Cystic fibrosis (CF) is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Initially, Cl- conductance in the sweat duct was discovered to be impaired in CF, a finding that has been extended to all CFTR-expressing cells. Subsequent cloning of the gene showed that CFTR functions as a cyclic-AMP-regulated Cl- channel; and some CF-causing mutations inhibit CFTR Cl- channel activity.
The identification of additional CF-causing mutants with normal Cl- channel activity indicates, however, that other CFTR-dependent processes contribute to the disease. Indeed, CFTR regulates other transporters, including Cl(-)-coupled HCO3- transport. Alkaline fluids are secreted by normal tissues, whereas acidic fluids are secreted by mutant CFTR-expressing tissues, indicating the importance of this activity. HCO3- and pH affect mucin viscosity and bacterial binding. We have examined Cl(-)-coupled HCO3- transport by CFTR mutants that retain substantial or normal Cl- channel activity.
Here we show that mutants reported to be associated with CF with pancreatic insufficiency do not support HCO3- transport, and those associated with pancreatic sufficiency show reduced HCO3- transport.
Our findings demonstrate the importance of HCO3- transport in the function of secretory epithelia and in CF.
Saturday, May 19, 2007
Saturday, May 12, 2007
Nutritional Benefits for Cystic Fibrosis
Background Many patients with cystic fibrosis are malnourished at the time of diagnosis. Whether newborn screening and early treatment may prevent the development of a nutritional deficiency is not known.
Methods We compared the nutritional status of patients with cystic fibrosis identified by neonatal screening or by standard diagnostic methods. A total of 650,341 newborn infants were screened by measuring immunoreactive trypsinogen on dried blood spots (from April 1985 through June 1991) or by combining the trypsinogen test with DNA analysis (from July 1991 through June 1994). Of 325,171 infants assigned to an early-diagnosis group, cystic fibrosis was diagnosed in 74 infants, including 5 with negative screening tests. Excluding infants with meconium ileus, we evaluated nutritional status for up to 10 years by anthropometric and biochemical methods in 56 of the infants who received an early diagnosis and in 40 of the infants in whom the diagnosis was made by standard methods (the control group). Pancreatic insufficiency was managed with nutritional interventions that included high-calorie diets, pancreatic-enzyme therapy, and fat-soluble vitamin supplements.
Results The diagnosis of cystic fibrosis was confirmed by a positive sweat test at a younger age in the early-diagnosis group than in the control group (mean age, 12 vs. 72 weeks). At the time of diagnosis, the early-diagnosis group had significantly higher height and weight percentiles and a higher head-circumference percentile (52nd, vs. 32nd in the control group; P = 0.003). The early-diagnosis group also had significantly higher anthropometric indexes during the follow-up period, especially the children with pancreatic insufficiency and those who were homozygous for the F508 mutation.
Conclusions Neonatal screening provides the opportunity to prevent malnutrition in infants with cystic fibrosis.
Methods We compared the nutritional status of patients with cystic fibrosis identified by neonatal screening or by standard diagnostic methods. A total of 650,341 newborn infants were screened by measuring immunoreactive trypsinogen on dried blood spots (from April 1985 through June 1991) or by combining the trypsinogen test with DNA analysis (from July 1991 through June 1994). Of 325,171 infants assigned to an early-diagnosis group, cystic fibrosis was diagnosed in 74 infants, including 5 with negative screening tests. Excluding infants with meconium ileus, we evaluated nutritional status for up to 10 years by anthropometric and biochemical methods in 56 of the infants who received an early diagnosis and in 40 of the infants in whom the diagnosis was made by standard methods (the control group). Pancreatic insufficiency was managed with nutritional interventions that included high-calorie diets, pancreatic-enzyme therapy, and fat-soluble vitamin supplements.
Results The diagnosis of cystic fibrosis was confirmed by a positive sweat test at a younger age in the early-diagnosis group than in the control group (mean age, 12 vs. 72 weeks). At the time of diagnosis, the early-diagnosis group had significantly higher height and weight percentiles and a higher head-circumference percentile (52nd, vs. 32nd in the control group; P = 0.003). The early-diagnosis group also had significantly higher anthropometric indexes during the follow-up period, especially the children with pancreatic insufficiency and those who were homozygous for the F508 mutation.
