The flexibility offered by Tecan’s MultiChannel Arm™ (MCA) 384 and Freedom EVO® liquid handling platform is vital to researchers in the Biology Department at the University of Konstanz, Germany, helping them to develop novel molecular tools for the investigation of cellular processes. Professor Thomas U Mayer explained: “We are investigating how small molecules affect protein activity, and how they may be used to activate or deactivate this activity during mitosis in living cells. We perform a variety of protein- and cell-based assays, using fluorescence-based techniques to follow the process of interest, and depend on a Freedom EVO platform equipped with the versatile MCA 384 option to reproducibly perform these screens.”
“We mainly work in 384-well format, but we also use 96-well plates for RNAibased screens, and so wanted a highly flexible system which could perform various assays as required. The MCA 384’s adapter plate concept allows us to automatically switch between 384- and 96-well pipetting, as well as use our existing 384-well pin tool for very low volume liquid transfers. This enables us to use a single workstation to perform a wide range of tasks, which is very important in academia, and we have been very happy with the system’s performance.”
16 August 2011
New tool to help predict death in overweight and obese people
A new tool -- the Edmonton obesity staging system (EOSS) -- improves on current methods to predict the risk of death in overweight and obese people, according to a study in CMAJ (Canadian Medical Association Journal). Body mass index (BMI) is the most common tool in measuring excess fat, although it is an indirect measure and cannot distinguish between lean and fat tissue. BMI also does not assess for the presence of any of the numerous conditions that may be associated with excess weight. Studies have reported that high BMI is associated with an increased risk of obesity-related health issues (morbidity) and death. Increased waist circumference is also associated with a higher risk of cardiovascular disease and the metabolic syndrome.
The EOSS, originally proposed by Dr. Arya Sharma from the University of Alberta, ranks overweight and obese people on a five-point scale according to their underlying health status and the presence or absence of underlying health conditions. EOSS was used to predict death using data from a population-representative survey of 8143 people in the 1988-1994 and 1999-2004 US National Health and Human Nutrition Examination Surveys (NHANES).
Researchers found that although 77% of overweight or obese people in the NHANES 1988-94 survey and 90% of those in the 1999-2004 survey were classified as stage 1 or 2 in the EOSS, their risk of dying was substantially lower than that of overweight or obese people classified as stage 3.
"Within a nationally representative cohort, higher Edmonton obesity staging system scores were a strong predictor of increasing mortality in both the overall population and in a cohort of people eligible for bariatric surgery. …independent of BMI and the presence of metabolic syndrome or hypertriglyceridemic waist," writes Dr. Raj Padwal, University of Alberta, with coauthors. "Even within strata of BMI categories, there was clear separation of survival curves according to Edmonton obesity staging system scores."
The tool could be used to prioritize patients for obesity treatments, including such interventions as bariatric surgery.
"Such enhanced risk assessment may enable a greater understanding of obesity-related prognosis and may also assist in determining the urgency of intervention," they write.
The authors conclude, "We propose that [the Edmonton Obesity Staging System] be considered adjunctive to current anthropometric classification systems in assessing obesity-related risk, determining prognosis and guiding treatment."
**Source: Canadian Medical Association Journal
The EOSS, originally proposed by Dr. Arya Sharma from the University of Alberta, ranks overweight and obese people on a five-point scale according to their underlying health status and the presence or absence of underlying health conditions. EOSS was used to predict death using data from a population-representative survey of 8143 people in the 1988-1994 and 1999-2004 US National Health and Human Nutrition Examination Surveys (NHANES).
Researchers found that although 77% of overweight or obese people in the NHANES 1988-94 survey and 90% of those in the 1999-2004 survey were classified as stage 1 or 2 in the EOSS, their risk of dying was substantially lower than that of overweight or obese people classified as stage 3.
"Within a nationally representative cohort, higher Edmonton obesity staging system scores were a strong predictor of increasing mortality in both the overall population and in a cohort of people eligible for bariatric surgery. …independent of BMI and the presence of metabolic syndrome or hypertriglyceridemic waist," writes Dr. Raj Padwal, University of Alberta, with coauthors. "Even within strata of BMI categories, there was clear separation of survival curves according to Edmonton obesity staging system scores."
The tool could be used to prioritize patients for obesity treatments, including such interventions as bariatric surgery.
"Such enhanced risk assessment may enable a greater understanding of obesity-related prognosis and may also assist in determining the urgency of intervention," they write.
