Baby Bacteria

Sept. 26, 2014

By Medical Discovery News

Fetus in utero

While we know for sure that the bacteria living in and on us are key to our own well-being, more evidence suggests that we acquire our microbiomes before we’re even born. While a baby does acquire bacterial flora from its mother as it moves through the birth canal, scientists now think that our symbiotic, life-long relationships with bacteria begin in utero long before birth. They found bacteria living in the placenta, an organ previously thought to be sterile. They also discovered a baby’s bacteria to be similar to the bacterial flora of the mother’s mouth, making oral hygiene during pregnancy extra important.

An experiment in 2008 by Spanish scientists indicated that bacteria are acquired in some way before birth. They inoculated pregnant mice with labeled bacteria, which were then found in the meconium, the first bowel movement after birth. This was true even when the babies had been delivered by C-section. So scientists knew then that bacteria are acquired before birth and even without the birth canal, changing what we thought we knew about the womb.

Since then, scientists at Baylor College of Medicine have been studying the inside of the womb and birth canal in both humans and animals. They discovered that the vaginal microbiome changed during pregnancy, but it did not resemble that of newborns. So where did they get their bacteria from?

Baylor scientists then examined placentas from 320 women immediately after birth. Using DNA sequencing, they identified the individual types of bacteria each placenta contained. Comparing them to bacteria growing in and on the mothers, they found that the types of bacteria living in the mothers’ mouths most closely resembled those in their own placentas. Interestingly, the bacteria in the placenta consisted of high proportions of bacteria responsible for synthesizing vitamins and other nutrients, which probably benefits a developing fetus and newborn. So a fetus is first exposed to bacteria from the placenta, then at birth additional bacteria are introduced, and then again when babies are exposed bacteria on their parent’s skin, in breast milk, and in their environment.

Other studies have shown the influence of the microbiome on a mother and her baby. In one experiment, monkeys who ate a high-fat diet while pregnant and lactating produced babies with different proportions of bacteria in their guts than those of monkeys fed a normal diet. The short- and long-term consequences of abnormal maternal and infant microbiomes are not yet known, but it’s speculated that these changes could influence the metabolism of the infant and the development of metabolic disorders.

Science is increasingly aware of the role and importance the microbiome has in various parts of the body and the part it plays in human health and disease.

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A Risk-Free Test for Down’s

April 18, 2014

By Medical Discovery News

Keep Calm, It's Only An Extra Chromosome

When it comes to chromosomes, extra copies are not a good thing. Every cell in the human body carries the same genetic information in two copies of 23 chromosomes. Having an extra copy of a chromosome is called trisomy, and an extra copy of chromosome number 21 is what causes Down syndrome.

Physical signs of Down syndrome include upward slanting of the eyes, flattened facial features, small and unusually shaped ears, small heads, and broad hands with short fingers. Down syndrome can also cause more serious conditions such as varying degrees of mental retardation, poor muscle tone, an increased risk of early onset dementia, and heart, stomach, and eye problems. No two cases of Down syndrome are the same, and with therapy and support people with Down syndrome can live long, productive lives.

The risk of Down syndrome increases with the mother’s age during pregnancy. The risk of having a baby with Down syndrome increases from one in 1,300 to one in 25 at ages 25 to 49.

Women who are pregnant with a child who might have Down syndrome typically undergo an ultrasound test and blood tests for markers such as pregnancy-associated plasma protein-A and a hormone known as human chorionic gonadotropin. Abnormal levels of these markers may indicate a problem with the baby. These tests are generally done during weeks 11-13 of pregnancy. The American College of Obstetrics and Gynecology now recommends that all women undergo prenatal testing for chromosomal abnormalities.

Until recently, Down syndrome could only be confirmed by invasive tests that collect cells from the amniotic fluid surrounding the fetus, the placenta, or the fetus itself. These tests can be risky, with a one percent chance of miscarriage. However, a new, noninvasive screening test called circulating cell-free fetal DNA analysis may reduce the need for invasive prenatal tests. Circulating cell-free DNA from the fetus makes up three to 13 percent of the DNA fragments circulating in the mother’s bloodstream during pregnancy.

