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Fungi
It is becoming increasingly apparent
that the incidence of fungemia, a disease that results from human fungal
pathogens, is on the rise.
One probable cause of this increase is the more common usage of immunosuppressive
agents as a result of AIDS and organ transplantation, as well as
the wider and improper use of antibiotics suppressing the immune
system. Suppression of the immune system, including mechanisms normally
instrumental in destroying invading microorganisms and viruses, allows
the survival of mutants of these organisms that are more infectious
and virulent than those originally present. Clinically, fungemia
presents unusual symptoms including depression, edema of the extremities,
and fibromyalgia in which many forms of fungemia are seen in high
resolution microscopy (Bradford Variable Projection Microscope [BVPM]).59 (See
Photos 2 and 3.) Associated with fibromyalgia is the presence of
fungal forms, including various species of Candida (including
white C. albicans) and/or several forms of melanized (black) fungi
including Cryptoccous neoformans, Mucor sp. and Aspergillus sp. (See Chart
4 and Photo
3.)
Chart 4: Fungi Associated with Fibromyalgia and Other Pathologies
- Mucor (black) Growth in brain aneurysm105
- Candida (white) albicans, cancer;88 AIDS72
- C. lambica, arthritis of joint102
- C. ciferri, invasive candidiasis94
- C. glabrata, arthritis of joint97
- Cryptococcus (black) neoformans, inhibits TNF-alpha production;85 arthritis in hand98
- Aspergillus(black) fumigatus, arthritis
of joint;101 pulmonary (lung) infection;104 endocarditis
(cardiomyopathy), immunosuppression, life-threatening69 (gliotoxin)
- Penicillium aurantiogriseum, produces
cyclopiazonic acid, inhibits calcium ATPase of sarcoplasmic reticulum,
increaseof cytosolic calcium, inducing prolonged muscle contractions.
- Fusarium (red) proliferatum, anemia, muscle weakness71
- Alternaria ((brown/black) alternata, growth on fruits, possible source of infection75
- Neocosmospora vasinfecta, osteoarthritis100
- Scedosporium prolificans, disseminated infection90
- Blastomycosis - adrenal insufficiency70
- Penicillium camemberti, (found in cheese), produces cyclopiazonic acid, inhibits calcium ATPase in SR, increases cytosolic
calcium, induces prolonged muscle contractions and pain.
- P. brevi-compactum, produces adenophostins, agonists of IP3 receptor, increases cytosolic calcium, damages mitochondria, inhibits respiration,
results in fatigue
- All pathogenic fungi - produce PGE2, promotes fungal growth, down-modulates tumor necrosis factor (TNF), upregulates interleukin-10 (IL-10). IL-10 inhibits helper T-cells,
mast cells, inducing immunodeficiency103
Phase Microscopy | Darkfield
Microscopy
Photo 2: Black Fungus
Photo 3: White Fungal Cluster
Phase Microscopy
Life-threatening infections resulting from fungal pathogens such as
Cryptococcus neoformans have been increasing steadily over the past
ten years because of the prevalence of AIDS and the widespread use
of immunosuppressive drugs.79
Mucormycosis is a devastating fungal
disease affecting mainly diabetic and immunosuppressed patients and
frequently causing death. Mucor rhizopus
(black fungus), the opportunistic fungus, has been controlled by Sulfoxime™ and
intravenous Amphotericin B. Most fungi have a strong antioxidant system
and tolerate oxygen very well. The fungus Mucor has been associated
with fibromyalgia55 and observed with the Bradford Peripheral Blood
Assessments (BPBA). (See Photo 2, above.)
Twenty systemic fungal infections arising
within a five-year period were analyzed among cancer patients. Aspergillosis
(black fungus) was
the most common invasive fungal disease (55%), followed by mucormycosis
(15%), and fusariosis (15%) from infection by Fusarium sp., a fungus
which attacks almost all grains in the field, including wheat, corn,
rice, and barley.121 (See Photo 2, above.) In this study 85% of the
patients were diagnosed with black fungus utilizing the Bradford High
Resolution
Microscope; 100% of the FMS patients had black or red fungus.
