Tag Archives: Jena University Hospital

German scientists battle tough mucus

A December 15, 2017 news item on ScienceDaily highlights cystic fibrosis research being done in Germany,

Around one in 3,300 children in Germany is born with Mucoviscidosis [cystic fibrosis; CF]. A characteristic of this illness is that one channel albumen on the cell surface is disturbed by mutations. Thus, the amount of water of different secretions in the body is reduced which creates a tough mucus. As a consequence, inner organs malfunction. Moreover, the mucus blocks the airways. Thus, the self regulatory function of the lung is disturbed, the mucus is colonized by bacteria and chronic infections follow. The lung is so significantly damaged that patients often die or need to have a lung transplant. The average life expectancy of a patient today is around 40 years. This is due to medical progress. Permanent treatment with inhaled antibiotics play a considerable part in this. The treatment can’t avoid the colonization by bacteria completely but it can keep it in check for a longer period of time. However, the bacteria defend themselves with a development of resistance and with the growth of so-called biofilms underneath the layer of mucus, which mostly block off the bacteria in the lower rows like a protective shield.

A complex way to the Pathogens

Scientists of the Friedrich Schiller University Jena, Germany succeeded in developing a much more efficient method to treat the airway infections which are often lethal. Crucial are nanoparticles that transport the antibiotics more efficiently to their destination….

A December 15, 2017 Friedrich Schiller University Jena press release (also on EurekAlert), which originated the news item, expands on the theme,

“Typically, the drugs are applied by inhalation in the body. Then they make a complicated way through the body to the pathogens and many of them don’t make it to their destination,” states Prof. Dr Dagmar Fischer of the chair for Pharmaceutical Technology at the University of Jena, who supervised the project together with her colleague Prof. Dr Mathias Pletz, a pulmonologist and infectious diseases physician, from the Center for Infectious Diseases and Infection Control at the Jena University Hospital. The project was supported by the Deutsche Forschungsgemeinschaft. First of all, the active particles need to have a certain size to be able to reach the deeper airways and not to bounce off somewhere else before. Ultimately, they have to penetrate the thick layer of mucus on the airways as well as the lower layers of the bacteria biofilm.

Nanoparticles travel more efficiently

To overcome the strong defense, the researchers encapsulated the active agents, like the antibiotic Tobramycin, in a polyester polymer. Thus, they created a nanoparticle which they then tested in the laboratory where they beforehand had simulated the present lung situation, in a static as well as in a dynamic state, i. e. with simulated flow movements. Therefore Pletz’s research group had developed new test systems, which are able to mimick the situation of the chronically infected CF-lung. The scientists discovered that their nanoparticle travels more easily through the sponge-like net of the mucus layer and is finally able to kill off the pathogens without any problems. Moreover, an additionally applied coating of polyethylenglycol makes it nearly invisible for the immune system. “All materials of a nanocarrier are biocompatible, biodegradable, nontoxic and therefore not dangerous for humans,” the researcher informs.

However, the Jena scientists don’t know yet exactly why their nanoparticle fights the bacteria so much more efficiently. But they want to finally get clarification in the year ahead. “We have two assumptions: Either the much more efficient transport method advances significantly larger amounts of active ingredients to the center of infection, or the nanoparticle circumvents a defense mechanism, which the bacterium has developed against the antibiotic,” the Jena Pharmacist Fischer explains. “This would mean, that we succeeded in giving back its impact to an antibiotic, which had already lost it through a development of resistance of the bacteria.”

“More specifically, we assume that bacteria from the lower layers of the biofilm transform into dormant persisters and hardly absorb any substances from outside. In this stadium, they are tolerant to most antibiotics, which only kill off self-dividing bacteria. The nanoparticles transport the antibiotics more or less against their will to the inner part of the cell, where they can unfold their impact,” Mathias Pletz adds.

