Viagra: The Little Blue Wonder Pill

If you’ve ever watched TV, I’m sure you have heard the all too familiar, “Why let erectile dysfunction get in your way. Talk to your doctor about Viagra today; 21 million men already have.” Viagra, Sildenafil, works to enhance the erectile response in sexually stimulated males. As we learned in class, a male must be under parasympathetic nervous system control to allow increased blood flow to the penis, but how does this work? When a male becomes sexually aroused, nitric oxide (NO) is released within the penis, stimulating the production of the messenger cyclic guanosine monophosphate (cGMP), which causes relaxation of smooth muscles (1). Arteries of the penis then dilate, allowing for increased blood flow, and ultimately engorgement, an erection. Sildenafil helps in erectile dysfunction, because it maintains cGMP levels within the smooth muscles. Sildenafil’s affect on cGMP level is an important characteristic that has been continually used to find new treatment options for a variety of medical problems.

As if helping erectile dysfunction was not enough, Mitschke et al. found that Sildenafil, through the actions of cGMP, can promote weight loss in mice (3). Sildenafil was shown to increase browning of white adipose tissue, which occurs when white adipose tissue takes on phenotypic characteristics of brown fat cells. White adipose tissue (WAT) serves as a place of triglyceride storage, whereas brown adipose tissue (BAT) metabolizes fatty acids to release energy as heat. Inducing browning of WAT could ultimately allow weight loss, since an increased ratio of BAT to WAT would promote increased energy expenditure. This weight loss potential of Sildenafil is a promising discovery for the treatment of obesity.

Interestingly, Sildenafil has also been shown to reverse the symptoms of nephrogenic diabetes insipidus (release of large quantities of dilute urine), and has been used in the treatment of pulmonary hypertension in pregnant women (2,4). Sildenafil’s affect on cGMP level is the key to such treatments. The role of cGMP in many different areas of the body supports the importance of second messenger systems we have studied in class.

1. British Pregnancy Advisory Service. (2010). Viagra (Sildenafil) Facts [Online]. BPAS. http://www.bpas.org/bpasman/Viagra [27 Oct. 2013].

2. Maharaj CH, O’Toole D, Lynch T, Carney J, Jarman J, Higgins BD, Morrison JJ, Laffey JG. Effects and mechanisms of action of sildenafil citrate in human chorionic arteries. Reproductive Biology Endocrinology 7: 34, 2009.

3. Mitschke MM, Hoffmann LS, Gnad T, Scholz D, Kruithoff K, Mayer P, Haas B, Sassmann A, Pfeifer A, Kilic A. Increased cGMP promotes healthy expansion and browning of white adipose tissue. The FASEB Journal 27(4): 1621-1630, 2013.

4. Sanches TR, Volpini RA, Shimizu MHM, de Braganca AC, Oshiro-Monreal F, Seguro AC, Andrade L. Sildenafil reduces polyuria in rats with lithium-induced NDI. American Journal of Physiology Renal Physiology 302: F216-F225, 2012.

The truth about the HCG diet

Human chorionic gonadotropin (hCG), also known as the "pregnancy hormone" is secreted by the syncytiotrophoblasts after conception to maintain the corpus luteum during pregnancy which in turn secretes progesterone during the first trimester of pregnancy to sustain the fetus. During pregnancy, hCG almost completely controls the woman's metabolic function (APA 2013).

Not only is hCG known for its role in pregnancy, but it has been recognized as a popular method for rapid weight loss. In non-pregnant individuals, it has been suggested that high levels of hCG will increase metabolism and lead to weight loss (JCMG 2012). The idea behind the hCG diet is that administration of hCG in conjunction with a low calorie diet will trick the body to release your stored fat and burn it through a process known as lipolysis. Taking hCG triggers the hypothalamus to use your stored, "unwanted" fats for its main source of energy.

From personal knowledge, the hCG diet consists of administering hCG either through injections or sublingually in conjunction with a 500 calorie per day diet. These calories must come from two six-ounce servings white meat, two to three pieces of fruit or vegetables and one cup of green tea or coffee in the morning. Today, a very low calorie diet is defined at 800 calories per day or lower which alone would result in very rapid weight loss (Salomon 2011). In order to function properly, your body burns on average 2100 calories per day--this does not include additional calories burned from daily activities such as walking, working out and/or simply moving around. In order to lose one pound of fat, you need to burn 3,500 calories. If you were to consume a 1200 calorie diet, you would roughly burn 6,300 calories per week. By this alone, you would lose almost 2 pounds per week. Keep in mind, this number only reflects what your body burns just to maintain your body's basic metabolic needs. Potentially, you could lose much more weight each week by altering the energy balance of your body (decrease calories consumption and increase calorie expenditure).

