Friday, 17 January 2020

Ancient feces reveal how 'marsh diet' left Bronze Age Fen folk infected with parasites


New research published today in the journal Parasitology shows how the prehistoric inhabitants of a settlement in the freshwater marshes of eastern England were infected by intestinal worms caught from foraging for food in the lakes and waterways around their homes.

The Bronze Age settlement at Must Farm, located near what is now the fenland city of Peterborough, consisted of wooden houses built on stilts above the water. Wooden causeways connected islands in the marsh, and dugout canoes were used to travel along water channels.
The village burnt down in a catastrophic fire around 3,000 years ago, with artefacts from the houses preserved in mud below the waterline, including food, cloth, and jewellery. The site has been called "Britain's Pompeii."

Also preserved in the surrounding mud were waterlogged "coprolites" -- pieces of human faeces -- that have now been collected and analysed by archaeologists at the University of Cambridge. They used microscopy techniques to detect ancient parasite eggs within the faeces and surrounding sediment.

Very little is known about the intestinal diseases of Bronze Age Britain. The one previous study, of a farming village in Somerset, found evidence of roundworm and whipworm: parasites spread through contamination of food by human faeces.
The ancient excrement of the Anglian marshes tells a different story. "We have found the earliest evidence for fish tapeworm, Echinostoma worm, and giant kidney worm in Britain," said study lead author Dr Piers Mitchell of Cambridge's Department of Archaeology.
"These parasites are spread by eating raw aquatic animals such as fish, amphibians and molluscs. Living over slow-moving water may have protected the inhabitants from some parasites, but put them at risk of others if they ate fish or frogs."

Disposal of human and animal waste into the water around the settlement likely prevented direct faecal pollution of the fenlanders' food, and so prevented infection from roundworm -- the eggs of which have been found at Bronze Age sites across Europe.

However, water in the fens would have been quite stagnant, due in part to thick reed beds, leaving waste accumulating in the surrounding channels. Researchers say this likely provided fertile ground for other parasites to infect local wildlife, which -- if eaten raw or poorly cooked -- then spread to village residents.


"The dumping of excrement into the freshwater channel in which the settlement was built, and consumption of aquatic organisms from the surrounding area, created an ideal nexus for infection with various species of intestinal parasite," said study first author Marissa Ledger, also from Cambridge's Department of Archaeology.

See:

Marissa L. Ledger, Elisabeth Grimshaw, Madison Fairey, Helen L. Whelton, Ian D. Bull, Rachel Ballantyne, Mark Knight, Piers D. Mitchell. Intestinal parasites at the Late Bronze Age settlement of Must Farm, in the fens of East Anglia, UK (9th century B.C.E.). Parasitology, 2019; 1 DOI: 10.1017/S0031182019001021

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 16 January 2020

New Veterinary Medicines Regulation


A new Veterinary Medicines Regulation (Regulation (EU) 2019/6) has been introduced to modernise the existing rules on the authorisation and use of veterinary medicines in the European Union (EU). This becomes applicable on 28 January 2022.

The regulation contains new measures for increasing the availability and safety of veterinary medicines and enhances EU action against antimicrobial resistance. The European Medicines Agency (EMA) is working closely with the European Commission and other EU partners in preparation for the implementation of the new Regulation.

The main objectives of the new Regulation are to:


  • Simplify the regulatory environment and reduce administrative burden for pharmaceutical companies developing veterinary medicines, for example through streamlined pharmacovigilance rules;
  • Stimulate the development of innovative veterinary medicines, including products for small markets (minor use and minor species);
  • Improve the functioning of the internal market for veterinary medicines;
  • Strengthen EU action to fight antimicrobial resistance through specific measures ensuring prudent and responsible use of antimicrobials in animals, including reserving certain antimicrobials for the treatment of infections in people

See EMA at: https://www.ema.europa.eu/en/veterinary-regulatory/overview/implementation-new-veterinary-medicines-regulation

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Wednesday, 15 January 2020

Updates on Ethylene Oxide Sterilization of Medical Devices: Recent FDA Actions



The U.S. Food and Drug Administration (FDA) is providing information on recent actions responding to ongoing concerns about ethylene oxide in commercial operations and encouraging innovative approaches to medical device sterilization.

