Author Archives: Sima

 This week a forceful statement paper was issued by more than 200 hundred scientists and health professionals expressing serious concerns about triclosan and triclocarban. This statement, called The Florence Statement on Triclosan and Triclocarban, asked that the use of these widely used antimicrobials be restricted due to their risks to human health, to wildlife, and its accumulation in water, land, wildlife, and humans. They stated that the negatives outweigh any benefits, and they also questioned the use of other antimicrobials (because they also have similar health and environmental concerns).

Not only do triclosan and triclocarban persist in the environment, they are also a source of toxic and carcinogenic compounds including dioxins, chloroform, and chlorinated anilines. They are endocrine disruptors that bioaccumulate (build-up) in humans and wildlife. They are toxic to aquatic and other organisms, yet they are found in the majority of people and freshwater streams. In other words, the chemicals are all around us and in us!

More than 2000 personal and consumer products, as well as building materials, contain triclosan and triclocarban. For example, they are found in soaps, toothpastes, detergents, clothing, toys, carpets, plastics, kitchen items, and paints. But the U.S. Centers for Disease Control and Prevention Healthcare Infection Control Practices Advisory Committee have concluded, “No evidence is available to suggest that use of [antimicrobial-impregnated articles and consumer items bearing antimicrobial labeling] will make consumers and patients healthier or prevent disease”. According to the FDA, which is responsible for regulation of foods, drugs, cosmetics, medical devices, and similar products, there is no evidence that antibacterial soaps are more effective than nonantibacterial soap and water. So why is it in so many products? It's a marketing gimmick!

What should one do? Read labels and avoid products containing triclosan, triclocarban, or anti-microbials, and products labeled anti-odor, antibacterial, or anti-germ. No, you don't need antibacterial or anti-odor socks or cutting boards! See earlier posts on this topic (here, here, and here). From Environmental Health News:

Hundreds of scientists call for caution on anti-microbial chemical use

Two ingredients used in thousands of products to kill bacteria, fungi and viruses linger in the environment and pose a risk to human health, according to a statement released today by more than 200 scientists and health professionals. The scientists say the possible benefits in most uses of triclosan and triclocarban—used in some soaps, toothpastes, detergents, paints, carpets—are not worth the risk.

The statement, published today in the Environmental Health Perspectives journal, urges “the international community to limit the production and use of triclosan and triclocarban and to question the use of other antimicrobials.” They also call for warning labels on any product containing triclosan and triclocarban and for bolstered research of the chemicals' environmental toll.

The statement says evidence that the compounds are accumulating in water, land, wildlife and humans is sufficient to merit action. The chemicals are used to kills microbes such as bacteria and viruses that make people ill. However, both chemicals affect animals’ hormone systems, causing reproductive and development problems.  And there is nascent evidence that the impacts may extend to humans as well—having been linked to reduced growth of fetuses, earlier births, and lower head circumference in boys at birth.

U.S. manufacturers are phasing out triclosan from hand soaps after the Food and Drug Administration banned it last year amid concerns that the compound disrupted the body's hormone systems. The FDA noted in the restriction that antibacterial hand soaps were no more effective than non-antibacterial soap and water at preventing illness. .... More worrisome, Lindeman said some manufactures of personal care products are simply substituting other antimicrobials for triclosan—some of which may pose the same risks to people and the environment. Because of the widespread use, most people have some levels of triclosan in them. A 2008 study of U.S. residents found it in the urine of about 75 percent of people tested.

Once the compounds get into the environment, they don’t readily go away.  Researchers have detected triclosan and triclocarban in water and sediment all over the world—including drinking water, oceans and streams. The U.S. Geological Survey found triclosan in 60 percent of U.S. streams. Studies have shown triclosan toxic to some algae, fish and other crustaceans.

The compounds impact hormones in animal studies. And there’s evidence that they may do the same to developing babies. Properly functioning hormones are critical for babies’ proper development. Last month Brown University researchers reported that mothers’ triclosan exposure during pregnancy was linked to lower birth weights, smaller heads and earlier births. ...In addition to endocrine disruption concerns, Lindeman and other signers outline two other potential human health impacts from exposure to triclosan: heightened sensitivity to allergens, and antibiotic resistance. Large studies of children in the United States and Norway have linked triclosan to allergies and worsening asthma. And there is evidence bacteria that develop resistance to triclosan also become resistant to other antibacterial compounds.

 Should the results of this study determine what kind of coffee one drinks? Does it really make a difference? Eh...Not for me (because all coffee seems to be beneficial), but it might for you.

Studies show that daily drinking of coffee appears to have health benefits. Studies have linked coffee consumption with lower rates of cancer (here and here), cardiovascular disease, and diabetes. Coffee contains beneficial chemicals (such as caffeine and chlorogenic acid) that are antioxidant and anti-inflammatory, and could help fight chronic inflammatory diseases. It turns out that how much coffee beans are roasted changes how much chlorogenic acid they contain, but the amount of caffeine basically stays the same among the different roasting levels.

Researchers in Korea compared the caffeine and chlorogenic acid components of Arabica coffee beans at different roasting levels: Light, Medium, City, and French roast. They then tested various protective antioxidant and anti-inflammatory properties of the different coffee extracts in various "cell models" (meaning in the lab, not on real people). They found that chlorogenic acid levels were higher in light roasted coffee extract than the other roasted groups, and also light roasted coffee extract had the highest antioxidant activity. The results found that increasing degrees of roasting reduced antioxidant and anti-inflammatory activities.