Research has proven the weight loss effect on the hCG diet is due to the dramatic reduction in calories and that hCG has no measurable effect on weight loss. HCG has been proven to have no value as a means to managing obesity and the diet has been "thoroughly discredited and thus rejected by the majority of the medical community" (Haupt 2011). Which is why it was no surprise that I was unable to find one medical association to endorse hCG as a weigh loss aid. Since the 1970s, the FDA has long maintained that hCG is ineffective for weight loss (Gavura 2013). Dr. Perter Cohen, an assistant professor of medicine at Harvard Medical school, called the hCG diet "reckless, irresponsible, and completely irrational [. . .] of course you can lose weight on it, but that's mainly because you're hardly consuming any calories. And any benefit is not going to last" (Haupt 2011).

Common knowledge is that if you don't eat, you lose weight. How is the hCG diet any different from what we already know? All the hCG diet consists of is a very low calorie diet and an unnecessary shot, which no one likes to administer themselves. Anyone who is malnourished is going to lose weight. Plain and simple. Wouldn't you rather lose weight the right way by exercising and eating healthy rather than use an exogenous source as a means to lose weight?

References:

Haupt A. Mar 2011. HCG Diet Dancers: Is Fast Weight Loss Worth the Risk? US News. Available at: http://health.usnews.com/health-news/diet-fitness/diet/articles/2011/03/14/hcg-diet-dangers-is-fast-weight-loss-worth-the-risk?page=2

Human Chorionic Gonadotropin (hCG); Pregnancy Hormone. American Pregnancy Association. Jan 2013. Available at: http://americanpregnancy.org/duringpregnancy/hcglevels.html.

Salomon J. 2011. What is hCG and How Does it Result in Rapid Weight Loss. Plastic Surgery and Med Spa. Available at: http://www.drjsalomon.com/pdf/hcg_q_and_a.pdf

Why You Should Avoid Using hCG for Weight Loss. 2012. Jefferson City Medical Group. Available at: http://www.jcmg.org/jcmg.nsf/web/Why-You-Should-Avoid-Using-HCG-for-Weight-Loss

Gavura S. July 2013. The HCG Diet: Yet another ineffective quick fix diet plan and supplement. Science Based Medicine. Available at: http://www.sciencebasedmedicine.org/the-hcg-diet-yet-another-ineffective-quick-fix-diet-plan-and-supplement/

Blondes may have more fun, but do redheads feel less pain?

Hair color has always had interesting stereotypes associated with it. For instance, almost everyone has heard a hundred times that blondes have more fun, or they've heard the (untrue) joke about "dumb blondes" and the things they do. Brunettes have the "girl next door" stereotype, or they're thought of as clever and confident. Redheads are typically thought of as hot-tempered, and recently, many people have been quite vocal about how redheads have a higher pain tolerance than most people. The question is, is any of this true? After all, many of us grew up hearing various nursery rhymes and old wives' tales that have no basis in reality. Chocolate doesn't lead to acne (unless you rub it all over your face), and despite making many silly faces you never see anyone walking around with their face permanently frozen in a goofy expression. However, recent medical discoveries may show that there's some basis to at least some of the stereotypes behind hair color. The assertion about redheads' pain tolerance is actually one that may be founded in medical science. Being a redhead is a genetic mutation that results in a non-functional melanocortin-1 receptor (MCR-1) (Mogil et al. 2005). This change in receptor results in an overexpression of pheomelanin, which results in red hair color (Liem et al. 2005). In addition to having control over the pigmentation of redheads, it also has interesting affects on pain reception response to commonly used anesthetics. MCR-1 has an effect on the perception of κ-opioid and μ-opioid receptor-mediated anesthetics (Mogil et al. 2005). This mutation in the receptor has interesting effects on the pain tolerance of redheads and their response to analgesics. Rumor has it that redheads have higher pain tolerance than people with other hair colors. However, when this was actually put into practice, red-headed women were found to have about the same current perception, pain perception, and pain tolerance thresholds as dark-haired women (Liem et al. 2005). However, it gets interesting when redheads' other tolerances are compared to those of dark-haired people. Redheads have more perception of pain associated with cold, pain associated with heat, and they also have a lower cold perception threshold (Liem et al. 2005). However, their mutated receptors also have a strange effect on how analgesics work on them. Lidocaine is an example of one of the drugs whose interaction is changed by this mutated receptor. When injected, subcutaneous lidocaine proved less effective in redheads as compared to people with dark hair, as redheads reported pain from 2000 Hz stimulation at 11.0 mA, while women with darker hair reported pain at >20 mA (Liem et al. 2005). In another study, redheads and brunettes were sedated with sevoflurane and then the sedation was maintained with desflurane, and then a noxious stimulus was administered through intradermal needles (100 Hz, 70 mA) (Liem et al. 2005). The effect of the sedation was monitored through the person's response to the stimulus: if the person moved, then the anesthetic was deemed ineffective and the dosage of desflurane was increased, and if the person did not move in response to the stimulus four times, then the sedation was deemed effective and the dosage was noted (Liem et al. 2005). Redheads needed higher desflurane leves in order to stay sedated (Liem et al. 2005). How is this at all significant in any way (in any other way besides confirming or debunking an old wives' tale)? Lidocaine is typically used topically as a method of sedation (Smith and Wilson 2013). Topical sedation typically allows the patient to remain awake during the procedure, or it can be used in addition to injectable anesthetic. The use of lidocaine is particularly important in surgeries where it is important to be conscious while the procedure is going on. For example, in a recent case study a woman presented with an endotracheal mass that caused breathing problems (Loizzi et al. 2013). In this case, lidocaine was an essential part of the procedure because it allowed the movement of the vocal cords during the surgery and thus they were not damaged in the procedure (Loizzi et al. 2013). It is important for surgeons and physicians to keep in mind that redheads have a higher tolerance for pain medication such as lidocaine so that there are no cases of the patient experiencing discomfort during a procedure. Old wives' tales may not make a lot of sense sometimes, but at others they have a basis in truth. Redheads do have an increased tolerance to anesthesia, but are more susceptible to pain from heat or cold. It is important for physicians to stay aware of groups that may experience pain during surgery if inadequately sedated so that patients remain satisfied with their care. References Liem EB, Joiner TV, Tseuda K, Sessler DI. 2005 Mar. Increased sensitivity to thermal pain and reduced subcutaneous lidocaine efficacy in redheads. Anesthesiology. 102(3): 509-514. Liem EB, Lin C-M, Suleman M-I, Doufas AG, Gregg RG, Veauthier JM, Loyd G, Sessler DI. 2004 Aug. Anesthetic requirement is increased in redheads. Anesthesiology. 101(2): 279-283. Loizzi D, Sollitto F, De Palma A, Pagliarulo V, di Giglio I, Loizzi M. 2013 Mar. Tracheal resection with patient under local anesthesia and conscious sedation. The Annals of Thoracic Surgery. 95(3): e63-e65. Mogil JS, Ritchie J, Smith SB, Strasburg K, Kaplan L, Wallace MR, Romberg RR, Biji H, Sarton EY, Fillingim RB et al. 2005 Jan. Melanocortin-1 receptor gene variants affect pain and μ-opioid analgesia in mice and humans. Journal of Medical Genetics. 42:583-587 doi:10.1136/jmg.2004.027698 Smith BC and Wilson AH. 2013 Jun. Topical versus injectable analgesics in simple laceration repair: an integrative review. The Journal for Nurse Practitioners. 9(6): 374-380.

