Heart failure and AKI

It is known that heart disease can cause kidney failure, but not much is known about how kidney failure can cause heart disease. Recently in the United States acute kidney injury (AKI) is on the rise. AKI can lead to chronic kidney disease (CKD), which increases the risk of heart failure. Kidney disease and heart failure are linked in a multifactorial fashion, for example disturbances in sodium handling, sympathetic stimulation, inflammation, up-regulation of the renin-angiotensin-aldosterone system (RAAS), and alterations of mineral metabolism (Bansal et al, 2017). These manifestations also exist in AKI (Bansal et al, 2017). The study used patients who had AKI, and excluded those with preexisting heart conditions. They determined that patients had AKI by using their creatinine laboratory values.

Patients who developed AKI were more likely to be older, be African American, use diuretics or RAAS inhibitors before admission, have diabetes, have hypertension, and sepsis during an hospitalization (Bansal et al, 2017). The body works as a system and it is known that water-retention regulation is way to mange or alter blood pressure. It is no surprise that these patients had blood pressure problems that caused them to take medicine that alters their water-retention. Patients with AKI had nearly a 2-fold increased risk of hospitalized heart failure (Bansal et al, 2017). The majority of these patients within two years of being discharged developed heart disease.

There are many ways to explain the link between AKI and heart failure.  AKI, even after recovery, quickly leads to impaired tubular sodium handling, reduced pressure natriuresis, and salt-sensitive hypertension (Bansal et al, 2017). Natriuresis is the excretion of sodium in urine. AKI has also been demonstrated to up-regulate inflammation in remote organs including the heart; this inflammation associates with apoptosis and functional consequences (Bansal et al, 2017).  Since heart failure and kidney problems are linked it would be beneficial to monitor patients with either closely in order to avoid major health concerns.

Reference

Bansal, N., Matheny, M. E., Greevy, R. A., Eden, S. K., Perkins, A. M., Parr, S. K., . . . Siew, E. D. (2017). Acute Kidney Injury and Risk of Incident Heart Failure Among US Veterans. American Journal of Kidney Diseases. doi:10.1053/j.ajkd.2017.08.027

The ethics behind diseases caused by chronic stress: It is not the same for us all!

Stress is a physical response of the body when it believes that it is under attack, at which point the body is moving into a “fight or flight” state resulting in the release of hormones like adrenaline, cortisol, and norepinephrine to help the body escape danger (“What is stress?”, n.d.).  The two major forms of stress are acute stress, an adaptive response occurring for short periods of time, and chronic stress, a maladaptive response that carries on for a prolonged time and can lead to disease (American Psychological Association, n.d.). 

In all individuals, chronic stress is known to be disrupting to all your body’s processes due to overexposure to cortisol and other stress hormones, and this continuous disruption of the body’s processes is what leads to an increased risk of disease, including heart disease, high blood pressure, depression, anxiety, diabetes, etc. (“Chronic stress puts your health at risk”, 2016).   Forty-three percent of all adults suffer from adverse health effects, costing America $300 billion annually (“The effects of stress on your body”, n.d.).  However, when you continue to break down this general statistic there is an alarming connection between socioeconomic status and ethnic minorities suffering more stress-related health consequences in comparison to the white American (APA, n.d.; Bulatao, 1970).

Individuals of ethnic minorities and lower socioeconomic status have additional stress in their lives including perceived discrimination, acculturative stress, environmental and neighborhood stress, and socioeconomic, daily, and family stress (APA, n.d.).  Perceived stress is the stress that accompanies experiencing daily racism and discrimination, and acculturative stress stems from the tension and anxiety that is felt when trying to adapt to the dominant culture’s orientation and values (APA, n.d.).  Environmental and neighborhood stress is stress associated with living in more dangerous and polluted neighborhoods, and the socioeconomic, daily, and family stress comes from the stress of being impoverished, having a lower social position, and poor family functioning (APA, n.d.). 

This means that you are more likely to suffer from a chronic disease just because you are poor or a person of color with, a lot of the time, socioeconomic status being tied to ethnicity creating compounding effects, and that is just a social injustice that should raise extreme concern. We should be critically thinking about how we have let this happen and the ways in which we can combat health disparities that should not exist.  

American Psychological Association (n.d.). Fact Sheet: Health Disparities and Stress. Retrieved December 03, 2017, from

                  http://www.apa.org/topics/health-disparities/fact-sheet-stress.aspx

Bulatao, R. A. (1970, January 01). Stress. Retrieved December 03, 2017, from https://www.ncbi.nlm.nih.gov/books/NBK24685/

Chronic stress puts your health at risk. (2016, April 21). Retrieved December 03, 2017, from

                  https://www.mayoclinic.org/healthy-lifestyle/stress-management/in-depth/stress/art-20046037

The Effects of Stress on Your Body. (n.d.). Retrieved December 03, 2017, from https://www.webmd.com/balance/stress-

                  management/effects-of-stress-on-your-body

What Is Stress? (n.d.). Retrieved December 03, 2017, from http://www.stress.org.uk/what-is-stress/

Sugar vs. Fat: Which is worse?

