Saturday, February 18, 2012

Weekend Reading: Paper Device Monitors Liver Health

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Weekend Reading

Hep Free 
My Journey Through HCV Triple Therapy
I’m 57, treatment na├»ve, have had Hep C genotype 1a for probably 30 to 40 years, depending on whether I contracted it from tainted blood in the 80s or early 70s.
I’ve been using herbal therapies for the past 21 years since I was first diagnosed.
My herbal therapies have been managed the whole time by a naturopathic doctor who is trained in oriental medicine and is a molecular biologist. He has kept my viral load very, very low for decades. I recently had a blood test to check fibrosis (Fibrosure?) and it said I was almost scarred to the point of cirrhosis. I freaked!  Had a biopsy and found out the blood test was way off (I was stage 3 out of 6), but it got me talking to western doctors and I heard there was the new triple therapy coming out the following year. I waited, and now is the time.
 Personal Stories From HCV Advocate
Read stories written by ordinary people as they tell us what it is like to live with and, in some cases, overcome hepatitis C.
Click here to start reading....

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American Liver Foundation Discussion Boards
The American Liver Foundation Support Community connects patients, families, friends and caregivers for support and inspiration. This community is sponsored by the American Liver Foundation, an Inspire trusted partner.

Posted @ ALF
Post Transplant Incivik Study
By titoswing · February 16, 2012 at 7:58 am · 4 replies
Hello everyone my name is Tito and I'm from Brooklyn NY. I am a post transplant liver patient 3 years who is now on the Incivik triple therapy study. I am from what i was told the first person to participate in this study and i was also informed that this triple therapy along with the interaction of cyclosporine( Neoral )would be very very risky but what the heck either that or face the fact that i might need another transplant in the near future because the hep c was back with a vengence , well let me say that after 1 month of the standard treatment and 2 weeks of Incivik i am now negative for hep c.... WOW Im in total shock and truly jumping for joy....My doctor had faith that we could do it together and with her managing the dosages of the Neoral and carefully monitoring my blood work everyday I can say that after walking around with this dragon in me for more than 35 years I am now Hep C free....YES i know that maybe it could come back and wreck havoc but for today i will continue to fight ....think positive and write beautiful music . I have a beautiful lady in my life who has been there for me since day 1 . She is my angel .... My Rock....I'm a lucky man.....YES.... looking forward to going back to the studio and working on my 4th production after the completion of this treatment....God Is Good. Peace Out ( Tito - Grupo Latin Vibe )
Edited February 16, 2012 at 2:54 pm
Click Here To Read Replies


Weekend News

 Paper Device Monitors Liver Health
Clinical Diagnostics: A cheap assay could diagnose liver damage in resource-strapped settings
 
An alarming side effect of many medications is liver damage, which if unchecked, can cause death. Monitoring liver damage is a challenge in developing regions without access to clinical tools and skilled personnel.

Now researchers have created a cheap device that quickly and easily measures a patient’s liver health without a hospital’s laboratory tools (Anal. Chem., DOI: 10.1021/ac203434x).

Researchers have been developing clinical diagnostics on paper devices for at least five years but none of the devices have been tested outside laboratory settings. Now chemist George Whitesides, with colleagues at Harvard University and Diagnostics For All, a nonprofit organization he helped to found, have designed a device that is close to ready for manufacturing for field tests.

The investigators’ postage-stamp-sized device consists of a filter membrane on top of a piece of paper. The paper carries a wax pattern that defines three microfluidic chambers. The chambers contain color-changing reagents that indicate the levels of three proteins used to monitor liver health: serum protein, alkaline phosphatase, and aspartate aminotransferase. In cases of liver damage, levels of the two enzymes rise while the serum protein level drops. “These tests that we put on the paper are exactly the ones used in a hospital,” says Whitesides. As a result, he and his team can compare their paper device’s results with those of conventional liver analysis.



Liver Check
When a patient adds a drop of her blood to a hole on the top of a paper device (top left), a circular filter membrane catches the red blood cells (top right). The paper below contains three microfluidic chambers (bottom left) that can measure the liver enzymes alkaline phosphatase (ALP) and aspartate aminotransferase (AST) as well as serum protein. Colors indicate levels of the enzymes and serum protein (bottom right).
Credit: Anal. Chem
 
The device is simple to use: A person presses a pricked fingertip against a hole in the top of the device. The filter membrane catches the red blood cells--so that they don’t interfere with the color-changing reagents--and lets the remainder of the blood seep onto the patterned paper. Nonexperts can take note of any color changes; if calibration curves are available, clinicians can quantitatively note changes in the protein levels as a patient follows a drug regimen. Plastic sheets enclose the device to let users handle it without coming into contact with blood. Finally, the user burns the blood-soaked device to eliminate any biologically hazardous waste.