Triathletes Train to Feel less Pain!

            I am a newly-born triathlete, and one of the most common comments I get from people is “Girl you are crazy, why do you enjoy pain?!” and my response always is “because it hurts so good”… but why? Why is it that only 1% of the population WANTS to endure through the pain of swimming for miles, then biking for twice as many, and then running?

 A new study confirms this interesting conundrum by concluding triathletes in fact can withstand more pain than the average human being. Why is this important? Researchers are now using this information to create treatments and therapies for people with chronic pain. Here’s how it works together.

In this study, a small population of 36 participants were pooled together. Of the 36, 19 were seasoned/veteran triathletes (10 men, 9 women) and 17 were non triathletes but active exercisers (runners, swimmers, lifters etc) (7 men, 10 women). Each person was then tested on their sensitivity to increasing intensity of heat and cold temperatures as well as length of time the temperature was endured. Interestingly enough, the pain threshold for both cold and hot was not significantly different between the triathletes and non-triathletes but the length of time endured was. Triathletes were able to withstand the extreme temperature for a significantly greater duration of time compared to the non-triathletes.

How could this be? There are many possible explanations. It is hypothesized that triathletes experience repetitive pain in different forms throughout training and races. This continual pain input also stimulated the area of the brain stem that is responsible for pain inhibition that over time would result in pain inhibition in a variety of forms that include emotional and physical pain (including pain proprioceptors). To assist with the physical changes that may be occurring with the pain receptors are the physiological mechanisms that occur from the reward achieved at the end of a training session or competition. The “euphoric” or “runners high” as we like to call it is the interaction between this physical pain inhibition and an increase in dopamine in reward pathways. Together, this enables triathletes to associate activities such as this with the intense pleasure rather than the pain. So it in the end it actually makes sense how training and competitions might “hurt so good”. All of these theories have not been officially tested, but the background is highly supportive of these mechanisms and experiments are looking promising.

These hypothesis and the results from this study indicate that this could be an important breakthrough in chronic pain management. An inspiring tale in this article talks of how she became a professional triathlete all while living with SEVERE CHRONIC rheumatoid arthritis, that at one point was so severe she could not get out of bed. She said that training and working with physical therapists forced her to learn the fine line between pain that she could push through and pain that was indicative of a potential injury. Don’t worry though; health specialists are going to start telling those of you with chronic pain to all start training for a triathlon! Instead, researchers are now aiming to study therapeutic techniques and exercise programs aimed to facilitate the resilience that is found within triathletes and to ultimately decrease the effects of their everyday pain without popping another pill! 

