Month: January 2009

Exercise lowers inflammation associated with heart disease

A study published in 2005 evaluated levels of C-reactive protein in sedentary men and women when placed on an exercise training program for five months. The patients significantly reduced the C-reactive proteins in the blood. 
High levels of C-reactive protein in the blood indicates inflammation associated with heart disease, stroke and hypertension. 
The patients who exercised also produced marked changes in body weight, glucose, LDL cholesterol, HDL cholesterol, triglycerides, and blood pressure. 
What does this mean? That despite all my efforts to avoid exercise by living an otherwise healthy lifestyle, I gotta head to the gym. Or else.  
Reference
Lakka TA, Lakka HM, Rankinen T, Leon AS, Rao DC, Skinner JS, Wilmore JH, Bouchard C. Effect of exercise training on plasma levels of C-reactive protein healthy adults: the HERITAGE Family Study. European Heart Journal, 26, 2018–2025, 2005 doi:10.1093/eurheartj/ehi394

What? Another possible risk factor for heart disease?

More research is needed to determine if hyperhomocysteinemia may be a risk factor to heart disease, but if it is, then that’s just another reason to eat less meat (1). Eating meat increases levels of homocysteine in the blood (1). Leafy greens and a variety of fruits in the diet supplies folic acid and B vitamins, which help break homocysteine down (1). Vitamin B12 (almost exclusive to meat) helps as well so choosing to give up meat entirely is not advisable (1).


Reference
Web MD. Homocysteine: Heart disease risk. Available at: http://www.webmd.com/heart-disease/guide/homocysteine-risk

Fats and Heart Disease

Just because fats don’t have a direct affect on heart disease, it doesn’t mean they shouldn’t be worried about. Saturated fats and trans fats increase LDL cholesterol in the blood (1) creating a greater situation of LDL oxidation, which contributes to inflammation that is the cause of heart disease. A diet with a high ratio of omega-6 to omega-3 oils creates a proinflammatory state (2), which also enhances risk. 
Through knowledge of fats and how they affect the body in different ratios, it is possible change course of health. Additional omega-3 fatty acids and lesser amounts of saturated fats, trans fats, and omega-6 fatty acids could largely benefit through reduction of LDL cholesterol in the blood, reduction of triglycerides and less inflammation.
References

Cause of Heart Disease: Inflammation? Yes, but don’t forget cholesterol’s role

The medical establishment in the U.S. has been professing benefits of controlling cholesterol since 1985, because of research linking cholesterol to atherosclerosis and coronary artery disease (1). Short sighted, however, is the regard to these diseases as based completely on excess cholesterol as often assumed (2-3). 
New research has proved that an assay of C-reactive proteins in the blood can predict coronary artery events (2). The higher C-reactive proteins are in the blood, the higher risk of an event and less likelihood of survival from the event (2). The C-reactive proteins, which increase during inflammation, suggest heart disease itself is an inflammatory condition (2). 
If inflammation is the cause of heart disease, then inflammation should be the target of therapy, but it’s important to not forget the link between cholesterol and heart disease. The atherogenic nature of LDL cholesterol in the arteries (now considered an independent factor to heart disease) leads to oxidation of LDL, which produces low-grade inflammation (2-3)! LDL is still partly to blame. Further, these findings bring oxidative stress in as a factor. 
There are also many other causes of low-grade inflammation associated with coronary artery disease such as smoking, high blood pressure and hyperglycemia (2). These also produce oxidation of LDL. In fact, those with insulin resistance due to hyperglycemia also show an increased amount of oxidized LDL (4). 
My opinion on heart disease is formed by all the different sides. Moving a patient from a pro-inflammatory state to a healthy state requires medical treatment and diet designed to take in all factors. These should include levels of C-reactive proteins, LDL cholesterol, oxidation of LDL cholesterol and other causes of inflammation.   
References
3. AHA. Atherogenic lipoprotein particles in atherosclerosis. Available at http://circ.ahajournals.org/cgi/content/full/109/23_suppl_1/III-2
4. Scazzocchio B, Varì R, D’Archivio M, Santangelo C, Filesi C, Giovannini C, Masella R. J Lipid Res. 2009 Jan 9. [Epub ahead of print] Links
Oxidized low-density lipoproteins impair adipocyte response to insulin by activating serine/threonine kinases. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19136667?ordinalpos=13&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Goods and Bads of Antipyretic Therapy

Should antipyretic therapy be used at all?