The authors conclude, "We propose that [the Edmonton Obesity Staging System] be considered adjunctive to current anthropometric classification systems in assessing obesity-related risk, determining prognosis and guiding treatment."
**Source: Canadian Medical Association Journal
More evidence that caffeine lowers risk of skin cancer
There might be a time when instead of just drinking that morning cup of coffee you lather it on your skin as a way of preventing harmful sun damage or skin cancer. A new Rutgers study strengthens the theory that caffeine guards against certain skin cancers at the molecular level by inhibiting a protein enzyme in the skin, known as ATR. Scientists believe that based on what they have learned studying mice, caffeine applied directly to the skin might help prevent damaging UV light from causing skin cancer.
Prior research indicated that mice that were fed caffeinated water and exposed to lamps that generated UVB radiation that damaged the DNA in their skin cells were able to kill off a greater percentage of their badly damaged cells and reduce the risk of cells becoming cancerous.
"Although it is known that coffee drinking is associated with a decreased risk of non-melanoma skin cancer, there now needs to be studies to determine whether topical caffeine inhibits sunlight-induced skin cancer," said Allan Conney, director of the Susan Lehman Cullman Laboratory for Cancer Research.
In this newly-published study, instead of inhibiting ATR with caffeinated water, Rutgers researchers, in collaboration with researchers from the University of Washington, genetically modified and diminished ATR in one group of mice. The results: the genetically modified mice developed tumors more slowly than the unmodified mice, had 69 percent fewer tumors than regular mice and developed four times fewer invasive tumors.
The study also found, however, that when both groups of mice were exposed to chronic ultraviolet rays for an extended period of time, tumor development occurred in both the genetically modified and regular mice. What this seems to indicate, says Conney, is that inhibiting the ATR enzyme works best at the pre-cancerous stage before UV-induced skin cancers are fully developed.
According to the National Cancer Institute, sunlight-induced skin cancer is the most prevalent cancer in the United States with more than 1 million new cases each year. Although multiple human epidemiologic studies link caffeinated beverage intake with significant decreases in several different types of cancer, including skin cancer, just how and why coffee protects against the disease is unknown.
"Caffeine might become a weapon in prevention because it inhibits ATR and also acts ad as a sunscreen and directly absorbs damaging UV light," said Conney.
**Source: Rutgers University
Prior research indicated that mice that were fed caffeinated water and exposed to lamps that generated UVB radiation that damaged the DNA in their skin cells were able to kill off a greater percentage of their badly damaged cells and reduce the risk of cells becoming cancerous.
"Although it is known that coffee drinking is associated with a decreased risk of non-melanoma skin cancer, there now needs to be studies to determine whether topical caffeine inhibits sunlight-induced skin cancer," said Allan Conney, director of the Susan Lehman Cullman Laboratory for Cancer Research.
In this newly-published study, instead of inhibiting ATR with caffeinated water, Rutgers researchers, in collaboration with researchers from the University of Washington, genetically modified and diminished ATR in one group of mice. The results: the genetically modified mice developed tumors more slowly than the unmodified mice, had 69 percent fewer tumors than regular mice and developed four times fewer invasive tumors.
The study also found, however, that when both groups of mice were exposed to chronic ultraviolet rays for an extended period of time, tumor development occurred in both the genetically modified and regular mice. What this seems to indicate, says Conney, is that inhibiting the ATR enzyme works best at the pre-cancerous stage before UV-induced skin cancers are fully developed.
According to the National Cancer Institute, sunlight-induced skin cancer is the most prevalent cancer in the United States with more than 1 million new cases each year. Although multiple human epidemiologic studies link caffeinated beverage intake with significant decreases in several different types of cancer, including skin cancer, just how and why coffee protects against the disease is unknown.
"Caffeine might become a weapon in prevention because it inhibits ATR and also acts ad as a sunscreen and directly absorbs damaging UV light," said Conney.
**Source: Rutgers University
Exercise may help prevent brain damage caused by Alzheimer's disease
Regular exercise could help prevent brain damage associated with neurodegenerative diseases like Alzheimer's, according to research published this month in Elsevier's journal Brain, Behavior, and Immunity. "Exercise allows the brain to rapidly produce chemicals that prevent damaging inflammation," said Professor Jean Harry, who led the study at the National Institute of Environmental Health Sciences in the United States. "This could help us develop a therapeutic approach for early intervention in preventing damage to the brain."