References 

http://www.nbcnews.com/health/its-true-triathletes-are-tougher-rest-us-8C11391282

http://journals.humankinetics.com/tsp-back issues/tspvolume22issue3september/bouncingbackfromadversityathletesexperienceofresilience

http://www.telegraph.co.uk/sport/10363906/Triathletes-push-themselves-because-they-feel-less-pain.html

Emotional Shivers: Goose bumps arising from Awe & Emotions

Regis University has been very fortunate in having great speeches delivered here on our campus. These speeches include Pope John Paul II & former President Bill Clinton speaking in 1993, Father Greg Boyle speaking this month as the founder of Homeboy Industries, which helps former gang members get new jobs, and we had a 50th anniversary tribute to Dr. Martin  Luther King Jr.'s "I Have a Dream" speech. If you have ever witnessed a very powerful or moving speech, there may be one physiological activity you may be experiencing besides shedding a few tears: forming goose bumps.

Goose bumps, known as piloerection, is when the muscles beneath the skin of a mammal contract, causing the skin to cause bumps and hair on the skin to rise stimulated by the sympathetic nervous system. When goose bumps form on the skin, we usually think they are formed because they are freezing on a cold winter day or when you are watching a frightening horror film during Halloween. However, there are some experiences we are a part of that give us the "chills and shivers down our spine" that are usually felt when we are in awe of something. These goose bumps that are caused by awe inspiring events have been found to have been formed by evolutionary precursors. These goose bumps have evolved to be from awe inspiring experiences today due to the evolutionary past from the idea of adapting to hierarchy status. The mechanism was formed by maintaining hierarchy status by past individuals of a higher status installing fear into individuals of a lower social status. This could show a correlation between goose bumps from awe-inspiring events and having fear in certain situations.

Goose bumps have also been found to be associated with envy. When we witness an event that has put us in awe, there has been a reaction to cause the person to go from full of awe to becoming envious. This envious response comes from our reaction to the physiological response from our goosebumps. The evolutionary response from goosebumps can result in two different outcomes: praise and awe in an amazing experience or turning that to a somewhat negative response of envy and jealousy of someone from a higher social status. Although both of these responses of awe and envy were found, it is more likely that an individual will find awe in a powerful and moving experience from someone than turning the powerful experience into envy. This unique physiological response of goose bumps show an interesting evolutionary transformation from warming up the body physically, to also being an emotional and mental stimulus from a powerful and moving experience.


Refernces:

Schurtz, D. R., Blincoe, S., Smith, R. H., Powell, C. A., Combs, D. J., & Kim, S. H. (2012). Exploring the social aspects of goose bumps and their role in awe and envy. Motivation and Emotion, 36(2), 205-217.

Keltner, D., & Haidt, J. (2003). Approaching awe, a moral, spiritual, and aesthetic emotion. Cognition and Emotion, 17, 297-314

Legalization of Marijuana: A Good Idea?

Marijuana, commonly referred to as 'weed', was a hot topic of debate during our previous elections as to whether or not it should be legalized. Many arguments in support of the legalization often compare the effects of this drug to the effects of alcohol on our system in that when under the influence, it is far less dangerous than alcohol; particularly when used in conjunction with operating a vehicle. However, is this drug truly less dangerous than the legalized drug alcohol? Further, is our society aware of the neurological and biological effects that this drug causes? Many discussions with the public discuss the 1960s and the 1970s when weed was extremely common, particularly during political movements. However, it is not accurate to compare the 'weed of the 60s and the 70s' to the 'weed of today,' because the potency of this drug, in particular the concentration of the active ingredient THC has substantially increased since the 1960s. In the 1960's the concentration of THC was approximately 1%; however, by 2011 this potency increased to a staggering 9.6% THC content. Even more alarming, is that in 2011 there was access to concentration levels up to 20%! Further, if you compare 1995 to 2000, we see an increase in THC related emergency room visits by 120%, and this trend is continuing! Further, many studies on human performance while under the influence of this drug have previously been on relatively low potency; however, with this tremendous increase in potency of THC in the past 50 years, it has become appropriate to perform studies at high-potency levels. Research on high-potency marijuana suggest a consistent impairment of executive functioning along with motor control and lasted up to six hours after the smoking of this drug occurred! Therefore, is the legalization of this drug, and I repeat DRUG, a good move? At the neurological level, and the only level I feel should be taken into consideration, I would have to argue against the legalization of marijuana. References: Meyer, J. S., & Quenzer, L. F. (2005). Psychopharmacology: drugs, the brain, and behavior. Sunderland, Mass.: Sinauer Associates, Publishers. Ramaekers, J. G., Kauert, G., van Ruitenbeek, P., Theunissen, E. L., Schneider, E., & Moeller, M. R. (2006). High-Potency Marijuana Impairs Executive Function and Inhibitory Motor Control. Neuropsychopharmacology, 31(10), 2296-2303.