From the Journal of Medicinal Food: Cellular Antioxidant and Anti-Inflammatory Effects of Coffee Extracts with Different Roasting Levels

During roasting, major changes occur in the composition and physiological effects of coffee beans. In this study, in vitro antioxidant effects and anti-inflammatory effects of Coffea arabica green coffee extracts were investigated at different roasting levels corresponding to Light, Medium, City, and French roast. Total caffeine did not show huge difference according to roasting level, but total chlorogenic acid contents were higher in light roasted coffee extract than other roasted groups. In addition, light roasted coffee extract had the highest antioxidant activity.... The expression of mRNA for tumor necrosis factor-alpha and interleukin-6 was decreased in cells treated with the coffee extracts and the expression decreased with increasing roasting levels. These data suggest that coffee has physiological antioxidant and anti-inflammatory activities and these effects are negatively correlated with roasting levels in the cell models.

Coffee is one of the most popular beverages worldwide. Increasing consumption of coffee is related to the pleasing taste and aroma, as well as its physiological effects. Coffee is proposed to exert beneficial effects against cancer, cardiovascular disease, obesity, and diabetes. Coffee contains phenolic compounds such as caffeic acid, chlorogenic acid, ferulic acid, vanillic acid, and other phytochemicals. The quality of coffee is significantly related to the roasting process.... During roasting, there are numerous changes in coffee bean compound profiles and the aroma is increased. Major changes in coffee bean composition occur during roasting as a result of the Maillard reaction..... Roasting markedly affects chlorogenic acid, leading to hydrolysis of chlorogenic acid. New compounds are formed during the roasting process; one of these is melanoidin. Its formation might alter the overall antioxidant capacity of coffee beans after roasting.

Coffee is a rich source of antioxidants that may contribute to prevention of oxidative stress-related diseases. The antioxidant properties of coffee may reflect the presence of both phenolic and nonphenolic bioactive compounds, such as caffeine and chlorogenic acids. Previous studies have shown that coffee has protective effects against oxidation and DNA damage in human cell models and has been shown to possess an in vitro antioxidant activity that lessens lipid peroxidation and neoplastic activity. 

Caffeine is the major component in coffee extract and has antioxidant property. Chlorogenic acid is another well-known efficient antioxidant in coffee extract; it was highest in Light roast coffee extract and highest with low roasting temperature and lowest in Dark roasted extract. Carbohydrates, protein, and chlorogenic acid are all decreased in coffee during the roasting process.... Caffeine contents showed no differences among roasting levels, but chlorogenic acid content decreased as roasting degree increased..... The effect of coffee roasting on the antioxidant properties of coffee extracts was investigated in several earlier studies; antioxidant capacity decreased in Dark roast coffee. The antioxidant property of coffee extracts prepared with different roasting levels was also determined in this study. The best antioxidant activity was evident in Light roast coffee extract and the lowest in French roast coffee.

Image result for pills wikipedia Hah!  A study that builds on what is already known by many women - that the non-prescription product D-mannose works for urinary tract infections (UTIs). D-mannose is amazingly effective for urinary tract infections caused by E. coli bacteria (up to 90% of UTIs), even infections that  keep recurring (30 to 50% of infections), and which don't respond to numerous antibiotics. D-mannose is effective because it attaches to E. coli bacteria, and prevents them from attaching to the walls of the urinary tract. But as women know, there are many (all effective) D-mannose products on the market - so the big pharmaceutical companies can't claim it as their own (with patents) for the big bucks $$$. So...this study is basically chemically reformulating the mannose sugar (which is in D-mannose) for a new product (mannosides) - one that they can claim as their own. Maybe it'll be a little better than ordinary D-mannose, and maybe not. Human studies are needed.

By the way, this study may be big news to physicians because most don't seem to know about D-mannose as a treatment for UTIs - they all seem to focus just on antibiotics and perhaps cranberry juice in treating UTIs. This may be because D-mannose is considered as an "alternative treatment". And I could find only one study that compares antibiotics and D-mannose for recurrent UTIs - and guess which one did a little better?  Yup...D-mannose (see post). From Medical Xpress:

New treatment reduces E. coli, may offer alternative to antibiotics

Urinary tract infections (UTIs) are among the most common infections, and they tend to come back again and again, even when treated. Most UTIs are caused by E. coli that live in the gut and spread to the urinary tractA new study from Washington University School of Medicine in St. Louis has found that a molecular decoy can target and reduce these UTI-causing bacteria in the gut. With a smaller pool of disease-causing bacteria in the gut, according to the researchers, the risk of having a UTI goes down...."This compound may provide a way to treat UTIs without the use of antibiotics."

Close to 100 million people worldwide acquire UTIs each year, and despite antibiotic treatment, about a quarter develop another such infection within six months. UTIs cause painful, burning urination and the frequent urge to urinate. In serious cases, the infection can spread to the kidneys and then the bloodstream, where it can become life-threatening. Most UTIs are caused by E. coli that live harmlessly in the gut. However, when shed in the feces, the bacteria can spread to the opening of the urinary tract and up to the bladder, where they can cause problems. Conventional wisdom holds that UTIs recur frequently because bacterial populations from the gut are continually re-seeding the urinary tract with disease-causing bacteria.

