Digitally enhanced image of human heart. Wellcome Images.
Caf-fiends in a can
If your heart beats faster at the thought of quaffing a cold can of energy drink (think Red Bull, Monster, Rockstar and their ilk), there may be something wrong with you more worrisome than your sense of taste.
Almost nobody drinks these hugely popular concoctions for their sublime flavor. They are consumed almost entirely for the much touted neurological jolt derived from an overabundance of stimulating caffeine (as much as three times more than in a comparable serving of coffee or soda) and ingredients like B vitamins, the amino acid taurine, guarana, a South American plant with a higher caffeine concentration than coffee, ginseng and ginkgo biloba.
Judging from sales - $12.5 billion in 2012 in the U.S. alone – these commercial energy drinks deliver their promised punch – and worse.
A report presented this week at the Radiological Society of North America found that energy drinks appear to adversely alter heart function. Specifically, they can cause rapid heart rate, palpitations, a blood pressure spike and, possibly, seizures or death.
If that’s not enough of an eye-opener, consider this statistic from the Substance Abuse and Mental Health Services Administration: Each year almost 21,000 energy drink consumers find themselves in hospital emergency rooms being treated for unwanted side effects of the beverages.
So next time you need something to snap you awake, try water – eight icy cold ounces dashed to the face generally does the trick.
Anopheles gambiae mosquitoes, a key vector of malaria and carrier of the Plasmodium falciparum parasite.
By targeting enzyme in mosquito-borne parasite, researchers aim to eliminate malaria
Using advanced methodologies that pit drug compounds against specific types of malaria parasite cells, an international team of scientists, including researchers at the University of California, San Diego School of Medicine and the Genomics Institute of the Novartis Research Foundation, have identified a potential new weapon and approach for attacking the parasites that cause malaria.
Their findings are published in the November 27, 2013 advanced online publication of Nature.
Despite advances in prevention and treatment in recent years, malaria remains one of the world’s great infectious scourges. In 2010, according to the World Health Organization, there were an estimated 219 million cases globally and 660,000 deaths, mostly among African children.
The disease is caused by Plasmodium parasites, which are transmitted to humans by the infectious bite of an Anopheles mosquito. Plasmodium vivax and Plasmodium falciparum are the most problematic of the parasite species. The former is the most widespread globally; the latter most deadly.
Principal investigator Elizabeth A. Winzeler, PhD, professor in the Division of Pharmacology and Drug Discovery, Department of Pediatrics and director of translational research at the UC San Diego Health Sciences Center for Immunity, Infection & Inflammation, and colleagues found a key metabolic enzyme (phosphatidylinositol 4-kinase or PI4K) that is used for intracellular development by Plasmodium species at each stage of infection in the vertebrate host.
The discovery could have significant ramifications for eventually eradicating malaria as a global disease. “Elimination efforts are more effective with better tools and infrastructure,” said Winzeler. “Clearly we have better infrastructure and communication now than we had in the 1960s. To make more progress, though, we need more effective drugs.”
A major obstacle has been the developmental nature of the P. vivax parasite. While some antimalarial drugs effectively kill P. vivax as it circulates in the host’s bloodstream, the parasite also produces an early-stage form called a hypnozoite that can lie dormant and undetected in the livers of infected persons for years before reinitiating development and triggering relapse.
“Most drugs selectively work on certain stages of the (parasite) lifecycle, but not all stages,” said Case McNamara, PhD, the study’s first author and a researcher at the Genomics Institute of the Novartis Research Foundation in San Diego. “Therefore, inhibitors of this drug target have the potential to not only cure individuals of a malaria infection, but to also prevent infections and even block transmission of the parasite back to the mosquito.”
Currently, the only licensed antimalarial drug capable of fully cleansing hidden hypnozoites and eliminating the possibility of relapse – known as the “radical cure” – is primaquine, a drug first tested in the 1940s and licensed by the Food and Drug Administration in 1952.
