Tuesday, 31 July 2018

Artificial Intelligenсe to Improve Cancer Diagnosis in NHS

British Prime Minister Theresa May is expected to challenge the National Health Service, health charities and artificial intelligence developers to work to together in order to transform how chronic diseases are diagnosed. Commentary by Tim Sandle.

Monday, 30 July 2018

Machine learning approach could accelerate bioengineering


Scientists from the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) have developed a way to use machine learning to dramatically accelerate the design of microbes that produce biofuel.

Their computer algorithm starts with abundant data about the proteins and metabolites in a biofuel-producing microbial pathway, but no information about how the pathway actually works. It then uses data from previous experiments to learn how the pathway will behave. The scientists used the technique to automatically predict the amount of biofuel produced by pathways that have been added to E. coli bacterial cells.

The new approach is much faster than the current way to predict the behavior of pathways, and promises to speed up the development of biomolecules for many applications in addition to commercially viable biofuels, such as drugs that fight antibiotic-resistant infections and crops that withstand drought.


See:

Zak Costello, Hector Garcia Martin. A machine learning approach to predict metabolic pathway dynamics from time-series multiomics datanpj Systems Biology and Applications, 2018; 4 (1) DOI: 10.1038/s41540-018-0054-3


Posted by Dr. Tim Sandle

Sunday, 29 July 2018

General Data on Cell Membrane and Membrane Traffic



Membrane trafficking refers to the mechanism through which proteins and other types of macromolecules become distributed throughout a cell. The trafficking also refers to the way that macromolecules, and pathogens, are released from the extracellular space. The activity of
membrane trafficking deploys membrane-bound vesicles as transport intermediaries. This transportation process can occur within different organelles within the same cell; or, alternatively, it can occur across the cell membrane in two directions: to and from the extracellular environment.

These are two basic pathways, depending upon the direction of movement: exocytosis (the outward pathway that carries material synthesized in the cytoplasm to the cell milieu) and endocytosis (the pathway which internalizes material from the environment to the inside of the cell). These pathways are part of the way a cell communication with its environment, a process that is critical for all tissue and organ function.

This short paper examines the latest theories relating to eukaryotic cell membranes around the fluid mosaic model (and the processes of exocytosis, endocytosis, phagocytosis, and transcytosis), and the implications that this model holds for biochemistry.

Reference:

Sandle, T. and Chesca, A. (2018) General Data on Cell Membrane and Membrane Traffic, SF J Anal Biochem 1 (2): 1-3

The paper can be accessed via Research Gate

Posted by Dr. Tim Sandle

Saturday, 28 July 2018

Hospital superbug uses tiny sticky fingers to infect medical tools


The antibiotic-resistant Acinetobacter baumannii bacterium is one of the most globally harmful bacteria that causes nosocomial infections. Researchers at the University of Turku have discovered that the bacterium attaches to plastic medical devices using tiny finger-like structures. The researchers were able to develop antibodies that prevent the bacterial spread.

Infections related to hospitals and medical devices form major healthcare problems worldwide. These infections are associated with the ability of pathogens to colonise both biotic and abiotic surfaces.

The research group discovered a unique molecular mechanism that enables Acinetobacter baumannii and related pathogenic bacteria to colonise medical devices. This mechanism enables the bacteria to spread in hospitals.


See:

Natalia Pakharukova, Minna Tuittila, Sari Paavilainen, Henri Malmi, Olena Parilova, Susann Teneberg, Stefan D. Knight, Anton V. Zavialov. Structural basis forAcinetobacter baumanniibiofilm formationProceedings of the National Academy of Sciences, 2018; 115 (21): 5558 DOI: 10.1073/pnas.1800961115

Posted by Dr. Tim Sandle

Friday, 27 July 2018

Secret to longevity may lie in the microbiome


The study, published in Scientific Reports, adds to a growing body of evidence of the influence that gut bacteria can have on health. The researchers incorporated a symbiotic -- made of probiotics with a polyphenol-rich supplement -- into the diet of fruit flies.

The flies fed with the synbiotic lived up to 66 days old -- 26 days more than the ones without the supplement. They also showed reduced traits of aging, such as mounting insulin resistance, inflammation and oxidative stress.

"Probiotics dramatically change the architecture of the gut microbiota, not only in its composition but also in respect to how the foods that we eat are metabolized," says Satya Prakash, professor of biomedical engineering in McGill's Faculty of Medicine and senior author of the study. "This allows a single probiotic formulation to simultaneously act on several biochemical signaling pathways to elicit broad beneficial physiological effects, and explains why the single formulation we present in this paper has such a dramatic effect on so many different markers."