Hultgren, graduate student Caitlin Spaulding, and colleagues reasoned that if they could reduce the number of dangerous E. coli in the gut, they could reduce the likelihood of developing a UTI and possibly prevent some recurrent infections. First, the researchers identified genes that E. coli need to survive in the gut. One set of genes coded for a kind of pilus, a hairlike appendage on the surface of E. coli that allows the bacteria to stick to tissues, like molecular velcro. Without this pilus, the bacteria fail to thrive in the gut. Earlier studies found that the identified pilus attaches to a sugar called mannose that is found on the surface of the bladder. Grabbing hold of mannose receptors on the bladder with the pilus allows the bacteria to avoid being swept away when a person urinates. Bacteria that lack this pilus are unable to cause UTIs in mice.

Previously, Hultgren and co-author, James W. Janetka, PhD, an associate professor of biochemistry and molecular biophysics at Washington University, chemically modified mannose to create a group of molecules, called mannosides, that are similar to mannose but changed in a way that the bacteria latch onto them more tightly with their pili. Unlike mannose receptors, though, these mannosides are not attached to the bladder wall, so bacteria that take hold of mannosides instead of mannose receptors are flushed out with urine.

Since the researchers found that this same pilus also allows the bacteria to bind in the gut, they reasoned that mannoside treatment could reduce the number of E. coli in the gut and perhaps prevent the spread of the bacteria to the bladder. To test this idea, they introduced a disease-causing strain of E. coli into the bladders and guts of mice to mirror the pattern seen in people. In women with UTIs, the same bacteria that cause problems in the bladder usually also are found living in the gut.

The researchers gave the mice three oral doses of mannoside, and then measured the numbers of bacteria in the bladders and guts of the mice after the last dose of mannoside. They found that the disease-causing bacteria had been almost entirely eliminated from the bladder and reduced a hundredfold in the gut, from 100 million per sample to 1 million. .... researchers measured the composition of the gut microbiome after mannoside treatment. They found that mannoside treatment had minimal effect on intestinal bacteria other than the ones that cause most UTIs. This is in stark contrast to the massive changes in the abundance of many microbial species seen after treatment with antibiotics. Furthermore, since mannoside is not an antibiotic, it potentially could be used to treat UTIs caused by antibiotic-resistant strains of bacteria, a growing problem. 

Image result for bdellovibrio bacteriovorus Great idea and one that this blog has been pushing for a long time - the use of beneficial bacteria to get rid of other harmful bacteria. Some researchers refer to the bacteria acting as "living antibiotics" when they overpower harmful bacteria.

Researchers such as Daniel Kadouri, a micro-biologist at Rutgers School of Dental Medicine in Newark, are studying bacteria that aggressively attack harmful  bacteria, and calling them "predator bacteria". They are focusing on one specific bacteria - Bdellovibrio bacteriovorus, a gram-negative bacteria that dines on other gram-negative bacteria. They hope to eventually be able to give this bacteria as a medicine to humans , and then this predator bacteria would overpower and destroy "superbugs" (pathogenic bacteria that are resistant to many antibiotics). A great idea, but unfortunately the researchers think that it'll take about 10 more years of testing and development before it's ready for use in humans. From Science News:

Live antibiotics use bacteria to kill bacteria

The woman in her 70s was in trouble. What started as a broken leg led to an infection in her hip that hung on for two years and several hospital stays. At a Nevada hospital, doctors gave the woman seven different antibiotics, one after the other. The drugs did little to help her. Lab results showed that none of the 14 antibiotics available at the hospital could fight the infection, caused by the bacterium Klebsiella pneumoniae.... The CDC’s final report revealed startling news: The bacteria raging in the woman’s body were resistant to all 26 antibiotics available in the United States. She died from septic shock; the infection shut down her organs.

Kallen estimates that there have been fewer than 10 cases of completely resistant bacterial infections in the United States. Such absolute resistance to all available drugs, though incredibly rare, was a “nightmare scenario,” says Daniel Kadouri, a micro-biologist at Rutgers School of Dental Medicine in Newark, N.J. Antibiotic-resistant bacteria infect more than 2 million people in the United States every year, and at least 23,000 die, according to 2013 data, the most recent available from the CDC.

It’s time to flip the nightmare scenario and send a killer after the killer bacteria, say a handful of scientists with a new approach for fighting infection. The strategy, referred to as a “living antibiotic,” would pit one group of bacteria — given as a drug and dubbed “the predators” — against the bacteria that are wreaking havoc among humans.

The notion of predatory bacteria sounds a bit scary, especially when Kadouri likens the most thoroughly studied of the predators, Bdellovibrio bacteriovorus, to the vicious space creatures in the Alien movies. B. bacteriovorus, called gram-negative because of how they are stained for microscope viewing, dine on other gram-negative bacteria. All gram-negative bacteria have an inner membrane and outer cell wall. The predators don’t go after the other main type of bacteria, gram-positives, which have just one membrane.

“It’s a very efficient killing machine,” Kadouri says. That’s good news because many of the most dangerous pathogens that are resistant to antibiotics are gram-negative (SN: 6/10/17, p. 8), according to a list released by the WHO in February. It’s the predator’s hunger for the bad-guy bacteria, the ones that current drugs have become useless against, that Kadouri and other researchers hope to harness.  Pitting predatory against pathogenic bacteria sounds risky. But, from what researchers can tell, these killer bacteria appear safe. “We know that [B. bacteriovorus] doesn’t target mammalian cells,” Kadouri says.

