Stick out your tongue: Tongue appearance and illness

Physicians often ask their patients to "Please stick out your tongue." The tongue can betray signs of illness, which combined with other symptoms such as a cough, fever, presence of jaundice, headache or bowel habits, can help the physician offer a diagnosis. For people in remote areas who do not have ready access to a physician, a new diagnostic system is reported in the International Journal of Biomedical Engineering and Technology that works to combine the soft inputs of described symptoms with a digital analysis of an image of the patient's tongue.

Karthik Ramamurthy of the Department of Information Technology, Rajalakshmi Engineering College, in Chennai, India, and colleagues, have trained a neural network that can take soft inputs such as standard questions about symptoms and a digitized image of the patient's tongue and offer a likely diagnosis so that professional healthcare might then be sought if needed. The digitized images of the patient's tongue reveal discoloration, engorgement, texture and other factors that might be linked to illness.

Smoothness and "beefiness" might reveal vitamin B12, iron, or folate deficiency, and anemia. Black discoloration could be indicative of fungal overgrowth in HIV patients or prolonged antibiotic use. Longitudinal furrows on the tongue are associated with syphilis. 

Ulcers may indicate the presence of Crohn's disease or colitis and various other conditions. 

The team's automated diagnostic, however, utilizes the condition of the tongue in combination with other symptoms to identify whether a patient has any of various illnesses: common cold, flu, bronchitis, streptococcal throat infection, sinusitis, allergies, asthma, pulmonary edema, food poisoning and diverticulitis.

The current system allows diagnosis of fourteen distinct conditions but the team adds that they will be able to add eye images and use those as an additional hard input for their neural network and so extend its repertoire significantly.

Source: Inderscience Publishers

Novel approach to treating asthma: Neutralize the trigger

Current asthma treatments can alleviate wheezing, coughing and other symptoms felt by millions of Americans every year, but they don't get to the root cause of the condition. Now, for the first time, scientists are reporting a new approach to defeating asthma by targeting the trigger -- the allergen -- before it can spark an attack. They describe their new compound, which they tested on rats, in ACS' Journal of Medicinal Chemistry.

Clive Robinson and colleagues explain that to prevent many health problems, the ideal approach to treatment or prevention involves getting to the cause of a condition and targeting it directly. Asthma, which occurs when the immune system goes into overdrive affecting the airway in response to an otherwise harmless substance, has posed a challenge to this model. That's because it can be set off by different allergens or irritants. But recent studies suggest that the picture might not be as complicated as previously thought. 

Scientists have found that dust mites are one of the most important triggers of allergic asthma. So Robinson's team wanted to find a way to neutralize mite allergens.

The researchers identified a compound that binds to a major dust mite allergen and turned it into an inhalable powder. They tested it on rats and found that it significantly dampened the animals' immune response when they were exposed to a variety of allergens. This compound and other similar inhibitors could hail a new direction in asthma treatment, say the researchers.

The authors acknowledge funding from the Wellcome Trust.

Source: American Chemical Society

Quest continues for peanut that won't cause allergic reaction

Peanuts (stock image). Scientists must eliminate peanut allergens below a certain threshold for patients to be safe, said Wade Yang, an assistant professor in food science and human nutrition and member of UF’s Institute of Food and Agricultural Sciences. Credit: © yurakp / Fotolia

University of Florida scientist has moved one step closer to his goal of eliminating 99.9 percent of peanut allergens by removing 80 percent of them in whole peanuts.

Scientists must eliminate peanut allergens below a certain threshold for patients to be safe, said Wade Yang, an assistant professor in food science and human nutrition and member of UF’s Institute of Food and Agricultural Sciences.

If Yang can cut the allergens from 150 milligrams of protein per peanut to below 1.5 milligrams, 95 percent of those with peanut allergies would be safe. It’s challenging to eliminate all peanut allergens, he said, because doing so may risk destroying peanuts’ texture, color, flavor and nutrition. But he said he’s using novel methods like pulsed light to reach an allergen level that will protect most people.

