Friday, 31 March 2017

Takeaways From The FDA's Revised Quality Metrics Guidance


On November 23, 2016, the Food and Drug Administration (FDA) published a revised draft guidance for Submission of Quality Metrics Data. The guidance includes significant changes to the earlier quality metrics draft guidance issued by the agency on July 28, 2015.

FDA's Quality Metrics Initiative, announced in April 2013, encourages pharmaceutical firms to embrace continuous improvement and foster a culture of quality by collecting and reporting manufacturing quality data. During the comment period for the 2015 draft guidance, manufacturers acknowledged that the initiative has the potential to transform the way the pharmaceutical industry approaches overall product quality and the reliability of the supply chain. However, manufacturers and participants in ISPE’s Wave 2 Quality Metrics Pilot Program, conducted across 28 companies (83 sites, 60 products), expressed concerns over lack of clarity regarding implementation, timelines, definitions, and evaluation guidelines.

The document has been reviewed by Aravindhan Ramakrishnan for Pharmaceutical Online. It makes for an interesting read, see PharmaOnline.

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Posted by Dr. Tim Sandle

Thursday, 30 March 2017

Risk Mitigation When Evaluating Cleanroom Construction Materials


Maik Jornitz, President, G-Con, has written an interesting white paper on cleanroom construction materials.

The introduction reads:

Reducing the cost of goods sold has become a focus of pharmaceutical facility, cleanroom, and process design, especially as blockbuster patents have begun to expire and generic competition has intensified. The need to minimize manufacturing costs sparked a multitude of creative ideas.
Unfortunately, this creativity has resulted in almost as many concerns. For example, eliminating redundant facilities or processes has resulted in single dedicated facilities, which can increase the risk of drug shortages.

Cleanroom ballroom designs with a lower cleanroom classification have been promoted, especially those utilizing single-use equipment processes. However, if designs are not well thought out, problems such as cross-contamination and batch rejections can result. Taking a short-term view to reducing capital expenses may result in cutting corners on the quality of the facility construction materials. These shortcuts can cause major manufacturing disruptions and quality problems. Cleanroom designs require thorough reflection on the intended purpose. In some cases, short-term solutions or lower-quality materials may be used when the process is expected to have a short life expectancy or the process environment does not pose critical risks. However, high-quality cleanrooms demand high-quality materials for wall and ceiling structures, doors, windows, electrical outlets, pipework, flooring, filters, duct work, etc.

The paper can be accessed here.



Posted by Dr. Tim Sandle

Why rare microbial species are sometimes important


Despite the small population of each rare species in a microbial community, such species may number as much as several hundred within a community, such that the so-called "rare biosphere" may account for roughly 20-30 percent of individual bacteria within an aquatic community. The sheer numbers of rare species result in the rare biosphere containing a large reservoir of genes that can degrade important organic pollutants, and that could help the entire microbial community maintain stability in the face of changing conditions, possibly including climate change.

To investigate this issue a team from Georgia Institute of Technology, Atlanta, established "mesocosms" -- indoor experimental systems -- containing 20 liters of water, each. They inoculated these with water samples from the nearby freshwater Lake Lanier.

The motivation for the study was to be able to better predict how microbial communities will respond to future perturbations such as pesticides, oil spills, and even climate change, said Konstantinidis. Questions it might help answer include that of how valuable microbial diversity is for ecosystem functioning, including for maintaining resilience to human-caused pollution. The results of this and future studies might also help enable predicting the consequences of loss of biodiversity, for example, in the wake of massive pollutant spills or climate change.

For the outcomes, see:

Yuanqi Wang et al. Quantifying the importance of the rare biosphere for microbial community response to organic pollutants in a freshwater ecosystem. Applied and Environmental Microbiology, March 2017 DOI: 10.1128/AEM.03321-16

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Posted by Dr. Tim Sandle

Wednesday, 29 March 2017

Targeting antimicrobial resistance in the short-term


While any antimicrobial resistance is concerning, the increasing incidence of antibiotic-resistant Gram-negative bacteria has become a particular problem as strains resistant to multiple antibiotics are becoming common and no new drugs to treat these infections (e.g., carbapenem-resistant Enterobacteriaceae) will be available in the near future. These Gram-negative bacteria are considered the most critical priority in the list of the 12 families of bacteria that pose the greatest threat to human health that was just released by the World Health Organization.