Whitesides says that his group tested the device on samples obtained from a volunteer and from a blood bank. The researchers spiked some of the samples with clinically relevant quantities of the enzymes and serum protein. The investigators found that correct answers for enzyme levels appeared within 30 minutes of the device’s receiving a blood drop. Diagnostics For All is now testing the devices using actual patients’ blood. The organization’s global health operations manager, Patrick Beattie, estimates the device will cost 10 cents or less to manufacture.

Polymer chemist Robert Pelton at McMaster University, who is also the scientific director of the Sentinel Bioactive Paper Network, a Canadian multi-organization partnership, says he can envision the device working in the field as is, without further research or development. He adds that, unlike proof-of-principle work done on other paper devices, Whitesides’ device already appears to be “a really strong prototype.”
Chemical & Engineering NewsISSN 0009-2347Copyright © 2012 American Chemical Society
 Source-


What if we could engineer a liver or kidney from a patient's own stem cells?


Released: 2/15/2012 12:15 PM EST
Embargo expired: 2/17/2012 4:00 PM EST
Source: University of California, Los Angeles (UCLA), Health Sciences
Embargoed for Use Until
4 p.m. (EST), Feb. 17, 2012

Newswise — What if we could engineer a liver or kidney from a patient's own stem cells? How about helping regenerate tissue damaged by diseases such as osteoporosis and arthritis? A new UCLA study bring scientists a little closer to these possibilities by providing a better understanding how tissue is formed and organized in the body.

A UCLA research team discovered that migrating cells prefer to turn right when encountering changes in their environment. The researchers were then able to translate what was happening in the cells to recreate this left–right asymmetry on a tissue level. Such asymmetry is important in creating differences between the right and left sides of structures like the brain and the hand.

The research, a collaboration between the David Geffen School of Medicine at UCLA and the Center for Cell Control at UCLA's Henry Samueli School of Engineering and Applied Science, appears in the Feb. 17 issue of the journal Circulation Research.

"Our findings suggest a mechanism and design principle for the engineering of tissue," said senior author Dr. Linda L. Demer, a professor of medicine, physiology and bioengineering and executive vice chair of the department of medicine at the Geffen School of Medicine. "Tissue and organs are not simply collections of cells but require careful architecture and design to function normally. Our findings help explain how cells can distinguish and develop highly specific left–right asymmetry, which is an important foundation in tissue and organ creation."

Using microtechnology, the team engineered a culture surface in the lab with alternating strips of protein substrates that were cell-adhesive or cell-repellent, analogous to a floor with narrow horizontal stripes of alternating carpet and tile. Cells may encounter such surface changes when they travel through the body.

The researchers observed that as the migrating cells crossed the interface between "carpet" and "tile" sections, they exhibited a significant tendency to turn right by 20 degrees, and, like a marching band, lined up in long, parallel rows, producing diagonal stripes over the entire surface.

"We had been noticing how these vascular cells would spontaneously form structures in cultures and wanted to study the process," said first author Ting-Hsuan Chen, a graduate student researcher in the department of mechanical and aerospace engineering at UCLA Engineering. "We had no idea our substrates would trigger the left–right asymmetry that we observed in the cells. It was completely unexpected.

"We found that cells demonstrated the ability to distinguish right from left and to self-organize in response to mechanical changes in the surfaces that they encounter. This provides insight into how to communicate with cells in their language and how to begin to instruct them to produce tissue-like architecture."

According to the researchers, the cells can sense the substrates beneath them, and this influences the direction of their migration and what shapes they form in the body. Of most interest, the researchers said, was the fact that the cells responded to the horizontal stripes by reorganizing themselves into diagonal stripes. 

The team hopes to harness this phenomenon to use substrate interfaces to communicate with cells and instruct them to produce desired tissue structures for replacement. By adjusting the substrates, the researchers say, they have the potential to guide what structures the cells and tissue form.
The next stage of the research will be to control and guide cells to self-organize into two-dimensional and, eventually, three-dimensional patterns chosen by the researchers.

According to the research team, this is one of the first studies to demonstrate that encountering a change in substrate can trigger a cell's preference for turning left or right. It is also one of the first studies showing that cells can integrate left–right asymmetry into a patterned structure of parallel diagonal stripes resembling tissue architecture.

"Applications for this research may help in future engineering of organs from a patient's own stem cells," Demer said. "This would be especially important given the limited supply of donor organs for transplant and problems with immune rejection."

The study was funded by the National Science Foundation and National Institutes of Health.
Additional authors included Jeffrey J. Hsu, Alan Garfinkel and Yin Tintut from the UCLA Department of Medicine; Yi Huang and Chih-Ming Ho from the UCLA Department of Mechanical and Aerospace Engineering; Xin Zhao, Chunyan Guo and Zongwei Li from the

Institute of Robotics and Automatic Information System at China's Nankai University; and Margaret Wong from the UCLA Department of Bioengineering.