In the 1960s it was commonly believed that fatty foods were the major culprits behind obesity, cardiovascular disease, diabetes, cholesterol issues, etc. This belief was greatly supported by the sugar industry and it prevailed in society until more recently when a much larger key player in those diseases was revealed to be sugar (sucrose). This story is newsworthy because it discusses the role that sugar plays on hyperlipidemia, heart disease, and cancer; a much larger role than that of fats (lipids).

Certain genes may affect an individual’s susceptibility to said diseases but the key cause of these diseases is the large amount of sucrose being ingested. When sucrose enters the body it is catabolized into monomers of glucose. The abundance of glucose in the body triggers the release of a peptide hormone called insulin. Insulin is released by the beta cells of the islets of Langerhans’s in the pancreas. The release of insulin activates the metabolic pathway, called glycolysis, that converts glucose into pyruvate and into energy molecules (ATP). However, many of us ingest much more glucose than is necessary for our bodies to convert into energy. As such, all the excess is stored in our bodies (mostly the liver and muscles) as glycogen via glycogenesis. When glucose is needed from these glycogen stores, such as during times of fasting or extraneous exercise for example, the hormone glucagon is secreted by the alpha cells in the pancreas which stimulates the breakdown of glycogen into glucose through the process of gluconeogenesis.

The article sheds light on the ethical bankruptcy of the sugar industry when they pulled the plug on a research investigation aimed at discerning the impacts of sugar on health. According to their representatives, they stopped funding the project due to the researchers having missed their deadline and having gone over budget. Whatever their true reasons were, their actions make the sugar industry appear as though they were attempting to cover up the truth and that they had prior knowledge of the role that sugar plays in health disparities. They probably wouldn’t seem so guilty of this if they had allowed the study they were funding to be completed and any results published. The reason this is so ethically crucial is because there could have been a large difference in the prevalence and incidence of sugar-related diseases we see today. Of course, we will never know for sure, but it is a valid conjecture. Preventative measures could have been enacted to improve the lives of the thousands of patients suffering with those diseases.

References:
Aubrey, A. (2017, November 21). What The Industry Knew About Sugar's Health Effects, But Didn't Tell Us. Retrieved November 23, 2017, from https://www.npr.org/sections/thesalt/2017/11/21/565766988/what-the-industry-knew-about-sugars-health-effects-but-didnt-tell-us

Aubrey, A. (2014, February 04). Sweet Tooth Gone Bad: Why 22 Teaspoons Of Sugar Per Day Is Risky. Retrieved November 23, 2017, from https://www.npr.org/sections/thesalt/2014/02/03/271130613/sweet-tooth-gone-bad-why-22-teaspoons-of-sugar-per-day-is-deadly

Kearns CE, Apollonio D, Glantz SA. (2017) Sugar industry sponsorship of germ-free rodent studies linking sucrose to hyperlipidemia and cancer: An historical analysis of internal documents. PLoS Biol. 15(11): e2003460. https:// doi.org/10.1371/journal.pbio.2003460

Fighting Myocardial Infraction with Nanoparticles

Heart disease is the number one leading cause of death in the United States and every year about 735,000 Americans will have a myocardial infraction, also known as a heart attack. The high numbers of people that are affected by myocardial infractions has caused for there to be a high demand for cardiac research. Researchers at the University of Bonn have recently made some exciting discovers in myocardial infraction treatments.

            In a heart attack, atherosclerosis, or a build of fats and cholesterols, within the coronary blood vessels prevents the muscles of the heart from getting adequate blood flow and eventually they die. Recent attempts in treating myocardial infractions have been focused on replacing the dead cardiac muscle cells, but an issue have arisen with this treatment. The main complication that must be overcome, is getting the injected replacement cells to stay within the heart muscles. The nature of the heart and the constant pumping and movement of blood thought it prevents the replacement cell from staying in place and taking “root”. The small amount of replacement cells that take root, limits the ability for repair. The team at the University of Bonn, headed by Dr Wilhelm Röll, has recently made a discovery that would overcome the previous complication.

            Dr. Röll and his team have done research in the use of magnetic nanoparticles and have had great success. Their research involves taking replacement muscle cells and loading them with magnetic nanoparticles. These loaded replacement cells are then administered into the area of damaged cardiac cells. A magnet is placed outside the body above the heart, which keeps the injected cells within the magnetic field and thus within the heart where they are needed. They found that having the magnetic field for just a short 10 minutes was sufficient time to allow the cells to take root. In the experiment, 60 percent of the cells treated with the nanoparticle and the magnetic stayed within the heart compared to the 25 percent of non-treated cells that remained in the heart.