Previous research has already demonstrated that exercise after brain injury can help the repair mechanisms. This new study shows that exercise before the onset of damage modifies the brain environment in such a way that the neurons are protected from severe insults. The study used an experimental model of brain damage, in which mice are exposed to a chemical that destroys the hippocampus, an area of the brain which controls learning and memory. Mice that were exercised regularly prior to exposure produced an immune messenger called interleukin-6 in the brain, which dampens the harmful inflammatory response to this damage, and prevents the loss of function that is usually observed.
Pharmacological therapies to downregulate inflammation and address cognitive decline in older adults, and those with Alzheimer's disease, have been less successful. This research helps understand how exercise could be used to affect the path of many human conditions, such as neurodevelopmental disorders and neurodegenerative diseases. In addition, as a chemical model of neuronal damage was used, it also raises the possibility that exercise could offer protection against the potentially harmful effects of environmental toxins.
"This elegant series of experiments reveals an alternative pathway by which voluntary physical exercise may protect hippocampal neurons," said Dr. Ruth Barrientos from the Department of Psychology and Neuroscience at the University of Colorado. "The study on the role of exercise as a therapeutic intervention will undoubtedly get a workout in the years to come. Perhaps the greatest challenge with this line of research will not be more discoveries of compelling evidence of the anti-neuroinflammatory effects of exercise, but instead, getting humans to exercise voluntarily and regularly."
The research was funded by the Division of Intramural Research, National Institute of Environmental Health Sciences, and the National Institutes of Health.
**Source: Elsevier
Previous research has already demonstrated that exercise after brain injury can help the repair mechanisms. This new study shows that exercise before the onset of damage modifies the brain environment in such a way that the neurons are protected from severe insults. The study used an experimental model of brain damage, in which mice are exposed to a chemical that destroys the hippocampus, an area of the brain which controls learning and memory. Mice that were exercised regularly prior to exposure produced an immune messenger called interleukin-6 in the brain, which dampens the harmful inflammatory response to this damage, and prevents the loss of function that is usually observed.
Pharmacological therapies to downregulate inflammation and address cognitive decline in older adults, and those with Alzheimer's disease, have been less successful. This research helps understand how exercise could be used to affect the path of many human conditions, such as neurodevelopmental disorders and neurodegenerative diseases. In addition, as a chemical model of neuronal damage was used, it also raises the possibility that exercise could offer protection against the potentially harmful effects of environmental toxins.
"This elegant series of experiments reveals an alternative pathway by which voluntary physical exercise may protect hippocampal neurons," said Dr. Ruth Barrientos from the Department of Psychology and Neuroscience at the University of Colorado. "The study on the role of exercise as a therapeutic intervention will undoubtedly get a workout in the years to come. Perhaps the greatest challenge with this line of research will not be more discoveries of compelling evidence of the anti-neuroinflammatory effects of exercise, but instead, getting humans to exercise voluntarily and regularly."
The research was funded by the Division of Intramural Research, National Institute of Environmental Health Sciences, and the National Institutes of Health.
**Source: Elsevier
Se incrementa la incidencia del melanoma
'Vuelta y vuelta al sol' es la receta de quienes ansían un bronceado veraniego. Un hábito muy repetido en las playas y las piscinas durante los meses de verano. Pero cuidado, porque también es el principal culpable de que la incidencia de melanoma haya aumentado un 237% en los últimos 30 años. Así lo advertían los expertos en el último Congreso Anual de la Sociedad Americana de Oncología Clínica (ASCO), celebrado el pasado mes de junio en Chicago (EEUU).
Si se diagnostica a tiempo, este tumor se cura en un 95% de los casos. Sin embargo, cuando la enfermedad no se detecta de forma precoz, el pronóstico no es muy positivo. Aparece metástasis en otras partes del cuerpo y no hay muchas opciones terapéuticas. Recientemente, en Europa se ha aprobado un fármaco (Ipilimumab) que prolonga la esperanza de vida de estos pacientes unos dos meses de media, pero aún queda mucho camino por recorrer.
La realidad de las cifras no ha cambiado. El melanoma avanzado sigue siendo el responsable del 75% de las muertes que ocurren por cáncer de piel (hay otros tipos como el carcinoma basocelular y el espinocelular). Por esta razón, aunque la genética también influye, los expertos recuerdan que algunos factores de riesgo sí se pueden evitar (tomar el sol entre las 11 y las 16 horas o no utilizar crema de protección solar) y hacen hincapié en la prevención y la vigilancia. Por ejemplo, "una persona de menos de 20 años que tenga más de 50 lunares debe ir al dermatólogo para que éste valore si son de riesgo o no", señala Aurora Guerra, jefe de Dermatología del Hospital 12 de Octubre de Madrid.
