Showing posts with label disease management. Show all posts
Showing posts with label disease management. Show all posts

Tuesday, September 01, 2009

Cells don’t like to be alone

Detached Early Cancer Cells May Die from Lack of Nourishment
Antioxidants Could Rescue Starving Tumors-to-be
http://focus.hms.harvard.edu/2009/082809/antioxidants.shtml

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Detached Early Cancer Cells May Die from Lack of Nourishment

Antioxidants Could Rescue Starving Tumors-to-be
Cells don’t like to be alone. In the early stages of tumor formation, a cell might be pushed out of its normal environment due to excessive growth. But a cell usually responds to this homeless state by dismantling its nucleus, packing up its DNA, and offering itself to be eaten by immune cells. Simply put, the homeless cell kills itself. This process, known as apoptosis, typically stops potential cancer cells before they have a chance to proliferate.
Joan Brugge
Photo by Liza Green, HMS Media Services
Joan Brugge and collaborators have identified metabolic defects with a lethal effect on cells that stray too far from their home environment. The defects might be a way for the body to stop potential tumor cells from proliferating.


Now, researchers from the lab of Joan Brugge, the Louise Foote Pfeiffer professor of cell biology and chair of that department, have discovered another mechanism that these precancerous, homeless cells use to commit suicide. By studying two different types of human breast epithelial cells, the researchers found that when separated from their natural environment, these cells lose their ability to harvest energy from their surroundings. Eventually, they starve.
“We originally thought that in order for cells to survive outside their normal environment, they would simply need to suppress apoptosis,” said Brugge, senior author on the paper, which appeared online Aug. 19 in Nature. “But our studies indicate that this activity is not sufficient to prevent the demise of homeless cells. Even if they escape apoptosis, these cells can’t transport enough glucose to sustain an energy supply.”
Surprisingly, metabolic function is restored if antioxidant activity is increased inside the cells, allowing them to use energy pathways that do not rely on glucose.
“It raises the interesting idea that antioxidants, which are typically thought to be protective because they prevent genomic damage, might be allowing these potentially dangerous cells to survive,” said first author Zachary Schafer, assistant professor at the University of Notre Dame and a former postdoc in Brugge’s lab.
“It raises the interesting idea that antioxidants, which are typically thought to be protective because they prevent genomic damage, might be allowing these potentially dangerous cells to survive.”
—Zachary Schafer
The authors caution against extrapolating too far from their data, which were based on cell culture. They also emphasize that the experiments were not designed to mimic the effect of dietary antioxidants. The researchers used two specific antioxidant compounds—chemically distinct from those found in food and supplements—only to understand how oxidants contribute to the metabolic defects.
“We think that genes with antioxidant activity play a much bigger role than antioxidant compounds administered from outside the body,” said Brugge.
Beyond Cell Suicide
The team had previously reported that when cells were endowed with a cancer-causing gene that prevents them from committing suicide, they still died when cut off from their extracellular environment. This puzzled the researchers since they had long thought that apoptosis was the only way the cells could die.
In the recent study, Schafer and colleagues took a closer look, measuring the levels of proteins and molecules associated with metabolic activity in the displaced, but apoptosis-resistant, cells. They found that the cells had become incapable of taking up glucose, their primary energy source. Under the microscope, the cells also displayed telltale signs of oxidative stress, a harmful accumulation of oxygen-derived molecules called reactive oxygen species (ROS). The result was a halt in the production of ATP, the molecular lifeblood that transports energy in the cells. The unmoored cells were literally starving to death.
“The idea that a lack of extracellular matrix can prevent cells from accessing nutrients hasn’t been shown conclusively before,” said Schafer. “Loss of glucose transport, decreased ATP production, increased oxidative stress—all those things turn out to be interrelated.”
Tumor Metabolism
To figure out what was wrong, the researchers took a direct approach: they tried to fix it. Schafer engineered the homeless cells to express high levels of a gene, HER2, known to be hyperactive in many breast tumors. He also treated the cells with antioxidants in an attempt to relieve oxidative stress and help the cells survive.
Both strategies worked. The cells with the breast cancer gene regained glucose transport, preventing ROS accumulation, and recovered their ATP levels. The antioxidant-treated cells also survived, but by using fatty acids instead of glucose as an energy source.


