Does the microbacteria in your gut play a role in obesity?

Obesity is a fairly recent disease that most people have been blaming on the food they eat and on the lack of physical activity.  Only recently have scientists thought about the role the Human Microbiome plays in weight.  Microbacteria colonies were studied in mice and they found that mice receiving microbiota from an obese mouse gained more weight in a two week period than mice receiving the lean microbes.  From gene sequencing of the microbiota, researchers found that there was an "enrichment in genes involved in energy extraction from food in the obese host's microbiome relative to that of the lean host's microbiome."
Fecal samples were taken from 154 participants at an initial point and then again two months later.  Researchers found that participants with a lower microbacterial diversity were obese.  From the mouse and human study researchers learned that the microbacteria associated with obesity were involved with carbohydrate and lipid metabolism.  Researchers have also begun to study the diversity of microbacteria in other parts of the body like saliva.  Since microbacteria live in saliva and play an initial role in the breakdown of food, they wanted to test if there was a difference there too.  They found that the bacteria, Selenomonas, was only found in overweight people.
The gut communicates with the endocrine system and tells it what to do.  The microbacteria also regulate the gut hormones directly.  A study done on patients after gastric bypass surgery showed that patients who were given probiotics lost weight faster than patients not given probiotics.  This supports the idea that "gut bacteria may be modulating gut hormones."  Since many different studies were done the next step in this research is to standardize it and to use the same approach.




http://www.medscape.com/viewarticle/714569

The “Mile High” fix shows promising outcomes for chronic pain patients

As a Colorado native, people often ask me my opinion on the use of medicinal marijuana. Even some of the patients at my physical therapy clinic use cannabis creams and oils for chronic pain relief when nothing else seems to work. We’ve all heard the arguments that marijuana use-even for medicinal purposes-will “make you stupider,” and the damaging effects of long term use to memory and overall cognitive function has been widely cited [1,2]. However, short term use has not shown a significant decrease in cognitive functions [2], and could be a valid treatment option when it is regulated by physicians.

Although studies have shown efficacy of marijuana in patients with chronic pain, not enough research has been done on the potential benefits and adverse effects to allow for physician involvement. A recent study in Canada [1] has begun to pave the way to answering the big question of short term usage side effects.

This study dispensed cannabis products with 12.5% THC to chronic pain patients who were failed by current treatments options. Safety and efficacy parameters were measured over a year time span. Safety considerations include normal blood, liver, kidney, and hormone functions, as well as, the larger concerns of brain and lung function.

Although there was no significant difference in the occurrence of serious side effects, this study showed a higher incidence of non-serious adverse events in the patients using THC as opposed to those who did not receive treatment with cannabis.  

However, all of the aforementioned safety considerations and the neurocognitive and pulmonary functions showed no significant changes, and chronic pain intensity decreased overall after a year of cannabis treatment. This combined with the improvement in physical functioning and mood of cannabis treated patients demonstrates an improvement in quality of life.

This study shows that there still are side effects to medicinal marijuana use, but the overall quality of life improvement may be worth it. This subject requires more research in order to compare benefits and side effects between common treatments for chronic pain (opioids-Percocet, Vicodin, etc.). Additionally, dosages will need to be optimized to provide benefits and minimize side effects-especially since legislation in the US has not fully recognized its use for medicinal purposes. Only research can tell us if “Mile High” medications will be the best solution to chronic pain.

Here is a link to the study if you want to know more: http://www.jpain.org/article/S1526-5900(15)00837-8/fulltext#sec3.2

References:

1.     Ware, M., Boulanger, A. et al. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS) 2015. The Journal of Pain

 2.   Solowij, N., Stephens, R.S., Roffman, R.A., Babor, T., Kadden, R., Miller, M. Christiansen, K., McRee, B., and Vendetti, J. Cognitive functioning of long-term heavy cannabis users seeking treatment.JAMA. 2002; 287: 1123–1131

Researchers at UCSF have created a switch to control CAR T cells

T cells are well known for their powerful ability to fight off pathogens and tumor cells. T cells’ ability to destroy tumor cells has been studied for the last two decades regarding the cell-surface sensors known as chimeric antigen receptors (CARs). By inserting CARs into T cells, which is now called CAR T cells, CAR T cells are guided to target and destroy the tumor cells in the patient’s body. The mechanism of action includes the releasing of cytokines to attract other T cells to the site and binding to the tumor cell’s surfaces to destroy them. Despite the promising ability to destroy tumor cells, T cells also exert a powerful side effect that could be lethal to the patients. For example, once administered, CAR T cells randomly destroy organs on their way such as the lungs and heart. This detrimental side effect renders CAR T cells to be impractical. To combat this, researchers from the University of California-San Francisco created an on switch for CAR T cells. CAR T cells will be administered in inactivated form by default. Delivering a drug that serves as an on switch will allow a delayed time necessary for CAR T cells to pass through vulnerable organs, i.e. heart and lungs, and become activated when they encounter the tumor cells. This controller drug offers a means to regulate CAR T cells activities. Additionally, based on the dosage of the drug, the amount of toxic waste, which is produced from the lysing of tumor cells, can be controlled. Although the controller drug is still under investigation, it sheds light on other researches such as using light or inserting multiple CARs into T cells to gain control on CAR T cells.

Reference

http://www.medicalnewstoday.com/articles/299952.php

New 'Pacemaker' May Just Help Your Achy-Breaky H̶e̶a̶r̶t̶ Stomach?!?

