U.S. patent application number 17/159932 was filed with the patent office on 2021-09-09 for method of treating a bacterial infection using colostrum.
The applicant listed for this patent is KING SAUD UNIVERSITY. Invention is credited to Adel Almogren, Khawla Ibrahim Alsamhary, Nagwa Mohamed Mohamed Amin Aref.
Application Number | 20210275593 17/159932 |
Document ID | / |
Family ID | 1000005362452 |
Filed Date | 2021-09-09 |
United States Patent
Application |
20210275593 |
Kind Code |
A1 |
Alsamhary; Khawla Ibrahim ;
et al. |
September 9, 2021 |
METHOD OF TREATING A BACTERIAL INFECTION USING COLOSTRUM
Abstract
The method of treating a bacterial infection using colostrum
includes administering an effective amount of colostrum to a
subject in need thereof. The infection can be caused by G+ or G-
bacteria. The colostrum administered may be selected from the group
consisting of bovine colostrum, camel colostrum, and a mixture of
bovine colostrum and camel colostrum. The bacterial infection may
be selected from the group consisting of Staphylococcus aureus
subs. aureus Rosenbach, Escherichia coli, Pseudomonas aeruginosa,
and Methicillin-resistant Staphylococcus aureus. A colostrum
composition can include a mixture of bone and camel colostrum and a
pharmaceutically acceptable carrier.
Inventors: |
Alsamhary; Khawla Ibrahim;
(Riyadh, SA) ; Aref; Nagwa Mohamed Mohamed Amin;
(Cairo, EG) ; Almogren; Adel; (Riyadh,
SA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
KING SAUD UNIVERSITY |
Riyadh |
|
SA |
|
|
Family ID: |
1000005362452 |
Appl. No.: |
17/159932 |
Filed: |
January 27, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
16809882 |
Mar 5, 2020 |
10933097 |
|
|
17159932 |
|
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|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61P 31/04 20180101;
A61K 35/20 20130101; A61K 9/19 20130101 |
International
Class: |
A61K 35/20 20060101
A61K035/20; A61K 9/19 20060101 A61K009/19; A61P 31/04 20060101
A61P031/04 |
Claims
1. A method of treating a bacterial infection using colostrum,
comprising: providing a therapeutically effective amount of
lyophilized colostrum, the lyophilized colostrum made by:
collecting colostrum from the mammary gland of a mammal; freezing
the colostrum at a temperature of at least -20.degree. C. for at
least a week; thawing the colostrum for at least 8 hours;
lyophilizing the colostrum; and suspending the lyophilized
colostrum in a saline solution to provide a colostrum composition;
identifying a subject in need of immune stimulation, and
administering the therapeutically effective amount of the
lyophilized colostrum to said subject; wherein the administration
of the lyophilized colostrum results in an increase in the
circulating levels of one or more immune system cytokines.
2. The method of treating an infection using colostrum according to
claim 1, wherein the lyophilized colostrum comprises bovine
colostrum.
3. The method of treating an infection using colostrum according to
claim 1, wherein the lyophilized colostrum comprises camel
colostrum.
4. The method of treating an infection using colostrum according to
claim 1, wherein the lyophilized colostrum comprises a mixture of
bovine colostrum and camel colostrum.
5. The method of treating an infection using colostrum according to
claim 1, wherein the immune system cytokines comprise
IFN-.gamma..
6. The method of treating an infection using colostrum according to
claim 1, wherein the immune system cytokines comprise
TNF-.alpha..
7. The method of treating an infection using colostrum according to
claim 1, wherein the immune system cytokines comprise IL-10.
8. The method of treating an infection using colostrum according to
claim 1, further comprising preventing the lethal effect of a
bacterium.
9. The method of treating an infection using colostrum according to
claim 8, wherein the bacterium is E. coli.
10. The method of treating an infection using colostrum according
to claim 8, wherein the bacterium is P. aeruginosa.
11. The method of treating an infection using colostrum according
to claim 8, wherein the bacterium is S. aureus.
12. The method of treating an infection using colostrum according
to claim 8, wherein the bacterium is MRSA.
13. The method of treating an infection using colostrum according
to claim 1, wherein the subject is a rat.
14-20. (canceled)
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a division of Ser. No. 16/809,882, filed
Mar. 5, 2020, pending, the priority of which is claimed.
BACKGROUND
1. Field
[0002] The disclosure of the present patent application relates to
a method of treating a bacterial infection by inducing an immune
response.
2. Description of the Related Art
[0003] The CDC identifies antibiotic resistance as one of the most
significant public health challenges of our time. In the United
States alone, at least 2 million people are diagnosed with
antibiotic-resistant infections annually, and at least 23,000 of
these are fatal.
[0004] Strategies for developing new treatments have mostly focused
on avoiding the rise of antibiotic resistance and on developing new
antibiotics. However, avoiding the rise of antibiotic resistance is
a failing rearguard action, given the prevalence of
antibiotic-resistant bacterial strains. Further, the rate of new
antibiotic development has slowed significantly. Most new classes
of antibiotics were developed in the 1940s and the 1950s, with only
two new classes developed since the year 2000. Antibiotics also
have many undesirable side effects, ranging from nausea and
diarrhea to liver and kidney damage.
[0005] Thus, a method of treating an infection solving the
aforementioned problems is desired.
SUMMARY
[0006] A method of treating a bacterial infection using mixed
colostrum can include administering a therapeutically effective
amount of colostrum to a patient in need thereof. Administering
colostrum to the patient can induce an immune response in the
patient. In an embodiment, the colostrum administered may be
selected from the group consisting of bovine colostrum, camel
colostrum, and a mixture of bovine colostrum and camel colostrum.
The infection can be bacterial. In an embodiment, the bacterial
infection may be selected from the group consisting of G+ and G-
bacteria: Staphylococcus aureus subs. aureus Rosenbach, Escherichia
coli, Pseudomonas aeruginosa, and Methicillin-resistant
Staphylococcus aureus.
[0007] An embodiment of the present subject matter is directed to a
pharmaceutical composition including the mixture of bovine and
camel colostrum and a pharmaceutically acceptable carrier.
[0008] An embodiment of the present subject matter is directed to a
method of making a pharmaceutical composition including mixing the
colostrum under sterile conditions with a pharmaceutically
acceptable carrier and preservatives, buffers, or propellants to
create the pharmaceutical composition; and providing the
pharmaceutical composition in a form suitable for daily, weekly, or
monthly administration. In an embodiment, the pharmaceutical
composition may be natural and/or organic, comprising exclusively
natural and/or organic ingredients
[0009] An embodiment of the present subject matter is directed to a
method of treating a bacterial infection, including administering
to a subject in need thereof a therapeutically effective amount of
a pharmaceutical composition according to the present subject
matter. The pharmaceutical composition can include a mixture of
bovine and camel colostrum. In an embodiment, the pharmaceutical
composition may be an organic pharmaceutical composition.
[0010] These and other features of the present disclosure will
become readily apparent upon further review of the following
specification and drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] The patent or application file contains at least one drawing
executed in color. Copies of this patent or patent application
publication with color drawing(s) will be provided by the Office
upon request and payment of the necessary fee.
[0012] FIG. 1 depicts a bar graph displaying IFN-.gamma. levels in
control subjects, subjects exposed to colostrum alone, subjects
exposed to E. coli alone, and subjects exposed to both E. coli and
colostrum, where the colostrum was either bovine colostrum, camel
colostrum, or a mixture of bovine and camel colostrum.
[0013] FIG. 2A depicts a bar graph displaying IFN-.gamma. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to E. coli alone, and subjects exposed to both E.
coli and colostrum, where the colostrum was camel colostrum.
[0014] FIG. 2B depicts a bar graph displaying IFN-.gamma. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to E. coli alone, and subjects exposed to both E.
coli and colostrum, where the colostrum was bovine colostrum.
[0015] FIG. 2C depicts a bar graph displaying IFN-.gamma. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to E. coli alone, and subjects exposed to both E.
coli and colostrum, where the colostrum was a mixture of camel
colostrum and bovine colostrum.
[0016] FIG. 3 depicts a bar graph displaying TNF-.alpha. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to E. coli alone, and subjects exposed to both E.
coli and colostrum, where the colostrum was bovine, camel, or a
mixture of bovine colostrum and camel colostrum.
[0017] FIG. 4A depicts a bar graph displaying TNF-.alpha. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to E. coli alone, and subjects exposed to both E.
coli and colostrum, where the colostrum was camel colostrum.
[0018] FIG. 4B depicts a bar graph displaying TNF-.alpha. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to E. coli alone, and subjects exposed to both E.
coli and colostrum, where the colostrum was bovine colostrum.
[0019] FIG. 4C depicts a bar graph displaying TNF-.alpha. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to E. coli alone, and subjects exposed to both E.
coli and colostrum, where the colostrum was a mixture of camel
colostrum and bovine colostrum.
[0020] FIG. 5 depicts a bar graph displaying IL-10 levels in
control subjects, subjects exposed to colostrum alone, subjects
exposed to E. coli alone, and subjects exposed to both E. coli and
colostrum, where the colostrum was either bovine colostrum, camel
colostrum, or a mixture of bovine colostrum and camel
colostrum.
[0021] FIG. 6A depicts a bar graph displaying IL-10 levels over
time in control subjects, subjects exposed to colostrum alone,
subjects exposed to E. coli alone, and subjects exposed to both E.
coli and colostrum, where the colostrum was camel colostrum.
[0022] FIG. 6B depicts a bar graph displaying IL-10 levels over
time in control subjects, subjects exposed to colostrum alone,
subjects exposed to E. coli alone, and subjects exposed to both E.
coli and colostrum, where the colostrum was bovine colostrum.
[0023] FIG. 6C depicts a bar graph displaying IL-10 levels over
time in control subjects, subjects exposed to colostrum alone,
subjects exposed to E. coli alone, and subjects exposed to both E.
coli and colostrum, where the colostrum was a mixture of camel
colostrum and bovine colostrum.
[0024] FIG. 7 depicts a bar graph displaying IFN-.gamma. levels in
control subjects, subjects exposed to colostrum alone, subjects
exposed to P. aeruginosa alone, and subjects exposed to both P.
aeruginosa and colostrum, where the colostrum was either bovine
colostrum, camel colostrum, or a mixture of bovine colostrum and
camel colostrum.
[0025] FIG. 8A depicts a bar graph displaying IFN-.gamma. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to P. aeruginosa alone, and subjects exposed to
both P. aeruginosa and colostrum, where the colostrum was camel
colostrum.
[0026] FIG. 8B depicts a bar graph displaying IFN-.gamma. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to P. aeruginosa alone, and subjects exposed to
both P. aeruginosa and colostrum, where the colostrum was bovine
colostrum.
[0027] FIG. 8C depicts a bar graph displaying IFN-.gamma. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to P. aeruginosa alone, and subjects exposed to
both P. aeruginosa and colostrum, where the colostrum was a mixture
of camel colostrum and bovine colostrum.
[0028] FIG. 9 depicts a bar graph displaying TNF-.alpha. levels in
control subjects, subjects exposed to colostrum alone, subjects
exposed to P. aeruginosa alone, and subjects exposed to both P.
aeruginosa and colostrum, where the colostrum was either bovine
colostrum, camel colostrum, or a mixture of bovine colostrum and
camel colostrum.
[0029] FIG. 10A depicts a bar graph displaying TNF-.alpha. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to P. aeruginosa alone, and subjects exposed to
both P. aeruginosa and colostrum, where the colostrum was camel
colostrum.
[0030] FIG. 10B depicts a bar graph displaying TNF-.alpha. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to P. aeruginosa alone, and subjects exposed to
both P. aeruginosa and colostrum, where the colostrum was bovine
colostrum.
[0031] FIG. 10C depicts a bar graph displaying TNF-.alpha. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to P. aeruginosa alone, and subjects exposed to
both P. aeruginosa and colostrum, where the colostrum was a mixture
of camel colostrum and bovine colostrum.
[0032] FIG. 11 depicts a bar graph displaying IL-10 levels in
control subjects, subjects exposed to colostrum alone, subjects
exposed to P. aeruginosa alone, and subjects exposed to both P.
aeruginosa and colostrum, where the colostrum was either bovine
colostrum, camel colostrum, or a mixture of bovine colostrum and
camel colostrum.
[0033] FIG. 12A depicts a bar graph displaying IL-10 levels over
time in control subjects, subjects exposed to colostrum alone,
subjects exposed to P. aeruginosa alone, and subjects exposed to
both P. aeruginosa and colostrum, where the colostrum was camel
colostrum.
