Glossary

1. Artesunate

Artesunate is a semi-synthetic derivative of the plant artemisia annua. Artesunate is currently and primarily used as an anti-malarial agent throughout the tropics. It is one of the most widely used drugs in the third world by men, women and children in malarial regions. It is used daily for brief periods of time (5 days) and then twice-thrice weekly as prophylaxis of malaria attacks. Recent publications out of the US and Germany have shown that artesunate is a potent anti-viral agent and may also have anti-cancer properties. It is well tolerated but like any drug is not without risk. It is a potent NF Kappa B inhibitor and from such inhibition is likely to be derived its anti-viral effects which are broad and significant and with no viral resistance seen to date. If swallowed, artesunate can have antiparasitic as well as broad antimicrobial properties in the GI tract that could prove useful in the emerging problem of gut dysbiosis in CFS.

2. B-12

Hydroxycobalamin is a form of B-12 which easily dissociates into free cobalamin or free B-12, a potent nitric oxide (NO) scavenger. Excess NO has been linked to CFS pathology and can cause increases in peroxynitrite (ONOO) which is very injurious to the brain. B-12 is also important to the function of key antioxidant systems such as the methylation pathway. Free B-12 from hydroxycobalamin also scavenges H2S which appears to be a problem in CFS as well. Hydroxycobalamin is used in CFS as a scavenger and not to repleat B-12 blood deficiency which is not very evident in CFS though functional impairment is much more evident as B-12 is easily oxidized and then becomes non-functional. B-12 had also been shown to be low in the brain even though normal in the blood. Methylcobalamin and Cyanocobalamin are not recommended and appear ineffective by ETM and even have negative effects.

3. Chronic Fatigue Syndrome

Chronic Fatigue Syndrome (CFS) is a disorder of unknown cause characterized by significant functional disability associated with fatigue, pain and neuropsychological complaints.

In the USA it is defined by the 1994 CDC case definition and affects approximately 1% of the population.

4. Doxepin

Doxepin or Sinequan is a member of the tricyclic antidepressant class of drugs but at low doses typically used in CFS, Doxepin acts more as an immunomodulator through its actions as a very potent Histamine-2 (H2) blocker and is highly sedating, even at very low doses ( 1-2 mg). It is used in CFS for its properties of sleep maintenance, especially in combination with Klonopin. It can also be used in CFS relapse as an immunomodulator and softens immune activation symptoms, especially sore throat, swollen glands and congestion.

5. Echo terrain map

ETM is a series of positive and negative IVRT patient responses to a sequence of specific interrogations on the echocardiograph table. Reponses to only two interrogations in real time by transdermal gel to two mammalian cell signaling factors (porcine Liver and porcine Adrenal) provides a highly sensitive (100%) and specific (100%) diagnosis of classic CFS. Atypical cases can be seen that do not have this classic negative response pattern but their history is also atypical for CFS. Other interrogations provide additional specific information about CFS cases that are less specific to CFS but very sensitive to important issues relevant to CFS but may also be found in other non-CFS disorders.

6. Echocardiography

Ultrasound interrogation of the heart is known as echocardiography. The field of echocardiography began some 30 years ago with M-Mode echocardiography. Today, two-dimensional or 2-D echocardiography dominates the field and the best systems also employ Doppler ultrasound and advanced computer processing to yield both velocity and time measures simultaneously of any arbitrary point in the heart at the same time.

7. EFA

The essential fatty acids (EFA�s) fall into two main categories known as the omega-3 and omega-6 series which are distinguished by the presence of a double bond at either the third or sixth carbon atom from the methyl-group end of the fatty acid chain which typically numbers 18-22 carbon atoms in length. These fatty acids are essential because the body cannot synthesize a double bond at either the 3-carbon or the 6-carbon positions and because these fatty acids are essential to the synthesis of a range of cell associated autocrine and paracrine hormones known as the eicosanoids. These eicosanoids are responsible for an extremely large range of cell functions without which life is not possible and a derangement of which will cause severe cellular dysfunction and important clinical consequences.