Present and future therapies for Parkinson's disease: A hopeful future

Those of us in the Biomedical Science Master’s program at Regis University where this post originates have spent the first quarter of the semester looking at lysosomal storage disorders including Parkinson’s disease.  Shachar et al. (2011) describes a causal relationship between these two diseases where mutations in the glucocerebrosidase gene caused by Parkinson’s disease results in an enzyme deficiency consistent with Gaucher disease, the most prevalent lysosomal storage disorder.  The main focus of our investigation of lysosomal storage disorders including Parkinson’s disease has been on gene therapy trials using murine models.  The current success in treating these diseases in the murine model and non-human primates is high and promising, however there is a large contrast in the success of treating these diseases in human subjects.  

Parkinson’s disease is the second most prevalent age related neurodegenerative disease with an average onset occurring close to 60 years of age, although early onset can occur.  The symptoms of the disease most commonly include tremor, rigidity, bradykinesia, and several non-motor symptoms more commonly associated with cognitive functioning (Douglas 2013).  Rush University Medical Center (2013) describes two methods currently being used for treating Parkinson’s disease in humans which include symptomatic therapies and protective therapies.  Symptomatic therapies focus on supplementing dopamine because the natural release of dopamine by cells is affected by the disease, many drugs fall into this category and have been available for many years to treat individuals with Parkinson’s disease.  Protective therapies work to delay the degenerative processes occurring in the brain and are largely focused on gene therapies, these treatments are currently only available to human participants in a handful of clinical trials. 

The success of treating Parkinson’s disease has recently hit the media with the full time return of Michael J. Fox to our television sets who postponed his acting career in 2000 because of his worsening symptoms of Parkinson’s disease.  His doctors have recently been able to find the right balance of medications and dosage levels that work for him.  While the exact treatment regimen used by Michael J. Fox is between him and his doctors, it is most likely through the use of current symptomatic therapies.  It is important to note that symptomatic therapies are not a cure for Parkinson’s disease and they are only able to mask the symptoms of the disease for some time. 

Symptoms of Parkinson’s disease are typically measured by the Unified Parkinson’s Disease Rating Scale, UPDRS (Kordower and Bjorklund 2013), which rates symptoms from zero to four with a score of zero representing normal functioning and a score of 4 representing severe impairment.  This rating scale can be used to measure both “on” and “off” scores.  “On” time is considered the period where therapies are successful in treating the symptoms and improving motor control with the right balance of dopamine supplemented to the system.  “Off” time is considered the period where the amount of dopamine being supplemented is out of balance and symptoms worsen, this can occur during the initial assessment of the appropriate dosage of dopamine which is highly variable per individual and as the effects of the drug where off which will typically occur after some time of the drug being effective.  Current symptomatic therapies are continually being improved to increase the amount of “on” time an individual experiences from the drugs and dosages are continually monitored by the prescribing doctors.

The most common symptomatic therapy is focused on increasing dopamine production within the nigral neurons and is accomplished through drugs like Levodopa and more often Levodopa in combination with Calbidopa (Douglas 2013).  Levodopa targets the remaining nigral neurons that are still exhibiting proper functioning to increase dopamine production. The first two years of Levodopa therapy on treating Parkinson’s disease shows large success in controlling the symptoms of the disease, however after this time the drug can show a wearing off effect and symptoms once masked by the therapy tend to return (Rush University 2013).  Following the wearing off effect of Levodopa dopamine agonist, Pramipexole and Ropinirole, along with COMT inhibitors, Entacapone and Tolcapone, can be used to increase delivery of Levodopa to the brain and decrease the breakdown of Levodopa (Rush University 2013).  Other symptomatic medications are available that work through similar mechanisms.

A second symptomatic treatment option for individuals with Parkinson’s disease is deep brain stimulation, referred to as DBS.  While the exact target within the brain is still widely debated, DBS is a surgical treatment that places an electrical wire into the brain tissue and high frequency stimulation is delivered through a small battery pack that is placed under the skin near the thoracic cavity (Rush University 2013).  DBS works by inhibiting glutamate release within the cells of the subthalamic nucleus (Douglas 2013).  This treatment is most often reserved for those individuals who show little improvement with symptomatic drug therapies.  While both DBS and combination drug therapies can work well to reduce symptoms of the disease for some time the future for treating Parkinson’s disease lies with protective therapies that aim to actually stop and reverse the effects of the disease on neurons within the CNS.

Current research being conducted on protective therapies is focused on gene therapy and stem cells.  The association of many mutated genes with Parkinson’s disease has been researched and includes, among many others, the PARK1 locus which encodes for alpha-synuclein, several autosomal recessive genes and proteins including Parkin, PINK1, DJ-1, and an autosomal dominant gene, LRRK2, which is the most correlated gene mutation found within individuals with Parkinson’s disease (Douglas 2013).  Protective therapies aim to stop and reverse the damage to the brain caused by Parkinson’s disease through introducing new stem cells to the affected areas of the brain or by introducing viral vectors that can deliver new functioning genes.  Although these therapies show positive clinical significance in the lab with both mice, rat, and non-human primate models, trials on humans have proven to be less effective.  The discrepancy of the effectiveness of treatment is related to both the blood brain barrier and general difficulties accessing the affected areas of the brain while delivering the therapy.

