Category Archives: Health Care

Search for Antibiotic Solutions Continues: Killing Sleeper Bacteria Cells

Killing Sleeper Cells and Superbugs with Assassin Janitors

Discovered in 2005 by scientists from Bayer Healthcare in Germany, ADEP4 killed a variety of different bacteria and cured lethal infections in mice and rats.

Here’s how it works. Proteins need to fold into very precise shapes to do their jobs, and misfolded proteins are wastes of space. Bacteria dispose of these useless molecules with ClpP—a janitorial protein that digests other proteins. It works with a partner, which recognises misfolded proteins, unfolds them, and threads them through a hole in the middle of ClpP so they can be broken down. But ADEP4 opens ClpP up so it no longer needs its partner. The janitor now becomes an assassin, running amok and chopping up any protein it comes across, misfolded or not.

The Bayer scientists showed that ADEP4 can force fast-growing cells to self-destruct, but Lewis suspected that it would do the same to persisters. Afterall, ClpP’s partner requires energy to do its job, but ClpP itself doesn’t. Once ADEP4 opens it up, it should go about its fatal business even in a dormant cell.

Lewis’ team found that ADEP4 did effectively kills persister populations of Staphylococcus aureus, but the bacteria bounce back. ClpP isn’t essential, so the bacteria just inactivated it to evolve their way around ADEP4. This, says Lewis, is why Bayer stopped working on the drug.

His solution was to pair ADEP4 with another antibiotic called rifampycin. ADEP4 would kill off the majority of the persisters, and if any of the rest started growing again, rifampycin would finish them off. He predicted that the double-whammy would leave very few survivors, maybe just a thousand cells or so.

“That’s not what we saw,” he says. “What we saw was complete sterilisation.”

This is a very nice effort. As our efforts fail to find “magic bullet” antibiotics fail and antibiotic resistance increases combo drug solutions offer some hope. While this is good news, the overall state of our ability to treat bacterial infections continues to decline as our misuse of antibiotics has greatly increased the speed at which antibiotic resistance has developed in bacteria.

This solution only works on gram positive antibiotics. ADEP4 is too big to pass through the extra outer layers of the gram-negative bacteria like ecoli and salmonella.

Related: Entirely New Antibiotic Developed, Platensimycin (2006) (2013 update: Platensimycin is a very effective antibiotic in vivo when continuously administered to cells, however this efficacy is reduced when administered by more conventional means. Efforts continue to find a way to create delivery options that are successful in treating people.) – New Family of Antibacterial Agents Discovered (2009) – Potential Antibiotic Alternative to Treat Infection (2012)

Outdoor Air Pollution Resulted in 223,000 Cancer Deaths in 2010

The specialized cancer agency of the World Health Organization, the International Agency for Research on Cancer (IARC), announced today that it has classified outdoor air pollution as carcinogenic to humans.

After thoroughly reviewing the latest available scientific literature, the world’s leading experts convened by the IARC Monographs Programme concluded that there is sufficient evidence that exposure to outdoor air pollution causes lung cancer. They also noted a positive association with an increased risk of bladder cancer.

Particulate matter, a major component of outdoor air pollution, was evaluated separately and was also classified as carcinogenic to humans.

The IARC evaluation showed an increasing risk of lung cancer with increasing levels of exposure to particulate matter and air pollution. Although the composition of air pollution and levels of exposure can vary dramatically between locations, the conclusions of the Working Group apply to all regions of the world.

Air pollution is already known to increase risks for a wide range of diseases, such as respiratory and heart diseases. Studies indicate that in recent years exposure levels have increased significantly in some parts of the world, particularly in rapidly industrializing countries with large populations. The most recent data indicate that in 2010, 223,000 deaths from lung cancer worldwide resulted from air pollution.

“The air we breathe has become polluted with a mixture of cancer-causing substances,” says Dr Kurt Straif.

The stories of amazingly high (and persistent) air pollution levels in China have been continuing for years. But, while China, likely represents several of the worst existing air pollution conditions hundreds of thousands have died outside China due to air pollution just in the last 5 years.

