Research Highlight: Lymphatic System Therapy as a Prospective Treatment for Neurological Diseases

by Kurtis Chien

Cerebrospinal fluid is the fluid that surrounds the brain.1 It is produced throughout the day in the cerebral ventricles and eventually drains out of the cranial cavity.1 Past researchers hypothesized that cerebrospinal fluid could drain through either veins or lymphatic vessels, but they were not adequately equipped to determine the exact pathway of drainage.1 Recent research by Ma et al. 2017 was able to determine the predominant pathway by which cerebrospinal fluid leaves the brain by using radiolabeled tracers.2 Researchers infused the lateral ventricles of mouse brains with tracer molecules of various sizes.2 When the brains were imaged, it was found that the tracer molecules were transported to the lymph nodes.2 The researchers also determined that the flow of cerebrospinal fluid exiting the cranial cavity decreased as the mice aged.2

The brain has few immune cells, so one of the purposes of cerebrospinal fluid is to wash out toxins.1 These toxins can include misfolded proteins, which could otherwise accumulate to cause neurodegenerative diseases such as Alzheimer’s disease.1 So, with the current mechanism of cerebrospinal fluid drainage in mind, a proposed method of treatment for these neurodegenerative diseases may be to increase the flow of the lymphatic system.1 The theory follows that a greater lymphatic flow would mean more cerebrospinal fluid exiting the cranial cavity, which would flush more toxic proteins from the brain.1

The concept would require further research, and a starting point could be to determine if mice with Alzheimer’s disease do express a slower rate of lymphatic flow, which would signify insufficient cerebrospinal fluid drainage.2 Such data could further clarify the role of the lymphatic system and support therapeutic techniques that interact with the lymphatic flow.2

 

References:

  1. ETH Zurich. (2017, November 10). Dementia treatment research: Exit through the lymphatic system. ScienceDaily. Retrieved November 11, 2017 from www.sciencedaily.com/releases/2017/11/171110084307.htm
  2. Ma, Q., Ineichen, B. V., Detmar, M., & Proulx, S. T. (2017, November 10). Outflow of cerebrospinal fluid is predominantly through lymphatic vessels and is reduced in aged mice. Retrieved November 10, 2017, from https://www.nature.com/articles/s41467-017-01484-6

 

 

Diet and Exercise Improve Blood Flow to the Brain for Patients with Type 2 Diabetes

By Allison Kannam

            New findings from a 10-year-long study suggest that Type 2 diabetics who reduce their caloric intake and increase physical activity may experience increased blood flow to the brain. Many individuals with Type 2 diabetes are overweight or obese, and while improving diet and exercise is widely recognized as a method to reduce many of diabetes’ negative effects, its impact on cognition and the brain is not well known. Researchers aimed to establish a clearer link between these interventions and blood flow to the brain given that Type 2 diabetes affects circulation and reduced brain circulation can influence decision-making and cognition.

             Recently, researchers investigated data from an existing 10-year study called Action for Health in Diabetes (Look AHEAD) in which participants learned to implement long-term behavior changes in their lives to improve management of their diabetes. In the first comparison group, the “Intensive Lifestyle Intervention” group, participants aimed to consume 1200 to 1800 calories per day and exercise 175 minutes per week and had frequent follow ups for several years. In the control group, participants completed Diabetes Support and Education classes. At the completion of Look AHEAD, 321 participants received an MRI brain scan.

            Participants in the intervention group showed greater blood flow to the brain, and the researchers believed their findings were most applicable to overweight rather than obese individuals. The Look AHEAD study also incorporated cognitive tests, and researchers noted that participants who had poorer performance on these tests showed greater blood flow to the brain, indicating how the brain may respond to cognitive decline.