            The discoveries made by Dr. Röll and his team show great promise in treating the damaged cells within the heart after a myocardial infraction. Sadly, the new treatment is still being tested in mice models and it will be some time before it is available in clinical settings. This discovery gives hope to the future of heart disease and the treatments used for heart attacks.

Annika Ottersbach, Olga Mykhaylyk, Alexandra Heidsieck, Dietmar Eberbeck, Sarah Rieck, Katrin Zimmermann, Martin Breitbach, Britta Engelbrecht, Tobias Brügmann, Michael Hesse, Armin Welz, Philipp Sasse, Daniela Wenzel, Christian Plank, Bernhard Gleich, Michael Hölzel, Wilhelm Bloch, Alexander Pfeifer, Bernd K. Fleischmann, Wilhelm Roell. Improved heart repair upon myocardial infarction: Combination of magnetic nanoparticles and tailored magnets strongly increases engraftment of myocytes. Biomaterials, 2018; 155: 176 DOI: 10.1016/j.biomaterials.2017.11.012

Brain Controlling Implants

We have seen electronic devices implanted in several locations of the body to aid in organ function(s). Just to name a few: cochlear implants to help with hearing, pacemaker to help control electrical rhythm of the heart, and an insulin pump to help with the delivery of insulin for diabetic individuals.

What if our mood can be manipulated as well with the help of electronic devices?

In recent news, the US military’s research agency known as Defense Advanced Research Projects Agency (DARPA) has funded a group and have begun preliminary trials to treat mental illness such as depression and post-traumatic stress disorder in human subjects using an electronic device (Holtzheimer et al., 2017). The electronic device is implanted by a neurosurgeon through a surgical procedure known as Deep Brain Stimulation (DBS) and another device, housing the battery and other electrical components, are implanted under the clavicle (Parastarfeizabadi & Kouzani, 2017). These electrodes deliver electrical pulses on certain areas of the brain acting as artificial neurons (transmitting action potentials resulting in the release of neurotransmitters).

The study funded by DARPA is investigating a “closed-loop” system of DBS which uses a sensor while an “open-loop” DBS lacks a sensor (Parastarfeizabadi & Kouzani, 2017). The sensor monitors the brain allowing the device to be operated efficiently (stimulating the region of the brain during specified state or time), while the “open-loop” system continually remains stimulatory regardless of the state of the brain and must be manually programmed (Parastarfeizabadi & Kouzani, 2017). The procedure has been successful in treating Parkinson’s disease (neurodegenerative disease specifically affecting the midbrain); however, mood disorders have been least successful with this procedure until now. The DARPA-funded teams have successfully generated algorithms to interpret patterns associated with mood disorders based on brain activity providing electrical pulses when needed (Holtzheimer et al., 2017).

There are many concerns and challenges associated with DBS procedure such as the possibility of developing adverse effects from overstimulation or over-correcting the mood, accessing a subject’s mood from their brain activity, the short battery life (average 3-5 years) of the device, and the possibility of the device malfunctioning. As technologies improve and more data concerning the use of DBS grows, there will be better treatment options for individuals with mental illnesses.             

References:

Holtzheimer, P.E., Husain, M.M., Lisanby, S.H., Taylor, S. F., Whitworth, L. A., McClintock, S., Slavin, K.V…….. (2017). Subcallosal cingulate deep brain stimulation for treatment resistant depression: a multisite, randomized, sham-controlled trail. The Lancet Psychiatry. 4(11) 839-849.

Parastarfeizabadi, M. & Kouzani, A.Z. (2017). Advances in closed-loop deep brain stimulation devices. Journal of NeuroEngineering and Rehabilitation. 14:79 1-20. DOI 10.1186/s12984-017-0295-1

Matrix Metalloproteinase-9 and its Role in Skeletal Muscle Tissue.

 During my time as an undergraduate research assistant, I was responsible for creating histology slides stained through immunohistochemistry  to monitor the activity of matrix metalloproteinase 9 (MMP-9) in mouse skeletal muscle tissue. Immunohistochemistry is the technique in which fluorescent dyes are created to “tag” specific proteins of interest and reflect a fluorescent pigment when exposed under the black light of a microscope. Matrix metalloproteinases are a group of enzymes that are often involved in the degradation of the extracellular matrix in normal physiological processes such as embryonic development, wound healing, and bone development. As these processes typically require the deconstruction of damaged or developing tissue before continuing cellular development can occur, matrix metalloproteinases aim to degrade extracellular proteins such as collagen and gelatin to allow for these development processes to occur.

