OF MICE AND BEER

By Pam Eastlick

Welcome to The Deep science and technology column where we cover topics from the deep sea to deep space and beyond.

Well, after looking over The Deep file folders, it looks like it’s time to do a column on medicine with some emphasis on how to avoid taking it. But our first article focuses on the research aspect of what ails us and why it’s bad that the research is primarily on something else besides us.

LEAVING THE MOUSE TRAP

Noted immunologist Dr. Mark Davis from the Stanford University School of Medicine says that the fabled laboratory mouse that has taught us many things about human disease can teach us only so much about how we humans get sick and what to do about it.

He says that the time has come for researchers to start weaning themselves from experimental rodents and to embark on a bold, industrial-scale assault on the causes and treatment of specifically human diseases. He proposes that the current mouse-centered, small-laboratory approach be supplemented by a broad, industrial-scale "systems biology" approach akin to the one that unraveled the human genome.

"We seem to be in a state of denial, where there is so much invested in the mouse model that it seems almost unthinkable to look elsewhere," Davis says. "The mouse has been incredibly valuable. That’s part of the problem."

Experiments that are common with lab mice, such as genetically engineering them to express a foreign protein or to be deficient in the expression of one of their own, would be unthinkable in a human. Because experimental mice can be used to get quick answers, Davis argues, researchers look to the mouse to tell them everything. "In humans it often takes years to find out anything. There are a lot more regulatory, financial and ethical hurdles," he said.

Unfortunately, researcher have discovered how to cure all kinds of infectious disease, cancers and autoimmune conditions in mice but when they try to adapt these cures for humans, the record isn’t very good. The vast majority of clinical trials designed to test these interventions in people end in failure.

There are probably some good reasons for this, said Davis. For starters, mice are rodents, separated from humans by some 65 million years of evolutionary divergence from our common ancestor.

That’s not all. While it takes about 20 years for a person to reach sexual maturity, a mouse gets there in three months. The roughly 100 years during which the furry, diminutive animals have been domesticated and bred in labs are, therefore, the mouse equivalent of 8,000 human years, during which they have been inbred and kept relatively disease-free. They would never survive in the wild.

"We can’t depend on the mouse for all the answers, because in some cases it’s not giving us the right answers," Davis said. "But think about what we can do with people. People come to hospitals, get vaccinations, give blood and tissue samples for routine lab tests and clinical trials. We’re not learning nearly as much as we could from these samples."

Davis sees the need for a national or even international infrastructure to capture information from blood and tissue samples. One example is Stanford’s Human Immune Monitoring Core. Researchers send human samples to this facility, where many assays of cell types and immune secretions in blood and tissues gather data about experimental subjects’ immune status, in a relatively short time.

The creation of these large country-scale labs could mean that tests could be quickly and cheaply conducted in a standardized fashion among very large groups of people, some in excellent health, others suffering from one or more diseases. This kind of database could establish normal ranges for many parameters and then see how those parameters are changed by infectious diseases or autoimmune disorders and even things like aging and vaccinations. This could allow medical scientists to see a developing problem very early and start applying remedies to restore the normal balance and prevent the disease’s progression.

These ‘experiments’ on humans make a lot more sense than the ongoing emphasis on learning about our diseases by studying another life form altogether.

I think that it is time to do more study on humans than on mice to learn about the diseases and conditions that kill us. But good health has always begun at home and now we present two cautionary tales about the things that make us sick that we do voluntarily!

A researcher holds a white laboratory mouse. (Credit: iStockphoto/Brandon Laufenberg)

THE SINGLE QUESTION

I have long said that if we really want to get out of the financial bind that periodically plagues us here on Guam, we don’t have to depend on the military or tourism or any of those things. All we have to do is charge a 50-cent sin tax on every can of beer sold on the island. Although beer sales would probably drop for a month or two, trust me, they would soon be back to normal levels and the government’s money problems would be gone.

