August 1, 2010

FOR IMMEDIATE RELEASE

Friday, July 30, 2010
Contact: HHS Press Office
(202) 690-6343

August 1, is National Minority Donor Awareness Day, an opportunity to honor minority organ donors and their families, encourage greater donor enrollment among all racial and ethnic groups, and promote healthy living to decrease the need for organ transplantation.

At no time has the need for organ donations been greater: today, more than 108,000 Americans are waiting for an organ transplant. Of these, 55 percent are minorities. In 2009, minorities accounted for approximately 35 percent of organ and tissue donors in the country.

People of minority backgrounds have a particularly high need for organ transplants because some diseases that can lead to organ failure are found more frequently in such populations compared to others. For example, African Americans, Asian Americans and Pacific Islanders, and Hispanics are more likely than whites to suffer from end-stage renal (kidney) disease, often as a result of high blood pressure and other conditions that damage the kidneys. Native Americans are more likely than whites to suffer from diabetes.

Although organs are not matched according to ethnicity, and people of different ethnicities are often matched through donation, those on waiting lists have a better chance of being a recipient if large numbers of donors are available from their ethnic background. This reflects the higher likelihood of compatible blood type and tissue markers – critical for donor/recipient matching – among members of the same ethnicity. Hence, greater diversity of donors may potentially increase access to transplantation for all patients on the waiting list.

To become part of the movement:

--Enroll in your state donor registry. Learn how at: www.organdonor.gov/donor/registry.shtm.

--Designate your decision on your driver’s license. Do this when you obtain or renew your license.

Talk to your family now about your donation decision. Help your family understand your wish to be an organ and tissue donor before a crisis occurs. Then they will be prepared to serve as your advocate for donation.

We can celebrate many gifts in this world. Encourage your family and friends to choose organ donation and give the greatest gifts of all – hope and life.

Howard K. Koh, M.D., M.P.H.
Assistant Secretary for Health
###

Note: All HHS press releases, fact sheets and other press materials are available at http://www.hhs.gov/news.

Last revised: July 30, 2010

Source

New insights into how stem cells determine what tissue to become

August 1, 2010

This is an immunofluorescence image of a human mesenchymal stem cell growing on a plate of microposts, which have the approximate consistency of Silly Putty. This image was taken after one day of culturing. The red dots are the microposts, which are relatively short in this sample. The green is the cell and the blue is its nucleus. This cell will differentiate into a bone cell. Credit: Michael T. Yang (University of Pennsylvania)

Within 24 hours of culturing adult human stem cells on a new type of matrix, University of Michigan researchers were able to make predictions about how the cells would differentiate, or what type of tissue they would become. Their results are published in the Aug. 1 edition of Nature Methods.

Differentiation is the process of stem cells morphing into other types of cells. Understanding it is key to developing future stem cell-based regenerative therapies.

"We show, for the first time, that we can predict stem cell differentiation as early as Day 1," said Jianping Fu, an assistant professor in mechanical engineering and biomedical engineering who is the first author on the paper.

"Normally, it takes weeks or maybe longer to know how the stem cell will differentiate. Our work could speed up this lengthy process and could have important applications in drug screening and regenerative medicine. Our method could provide early indications of how the stem cells are differentiating and what the cell types they are becoming under a new drug treatment."

In this study, Fu and his colleagues examined stem cell mechanics, the slight forces the cells exert on the materials they are attached to. These traction forces were suspected to be involved in differentiation, but they have not been as widely studied as the chemical triggers. In this paper, the researchers show that the stiffness of the material on which stem cells are cultivated in a lab does, in fact, help to determine what type of cells they turn into.

"Our research confirms that mechanical factors are as important as the chemical factors regulating differentiation," Fu said. "The mechanical aspects have, until now, been largely ignored by stem cell biologists."

The researchers built a novel type of stem cell matrix, or scaffold, whose stiffness can be adjusted without altering its chemical composition, which cannot be done with conventional stem cell growth matrices, Fu said.

This is an image taken with a scanning electron microscope of a human mesenchymal stem cell growing on a plate of long microposts approximately 13 microns in length. After one day of culturing, this cell exerts centripetal force, which can be seen in the bending of the microposts. This cell will differentiate into a fat cell. Credit: Jianping Fu (University of Michigan)

The new scaffold resembles an ultrafine carpet of "microposts," hair-like projections made of the elastic polymer polydimethylsiloxane---a key component in Silly Putty, Fu said. By adjusting the height of the microposts, the researchers were able to adjust the rigidity of the matrix.

In this experiment, the engineers used human mesenchymal stem cells, which are found in bone marrow and other connective tissues such as fat. The stem cells differentiated into bone when grown on stiffer scaffolds, and into fat when grown on more flexible scaffolds.

Once the researchers observed the cells differentiating according to the mechanical stiffness of the substrate, they decided to measure the cellular traction forces throughout the culturing process to see if they could predict how the cells would differentiate.

Using a technique called fluorescent microscopy, the researchers measured the bending of the microposts in order to quantify the traction forces.

This is an image taken with a scanning electron microscope of human mesenchymal stem cells growing on a plate of short microposts. After one day of culturing, these cells spread more than cells cultured on long microposts. These will differentiate into bone cells. Even though these cells bend their shorter microposts less than their counterparts growing on longer microposts, they exert greater force to do so. Credit: Jianping Fu (University of Michigan)

"Our study shows that if the stem cells determine to differentiate into one cell type then their traction forces can be much greater than the ones that do not differentiate, or that differentiate into another cell type," Fu said. "We prove that we can use the evolution of the traction force as early indicators for stem cell differentiation."