Predatory bacteria can efficiently eat other gram-negative bacteria, munch through biofilms and even save zebrafish from the jaws of an infectious death. But are they safe? Kadouri and the other researchers have done many studies, though none in humans yet, to try to answer that question.... Other studies looking for potential toxic effects of B. bacteriovorus have so far found none. Both Mitchell and Kadouri tested B. bacteriovoruson human cells and found that the predatory bacteria didn’t harm the cells or prompt an immune response. The researchers separately reported their findings in late 2016 in Scientific Reports and PLOS ONE.

Image result for bdellovibrio bacteriovorus Bdellovibrio bacteriovorus  Credit: BBC

Bdellovibrio bacteriaBACTERIAL COMBATANTS Bdellovibrio bacteria (yellow) attack larger bacteria (blue), using the prey’s remains to replicate. Bdellovibrio microbes are a kind of living antibiotic (predator bacteria). Credit: Science News

Image result for pills wikipedia Nowadays there is tremendous concern about the spread of antibiotic resistant bacteria  or "superbugs" throughout the world. Articles frequently mention India being at the epicenter of this crisis - that is, the source of many antibiotic resistant strains (both in and out of hospitals), which then travel throughout the world due to global travel. The massive overuse and misuse of antibiotics (whether in humans, animals, and even crops) is usually given as the major reason for the development of antibiotic resistant strains of bacteria (here, here, and here).

Thus the following article about unchecked pollution from pharmaceutical companies in India fueling the creation of deadly superbugs was shocking to read - and it may explain why the problem is so severe there. Note that the Indian companies supply just about all the world's major drug companies with antibiotics and anti-fungals. It appears that the companies are ignoring local laws (which have been called "toothless") which would cut down on the pollution. What is stressed in the article is that one of the world’s biggest drug production hubs (the Indian city of Hyderabad) is producing dangerous levels of pharmaceutical pollution, and the international agencies that ensure drug safety are basically ignoring this problem (and doing little to address it).

Thousands of tons of pharmaceutical waste is produced each day by the many pharmaceutical companies in Hyderabad, India, which is then contaminating the water sources in the area. With the result that water samples (from rivers, lakes, groundwater, drinking water, surface water, treated sewage water) in  that area contain bacteria and fungi resistant to multiple drugs (superbugs), and these superbugs then get spread to humans throughout India and eventually globally.   This article is definitely worth reading in its entirety. Excerpts from The Bureau of Investigative Journalism:

Big Pharma's Pollution Is Creating Deadly Superbugs While The World Looks The Other Way

Industrial pollution from Indian pharmaceutical companies making medicines for nearly all the world’s major drug companies is fueling the creation of deadly superbugs, suggests new research. Global health authorities have no regulations in place to stop this happening. A major study published today in the prestigious scientific journal Infection found “excessively high” levels of antibiotic and antifungal drug residue in water sources in and around a major drug production hub in the Indian city of Hyderabad, as well as high levels of bacteria and fungi resistant to those drugs. Scientists told the Bureau the quantities found meant they believe the drug residues must have originated from pharmaceutical factories.

The presence of drug residues in the natural environment allows the microbes living there to build up resistance to the ingredients in the medicines that are supposed to kill them, turning them into what we call superbugs. The resistant microbes travel easily and have multiplied in huge numbers all over the world, creating a grave public health emergency that is already thought to kill hundreds of thousands of people a year.

When antimicrobial drugs stop working common infections can become fatal, and scientists and public health leaders say the worsening problem of antibiotic resistance (also known as AMR) could reverse half a century of medical progress if the world does not act fast. Yet while policies are being put into place to counter the overuse and misuse of drugs which has propelled the crisis, international regulators are allowing dirty drug production methods to continue unchecked. Global authorities like the Food and Drug Administration and the European Medicines Agency strictly regulate drug supply chains in terms of drug safety - but environmental standards do not feature in their rulebook. Drug producers must adhere to Good Manufacturing Practices (GMP) guidelines - but those guidelines do not cover pollution.

The international bodies say the governments of the countries where the drugs are made are the ones responsible for stopping pollution - but domestic legislation is having little impact on the ground, say the study's authors. The lack of international regulation must be addressed, they argue, highlighting the grave public health threat faced by antibiotic resistance as well as the rampant global spread of superbugs from India, which has become an epicentre of the crisis.

A group of scientists based at the University of Leipzig worked with German journalists to take an in-depth look at pharmaceutical pollution in Hyderabad, where 50% of India’s drug exports are produced. A fifth of the world’s generic drugs are produced in India, with factories based in Hyderabad supplying Big Pharma and public health authorities like World Health Organisation with millions of tons of antibiotics and antifungals each year.

The researchers tested 28 water samples in and around the Patancheru-Bollaram Industrial zone on the outskirts of the city, where more than than 30 drug manufacturing companies supplying nearly all the world’s major drug companies are based. Thousands of tons of pharmaceutical waste are produced by the factories each day, the paper says. Almost all the samples contained bacteria and fungi resistant to multiple drugs (known as MDR pathogens, the technical name for superbugs). Researchers then tested 16 of the samples for drug residues and found 13 of them were contaminated with antibiotics and antifungals. Previous studies have shown how exposure to antibiotics and antifungals in the environment causes bacteria and fungi to develop immunity to those drugs.

Environmental pollution and poor management of wastewater in Hyderabad is causing “unprecedented antimicrobial drug contamination” of surrounding water sources, conclude the researchers - contamination which appears to be driving the creation and spread of dangerous superbugs which have spread across the world. Combined with the mass misuse of antibiotics and poor sanitation, superbugs are already having severe consequences in India - an estimated 56,000 newborn babies die from resistant infections there each year.

