Iatrogenic Immunodeficiency

Mark Peters gquest at nol.net
Sun Dec 8 23:26:27 EST 1996


1950
Rare and sporadic cases of systemic STEALTH MICROBE (C. albicans)
occurred prior to 1950.
Dermatoligic Clinics Vol 7, No. 2 Apr 1989

1992
"Candida albicans is the most common fungal pathogen causing
life-threatening
infections in immunocompromised patients and in recent surveys is the
fifth most
common pathogen isolated from the blood of hospitalized
individuals.[es-ji.92] !ca^aids.5mc

The following agents - Antibiotics and antibacterial, Corticosteroids ,
Birth control pills,
Cytotoxic therapy, Integumentary breaches,  Histamine h2 antagonists,
Anti-ulcer
medications and Tricyclic antidepressant are responsible for the
increasing incidence
of......Then Candida uses its vast arsenal of bio-weaponry and destroys
cellular and
humoral immunity.


ANTIBIOTICS AND ANTIBACTERIAL PROMOTE FUNGAL INFECTIONS

     "Broad spectrum antibiotic regiments are also considered
significant predisposing
factors to candidiasis. "[15]
     "Antibacterial therapy, especially if prolonged, may predispose to
fungal infections
even in the immunocompetent host.[1]


CORTICOSTEROIDS PROMOTE FUNGAL INFECTIONS


     "Corticosteroid use promotes fungal infection via multiple
mechanisms. Leukotaxis is
depressed, transient T-lymphopenia and monocytopenia  occur, and
alterations in
blastogenesis and monocyte function, as well as decreased response to
lymphokines 
have all been reported."[1]

     "Prolonged use of moderate to high-dose adrenal corticosteroids is
a common
feature in patients with systemic candidiasis.  Steroids enhance
invasive disease by
impairing phagocytic cell function, suppressing acute and chronic
inflammatory  mechanisms, retarding wound healing, and interfering with
cell mediated immunity and
antibody production. There is considerable evidence that steroids
facilitate Candida 
colonization and infections, both in humans and experimental animals. 
The epidemiologic data further substantiate steroids as a major
predisposing factor in most
cases.[15]


BIRTH CONTROL PILLS


     "The most wide spread use of steroids , however, is not in the
treatment of disease but in the contraceptive pill.  The long-term use
of this type of medication can have a devastating effect on the immune
system in general, and on the ability of Candida to proliferate
unchecked, in particular".[50]


CYTOTOXIC THERAPY PROMOTES FUNGAL INFECTIONS 


     Cytotoxic chemotherapy, is given for leukemia and bone marrow
transplantation, results in granulocytopenia and defects of
cell-mediated immunity;[1]

     "It is in the setting of granulocytopenia induced by cytotoxic
chemotherapy for malignancies that the most rapidly progressive and
potentially devastating opportunistic fungal infection may occur,
especially disseminated Candidiasis,..."[1]

INTEGUMENTARY BREACHES PROMOTE FUNGAL INFECTIONS 


     "The presence of indwelling intravenous catheters used throughout
medicine and particularly in seriously ill patients carries a
predilection for Candida fungemia.  The apparatus, solutions, and/or
wound of intravenous therapy can be colonized by Candida sp., thereby
seeding the bloodstream.  Candida albicans is the most common isolate
responsible for intravenous associated fungemia..."[15]


HISTAMINE H2 ANTAGONISTS PROMOTE FUNGAL INFECTIONS 


     Histamine H2 antagonists that block gastric acid secretions promote
Candida albicans growth and adherence to mucosa.[15]




ANTI-ULCER MEDICATIONS CAUSE CANDIDA OVERGROWTH


     "Patients on the anti-ulcer drugs Tagamet(cimetidine) or
Zantac(ranitidine) actually develop candida overgrowth in the stomach,
this highlights the importance of hydrochloric acid in the prevention of
candida overgrowth."[49]

     "Digestive secretions such as hydrochloric acid, pancreatic enzymes
and bile normally prevent the overgrowth of candida and its penetration
into the absorptive surfaces of the intestines.  A lack of any of these
digestive factors will allow the yeast to overgrow."[49]


TRICYCLIC ANTIDEPRESSANT & SALIVARY DYSFUNCTION

"Many instances of salivary dysfunction in humans can be traced to the
use of medications that have hyposalivary side-effects."[70]
 
" Xerostomia (A dryness of the mouth) is frequently reported as a side
effect of tricyclic antidepressants... Beta-adrenergic signal
transduction regulates the secretion of many salivary proteins. It was
reported that administration of desipramine resulted in a decrease in
the concentration of secreted salivary protein.[71] I

SALIVARY HISTIDINE-RICH GERMINATION inhibitor

"The neutral histidine-rich polypeptide (HRP) from human parotid
secretion is a potent inhibitor of Candida albicans germination and
therefore may be a significant component of the antimicrobial host
defense system in the oral cavity."[72]

access to the blood.  Catheters allow Candida direct access to internal
organs.  