The new matrix---manufactured through an inexpensive molding process---is so cheap to make that the researchers are giving it away to any interested scientists or engineers.

"We think this toolset provides a newly accessible, practical methodology for the whole community," Fu said.

More information: "Mechanical regulation of cell function using geometrically modulated elastomeric substrates," Nature Methods.

Provided by University of Michigan

Source
Article Date: 01 Aug 2010 - 0:00 PDT

The European Association for the Study of the Liver (EASL) - the leading European scientific society dedicated to promoting research and education in hepatology - publishes clinical practice guidelines for the management of ascites, the most common complication of cirrhosis. The peer reviewed guidelines will be available in the September 2010 issue, (Volume 53, No.3) of the Journal of Hepatology and online in advance of publication here. They also provide recommendations for the management of spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome, which often affect patients with cirrhosis[1].

An estimated 75 percent of patients presenting with ascites in Western Europe and the USA have cirrhosis as the underlying cause. The development of ascites is an extremely common yet debilitating complication for cirrhotic patients and has a huge impact on their life expectancy and quality of life. SBP and hepatorenal syndrome are ominous complications of which patients with ascites are at risk. They carry a high mortality and prophylactic measures, early diagnosis and appropriate treatments are crucial, especially to bridge eligible patients to liver transplantation.

"It is estimated that almost 60 percent of cirrhotic patients develop ascites within 10 years of their disease, which is a huge proportion of patients. These guidelines provide clinicians with the latest recommendations from a panel of experts on the management of ascites, SBP and hepatorenal syndrome. It is hoped that the guidelines will improve and facilitate best practice and ultimately improve disease outcomes and symptoms for cirrhotic patients in the future," stated Pere Ginès, lead contributor of the guidelines.

These guidelines aim to assist clinicians in the decision making and management process for ascites, SBP and hepatorenal syndrome, as well as inform patients and their carers of optimal treatment and care. New and updated best practice for the screening, diagnosis and management of these conditions are offered, with particular emphasis on:

-- Prevalence and prognosis of ascites
-- Management of the various stages of its development
-- Diagnostic strategies for ascites, SBP and hepatorenal syndrome
-- The use of drugs, antibiotics and diuretics and their associated complications
-- Ascitic fluid analysis for assessing peritoneal infections
-- Methods to improve renal function and considerations of liver transplantation

"EASL is dedicated to promoting research and education in the field of hepatology to improve the treatment of liver disease throughout the world. Its series of clinical practice guidelines aims to promote best practise to drive better clinical outcomes and inform both the scientific community and the wider public of the latest developments in the field. We hope these new ascites guidelines provide clinicians with the most up-to-date, evidence based methods for the management of patients affected by this common and debilitating disease" added Professor Heiner Wedemeyer, EASL Secretary General.

[1] Cirrhosis is associated with portal hypertension which increases pressure in the portal venous system and forces fluid into the abdominal cavity (ascites). This leads to fluid retention in the kidneys and decreased renal perfusion, which can eventually progress to hepatorenal syndrome. Another possible complication is spontaneous bacterial peritonitis, an acute bacterial infection of ascitic fluid.

Source:
European Association for the Study of the Liver

Source
 Hepatology
Volume 9999 Issue 999A, Page NA
Published Online: 30 Jun 2010
Copyright © 2010 American Association for the Study of Liver Diseases

F Poordad 1 *, E Lawitz 2, ML Shiffman 3, T Hassanein 4, AJ Muir 5, B Bacon 6, J Heise 7, D Halliman 7, E Chun 7, J Hammond 7

1 Cedars-Sinai Medical Center, Los Angeles, CA, USA
2 Alamo Medical Research, San Antonio, TX, USA
3 McGuire Research Institute, McGuire Veterans Administration Medical Center, Richmond, VA, USA
4 Southern California Liver Centers, San Clemente, CA, USA
5 Duke Clinical Research Institute, Duke University, Durham, NC, USA
6 Saint Louis University School of Medicine, St. Louis, MO, USA
7 Valeant Pharmaceuticals North America, Aliso Viejo, CA, USA

email: F Poordad (fred.poordad@cshs.org)

*Correspondence to F Poordad, Cedars -Sinai Medical Center, Hepatology and Liver Transplantation, Los Angeles, California, United States

Keywords
anemia • erythropoiesis-stimulating agents • weight-based dosing • antiviral dosing • clinical trial

Abstract

BACKGROUND:
Ribavirin-induced hemolytic anemia can prompt dose reductions and lower sustained virologic response (SVR) rates in the treatment of chronic hepatitis C patients.

The study aimed to determine if weight-based dosing (WBD) of taribavirin (TBV), an oral pro-drug of ribavirin (RBV), demonstrated efficacy comparable to RBV while maintaining its previously demonstrated anemia advantage with fixed dose administration.

METHODS:
A US phase 2b randomized, open-label, active-controlled, parallel-group study was conducted in 278 treatment-naïve, genotype 1 patients stratified by body weight and baseline viral load. Patients were randomized 1:1:1:1 to receive TBV (20, 25, or 30 mg/kg/day) or RBV (800 -1400 mg/day) with pegylated interferon alfa-2b for 48 weeks.

