Patent US6541265B2 successfully refreshed from Google Patents.
US6541265B2
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US
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Method and system to test a substance for inflammatory or oxidant properties
Assignee: University of Florida
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Filing: 2001-05-09
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Granted: 2003-04-01
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Expires: 2021-05-09
Abstract
Abstract The subject invention pertains to methods and systems for testing a substance for inflammatory or oxidant properties under acute inflammatory conditions characterized by increased levels of redox-active metal ions. The method includes the steps of applying an eccentric exercise stimulus to a subject, thereby inducing a muscle injury; administering a substance of interest to the subject; measuring one or more biological markers of inflammation, oxidative stress, and muscle damage, or combinations thereof, within the subject; and correlating the measured value of the biological marker(s) with the inflammatory or oxidative properties of the substance administered. The systems of the subject invention include means for obtaining a biological sample from a subject, means for applying eccentric exercise stimulus to the subject; means for measuring the amount of the biological marker(s) within the biological sample; and means for correlating the measured amounts of the biological marker(s) with the inflammatory or oxidant properties of the substance administered.
Inventors
- 👤 Christiaan Leeuwenburgh
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 18:49
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/5005; G01N33/5008; G01N33/5082; G01N33/68; G01N33/6893
Claims Analysis
Total Claims: 51
Claim 1
Independent Claim
105 words
A method for screening a substance for inflammatory or oxidant properties comprising: (a) applying an eccentric exercise stimulus to a subject, thereby inducing a muscle injury in the subject; (b) administering a substance to the subject; (c) measuring at least one biological marker from said subject to obtain a value of said biological marker, wherein said biological marker is selected from the group consisting of free iron, total antioxidant status, 8-isoprostane, superoxide dismutase, glutathione peroxidase, lactate dehydrogenase, C-reactive protein, lipid hydroperoxidase, myeloperoxidase, interleukin-6, dityrosine, and 8-hydroxyguanine; and (d) correlating the measured value of said biological marker with the inflammatory or oxidant properties of said substance.
Claim 2
Independent Claim
105 words
A method for screening a substance for inflammatory or oxidant properties comprising: (a) applying an eccentric exercise stimulus to a subject, thereby inducing a muscle injury in the subject; (b) administering a substance to the subject; (c) measuring at least one biological marker from said subject to obtain a value of said biological marker, wherein said biological marker is selected from the group consisting of free iron, total antioxidant status, 8-isoprostane, superoxide dismutase, glutathione peroxidase, lactate dehydrogenase, C-reactive protein, lipid hydroperoxidase, myeloperoxidase, interleukin-6, dityrosine, and 8-hydroxyguanine; and (d) correlating the measured value of said biological marker with the inflammatory or oxidant properties of said substance.
Claim 3
Dependent Claim
29 words
The method according to claim 1 , wherein said muscle injury resulting from said eccentric exercise stimulus induces an acute inflammatory response causing increased levels of redox-active metal ions.
Claim 4
Dependent Claim
12 words
The method according to claim 1 , wherein free iron is measured.
Claim 5
Dependent Claim
13 words
The method according to claim 1 , wherein total antioxidant status is measured.
Claim 6
Dependent Claim
11 words
The method according to claim 1 , wherein 8-isoprostane is measured.
Claim 7
Dependent Claim
12 words
The method according to claim 1 , wherein superoxide dismutase is measured.
Claim 8
Dependent Claim
12 words
The method according to claim 1 , wherein glutathione peroxidase is measured.
Claim 9
Dependent Claim
12 words
The method according to claim 1 , wherein lactate dehydrogenase is measured.
Claim 10
Dependent Claim
12 words
The method according to claim 1 , wherein C-reactive protein is measured.
Claim 11
Dependent Claim
12 words
The method according to claim 1 , wherein lipid hydroperoxidase is measured.
Claim 12
Dependent Claim
11 words
The method according to claim 1 , wherein myeloperoxidase is measured.
Claim 13
Dependent Claim
11 words
The method according to claim 1 , wherein interleukin-6 is measured.
Claim 14
Dependent Claim
11 words
The method according to claim 1 , wherein dityrosine is measured.