The companies in question strongly deny that their factories pollute the environment, and the sheer number of factories operating in Hyderabad means it is impossible to identify exactly which companies are responsible for the contamination found in the samples tested. What is clear is one of the world’s biggest drug production hubs is producing dangerous levels of pharmaceutical pollution, and the international bodies tasked with ensuring drug safety are doing little to address it.

Around 170 companies making bulk drugs like antibiotics operate in and around Hyderabad, the majority clustered in sprawling industrial estates along the banks of the Musi river. Companies in Europe and the US, as well as health authorities like WHO and the UK’s NHS are reliant on drugs being produced in these factories.

The area has long been criticised for its pollution, which has continued unabated despite decades of campaigning by Indian NGOs, say the report authors. In 2009 the Patancheru-Bollaram zone was classified as “critically polluted” in India’s national pollution index and construction in the area was banned. But the government relaxed the rules in 2014 and building was allowed to begin again. Last year India’s Supreme Court ordered the country’s pharmaceutical companies to operate a zero liquid waste policy, but “massive violations” have reportedly occurred, says the Infection report....India has become the epicentre of the global drug resistance crisis, with 56,000 newborn Indian babies estimated to die each year from drug-resistant blood infections, and 70 to 90% of people who travel to India returning home with multi-drug-resistant bacteria in their gut, according to the study.

Researchers took water samples from rivers, lakes, groundwater, drinking water and surface water from rural and urban areas in and around the industrial estate, as well as pools near factories and water sources contaminated by sewage treatment plants. Four were taken from taps, one from a borehole, and the remaining 23 were classed as environmental samples. The samples were tested for bacteria resistant to multiple drugs (known as MDR pathogens, the technical name for superbugs). The researchers then tested 16 of the samples for the antibiotics and antifungals used to treat infections. All samples apart from one taken from tap water at a four star hotel were found to contain drug-resistant bacteria. All 23 environmental samples contained carbapenemase-producing bacteria - a group of bugs dubbed the “nightmare bacteria” because they are virtually untreatable and kill 40-50% of people whose blood gets infected with them.

Of the 16 samples then tested for drug residue, 13 were found to be contaminated with antibiotics and antifungals, some in disturbingly high levels. The researchers compared the levels of residue to limits recommended by leading microbiologists; once levels exceed those limits it is likely that superbugs will develop. The amounts of antimicrobials found in the new tests were “eye-wateringly high”, said Dr Mark Holmes, a microbiologist at the University of Cambridge. “The quantities involved mean the amount in the water is almost the same as a therapeutic dose,” he said, calling on the Indian authorities to investigate immediately by testing each factory’s effluent. 

There are reams of regulations and stipulations that manufacturers have to adhere to in order to export their products to the US and Europe – known as the Good Manufacturing Practices (GMP) framework. These focus on making sure drugs are safe, pure, and effective. Stringent inspections by the FDA, WHO and European authorities check that these rules are being followed. However these regulations do not address environmental concerns. Inspectors have no mandate to sanction a factory for polluting, failing to treat its waste or other environmental problems – this falls within the remit of local governments.

Image result for pills wikipedia Sometimes there is a need to take antibiotics during pregnancy. A recent study of 182,369 pregnant women found that the use of certain antibiotics during early pregnancy was linked with a higher rate of miscarriage before 20 weeks. These antibiotics included quinolones (Avelox, Cipro, Levaquin, Tequin), tetracyclines, sulfonamides (Septra, Bactrim), metronidazole (Flagyl), and macrolides (such as azithromycin, clarithromycin, but not erythromycin).

Certain antibiotics were not associated with spontaneous abortions. These antibiotics were penicillins, cephalosporinsnitrofurantoin, and erythromycin. The researchers pointed out that nitrofurantoin is a good antibiotic option for urinary tract infections - which is one of the most common infections in pregnancy. From Medscape:

Antibiotics During Pregnancy May Increase Miscarriage Risk

Use of certain antibiotics early in pregnancy is associated with an increased risk for spontaneous abortion, the authors of a new study report. Macrolides (except erythromycin), quinolones, tetracyclines, sulfonamides, and metronidazole all were associated with a greater risk, compared with penicillins, cephalosporins, or no antibiotic exposure at all, Flory T. Muanda, MD, and colleagues write in an article published in the May 1 issue of CMAJ. 

To assess the potential effect of antibiotics on miscarriage risk, Dr Muanda, from the Faculty of Pharmacy, Université de Montréal, Quebec, Canada, and colleagues analyzed data from the Quebec Pregnancy Cohort on pregnancies that occurred between January 1998 and December 2009....Women who experienced a clinically detected spontaneous abortion before gestational week 20 were considered cases, with the calendar date of the spontaneous abortion designated the index date.  Antibiotic exposure was defined as "having filled at least 1 prescription for any type of antibiotic either between the first day of gestation and the index date, or before pregnancy but with a duration that overlapped the first day of gestation," the authors explain. 

Antibiotic exposure occurred in 12,446 (13%) of those pregnancies, including 1428 that ended in spontaneous abortion (16.4% of all pregnancies ending in spontaneous abortion). Among the control patients, 11,018 (12.6% of all controls) were exposed to antibiotics.

In some instances, these findings support data from other studies, the authors point out. The class effect observed of tetracyclines and quinolones "supports current guidelines used in obstetrics that do not recommend use of these drugs in early pregnancy." Their finding that metronidazole was associated with a 70% increase in the risk for spontaneous abortion is similar to that of a study among Medicaid patients showing a 67% increased risk.... No increased risk was associated with nitrofurantoin, erythromycin, penicillins, or cephalosporins.