Continue reading →

Go Slow with Genetically Modified Food

My thoughts on Genetically Modified Organisms (GMO), specifically GM foods, basically boil down to:

messing with genes could create problems
we tend to (and especially those seeking to gain an advantage tend to – even if “we” overall wouldn’t the people in the position to take aggressive measures do) ignore risks until the problems are created (often huge costs at that point)
I think we should reduce risk and therefore make it hard to justify using GMO techniques
I agree occasionally we should do so, like it seems with oranges and bananas.
I agree the practice can be explained in a way that makes it seem like there is no (or nearly no) risk, I don’t trust we will always refrain from stepping into an area where there is a very bad result

Basically I would suggest being very cautious with GMO. I like science and technology but I think we often implement things poorly. I think we are not being cautious enough now, and should reduce the use of GMO to critical needs to society (patents on the practices need to be carefully studied and perhaps not permitted – the whole patent system is so broken now that it should be questioned at every turn).

Antibiotic misuse and massive overuse is an obvious example. We have doctors practicing completely unjustified misuse of antibiotics and harming society and we have factory farms massively overusing antibiotics causing society harm.

The way we casually use drugs is another example of our failure to sensibly manage risks, in my opinion. This of course is greatly pushed by those making money on getting us to use more drugs – drug companies and doctors paid by those companies. The right drugs are wonderful. But powerful drugs almost always have powerful side effects (at least in a significant number of people) and those risks are multiplied the more we take (due to interactions, weakness created by one being overwhelmed by the next etc.). We should be much more cautious but again we show evidence of failing to act cautiously which adds to my concern for using GMO.

I love antibiotics, but the way we are using them is endangering millions of lives (that is a bad thing). I don’t trust us to use science wisely and safely. We need to more consciously put barriers in place to prevent us creating massively problems.

Medical Study Findings too Often Fail to Provide Us Useful Knowledge

There are big problems with medical research, as we have posted about many times in the past. A very significant part of the problem is health care research is very hard. There are all sorts of interactions that make conclusive results much more difficult than other areas.

But failures in our practices also play a big role. Just poor statistical literacy is part of the problem (especially related to things like interactions, variability, correlation that isn’t evidence of causation…). Large incentives that encourage biased research results are a huge problem.

Lies, Damned Lies, and Medical Science

He discovered that the range of errors being committed was astonishing: from what questions researchers posed, to how they set up the studies, to which patients they recruited for the studies, to which measurements they took, to how they analyzed the data, to how they presented their results, to how particular studies came to be published in medical journals. The systemic failure to do adequate long term studies once we approve drugs, practices and devices are also a big problem.

This array suggested a bigger, underlying dysfunction, and Ioannidis thought he knew what it was. “The studies were biased,” he says. “Sometimes they were overtly biased. Sometimes it was difficult to see the bias, but it was there.” Researchers headed into their studies wanting certain results—and, lo and behold, they were getting them. We think of the scientific process as being objective, rigorous, and even ruthless in separating out what is true from what we merely wish to be true, but in fact it’s easy to manipulate results, even unintentionally or unconsciously. “At every step in the process, there is room to distort results, a way to make a stronger claim or to select what is going to be concluded,” says Ioannidis. “There is an intellectual conflict of interest that pressures researchers to find whatever it is that is most likely to get them funded.”

Another problem is that medical research often doesn’t get the normal scientific inquiry check of confirmation research by other scientists.

Most journal editors don’t even claim to protect against the problems that plague these studies. University and government research overseers rarely step in to directly enforce research quality, and when they do, the science community goes ballistic over the outside interference. The ultimate protection against research error and bias is supposed to come from the way scientists constantly retest each other’s results—except they don’t. Only the most prominent findings are likely to be put to the test, because there’s likely to be publication payoff in firming up the proof, or contradicting it.

Exercise Reduces Anxiety While Also Promoting the Growth of New Neurons

Exercise reorganizes the brain to be more resilient to stress

These findings potentially resolve a discrepancy in research related to the effect of exercise on the brain — namely that exercise reduces anxiety while also promoting the growth of new neurons in the ventral hippocampus. Because these young neurons are typically more excitable than their more mature counterparts, exercise should result in more anxiety, not less. The Princeton-led researchers, however, found that exercise also strengthens the mechanisms that prevent these brain cells from firing.
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From an evolutionary standpoint, the research also shows that the brain can be extremely adaptive and tailor its own processes to an organism’s lifestyle or surroundings, Gould said. A higher likelihood of anxious behavior may have an adaptive advantage for less physically fit creatures. Anxiety often manifests itself in avoidant behavior and avoiding potentially dangerous situations would increase the likelihood of survival, particularly for those less capable of responding with a “fight or flight” reaction, she said.
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The anxiety-reducing effect of exercise was canceled out when the researchers blocked the GABA receptor that calms neuron activity in the ventral hippocampus.