But primaquine has significant adverse side effects and shortcomings, according to Winzeler, most notably that it can cause life-threatening anemia in people with a specific inherited metabolic enzyme deficiency frequently found in malaria-endemic regions.
“In addition, it may not work all of the time and it requires a prolonged dosing schedule, up to 14 days, which means compliance is an issue. People often do not take the full dose,” Winzeler said. “Primaquine is an old drug and it’s not clear that it would ever be licensed in today’s regulatory environment.”
Primaquine was developed “by simply injecting a lot of compounds into monkeys and seeing which compound cured malaria infections,” said Winzeler. It was later tested in humans using prisoners.
The new approach is far more finely tuned, based on a series of detailed cellular assays that seek to model different parasite lifecycle stages in miniature test tubes. The researchers looked for the rare compound class that had activities in all parasite stages, but no activity against human cells and which was also drug-like. A new chemical class, called imidazopyrazines, possessed these properties. The researchers then identified the protein target of these compounds as PI4K.
“(Dr. Winzeler) had a very creative and powerful idea to help identify malaria drug targets,” said McNamara. “By patiently evolving drug-resistant parasites against the drug of interest, we can probe the genome for the changes responsible for conferring resistance.
“Fortunately, malaria parasites will often try to alter the drug target in subtle ways to prevent the drug from working effectively. So, by identifying these changes we, in turn, identify the drug target. This approach has worked so well that it has quickly become a standard technique in our field to help study and characterize all new antimalarials.”
Because PI4K is also found in humans, Winzeler said the next challenge is to develop a superior drug that continues to discriminate between the parasite and human versions of this enzyme. “Since we know the identity of this protein and will hopefully soon solve its structure, this task will be much easier,” she said.
Grant Will Help Program Continue Training for Safe Senior Driving -
For the seventh consecutive year, the Training, Research and Education for Driving Safety (TREDS) program at the University of California, San Diego School of Medicine has been awarded a grant from the California Office of Traffic Safety (OTS) that will help keep our roadways and senior drivers safe through professional training.
TREDS works with health care providers and law enforcement to identify and assist older drivers with health issues that may put them and other drivers at risk. Driving abilities decrease with age due to physical impairments such as vision, cognition, frailty and the use of medications. Prescription and over-the-counter medications can significantly impair necessary driving skills, including eye sight, reaction time, judgment, hearing, simultaneous task processing and motor skills. Additionally, when drugs are mixed with alcohol, the results can be devastating. According to studies, a 10 mg of Valium has been found to be equivalent to a blood alcohol content (BAC) of 0.10 in its ability to impair driving.
“Physicians have a responsibility to their patients and to the public to help minimize driving risks through appropriate prescribing practices and patient counseling,” said Linda Hill, MD, MPH, professor of Family and Preventive Medicine, UC San Diego School of Medicine and TREDS program director. “It is estimated that 78 percent of drivers 55-years-old and older are using at least one prescription medication with the potential to impair driving, yet only 28 percent of senior drivers are aware that their medications have this potential effect. Patients over 65-years-old make up 12 percent of the population, yet they consume 31 percent of prescribed drugs.”
Antidepressants are an example where both the medication and the disease being treated can affect driving safety. Depression increases the crash risk two to three times, and equally worrisome is that antidepressant medications have been associated with more than double the crash risk in the elderly. Muscle relaxers, anti-anxiety and anti-insomnia medications also adversely affect the safety of senior drivers.
Diabetes drugs, chemotherapy and narcotics can also result in impaired judgment, confusion, drowsiness, nausea and dehydration, all likely to impair driving safety.
“The frailness associated with cancer and chemotherapy alone reduces driving skills and increases crash risks,” said Hill. “Individuals should understand the medications they are taking and how they can impair their driving abilities.”
