Celiac Disease Controls Your Life

Celiac disease is a disease that damages the lining of your small intestine resulting in an inability to effectively absorb essential nutrients. When people with celiac disease eat or drink substances containing gluten, the immune system attacks and damages the part of the lining responsible for nutrient absorption. Celiac disease can develop at any point in life but my cousin Sarah was 14 when she was diagnosed. Celiac disease can cause many problems to the patients and the only treatment is to go on a completely gluten free diet.

When she was diagnosed, there were not a lot of options for gluten free and most products in the super market contained gluten and so she could not eat them. It took her forever in the grocery store because anything that she wanted she had to read all of the ingredients to double and triple check to make sure that there was no gluten. When she went to she gave up going to restaurants for a while because they could never assure her that there was no gluten in their dishes. If she accidentally had even a trace of gluten, she would have abdominal pain, diarrhea, and nausea for hours after the fact.

In addition to her abdominal pain, diarrhea, and nausea symptoms, she also frequently had tingling in her hands and was fatigued all of the time. She became depressed because she could never go out with her friends and couldn't eat what she wanted and what everyone else was eating. Because so many people have been diagnosed and celiac disease is more widely known t is much easier because there are so many options in the grocery store that are gluten free. At every restaurant you go to you can ask for their gluten free menu or they have a section dedicated to that on their regular menu. It is much more convenient for people with celiac disease and it allows them to go out and eat food that tastes good and feel normal again.

People who have celiac disease are more likely to get many other disorders but a common one that Sarah also got is problems with your thyroid. She had a hyperactive thyroid and they had to give her radiation to stop her thyroid from functioning and now she has to take a supplemental thyroid hormone to manage symptoms from that. Although all of her symptoms are under control now, celiac disease has changed her life. Now that she has children, all of them are on gluten free diets as well. She is paranoid because you are more likely to get celiac disease if you have a family member with it. She doesn't want them to go through what she went through so she would rather them just start out gluten free.

I think that it is interesting that all of a sudden there were so many options for gluten free food and drinks. I even saw that they have a completely gluten free booth at Coors Field to serve baseball lovers that cant or choose not to eat gluten. I wonder if it is just because more people know about celiac disease or if more people really are being diagnosed with celiac disease or maybe it is a combination of the two. Also do you guys think that it is a good idea for people who do not have celiac disease to go gluten free to prevent from getting symptoms if the do end up developing it? I think it is a little paranoid and there is no guarantee that you will even develop the disease, if you notice that you are getting sick when you eat something then you can change your diet but I don't see the point before the fact.

Electrospinning lecithin to prevent adhesions

The goal of electrospinning is to produce nanofibers that contain a desired set of properties. Electrospinning occurs because the high voltage supplied causes charges to build up on the surface of a droplet of the solution. As the charges on the droplet interact with the electric field a Taylor cone is produced and a threshold is met, causing a jet of polymer to be expelled to the ground collector. The solvent is evaporated away during the process.

Internal organs in the peritoneal cavity are layered with mesothelial cells to prevent adhesions forming between organs. The body’s healing process may respond to irritation, inflammation, or infection by forming adhesions. Many times this is caused by some form of surgery in the abdomen or pelvic area. Symptoms and adverse effects that may occur from adhesions are infertility, chronic pelvic pain, abdominopelvic pain, bowel obstruction, longer surgical procedures, and reoperations. It is estimated that in the United States 1.2 billion dollars per year is spent on adhesions, not including outpatient expenses or missed work. In women adhesions are to blame for approximately 20%-40% of infertility cases and occur in nearly all abdominopelvic surgeries. Laparoscopic surgery and advances in surgical techniques are much more common and have helped reduce the occurrences of adhesions but these methods are still not satisfying the need of adhesion prevention.

The properties of lecithin could play a valuable role in adhesion prevention. Lecithin is a type of phospholipid, which is a major component of the lipid bilayer in cell membranes. Phospholipids are amphipathic because they are comprised of a polar hydrophilic head group and a non-polar hydrophobic carbon tail. Lecithin is also specifically known as phosphatidylcholine because choline makes up the polar head group. Lecithin has a soapy or oily feel because of the amphipathic behavior; this property could be used to prevent adhesions.