FDA innovation Challenges

On June 15, 2019, the FDA announced two Innovation Challenges to identify sterilization alternatives and reduce ethylene oxide emissions.

The FDA received 46 applications from companies large and small. After careful review using an established set of criteria, 12 challenge applicants have been selected to participate.

Ethylene Oxide Sterilization Master File Pilot Program

On Novembr 25, 2019, the FDA announced its Ethylene Oxide Sterilization Master File Pilot Program (EtO Pilot Program).

This voluntary program is intended to streamline the submission process, so that sterilization providers that sterilize single-use medical devices using fixed chamber sterilization processes may submit a Master File to the FDA when making certain changes between sterilization sites, or when making certain changes to sterilization processes that utilize reduced ethylene oxide concentrations, and PMA holders can reference such a Master File in a postapproval report instead of submitting a traditional PMA supplement.



General Hospital and Personal Use Devices Panel Advisory Committee Meeting


On November 6 and 7, 2019, the FDA held an advisory committee meeting to discuss ethylene oxide sterilization of medical devices and its role in maintaining public health. Based on panel discussions, the FDA is encouraging device manufacturers to move to electronic labeling and instructions for use in the near term and is committed to working with industry to make this change.

See:  https://www.fda.gov/media/132494/download?utm_campaign=2019-11-25%20Updates%20on%20Ethylene%20Oxide%20Sterilization%20of%20Medical%20Devices&utm_medium=email&utm_source=Eloqua

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Tuesday, 14 January 2020

Sleep and Energy: The Energy Consumed By Your Brain While Sleeping


Irrespective of all the research that has been going on throughout the years, there is a lot of important information that is not known regarding the human brain. Numerous mental diseases, as well as sleeping disorders, still exist and their causes along with no proper mental therapy are known. For any adult, the brain is responsible for taking up almost 20% of the total energy, especially when the adult is resting.

This can sound weird but the main objective of the brain is processing as well as transmitting information with the help of electrical signals. It is important to understand the energy consumed by the brain when an individual is sleeping. When you understand about sleep and energy, it will be easier for you to plan your regular activities. Also, to sleep properly, make sure that you are removing all the gadgets from your room, as stated by https://www.forbes.com.

A guest post by Silvia Watson.

The overview


An adult is responsible for using almost 20% energy of the brain constantly. When considered in detail, almost 15% of the cardiac output is responsible for going towards the activity of the human brain. Apart from that, 25% of the glucose from the entire body is also responsible for helping the brain. Glucose is undoubtedly one of the most important sources of energy within the body and it is normally stored in the skeletal muscles as well as liver as glycogen.

Depending on the sleep stage that you are in, the body is responsible for distributing energy in more than a single way. During stage 2 as well as stage 3, which mean light as well as deep sleep, the brain is not as active. One misconception that constantly floats around is that most of the energy is being used by the brain when any difficult task is being solved. However, it is important to understand that this is not true. This is why you should understand the important question, "How Much Energy Does the Brain Consume While Sleeping?"

What happens to the brain when you are sleeping?


Several studies have revealed that the energy expenditure of the human body is not responsible for changing between the different stages of sleep. There is one important example, which can help in proving that. While all the muscles are not that active when you are in the REM stage, the increased activity of the brain is responsible for making up for that, thereby, evening the usage of energy. On the other hand, the NREM stage is responsible for boosting high expenditure of energy and the muscles when the positions are being switched during sleeping, however, the brain is not as active.

Scientists have already found out that sleep deprivation is responsible for increasing the expenditure of energy even when you are sleeping. People who are dealing with problems of sleep deprivation also report feeling cold. However, it cannot be confirmed because fragmented sleep can leave you in the state of waking up when dealing with an unsuitable environment.

Conclusion

Therefore, it can be said that sleep and energy are highly related to one another. You need to understand how your brain is functioning when you are sleeping so that you can understand the conservation of energy within your body while you are in the resting phase.