For more news, visit the UCLA Newsroom and follow us on Twitter.

Abstracts

Cerebral microglial activation in Hep C
The most recent issue of the Journal of Viral Hepatitis investigates cerebral microglial activation in patients with hepatitis c, and reports on evidence of neuroinflammation.

Patients with chronic hepatitis C infection may exhibit neuropsychological symptoms and cognitive impairment.

Post-mortem studies of hepatitis C virus HCV quasispecies and replicative intermediates indicate that the brain might act as a separate compartment for viral replication and microglia may be the locus for infection and subsequent neuroinflammatory activity.

Dr Grover and colleagues from Korea to use 2 independent in vivo imaging techniques to determine evidence of neuroinflammation in patients with histologically mild chronic hepatitis C.

Using positron emission tomography (PET) with a ligand for microglial/brain macrophage activation, 11C-(R)-PK11195 (PK11195) and cerebral proton magnetic resonance spectroscopy, the team determined whether there was evidence of neuroinflammation in a pilot study of 11 patients with biopsy-proven mild chronic hepatitis C, compared to healthy volunteers.

Patients were characterized by cognitive testing and the fatigue impact scale to assess for CNS impairment.
Choline/creatine ratios were also elevated with chronic hepatitis
Journal of Viral Hepatitis

The research team found that PK11195 binding potential was significantly increased in the caudate nucleus of patients, compared to normal controls.

The researchers observed that caudate and thalamic binding potential were more significantly increased in 6 patients with genotype 1 infection, and positively correlated with viraemia.

The team found that basal ganglia myo-inositol/creatine and choline/creatine ratios were also significantly elevated in patients with chronic hepatitis C compared to normal controls.

Dr Grover's team concluded, "Using PET, we demonstrated evidence of microglial activation, which positively correlated with HCV viraemia and altered cerebral metabolism in the brains of patients with mild hepatitis C."

"This provides further in vivo evidence for a neurotropic role for HCV."

 Source: GastroHep News


Upper limits of normal for alanine aminotransferase activity in the USA 
The most recent issue of Hepatology investigates upper limits of normal for alanine aminotransferase activity in the United States population.

Alanine aminotransferase (ALT) is an important test for liver disease, yet there is no generally accepted upper limit of normal (ULN) in the United States.

Furthermore, the ability of alanine aminotransferase to differentiate persons with and without liver disease is uncertain.

Drs Constance Ruhl and James Everhart from Maryland, USA examined cut-offs for alanine aminotransferase for their ability to discriminate between persons with positive hepatitis C virus (HCV) RNA and those at low risk for liver injury in the U.S. population.

Among adult participants in the 1999-2008 U.S. National Health and Nutrition Examination Survey, 259 were positive for serum hepatitis C virus RNA and 3,747 were at low risk for liver injury.

The team measured serum alanine aminotransferase activity.
If the cut-offs were applied, 28% of women would have abnormal ALT
Hepatology

Maximum correct classification was achieved at alanine aminotransferase of 29 IU/L for men, and 22 IU/L for women.

The research team found that the cut-off for 95% sensitivity was an alanine aminotransferase of 24 IU/L for men, and 18 IU/L for women.

The cut-off for 95% specificity was alanine aminotransferase of 44 IU/L for men, and 32 IU/L for women.

The researchers found that area under the curve was 0.93 for men, and 0.92 for women.

If the cut-offs with the best correct classification were applied to the entire population, 36% of men, and 28% of women would have had abnormal alanine aminotransferase.

Dr Ruhl and colleague concluded, "Alanine aminotransferase discriminates persons infected with hepatitis C virus from those at low risk of liver disease, but would be considered elevated in a large proportion of the United States population."

17 February 2012


FYI

University at Buffalo researchers are expressing concern about a new, under-recognized, much more potent variant of a common bacterium that has surfaced in the US.
National Institutes of Health

Healthy You 

During the month of January, Chuck Garcia and I posted 31 entries to reflect a broad range of topics related to health and wellness – topics that you can review for the entire year. To make them easily accessible, I have re-posted them on a single blog entry. Enjoy them again, and share them with your friends and family. Check it out here


Cranky today? Even mild dehydration can alter our moods
Most people only think about drinking water when they are thirsty; but by then it may already be too late.