Several studies investigating the effects of glial cell line derived neurotrophic factor, GDNF, have found that protection and restoration of neurons in animal models was possible.  Clinical trials in humans were conducted by Nutt et al. (Kordower and Bjorklund 2013) and used infusions of recombinant GDNF proteins that were directly administered into the lateral ventricles through mechanical pumps. However the double blind study did not produce any significant results and a number of side effects of the treatment were reported.  A postmortem autopsy revealed that the GDNF was unable to diffuse out of the lateral ventricles and therefore unable to have an effect.  A second open label study used a similar method but injected the GDNF directly into the postcommissural putamen which showed promising results in phase I clinical trials and improvement of motor symptoms by about 33% were seen.   PET scans revealed increased fluoradopa uptake after about a half year of treatment.  However when taken to phase II clinical trials no significant benefit was seen and antibodies towards GDNF were found along with an identified risk for cerebellar damage that caused early termination of the trial (Kordower and Bjorklund 2013).

Other methods of delivery of GDNF proteins have been developed but have been yet to see human trials.  These include genetically engineered cells that are encapsulated in a semi-permeable membrane that can be delivered to the brain and avoid detection by the immune system while delivering therapeutic agents to the cell (Kordower and Bjorklund 2013).  Brendan Harmon from Northeastern University (Science Daily 2013) has also developed an intranasal approach for delivery of GDNF to the brain that is able to pass the blood brain barrier that may create a noninvasive method for delivery of therapeutic agents to the brain.  This method has proven to be successful in rat models but has not yet seen human trials (Science Daily 2013).

Other human trials investigated the use of adeno-associated virus vectors to deliver NTN to the brain, NTN is similar to and works in the same way as GDNF (Douglas 2013). This AAV2-NTN technique showed an 80% improvement level that lasted for up to 12 months following administration in Rhesus monkeys.  However when taken to clinical trials in humans complications in the delivery to the brain during surgery resulted in one death and other individuals who underwent successful surgeries showed several major side effects.  Despite these complications results were promising and this method was taken to a phase II clinical trial but again no significant results were found using human subjects after one year (Douglas 2013).  A follow up study did find significant results after 18 months which may suggest that the procedure was a success but may need more time to work and show corrections within human subjects, further trials with longer follow up times is under way. 

Within the dopaminergic biosynthetic pathway dopamine is converted to another molecule known as AADC and AADC has been used therapeutically to reduce Parkinsonism symptoms.  Adeno associated vectors using AADC have reached Phase I clinical trials and motor improvements up to 75% have been seen (Douglas 2013).  Outweighing the clinical success of the AAV-AADC many patients within the sample developed brain hemorrhages which were related to the surgery delivering the AAV.  A follow up to this particular study was performed and it was found that the positive effected waned after a one year period (Douglas 2013).

AAV vectors using CERE-120, which encodes for Neurturin, also known as NTRN, have also reached Phase II trials in humans based upon highly positive results in monkeys (Kordower and Bjorklund 2013).  Phase I trials using this vector again showed positive results although no significant difference was found to exist between low and high dosage groups but very few side effects were reported.  Given the low amount of side effects the AAV-CERE-120 vector reached Phase II clinical trials but again showed no significant results with only limited clinical benefit (Kordower and Bjorklund 2013).  Interestingly a follow up study did show more significant results after 15 and 18 month periods again suggesting that longer treatment follow ups may be necessary.

The first successful Phase II clinical trials seen in humans was with a gene therapy known as NLX-P101 which significantly reduced motor symptoms (USA Today Magazine 2012).  This treatment used glutamic acid decarboxylase, known as GAD, was injected into the brain using a virus vector.  GAD is able to produce GABA which is an inhibitory neurotransmitter that is able to decrease the firing of neurons.  So while dopamine loss within the brain is most often associated with the major mechanism of the symptoms of Parkinson’s disease a decrease in GABA is also seen.  By reintroducing GABA into the brain the dysfunction of the circuitry responsible for motor coordination can also be reduced (USA Today Magazine 2013).

In summary new methods for treating Parkinson’s disease are being developed and tested and the results are promising.  Both mouse and rat studies along with studies on non-human primates have produced significant data that at the very least gives hope in reducing and eliminating the effects of Parkinson’s disease on the brain.  However transferring the success of these trials to human trials have proved to be difficult for several reasons including the inability of therapeutic agents to cross the blood brain barrier and difficulties of surgical methods used to directly deliver the therapeutic agents to the correct regions of the brain.  The future for an individual diagnosed with Parkinson’s disease is getting better every day, with increased efficacy of symptomatic drugs that able to mask the symptoms for several years and the advancement and success of therapeutic drugs in correcting the effects on the brain gives hope that someday a cure for Parkinson’s disease may be found.  

References

Douglas MR.  2013.  Gene therapy for Parkinson’s disease.  Expert Rev Neurother.  13(6): 695-705

Federation of American Societies for Experimental Biology.  2013.  Science Daily.  A noninvasive avenue for Parkinson’s disease gene therapy.

