.
Many of the diseases of the peripheral nervous system may present similarly to muscle problems (myopathies), and so it is important to develop approaches for assessing sensory and motor disturbances in patients so that a physician may make an accurate diagnosis.

Treatment

Many treatment strategies for peripheral neuropathy are symptomatic. Some current research in animal models has shown that neurotrophin-3 can oppose the demyelination present in some peripheral neuropathies.

A range of drugs that act on the central nervous system such as drugs originally intended as antidepressants and antiepileptic drugs have been found to be useful in managing neuropathic pain. Commonly used treatments include using a tricyclic antidepressant (such as amitriptyline) and antiepileptic therapies such as gabapentin or sodium valproate. These have the advantage that besides being effective in many cases they are relatively low cost.

A great deal of research has been done between 2005 and 2010 which indicates that synthetic cannabinoids and inhaled cannabis are effective treatments for a range of neuropathic disorders. Research has demonstrated that the synthetic oral cannabinoid Nabilone is an effective adjunct treatment option for neuropathic conditions, especially for people who are resistant, intolerant, or allergic to common medications. Orally, opiate derivatives were found to be more effective than cannabis for most people. Smoked cannabis has been found to provide relief from HIV-associated sensory neuropathy. Smoked cannabis was also found to relieve neuropathy associated with CRPS type I, spinal cord injury, peripheral neuropathy, and nerve injury.

Pregabalin® is an anticonvulsant drug used for neuropathic pain. It has also been found effective for generalized anxiety disorder. It was designed as a more potent successor to gabapentin but is significantly more expensive, especially now that the patent on gabapentin® has expired and gabapentin® is available as a generic drug. Pregabalin® is marketed by Pfizer under the trade name Lyrica®. Duloxetine®, a serotonin-norepinephrine reuptake inhibitor, is also being used to reduce neuropathic pain. (Not recommended by the manufacturer (Pfizer) for HIV-related neuropathy amongst others - check with your doctors Ed:)

TENS (Transcutaneous Electrical Nerve Stimulation) therapy may be effective and safe in the treatment of diabetic peripheral neuropathy. A recent review of three trials involving 78 patients found some improvement in pain scores after 4 and 6 but not 12 weeks of treatment, and an overall improvement in neuropathic symptoms at 12 weeks. A second review of four trials found significant improvement in pain and overall symptoms, with 38% of patients in one trial becoming asymptomatic. The treatment remains effective even after prolonged use, but symptoms return to baseline within a month of treatment cessation.

External Links

JAMA Patient Page: Peripheral Neuropathy - American Medical Association - PDF.
Peripheral Neuropathy - Mayo Foundation for Medical Education and Research.
Peripheral Neuropathy - National Institute of Neurological Disorders and Stroke. (Short Summary).

Diagnosis/Symptoms
Electrodiagnostic Testing - American Academy of Orthopaedic Surgeons.
Learn about an EMG - American Association of Neuromuscular & Electrodiagnostic Medicine.
Numbness and Tingling in the Arm and Hand - American Society for Surgery of the Hand.
About Peripheral Neuropathy: Symptoms and Signs - Neuropathy Association.
Specialized Nerve Tests: EMG, NCV and SSEP - North American Spine Society.

Treatment

Anti-Seizure Medications: Relief from Nerve Pain - Mayo Foundation for Medical Education and Research.
Anticonvulsants Drugs: Summary of Recommendations - Consumers Union of U.S.
Nerve Blocks - American College of Radiology, Radiological Society of North America.

Disease Management

Living with Neuropathy: Managing Your Own Treatment - Neuropathy Association.
Quality of Life Scale: A Measure of Function for People with Pain - American Chronic Pain Association - PDF.

Clinical Trials

ClinicalTrials.gov: Peripheral Nerve Injuries, Peripheral Nervous System Diseases- National Institutes of Health.