 Guess what? Instead of babying our backs, we may have to be sure to get plenty of running, jogging, or brisk walking to make our backs stronger - specifically, to strengthen the discs in our spines. Once again, a study finds that exercise (here the upright exercise of running, jogging, or fast walking) has benefits. The authors of the study state that the research results go against conventional medical wisdom - that instead of weakening the spine (conventional view), those people who run or jog  many miles each week may actually be strengthening the discs of the spine. And maybe... the researchers suggest (though it needs to be verified first)... in the future, we may get medical prescriptions to jog or fast walk a certain number of miles each week to strengthen the discs in our spines.

The study found that the ideal speed for the spine health was a slow run or a fast walk (4 miles per hour). Specifically fast walking and slow running at about 2 meters per second (m/s) appeared the most beneficial. However, high impact exercises, or aerobic exercises, slower walking, or no exercise did not have these benefits.

Until now, discs had been considered a "slow tissue," thought to take much longer to respond to exercise than muscle. And that with age and use the discs degenerate, and nothing could really be done to improve them. But the study's findings suggest that exercise can benefit and strengthen the intervertebral disc (IVD) in the spine. As researcher Dr. Belavy said: "It's also important to reduce the amount of time spent in static postures, such as sitting or even standing still. Even going for a walk during a break at work, or choosing to take the stairs rather than the elevator is good for the discs, as well as for overall back health."

From NY Times: Why Running May Be Good for Your Back

People who regularly run or walk briskly appear to have healthier discs in their spines than people who do not exercise, according to one of the first studies to closely examine links between movement and disc health. The findings refute a widely held belief that activities like running might overtax the spine and indicate that, instead, they make it sturdierThe human spine is a complicated mechanism, composed of vertebral bones cushioned between intervertebral discs. These discs, shaped like tiny whoopee cushions, contain a viscous fluid that compresses and absorbs pressure during movement, keeping the back in good working form. With age, disease or injury, spinal discs can degenerate and bulge, resulting in back pain, which can be debilitating.

There were tantalizing hints in animal studies, however, that this idea could be out of date. ....So for the new study, which was published in April in Scientific Reports, researchers at Deakin University in Australia and other institutions decided to examine the backs of people who run and others who do not. Eventually they recruited 79 adult men and women, two-thirds of whom said that they were runners. Some of these told the researchers that they covered more than 30 miles (about 50 kilometers) a week in training. The researchers designated these as the “long-distance” group. The others said that they ran between 12 and 25 miles a week. All had been training for at least five years. The final group rarely exercised at all.

To ensure that people’s reported activity levels were accurate, the researchers asked their volunteers to wear accelerometers for a week. Then they scanned everyone’s spines, using a sophisticated type of M.R.I. that precisely measures the size and liquidity of each disc. And they found differences. In general, the runners’ discs were larger and contained more fluid than the discs of the men and women who did not exerciseSince both greater size and increased levels of internal fluid indicate better disc health, the runners harbored fundamentally healthier spines than the people who were sedentary, says Daniel Belavy, a professor of physical activity and nutrition at Deakin University who led the study. Interestingly, mileage barely mattered

 Uh-oh... looks like any benefits of moderate alcohol consumption may not extend to the brain, at least in men. A  recent study found that moderate alcohol consumption over the course of a 30 years was associated with increased odds of hippocampal atrophy (brain damage in the hippocampus of the brain) - when compared to abstainers. Hippocampal atrophy causes memory problems and affects spatial navigation, and is also an early characteristic of Alzheimer's disease and other dementias. This result occurred in a dose dependent fashion - meaning the more that was drunk regularly, the more the atrophy in that area of the brain.

The heavier drinkers (when compared to abstainers) also had a faster decline in verbal skills ('verbal fluency") and changes in the white matter of the brain (specifically "corpus callosum microstructure"). There was no protective effect of light drinking when compared to abstainers (the 2 groups had similar results). **However, the researchers also reported: "The hippocampal atrophy associations we found in the total sample were replicated in men alone but not in women." Note: there were few women in the study (only 103 out of 527 studied) and even fewer were "heavy" drinkers (14 women), but one wonders - why not? Why didn't women drinkers have these brain changes?**

So how much did the moderate drinkers drink? They really didn't drink that much, but there were different groups: the abstainers (less than 1 unit of alcohol a week), “light” drinking was between 1 and <7 units, “moderate” drinking as 7 to <14 units a week for women and 7 to <21 units for men, and the heavier drinkers - those that drank more units per week, for an average of 30 units a week. What is a "unit" of alcohol? A medium glass of wine has about two units of alcohol, and so does a pint of  ordinary strength beer or lager. Thus the male moderate drinkers drank about a medium glass of wine or a beer each night, and maybe a little extra on the weekends. (In other words, not that much.) And the heaviest drinkers had a little more than two medium glasses of wine or two beers every night of the week, plus a little more on weekends.