(PMR: http://www.pharmamicroresources.com/)

Audit and Control for Healthcare Manufacturers (book)

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 13 January 2020

Audit and Control for Healthcare Manufacturers: A Systems-Based Approach

Compliance is an affirmative indication or judgement that the supplier of a product or service has met the requirements of the relevant specifications, contract or regulation; also the state of meeting the requirements. Compliance is something that meets both the text and the spirit of a requirement. A key way to assess compliance is through auditing. For further details, see the PDA Bookstore: https://www.pda.org/bookstore/product-detail/5014-audit-and-control-for-healthcare-manufacturers


Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Sunday, 12 January 2020

New toxin impedes bacterial growth



An international research collaboration has discovered a new bacteria-killing toxin that shows promise of impacting superbug infectious diseases.

The discovery of this growth-inhibiting toxin, which bacteria inject into rival bacteria to gain a competitive advantage is the result of teamwork by co-senior authors John Whitney, assistant professor of the Department of Biochemistry and Biomedical Sciences at McMaster University, and Mike Laub, professor of biology at the Massachusetts Institute of Technology (MIT).

Whitney and his PhD student Shehryar Ahmad at McMaster's Michael G. DeGroote Institute for Infectious Disease Research were studying how bacteria secrete antibacterial molecules when they came across a new toxin. This toxin was an antibacterial enzyme, one the researchers had never seen before.
After determining the molecular structure of this toxin, Whitney and Ahmad realized that it resembles enzymes that synthesize a well-known bacterial signalling molecule called (p)ppGpp. This molecule normally helps bacteria survive under stressful conditions, such as exposure to antibiotics.

Boyuan Wang, a postdoctoral researcher in the Laub lab who specializes in (p)ppGpp signaling, examined the activity of the newly discovered enzyme. He soon realized that rather than making (p)ppGpp, this enzyme instead produced a poorly understood but related molecule called (p)ppApp. Somehow, the production of (p)ppApp was harmful to bacteria.
The researchers determined that the rapid production of (p)ppApp by this enzyme toxin depletes cells of a molecule called ATP. ATP is often referred to as the 'energy currency of the cell' so when the supply of ATP is exhausted, essential cellular processes are compromised and the bacteria die.

"I find it absolutely fascinating that evolution has essentially "repurposed" an enzyme that normally helps bacteria survive antibiotic treatment and, instead, has deployed it for use as an antibacterial weapon," said Whitney.


The research conducted at McMaster University was funded by the Canadian Institutes for Health Research and is affiliated with the CIHR Institute for Infection and Immunity (CIHR-III) hosted at McMaster University with additional funding from the David Braley Centre for Antibiotic Discovery. The research at MIT was supported by the Howard Hughes Medical Institute and the U.S. National Institutes of Health.

See:

Shehryar Ahmad, Boyuan Wang, Matthew D. Walker, Hiu-Ki R. Tran, Peter J. Stogios, Alexei Savchenko, Robert A. Grant, Andrew G. McArthur, Michael T. Laub, John C. Whitney. An interbacterial toxin inhibits target cell growth by synthesizing (p)ppApp. Nature, 2019; DOI: 10.1038/s41586-019-1735-9

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Saturday, 11 January 2020

DNA is only one among millions of possible genetic molecules



Biology encodes information in DNA and RNA, which are complex molecules finely tuned to their functions. But are they the only way to store hereditary molecular information? Some scientists believe life as we know it could not have existed before there were nucleic acids, thus understanding how they came to exist on the primitive Earth is a fundamental goal of basic research.

The central role of nucleic acids in biological information flow also makes them key targets for pharmaceutical research, and synthetic molecules mimicking nucleic acids form the basis of many treatments for viral diseases, including HIV. Other nucleic acid-like polymers are known, yet much remains unknown regarding possible alternatives for hereditary information storage.

Using sophisticated computational methods, scientists explored the "chemical neighbourhood" of nucleic acid analogues. Surprisingly, they found well over a million variants, suggesting a vast unexplored universe of chemistry relevant to pharmacology, biochemistry and efforts to understand the origins of life. The molecules revealed by this study could be further modified to gives hundreds of millions of potential pharmaceutical drug leads.

Nucleic acids were first identified in the 19th century, but their composition, biological role and function were not understood by scientists until the 20th century. The discovery of DNA's double-helical structure by Watson and Crick in 1953 revealed a simple explanation for how biology and evolution function. All living things on Earth store information in DNA, which consists of two polymer strands wrapped around each other like a caduceus, with each strand being the complement of the other.