RESULTS:
The SVR rates in this difficult to cure patient demographics (mean age 49 yrs; 61% male; 30% African-American or Latino; high viral load; advanced fibrosis; and mean weight 82 kg) were 28.4%, 24.3%, 20.6% and 21.4% in the 20, 25, 30 mg/kg TBV groups and RBV group, respectively. There were no statistical differences in the efficacy analyses. Anemia rates were significantly lower (p<0.05) in the 20 and 25 mg/kg/day TBV treatment groups (13.4% and 15.7% respectively) compared to RBV (32.9%). The most common adverse events in all groups were fatigue, diarrhea, and insomnia. Diarrhea, reported in 38% of TBV patients versus 21% of RBV patients, was generally mild and not dose-limiting.

CONCLUSIONS:
All TBV doses demonstrated efficacy and tolerability comparable to that of RBV, however the 25 mg/kg dose demonstrated the optimal balance of safety and efficacy. Anemia rates were significantly lower for TBV 20-25 mg/kg than RBV. These data suggest WBD with TBV provides a safe and effective treatment alternative to RBV for chronic hepatitis C. (HEPATOLOGY 2010.)

Received: 24 April 2010; Revised: 18 June 2010; Accepted: 22 June 2010

Digital Object Identifier (DOI)
10.1002/hep.23827 About DOI

Source
José A. Carrión, Miquel Navasa, Xavier Forns

Received 10 November 2009; received in revised form 8 June 2010; accepted 10 June 2010. published online 30 July 2010.

Uncorrected Proof

HCV-infection recurs universally after liver transplantation (LT) and fibrosis progression is accelerated in the graft. Retransplantation (RT) is the only therapeutic option to achieve long-term survival in patients with decompensated cirrhosis after LT. Patient and graft survival rates after RT are inferior to those after primary LT. It is generally accepted that severe hepatitis C recurrence (cholestatic hepatitis) and forms with rapid fibrosis progression have a poor survival after RT. However, it is not clear whether rapid fibrosis progression in the first graft will be followed by the same rate of fibrosis progression in the second graft. The use of prognostic scores as screening tools has shown an improvement in survival in HCV-infected patients after RT, reaching similar survival rates as those obtained in non HCV-infected patients. Moreover, these scores can identify candidates with a high risk of mortality in whom the use of a new organ would be unreasonable. Prevention of severe hepatitis C recurrence could be the first step to avoid RT. Thus, antiviral treatment on the waiting list (if possible) and early identification and treatment of patients with severe hepatitis C recurrence may be a good strategy to avoid RT. In addition, active management of factors which can accelerate fibrosis progression (donor age, post-transplant diabetes, high dose of corticosteroids) might reduce the incidence of severe forms of hepatitis C recurrence.

Abbreviations: RT, retransplantation, LT, liver transplantation, HCV, hepatitis C virus, PNF, primary non-function, HAT, hepatic artery thrombosis, UNOS, United Network for Organ Sharing, MELD, model for end-stage liver disease, ECD, extender criteria donors, HCC, hepatocellular carcinoma, SVR, sustained virological response

Keywords: Severe recurrence, Cirrhosis, MELD, Survival

Liver Unit, Institut de Malalties Digestives, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain

Corresponding author. Address: Liver Unit, Escala 7, 3 pis., Villarroel 170, Hospital Clinic, Barcelona 08036, Spain. Tel.: +34 93 227 54 99; fax: +34 93 451 55 22.

PII: S0168-8278(10)00623-9

doi:10.1016/j.jhep.2010.06.006

© 2010 Published by Elsevier Inc.

Source
Gastroenterology
Volume 139, Issue 2 , Pages 456-463, August 2010

Jody Dushay, Patricia C. Chui, Gosala S. Gopalakrishnan, Marta Varela–Rey, Meghan Crawley, Ffolliott M. Fisher, Michael K. Badman, Maria L. Martinez–Chantar, Eleftheria Maratos–Flier

Received 21 January 2010; accepted 29 April 2010. published online 07 May 2010.

Abstract

Background & Aims
Fibroblast growth factor 21 (FGF21) is an hepatic protein that plays a critical role in metabolism, stimulating fatty acid oxidation in liver and glucose uptake in fat. Systemic administration to obese rodents and diabetic monkeys leads to improved glucose homeostasis and weight loss. In rodents, FGF21 increases with fasting and consumption of a ketogenic diet (KD). In humans, FGF21 correlates with body mass index (BMI), but studies evaluating other parameters show inconsistent results. We examined FGF21 serum levels in lean and obese individuals and in response to dietary manipulation. We also evaluated FGF21 serum levels and liver messenger RNA (mRNA) expression in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).

Methods
Serum FGF21 was measured after an overnight fast in individuals with BMI ranging from normal to obese. Volunteers fasted for 16 or 72 hours and then ate a standard meal. Another group consumed KD for 12 days. Serum FGF21 and hepatic mRNA expression were measured in obese individuals with NAFLD or NASH.

Results
There was a positive correlation between BMI and FGF21. There was no change in FGF21 in response to a short fast or KD. A nonstatistically significant fall in FGF21 levels was seen after a 72-hour fast. Hepatic FGF21 mRNA expression was significantly elevated in NAFLD, which correlated with a substantial increase in serum FGF21. In NASH, serum FGF21 but not liver mRNA was increased.