Human goblet cell. Image courtesy of the University of Edinburgh, Wellcome Images
Raise a glass to the goblet cell
In a paper published last week in Virology Journal, Pascal Gagneux and colleagues at UC San Diego School of Medicine describe how influenza A viruses snip through the protective mucus net to both infect respiratory cells – and then later cut their way out infect other cells.
Mucus is usually deemed a disgusting annoyance, but really it’s not. (Sorry, couldn’t resist.) It is oil in the human engine, lubricating the passages of the mouth, nose, sinuses, throat, lungs and gastrointestinal tract, preventing underlying epithelial tissues from drying out. It’s also a sort of sticky flypaper, trapping unwanted substances like bacteria and dust before they can too deeply penetrate the fairly pristine and sterile inner body.
Each day, a healthy person churns out about 4 to 6 cups of mucus. Most of it trickles down your throat unnoticed. The little factories that make mucus are called goblet cells. It’s an apt moniker because goblet cells are little more than vessels filled to the brim with globules of mucin. That’s a globule cell in the image above; the mucin globules colored blue.
Mucins are glycosylated proteins, but you can think of them more simply as dehydrated bits of mucus packed inside a globule cell. Once released into the water-rich environment of your airways, however, they expand rapidly, absorbing water to reach full, gooey size within 20 milliseconds. That’s one-thousandth of a second. That’s fast. A single flap of a hummingbird’s wing takes 5 to 80 milliseconds.
The rapid release allows goblet cells to respond almost instantly to many different stimuli, from inhaled microbes to a mouthful of eye-watering wasabi.
All things anthropogeny
Established in 2008 by co-founders Ajit Varki, Margaret Schoeninger and Fred Gage, the Center for Academic Research and Training in Anthropogeny (CARTA) promotes transdisciplinary research in the study of human origins.
Anthropogeny is not a synonym for human evolution, but rather encompasses investigation of all factors involved in human origins, including climate, cultural, geographic, social and ecological. The word was popularized by the noted German zoologist Ernst Haeckel.
Not surprisingly, it’s a rich and diverse topic of conversation. Consider CARTA’s regular symposia, which have produced more than 150 scholarly presentations on subjects ranging from language and the biology of altruism to the evolution of nutrition and whether the human mind is unique. Future symposia will discuss child-rearing in human evolution and the role of male aggression and violence.
All CARTA symposia are recorded by UCSD-TV and archived on multiple sites: CARTA, UCSD-TV, iTunes and YouTube.
Recently, the number of online hits of CARTA videos topped 10 million in just four years – a big number in a blink of geologic time.
A colored scanning electron micrograph of a human T lymphocyte. Image courtesy of the National Institute of Allergy and Infectious Disease
Using microRNA Fit to a T (cell)
Researchers show B cells can deliver potentially therapeutic bits of modified RNA
Researchers at the University of California, San Diego School of Medicine have successfully targeted T lymphocytes – which play a central role in the body’s immune response – with another type of white blood cell engineered to synthesize and deliver bits of non-coding RNA or microRNA (miRNA).
The achievement in mice studies, published in this week’s online early edition of the Proceedings of the National Academy of Sciences, may be the first step toward using genetically modified miRNA for therapeutic purposes, perhaps most notably in vaccines and cancer treatments, said principal investigator Maurizio Zanetti, MD, professor in the Department of Medicine and director of the Laboratory of Immunology at UC San Diego Moores Cancer Center.
“From a practical standpoint, short non-coding RNA can be used for replacement therapy to introduce miRNA or miRNA mimetics into tissues to restore normal levels that have been reduced by a disease process or to inhibit other miRNA to increase levels of therapeutic proteins,” said Zanetti.
“However, the explosive rate at which science has discovered miRNAs to be involved in regulating biological processes has not been matched by progress in the translational arena,” Zanetti added. “Very few clinical trials have been launched to date. Part of the problem is that we have not yet identified practical and effective methods to deliver chemically synthesized short non-coding RNA in safe and economically feasible ways.”
