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Article: Pembrolizumab-Induced Adrenal Insufficiency Presenting Eight Months After Cessation of Treatment.

Zilberman, Stephanie / Rafii, Daniel C / Giunta, Judith

2023 Volume 15, Issue 6, Page(s) e41049

Abstract: Pembrolizumab is a monoclonal antibody that functions as an immune checkpoint inhibitor. It is an FDA-approved immunotherapy used to treat various malignancies. With its wide use in cancer therapy, there are many known side effects. It is a common cause ... ...

Abstract	Pembrolizumab is a monoclonal antibody that functions as an immune checkpoint inhibitor. It is an FDA-approved immunotherapy used to treat various malignancies. With its wide use in cancer therapy, there are many known side effects. It is a common cause of endocrinopathies such as thyroid disease and adrenal insufficiency (AI). AI has been most commonly reported during active treatment cycles with pembrolizumab, as well as quickly after the termination of treatment. However, we describe a case of pembrolizumab-induced AI with an onset at eight months following the discontinuation of treatment and discuss prompt treatment when AI is diagnosed.
Language	English
Publishing date	2023-06-27
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.41049
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Article ; Online: A Delayed Presentation of Bilateral Adrenal Hemorrhage Secondary to COVID-19.

Zilberman, Stephanie / Winner, Laura / Giunta, Judith / Rafii, Daniel C

AACE clinical case reports

2023 Volume 9, Issue 3, Page(s) 71–73

Abstract: Background/objective: Bilateral adrenal hemorrhage is a rare cause of adrenal insufficiency. Cases have been reported of acute adrenal crisis with bilateral adrenal hemorrhage during acute coronavirus disease of 2019 (COVID-19). Our objective was to ... ...

Abstract	Background/objective: Bilateral adrenal hemorrhage is a rare cause of adrenal insufficiency. Cases have been reported of acute adrenal crisis with bilateral adrenal hemorrhage during acute coronavirus disease of 2019 (COVID-19). Our objective was to report a delayed presentation of acute adrenal crisis with bilateral adrenal hemorrhage 2 months after COVID-19. Case report: An 89-year-old man who was hospitalized for COVID-19 pneumonia 2 months prior presented with lethargy. He was disorientated and hypotensive to 70/50 mm Hg without improvement with intravenous fluids. According to his family, since his previous hospitalization for COVID-19, his mental status had continued to deteriorate, and he was no longer able to perform activities of daily living. A computed tomography scan of the abdomen revealed bilateral heterogeneous enlargement of the adrenal glands. Laboratory values were significant for an am cortisol level of 8.42 mcg/dL, a sodium level of 134 mEq/L, and a bicarbonate level of 17 mEq/L. He was treated intravenously with hydrocortisone 100 mg and showed rapid improvement. Discussion: It has been shown that COVID-19 disease may cause an increased risk of bleeding or thromboembolism. The exact frequency of bilateral adrenal hemorrhage secondary to COVID-19 is unknown. Although there are a handful of cases reported, there are none to our knowledge with a delayed presentation, as exhibited in our patient. Conclusion: The patient's presentation was consistent with acute adrenal crisis due to bilateral adrenal hemorrhage from prior COVID-19 disease. We aimed to highlight the importance of clinicians being aware of adrenal hemorrhage and adrenal insufficiency as a possible delayed consequence in patients with a history of COVID-19.
Language	English
Publishing date	2023-02-24
Publishing country	United States
Document type	Case Reports
ISSN	2376-0605
ISSN (online)	2376-0605
DOI	10.1016/j.aace.2023.02.005
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Article: Visual Vignette.

Rafii, Daniel C / Greif, Eric F / Finestone, Howard / Karam, Jocelyne

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

2017 Volume 23, Issue 7, Page(s) 891

MeSH term(s)	Adenolymphoma/diagnostic imaging ; Carcinoma/diagnostic imaging ; Carcinoma/secondary ; Carcinoma, Papillary ; Diagnosis, Differential ; Humans ; Iodine Radioisotopes ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Parotid Neoplasms/diagnostic imaging ; Radionuclide Imaging ; Thyroid Cancer, Papillary ; Thyroid Neoplasms/diagnostic imaging ; Thyroid Neoplasms/secondary ; Ultrasonography ; Whole Body Imaging
Chemical Substances	Iodine Radioisotopes
Language	English
Publishing date	2017-01-17
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	1473503-9
ISSN	1530-891X
ISSN	1530-891X
DOI	10.4158/EP161687.VV
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Zs.A 5034: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Retinal Pigment Epithelium-Secreted VEGF-A Induces Alpha-2-Macroglobulin Expression in Endothelial Cells.