But much more importantly, it’s time that we started making alcohol pay for the terrible toll it extracts on our islands. And don’t tell me you don’t know what I’m talking about. Too many car accidents, too many beatings, too many kids who don’t get enough to eat.

So, you say. I’m in total agreement with you. This won’t affect me at all, because I certainly don’t have a drinking problem. Are you sure?

Researchers at the Boston Medical Center have found that a single question accurately identifies anyone who has unhealthy alcohol usage.

Unhealthy alcohol use, which covers the spectrum from risky consumption to alcohol use disorders, alcohol abuse and dependence, is extremely common but under-diagnosed by doctors. Many commonly used questionnaires to detect problems with alcohol have too many questions, often don’t cover the full spectrum of unhealthy use, and can be time consuming to administer. Consequently, many patients are not screened.

In the current research, a single question was asked of 286 people. The test revealed unhealthy alcohol use in 31% of the participants. The single-question screen was 81.8% sensitive and 79.3% specific for the detection of unhealthy alcohol use. It was slightly more sensitive and less specific for the detection of a current alcohol use disorder.

So . . . what was the question? Do you have alcohol abuse problems? Here it is!

"How many times in the past year have you had five or more drinks in a day?" Too many times, you say? Well, there’s your answer!

And lest you think that you’re home free because you’re a tee-totaller and never drink beer, read on!

IT’S NOT JUST BEER

Doctors have recently issued a warning about excessive cola consumption after noticing an increase in the number of patients suffering from muscle problems. We’re consuming more soft drinks than ever before and a number of health problems have already been identified that include tooth decay (why do you think your six-year old nephew has silver teeth?), bone demineralization and diabetes.

Now, evidence is increasing that suggests that excessive cola consumption can also lead to hypokalaemia, in which blood potassium levels fall to the point that it affects vital muscle functions. (Don’t forget that your heart is also a muscle!)

A research review has shown that symptoms can range from mild weakness to profound paralysis. Luckily, all the patients studied made a rapid and
full recovery after they stopped drinking cola and took oral or intravenous potassium.

The case studies looked at patients whose consumption ranged from two to nine liters of cola a day. They included two pregnant women admitted to the hospital with low potassium levels.

The first, a 21 year-old woman, was consuming up to 3 liters of cola a day She complained of fatigue, appetite loss and persistent vomiting. Her blood tests showed she had extremely low potassium levels. The second woman also had low potassium levels and was suffering from increasing muscular weakness. She had been drinking up to 7 liters of cola a day for the previous 10 months.

Another example highlighted the strange case of the ostrich farmer who returned from the Australian outback with muscle weakness. He had been drinking 4 liters of cola a day for the past three years and drank up to 10 liters a day when he was in the outback, causing a rapid reduction in his potassium levels.

Another doctor solved the case of his patient’s muscle weakness when the patient turned up at his office with a two-liter bottle of cola in the basket of his electric scooter. It turned out he routinely drank up to 4 liters a day. He refused to stop drinking cola, but halved his consumption and the muscle weakness he had been complaining of improved.

In 2007, the worldwide annual consumption of soft drinks reached 552 billion liters, the equivalent of just under 83 liters per person per year. This is projected to increase to 95 liters per person per year by 2012. However, the figure for the United States is already 212 liters per person per year.

So why does cola cause this? Hypokalaemia is caused by excessive consumption of three of the most common ingredients in cola drinks – glucose, fructose and caffeine.

The researchers said that in most cases, caffeine intoxication was thought to play the most important role. This has been borne out by case studies that focus on other products that contain high levels of caffeine but no glucose or fructose. However, caffeine-free cola products can also cause hypokalaemia because the fructose they contain can cause diarrhea.

Although most patients recover when they stop drinking cola and take potassium supplements, cola-induced chronic hypokalaemia can make them more susceptible to potentially fatal complications, such as an irregular heartbeat. (What did I say about the heart?)

