The Better to See you With: One Grade Improvements for Cataracts

Cataracts effect over half of the United States population over 70 years old. However, this condition is not restricted to humans, many animals also suffer from cataracts. Often an age related disorder, cataracts may occur in one eye or both resulting from a variety of causes including: environmental exposure (excessive sunlight), certain behaviors (regularly consuming alcohol), and as a side effect of certain diseases (like diabetes). Cataracts are caused by protein aggregations within the eye which lead to cloudiness and blurry vision. This may have a huge impact on the quality of life of an individual. Those with cataracts may have a hard time driving at night, double vision, faded colors, and many changes in prescription of eyeglasses. Cataracts are rated on a scale of 1-4 as the condition becomes increasingly worse. Prior to a study by Gestwicki, the only treatment was surgery. While surgery has high success rate, healing can take as long as 8 weeks. Additionally, surgery may be costly, some individuals may not be able to afford this treatment.

Chaperone proteins CRYAA and CRYAB generally keep proteins which are misfolded or otherwise dysfunctional from aggregating allowing for clear vision. However, as humans age the sheer number of misfolded and damaged proteins begin to overwhelm these proteins. These proteins are really unique-they are undruggable. Boosting the function of these proteins would seem like a great target to help prevent aggregation of the increasing numbers of damaged proteins; however, the activity of these proteins are immeasurable.

In a type of hereditary cataract, there is a mutation of CRYAB which increases the melting point of the protein rendering it dysfunctional. Gestwicki's research team tested many molecules, finally settling on compound 29. This is a steroid normally found in the bloodstream which has the ability to bind to the mutant CRYAB and lower the melting point, thereby restoring function. Mice receiving this steroid in the form of an eye drop experienced a one-grade improvement in as little as a few weeks.

This treatment causes significant improvements over a short time scale. Eye drops may be a cheaper and more accessible option for many patients and do not have the long recovery time associated with surgery. While more research is needed before human trials are begun, this is a promising treatment to restore eye sight for many seniors who may be coping with many challenges every day stemming from reduced eye sight.

Sources:

http://news.sciencemag.org/health/2015/11/steroid-eye-drops-reverse-cataracts-mice

https://nei.nih.gov/health/cataract/cataract_facts

http://www.eyecareforanimals.com/conditions/cataracts/

An aspirin a day keeps the neurologist away?

Aspirin, or acetylsalicylic acid, has been the most widely used medication across the globe for the past two centuries to prevent platelet aggregation and to treat symptoms of pain, fever, and inflammation. With so many pharmacological effects, researchers at Boyce Thompson Institute and John Hopkins University sought to identify all of aspirin’s actions. The primary metabolite of aspirin, salicylic acid (SA), was found to target several human proteins in a high-throughput screen of SA binding activity; glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was one of the proteins discovered to be a target of SA.

GAPDH is well-known for facilitating the production of energy from glucose. In addition to catalyzing the sixth step of glycolysis, GAPDH has been implicated to aid in transcription activation, DNA repair, and more recently, to initiate apoptosis and cell death. GAPDH’s apoptotic actions affect multiple cell types, most interestingly neuronal cells in the presence of reactive oxygen species (ROS). GAPDH therefore is a major suspect in neurodegenerative diseases including Huntington’s, Parkinson’s, and Alzheimer’s diseases.

Under oxidative stress, such as in excess of the ROS nitric oxide and other reactive compounds, GAPDH enters the nucleus of a neuron where it then upregulates the transcription of inappropriate proteins. This distorted production of proteins initiates the apoptosis cascade, kills the cell, and eventually results in the neurodegeneration of the individual. SA, similarly to a current anti-Parkinson’s drug (deprenyl), prevents the modification of GAPDH that allows it to enter a neuron’s nucleus, thus preventing the downstream death of that neuron.

The suggested neuroprotective properties of SA led researchers to investigate additional compounds that have a greater affinity for GAPDH than aspirin-derived SA and found that SA in licorice, a Chinese medicinal herb, better binds GAPDH. Researchers are currently screening for even more potent forms of SA, anticipating that a stronger compound will exhibit greater ability to suppress GAPDH’s entry into neural nuclei and potentially arrest neurodegenerative diseases.