Yang, whose study is published online in this month’s issue of the journal Food and Bioprocess Technology, cautioned that he has done peanut allergen experiments only in a laboratory setting so far. He hopes to eventually conduct clinical trials on animals and humans.

Dr. Shih-Wen Huang, professor emeritus in the Department of Pediatrics and Head of the Pediatric Allergy Clinic at UF Health, is familiar with the UF/IFAS research. Huang outlined more steps in the peanut allergen research.

The first is to see if the allergic antibody in the serum of peanut allergy patients will still bind with the residual allergy protein from the refined peanut products. The second is to see if the refined peanut extract would elicit skin-test reactions in peanut allergy patients.

The third step would be to conduct a double blind, placebo-controlled test to see if patients develop allergy symptoms after eating the refined products.

“I am pleased to see their work is progressing well,” Huang said. “However, more challenges are waiting until the final products are accepted from the public, especially the patients with peanut allergies.”

Two years ago, Yang was using his technique on peanut extract. He’s now testing it on the peanut itself. In his 2012 study, he removed up to 90 percent of the allergic potential from peanut protein extracts.

“This process proves that pulsed light can inactivate the peanut allergenic proteins and indicates that pulsed light has a great potential in peanut allergen mitigation,” Yang said.

About 1.9 million people, or 0.6 percent of U.S. residents, are allergic to peanuts, according to the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

Reactions can range from skin rashes to anaphylaxis, which can be fatal. Currently, the best way for those allergic to peanuts to stay safe is to avoid them, according to the NIH. Many people carry epinephrine injectors that help offset their allergy symptoms until they reach a hospital.

In the latest study, Yang and his colleagues applied the pulsed ultraviolet light technology to whole peanuts. That makes the findings more useful, because peanut processing usually starts from whole-peanut roasting, and roasted peanuts are then packaged to sell as whole peanuts or made into peanut butter, he said.

“The latest study moves one step closer to the actual production,” Yang said.

For the study, Yang used a pulsating light system – two lamps filled with xenon, two cooling blowers, one treatment chamber with a conveyor belt and a control module ─ to direct concentrated bursts of light to modify the peanut allergenic proteins. That way, human antibodies can’t recognize them as allergens and begin to release histamines.

Histamines create allergy symptoms such as itching, rashes and wheezing. The pulsing light reduced the allergenic potential of the major peanut proteins Ara h1-h3.

Source: University of Florida Institute of Food and Agricultural Sciences

Multiple allergic reactions traced to single protein

This is a mast cell. Credit: Priyanka Pundir/University of Alberta

Johns Hopkins and University of Alberta researchers have identified a single protein as the root of painful and dangerous allergic reactions to a range of medications and other substances. If a new drug can be found that targets the problematic protein, they say, it could help smooth treatment for patients with conditions ranging from prostate cancer to diabetes to HIV. Their results appear in the journal Nature on Dec. 17.

Previous studies traced reactions such as pain, itching and rashes at the injection sites of many drugs to part of the immune system known as mast cells. When specialized receptors on the outside of mast cells detect warning signals known as antibodies, they spring into action, releasing histamine and other substances that spark inflammation and draw other immune cells into the area. Those antibodies are produced by other immune cells in response to bacteria, viruses or other perceived threats. However, "although many of these injection site reactions look like an allergic response, the strange thing about them is that no antibodies are produced," says Xinzhong Dong, Ph.D., an associate professor of neuroscience in the Institute for Basic Biomedical Sciences at the Johns Hopkins University School of Medicine.

To zero in on the cause of the reactions, Benjamin McNeil, Ph.D., a postdoctoral fellow in Dong's laboratory, first set out to find which mast cell receptor -- or receptors -- responded to the drugs in mice. Previous studies had identified a human receptor likely to be at fault in the allergic reactions; McNeil found a receptor in mice that, like the human receptor, is found only in mast cells. He then tested that receptor by putting it into lab-grown cells and found that they did react to medications that provoke mast cell response. He found similar results for the human receptor that previous studies had indicated was a likely culprit.