Even mild dehydration can alter a person's mood, energy level, and ability to think clearly, according to two studies recently conducted at the University of Connecticut's Human Performance Laboratory.
The tests showed that it didn't matter if a person had just walked for 40 minutes on a treadmill or was sitting at rest – the adverse effects from mild dehydration were the same. Mild dehydration is defined as an approximately 1.5 percent loss in normal water volume in the body.
The test results affirm the importance of staying properly hydrated at all times and not just during exercise, extreme heat, or exertion, says Lawrence E. Armstrong, one of the studies' lead scientists and a professor of physiology in UConn's Department of Kinesiology in the Neag School of Education.

"Our thirst sensation doesn't really appear until we are 1 [percent] or 2 percent dehydrated. By then dehydration is already setting in and starting to impact how our mind and body perform," says Armstrong, an international expert on hydration who has conducted research in the field for more than 20 years. "Dehydration affects all people, and staying properly hydrated is just as important for those who work all day at a computer as it is for marathon runners, who can lose up to 8 percent of their body weight as water when they compete."

Separate groups of young women and men were tested. Twenty-five women took part in one study. Their average age was 23. The men's group consisted of 26 men with an average age of 20. All of the participants were healthy, active individuals, who were neither high-performance athletes nor sedentary – typically exercising for 30 to 60 minutes per day.

Each participant took part in three evaluations that were separated by 28 days. All of the participants walked on a treadmill to induce dehydration, and all of the subjects were hydrated the evening before the evaluations commenced. As part of the evaluation, the subjects were put through a battery of cognitive tests that measured vigilance, concentration, reaction time, learning, memory, and reasoning. The results were compared against a separate series of tests when the individuals were not dehydrated.

In the tests involving the young women, mild dehydration caused headaches, fatigue, and difficulty concentrating, according to one of the studies, which appears in the February issue of The Journal of Nutrition. The female subjects also perceived tasks as more difficult when slightly dehydrated, although there was no substantive reduction in their cognitive abilities.

In the tests involving the young men, mild dehydration caused some difficulty with mental tasks, particularly in the areas of vigilance and working memory, according to the results of the second UConn study. While the young men also experienced fatigue, tension, and anxiety when mildly dehydrated, adverse changes in mood and symptoms were "substantially greater in females than in males, both at rest and during exercise," according to the study. The men's study was published in the British Journal of Nutrition in November 2011.

"Even mild dehydration that can occur during the course of our ordinary daily activities can degrade how we are feeling – especially for women, who appear to be more susceptible to the adverse effects of low levels of dehydration than men," says Harris Lieberman, one of the studies' co-authors and a research psychologist with the Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine in Natick, Mass. "In both sexes these adverse mood changes may limit the motivation required to engage in even moderate aerobic exercise. Mild dehydration may also interfere with other daily activities, even when there is no physical demand component present."

Why women and men are so adversely affected by mild dehydration is unclear, and more research is necessary. But other research has shown that neurons in the brain detect dehydration and may signal other parts of the brain regulating mood when dehydration occurs. This process could be part of an ancient warning system protecting humans from more dire consequences, and alerting them to the need for water to survive.

In order to stay properly hydrated, experts like Armstrong recommend that individuals drink eight, 8-ounce glasses of water a day, which is approximately equivalent to about 2 liters of water. People can check their hydration status by monitoring the color of their urine. Urine should be a very pale yellow in individuals who are properly hydrated. Urine that is dark yellow or tan in color indicates greater dehydration. Proper hydration is particularly important for high-risk groups, such as the elderly, people with diabetes, and children.


The dehydration studies were supported by Danone Research of France and were conducted in partnership with the U.S. Army Research Institute of Environmental Medicine, University of Arkansas, and Texas Health Presbyterian Hospital's Institute for Exercise and Environmental Medicine in Dallas, Texas. UConn professor Douglas Casa, adjunct assistant professor Elaine Lee, and members of the graduate student team at UConn's Korey Stringer Institute for the prevention of sudden death in sport helped gather data for the two studies.



Recalled

Infant Tylenol yanked after parents complain about new bottle design
Pharmaceutical giant recalling 574,000 containers of grape-flavored medicine
By Braden Goyette / NEW YORK DAILY NEWS
Saturday, February 18, 2012, 6:55 PM

Infant Tylenol
Johnson & Johnson is pulling all infant Tylenol from U.S. shelves after parents raised concerns about the redesigned bottles.

The company announced Friday that it was recalling all 574,000 bottles of grape-flavored liquid infant Tylenol.

The new bottles included a plastic cover that was intended to make it easier for parents to extract the right dosage of the medicine with a plastic syringe.

But some parents reported that when they inserted the syringe into the top of the bottle as instructed, it pushed the cover right into the bottle — making it difficult to measure the correct amount of medicine.

In a news release announcing the recall,
Johnson & Johnson said there was nothing wrong with the medicine itself.

Johnson & Johnson has had at least 28 recalls since July 2009, according to The Wall Street Journal, for products including contact lenses, syringes, and medications.

Source

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