Friday, July 20, 2012

People Carrying Guns Kill people not the Guns

Saturday, July 14, 2012

Depressed and Fat?? Your Fat Tissue is Making it Worse

There has been a long and strong correlation between depression and obesity. Depression very often leads to overeating which in turn results in obesity. Then one becomes more depressed because of their physical appearance, eating to sooth the emotional pain resulting in a vicious cycle. Adding to this mix is the close association between obesity and type 2 diabetes. Of note is the fact that the prevalence of depression is twice as high in type 2 diabetics compared to the general population. As I said, a vicious cycle. The problem with some antidepressant medications is that they increase the risk of developing type 2 diabetes in high risk populations.

Now some very surprising results have emerged from studies in mice that demonstrate a strong correlation between a hormone secreted exclusively from fat tissue (adipose tissue) and depressive behaviors. This hormone is known as adiponectin. Visit the Adipose Tissue page for more information on this hormone. Adiponectin is exclusively secreted from adipose tissue and possesses strong anti-diabetic properties primarily due to the fact that its actions in the liver and skeletal muscle leads to increased insulin sensitivity. There is emerging clinical evidence pointing to a correlation between the levels of adiponectin in the blood and depression. What is not completely known is whether adiponectin plays a role in the pathophysiology of depression or whether the hormone is modulating depressive behaviors.

Results from a study published online July 9, 2012 in the Proceedings of the National Academy of Sciences ( demonstrate that adiponectin levels are a critical determinant of susceptibility to depression and most surprisingly that the hormone itself exhibits antidepressant-like activity.

The study was performed in mice and involved what is called a chronic social defeat stress model. Basically, weaker male mice are placed in a cage with a dominant male who proceeds to challenge and antagonize the weaker male. The outcomes of this type of model are highly similar to symptomsof depressionin humans including social withdrawal and anhedonia (defined as the inability to experience pleasure from activities usually found enjoyable). When the plasma levels of adiponectin were analyzed in these mice they were found to be reduced. Of note is that the reduced levels of circulating adiponectin in the defeated mice werenot correlated to reduced fat mass. In addition, there were no significant changes in adiponectin mRNAlevels in adipose tissue of defeated mice compared to nondefeated control mice. In mice that have one adiponectin gene knocked out (referred to as haploinsufficiency), there was found to be a correlation to depressive behavior susceptibility similar to that seen in the defeated mice with who carry both wild-type copies of the adiponectin gene. In addition, if neutralizing antibodies to adiponectin are injected into the brains of mice they exhibitincreased susceptibility to depressive-likebehaviors.Conversely, if adiponectin is injected into the brains of mice the result is anti-depressive as measured by by the forced swim test and tail suspension tests that are widely used in the screening of antidepressant medications.

So here's the take home from this study. In humans with depression there is an increased tendancy toward obesity which results in further depressive-like behaviors. As the level of fat tissue increases there is a concomitant drop inthelevel of circulating adiponectin. Thus, as one gets fatter the corresponding drop in the levels of the fat tissue hormone adiponectin result in increased depressive tendancies and also to increased likelihoods of developing type 2 diabetes.

Monday, July 9, 2012

Metformin: The diabetes drug may actually make you smarter

Metformin is a drug that is a member of the biguanide class. It is currently the most widely prescribed insulin-sensitizing drug in current clinical use for the treatment of type 2 diabetes. For more information on metformin action in treating type 2 diabetes visit the Diabetes page on The Medical Biochemistry Page. Metformin administration does not lead to increased insulin release from the pancreas and as such the risk of hypoglycemia is minimal. The major site of action for metformin is the liver. A major mechanism for metformin action is the activation AMP kinase (AMPK: for more on AMPK function visit the AMPK page). Recent work has shown that AMPK activation in turn activates a class of protein kinase C (PKC) isoforms referred to as atypical PKC (aPKC), in particular aPKC iota and aPKC zeta. These two aPKC enzymes then can phosphorylate a transcriptional coactivator known as cAMP response element-binding protein (CREB)-binding protein (CBP). CBP has been shown to be necesasary for optimal differentiation of embryonic neural progenitors. Taken together it is suggestive that metformin might indeed activate aPKC in neural stem cells and allow their recruitment into the adult brain.

In a study published July 6, 2012 in Cell Stem Cell the ability of metformin to induce neurogenesis and enhance spatial memory formation was demonstrated. The study showed that metformin did in fact activate aPKC iota and aPKC zeta and that this resulted in rodent and human neurogenesis in a cell culture system. Within the adult mouse CNS, metformin was also shown to activate neurogenesis in the hippocampus. This metformin-induced neurogenesis required the action of CBP and was measured via spatial learning tasks involving a water maze.