"It's fortunate that all of the drugs turn out to trigger a single receptor -- it makes that receptor an attractive drug target," McNeil says.

To find out whether eliminating the receptor really would eliminate the allergic reactions, the research team also disabled the gene for the suspect receptor in mice. These "knockout" mice did not have any of the drug allergy symptoms that their genetically normal counterparts displayed.

The researchers are now working to find compounds that could safely block the culprit receptor in humans, known as MRGPRX2. Such a drug would not prevent true allergic reactions, which produce antibodies, but only the pseudoallergic reactions triggered by MRGPRX2. Still, it could improve the lives of many patients, says McNeil, by lessening the drug side effects they currently endure. Medications that trigger MRGPRX2 include cancer drugs cetrorelix, leuprolide and octreotide; HIV drug sermorelin; fluoroquinolone antibiotics; and neuromuscular blocking drugs used to paralyze muscles during surgeries.

Dong's research group is also looking into the possibility that MRGPRX2 could be behind immune conditions such as rosacea and psoriasis that don't stem from medication use.

Source: Johns Hopkins Medicine

Sharing that crowded holiday flight with countless hitchhiking dust mites

Predicted structure of the group 1 allergen protein from an American house dust mite. Arrow points to the location of a novel mutation discovered by the University of Michigan-led team.
Credit: Rubaba Hamid

As if holiday travel isn't stressful enough. Now University of Michigan researchers say we're likely sharing that already overcrowded airline cabin with countless tiny creatures including house dust mites.

"What people might not realize when they board a plane is that they can share the flight with a myriad of microscopic passengers-- including house dust mites--that take advantage of humanity's technological progress for their own benefit," said U-M biologist Pavel Klimov.

"House dust mites can easily travel on an airline passenger's clothes, skin, food and baggage," said Klimov, an assistant research scientist in the U-M Department of Ecology and Evolutionary Biology. "Like humans, they use air travel to visit new places, where they establish new populations, expand their ranges and interact with other organisms through various means."

Air travel likely explains some of the findings of a new genetic study conducted by Klimov and U-M visiting scholar Rubaba Hamid that looked at the connections between house dust mite populations in the United States and South Asia.

They found genetic mutations shared by mites in the U.S. and Pakistan that demonstrate the eight-legged creatures' propensity for intercontinental dispersal, according to a research paper scheduled for online publication Dec. 10 in the journal PLOS ONE.

"What we found suggests that mite populations are indeed linked through migration across continents, though geographic differences still can be detected," Hamid said. "Every time a mite successfully migrates to a new place, it brings its own genetic signature that can be detected in the resident population a long time after the migration event."

The study focused on two medically important mite species, the American and European house dust mite. Both species have global distributions, though the former is more abundant in the U.S.

Ancestors of the two species probably separated from each other nearly 81 million years ago--long before the origin of humans--when they inhabited bird nests. Today, house dust mites are blamed for causing allergic reactions in more than 65 million people worldwide and thrive in the mattresses, sofas and carpets of even the cleanest homes.

Hamid, Klimov and their colleagues examined genetic variation in the group 1 allergen gene from samples of the two mite species collected in the U.S. and Pakistan. The group 1 allergen gene encodes for the most important allergy-causing protein in house dust mites.

An inactive form of this protein is used in clinics worldwide as part of the standard skin-prick test for allergies. Though the test can be inaccurate if it does not include local genetic variants of the allergy-causing protein, geographical variation in group 1 allergen proteins has not been extensively studied in the U.S., Klimov said.

"We need to have a better idea about the diversity of allergenic proteins around the world, and particularly in the United States," he said.

In genetic sequences from American house dust mites (Dermatophagoides farinae), the 
researchers observed mutations at 14 positions along the length of the group 1 allergen gene.