A fever is a natural response to infections, toxins, immunologic diseases or injury in many a warm-blooded animal (1p58). It can help enhance immune system function and filtering out of infection through phagocytosis (1p58). The elevated temperature also can interfere with bacteria’s ability to grow and reproduce (1p58). 
“Goods” of Antipyretic Therapies
 A fever should max out at 105 degrees Fahrenheit, but if it reaches 106 degrees then a potential malfunctioning hypothalamus means it’s time to go to the emergency medical care (1p58). The fever is to the point that cranial pressure is posing a risk to the brain, the heat may interfere with cardiac function in compromised patients, and the elevated core temperature could hurt a fetus if pregnant (1p58). 
It’s time to intervene with antipyretic therapy. Wet cloths, cool blankets, ice baths and cold IVs all help to offset the elevated temperature (1p59). Drugs like aspirin, or acetylsalicylic acid), and acetaminophen work by inhibiting prostaglandin production in the hypothalamus blocking their signals and effectively reducing the body’s temperature set point to that of near normal levels (1p59). 
“Bads” of Antipyretic Therapies

Aspirin and acetaminophen all are blockers of cyclooxygenase (COX) activity (1pp40-41). There are two isoforms of COX. COX-1 maintains the the gastric mucosa, regulates perfusion in the kidneys and is involved in platelet aggregation needed for coagulation (1pp40-41). COX-2 mediates inflammation and prostaglandin production. Because the antypyretics are not selective in which COX they inhibit, they damage the gastric mucosa, acetaminophen is toxic to the kidneys, and aspirin diminishes platelet function (1pp40-41). Children should also avoid use of aspirin because of it is associated with Reyes syndrome (1p59).
Reference
1. Nowak TJ, Hanfod AG. Pathophysiology: Concepts and applications for health care professionals, 3rd ed. 2004. New York, McGraw-Hill, pp58-60. 

Don’t mix Tylenol and Motrin

I’ve got a fever right now that’s driving my head crazy. After reading my Pathophys chapters I’ve got a wet cloth on my forehead. But still it’s making it very difficult to take the dive into my exam. 
Pain stinks. I’m strongly considering that Tylenol/Motrin combination. But, no… 
While multimodual analgesic combinations such as Tylenol and Motrin do provide significantly more pain relief, the safety of this kind of use has not been completely determined, at least since 2001 (1). But, pending further, research, combinations could be useful such as before surgery (2-3). 
Reference
2. http://linkinghub.elsevier.com/retrieve/pii/S1366007104000749

Don’t take Tylenol without protecting your liver

Acetaminophen like Tylenol depletes glutathione and damages the liver (1), but chances are people won’t be getting away from using them anytime soon. What can be done is help protect the liver from damage induced through supplementation. 

Silymarin (from milk thistle) may serve as a support while taking acetaminophen. In a rat study, acetaminophen decreased glutathione and glycogen quickly (1). Unlike the control, rats taking silymarin showed no significant increase in lipid peroxidation or disruption of enzyme activities (1). Thus, while the silymarin didn’t prevent glutathione depletion in rats, it did protect the liver possibly through antioxidant properties and helped with restoring glycogen (1). 
Human studies have not yet been conducted, but many doctors already recommend silymarin supplements based on its recent research (2). 
Reference
1. Muriel, P; Garciapina, T; Perez Alvarez, V; Mourelle, M. Silymarin protects against paracetamol-induced lipid peroxidation and liver damage. J Appl Toxicol. 1992 Dec; 12(6): 439-42

What’s the most important part of the cell?

