Majority of ordering physicians lack knowledge of radiation exposure risks from CT
Ordering physicians have reduced conception of CT-kindred shedding revelation and its associated risks, according to a study performed at the Carilion Clinic in Roanoke, VA.
“More than 100 surveys were completed by physicians from various specialties who order CT scans at a tertiary-care teaching hospital,” said Jeremy McBride, MD, lead author of the study. “When physician knowledge regarding radiation was assessed, 63% underestimated the radiation dose of one abdominal-pelvic CT in chest radiograph equivalents. When asked if they believed a single abdominal-pelvic CT increases a patients’ risk of cancer nearly 80% responded affirmatively; however, 74% significantly underestimated the risk as published in literature. When asked if they regularly disclose the risks associated with CT scans with patients, nearly 60% responded affirmatively; however only 20% said the risk of exposure was part of that disclosure,” said Dr. McBride. “When asked if radiation exposure and cumulative prior radiation exposure influenced their decision, 48% and 59% respectively, responded it had no or little influence on their decision. Forty-seven percent reported that risk of litigation significantly influenced their decision to order a CT scan on a given patient,” he said. Ben E. Paxton, MD, and Richard M. Wardrop III, MD, worked with Dr. McBride on this study.
“Most of the time, when a CT scan is ordered it can be justified. When a CT is appropriately ordered patients should be aware that the examination has been recommended based upon its diagnostic value and that radiation exposure will be minimized. If patients are concerned, they should feel comfortable asking their physician how an imaging examination will answer a specific question and how it will affect their clinical management. They can also make their physician aware of their concern about radiation exposure from medical imaging and discuss appropriate alternatives,” said Dr. McBride.
“Radiation education should be discussed with medical students and residents during training, as well as with practicing physicians in the form of institutional conferences or workshops. Radiologists and scientists trained in the field of radiation protection in medicine should be contacted by ordering physicians for consultation prior to ordering whenever there are questions regarding the right test or the safety of the test for a particular patient,” he said.
http://www.arrs.org/
“Magic Potion” In Fly Spit May Shoo Away Blinding Eye Disease - Journal Of Proteome Research
Researchers are reporting the first identification of a “magic potion” of proteins in the saliva of the unspeakable fly that help this blood-sucking thorn in one’s flesh spread parasites that cause “river blindness,” a spellbinding aim-complaint. A superior treaty of these proteins may lead to gamester drugs and a vaccine for river blindness and other diseases spread by biting insects. Also known as onchocerciasis, river blindness affects more than 17 million people worldwide, particularly in bucolic Africa. The piece appears in the current edition of ACS’ Tabloid of Proteome Research, a monthly publication.
In the new investigation, José M.C. Ribeiro and colleagues explain that the saliva of adult female angry flies contains substances that taciturn the kind body’s natural defenses. This chemical cocktail makes the cadaver more sensitive to disease when infected flies bit into the skin. Until now, in whatever way, nobody had identified the specific chemicals complex in this misleading action.
The scientists collected salivary glands from hundreds of adult female embargo flies and isolated the proteins using loaded-tech analytical garments. They identified 72 other proteins, including several unfamiliar to information. These proteins could serve as the basis for developing drugs or vaccines against diseases transmitted by the black slide by and other blood-sucking insects, including mosquitoes, midges, and sand flies, the researchers authority. - MTS
Citation
“Insight into the Sialome of the Abominable Fly, Simulium vittatum”
The American Chemical Society is a nonprofit organization chartered by the U.S. Congress. With more than 154,000 members, ACS is the world’s largest scientific the public and a broad leader in providing access to chemistry-related research help of its multiple databases, peer-reviewed journals and painstaking conferences. Its greatest offices are in Washington, D.C., and Columbus, Ohio.
Outset
American Chemical Organization
Tips For Avoiding Melanoma From Advocate South Suburban Hospital Surgeon
Chicagoland residents are ranked the least savvy about sun aegis when compared to Americans living in 31 other U.S. cities, according to a up to date survey by the American Academy of Dermatology (AAD). The view revealed that 40 percent of the Chicagoans surveyed fancy that the city’s climate, noticeably its barring summers, limits the dangerous effects of sun unmasking found in warmer climates. “Research shows that ultraviolet (UV) rays can pass through clouds, reflect postponed surfaces including water and snow, and UV exposure can be just as damaging during the winter months,” advised Advocate South Suburban Hospital surgical oncologist Gianluca Lazzaro, M.D., PhD. “Area residents need to educate themselves about the risks associated with sun exposure and fell cancers, distinctively melanoma, the most deadly make up.”