All but one of the mutations are "silent," meaning they occur at the DNA level without changing the amino acid structure of the protein. Only mutations at the protein level have medical significance because they can change allergenic properties.

"The most unexpected result was the finding that a previously unknown mutation occurred at the active site of the protein at position 197," Klimov said. "This was a rare mutation, found in only a single population of house dust mite in South Asia.

"Our analysis indicates that this mutation might alter the enzyme activity of the protein. But allergenic properties, immune response and cross-reactivity of the protein are unknown at this time," he said. "Follow-up experiments to elucidate these issues are underway in our lab."

Source: University of Michigan

Simple textiles can be used with catalysts to enable complex chemical reactions

To attach the "chemical tools" to the nylon fibers the chemist simply irradiate the soaked textile with UV light.

In future, it will be much easier to produce some active pharmaceutical substances and chemical compounds than was the case to date. An international team working with chemists from the Max-Planck-Institut für Kohlenforschung in Mülheim an der Ruhr have immobilised various catalysts on nylon in a very simple way. Catalysts mediate between the reagents in a chemical reaction and control the process leading to the desired end product. When textile material is used as a support for the chemical auxiliaries, the reaction can proceed on a large surface thereby increasing its efficiency.

One of the catalysts that the researchers used in this way plays an important role in the synthesis of a pharmaceutical agent which could only be used previously in dissolved form, making the production process very complicated and expensive. Immobilising this catalyst on fabric simplifies production considerably. This process may be expected to yield similar advantages for other chemical processes.

Functional textiles are usually understood as the textiles used to make windproof jackets, breathable footwear and particularly effective thermal underwear. However, the term could soon refer to something else -- textiles which are "functionalised" with the help of organic catalysts. Working in collaboration with scientists from the Deutsches 

Textilforschungszentrum in Krefeld and Sungkyunkwan University in Suwon, Korea, researchers at the Max-Planck-Institut für Kohlenforschung in Mülheim an der Ruhr have developed a process for immobilising different organic catalysts on textiles with the help of ultraviolet light. The fabric thereby acts as a support for the substances on which a chemical reaction occurs.

Up to now, science has focused more on the macroscopic functionality of textiles, for example clothing, explains Dr. Ji-Woong Lee, who recently completed his doctorate at the Max-Planck-Institut für Kohlenforschung under the supervision of Professor Benjamin List, head of the Institute's Homogenous Catalysis Group. "As opposed to this, our method can give simple textiles microscopic functionalities," explains the Korean scientist. Together with his colleagues, Dr. Lee armed pieces of nylon with catalysts. The latter can be imagined as chemical tools which fulfil various tasks during chemical reactions.

Excellent yields, little wear and tear

For their tests, the Mühlheim-based researchers used three organic catalysts: a base (dimethylaminopyridine, DMAP), a sulfonic acid and a catalyst which functions as both an acid and a base. The latter is used in the pharmaceuticals industry to steer a reaction to one of two products, which are chemically completely identical. The two forms have mirror-image structures, like a left and right hand, but only one variant has the desired medical effect. Up to now, the catalyst that generates this variant could only be used in dissolved form and then had to be separated again. The complicated separation process could be avoided using a catalyst immobilised on fabric.

To attach the catalysts to the nylon fibres, the chemists irradiated the textile to which a catalyst was applied with UV light for five minutes -- but no longer, as this would impede the activity of the catalyst and its immobilisation on the nylon. A comparable process did not exist up to now.

The catalysts, which were practically interwoven with the fabric, displayed all of the characteristics that the chemists expect from such a system: the result of the chemical reactions which the scientists undertook with the catalyst-loaded nylon strips is impressive. 

All three catalysts converted around 90 percent of the source materials to the desired products. And the catalyst which is used in the pharmaceutical industry and only generates one out of two mirror-image molecules, achieved a success rate of over 95 percent without showing any major signs of wear and tear. Ji-Woong Lee carried out several hundred test-runs and observed that the catalysts relinquished little of their functionality.