Interesting research (with mice) that explores how exercise makes us more resilient to stress. I know for me, exercise seems to help relieve stress.

Drugmakers Are Desperate to Know Why Placebos Are Getting More Effective

Fascinating article from Wired: Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why.

The fact that an increasing number of medications are unable to beat sugar pills has thrown the industry into crisis. The stakes could hardly be higher. In today’s economy, the fate of a long-established company can hang on the outcome of a handful of tests.
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Potter discovered, however, that geographic location alone could determine whether a drug bested placebo or crossed the futility boundary. By the late ’90s, for example, the classic antianxiety drug diazepam (also known as Valium) was still beating placebo in France and Belgium. But when the drug was tested in the US, it was likely to fail. Conversely, Prozac performed better in America than it did in western Europe and South Africa. It was an unsettling prospect: FDA approval could hinge on where the company chose to conduct a trial.
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In one study, Benedetti found that Alzheimer’s patients with impaired cognitive function get less pain relief from analgesic drugs than normal volunteers do. Using advanced methods of EEG analysis, he discovered that the connections between the patients’ prefrontal lobes and their opioid systems had been damaged. Healthy volunteers feel the benefit of medication plus a placebo boost. Patients who are unable to formulate ideas about the future because of cortical deficits, however, feel only the effect of the drug itself. The experiment suggests that because Alzheimer’s patients don’t get the benefits of anticipating the treatment, they require higher doses of painkillers to experience normal levels of relief.

Benedetti often uses the phrase “placebo response” instead of placebo effect. By definition, inert pills have no effect, but under the right conditions they can act as a catalyst for what he calls the body’s “endogenous health care system.” Like any other internal network, the placebo response has limits. It can ease the discomfort of chemotherapy, but it won’t stop the growth of tumors. It also works in reverse to produce the placebo’s evil twin, the nocebo effect. For example, men taking a commonly prescribed prostate drug who were informed that the medication may cause sexual dysfunction were twice as likely to become impotent.
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Moreover, a pill’s shape, size, branding, and price all influence its effects on the body. Soothing blue capsules make more effective tranquilizers than angry red ones, except among Italian men, for whom the color blue is associated with their national soccer team—Forza Azzurri!

Medical research presents significant difficulties. The funding of the health care system also distorts behavior and pushes companies to focus on being able to justify selling drugs instead of focusing on finding effective solutions. Even without incentives distorting behavior, the challenges are difficult enough. Adding the distortions just makes it worse.

It is wonderful we have so many scientists accepting these challenges and spending their careers fighting the odds to help find us wonderful health breakthroughs.

Appropriate Technology Health Care Solution Could Save 72,000 Lives a Year

We need more medical solutions that serve the majority of humanity instead of just the rich. Some medical research is innately costly and therefore require large costs to pay back the investment. But too little concern is shown for solutions that help people (with so much focus only on solutions that will make organizations rich).

Cheap vinegar test cut cervical cancer deaths in India; could help many poor countries

This low-tech visual exam cut the cervical cancer death rate by 31 percent, the study found. It could prevent 22,000 deaths in India and 72,600 worldwide each year, researchers estimate.
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More progress against cervical cancer may come from last month’s announcement that two companies will drastically lower prices on HPV vaccines for poor countries. Pilot projects will begin in Asia and Africa; the campaign aims to vaccinate more than 30 million girls in more than 40 countries by 2020.

India continues to invest in medical research for solutions that are affordable to a majority of the world. The rich health care companies largely neglect the majority to focus on the most wealthy.

Clay Water Filters for Ghana

Pure Home Water, Ghana manufactures and distributes AfriClay Filters in an effort to bring clean water to 1 million people. So far they have delivered filters to provide 100,000 people clean water.

The process is simple. Water is placed in a clay filter and gravity pulls the water through the pores left in the clay during firing.

Sediment and bacteria are filtered out in several ways:

Physical straining: the particles are too large to fit through the pores in the clay
Sedimentation or adsorption: particles come to rest on or stick to the clay
Inertia: friction in the pores keeps the particles from passing through

Bacteria are also killed by a coating of colloidal silver (a disinfectant), which we apply to all filters that pass our quality control tests. While sediment and bacteria are filtered out, the molecules of water are small enough to pass through the pores in the clay.