 

American Geriatrics Society. (2017, October 30). For older adults with diabetes, losing weight with diet, exercise can improve circulation. ScienceDaily. Retrieved November 13, 2017 from www.sciencedaily.com/releases/2017/10/171030141329.htm

Increased involvement in Online Community is Correlated with Increased Likelihood to Quit Smoking

By Sidharth Anand

BecomeanEX.org is an online community created by Truth Initiative in partnership with Mayo Clinic. The community has over 800,000 users who share personal stories and information through various blogs and online forums. The site is focused on helping users quit smoking, and a study by the University of Iowa and the Truth initiative studied its success. The study tracked the tobacco use of 2600 participants in the community to see how varying levels of involvement impacted the likelihood of users to quit. Kang Zhao, a leader of the study from the Trippie College of Business at the University of Iowa, mentioned that studying online participation was key in determining the behavior of the users in real life. For those who were more involved in the website, this was a good indicator of increased quitting following participation. 21% of active participants, those who had actively posted their own content, quit smoking and 11% of those who had read other's blog posts alone quit smoking compared to only 8% of those who had never visited any of the blog posts. The study did not look at why an increased level of participation and involvement in the community correlated with an increased likelihood to quit smoking. However, it was surmised by Amanda Graham of Truth Initiative that the sense of community, and of supportive users encouraging one another was indicative of how these relationships could have a palpable impact on tobacco users.

 

University of Iowa. (2017, November 3). Kicking the habit, online. ScienceDaily. Retrieved November 10, 2017 from www.sciencedaily.com/releases/2017/11/171103105949.htm

Gecko’s can regrow their spinal cords, what about humans?

By Kaya Jordan

Matthew Vickaryous, a researcher and professor at the University of Guelph discovered the type of stem cell responsible for the gecko’s tail regeneration, which could be valuable information in the treatment of human spinal cord injuries. When a gecko is grabbed by a predator, it detaches its tail in order to escape unscathed. The gecko will then grow a new tail and spinal cord within 30 days. This phenomenon was simulated in the lab by pinching the gecko’s tail, which was followed by the natural process of new cell growth. From this experiment it was discovered that radial glia, a specific type of stem cell, was responsible for the regeneration. These cells usually maintain themselves in a resting state and only activate in response to an injury where they ultimately make a new spinal cord for the gecko. In contrast, the human body responds to a spinal cord injury by creating scar tissue, which inhibits any cell regeneration. It seems humans are missing the key cells responsible for healing their own spinal cords, but a lot can be learned from this incredible feat of spinal cord regeneration.

 

University of Guelph. (2017, November 2). Cells driving gecko's ability to re-grow its tail identified: Discovery of which cells are behind the gecko's ability to re-grow its tail has implications for spinal cord treatment in humans. ScienceDaily. Retrieved November 12, 2017 from www.sciencedaily.com/releases/2017/11/171102120954.htm

potential fragile x treatment

By Machlan Sawden

Work at Rockefeller University’s Laboratory of Chromatin Biology and Epigenetics has revealed a potential treatment for the most prominent genetic cause of intellectual disability and autism, Fragile X. This disease stems from a single defective gene called FMRP. Normally, FMRP binds to messenger RNA that codes for chromatin remodelers which are responsible for the rate of gene expression, limiting their production. The mutated gene cannot regulate chromatin remodelers, and uninhibited chromatin remodeling activity causes an increase in the production of proteins involved in neural function, specifically those associated with the synapses through which information is exchanged. Too much of these proteins alters the complex signaling chemistry of our neurons, which is the cause of Fragile X’s symptoms. However, Rockefeller’s study author and postdoctoral researcher Erica Korb and her team have identified a potential treatment for the condition. While drugs to inhibit the proteins causing the signaling errors have been mostly ineffective, Korb’s group found that inhibiting remodeling protein Brd4 led to a return to normal number of neuronal synapses and a decrease in the behavioral symptoms of Fragile X in animal models. The interfering proteins had been prevented from being synthesized in the first place, restoring normal function. This breakthrough has implications beyond that of just treating Fragile X, for other research done by Rockefeller’s Robert B. Darnell suggests that other autism spectrum disorders involve malfunctioning or overactive chromatin remodeling proteins as well. Their work further reveals the mystery of gene expression and how it affects human behavior.