Conclusions Neonatal screening provides the opportunity to prevent malnutrition in infants with cystic fibrosis.
Tuesday, May 08, 2007
Cystic Fibrosis And Omega 3
The primary aim of medical and scientific research on cystic fibrosis is to understand, treat and cure cystic fibrosis. An inherited disease, cystic fibrosis is thought to affect about 30,000 Americans and is the most common, life-shortening genetic disease known. Cystic fibrosis is a life-threatening disease caused by a defective gene and affecting about 30,000 children in America.
Researchers from the Beth Israel Deaconess Medical Centre, the University of Massachusetts and Massachusetts General Hospital took tissue samples from 38 patients with cystic fibrosis. It was found they had extremely high levels of arachidonic acid (AA) and abnormally low levels of docosahexaenoic acid (DHA). People who did not have CF did not have the fatty acids imbalance.
Researchers believe that many of the symptoms of cystic fibrosis follow the same pattern: mutated gene produces a mutated glycoconjugate resulting in a defective cellular component. There are approximately ten million symptomless carriers of the defective cystic fibrosis gene in America.
They say too much of one acid and too little of another means patients' bodies are more prone to inflammation. In the New England Journal of Medicine, they suggest Omega-3 oils, found in fish, could help correct the imbalance.
Each week three young people in the UK die from the disease, which is caused by the faulty CFTR gene. CF causes an abnormally thick, sticky mucus to be produced in the body, causing chronic inflammation of the lungs leading to life-threatening infections. The average life expectancy for a person with CF is around 31.
To diagnose cystic fibrosis, the laboratory carries out a sweat test. When the lungs and airways are choked, the cystic fibrosis patient coughs and produces very thick sputum. The authors concluded that forced ionisation of the indoor air represents a natural and efficient treatment for respiratory diseases in patients with cystic fibrosis.
When the cystic fibrosisTR is not normal, the regulation of salt through the membranes becomes defective. In the respiratory system the thin mucus lining becomes thick and sticky. As the digestive juices do not reach the intestine, due to blocked ducts from the pancreas and liver, the fats and protein are not digested.
Dr Steven Freedman of the gastroenterology division at Beth Israel Deaconess Medical Center, who led the research, said: "Since 1989, we have known that the defective CFTR gene is responsible for CF. "But we didn't understand how this defective gene leads to the symptoms of the disease. "This new study sheds light on what may be happening and provides a link between CFTR function and fatty acid metabolism." He added: "It is known that high amounts of AA and low amounts of DHA would predispose to inflammation. "This discovery may help explain why there is an excessive inflammatory response among CF patients. "This is the basis for why Omega-3 fish oils, found in cold-water fish as well as supplements, reduce inflammation since they increase levels of DHA and suppress AA." 'No diet change'
Dr Adam Jaffe, head of the CF Research Group at London's Institute of Child Health, told BBC News Online the research was interesting but not conclusive. "Patients shouldn't change their diet based on spurious associations between fatty acids and inflammation. "But I would not be against them adding supplements to their diets."
About the Author
Tom O`Connor is an expert on the benefits of Omega-3 fatty acids. http://www.1st-Omega-3.Com.
Researchers from the Beth Israel Deaconess Medical Centre, the University of Massachusetts and Massachusetts General Hospital took tissue samples from 38 patients with cystic fibrosis. It was found they had extremely high levels of arachidonic acid (AA) and abnormally low levels of docosahexaenoic acid (DHA). People who did not have CF did not have the fatty acids imbalance.
Researchers believe that many of the symptoms of cystic fibrosis follow the same pattern: mutated gene produces a mutated glycoconjugate resulting in a defective cellular component. There are approximately ten million symptomless carriers of the defective cystic fibrosis gene in America.
They say too much of one acid and too little of another means patients' bodies are more prone to inflammation. In the New England Journal of Medicine, they suggest Omega-3 oils, found in fish, could help correct the imbalance.