Lehmann, Guillermo L / Ginsberg, Michael / Nolan, Daniel J / Rodríguez, Cristina / Martínez-González, José / Zeng, Shemin / Voigt, Andrew P / Mullins, Robert F / Rafii, Shahin / Rodriguez-Boulan, Enrique / Benedicto, Ignacio

Cells

2022 Volume 11, Issue 19

Abstract: Alpha-2-macroglobulin (A2M) is a protease inhibitor that regulates extracellular matrix (ECM) stability and turnover. Here, we show that A2M is expressed by endothelial cells (ECs) from human eye choroid. We demonstrate that retinal pigment epithelium ( ... ...

Abstract	Alpha-2-macroglobulin (A2M) is a protease inhibitor that regulates extracellular matrix (ECM) stability and turnover. Here, we show that A2M is expressed by endothelial cells (ECs) from human eye choroid. We demonstrate that retinal pigment epithelium (RPE)-conditioned medium induces A2M expression specifically in ECs. Experiments using chemical inhibitors, blocking antibodies, and recombinant proteins revealed a key role of VEGF-A in RPE-mediated A2M induction in ECs. Furthermore, incubation of ECs with RPE-conditioned medium reduces matrix metalloproteinase-2 gelatinase activity of culture supernatants, which is partially restored after A2M knockdown in ECs. We propose that dysfunctional RPE or choroidal blood vessels, as observed in retinal diseases such as age-related macular degeneration, may disrupt the crosstalk mechanism we describe here leading to alterations in the homeostasis of choroidal ECM, Bruch's membrane and visual function.
MeSH term(s)	Antibodies, Blocking ; Culture Media, Conditioned ; Endothelial Cells ; Female ; Gelatinases ; Humans ; Matrix Metalloproteinase 2 ; Pregnancy ; Pregnancy-Associated alpha 2-Macroglobulins ; Protease Inhibitors ; Recombinant Proteins ; Retinal Pigment Epithelium ; Transcription Factors ; Vascular Endothelial Growth Factor A
Chemical Substances	Antibodies, Blocking ; Culture Media, Conditioned ; Pregnancy-Associated alpha 2-Macroglobulins ; Protease Inhibitors ; Recombinant Proteins ; Transcription Factors ; Vascular Endothelial Growth Factor A ; Gelatinases (EC 3.4.24.-) ; Matrix Metalloproteinase 2 (EC 3.4.24.24)
Language	English
Publishing date	2022-09-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11192975
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Article: A PROSPECTIVE STUDY OF COMMONLY UTILIZED REGIMENS OF VITAMIN D REPLACEMENT AND MAINTENANCE THERAPY IN ADULTS.

Rafii, Daniel C / Ali, Farah / Farag, Amal / Iyer, Bhanu / Otterbeck, Philip E / Chaudhari, Ronak / Potter, Natia / Stefanov, Dimitre G / Guber, Helena A

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

2018 Volume 25, Issue 1, Page(s) 6–15

Abstract: Objective: To determine which vitamin D dose, formulation, and schedule most effectively and safely achieves a 25-hydroxyvitamin D (25[OH]D) level of >30 ng/mL (75 nmol/L).: Methods: In this prospective study, 100 subjects from the NY Harbor HCS ... ...