The fruit fly is remarkably similar to mammals with about 70 % similarity in terms of their biochemical pathways, making it a good indicator of what would happen in humans, adds Prakash.


"The effects in humans would likely not be as dramatic, but our results definitely suggest that a diet specifically incorporating Triphala along with these probiotics will promote a long and healthy life."

The authors also say that the findings can be explained by the "gut-brain axis," a bidirectional communication system between microorganisms residing in the gastrointestinal tract -- the microbiota -- and the brain. In the past few years, studies have shown the gut-brain axis to be involved in neuropathological changes and a variety of conditions such as irritable bowel syndrome, neurodegeneration and even depression. Few studies, however, have successfully designed gut microbiota-modulating therapeutics having effects as potent or broad as the formulation presented in the new study.

See:

Susan Westfall, Nikita Lomis, Satya Prakash. Longevity extension in Drosophila through gut-brain communicationScientific Reports, 2018; 8 (1) DOI: 10.1038/s41598-018-25382-z

Posted by Dr. Tim Sandle

Thursday, 26 July 2018

4 Cash-Saving Hacks for the Pharmaceutical Industry


It can be very easy to turn a blind eye to the fact that your pharmaceutical company might be losing thousands of dollars every year in tax savings – savings that are actually rightfully yours.

Guest post by Selwyn Stein (Managing Director VAT IT U.K)

This is because the worlds of both domestic and foreign VAT and tax recovery is intimidating. The are many laws to know and they’re complex and the process of seeking refunds is complicated and burdensome.

There are so many ways to save your company money and contribute it to your bottom line. And you’re not expected to know them all. Speaking to an expert in the industry can really help you unlock those extra cash savings lying around your business. All you have to do is ask someone who knows how to find it.

Here are 4 ways to save cash through VAT/Tax recovery:

1. Recover VAT on travel-related employee expenses

You can recover both Domestic and Foreign travel related expenses. While larger supplier invoices are by standard put through local VAT returns often local travel goes amiss due to it’s cumbersome volume. The same applies for the often more neglected foreign travel expenses. A company can recover VAT charged on accommodation, food, transport and mobile phone use.

2. Recover VAT on Tooling

Tooling costs are incurred when acquiring the components and machines needed for production such as fixtures, injection moulding, gauges, cutting equipment and patterns.

Typically, a pharmaceutical company will design a medical product and based on their own design they will order the parts for it from their supplier. Here’s the thing, the supplier who is capable of creating the machinery or parts to make the product is often not in the same country as the automotive manufacturer or pharmaceutical company. So instead of importing an entire machine to their country, the company will opt to keep the production machines or moulds in the country it was manufactured so it can continue to create the custom design parts that are then imported to the pharmaceutical company.

Tooling VAT can accumulate into the millions and can seriously contribute to your business’s profit.

3. Recover Import VAT on Clinical Trials

This is another area where pharmaceutical companies have opportunities to save money through VAT recovery. Import VAT is charged on any goods that are shipped to Europe for testing and trials and you can claim this import VAT on the value of your medication or medical units that are shipped DDP.

4. Goods VAT Raw Materials

A pharmaceutical company can also recover VAT incurred on the purchase of drugs, supplies and raw materials in Europe and Australiasia as well as on CRO invoices for international services.

If you think your automotive or pharmaceutical company is losing money as a result of unclaimed VAT on tooling, speak to us today for guidance.

These are just some of the many ways that VAT IT can help your business save. Other costs such as employee travel, exhibitions, trade shows and supplier invoices are other costs where a VAT reclaim opportunity exists. VAT IT has always stood for maximising your savings; this allows you to get on with what’s important – growing your business.

Please note that should any of the readers request a quote, they can contact Selwyn Stein (Managing Director VAT IT U.K) at selwyns@vatit.com or alternatively call on +44 (0) 203 929 2114.

Pharmaceutical Microbiology Resources

Wednesday, 25 July 2018

ASTM International Standard Supports Hazardous Materials Packaging


Dangerous goods (hazardous materials) regulations require performance tests to be conducted on packaging or IBC designs before being authorized for use. The regulations do not include standardized procedures for conducting performance tests and, because of this, may result in a non-uniform approach and differences in test results between testing facilities.

