Licorice May Block Effectiveness Of Drug Widely Used By Transplant Patients

Licorice May Block Effectiveness Of Drug Widely Used By Transplant Patients
ScienceDaily (Mar. 31, 2009) —

Chemists in Taiwan are reporting that an ingredient in licorice — widely used in various foods and herbal medicines — appears to block the absorption of cyclosporine, a drug used by transplant patients to prevent organ rejection. This drug interaction could potentially result in transplant rejection, causing illness and even death among patients worldwide who take cyclosporine and licorice together, the researchers caution.

The study is the first report of this potential drug interaction, the scientists say. Their findings will be presented at the American Chemical Society's 237th National Meeting.

"I would suggest that transplant patients avoid taking licorice," warns Pei-Dawn Lee Chao, Ph.D., a chemist at China Medical University in Taichung, Taiwan.

The researchers say they do not know exactly how much licorice it takes to have a toxic effect in humans. Since licorice-based products vary widely in their content of its main active ingredient, a substance called glycyrrhizin, Chao suggests that patients taking cyclosporine avoid licorice altogether. Thousands of patients also take cyclosporine for rheumatoid arthritis, certain skin conditions, and other diseases.

Researchers have known for years that certain medications, foods, and herbs can reduce levels of cyclosporine in the body and should be avoided when taking that immunosuppressant drug. These include St. John's wort, quercetin (an ingredient found in onions and other plants that's also a dietary supplement), onions, ginger, and ginkgo. Other studies show that some substances, such as grapefruit juice, can actually boost cyclosporine levels. Now, it appears that licorice will join the growing list of substances that reduce the absorption of cyclosporine, the researchers say.

In the new study, Chao and colleagues fed cyclosporine to laboratory rats with and without various doses of pure glycyrrhizin and natural licorice extract. Much to the scientists' surprise, levels of cyclosporine dropped in the animals fed licorice or glycyrrhizin.

The researchers are trying to find out why licorice interferes with cyclosporine. Chao says there are no known scientific reports linking consumption of licorice to ill effects in transplant patients. Doctors, however, have not been looking for such a link, she added. The government of Taiwan funded the research through the Committee of Chinese Medicine and Pharmacy, Ministry of Health, R.O.C.

Licorice is a popular herb that has been used in food and medicines for thousands of years. Its active ingredient, glycyrrhizin, is 50 times sweeter than sugar, leading to herb's popular use in candy, herbal teas, and other foods. Some alternative health care providers use licorice root to treat a wide range of illnesses, including the common cold, stomach ulcers, and liver disease.
The new study adds to a growing number of reports indicating that licorice can trigger potentially dangerous drug interactions. Other studies have shown that licorice can interfere with the effectiveness of high blood pressure medications, aspirin, anti-inflammatory drugs, insulin and oral contraceptives. Chao and colleagues say patients should check with their doctor before consuming licorice with any critical drugs that might trigger unhealthy interactions.

Pig Lungs Could Be Transplanted Into Humans by 2015

Pig Lungs Could Be Transplanted Into Humans by 2015

Tuesday, February 02, 2010

Pig lungs could be transplanted into humans following an Australian medical breakthrough bringing new hope to patients awaiting life-saving operations.

Until now pig organs have been incompatible with human blood, meaning the blood would clot almost immediately and could not pass through the lungs.

But scientists at Melbourne's St Vincent's Hospital were able to remove a section of swine DNA called the Gal gene and add human DNA to control blood clotting and rejection in humans.

They have kept pig lungs functioning with human blood, paving the way for animal-human transplants — called xenotransplantation — in as little as five years.

Dr. Glenn Westall said the discovery made in the past three months meant pig-human lung transplants were a real prospect.

"The blood went into the lungs without oxygen and came out with oxygen, which is the exact function of the lungs," he said.

"This is a significant advance compared to the experiments that have been performed over the past 20 years."