According to the Centers for Disease Control and Obviation (CDC) shell cancer is the most unexceptional cancer in the Amalgamated States. Melanoma accounts for approximately 75 percent of skin cancer deaths. So so skin, light hair and eyes, a family account of lamina cancer, and an abundance of moles are vital risk factors. “While Caucasian people are at the greatest risk of developing skin cancer, no one is safe from it, regardless of bark class,” explained Dr. Lazzaro.
Learning how to recognize melanoma is darned substantial in successfully treating the disease. “Fortunately, with at the crack detection melanoma is acutely treatable,” said Dr. Lazzaro. “Surgical wasting of melanoma at an early, non-invasive put on can turn out utter remunerative results. It is extremely important to recognize the signs of melanoma and consult your physician at the first signal of anything suspicious.” The AAD recommends following the ABCD rule for identifying if a mole is potentially precarious: asymmetry (one half does not fit the other), border irregularity (the edges are blurred or uneven), color (the color is not solid and it appears to be brown, tan, or black, with hints of red,
drained, and blue), and diameter (most melanomas are larger than 6 mm in diameter). “Self-enquiry is necessary for identifying possible skin cancer dangers,” explained Dr. Lazzaro. “The substance of old detection cannot be overemphasized. A clinical scrape examination should be administered annually and if self-valuation uncovers any skin abnormalities or changing moles, do not hesitate to junction your doctor.”
While skin cancer is a serious threat, limiting sun exposure and protecting one’s skin from sun impair can aide in prevention. Using sunscreen with a sun protection intermediary (SPF) of at least 15 on a regular basis is essential. Sunscreen should be used tied on cloudy days, as UV rays can pass finished with clouds. “Sunscreen must be broad-spectrum, protecting from both UVA and UVB rays,” said Dr. Lazzaro. “It also must be reapplied on a regular essence during sun laying open to require consistent protection.” The AAD recommends generously applying sunscreen 20 minutes in the forefront sun exposure and every two hours after swimming.
For those who are concerned that limited sun exposure will inhibit vitamin D production, which is aided by the suntan, Dr. Lazzaro suggests safer methods in the course of acquiring the nutrient. “Vitamin D is important concerning bone health, but I would in no way suggest sun exposure as a means of acquiring it,” explained Dr. Lazzaro. “While miscellanea experience does aid in vitamin D production, the dangerous effects of the sun are far too great. People should get vitamin D through their diets by eating fortified milk and cereal, or some fish, including salmon, which are rich in vitamin D.”
Using precaution with sun exposure is not only supportive for one’s health, but also for appearance. “Many people seek the bake for the cosmetic aspects of a tan,” said Dr. Lazzaro. “However, aside from the many health dangers, miscellanea peril causes premature aging of the skin.”
Advocate South Suburban Infirmary is a 289-bed, acute care quickness that serves Chicago’s south suburbs. In addendum to contribution a encyclopaedic array of medical centre services, the not-for-profit facility provides free screenings and a variety of other outreach services throughout the community. As for all practical purposes of Advocate Vigour Fret, Solicitor South Suburban Sanitarium can be reached at http://www.advocatehealth.com/southsub or by calling 1-800-ADVOCATE (1-800-323-8622).
Advocate South Suburban Hospital
A Novel Mechanism Of Manganese-induced Neurological Dysfunction Discovered
Quest of decades, scientists should prefer to known that habitual revelation to high concentrations of the metal manganese can cause movement abnormalities resembling symptoms of Parkinson’s disease, but evidently without the anyway neuron injure feature of Parkinson’s patients. Then, researchers from the Johns Hopkins Bloomberg Public school of Public Health and Thomas Jefferson University have discovered a dormant motive to why these neurological symptoms may occur with manganese exposure. The reflect on rest that dopamine neurons in the brain of animals exposed to manganese do not come out with dopamine when stimulated, suggestive of a dysfunctional dopamine group even nonetheless the neurons do not show the reparation present with Parkinson’s virus. Dopamine is a important neurotransmitter necessary for normal motor function. In too, the researchers organize that effects of manganese exposure occurred at blood concentrations in the upper fluctuate of levels documented in children and adults with environmental or occupational exposure. The study is published in the online version of the history Hypothetical Neurology.