When the strands are pulled apart, copying the complement on either template results in two copies of the original. The DNA polymer itself is composed of a sequence of "letters," the bases adenine (A), guanine (G), cytosine (C) and thymine (T), and living organisms have evolved ways to make sure during DNA copying that the appropriate sequence of letters is almost always reproduced. The sequence of bases is copied into RNA by proteins, which then is read into a protein sequence. The proteins themselves then enable a wonderland of finely-tuned chemical processes which make life possible.

Small errors occasionally occur during DNA copying, and others are sometimes introduced by environmental mutagens. These small errors are the fodder for natural selection: some of these errors result in sequences which produce fitter organisms, though most have little effect, and many even prove lethal. The ability of new sequences to allow their hosts to better survive is the "ratchet" which allows biology to almost magically adapt to the constantly changing challenges the environment provides.

This is the underlying reason for the kaleidoscope of biological forms we see around us, from humble bacteria to tigers, the information stored in nucleic acids allows for "memory" in biology. But are DNA and RNA the only way to store this information? Or are they perhaps just the best way, discovered only after millions of years of evolutionary tinkering?
"There are two kinds of nucleic acids in biology, and maybe 20 or 30 effective nucleic acid-binding nucleic acid analogues. We wanted to know if there is one more to be found or even a million more. The answer is, there seem to be many, many more than was expected," says professor Jim Cleaves of ELSI.

Though biologists don't consider them organisms, viruses also use nucleic acids to store their heritable information, though some viruses use a slight variant on DNA, RNA, as their molecular storage system. RNA differs from DNA in the presence of a single atom substitution, but overall RNA plays by very similar molecular rules as DNA. The remarkable thing is, among the incredible variety of organisms on Earth, these two molecules are essentially the only ones biology uses.

Biologists and chemists have long wondered why this should be. Are these the only molecules that could perform this function? If not, are they perhaps the best, that is to say, other molecules could play this role, and perhaps biology tried them out during evolution?
The central importance of nucleic acids in biology has also long made them drug targets for chemists. If a drug can inhibit the ability of an organism or virus to pass its knowledge of how to be infectious on to offspring, it effectively kills the organisms or virus. Mucking up the heredity of an organism or virus is a great way to knock it dead. Fortunately for chemists, and all of us, the cellular machinery which manages nucleic acid copying in each organism is slightly different, and in viruses often very different.

Organisms with large genomes, like humans, need to be very careful about copying their hereditary information and thus are very selective about not using the wrong precursors when copying their nucleic acids. Conversely, viruses, which generally have much smaller genomes, are much more tolerant of using similar, but slightly different molecules to copy themselves.

This means chemicals that are similar to the building blocks of nucleic acids, known as nucleotides, can sometimes impair the biochemistry of one organism worse than another. Most of the important anti-viral drugs used today are nucleotide (or nucleoside, which are molecule differing by the removal of a phosphate group) analogues, including those used to treat HIV, herpes and viral hepatitis. Many important cancer drugs are also nucleotide or nucleoside analogues, as cancer cells sometimes have mutations that make them copy nucleic acids in unusual ways.

Since most scientists believe the basis of biology is heritable information, without which natural selection would be impossible, evolutionary scientists studying the origins of life have also focused on ways of making DNA or RNA from simple chemicals that might have occurred spontaneously on primitive Earth. Once nucleic acids existed, many problems in the origins of life and early evolution would make sense. Most scientists think RNA evolved before DNA, and for subtle chemical reasons which make DNA much more stable than RNA, DNA became life's hard disk.


However, research in the 1960s soon split the theoretical origins field in two: those who saw RNA as the simple "Occam's Razor" answer to the origins-of-biology problem and those who saw the many kinks in the armour of RNA's abiological synthesis. RNA is still a complicated molecule, and it is possible structurally simpler molecules could have served in its place before it arose.

Examining all of these basic questions, which molecule came first, what is unique about RNA and DNA, all at once by physically making molecules in the laboratory, is difficult. On the other hand, computing molecules before making them could potentially save chemists a lot of time.