Abstract	Objective: To determine which vitamin D dose, formulation, and schedule most effectively and safely achieves a 25-hydroxyvitamin D (25[OH]D) level of >30 ng/mL (75 nmol/L). Methods: In this prospective study, 100 subjects from the NY Harbor HCS Brooklyn Campus, ages 25 to 85 years, with 25(OH)D <30 ng/mL (<75 nmol/L), were randomized into four groups: cholecalciferol (D3) 2,000 international units (IU) daily; D3 3,000 IU daily; ergocalciferol (D2) 50,000 IU weekly; and D2 50,000 IU twice weekly. All were supplemented with 500 mg calcium carbonate daily. 25(OH)D, parathyroid hormone (PTH), urinary calcium, urinary creatinine, and other variables were measured during 7 visits over 12 months. Results: All groups achieved a mean vitamin D level >30 ng/mL (>75 nmol/L) by visit 4 (5 months). Those receiving 50,000 IU D2 twice weekly displayed the most rapid and robust response, with 25(OH)D reaching >30 ng/mL (>75 nmol/L) after only 1 month and plateauing at 60 ng/mL (150 nmol/L) by 7 months. Although no statistically significant difference was seen in mean 25(OH)D levels between groups 1 through 3, subjects on 50,000 IU D2 weekly more consistently showed higher mean levels than either groups 1 or 2. No episodes of significant hypercalcemia occurred. There was a negative correlation in mean PTH levels and mean vitamin D levels in group 4 and all groups combined. Conclusion: All four schedules of vitamin D replacement were effective in safely achieving and maintaining 25(OH)D >30 ng/mL (>75 nmol/L). D2 50,000 IU twice weekly provided the most rapid attainment and highest mean levels of vitamin D. Abbreviations: 25(OH)D = 25-hydroxyvitamin D; BMI = body mass index; BUN = blood urea nitrogen; Ca/Cr = calcium/creatinine; D2 = ergocalciferol; D3 = cholecalciferol; IU = international units; PTH = parathyroid hormone.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Cholecalciferol ; Dietary Supplements ; Humans ; Middle Aged ; Parathyroid Hormone ; Prospective Studies ; Vitamin D/pharmacology ; Vitamin D Deficiency ; Vitamins
Chemical Substances	Parathyroid Hormone ; Vitamins ; Vitamin D (1406-16-2) ; Cholecalciferol (1C6V77QF41)
Language	English
Publishing date	2018-11-01
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	1473503-9
ISSN	1530-891X
ISSN	1530-891X
DOI	10.4158/EP-2018-0219
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Article ; Online: Reversal of emphysema by restoration of pulmonary endothelial cells.

Hisata, Shu / Racanelli, Alexandra C / Kermani, Pouneh / Schreiner, Ryan / Houghton, Sean / Palikuqi, Brisa / Kunar, Balvir / Zhou, Aiyuan / McConn, Keith / Capili, Allyson / Redmond, David / Nolan, Daniel J / Ginsberg, Michael / Ding, Bi-Sen / Martinez, Fernando J / Scandura, Joseph M / Cloonan, Suzanne M / Rafii, Shahin / Choi, Augustine M K

The Journal of experimental medicine

2021 Volume 218, Issue 8

Abstract: Chronic obstructive pulmonary disease (COPD) is marked by airway inflammation and airspace enlargement (emphysema) leading to airflow obstruction and eventual respiratory failure. Microvasculature dysfunction is associated with COPD/emphysema. However, ... ...