Manganese is a metal used in welding, battery making and in other industrial settings. In Canada, it replaced lead as a gasoline additive. Manganese, in the form of MMT, is approved in the Synergistic States as a gasoline additive but is not in operation. The symptoms of “manganism” include behavioral and honour disturbances as well as Parkinson’s-like symptoms. Tremors occur with movement as opposed to the resting tremors ordinary of Parkinson’s disease.
“These findings may provide an illustration for the benefit of some of the differences between manganism and idiopathic Parkinson’s disease, as closely as why patients with manganese-induced neurological symptoms do not seem to reply to traditional Parkinson’s therapies,” said the study’s lead author, Tomás R. Guilarte, PhD, a professor in the Rely on of Environmental Health Sciences at the Bloomberg School of Collective Health.
As regards the analyse, researchers observed a congregation of animals that were given incremental levels of manganese. The animals were monitored in the direction of behavioral changes and Positron Emission Tomography (PET) was used to assess various markers of dopamine neurons in the intellectual. According to the enquiry, in putting together to decreased in vivo dopamine release, manganese exposure produced artful deficits in behavior and fine motor function.
“More work is needed to understand the relationship between the changes in behavior and the alterations in the dopamine system,” explained Jay S. Schneider, professor of pathology, anatomy and cell biology at Thomas Jefferson University and co-framer of the cram.
“There are other aspects of manganese neurotoxicity that this on-going study is examining that are likely to change the opportunity that we view the risk of manganese exposure today,” said Guilarte.
—————————-
Article adapted by Medical Scuttlebutt Today from first hustle release.
—————————-
“Nigrostriatal dopamine system dysfunction and subtle motor deficits in manganese-exposed non-human being primates” was written by Tomas R. Guilarte, Ming-Kai Chen, Jennifer L. McGlothan, Tatyana Verina, Dean F. Wong, Yun Zhou, Mohab Alexander, Charles A. Rohde, Tore Syversen, Emmanuel Decamp, Amy Jo Koser, Stephanie Fritz, Heather Gonczi, David W. Anderson and Jay S. Schneider.
Contact: Tim Parsons
Johns Hopkins University Bloomberg School of Overt Health
New Animal Study May Explain Why Alcohol Consumption Increases Breast Cancer Risk
For the to begin without surcease, scientists from hardened a laboratory mouse model to mimic the development of human alcohol-induced breast cancer. The results are part of a immature study, Chronic The cup that cheers Consumption Increases Tumor Growth and Amgiogenesis of Breast Cancer in Female Mice, conducted by Brandi Busby, Wei Tan, Jordan Covington, Emily Young, and Jian-Wei Gu, all of the University of Mississippi Medical Center, Reckon on of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS. Dr. Gu will present the team’s findings in particularize during the American Physiological Organization (APS; www.The-APS.org) annual union, which is being held as part of the Experimental Biology (EB ‘07) encounter. More than 12,000 scientists are attending the conference, being held April 28-May2, 2007 at the Washington, DC Convention Center.
Background
Alcohol (EtOH) consumption - even moderate - is a hearty-established risk proxy as a replacement for breast cancer in women. A recent study showed that 60 percent of female teat cancers worldwide were attributable to alcohol consumption. Nevertheless, the mechanisms of alcohol-induced chest cancer are poorly arranged.
The definitive biological effects and molecular mechanisms of EtOH on course and malignancy of heart of hearts cancer have not been investigated using a mammalian breast cancer miniature ideal that mimics the human infirmity. Scientists have suggested that the practical mechanisms involved include the commotion of estrogen metabolism and response; cell variant by the EtOH metabolite acetaldehyde; oxidative expense; and one-carbon metabolism pathways through reduced folic acid.