The purpose of the new standard is to provide guidance and to establish a set of common practices for conducting hydrostatic pressure tests on IBC designs subjected to UN certification testing.


The new standard (soon to be published as D8134) was developed by ASTM International’s committee on packaging.

See: https://www.astm.org/Standards/D8134.htm

Posted by Dr. Tim Sandle

Tuesday, 24 July 2018

FDA - key actions on bulk drug substances used for compounding


As part of its ongoing implementation of the Drug Quality and Security Act and to advance the goals of its 2018 Compounding Policy Priorities Plan, the U.S. Food and Drug Administration is announcing several actions to protect public health related to the compounding of human drug products.

“We continue to implement the compounding provisions of federal law and advance a modern framework for the development of compounded drugs,” said FDA Commissioner Scott Gottlieb, M.D. “Our actions underscore our focus on protecting patients while making sure we have an enduring framework for better compounding that is well informed by input from the clinical community. Our aim is to be responsive to the medical needs of patients who require compounded medicines, while making sure that these products are compounded under appropriate standards. We recognize that there continues to be great interest in our work in this important policy area and we’re committed to providing updates as we take a continuing series of actions to implement the comprehensive plan that we outlined earlier this year.”

The FDA has issued an alert warning about a bulk drug substance (active pharmaceutical ingredient) used in compounding that carries significant safety risks for patients. The FDA is also taking steps regarding its approach to bulk drug substances that are used to make compounded drugs.

“Addressing bulk drug substances used in compounding is an important priority for the agency,” said Anna Abram, Deputy Commissioner for Policy, Planning, Legislation and Analysis. “The FDA seeks to implement the statutory requirements for bulk drug substances that can be used in compounding in a way that strikes a balance between preserving access to compounded drugs for patients who have a medical need for them while reducing the safety risks and protecting the FDA drug approval process. Input from stakeholders, including health care professionals, is critical to achieving this balance.”

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Monday, 23 July 2018

European and Indian Pharmacopoeias to cooperate


The EDQM/European Pharmacopoeia (Ph. Eur.) and the Indian Pharmacopoeia Commission (IPC) held a symposium in Mumbai to discuss the quality control of medicines in the context of the pharmaceutical legislation and regulatory requirements that exist in Europe and India.

The event was attended by authorities and manufacturers alike, in particular those involved in the manufacture of APIs, from production, quality control and regulatory affairs. The programme covered an overview of the roles of the EDQM/ Ph. Eur. and the IPC in the quality control of medicines including harmonisation activities. Practical advice was also given on using and interpreting the European Pharmacopoeia General Chapters and Monographs, together with an overview of the policies and processes used to establish Pharmaceutical Reference Standards.

Discussions also covered the EDQM’s Procedure for Certification of Suitability, or CEP as it is more commonly known.

See: EDQM

Posted by Dr. Tim Sandle

Sunday, 22 July 2018

Human Microbiome and Implications for Contamination Control: Webinar


People are the biggest source of contamination in cleanrooms. The findings from the human microbiome project suggest an overview of controls is required. This presentation reviews the latest research into the human microbiome, especially in relation to the skin, and looks at the levels of controls and risks required, such as behaviors and gowning practices. The presentation also considers the impact of the knowledge on the use of environmental isolates for culture media testing and applied areas like disinfectant efficacy testing.

Webinar:

Date: Thursday, 26 July 2018 | Time: 10:00 AM PDT, 01:00 PM EDT | Duration: 60 Minutes

Most contamination within the pharmaceutical facility can be traced to humans working in cleanrooms. This is, in some way, evidenced from the association of microorganisms transient or residential to a skin being the primary isolates from environmental monitoring in controlled environments. Human personnel shed high numbers of skin cells mostly as skin flakes. The cleanroom garments worn by personnel cannot contain all human detritus. How effective are these controls in relation to new insights into the human microbiome?

See: Online Compliance Panel.
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

The US Food and Drug Administration Good ANDA submission practices


This draft guidance intended to assist applicants preparing to submit to FDA abbreviated new drug applications (ANDAs).

This guidance highlights common, recurring deficiencies that may lead to a delay in the approval of an ANDA. It also makes recommendations to applicants on how to avoid these deficiencies with the goal of minimizing the number of review cycles necessary for approval.

FDA is also issuing a Good ANDA Assessment Practices Manual of Policies and Procedures which establishes good ANDA assessment practices for the Office of Generic Drugs and the Office of Pharmaceutical Quality to increase their operational efficiency and effectiveness.