Each week three young people in the UK die from the disease, which is caused by the faulty CFTR gene. CF causes an abnormally thick, sticky mucus to be produced in the body, causing chronic inflammation of the lungs leading to life-threatening infections. The average life expectancy for a person with CF is around 31.
To diagnose cystic fibrosis, the laboratory carries out a sweat test. When the lungs and airways are choked, the cystic fibrosis patient coughs and produces very thick sputum. The authors concluded that forced ionisation of the indoor air represents a natural and efficient treatment for respiratory diseases in patients with cystic fibrosis.
When the cystic fibrosisTR is not normal, the regulation of salt through the membranes becomes defective. In the respiratory system the thin mucus lining becomes thick and sticky. As the digestive juices do not reach the intestine, due to blocked ducts from the pancreas and liver, the fats and protein are not digested.
Dr Steven Freedman of the gastroenterology division at Beth Israel Deaconess Medical Center, who led the research, said: "Since 1989, we have known that the defective CFTR gene is responsible for CF. "But we didn't understand how this defective gene leads to the symptoms of the disease. "This new study sheds light on what may be happening and provides a link between CFTR function and fatty acid metabolism." He added: "It is known that high amounts of AA and low amounts of DHA would predispose to inflammation. "This discovery may help explain why there is an excessive inflammatory response among CF patients. "This is the basis for why Omega-3 fish oils, found in cold-water fish as well as supplements, reduce inflammation since they increase levels of DHA and suppress AA." 'No diet change'
Dr Adam Jaffe, head of the CF Research Group at London's Institute of Child Health, told BBC News Online the research was interesting but not conclusive. "Patients shouldn't change their diet based on spurious associations between fatty acids and inflammation. "But I would not be against them adding supplements to their diets."
About the Author
Tom O`Connor is an expert on the benefits of Omega-3 fatty acids. http://www.1st-Omega-3.Com.
Thursday, May 03, 2007
Liver Disease in Cystic Fibrosis
The median age of the population with cystic fibrosis (CF) has increased worldwide, which has led to the suggestion that the prevalence of liver disease would increase. The aim of this study was to evaluate the natural history of CF-associated liver disease over a 15-year period in a well-controlled population of patients with CF. During the years 1976 through 1993, 124 patients were followed up by yearly liver function tests (LFTs). Fifteen patients were followed up with liver biopsies throughout the whole study period.
More than 50% of the patients had pathological LFTs in infancy, later being normalized. Approximately 25% of children 4 years of age or older had biochemical markers of liver disease during the study period. In about 10% of the patients, cirrhosis or advanced fibrosis was confirmed at biopsy and 4% of patients had cirrhosis with clinical liver disease.
Severe liver disease developed mainly during prepuberty and puberty. Of the 15 patients prospectively followed up with liver biopsies, only 3 had progressive fibrosis. No specific risk factor was identified, but deficiency of essential fatty acids was found more often in patients with marked steatosis (P < .05).
No patient developed clinical liver disease in adulthood and the histological changes in the liver biopsies were usually not progressive. Liver disease was no more frequent at the end of the study period although the median age of the patient population had increased.
Modern treatment might positively influence liver disease because it seemed less common, less progressive, and less serious than previously reported.
More than 50% of the patients had pathological LFTs in infancy, later being normalized. Approximately 25% of children 4 years of age or older had biochemical markers of liver disease during the study period. In about 10% of the patients, cirrhosis or advanced fibrosis was confirmed at biopsy and 4% of patients had cirrhosis with clinical liver disease.
Severe liver disease developed mainly during prepuberty and puberty. Of the 15 patients prospectively followed up with liver biopsies, only 3 had progressive fibrosis. No specific risk factor was identified, but deficiency of essential fatty acids was found more often in patients with marked steatosis (P < .05).
No patient developed clinical liver disease in adulthood and the histological changes in the liver biopsies were usually not progressive. Liver disease was no more frequent at the end of the study period although the median age of the patient population had increased.
Modern treatment might positively influence liver disease because it seemed less common, less progressive, and less serious than previously reported.
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