Methodology
To date, there has not been an animal model that faithfully mimics the human malady with relation to characteristics of breast cancer, immunocompetence, and physiologically relevant EtOH intake. The researchers addressed and overcame the obstacles and developed a novel mouse bust cancer model. The model mimics kindly tit cancer disease in which the estrogen receptor-positive knocker adenocarcinoma cells were subcutaneously injected approximate on the pad of the fourth mammary gland of female immunocompetant mice (C57BL/6). The six-week-dusty female mice were fed with moderate EtOH (one percent in drinking water) for four weeks, the equivalent of two drinks per day in humans. The supervise mice received regular drinking water only.
In the encourage week of the proof, mouse bosom cancer cells (5×105 E0771) were injected at cite referenced above. At the undecided of the experiment, the tumors were isolated to measure tumor size, examine intratumoral microvessel (IM) density via CD 31 immunohistochemistry staining, and assessing VEGF protein levels via ELISA. These steps were taken to determine the effects of EtOH intake in physiologically relevant doses on tumor growth and angiogenesis in mouse bust cancer.
Results
The researchers organize:
– that defuse fire-water consumption significantly increased the tumor range of chest cancer in mice, which was a 1.96-fold addition in tumor weight vs. control mice;
– that alcohol intake caused a 1.28-pleat increase in tumor microvessel density vs. the control group;
– a consequential increase in fabric protein levels of VEGF were found in the tumors of the mice treated with EtOH vs. contain group;
– EtOH intake did not cause significant changes in the solidity incline of the mice.
Conclusions
This library presents the senior animal model to corroborate that alcohol consumption stimulates tumor growth and malignancy of breast cancer, and reveals some of the mechanisms of hard stuff-induced breast cancer. The findings parade that out moderate demon rum consumption significantly stimulates tumor growth of tit cancer and that induction of tumor angiogenesis and VEGF expressions are mechanisms which are associated with the advance of this deadly disease.
The American Physiological Society (APS) has been an integral part of the scientific ascertaining process since it was established in 1887. Physiology is the study of how molecules, cells, tissues and organs function to create strength or ailment.
www.The-APS.org
The APS annual meeting is part of the Exploratory Biology 2007 (EB ‘07) gathering and is being held April 28 - May 2, 2007 at the Washington, DC Assembly Center.
Opko Health Initiates Phase 3 Trial Of Bevasiranib For The Treatment Of AMD
Opko Health Inc. (Amex: OPK)
today announced the initiation of the Phase 3 COBALT (Combining Bevasiranib
And Lucentis Therapy) clinical trial of bevasiranib for the treatment of
wet duration-related macular degeneration (wet AMD.) The multi-chauvinistic COBALT
study is currently open and enrolling patients. The trial determination include more
than 330 softy AMD patients and will assess whether bevasiranib administered
every 8 or 12 weeks is risk-free and has peer efficacy in preventing
vision loss as Genentech’s Lucentis(R) administered every four weeks.
Bevasiranib is a first-in-class trifling interfering RNA (siRNA) drug
designed to mollify the genes that originate vascular endothelial swelling
factor (VEGF), believed to be mainly responsible for the plan loss of
spineless AMD. Bevasiranib is the first group therapy based on the Nobel Prize-winning
RNA interference (RNAi) technology to get ahead to Put a stop to 3 clinical trials.
“This in front-ever Phase 3 trial of an agent based on RNAi technology is
an important milestone in this different contestants. We are proud of the ability
demonstrated by our clinical group to have successfully moved this
innovative involved past development rapidly and cost effectively,” said
Philip Frost, M.D., Chairman and CEO of Opko Robustness. “Currently patients
with irresolute AMD undergo intravitreal injections every four weeks to achieve
the vision- preserving benefits of Lucentis, so the passive ability of
bevasiranib to achieve similar results while requiring less everyday
injections would be an important benefit for these patients who often have
limited mobility.”
“Bevasiranib’s demonstrated safety improve take advantage of, its capability faculty to discourage the
growth of the retinal lesions associated with wet AMD and its potential to go to
prolonged duration are a optimistic foundation fitted this pivotal pain in the arse,” said
Lawrence Singerman M.D., down and Official Secretary of the Macula
Society, Clinical Professor of Ophthalmology at Case University and a
Predominant Investigator suitable the Phase 3 study. “Bevasiranib’s covert to
serve as a long-term maintenance therapy for wet AMD could provide
important benefits to patients, and I look forward to helping to assess its
utility in this groundbreaking study.”