What do the results mean?  The researchers said that  they don't have any evidence linking the brain changes they saw on the MRI brain scans to any negative general cognitive effects, but they did lose more "language fluency" with time. (They gave the people various tests.) The abstainer group (37 people) was very small - perhaps other lifestyle factors (e.g., nutrition) may be playing a part in the results. Also, if people  under-reported actual alcohol consumption - then it would throw off the results. While studies show that drinking can increase cancer risk, other studies have found that moderate drinkers seem to live longer than abstainers. From Medical Xpress:

Even moderate drinking linked to a decline in brain health, finds study

Alcohol consumption, even at moderate levels, is associated with increased risk of adverse brain outcomes and steeper decline in cognitive (mental) skills, finds a study published by The BMJ today. Heavy drinking is known to be associated with poor brain health, but few studies have examined the effects of moderate drinking on the brain—and results are inconsistent. So a team of researchers based at the University of Oxford and University College London set out to investigate whether moderate alcohol consumption has a beneficial or harmful association—or no association at all—with brain structure and function.

They used data on weekly alcohol intake and cognitive performance measured repeatedly over 30 years (1985-2015) for 550 healthy men and women who were taking part in the Whitehall II study. This study is evaluating the impact of social and economic factors on the long term health of around 10,000 British adults. Participants had an average age of 43 at the start of the study and none were alcohol dependent. Brain function tests were carried out at regular intervals and at the end of the study (2012-15), participants underwent an MRI brain scan.... After adjusting for these confounders, the researchers found that higher alcohol consumption over the 30 year study period was associated with increased risk of hippocampal atrophy - a form of brain damage that affects memory and spatial navigation.

While those consuming over 30 units a week were at the highest risk compared with abstainers, even those drinking moderately (14-21 units per week) were three times more likely to have hippocampal atrophy compared with abstainers. There was no protective effect of light drinking (up to 7 units per week) over abstinence.

Higher consumption was also associated with poorer white matter integrity (critical for efficient cognitive functioning) and faster decline in language fluency (how many words beginning with a specific letter can be generated in one minute). But no association was found with semantic fluency (how many words in a specific category can be named in one minute) or word recall. The authors point out that this is an observational study, so no firm conclusions can be drawn about cause and effect, and say some limitations could have introduced bias. [Original study.]

T-Cells and cancer Everyone has heard about the miraculous stories of recovery from cancer using immunotherapy. Immunotherapy involves giving the sick person substances which stimulate the person's own immune system to battle the cancer. And when it works, it's wonderful. But...there's another side - a dark side of the harms from these treatments - that is rarely discussed, and why we should be very careful going forward.

Here are two articles that do point out the problems - such as in some people the immunotherapy actually accelerates the cancer being treated (called "hyperprogression of tumors"). Studies suggest that these people share certain genetic characteristics or they are over the age of 65. In general, many patients undergoing immunotherapy have side-effects, some even developing life-threatening ones, from the treatments. Also, most patients do not respond to the immunotherapy treatments, for reasons that remain largely unknown. Obviously more studies are needed. Remember, this field is in its infancy.

Excerpts from Bob Tedeschi's article, from STAT: Cancer researchers worry immunotherapy may hasten growth of tumors in some patients

For doctors at the University of California, San Diego, it was seemingly a no-lose proposition: A 73-year-old patient’s bladder cancer was slowly progressing but he was generally stable and strong. He seemed like the ideal candidate for an immunotherapy drug, atezolizumab, or Tecentriq, that had just been approved to treat bladder cancer patients. Doctors started the patient on the drug in June. It was a spectacular failure: Within six weeks, he was removed from the drug, and he died two months later.

In a troubling phenomenon that researchers have observed in a number of cases recently, thetreatment appeared not only to fail to thwart the man’s cancer, but to unleash its full fury. It seemed to make the tumor grow faster. The patient’s case was one of a handful described last week in the journal Clinical Cancer Research. Of the 155 cases studied, eight patients who had been fairly stable before immunotherapy treatment declined rapidly, failing the therapy within two months. Six saw their tumors enter a hyperactive phase, where the tumors grew by between 53 percent and 258 percent.

“There’s some phenomenon here that seems to be true, and I think we cannot just give this therapy randomly to the patient,” the author of the study, Dr. Shumei Kato, an oncologist at UC San Diego, said in an interview with STAT. “We need to select who’s going to be on it.” .... But similar findings were published last year by cancer researchers at the Gustave Roussy Institute in France. These results were considered controversial by some, since they hadn’t been widely confirmed by other oncologists.

In the latest Clinical Cancer Research findings, those who experienced the hyperprogression of tumors, as the phenomenon is known, shared specific genetic characteristics. In all six patients with so-called amplifications in the MDM2 gene family, and two of 10 patients with alterations in the EGFR gene, the anti-PD-1 or anti-PD-L1 immunotherapies quickly failed, and the patients’ cancers progressed rapidly. ....Doctors who prescribe immunotherapies may be able to identify at-risk patients by submitting tumors for genetic testing, Kato and his coauthors suggested.

The findings published last year by the Gustave Roussy team also appeared in Clinical Cancer Research. In that study, of 131 patients, 12 patients, or 9 percent, showed hyperprogressive growth after taking anti-PD-1 or anti-PD-L1 immunotherapies. The lead author of that study, Stephane Champiat, acknowledged that the research so far raises more questions than it answers. ... Champiat suggested factors that could be associated with the effect. In his study’s patients, for instance, those who were older than 65 showed hyperprogressive growth at twice the rate of younger patients.

Oncologists studying this phenomenon said it could complicate treatment strategies, becausesome patients who receive immunotherapies can exhibit what’s known as “pseudo-progression,” in which tumor scans reveal apparent growth. In reality, however, the scans are instead showing areas where the cancer is being attacked by armies of immune cells. Roughly 10 percent of melanoma patients on immunotherapies, for instance, experience this phenomenon.