Approximately 900 lung transplants are performed each year in the United States, according to the Cystic Fibrosis Foundation.

http://www.foxnews.com/story/0,2933,584552,00.html

Conference Findings for Lung Transplantation in CF

International leaders in transplantation and cystic fibrosis (CF) met in June 2008 in Lansdowne, Virginia in a roundtable conference to consider the state of the art in lung transplantation for CF. The meeting brought together different members of the pediatric and adult lung transplant community, experts in biostatistics, clinical research techniques, quality of life, and advocates of the CF community.

Lung transplantation for CF was first performed using a combined heart–lung transplant in 1983, with the first bilateral lung transplants for CF performed a few years later. Short-term success with lung transplantation prompted growth in the use of the procedure for CF and fostered hope in children and adults whose CF lung disease had progressed to end stage. According to the Organ Procurement and Transplantation Network, approximately 200 patients with CF, including approximately 25 children, undergo lung transplantation in the United States each year.

As with all transplantation, there are more candidates than available donors. Another issue with CF patients is the fact that lung transplant is not a cure for CF lung disease. Adult CF patients have a the median survival after lung transplantation of only 6.4 years. This makes choosing the time to list a patient with CF for a lung transplant crucial.

Reports intended to provide guidance to physicians and surgeons regarding the timing of listing began to appear in the early 1980s. One of the first and most widely referenced reports is from the Toronto Lung Transplant Program. Subsequent studies have attempted to refine those criteria.

The authors of the Toronto paper found that in their experience, patients with a forced expiratory volume in one second (FEV1) of 20% of predicted had a 70% chance of death within 2 years, but the chance of death halved for every 10 percentage-point increase in FEV1. Using that information, the authors concluded that CF patients should be considered candidates for lung transplantation when the FEV1 falls below 30% of the predicted value. The conference agreed that better clinical predictors of short-term mortality among patients with CF are needed as “prediction of the appropriate time to offer transplant for CF remains largely subjective.”
Lung transplantation is an option for selected pediatric and adult patients with advanced or severe lung disease that has failed to respond to standard therapy. Despite the steady increase in the number of candidates listed for lung transplantation, there have been few population-based studies on the benefits (including survival) of lung transplantation for adults and children with end-stage lung disease. The June 2008 Lansdowne Conference participants agreed that:
Conference participants agreed that:

Optimal care for CF children and adults, whether before or after lung transplantation, should remain a primary goal.

Lung transplantation should remain an option for selected patients with CF and advanced lung disease.

Multiple factors influence the outcome of lung transplant recipients including:

• physiological variables
• patient-specific variables
• lung transplant and CF Center-specific practices
• infectious agents
  

There is a need for evidence-based practice guidelines for lung transplant centers
A prospective, multicenter study on patients with CF and lung transplant is necessary to answer important questions on criteria for candidate selection and transplant practice guidelines

J Heart Lung Transplant. 2009 Nov 19. [Epub ahead of print]

Factors Indicative of Long-term Survival After Lung Transplantation: A Review of 836 10-Year Survivors.

Weiss ES, Allen JG, Merlo CA, Conte JV, Shah AS.

Division of Cardiac Surgery, Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland.

INTRODUCTION: Despite 20 years of lung transplantation (LTx), factors influencing long-term survival remain largely unknown. The United Network for Organ Sharing (UNOS) data set provides an opportunity to examine long-term LTx survivors.

METHODS: We conducted a case-control study embedded within the prospectively collected UNOS LTx cohort to identify 836 adults from 1987 to 1997 who survived >/= 10 years after first LTx. LTx patients within the same era and surviving 1 to 5 years served as controls. Multivariable logistic regression with incorporation of spline terms evaluated the odds of being a 10-year survivor. Two separate models were constructed. Model A incorporated pre-operative, operative, and donor-specific factors. Model B incorporated the factors used in Model A with post-operative covariates. Additional outcomes evaluated included hospitalizations for infection, rejection, and bronchiolitis obliterans.