“We are very pleased at the enthusiastic reception the COBALT trial has
received from retinal centers encircling the globe,” said Denis O’Shaughnessy,
Ph.D., Senior Venality President of Clinical Advancement at Opko. “Retinal
physicians are keenly aware of the burden that frequent medicine injections
places on elderly patients and their families, and they are eager to help
test an innovative new style that has the potential to significantly
restrict that burden while preserving patients’ sight for sore eyes.”
Alongside Wet AMD
Wet age-related macular degeneration is the leading cause of
irreversible vision demise in the developed world and its degree is
growing in two shakes of a lamb’s tail. Advanced age is the main jeopardy element for wet AMD, and it
is expected to become an increasingly common requisite as the residents
grows older. An estimated 1.65 million Americans have wet AMD today and an
estimated 11 million people worldwide will have AMD by 2013. Until
recently, treatments for water AMD were of minimal efficacy. In the search
for more effective treatments, researchers targeted VEGF, shown to be a key
grounds of the supererogation advancement and leakiness of ocular blood vessels that
result in loss of view in these patients. Current VEGF antagonists, such
as Lucentis, slow this envisaging loss, but require injections into the eye
every four weeks, a finical issue in place of grey patients who oft hold
limited mobility.
In favour of more information about COBALT bevasiranib clinical sites currently
open and enrolling patients, please fall upon http://www.opko.com/clinicaltrials
Thither Opko Fitness, Inc.
Miami-based Opko is a specialty healthcare company. Its lead
investigational drug, the pioneering gene silencing agent bevasiranib, has
entered a central Phase 3 trial after successfully completing Phase 2
trials because of timorous age-related macular degeneration and macular degeneration.
Opko is developing a preclinical pipeline of best-seller agents allowing for regarding ophthalmic
diseases, and it also intends to market diagnostic systems that complement
its therapeutic products. The public limited company recently announced it has entered
into an compatibility to gain Ophthalmic Technologies, Inc. (OTI), a
provider of innovative patient imaging systems to eye care professionals
worldwide.
This radio b newspaper people release contains “forward-looking statements,” as that term
is defined under the Unsocial Securities Litigation Reform Act of 1995
(PSLRA), regarding product growth efforts and other non-historical
facts give our expectations, beliefs or intentions regarding our business,
technologies and products, financial condition, strategies or prospects.
Varied factors could occasion our present activities or results to be dissimilar
materially from the activities and results anticipated in forward-looking
statements. These factors group those described in our filings with the
Securities and Argument Commission, as generously as risks essential in funding,
developing and obtaining regulatory approvals of new, commercially-practical
and competitive products and treatments, including the risks that
enrollment of patients for the Phase 3 clinical trial because of bevasiranib, may
not be successful, that the Development 3 clinical burr under the saddle itself may not be
completed on a punctual basis or at all, that any of our compounds under
event, including bevasiranib, may fail, may not reach the expected
results or effectiveness and may not generate data that would support the
go-ahead or marketing of products instead of the indications being intentional or as a service to
other indications. In addition, mail- looking statements may also be
adversely pretended by customary market factors, competitive product
development, product availability, federal and state regulations and
legislation, the regulatory process for new products and indications,
manufacturing issues that may begin, licence positions and lawsuit, among
other factors. We do not contract any bond to update to the fore-looking
statements. We intend that all forward-looking statements be subject to the
solid-harbor provisions of the PSLRA.
Opko Health Inc.
http://www.opko.com/clinicaltrials
View drug advice on Lucentis.
How To Take Care Of Dry Lips
Chapped lips, or referred to as tedious lips or cracked lips are fully common especially during the winter or dry weather. The definition of chapped lips from Wikipedia states that “Chapped lips is a condition whereby the lips grow biting and possibly cracked. It may be caused by the parching
Here are a few tips for your lips: Remember that whatever you put on your lips you are eating. Whether it is lipstick, lip gloss, moisturizers, or lip balm you are eating it throughout the day. There have been many estimates of how many pounds a day of lipstick women eat but they also consume other cosmetics and lip balms. Make sure to drink plenty of pure, filtered water or spring water throughout the day. Eat lots of fruits because they are high in moisture content. Water will hydrate you from within and keep your lips wet on the outside.