 

Rockefeller University. (2017, November 3). Potential new treatment for Fragile X targets one gene to affect many. ScienceDaily. Retrieved November 7, 2017 from www.sciencedaily.com/releases/2017/11/171103134639.htm

You Can’t Have Your Cells and Age Them Too

By Kurtis Chien

Along the current model of evolutionary biology, it is mathematically impossible to stop aging. As people age, their cells gradually lose function and stop dividing. The accumulation of inefficient cells is expressed through changes in appearance and physical fortitude. A proposed method of slowing aging would be to remove cells that have lost function. In theory, this method could work to promote the development of healthy cells. However, each human body contains a minority of cancerous cells. These cells multiply rapidly, even as a person reaches old age. If an older person continues to generate dysfunctional cells that have to be removed, then their cancerous cells would quickly fill in the vacancy.

Joanna Masel, an evolutionary biologist at the University of Arizona, explains it like this: “the basic reason is that things break.” As the number of healthy, functional cells in an aging human dwindles, they will inevitably be replaced by either obsolete cells or cancerous growth. The proposed solutions cannot both promote cell growth and hinder it at the same time. The unpleasant options are reality until some method of preventing the genetic breakdown in cell division is determined. Even then, such anti-aging methods may have unforeseen consequences.

 

University of Arizona. (2017, October 30). It's mathematically impossible to beat aging, scientists say. ScienceDaily. Retrieved November 6, 2017 from www.sciencedaily.com/releases/2017/10/171030154430.htm

Faster Drug Identification

By Anna Kolchinski

Frequently, drug screening in hospitals is a lengthy and expensive process that puts patients at risk, with results frequently coming back only when it is too late to effectively treat the patient. As drug abuse rates, especially those of difficult to identify drugs like synthetic opiates and new hallucinogens, rise, the need for a quicker and more effective method has become crucial. Current techniques cannot keep up with the chemistry of newer compounds, and they frequently come back with high false positives and negatives. This is also a problem in patient drug compliance. If a patient is not adhering to their prescribed drug regimen, the lack of medication in their system is just as crucial to identify as the presence of drugs in an abuser's body. Researchers at McMaster University have published a paper in the journal Analytical Chemistry detailing a possible solution. Their method uses mass spectroscopy, and is thus able to identify new drugs through their similarities to known drugs. This method also has significantly fewer false positives and negatives, eliminating the need for second rounds of screening. With the rise of drugs like fentanyl and molly, the possibility of a quicker and more effective method that could save thousands of lives is revolutionary. 

McMaster University. (2017, November 3). Chemists develop method to quickly screen, accurately identify fentanyl. ScienceDaily. Retrieved November 6, 2017 from www.sciencedaily.com/releases/2017/11/171103155212.htm

CARSs Enzyme Helping the Powerhouse of the Cell

By Meghan Mulvey

As cells perform their daily functions to support life, they produce waste materials that need to be removed. Various compounds, such as persulfates like CysSSH, are antioxidants that prevent cells from the damage of free radicals, harmful byproducts of cellular reactions. Until recently, the intricacies of these compounds were not known. However, a research team from Tohoku University along with others across the world studied a specific pathway where CysSSH is produced. They identified certain amino acid building blocks and enzymes, such as CARSs, that allow for the formation of CysSSH. Going even further, they discovered two different kinds of CARSs enzymes. The first is found within the cytoplasm of the cell and the second within the mitochondria. While both are important, the CARSs enzyme within the mitochondria produces the majority of CysSSH and helps with other crucial processes such as energy production and maintenance. By exploring CARSs, these researchers found an enzyme linked to energy and persulfate production. This research has important implications for treating diseases that involve mitochondria problems or abnormally high oxidant levels, such as diabetes, COPD, and cardiovascular disease. Moreover, this enzyme can overall help with increasing the quality of life or even cancer diagnosis.