10A
10A Trolox
Courtesy Zachary Schafer
In these microscope images, human mammary cells (blue) grow in clusters surrounded by a membrane of extracellular matrix (red), which usually keeps them alive. Normally (left), the cells in the middle of the cluster die due to lack of contact with the extracellular matrix, leaving an empty space. In cells treated with Trolox (right), an antioxidant derived from Vitamin E, cells separated from the extracellular matrix survive, filling up the middle of the cluster.

“Our results raise the possibility that antioxidant activity might allow early-stage tumor cells to survive where they otherwise would die from these metabolic defects,” said Schafer.
The researchers are currently planning to test the effects of antioxidant genes, some of which are abnormally regulated in human tumors, and a wider range of antioxidants in animal models. They also plan on characterizing the metabolic consequences of matrix detachment in more detail.
“Ultimately,” Brugge said, “we want to understand enough about the metabolism of tumor cells so that new types of drugs can be designed to target them.”
Students may contact Joan Brugge at joan_brugge@hms.harvard.edu for more information.
Conflict Disclosure: The authors declare no conflict of interest.
Funding Sources: The National Cancer Institute and the National Institutes of Health; the authors are solely responsible for the content of this work.

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Monday, August 31, 2009

Men with hypertension may effectively reduce that hypertension with whole grains and bran

Whole grains, bran may fight hypertension in men
U. S. News & World Report as reported by HealthDay News, August 28, 2009 – By Steven Reinberg
Harvard researchers that found that whole grain foods and foods high in bran bring a boost to heart health. Although the study focused on men, data from the Women's Health Study is consistent with the results. Lead researcher Dr. Alan J. Flint, Harvard School of Public Health research scientist and project director of the Health Professionals Follow-up Study, comments.
http://health.usnews.com/articles/health/healthday/2009/08/28/whole-grains-bran-may-fight-hypertension-in-men.html

HealthDay

Whole Grains, Bran May Fight Hypertension in Men

New findings replicate similar data for women, experts say

Posted August 28, 2009
By Steven Reinberg
HealthDay Reporter
FRIDAY, Aug. 28 (HealthDay News) -- Men, want to keep high blood pressure at bay? Try reaching for whole grains.
That's the message from a Harvard study that found that whole grain foods and foods high in bran bring a boost to heart health. Although this study is among men, data from the Women's Health Study found similar results, the researchers say.

"Whole grains as a part of a prudent, balanced diet may help promote cardiovascular health," said lead researcher Dr. Alan J. Flint, project director at Harvard School of Public Health of the Health Professionals Follow-Up Study, on which the new analysis was based. "Higher intake of whole grains was associated with a lower risk of hypertension in our cohort of over 31,000 men," Flint said.
The report is published in the September issue of the American Journal of Clinical Nutrition.
For the study, Flint's team collected data on 31,684 men who participated in the Health Professionals Follow-Up Study. When these men were enrolled in the study, none had high blood pressure, cancer, heart disease or had had a stroke.
During 18 years of follow-up, over 9,200 men developed high blood pressure. The researchers found that men who ate the highest amount of whole grains were 19 percent less likely to develop high blood pressure compared with men who ate the least amount of whole grains.
In addition, men who ate the most bran reduced their risk of developing high blood pressure by 15 percent compared with men who ate the least bran, the study found.
Flint noted that these findings remained even after adjusting their data for other healthy lifestyle and diet factors. "When the associations persist despite these adjustments, as in the current analysis, it supports the conclusion that it is not due to these other factors," he said.
There have been several suggestions as to why whole grains seem to have an effect on blood pressure. These include improved insulin sensitivity, reduced food intake, lower blood sugar, better control of high blood pressure and less need for blood pressure medications, the researchers noted.
The authors say the findings could help in evaluating diet guidelines to help lower blood pressure.
Connecticut-based nutritionist Samantha Heller agreed that whole grains are an important part of a healthy diet.
"Whole grains have nutrients and antioxidants that are important for good health and they help manage insulin response," Heller said. "People who eat whole grains seem to have lower incidents of diseases like diabetes," she said.
Since whole grains also help manage weight, they seem to reduce the risk of heart disease, she said.
However, Dr. Harlan M. Krumholz, the Harold H. Hines, Jr. Professor of Medicine and Epidemiology and Public Health at Yale University School of Medicine doesn't think this finding has any implications for dietary guidelines.
"This epidemiologic study is an interesting academic study but lacks any policy implications," Krumholz said. "We do not know whether enriching your diet with fiber will have any benefit on the development of hypertension," he said.
More information
For more information on a healthy diet, visit the U.S. Department of Agriculture .