Jimmy Carter is perhaps the best-known immunotherapy success story. But most patients do not respond to the immunotherapy treatments, for reasons that remain largely unknown. In a study by Prasad and Dr. Nathan Gay, also of Oregon Health and Science University, nearly 70 percent of Americans die from forms of cancer for which there is no immunotherapy option, and for the rest who do qualify forimmunotherapy, only 26 percent actually see their tumors shrink.

And while immunotherapies typically include less intrusive side effects than chemotherapy, those side effects, when they happen, can be life-threatening. Researchers have reported cases in which immunotherapies attacked vital organs, including the colon, liver, lungs, kidney, and pancreas, with some patients experiencing acute, rapid-onset diabetes after receiving the treatments. But in those cases, the treatments were at least attacking the cancer. Such reports didn’t raise the specter of these treatments possibly working on the cancer’s behalf to shift it into overdrive.

 T-Cells and cancer A group of killer T cells (green and red) surrounds a cancer cell (blue, center). Credit: NIH.

From Health News Review: Cancer immunotherapy: more reason for concern?

Immunotherapy for cancer — which basically involves manipulating our immune system to attack cancer cells — is ever so slowly creeping toward the scrutiny phase. This slow crawl is something we reported on four months ago. With few exceptions, like this deep dive by the New York Times (the Cell Wars series ), we found many journalists completely overlooked the harms (some life-threatening) of this oft-vaunted treatment.

Image result for teeth wikipedia Interesting new study! Researchers analyzed baby teeth among twins - sets of twins where both are healthy, and sets of twins where one has autism spectrum disorder (ASD), but not the other twin (the control). They found that in the children that developed ASD, the teeth revealed that during the second and third trimester and 30 weeks after birth they had higher levels of lead (which is a neurotoxin) and lower levels of the essential nutrients manganese and zinc. There were also differences between ASD and controls in levels of other elements including tin, strontium and chromium - but each of these elements differed the most between the ASD and control twin at different points of time.

How many people know that during fetal and childhood development, a new tooth layer is formed every week or so in the developing baby, which leaves an "imprint" in the tooth layer of the chemicals exposed to? So there's a chronological record of exposure - similar to using growth rings on a tree to find out the tree's growth history. A laser removed a tiny bit of the tooth dentine layer and then it was analyzed for various metals (see the illustration below).

Now studies are needed to determine whether the differences in the amount of lead and metals are due to differences in how much a fetus or baby is exposed to them, or whether it occurs because of a genetic difference in how a baby takes in and handles these metals and nutrients. And, of course, other studies suggest that other environmental exposures (e.g., pesticides) may also play a part in ASD development. From Science Daily:

Exposure to specific toxins and nutrients during late pregnancy and early life correlate with autism risk

Using evidence found in baby teeth, researchers from The Senator Frank R. Lautenberg Environmental Health Sciences Laboratory and The Seaver Autism Center for Research and Treatment at Mount Sinai found that differences in the uptake of multiple toxic and essential elements over the second and third trimesters and early postnatal periods are associated with the risk of developing autism spectrum disorders (ASD), according to a study published June 1 in the journal Nature Communications.

The critical developmental windows for the observed discrepancies varied for each element, suggesting that systemic dysregulation of environmental pollutants and dietary elements may serve an important role in ASD. In addition to identifying specific environmental factors that influence risk, the study also pinpointed developmental time periods when elemental dysregulation poses the biggest risk for autism later in life.

According to the U.S. Centers for Disease Control and Prevention, ASD occurs in 1 of every 68 children in the United States. The exact causes are unknown, but previous research indicates that both environmental and genetic causes are likely involved. While the genetic component has been intensively studied, specific environmental factors and the stages of life when such exposures may have the biggest impact on the risk of developing autism are poorly understood. Previous research indicates that fetal and early childhood exposure to toxic metals and deficiencies of nutritional elements are linked with several adverse developmental outcomes, including intellectual disability and language, attentional, and behavioral problems.

"We found significant divergences in metal uptake between ASD-affected children and their healthy siblings, but only during discrete developmental periods," said Manish Arora, PhD, BDS, MPH, Director of Exposure Biology at the Senator Frank Lautenberg Environmental Health Sciences Laboratory at Mount Sinai and Vice Chair and Associate Professor in the Department of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai. "Specifically, the siblings with ASD had higher uptake of the neurotoxin lead, and reduced uptake of the essential elements manganese and zinc, during late pregnancy and the first few months after birth, as evidenced through analysis of their baby teeth. Furthermore, metal levels at three months after birth were shown to be predictive of the severity of ASD eight to ten years later in life."

To determine the effects that the timing, amount, and subsequent absorption of toxins and nutrients have on ASD, Mount Sinai researchers used validated tooth-matrix biomarkers to analyze baby teeth collected from pairs of identical and non-identical twins, of which at least one had a diagnosis of ASD. They also analyzed teeth from pairs of normally developing twins that served as the study control group. During fetal and childhood development, a new tooth layer is formed every week or so, leaving an "imprint" of the micro chemical composition from each unique layer, which provides a chronological record of exposure. The team at the Lautenberg Laboratory used lasers to reconstruct these past exposures along incremental markings, similar to using growth rings on a tree to determine the tree's growth history. [Original study.]

  Cross-section of tooth showing laser removal of the dentine layer (in tan), for analysis of metal content. Credit: J. Gregory, Copyright Mount Sinai Health System, 2017