The reasons for the high levels of antimicrobial resistance observed in these critical Gram-negative organisms are explained in another paper in the same issue written by the Guest Editor of the journal, Dr Rietie Venter, University of South Australia, Adelaide, and colleagues. According to the authors, one of the main contributing factors to the increased resistance observed in Gram-negative bacteria is the permeability barrier caused by their additional outer membrane.

An innovative strategy that is gaining momentum is the synergistic use of antibiotics with FDA-approved non-antibiotics. Using this novel approach, an FDA-approved non-antibiotic drug is combined with a specific antibiotic that enables it to breach the outer membrane barrier and so restore the activity of an antibiotic. The Monash University authors discuss how combining antibiotics with other non-antibiotic drugs or compounds can boost their effectiveness against Gram-negative 'superbugs'.

For example, loperamide, an anti-diarrheal medication sold in most pharmacies, enhances the effectiveness of eight different antibiotics (all in the tetracycline class). In particular, when added to the tetracycline antibiotic minocycline, along with the Parkinson's disease drug benserazide, it significantly increased antibiotic activity against multi-drug resistant Pseudomonas aeruginosa, a causative agent in hospital-acquired infections such as ventilator-associated pneumonia.

Polymyxins are a type of antibiotics that target Gram-negative bacterial infections and have traditionally been used as a last resort to treat serious infections such as those caused by Gram-negative 'superbugs' Klebsiella pneumoniae, P. aeruginosa and Acinetobacter baumannii. Resistance to polymyxins is not common, but in late 2015 the first transferable resistance gene to colistin (polymyxin E) was discovered (plasmid-borne mcr-1 gene). This caused significant concerns, as once resistance to polymyxins is established, often no other treatments are available.

Some interesting findings have ensued, with a number of different combinations having a beneficial effect. Some notable examples that increased antibiotic activity when combined with polymyxin B include: ivacaftor and lumacaftor, two new drugs used to treat cystic fibrosis; and closantel, a drug used to treat parasitic worm infections.


Another interesting combination that has shown promise against methicillin-resistant Staphylococcus aureus (MRSA), according to Schneider and co-authors, is combining the antibiotics ampicillin or oxacillin with berberine. Berberine is extracted from the roots, stems and bark of plants such as barberry.

For the latest research see:

Elena K. Schneider, Felisa Reyes-Ortega, Tony Velkov, Jian Li. Antibiotic–non-antibiotic combinations for combating extremely drug-resistant Gram-negative ‘superbugs’. Essays In Biochemistry, 2017; 61 (1): 115 DOI: 10.1042/EBC20160058

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Posted by Dr. Tim Sandle

Tuesday, 28 March 2017

Journal of GXP Compliance Author of the Year award


Tim Sandle has won the Journal of GXP Compliance Author of the Year award. This was for the following papers submitted to the journal during 2016:

“Control of WFI and Clean Steam Systems for Bacterial Endotoxins”

“Designing Aseptic Process Simulations: The Time and Container Number Conundrum”

“Approaching Microbiological Method Validation”

The papers can be accessed via the IVT Network.

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Monday, 27 March 2017

Top 10 Things to Avoid to Ensure Good Data Integrity Practice


Bioscience Technology has issued a guide on data integrity, which is free to download.

The science site states: “With the advances of technology and the migration of data onto digital platforms, the need for properly and safely sustaining the integrity of your data is more prevalent than ever.

The truth is, maintaining your data’s integrity takes practice.  This quick reference guide provides a list of the top 10 things to avoid when practicing good data integrity.”

The guide can be accessed here.