[0034] FIG. 12B depicts a bar graph displaying IL-10 levels over
time in control subjects, subjects exposed to colostrum alone,
subjects exposed to P. aeruginosa alone, and subjects exposed to
both P. aeruginosa and colostrum, where the colostrum was bovine
colostrum.
[0035] FIG. 12C depicts a bar graph displaying IL-10 levels over
time in control subjects, subjects exposed to colostrum alone,
subjects exposed to P. aeruginosa alone, and subjects exposed to
both P. aeruginosa and colostrum, where the colostrum was a mixture
of camel colostrum and bovine colostrum.
[0036] FIG. 13 depicts a bar graph displaying IFN-.gamma. levels in
control subjects, subjects exposed to colostrum alone, subjects
exposed to S. aureus alone, and subjects exposed to both S. aureus
and colostrum, where the colostrum was either bovine colostrum,
camel colostrum, or a mixture of bovine colostrum and camel
colostrum.
[0037] FIG. 14A depicts a bar graph displaying IFN-.gamma. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to S. aureus alone, and subjects exposed to both
S. aureus and colostrum, where the colostrum was camel
colostrum.
[0038] FIG. 14B depicts a bar graph displaying IFN-.gamma. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to S. aureus alone, and subjects exposed to both
S. aureus and colostrum, where the colostrum was bovine
colostrum.
[0039] FIG. 14C depicts a bar graph displaying IFN-.gamma. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to S. aureus alone, and subjects exposed to both
S. aureus and colostrum, where the colostrum was a mixture of camel
colostrum and bovine colostrum.
[0040] FIG. 15 depicts a bar graph displaying TNF-.alpha. levels in
control subjects, subjects exposed to colostrum alone, subjects
exposed to S. aureus alone, and subjects exposed to both S. aureus
and colostrum, where the colostrum was either bovine colostrum,
camel colostrum, or a mixture of bovine colostrum and camel
colostrum.
[0041] FIG. 16A depicts a bar graph displaying TNF-.alpha. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to S. aureus alone, and subjects exposed to both
S. aureus and colostrum, where the colostrum was camel
colostrum.
[0042] FIG. 16B depicts a bar graph displaying TNF-.alpha. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to S. aureus alone, and subjects exposed to both
S. aureus and colostrum, where the colostrum was bovine
colostrum.
[0043] FIG. 16C depicts a bar graph displaying TNF-.alpha. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to S. aureus alone, and subjects exposed to both
S. aureus and colostrum, where the colostrum was a mixture of camel
colostrum and bovine colostrum.
[0044] FIG. 17 depicts a bar graph displaying IL-10 levels in
control subjects, subjects exposed to colostrum alone, subjects
exposed to S. aureus alone, and subjects exposed to both S. aureus
and colostrum, where the colostrum was either bovine colostrum,
camel colostrum, or a mixture of bovine colostrum and camel
colostrum.
[0045] FIG. 18A depicts a bar graph displaying IL-10 levels over
time in control subjects, subjects exposed to colostrum alone,
subjects exposed to S. aureus alone, and subjects exposed to both
S. aureus and colostrum, where the colostrum was camel
colostrum.
[0046] FIG. 18B depicts a bar graph displaying IL-10 levels over
time in control subjects, subjects exposed to colostrum alone,
subjects exposed to S. aureus alone, and subjects exposed to both
S. aureus and colostrum, where the colostrum was bovine
colostrum.
[0047] FIG. 18C depicts a bar graph displaying IL-10 levels over
time in control subjects, subjects exposed to colostrum alone,
subjects exposed to S. aureus alone, and subjects exposed to both
S. aureus and colostrum, where the colostrum was a mixture of camel
colostrum and bovine colostrum.
[0048] FIG. 19 depicts a bar graph displaying IFN-.gamma. levels in
control subjects, subjects exposed to colostrum alone, subjects
exposed to MRSA, and subjects exposed to both MRSA and colostrum,
where the colostrum was either bovine colostrum, camel colostrum,
or a mixture of bovine colostrum and camel colostrum.
[0049] FIG. 20A depicts a bar graph displaying IFN-.gamma. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to MRSA alone, and subjects exposed to both MRSA
and colostrum, where the colostrum was camel colostrum.
[0050] FIG. 20B depicts a bar graph displaying IFN-.gamma. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to MRSA alone, and subjects exposed to both MRSA
and colostrum, where the colostrum was bovine colostrum.
[0051] FIG. 20C depicts a bar graph displaying IFN-.gamma. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to MRSA alone, and subjects exposed to both MRSA
and colostrum, where the colostrum was a mixture of camel colostrum
and bovine colostrum.
[0052] FIG. 21 depicts a bar graph displaying TNF-.alpha. levels in
control subjects, subjects exposed to colostrum alone, subjects
exposed to MRSA, and subjects exposed to both MRSA and colostrum,
where the colostrum was either bovine colostrum, camel colostrum,
or a mixture of bovine colostrum and camel colostrum.
[0053] FIG. 22A depicts a bar graph displaying TNF-.alpha. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to MRSA alone, and subjects exposed to both MRSA
and colostrum, where the colostrum was camel colostrum.
[0054] FIG. 22B depicts a bar graph displaying TNF-.alpha. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to MRSA alone, and subjects exposed to both MRSA
and colostrum, where the colostrum was bovine colostrum.
[0055] FIG. 22C depicts a bar graph displaying TNF-.alpha. levels
over time in control subjects, subjects exposed to colostrum alone,
subjects exposed to MRSA alone, and subjects exposed to both MRSA
and colostrum, where the colostrum was a mixture of camel colostrum
and bovine colostrum.
[0056] FIG. 23 depicts a bar graph displaying IL-10 levels in
control subjects, subjects exposed to colostrum alone, subjects
exposed to MRSA, and subjects exposed to both MRSA and colostrum,
where the colostrum was either bovine colostrum, camel colostrum,
or a mixture of bovine colostrum and camel colostrum.
[0057] FIG. 24A depicts a bar graph displaying IL-10 levels over
time in control subjects, subjects exposed to colostrum alone,
subjects exposed to MRSA alone, and subjects exposed to both MRSA
and colostrum, where the colostrum was camel colostrum.
[0058] FIG. 24B depicts a bar graph displaying IL-10 levels over
time in control subjects, subjects exposed to colostrum alone,
subjects exposed to MRSA alone, and subjects exposed to both MRSA
and colostrum, where the colostrum was bovine colostrum.
[0059] FIG. 24C depicts a bar graph displaying IL-10 levels over
time in control subjects, subjects exposed to colostrum alone,
subjects exposed to MRSA alone, and subjects exposed to both MRSA
and colostrum, where the colostrum was a mixture of camel colostrum
and bovine colostrum.
[0060] Similar reference characters denote corresponding features
consistently throughout the attached drawings.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0061] A method of treating a bacterial infection may include
administering colostrum to a subject in need thereof. In an
embodiment, the colostrum administered may be selected from the
group consisting of bovine colostrum, camel colostrum, and a
mixture of bovine colostrum and camel colostrum. In an embodiment,
the infection is a bacterial infection or an infection caused by
bacteria. The bacterial infection may be selected from the group
consisting of G+ bacteria and G- bacteria. The bacterial infection
may be selected from the group consisting of Staphylococcus aureus
subs. aureus Rosenbach (S. aureus), Escherichia coli (E. coli),
Pseudomonas aeruginosa (P. aeruginosa), and Methicillin-resistant
Staphylococcus aureus (MRSA).
[0062] As used herein, a "subject" includes mammals, e.g., humans,
dogs, cats, sheep, cows, rats, mice, and the like.
[0063] As used herein, the term "about," when used to modify a
numerical value, means within ten percent of that numerical
value.
[0064] As used herein, "colostrum" is the first form of milk
produced by the mammary gland of a mammal just before and/or
shortly after giving birth. Colostrum contains maternal antibodies
intended to protect the newborn against disease, and frequently
contains significantly more protein than non-colostrum milk.
[0065] In an embodiment, the colostrum may be collected after
parturition and stored at -20.degree. C. for at least a week. In an
embodiment, the colostrum may then be thawed at -4.degree. C. for
at least 8 hours, and then lyophilized. In an embodiment, the
lyophilized colostrum may then be suspended in sterilized saline
solution at a concentration of 28 g lyophilized colostrum per liter
of sterilized saline solution, forming a colostrum composition for
use as discussed herein. In an embodiment, a colostrum composition
may include bovine colostrum, camel colostrum, or a mixture of
bovine colostrum and camel colostrum. An embodiment of the present
subject matter may include the colostrum composition including at
least a mixture of one of the bovine colostrum and the camel
colostrum and a pharmaceutically acceptable carrier.
[0066] In an embodiment, the administration of colostrum or a
colostrum composition of the present subject matter may include
daily administration. In an embodiment, the daily administration
may be administered in the early morning hours. In an embodiment,
administration of colostrum or a colostrum composition of the
present subject matter may include injecting one ml of a solution
of 28 g lyophilized colostrum per liter of sterilized saline
solution every day at eight in the morning for at least a
month.
[0067] In an embodiment, administration of the colostrum or
colostrum composition as described herein may prevent the lethal
effect of a lethal dose of an infectious bacterium. In an
embodiment, the infectious bacterium may be selected from the group
consisting of E. coli, P. aeruginosa, S. aureus, and MRSA.
[0068] In an embodiment, administration of the colostrum or
colostrum composition of the present subject matter may stimulate
the immune system. In an embodiment, the immune system stimulation
may include an increase in the level of one or more cytokines in
the blood. In an embodiment, the cytokines may be selected from the
group consisting of Interferon-.gamma. (IFN-.gamma.), Tumor
Necrosis Factor .alpha. (TNF-.alpha.), and Interleukin-10
(IL-10).
[0069] An embodiment of the present subject matter is directed to a
pharmaceutical composition comprising the mixture of bovine and
camel colostrum and a pharmaceutically acceptable carrier.
[0070] An embodiment of the present subject matter is directed to a
method of making a pharmaceutical composition, including mixing an
effective amount of the bovine and camel mixture colostrum with a
pharmaceutically acceptable carrier. For example, the method of
making a pharmaceutical composition can include mixing the
colostrum under sterile conditions with a pharmaceutically
acceptable carrier, preservatives, buffers, and/or propellants to
create the pharmaceutical composition. In an embodiment, the
pharmaceutical composition may be natural and/or organic and the
pharmaceutically acceptable carrier may also be natural
and/organic.
[0071] To prepare the pharmaceutical composition, at least one of
the bovine colostrum and camel colostrum, as the active ingredient,
is intimately admixed with a pharmaceutically acceptable carrier
according to conventional pharmaceutical compounding techniques.
Carriers are inert pharmaceutical excipients, including, but not
limited to, binders, suspending agents, lubricants, flavorings,
sweeteners, preservatives, dyes, and coatings. In preparing
compositions in oral dosage form, any of the pharmaceutical
carriers known in the art may be employed. For example, for liquid
oral preparations, suitable carriers and additives include water,
glycols, oils, alcohols, flavoring agents, preservatives, coloring
agents, and the like. Further, for solid oral preparations,
suitable carriers and additives include starches, sugars, diluents,
granulating agents, lubricants, binders, disintegrating agents, and
the like.
[0072] The present compositions can be in unit dosage forms such as
tablets, pills, capsules, powders, granules, ointments, sterile
parenteral solutions or suspensions, metered aerosol or liquid
sprays, drops, ampules, auto-injector devices or suppositories, for
oral parenteral, intranasal, sublingual or rectal administration,
or for administration by inhalation or insufflation. The active
compound can be mixed under sterile conditions with a
pharmaceutically acceptable carrier and, if required, any needed
preservatives, buffers, or propellants. The composition can be
presented in a form suitable for daily, weekly, or monthly
administration. The pharmaceutical compositions herein will
contain, per dosage unit, e.g., tablet, capsule, powder, injection,
teaspoonful, suppository and the like, an amount of the active
ingredient necessary to deliver an effective dose. A
therapeutically effective amount of the colostrum compositions or
an amount effective to treat a disease, such as a bacterial
infection, may be determined initially from the Examples described
herein and adjusted for specific targeted diseases using routine
methods.
[0073] The colostrum or colostrum compositions can be administered
to a subject in need thereof. For example, the colostrum or
colostrum compositions can be used to treat a subject suffering
from a bacterial infection. The bacterial infection can be caused
by E. coli, P. aeruginosa, S. aureus, MRSA, or the like.
[0074] An embodiment of the present subject matter is directed to a
method of treating a bacterial infection, comprising administering
to a subject in need thereof a therapeutically effective amount of
the pharmaceutical composition according to the present subject
matter. In an embodiment, the pharmaceutical composition may be
organic.