 

Tohoku University. (2017, October 30). Sulfur respiration in mammals and antioxidant activity: A common sulfur metabolite having antioxidant activity appears to be formed with the help of an enzyme found in mitochondria, highlighting a potential area of research for future treatments of various diseases.. ScienceDaily. Retrieved November 3, 2017 from www.sciencedaily.com/releases/2017/10/171030092835.htm

Genome Sequencing of Pumpkins Reveals An Interesting Evolutionary History

By Amanda Moises

Researchers at Boyce Thompson Institute and the National Engineering Research Center in Beijing have discovered the genome sequences of two pumpkin species known as Cucurbita maxima and Cucurbita moschata. This discovery is essential for further scientific research into the desirable traits of the two species as well as more information about breeding them. C. maxima is more desirable for fruit quality and nutrition while C. moschata is more desirable for resistance to disease. However, the hybrid of the two species, known as “Shintosa,” has an even higher resistance to disease and other stresses. Knowing the genomes of both species allows scientists to understand which genes are linked to these desirable traits and therefore maximize them for future hybrids.

The genome sequences also revealed an interesting evolutionary history about the ancestry of pumpkins. Researchers discovered that the pumpkin genome is actually a combination of two ancient genomes which combined to form an allotetraploid. In other words, pumpkins originally had four copies of each chromosome from two different species. However, modern pumpkins are diploid because the genome lost duplicated genes randomly from each ancestor over time. This is a strange occurrence for allotetraploid organisms because usually one genome dominates the other and retains the majority of its genes in the diploid species. Overall, the researchers were excited to uncover the pumpkin’s unusual evolutionary background and use the genome sequence to improve pumpkins for people around the world.

 

Boyce Thompson Institute. (2017, October 30). Pumpkin genomes sequenced, revealing uncommon evolutionary history. ScienceDaily. Retrieved November 6, 2017 from www.sciencedaily.com/releases/2017/10/171030095428.htm

Could the annual flu shot see big changes?

By Grace Materne

Most individuals will receive a flu shot annually without much thought; however, recent studies suggest an overwhelming need for flu vaccine research.  Traditionally, flu vaccines are manufactured by injecting the virus into chicken eggs and allowing it to replicate; the virus found in the fluid of the eggs can then be isolated and used in vaccines. A recent study examining the H3N2 subtype of influenza found that when replicating inside the chicken eggs, the influenza virus must adapt and mutate in order to grow in the new environment. In the case of the H3N2 subtype, however, the mutations during replication are causing vaccines to be only 33% effective. To further study the mutation, researchers use X-ray crystallography, a high-resolution imaging technique. The data indicates that while inside the chicken eggs, the H3N2 subtypes mutates the protein L194P on the hemagglutinin glycoprotein (HA). This mutation results in the human immune system being less effective in recognizing the virus. Thus, if a vaccine for H3N2 subtype contains the mutated protein, it will be unsuccessful in establishing immunity against this strain of influenza. Current research is investigating alternatives to the chicken egg test method and instead looking at the possibility of mammalian cells and recombinant HA protein vaccines.

 

Scripps Research Institute. "How flu shot manufacturing forces influenza to mutate: Egg-based production causes virus to target bird cells, making vaccine less effective." ScienceDaily. ScienceDaily, 30 October 2017. <www.sciencedaily.com/releases/2017/10/171030134625.htm>.

Mefloquine and its Psychological Effects

By Ursula Biba 

Travelers to areas with high prevalence of malaria are commonly given drugs like atovaquone-proguanil, doxycycline and mefloquine to prevent contracting the disease. However, practitioners are concerned with the safety of mefloquine. Introduced in the 1980s, the drug has been linked to various psychological side effects, prompting the creation of a large scale review with 50 randomized studies and 1 million total participants. Findings reveal that mefloquine is related to increased rates of sleeplessness, abnormal dreams, anxiety and depression. Although these links are primarily from patient self-reports, studies have also determined mefloquine to be the cause of one attempted suicide and associated with two deaths. As only less than 1% of travelers treated with mefloquine develop serious side effects, there is no proven increase in formal diagnoses. Thus, more studies need to be performed to determine the true link between the drug and psychosis.