RESULTS: Of 4,818 LTx patients from 1987 to 1997, 836 (17.3%) survived >/= 10 years with a mean follow-up of 148.8 +/- 21.6 months. Mean follow-up for 1,657 controls was 34.0 +/- 13.9 months. The distribution of 10-year survivors by disease was cystic fibrosis, 170 (20%); chronic obstructive pulmonary disease, 254 (30%); and idiopathic pulmonary fibrosis, 92 (11%). On multivariable logistic regression, significant factors influencing 10-year survival included age

CONCLUSIONS: Examination of a cohort of long-term LTx survivors in the UNOS data set indicates that bilateral LTx and fewer hospitalizations for rejection may portend improved long term-survival after LTx.

Stem cells may offer alternative to lung transplants

Stem cells may offer alternative to lung transplants

Belgian scientists who used embryonic stem cells to create lung tissue said this technique could provide an alternative to lung transplants for patients with chronic obstructive pulmonary disease (COPD) and cystic fibrosis.

This is the first time it's been shown that embryonic stem cells can be converted into airway epithelial-like cells without the use of specific growth factors or embryoid body formation. The researchers achieved this using an “air-liquid interface” system that mimics the conditions found in an adult trachea. “Efforts will be made to further improve this novel culture protocol, trying to increase the number of differentiated cells or to guide the differentiation into particular cell types by adding certain growth factors to this system,” Lindsey Van Haute, of the department of embryology and genetics at the Free University of Brussels, said in a news release.

She and her colleagues may start with fibroblast growth factors, which play an important role in lung development. Human embryonic stem cells “have the capacity to differentiate in vivo and in vitro into cells from all three germ lineages, making them particularly important in developmental biology, regenerative medicine and in vitro pharmacological studies,” Van Haute said. (Source: HealthDay News)

http://www.tehrantimes.com/index_View.asp?code=208413

New Lung Tx Technology

Patients Waiting for Lung Transplants May Soon Breathe a Sigh of Relief


lung-transplantEmphysema and cystic fibrosis patients who need new lungs are faced with a life-threatening problem: more than 80 percent of donated lungs can’t be used—they’re inflamed and barely functional [Scientific American]. Transplanted lungs also fail at a much higher rate than other transplanted organs, as they’re more likely to be rejected by the recipient’s body. But a new procedure that makes use of gene therapy may soon double or triple the supply of undamaged donated lungs, and may also improve their function once transplanted.

In both pre- and post-transplant lungs, the problem is inflammation caused by insufficient amounts of an immune molecule called IL-10. Donated lungs are immediately chilled on ice, which destroys any IL-10 that may remain in the lungs, allowing substantial damage to occur before the organ can be implanted. And a lack of the molecule after transplantation increases the likelihood that inflammation will damage the organ and induce rejection [Los Angeles Times].

To get around these problems, the researchers first built a domed chamber where pig lungs were kept at body temperature with a steady flow of oxygen and nutrients moving through them. That arrangement alone prevented substantial damage to the lungs. Next, in the gene therapy stage, the researchers used a harmless virus to bring a gene that produces IL-10 into the lung cells.

Lead researcher Shaf Keshavjee explains that the lungs that received the therapy had better blood flow and were more able to take in oxygen and expel carbon dioxide, the study showed. “It’s as if gene therapy turbocharges each individual cell to manufacture many more proteins in its own IL-10 factory,” Keshavjee said [Bloomberg]. The lungs also performed better and were better tolerated by the pigs who received the transplants, according to the study published in Science Translational Medicine.

The researchers also tried the first parts of the procedure on donated human lungs that were too damaged to transplant. The human lungs showed the same improvements in blood flow and respiration, suggesting that the therapy could repair lungs that would otherwise have been discarded, and could therefore increase the stock of available organs. Last year, 234 people in the U.S. died while waiting for a lung transplant…. Currently, more than 1,800 people in the U.S. are waiting for a lung [Bloomberg].

The human lungs weren’t transplanted into sick patients, but if Keshavjee’s experiments continue to go well human trials could begin in about a year. While questions about gene therapy remain–in some cases, the viral vectors used to transport genes have been found to cause serious side effects–the new approach has the potential to be a breath of fresh air.

http://blogs.discovermagazine.com/80beats/2009/10/29/patients-waiting-for-lung-transplants-may-soon-breathe-a-sigh-of-relief/