[0075] The colostrum or pharmaceutical compositions thereof can be
administered to a subject by any suitable route. For example, the
colostrum or pharmaceutical compositions can be administered orally
(including buccally and sublingually), nasally, rectally,
intracisternally, intra-vaginally, intraperitoneally, topically,
transdermally (as by powders, ointments, or drops), and/or
parenterally. As used herein, "parenteral" administration refers to
modes of administration other than through the gastrointestinal
tract, which includes intravenous, intramuscular, intraperitoneal,
intrasternal, intramammary, intraocular, retrobulbar,
intrapulmonary, intrathecal, subcutaneous and intraarticular
injection and infusion. Surgical implantation may also be
contemplated, including, for example, embedding a composition of
the disclosure in the body such as, for example, in a tissue, in
the abdominal cavity, under the splenic capsule, brain, or in the
cornea.
[0076] Accordingly, the route of administration can include
intranasal administration, oral administration, inhalation
administration, subcutaneous administration, transdermal
administration, intradermal administration, intra-arterial
administration with or without occlusion, intracranial
administration, intraventricular administration, intravenous
administration, buccal administration, intraperitoneal
administration, intraocular administration, intramuscular
administration, implantation administration, topical
administration, intratumor administration, and/or central venous
administration.
[0077] The following examples illustrate the present teachings.
Example 1
Determining the Lethal Dose and Optimum Route of Infection for Four
Gram-Positive and Gram-Negative Bacteria in a Rat Model
[0078] The ethical committee of King Saud University provided prior
approval before any animal studies were commenced. All animals were
fed with standard laboratory rat chow (Basal diet 5755, PMI
Nutrition International, Inc., Richmond, Calif., USA) according to
the National Institute of Health guidelines. Rats were quarantined
for six days before commencing experiments. Chemical restraint
anesthesia was achieved using injectable sedation, such as a
Ketamine/Xylazine mix administered subcutaneously.
[0079] The Riyadh Military Hospital Bacteriology Laboratory
provided American Type Culture Collection (ATCC) Escherichia coli
(E. coli) (ATTC 25922). The bacterium is Enteropathogenic E. coli
(EPEC) but not Enterotoxigenic E. coli (ETEC). It does not produce
verotoxin and is used for media testing and as a negative control
for LT toxin production. This organism is a CLSI control strain for
antimicrobial susceptibility testing. Other bacterial strains
obtained from the same source include Staphylococcus aureus subsp.
aureus Rosenbach (S. aureus) (ATCC 29213), Methicillin-resistant
Staphylococcus aureus (MRSA) (ATCC 12498), Pseudomonas aeruginosa
(P. aeruginosa) (ATCC 27853).
[0080] Bacterial propagation was performed in Trypticase Soy Broth
(TSB) for seven hours at 26.degree. C., and stock aliquots were
frozen at -79.degree. C. until used. A frozen stock sample was
thawed and plated onto Trypticase Soy Blood Agar plates in
preparation for a bacterial inoculum lethal dose trial using rats
injected subcutaneously and intravenously. The results of this
trial are compiled in Table 1 and Table 2 below.
[0081] Virus and antibody-free male Wistar rats were acquired from
the Pharmacy College of King Saud University. Animals were housed
up to 6 animals in a cage. Male Wistar rats (n=118) weighing
190-300 g were randomly selected to receive either intravenous
(i.v.) or intraperitoneal (i.p.) injection with either E. coli or
one of the other three studied bacteria (n=20-40 per group).
Control rats were kept in a separate compartment. Animals were
observed after bacterial injection to record the number of dead
animals. The results are summarized in Table 1. At six hours after
bacterial administration through either injection route, animals
appeared weak and lethargic. Estimated lethal doses of each
pathogenic microbe were determined as shown in Table 2. In summary,
the optimized lethal doses were determined to be
.about.6.times.10.sup.8/ml Colony Forming Units (CFU) for E. coli,
9.times.10.sup.8/0.5 ml CFU S. aureus, .about.9.5.times.108/0.5 ml
CFU P. aeruginosa, and 12.times.10.sup.8/1.5 ml CFU MRSA. The i.v.
route of administration was preferred for all microbes.
TABLE-US-00001 TABLE 1 Lethal Dose in Rats Demonstration for
Studied Groups Over One Week Bacterial strains Concentration per ml
Injection Site No. Deaths in 1 week Escherichia coli 10.sup.8/0.5
ml i.p. (3) One - 4 days ATTC 25922 10.sup.8/1 ml (3 rats) i.p.(3)
i.v.(3) Zero 10.sup.8/2 ml (3 rats) i.p.(3) i.v.(3) One (i.v.) - 7
days 10.sup.8/3 ml (6 rats) i.p.(3) Zero 10.sup.16/0.1 ml (2 rats)
i.p.(2) Two - 2 days 10.sup.16/0.5 ml (1 rat) i.p.(3) i.v.(3) Zero
10.sup.16/1 ml (1 rat) i.v.(3 + 3) Three - 1 day 10.sup.16/1.5 ml
(1 rat) 10.sup.18/1 ml (6 rats) 10.sup.36/1 ml (6 rats) Pseudomonas
aeruginosa 10.sup.8/0.5 ml (3 rats) i.p.(3) Zero ATCC27853
10.sup.8/1 ml (2 rats) i.p.(2) i.v.(2) One (i.v., 10.sup.8/2 ml) 1
day 10.sup.8/2 ml (2 rats) i.p.(1) i.v.(1) Zero 10.sup.8/3 ml (2
rats)t i.p.(3) One (10.sup.40/0.5 ml) 3 days 10.sup.40/0.1 ml (2
rats) i.p.(2) Zero 10.sup.40/0.5 ml (rat) i.p.(3 + 3) i.v.(3 + 3)
Three (i.v., 10.sup.72) 3 days 10.sup.40/1 ml (1 rat) 10.sup.40/1.5
ml (1 rat) 10.sup.40/0.5 ml (6 rats) 10.sup.72/0.5 ml (6 rats)
Staphylococcus aureus 10.sup.8/0.5 ml (3 rats) i.p.(3) One - 4 days
ATCC12498 10.sup.8/1 ml (2 rats) i.p.(2) i.v.(2) Zero 10.sup.8/2 ml
(2 rats) i.p.(1) i.v.(1) Zero 10.sup.8/3 ml (2 rats) i.p.(3) Zero
10.sup.20/0.1 ml (2 rats) i.p.(2) Zero 10.sup.20/0.5 ml (1 rat)
i.v.(3 + 3) Three (i.v., 10.sup.64/0.5 ml) 2 days 10.sup.20/1 ml (1
rat) 10.sup.20/1.5 ml (1 rat) 10.sup.40/0.5 ml (3 rats)
10.sup.64/0.5 ml (3 rats) Methicillin-resistant 10.sup.8/0.5 ml (3
rats) i.p.(3) Zero Staphylococcus aureus 10.sup.8/1 ml (2 rats)
i.p.(2) i.v.(.2) Zero ATCC12498 10.sup.8/2 ml (2 rats) i.p.(1)
i.v.(1) Zero 10.sup.8/3 ml (2 rats) i.p.(3) Zero 410.sup.20/0.1 ml
(2 rats) i.p.(2) Zero 10.sup.20/0.5 ml (1 rat) i.p.(3 + 3) i.v.(3 +
3) Zero 10.sup.20/1 ml (1 rat) i.v.(3 + 3) Zero 10.sup.20/1.5 ml (1
rat) i.p.(3) Seven - 6 days 10.sup.40/0.5 ml (6 rats) i.p.(2)
10.sup.64/0.5 ml (6 rats) i.v.(2) 10.sup.60/1 ml (3 rats)
10.sup.72/1 ml (3 rats) 10.sup.90/1 ml (2 rats) 10.sup.90/1.5 ml (1
rat) 10.sup.120/1 ml (2 rats) 10.sup.120/1.5 ml (2 rats)
TABLE-US-00002 TABLE 2 Recommended Lethal Dose for Studied Bacteria
Bacterial strains Concentration per ml Injection Site No. Deaths in
1 Week Escherichia coli ~6 .times. 10.sup.8/1 ml i.v. (3 rats)
Three - 1 day ATTC 25922 CFU/ml Pseudomonas aeruginosa ~9.5 .times.
10.sup.8/0.5 ml i.v. (3 rats) Three - 3 days ATCC27853 CFU/ml
Staphylococcus aureus 9 .times. 10.sup.8/0.5 ml i.v. (3 rats) Three
- 2 days ATCC12498 CFU/ml Methicillin-resistant 12 .times.
10.sup.8/1.5 ml i.v. (3 rats) Three - 6 days Staphylococcus aureus
CFU/ml ATCC12498
Example 2
Determining Effect of Camel Colostrum, Bovine Colostrum, and a
Mixture of Camel Colostrum and Bovine Colostrum on Survival of Rats
Infected with Gram-Positive and Gram-Negative Bacteria
[0082] Three types of colostrum were used from different sources.
Camel colostrum was sourced from 10 healthy individual camels
(Camelus dromedarius) that were chosen randomly (average age, six
years) from the Conservation and Genetic Improvement Center in
Al-karj, Saudi Arabia. Samples were obtained manually from all
camels' udders and were collected immediately after
parturition.
[0083] Bovine colostrum samples were sourced from 10 healthy
Holstein cows (average age, 3.8 years) provided by the Almarai
Company. The Immunology Lab, King Khaled Hospital, Medicine
College, King Saud University Hospital, collected the samples and
confirmed that the source cows were in good health and had no
clinical evidence of mastitis or tuberculosis, delivered healthy
full-term infants, and had not consumed medications within one week
before collection.
[0084] The colostrum samples were collected using the following
protocol: 20 samples collected at the first-day parturition after
thorough hand washing and cleansing of the breast and nipple with
soap and tap water. Milk samples were expressed manually into
sterile Erlenmeyer flasks, pooled, dispensed into sterile test
tubes and stored on at -20.degree. C.
[0085] The study included a control group with no graft
contamination and no antibiotic prophylaxis (Group 1), a bacterial
treatment group (Group 2), a colostrum treatment group (Group 3),
and a bacterial treatment and colostrum treatment group (Group 4).
(See Table 3) Group 3 included three different sub-groups,
designated camel colostrum, bovine colostrum, and mix colostrum.
One ml of prepared colostrum solution (28 g lyophilized
colostrum/liter sterilized saline solution (w/v)) was administered
by intraperitoneal injection every day early in the morning for 30
days.
[0086] The rats of Group 2 and Group 4 were then anesthetized with
chloroform or ether and injected intravenously with the recommended
lethal dose of one of the studied bacteria in the tail vein.
Survival rates in each group were observed for two weeks after
injection.
TABLE-US-00003 TABLE 3 The Study Groups Group 1 Control group:
Sterilized saline was administered every day at eight AM for 30
days Group 2 Bacterial groups: four bacterial sub-groups were
designated, one for each bacterium: Escherichia coli ATTC 25922
Pseudomonas aeruginousa ATCC27853 Staphylococcus aureus ATCC12498
Methicillin-resistant Staphylococcus aureus ATCC12498 The lethal
dose of each bacterium established in Table 1 was administered
intravenously once in the tail vein of each rat using a 14-gauge
needle at eight AM on the starting day. Group 3 Colostrum groups:
Three colostrum sub-groups were designated: Camel Colostrum Bovine
Colostrum Mix Colostrum One ml of prepared colostrum solution (28 g
lyophilized colostrum/liter sterilized saline solution (w/v)) was
injected i.p. daily at eight AM for 30 days. Group 4 Bacterial and
Colostrum groups: Sub-groups were designated for all possible
combinations of Group 2 and Group 3.
[0087] At zero time up to one month and after inoculation with the
four studied bacteria and induction by colostrum as in Table 4 and
Table 5, animals appeared weak and lethargic with the microbial
treatments. In controls without bacterial treatment, camel
colostrum, bovine colostrum, and mix (a mixture of both camel and
bovine colostrum) produced a similar survival rate without evidence
of concentration of disease (See Table 4). Compared with the
control treatment, bacterial treatment with colostrum improved
mortality rates associated with the bacterial variable and route of
treatment. These animals lived through one month of observation.
The death of animals started from the second day until the
22.sup.nd day, with most deaths occurring in the administrated
pathogenic bacteria only group (Group 2). As shown in Table 4, the
fastest and the best-protected treatment was lethal S. aureus with
50-100% mortality.
[0088] Moreover, 100% of rats injected with S. aureus and
vaccinated i.p. by one of the three types of colostrum survived.