Kordower JH, Bjorklund A. 2013. Trophic factor gene therapy for Parkinson’s disease.  Movement Disorder Society. 28(1): 96-109

Rush University Medical Center.  2013.   Clinical Services Parkinson’s disease.  Chicago

USA Today Magazine.  2013.  Gene therapy reverses symptoms.  The Society for Advancement in Medicine.  McLean, VA.

    

Procrastination and Executive Functioning - a Correlational Analysis

The act of procrastination dates itself back to the ancient civilizations. The Greek poet Hesiod, acknowledging the detriments of procrastination, cautioned not to "put your work off till tomorrow and the day after." Roman consul Cicero condemned procrastination as "hateful" in regards to political affairs. Even the great artist and inventor, Leonardo da Vinci — the genius who changed the world — was known to be a chronic procrastinator. These are just some of the recorded instances of procrastination in history; for all we know, anyone could have been a procrastinator. They'd just never admit it. 

For us students, the temptations to procrastinate are high given the alternative of a stressful assignment. Procrastinating could represent our way to avoid adverse effects of stress and high emotions, which in turn affects our health and mental states. This is one of the ways that we self regulate our impulses, emotions, and desires. But the inability and deficiency to do so effectively would create a very intense and disadvantageous situation for us. Chronic procrastination, therefore, causes emotional distress and regulatory failures. In a study by the Case Western Reverse University, self-control was found to break down under emotional distress. Much like how a person will overeat in order to reverse the effects of a bad mood, procrastination is a destruction of our resistance to short term gratification. The mechanism between regulation and distress aren't exactly clear, but there are neuropsychological theories to explain the correlation. 

Laura Rabin of Brooklyn College recognized and ascribed the frontal systems of the brain to be related to self regulation, which comprises itself of executive functional behaviors. These behaviors include planning, self-control, and problem solving. Rabin and her colleagues examined 212 students and observed first their level of procrastination, and then the correlation to nine clinical subdivisions of executive functioning: impulsivity, self-monitoring, planning and organization, activity shifting, task initiation, task monitoring, emotional control, general orderliness, and working memory. What she found was that procrastinators assigned themselves to all of the nine subscales according to a BRIEF-A (Behavior Rating Inventory of Executive Functioning - Adult version) self report, indicating that many dysfunctional behaviors of executive functioning leads itself to procrastination. Of course, all of this is correlational rather than causational, and done relied itself on self reports. Still, this study might indicate that procrastination is an expression of subtle executive dysfunction. 

References:

Rabin, L., Fogel, J., Nutter-Upham, K. 2011. Academic procrastination in college students: The role of self-reported executive function. Journal of Clinical and Experimental Neuropsychology. 33(3): 344-357.

Tice, D., Bratslavsky, E., Baumeister, R. 2001. Emotional Distress Regulation Takes Precedence Over Impulse Control: If You Feel Bad, Do It!. Journal of Personality and Social Psychology. 80(1): 53-67. 

Music to My Ears: Soothing Sounds Can Reduce Anxiety

            Music therapy is not a new thing.  Aesculapius, the Greek god of medicine and healing was said to use song and music to cure mental diseases.  Plato taught that “music is a moral law. It gives soul to the universe, wings to the mind, flight to the imagination, a charm to sadness, gaiety and life to everything.”  Today, music therapy is most commonly used to treat neurological disorderse like dementia, schizophrenia, and depression.  Recently, though, a study found that music therapy could significantly reduce patients’ anxiety during cataract surgery through the administration of binaural beats.

            In the study, researchers used binaural beats combined with soothing music and nature sounds to provide a pleasant experience for patients.  The audio track was similar to music one would find in a spa.  Binaural beats consists of two tones with slightly different frequencies, each delivered to a separate ear.  This technique is thought to stimulate alpha-frequency brain waves.  In the study, patients who received the therapy before, during, and after cataract surgery had slower heart rates, reduced blood pressure and overall less anxiety than patients who received regular music or listened to usual sounds that occurred during surgery. 

            While music therapy as a treatment has been around since World War II, (I find listening to piano music while I study for exams to be quite soothing) this study shows that music therapy can be applied beyond treatment for neurological disorders.  It provides an inexpensive and creative way to improve patient care, especially during stressful procedures like surgery.  Perhaps it can be extended to use during other procedures that use local anesthesia such as root canals or hand/foot surgeries.

http://www.aao.org/newsroom/release/20121112b.cfm

Muscle Types: Arm Wrestler vs. Body Builders

Arm wrestling is a simple sport/pastime that can be done virtually anywhere with a flat surface. It is a universal macho man competition as old as time itself; it pits two individuals against each other, where the victor walks away with bragging rights of his or her relative strength. In the past couple decades, arm wrestling has evolved into an official sport, with leagues and championships.

