Saturday, October 18, 2014

Ebola infection: Will melatonin help you to survive? by Jerry Brainum

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The Ebola virus

To calm increasing national fears, President Obama in his weekly radio address on October 18, 2014 pointed out that in the nation of 300 million people, only three have contracted the Ebola virus, and only one person has died. This, however, is scant solace to those who hear that there is neither a cure nor a treatment for Ebola. This doesn't mean that if you contract the disease you will die, but rather that your chances of death range from 25% to 90% with an average of half those infected succumbing to the virus. The Ebola virus was first identified in the Sudan in 1976. It was thought to have been transmitted to humans by fruit bats, who are immune to the disease, but act as vectors of transmission. Prior to the current outbreak of Ebola, the World Health Organization (WHO)  identified a total of 1,716 cases. In contrast, the numbers for the current epidemic involve 9,216 cases, with 4,555 deaths. Again, about half of those who are infected, die.
   What is particularly alarming about Ebola is that there currently is no well-defined medical treatment for the disease. The treatment provided is what's called "palliative," which means indirect measures are provided in an attempt to keep the infected person alive long enough for his immune system to combat the infection. In fact, however, it's aberrations in the immune response to the disease that cause many of the problems that do result in mortality. As such, patients are provided with oral rehydration therapy, or sugar and salt water provided intravenously. Some emerging research shows that some common drugs may be able to prevent the Ebola virus from entering cells. One such class of drugs are calcium-channel blockers, normally used to treat high blood pressure. Thus far, however, these drugs have shown efficiency mainly in isolated cell studies, where the cells are infected with Ebola. Other emerging drugs, mostly still experimental, are already being provided to Ebola patients. These drugs are antiivirals, similar to the drugs used to treat viral infections such as herpes. Two such drugs are Favipiravir and Brincidofovir, with the latter drug provided to the one person thus far who had died from the Ebola infection in the United States. Clearly, it is not a cure. There is also an experimental antibody drug approved by WHO called Zmapp that seems capable of successfully treating Ebola infections, but there is not enough available yet to handle the current epidemic. Russia claims to also have an antibody drug that can knock out Ebola, but few details are available, and in any case, that drug isn't yet widely available, either.
     The virus is normally acquired by contact with blood and body fluids, including semen. In that latter fluid, it can last for up to 7 weeks, which means it can be sexually transmitted. Ebola can also survive on various surfaces for a few hours, a fact made only too clear after a few Texas nurses acquired the disease by not observing correct sterility procedures following the treatment of an Ebola patient (who died). The symptoms of Ebola usually begin about 2-3 days after being infected. Since the initial symptoms are similar to that of the flu, it's easy to mistake Ebola for the flu. These symptoms include fever, sore throat,muscle aches and pains, and headaches. This is followed by more serious symptoms that include vomiting, diarrhea, and a rash. The infection then progresses to liver and kidney failure, along with internal and external bleeding. Death follows in 6 to 16 days, often from low blood pressure due to excess fluid loss. This explains why rehydration therapy is the initial step in trying to control the disease and prevent death.
     Although Ebola isn't epidemic in the United States, and likely won't be, it is in several West African nations, including Guinea, Sierra Leone, Liberia, and Nigeria. The current outbreak in Africa began in December, 2013, and shows no signs of abating.
   Although death from Ebola is often caused by excess fluid loss, that's only the tip of the proverbial iceberg as to what really happens in the body with this infection. The primary specific causes of death are a disruption of the vascular endothelium or the lining of blood vessels, which causes the large degree of internal bleeding associated with Ebola; disseminated intravascular coagulation (DIC), which involves an initial overactivity of blood clotting proteins, leading to excess blood clots, followed by a loss of these clotting proteins, resulting in excessive bleeding; fibrinolysis, or the excessive breakdown of blood clots, eventually resulting in extreme bleeding in many internal organs. These major problems begin with the breakdown of the lining of blood vessels, the endothelium.
    But it's not the virus itself that attacks the endothelium, but rather is the result of the massive release of several immune mediators usually linked to inflammation in the body. These substances are collectively called cytokines and chemokines, and are released in response to inflammation and infection by immune cells. It is these mediators that activate the coagulation system, revving it to an excessively high level, that causes the endothelial damage. When a specific anticoagulant protein was provided to monkeys infected with Ebola, the monkeys survived the disease, giving credence to the notion that it's the uncontrolled coagulation reactions set off by Ebola that cause death from the disease.
   A recent article in the Journal of Pineal Research, suggests that ingesting melatonin, which is synthesized each day in the pineal gland in the brain from the amino acid, L-tryptophan, can protect the endothelium from the damage caused by exposure to the Ebola virus. Melatonin works in this manner by shielding the vulnerable endothelial lining from the damaging effects of the massive release of cytokines and chemokines that would otherwise compromise the integrity of the blood vessel lining. Melatonin also prevents the onset of DIC by upregulating certain natural clotting factors in the blood.
  The authors of the new paper also note that some of the effects of Ebola overlap with what occurs during septic shock, which usually causes death by the same route as Ebola, i.e., extreme loss of blood pressure. Providing melatonin appears to block the release of the various inflammatory mediators that are released in such great quantity during both Ebola infection and septic shock. While melatonin is not a cure for the virus itself, it may allow an infected person to survive long enough for their bodies to overcome the initial infection. It does this through preventing the inflammatory cascade that leads to destruction of blood vessels and out of control bleeding and coagulation. According to the authors, melatonin should be given to those diagnosed with Ebola as soon as possible in larger doses of 20 milligrams, several times a day for a prolonged period. It can be provided either orally or intravenously depending on the condition of the patient. In contrast, the body synthesizes melatonin in microgram amounts. One thousand micrograms equal one milligram. The usual dose suggested when melatonin is used as a sleep aid is 1 to 3 milligrams.
   As the study authors point out, since there is no current effective treatment for Ebola, it wouldn't hurt to try a course of high dose melatonin, since it may control the underlying mechanisms that overwhelm the body and lead to death.

 Xian-tan, D, et al. Ebola virus disease: Potential use of melatonin as a treatment. J Pineal Res 2014;In press.


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