Claim 15
Dependent Claim
11 words
The method according to claim 1 , wherein 8-hydroxyguanine is measured.
Claim 16
Dependent Claim
22 words
The method according to claim 1 , wherein said biological marker is selected from the group consisting of free iron and 8-isoprostane.
Claim 17
Dependent Claim
14 words
The method according to claim 1 , wherein 8-isoprostane, myeloperoxidase, and dityrosine are measured.
Claim 18
Dependent Claim
16 words
The method according to claim 1 , wherein lactate dehydrogenase, dityrosine, and C-reactive protein are measured.
Claim 19
Dependent Claim
14 words
The method according to claim 1 wherein free iron, interleukin-6, and 8-hydroxyguanine are measured.
Claim 20
Dependent Claim
31 words
The method according to claim 1 , wherein said eccentric exercise stimulus is selected from the group consisting of eccentric arm curl exercises, eccentric leg curl exercises, and downhill running exercises.
Claim 21
Dependent Claim
26 words
The method according to claim 1 , wherein said eccentric exercise stimulus is applied to the subject at between about 60% and about 95% maximum intensity.
Claim 22
Dependent Claim
36 words
The method according to claim 20 , wherein said maximum intensity of said eccentric exercise stimulus is selected from the group consisting of the subject's one repetition maximum weight equivalent and the subject's maximum heart rate.
Claim 23
Dependent Claim
26 words
The method according to claim 1 , wherein said eccentric exercise stimulus is applied to the subject at between about 70% and about 90% maximum intensity.
Claim 24
Dependent Claim
52 words
The method according to claim 1 , wherein the measuring step comprises taking a first biological sample from the subject before said eccentric exercise stimulus, taking a second biological sample after said eccentric exercise stimulus and after said substance administration, and measuring said biological marker in said first and second biological samples.
Claim 25
Dependent Claim
36 words
The method according to claim 23 , wherein said correlating step comprises comparing the measured value of said biological marker in said first sample with the measured value of said biological marker in said second sample.
Claim 26
Dependent Claim
25 words
The method according to claim 1 , wherein said correlating step further comprises comparing the measured value of said biological marker with a control value.
Claim 27
Dependent Claim
47 words
The method according to claim 25 , wherein said control value comprises a measured value of the same biological marker from a different subject, wherein said eccentric exercise stimulus has been applied to the different subject, but wherein the different subject has not been administered said substance.
Claim 28
Dependent Claim
46 words
The method according to claim 1 , wherein said substance administration is carried out after said application of eccentric exercise stimulus; and said measuring is carried out at least twice, including before said application of eccentric exercise stimulus and after said application of eccentric exercise stimulus.
Claim 29
Dependent Claim
13 words
The method according to claim 1 , wherein said subject is a mammal.
Claim 30
Independent Claim
76 words
A method for screening a substance for inflammatory or oxidant properties comprising: (a) applying an eccentric exercise stimulus to a subject, thereby inducing a muscle injury in the subject; (b) administering a substance to the subject; (c) measuring at least one oxidative stress marker from said subject to obtain a value of said oxidative stress marker; and (d) correlating the measured value of said oxidative stress marker with the inflammatory or oxidant properties of said substance.
Claim 31
Independent Claim
76 words
A method for screening a substance for inflammatory or oxidant properties comprising: (a) applying an eccentric exercise stimulus to a subject, thereby inducing a muscle injury in the subject; (b) administering a substance to the subject; (c) measuring at least one oxidative stress marker from said subject to obtain a value of said oxidative stress marker; and (d) correlating the measured value of said oxidative stress marker with the inflammatory or oxidant properties of said substance.
Claim 32
Dependent Claim
29 words
The method according to claim 29 , wherein said oxidative stress marker is selected from the group consisting of free iron, 8-isoprostane, superoxide dismutase, glutathione peroxidase, dityrosine, and 8-hydroxyguanine.