Here is a link to the study!

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143447

Not-So-Friendly Fire: The Elusive Nature of Autoimmunity

Autoimmunity is a devastating contradiction of human biology in which the very system that exists to protect an individual from illness launches an attack against that person’s own body. While some autoimmune diseases can be accurately diagnosed by identifying particular biological markers in a patient’s blood or tissues, many patients who suffer from autoimmunity gradually present an array of symptoms and test negatively for specific disease-markers, making their illness very difficult to diagnose.

In the last decade, physicians and researchers have shed light upon a tragic and deceptive manifestation of autoimmunity—anti-NMDA Receptor Encephalitis—in which self-reactive (auto-) antibodies cause inflammation of the brain. This syndrome provides an example of the immense challenge of diagnosing an autoimmune disease in that it presents clinically in stages as a psychiatric disorder. Patients who suffer from anti-NMDAR encephalitis develop symptoms of acute psychosis, including anxiety, fear, delusions, mania, and paranoia. As a result, the first care-providers that these patients see are often psychiatrists rather than neurologists, which unfortunately can allow the syndrome to worsen before a diagnosis is made.

The elusive nature of autoimmune diseases that anti-NMDAR encephalitis exemplifies raises an important topic of discussion regarding the common approach to treating and diagnosing cases of autoimmunity. Having witnessed a great deal of suffering from undiagnosed autoimmunity in my own family, I have become a strong proponent for an interdisciplinary approach to patient care in medicine. While it is undoubtedly an immense feat, I believe it would be of great value for care-providers in different specialties to collaborate more extensively through direct communication, rather than indirectly via their patient. In doing so, physicians might be able to establish a more comprehensive patient profile that leads to more efficiency in patient diagnosis.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158385/pdf/nihms316554.pdf

Fat Hormones Increase Running!

Run Forever Thanks to Your Fat Hormones!

                This article tells a story of a lady named Bethany Brookshire who noticed her amazing runners high while running the Navy-Air Force half marathon! There have been several studies done to try and understand what exactly is going on in the brain during this experience. They found that chemical components such as endorphins and cannabinoids increase in the brains of athletes while running, which gives this happy high that runners explain they feel. But, endorphins and cannabinoids are not the only thing that can be responsible for this great feeling.

 

 

Leptin is a fat hormone that regulates eating but also affects movement and running. Tests were done on rats to see how levels of leptin would affect eating, but nothing happened. What they did notice was that the mice ran, and they ran a lot when the levels of leptin were low. Leptin is responsible for the motivation to start running which is really important! In order to keep running you have to be motivated to start in the first place!

                Obviously Leptin does not work by itself as I mentioned earlier that other chemicals such as endorphins and cannabinoids play a key role in creating the high while running. It is unsure exactly how all of these work together, but all of them are necessary in creating this indescribable high while running!

Reference:

Brookshire, B. (n.d.). How a fat hormone might make us born to run. Retrieved December 1, 2015, from https://www.sciencenews.org/blog/scicurious/how-fat-hormone-might-make-us-born-run

Jumping & Landing Mechanics - Become More Functional!

I have been working in the sports industry as both a basketball coach and performance enhancement specialist for about three years now. One of the things we notice most at my training facility is the lack of functional movement in athletes, especially middle school/high school athletes. Something about hitting the age where your muscles begin to tighten and you are suddenly not as flexible as before hits them hard. Working to help them understand their bodies and why we should jump, run, and bend certain ways is critical to ensuring they will not only progress in their athletic endeavours, but maintain a healthy and functional lifestyle in the future. By allowing yourself to continue performing an activity that is damaging your body; you are setting yourself up little by little for an injury to occur.

The study I found demonstrated this lack of functional movement by observing a group of 18 year old male athletes performing one legged jumps and landing in different directions. The participants jumped 30 cm in four different directions and through these movements, meanwhile, their hip, ankle, and knee flexion angles were measured. Similar to what I have been seeing in my own work, they found that the majority of the participants had a stiff landing with very little hip and knee flexion. Should this trend continue, these athletes will continually put pressure on joints unnecessarily and leave them at risk for injury.