Additionally, the Jena research team had to prepare the nanoparticles for the inhalation. Because at 200 nanometers the particle is too small to get into the deeper airways. “The breathing system filters out particles that are too big as well as those which are too small,” Dagmar Fischer explains. “So, we are left with a preferred window of between one and five micrometers.” The Jena researchers also have promising ideas for resolving this problem.

Coating of Nanoparticles enhances the impact of Antibiotics against Biofilms

The scientists from Jena are at this point already convinced to have found a very promising method to fight respiratory infections of patients with mucoviscidosis. Thus they may be able to contribute to a higher life expectancy of those affected. “We were able to show that the nanoparticle coating improves the impact of the antibiotics against biofilm by a factor of 1,000,” the pulmonologist and infectious diseases physician is happy to say.

It’s exciting news and I wish the researchers great success. Perhaps, one day, they will publish a paper about their work.

Breakthrough (science in six episodes on the National Geographic Channel)

US producing partners (television and movies), Ron Howard and Brian Grazer have decided to make science sexy according to the headline for an Oct. 30, 2015 article by Reid Nakamura for The Wrap. Reading the article which has no mention of sexiness reveals the producing partners had something else in mind,

In the era of “too much TV,” Grazer argues that people taking risks is what will help the industry survive. “People just have to make quality programs,” he said in an interview with TheWrap. “Taking chances usually will produce some trend creation that is really valuable to our business.”

Howard added that because “Breakthrough” has the potential to stand out.

“In reality, I don’t really agree that there’s too much, but there’s never enough good stuff that really does break through,” he said. “And it’s getting harder and harder to get fresh ideas, but I think that in all honesty, something like Brian and I coming in and doing this kind of science series offers that potential. Because it’s a different mindset creating this kind of content.”

To date, four episodes have been broadcast (from the Breakthrough episode page on the Internet Movie DataBase [IMDB]),

Fighting Pandemics

Viral outbreaks can become deadly pandemics in a matter of days. To prevent catastrophe, courageous scientists are fighting back with new treatments and vaccines.

More Than Human

Advances in science are fusing biology and technology to make us better, stronger, faster, and smarter; manipulating our genetic code; building exoskeletons that give us super strength; giving hope to people with traumatic spine injuries.

Decoding the Brain

After millennia of speculation about what goes on inside the human brain, we now have the tools to explore its hidden reaches. These tools are leading to research that may help those suffering from afflictions such as epilepsy and Alzheimer’s disease. They are also shedding light on the mystery of consciousness and what makes us who we are.

In recent years, close study of the aging process has opened up new ways that could help us all live healthier for longer. Can we move beyond treating individual diseases, and instead treat the aging process itself? But would a longer life necessarily be a better life? A loose-knit group of researchers believe the real breakthrough is extending our health span – the period of life spent free of disease.

Energy on the Edge

Not yet broadcast

Water Apocalypse

Not yet broadcast

Strangely there is no science advisor listed as part of the crew for these programmes and, even more strangely, the researcher for the series, A. Christine Maxfield, is a travel writer and tv host who seems not to have any science background or previous experience with science programmes.

Once an episode has been broadcast it is possible to view it online afterwards but you do need to be a subscriber. The first three episodes can be found here.

Some of the promotional material seems a bit odd to me. For example, there’s this in the material promoting The Age of Aging episode (broadcast Nov. 29, 2015) directed by Ron Howard and in which he also appears,

… Ron Howard explores the latest scientific studies trying to answer one question. Can aging be cured?

I find the thinking fundamentally disturbing. Aging is not a disease; it’s a process or a series of processes leading to death. If it’s thought of as a disease, then there’s an implication that it can be cured. However, I have no objection to aging as well as possible. On that note, there’s some rather interesting research coming out of Switzerland, from a Dec. 1, 2015 ETZ Zurich press release on EurekAlert,

Researchers at ETH Zurich and the JenAge consortium from Jena have now systematically gone through the genomes of three different organisms in search of the genes associated with the ageing process that are present in all three species – and thus derived from the genes of a common ancestor. Although they are found in different organisms, these so-called orthologous genes are closely related to each other, and they are all found in humans, too.