Zanetti and colleagues transfected primary B lymphocytes, a notably abundant type of white blood cell (about 15 percent of circulating blood) with engineered plasmid DNA (a kind of replicating but non-viral DNA), then showed that the altered B cells targeted T cells in mice when activated by an antigen – a substance that provokes an immune system response.
“This is a level-one demonstration for this new system,” said Zanetti. “The next goal will be to address more complex questions, such as regulation of the class of T cells that can be induced during vaccination to maximize their protective value against pathogens or cancer.
Microscopic view of an influenza virus. Image courtesy of Sanofi Pasteur.
You, the flu, some Qs - answers too.
We are well into the official flu season, which typically begins in October and may run as long as May. For most healthy people, a bout of the flu is a discomfiting but passing annoyance, a few days of fever, aches, pains, coughing and a sore throat. We recover and get on with our lives.
For some, though, most notably the very young, old and immune suppressed, influenza can be life-threatening. Each year, depending upon prevailing strains and other factors, approximately 3,000 to 49,000 Americans die from complications caused by seasonal flu viruses.
Preventing infection is obviously the best option, which means (aside from good hygiene like washing your hands regularly and thoroughly, coughing into your sleeve and not going to work when you’re sick), getting vaccinated.
We asked Kim M. Delahanty, a registered nurse and administrative director of the Infection Prevention/Clinical Epidemiology and TB Controlat the UC San Diego Health System, to answer a few commonly asked questions about getting “the flu shot.”
Q: After getting a flu shot, some folks complain that they invariably come down with the flu – or at least do not feel well for a few days. What is the risk of becoming sick after being vaccinated?
A: Flu vaccines cause antibodies to develop in the body about two weeks after vaccination. These antibodies provide protection against infection by the viruses that are in the vaccine. So, if the influenza virus is circulating in the community before the person receives their flu vaccination, there is a potential risk in that two-week period that they could be exposed to influenza and come down with a much milder case.
The vaccine does not cause the flu. It is the lack of an immune response in your body and exposure to someone with influenza that causes flu within that two-week period after you received the vaccine. This is why it is recommended to get your flu shot earlier than later in the season.
Also, there are a lot of respiratory illnesses the influenza vaccine does not cover, such as the common cold. You may still get one of these during influenza season.
And remember nausea, vomiting and diarrhea are not traditionally signs and symptoms of influenza, but more indicative of “stomach flu,” which may be causes by a variety of things.
Q: Are there any complications or concerns if you got your last flu shot late in the season and now, just a few months later, are getting vaccinated for the new flu season?
A: None that I’m aware of.
Q: A recent study confirmed that the seasonal flu vaccine is safe for pregnant women. Are there groups of people for whom the vaccine poses sufficient risk that they should not get the shot?
A: There are very few true contraindications and precautions for getting the influenza vaccine. Children under six months of age and people who have ever had a severe allergic reaction to influenza vaccine are contraindicated and should consult their physician.
There are other precautions. People with a history of Guillain-Barré Syndrome (a severe paralytic illness, also called GBS) that occurred after receiving influenza vaccine and who are not at risk for severe illness from influenza should generally not receive vaccine. Tell your doctor if you’ve had Guillain-Barré Syndrome. He or she will help you decide whether the vaccine is recommended for you.
People who are moderately or severely ill with or without fever should usually wait until they recover before getting flu vaccine. If you are ill, talk to your doctor about whether to reschedule the vaccination. People with a mild illness can usually get the vaccine.
Q: How do allergies complicate getting the flu vaccine?
A: There is now an egg-free version of the influenza vaccine called RIV Recombinant Influenza Vaccine. If you have an egg allergy, consult your physician before getting the flu vaccine. People who have had a severe allergic reaction to influenza vaccine in the past are contraindicated.
Q: Is there a difference between getting the vaccine as a shot or as a nasal spray? Is one better than the other?