Below are are two SEM (scanning electron microscope) images I took. The top image is 1000x magnification, and the bottom image is 2000x magnification.

Lee SW, Kim YU, Choi SS, Park TY, Joo YL, Lee SG. Preparation of SiO2/TiO2 composite fibers by sol-gel reaction and electrospinning. Materials Letters 2007;61(3):889-893.

Xie J, Xia Y. Electrospinning: An Enabling Technique for Nanostructured Materials. Materials Letters 2008;3.1:19.

Vassalli T. Development of Electrospun Bioabsorbable Fibers. Columbia: University of Missouri; 2008. 10-15 p.

Garrett RH, Grisham CM. Biochemistry. Second ed: Academic Press; 1999.

Chegini N, Kotseos K, Zhao Y, Ma C, McLean F, Diamond MP, Holmdahl L, Burns J. Expression of matrix metalloproteinase (MMP-1) and tissue inhibitor of MMP in serosal tissue of intraperitoneal organs and adhesions. Fertility and Sterility 2001;76(6):1212-1219.

Johns DB, Keyport GM, Hoehler F, DiZerega GS. Reduction of postsurgical adhesions with intergel® adhesion prevention solution: A multicenter study of safety and efficacy after conservative gynecologic surgery. Fertility and Sterility 2001;76(3):595-604.

Brown CB, Luciano AA, Martin D, Peers E, Scrimgeour A, diZerega GS. Adept (icodextrin 4% solution) reduces adhesions after laparoscopic surgery for adhesiolysis: a double-blind, randomized, controlled study. Fertility and Sterility 2007;88(5):1413-1426.

Diamond MP, Bachus K, Bieber E, Bradshaw K, Falcone T, Frishman G, Grunert G, Hansen K, Hemmings R, Lobo R and others. Reduction of de novo postsurgical adhesions by intraoperative precoating with Sepracoat* (HAL-C) solution: A prospective, randomized, blinded, placebo-controlled multicenter study. Fertility and Sterility 1998;69(6):1067-1074.

Low levels of MIP-3α and HBD-3 put people with atopic dermatitis at risk

I just started learning about atopic dermatitis (AD), a chronic inflammatory skin disease that occurs in approximately 17% of children. I came across this genetic disorder in my research for my honors thesis because stress plays a role in its onset and severity. AD is characterized by rashes that arise from bacteria and viruses. Individuals with AD cannot safely be vaccinated against smallpox with vaccine virus (VV) because this could give rise to an adverse skin reaction called eczema vaccinatum. Therefore, researchers have been trying to figure out how to clinically prevent this from happening.

Patients with AD have a compromised immune response to the bacteria and viruses that cause rashes. This partially occurs because AD individuals have a decreased expression of macrophage inflammatory protein 3α (MIP-3α), an important chemokine that recruits Langerhans cells (a type of antigen-presenting cell). Therefore, this chemokine helps kill pathogens in the epidermis. Byung et al. (2007) collected skin biopsies from normal subjects and from patients with AD and psoriasis. They found that MIP-3α gene expression was 50% lower in AD skin than in psoriasis skin. This suggests that patients with AD don’t have enough MIP-3α to prevent a disseminated VV infection. Also, they found that cytokines from a certain type of T helper cell, called TH2, down-regulate MIP-3α gene expression. The authors propose that increasing MIP-3α or neutralizing TH2 cytokines could help against eczema vaccinatum.

Furthermore, Howell, Streib and Leung (2007) researched a type of antimicrobial peptide called human β-defensin (HBD)-3. Infection with VV induced the expression of HBD-3 in keratinocytes. Similar to the previous study, these authors suggest that a shortage of HBD-3 in AD patients makes them more susceptible to systemic VV infection after smallpox vaccination.