Through my work under guide of Ryan Mehan, the graduate student at the time, we noticed that MMP-9 in particular was highly active in mouse skeletal muscle tissue, especially after the mice were exercised for prolonged periods of time. We could tell that this was the case since its upregulation could be visualized by increases in reflective light intensity of the MMP-9-specific dye under the microscope’s black light. This was done after both wildtype and knockout mice null in the MMP-9 gene had gone through controlled exercise bouts and after we created immunohistochemically stained histology slides of the mice’s hindlimb muscles one, three, and  seven days post-exercise.

By comparing the results of wildtype and knockout mice, the research personnel noticed that, through cross-sectional analysis, there were decreases in primary skeletal muscle fiber type (i.e. type I in the soleus, type IIb in the tibialis anterior, and type IId in the gastrocnemius muscle) in exercised mice null in MMP-9. However, oddly enough, Dr. Mehan noticed that the average force generated by the null mice during the exercise trials was not significantly different than that of the wildtype mice; the extracellular concentrations of both collagen and gelatin were not significantly altered between the two control groups either. This may suggest that there are other compensatory mechanism by which the knockout mice’s physiology could overcome any deficits in skeletal muscle maintenance and development.

Mehan, R.S., Grebeck, B.J., Emmons, K., Byrnes, W.C., Allen, D.L. (2011). Matrix metalloproteinase-9 deficiency results in decreased fiber cross-sectional area and alters fiber type distribution in mouse hindlimb skeletal muscle. Cells, Tissues, Organs, 194(6): 510-520. https://www.ncbi.nlm.nih.gov/pubmed/21389674

Physician Assisted Suicide

This month on the 16^th comes the one-year anniversary of the Colorado End of Life Options Act going into effect. This act allows “an eligible terminally ill individual with a prognosis of six months or less to live to request and self-administer medical aid-in-dying medication in order to voluntarily end his or her life” (1) This act also allows a physician to prescribe aid-in-dying medication and makes it a criminal act to tamper with a person’s request for aid-in-dying medication (1). The passing of Proposition 106 made Colorado the sixth state that allows for the legal prescription and consumption of aid-in-dying medication.

Physician assisted suicide, otherwise referred to as death with dignity or physician aid-in-dying, is the “act of intentionally killing yourself with the aid of someone who provides the knowledge or the means to do so” (2). Physician assisted suicide is different from euthanasia. Euthanasia is the administering of life ending drugs by a doctor or other individual. This act is illegal in most the United States, however Colorado has discriminated it, with other states possibly following suit. In other countries, such as the Netherlands, Belgium, and Luxembourg allow it under certain restrictions (2).

 With the number of countries and states considering similar litigation allowing physician assisted suicide, the ethics of physician assisted suicide is once again in the spotlight. Those that are for physician assisted suicide claim autonomy- the independence and the right to make their own life, or death, decisions.  Supporters say that in many cases, it could relive physical pain and suffering that would continually worsen for the patient. Diane Rehm, a former NPR host, is an advocate for physician assisted suicide after her husband starved himself death in Maryland, a state where physician assisted suicide is illegal (3). Rehm believes that the way her husband had to die was inexcusable, and since become a high-profile advocate working with Compassion & Choices (4). Rehm believes in this cause so strongly that if asked to testify before congress, she would (4).

While there is support for physician assistant suicide, opponents argue that helping take lives is ethically wrong. Many people justify their argument against this legislation on religious grounds. In the Catholic church, suicide is a one-way ticket to hell. Therefore, many members of the Catholic church view physician assisted suicide as the ultimate sin and must therefore be protected against (5). Activists in the disability community have largely critiqued the language used in the debate (3). Some claim that the “right-to-die” is discriminatory because “life isn’t worth living if you’re disabled” (6). There is also concern within the opposition that legalization now leads to a moral slippery slope. The assumption is that people will become to quick to use the physician assisted suicide option, or that the guidelines will become too lax (3).

In the United States, there are no federal laws regarding physician assisted suicide, thus, states are passing their own laws (3). With other states following the lead of Oregon, California, and Colorado, there may soon be pressure to address the rising issue of physician assisted suicide and euthanasia on a national level.

(1)   https://www.colorado.gov/pacific/cdphe/medical-aid-dying

(2)   http://www.berkeleywellness.com/healthy-community/health-care-policy/article/physician-assisted-suicide-ethical

(3)   https://www.theverge.com/2016/11/8/13520908/assisted-suicide-colorado-death-dignity-right-die-election-2016

(4)   https://www.washingtonpost.com/local/npr-host-diane-rehm-emerges-as-a-key-force-in-the-right-to-die-debate/2015/02/14/12b72230-ad50-11e4-9c91-e9d2f9fde644_story.html?utm_term=.b68e39b96c25

(5)   https://euthanasia.procon.org/view.answers.php?questionID=000153

(6)   http://www.lifenews.com/2016/11/01/brittany-maynards-husband-if-youre-disabled-live-isnt-worth-living/