Conclusions
FGF21 correlates with BMI and may be a novel biomarker for NAFLD, but is not nutritionally regulated in humans.

Keywords: FGF21, NAFLD, NASH, Obesity

Abbreviations used in this paper: BMI, body mass index, FGF21, fibroblast growth factor 21, GCRC, General Clinical Research Center, KD, ketogenic diet, mRNA, messenger RNA, NAFLD, nonalcoholic fatty liver disease, NASH, nonalcoholic steatohepatitis, PPARα, peroxisome proliferator−activated receptor-α

Conflicts of interest The authors disclose no conflicts.

Funding This study was supported in part by National Institutes of Health (NIH) grant M01-RR01032, Beth Israel Deaconess Medical Center General Clinical Research Center, NIH grant AT-1576, SAF2005-00855, and HEPADIP-EULSHM-CT-205 (to M.L.M.-C.), NIH grants 5R01DK069983-04 and NIH/5P01DK056106-10 (to E.M.F.), and the Boston Obesity and Nutrition Research Center DK46200.

PII: S0016-5085(10)00662-1

doi:10.1053/j.gastro.2010.04.054

© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Source

Eating Spicy Curry food could Reduce Liver Damage


A chief constituent of the Indian spice turmeric was found to reduce the inflammation and fibrosis (Development of excess fibrous tissue in an organ) in an animal study. Research work in rodents with chemically induced liver injury found that curcumin, a chemical in turmeric which is responsible for giving curry a yellow colour, has anti-inflammatory and anti-oxidative activities. The compound has been used since years in Ayurvedic medical specialty to treat a various gastrointestinal problems. However, latest research indicates that the compound may have other therapeutic applications, with potential effects on liver disorders. The new study proposed that that mice fed with curcumin had very less liver damage than other group which was on a normal diet.

The investigators in this study have looked into how curcumin saved mice that had been grew for inflammation in their bile ducts and liver injury. The study was aimed for screening out of mice model for a group of disease known as cholangiopathy. It is caused by inflammatory process and fibrosis of bile duct in liver which may cause blockage of bile flow to gut and may result in to jaundice, liver failure, liver cancer or other injuries to liver. The mice used in the study were bred to have a type of chronic cholangiopathy. The investigators did screening of various liver function tests for finding any sign of liver injury before and after the mice were fed with curcumin.

The results of this study indicated that liver injury, jaundice and scarring (which may lead to fibrosis) are reduced by the curcumin intake. The results also showed that curcumin may work on multiple targets in liver and thereby regulating numerous cellular events in mice. The underlying cellular process that is affected be curcumin rich diet might turn out to be promising targets for developing new drugs. As the efficacy of available medical alternatives to slow the progression of liver diseases is very narrow, there is a requirement for new and effectual medical intervention strategy. The finding of this study has opened the doors for newer treatment option for liver damage.

On the other hand, the hypothesis is in its early stage and it will be too early to say that the new treatment option might develop from this spice. There is no proposal from the study that consumption of turmeric will comprise the similar result or be a helpful treatment for human being. Nevertheless, researchers are taking this finding in positive ways and have started working in this direction.
 
Source

Ablate and Wait in Liver CA, Experts Suggest

By Charles Bankhead, Staff Writer, MedPage Today

Published: July 30, 2010

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
 
Outcomes in all patients with hepatocellular carcinoma might improve with an "ablate- and-wait" strategy versus rapid transplantation, according to a group of clinicians who have regularly used the strategy.

Use of radiofrequency ablation and chemoembolization to downstage large tumors has shown that about 30% of patients do not qualify for transplantation because of disease progression. The strategy warrants consideration for all patients with hepatocellular carcinoma, regardless of whether they fall within the Milan criteria, according to authors of an article in the August issue of Liver Transplantation.

"Those patients who make it to transplantation have an excellent outcome as compared to patients transplanted with tumors beyond the Milan criteria who are not treated," John Roberts, MD, of the University of California San Francisco, and colleagues wrote in an opinion piece.

"The median time between the first ablative procedure and transplantation was 8.2 months with a range of 3 to 25 months. This approach suggests that the test of time may be the surest method to select patients with hepatocellular carcinoma who are destined to have good transplant outcomes."

The authors argue that their approach of ablating the tumor and then waiting to see whether it recurs or progresses should be expanded to all patients listed for transplantation because of hepatocellular carcinoma. Treating and waiting could help reduce the use of scarce donor organs in patients who will have recurrent disease.

"Our experience with ablative treatment and then observation suggests that the ultimate outcomes of transplantation are not dependent on the primary tumor but more on time spent waiting for transplantation," the authors wrote in their conclusion. "It would seem logical that smaller and/or fewer tumors, though more unlikely to have spread, would also benefit from a period of time if the primary tumor can be controlled."

"The waiting period may be able to decrease the 10% recurrence rate seen in patients transplanted within Milan," they added.

Published more than a decade ago, the Milan criteria for liver transplantation in patients with hepatocellular carcinoma won support because they seemed to identify patients likely to have good transplantation outcomes (N Engl J Med 1996; 334: 693-699). Based on tumor size and number, the criteria fell victim to the same fallacy as other criteria have, according to the authors.