First, DNA is isolated from the mother’s plasma, the liquid component of blood. Then, there are two ways to determine if there are any chromosomal abnormalities. Massive parallel DNA genomic sequencing can be used to quantify millions of DNA fragments in just a few days and can accurately detect trisomies. Another approach is called Digital Analysis of Selected Regions, which analyzes only the chromosomes in question to evaluate them for any abnormalities.    

These tests are 99 percent accurate, can be done as early as the 10th week of pregnancy, and are more reliable. They can also diagnose other trisomies, like the ones that affect chromosome 18 (Edwards syndrome) and chromosome 13 (Patau syndrome). At this stage, invasive testing is still required to confirm the diagnosis of a trisomy. But in the near future this new technology will reduce or eliminate the need for additional invasive tests that put the fetus at risk. This is only the beginning of the development of safer and more accurate genetic tests.

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An Itchy Situation

Nov. 1, 2013

By Medical Discovery News

Anyone ever bitten by a mosquito can attest to its itchy consequences. New research has discovered just how our bodies detect and process itching, leading to a better understanding of our reaction to itching and hopefully better treatments for it.

The clinical term for an itch is pruritus, and at least 16 percent of people experience an itch that just doesn’t go away. The most common dermatological complaint, long-term itching can be caused by chronic renal disease, cirrhosis, some cancers, multiple sclerosis, diabetes, shingles, allergic reactions, drug reactions, and pregnancy.

Prolonged itching and scratching can increase the intensity of the itch, possibly leading to neurodermatitis, a condition in which a frequently scratched area of skin becomes thick and leathery. The patches can be raw, red, or darker than the rest of the skin. Persistent scratching can also lead to a bacterial skin infection, permanent scars, or changes in skin color. The super strong pain reliever morphine can cause such a severe whole-body itch that some patients choose to forgo it and live with the pain.

Sensory neurons called TRPV1 cells detect itchy substances on skin. TRPV1 cells have long nerve fibers that extend into skin, muscle, and other tissues to help monitor conditions. It has not been clear how these neurons sort through different sensations like pain and temperature and route the signal along the proper pathway to the appropriate area of the brain for perception.

New research has revealed a small group of those neurons produce a substance called natriuretic polypeptide b (Nppb), a hormone known to be involved in regulating the heart. Surprisingly, when Nppb is produced by TRPV1 cells it acts as a neurotransmitter, a chemical messenger secreted by neurons to carry, boost, and control signals between neurons and other cells.

When scientists genetically modified mice to eliminate Nppb, they did not itch. Nppb binds to a specific receptor called Npra on particular nerves in the spinal column. When those cells were eliminated in mice, again, they did not itch. Interestingly, removing these cells did not impact other sensory sensations such as temperature, pain, and touch.

A similar transmission presumably exists in humans, but that has not yet been determined. Knowing which molecules and cells are involved will help scientists study how humans perceive itch signals. Before these findings, scientists thought a molecule called gastrin releasing peptide was responsible for transmitting the itch signal from nerves, and that itching was a low level form of pain.

Understanding the itch signaling pathway offers the opportunity to create drugs that specifically block that signal and alleviate unpleasant and chronic itching with fewer side effects.

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Thalidomide: A Nightmare Revisited

Spet. 20, 2013

By Medical Discovery News

While thalidomide is now being tapped for its cancer-fighting properties, it has a more notorious history. Starting in 1957, doctors recommended thalidomide as a mild over-the-counter sleeping pill supposedly safe enough for even pregnant women. That it also reduced morning sickness made it even more popular. The company that made thalidomide aggressively marketed the drug in 46 countries even after the wife of an employee who took the drug before its release gave birth to a child with no ears. Within two years, an estimated 1 million people in West Germany were taking the drug daily. However, thousands of babies born with severely malformed limbs revealed that this drug was not safe, but that connection was not made until 1961.