Camel colostrum had a tremendous protective effect from lethal
MRSA, converting 100% mortality to 100% survival. Camel and bovine
colostrum enhanced survival against lethal P. aeruginosa from 0% to
33% survival in the former and from 50% to 66% survival in the
latter (see Table 4). Lethal E. coli caused 84% mortality, and
camel colostrum enhanced survival of up to 83%. On the other hand,
mixed colostrum also enhanced survival, up to 50%.
TABLE-US-00004 TABLE 4 Morbidity and Mortality (Survival %) in
Lethal Dose Induction for Four Pathogenic Bacteria using Three
Colostrum Groups as Anti-Microbial Agents Colostrum Bacteria
Healthy Bacteria & Colostrum Healthy Dose Rats per Healthy
Healthy Rats or Dead(Day) Rats or Dead(Day) Rats (~CFU/ml) Group
Rats Camel Bovine Mix Camel Bovine Mix Camel Bovine Mix E. coli: 6
6 6 6 6 6 2(3) 6 1(2) 1(2) 3(22) 6 .times. 10.sup.8/ml 2(7) 2(9)
1(13) 3(16) % Survival 100 100 100 100 100 100 16 100 83 0 50 P.
aeruginosa: 6 6 6 6 6 2(2) 1(2) 6 2(5) 2(20) 6 9.5 .times.
10.sup.8/0.5 ml 3(3) 1(8) 1(9) 1(7) 1(15) 1(11) % Survival 100 100
100 100 100 0 50 100 33 66 100 S. aureus 6 6 6 6 6 1(3) 2(4) 1(3) 6
6 6 9 .times. 10.sup.8/0.5 ml 1(5) 2(7) 1(4) 1(17) 1(10) 1(12)
1(11) % Survival 100 100 100 100 100 50 0 50 100 100 100 MRSA: 6 6
6 6 6 2(2) 6 6 6 6 6 12 .times. 10.sup.8/1.5 ml 1(4) 1(8) 1(12)
1(16) % Survival 100 100 100 100 100 0 100 100 100 100 100
Example 3
Determining Effect of Camel Colostrum, Bovine Colostrum, and a
Mixture of Camel Colostrum and Bovine Colostrum on Percentage
Change in Weight of Rats Infected with Gram-Positive and
Gram-Negative Bacteria
[0089] The effect of the treatment on the percentage change of the
weight of rats (grams) for each studied pathogenic bacterium was
determined using three types of colostrum; Camel, Bovine, and Mix.
The results of this experiment are illustrated in Table 5 and Table
6. The range of percent change in the weight of healthy rats was
revealed in minimum and maximum (Min 10%-Max 29%) through one month
of observation. Camel colostrum and Mix colostrum induced a
remarkable 6%-59% increase in the weight of rats. Bacterial
injections dramatically decreased the percent weight change in rats
from -12% to 12%. The most notable max increase values in percent
change of weight of rats after colostrum treatment were observed
when comparing the weight of rats infected with MRSA alone with the
weight of the rats treated with mix colostrum. Mix colostrum
induced 43% change in the weight of rats compared to -21% weight
change in rats injected with a lethal dose of MRSA alone.
TABLE-US-00005 TABLE 5 Treatment Effects on Average % Change in
Weight (g) of Rats (Healthy & Bacteria Treatment Groups) Group
Healthy Bacteria Day 1 10 20 30 Avg % 1 10 20 30 Avg % Camel
Colostrum E. coli 226 256 276 292 29% 210 205 209 214 1.9 P.
aeruginosa 236 215 250 287 21% 228 232 230 245 7.4 S. aureus 227
205 228 250 10% 230 239 243 235 2.1 MRSA 235 225 247 290 23% 207
210 222 205 -0.9 Bovine Colostrum E. coli 226 256 276 292 29% 215
224 230 235 9.3 P. aeruginosa 236 215 250 287 21% 234 230 227 220
-5.9 S. aureus 251 205 228 250 10% 215 224 230 235 9.3 MRSA 235 225
247 290 23% 234 230 227 220 -5.9 Mix Colostrum E. coli 226 256 276
292 29% 242 250 267 259 7 P. aeruginosa 236 215 250 287 21% 247 255
247 279 12 S. aureus 251 205 228 250 10% 273 249 231 213 -21 MRSA
235 225 247 290 23% 252 270 263 267 5.9
TABLE-US-00006 TABLE 6 Treatment Effects on Average % Change in
Weight (g) of Rats (Bacteria & Colostrum and Colostrum
Treatment Groups) Group Bacteria & Colostrum Colostrum Day 1 10
20 30 Avg % 1 10 20 30 Avg % Camel Colostrum E. coli 227 235 245
240 5.7% 213 246 278 286 34 P. aeruginosa 260 252 254 259
-0.3%.sup. 227 239 345 354 55 S. aureus 234 239 244 260 11% 243 275
288 295 21 MRSA 250 253 255 259 3.6% 252 258 261 269 6 Bovine
Colostrum E. coli 236 264 285 298 26% 230 236 254 270 17 P.
aeruginosa 241 265 273 295 37% 242 265 277 293 21 S. aureus 236 264
285 298 26% 230 236 254 270 17 MRSA 241 265 273 295 22.4 218 244
279 298 36 Mix Colostrum E. coli 270 284 312 326 20% 205 240 276
288 40 P. aeruginosa 234 255 288 310 32% 272 281 301 321 18 S.
aureus 230 252 284 329 43% 209 225 246 280 33 MRSA 202 235 272 280
38% 193 225 286 307 59
Example 4
Effect of Infection and/or Colostrum on Expression of Three
Cytokines in Rats
[0090] For circulating blood analysis, animals were anesthetized
with an ether mask. Circulating levels of IFN-.gamma., IL-10, and
TNF-.alpha. were measured in serum samples of all rats obtained
from the eye vein. Blood samples were collected in heparinized
syringes to assess cytokine level assessed of IFN-.gamma., IL10,
and TNF-.alpha.. Serum concentrations of each cytokine were
monitored at 0 days post-treatment, 24 hours post-treatment, 7-25
days post-treatment (midpoint or Mid), and 30 days post-treatment
(Last or Final) by ELISA. Briefly, blood samples (2 ml) were
centrifuged for 10 minutes at 3500 rpm, at 4.degree. C., and the
serum samples were kept at -20.degree. C. in a freezer until
examined. Commercial reagents used to identify individual cytokines
included Quantikine.RTM. ELISA, Rat TNF-.alpha. Immunoassay,
Catalog Number RTA00, Quantikine.RTM. ELISA, Rat IL-10 Immunoassay,
Quantikine.RTM. ELISA, and Rat IFN-.gamma. Immunoassay. These kits
were used according to the manufacturer's recommendations (USA
& Canada R&D Systems, Inc. Minneapolis). The limits of
sensitivity of the assay were determined to be five pg/ml for
TNF-.alpha. and ten pg per ml for IFN-.gamma. and IL-10,
respectively. The intra- and inter-assay coefficients of deviation
were less than 5% and 10%, respectively.
[0091] Quantitative data were statistically represented in terms of
minimum, maximum, and median. A comparison between different groups
in the present study was done using the Kruskal-Wallis test to
compare between more than two nonparametric groups.
[0092] Correlation between various variables was determined using
Spearman rank correlation coefficient (R) with graph
representations using linear regression.
[0093] A probability value (p-value) less than or equal to 0.05 was
considered significant. All statistical analyses were performed
using statistical software SPSS (Statistical Package for Social
Science) statistical program version 16.0. Graphs were created
using SPSS statistical program version 16.0 with Microsoft Excel
program version 2010.
[0094] Initial results for IFN-.gamma. expression as a measure of
the immune response in the presence of colostrum, E. coli, or E.
coli and colostrum are presented in Table 7 and FIG. 1.
TABLE-US-00007 TABLE 7 E. Coli and IFN-y Immune Response in the
Presence of Colostrum (Expressed as Median pg/ml (Min-Max))
Colostrum Type Camel Colostrum Bovine Colostrum Mix Colostrum P
value.sup.A Healthy Control 2.20 (0.00-43.91) 2.20 (0.00-43.91)
2.20 (0.00-43.91) 1.000 Colostrum 0.00 (0.00-0.03) 0.09
(0.00-209.50) 17.82 (0.00-125.00) 0.055 Bacteria 0.02 (0.00-0.07)
0.06 (0.01-74.24) 0.11 (0.00-125.00) 0.219 Colostrum & 0.01
(0.00-0.03) 0.06 (0.00-117.10) 0.12 (0.00-93.75) 0.098 Bacteria P
value.sup.B 0.018 0.808 0.901 .sup.A= Comparison between different
treatments within a single colostrum type using a nonparametric
test (Kruskal-Wallis Test). .sup.B= Comparison between different
colostrum types in each treatment using a nonparametric test
(Kruskal-Wallis Test).
[0095] Data from the full month-long experiment are presented in
Table 8 and FIGS. 2A-2C. In the model of E. coli bacterial
infection treated with either bovine colostrum or with the mixed
colostrum, IFN-.gamma. elevated up to 0.12 pg/ml in the mixed
colostrum treatment group but was 0.06 pg/ml in the bovine
colostrum treatment group. At the end of the trial (Last)
IFN-.gamma. exhibited a steady level of the immune response in the
mixed colostrum treatment group (93.750 pg/ml) as well as the
bacterial infection and mixed colostrum treatment group. (See Table
8). This experiment confirms the synergistic effect of mixed
colostrum, as it triggers a more significant immune response than
bovine colostrum or camel colostrum alone.
TABLE-US-00008 TABLE 8 E. coli and IFN-.gamma. Immune Response in
the Presence of Colostrum at 0 h, 24 h, 7-25 days (M), and 30 days
(Last) (Expressed as Median (Min-Max) Treatment Group Time Camel
Bovine Mix Healthy 0 h 1.496(0.220-2.770) 1.496(0.220-2.770)
1.496(0.220-2.770) 24 h 3.587(1.630-5.550) 3.587(1.630-5.550)
3.587(1.630-5.550) M 42.175(40.440-43.910) 42.175(40.440-43.910)
42.175(40.440-43.910) Last 0.005(0.000-0.010) 0.005(0.000-0.010)
0.005(0.000-0.010) P value 0.104 0.104 0.104 Colostrum 0 h
0.019(0.010-0.030) 1.055(0.120-1.990) 3.129(0.000-6.260) 24 h
0.002(0.000-0.000) 0.058(0.060-0.060) 1.667(0.000-3.330) M
0.002(0.000-0.000) 128.800(48.10-209.50) 30.327(29.390-31.260) Last
0.005(0.000-0.010) 0.001(0.000-0.000) 93.750(62.50-125.00) P value
0.160 0.078 0.106 Bacteria 0 h 0.025(0.010-0.040)
1.019(0.050-1.990) 0.003(0.000-0.000) 24 h 0.003(0.000-0.010)
0.051(0.040-0.070) 0.003(0.000-0.000) M 0.016(0.000-0.030)
37.183(0.130-74.240) 19.633(0.200-39.060) Last 0.049(0.020-0.070)
0.013(0.010-0.020) 125.00(125.00-125.00) P value 0.280 0.139 0.103
Colostrum & 0 h 0.018(0.010-0.030) 0.048(0.020-0.070)
0.061(0.000-0.120) Bacteria 24 h 0.001(0.000-0.000)
0.067(0.040-0.090) 0.008(0.010-0.010) M 0.016(0.000-0.030)
77.905(38.71-117.10) 20.840(20.840-20.840) Last 0.000(0.000-0.000)
0.012(0.000-0.020) 93.750(93.750-93.750) P value 0.165 0.104
0.362
[0096] In the model of E. coli bacterial infection, both camel
colostrum and mixed colostrum stimulated TNF-.alpha.. The highest
enhancement was for camel colostrum in all treatments (0.56 pg/ml,
0.57 pg/ml, and 0.60 pg/ml for colostrum alone, bacteria alone, and
colostrum with bacteria, respectively). These results are
summarized in Table 9 and FIG. 3. Data from the full month-long
experiment are presented in FIGS. 4A-4C.
TABLE-US-00009 TABLE 9 E. coli and TNF-.alpha. Immune Response in
the Presence of Colostrum (Expressed as Median pg/ml (Min-Max))
Colostrum Type Camel Bovine Mix P value.sup.A Healthy 0.00
(0.00-0.60) 0.00 (0.00-0.60) 0.00 (0.00-0.60) 1.000 Colostrum 0.56
(0.00-0.94) 0.00 (0.00-194.80) 0.03 (0.00-0.62) 0.261 Bacteria 0.57
(0.00-1.13) 0.00 (0.00-0.22) 0.18 (0.00-0.96) 0.033 Colostrum &
0.60 (0.25-1.00) 0.00 (0.00-0.00) 0.23 (0.00-0.76) 0.002 Bacteria P
value.sup.B 0.101 0.331 0.373 .sup.A= Comparison between different
treatments within a single Colostrum type using a Nonparametric
Test (Kruskal-Wallis Test). .sup.B= Comparison between different
Colostrum types in each treatment using a Nonparametric Test
(Kruskal-Wallis Test).