"It has not been shown that there is any particular tumor size that represents no risk of recurrence, at least among those tumors that can be detected radiologically," Roberts and co-authors wrote in their introduction. "Furthermore, the degree of risk is not the same for all patients within the Milan criteria."

The San Francisco group's experience with a strategy of ablate and wait has indicated that patients who fall far outside the Milan criteria do quite well after transplantation, if time is added as a criterion for transplantation. A report covering their experience with 61 patients showed successful downstaging of 43, all but eight of whom had successful orthoptic liver transplants (Hepatol 2008; 48: 819-827).

Intention-to-treat analysis showed one- and four-year survival rates of 87.5% and 69.3%, respectively. One- and four-year survival after transplantation was 96.2% and 92.1%, respectively.

The authors also cited several small clinical studies that have added support to the ablate-and-wait strategy for patients outside the Milan criteria. Cumulatively, the data suggest that a waiting period of about six months after therapy might be appropriate.

Less evidence has emerged in support of ablate and wait for patients within the Milan criteria. In general, the data suggest that tumor status does not deteriorate between treatment and transplantation.

Geographic variation in the time to transplantation complicates the ablate-and-wait strategy. Roberts and co-authors cited 2007 data showing that 62% of patients underwent liver transplantation within three months after receiving exception points for hepatocellular carcinoma. A shorter waiting time might increase risk of cancer recurrence, but data on recurrence of hepatocellular carcinoma are incomplete.

"The more rapid transplantation rate in some geographic areas is going to create some issues if transplantation is delayed under an ablate-and-wait strategy," the authors acknowledged. "Fortunately, if the wait is six months long, major effects on center transplant numbers are likely to be small."

The authors reported that they had no relevant disclosures.

Primary source: Liver Transplantation

Source reference:
Roberts JP, et al "Hepatocellular carcinoma: ablate and wait versus rapid transplantation" Liver Transpl 2010; DOI: 10.1002/lt.22103.

Source

New Cellular 'Armor' Developed to Prevent Infection by AIDS Virus

ScienceDaily (July 30, 2010) — Research by the Consejo Superior de Investigaciones Científicas (CSIC) and led by Mr Félix Goñi, director of the Biophysics Unit at the CSIC-University of the Basque Country Mixed Centre, has led to the development of a novel method of attack against the AIDS virus. The method involves creating a prevention system, i.e. an 'armour' in the cells that are likely to be infected and thus impede the virus from accessing them and starting to act on their immunological system.

The study, which appears in the journal Chemistry & Biology, published by Cell Press, lays down the bases of possible future pharmaceutical drugs that will enable combating the AIDS virus at its initial phase. Participating in the research, apart from Mr Goñi, was a team from the National Biotechnology Centre (CSIC-Universidad Autónoma de Madrid) and another from the Institute of Applied Chemistry of Cataloniaa (CSIC, Barcelona).

The research is based on the regulation of the fluidity of the cell membranes and seeks to avoid the phenomenon known as the fusion of membranes, a consequence of contact between the cell membranes and the membrane of the virus itself.

The membrane is the "coating" of the cell cytoplasm and which protects it from the outside, and which has a structure similar to that of the membranes of the AIDS virus. When both membranes come into contact, and due to the fact that the cell membrane is very "fragile," an orifice is created and fusion occurs -- and a route is opened for the AIDS virus to enter, connect to a specific "receptor" of the cell and commence its viral activity.

What the researchers are seeking with this study is to strengthen the membrane structure, making it more rigid, in order to avoid this fusion of membranes and, thus, the inoculation of the cell by the AIDS virus.

Practically all treatment for the AIDS virus currently being applied is based on halting the progress of the virus once it is inside the host cell. There is but one treatment, commercially known as Enfurvitide, which attempts to stop the virus actually entering the cell. The research published in Chemistry & Biology comes to the same conclusion, but by a totally different and novel route.

"For the cell membranes and the virus to come together and this orifice be opened to allow the entrance of the virus, the membranes have to have a certain degree of fluidity, of mobility. We discovered a procedure to make the cell membranes more rigid. This could well give rise to a new pharmaceutical drug which makes the membranes more rigid and impede the entrance of the AIDS virus. Instead of the membrane being flexible, a kind of armour is established which makes the cell impenetrable," explained Félix Goñi.

The research started three years ago and has employed various techniques in the field of chemistry and molecular biology.

At the Institute of Applied Chemistry of Catalonia (CSIC, Barcelona), Ms Gemma Fabriàs has synthesised the GT11 molecule by means of organic chemistry synthesis techniques. Mr Santos Mañes, from the National Biotechnology Centre, studied the viral infection of the cells, and from the Biophysics Unit at the CSIC-University of the Basque Country work has been undertaken at molecular level to demonstrate that there are changes in the rigidity of the membranes when the GT11 molecule is incorporated into them, and that when the membranes are more rigid the virus cannot fuse with the cell membrane and, thus, from penetrating the cell. A highly important role was also placed by Mr José Luis Nieva, from the Biophysics Unit, in studying this fusion of the membranes induced by the AIDS virus.

This scientific discovery by this consortium represents, in the opinion of Mr Goñi, "a completely new means for attacking the virus, and which makes this original."