Sunday, August 30, 2009

Animal byproducts in common medicines and over-the-counter preparations

Why doctors should inform their patients where the medicines comes from

My many readers will know - from my many blogs (one Yahoo! 360 blog, recently closed by Yahoo! - had 1.3 million readers) that (a) I am NOT A FAN OF NOMINAL RELIGIOUS IDENTIFICATION - (b) nor am I supportive of arbitrary defections of any kind to lower moral standards.

An infrequently recurring question on vegetarian medical discussion lists in including those on topical medical concerns, where some clinicians and medical trained professionals are signed up, is animal ingredients in common medications. Some great servants of the vegetarians community like the Michaels - Dr. Michael Greger and Dr. Michael Klaper, have tried to help us steer clear of common over-the-counter preparations with animal ingredients, as have some pro-animal organizations (not only PETA, but others, too). You'll noted that, to the discredit of both vegetarians and presumptive vegetarians who are clinicians who ought to know the products AND our ethical and moral scruples about animal byproducts, many clinicians - including nominal Hindus, nominal Jains, nominal Adventists, and others - have failed to engage in pro-active HELP and service to the vegetarian communities, though they MAY be uniquely qualified to do so. Is it laziness or a misshapen sense that their NEW 'higher calling' is professional loyalty, a a jingoistic chauvinism to their professional colleagues, even when the profession is doing the wrong thing.


Let's get one thing clear: NO product of ANY kind should have ANY kind of animal ingredient or byproduct in it.

Therefore, no MEDICAL product of ANY kind should have ANY kind of animal ingredient or byproduct in it.

There's wide-ranging ignorance of this moral truth, but medical and health professionals who are NOT ignorant have even less to say in their defense when they err than have those whose moral laziness merely REFLECTS the social backgrounds from which they come.


In a column in the New York Times this week, Randy Cohen fields a question from an anaesthetist.

Should the doctor ask a devoutly religious patient whether he minds that his anticoagulant (heparin) is derived from pigs?

In his reply, Randy Cohen suggests that the doctrine of informed consent requires the doctor to consider the non-medical preferences of the patient and to make sure Muslims, Jews, and vegetarians (like us) know where medicine to be used in their treatment is coming from.

That's a second best (or third best, or not good) standard at best, but that's what Randy Cohen offers. It's a standard that's been around, has been widely accepted by medical ethicists and others in our culture, and seems to work with little additional thought. After all, clinicians should have a laboratory 'sense of things' that would include routinely understanding the chemical nature of stuffs, stuffs used in clinical treatment.

Are you with us so far? Good!

So Randy Cohen, in his New York Times article a week or so ago, suggests that the doctor's role includes a duty to provide whatever information patients need in order to make decisions about, decide, and effectively manage or control their care. But some doubt that it is a doctor's responsibilityto take into account what they call "preferences" (because they don't clearly understand the moral status of animals d they dismissive discount or deny their personhood.

These deniers claim that the doctors' role is too greatly extended.

:

"Imagine a vegan who takes particular exception to drugs that have been tested in higher order primates. Is the doctor expected to ask about all possible preferences and provide corresponding advice about treatments that conform to these? If so, this seems to be unreasonably demanding."

Briton Wikinson goes on to distinguish what he terms "the normative force of different claims about information-giving" (in other words, different nuances have different moral claims and intellectual legitimacy):

"There is a difference between

1. what would be good for the doctor to do, and
2. what we should expect the doctor to do, and
3. what we should sanction the doctor if they don't do?

If your doctor knows that you are a devout religious adherent, and that you may have an objection to a medical product that they know contains animal products, the doctor should inform you that the drug she is about to prescribe is derived from pigs. It would be good for them do so (level 1 above)."

So far, so good.

"And if you ask your doctor - does this drug contain animal products then the doctor should (stronger - probably level 2, maybe 3) find out about the drug and let you know."

Here's where we can take issue:

"Whether we should expect them (2) if you haven't asked or sanction them (3) if they didn't tell you is less clear to me.

We might also note that there is another side to responsibility when it comes to personal preferences for different treatments. If your preference is idiosyncratic or unusual you, the patient, probably have a responsibility to find out which potential treatments may contain animal products, as well as to let your doctor know that you really don't want animal products (or blood products etc). On the other hand if the preference is very common within the population perhaps the onus should be on the doctor."