Posted by Dr. Tim Sandle

Sunday, 26 March 2017

Antimicrobial substances identified in Komodo dragon blood


The world's largest lizard, Komodo dragons live on five small islands in Indonesia. The saliva of these creatures contains at least 57 species of bacteria, which are believed to contribute to the demise of their prey. Yet, the Komodo dragon appears resistant to these bacteria, and serum from these animals has been shown to have antibacterial activity. Substances known as cationic antimicrobial peptides (CAMPs) are produced by nearly all living creatures and are an essential part of the innate immune system. So, Barney Bishop, Monique van Hoek and colleagues at the College of Science at George Mason University wondered whether they could isolate CAMPs from Komodo dragon blood, as they previously had done with alligator blood to expand the library of known CAMPs for therapeutic studies.
The team used an approach known as bioprospecting. They incubated Komodo dragon blood with negatively charged hydrogel particles that they developed to capture the peptides, which are positively charged. With this method, they identified and sequenced 48 potential CAMPs with mass spectrometry. All but one of these was derived from histone proteins, which are known to have antimicrobial activities. Eight were synthesized and tested against Pseudomonas aeruginosa and Staphylococcus aureus. Seven of the peptides showed significant potency against both bacteria. The eighth was only effective against P. aeruginosa. The researchers conclude that Komodo dragon blood plasma contains a host of potentially viable antimicrobial peptides that could help lead to new therapeutics.

See:

Barney M. Bishop, Melanie L. Juba, Paul S. Russo, Megan Devine, Stephanie M Barksdale, Shaylyn Scott, Robert Settlage, Pawel Michalak, Kajal Gupta, Kent Vliet, Joel M. Schnur, Monique L. van Hoek. Discovery of Novel Antimicrobial Peptides from Varanus komodoensis (Komodo dragon) by Large Scale Analyses and De Novo-Assisted Sequencing using Electron Transfer Dissociation Mass Spectrometry. Journal of Proteome Research, 2017; DOI: 10.1021/acs.jproteome.6b00857



Posted by Dr. Tim Sandle

Saturday, 25 March 2017

Common bacterium helps control disease-bearing mosquitoes


Genes from a common bacterium can be harnessed to sterilize male insects, a tool that can potentially control populations of both disease-bearing mosquitoes and agricultural pests, researchers at Yale University and Vanderbilt University report.

Researchers report finding two genes encoded by Wolbachia that when introduced into fruit flies can completely sterilize male insects. The sterility is triggered by a specific enzyme mechanism operating in the sperm and embryo, Yale researchers report in the journal Nature Microbiology. The discovery may allow public health officials to control the size of insect populations by introducing sterile males into the wild.

Wolbachia, however, is not found in some insects -- most notably Aedes aegypti mosquitoes, which are the primary transmitters of diseases such as Zika and dengue fever. Understanding the molecular mechanisms of Wolbachia's effect on reproduction may help researchers produce sterile male Aedes by direct insertion of the genes. When released into the wild, these males could help control mosquito populations.

See: Yale University

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Posted by Dr. Tim Sandle

Friday, 24 March 2017

How cells adapt rapidly to zero gravity


Mammalian cells are optimally adapted to gravity. But what happens in the microgravity environment of space if the earth's pull disappears? Previously, many experiments exhibited cell changes -- after hours or even days in zero gravity. Astronauts, however, returned to Earth without any severe health problems after long missions in space, which begs the question as to how capable cells are of adapting to changes in gravity. Based on real-time readings on the ISS, UZH scientists can now reveal that cells are able to respond to changes in gravitational conditions extremely quickly and keep on functioning. Therefore, the study also provides direct evidence that certain cell functions are linked to gravity.

See:

Cora S. Thiel, Diane de ZĂ©licourt, Svantje Tauber, Astrid Adrian, Markus Franz, Dana M. Simmet, Kathrin Schoppmann, Swantje Hauschild, Sonja Krammer, Miriam Christen, Gesine Bradacs, Katrin Paulsen, Susanne A. Wolf, Markus Braun, Jason Hatton, Vartan Kurtcuoglu, Stefanie Franke, Samuel Tanner, Samantha Cristoforetti, Beate Sick, Bertold Hock, Oliver Ullrich. Rapid adaptation to microgravity in mammalian macrophage cells. Scientific Reports, 2017; 7 (1) DOI: 10.1038/s41598-017-00119-6

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Posted by Dr. Tim Sandle

Thursday, 23 March 2017

New TB drug candidates developed from soil bacteria


A new treatment for tuberculosis (TB) is set to be developed using compounds derived from bacteria that live in soil -- according an international collaboration of researchers, including the University of Warwick.

The group looked at soil bacteria compounds, known to effectively prevent other bacteria growing around them. Using synthetic chemistry, the researchers were able to recreate these compounds with structural variations, turning them into more potent chemical analogues.