However, not just any Average Joe can win an arm wrestling championship--success is contingent upon training for technique and strength, obviously. Biomechanical analysis shows that the humeral bone is put under significant pressure by the pectoralis major, the biceps brachii, and brachialis muscles that drive the humerus with a medial rotation towards the body (Kruczynski et al. 2013). But what type of strength is best for arm wrestling, and what does your run-of-the-mill arm wrestler's muscle composition look like? We know that there are three muscle types: Type I, Type IIa, and Type IIb. Since Type II muscle fibers are involved with short, intense bursts of contractile strength, we would imagine that arm wrestlers' arms are mostly composed of these muscles. We also know that contractile strength is associated with muscle size, or number of muscle fibers (Klein et al. 2003). With this knowledge, we could make the assumption that an individual with massive pectoralis major and biceps would dominate at the sport of arm wrestling. How would we then explain the following video? Here we see an arm wrestling match between Daniel Racoveanu, a professional bodybuilder, matched up against Ion Oncescu, a professional armwrestler. Pay close attention to the smirk on Mr. Oncescu's face and the soft pat on the opponent's hand before he gently takes his arm down with a comical amount of ease.



Does the amount of Type II muscle fibers in the arm wrestler outnumber the bodybuilder's? We know that muscle composition can change with training. Are the bodybuilder's muscles all for show (they look pretty vascular to me)? Is the arm wrestler just more resistant to fatigue? Maybe it's a combination between all of these. What do you guys think?

P.S. Here's a picture of German arm wrestler Matthias Schlitte, showing us how muscle composition (fiber type/size) can change with training. Wow.

References:

Kruczynski J, Nowicki JJ, Topolinski T, Srokowski G, Manko G, Chantsoulis M, Frankowska M, Frankowski P. 2012 May. Radiological and biomechanical analysis of humeral fractures occurring during arm wrestling. Med Sci Monit. 18(5).

Klein CS, Marsh GD, Petrella RJ, Rice CL. 2003 Jul. Muscle fiber number in the biceps brachii muscle of young and old men. Muscle Nerve. (1):62-8.

Psychological Stress: "It Comes With the Territory"

Many of us have recently just finished up our mid-term week for the Fall semester and if it was like most college student’s experience, it was filled with copious amounts of stress.  We all experience stress in varying degrees, and to an extent it can be good for us; it keeps us alert, motivated and often people report they work best under high-pressure situations.  I must admit I have many times waited until the last minute to do an assignment, not necessarily because I was lazy, but because a little part of me knows that if I wait, then at that moment I will be forced to put all of my efforts into that assignment to get it done quickly and efficiently with exceptional results.  But isn't this what we all signed up for?  It is a known fact that being a student in a rigorous academic major comes with stress and high expectations, so should we really care to pay attention to it? Or should we just suck it up and get used to the stress that comes with the territory of the paths we have chosen? A recent article however points out that too much stress can come at a price, I know this is nothing we haven’t heard before but I think many of us fail to really look at what our day-to-day psychological stressors are doing to us physically.

            In this article it focused on nurses in particular, and the occupational stress that comes with being a nurse.  Many of us plan to work in some sort of health profession so I found this to be particularly applicable. Our physiological responses to stress are our body’s attempts to regulate itself and adapt to these outside stressors in triggering a new stress response within (Gaillard and Kramer, 2000). When this fight or flight response is activated to increase the body’s metabolism for an expected needed energy expenditure it stops other unessential functions. If disrupted over a long period of time this can result in a number of short-term and long-term physiological effects.

            Stress is obviously a crucial factor in many mental illnesses such as anxiety and depression.  However, it seems like in today’s society these mental illnesses are often over looked or dismissed to people “making it all up in their heads”, but I think it is necessary to see the physiological effects that our mental wellbeing has on us.  It is clear to see how health professionals would have enormous amounts of stress put on them by their job, but does that mean that this okay just because it is expected?  In the book titled, “Why Zebras Don’t Get Ulcers” by Robert M. Sapolsky he discusses how there are many ways that we can reduce our psychological stress responses and expectation was a crucial one in if our bodies are prepared for a stressor, then we can better respond to it (Sapolsky, 2004).   But like I said, just because it is expected doesn’t necessarily lighten the blow at all.  Occupational stress in the work place is an important issue and I think that as students who are preparing to enter into these fields of high psychological and physical demand, we need to become aware of this issue so that we may begin to formulate a solution to where this doesn’t have to be something we just deal with because it “comes with the job”.  Psychological stress is not something that stays confined to our mind, it is connected to our entire body and if not taken care of can lead to detrimental effects. 

References:

Donovan, R. O., Doody, O., & Lyons, R. (2013). The effect of stress on health and its implications for nursing. British Journal of Nursing,22(16), 969-973.

Gaillard AW, Kramer AF (2000) Theoretical and methodological issues in

psychophysiological research. In: Backs RW, Boucsein W, eds. Engineering

Psychophysiology: Issues and Applications. Lawrence Erlbaum Associates,

Mahwah: 31–54

Sapolsky, Robert M. Why Zebras Don't Get Ulcers. New York: Owl Book/Henry Holt and, 2004. Print.