See:

Henderson James Cleaves, Christopher Butch, Pieter Buys Burger, Jay Goodwin, Markus Meringer. One Among Millions: The Chemical Space of Nucleic Acid-Like Molecules. Journal of Chemical Information and Modeling, 2019; 59 (10): 4266 DOI: 10.1021/acs.jcim.9b00632

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Friday, 10 January 2020

New understanding of antibiotic synthesis


Researchers at McGill University's Faculty of Medicine have made important strides in understanding the functioning of enzymes that play an integral role in the production of antibiotics and other therapeutics.

"Many of the medicines that we rely on today are natural products, made by the Earth's flora," explains Dr. Martin Schmeing, Associate Professor in the Department of Biochemistry at McGill and the study's senior author. "This includes compounds made in microbes by massive enzymes called nonribosomal peptide synthetases, or NRPSs. NRPSs synthesize all sorts of antibiotics, which can kill dangerous fungi and bacteria, as well as compounds to help us fight off viral infections and cancers. For example, these compounds include viomycin, an antibiotic used for the treatment of multidrug-resistant tuberculosis; cyclosporin, which has been widely used as an immunosuppressant in organ transplants; and the familiar antibiotic penicillin."

In order to synthesize these drugsv, NRPSs operate similar to a factory assembly line, consisting of a series of workstations. Each station, called a "module," has multi-step workflows and moving parts that allow it to add one building block component to the growing drug.

For the first time, they were able to make high quality observations about how an individual module relates to the bigger assembly line, by visualizing a two-module portion of the NRPSs that makes the antibiotic linear gramicidin (found in Polysporin treatments). The study found a surprising lack of synchronisation between modules at all points other than when they must coordinate to pass the intermediate from one workstation to the next. Additionally, they found that the modules don't line up in a straight line or other organized fashion, but instead can line up in many different relative positions. "This level of massive flexibility was not expected," notes Dr. Schmeing, who is also Director of McGill's Centre for Structural Biology. "The enzymes are performing gymnastics."

Because the proteins are trapped in a crystal, care was taken to confirm that the results were representative of what happens in real life. Dr. Schmeing worked with his colleague, Dr. Alba Guarné, Professor in the Department of Biochemistry at McGill, to use complementary solution data, collected at the Advanced Light Source in Berkeley to validate the observations. "The structural biology community is very strong at McGill. We work together to help each other in collaborations, to obtain the biophysical equipment required for cutting-edge experiments, and to train our students" says Dr. Schmeing, noting that the experimentalists on the paper, Janice Reimer, Max Eivanskhani and Ingrid Harb, are all talented McGill graduate students. "The environment and colleagues at the McGill Centre for Structural Biology are important for the continued success of our labs."


The results could have implications for the production of new antibiotics and therapeutics in the long term.

See:

Janice M. Reimer, Maximilian Eivaskhani, Ingrid Harb, et al. Structures of a dimodular nonribosomal peptide synthetase reveal conformational flexibility. Science, 2019; 366 (6466): eaaw4388 DOI: 10.1126/science.aaw4388

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Thursday, 9 January 2020

Bacteria in the gut can alter aging process


A new study has found that microorganisms living in the gut may alter the ageing process, which could lead to the development of food-based treatment to slow it down.

All living organisms, including human beings, coexist with a myriad of microbial species living in and on them, and research conducted over the last 20 years has established their important role in nutrition, physiology, metabolism and behaviour.

Researchers transplanted gut microbes from old mice (24 months old) into young, germ-free mice (6 weeks old). After eight weeks, the young mice had increased intestinal growth and production of neurons in the brain, known as neurogenesis.

The team showed that the increased neurogenesis was due to an enrichment of gut microbes that produce a specific short chain fatty acid, called butyrate.

Butyrate is produced through microbial fermentation of dietary fibres in the lower intestinal tract and stimulates production of a pro-longevity hormone called FGF21, which plays an important role in regulating the body's energy and metabolism. As we age, butyrate production is reduced.

The researchers then showed that giving butyrate on its own to the young germ-free mice had the same adult neurogenesis effects.

The team also explored the effects of gut microbe transplants from old to young mice on the functions of the digestive system.

