Biomedical Engineering Reference
In-Depth Information
large uncharged colloidal particles, especially in systems with charged small spheres
or large asymmetry in shape and/or charge.
The present contribution is concerned with nm scaled ordered assemblies of a
unique composition of nontoxic lipid A-phosphate analogs which can be obtained from
non-pathogenic and non-replicating Gram-negative bacteria. The lipid A-phosphate
analogs are acquired according to a strongly defined protocol under non-denaturing
conditions, by applying purification steps using preparative HPLC. The structural
characterization is carried out using a MALDI-TOF mass spectroscopy, NMR and
FT-IR. Where the starting materials consist of inactivated, non-replicating gram-neg-
ative commensal bacteria for example Enterobacteriaceae such as
E. coli
grown and
harvested
in vitro
or in reactors for up-scaled production of the desired and specified
material. These preparations reveal strong attenuating immune-regulating responses
on the interleukin,
Figure 2.
(A) Changes in determined clinical parameters during the administration of “
E. coli
autovaccines
” to patients (n = 78) suffering from chronic sinusitis over a period of time of between 4
and 6 weeks (Rusch et al., 2001; Zimmermann et al., 2003). The various levels of the stimulation of the
cellular and humoral immunological defense are shown: IFN-
γ
: interferon-
γ
; GM-CSF: granulocyte-
macrophage colony factor; IL-6: interleukin-6; IL-1
b
: interleukin-1
b
; CRP: C-reactive protein; s-IL-
2R: soluble interleukin-2 receptor; IgX: the various immunoglobulins, (B) Randomized double-blind
and placebo controlled clinical study encompassing 114 patients suffering from chronic sinusitis
before and after treatment with “
E. coli autovaccines
” (p = 0.0003).
table 1.
Endotoxicity and TNF induction in murine bone marrow macrophage cultures of various
lipid A-phosphates
.
Results obtained according to the protocol of Sayers et al. (1987).
Source
Concentration
µ
g/mL
TNF units
(-) interferon-
g
TNF units
(+)
interferon-
g
(100 units)
Lipid A-diphosphate
+ compound B
+compound C
+compound B & C
Lipid-4 phosphate
+Compound B
+Compound C
+Compound B & C
1.0
0.1
0.01
0.01
10.0
1.0
10.0
1.0
1,700 ± 20
850 ± 20
120 ± 25
10 ± 5
350 ± 22
100 ± 20
500 ± 22
50 ± 9
3,900 ± 35
2,750 ± 30
1,300 ± 20
900 ± 20
890 ± 22
310 ± 20
790 ± 20
100 ± 18
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