Organizations


American Chronic Pain Association.
National Institute of Neurological Disorders and Stroke.
The Foundation for Peripheral Neuropathy.
Canadian Neuropathy Association.
National Diabetes Information Clearinghouse.
The Neuropathy Association.
Reference Centre for Rare Neuropathies.

References

"Peripheral Neuropathy Fact Sheet: National Institute of Neurological Disorders and Stroke (NINDS)". http://www.ninds.nih.gov/disorders/peripheralneuropathy/detail_peripheralneuropathy.htm. Retrieved 2008-11-30.
http://www.neurologychannel.com/neuropathy/symptoms.shtml"Dorlands Medical Dictionary:mononeuropathy".http://www.mercksource.com/pp/us/cns/cns_hl_dorlands_split.jsp?pg=/ppdocs/us/common/dorlands/dorland/five/000067367.htm
"neuritis" at Dorland's Medical Dictionary
http://emedicine.medscape.com/article/819426-overview
Gabriel JM, Erne B, Pareyson D, Sghirlanzoni A, Taroni F, Steck AJ (1997). "Gene dosage effects in hereditary peripheral neuropathy. Expression of peripheral myelin protein 22 in Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies nerve biopsies". Neurology 49 (6): 1635–40. PMID 9409359.
Kiziltan ME, Akalin MA, Sahin R, Uluduz D (2007). "Peripheral neuropathy in patients with diabetes mellitus presenting as Bell's palsy". Neuroscience Letters 427 (3): 138. doi:10.1016/j.neulet.2007.09.029. PMID 17933462.
Cohen JS (December 2001). "Peripheral Neuropathy Associated with Fluoroquinolones" (PDF). Ann Pharmacother 35 (12): 1540–7. doi:10.1345/aph.1Z429. PMID 11793615.http://fqvictims.org/fqvictims/News/neuropathy/Neuropathy.pdf
Heck AW, Phillips LH 2nd (1989). "Sarcoidosis and the nervous system". Neurol Clin 7 (3): 641–54. PMID 2671639.
Gonzalez-Duarte A, Cikurel K, Simpson DM (2007). "Managing HIV peripheral neuropathy". Current HIV/AIDS reports 4 (3): 114–8. doi:10.1007/s11904-007-0017-6. PMID 17883996.
Wilkes G (2007). "Peripheral neuropathy related to chemotherapy". Seminars in oncology nursing 23 (3): 162–73. doi:10.1016/j.soncn.2007.05.001. PMID 17693343.
Liu N, Varma S, Tsao D, Shooter EM, Tolwani RJ (2007). "Depleting endogenous neurotrophin-3 enhances myelin formation in the Trembler-J mouse, a model of a peripheral neuropathy". J. Neurosci. Res. 85 (13): 2863–9. doi:10.1002/jnr.21388. PMID 17628499.
http://www.cannabis-med.org/data/pdf/en_2010_01_special.pdf
Skrabek RQ, Galimova L, Ethans K, Perry D (2008). "Nabilone for the treatment of pain in fibromyalgia". J. Pain 9 (2): 164–73. doi:10.1016/j.jpain.2007.09.002. PMID 17974490.
Frank B, Serpell MG, Hughes J, Matthews JN, Kapur D (2008). "Comparison of analgesic effects and patient toleration of nabilone and dihydrocodeine for chronic neuropathic pain: randomized, crossover, double blind study". BMJ 336 (7637): 119–201.
Abrams DI, Jay CA, Shade SB, Vizozo H, Reda H, Press S, Kelly ME, Rowbotham Mc, Petersen KL (2007). "Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trail". J. Neurology 68 (7): 515–21. doi:10.1212/01.wnl.0000253187.66183.9c. PMID 17296917.
Wilsey B, Marcotte T, Tsodikov A, Millman J, Bentley H, Gouaux B, Fishman S (2008). "A randomized, placebo-controlled, crossover trail of cannabis cigarettes in neuropathic pain". J. Pain 9 (6): 506–21. doi:10.1016/j.jpain.2007.12.010. PMID 18403272.
Jin DM, Xu Y, Geng DF, Yan TB (July 2010). "Effect of transcutaneous electrical nerve stimulation on symptomatic diabetic peripheral neuropathy: a meta-analysis of randomized controlled trials". Diabetes Res. Clin. Pract. 89 (1): 10–5. doi:10.1016/j.diabres.2010.03.021. PMID 20510476.
Pieber K, Herceg M, Paternostro-Sluga T (April 2010). "Electrotherapy for the treatment of painful diabetic peripheral neuropathy: a review". J Rehabil Med 42 (4): 289–95. doi:10.2340/16501977-0554. PMID 20461329.