German pharmaceutical company Chemie Grünenthal GmbH originally developed thalidomide to treat convulsions, but users reported feeling sleepy. During testing, the company discovered that it was almost impossible to take enough thalidomide to be fatal. The company did not test the drug’s effects during pregnancy. Though approved for use in Germany and elsewhere in Europe, a U.S. Food and Drug Administration medical officer named Frances Oldham Kelsey denied its license because there was insufficient clinical evidence about its side effects. This decision limited the impact of the drug in America. In 1962, President John F. Kennedy awarded Kelsey the President’s Medal for Distinguished Federal Civilian Service. 

Warnings of the drug’s possible toxicity began to emerge in 1959. Adults taking the drug reported peripheral neuritis or inflammation of the nerves and the resulting nervous system damage. Even after an Australian and a German physician independently linked thalidomide to birth defects in 1961, it was four months before the company withdrew the drug from the market, and it was banned even later in some countries. It is thought that at least 100,000 pregnant women were affected by the drug leading to more than 90,000 miscarriages. Even a single dose of thalidomide during early pregnancy may cause severe birth defects. About 40 percent of babies exposed to the drug die before or soon after delivery. Over 10,000 children were born with thalidomide-related birth defects such as missing or shortened limbs. Still others were born deaf and blind, some had curved spines and some had damaged hearts and brains and many other abnormalities.

The company refused to pay compensation for many years until 1970 when they established a $28 million fund in return for legal immunity. When those funds were depleted, the German government paid compensation to victims. In 2009, Grünenthal provided another $63 million in compensation. The company did not publicly apologize for its actions until August 2012.  However, dissatisfaction with that statement and the level of compensation by the company continues.

Researchers are actively seeking drugs that work similarly to thalidomide but without the side effects. The thalidomide tragedy prompted creation of and reforms in the laws and policies that govern drug testing and approval, reducing the chances of another such incident, but it must not be forgotten lest history repeats itself.

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The Male Pill

July 26, 2013

By Medical Discovery News

“Birth control pills should be made for men. It makes more sense to unload a gun than shoot at a bulletproof vest.” While the first person to post the comment is unknown, it has since been posted on many a Facebook wall, Pinterest board, and Twitter feed. But science has long been working on such a pill, which is now undergoing clinical trials.

While more than 100 million women take the pill for contraception, it remains a topic of controversy in the realms of religion and politics. It works by using synthetic estrogen and progesterone hormones to prevent ovulation, the production of an egg. No egg equals no possibility of pregnancy.

The male pill that is currently being evaluated as a contraceptive also relies on hormones, a combination of progesterone and testosterone (or an equivalent). Progesterone lowers the levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH). Both are essential for stem cells to develop into sperm and mature, a process called spermatogenesis. Just as no pregnancy can occur without an egg, likewise pregnancy cannot occur without mature sperm to fertilize the egg.

So far, one version of the male pill has been tried in limited studies of about 50 men with 100 percent effectiveness. However, it comes with some side effects. Since LH reduces testosterone levels, a man taking the male birth control pill must also take extra testosterone. Low testosterone causes low sex drive, depression, infertility, and hair loss.

However, new research has developed a non-hormonal approach to male birth control that appears to have great promise. Scientists at Baylor College of Medicine and Harvard University have identified a small molecule called JQ1 that sticks to a protein in immature sperm cells called BRDT. Normally, BRDT allows sperm to become fully mature by binding to specific areas in the genome and causing genes to activate. But JQ1 binds to BRDT and prevents it from effectively interacting with the genome, so genes are not turned on and the sperm cells do not develop. So far, these experiments have only been performed in mice, but their sperm count was reduced by 90 percent and the motility of the remaining sperm was reduced by 75 percent.  When male mice are on this treatment, they are essentially sterile. 

Furthermore, there were no observable side effects; in fact, testosterone levels remained the same. And when JQ1 treatment was stopped, sperm development and fertility returned to normal. Currently, JQ1 is injected, so an oral pill form would need to be developed for widespread acceptance. The next step is to begin clinical trials to test safety, efficacy, and long-term effects in humans.

While this treatment requires further research, in the future it may take some of the pressure to swallow “the pill” off women, especially since female birth control comes with its own set of side effects and long-term health issues. A male birth control pill may even shift the responsibility to prevent pregnancy and take an active role in family planning to men, which may then be met with a sigh of relief from the other half of the population.

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