See: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM591134.pdf

Posted by Dr. Tim Sandle

Saturday, 21 July 2018

Mixing, diluting, or repackaging biological products outside the scope of an approved Biologics License Application


This final guidance sets forth FDA’s policy regarding the mixing, diluting, and repackaging of certain types of biological products that have been licensed under section 351 of the Public Health Service Act (PHS Act) when such activities are not within the scope of the product’s approved biologics license application (BLA) as described in the approved labeling for the product.



Posted by Dr. Tim Sandle

Friday, 20 July 2018

3-D structure of 1918 influenza virus


Virus-like particles (VLPs) are protein-based structures that mimic viruses and bind to antibodies. Because VLPs are not infectious, they show considerable promise as vaccine platforms for many viral diseases, including influenza. Realizing that fine details about influenza VLPs were scant, a team of researchers who specialize in visualizing molecular structures developed a 3D model based on the 1918 H1 pandemic influenza virus. They say their research, which appears online in Scientific Reports, could benefit VLP vaccine projects, targeting a range of viruses from HIV to Ebola and SARS coronavirus. The research was conducted by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Other researchers had produced VLPs for 1918 H1 influenza that successfully protected animals from different influenza viruses. The NIAID group prepared hundreds of such VLP samples and analyzed their structure with a technique called cryo-electron microscopy, which quick-freezes samples with glass-like clarity. They then sliced through those VLP 3D structures -- like slicing through a loaf of bread -- to analyze their internal structure, using computers to document the size and placement of key molecules. After averaging all their data, the group then created a 3D 1918 influenza VLP model.

The scientists found that about 90 percent of the VLPs are hemagglutinin (HA) proteins (by weight) found on the VLP surface. In contrast, HAs comprise less than half of the viral proteins of natural influenza viruses. The number and location of HA molecules may influence the efficacy of VLP vaccines, influencing the binding of antibodies to specific epitopes on the HA protein. Those antibodies can similarly bind live influenza viruses, preventing them from infecting cells.

The research group, in NIAID's Laboratory of Infectious Diseases, is continuing its work by comparing its VLP data to data from other natural influenza viruses. They believe the more that is understood about the molecular organization of influenza VLPs, the better scientists will be able to develop effective seasonal and universal influenza vaccines.

See: Dustin M. McCraw, John R. Gallagher, Udana Torian, Mallory L. Myers, Michael T. Conlon, Neetu M. Gulati, Audray K. Harris. Structural analysis of influenza vaccine virus-like particles reveals a multicomponent organization. Scientific Reports, 2018; 8 (1) DOI: 10.1038/s41598-018-28700-7
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Thursday, 19 July 2018

New approach to treating infectious diseases


Enterotoxigenic Escherichia coli (ETEC) is known as a major cause of diarrhea in travelers and people living in developing countries. According to the World Health Organization (WHO), ETEC is responsible for 300,000 ~ 500,000 deaths a year, constituting a serious problem.

Effective vaccines for ETEC have not been developed, so patients infected with ETEC are treated with antibiotics and supporting measures. However, the emergence of multidrug-resistant bacteria has become a social issue, so the development of new treatment methods is sought after.

Adherence to the host intestinal epithelium is an essential step for ETEC infection in humans. It was thought that a filamentous structure on the surface of bacteria called 'type IV pilus' was important for bacterial attachment, but its detailed adhesion mechanism was not known.

Osaka University-led researchers clarified how pathogenic E.coliattached to the host intestinal epithelium using type IV pili and secreted proteins. Their research results were published in PNAS.

One of the corresponding authors, Shota Nakamura, says, "We demonstrated that type IV pili on the surface of the bacteria were not sufficient for ETEC adherence to intestinal epithelial cells and that proteins secreted by E.coli were also necessary. The administration of antibodies against the secreted proteins inhibited attachment of the E.coli."

Using X-ray crystallography, the researchers studied how a protein located only at the pilus-tip interacts with a protein secreted by E.coli in the intestines, clarifying the attachment mechanism of ETEC; that is, secreted proteins serve as molecular bridges that bind both type IV pili on the surface of the bacteria and intestinal epithelial cells in humans.

Nakamura also says, "It's possible that this attachment is a common feature in many type IV pili expressing enteropathogens such as Vibrio cholerae and constitutes a new therapeutic target against such bacterial pathogens."