Precisamente los jóvenes son quienes más descuidan su protección frente a los rayos ultravioleta. Según un estudio publicado en 'Journal British Association of Dermatologists', la parte de la población que peor protege su piel del sol es aquella que está entre los 16 y los 30 años, "a pesar de que el melanoma sea el segundo cáncer más común en este grupo de edad". Y, a tenor de los resultados de una investigación realizada por el Observatorio del Cáncer de la Asociación Española contra el Cáncer (AECC) en junio, los hábitos de esta parte de la población en España no son mucho mejores. Se queman más, se exponen con gran frecuencia a las radiaciones solares durante las horas centrales del día y se protegen mucho menos que el resto de la población. "Son los que menos importancia dan a los diferentes tipos de protección solar", aseguraba Naiara Cambas, la directora del Observatorio.
Dado que los efectos de la radiación solar sobre el organismo son acumulativos, afirman los especialistas, es importante comenzar con la fotoprotección a edades tempranas. De hecho, "está demostrado que las quemaduras del sol que se producen antes de los 15 años constituyen un factor de riesgo para el melanoma", subraya Guerra.
Si se diagnostica a tiempo, este tumor se cura en un 95% de los casos. Sin embargo, cuando la enfermedad no se detecta de forma precoz, el pronóstico no es muy positivo. Aparece metástasis en otras partes del cuerpo y no hay muchas opciones terapéuticas. Recientemente, en Europa se ha aprobado un fármaco (Ipilimumab) que prolonga la esperanza de vida de estos pacientes unos dos meses de media, pero aún queda mucho camino por recorrer.
La realidad de las cifras no ha cambiado. El melanoma avanzado sigue siendo el responsable del 75% de las muertes que ocurren por cáncer de piel (hay otros tipos como el carcinoma basocelular y el espinocelular). Por esta razón, aunque la genética también influye, los expertos recuerdan que algunos factores de riesgo sí se pueden evitar (tomar el sol entre las 11 y las 16 horas o no utilizar crema de protección solar) y hacen hincapié en la prevención y la vigilancia. Por ejemplo, "una persona de menos de 20 años que tenga más de 50 lunares debe ir al dermatólogo para que éste valore si son de riesgo o no", señala Aurora Guerra, jefe de Dermatología del Hospital 12 de Octubre de Madrid.
Precisamente los jóvenes son quienes más descuidan su protección frente a los rayos ultravioleta. Según un estudio publicado en 'Journal British Association of Dermatologists', la parte de la población que peor protege su piel del sol es aquella que está entre los 16 y los 30 años, "a pesar de que el melanoma sea el segundo cáncer más común en este grupo de edad". Y, a tenor de los resultados de una investigación realizada por el Observatorio del Cáncer de la Asociación Española contra el Cáncer (AECC) en junio, los hábitos de esta parte de la población en España no son mucho mejores. Se queman más, se exponen con gran frecuencia a las radiaciones solares durante las horas centrales del día y se protegen mucho menos que el resto de la población. "Son los que menos importancia dan a los diferentes tipos de protección solar", aseguraba Naiara Cambas, la directora del Observatorio.
Dado que los efectos de la radiación solar sobre el organismo son acumulativos, afirman los especialistas, es importante comenzar con la fotoprotección a edades tempranas. De hecho, "está demostrado que las quemaduras del sol que se producen antes de los 15 años constituyen un factor de riesgo para el melanoma", subraya Guerra.
-Aprender a protegerse del sol
Según un estudio realizado por un laboratorio farmacéutico, independientemente de la edad, cuatro de cada 10 españoles siguen sin protegerse frente al sol y el 20% continúa tumbándose en la hamaca sin protección solar entre las 11 y las 16 horas. "No sólo hay que evitar esta franja horaria, sino que, además, es preciso protegerse con filtros solares y con sombreros y ropa holgada", recomienda la dermatóloga española. Y aún más, "no vale con aplicarse cremas protectoras, éstas deben usarse adecuadamente".