"There is medication, and which is working very well, to avoid the propagation of the virus once it is inside the cell. But to impede this inoculation in the first place, only one product (Enfurvitide) exists, but this drug is based on a completely distinct principle. The idea of modifying the rigidity of the membranes is completely new and also demonstrating that, by equipping these membranes with greater rigidity, the AIDS virus cannot penetrate," stated Mr Goñi. This same strategy may well serve for other viruses with membrane, such as, for example, the flu virus.

Source

Dialysis mix-up prompts discussion over equipment re-use

August 01, 2010 9:00 AM
BARBARA COTTER
THE GAZETTE

For three years, 62-year-old Preston Price has been undergoing dialysis to do what his failing kidneys can’t: filter out impurities in his blood. It’s a process that eats up four hours of his day, three days a week, but typically it’s so uneventful that he tends to doze through it.

In April, however, Price’s routine at Pikes Peak Dialysis Center went awry when he was mistakenly hooked up to a reusable filter, a dialyzer, that belonged to another patient — a person who had a virulent bacterial infection commonly known as MRSA. Price’s health was probably not in danger, his doctors say, and giving one person’s dialyzer to another patient is a mistake that doesn’t happen often at Colorado dialysis centers.

But it happened to Price, and it happened in February at a sister clinic when a patient was given a dialyzer belonging to someone infected with Hepatitis C.

For Pikes Peak Dialysis Center and Printers Place Dialysis Center, both owned by Denver-based DaVita, the mix-ups resulted in an investigation by the Colorado Department of Public Health and Environment.

Investigators cited the centers for failing to notify the department about the incidents and not immediately revising their policies. They also found a number of deficiencies in the centers’ operations, and ordered them to come up with corrective actions to prevent such mix-ups and address unrelated issues, most of them centering around record-keeping.

For dialysis patients, the cases go to the heart of an issue that has long been debated in the medical field but might not be on their radar: Should they opt to be treated with a reusable dialyzer — one that is supposed to be used on that patient only and sterilized after each use? Or is it better to go with single-use dialyzers, which are used once, then tossed?

Re-use became more than a trend

Beginning in the early 1980s, re-use became the status quo. Reusable dialyzers were cheaper, and they didn’t produce the anaphylactic-like “first-use” symptoms associated with single-use dialyzers. In 2000, according to the U.S. Center for Disease Control and Prevention, 80 percent of dialysis centers opted for reusable dialyzers.

But a new generation of single-use dialyzers that were cheaper and less likely to produce first-use issues came on the market. According to a 2007 study by researchers from Tufts University Medical School and Boston’s St. Elizabeth’s Medical Center, the percentage of centers going the re-use route had dropped to 40 percent by 2005.

Still, dialysis experts say re-use is safe — if done correctly and according to quality control standards. That’s a big “if,” however, because re-use relies on a series of human protocols to get everything right, and that boosts the chances for mistakes, the researchers concluded.

“Full compliance in a practical setting ... is difficult to attain, and rigorous quality control standards are vulnerable to poor implementation,” wrote the authors, who declined to be interviewed.

Dr. Michael Lazarus, who taught nephrology at Harvard University, ran the dialysis program at a Boston hospital and is considered a pioneer in the field, put it more succinctly: “When you have humans doing things, they make mistakes.”

Lazarus used to be in the re-use camp, but changed his opinion after he went to work as chief medical officer for a division of Fresenius, a global health company and a major player in the dialysis business. He knows some people will say he became a single-use devotee because Fresenius manufactures the devices, but he said it wouldn’t matter where he worked. Single-use is safer, he contends.

“You remove that potential for human error; it’s gone,” he said.

Mix-ups with reusable dialyzers don’t occur often, though. An official with the Colorado health department said the Colorado Springs cases are the first she’s encountered in seven years at the agency, and Dr. Stephen Fox of Pikes Peak Nephrology Associates said he had seen only one in his 22 years of practice.

“So to have two incidents in a short span of time is very unusual and very troubling,” said Fox.

Lazarus said that getting the wrong dialyzer rarely puts the patient at risk. Sterilization of dialyzers after each use kills most pathogens, including MRSA, he said, so Preston Price is likely in the clear.

“In 99 percent of the cases, it doesn’t matter. It’s like wearing someone else’s underwear; it’s not pleasant, but it doesn’t hurt anyone,” said Lazarus. “There’s a big psychological issue: ‘My blood is going through this artificial kidney that someone else has used.’”

More troubling, he said, is the patient who was exposed to Hepatitis C, because neither that virus nor AIDS can be killed with current sterilization techniques.

And there’s no guarantee that the cleaning and sterilization process will go according to plan. In 2007, a 71-year-old Muskegon, Mich., woman being treated at a DaVita center died after being hooked to a dialyzer that wasn’t properly rinsed after cleaning. The corrosive cleaning agent got into her bloodstream and killed her.

“You can set up all kinds of systems — ‘we’ll do this and we’ll do that’ — but sooner or later, if you don’t have an absolutely perfect system, you’’ll make mistakes,” Lazarus said.

Many companies support single-use only

In the two Springs cases and the one in Michigan, dialysis technicians were blamed for the mistakes, lending ammunition to the argument by Lazarus and the researchers who conducted the 2007 study that re-usable dialyzers leave the door open to potentially serious errors.