[0097] In the model of E. coli bacterial infection, mixed colostrum
alone triggered the IL-10 immune response more than the other
treatments (83.30 pg/ml). The most enormous increase was observed
in the presence of mixed colostrum and E. coli bacteria (1000.0
pg/ml at the Last point). (See Table 10 and FIG. 5)
TABLE-US-00010 TABLE 10 E. coli and IL-10 Immune Response in the
Presence of Colostrum (Expressed as Median pg/ml (Min-Max))
Colostrum Type Camel Bovine Mix P value.sup.A Healthy 0.00
(0.00-36.76) 0.00 (0.00-36.76) 0.00 (0.00-36.76) 1.000 Colostrum
0.00 (0.00-16.30) 0.14 (0.00-38.65) 83.30 (0.00-1000.00) 0.115
Bacteria 0.00 (0.00-0.64) 0.02 (0.00-0.26) 31.62 (0.00-1000.00)
0.159 Colostrum & 0.00 (0.00-0.14) 0.01 (0.00-0.29) 0.01
(0.00-1000.00) 0.290 Bacteria P value.sup.B 0.750 0.353 0.632
.sup.A= Comparison between different treatments within a single
Colostrum type using a Nonparametric Test (Kruskal-Wallis Test).
.sup.B= Comparison between different Colostrum types in each
treatment using a Nonparametric Test (Kruskal-Wallis Test).
[0098] Data from the full month-long experiment are presented in
Table 11 and FIGS. 6A-6C. IL-10 started to increase after 24 hours
in the bacterial infection with 80.308 pg/ml. Moreover, colostrum
continued to induce IL-10 from 7 days-25 days up to 166.60
pg/ml.
TABLE-US-00011 TABLE 11 E. coli and IL-10 Immune Response in the
Presence of Colostrum at 0 h, 24 h, 7-25 days (M), and 30 days
(Last) (Expressed as Median (Min-Max)) Treatment Group Time Camel
Bovine Mix Healthy 0 h 0.016 (0.000-0.030) 0.016 (0.000-0.030)
0.016 (0.000-0.030) 24 h 18.378 (0.000-36.760) 18.378
(0.000-36.760) 18.378 (0.000-36.760) M 0.018 (0.000-0.030) 0.018
(0.000-0.030) 0.018 (0.000-0.030) Last 0.004 (0.000-0.010) 0.004
(0.000-0.010) 0.004 (0.000-0.010) P value 0.935 0.935 0.935
Colostrum 0 h 0.000 (0.000-0.000) 19.621 (0.590-38.650) 0.001
(0.000-0.000) 24 h 0.000 (0.000-0.000) 0.810 (0.150-1.470) 0.002
(0.000-0.000) M 8.152 (0.000-16.300) 0.077 (0.020-0.130) 166.63
(166.60-166.66) Last 0.005 (0.000-0.000) 0.001 (0.000-0.000) 750.0
(500.0-1000.0) P value 0.105 0.104 0.091 Bacteria 0 h 0.000
(0.000-0.000) 0.156 (0.050-0.260) 0.010 (0.000-0.020) 24 h 0.318
(0.000-0.640) 0.017 (0.010-0.020) 80.308 (63.220-97.400) M 0.009
(0.000-0.020) 0.044 (0.020-0.070) 0.001 (0.000-0.000) Last 0.056
(0.060-0.060) 0.002 (0.000-0.000) 750.0 (500.0-1000.0) P value
0.467 0.139 0.080 Colostrum & 0 h 0.000 (0.000-0.000) 0.162
(0.030-0.290) 0.005 (0.000-0.010) Bacteria 24 h 0.000 (0.000-0.000)
0.010 (0.010-0.010) 0.013 (0.010-0.010) M 0.006 (0.000-0.010) 0.010
(0.010-0.010) 0.001 (0.000-0.000) Last 0.089 (0.040-0.140) 0.006
(0.000-0.010) 1000.0 (1000.0-1000.0) P value 0.116 0.276 0.284
[0099] In the model of P. aeruginosa infection, the mixed colostrum
induced IFN-.gamma. expression of 17.82 pg/ml. Further, the mixed
colostrum combined with bacterial infection resulted in an
IFN-.gamma. expression of 32.22 pg/ml. These results are presented
in Table 12 and FIG. 7. Data from the full month-long experiment
are presented in FIGS. 8A-8C.
TABLE-US-00012 TABLE 12 P. aeruginosa and IFN-.gamma. Immune
Response in the Presence of Colostrum (Expressed as Median pg/ml
(Min-Max)) Colostrum Type Camel Bovine Mix P value.sup.A Healthy
2.20 (0.00-43.91) 2.20 (0.00-43.91) 2.20 (0.00-43.91) 1.000
Colostrum 0.00 (0.00-0.03) 0.09 (0.00-209.50) 17.82 (0.00-125.00)
0.055 Bacteria 0.01 (0.00-74.40) 0.07 (0.02-105.79) 0.50
(0.01-62.50) 0.284 Colostrum 0.00 (0.00-0.00) 0.06 (0.03-0.49)
32.22 (0.00-457.20) 0.002 &Bacteria P value.sup.B 0.007 0.712
0.578 .sup.A= Comparison between different treatments within a
single Colostrum type using a Nonparametric Test (Kruskal-Wallis
Test). .sup.B= Comparison between different Colostrum types in each
treatment using a Nonparametric Test (Kruskal-Wallis Test).
[0100] In the model of P. aeruginosa infection, the most
considerable enhancement of TNF-.alpha. expression was detected in
the group administered camel colostrum, which demonstrated 0.56
pg/ml, 1.54 pg/ml and 1.00 pg/ml for colostrum treatment alone,
bacterial treatment alone, and colostrum and bacterial treatment,
respectively. These results are presented in Table 13 and FIG.
9.
TABLE-US-00013 TABLE 13 P. aeruginosa and TNF-.alpha. Immune
Response in the Presence of Colostrum (Expressed as Median pg/ml
(Min-Max)) Colostrum Type Camel Bovine Mix P value.sup.A Healthy
0.00 (0.00-0.60) 0.00 (0.00-0.60) 0.00 (0.00-0.60) 1.000 Colostrum
0.56 (0.00-0.94) 0.00 (0.00-194.80) 0.03 (0.00-0.62) 0.261 Bacteria
1.54 (0.54-1.91) 0.00 (0.00-0.00) 0.00 (0.00-1.09) 0.004
Colostrum& 1.00 (0.00-12.50) 0.00 (0.00-0.00) 0.55 (0.00-4.58)
0.006 Bacteria P value.sup.B 0.025 0.185 0.663 .sup.A= Comparison
between different treatments within a single Colostrum type using a
Nonparametric Test (Kruskal-Wallis Test). .sup.B= Comparison
between different Colostrum types in each treatment using a
Nonparametric Test (Kruskal-Wallis Test).
[0101] Data from the month-long experiment are presented in Table
14 and FIGS. 10A-10C. P. aeruginosa administration increased
TNF-.alpha. expression after 24 hours to 1.171 pg/ml. In
comparison, an expression level of 0.828 pg/ml was detected for
camel colostrum administration. The most efficient change in
TNF-.alpha. expression was observed for the administration of both
camel colostrum and P. aeruginosa (8.931 pg/ml 24 hours after
administration of the bacterium).
TABLE-US-00014 TABLE 14 P. aeruginosa and TNF-.alpha. Immune
Response in the Presence of Colostrum at 0 h, 24 h, 7-25 days (M),
and 30 days (Last) (Expressed as Median(Min-Max)) Treatment Time
Camel Bovine Mix Healthy 0 h 0.300(0.000-0.600) 0.300(0.000-0.600)
0.300(0.000-0.600) 24 h 0.220(0.000-0.440) 0.220(0.000-0.440)
0.220(0.000-0.440) M 0.269(0.000-0.540) 0.269(0.000-0.540)
0.269(0.000-0.540) Last 0.000(0.000-0.000) 0.000(0.000-0.000)
0.000(0.000-0.000) P value 0.675 0.675 0.675 Colostrum 0 h
0.558(0.540-0.580) 0.000(0.000-0.000) 0.000(0.000-0.000) 24 h
0.828(0.720-0.940) 0.000(0.000-0.000) 0.000(0.000-0.000) M
0.430(0.170-0.690) 104.749(14.70-194.80) 0.177(0.050-0.300) Last
0.000(0.000-0.000) 0.000(0.000-0.000) 0.490(0.360-0.620) P value
0.108 0.077 0.078 Bacteria 0 h 1.594(1.280-1.910)
0.000(0.000-0.000) 0.000(0.000-0.000) 24 h 1.171(0.540-1.800)
0.000(0.000-0.000) 0.000(0.000-0.000) M -- 0.000(0.000-0.000)
0.185(0.000-0.360) Last -- 0.000(0.000-0.000) 0.550(0.010-1.090) P
value 0.439 1.000 0.100 Colostrum& 0 h 0.769(0.540-1.000)
0.000(0.000-0.000) 0.000(0.000-0.000) Bacteria 24 h
8.931(5.360-12.500) 0.000(0.000-0.000) 0.000(0.000-0.000) M
0.861(0.360-1.360) 0.000(0.000-0.000) 2.568(0.550-4.580) Last
0.000(0.000-0.000) 0.000(0.000-0.000) 0.695(0.560-0.830) P value
0.185 1.000 0.183
[0102] In the model of P. aeruginosa infection, the administration
of the mixture of colostrum alone caused the greatest change in
IL-10 levels (83.30 pg/ml), as shown in Table 15 and FIG. 11. Data
from the month-long experiment are presented in Table 16 and FIGS.
12A-12C.
TABLE-US-00015 TABLE 15 P. aeruginosa and IL-10 Immune Response in
the Presence of Colostrum (Expressed as Median pg/ml (Min-Max))
Colostrum Type Camel Bovine Mix P value.sup.A Healthy
0.00(0.00-36.76) 0.00(0.00-36.76) 0.00(0.00-36.76) 1.000 Colostrum
0.00(0.00-16.30) 0.14(0.00-38.65) 83.30(0.00-1000.00) 0.115
Bacteria 0.00(0.00-0.01) 0.01(0.01-0.03) 0.07(0.00-500.00) 0.019
Colostrum & 0.00(0.00-72.69) 0.08(0.00-1.67) 1.31(0.00-500.00)
0.388 Bacteria P value.sup.B 0.749 0.321 0.286 .sup.A= Comparison
between different treatments within a single Colostrum type using a
Nonparametric Test (Kruskal-Wallis Test). .sup.B= Comparison
between different Colostrum types in each treatment using a
Nonparametric Test (Kruskal-Wallis Test).
TABLE-US-00016 TABLE 16 P. aeruginosa and IL-10 Immune Response in
the Presence of Colostrum at 0 h, 24 h, 7-25 days (M), and 30 days
(Last) (Expressed as Median(Min-Max)) Treatment Time Camel Bovine
Mix Healthy 0 h 0.016(0.000-0.030) 0.016(0.000-0.030)
0.016(0.000-0.030) 24 h 18.378(0.000-36.760) 18.378(0.000-36.760)
18.378(0.000-36.760) M 0.018(0.000-0.030) 0.018(0.000-0.030)
0.018(0.000-0.030) Last 0.004(0.000-0.010) 0.004(0.000-0.008)
0.004(0.000-0.010) P value 0.935 0.935 0.935 Colostrum 0 h
0.000(0.000-0.000) 19.621(0.590-38.650) 0.001(0.000-0.000) 24 h
0.000(0.000-0.000) 0.810(0.150-1.470) 0.002(0.000-0.000) M
8.152(0.000-16.300) 0.077(0.020-0.130) 166.63(166.60-166.66) Last
0.005(0.000-0.000) 0.001(0.001-0.001) 750.00(500.0-1000.0) P value
0.105 0.104 0.091 Bacteria 0 h 0.001(0.001-0.001)
0.020(0.010-0.030) 0.029(0.020-0.040) 24 h 0.004(0.000-0.008)
0.007(0.010-0.010) 8.914(0.070-17.760) M -- 0.008(0.010-0.010)
83.301(0.000-166.600) Last -- 0.009(0.010-0.010)
500.00(500.00-500.00) P value 1.000 0.701 0.375 Colostrum& 0 h
0.000(0.000-0.000) 0.008(0.000-0.020) 0.043(0.040-0.050) Bacteria
24 h 36.414(0.140-72.690) 1.173(0.670-1.670) 3.653(2.570-4.740) M
3.601(0.000-7.200) 0.030(0.030-0.030) 0.002(0.001-0.002) Last
0.002(0.000-0.000) 0.128(0.130-0.130) 500.00(500.00-500.00) P value
0.297 0.194 0.080
[0103] In the model of S. aureus subsp. aureus Rosenbach infection,
IFN-.gamma. levels increased to 78.10 pg/ml when the mixed
colostrum and bacteria were administered, as compared to 17.82
pg/ml when the mixed colostrum alone was administered (see Table 17
and FIG. 13).