 

Liverpool School of Tropical Medicine. (2017, October 30). New review looks at the effectiveness, side effects of mefloquine. ScienceDaily. Retrieved October 31, 2017 from www.sciencedaily.com/releases/2017/10/171030112225.htm

Scalpel Free Surgery for Parkinson’s Tremor Might be on the Horizon

By: Katie Campbell

            Parkinson’s disease, a progressive, neurodegenerative disease that destroys dopamine-producing neurons in the midbrain, is responsible for over 100,000 deaths per year. Characterized by motor symptoms such as tremors and muscular rigidity, there is no cure for Parkinson’s, so treatment focuses on controlling the symptoms. Sometimes this treatment can include surgery on the affected region of the brain.

            Dr. Jeff Elias at the University of Virginia School of Medicine has pioneered a less-invasive, scalpel-free, way to treat Parkinson’s patients though the use of focused ultrasound. This technology focuses sound waves into a small, hot spot in the body. This hot spot interrupts faulty circuitry or destroys unwanted tissue without needing to cut into the skull. MRI imaging is used during the surgery to monitor the location of the procedure.

            An initial test, published in JAMA Neurology used this form of brain surgery to patients diagnosed with Parkinson’s disease. 62% of patients treated with focused ultrasound showed improvement in their hand tremor as compared to patients treated with a placebo procedure who showed a moderate reduction in symptoms suggesting a placebo effect. Despite this, the researchers believe that the decrease in side-effects associated with the less-invasive treatment warrants further, large-scale studies of the efficacy of focused ultrasound. Overall, the researchers are optimistic that this provides a new, safe way to relieve Parkinson-related symptoms and significantly improve patient’s quality of life.

 

University of Virginia Health System. "Focused ultrasound shows promise for treating Parkinson's tremor: Study examines potential of scalpel-free surgery to manage tremor." ScienceDaily. ScienceDaily, 30 October 2017. <www.sciencedaily.com/releases/2017/10/171030141327.htm>.

Kalia, Lorraine V, and Anthony E Lang. “Parkinson’s disease.” Lancet, 20 Apr. 2015, pp. 896–912., https://www.ncbi.nlm.nih.gov/pubmed/25904081

Climate Change is Real: An Increase in Forest Fires Connected with Health Implications

By Jacqueline Katz

The European Commission Joint Research Centre (JRC) has just released its 2016 annual forest files report, which is the “only official source of information” on the fire count and the acreage scorched by the flames for countries in and bordering the European Union. As such, the policymaking efforts to limit the number of forest fires is heavily reliant on the data shared in these reports.

This issue has received significant attention because of the ominous future the report predicted. Researchers have picked apart the numbers and have found a “trend towards longer and more intense fire seasons in Europe and neighboring regions.” And, it is not only the routine catastrophes that come with forest fires -- depleted soil, the uprooting of families, and the destruction of homes and shelters -- that breed concern, but also the publication of a new study in the esteemed scientific journal Atmospheric Chemistry and Physics. The finding indicates that as wildfires continue to pollute the air and as the rate at which these natural disasters occur increase exponentially, we could start seeing substantial health-related consequences.

What can be done? European legislature on air quality currently has no mention of wildfires. Furthermore, as of now, there is no “widely accepted method for wildfire management that has been shown to lead to lasting reductions in fire activity or [pollution].”

On a lighter note, more and more countries have agreed to come together in an effort to effectively limit emissions. Participation in the JRC report started with just five European Union member states in 2000 and has grown, over the past decade-plus, to include more than 30 countries in Europe, the Middle East, and Africa. Making additional strides, forty nations around the globe have contributed their own scientists to participate in the expert group on forest fires.

 

European Commission Joint Research Centre. (2017, October 19). Danger to Air Quality from Forest Fires. ScienceDaily. Retrieved October 22, 2017 from www.sciencedaily.com/releases/2017/10/171019100805.htm

The First Lethal and Transmissible Avian Virus

By Akari Miki

In 2013, a previously unknown avian virus, H7N9, began infecting poultry in China, and by late July 2017, 1,600 people contracted the virus. Of the infected people, 40 percent died, prompting researchers at the University of Wisconsin-Madison School of Veterinary Medicine to immediately begin investigation. According to the principal investigator, Professor Yoshihiro Kawaoka, this is the first case of an avian virus that is lethal and transmissible between animals.