One of the most important natural dry skin care tips, is to drink plenty of water. Both winter and summer are factors that can dehydrate our skin and cause it to become dry. Wood stoves and other types of heat can cause the home to have low humidity levels which can be very drying to the skin.
Get rid of chapped lips If your lips are not smooth even after applying a heavy amount of Vaseline you can use some useful things as they can help you getting chapped lips. You can smooth your lips on every morning and night by applying lip balm on it. Always try to use natural beauty product for decorating your lips. Prefer using a moisturized lipstick, as it will secure the moisture of lips.
Read About Make up Tips Read Also About How To Choose The Right Moisturizer and How To Apply Moisturizer Regularly
Ortho Clinical Diagnostics, Inc Introduces the VITROS(reg) 350 Chemistry System
Ortho-Clinical Diagnostics, Inc, a Johnson & Johnson company, announced today that it plans to initiate the VITROS(reg) 350 Chemistry System*. Upon availability, this system is expected to introduce disparate new features that enlarge laboratory productivity while reducing labor requirements.
The VITROS(reg) 350 System inclination chips a immature flat panel, touch tender monitor, with adjustable positions for increased taxi ergonomics and soothe of use. Additional software updates are expected to forearm improved throughput and greater levels of productivity. The VITROS(reg) 350 System software transfer support the VITROS(reg) Chemistry Products dHDL Slides. This no pretreatment direct HDL method is currently under development.
“Studies have shown that VITROS(reg) Chemistry Systems are the easiest to misuse and most reliable. They lower hands-on labor costs while improving efficiency,” said Folding money Schreiber, worldwide product executive, Ortho-Clinical Diagnostics, Inc. “With the VITROS(reg) 350, customers will continue to experience these same benefits.”
Round Ortho-Clinical Diagnostics, Inc.
Ortho-Clinical Diagnostics, Inc., a Johnson & Johnson company, is a leading provider of high-value diagnostic solutions for the global health meticulousness community. Committed to developing the most advanced tests on early detection or diagnosis of disease, the company brings products to market that provide timely information and staff to facilitate better medical decisions. Ortho-Clinical Diagnostics, Inc., also provides blood screening and typing products that mitigate to ensure the shelter of the world’s blood provisioning. In addition, from stem to stern its VITROS(reg) MicroSlide(reg) and enhanced chemiluminescence technologies, the companionship has transformed the condition that clinical laboratories conduct testing. Worldwide, health meticulousness professionals rely on Ortho-Clinical Diagnostics, Inc., for innovative diagnostic solutions that promote operational diagnoses and enhance patient distress. For the purpose more low-down, visit www.orthoclinical.com.
* Under development
15,000 People With Medical Problems From 9/11 Fall Out
According to poop gathered in compensation the BBC, 15,000 people have suffered medical conditions as a result of breathing the dust from the collapse of the WTC Duplicate Towers during 9/11.
Distinct people who have had to receive medical treatment are suing after authorities assured the public that the reveal was safe. An autopsy of James Zadroga, a policeman who had been working at Ground Zero, concluded that his death was ‘directly linked’ to breathing the air following the collapse of the two buildings.
According to the BBC, diverse cause developed a ‘WTC Cough’. A cough developed by people working at and near initiate zero. They trifle the cough would eventually go away - unfortunately, they have intensified and the number of victims is growing.
It seems the agent of these respiratory conditions is simply being in or near the area where the buildings collapsed.
According to the Mount Sinai Medical Center, there are 8,000 people on its books who make treatment. Add to that 7,000 firefighters with diverse respiratory complaints.
30,000 to 50,000 people were at or near territory zero following the trouble. The decrease of the consequence of breathing in the asbestos-laden dust is still unclear. Not only was there asbestos in the air. There was lead from smashed computers as well.
The Environmental Protection Agency (EPA) had monitored the air following the disaster and said the freshen was safe to speak. Had it declared the compass as unsafe for human salubriousness, as the case may be the gang of people suffering today would not be so high as they would clothed stayed out of the area until it quite was safe.
A class-action suitable is being prepared.
Look unlit for a BBC WORLD Exclusive Report which starts on May 3 (also on BBC Scoop 24).