The researchers highly recommend that sports clinicians and athletes should learn to land softly by increasing both hip and knee flexion; at the same time learning to become more functional. It has been proven that landing softly will distribute the force of your body coming down much more evenly and reduce the risk of injury greatly.

Identifying potential risks for injuries is something all health care providers should be able to do. From reading an EKG to watching a patient walk; being able to identify a problem and give a solution that can increase the quality of that patients life is what our jobs are all about.


Sinsurin, K., Vachalathiti, R., Jalayondeja, W., & Limroongreungrat, W. (2013). Different sagittal angles and moments of lower extremity joints during single-leg jump landing among various directions in basketball and volleyball athletes.Journal of physical therapy science, 25(9), 1109.

Your Health Food might be Unhealthy for Me

We can all agree that what we like to eat is a personal preference, and we also generally know what is a healthy food and what isn’t.  However, in the most recent issue of Cell two Israeli research teams have demonstrated that there can be significant physiological difference between individuals when eating the exact same food.

As we all know, after you eat a meal, your blood glucose levels go up. Using a derived glycemic index we are able to guesstimate a person’s post-prandial glycemic response (PPGR). These glycemic estimations are based entirely off the innate, chemical makeup of the food you’re eating and those estimations are what you use to calculate your daily food intake. What researcher David Zeevi found, along with another team, is that various factors such as genetics, activity levels, insulin sensitivity, and intestinal microbiota had varying effects on PPGR levels in individuals eating the exact same food.

Over the course of a week, and with 800 participants, Zeevi’s research teams were able to collect 1.6 million measurements of interstitial glucose levels and subsequently devise an analytical algorithm to determine the difference in PPGR between individuals eating the same food. One example is of a woman, who after eating a tomato (undeniably a healthy food) had her blood glucose rose to an unhealthy level, while in other participants there was no dangerous spike. This example, along with many more, demonstrated that while you can make an estimate of a food’s effect on an individual, there are far more factors in play than just what chemicals are present. This research shows that in order to accurately determine what foods are best for you, a personalized diet that accounts for individual glucose response to foods is needed to reduce your risk of high post meal glucose levels.

http://dx.doi.org/10.1016/j.cell.2015.11.001

Go Ahead and Turn Up Your Music

As most of us know, blasting loud music can damage your hearing, but researchers at Rockefeller University may have found the solution. But first, lets have a small refresher on how loud music can damage our ears.

Sound waves are a form of energy that are collected and funneled by our auricles and travel down our external auditory canal to strike the tympanic membrane. The vibrations from the tympanic membrane in turn vibrate the auditory ossicles and transfer the energy to the oval window. The oval window then transmits the pressure waves down into the fluid filled, scala vestibuli. Finally, the waves go through the cochlear duct to vibrate the basilar membrane and cause the hairs on inner hair cells to move.  Movement of those hairs cells causes neurotransmitters to be released and an action potential is generated. That action potential is transmitted to the brain where it makes sense of those sweet Bieber tunes.

The one downside to this wonderful system is that loud noises, prolonged exposure to loud music, and just growing old can damage or destroy those inner hair cells. Here’s the kicker; they don’t grow back and once they’re gone and you’ll be left with only the memories of sounds.

This is where Ksenia Gnedeva’s research at Rockefeller University can save the day.  Her team discovered two genes that are crucial for hair cell growth and proliferation within the utricle of newborn mice. Newborn mice, like newborn people, also stop producing inner ear hair cells just after birth. They found that those genes, Sox4 and Sox11,  (both transcription factors) were down regulated at the end of hair cell proliferation. The next question then is what happens when you up regulate them in adult mice? Well, Ms. Gnedeva’s team did just that and found they were able to not only restore hair cell function but also to generate new hair cells. These are of course in vitro studies but the findings are very promising for all of us on the road to hearing loss and those who are deaf.

http://www.pnas.org/content/112/45/14066

http://www.neuroscientistnews.com/research-news/discovery-genes-involved-inner-ear-development-hints-way-restore-hearing-and-balance