When tested in a containment laboratory, these analogues proved to be effective killers of Mycobacterium tuberculosis -- the bacterium which causes TB.

These chemicals target an enzyme in Mycobacterium tuberculosis called MraY, which catalyses a crucial step in building the cell wall around a bacterium. Attacking this part -- a potential 'Achilles' heel' of the bacterium -- provided an essential pathway for the antibacterial compounds to attack and destroy TB strains.

For further details see:

Anh T. Tran, Emma E. Watson, Venugopal Pujari, Trent Conroy, Luke J. Dowman, Andrew M. Giltrap, Angel Pang, Weng Ruh Wong, Roger G. Linington, Sebabrata Mahapatra, Jessica Saunders, Susan A. Charman, Nicholas P. West, Timothy D. H. Bugg, Julie Tod, Christopher G. Dowson, David I. Roper, Dean C. Crick, Warwick J. Britton, Richard J. Payne. Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis. Nature Communications, 2017; 8: 14414 DOI: 10.1038/ncomms14414

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Posted by Dr. Tim Sandle

Wednesday, 22 March 2017

10 Healthy Eating Tips for the Student


College students must know how to maintain their body healthily and strong. Their food diet should be well-planned, and they should take their food in time. Eating is compulsory for all of us. But for students, it is more than necessary. They must choose healthy foods for their mental health as well as their physical health. There are 10 Healthy Eating Tips for Student.

Guest post by Anthony J Maldonado

1- Never skip breakfast

Breakfasts are necessary to make your day awesome. It indeed helps in the study too. If you take breakfast, you will have a healthy mood. If you miss it somehow, take it whenever you have time. It assists you to focus on your study. It kicks starts your metabolism. Your metabolism will start slow if you miss your breakfast. You’ll feel a lot hungry and might get enticed to eat a larger meal. In short, your metabolism will get affected.
2- Take snacks at regular intervals

Take easy snacks when you study. In every 3 hours, take light foods. Don’t skip your meals because it hampers your body weight by making you obese or overweight. You can take apples, bananas, applesauce, etc. as easy snacks.

3- Maintain your class schedules

As a student, you must know how to manage your class schedules. You need to find out when your English tuition and where you should have to go for private tuition. In this way, you can routine your diet also. You can plan what to eat and what to not.

4- Avoid empty calories

Students often hang out with friends. They get tempted to junk foods. Try avoiding empty calories as it is harmful to your health. They contain high calories but little nutrition. Foods such as cakes, cookies, pastries, donuts, fat cheese, bacon, sausages, ice creams, etc. are less useful for human body.

 
5- Drink lots of water

Every day take at least 2litres of water. It aids your health a lot. It helps to manage your body fluids as your body is composed of about 60% of water. It controls calories and energizes body muscles also. It helps your kidney because if you take little water, you’ll be at high risk for a kidney stone. It removes toxins and promotes weight-loss.

6- Physical Exercise

Every day do physical exercise to build yourself fit and healthy. Schedule your time for physical exercise. It burns your calories and makes your body strong and stout. It combats health conditions and diseases. It also helps you to have a better sleep. When you’re at the college, try visiting the gym center. There you can try attending light body work to keep your body smooth. Every day if you continue to do so, you’ll have a sizzling healthy body. Physical exercise such as swimming, cricket, running, etc. can be useful to you too.

7. Have a sensible diet

Diet is a significant part of your health. Try maintaining it correctly. Include omelet’s, casseroles, soups, pasta, lentils and rice in your food plan. Try fresh herbs and spices in your meals. A healthy eating habit is behind the success of a healthy body. A sensible diet should contain protein, fats, carbohydrates and fiber so that the body can be maintained smoothly. Overall, the balance of food is vital to keep your body fit and active.


8. Maintain hygiene

Keep your kitchen and kitchenware clean. Always wash hands before you prepare food. It does not allow the other person to get the germs from you. Maintain hygiene in the fridge as well. Make sure to have your fridge temperature below 5C.Hygiene is vital in social life too. Lack of hygiene is a sign of offensive behavior and illness.