A: The Centers for Disease Control and Prevention does not have a preference for which of the available flu vaccine options people should get this season. All are acceptable options, but some vaccines are intended for specific age groups. Talk to your doctor or nurse about the best options for you and your loved ones. The important thing is to get a flu vaccine every year.
There are three versions: Inactivated Influenza Vaccine (IIV) is not a live-virus vaccine. This is the flu vaccine most people receive. Recombinant Influenza Vaccine (RIV) Live does not use the influenza virus in its production and contains no egg proteins, antibiotics or preservatives. It is indicated for active immunization against disease caused by influenza virus subtypes A and type B and is approved for persons 18 through 49 years of age. People with egg allergies may take this. Live Attenuated Influenza Vaccine (LAIV) is administered intra-nasally (through the nose) for those that are adverse to needles.
All of these vaccines have different instructions for use.
In this cartoon, experimental magnetic beads are coated with human or pig mucins (grey mesh), which are proteins containing sialic acids (red or blue diamonds), part of a protective mucus net secreted by respiratory cells. Humans and pigs have different sialic acids on their mucins, as indicated by the bottom molecular structures. The flu virus (green stars) bind to and cleave off sialic acids, snipping through the host mucus net to infect cells.
Stuck on Flu
How a sugar-rich mucus barrier traps the virus – and it gets free to infect
Researchers at the University of California, San Diego School of Medicine have shown for the first time how influenza A viruses snip through a protective mucus net to both infect respiratory cells and later cut their way out to infect other cells.
The findings, published online today in Virology Journal by principal investigator Pascal Gagneux, PhD, associate professor in the Department of Cellular and Molecular Medicine, and colleagues, could point the way to new drugs or therapies that more effectively inhibit viral activity, and perhaps prevent some flu infections altogether.
Scientists have long known that common strains of influenza specifically seek and exploit sialic acids, a class of signaling sugar molecules that cover the surfaces of all animal cells. The ubiquitous H1N1 and H3N2 flu strains, for example, use the protein hemagglutinin (H) to bind to matching sialic acid receptors on the surface of a cell before penetrating it, and then use the enzyme neuraminidase (N) to cleave or split these sialic acids when viral particles are ready to exit and spread the infection.
Mucous membrane cells, such as those that line the internal airways of the lungs, nose and throat, defend themselves against such pathogens by secreting a mucus rich in sialic acids – a gooey trap intended to bog down viral particles before they can infect vulnerable cells.
UC San Diego neurosurgeons color code the brain with tractography - the circular object is a tumor.
Brain Surgeons Go with the Flow
Water-Based Imaging Technique Maps Brain Neurons Prior to Surgery
Neurosurgeons at UC San Diego Health System are using a new approach to visualize the brain’s delicate anatomy prior to surgery. The novel technique allows neurosurgeons to see the brain’s nerve connections thus preserving and protecting critical functions such as vision, speech and memory. No needles, dyes or chemicals are needed to create the radiology scan. The main imaging ingredient? Water.
“The brain can be mapped by tracking the movement of its water molecules,” said Clark Chen, MD, PhD, neurosurgeon and vice-chairman of neurosurgery at UC San Diego Health System. “Water molecules in brain nerves move in an oriented manner. However, outside the nerves, the molecules move randomly. Neurosurgeons at UC San Diego can use these distinct properties to locate important connections and to guide where surgery should occur or not.”
The technique, called tractography or diffusion tensor imaging (DTI), has been used for investigational and diagnostic purposes to better understand the effect of stroke and neurological diseases, such as Alzheimer’s. UC San Diego Health System neurosurgeons are among the first in the nation to apply this technology to guide brain tumor surgery.
“There are no margins for error in the brain. Every centimeter of brain tissue contains millions of neural connections so every millimeter counts,” said Chen. “With tractography, we can visualize the most important of these connections to avoid injury. In doing so, we will preserve the quality of life for our patients with brain cancer.”