His team received a sample of the H7N9 from a deceased patient and performed genomic analysis on it. Their most significant finding was that the virus had two different populations: one that was vulnerable to Tamiflu, a common flu drug, and another that was resistant. This observation suggested that after infecting the patient, the virus was accumulating mutations, improving its resistance to the drug.

The next step was to determine whether H7N9 is transmissible among ferrets, the most accurate animal model for studying human infections. Each experimental trial consisted of two ferrets, a healthy one and one that was deliberately infected with H7N9. Each ferret was placed in two adjacent cages with a barrier in between them that allowed the passage of respiratory droplets. All of the previously healthy ferrets became infected, and the deliberately infected ferrets as well as the ferrets to which they transmitted the virus died, confirming the lethality and infectiousness of the virus.

Professor Kawaoka predicts that H7N9 will continue to accumulate mutations that enhance their pathogenicity and transmissibility, a phenomenon known as gain-of-function. Prior to this study, he published a commentary that emphasizes the importance of research on gain-of-function of viruses in transmissibility, drug resistance, pathogenicity, and ability to replicate, because it would facilitate the development of pre-pandemic vaccines and antiviral drugs. As gain-of-function studies get underway, the best measure for global public health is to improve close surveillance on the circulating virus.

 

University of Wisconsin-Madison. (2017, October 19). H7N9 influenza is both lethal and transmissible in animal model for flu. ScienceDaily. Retrieved October 29, 2017 from www.sciencedaily.com/releases/2017/10/171019143007.htm

The Self-Modifying Herpes Simplex Virus

By Alexander Pan

Researchers from Penn State investigated the Herpes Simplex Virus type 1 (HSV-1), which is a common infection that causes genital and oral lesions. To this day, HSV-1 has no cure and can spread easily through sores, saliva, and sex. Since the virus affects millions of people around the world, there are variations of the virus in different regions, implying that the HSV-1 diversifies and evolves. The researchers studied HSV-1 in the samples from a father and son to examine their transmissions. Through the method of genomic sequencing, each virus was investigated in an animal model in order to compare levels of virulence. Animal models were used to provide an environment that affects the virus such as the immune system and the nervous system. The results show that the HSV-1 did not change much when transmitted to related individuals. The HSV-1 between related individuals had similar growth rates and pathology. However, when the viruses were compared between different father-son virus pairs from different geographical regions, the HSV-1 was differentiated between unrelated individuals.  Therefore, this supports the idea that the virus modifies itself in different people from different geographical regions. Moving forward, therapeutics and vaccines should be created based on particular regions to increase effectiveness. Furthermore, researchers plan to study the molecular mechanisms of how the virus changes and modifies itself between unrelated individuals in order to determine a treatment for HSV-1. 

 

Penn State. (2017, October 20). Exploring how herpes simplex virus changes when passed between family members. ScienceDaily. Retrieved October 29, 2017 from www.sciencedaily.com/releases/2017/10/171020182547.htm

Utsav Pandey, Daniel W. Renner, Richard L. Thompson, Moriah L. Szpara, Nancy M. Sawtell. Inferred father-to-son transmission of herpes simplex virus results in near-perfect preservation of viral genome identity and in vivo phenotypes. Scientific Reports, 2017; 7 (1) DOI: 10.1038/s41598-017-13936-6

Smartphone usage may be implicit in trend of lack of sleep in teens

By Mohamad Hamze

For teenagers, increasing smartphone use may mean less sleep – historically low amounts of it, in fact. Results from two national surveys conducted in 2015 found that two in five (40%) high-school students are getting less than seven hours of sleep on average per night, compared with 34% in 2009 and around 25% in 1991. Professor Jean Twenge and her team of researchers at San Diego State University’s department of Psychology wanted to come up with an explanation for this trend towards lack of adequate sleep. Looking at online presence of teens, the researchers proposed that the large jump from 2009 to 2015 in the percentage of teenagers not getting enough sleep may have been associated with the increasing ubiquity of smartphone use during that time, and for a couple of reasons.

