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Mitochondrial Damage
The inner mitochondrial membrane normally maintains a potential difference or gradient of H⁺ ions (protons). With the accumulation of excess calcium (Ca⁺²) in the cytosol, mitochondria swell, triggering the mitochondrial permeability transition (MPT) pore to open with the loss of membrane potential. From this point, a cell may take one of two possible paths. The loss of membrane potential results in lower ATP (the energy molecule) production and the accompanying fatigue. The second path leads to cell destruction through apoptosis. If cytochrome C is released through the MPT pore, this triggers through caspase-3 the mechanism of apoptosis and cell destruction.¹¹⁸ See Figure 7 (15KB .pdf) and Chart 5.

Chart 5: Activities of Cyclopiazonic Acid, Gliotoxin, Adenophostins

Cyclopiazonic Acid
Inhibits Ca+2-ATPase (Decreases calcium influx into SR)
Increases cytosol calcium
Negative effect on cardiac muscle contraction
48% of administered cyclopiazonic acid is bound to muscle

Gliotoxin
Immunosuppressant, decreases CD4+/CD8+ ratio
Inhibits ATP production in muscle
Inactivates enzymes, proteins, causes DNA strand breaks

Adenophostins
Activate IP3 receptor (Increases calcium efflux from SR, cytosolic calcium)

RECENTLY DISCOVERED FIBROMYALGIA SYMPTOMS

In addition to the familiar fibromyalgia symptoms of muscle pain, sleep disturbances, and others described above, there have been discovered recently additional symptoms previously unrecognized. These symptoms were discovered through a survey of 554 individuals suffering from fibromyalgia and compared with 169 controls. Some newly discovered symptoms include bursitis, softening of cartilage, constipation, diarrhea, vertigo, tinnitus, and sinus and thyroid problems. Of this group, 70% reported that their symptoms were aggravated by noise, lights, stress, posture, and weather.⁶² See Chart 6. Additional research has shown increased sensitivity to non-painful warmth over tender points and a tendency to increased sensitivity to non-painful cold, compared to controls.⁶³

Chart 6: Additional Symptoms of Fibromyalgia from a Study of 554 Individuals

• Bursitis
• Cartilage Softening
• Constipation
• Diarrhea
• Vertigo
• Sinus Problem
• Thyroid Problem
• Concentration Problems
• Swollen Glands
• Sensory Symptoms
• Tinnitus
• Chronic Cough
• Tachycardia
• Weakness
  
  Reference: Am J Phys Med Rehabil 1992;71:343-8.
  

Dry Eyes and Mouth
In another study of 118 fibromyalgia patients, 35 patients (30%) had a history of Raynaud's phenomenon (spasm of finger arteries leading to whitening of the finger), while 18% had symptomatic dry eyes and mouth. These symptoms and others are suggestive of a systemic connective tissue disorder.⁶⁴

Environmental Chemical Sensitivity
Severe chemical intolerance (CI) or sensitivity to environmental chemicals is a characteristic of 20-47% of individuals with apparent CFS and/or FMS, but appears in only four to six percent of the general population. One site for this increased sensitivity may be the limbic system of the brain, receiving input from the olfactory pathways and sending efferents to the hypothalamus. Research-to-date has demonstrated the initiation of neurobehavioral sensitization by volatile organic compounds and pesticides in animals, as well as sensitization of cardiovascular parameters, beta-endorphin levels, resting EEG alpha-wave activity, and divided attention task performance in persons with CI.⁶⁵

Inflammatory Response System
In a study of 21 fibromyalgia patients (by American College of Rheumatology criteria) there was demonstrated a significantly higher concentration of the receptor for the cytokine interleukin-6 (IL-6) and other blood proteins than in normal controls. These results support the contention that pain and stiffness in fibromyalgia may be accompanied by a suppression of some aspects of the inflammatory response system (IRS).⁶⁶

Edema
Fluid retention syndrome or idiopathic edema is almost exclusively seen in women. It can produce a variety of symptoms ranging from headaches and blurring of vision to abdominal pains and diarrhea. This reference describes four edema cases that also show signs and symptoms of fibromyalgia.⁶⁷

Adrenal Insufficiency
One case is reported of disseminated blastomycosis showing adrenal insufficiency.⁷⁰

Muscle Weakness
Tissue and blood cultures of a 59-year-old man revealed infection by Fusarium proliferatum, a fungus that infects many grains in the field. The patient showed symptoms of anemia and muscle weakness. These symptoms were alleviated by antifungal chemotherapy.⁷¹