I don’t know about you, but oftentimes I take normally-functioning skin for granted. Because normal levels of MIP-3α and HBD-3 strengthen our barrier against pathogens, I hope that our growing understanding of the immune response to VV will give rise to new therapies to alleviate AD symptoms and prevent eczema vaccinatum.

Byung, E.K. et al. (2007). Macrophage inflammatory protein 3α deficiency in atopic dermatitis skin and role in innate immune response to vaccinia virus. Journal of Allergy and Clinical Immunology, 119(2), 457-463.

Howell, M.D., Streib, J.E., & Leung, D.Y.M. (2007). Antiviral activity of human β-defensin 3 against vaccinia virus. Journal of Allergy and Clinical Immunology, 119(4), 1022-1025.

Being an involved father leads to lower testosterone levels

A study following 600 men for over 5 years demonstrated that fatherhood and being involved in the raising of a child lowers testosterone levels (Gettler, L. et al., 2011). While the study is very interesting it raises many questions for me that are left unanswered.

It is known that testosterone levels decrease over a man’s lifetime, but it was shown in this study that the men that fathered children and had a relationship with the child had lower testosterone levels than their child-less counterparts. It was also found that those that spent three hours or more per day involved with the child had even lower testosterone levels. This leads me to question if a possible feedback loop is involved. The more involved the men are, the lower the testosterone levels indicating a possible positive feedback loop.

Having lower testosterone levels was linked in the study to possibly being a “better” father. It could be suggested that these lower testosterone levels allow the men to be more driven to tend to their children and less driven to seek out another mate. Men do not have the same physiological effects in becoming a parent that women do. Women have the physiological experiences of carrying the child, giving birth and suckling the young, all of which allow the woman to become emotionally connected with the child. Possibly this lowering of testosterone levels allows the men to become emotionally connected with the child much as the physiological effects that women experience do.

Women “nest” after having a child by securing a healthy and sheltered home and providing for their child. Does the drop in testosterone levels allow men to have a similar urge to “nest”? Our young are not self-sufficient and require many years of care; many parents would even argue that the work required to raise a successful child never ends. This child care is generally socially and culturally considered the responsibility of the women, but does this drop in testosterone levels suggest that men are physiologically wired to be involved in their children’s lives and help women in the child care?

This study brings up another question: is the most involved father, the one with the lowest levels of testosterone, “less of man” or “more of a man”?

Cancer, multi-drug resistance, and P-gp

The leading cause of treatment failure in cancer patients is multi-drug resistance. One type of multidrug resistance is the result of a tumor cell excreting the drugs that would destroy it; these drugs are rejected via specific transport proteins. P-glycoprotein (P-gp) is a membrane protein in normal human cells, but it is also expressed in tumor cells and contributes to multidrug resistance.¹ The goal one of my projects during my time in undergraduate research (at the University of Denver) was to purify P-gp and test its functionality. A fluorescent dye, rhodamine 123, has been identified as a P-gp substrate. P-gp has a relatively unspecific binding capacity, so dyes structurally similar to rhodamine 123 may also be P-gp substrates. My ultimate goal for this project—working alongside another undergraduate student—was to more thoroughly understand the mechanism by which P-gp rejects toxins in order to better design chemotherapy drugs in the future.

In terms of methods, we used multiple procedures to purify P-gp and test its functionality, including:

a. Yeast transformation: the MDR1 gene which expresses the P-gp was transformed into the yeast cells.

b. Western blot: Once the yeast cells were grown, they were lysed and homogenized in order to isolate P-gp from the yeast membranes. A western blot was performed to determine that P-gp was present.

c. Purification: P-gp was purified by exposing the cells to: centrifugation, homogenization, and Ni-NTA resin. The elution from the resin was concentrated using a filter with a 150 kDa cutoff for better detection on a western blot. A western blot was performed to ensure that P-gp was still intact after the purification.

d. Fluorimetry: The intensity of two rhodamine dyes, tetramethyl rhodamine methyl ester (TMRM) and rhodamine B (RhB), were each measured in ethanol and phosphate buffered saline (PBS). The goal was to determine which dye would provide the greatest difference in intensity in ethanol and PBS.