8. ETM

9. Gabapentin

Neurontin or Gabapentin is a brain and nerve active agent that appears to act like a GABA agonist though the exact mechanism of action is unknown. Neurontin increases the neuronal depolarization threshold potential and therefore intrinsically neuroprotective, It is known to be sedating and thought to positively improve stage 4 sleep. It is also known to improve neuropathic pain such as postherpetic neuralgia and can be effective in treating hot flashes, tinnitus and restless leg syndrome. In CFS, we combine low doses of Neurontin (100-300 mg) with Klonopin and Doxepin to improve deep sleep.

10. HLA

HLA is the name given to a major gene locus on chromosome 6 called the major histocompatibility complex or MHC complex. There are six major antigens coded and hundreds of individual variations or specific genetic alleles as well as two sets per person, called the HLA haplotype. The term antigen is misleading and due to the historical observation that the proteins coded by this region were responsible for transplant rejection. In fact, they are human proteins which form membrane structures responsible for self vs. non-self immune recognition (HLA Class I) and for binding non-self proteins for immune recognition by immune competent cells (HLA Class II). The major HLA Class I found on most cell membranes of the body are called HLA-A, B and C. The major Class II antigens are found only on antigen processing immune cells and are called HLA-DR, DP and DQ.

11. human leukocyte antigen

12. Hydroxycobalamin or Hydroxy B-12

13. Inosine

Inosine is a nucleoside derived from a naturally occurring purine called hypoxanthine. Nucleosides are the building blocks of RNA and DNA. With the breakdown of cellular DNA and RNA, the broken down nucleosides are metabolized to uric acid through the xanthine pathway. Uric acid is a potent antioxidant and peroxinitrite scavenger. Inosine is classified as an anti-viral compound and currently under trials for the treatment of MS. A derivative of Inosine is known as Immunovir or Isoprinosine and sold as an anti-viral in Canada and Europe. Immunovir has been proven useful to treat a serious childhood post-viral illness involving the brain called SSPE. Inosine appears to block the effects of iNOS induced production of peroxynitrite (ONOO) during a more serious immune activation state.

14. IVRT

The interval in milliseconds between aortic closure and mitral opening is known as the IVRT or the isovolumetric relaxation time. It is measured by echocardiography and is not a trivial measurement to make. . Physiologically, it is the time it takes to pump free calcium out of the myocardium to produce relaxation of the myofibrils to allow ventricular filling and takes all the available free energy in the heart to do so. IVRT is inversely related to the cellular free energy. The higher the IVRT, the lower the cellular free energy.

15. Klonopin

Klonopin or Clonazepam is a sedative hypnotic of the benzodiazepine class. Klonopin was first approved for use in children as an anti-seizure drug. It raises the threshold for neuronal depolarization and is therefore inherently neuroprotective. It is used in CFS for sleep induction and has interesting additional properties as an indirect antioxidant through receptor binding within the mitochondria that reduces RIRR (ROS Induced Release of ROS) by the mitochondria. Klonopin seems to work better then Clonazepam.

16. Magnesium

Magnesium and Taurine � can reduce the neuronal depolarization threshold and therefore inherently neuroprotective. Magnesium can help sleep through this same mechanism and also helps anxiety and panic as well as night-time mental processing that interferes with sleep. Finally, magnesium can reduce pain thresholds. Magnesium blocks excess calcium entry into the mitochondria and this can help energy as well as helps the utilization of ATP that is produced. Taurine is often used in conjunction with Magnesium. Taurine is a sulfur containing amino acid and helps to magnify magnesium dosing by keeping more of it in the cell and Taurine has interesting antioxidant properties similar to SOD.