The filters are sold to those who will use them. The effort has shown a willingness to pay by villagers in remote Northern Ghana (those earning < US$1/day). I imagine (I am just guessing) the prices are subsidized; in the last decade more (most?) appropriate technology solutions will have those benefiting pay something for the benefits they receive. My nephews are working on a similar effort in India, using bio sand filters, I plan to post more on that later. There is current a campaign to help fund the delivery of water filters to Indian villages.

Cell Aging and Limits Due to Telomeres

When cells divide the process fails to copy DNA all the way to the end. Telomeres are are the end of DNA strands, as essentially a buffer of material that won’t cause information to be lost when part of the telomere isn’t copied. As DNA is copied, as new cells are created, the length of telomeres at the end is reduced. Once the telomeres are gone the cell will no longer divide.

The 2009 Nobel Prize in Physiology or Medicine went to 3 scientists for discovering how the chromosomes can be copied in a complete way during cell divisions and how they are protected against degradation. The Nobel Laureates have shown that the solution is to be found in the ends of the chromosomes – the telomeres – and in an enzyme that forms them – telomerase.

There is some debate over the benefit of the mechanism of cells not dividing do to lack of telomere. This can prevent cancerous cells from replicating (once they replicate to the extent that the necessary telomere buffer is gone). It is also seen that as telomeres get shorter the cells become more likely to become cancerous.

Cancer also can stimulate the production of telomerase which can stop telomeres from getting shorter as cells divide and thus allow the cancer cells to keep dividing (thus producing more cancer cell and increasing the amount of cancerous cells). Using telomerase to allow health cells to avoid the limits of division is being researched.

Are Telomeres the Key to Aging and Cancer? (University of Utah)

An enzyme named telomerase adds bases to the ends of telomeres. In young cells, telomerase keeps telomeres from wearing down too much. But as cells divide repeatedly, there is not enough telomerase, so the telomeres grow shorter and the cells age.
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Cells normally can divide only about 50 to 70 times, with telomeres getting progressively shorter until the cells become senescent, die or sustain genetic damage that can cause cancer.
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shorter telomeres are associated with shorter lives. Among people older than 60, those with shorter telomeres were three times more likely to die from heart disease and eight times more likely to die from infectious disease.

While telomere shortening has been linked to the aging process, it is not yet known whether shorter telomeres are just a sign of aging – like gray hair – or actually contribute to aging.

CDC Again Stresses Urgent Need to Adjust Practices or Pay a Steep Price

Untreatable and hard-to-treat infections from Carbapenem-resistant Enterobacteriaceae (CRE) germs are on the rise among patients in medical facilities. CRE germs have become resistant to all or nearly all the antibiotics we have today. Types of CRE include Klebsiella pneumoniae Carbapenemase (KPC) and New Delhi metallo-beta-lactamase (NDM). By following the United States Center for Disease Control (CDC) guidelines, we can slow the penetration of CRE infections in hospitals and other medical facilities and potentially spread to otherwise healthy people outside of medical facilities.

The CDC has worked with hospitals to successfully apply these measures. The CDC worked with Florida to stop a year-long CRE outbreak in a long-term acute care hospital. With the improved use of CDC recommendations (such as educating staff; dedicating staff, rooms, and equipment to patients with CRE; and improving use of gloves and gowns) the percentage of patients who got CRE at the facility dropped from 44% to 0.

One travesty has been how poorly health care professionals have been about prescribe antibiotics wisely We need to improve and follow CDC antibiotics guidelines (stop the overuse of antibiotics) and use culture results (for patients undergoing treatment) to modify prescriptions, if needed. Antibiotic overuse contributes to the growing problems of Clostridium difficile (c-diff) infection and antibiotic resistance in healthcare facilities. Studies indicate that nearly 50% of antimicrobial use in hospitals is unnecessary or inappropriate (per CDC web site).

Israel decreased CRE infection rates in all 27 of its hospitals by more than 70% in one year with a coordinated prevention program. The USA is at a critical time in which CRE infections could be controlled if addressed in a rapid, coordinated, and consistent effort by doctors, nurses, lab staff, medical facility leadership, health departments/states, policy makers, and the federal government.

As I have been saying for years the damage we are creating due to our actions around the use and abuse of antibiotics is likely to kill tens of thousands, or more people. Because the deaths are delayed and often not dramatic we have continued dangerous practices for years when we know better. It is a shame we are condemning so many to increased risks. The CDC, and others, are doing good work, unfortunately too much bad work is continuing in the face of evidence of how dangerous that is.