DISCLAIMER
These statements have not been approved by the U.S. Food and Drug Administration (FDA). This information is not intended to diagnose, treat, cure or prevent any disease. Information conveyed herein is based on pharmacological and other records - both ancient and modern. No claims whatsoever can be made as to the specific benefits accruing from the use of any herb, essential oil, or nutritional supplement.

Holistic Lifestyle Community Blog has provided this material for information and education purposes only. It is not intended as a substitute for or to take the place of medical advice. We encourage you to discuss any decisions about your interest in, questions about, treatment or care, or the use of complementary and alternative medicine (CAM), or any other therapy, and what may be best for your overall health with a licensed physician or other qualified health care provider. The mention of any product, service, or therapy is not an endorsement by Holistic Lifestyle Community Blog. Any mention in the Holistic Lifestyle Community Blog of a specific brand name is not an endorsement of the product.

http://holisticlifestylecommunityblog.blogspot.com/2012/02/peripheral-neuropathy.html#.UP0ZaCcaZno

Simple Genetic Cheek Swab Tells You If A Drug Is Suitable Or Not

Today's fascinating post from wsj.com (see link below) looks at how tiny genetic variations can significantly change the way we absorb common and not-so-common drugs. This has far-reaching implications for many neuropathy patients, who need to be on a cocktail of drugs to control their main condition and the neuropathy caused by it. There is a simple genetic test (cheek swab) that can alert doctors as to how well, or not, a drug will be absorbed. Sometimes, your genetic make up can make even a single dose of a common drug toxic, or create the need for higher than normal doses to achieve the right effects. Experienced neuropathy patients who have already been through the mill regarding neuropathy drugs ( originally intended for other conditions) will be very much aware that certain drugs work well and others not at all. How much simpler would life be, if a genetic test could predict how you will react to a certain drug before taking it! Worth a read.

Is Your Medicine Right for Your Metabolism? By Melinda Beck Updated March 14, 2016   

More genetic tests aim to help predict how people might respond to many common medications

Medications don’t work the same way for everyone--depending in part on genetic factors that influence metabolism. 

People can respond to drugs very differently. A medication that brings relief for some patients might show no benefit at all in others, or even cause harmful side effects.

A growing array of genetic tests is designed to help predict how people are likely to respond to many common medications, from antidepressants and antihistamines to pain relievers and blood thinners. The tests, which are controversial, look for tiny variations in genes that determine how fast or slow we metabolize medications.

Because of such gene variations, codeine, frequently prescribed to relieve pain, has little effect on as much as 20% of the population, while 2% of people have such a strong reaction that a normal dose can be life-threatening. About 25% of people can’t effectively absorb Plavix, a clot-busting drug, putting them at increased risk for a heart attack or stroke.

Even everyday drugs such as Advil and Motrin, for pain relief, and Zocor, to lower cholesterol, can have widely varying effects.

The speed at which people metabolize medications can dramatically influence a drug’s effectiveness. Illustration: Jason Mecier for The Wall Street Journal

Testing patients for gene variations could avoid some of the 700,000 serious drug reactions in the U.S. each year, some experts say. Proponents of the tests, which are done with a cheek swab, say they also could help doctors rely less on trial and error in choosing the right drug and the right dosage for individual patients.