     Candida infections are genuinely difficult to detect. Candida is
capable of adapting its survival strategy to evade different host
defense mechanisms and may present a false negative diagnose by skin
test.  Gut colonization with Candida increases your susceptibility to
other infections and Candida can translocate through intestinal cells
into to blood stream and lymphatic system. Antifungal drugs are unduly
toxic and some Candida's nine various phenotypes are resistant to the
antifungal's killing action.  

     Candida causes depression of delayed type hypersensitivity
responses and significantly increases suppressor cell activity.  Candida
impairs PMN (neutrophils) anticandidal function and the PMN impairment
corresponds to increased bacterial infections as verified in patients
with elevated candida antigen titers.

     Candida's proteinase attacks the skin and mucous membranes, reduces
opsonization activity, degrades complement C3 bactericidal activity, and
cleaves a number of immunoglobulins, including secretory IgA and both
isotopes IgA1 and A2.  

     Candida proteinase degrades endogenous proteinase inhibitors, alpha
2 macroglobulin and alpha 1 proteinase inhibitor which are involved in
regulating inflammation and degrades the fc portion of immunoglobulin G.
 

     Gliotoxin is a highly toxic poison produced my many Candida species
and is detected in vaginal samples of women with candidiasis.

     Gliotoxin causes cellular damage : (1)attacks mucociliary action,
(2) causes perturbation of cytoskeletal microfilament cables, (3)
induces microvilli loss, (4) causes reorganization of cortical
cytoplasm, (5) cell detachment and (6) cell vacuolation.

     Gliotoxin altered bile acid uptake, and afflux and modified hormone
responsiveness.

     Gliotoxin induces apoptosis with DNA fragmentation in macrophages,
morphological changes typical of apoptosis in concanavalin a-stimulated
T blasts and can kill non-hematopoietic cells.

     Gliotoxin, by reaching the lymphoid organs, probably has a direct
action on cell of these organs and has increased toxicity in mice after
irradiation.

     Gliotoxin inhibits secretin of interleukins and interferon, and
inhibits the ability of stimulator cells in mixed lymphocyte reactions
(MLR) to induce alloreactive and MHC- restricted cytotoxic t cells.

     Gliotoxin can reduce the number of B lymphocytes, completely
inhibits phagocytosis by macrophages and has significant deleterious
effects on alveolar M0.

     Gliotoxin depletes murine epidermal Langerhans cells by causing
cell injury, completely prevents T and B cell DNA synthesis and severely
damages the genomes of the T and B cells.

     Mannan, part of Candida's cell wall, can have a nonspecific or
specific inhibitory influence on stimulated proliferative responses of
human lymphocytes in vitro.  Mannan inhibits myeloperoxidase release and
increases hydrogen peroxide production.  Candida mannans, cell wall
glycoprotein, and  polysaccharide antigens inhibit
lymphoproliferation.   

     adomdl.mas
 Adenosine is a  modulator of neural function, cardiovascular and renal
processes, respiratory physiology, and hormone actions, as well as the
immune functions . es-ji.92]

adochip.prl
"In studies to further characterize this Candida hyphal inhibitory
product (CHIP), we noted several physicochemical parallels with the
purine nucleoside adenosine(Ado).[es- ji.92]

"There was no statistically significant difference between the
inhibition induced by maximally effective doses of CHIP and
Ado,.[es-ji.92]


.Activation of the respiratory burst by opsonized C. albicans yeast was
also inhibited by chip and ado,... [es-ji.92]


_atbpdt.rbc
Adenosine declined the production of antibody in mice immunized by sheep
erythrocytes(rbc red blood cells).  [yf-ckylh.94]


_lszmmd.cct
  Adenosine 13, 130 mg.kg-1 ip decreased the mouse serum muramidase
(lysozyme destructive to cell walls of certain bacteria;) concentration.
[yf-ckylh.94]

inhsflab.pgc
Adenosine (ado) 1.3, 13, 130 mg,kg-1 ip inhibited the ability of
peripheral leukocytes and peritoneal macrophages in phagocytosing the
Staphylococcus albus with [3H)TdR incorporation in mice. [yf-ckylh.94]


Killing of opsonized Streptococcus pneumoniae was also inhibited.
[es-ji.92]

There is much much more, but it will take some time to organize and
condense it into readable format.



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