Abstract	Chronic obstructive pulmonary disease (COPD) is marked by airway inflammation and airspace enlargement (emphysema) leading to airflow obstruction and eventual respiratory failure. Microvasculature dysfunction is associated with COPD/emphysema. However, it is not known if abnormal endothelium drives COPD/emphysema pathology and/or if correcting endothelial dysfunction has therapeutic potential. Here, we show the centrality of endothelial cells to the pathogenesis of COPD/emphysema in human tissue and using an elastase-induced murine model of emphysema. Airspace disease showed significant endothelial cell loss, and transcriptional profiling suggested an apoptotic, angiogenic, and inflammatory state. This alveolar destruction was rescued by intravenous delivery of healthy lung endothelial cells. Leucine-rich α-2-glycoprotein-1 (LRG1) was a driver of emphysema, and deletion of Lrg1 from endothelial cells rescued vascular rarefaction and alveolar regression. Hence, targeting endothelial cell biology through regenerative methods and/or inhibition of the LRG1 pathway may represent strategies of immense potential for the treatment of COPD/emphysema.
MeSH term(s)	Administration, Intravenous ; Animals ; Biomarkers/metabolism ; Disease Models, Animal ; Endothelial Cells/pathology ; Endothelial Cells/transplantation ; Gene Expression Profiling ; Gene Expression Regulation ; Glycoproteins/metabolism ; Humans ; Lung/blood supply ; Lung/pathology ; Lung/physiopathology ; Mice, Inbred C57BL ; Neovascularization, Physiologic ; Pancreatic Elastase/metabolism ; Phenotype ; Pulmonary Disease, Chronic Obstructive/genetics ; Pulmonary Disease, Chronic Obstructive/pathology ; Pulmonary Disease, Chronic Obstructive/physiopathology ; Pulmonary Emphysema/genetics ; Pulmonary Emphysema/pathology ; Pulmonary Emphysema/physiopathology ; Severity of Illness Index ; Smoking ; Transcriptome/genetics ; Mice
Chemical Substances	Biomarkers ; Glycoproteins ; LRG1 protein, mouse ; Pancreatic Elastase (EC 3.4.21.36)
Language	English
Publishing date	2021-07-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20200938
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Article ; Online: Quality contract 'prevention of postoperative delirium in the care of elderly patients' study protocol: a non-randomised, pre-post, monocentric, prospective trial.

Yürek, Fatima / Zimmermann, Julian-Dominic / Weidner, Elisa / Hauß, Armin / Dähnert, Enrico / Hadzidiakos, Daniel / Kruppa, Jochen / Kiselev, Joern / Sichinava, Natia / Retana Romero, Oscar Andrés / Hoff, Laerson / Mörgeli, Rudolf / Junge, Lennart / Scholtz, Kathrin / Piper, Sophie K / Grüner, Luzie / Harborth, Antonia Eva Maria / Eymold, Lisa / Gülmez, Tuba /

Falk, Elke / Balzer, Felix / Treskatsch, Sascha / Höft, Moritz / Schmidt, Dieter / Landgraf, Franziska / Marschall, Ursula / Hölscher, Andreas / Rafii, Mani / Spies, Claudia

BMJ open

2023 Volume 13, Issue 3, Page(s) e066709

Abstract: Introduction: Postoperative delirium (POD) is seen in approximately 15% of elderly patients and is related to poorer outcomes. In 2017, the Federal Joint Committee (Gemeinsamer Bundesausschuss) introduced a 'quality contract' (QC) as a new instrument to ...

Abstract	Introduction: Postoperative delirium (POD) is seen in approximately 15% of elderly patients and is related to poorer outcomes. In 2017, the Federal Joint Committee (Gemeinsamer Bundesausschuss) introduced a 'quality contract' (QC) as a new instrument to improve healthcare in Germany. One of the four areas for improvement of in-patient care is the 'Prevention of POD in the care of elderly patients' (QC-POD), as a means to reduce the risk of developing POD and its complications.The Institute for Quality Assurance and Transparency in Health Care identified gaps in the in-patient care of elderly patients related to the prevention, screening and treatment of POD, as required by consensus-based and evidence-based delirium guidelines. This paper introduces the QC-POD protocol, which aims to implement these guidelines into the clinical routine. There is an urgent need for well-structured, standardised and interdisciplinary pathways that enable the reliable screening and treatment of POD. Along with effective preventive measures, these concepts have a considerable potential to improve the care of elderly patients. Methods and analysis: The QC-POD study is a non-randomised, pre-post, monocentric, prospective trial with an interventional concept following a baseline control period. The QC-POD trial was initiated on 1 April 2020 between Charité-Universitätsmedizin Berlin and the German health insurance company BARMER and will end on 30 June 2023. Inclusion criteria: patients 70 years of age or older that are scheduled for a surgical procedure requiring anaesthesia and insurance with the QC partner (BARMER). Exclusion criteria included patients with a language barrier, moribund patients and those unwilling or unable to provide informed consent. The QC-POD protocol provides perioperative intervention at least two times per day, with delirium screening and non-pharmacological preventive measures. Ethics and dissemination: This protocol was approved by the ethics committee of the Charité-Universitätsmedizin, Berlin, Germany (EA1/054/20). The results will be published in a peer-reviewed scientific journal and presented at national and international conferences. Trial registration number: NCT04355195.
MeSH term(s)	Aged ; Humans ; Emergence Delirium ; Prospective Studies ; Academies and Institutes ; Anesthesia ; Insurance, Health
Language	English
Publishing date	2023-03-06
Publishing country	England
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2022-066709
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Article ; Online: Therapeutic metabolic inhibition: hydrogen sulfide significantly mitigates skeletal muscle ischemia reperfusion injury in vitro and in vivo.