TABLE-US-00017 TABLE 17 S. aureus and IFN-.gamma. Immune Response
in the Presence of Colostrum (Expressed as Median pg/ml (Min-Max))
Colostrum Type: Camel Bovine Mix P value.sup.A Healthy
2.20(0.00-43.91) 2.20(0.00-43.91) 2.20(0.00-43.91) 1.000 Colostrum
0.00(0.00-0.03) 0.09(0.00-209.50) 17.82(0.00-125.00) 0.055 Bacteria
0.01(0.00-64.78) 0.44(0.04-75.23) 0.50(0.01-62.50) 0.076 Colostrum
& 0.02(0.00-2.91) 23.76(0.01-94.87) 78.10(0.03-6541.00) 0.008
Bacteria P value.sup.B 0.026 0.436 0.362 .sup.A= Comparison between
different treatments within a single Colostrum type using a
Nonparametric Test (Kruskal-Wallis Test). .sup.B= Comparison
between different Colostrum types in each treatment using a
Nonparametric Test (Kruskal-Wallis Test).
[0104] In the month-long experiment, administration of the mixture
of colostrum and S. aureus resulted in an increased level of
IFN-.gamma. of 3333.0 pg/ml by the final time-point. In comparison,
at days 7-25 (M), the median IFN-.gamma. level of rats administered
mixed colostrum and S. aureus was 278.15 pg/ml. At the 24 hour
time-point this level was only 15.647 pg/ml. These results are
presented in Table 18 and FIGS. 14A-14C.
TABLE-US-00018 TABLE 18 S. aureus and IFN-.gamma. Immune Response
in the Presence of Colostrum at 0 h, 24 h, 7-25 days (M), and 30
days (Last) (Expressed as Median(Min-Max)) Treatment Time Camel
Bovine Mix Healthy 0 h 1.496(0.220-2.770) 1.496(0.220-2.770)
1.496(0.220-2.770) 24 h 3.587(1.630-5.550) 3.587(1.630-5.550)
3.587(1.630-5.550) M 42.175(40.440-43.910) 42.175(40.440-43.910)
42.175(40.440-43.910) Last 0.005(0.000-0.010) 0.005(0.000-0.010)
0.005(0.000-0.010) P value 0.104 0.104 0.104 Colostrum 0 h
0.019(0.008-0.030) 1.055(0.120-1.990) 3.129(0.000-6.260) 24 h
0.002(0.000-0.004) 0.058(0.060-0.060) 1.667(0.000-3.330) M
0.002(0.001-0.002) 128.800(48.10-209.50) 30.327(29.390-31.260) Last
0.005(0.003-0.006) 0.001(0.001-0.001) 93.750(62.50-125.00) P value
0.160 0.078 0.106 Bacteria 0 h 32.400(0.020-64.780)
6.787(0.090-13.480) 0.194(0.110-0.280) 24 h 0.066(0.001-0.130)
0.356(0.050-0.670) 2.022(0.710-3.330) M 0.005(0.003-0.007)
2.241(0.210-4.270) 10.450(0.070-20.830) Last 0.002(0.000-0.002)
37.639(0.040-75.230) 31.256(0.010-62.500) P value 0.426 0.919 0.881
Colostrum & 0 h 1.558(0.210-2.910) 47.440(0.010-94.870)
0.140(0.030-0.250) Bacteria 24 h 0.010(0.000-0.010)
0.355(0.360-0.360) 15.647(0.090-31.200) M 0.008(0.000-0.010)
18.174(12.590-23.760) 278.15(173.90-382.40) Last 0.033(0.020-0.050)
46.956(37.680-56.230) 3333.00(125.0-6541.0) P value 0.106 0.587
0.139
[0105] In the model of S. aureus subsp. aureus Rosenbach infection,
the most excellent enhancement in TNF-.alpha. levels was observed
after administration of camel colostrum, which had 0.56 pg./m.,
1.21 pg./m and 0.50 pg./m for Colostrum, Bacteria, and Colostrum
with Bacteria respectively (See Table 19 and FIG. 15). Data from
the month-long experiment are presented in Table 20 and FIGS.
16A-16C.
TABLE-US-00019 TABLE 19 S. aureus and TNF-.alpha. Immune Response
in the Presence of Colostrum (expressed as median pg/ml (Min-Max))
Colostrum Type: Camel Bovine Mix P value.sup.A Healthy
0.00(0.00-0.60) 0.00(0.00-0.60) 0.00(0.00-0.60) 1.000 Colostrum
0.56(0.00-0.94) 0.00(0.00-194.80) 0.03(0.00-0.62) 0.261 Bacteria
1.21(0.00-9.85) 0.00(0.00-0.00) 0.00(0.00-1.09) 0.002 Colostrum
& 0.50(0.00-6.55) 0.00(0.00-0.00) 0.12(0.00-116.44) 0.014
Bacteria P value.sup.B 0.043 0.118 0.931 .sup.A= Comparison between
different treatments within a single Colostrum type using a
Nonparametric Test (Kruskal-Wallis Test). .sup.B= Comparison
between different Colostrum types in each treatment using a
Nonparametric Test (Kruskal-Wallis Test).
TABLE-US-00020 TABLE 20 S. aureus and TNF-.alpha. Immune Response
in the Presence of Colostrum at 0 h, 24 h, 7-25 days (M), and 30
days (Last) (Expressed as Median(Min-Max)) Treatment Time Camel
Bovine Mix Healthy 0 h 0.300(0.000-0.600) 0.300(0.000-0.600)
0.300(0.000-0.600) 24 h 0.220(0.000-0.440) 0.220(0.000-0.440)
0.220(0.000-0.440) M 0.269(0.000-0.540) 0.269(0.000-0.540)
0.269(0.000-0.540) Last 0.000(0.000-0.000) 0.000(0.000-0.000)
0.000(0.000-0.000) P value 0.675 0.675 0.675 Colostrum 0 h
0.558(0.540-0.580) 0.000(0.000-0.000) 0.000(0.000-0.000) 24 h
0.828(0.720-0.940) 0.000(0.000-0.000) 0.000(0.000-0.000) M
0.430(0.170-0.690) 104.749(14.70-194.80) 0.177(0.050-0.300) Last
0.000(0.000-0.000) 0.000(0.000-0.000) 0.490(0.360-0.620) P value
0.108 0.077 0.078 Bacteria 0 h 5.930(2.010-9.850)
0.000(0.000-0.000) 0.000(0.000-0.000) 24 h 0.962(0.720-1.210)
0.000(0.000-0.000) 0.000(0.000-0.000) M 0.900(0.580-1.220)
0.000(0.000-0.000) 0.185(0.000-0.360) Last 0.000(0.000-0.000)
0.000(0.000-0.000) 0.550(0.010-1.090) P value 0.185 1.000 0.100
Colostrum & 0 h 6.184(5.820-6.550) 0.000(0.000-0.000)
0.000(0.000-0.000) Bacteria 24 h 0.600(0.580-0.620)
0.000(0.000-0.000) 0.000(0.000-0.000) M 0.352(0.280-0.430)
0.000(0.000-0.000) 58.336(0.230-116.440) Last 0.000(0.000-0.000)
0.000(0.000-0.000) 0.589(0.560-0.620) P value 0.080 1.000 0.109
[0106] In the model of S. aureus subsp. aureus Rosenbach infection,
treatment with mixed colostrum alone and treatment with mixed
colostrum and bacteria led to the highest increase in IL-10 levels
(See Table 21 and FIG. 17).
TABLE-US-00021 TABLE 21 S. aureus and IL-10 Immune Response in the
Presence of Colostrum (Expressed as Median pg/ml (Min-Max))
Colostrum Type: Camel Bovine Mix P value.sup.A Healthy
0.00(0.00-36.76) 0.00(0.00-36.76) 0.00(0.00-36.76) 1.000 Colostrum
0.00(0.00-16.30) 0.14(0.00-38.65) 83.30(0.00-1000.00) 0.115
Bacteria 0.00(0.00-0.98) 0.04(0.00-23.78) 0.07(0.00-500.00) 0.023
Colostrum & 0.00(0.00-0.07) 0.03(0.00-0.39) 83.38(0.01-1000.00)
0.021 Bacteria P value.sup.B 0.677 0.428 0.153 .sup.A= Comparison
between different treatments within a single Colostrum type using a
Nonparametric Test (Kruskal-Wallis Test). .sup.B= Comparison
between different Colostrum types in each treatment using a
Nonparametric Test (Kruskal-Wallis Test).
[0107] In the month-long experiment, treatment with mixed colostrum
and treatment with either mixed colostrum alone or with mixed
colostrum and bacteria resulted in a similar increase in IL-10
levels (166.63 and 166.60 respectively at 7-25 days and 750.00
pg/ml at the end of the month). These results are presented in
Table 22 and FIGS. 18A-18C.
TABLE-US-00022 TABLE 22 S. aureus and IL-10 Immune Response in the
Presence of Colostrum at 0 h, 24 h, 7-25 days (M), and 30 days
(Last) (Expressed as Median(Min-Max)) Treatment Time Camel Bovine
Mix Healthy 0 h 0.016(0.000-0.030) 0.016(0.000-0.030)
0.016(0.000-0.030) 24 h 18.378(0.000-36.760) 18.378(0.000-36.760)
18.378(0.000-36.760) M 0.018(0.000-0.030) 0.018(0.000-0.030)
0.018(0.000-0.030) Last 0.004(0.000-0.010) 0.004(0.000-0.010)
0.004(0.000-0.010) P value 0.935 0.935 0.935 Colostrum 0 h
0.000(0.000-0.000) 19.621(0.590-38.650) 0.001(0.001-0.001) 24 h
0.000(0.000-0.000) 0.810(0.150-1.470) 0.002(0.001-0.002) M
8.152(0.000-16.300) 0.077(0.020-0.130) 166.63(166.60-166.66) Last
0.005(0.005-0.005) 0.001(0.000-0.001) 750.00(500.0-1000.0) P value
0.105 0.104 0.091 Bacteria 0 h 0.491(0.000-0.980)
0.089(0.010-0.170) 0.029(0.020-0.040) 24 h 0.000(0.000-0.000)
0.040(0.020-0.060) 8.914(0.070-17.760) M 0.000(0.000-0.000)
11.890(0.000-23.780) 83.301(0.000-166.600) Last 0.009(0.010-0.010)
0.103(0.010-0.200) 500.00(500.00-500.00) P value 0.166 0.983 0.375
Colostrum & 0 h 0.001(0.000-0.000) 0.216(0.040-0.390)
0.010(0.010-0.010) Bacteria 24 h 0.000(0.000-0.000)
0.012(0.000-0.020) 0.085(0.010-0.160) M 0.001(0.000-0.000)
0.045(0.020-0.070) 166.60(166.60-166.60) Last 0.053(0.040-0.070)
0.000(0.000-0.000) 750.00(500.0-1000.0) P value 0.143 0.276
0.100
[0108] In the model of MRSA infection, the administration of a
lethal dose of MRSA also raised IFN-.gamma. levels to 78.13 pg/ml
when treated with mixed colostrum and bacteria. These results are
similar to the IFN-.gamma. levels reported above for rats
administered a combination of mixed colostrum and S. aureus of
78.10 pg/ml. This result compares favorably to the IFN-.gamma.
levels reported for rats administered Bovine Colostrum and S.
aureus of 23.76 pg/ml. Thus, these results confirm the improved
immune response to treatment with mixed colostrum. The MRSA
experimental results are summarized in Table 23 and FIG. 19. The
month-long MRSA experimental results are summarized in Table 24 and
FIGS. 20A-20C.