            First, as psychologist Zlatan Krizan hypothesizes, teens may simply be using their phones more often during the day and for longer periods of time, leading to their tendency to sleep for fewer hours at night. This is based on collected data that reported “teens who spent 5 hours a day online were 50% more likely to not sleep enough than their peers who only spent an hour online each day.” In such a media-driven society, 5 hours of smartphone usage is by no means unfathomable, so it is easy to imagine how many adolescents may meet this threshold. Second, Twange comments on the blue light wavelengths emitted by smart phone screens that may “interfere with the body’s natural sleep-wake rhythm,” especially at night.

 With these two concerns in mind, Twenge and her team suggest that teenagers and should consider the amount of sleep they are getting, whether smartphone usage may be a detriment to their sleep schedules, and how they can limit it as such.   

 

San Diego State University. "More teens than ever aren't getting enough sleep: A new study finds young people are likely sacrificing sleep to spend more time on their phones and tablets." ScienceDaily. ScienceDaily, 19 October 2017.

Research Highlight: The Bottom-Up Approach with Diazepam

By Kurtis Chien

Diazepam, originally sold under the brand-name Valium, is a sedative drug used to treat anxiety symptoms (1). Despite the sedative properties, current and past research indicate that diazepam can amplify aggressive behavior (1).

I spoke with Dr. Klaus Miczek, a professor of psychology, pharmacology, and neuroscience. Dr. Miczek’s laboratory researches the relationship between stress and drug abuse, as well as the brain mechanisms involved with aggression.

Dr. Miczek has researched diazepam and similar benzodiazepines in animal models. In his experiments, mice, rats, or monkeys could receive a drug treatment before encountering another animal (2). The drug’s effects on the experimental animal’s behavior toward the intruding animal could then be observed and manipulated with adjustments to the drug dosage (2). “These drugs follow in a very lawful manner, an inverted U-shape dose-effect curve,” Dr. Miczek tells me (2). That is, along the initial segment of the curve, increasing dosage results in a subsequent increase in aggressive behavior (2). As for the latter segment, the higher doses have a sedative effect, sometimes enough to put the animal to sleep (2).

With the drug action in mind, Dr. Miczek and other researchers set out to determine the mechanism of action. By using benzodiazepine receptor antagonists, it was discovered that benzodiazepines change the conformation of the GABAA receptor molecule (2). These receptors are targeted by the inhibitory neurotransmitter GABA, also known as gamma-aminobutyric acid, which allows chloride ions to flow into the cell (2). “Turns out, that benzodiazepines share this action with alcohol,” Dr. Miczek remarks (2). Unsurprisingly, the graph of aggression vs. alcohol resembles the dose-effect curve for aggression vs. diazepam.

GABAA is a receptor molecule with five subunits (2). The α2 subunit is relevant to the regulation of aggression, and it is the subunit that benzodiazepines interact with (2). Now, what is left to be done is to experimentally determine the genes that express these subunits (2). Perhaps, once the genes responsible have been discovered, they can be manipulated so that inactivation of aggression-related receptors can prevent the aggression-heightening effects of alcohol and diazepam (2).

However, to approach aggression in a bottom-up manner would be getting just half of the picture (2). Seeking and manipulating the gene that codes for the α2 subunit on the GABAA receptor cannot account for the complexity of the polygenic phenomenon that mediates aggression (2). A top-down approach would then be to take the domain of aggression and to study the myriad of factors that control it (2). The picture would be complete when the two approaches complement each other (2). “But we’re far from it,” says Dr. Miczek (2). Until then, he notes, “it’s important to remember that aggression is not explained by a single gene” (2).

 

References:

  1. Diazepam. (2005, March 25). Retrieved October 26, 2017, from https://pubchem.ncbi.nlm.nih.gov/compound/diazepam#section=Top
  2. Miczek, K. (2017, October 20). Personal Interview.