With age, the viability of small intestinal cells is reduced, and this is associated with reduced mucus production that make intestinal cells more vulnerable to damage and cell death.
However, the addition of butyrate helps to better regulate the intestinal barrier function and reduce the risk of inflammation.

The team found that mice receiving microbes from the old donor gained increases in length and width of the intestinal villi -- the wall of the small intestine. In addition, both the small intestine and colon were longer in the old mice than the young germ-free mice.


The discovery shows that gut microbes can compensate and support an ageing body through positive stimulation. This points to a new potential method for tackling the negative effects of ageing by imitating the enrichment and activation of butyrate.

See:

Parag Kundu, Hae Ung Lee, Isabel Garcia-Perez, Emmy Xue Yun Tay, Hyejin Kim, Llanto Elma Faylon, Katherine A. Martin, Rikky Purbojati, Daniela I. Drautz-Moses, Sujoy Ghosh, Jeremy K. Nicholson, Stephan Schuster, Elaine Holmes, Sven Pettersson. Neurogenesis and prolongevity signaling in young germ-free mice transplanted with the gut microbiota of old mice. Science Translational Medicine, 2019; 11 (518): eaau4760 DOI: 10.1126/scitranslmed.aau4760

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Wednesday, 8 January 2020

New link between health and size of social group


A new study has found that crows living in large social groups are healthier than crows that have fewer social interactions.

The research, led by Dr Claudia Wascher of Anglia Ruskin University (ARU), has been published this week in the journal Animal Behaviour. Dr Wascher and her colleagues studied a population of captive carrion crows over a six-year period. They monitored the behaviour of the crows in different sized groups and measured friendship by ranking the birds using a sociality index.

At the same time, they studied the crows' droppings to measure for the presence of coccidian oocyst, a gastrointestinal parasite that can represent an important health threat for birds.
Increased exposure to parasites and disease transmission is considered as one of the major disadvantages of group living. This new study, however, shows the opposite effect.

The researchers found that crows with strong social bonds, living with more relatives, and in larger groups, excreted a significantly smaller proportion of droppings containing parasites than less sociable crows.
The study did not find a connection between health and the crow's dominance within the group, but found that male crows (33%) were slightly more likely to carry the parasite than females (28%).

Dr Wascher, Senior Lecturer in Biology at Anglia Ruskin University (ARU), said: "Crows are a highly social bird and we found that crows with the strongest social bonds excreted fewer samples containing coccidian oocyst, which is a common parasite in birds.

"It is a commonly-held belief that animals in larger groups are less healthy, as illness spreads from individual to individual more easily. We also know from previous studies that aggressive social interactions can be stressful for birds and that over time chronic activation of the physiological stress response can dampen the immune system, which can make individuals more susceptible to parasites.

"Therefore the results from our six-year study, showing a correlation between sociability and health, are significant. It could be that having close social bonds reduces stress levels in crows, which in turn makes them less susceptible to parasites.

"It could also be that healthier crows are more sociable. However, as many of the birds we studied were socialising within captive family groups, dictated by the number of crows within that family, we believe that social bonds in general affect the health of crows, and not vice versa."


See:

Claudia A.F. Wascher, Daniela Canestrari, Vittorio Baglione. Affiliative social relationships and coccidian oocyst excretion in a cooperatively breeding bird species. Animal Behaviour, 2019; 158: 121 DOI: 10.1016/j.anbehav.2019.10.009

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Tuesday, 7 January 2020

Approved OTC medically important antimicrobial drugs under veterinary oversight



FDA has released draft guidance for industry (GFI) #263 to explain the recommended process for voluntarily bringing remaining approved animal drugs containing antimicrobials of human medical importance (i.e., medically important) under the oversight of licensed veterinarians by changing the approved marketing status from over-the-counter (OTC) to prescription (Rx). 

This is part of the FDA’s Five-Year Plan for supporting antimicrobial stewardship in  veterinary settings and builds upon the momentum generated by the implementation  of GF#213. Under GFI #213, animal drug sponsors worked in collaboration. with FDA over a 3-year period to voluntarily change OTC medically important antimicrobials used in the feed or drinking water of food-producing animals to VFD/Rx marketing status and eliminated the use of these products for production purposes (e.g., growth promotion).


