The effects of procalcitonin on the endothelium: novel therapeutic strategies for the preservation of vascular integrity during sepsis
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| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
Münster
2022
|
| Subjects: | |
| Online Access: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Physical Description: | 83 Blätter Illustrationen, Diagramme 31 cm |
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| 100 | 1 | |a Hellenthal, Katharina Emily Marie |d 1998- |e Verfasser |0 (DE-588)1269450891 |4 aut | |
| 245 | 1 | 0 | |a The effects of procalcitonin on the endothelium |b novel therapeutic strategies for the preservation of vascular integrity during sepsis |c vorgelegt von Hellenthal, Katharina Emily Marie |
| 264 | 1 | |a Münster |c 2022 | |
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| 502 | |b Dissertation |c Westfälische Wilhelms-Universität Münster |d 2022 |g Beschränkt für den Austausch | ||
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| adam_text | TABLE
OF
CONTENTS
1
INTRODUCTION
.....................................................................................................
1
1.1
SEPSIS
-
A
LIFE-THREATENING
DISEASE
................................................................
1
1.2
THE
ENDOTHELIUM
-
A
KEY
DETERMINANT
IN
THE
ADVERSE
SEPSIS
HOST
RESPONSE.
.2
1.3
INTERCELLULAR
JUNCTIONS
-
A
CRITICAL
INTERFACE
IN
SEPSIS
PATHOLOGY
......................
3
1.4
PROCALCITONIN
-
A
USEFUL
BACTERIAL
SEPSIS
BIOMARKER
......................................
5
1.5
PROCALCITONIN
-
A
POTENTIAL
SEPSIS
PLAYER
........................................................
7
1.6
HYPOTHESES
OF
THE
PRESENT
WORK
....................................................................
10
2
MATERIAL
AND
METHODS
....................................................................................
11
2.1
CELL
CULTURE
....................................................................................................
11
2.2
WESTERN
BLOT
..................................................................................................
12
2.2.1
CELL
LYSIS
.....................................................................................................
12
2.2.2
PROTEIN
QUANTIFICATION
..................................................................................
13
2.2.3
IMMUNOBLOTTING
...........................................................................................
14
2.3
IN
VIVO
STUDIES
................................................................................................
17
2.3.1
WILD
TYPE
(WT)
MICE
...................................................................................
17
2.3.2
VE-CADHERIN
KNOCK-IN
(KI)
MICE
(VEC-Y685F)
..........................................
17
2.3.3
SUBSTANCE
APPLICATION
................................................................................
18
2.3.4
PRODUCTION
OF
RECOMBINANT
PCTI-NEAND
PCT3-116
...................................
21
2.3.5 SEPSIS
INDUCTION
BY
CECAL
LIGATION
AND
PUNCTURE
(CLP)
.............................
22
2.3.6
SHAM
SURGERY
.............................................................................................
22
2.3.7
MILES
ASSAY
.................................................................................................
23
2.3.8
HISTOLOGY
OF
MURINE
LUNGS
...........................................................................
24
2.4
STATISTICAL
ANALYSIS
.........................................................................................
26
3
RESULTS
............................................................................................................
27
3.1
PROCALCITONIN
INDUCES
PULMONARY
EDEMA
FORMATION
IN
WILD
TYPE
MICE
.........
27
3.2
VE-CADHERIN
IS
A
DOWNSTREAM
TARGET
OF
PROCALCITONIN
...................................
30
3.3
CRLR/RAMP1
BLOCKADE
BY
OLCEGEPANT
CONTROLS
PROCALCITONIN
INDUCED
EDEMA
FORMATION
.................................................................................................
33
3.4
CRLR/RAMP1
BLOCKAGE
BY
OLCEGEPANT
AMELIORATES
SEPSIS
INDUCED
EDEMA
FORMATION
.............................................................................................................
35
3.5
CRLR/RAMP1
ACTIVATION
REQUIRES
PROCALCITONIN
S
N-TERMINUS
......................
37
3.6
BOTH
NATIVE
PCTI-NEAND
TRUNCATED
PCT3-116
INDUCE
EDEMA
FORMATION
.......
40
3.7
PROCALCITONIN
EFFECTS
DEPEND
ON
N-TERMINAL
TRUNCATION
BY
DPP4
..................
42
3.8
DPP4
INHIBITION
ABOLISHES
PROCALCITONIN
EDEMA
INDUCING
EFFECTS
IN
VIVO
.....
43
3.9
DPP4
INHIBITORS
AS
POSSIBLE
MEANS
TO
PRESERVE
VASCULAR
INTEGRITY
IN
SEPSIS48
4
DISCUSSION
......................................................................................................