Finally, Wilkinson quibbles further:

"As for the relevance of all of this for orthodox judaism, Randy Cohen notes that since Heparin is administered subcutaneously rather than orally it is apparently not proscribed."

Thinking here of being carried away kicking and screaming while refusing ill-intentioned treatment, I rephrase German Lutheran Pastor Martin Niemoller just a little:

First they came for the Muslims, but I wasn't a Muslim...

Then they came for the Orthodox Jews, but I wasn't an Orthodox Jew...

Then they can for the ethical vegans, and I wasn't an ethical vegan...

Then they came for me, kicking and screaming (and what did they want to do surreptitiously to MY body, about which I would object?)...

Let's put it this way:

Ethicists, particularly bioethicists should be thankful (or, if they don't believe in thankfulness, count themselves fortunate) to HAVE observant Muslims, Orthodox Jews, careful SDAs, self-caring body-owning feminists, and us ethical vegans BECAUSE we help to clarify the case that humans DO object to anyone's surreptitiously sneaking objectionable methods into their treatment and materials and substances into our bodies - in the same way we object to the USDA's approval of GMOs, irradiation, chemicalized agriculture, and more.

We should be THANKFUL that the woman's movement in the West and around the world has joined this chorus of these serious moral objections, and we should WELCOME American Republicanswho are yelling at the top of their lungs:

"Just one moment! What's going to be IN this treatment? What's going to be IN this health care program?"

We psychophysical unities of every stripe, brand, variety, background, persuasion, and pattern of human dignity demand no less than a transparent and open discussion of all these issues, even if it means that some well-intentioned measures can't be ramrodding into law quite so quickly.

Those who KNOW there is objection should be especially eager to fund research into NON-objectionable methods of caring for and preserving human health and for restoring it when illness and disease emerge (and for reducing and eliminating pain and providing proper care and treatment when that's the limit of suitable medical intervention).

We all know that the status quo in healthcare is not good enough, but it's more than access to currently-available treatments and their funding that's a mess. What is also all messed up is the WAY our society thinks about health and healthcare. I can give Ted Kennedy credit for noting that we ought to be paying doctors for keeping patients well, but I only puzzle whether or not we have trained these physicians to KEEP people well (when so much emphasis is placed on listening to complaints and treating post-diagnosisconditions.

Why not listyen to us? Of coruse, they ARE listening to us, and if it flies and flies far, they can claim it as their own.

And who should we be to com,plain if they DO develop treatment modalities that are agree of animal exploitation and abuse, focus first on primary prevention, emphasize a strong role for individual responsibility for health andsocial support for enabling that personal responsibility (safe and suitable exercise facilities in all workplace regions and residential areas, designing urban and suburban areas for exercise, and eliminating all subsidies for animal agriculture and making fresh produce afforcable and safe; shifting emphasis from high tech medicine to wards the low-hanging fruit of primary prevention, etc.). After all, what does it mean sociologically to be a servant of the greater public good, the good of all society? It means to serve wisely and effectively; it does NOT mean taking the credit. In the long run, the HEALTH of the people is FAR MORE IMPORTANT than the healthcare delivery of the people UNLESS that healthcare delivery PREVENTS the problems in the first place.

It is BETTER to have NOT suffered at all than to have suffered ravaging illness and disease, then, after costly treatment funded socially, to have recuperated (at least temporarily). Treatment costs money directly AND in lost productivity AND in lost happiness AND in suffering AND in grief for significant others and workplace colleagues. Being HEALTHY IS a savings. That's "IN THE NATURE OF THINGS" for all of us.

If you're looking for healthcare delivery savings, it's in keeping people well; that's why we're shifting to the IDEA of paying healthcare providers differently: paying healthcare systems (not just the doctors) for keeping people well.

In the search for cost savings, Peter Orszag should be exploring primary prevention. Shouldn't we all?

But don't put those animal ingredients in MY treatment protocols (and if we're well, we're less at risk for the medical violation of our bodies).

And the lowest common denominator, and thus the cheapest path for pharmaceutical companies, is to make ALL medicaments FREE of all animal ingredients and byproducts.

The ethicist (note point 3 above) told us that those who object the most should object the loudest because they're the ones who are hardest for the dulled mainstream to hear. We need to make OUR cases that we want an ethical and above-board system of providing health services to our species that don't violate the inherent rights of persons - nonhuman AND human.

And it's better to proactively make the case early than to resort to attorneys 'post-diagnosis' (after our bodies - and bodily rights - have been violated).