At the conclusion of our project, P-gp was not intact after the purification process, so our next task was to determine what caused P-gp to be lost. Once we successfully purified enough P-gp in subsequent projects, our goal became to place P-gp into liposomes and use rhodamine to track the efflux mechanism of P-gp. To learn more about PGP, please refer to a great review article in Nature. Here’s the citation: Gottesman, M. M. et al. (2002).Multidrug Resistance in Cancer: Role of ATP-Dependent Transporters. Nature Reviews: Cancer. 2, 48-58. http://www.nature.com/nrc/journal/v2/n1/abs/nrc706.html

Sources:

Figler, R. A. et al. (2000).Use of Chemical Chaperones in the Yeast Saccharomyces cerevisiae to Enhance Heterologous Membrane Protein Expression: High-Yield Expression and Purification of Human P-Glycoprotein. Archives of Biochemistry and Biophysics. 376, 34-36.

The HCG Diet

As a physical fitness trainer for the Air Force, I've received several questions regarding diets, the most intriguing being the HCG diet. After doing some research, I learned that the HCG diet is a weight-loss plan combining daily injections of human chorionic gonadotropin (HCG) hormone with the ingestion of only 500 calories per day (Robb-Nicholson, 2010).

HCG is released during pregnancy and is located in a pregnant woman's urine (Robb-Nicholson, 2010). In the 1950s, British physician Dr. Albert T. Simeons claimed that the HCG injections caused the body to burn stored fat from the stomach, hips, and thighs, and assured that muscle would not deteriorate (Robb-Nicholson, 2010).

Several studies have been conducted on this diet; the FDA has shown that the low-caloric intake, NOT the injections, cause the weight loss (Robb-Nicholson, 2010). There also exist reports of adverse side effects from the injections themselves, including blood clots and headaches (Robb-Nicholson, 2010).

Unfortunately, due to the media and online blogging. interest in this diet has only increased over the past few years. Today, the hormone is now available in a sublingual form (Robb-Nicholson, 2010), thus increasing its popularity.

I personally advise against this diet, as such a low caloric intake only causes fatigue, depression, dizziness, fainting, and a plethora of other negative side effects. Honestly, it's amazing what sleep, a balanced diet, and moderate exercise can do for one's general health and wellness. My clients are constantly amazed at how quickly such simple lifestyle changes can yield desired results. Generally, fad diets don't work, and those that do "work" are extremely unhealthy for you.

So I'm posting this for two main reasons: First, what are your thoughts on fad diets, particularly this HCG diet? Second, what does the HCG hormone do to the human body (particularly the male body) after long-term use? Pregnant women release this hormone during pregnancy, but no one produces it in such quantities over an extended period of time. How would the presence of an unnatural hormone alter the body?

For more information on this, see the article "By the way, doctor. I've been trying to lose weight for a long time and nothing seems to work. What do you know about the HCG diet?" in Harvard Women's Health Watch, written by Celeste Robb-Nicholson. You should also check out what people write on health blogs and websites...it's pretty fascinating!

Stressed about short telomeres? Exercise can help!

Although a functioning stress response is absolutely essential in fight-or-flight situations, chronic activation of this response can eventually have detrimental effects on physical health. For instance, many chronically stressed individuals have shorter telomeric DNA on the ends of chromosomes. High levels of cortisol have been shown to cause oxidative stress damage and to dampen the activity of telomerase, which adds DNA sequence repeats with each cell division. Short telomeres are unfavorable because they can ultimately prevent cells from multiplying and functioning normally.

In the case of immune system cells, critically short telomeres can cause a loss of antigen recognition in leukocytes. Tyrka et al. (2010) tested the length of leukocyte telomeres in 31 adults who reported varying degrees of childhood maltreatment. After controlling for age, sex, smoking status, BMI, level of education, medical or psychiatric illness, and childhood socioeconomic adversity, the maltreatment group had significantly shorter telomeres than the group reporting no childhood maltreatment. Hence, even long-past childhood events have the potential to disrupt proper immune function.