The Food and Drug Administration has included cautionary information for people with certain gene variations on the labels of more than 100 prescription medications. As yet, only about 20% of doctors order such tests, according to a survey by the American Medical Association, and many patients don’t know they exist.

Some major medical associations, including the American College of Cardiology and the American Psychiatric Association, have been slow to endorse the testing, mainly because there are no large, randomized controlled trials showing the technique significantly improves patient care. And the tests, which range from $500 to $2,000, are only covered by some insurers in some cases.
Alan Pocinki, an internist in Rockville, Md., says he orders gene testing for patients who have a history of unexplained symptoms or who haven’t gotten relief from drugs in the past. In many cases, he is able to find a better treatment based on their DNA, he says. “It makes a huge difference clinically among people I see every day.”

How people’s genes affect their response to medications is called pharmacogenetics. One of the first such drug-gene interactions was identified at the Mayo Clinic in Rochester, Minn., in the 1970s. Researchers discovered that about 1 in 300 children being treated for childhood leukemia had a gene variation that made the drug thiopurine destroy their bone marrow. Now, children are routinely tested before undergoing treatment with the drug.

Scientists have since discovered that about 75% of prescription and over-the-counter drugs depend on a handful of liver enzymes to be absorbed and eliminated from the body. Minor variations in the genes that regulate those enzymes are very common—95% of people have at least one.

People who get two impaired copies of an enzyme gene—one from each parent—are likely to be “poor metabolizers” and absorb drugs so slowly that even a normal dose can become toxic. “Intermediate metabolizers”—with one impaired and one normal gene—allow drugs to build up in the body and over time can cause side effects. People sometimes get extra copies of enzyme genes, which can make them “ultrarapid metabolizers” of some drugs and flush them out of the body so fast they have little effect.

Gene variations that affect drug metabolism tend to run in families and ethnic groups. Other factors, including alcohol and dietary supplements, can also affect how a person reacts to a drug. Some medications, such as Plavix and the acid-blocker Prilosec, shouldn’t be taken together because they can impair each other’s ability to be absorbed. Cigarette smoking speeds up the absorption of the schizophrenia drug clozapine, so patients who smoke need a higher dose.

Some people say learning they have drug-gene sensitivities explains a lifetime of health mysteries. Elise Astleford, 75, a retired Episcopal priest in Vancouver, Wash., says she experienced hallucinations, a deep depression and symptoms of dementia while taking various drugs over the years. After spotting a newspaper ad for gene testing, she convinced her primary-care doctor to order it. She learned she has variations in three key liver enzymes that make her an intermediate metabolizer of dozens of common drugs.

Ms. Astleford still takes a variety of medications for thyroid, blood pressure and other conditions, but she makes sure they all use different enzyme pathways. “Now, whenever I get a new prescription, I check with the pharmacist to see how they are metabolized,” she says.

Dr. Mark Dunnenberger heads the pharmacogenomics clinic at NorthShore University HealthSystem in Evanston, Ill. The clinic, which opened last year, offers a panel of 14 gene tests aimed at predicting how a patient will respond to various medications, for as little as $500. Photo: Photo by Jonathan Hillenbrand

Some tests for gene reactions to individual drugs have been available for years. More lab companies, including Assurex Health Inc., in Mason, Ohio, and OneOme LLC, in Minneapolis, offer panels of tests aimed at advising patients with psychiatric, cardiac or chronic-pain conditions what medications would be the best fit based on their genes. Genelex Corp., in Seattle, says its YouScript software program analyzes how multiple medications, over-the-counter drugs and supplements react with each other and with patients’ DNA. The testing and analysis costs roughly $1,000. “Your results don’t change; you’ll have that information the rest of your life,” says Genelex Chief Executive Kristine Ashcraft.

Medicare pays for pharmacogenomic tests in some cases, such as before patients take certain antidepressants and anticoagulant drugs, but stopped covering many others last year after one company was investigated for allegedly making improper payments to doctors. Private-insurance coverage is spotty but costs for the tests are dropping. NorthShore University HealthSystem in Evanston, Ill., opened a pharmacogenomics clinic last year that offers a panel of 14 gene tests for less than $500.