A large surface makes chemical reactions more efficient

Compared with other ways of immobilising catalysts, "organotextile catalysis" has several advantages: in particular, it provides the reagents with a larger surface than other supports, for example plastic spheres or foils -- the larger the surface, the more efficiently a reaction proceeds. Moreover, nylon is flexible and very inexpensive. Dry textiles loaded with catalysts are easy to transport, which means that it is simpler to meet the requirements for some chemical processes where it is practically impossible to set up sophisticated chemical systems. For example, organotextile catalysis could help in the treatment of water in locations where people are cut off from the water supply.

"Our method enables the low-cost production of long-term functionalised textiles without causing any pollution," says Ji-Woong Lee. He is entirely convinced that the process can be applied in several scientific areas -- and industrial processes. "In addition to chemistry, these could include biology, the materials science and pharmaceutics."

Source: Max-Planck-Institut für Kohlenforschung

Expect higher grass pollen, allergen exposure in coming century

A study provides the first evidence that pollen production is significantly stimulated by elevated carbon dioxide in a grass species as a result of climate change, which may have significant impact on human health. Credit: UMass Amherst

Results of a new study by scientists at the University of Massachusetts Amherst strongly suggest that there will be notable increases in grass pollen production and allergen exposure up to 202 percent in the next 100 years, leading to a significant, worldwide impact on human health due to predicted rises in carbon dioxide (CO2) and ozone (O3) due to climate change.

While CO2 stimulates reproduction and growth in plants, ozone has a negative impact on plant growth, the authors point out. In this study in Timothy grass, researchers led by environmental health scientist Christine Rogers of the UMass Amherst School of Public Health and Health Sciences (SPHHS) determined the interactive effects of CO2 and ozone at projected higher levels on pollen production and concentrations of a Timothy grass pollen protein that is a major human allergen. Findings are reported in the current issue of PLOS ONE.

Rogers and plant science colleagues at UMass Amherst, with postdoctoral researcher and first author Jennifer Albertine, write, "The implications of increasing CO2 for human health are clear. Stimulation of grass pollen production by elevated CO2 will increase airborne concentrations and increase exposure and suffering in grass pollen-allergic individuals."

Rogers notes that, "This is the first evidence that pollen production is significantly stimulated by elevated carbon dioxide in a grass species and has worldwide implications due to the ubiquitous presence of grasses in all biomes and high prevalence of grass pollen allergy. These results are similar to our other studies performed in other highly allergenic taxa such as ragweed but with more extreme outcomes and wider impacts."

For these experiments, the researchers exposed grass plants in specially designed continuously stirred tank reactor chambers that allow researchers to expose plants to different atmospheric gas concentrations. They established four experimental atmospheric treatments:

• control, current atmosphere (30 ppb O3 and 400 ppm CO2)
• elevated O3, current CO2 (80 ppb O3, 400 ppm CO2)
• current O3, elevated CO2 (30 ppb O3, 800 ppm CO2)
• elevated O3, elevated CO2 (80 ppb O3, 800ppm CO2)

At the appropriate plant development stage, Albertine and colleagues bagged flowers, captured and measured pollen amounts and extracted the allergen protein Phl p 5 from pollen samples for measurement by enzyme-linked immunosorbent assay (ELISA).

They found that elevated CO2 of 800 ppm, increased pollen production per flower by 53 percent while the different ozone levels had no effect on the amount of pollen produced. There was also a trend of increased number of plants flowering in response to elevated CO2 further increasing pollen production up to 200 percent. While elevated ozone did decrease the Phl p 5 allergen content in pollen, "the strong CO2-stimulation of pollen production suggests increased exposure to Timothy grass allergen overall," even if O3 projections are realized, the authors note.

They add that the health implications of increased ozone are "more complex" because higher levels of this greenhouse gas irritate mucous membranes and worsen the allergic airway response. Projected ozone increases "would likely elicit negative respiratory health effects independent of any health effects as a result of increased pollen by elevated CO2."

Source:  University of Massachusetts at Amherst