9.  Do food-shopping

Never buy food from one shop only. Try observing the market a lot to know the real price. It will allow you to know what to buy and from where to buy. You will also get an idea on how much you cost for food. In this way, you can limit your expenses and focus on your health too.


10. Look for available cafeteria


Be like a nutritionist. Look for open cafeteria around your area where you can have healthy food. You can change your taste in cheap rate. You can spend quality time too with your friends at the cafeteria.

Tuesday, 21 March 2017

TB Alliance Calls on WHO to Add Tuberculosis to List of Critical Group of Bacteria


TB Alliance and the broader TB community urge that the World Health Organization (WHO) add Mycobacterium tuberculosis to the critical group within the list of drug-resistant bacteria identified as urgent priorities for research and development.

“The absence of TB from this list is shocking,” said Mel Spigelman, President and CEO of TB Alliance. “The effort to develop new drugs to cure TB has always been chronically underfunded despite the disease’s impact.” TB is the world's deadliest infectious disease, killing 1.8 million people each year.

TB patients urgently need new and better antibiotics. Treatment for drug-resistant TB is long, toxic, complicated, and expensive. It can consist of more than two years of a dozen or more pills per day, along with six months of daily injections. And for those unfortunate enough to have extensively resistant TB, even if they take every one of those 20,000 toxic pills and hundreds of injections, they will still have less than a one in three chance of survival. Put simply, TB has evolved at a speed that outpaces our underfunded research community.

This year alone, approximately half a million people will develop drug-resistant TB. Multidrug-resistant TB (MDR-TB) is caused by TB bacteria that is resistant to at least isoniazid and rifampin, the two most potent TB drugs. Less than 20 percent of people with MDR-TB receive treatment; of that small fraction, about half are cured. To place the drug resistant TB situation in perspective, patients with Ebola, for whom there is no available drug therapy, have the same chances of survival that patients with drug-resistant TB patients have, accessing today’s available medicines. MDR-TB is also the most contagious of all the pathogens noted on the WHO’s list, spreading readily from person to person, and is especially dangerous to children, people with HIV, and other vulnerable populations.

About 29 percent of deaths caused by antimicrobial infections are due to drug-resistant TB, according to the US Centers for Disease Control and Prevention. MDR-TB could cost the world $16.7 trillion by 2050, according to a study commissioned by the UK government. Last year's high-level meeting on AMR at the UN General Assembly affirmed that TB is critical to the antimicrobial resistance (AMR) agenda.

New tools, including vaccines, diagnostics, and treatments, cannot be developed without adequate resources, and the global TB community faces significant underfunding. The WHO’s 2011-2015 Global Plan to Stop TB saw a five-year funding deficit of $2.4 billion in drug R&D, and 2015 saw the biggest decline in R&D funding for TB in over a decade. Even efforts to treat and prevent the disease are underfunded by almost $2 billion, according to the WHO.

Drug resistant TB is an urgent and critical priority. Without more attention and new antibiotics, the disease will continue to wreak havoc among the world’s poorest communities. It is not enough to say that TB is being addressed by other health programs; drug resistant TB is the biggest global threat in AMR and it must be recognized as such, especially by the WHO. The absence of TB from the WHO list is an irresponsible public health statement, sending the wrong message about global health priorities.

WHO did issue a follow-up release affirming the critical need for R&D of new antibiotics to tackle drug-resistant tuberculosis. This effort, however, should not be separate from efforts to address other drug-resistant pathogens.

Every global effort to address the burgeoning AMR emergency must include TB, and the WHO should be taking a leadership role in this effort, starting with the inclusion of TB on the new WHO list of priority pathogens.

Monday, 20 March 2017

National Poison Prevention Week


In recognition of National Poison Prevention Week (March 19-25), the National Capital Poison Center urges all parents to take 2 minutes to learn how to prevent and respond to a poison emergency. More than a million poison exposures occur every year in U.S. children younger than 6 years.

“There are two ways to get free, confidential, expert help if a poisoning occurs”, says Dr. Toby Litovitz, MD, Director of the National Capital Poison Center.

There’s no need to memorize that contact info. The National Capital Poison Center provides a new “text-to-save” functionality. Text “poison” to 484848 (don’t type the quotes) to save the contact info directly to your smart phone (standard text messaging rates apply).