These changes took effect in January 2017. A limited number of other dosage forms of medically important antimicrobials, such as injectables, are currently marketed as OTC products for both food-producing and companion animals. When Draft GFI #263 has been finalized and fully implemented, all dosage forms of all approved medically important antimicrobials for all animal species can only be administered under the supervision of a licensed veterinarian and only when necessary for the treatment, control or prevention of specific diseases.

See: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-263-recommendations-sponsors-medically-important-antimicrobial-drugs-approved-use-animals

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Monday, 6 January 2020

Use of Hazard Analysis Critical Control Point (HACCP) methodology for biocontamination control


The concept of Hazard Analysis and Critical Control Points (HACCP) methodology is a system that enables the production of safe products, be they pharmaceuticals or health care products and devices or, as with the origins of HACCP, food. HACCP is an example of a risk assessment tool, and the use of risk assessment, especially proactive risk assessment, is encouraged by regulators as part of Quality Risk Management philosophies.

In terms of applying HACCP to environmental monitoring, a new peer reviewed paper of interest, from Tim Sandle and colleagues, has been published. Here is the abstract:

Quality Risk Management has been an essential feature relating to the manufacture of pharmaceutical and healthcare products for several decades, and its centrality is embedded in key regulatory documents, such as Annex 1 to EU GMP where risk assessment needs to be part of the overall biocontamination control strategy. While the message for constructing pro-active risk assessment sis clear, where the industry lacks direction is with case studies. This paper presents one risk assessment tool, and one which is perhaps best suited to microbiological assessments of pharmaceutical processes and presents a case study for its application. The tool discussed is Hazard Analysis and Critical Control Points (HACCP) and the application is with assessing microbiological risks and then establishing locations for environmental monitoring. The case study is a sterility testing isolator. The paper first discusses what HACCP is and how it can be applied in general, before demonstrating how HACCP can be deployed as a robust tool for constructing or reviewing an environmental monitoring regime.


The reference is:

Sandle, T., Di Mattia, M., and Leavy, C. (2019) Use of Hazard Analysis Critical Control Point (HACCP) methodology for biocontamination control: Assessing microbial risks and to determining environmental monitoring locations, European Journal of Parenteral and Pharmaceutical Science, 24 (3): 1-36 (link: https://phss.preview.foleon.com/publications/ejpps-2019-vol243/use-of-hazard-analysis-critical-control-point-haccp-methodology-for-biocontamination-control-assessing-microbial-risks-and-to-determining-environmental-monitoring-locations/)

For further details, please contact Tim Sandle

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

How bacteria control their cell cycle


Researchers at the Biozentrum of the University have demonstrated how bacteria coordinate cell division with the replication of their genetic material. In an interdisciplinary study they explain why the current concept of the bacterial cell cycle has to be rewritten.

Each living cell grows and divides, thus generating new offspring. This process is also known as the cell cycle. Strictly speaking, it describes a periodic repetition of two coordinated cycles: the duplication of a cell's genetic information on the one hand and cell division on the other. Although the cell cycle in plant and animal cells has been elucidated quite precisely in the past decades, it has remained unclear how these two processes are coordinated in bacteria.

Although it is natural to think that the cell cycle begins with the birth of the cell and ends with the next cell division, the new research argues for a major shift in this concept. Their findings show that, in bacteria, the cell cycle starts and ends with the initiation of DNA replication, with the cell division event occurring between two DNA replication events.

The researchers, led by Prof. Erik van Nimwegen at the Biozentrum of the University of Basel, used a highly interdisciplinary approach combining microfluidics, automated time-lapse microscopy, sophisticated image analysis, and computational modeling. They observed the behavior of individual E. coli cells over long periods of time and systematically quantified multiple variables describing growth, cell division and DNA replication for thousands of cell cycles in several growth conditions. Computational modelling was then applied to this data to uncover the control mechanisms of the cell cycle.

"Our model indicates that the cell cycle in E. coli starts with the initiation of DNA replication, at which point two different counters start running; one determining when the next cell division should occur, and the other determining when the next initiation of DNA replication should occur," explains Thomas Julou, head of the study. "Even though we have not yet identified the molecular basis of these two counters, the biomass produced since the last counter reset appears to be the variable controlling when the next division and replication events take place."