 

 

ECT in England: Medical Negligence in Specific Populations

By Leili Najmabadi 

ECT, or electroconvulsive therapy, is continuously in practice in England, despite controversies regarding its use. Most recipients who receive ECT are women and the elderly (at 66% and 56%), and 39% of all recipients receive this treatment without consent. The total recipient count in England is currently 2100-2700 people. Fifty-six National Health Service Trusts in the country received requests from the Freedom of Information Act, and 30% of these Trusts were found to violate legislation regarding patients receiving a second opinion. Violations concerning efficacy and adverse effects were also studied through information on usage, demographics, consent, and adherence to the National Institute of Clinical Excellence guidelines, as well as those from England’s Mental Health Act. Four of these Trusts were able to give information on positive and negative outcomes in this study, and none of the Trusts gave information on post-treatment efficacy. Of the 56 Trusts, only 10 reported the number of people that experienced psychological treatment and followed government guidelines before using ECT.

These findings in England raise the issue of medical negligence, which Professor John Read from University of East London attributes to the variability of ECT usage between regions in the country based on local psychiatrists’ individual opinions. The possibility of more regulations for ECT could prove to have a large effect on treatment against will and more effective treatment that does not include this dangerous procedure. Also, elderly women, who are the target population of this treatment, will hopefully be able to participate in an evidence-based mental health system that promotes education, consent, and a variety of options.

 

Wiley. (2017, October 20). Audit uncovers concerns about the use of electroconvulsive therapy in England. ScienceDaily. Retrieved October 27, 2017 from www.sciencedaily.com/releases/2017/10/171020105352.htm

Study shows increasing rates of IBD keeps pace with industrialization

By Dominic Kleinknecht
Eberhard-Karls-Universität Tübingen

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine. It has a pathology that has come with increased wealth and standard of living, and has been rising in prevalence in North America, Europa, and Australia since the 1950s. It has recently reached a plateau, but the western world has been grappling with the mounting challenge of IBD for the last century. Research from Dr. Gilaad Kaplan from the Cummings School of Medicine at the University of Calgary and Siew Ng, PhD, from the Chinese University in Hong Kong indicates that the cycle of emergence and plateauing of IBD has also been entered in formerly less developed countries. They brought together data from all population-based studies reporting on IBD since 1990 and found that IBD emerged and dramatically rose in incidence in countries in Asia, South America and the Middle East that have become more and more westernized recently, which made IBD a global disease at the turn of the 21st century. Kaplan and Ng point out that identifying environmental risk factors during the early stages of industrialization should now be prioritized in order to lay the groundwork for coordinated, global prevention strategies of IBD to tackle this costly disease. Their findings will be presented at the World Congress of Gastroenterology on Oct. 16 in Orlando, Florida.

 

University of Calgary. (2017, October 20). Increase in inflammatory bowel disease in developing world predicted: Study shows increasing rates of IBD keep pace with industrialization. ScienceDaily. Retrieved October 28, 2017 from www.sciencedaily.com/releases/2017/10/171020125752.htm

Could Patient’s own immune cells be reengineered to fight HIV?

By Kaya Jordan

Rachel Leibman and colleagues in the Perelman School of Medicine at the University of Pennsylvania, have improved a protein called chimeric antigen receptor (CAR) and are using it to specifically target the HIV virus when added to T cells (white blood cells involved in the immune response). Leibman and colleagues have designed a way to extract T cells from a patient's blood to be replaced with T cells reengineered in the lab to express HIV-specific CARs. They discovered that “T cells expressing the new CAR were over 50 times more effective than those with the original CAR in preventing viral spread between human cells in the lab” (PLOS).

When the researchers tested the new CAR in mice infected with HIV, they found that mouse T cells reengineered to express the new CAR could protect other T cells in the mice from being attacked and depleted by HIV and prevent viral rebound, which occurs when the HIV levels in the blood return after a time of absence when receiving antiretroviral therapy (PLOS). The success with mice shows promise for the clinical testing of this technique, which could prove to be a more successful treatment for HIV.

PLOS. (2017, October 12). Reengineered immune system cells show early promise against HIV: Scientists make improvements to a previously promising treatment that fell short in clinical trials. ScienceDaily. Retrieved October 15, 2017 from www.sciencedaily.com/releases/2017/10/171012143131.htm