You can also download the vcard at http://vcrd.co/poison/4222. Litovitz: “Share that vcard info with babysitters, grandparents, family and friends“.

“Here are 6 important ways to keep your home poison safe”, continues Dr. Litovitz:
  1. Up, up and away! Keep medications and poisonous household products out of your child’s sight and reach. Locked up is best.
  2. Avoid container transfer. Some of the most devastating poisonings occur when toxic products are poured into food or beverage containers, then mistaken for food or drink.
  3. Read the label and follow the directions. Misusing products has dire consequences.
  4. Use child-resistant packaging. It’s not child-proof, but so much better than nothing. Sorry it’s inconvenient, but using it could save a life.
  5. Keep button batteries away from children. Swallowed batteries can burn through your child’s esophagus and cause permanent injury or even death.
  6. Keep laundry pods out of your child’s reach. They are as toxic as they are colorful and squishy.
Need more prevention reminders? Text “poison” to 22828 to subscribe to The Poison Post® for free, quarterly poison prevention updates by email. Or go to www.poison.org for more tips.

About the National Capital Poison Center

The National Capital Poison Center is an independent, not-for-profit organization and an accredited poison center. Its nurse and pharmacist Certified Specialists in Poison Information provide 24/7 telephone guidance for poison emergencies, free of charge. It also provides online guidance for poison emergencies through the webPOISONCONTROL® tool, health professional education in toxicology, and poison prevention education. Service focuses on the metro DC area with a national scope for projects such as webPOISONCONTROL, the National Battery Ingestion Hotline (202-625-3333), and The Poison Post®.

Sunday, 19 March 2017

Which Medicine For Ed Has The Lowest Number Of Side Effects?


Erectile dysfunction (ED) is pretty common among men with almost half of men between the ages 40 to 70 have some kind of erectile problems.  The Journal of the American Medical Association reported that
7 percent of men aged 18 to 29 and 9 percent of men aged 30 to 39 have problems to achieve orgasm. After taking an ED drugs, 70 percent of healthy men have reported in achieving an erection sufficient for intercourse.

Guest post by Jennifer Lia.

How Do Erectile Dysfunction Medicines Or Drugs Work?

Erectile dysfunction medicines or drugs such as Viagra, Levitra, Cenforce 100mg, Stendra, Cialis, Kamagra 100mg, etc., work by relaxing the tight blood vessels in the penis. This allows more blood to enter the penis which results in an erection. These pills are effective to more than two-thirds of men with erectile dysfunction (ED).  ED drugs also reduce the recovery period between sexual intercourses. It is extremely helpful for men who are suffering from premature ejaculation.

Do Erectile Dysfunction (ED) Drugs Have Side Effects?

Every drug has side effects. Viagra, Levitra, Cenforce 100mg, Stendra, Cialis, Kamagra 100mg, etc., might cause headaches, dizziness, indigestion or a runny nose. However, most men have reported that they hardly experienced any side effects, and even if they did, they didn’t mind them. If you want to reduce the risk of potential side effects, start initially with a small dose. Up your dosage slowly if it works. 

If you’ve erectile dysfunction, at best you might have a nasal congestion, says Dr. Harry Fisch of Weill Cornell Medical College and New York-Presbyterian Hospital. Meanwhile, don’t worry you’ll get addicted or dependent on ED drugs. Most erectile dysfunction (ED) drugs aren’t addictive or cause dependencies, according to Dr. Michael Eisenberg of Stanford University.

Which Erectile Dysfunction Drug Comes With The Least Side Effects?

Sildenafil or commonly known as Viagra is prescribed by most doctors to men suffering from erectile dysfunctions. Viagra has have been in the market for a very long time, and its side effects are well-known and addressed. Meanwhile, there is new ED drug, Avanafil or Stendra, which is said to have the least side effects all other ED drugs.


What Are The Causes Of Erectile Dysfunction?

Most doctors have blamed diabetes, hypertension, high cholesterol and various heart diseases for erectile dysfunction. Men suffering from these ailments restrict blood flow in an extreme way to the penis, which makes it harder for these men to have a strong and long-lasting erection, says Dr. Fisch.

How to Have Better Erections without Taking ED Drugs?