The researchers say that excessive consumption of any kind of cola can lead to a range of health problems including fatigue, loss of productivity and muscular symptoms that vary from mild weakness to profound paralysis. They believe that further studies are needed to establish how much is too much when it comes to the daily consumption of cola drinks.

So . . . .what are you drinking today?

EATING WHAT’S GOOD FOR YOU

By Pam Eastlick

Well, I usually choose my topic-of-the-week by which file is bulging the worst and this week is no exception. The medical file is just full of juicy stories about what ails us so off we go on another excursion in the wonderful world of medicine. We’ll start off with some things that are good for us.

GO FOR THE CURRY

Have you ever tried Indian food? Do you like curry? Well, it turns out that it’s good for you and you might want to eat some more of it. The spice turmeric is the main ingredient in curry powder and the active chemical in turmeric is curcumin. A recent study on curcumin by researchers at the Medical College of Georgia shows that it not only lowers your chances of getting cancer and Alzheimer’s disease, but may reduce the size of a hemorrhagic stroke.

The researchers are using animal models to study curcumin’s effect on intracerebral hemorrhages, bleeding in the brain caused by ruptured vessels. Patients with this type of stroke are often treated for symptoms – such as headache and nausea – with medications, but not the stroke itself. Invasive surgery to remove the clot is usually needed, but many of the patients who suffer this kind of stroke are not good candidates for surgery. About 17 percent of all strokes are hemorrhagic, according to the American Stroke Association, and they usually occur in people with high blood pressure.

The researchers discovered that curcumin significantly decreased the size of a blood clot but they remain unsure about why it does so. Curcumin is a potent anti-inflammatory and antioxidant.

Timing is critical for patients who often don’t know they have had a stroke and may not be seen by a physician for several hours. Stroke victims experience symptoms like seizures, vision or cognitive problems but sometimes they ignore the symptoms. Head injuries can also cause hemorrhagic bleeding. But treating the victims can become tricky after an hour or so.

Patients likely will need to get curcumin intravenously. The researchers believe it may also help prevent strokes; they intend to pursue this line of study with the idea of also making it available in a concentrated tablet form for those at-risk.

So next time you eat out choose an Indian restaurant. Or learn to make dynamite curry at home!

And now, a new benefit from one of the oldest drugs in the pharmacopoeia

AN ASPIRIN A DAY

Although I take my daily aspirin, I’m one of those people who bleeds a little more freely because of it. I was actually thinking about asking my doctor if I really need to take it because it doesn’t appear to make much difference with heart attacks in women. But apparently the heart isn’t the whole story for this ancient drug.

Simple aspirin may prevent liver damage in millions of people suffering from side effects of common drugs, alcohol abuse, and obesity-related liver disease, a new Yale University study suggests. The study documents that in mice, aspirin reduced mortality caused by Tylenols overdoses. It further showed that molecules known as TLR antagonists, which block receptors known to activate inflammation, have a similar effect as aspirin.

Since these agents seem to work by reducing injury-induced inflammation, the results suggest aspirin may help prevent and treat liver damage from a host of non-infectious causes like drugs and alcohol.

Aspirin and the TLR antagonists apparently block a central pathway responsible for liver injury caused by these factors. Many promising drugs have failed their clinical trials because they were toxic to the liver and they just might work if they were combined with aspirin.

And even though I don’t do drugs or alcohol, a healthy liver just might be worth putting up with the “Where did all this blood come from?” episodes a little longer.

I do take my daily aspirin, but for years I’ve defied the “Eat a healthy breakfast every day” because I don’t like most breakfast foods like eggs and cereal. But what I have done every day for many years is eat a Golden Delicious apple for breakfast. And it turns out I may have had the right idea all along.

An Apple  a Day

Six studies published in the past year by a Cornell researcher add to growing evidence that an apple a day — as well as daily helpings of other fruits and vegetables — can help keep the breast-cancer doctor away.

In one of his recent papers, Rui Hai Liu, Cornell associate professor of food science, reports that fresh apple extracts significantly inhibited the size of mammary tumors in rats; and the more extracts they were given, the greater the inhibition.