In order to detect these genes, the researchers examined around 40,000 genes in the nematode C. elegans, zebra fish and mice. By screening them, the scientists wanted to determine which genes are regulated in an identical manner in all three organisms in each comparable ageing stage – young, mature and old; i.e. either are they upregulated or downregulated during ageing.

As a measure of gene activity, the researchers measured the amount of messenger RNA (mRNA) molecules found in the cells of these animals. mRNA is the transcript of a gene and the blueprint of a protein. When there are many copies of an mRNA of a specific gene, it is very active; the gene is upregulated. Fewer mRNA copies, to the contrary, are regarded as a sign of low activity, explains Professor Michael Ristow, coordinating author of the recently published study and Professor of Energy Metabolism at ETH Zurich.

Out of this volume of information, the researchers used statistical models to establish an intersection of genes that were regulated in the same manner in the worms, fish and mice. This showed that the three organisms have only 30 genes in common that significantly influence the ageing process.

Reduce gene activity, live longer

By conducting experiments in which the mRNA of the corresponding genes were selectively blocked, the researchers pinpointed their effect on the ageing process in nematodes. With a dozen of these genes, blocking them extended the lifespan by at least five percent.

One of these genes proved to be particularly influential: the bcat-1 gene. “When we blocked the effect of this gene, it significantly extended the mean lifespan of the nematode by up to 25 percent,” says Ristow.

The researchers were also able to explain how this gene works: the bcat-1 gene carries the code for the enzyme of the same name, which degrades so-called branched-chain amino acids. Naturally occurring in food protein building blocks, these include the amino acids L-leucine, L-isoleucine and L-valine.

When the researchers inhibited the gene activity of bcat-1, the branched-chain amino acids accumulated in the tissue, triggering a molecular signalling cascade that increased longevity in the nematodes. Moreover, the timespan during which the worms remained healthy was extended. As a measure of vitality, the researchers measured the accumulation of ageing pigments, the speed at which the creatures moved, and how often the nematodes successfully reproduced. All of these parameters improved when the scientists inhibited the activity of the bcat-1 gene.

The scientists also achieved a life-extending effect when they mixed the three branched-chain amino acids into the nematodes’ food. However, the effect was generally less pronounced because the bcat-1 gene was still active, which meant that the amino acids continued to be degraded and their life-extending effects could not develop as effectively.

Conserved mechanism

Ristow has no doubt that the same mechanism occurs in humans. “We looked only for the genes that are conserved in evolution and therefore exist in all organisms, including humans,” he says.

In the present study, he and his Jena colleagues from the Leibniz Institute on Aging, the Leibniz Institute for Natural Product Research and Infection Biology, the Jena University Hospital and the Friedrich Schiller University purposefully opted not to study the impact on humans. But a follow-up study is already being planned. “However we cannot measure the life expectancy of humans for obvious reasons,” says the ETH professor. Instead, the researchers plan to incorporate various health parameters such as cholesterol or blood sugar levels in their study to obtain indicators on the health status of their subjects.

Health costs could be massively reduced

Ristow says that the multiple branched-chain amino acids are already being used to treat liver damage and are also added to sport nutrition products. “However, the point is not for people to grow even older, but rather to stay healthy for longer,” [emphasis mine] says the internist. The study will deliver important indicators on how the ageing process could be influenced and how age-related diseases such as diabetes or high blood pressure could be prevented. In light of unfavourable demographics and steadily increasing life expectancy, it is important to extend the healthy life phase and not to reach an even higher age that is characterised by chronic diseases, argue the researchers. With such preventive measures, an elderly person could greatly improve their quality of life while at the same time cutting their healthcare costs by more than half.

” … the point is not for people to grow even older, but rather to stay healthy for longer, ” I couldn’t agree more. Good luck with the gene work.

Finally, the next episode of Breakthrough, Energy on the Edge, is due to be broadcast in the US on Sunday, Dec. 6, 2015 on the National Geographic Channel.