You can have better erections without taking any erectile dysfunction (ED) drugs. Here’s how:
  • Quit smoking. Smoking restricts the blood vessels from relaxing, which is vital if you want to have erections. Stop smoking is much better than taking ED drugs. 
  • Shed excess body weight, and do anything to keep your blood pressure in check. If you lose weight, you can keep your blood pressure under control. With Hypertension, the blood vessels lose its ability to dilate properly. 
  • Cut back on alcoholic beverages or drink in moderation. Your sex drive may get a boost if you drink alcohol, but will decrease your performance, says Dr. Fisch 
  • Try to have sex in the morning instead of night. You can have better erections at that time as your testosterone levels increases in the morning.
5.       Check out on medications that cause you some problems to have an erection. For example, avoid taking a nasal decongestant like Sudafed, antidepressants such as Prozac, or anti-hypertension medicines like thiazines before sexual intercourse.

New way to classify viruses based on structure


Professor Robert Sinclair at the Okinawa Institute of Science and Technology Graduate University (OIST) and Professor Dennis Bamford and Dr. Janne Ravantti from the University of Helsinki have found new evidence to support a classification system for viruses based on viral structure.

The team developed a new highly-sensitive computational prototype tool, and used it to detect similarities in the genetic code of viruses with similar outer structures, that conventional tools have failed to detect, suggesting that they share a common ancestor. This is not what would have been expected if similarities in the structure of viruses were due to similar environmental pressures -- a phenomenon known as convergence.

The results, published in the Journal of Virology, suggest that viral structure could provide a means of categorizing viruses with their close relatives -- a potentially superior approach to current classification systems. Application of this new structure-based classification system could make it easier to identify and treat newly emerging viruses that cannot easily be classified with existing classification systems.

Viruses are notoriously difficult to classify due to their enormous diversity, high rates of change and tendency to exchange genetic material. They challenge the very concept of a clear distinction between the living and the dead, with many characteristics resembling those of living things, but lacking the ability to reproduce themselves, without the help of a host cell. As such, they do not fit neatly into the established biological classification system for cellular organisms.

Existing classification systems are imperfect and often lead to very similar viruses being categorized as entirely different entities. These systems are also unable to account for the fact that viruses are constantly changing.

If scientists could identify something that viruses are unable to change, it could provide a basis for a more meaningful approach to classification and enable the scientific community to tackle emerging viruses, such as HIV, SARS coronavirus and Zika virus, more easily.

Previously observed similarities between the protein shell, or 'capsid', of viruses -- that encloses and protects the genetic material -- provide a basis for a classification system based on capsid structure, as previously proposed by Prof. Bamford. The few ways in which viruses package themselves are very similar, even between viruses that are likely to have had their common relative more than a billion years ago. Whether this conservation is due to convergence or common descent has been disputed.


For a classification system based on virus capsid structure to be meaningful, the amino acids that provide the building blocks of the capsid proteins should be similar in related viruses. A seeming lack of sufficient amino acid sequence similarity picked up by conventional sequence analysis tools previously undermined capsid structure as a viable way to classify viruses.

Using ideas from mathematics and computer science, Professor Sinclair from OIST's Mathematical Biology Unit worked with scientists at the University of Helsinki to reinvestigate whether the structure-based classification for viral capsids is in fact supported by previously undetected sequence similarity.

See:

Robert M. Sinclair, Janne J. Ravantti, Dennis H. Bamford. Nucleic and amino acid sequences support structure-based viral classification. Journal of Virology, 2017; JVI.02275-16 DOI: 10.1128/JVI.02275-16

Posted by Dr. Tim Sandle

Saturday, 18 March 2017

Novel genetic switch boosts bacteria cells' production of useful chemicals


MIT chemical engineers have designed a novel genetic switch that allows them to dramatically boost bacteria's production of useful chemicals by shutting down competing metabolic pathways in the cells.

Researchers have been trying to engineer microbes to generate more complex products, including pharmaceuticals and biofuels. This usually requires adding several genes encoding the enzymes that catalyze each step of the overall synthesis.


In many cases, this approach also requires shutting down competing pathways that already exist in the cell. However, the timing of this shutdown is important because if the competing pathway is necessary for cell growth, turning it off limits the population size, and the bacteria won't produce enough of the desired compound.