The take home from this study is that there may be a new and potentially powerful function for metformin in humans. The drug may be used for therapeutic intervention in treating the injured or degenerating nervous system.

Saturday, July 7, 2012

Hey All You Idiot Teapublicans: The US Constitution GUARANTEES Separation of Church & State

Some of the more radically stupid conservative TeaPublicans in this country claim that our politics needs to return to the foundations established by the Constitution. The problem with these dumbasses is that they don't even know what is actually written in the Constitution and the original Amendments, in particular the First Amendment, nor do they have the slightest notion as to the reasons for the founding of this new country. Here are a few pertinent quotes from a couple of our founding fathers. It would be wise for everyone in this country, those on the right, left, independent, conservative, liberal, libertarian, etc. to actually read of the lessons of our founding fathers before opening a vacuous stupid mouth and release inane comments.

“If I could conceive that the general government might ever be so administered as to render the liberty of conscience insecure, I beg you will be persuaded, that no one would be more zealous than myself to establish effectual barriers against the horrors of spiritual tyranny, and every species of religious persecution.”
~George Washington, letter to the United Baptist Chamber of Virginia, May 1789

“I am for freedom of religion and against all maneuvers to bring about a legal ascendancy of one sect over another.”
~Thomas Jefferson, letter to Elbridge Gerry, January 26, 1799

 “The civil government … functions with complete success … by the total separation of the Church from the State.”
~James Madison, 1819, Writings, 8:432, quoted from Gene Garman, “Essays In Addition to America’s Real Religion”

Sunday, July 1, 2012

Docosahexaenoic Acid (DHA) and Turmeric Protect from Spinal Injury

Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (PUFA) found in high concentration in krill oils and cold water fish oils. There are three major types of omega-3 fatty acids that are ingested in foods and used by the body: Alpha-linoleic acid (ALA), eicosapentaenoic acid (EPA), and DH). Once eaten, the body converts ALA to EPA and then to DHA. EPA and DHA are the two types of omega-3 fatty acids that serve as important precursors for lipid-derived modulators of cell signaling, gene expression and inflammatory processes. For more details on the functions of DHA and EPA visit the Omega Fatty Acids page within The Medical Biochemistry Page or in the Supplement Sciences site. Among many physiological benefits, DHA and EPA have been shown to be important for normal brain development and function. Several studies have demonstrated that DHA is essential for proper development of the prenatal and postnatal central nervous system. In addition, studies have shown that dietary supplementation with DHA has beneficial effects on cerebral function and enhancing neural repair of damage caused by pathological processes.

Curcumin (chemical name diferuloylmethane) is the yellow compound found in the spice turmeric. Curcumin has been shown to suppress tumor promotion and proliferation, inflammatory signaling, and angiogenesis (the development of new blood vessels). The anti-inflammatory activity of curcumin is, in part, due to its ability to inhibit enzymes that are necessary for the synthesis of lipid mediators of inflammation. Recent studies have also shown that curcumin has therapeutic potential within the CNS in the treatment of Alzheimer disease and ischemic stroke. More details on the activities of curcumin can be found inthe Antioxidants page of the Supplement Science website.

A recent study published on June 26, 2012 in the Journal of Neurosurgery: Spine ( has demonstrated a potentially powerful function for these two chemically distinct compounds in the treatment and prevention of further damage in spinal cord injury patients. The studies were performed in ratsbut are applicable to human patients. Cervical spondylotic myelopathy (CSM) is the result of both primary mechanical and secondary biological spinal cord injury (SCI). In the study rats were surgically treated to produce a spinal compression injury via bilateral partial laminectomy in the cervical spine. I am of course greatly abbreviating the details of the spinal injury model used and it is necessary to read the manuscript to fully appreciate these details. Treated animals divided into 3 groups and were fed either a standard rat chow, a diet that replicated a Western society style diet (composed of 62% saturated fats and 32% sucrose), or a diet containing DHA (1.2%) plus 500ppm curcumin. The outcomes of this study were analyzed using a number of well established criteria to document spinal cord pathology and function. The takehome is indeed quite dramatic. The rats that received the DHA and curcumin containing diet maintained significantly higher levels of the neural growth factor brain-derived neurotrophic factor (BDNF), exhibited decreased cellular membrane damage, and preserved significant neurological function when compared to the Western-style diet or the normal rat chow diet.

These results indicate that there is significant potential for the use of dietary supplementation in the treatment of some forms of spinal cord injury. It is important to note that these studies were performed to mimic spinal crush injuries and not injury that results in partial or complete severing of spinal cord neurons. Still, the result are compelling and it is worth considering supplementation of ones diet with DHA and curcumin even without injury to the spine given the plethora of positive physiological and biochemical functions associated with these compounds.