The earliest cell is thought to have emerged at least 3.8 billion years ago at a time when the environment was anaerobic in nature (1-2). It is suggested that simple organic molecules formed and gave rise to a self-replicating RNA that found itself within a phospholipid membrane (2).   
The evolution of metabolism began with glycolysis (2), the sequence of reactions would produce life’s universal energy source: ATP (1-3). Photosynthesis and oxidative phosphorylation would come later (2). 
While cells may not need certain parts to remain living, all still depend on glycolysis to generate energy (2). The pathway is contained within the cytoplasmic matrix (1-2). Thus, I propose the cytoplasmic matrix is the most important part of the cell. 
References
1. Dennison KJ, Topping J, Caret RL. General, Organic, and Biochemistry. New York: McGraw-Hill, 2007.
2. Cooper, G.M. “The Origin and Evolution of Cells.” The Cell: A Molecular Approach. Available at: http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cooper.section.90.
3. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism, 5th ed. Belmont, CA: Thomson Wadsworth, 2009.

Trust a biochemist

At the molecular level of life matters may be small and energy gains and losses seemingly insignificant, but a broad understanding of biochemistry leads to profound, larger conclusions of cell biology and the energy of which is ultimately the existence of life. Just as the smallest ingredient such as a dash of salt can change the flavor of a recipe, the cell can be affected by the slightest difference that ultimately means life or death.

Biochemical knowledge, in short, is fundamental for comprehending cells. And because cell biology is fundamental to all biological sciences, lack of biochemistry training severely limits the would-be biologist, medical practitioner, and health practitioner. 

So be sure to ask your doctor, nutritionist and nutrition science writer, “How’s your biochemistry?” If they can adequately explain the difference between activation energy and change in free energy (see last post), then they pass the test. If they roll their eyes at you, be cautious.

The reason why hemolytic anemia probably exists

Hemolytic anemia

Within the cytoplasmic matrix of a red blood cell occurs an anaerobic pathway of glucose catabolism known as glycolysis consisting of 10 reactions (1). The enzyme that catalyzes the last reaction is pyruvate kinase (1). The reaction is one of two that produces ATP and also pyruvate, the molecule generally converted to acetyl CoA for entry into aerobic respiration (1). A deficiency of pyruvate kinase results in low ATP levels (2). It is one of the most common defects of a blood cell (2).

A young red blood cell, or reticulocyte, starts out with organelles and then loses them. While retaining their mitochondria they require a lot more oxygen and if it goes through the spleen while in this stage it could mean its failure, since the spleen is deficient in oxygen and glucose (2).
Lack of sufficient energy causes failure of ion pumps leading to a disrupted intracellular electrolyte concentration (2). The performance of the pentose phosphate pathway is diminished (2). The pathway is necessary for anabolism of glutathione, necessary for the cell’s defense against oxidative stress (2). Membrane injury results in distortion, rigidity and dehydration of the cell (2).

Eventually the red blood cell is filtered out by the spleen or liver (2). A hemolytic anemia occurs due to low blood count resulting from the rate of red blood cells lost outnumbering the rate of production of red blood cells by bone marrow (3). Because red blood cells carry oxygen via their hemoglobin, anemia reduces oxygen distributed in the body (3).

How did a defect such as hemolytic anemia such as sickle cell make it into the human gene pool?
You might find it interesting to learn that the latest research into sickle cell and other hemolytic anemias suggest the diseases may have acted as a protective mechanism against malaria. The theory has been tested in mice and humans (4-6). It is suggested that the rapid elimination of infected red blood cells may have increased overall survival to infection (4;6).
References

1. Dennison KJ, Topping J, Caret RL. General, Organic, and Biochemistry. New York: McGraw-Hill, 2007.

2. Frye, R. E. and Deloughery, T. G. Pyruvate Kinase Deficiency. WebMD . 12-31-2008. Ref Type: Online Source

3. National Heart and Lung Institute. Hemolytic Anemia. Diseases and Conditions Index . 2006. Ref Type: Online Source

4. Min-Oo G, Fortin A, Tam MF, Gros P, Stevenson MM. Phenotypic expression of pyruvate kinase deficiency and protection against malaria in a mouse model. Genes Immun 2004;5:168-75.
5. Min-Oo G, Tam M, Stevenson MM, Gros P. Pyruvate kinase deficiency: correlation between enzyme activity, extent of hemolytic anemia and protection against malaria in independent mouse mutants. Blood Cells Mol Dis 2007;39:63-9.
6. Durand PM, Coetzer TL. Pyruvate kinase deficiency protects against malaria in humans. Haematologica 2008;93:939-40.