17. Neurontin

18. Oxygen toxicity

When the application of small amounts of oxygen, typically by nasal cannula, causes a negative shift in cellular energetics as measured by any objective means is called oxygen toxicity. A negative energetic shift of IVRT on echocardiography as a result of oxygen administration is indicative of oxygen toxicity. Oxygen toxicity may not be perceived by the patient on oxygen. Almost all CFS patients are toxic to oxygen if untreated.

19. Patent Foramen Ovale

A patent foramen oval or PFO is essentially a normal variant found in approximately one in four adults in which two tissue flaps between the two upper chambers of the heart (left and right atria), which are fully open during fetal life, fail to properly seal during the first 1-2 years after birth. The defect is typically asymptomatic and found serendipitously on evaluation of the heart for other reasons.

20. Redox

Redox refers to reduction-oxidation reactions which are very important in driving energy production (i.e. ATP generation) reactions in mammalian cells but which also involves the stability and performance of many cellular enzymatic reactions. Redox reactions involve the transfer (reduction) and acceptance (oxidation) of electrons. The redox state of a system represents the relative ratio of electrons available to be transferred from a high energy to a lower energy state as against the electrons that are in a final or near final, low energy or oxidized state. When all the electrons are in their final, low energy state then the system is fully oxidized and at its lowest energy level. When all the electrons are in their highest energy state, ready to be offloaded, then the system is in its most reduced or highest, though potential, energy state. Paradoxically, the mid-point of the redox continuum or redox state is associated with the highest free energy with the most energy available to do work in the form of ATP. ATP energy is essentially the captured bond energy as the electrons move from more reduced forms of high energy fuel molecules (ie glucose) to more oxidized low energy molecular forms such as CO2 or H2O.

21. RNase-L

This is an endogenous enzyme produced by human cells that is activated by the cytokine alpha-interferon and protects the cell from viral invasion. It is the primary and last line of anti-viral defense. Dysregulation of the RNase-L enzyme system can arise for reasons related and unrelated to a viral infection.

22. stem cell

Stem cells are a diverse group of cells found in nearly all multi-cellular organisms. They have the capability to multiply and differentiate into a large range of fully committed cell types from any organ system. There are two main types, embryonic and adult stem cells. Embryonic stem cells can differentiate into a fully competent and complete organism whereas adult stem cells are more limited in the types of tissue they can become or can repair. Stem cells can be obtained for use from the donor back to the donor (allogeneic) or from the donor to a non-related recipient (non-allogeneic). It is important to recognize that stem cells are a diverse group and can be synergistic when given together. There is no one type of stem cell. They can also be grown in tissue culture to very large numbers and frozen for use later.

23. Stem Cells

24. Taurine

Taurine is a sulfur containing amino acid and can be synthesized in man through the transulfuration pathway. Taurine helps to magnify magnesium dosing by keeping more of it in the cell and Taurine has interesting antioxidant properties similar to SOD. Taurine also has important membrane stabilizing effects that can positively influence cardiac arrythmias. Cats who cannot synthesize Taurine and who do not eat meat which is a primary source of Taurine, go blind.

25. Terrain Map

Terrain Map as an echocardiographic derived terrain map or ETM is a series of positive and negative IVRT patient responses to a sequence of specific interrogations on the echocardiograph table. Reponses to only two interrogations in real time by transdermal gel to two mammalian cell signaling factors (porcine Liver and porcine Adrenal) provides a highly sensitive (100%) and specific (100%) diagnosis of classic CFS. Atypical cases can be seen that do not have this classic negative response pattern but their history is also atypical for CFS. Other interrogations provide additional specific information about CFS cases that are less specific to CFS but very sensitive to important issues relevant to CFS but may also be found in other non-CFS disorders.

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Glossary

Learn about Chronic Fatigue Syndrome

They’re always wonderful at the clinic.
They’re never short with you.
They never act like they’re too busy to talk to you.
The whole staff is just wonderful.
— D.R., Tallahassee, FL, USA