In fact, the researchers strongly come down on the side of single-use dialyzers, concluding that “there is no compelling medical indication for reprocessing dialyzers in the new millennium” and the only reason providers like reusable dialyzers is because it saves them money.

But DaVita, second only to Fresenius as the biggest dialysis provider in the U.S., defends its use of reusable dialyzers, and cites a recent article in Nephrology News & Issues showing that seven of the top 10 dialysis operations still offer reusable versions — though DaVita is the only one in El Paso County to do so.

“The reuse of dialyzers is a safe, widely utilized practice throughout the industry,” DaVita spokesman Vince Hancock said in an e-mailed statement.

“The federal government, which oversees dialysis safety, approves reuse of dialyzers through the Association for the Advancement of Medical Instrumentation’s stringent standards which we have always been fully compliant with,” Hancock added. “Also, the National Kidney Foundation has published literature validating that reuse is a safe and commonly accepted practice in kidney care.”

Hancock said there’s independent research showing dialyzer reuse reduces patient exposure to chemicals that coat new dialyzers. It’s true that in the early 2000s, 50 people died from exposure to a chemical used in single-use dialyzers that had not been properly removed before the device was hooked up to a patient.

But Dr. Jesse Flaxenburg of Pikes Peak Nephrology Associates said the chemical is no longer used.

“In other words, advancing technology has made the ‘chemical exposure’ argument a non-starter,” he said.

Flaxenburg and the other doctors at Pikes Peak Nephrology were so alarmed by the back-to-back incidents at the Springs clinics that they sent a letter to their patients in May to say they could “no longer support dialyzer reuse,” and to educate patients on how to protect themselves if they decided to continue with reusable dialyzers. Flaxenburg also said the doctors at the practice, which is being sued by DaVita over an unrelated issue that involves support for a competitor, have started educating patients about the two types of dialyzers since the cases came to light.

“It never really popped into our frame of reference until this,” said Flaxenburg. “It’s a standard educational piece now.”

Hancock says it’s also DaVita’s practice to educate patients about their dialyzers options and give them a choice which to use. Patients then sign a consent form. But Preston Price says he was never given the option, and a few former DaVita patients told doctors they signed a lot of papers when they started dialysis, but don’t recall being informed about their choices.

At this point, the clinics are working with the state on their plans of correction to ensure.

“Patient care is our number one priority, but mistakes can and sometimes do occur,” Hancock said in his statement. “We have rigorous processes and controls in place to minimize errors such as this, but when they do happen we respond aggressively, even when no patient harm occurs. We have also re-emphasized our policies and procedures with our employees to further reduce the likelihood that this could occur again.”

But Preston Price isn’t hanging around to find out. He switched to a competing dialysis provider that does not offer reusable dialyzers, and said the center where he was receiving treatment dropped the ball.

“If you’re a professional, you’re supposed to know what you’re doing,” Price said. “Three people are supposed to check that dialyzer before it goes into my body, but something happened that day, because they let it slip through their hands.”

WASTE NOT

A topic that often comes up in the reuse vs. single-use debate centers on the environment and medical waste. Re-use proponents say single-use dialyzers produce much more waste that ends up in landfills.

“On average, it takes 9.6 reuse dialyzers to treat one patient for a year, versus 153 single-use dialyzers,” said DaVita spokesman Vince Hancock. “Multiply that by the number of patients (on dialysis), and you’re talking about significant environmental reduction in waste.”

A 2007 study by a team from Tufts University and a Boston hospital, however, cites a number of environmental issues associated with reusable dialyzers as well, including the liquid waste from germicides.

They call for more research into the environmental fallout from dialysis, “including the need for more optimal management of disinfectant-related waste with reuse, and solid waster with single-use.”

MORE ABOUT DIALYSIS

There are two main types of dialysis: hemodialysis and peritoneal dialysis. Hemodialysis, the one that’s likely most familiar to people, takes place at a clinic or in a hospital setting, and uses a dialyzer that acts like an artificial kidney to clean the blood. Blood flows from the patient through a tube and into the dialyzer, where it’s cleaned and then pumped back into the body. Peritoneal dialysis essentially uses the body itself and a dialysis solution to clean the blood.

Sources: mayoclinic.com; medicinenet.com

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'Body's natural cell-suicide program can fuel tumour development'

2010-08-01 17:00:00

Researchers at the Walter and Eliza Hall Institute researchers in Melbourne, Australia, have made a discovery that has turned on its head scientists' understanding of programmed cell death and its role in tumour formation. The body's natural cell-suicide program can add to tumour development, according to the new study.

Programmed cell death (apoptosis) is an important process in human biology as it removes unwanted and damaged cells from our bodies. This process protects us against cancer development and autoimmune disease.

The research team's discovery, led by Professor Andreas Strasser from the institute's Molecular Genetics of Cancer Division, has implications for the understanding of how cancers develop and will inform the ongoing development of a new class of anti-cancer drugs called BH3 mimetics.

"Until now everybody believed that a failure of damaged cells to undergo suicide allowed mutated cells to proliferate, which contributes to tumour development. That's certainly still true but we discovered that, in certain settings, the opposite holds: the body's natural cell-suicide program can fuel tumour development," said Professor Strasser.

The research team's experiments revealed that repeated cycles of cellular depletion and tissue regeneration, by activating stem cells, could promote tumour development.

In situations where the DNA in many cells is damaged, such as when the body is repeatedly exposed to low doses of radiation, there are repeated cycles of cell death in the body's tissues.