Tal y como muestra la Encuesta Nacional sobre Fotoprotección, el 87% de los españoles no se aplica correctamente este producto. La doctora Guerra explica que hay que "elegir el factor adecuado a la piel de cada uno, aplicarlo media hora antes de tomar el sol, en cantidades generosas (la dosis recomendada es de 2 mg por cm2) y repetir esta aplicación cada dos horas y después del baño".
Con el objetivo de recordar estos mensajes, año tras año, se ponen en marcha varias campañas informativas. Desde el año 2000, la Academia Española de Dermatología y Venereología (AEDV) desarrolla varias actividades de concienciación y, durante aproximadamente un mes, ofrece una consulta móvil para diagnosticar posibles casos de cáncer de piel a través del 'Bus de la Prevención', que este año ha pasado por 11 ciudades españolas y ha examinado a más de 2.000 pacientes.
A todos ellos se les ha explicado que "los fotoprotectores de menos de 15 no protegen del cáncer de piel, que los que prometen resistir los baños de agua no son efectivos y que no sólo deben proteger de los rayos ultravioleta de tipo B, también frente a los UVA".
Durante los primeros años, los expertos de la AEDV intentaban luchar contra la idea de que "estar moreno era sinónimo de belleza". Por eso, sus carteles y los folletos informativos tenían titulares como: 'De la belleza de un lugar al peligro de un melanoma'. A lo largo de estos años, se han divulgado otros aspectos importantes: la regla del ABCDE, el papel del dermatólogo como el único especialista capacitado para diagnosticar un melanoma y el envejecimiento prematuro de la piel, la autoexploración, factores de riesgo como el deporte...
Diez de cada 100 personas padecerán un cáncer de piel a lo largo de su vida. Teniendo en cuenta que el factor genético no se puede cambiar y que las radiaciones solares son un importante factor riesgo, quizás merezca la pena pensar que la belleza no está en el bronceado sino en los hábitos sanos y en la prevención de esta enfermedad.
Según un estudio realizado por un laboratorio farmacéutico, independientemente de la edad, cuatro de cada 10 españoles siguen sin protegerse frente al sol y el 20% continúa tumbándose en la hamaca sin protección solar entre las 11 y las 16 horas. "No sólo hay que evitar esta franja horaria, sino que, además, es preciso protegerse con filtros solares y con sombreros y ropa holgada", recomienda la dermatóloga española. Y aún más, "no vale con aplicarse cremas protectoras, éstas deben usarse adecuadamente".
Tal y como muestra la Encuesta Nacional sobre Fotoprotección, el 87% de los españoles no se aplica correctamente este producto. La doctora Guerra explica que hay que "elegir el factor adecuado a la piel de cada uno, aplicarlo media hora antes de tomar el sol, en cantidades generosas (la dosis recomendada es de 2 mg por cm2) y repetir esta aplicación cada dos horas y después del baño".
Con el objetivo de recordar estos mensajes, año tras año, se ponen en marcha varias campañas informativas. Desde el año 2000, la Academia Española de Dermatología y Venereología (AEDV) desarrolla varias actividades de concienciación y, durante aproximadamente un mes, ofrece una consulta móvil para diagnosticar posibles casos de cáncer de piel a través del 'Bus de la Prevención', que este año ha pasado por 11 ciudades españolas y ha examinado a más de 2.000 pacientes.
A todos ellos se les ha explicado que "los fotoprotectores de menos de 15 no protegen del cáncer de piel, que los que prometen resistir los baños de agua no son efectivos y que no sólo deben proteger de los rayos ultravioleta de tipo B, también frente a los UVA".
Durante los primeros años, los expertos de la AEDV intentaban luchar contra la idea de que "estar moreno era sinónimo de belleza". Por eso, sus carteles y los folletos informativos tenían titulares como: 'De la belleza de un lugar al peligro de un melanoma'. A lo largo de estos años, se han divulgado otros aspectos importantes: la regla del ABCDE, el papel del dermatólogo como el único especialista capacitado para diagnosticar un melanoma y el envejecimiento prematuro de la piel, la autoexploración, factores de riesgo como el deporte...
Diez de cada 100 personas padecerán un cáncer de piel a lo largo de su vida. Teniendo en cuenta que el factor genético no se puede cambiar y que las radiaciones solares son un importante factor riesgo, quizás merezca la pena pensar que la belleza no está en el bronceado sino en los hábitos sanos y en la prevención de esta enfermedad.