More top medical centers—including those at Vanderbilt University, the University of Pittsburgh, the Mayo Clinic and St. Jude Children’s Research Hospital—are testing patients’ DNA and studying whether gene-based drug targeting makes a difference in their care. Insurers sometimes cover the cost of testing for such research trials; other times grants or the hospitals themselves provide the funding.

In many cases, hospitals are incorporating the information into patients’ electronic-medical records, so it can help doctors choose the most useful drugs and dosages for them in the future.

“Pharmacogenomics is never going to be a crystal ball to tell you which medications will work and which won’t. Too many other factors come into play,” says Dr. Mark Dunnenberger, who heads the NorthShore University clinic. “But we can take advantage of a patient’s DNA and say, ‘You have a high likelihood of a suboptimal response from these drugs, so let’s try another medication that works a different way.’” 





Not Right for Everyone

Many common medications can affect people differently depending on minor variations in the genes that regulate key enzymes. The variations can make people metabolize certain drugs either more slowly or rapidly than normal. 

Some examples:
DRUGS
Pain relievers codeine or oxycodone, including Tylenol 3 and Percocet
ENZYME PATHWAY AT WORK
CYP2D6
IMPACT
A standard dose can have little effect in up to 20% of people, while as many as 2% can have a life-threatening reaction. 

DRUGS
Blood thinner Plavix (clopidogrel) and acid reducers Prilosec (omeprazole) and Prevacid (lansoprazole)
ENZYME PATHWAY AT WORK
CYP2C19
IMPACT
Up to 15% of people metabolize these drugs very slowly, resulting in a higher effective dose and greater risk of side effects.

DRUG
Blood thinner Coumadin (warfarin)
ENZYME PATHWAY AT WORK
CYP2C9
IMPACT
People with some gene variants have twice the risk of severe bleeding, but other factors are involved and population percentages are unclear.

DRUG
Cholesterol reducer Zocor (simvastatin)
ENZYME PATHWAY AT WORK
SLCO181
IMPACT
Up to 40% of people have impaired ability to metabolize this drug, giving them increased risk of muscle pain and other side effects.
 
Source: Clinical Pharmacogenetics Implementation Consortium
Write to Melinda Beck at HealthJournal@wsj.com

http://www.wsj.com/articles/is-your-medicine-right-for-your-metabolism-1457982384

SIMPLE TIPS TO PREVENT URINARY TRACT INFECTIONS

A urinary tract infection (UTI) can be defined as an infection involving the kidneys, ureters, bladder, or urethra. While not all urinary tract infections (UTIs) can be prevented, experts suggest one can still reduce the risk by taking certain steps and precautions.

Fluids intake: Drink plenty of water and other liquids, but cut back on caffeine and alcohol, which can irritate the bladder. This will make you urinate frequently, which flushes bacteria from your urinary tract. If the urine appears darker than the usual very pale yellow colour, you should increase the fluid intake.

Cranberry juice has been shown to help prevent urinary tract infections.

Toilet hygiene: Do not hold your urine for a long time, urinate when you have the urge. When you're done, always wipe from front to back to prevent bacteria from the anus entering the urethra.  

Constipation: Try to avoid constipation as it has been linked to increase the chances of getting a UTI. Steps like increasing the amount of fibre in your diets, drinking plenty of water and other natural fluids can help relieve constipation.

Sexual intercourse: Take special precaution when you engage in sexual activity since it may also increase the risk as it can bring bacteria into the bladder area. Practice good hygiene by washing your genitals every day using a mild detergent and before having sex. Make sure that the bladder is emptied after intercourse by drinking plenty of water and other fluids.

Clothing: Avoid wearing tight-fitting undergarments, which is made of non-breathing materials. Instead opt for loose-fitting and cotton materials, which allows a woman's private part to remain dry preventing from bacteria growth.