Melanin is a pigment widely dispersed in nature, found in hair, butterfly
wings, beetles, the human brain (substantia nigra), black fungus, and
many biological structures having a black appearance. Chemically, melanin
is a three-dimensional polymer composed of several basic building blocks
or monomers connected in a random manner. The precursor for many melanins
is the amino acid phenylalanine, forming such substances as dopamine
and L-dopa.
C. neoformans is one example of several pathogenic fungi containing melanin
granules, giving them a black appearance. Another example is Aspergillus
niger or black bread mold.
An examination of any of the melanins in an electron spin resonance
(ESR) device reveals that melanin is a multi-site polymeric free radical
containing stable unpaired electrons. This implies that melanin is
capable of acting as a scavenger of free radicals (since free radicals
annihilate each other) and is thereby able to protect a melanin-containing
fungus from an oxidative burst released by immunocompetant cells.80
Additional studies have shown that there is indeed a transfer of electrons
between melanin and free radicals present in the surrounding medium.81
These studies also demonstrate that some strains of melanin-containing
fungus may differ in melanin content by as much as eightfold. Quantitative
analysis revealed that melanin comprised greater than 15% of the dry
mass of the cell after a ten-day growth in a medium supplying the necessary
ingredients for melanin synthesis. The virulence of pathogenic strains
of black fungi is shown to be directly related to the melanin content.
Those fungi grown in media containing the precursors of melanin were
more virulent than those deprived of these substances.82 A corollary
to this research is that those suffering from infection by a melanin-containing
(black) fungal pathogen should avoid foods that contain large amounts
of phenylalanine. The food containing the largest amount of this amino
acid is the soybean. Soybean products also include tofu and soymilk.
Exposure of melanized black fungal
cells to 0.1–0.5% sodium
hypochlorite (NaOCl) bleached the cells white and abolished the ESR
signal, consistent with melanin disruption.15 It may also be safely
said that any substance tolerated by the body and supplying nascent
oxygen would also be effective in bleaching melanin granules in vivo.
A second example of such a substance is Proprietary Stabilized Active
Oxygen Carrier, used in clinics worldwide for this purpose.
C. neoformans is a human pathogenic
fungus that is unusual in two respects: (1) it has a polysaccharide
capsule similar to that found
in encapsulated bacteria, and (2) it can produce melanin. Cells of
C. neoformans are significantly more negatively charged than cells
of baker's yeast (Saccharomyces cerevisiae). This negative charge
is a repulsive force to the negative charge on circulating formed cells
that conveys a degree of immunological privilege for most fungi. The
polysaccharide capsule is responsible for the high negative surface
charge. In addition, the melanin of this organism is also negatively
charged, giving an increased negative charge per cell. It has been
established that macrophage phagocytosis is affected by the electrical
potential of targeted microorganisms.83
Cryptococcus neoformans must reduce ferric iron (Fe+3) to the ferrous
form (Fe+2) before uptake. Detailed studies have shown that melanized
cells reduce iron from the ferric to the ferrous state at a rate 16
times that of nonmelanized cells.84 Iron is required for the continued
growth of this organism. If the melanin in melanized cells is bleached,
the ability of this fungus to reduce iron to an available form is thereby
thwarted.
Intra-tracheal 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 differ 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.85
Various drugs are known to bind to melanin with high affinity, including
the antipsychotic agent trifluoperazine and the antimalarial agent
chloroquine. When C. neoformans was exposed to trifluoperazine, melanized
cells were more susceptible than nonmelanized cells. Chloroquine had
no fungicidal effect on either melanized or nonmelanized cells. These
results suggest that antifungal drugs of the future intended to target
melanized fungal cells may be found among those substances having a
high binding affinity for melanin.86
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