“We not only observed that the treated animals had fewer tumors, but the tumors were smaller, less malignant and grew more slowly compared with the tumors in the untreated rats,” said Liu, pointing out that the study confirmed the findings of his preliminary study in rats published in 2007.

In his latest study, he found that a type of adenocarcinoma — a highly malignant tumor and the main cause of death of breast-cancer patients, as well as of animals with mammary cancer — was evident in 81 percent of tumors in the control animals. However, it developed in only 57 percent, 50 percent and 23 percent of the rats fed low, middle and high doses of apple extracts.

Liu found that phytochemicals (active chemicals produced by plants) called phenolics were the agents that were involved. Phenolics are mainly found in apple peel, so if you routinely peel your apples before eating them, you don’t get the benefits. Liu found that apples provide 33% of the phenolics that Americans consume annually.

Breast cancer is the most frequently diagnosed invasive cancer and the second leading cause of cancer deaths in women in the United States. Liu said that his studies add to the growing evidence that increased consumption of fruits and vegetables, including apples, would provide consumers with more phenolics, which are proving to have important health benefits. He encourages consumers to eat more and a wide variety of fruits and vegetables daily.

I certainly agree with him about the fruits and vegetables, but I did find one thing rather disconcerting about his study. The breast cancer developed in only 57 percent, 50 percent and 23 percent of the rats fed low, middle and high doses of apple extracts. These low, middle and high doses were the equivalent of one, three and six apples a day in humans. I like apples, but I’m not sure I’m ready to eat six a day!

Americans get about 33 percent of phenolics from apples. This chart from one of Liu’s recent papers shows the percentage of phenolics (phytochemicals) that Americans get from various fruits. (Credit: Image courtesy of Cornell University)

Well, we’ve had three positive stories that tell you to eat more curry, eat more apples and take your medicine. Now we’ll end on something that research says you should do less of.

EAT LESS MEAT

A new study has shown that people who eat more red meat and processed meat appear to have a modestly increased risk of death from all causes and also from cancer or heart disease over a 10-year period, according to a new article. In contrast, a higher intake of white meat appeared to be associated with a slightly decreased risk for overall death and cancer death.

Rashmi Sinha, Ph.D., and colleagues at the National Cancer Institute, Rockville, Md., assessed the association between meat intake and risk of death among more than 500,000 individuals who were part of the National Institutes of Health-AARP Diet and Health Study. Participants, who were between 50 and 71 years old when the study began in 1995, provided demographic information and completed a food frequency questionnaire to estimate their intake of white, red and processed meats. They were then followed for 10 years through Social Security Administration Death Master File and National Death Index databases.

During the follow-up period, 47,976 men and 23,276 women died. The one-fifth of men and women who ate the most red meat had a higher risk for overall death, death from heart disease and death from cancer than the one-fifth of men and women who ate the least red meat, as did the one-fifth of men and women who ate the most vs. the least amount of processed meat.

When comparing the one-fifth of participants who ate the most white meat to the one-fifth who ate the least white meat, those with high white meat intake had a slightly lower risk for total death, death from cancer and death from causes other than heart disease or cancer. The researchers say that 11 percent of deaths in men and 16 percent of deaths in women could have been prevented if the people had decreased their red meat consumption.

So why would eating meat cause you to die early? There are several reasons. Cancer-causing compounds are formed during high-temperature cooking of meat. Meat also is a major source of saturated fat, which has been associated with breast and colorectal cancer. In addition, lower meat intake has been linked to a reduction in risk factors for heart disease, including lower blood pressure and cholesterol levels.

Individuals who eat more red meat and processed meat appear to have a modestly increased risk of death from all causes and also from cancer or heart disease over a 10-year period, according to a new article. (Credit: iStockphoto/Ron Bailey)

Eat more, eat less. Just work at what keeps you healthy and you’ll live a lot longer.