51
4.1
PROCALCITONIN
INDUCES
VASCULAR
LEAKAGE
IN
SEPSIS
........................................
51
4.2
VE-CADHERIN
IS
THE
DOWNSTREAM
TARGET
MEDIATING
PROCALCITONIN
EDEMA
INDUCING
EFFECTS
...................................................................................................
53
4.3 PROCALCITONIN
EFFECTS
ARE
MEDIATED
BY
THE
CRLR/RAMP1
COMPLEX
...............
55
4.4 PROCALCITONIN
EFFECTS
DEPEND
ON
N-TERMINAL
CLEAVAGE
BY
DPP4
....................
56
4.5
DPP4
INHIBITION
CONTROLS
SEPSIS-INDUCED
VASCULAR
BARRIER
DYSFUNCTION
.........
58
5
SUMMARY
........................................................................................................
62
6
REFERENCES
.....................................................................................................
64
7
APPENDIX
........................................................................................................
73
7.1
LIST
OF
FIGURES
.................................................................................................
73
7.2
LIST
OF
TABLES
..................................................................................................
74
7.3
LIST
OF
ABBREVIATIONS
......................................................................................
75
7.4
ACKNOWLEDGMENTS
.........................................................................................
77
7.5
CURRICULUM
VITAE
............................................................................................
78
7.6
APPROVAL
OF
IN
VIVO
STUDIES
.............................................................................
79
|
| adam_txt |
TABLE
OF
CONTENTS
1
INTRODUCTION
.
1
1.1
SEPSIS
-
A
LIFE-THREATENING
DISEASE
.
1
1.2
THE
ENDOTHELIUM
-
A
KEY
DETERMINANT
IN
THE
ADVERSE
SEPSIS
HOST
RESPONSE.
.2
1.3
INTERCELLULAR
JUNCTIONS
-
A
CRITICAL
INTERFACE
IN
SEPSIS
PATHOLOGY
.
3
1.4
PROCALCITONIN
-
A
USEFUL
BACTERIAL
SEPSIS
BIOMARKER
.
5
1.5
PROCALCITONIN
-
A
POTENTIAL
SEPSIS
PLAYER
.
7
1.6
HYPOTHESES
OF
THE
PRESENT
WORK
.
10
2
MATERIAL
AND
METHODS
.
11
2.1
CELL
CULTURE
.
11
2.2
WESTERN
BLOT
.
12
2.2.1
CELL
LYSIS
.
12
2.2.2
PROTEIN
QUANTIFICATION
.
13
2.2.3
IMMUNOBLOTTING
.
14
2.3
IN
VIVO
STUDIES
.
17
2.3.1
WILD
TYPE
(WT)
MICE
.
17
2.3.2
VE-CADHERIN
KNOCK-IN
(KI)
MICE
(VEC-Y685F)
.
17
2.3.3
SUBSTANCE
APPLICATION
.
18
2.3.4
PRODUCTION
OF
RECOMBINANT
PCTI-NEAND
PCT3-116
.
21
2.3.5 SEPSIS
INDUCTION
BY
CECAL
LIGATION
AND
PUNCTURE
(CLP)
.
22
2.3.6
SHAM
SURGERY
.
22
2.3.7
MILES
ASSAY
.
23
2.3.8
HISTOLOGY
OF
MURINE
LUNGS
.
24
2.4
STATISTICAL
ANALYSIS
.
26
3
RESULTS
.
27
3.1
PROCALCITONIN
INDUCES
PULMONARY
EDEMA
FORMATION
IN
WILD
TYPE
MICE
.
27
3.2
VE-CADHERIN
IS
A
DOWNSTREAM
TARGET
OF
PROCALCITONIN
.
30
3.3
CRLR/RAMP1
BLOCKADE
BY
OLCEGEPANT
CONTROLS
PROCALCITONIN
INDUCED
EDEMA
FORMATION
.
33
3.4
CRLR/RAMP1
BLOCKAGE
BY
OLCEGEPANT
AMELIORATES
SEPSIS
INDUCED
EDEMA
FORMATION
.
35
3.5
CRLR/RAMP1
ACTIVATION
REQUIRES
PROCALCITONIN
'
S
N-TERMINUS
.
37
3.6
BOTH
NATIVE
PCTI-NEAND
TRUNCATED
PCT3-116
INDUCE
EDEMA
FORMATION
.
40
3.7
PROCALCITONIN
EFFECTS
DEPEND
ON
N-TERMINAL
TRUNCATION
BY
DPP4
.