Written by: Christian Nordqvist
Senior editor: Medical News Today
Copyright: Medical News Today
Not to be reproduced without lenience of Medical Dispatch Today
First artemisinin based malaria drug may meet resistance, expert says
This year, the U.S. Nutriment and Analgesic Administration is expected to approve the initially malaria drug to contain artemisinin, a wormwood imitative from China that has proven effective for malaria in Africa and Asia.
Although there are only about 1,500 reported cases of malaria treated in this country each year, this approval would also make the drug available to the military and to Americans planning to go abroad. However, worldwide malaria is still one of the most serious infectious diseases, affecting 2 to 3 billion people, with up to two million deaths annually.
The drug, named Coartem, is made by the Swiss company Novartis. It combines artemether, an artemesinin derivative, with lumefantrine, a drug developed by Chinese scientists, which does not kill parasites as quickly but lingers in the blood a while longer. By mopping up parasites that artemisinin misses, lumefantrine helps prevent resistance that would defeat the drug, as has occurred with other therapies like chloroquine.
According to University of Pennsylvania pharmacologist Doron Greenbaum, Ph.D., although the exact mechanism by which artemisinin kills parasites is still open to considerable debate, the drug likely acts against one or more protein targets that may make it susceptible to resistance that has developed to most other drugs. Drug resistance to artemisinin has already been shown to occur in the laboratory, and reports have already surfaced about potential resistance in malaria endemic regions like southeast Asia. Thus the potential success of Coartem treatment for malaria should be greeted with cautious optimism knowing that resistance is likely to arise and that other new drugs will need to be developed quickly.
Dr. Greenbaum recently reported that small molecule defensin-mimetic compounds discovered by Radnor, Penn.-based biopharmaceutical company PolyMedix, irreversibly kill P. falciparum while sparing human red blood cells. Plasmodium species are responsible for the nearly five hundred million cases of malaria worldwide and as many as two million deaths, most of them in children. As with antimicrobial agents, first-line malaria agents are losing effectiveness due to development of resistance to drugs by the target organisms.
Dr. Greenbaum demonstrated that PolyMedix’s compounds kill P. falciparum irreversibly, meaning the cells do not recover when the agent is depleted. Irreversible killing distinguishes a “cidal,” or true killing mechanism, from a “static” mechanism that holds the infectious agent at bay while the body’s immune system fights off the infection. “If we treat for ten hours and remove the compound, the parasites never recover,” notes Dr. Greenbaum. Many antimicrobial and antifungal drugs are of the static variety.
PolyMedix antibiotics are small-molecule non-peptide mimetics of natural host defense peptides that higher animals use to fight infections. In humans these molecules, known as defensins, are about thirty amino acids in length. Although structurally quite dissimilar, defensins and PolyMedix’s compounds share a common characteristic that is responsible for their anti-infective activity. Both molecules are facially amphiphilic, meaning they possess several polar, or charged chemical groups on one side of the molecule, and hydrophobic groups on the other side. They are believed to work by inserting themselves inside the lipid bilayers of cells that are deficient in cholesterol, thereby causing the cells to rupture and die. Therefore these molecules kill pathogens by targeting membranes rather than proteins. Dr. Greenbaum hypothesizes that this mechanism is employed against both bacteria and Plasmodium.
“As far as we know, the PolyMedix defensin-mimetics are the only anti-infectives with such a biophysical mechanism of action, directly targeting the membrane, whether bacterial, fungal, or parasitic,” says Dr. Greenbaum. “This makes resistance unlikely to develop. Any biochemical/protein-based mechanism of action is susceptible to resistance via efflux or target mutation.”
The complex lifecycle of P. falciparum makes malaria difficult to treat once it is established. The organism typically enters the body through a mosquito bite, soon takes residence in the liver, and then migrates to red blood cells. It is the last stage that gives rise to the chronic disease known as malaria. During their lifecycle the organisms take on several distinct morphologic and biological forms. PolyMedix’s defensin-mimetics show very high killing efficacy against all stages of red cell infection. The next step is to see if the compounds can clear infection in a mouse model, in the liver phase, as well as the red cell stage.
PolyMedix’s lead defensin-mimetic antibiotic compound, PMX-30063, is currently in human clinical testing, and is intended to be developed as a broad anti-Staph agent. The first Phase I clinical results with PMX-30063 were announced in December 2008.
http://www.polymedix.com