I saw this on the local news last week and found this super interesting.  A new device called the vBloc may be the newest weight loss solution for those who have had prolonged futile attempts at diets, exercise, and other weight-loss measures.  vBloc works similarly to the LapBand, in that it is designed to restrict the feeling of hunger.  Unlike the LapBand, which physically constricts the upper portion of the stomach, vBloc works by constricting the nervous system.  The system contains two electrical leads, which connect to the two vagal trunks, the nerves which allow the stomach to communicate with the brain; signals from the vagal trunks give one the sense of hunger and fullness.  vBloc's electrical impulses distort vagal communication, allowing one to fill satisfied with a shorter amount of food.  Better yet, unlike physical constrictors like the LapBand, vBlock is electronically adjustable, able to adapt as one's hunger sensations change.

vBloc just received FDA certification this past January and the device is already showing promising results.  A 2008 study* on 31 patients with the device installed, published in the Journal of Surgery, found that after 4 weeks, 12 weeks, and 6 months, patients had 7.5%, 11.6%,and 14.2% mean excess weight loss, respectively.  As compared with the baseline, these results yielded p < 0.0001, suggesting that the excess weight loss is statistically higher in patients with vBlock implanted.  In the same 31 patients, mean caloric intake over the course of 6 months after vBlock implantation decreased by over 30% ( p ≤ .01), with earlier satiation and reduced hunger, with p-values of p < .001 and p = 0.005, respectively (indicating statistically significant results).  Clearly, the device is changing one's diet rather drastically.

It always amazes me how one solution to one problem can easily be modified to solve another problem.  In this case, the pacemaker is still continuing to set the beat; only this time, the beat lies not in the heart, but in the desire to eat.

*The link for the 2008 study leads you to an online abstract. The actual article must be accessed via use of the Regis University library and may be found here.

Lethal diseases that save lives: Sickle Cell Anemia and Malarial resistance

As a go-to example for a classic genetic disorder, sickle cell anemia has been used in many a college biology course. It is a recessive autosomal disease due to a base pair substitution mutation in the ß-globin gene of hemoglobin that, when present, causes red blood cells to become shriveled and shaped like the farm tool for which the illness was named.  Individuals with both alleles for sickle cell suffer through a painful daily struggle with normal blood circulation and rarely mature to a reproductive age. So why has this disease persisted through the years? Despite the terrible consequences that accompany a homozygous sickle genotype, evolution may have provided an answer. Malaria has long been known for the damage that it causes to the human populous in tropical regions. Which conveniently, is where sickle cell disease is typically seen the most. Malarial transmission through mosquitos from one host to another can be fatal. In 2010, there was an estimated 863,000 deaths globally due to malaria (Hedrick, 2012). The heterozygous individuals with a single sickle cell allele and a normal adult hemoglobin allele interestingly show a partial phenotype of sickle cell anemia that is accompanied with a resistance to severe malaria. 

The HbS allele has been hypothesized to correlate with symptomatic variants of malaria. The presence of the HbS allele has shown a resistance to symptomatic malaria, but not asymptomatic (Shim, 2013). This means that the HbS allele does not prevent infection of the host but the manifestation of the parasite into full-blown malaria. Three plausible mechanisms for prevention of parasite maturation have been suggested by modern research: 

1. Once a red blood cell is infected, the parasite forces the cell into a state of rapid oxygen consumption as it mines its host’s actin to transport proteins to the red blood cell surface. This causes a decrease in the cell’s partial pressure of oxygen, which could induce the sickling of the red blood cell marking it for macrophage uptake (Taylor, 2013).  

2. When a sickled cell is infected, parasitic knob proteins like PFEMP1 typically used to adhere to epithelial tissue are prevented by the deformed hemoglobin aggregates from being transported to the outer membrane of the infected cell.  Preventing further propagation of the disease through the body. Figure 1 illustrates suggested mechanisms 1 and 2 (Bunn, 2013).

 3. Host integration of microRNAs (miRNA) into the parasitic mRNA inhibits parasitic protein translation via the creation of chimeric mRNA. Transfection of these miRNAs into infected HbAA cells showed a roughly 50% decrease in parasite proliferation. Upon closer examination, it was seen that this effect was caused by the integration of the miRNA into host mRNA. Figure 2 represents the third suggested mechanism (Bunn, 2013). 

Although the exact mechanism for sickle cell's contribution to malarial resistance has not been determined, it provides us with an opportunity to learn more from the disease. Nature has provided its own imperfect antidote to malaria. Perhaps if we can figure out how sickled cells prevent symptomatic malaria we may be able to develop a drug using a similar approach.

Figure 1: Mechanisms underlying protection by AS RBS against falciparum malaria

Figure 2: Inhibition of translation of parasite mRNAs by micro RNAs in AS RBCs

References:

Bunn, H. F. (2013). The triumph of good over evil: Protection by the sickle gene against malaria. Blood, 121(1), 20-25.

Hedrick, P. W. (2012). Resistance to malaria in humans: The impact of strong, recent selection. Malaria Journal, 11, 349.

Taylor, S. M., Cerami, C., & Fairhurst, R. M. (2013). Hemoglobinopathies: Slicing the gordian knot of plasmodium falciparum malaria pathogenesis. Plos Pathogens, 9(5), e1003327.