Henderson, Peter W / Singh, Sunil P / Weinstein, Andrew L / Nagineni, Vijay / Rafii, Daniel C / Kadouch, Daniel / Krijgh, David D / Spector, Jason A

Plastic and reconstructive surgery

2010 Volume 126, Issue 6, Page(s) 1890–1898

Abstract: Background: Recent evidence suggests that hydrogen sulfide is capable of mitigating the degree of cellular damage associated with ischemia-reperfusion injury. The purpose of this study was to determine whether it is protective in skeletal muscle.: ... ...

Abstract	Background: Recent evidence suggests that hydrogen sulfide is capable of mitigating the degree of cellular damage associated with ischemia-reperfusion injury. The purpose of this study was to determine whether it is protective in skeletal muscle. Methods: This study used both in vitro (cultured myotubes subjected to sequential anoxia and normoxia) and in vivo (mouse hind-limb ischemia followed by reperfusion) models in which hydrogen sulfide (0 to 1000 μM) was delivered before the onset of oxygen deficiency. Injury score and apoptotic index were determined by analysis of specimens stained with hematoxylin and eosin and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, respectively. Results: In vitro, hydrogen sulfide reduced the apoptotic index by as much as 99 percent (p=0.001), with optimal protection conferred by raising intravascular hydrogen sulfide to 10 μM. In vivo, 10 μM hydrogen sulfide delivered before 3 hours of hind-limb ischemia followed by 3 hours of reperfusion resulted in protection against ischemia-reperfusion injury-induced cellular changes, as evidenced by significant decreases in injury score and apoptotic index (by as much as 91 percent; p=0.001). These findings were consistent at 4 weeks after injury and reperfusion. Conclusion: These findings confirm that the preischemic delivery of hydrogen sulfide limits ischemia-reperfusion injury-induced cellular damage in myotubes and skeletal muscle and suggests that, when given in the appropriate dose, this molecule may have significant therapeutic applications in multiple clinical scenarios.
MeSH term(s)	Administration, Inhalation ; Animals ; Apoptosis/drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Hydrogen Sulfide/administration & dosage ; Hydrogen Sulfide/pharmacology ; In Situ Nick-End Labeling ; In Vitro Techniques ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/blood supply ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/pathology ; Myoblasts/drug effects ; Myoblasts/pathology ; Premedication ; Reperfusion Injury/prevention & control ; Tissue Survival/drug effects
Chemical Substances	Hydrogen Sulfide (YY9FVM7NSN)
Language	English
Publishing date	2010-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208012-6
ISSN	1529-4242 ; 0032-1052 ; 0096-8501
ISSN (online)	1529-4242
ISSN	0032-1052 ; 0096-8501
DOI	10.1097/PRS.0b013e3181f446bc
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Zs.MO 293: Show issues

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Article ; Online: Stromal-derived factor-1 delivered via hydrogel drug-delivery vehicle accelerates wound healing in vivo.

Henderson, Peter W / Singh, Sunil P / Krijgh, David D / Yamamoto, Masaya / Rafii, Daniel C / Sung, Josephine J / Rafii, Shahin / Rabbany, Sina Y / Spector, Jason A

Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society

2011 Volume 19, Issue 3, Page(s) 420–425

Abstract: Topical treatment of superficial wounds has many advantages including decreased cost and increased ease of application compared with systemic treatments. Many of the advantages, however, are lost when it is necessary for repeated doses of topical ... ...