However, exercise can be a useful deterrent of telomere shortening, according to Puterman et al. (2010). For 63 healthy post-menopausal women, the relationship between telomere length (TL) and the amount of time spent exercising per week was tested. Participants who vigorously exercised at least 75 minutes per week were labeled as “active” and the others were labeled as “sedentary.” This is the amount of time recommended by the Centers for Disease Control (CDC). Participants with higher perceived stress were significantly less likely to be “active,” had shorter TL, a higher body mass index and fewer years of education. After controlling for age, BMI, education, and antioxidant vitamin use, the authors found that exercise was able to significantly buffer telomere shortening. Although excessive exercise can promote cell damage, this study makes it clear that a reasonable amount of exercise per week can greatly reduce the effects of stress on premature cellular aging.

Puterman et al. (2010). The power of exercise: Buffering the effect of chronic stress on telomere length. PLoS ONE, 5(5), 1-6.

Tyrka et al. (2010). Childhood maltreatment and telomere shortening: Preliminary support for an effect of early stress on cellular aging. Biological Psychiatry, 67(6), 531-534.

Importance of Bystander CPR in Out of Hospital Cardiac Arrest

Out of hospital cardiac arrest (OHCA) is a leading cause of death among adults in the United States. Approximately 300,000 OHCA events happen each year in the U.S. and about 92% of the victims die. An OHCA is defined as cessation of cardiac mechanical activity that is confirmed by the absence of signs of circulation that occurs outside the hospital setting. The majority of those who experience an OHCA event do not receive bystander CPR or defibrillation by AED which have both proven to increase survival rates. Because over half of OHCA events are witnessed, efforts to increase survival rates should focus on timely and effective delivery of interventions by bystanders and EMS personnel. In 2004, the Center of Disease Control (CDC) established the Cardiac Arrest Registry to Enhance Survival (CARES) that seeks to evaluate OHCA events of a presumed cardiac etiology (not including CA caused by trauma, asphyxiation, drowning etc) that involve persons who received resuscitative efforts, including CPR and defibrillation in a voluntary study from sources that define the continuum of emergency cardiac care: 1. 911 centers, 2. EMS providers and 3. receiving hospitals.

In the period between 10/1/2005 and 12/31/2010, 31,689 OHCA events of presumed cardiac etiology (i.e. myocardial infarction or arrhythmia) that received pre-hospital resuscitation were recorded and analyzed. The mean age was 64.0 years and 61.1% were male. The survival rate to hospital discharge was 9.6%. Approximately 36.7% of OHCA were witnessed, of which only 33.3% received bystander CPR and only 3.7% were treated with early defibrillation before arrival of EMS. The group most likely to survive was those whose OHCA event was witnessed by a bystander and found in a “shockable rhythm” (ventricular fibrillation or pulseless ventricular tachycardia). Among this group, survival to discharge was 30.1% as opposed to 9.6% of those who did not receive early intervention.

This study helped CARES identify room for improvement in out of hospital cardiac arrest care. The data from this study confirms that patients who receive CPR/AED care from bystanders have a greater chance of surviving OHCA than those who do not. Public health professionals have used this study to spark a wide action for education of public officials and community members on the importance of bystander CPR as well as promoting the use of early defibrillation by lay and professional rescuers.

(B McNally et al., CDC's Morbidity and Mortality Weekly Report. 29 July 2011. Vol. 60 No. 8: 1-19)

PhysioBLOGology: Vaccination and Herd Immunity

PhysioBLOGology: Vaccination and Herd Immunity: Outreach efforts have boosted the percentage of Colorado school children who are fully vaccinated by age 2 to 79 percent, 15th highest ra..

Statistically, when a population is educated about the risk of an outbreak of an infectious disease they become more engaged in the eradication process. The threat of an outbreak in the United States could be countered by bringing awareness to the general population so that parents may deem it necessary to get themselves and their children vaccinated, which in essence will increase the percentage of immunized individuals within the population. My question is what would be the most effective medium to achieve this campaign of awareness against another outbreak of mumps?