TABLE-US-00023 TABLE 23 MRSA and IFN-.gamma. Immune Response in the
Presence of Colostrum (Expressed as Median pg/ml (Min-Max))
Colostrum Type: Camel Bovine Mix P value.sup.A Healthy
2.20(0.00-43.91) 2.20(0.00-43.91) 2.20(0.00-43.91) 1.000 Colostrum
0.00(0.00-0.03) 0.09(0.00-209.50) 17.82(0.00-125.00) 0.055 Bacteria
0.01(0.00-0.07) 0.57(0.01-25.05) 0.01(0.00-0.07) 0.024 Colostrum
& 0.00(0.00-0.87) 0.08(0.00-38.71) 78.13(0.01-300.06) 0.004
Bacteria P value.sup.B 0.009 0.646 0.057 .sup.A= Comparison between
different treatments within a single Colostrum type using a
Nonparametric Test (Kruskal-Wallis Test). .sup.B= Comparison
between different Colostrum types in each treatment using a
Nonparametric Test (Kruskal-Wallis Test).
TABLE-US-00024 TABLE 24 MRSA and IFN-.gamma. Immune Response in the
Presence of Colostrum at 0 h, 24 h, 7-25 days (M), and 30 days
(Last) (Expressed as Median(Min-Max)) Treatment Time Camel Bovine
Mix Healthy 0 h 1.496(0.220-2.770) 1.496(0.220-2.770)
1.496(0.220-2.770) 24 h 3.587(1.630-5.550) 3.587(1.630-5.550)
3.587(1.630-5.550) M 42.175(40.440-43.910) 42.175(40.440-43.910)
42.175(40.440-43.910) Last 0.005(0.000-0.010) 0.005(0.000-0.010)
0.005(0.000-0.010) P value 0.104 0.104 0.104 Colostrum 0 h
0.019(0.010-0.030) 1.055(0.120-1.990) 3.129(0.000-6.260) 24 h
0.002(0.000-0.000) 0.058(0.060-0.060) 1.667(0.000-3.330) M
0.002(0.000-0.000) 128.800(48.10-209.50) 30.327(29.390-31.260) Last
0.005(0.000-0.010) 0.001(0.000-0.000) 93.750(62.50-125.00) P value
0.160 0.078 0.106 Bacteria 0 h 0.043(0.020-0.070)
0.904(0.320-1.490) 0.043(0.020-0.070) 24 h 0.007(0.000-0.010)
0.046(0.010-0.080) 0.007(0.000-0.010) M 0.000(0.000-0.000)
12.798(0.540-25.050) 0.000(0.000-0.000) Last 0.013(0.000-0.070)
1.759(0.600-2.920) 0.000(0.000-0.000) P value 0.121 0.212 0.121
Colostrum & 0 h 0.600(0.330-0.870) 0.130(0.070-0.180)
0.012(0.010-0.020) Bacteria 24 h 0.001(0.000-0.000)
0.056(0.020-0.090) 222.78(145.50-300.06) M 0.002(0.000-0.000)
20.951(3.190-38.710) 85.565(53.92-117.21) Last 0.002(0.000-0.000)
0.009(0.000-0.010) 78.125(62.500-93.750) P value 0.104 0.104
0.112
[0109] In the model of MRSA infection, administration of camel
colostrum raised TNF-.alpha. levels to 0.56 pg/ml, compared to 0.03
pg/ml for the administration of mixed colostrum. The greatest
increase in TNF-.alpha. levels was observed for camel colostrum,
which recorded 0.69 pg/ml. These results are summarized in Table 25
and FIG. 21. The month-long experimental results are summarized in
Table 26 and FIGS. 22A-22C.
TABLE-US-00025 TABLE 25 MRSA and TNF-.alpha. Immune Response in the
Presence of Colostrum (Expressed as Median pg/ml (Min-Max))
Colostrum Type: Camel Bovine Mix P value.sup.A Healthy
0.00(0.00-0.60) 0.00(0.00-0.60) 0.00(0.00-0.60) 1.000 Colostrum
0.56(0.00-0.94) 0.00(0.00-194.80) 0.03(0.00-0.62) 0.261 Bacteria
1.17(0.50-4.15) 0.00(0.00-0.00) 1.17(0.50-4.15) 0.002 Colostrum
& 0.69(0.00-4.73) 0.00(0.00-0.00) 0.08(0.00-3707.00) 0.013
Bacteria P value.sup.b 0.064 0.118 0.050 .sup.A= Comparison between
different treatments within a single Colostrum type using a
Nonparametric Test (Kruskal-Wallis Test). B = Comparison between
different Colostrum types in each treatment using a Nonparametric
Test (Kruskal-Wallis Test).
TABLE-US-00026 TABLE 26 MRSA and TNF-.alpha. Immune Response in the
Presence of Colostrum at 0 h, 24 h, 7-25 days (M), and 30 days
(Last) (Expressed as Median(Min-Max)) Treatment Time Camel Bovine
Mix Healthy 0 h 0.300(0.000-0.600) 0.300(0.000-0.600)
0.300(0.000-0.600) 24 h 0.220(0.000-0.440) 0.220(0.000-0.440)
0.220(0.000-0.440) M 0.269(0.000-0.540) 0.269(0.000-0.540)
0.269(0.000-0.540) Last 0.000(0.000-0.000) 0.000(0.000-0.000)
0.000(0.000-0.000) P value 0.675 0.675 0.675 Colostrum 0 h
0.558(0.540-0.580) 0.000(0.000-0.000) 0.000(0.000-0.000) 24 h
0.828(0.720-0.940) 0.000(0.000-0.000) 0.000(0.000-0.000) M
0.430(0.170-0.690) 104.749(14.70-194.80) 0.177(0.050-0.300) Last
0.000(0.000-0.000) 0.000(0.000-0.000) 0.490(0.360-0.620) P value
0.108 0.077 0.078 Bacteria 0 h 2.884(1.620-4.150)
0.000(0.000-0.000) 2.884(1.620-4.150) 24 h 0.607(0.500-0.720)
0.000(0.000-0.000) 0.607(0.500-0.720) M 0.000(0.000-0.000)
0.000(0.000-0.000) 0.000(0.000-0.000) Last 1.166(0.500-4.150)
0.000(0.000-0.000) 0.000(0.000-0.000) P value 0.121 1.000 0.121
Colostrum & 0 h 4.098(3.470-4.730) 0.000(0.000-0.000)
0.000(0.000-0.000) Bacteria 24 h 1.422(0.940-1.910)
0.000(0.000-0.000) 0.000(0.000-0.000) M 0.383(0.330-0.440)
0.000(0.000-0.000) 1853.58(0.16-3707.00) Last 0.000(0.000-0.000)
0.000(0.000-0.000) 0.622(0.560-0.680) P value 0.080 1.000 0.109
[0110] In the model of MRSA infection, administration of mixed
colostrum raised IL-10 levels during the extended testing period to
similar levels observed for S. aureus. Moreover, the administration
of bovine colostrum increased IL-10 to 0.810 pg/ml after 24 hours.
These results are summarized in Table 27 and FIG. 23. The
month-long experimental results are summarized in Table 28 and
FIGS. 24A-24C.
TABLE-US-00027 TABLE 27 MRSA and IL-10 Immune Response in the
Presence of Colostrum (Expressed as Median pg/ml (Min-Max))
Colostrum Type: Camel Bovine Mix P value.sup.A Healthy
0.00(0.00-36.76) 0.00(0.00-36.76) 0.00(0.00-36.76) 1.000 Colostrum
0.00(0.00-16.30) 0.14(0.00-38.65) 83.30(0.00-1000.00) 0.115
Bacteria 0.00(0.00-0.00) 0.04(0.02-0.34) 0.00(0.00-0.00) 0.001
Colostrum & 0.00(0.00-0.04) 0.03(0.00-6.41) 0.01(0.00-500.00)
0.035 Bacteria P value.sup.B 0.057 0.348 0.002 .sup.A= Comparison
between different treatments within a single Colostrum type using a
Nonparametric Test (Kruskal-Wallis Test). .sup.B= Comparison
between different Colostrum types in each treatment using a
Nonparametric Test (Kruskal-Wallis Test).
TABLE-US-00028 TABLE 28 MRSA and IL-10 Immune Response in the
Presence of Colostrum at 0 h, 24 h, 7-25 days (M), and 30 days
(Last) (Expressed as Median(Min-Max)) Treatment Time Camel Bovine
Mix Healthy 0 h 0.016(0.000-0.030) 0.016(0.000-0.030)
0.016(0.000-0.030) 24 h 18.378(0.000-36.760) 18.378(0.000-36.760)
18.378(0.000-36.760) M 0.018(0.000-0.030) 0.018(0.000-0.030)
0.018(0.000-0.030) Last 0.004(0.000-0.010) 0.004(0.000-0.010)
0.004(0.000-0.010) P value 0.935 0.935 0.935 Colostrum 0 h
0.000(0.000-0.000) 19.621(0.590-38.650) 0.001(0.000-0.000) 24 h
0.000(0.000-0.000) 0.810(0.150-1.470) 0.002(0.000-0.000) M
8.152(0.000-16.300) 0.077(0.020-0.130) 166.63(166.60-166.66) Last
0.005(0.000-0.000) 0.001(0.000-0.000) 750.00(500.0-1000.0) P value
0.105 0.104 0.091 Bacteria 0 h 0.000(0.000-0.000)
0.207(0.070-0.340) 0.000(0.000-0.000) 24 h 0.000(0.000-0.000)
0.024(0.020-0.020) 0.000(0.000-0.000) M 0.000(0.000-0.000)
0.037(0.030-0.050) 0.000(0.000-0.000) Last 0.000(0.000-0.000)
0.036(0.030-0.040) 0.000(0.000-0.000) P value 1.000 0.108 1.000
Colostrum & 0 h 0.019(0.000-0.040) 1.089(0.030-2.150)
0.008(0.000-0.010) Bacteria 24 h 0.000(0.000-0.000)
3.225(0.040-6.410) 0.006(0.000-0.010) M 0.001(0.000-0.000)
0.034(0.020-0.040) 0.006(0.000-0.010) Last 0.003(0.000-0.000)
0.002(0.000-0.000) 500.00(500.00-500.00) P value 0.392 0.198
0.222
[0111] Overall, the S. aureus lethal dose experiments confirm that
treatment with bovine colostrum resulted in lower stimulation of
immune system cytokines than other tested treatments. For example,
both the administration of colostrum mix alone and the
administration of colostrum mix and the lethal dose of bacteria
resulted in the same increase in IL-10 levels (83.30 pg/ml compared
to administration of bacteria alone at 0.07 pg/ml) Administration
of mixed colostrum alone and administration of mixed colostrum and
bacteria raised IL-10 levels to 166.63 pg/ml at days 7-25 (M) and
to 750.00 pg/ml by the final day of the experiment. Both camel
colostrum and mixed camel colostrum and bovine colostrum stimulated
TNF-.alpha. levels. The most enormous change was for camel
colostrum in all treatments, which resulted in 0.56 pg/ml, 0.50
pg/ml, and 1.21 pg/ml for colostrum alone, bacteria alone, and
colostrum and bacteria respectively.
Example 5
Calculating Correlations Between the Studied Cytokines and the
Colostrum Sources
[0112] The immunomodulatory effect of pro-inflammatory cytokines
varied depending upon the bacterial species tested. IFN-.gamma.
exhibited a steady level of immune response in mixed colostrum
treatment (93.750 pg/ml in the E. coli model). In the S. aureus
model, IFN-.gamma. levels increased to 78.10 pg/ml when the mixture
of colostrum was administered compared to 17.82 pg/ml in the
control colostrum. In the MRSA experiments, IFN-.gamma. levels
increased to 78.13 pg/ml when the mixed colostrum was administered.
TNF-.alpha., in the P. aeruginosa experiments showed the most
considerable change in level when camel colostrum and bacteria were
administered (8.931 pg/ml after 24 hours compared to 1.171 pg/ml
for bacterial injection only).
[0113] IL-10 is a crucial cytokine marker. In E. coli treated with
mixed colostrum, IL-10 was elevated to 83.30 pg/ml compared to
31.62 pg/ml when bacteria alone were administered. Early cytokine
transcriptional changes could be useful as a forecasting tool.
IL-10 started to increase after 24 hours in the E. coli
experiments, up to 80.3080 pg/ml. In S. aureus administered mixed
colostrum and bacteria, IL-10 levels rose to 166.60 pg/ml after
7-25 days, and this increase was sustained over time and ended with
750.00 pg/ml after one month.
[0114] The best survival effect was in camel colostrum and mixed
colostrum for all the tested bacteria (83% in E-coli--100% in MRSA)
in the infected rats in the presence of colostrum.
[0115] Camel colostrum and mixed colostrum blocked adherence of
bacteria to cultured tissue cells. Mixed colostrum (bovine
colostrum and camel colostrum) can stimulate the immune response
more than the bovine colostrum or camel colostrum alone. Colostrum
has been shown to be a constant source of potentially probiotic
bacteria in an infant's gut, including staphylococci, streptococci,
and lactic acid bacteria. The immunomodulatory effect of
pro-inflammatory cytokines varied due to the bacterial species.