"Attempts by the body's stem cells to repopulate the depleted tissue can then actually drive the tumour development. That's because the radiation, while killing many cells within a tissue, will create mutations in some of the surviving stem cells. When such abnormal (mutated) stem cells repopulate the tissue, they will divide many times and this can promote the development of tumours," said Professor Strasser.

The research, done in collaboration with Dr Ewa Michalak, Dr Cassandra Vandenberg, Mr Alex Delbridge, Dr Li Wu, Dr Clare Scott and Professor Jerry Adams, appears in journal Genes and Development.

Crucial to the team's research was an understanding of what happens to mice exposed to radiation when a gene called Puma is missing.

Professor Strasser said: "If normal mice (which have the Puma gene) are given a low dose of radiation it destroys around 80 per cent of the white blood cells. That does not kill the mouse but it does mean the stem cells in the bone marrow have to work extra hard to replenish the blood system. This can lead to the formation of tumours of white blood cells, called leukaemias, if the stem cells doing the repopulating have cancer-causing mutations.

"The surprise was that mice that don't carry the Puma gene are protected from this type of tumour development. Puma is essential for the death of cells that have damaged DNA. If mice don't have the Puma gene when they receive low doses of radiation the white blood cells are not destroyed, so you don't force mutated stem cells to become activated (and divide) to replenish the blood system."

Professor Strasser said the research suggested that the risk of cancer was increased in people who experienced cycles of tissue destruction followed by tissue re-population by stem cells.

He said: "Such cycles may account for the liver cancers frequently associated with viral (hepatitis C) infection or alcohol-related liver damage."

The research also helps explain the so-called secondary cancers that sometimes arise in patients who were cured of their primary cancer by chemotherapeutic drugs that cause DNA damage." he findings will also inform the ongoing development of a new class of anti-cancer drugs called BH3 mimetics. These drugs are designed to kill cancer cells.

Professor Strasser said: "Chronic exposure to such drugs could lead to the death of large numbers of normal cells that would then need to be replaced. In certain circumstances this could promote the development of secondary cancers, particularly if patients are receiving treatments such as chemotherapy or gamma-radiation that can lead to cancer-causing mutations in stem cells." (ANI)

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Hepatitis C Remains a Major Health Challenge for HIV-infected Persons


by VR Sreeraman on August 01, 2010 at 12:14 PM

Hepatitis C virus (HCV) co-infection occurs in an estimated one quarter of HIV-infected persons in Europe, Australia, and the United States. “As use of highly active antiretroviral drugs has markedly reduced opportunistic infections, HCV-related liver disease has emerged as a leading cause of death. HIV infection adversely affects both the natural history and the treatment of hepatitis C” said Dr David L Thomas, Division of Infectious Diseases, Johns Hopkins School of Medicine, USA.

For people living with HIV (PLHIV) Hepatitis C (Hep C) is a major public health challenge that can and should be controlled.

“We have a serious condition and we have clear evidence that it can be controlled” said Dr David Thomas.

Two clear solid grounds why it is important to control HCV are: It is common and very severe.

The incidence of Hep C is scary – in Baltimore, Europe or Australia, HCV occurs in 70% to up to 100% among PLHIV who acquire infection through injecting drug use (IDU).

In India, whether it is Chennai in South India, or north-east India, Hep C rates among PLHIV who acquire HIV through injecting drug use are very similar and shocking. However there are several others who just have HCV and not HIV, said Dr David.

Hep C also infects PLHIV who acquired infection through heterosexual or homosexual routes.

60% of persons who acquire HCV go on to have chronic hepatitis infection. HCV viral load is also high if person is co-infected with HIV.

“HIV decreases response to HCV treatment – can have half of treatment outcome than HIV negative individuals” said Dr David Thomas. HCV treatment costs are over USD 20,000 per person.

HIV infection adversely affects all stages of Hep C or HCV infection.

“Risk of liver failure was higher among individuals living with HIV than those individuals who were similar with regards to HCV but HIV negative” said Dr Thomas.

The antiretroviral (ARV) therapy is not sufficient to:

• Reduce the HCV RNA load
• Restore treatment response
• Prevent cirrhosis or liver failure

However antiretroviral therapy (ART) significantly reduces mortality among people co-infected with HIV and HCV.

“Markedly lower survival for HIV/HCV co-infected persons was observed in Denmark (2000-2005)” said Dr Thomas.

HCV transmission can be prevented. Dr Thomas listed few clear points of action to prevent HCV:

• Transfusion transmission has stopped where screening is done
• Nosocomial spread reduced where bloodborne precautions observed
• HCV incidence among IDU has declined

“Even in places where harm reduction measures are in place, HCV continues. HCV is more transmissible than HIV, so measures to control HIV are not going to be enough, they need to be intensified” said Dr Thomas.

Very few people co-infected with HIV and HCV are currently receiving testing, and treatment for HCV.

There is a clear need for harm reduction measures to intensified and expanded, testing for HCV to be expanded and HCV treatment be made available widely.

“Let’s rejoice in the fact that today we have treatments that work... what we need I the political will to go the extra mile to deliver universal access” had said J Montaner, which is so much in context to improve responses to HCV and HIV co-infection.

Contributed by: Bobby Ramakant

Source-Medindia

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