Abstract	Topical treatment of superficial wounds has many advantages including decreased cost and increased ease of application compared with systemic treatments. Many of the advantages, however, are lost when it is necessary for repeated doses of topical medications to be given over an extended period of time. Therefore, a drug-delivery vehicle that delivers biologically appropriate doses in a sustained fashion would prove valuable. In this study, an alginate hydrogel scaffold impregnated with the angiogenic chemokine stromal-derived factor-1 was used to provide targeted, though short-term, delivery directly into the wound bed. Wounds were created on the dorsum of mice, and either a stromal-derived factor-1-impregnated or a saline-impregnated scaffold was applied. Wounds were explanted after 1, 3, 7 days, wound area was measured, and histology and immunohistochemistry for endothelial markers were performed. The remaining wound area in stromal-derived factor-1-treated wounds vs. controls was not significant 1 day after wounding (96.7 ± 0.1 vs. 97.5 ± 1.1%, p=0.317), but was significant after 3 days postwounding (46.7 ± 0.1 vs. 82.3 ± 2.4%, p=0.046) and 7 days postwounding (2.3 ± 1.3 vs. 32.0 ± 4.0%, p=0.049). Immunohistochemistry revealed a greater degree of endothelial cell invasion into the wound bed infiltration compared with controls. The results of this study suggest significant clinical promise for our hydrogel-delivery vehicle in the treatment of wounds.
MeSH term(s)	Animals ; Antigens, CD/metabolism ; Cadherins/metabolism ; Cell Culture Techniques ; Chemokine CXCL12 ; Drug Delivery Systems ; Hydrogel, Polyethylene Glycol Dimethacrylate ; Male ; Mice ; Mice, Inbred C57BL ; Tissue Engineering/methods ; Tissue Scaffolds ; Wound Healing/physiology ; von Willebrand Factor/metabolism
Chemical Substances	Antigens, CD ; Cadherins ; Chemokine CXCL12 ; cadherin 5 ; von Willebrand Factor ; Hydrogel, Polyethylene Glycol Dimethacrylate (25852-47-5)
Language	English
Publishing date	2011-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1174873-4
ISSN	1524-475X ; 1067-1927
ISSN (online)	1524-475X
ISSN	1067-1927
DOI	10.1111/j.1524-475X.2011.00687.x
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Article ; Online: Regulation of vasculogenesis by platelet-mediated recruitment of bone marrow-derived cells.

Rafii, Daniel C / Psaila, Bethan / Butler, Jason / Jin, David K / Lyden, David

Arteriosclerosis, thrombosis, and vascular biology

2008 Volume 28, Issue 2, Page(s) 217–222

Abstract: Bone marrow-derived cells contribute to physiological and pathological vascular remodeling throughout ontogenesis and adult life. During tissue regeneration and tumor growth, the release of cytokines and chemokines mediates the recruitment of ... ...

Abstract	Bone marrow-derived cells contribute to physiological and pathological vascular remodeling throughout ontogenesis and adult life. During tissue regeneration and tumor growth, the release of cytokines and chemokines mediates the recruitment of hematopoietic and endothelial progenitor cells that contribute to the assembly of neovessels. Current evidence implies that platelets contribute structurally and instructively to vascular remodeling. Platelets adhere almost immediately to exposed or activated endothelium, and they are major storage and delivery vehicles for pro- and antiangiogenic growth factors including VEGF-A and thrombospondin (TSP), and cytokines and chemokines, such as stromal-derived factor 1 (SDF-1). By site-specific deployment of these factors, platelets orchestrate the local angiogenic stimulus within a tissue and direct the recruitment and differentiation of circulating bone marrow-derived cells. These insights have profound clinical implications; inhibition of platelet-deployed growth factors or their receptors may be an effective strategy to block tumor growth, whereas activation of these pathways may be used to accelerate revascularization and tissue regeneration.
MeSH term(s)	Blood Platelets/physiology ; Bone Marrow Cells/physiology ; Cell Differentiation/physiology ; Chemokine CXCL12/physiology ; Endothelial Cells/physiology ; Humans ; Neovascularization, Physiologic/physiology ; Thrombospondins/physiology ; Vascular Endothelial Growth Factor A/physiology
Chemical Substances	Chemokine CXCL12 ; Thrombospondins ; Vascular Endothelial Growth Factor A
Language	English
Publishing date	2008-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.107.151159
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