A laboratory has engineered E. coli to produce glucaric acid by adding three genes -- one each from yeast, mice, and a strain of bacteria called Pseudomonas syringae. Using these three genes, bacteria can transform a compound called glucose-6-phosphate into glucaric acid. However, glucose-6-phosphate is also an intermediate in a critical metabolic pathway that breaks down glucose and converts it into the energy cells need to grow and reproduce.

To generate large quantities of glucaric acid, the researchers had to come up with a way to shut down the glucose-breakdown pathway, allowing glucose-6-phosphate to be diverted into their alternative metabolic pathway. However, they had to carefully time the shutdown so that the cell population would be large enough to produce a substantial amount of glucaric acid. More importantly, they wanted to do so without adding any new chemicals or changing the process conditions in any way.

In addition to adding the genes for glucaric acid production, the researchers engineered each cell to produce a protein that synthesizes a small molecule called AHL. The cells secrete this molecule into their environment, and when the concentration surrounding the cells gets to a certain point, it activates a switch that makes all of the cells stop producing an enzyme called phosphofructokinase (Pfk), which is part of the glucose breakdown pathway. With this enzyme turned off, glucose-6-phosphate accumulates and gets diverted into the alternative pathway that produces glucaric acid. By constructing a library of cells that produce AHL at different rates, the researchers could identify the best time to trigger shutdown of Pfk.

Using this switch, the researchers were able to generate about 0.8 grams of glucaric acid per liter of the bacterial mixture, while cells that were engineered to produce glucaric acid but did not have the metabolic switch produced hardly any.

To demonstrate this versatility, the researchers tested their approach with a metabolic pathway that produces a molecule called shikimate, which is a precursor to several different amino acids and is also an ingredient in some drugs including the influenza drug Tamiflu. They used the AHL quorum-sensing molecule to shut off an enzyme that moves shikimate further along in the amino acid synthesis pathway, allowing shikimate to build up in the cells. Without the switch, the cells could not accumulate any shikimate.

See:

Apoorv Gupta, Irene M Brockman Reizman, Christopher R Reisch, Kristala L J Prather. Dynamic regulation of metabolic flux in engineered bacteria using a pathway-independent quorum-sensing circuit. Nature Biotechnology, 2017; DOI: 10.1038/nbt.3796

Posted by Dr. Tim Sandle

Friday, 17 March 2017

Gut inflammation controlled by changing bacterial balance


Numerous human diseases, including inflammatory bowel disease, diabetes and autism spectrum disorders have been linked to abnormal gut microbial communities, or microbiomes, but an open question is whether these altered microbiomes are drivers of disease.
A new study at the University of Oregon, led by postdoctoral fellow Annah Rolig, took aim at that question with experiments in zebrafish to dissect whether changes in the abundance of certain gut bacteria can cause intestinal inflammation.

The researchers successfully tracked how gut bacterial abundances influenced inflammation. Fish with intestinal inflammation had a larger abundance of a subset of bacteria that appeared to be pro-inflammatory, which they confirmed by dosing the fish with one of these bacteria and finding that it increased the severity of disease symptoms.

They also found a subset of bacteria that was depleted in the inflamed intestines, but present in the mutant fish that remained disease-free. Dosing the fish with a strain of these depleted bacteria ameliorated the disease. Finally, they showed that they could cure the inflammation by transplanting gut neurons from healthy fish into the diseased fish.

These studies demonstrate that inflammatory intestinal pathologies, such as Hirschsprung-associated enterocolitis or inflammatory bowel disease, can be explained as an overgrowth of certain pro-inflammatory groups of bacteria or a loss of anti-inflammatory bacteria, said Judith Eisen, a professor of biology and an expert on gut neurons in zebrafish.

Identifying the bacteria that drive and protect against disease is the first step toward developing microbial interventions and therapies.

For further details see:

Annah S. Rolig, Erika K. Mittge, Julia Ganz, Josh V. Troll, Ellie Melancon, Travis J. Wiles, Kristin Alligood, W. Zac Stephens, Judith S. Eisen, Karen Guillemin. The enteric nervous system promotes intestinal health by constraining microbiota composition. PLOS Biology, February 2017 DOI: 10.1371/journal.pbio.2000689

Posted by Dr. Tim Sandle