Claim 33
Independent Claim
217 words
A method for screening a substance for inflammatory or oxidant properties comprising: (a) applying an eccentric exercise stimulus to a subject, thereby inducing a muscle injury in the subject, wherein the muscle injury causes an acute inflammatory response characterized by an increase in redox-active metal ions; (b) administering a substance to the subject; (c) measuring biological markers within the subject to obtain a value of the biological markers, wherein the biological markers include at least one inflammatory marker selected from the group consisting of 8-isoprostane, myeloperoxidase, interleukin-6, and C-reactive protein, and at least one oxidative stress marker selected from the group consisting of free iron, superoxide dismutase, glutathione peroxidase, lipid hydroperoxidase, dityrosine, and 8-hydroxyguanine, wherein said measuring comprises taking a first biological sample from the subject before said eccentric exercise stimulus, taking a second biological sample after said eccentric exercise stimulus and after said substance administration, and measuring said biological markers in said first and second biological samples; and (d) correlating the measured values of the biological markers with the inflammatory or oxidant properties of the substance, wherein said correlating comprises comparing the measured value of the biological markers in the first sample with the measured value of the biological markers in the second sample to determine if said measured values increase, decrease, or remain the same.
Claim 34
Independent Claim
217 words
A method for screening a substance for inflammatory or oxidant properties comprising: (a) applying an eccentric exercise stimulus to a subject, thereby inducing a muscle injury in the subject, wherein the muscle injury causes an acute inflammatory response characterized by an increase in redox-active metal ions; (b) administering a substance to the subject; (c) measuring biological markers within the subject to obtain a value of the biological markers, wherein the biological markers include at least one inflammatory marker selected from the group consisting of 8-isoprostane, myeloperoxidase, interleukin-6, and C-reactive protein, and at least one oxidative stress marker selected from the group consisting of free iron, superoxide dismutase, glutathione peroxidase, lipid hydroperoxidase, dityrosine, and 8-hydroxyguanine, wherein said measuring comprises taking a first biological sample from the subject before said eccentric exercise stimulus, taking a second biological sample after said eccentric exercise stimulus and after said substance administration, and measuring said biological markers in said first and second biological samples; and (d) correlating the measured values of the biological markers with the inflammatory or oxidant properties of the substance, wherein said correlating comprises comparing the measured value of the biological markers in the first sample with the measured value of the biological markers in the second sample to determine if said measured values increase, decrease, or remain the same.
Claim 35
Independent Claim
165 words
A method for screening a substance for inflammatory or oxidant properties comprising: (a) applying an eccentric exercise stimulus to a subject, thereby inducing a muscle injury in the subject, wherein the muscle injury causes an acute inflammatory response characterized by an increase in redox-active metal ions; (b) administering a substance to the subject; (c) measuring 8-isoprostane within the subject to obtain a value of said 8-isoprostane, wherein said measuring comprises taking a first biological sample from the subject before said eccentric exercise stimulus, taking a second biological sample after said eccentric exercise stimulus and after said substance administration, and measuring said 8-isoprostane in said first and second biological samples; and (d) correlating the measured value of the 8-isoprostane with the inflammatory or oxidant properties of the substance, wherein said correlating comprises comparing the measured value of said 8-isoprostane in the first sample with the measured value of the 8-isoprostane in the second sample to determine if said measured values increase, decrease, or remain the same.
Claim 36
Independent Claim
165 words
A method for screening a substance for inflammatory or oxidant properties comprising: (a) applying an eccentric exercise stimulus to a subject, thereby inducing a muscle injury in the subject, wherein the muscle injury causes an acute inflammatory response characterized by an increase in redox-active metal ions; (b) administering a substance to the subject; (c) measuring 8-isoprostane within the subject to obtain a value of said 8-isoprostane, wherein said measuring comprises taking a first biological sample from the subject before said eccentric exercise stimulus, taking a second biological sample after said eccentric exercise stimulus and after said substance administration, and measuring said 8-isoprostane in said first and second biological samples; and (d) correlating the measured value of the 8-isoprostane with the inflammatory or oxidant properties of the substance, wherein said correlating comprises comparing the measured value of said 8-isoprostane in the first sample with the measured value of the 8-isoprostane in the second sample to determine if said measured values increase, decrease, or remain the same.