**Publicado en "EL MUNDO"
15 August 2011
Warning signs predict kidney injury after surgery
Acute kidney injury (AKI) is a common -- but preventable -- complication after surgery that can lead to other complications or even death. The use and development of biomarkers will help physicians diagnose and treat acute kidney injury. Three protein measurements indicate who has a high risk of developing kidney injury after heart surgery, according to two studies appearing in an upcoming issue of the Journal of the American Society of Nephrology. "To date, these are the largest studies in adults and children comparing and validating the performance of three of the most frequently studied markers of kidney injury," said author Chirag Parikh, MD, PhD (Yale University School of Medicine).
The studies included more than 1,200 adults and 300 children undergoing heart surgery throughout North America. Frequent urine and blood samples were collected to measure levels of three proteins -- urine interleukin-18 (IL-18) and urine and plasma (blood) neutrophil gelatinase-associated lipocalin (NGAL) -- and assess their ability to predict who will develop kidney injury after surgery.
Traditionally, kidney trouble is assessed by measuring the blood protein creatinine, which is not ideal because it has a delayed result -- it does not pick up early damage and injury to the kidneys.
"We demonstrated that the three proteins in our study identify kidney injury soon after surgery and 24 to 48 hours earlier than creatinine, and shows a similar result," according to Parikh.
Risk of kidney injury was especially high -- more than six times higher -- for adults and children with the highest levels of urine IL-18. Plasma NGAL also predicted kidney injury in adults, whereas urine NGAL was not an accurate predictor in adults once results were adjusted for other factors. Urine IL-18 and urine, but not plasma, NGAL were accurate predictors in children.
Doctors may wish to measure these urine or blood proteins immediately after surgery to predict which patients are at high risk of developing kidney injury. These patients might benefit from kidney protective therapies.
The studies' results could also transform the diagnosis of kidney disease, Parikh believes. "Developing markers of structural kidney damage, before kidney function fails, is a top priority," he said.
The research's main limitation was that the adults enrolled were mainly Caucasian. Future studies should consider whether the results are the same in other races.
**Source: American Society of Nephrology
The studies included more than 1,200 adults and 300 children undergoing heart surgery throughout North America. Frequent urine and blood samples were collected to measure levels of three proteins -- urine interleukin-18 (IL-18) and urine and plasma (blood) neutrophil gelatinase-associated lipocalin (NGAL) -- and assess their ability to predict who will develop kidney injury after surgery.
Traditionally, kidney trouble is assessed by measuring the blood protein creatinine, which is not ideal because it has a delayed result -- it does not pick up early damage and injury to the kidneys.
"We demonstrated that the three proteins in our study identify kidney injury soon after surgery and 24 to 48 hours earlier than creatinine, and shows a similar result," according to Parikh.
Risk of kidney injury was especially high -- more than six times higher -- for adults and children with the highest levels of urine IL-18. Plasma NGAL also predicted kidney injury in adults, whereas urine NGAL was not an accurate predictor in adults once results were adjusted for other factors. Urine IL-18 and urine, but not plasma, NGAL were accurate predictors in children.
Doctors may wish to measure these urine or blood proteins immediately after surgery to predict which patients are at high risk of developing kidney injury. These patients might benefit from kidney protective therapies.
The studies' results could also transform the diagnosis of kidney disease, Parikh believes. "Developing markers of structural kidney damage, before kidney function fails, is a top priority," he said.
The research's main limitation was that the adults enrolled were mainly Caucasian. Future studies should consider whether the results are the same in other races.
**Source: American Society of Nephrology
Study sheds light on late phase of asthma attacks
New research led by scientists from Imperial College London explains why around half of people with asthma experience a 'late phase' of symptoms several hours after exposure to allergens. The findings, published in the journal Thorax, could lead to better treatments for the disease. An estimated 300 million people suffer from asthma, and the prevalence is rising. Symptoms are commonly triggered by allergens in the environment, such as pollen and dust mites. These stimuli can cause the airways to tighten within minutes, causing breathing difficulties which range from mild to severe. Many sufferers also experience a 'late asthmatic response' three to eight hours after exposure to allergens, causing breathing difficulties which can last up to 24 hours.
In the early asthmatic response, the allergen is recognised by mast cells, which release chemical signals that cause the airways to narrow. In contrast, the mechanism behind the late phase has remained unclear.