[0116] IL-10 and IFN-.gamma. showed a significant interaction at 24
hours. The significant elevations of the IL-10 and TNF-.alpha.
transcriptional levels most likely indicate their essential role in
the regulation of the immune responses of the bovine mammary gland
in S. aureus infection. That could reflect the suppressive nature
of the S. aureus mastitis. Early cytokine transcriptional changes
could be useful as a forecasting tool in the detection of the
subclinical S. aureus mastitis. The transcriptional patterns of
these cytokines in the early stages of S. aureus infection could
help to unravel their role in the pathophysiology of S. aureus
mastitis. Finally, vital, crucial cytokine marker(s) could emerge
that provide efficient diagnostic and therapeutic means for the
early detection of S. aureus mastitis. Early cytokine
transcriptional changes could be useful as a forecasting tool in
the detection of the subclinical S. aureus mastitis.
[0117] These experiments demonstrate that camel colostrum, bovine
colostrum and mixed colostrum (bovine and camel colostrum) can
provide protective and immune-stimulatory effects against the
studied pathogenic bacteria in vitro and in vivo. The lyophilized
colostrum derivative studied maintained most of the bioactive
factors that appear to be at the basis of its many nutritional,
modulatory, or even therapeutic, applications.
[0118] The fastest and the best-protected treatment was for lethal
S. aureus with a baseline of 50-100% mortality. 100% survival was
obtained for all six rats injected with S. aureus and administered
the three types of colostrum by i.p. injection. Camel colostrum had
a tremendous protective effect from lethal MRSA, demonstrating 100%
survival versus 100% mortality in MRSA administration alone. Also,
MRSA showed the highest maximum increased values in % change in
weight of rats administered mixed colostrum (43% compared to -21%
for rats administered only the lethal dose of MRSA).
[0119] Camel colostrum and mixed colostrum alone induced a
remarkable increase in the weight of rats ranging from (6%-59%).
Bacterial injection led to a dramatic decrease in the percent
weight change in rats from -12% to 12%. MRSA demonstrated the most
significant maximum increased values in percent change of weight of
rats treated with mixed colostrum (43% compared to -21% when
administered MRSA alone).
[0120] Calculations of the correlation between IFN-.gamma., IL-10,
and TNF-.alpha. are summarized in Tables 29-31. Table 29 shows that
without the presence of Colostrum, the value of the correlation
coefficient between IL-10 and TNF-.alpha. was -0.773**, indicating
a significant negative strength of association, while the value of
the correlation coefficient between IFN-.gamma. and TNF-.alpha. was
0.464*, demonstrating a less significant positive strength of
association. With the presence of Colostrum, the only significant
value of the correlation coefficient was 0.647**, between IL-10 and
IFN-.gamma.. In the absence of Colostrum, the administration of
bacterial strains did not demonstrate a significant value of the
correlation coefficient between the three tested cytokines in gram
negative E. coli and P. aeruginosa; however, gram-positive S.
aureus and MRSA has significant values of the correlation
coefficient between IL-10 and IFN-.gamma.. In the presence of both
Colostrum and bacterial strains, the correlation coefficient
between IL-10 and IFN-.gamma. demonstrated a positive strength of
association for S. aureus (0.701*) and MRSA (0.503*). Further, in
the presence of E. coli, the correlation coefficient between IL-10
and TNF-.alpha. had a significant negative strength of association
(-0.470*).
[0121] Table 30 shows the correlation between IFN-.gamma., IL-10,
and TNF-.alpha. in the presence of Colostrum when treated with S.
aureus or MRSA. A significant value of a correlation coefficient
was observed in the presence of Camel Colostrum, with the
coefficient between IL-10 and TNF-.alpha. having a negative
strength of association for S. aureus of -0.517** and for MRSA of
-0.585**. A significant value of a correlation coefficient was
observed in the presence of Bovine Colostrum, with the coefficient
between IFN-.gamma. and TNF-.alpha. having a positive strength of
association for S. aureus of 0.415* and for MRSA of 0.551**. A
number of significant values of correlation coefficients were
observed in the presence of Mixed Camel and Bovine Colostrum, with
the coefficient between IFN-.gamma. and IL-10, IFN-.gamma. and
TNF-.alpha., and IL-10 and TNF-.alpha. all having respective
positive strength of association for S. aureus of 0.659**, 0.694**,
and 0.439*. For MRSA, the coefficient between IFN-.gamma. and IL-10
also showed a positive strength of association of 0.512**.
TABLE-US-00029 TABLE 29 Correlation between IFN-.gamma., IL-10, and
TNF-.alpha. R (Spearman Treatments Parameters Correlation) Sig.
Healthy IFN-.gamma. with IL10 -0.036 0.867 N.sup.b IFN-.gamma. with
TNF-.alpha. 0.464* 0.022 P.sup.a IL10 with TNF-.alpha. -0.773**
0.000 N.sup.b Colostrum IFN-.gamma. with IL10 0.647** 0.001 P.sup.a
IFN-.gamma. with TNF-.alpha. 0.269 0.203 P.sup.a IL10 with
TNF-.alpha. 0.025 0.908 P.sup.a E. coli IFN-.gamma. with IL10 0.242
0.267 P.sup.a IFN-.gamma. with TNF-.alpha. 0.056 0.811 P.sup.a IL10
with TNF-.alpha. -0.295 0.207 N.sup.b Colostrum & IFN-.gamma.
with IL10 0.353 0.151 P.sup.a E. coli IFN-.gamma. with TNF-.alpha.
-0.144 0.557 N.sup.b IL10 with TNF-.alpha. -0.470* 0.049 N.sup.b P.
aeruginosa IFN-.gamma. with IL10 0.490 0.054 P.sup.a IFN-.gamma.
with TNF-.alpha. -0.226 0.384 N.sup.b IL10 with TNF-.alpha. -0.329
0.214 N.sup.b Colostrum & IFN-.gamma. with IL10 0.186 0.418
P.sup.a P. aeruginosa IFN-.gamma. with TNF-.alpha. -0.082 0.732
N.sup.b IL10 with TNF-.alpha. 0.150 0.528 P.sup.a S. aureus
IFN-.gamma. with IL10 0.755** 0.000 P.sup.a IFN-.gamma. with
TNF-.alpha. -0.168 0.443 N.sup.b IL10 with TNF-.alpha. -0.278 0.211
N.sup.b Colostrum & IFN-.gamma. with IL10 0.701** 0.000 P.sup.a
S. aureus IFN-.gamma. with TNF-.alpha. 0.061 0.782 P.sup.a IL10
with TNF-.alpha. -0.135 0.550 N.sup.b MRSA IFN-.gamma. with IL10
0.796** 0.000 P.sup.a IFN-.gamma. with TNF-.alpha. -0.512* 0.043
N.sup.b IL10 with TNF-.alpha. -0.863** 0.000 N.sup.b Colostrum
& IFN-.gamma. with IL10 0.503* 0.014 P.sup.a MRSA IFN-.gamma.
with TNF-.alpha. 0.009 0.968 P.sup.a IL10 with TNF-.alpha. -0.288
0.182 N.sup.b *= Correlation is significant at the 0.05 level. **=
Correlation is significant at the 0.01 level. .sup.a= Positive
correlation. .sup.b= Negative correlation.
TABLE-US-00030 TABLE 30 Correlation between IFN-.gamma., IL-10, and
TNF-.alpha. in the presence of colostrum for S. aureus and MRSA R
(Spearman Colostrum Type Parameters Correlation) Sig. S. aureus
Camel IFN-.gamma. with IL10 0.140 0.452 P.sup.a IFN-.gamma. with
TNF-.alpha. 0.090 0.628 P.sup.a IL10 with TNF-.alpha. -0.517**
0.003 N.sup.b Bovine IFN-.gamma. with IL10 0.242 0.207 P.sup.a
IFN-.gamma. with TNF-.alpha. 0.415* 0.020 P.sup.a IL10 with
TNF-.alpha. -0.290 0.121 N.sup.b Mix IFN-.gamma. with IL10 0.659**
0.000 P.sup.a IFN-.gamma. with TNF-.alpha. 0.694** 0.000 P.sup.a
IL10 with TNF-.alpha. 0.439* 0.013 P.sup.a MRSA Camel IFN-y with
IL10 0.116 0.566 P.sup.a IFN-y with TNF-.alpha. 0.030 0.880 P.sup.a
IL10 with TNF-.alpha. -0.585** 0.001 N.sup.b Bovine IFN-y with IL10
0.216 0.236 P.sup.a IFN-y with TNF-.alpha. 0.551** 0.001 P.sup.a
IL10 with TNF-.alpha. -0.325 0.070 N.sup.b Mix IFN-y with IL10
0.512** 0.005 P.sup.a IFN-y with TNF-.alpha. 0.221 0.258 P.sup.a
IL10 with TNF-.alpha. -0.219 0.264 N.sup.b *= Correlation is
significant at the 0.05 level. **= Correlation is significant at
the 0.01 level. .sup.a= Positive correlation. .sup.b= Negative
correlation.
[0122] Table 31 shows the correlation between IFN-.gamma., IL-10,
and TNF-.alpha. in the presence of Colostrum when treated with E.
coli or P. aeruginosa. A significant value of a correlation
coefficient was observed in the presence of Camel Colostrum, with
the coefficient between IL-10 and TNF-.alpha. having a negative
strength of association for E. coli of -0.595**. A significant
value of a correlation coefficient was observed in the presence of
Bovine Colostrum, with the coefficient between IFN-.gamma. and
TNF-.alpha. having a positive strength of association for E. coli
of 0.559** and for P. aeruginosa of 0.548**. A number of
significant values of correlation coefficients were observed in the
presence of Mixed Camel and Bovine Colostrum, with the coefficient
between IFN-.gamma. and TNF-.alpha. having a positive strength of
association for E. coli of 0.625** and for P. aeruginosa of
0.739**. Further, significant values of correlation coefficients
were observed in the presence of Mixed Camel and Bovine Colostrum,
with the coefficient between IFN-.gamma. and IL-10 also showing a
positive strength of association of 0.412* for E. coli and of
0.374* for P. aeruginosa.
TABLE-US-00031 TABLE 31 Correlation between IFN-.gamma., IL-10, and
TNF-.alpha. in the presence of colostrum for E. coli and P.
aeruginosa R (Spearman Colostrum Type Parameters Correlation) Sig.
E. coli Camel IFN-.gamma. with IL10 0.078 0.688 P.sup.a IFN-.gamma.
with TNF-.alpha. -0.203 0.282 N.sup.b IL10 with TNF-.alpha.
-0.595** 0.001 N.sup.b Bovine IFN-.gamma. with IL10 0.345 0.057
P.sup.a IFN-.gamma. with TNF-.alpha. 0.559** 0.002 P.sup.a IL10
with TNF-.alpha. -0.209 0.287 N.sup.b Mix IFN-.gamma. with IL10
0.413* 0.026 P.sup.a IFN-.gamma. with TNF-.alpha. 0.625** 0.000
P.sup.a IL10 with TNF-.alpha. 0.210 0.274 P.sup.a P. aeruginosa
Camel IFN-.gamma. with IL10 0.088 0.664 P.sup.a IFN-.gamma. with
TNF-.alpha. -0.120 0.550 N.sup.b IL10 with TNF-.alpha. -0.043 0.832
N.sup.b Bovine IFN-.gamma. with IL10 0.198 0.323 P.sup.a
IFN-.gamma. with TNF-.alpha. 0.548** 0.003 P.sup.a IL10 with
TNF-.alpha. -0.277 0.162 N.sup.b Mix IFN-.gamma. with IL10 0.374*
0.038 P.sup.a IFN-.gamma. with TNF-.alpha. 0.739** 0.000 P.sup.a
IL10 with TNF-.alpha. 0.214 0.257 P.sup.a *= Correlation is
significant at the 0.05 level. **= Correlation is significant at
the 0.01 level. .sup.a= Positive correlation. .sup.b= Negative
correlation.
[0123] Overall, these examples illustrate at least that mixed
colostrum can trigger a greater immune response than the
administration of either bovine colostrum or camel colostrum alone.
Further, the administration of any of the three colostrum groups
increased survival against lethal doses of gram-positive and
gram-negative bacteria, with camel colostrum and mixed colostrum
providing the greatest increase in survival.
[0124] It is to be understood that the methods described herein are
not limited to the specific embodiments described above, but
encompasses any and all embodiments within the scope of the generic
language of the following claims enabled by the embodiments
described herein, or otherwise shown in the drawings or described
above in terms sufficient to enable one of ordinary skill in the
art to make and use the claimed subject matter.
* * * * *