Latent HIV Activation
Both candidiasis (from Candida albicans and other C. species) and cryptococcosis (from Cryptococcus neoformans) are common in human immunodeficiency virus (HIV-1)-infected persons. Stimulation of the latently HIV-infected myelomonocytic cell line OM-10.1 with C. neoformans and C. albicans in the presence of human serum caused a ratio-dependent increase in HIV production. Both C. neoformans and C. albicans enhance HIV expression in monocytes through a TNF-alpha-dependent mechanism. Such enhancement may further impair host immunity and could accelerate the course of HIV disease.⁷²

Inhibition of TNF-alpha Production by T-Cells
Intratracheal inoculation of C. neoformans-strain 52 induced a vigorous T-cell-mediated pulmonary inflammatory response that controlled the growth of the organism. In contrast, strain 145 induced a pulmonary response that was delayed in onset, slower to develop, and ineffective in controlling the infection.

These two strains differed only in melanin production with strain 52 low and strain 145 high. In addition, the high melanin-containing strain 145 inhibited TNF-alpha production and lymphocyte proliferation by T-cells. By inhibiting the production of TNF-alpha by T-cells, melanin can inhibit the recognition of the organism by host defenses and block the resulting activation of apoptosis in this fungus.⁷³

Fibrinolysis Inhibition
A protein found in the blood, plasminogen, is an inactive form of the enzyme plasmin. When activated by a specific protein, plasminogen activator (PA) (which is under steroid hormonal control), plasminogen is converted to plasmin, a broad-based, nonspecific, proteolytic enzyme capable of digesting and solubilizing both the soluble and insoluble polymeric protein fibrin and fibrin complex (SFC).

It has been found that the gene for plasminogen activator (PA) is a late gene resulting in the late response protein PA. Late response proteins arise from the initial presence in the cell of a steroid. The germination of yeast buds in Candida infection also involves the steroid-steroid receptor complex. As only a fragment of the intact hsp90 of Candida, hsp47 is apparently able to bind to the steroid receptor responsible for the transcription of PA activator protein, blocking that receptor and preventing the activation of plasminogen, thereby inhibiting fibrinolysis.⁷⁴

Muscle Cramps and Spasms
The growth of the black/brown fungus Alternaria alternata was examined on a variety of fruits including strawberries; seedless grapes; concord grapes; red delicious, golden delicious, and gala apples; and blueberries. A. alternata was found not to be a major problem in strawberries because of other fast-growing fungi, however, this fungus was found to grow exceptionally well on the golden delicious and gala apple varieties. Restricted growth without toxin production (tenuazonic acid and others)⁷⁶ occurred in blueberries.⁷⁵ One of the symptoms resulting from ingestion of Alternaria sp. is pronounced muscle spasms and cramps.⁷⁷

Mucormycosis
Mucormycosis is a devastating fungal disease affecting mainly diabetic and immunosuppressed patients, frequently causing death. Mucor rhizopus (black fungus), the opportunistic fungus, has been controlled by Sulfoxime™, intravenous Amphotericin B as well as hyperbaric oxygen. The fungus Mucor has been associated with fibromyalgia.⁵⁵ and observed with the Bradford Variable Projection Microscope (BVPM).

Edema, Cataracts and Psychological Responses/Depression
Those practitioners treating both fibromyalgia and fungemia have observed the symptoms of fluid retention in the extremities (edema), psychological problems, including depression, and cataracts in those patients suffering from these diseases.⁷⁷

COMPARISON OF FIBROMYALGIA/FUNGEMIA SYMPTOMS

Many of the more common symptoms of fungemia are illustrated in Figure 10.(10KB .pdf) There has been noted a striking similarity between the symptoms of fibromyalgia and the systemic fungal infection fungemia. Some of these relationships are shown in Chart 7.

Chart 7: Comparison of Fibromyalgia and Fungemia

Symptoms common to both include:
Muscle Fatigue, Pain/Cramping
Neuroendocrine Defects (Adrenal)
Edema
SleepDisturbances
Depression/Anxiety
Cardio- :Tachycardia, Palpitation, etc.
Antibodies to Serotonin
Chemical Sensitivities (20-47%)
Respiratory Abnormalities
Immune System System Deficiency
Constipation

Cardio/Respiratory Insufficiency
Aspergillosis was diagnosed in 35 patients; of this group, 13 died of cardio-respiratory insufficiency.⁶⁸

A case of aspergillus endocarditis (cardiomyopathy) was corrected by valve replacement and antifungal chemotherapy. Following therapy, blood cultures failed to reveal the presence of Aspergillus.⁶⁹

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