In research on mice and rats, the Imperial team have now found evidence that the late asthmatic response happens because the allergen triggers sensory nerves in the airways. These nerves activate reflexes which trigger other nerves that release the neurotransmitter acetylcholine, which causes the airways to narrow. If the findings translate to humans, it would mean that drugs that block acetylcholine -- called anticholinergics -- could be used to treat asthma patients that experience late phase responses following exposure to allergens.
Steroids are the main treatments for asthma prescribed now, but they are not effective for all patients. A recent clinical trial involving 210 asthma patients found that the anticholinergic drug tiotropium improved symptoms when added to a steroid inhaler, but the reason for this was unexplained.
"Many asthmatics have symptoms at night after exposure to allergens during the day, but until now we haven't understood how this late response is brought about," said Professor Maria Belvisi, from the National Heart and Lung Institute at Imperial College London, who led the research. "Our study in animals suggests that anticholinergic drugs might help to alleviate these symptoms, and this is supported by the recent clinical data. We are seeking funding to see if these findings are reproduced in proof of concept clinical studies in asthmatics."
The researchers hypothesised that sensory nerves were involved after observing that anaesthesia prevented the late asthmatic response in mice and rats. They succeeded in blocking the late asthmatic response using drugs that block different aspects of sensory nerve cell function, adding further evidence for this idea.
After establishing that sensory nerves detect the allergen, the researchers tested the effect of tiotropium, an anticholinergic drug that is used to treat chronic obstructive pulmonary disease. Tiotropium blocks the receptor for acetylcholine, which is released by nerves in the parasympathetic nervous system. Tiotropium also blocked the late asthmatic response, suggesting that parasympathetic nerves cause the airways to constrict.
The study was funded by the Medical Research Council (MRC). Professor Stephen Holgate, MRC funding board chair and an expert on asthma, said: "Unravelling the complex biology of asthma is vitally important, as it is an extremely dangerous condition which exerts lifelong damaging effects. The Medical Research Council is committed to research that opens doors to improving disease resilience, particularly in conditions which attack our body over the long-term. Studies like this are making really important progress and whilst we must always be cautious when taking findings from rodents into humans, these are very interesting and potentially important results."
**Source: Imperial College London
In the early asthmatic response, the allergen is recognised by mast cells, which release chemical signals that cause the airways to narrow. In contrast, the mechanism behind the late phase has remained unclear.
In research on mice and rats, the Imperial team have now found evidence that the late asthmatic response happens because the allergen triggers sensory nerves in the airways. These nerves activate reflexes which trigger other nerves that release the neurotransmitter acetylcholine, which causes the airways to narrow. If the findings translate to humans, it would mean that drugs that block acetylcholine -- called anticholinergics -- could be used to treat asthma patients that experience late phase responses following exposure to allergens.
Steroids are the main treatments for asthma prescribed now, but they are not effective for all patients. A recent clinical trial involving 210 asthma patients found that the anticholinergic drug tiotropium improved symptoms when added to a steroid inhaler, but the reason for this was unexplained.
"Many asthmatics have symptoms at night after exposure to allergens during the day, but until now we haven't understood how this late response is brought about," said Professor Maria Belvisi, from the National Heart and Lung Institute at Imperial College London, who led the research. "Our study in animals suggests that anticholinergic drugs might help to alleviate these symptoms, and this is supported by the recent clinical data. We are seeking funding to see if these findings are reproduced in proof of concept clinical studies in asthmatics."
The researchers hypothesised that sensory nerves were involved after observing that anaesthesia prevented the late asthmatic response in mice and rats. They succeeded in blocking the late asthmatic response using drugs that block different aspects of sensory nerve cell function, adding further evidence for this idea.
After establishing that sensory nerves detect the allergen, the researchers tested the effect of tiotropium, an anticholinergic drug that is used to treat chronic obstructive pulmonary disease. Tiotropium blocks the receptor for acetylcholine, which is released by nerves in the parasympathetic nervous system. Tiotropium also blocked the late asthmatic response, suggesting that parasympathetic nerves cause the airways to constrict.
The study was funded by the Medical Research Council (MRC). Professor Stephen Holgate, MRC funding board chair and an expert on asthma, said: "Unravelling the complex biology of asthma is vitally important, as it is an extremely dangerous condition which exerts lifelong damaging effects. The Medical Research Council is committed to research that opens doors to improving disease resilience, particularly in conditions which attack our body over the long-term. Studies like this are making really important progress and whilst we must always be cautious when taking findings from rodents into humans, these are very interesting and potentially important results."
**Source: Imperial College London
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