Their research results will lead to the development of not only new vaccines for ETEC, but also anti-adhesion agents for preventing the binding of proteins implicated in bacterial attachment. Anti-adhesion agents can rinse pathogenic bacteria out from the body without destroying them, so there is no danger of producing drug-resistant bacteria. These agents, once developed, will act as a novel treatment approach that may serve as an alternative to antibiotics.

See: Hiroya Oki, Kazuki Kawahara, Takahiro Maruno, Tomoya Imai, Yuki Muroga, Shunsuke Fukakusa, Takaki Iwashita, Yuji Kobayashi, Shigeaki Matsuda, Toshio Kodama, Tetsuya Iida, Takuya Yoshida, Tadayasu Ohkubo, Shota Nakamura. Interplay of a secreted protein with type IVb pilus for efficient enterotoxigenicEscherichia colicolonization. Proceedings of the National Academy of Sciences, 2018; 115 (28): 7422
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

Wednesday, 18 July 2018

Herpes linked to Alzheimer's: Antivirals may help


A new commentary by scientists at the Universities of Manchester and Edinburgh on a study by Taiwanese epidemiologists supports the viability of a potential way to reduce the risk of Alzheimer's disease.

When the Taiwanese authors looked at subjects who suffered severe herpes infection and who were treated aggressively with antiviral drugs, the relative risk of dementia was reduced by a factor of 10.

Manchester's Professor Ruth Itzhaki and Edinburgh's Professor Richard Lathe say the paper, by Tzeng et al. and published in Neurotherapeutics in February 2018, also shows that herpes simplex virus type 1 (HSV1) leads to an increased risk of developing the disease.

"This article and two others by different research groups in Taiwan provide the first population evidence for a causal link between herpes virus infection and Alzheimer's disease, a hugely important finding," said Professor Itzhaki.

They publish a commentary in the Journal of Alzheimer's Disease on the three articles, arguing that they provide the strongest evidence yet for a causal link between herpes infection and Alzheimer's disease, backing 30 years of research by Professor Itzhaki.

Professor Itzhaki said: "I believe we are the first to realise the implications of these striking data on this devastating condition which principally affects the elderly. No effective treatments are yet available.

"Almost 30 million people worldwide suffer from it and sadly, this figure will rise as longevity increases.

"But we believe that these safe and easily available antivirals may have a strong part to play in combating the disease in these patients.

"It also raises the future possibility of preventing the disease by vaccination against the virus in infancy.

"Successful treatment by a specific drug, or successful vaccination against the putative microbe, are the only ways to prove that a microbe is the cause of a non- infectious human disease."

Most Alzheimer's disease researchers investigate its main characteristics -- amyloid plaques and neurofibrillary tangles; however, despite the vast amount of research, the causes of their formation are unknown.

HSV1 infects most humans in youth or later and remains lifelong in the body in dormant form within the peripheral nervous system.

From time to time the virus becomes activated and in some people it then causes visible damage in the form of cold sores.

The Taiwanese study identified 8,362 subjects aged 50 or more during the period January to December 2000 who were newly diagnosed with severe HSV infection.

The study group was compared to a control group of 25,086 people with no evidence of HSV infection.

The authors then monitored the development of dementia in these individuals over a follow-up period of 10 years between 2001 and 2010.

The risk of developing dementia in the HSV group was increased by a factor of 2.542. But, when the authors compared those among the HSV cohort who were treated with antiviral therapy versus those who did not receive it, there was a dramatic tenfold reduction in the later incidence of dementia over 10 years.

Professor Richard Lathe added: "Not only is the magnitude of the antiviral effect remarkable, but also the fact that -- despite the relatively brief duration and the timing of treatment -- in most patients severely affected by HSV1 it appeared to prevent the long-term damage in brain that results in Alzheimer's.

Professor Itzhaki said: "It was as long ago as 1991 when we discovered that, in many elderly people infected with HSV1, the virus is present also in the brain, and then in 1997 that it confers a strong risk of Alzheimer's disease in the brain of people who have a specific genetic factor.

"In 2009, we went on to show that HSV DNA is inside amyloid plaques in Alzheimer's patients' brains.

"We suggested that the virus in brain is reactivated by certain events such as stress, immunosuppression, and infection/inflammation elsewhere.

"So we believe the cycle of HSV1 reactivation in the brain eventually causes Alzheimer's in at least some patients."

See: Ruth F. Itzhaki, Richard Lathe. Herpes Viruses and Senile Dementia: First Population Evidence for a Causal Link. Journal of Alzheimer's Disease, 2018; 64 (2): 363

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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