42
3.8
DPP4
INHIBITION
ABOLISHES
PROCALCITONIN
EDEMA
INDUCING
EFFECTS
IN
VIVO
.
43
3.9
DPP4
INHIBITORS
AS
POSSIBLE
MEANS
TO
PRESERVE
VASCULAR
INTEGRITY
IN
SEPSIS48
4
DISCUSSION
.
51
4.1
PROCALCITONIN
INDUCES
VASCULAR
LEAKAGE
IN
SEPSIS
.
51
4.2
VE-CADHERIN
IS
THE
DOWNSTREAM
TARGET
MEDIATING
PROCALCITONIN
EDEMA
INDUCING
EFFECTS
.
53
4.3 PROCALCITONIN
EFFECTS
ARE
MEDIATED
BY
THE
CRLR/RAMP1
COMPLEX
.
55
4.4 PROCALCITONIN
EFFECTS
DEPEND
ON
N-TERMINAL
CLEAVAGE
BY
DPP4
.
56
4.5
DPP4
INHIBITION
CONTROLS
SEPSIS-INDUCED
VASCULAR
BARRIER
DYSFUNCTION
.
58
5
SUMMARY
.
62
6
REFERENCES
.
64
7
APPENDIX
.
73
7.1
LIST
OF
FIGURES
.
73
7.2
LIST
OF
TABLES
.
74
7.3
LIST
OF
ABBREVIATIONS
.
75
7.4
ACKNOWLEDGMENTS
.
77
7.5
CURRICULUM
VITAE
.
78
7.6
APPROVAL
OF
IN
VIVO
STUDIES
.
79 |
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| index_date | 2024-07-03T21:50:58Z |
| indexdate | 2024-07-10T09:49:18Z |
| institution | BVB |
| language | English |
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| oclc_num | 1349709188 |
| open_access_boolean | |
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| physical | 83 Blätter Illustrationen, Diagramme 31 cm |
| publishDate | 2022 |
| publishDateSearch | 2022 |
| publishDateSort | 2022 |
| record_format | marc |
| spelling | Hellenthal, Katharina Emily Marie 1998- Verfasser (DE-588)1269450891 aut The effects of procalcitonin on the endothelium novel therapeutic strategies for the preservation of vascular integrity during sepsis vorgelegt von Hellenthal, Katharina Emily Marie Münster 2022 83 Blätter Illustrationen, Diagramme 31 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Westfälische Wilhelms-Universität Münster 2022 Beschränkt für den Austausch (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf https://d-nb.info/1261764226/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034165344&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p emakn 0,20685 20221013 DE-101 https://d-nb.info/provenance/plan#emakn 2\p dnb 20221013 DE-101 https://d-nb.info/provenance/plan#dnb |
| spellingShingle | Hellenthal, Katharina Emily Marie 1998- The effects of procalcitonin on the endothelium novel therapeutic strategies for the preservation of vascular integrity during sepsis |
| subject_GND | (DE-588)4113937-9 |
| title | The effects of procalcitonin on the endothelium novel therapeutic strategies for the preservation of vascular integrity during sepsis |
| title_auth | The effects of procalcitonin on the endothelium novel therapeutic strategies for the preservation of vascular integrity during sepsis |
| title_exact_search | The effects of procalcitonin on the endothelium novel therapeutic strategies for the preservation of vascular integrity during sepsis |
| title_exact_search_txtP | The effects of procalcitonin on the endothelium novel therapeutic strategies for the preservation of vascular integrity during sepsis |
| title_full | The effects of procalcitonin on the endothelium novel therapeutic strategies for the preservation of vascular integrity during sepsis vorgelegt von Hellenthal, Katharina Emily Marie |
| title_fullStr | The effects of procalcitonin on the endothelium novel therapeutic strategies for the preservation of vascular integrity during sepsis vorgelegt von Hellenthal, Katharina Emily Marie |
| title_full_unstemmed | The effects of procalcitonin on the endothelium novel therapeutic strategies for the preservation of vascular integrity during sepsis vorgelegt von Hellenthal, Katharina Emily Marie |
| title_short | The effects of procalcitonin on the endothelium |
| title_sort | the effects of procalcitonin on the endothelium novel therapeutic strategies for the preservation of vascular integrity during sepsis |
| title_sub | novel therapeutic strategies for the preservation of vascular integrity during sepsis |
| topic_facet | Hochschulschrift |
| url | https://d-nb.info/1261764226/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034165344&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT hellenthalkatharinaemilymarie theeffectsofprocalcitoninontheendotheliumnoveltherapeuticstrategiesforthepreservationofvascularintegrityduringsepsis |
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