In contrast to classical molecular biology approaches where the effects of mutations are analyzed, the current study uses a new approach in which analysis of the subtle fluctuations that normally growing cells exhibit is used to infer how the underlying process is controlled.

The approach enabled the scientists to reveal the control mechanism of the bacterial cell cycle, but this method will be generally applicable to studying other biological processes and organism.

See:

Guillaume Witz, Erik van Nimwegen, Thomas Julou. Initiation of chromosome replication controls both division and replication cycles in E. coli through a double-adder mechanism. eLife, 2019; 8 DOI: 10.7554/eLife.48063

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Sunday, 5 January 2020

Neglected Tropical Diseases - spotlight on 2020


2020 is a defining year for the next, bolder phase of efforts to combat NTDs. Dr. Mwele Malecela, WHO NTD Director states: “I was asked to speak today about WHO’s vision post-2020...but my main aim today is to talk of our shared vision. We would not be where we are today and would not have made the significant progress we have without the spirit of collaboration which I believe defines our NTD community.” In 2020, NNN members will champion a new ambitious WHO NTD Roadmap 2021 - 2030, underpinned by cross-cutting approaches.

New from the Neglected Tropical Diseases Network.

Over the last decade, NNN members have worked together to make significant contributions to global progress on combating NTDs. The NNN successfully championed the inclusion of an indicator on NTDs in the SDG framework. In 2016 the NNN launched its BEST (Behaviour, Environment, Social inclusion, Treatment & Care) framework, which sets out the NTD community’s commitment to forging new partnerships and working across sectors to ensure equity and inclusion in efforts needed to reach control, elimination, and eradication targets for NTDs. In 2019, the NNN’s WASH working group partnered with the World Health Organization to publish a collaboration toolkit, WASH and health working together: A ‘how-to’ guide for Neglected Tropical Disease Programmes. It provides NTD programme managers and partners with practical guidance to build and deliver multi-sectoral partnerships and action.

With over 70 members worldwide, the NNN is a forum for partners working together to improve health for the world's poorest populations and build a brighter future for all people.

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

Saturday, 4 January 2020

Discovery reveals mechanism that turns herpes virus on and off


New research has identified a new mechanism that plays a role in controlling how the herpes virus alternates between dormant and active stages of infection.

The herpes virus causes cold sores and genital sores, as well as life-threatening infections in newborns, encephalitis and corneal blindness.

Treatment of the virus is difficult, because it hides out in nerve cells and emerges months or years later to reactivate the infection.

Researchers have discovered that the virus switches between the "latent" stage and the "lytic" stage, in which it is actively replicating, depending on how tightly its DNA is packaged into bundles called chromatin.

When the herpes virus enters a cell, the cell tries to protect itself by wrapping the viral DNA tightly around spool-like proteins called histones and condensing it into chromatin, which causes the virus to go dormant. But if the cells are unsuccessful, the chromatin is only loosely bundled, leaving the viral DNA accessible. The virus particles can then turn on their genes and replicate using the cell's machinery to start a lytic infection, causing disease.

The researchers showed that the dynamics of the chromatin regulate whether the entire herpes virus genome is turned on, which must occur before any individual genes can be expressed. This new mechanism represents a previously overlooked way to regulate gene expression at the level of the entire viral chromosome.

With this new knowledge, researchers can further explore the interplay between the virus and host cells that determines whether viral DNA is expressed. Antiviral drugs to treat herpes have existed since the 1960s, but thus far a cure or an effective vaccine has been out of reach.


The discovery opens up new directions for exploring how the virus reactivates after lying dormant. Herpes' ability to lay low has thwarted efforts to create effective vaccines or antiviral drugs that fully prevent or cure the infection.

See:

MiYao Hu, Daniel P. Depledge, Esteban Flores Cortes, Judith Breuer, Luis M. Schang. Chromatin dynamics and the transcriptional competence of HSV-1 genomes during lytic infections. PLOS Pathogens, 2019; 15 (11): e1008076 DOI: 10.1371/journal.ppat.1008076

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)

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