Claim 37
Independent Claim
99 words
A system for determining the inflammatory or oxidant properties of a substance comprising: (a) a sampling means for taking a biological sample from a subject; (b) a stimulus means for applying eccentric exercise to the subject before, during, or after a substance has been administered to the subject; and (c) a measuring means for measuring the amount of at least one biological marker in the biological sample, wherein the biological marker is selected from the group consisting of free iron, total antioxidant status, 8-isoprostane, superoxide dismutase, glutathione peroxidase, lactate dehydrogenase, C-reactive protein, lipid hydroperoxidase, myeloperoxidase, interleukin-6, dityrosine, and 8-hydroxyguanine.
Claim 38
Independent Claim
99 words
A system for determining the inflammatory or oxidant properties of a substance comprising: (a) a sampling means for taking a biological sample from a subject; (b) a stimulus means for applying eccentric exercise to the subject before, during, or after a substance has been administered to the subject; and (c) a measuring means for measuring the amount of at least one biological marker in the biological sample, wherein the biological marker is selected from the group consisting of free iron, total antioxidant status, 8-isoprostane, superoxide dismutase, glutathione peroxidase, lactate dehydrogenase, C-reactive protein, lipid hydroperoxidase, myeloperoxidase, interleukin-6, dityrosine, and 8-hydroxyguanine.
Claim 39
Dependent Claim
34 words
The system according to claim 33 , wherein said system further comprises: (d) a correlating means for correlating the measured amounts of the biological marker with the inflammatory or oxidant properties of the substance.
Claim 40
Dependent Claim
22 words
The system according to claim 33 , wherein the biological marker is selected from the group consisting of free iron and 8-isoprostane.
Claim 41
Dependent Claim
14 words
The system according to claim 33 , wherein 8-isoprostane, myeloperoxidase, and dityrosine are measured.
Claim 42
Dependent Claim
16 words
The system according to claim 33 , wherein lactate dehydrogenase, dityrosine, and C-reactive protein are measured.
Claim 43
Dependent Claim
15 words
The system according to claim 33 , wherein free iron, interleukin-6, and 8-hydroxyguanine are measured.
Claim 44
Dependent Claim
46 words
The system according to claim 33 , wherein said measuring means further comprises means for recording the measured amount of the biological marker in the sample as a function of the time of occurrence of the eccentric exercise, so as to identify the relationship there between.
Claim 45
Dependent Claim
15 words
The system according to claim 33 , wherein the biological sample is a blood sample.
Claim 46
Dependent Claim
33 words
The system according to claim 33 , wherein said stimulus means induces an acute inflammatory injury in the subject and wherein the injury causes an increase in redox-active metal ions in the subject.
Claim 47
Dependent Claim
30 words
The system according to claim 33 , wherein said eccentric exercise is selected from the group consisting of eccentric arm curl exercises, eccentric leg curl exercises, and downhill running exercises.
Claim 48
Dependent Claim
26 words
The system, according to claim 33 , wherein said correlating means comprises means for comparing the measured amounts of the biological marker with a control value.
Claim 49
Independent Claim
68 words
A system for determining the inflammatory or oxidant properties of a substance comprising: (e) a sampling means for taking a biological sample from a subject; (f) a stimulus means for applying eccentric exercise to the subject before, during, or after a substance has been administered to the subject; and (g) a measuring means for measuring the amount of at least one oxidative stress marker in the biological sample.
Claim 50
Independent Claim
68 words
A system for determining the inflammatory or oxidant properties of a substance comprising: (e) a sampling means for taking a biological sample from a subject; (f) a stimulus means for applying eccentric exercise to the subject before, during, or after a substance has been administered to the subject; and (g) a measuring means for measuring the amount of at least one oxidative stress marker in the biological sample.
Claim 51
Dependent Claim
29 words
The system according to claim 44 , wherein the oxidative stress marker is selected from the group consisting of free iron, 8-isoprostane, superoxide dismutase, glutathione peroxidase, dityrosine, and 8-hydroxyguanine.
References Cited (Backward Citations)
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