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  • 1
    Online Resource
    Online Resource
    Acute alcohol consumption increases systemic endotoxin bioactivity for days in healthy volunteers—with reduced intestinal barrier loss in female
    Springer Science and Business Media LLC ; 2022
    In:  European Journal of Trauma and Emergency Surgery Vol. 48, No. 3 ( 2022-06), p. 1569-1577
    Details
    In: European Journal of Trauma and Emergency Surgery, Springer Science and Business Media LLC, Vol. 48, No. 3 ( 2022-06), p. 1569-1577
    Abstract: Trauma is the most common cause of death among young adults. Alcohol intoxication plays a significant role as a cause of accidents and as a potent immunomodulator of the post-traumatic response to tissue injury. Polytraumatized patients are frequently at risk to developing infectious complications, which may be aggravated by alcohol-induced immunosuppression. Systemic levels of integral proteins of the gastrointestinal tract such as syndecan-1 or intestinal fatty acid binding proteins (FABP-I) reflect the intestinal barrier function. The exact impact of acute alcohol intoxication on the barrier function and endotoxin bioactivity have not been clarified yet. Methods 22 healthy volunteers received a precisely defined amount of alcohol (whiskey–cola) every 20 min over a period of 4 h to reach the calculated blood alcohol concentration (BAC) of 1‰. Blood samples were taken before alcohol drinking as a control, and after 2, 4, 6, 24 and 48 h after beginning with alcohol consumption. In addition, urine samples were collected. Intestinal permeability was determined by serum and urine values of FABP-I, syndecan-1, and soluble (s)CD14 as a marker for the endotoxin translocation via the intestinal barrier by ELISA. BAC was determined. Results Systemic FABP-I was significantly reduced 2 h after the onset of alcohol drinking, and remained decreased after 4 h. However, at 6 h, FABP-I significantly elevated compared to previous measurements as well as to controls ( p   〈  0.05). Systemic sCD14 was significantly elevated after 6, 24 and 48 h after the onset of alcohol consumption ( p   〈  0.05). Systemic FABP-I at 2 h after drinking significantly correlated with the sCD14 concentration after 24 h indicating an enhanced systemic LPS bioactivity. Women showed significantly lower levels of syndecan-1 in serum and urine and urine for all time points until 6 h and lower FABP-I in the serum after 2 h. Conclusions Even relative low amounts of alcohol affect the immune system of healthy volunteers, although these changes appear minor in women. A potential damage to the intestinal barrier and presumed enhanced systemic endotoxin bioactivity after acute alcohol consumption is proposed, which represents a continuous immunological challenge for the organism and should be considered for the following days after drinking.
    Type of Medium: Online Resource
    ISSN: 1863-9933 , 1863-9941
    URL: Article
    DOI: 10.1007/s00068-021-01666-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2276432-X
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  • 2
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    Online Resource
    Hemorrhagic shock alters fracture callus composition and activates the IL6 and RANKL/OPG pathway in mice
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Journal of Trauma and Acute Care Surgery Vol. 85, No. 2 ( 2018-8), p. 359-366
    Details
    In: Journal of Trauma and Acute Care Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 85, No. 2 ( 2018-8), p. 359-366
    Abstract: Fracture and hemorrhagic shock often lead to impaired fracture healing. To elucidate underlying pathogenesis, this study aimed to analyze histological properties during fracture healing after hemorrhagic shock and involved signaling pathways in mice. METHODS Male C57BL/6NCrl mice were assigned into five groups. Control group underwent no interventions. Sham group had a catheter and external fixator but neither blood loss nor osteotomy. Trauma-hemorrhage (TH) group received a pressure-controlled hemorrhagic shock; osteotomy (Fx) group, an osteotomy and fixator; and combined trauma (THFx) group, both hemorrhagic shock and externally fixed osteotomy. After 1, 2, 3, and 4 weeks, the animals were killed. Undecalcified bones were analyzed histologically and signaling pathways relevant for fracture healing by polymerase chain reaction and Western blot. Statistical significance was set at 0.05 or less. Comparisons were performed using the Mann-Whitney U or Kruskal-Wallis test. RESULTS In the THFx group, a decreased bone formation after 3 weeks, a reduction of both bone and cartilage after 2 weeks, and an enhanced activation of the RANKL / OPG and IL6 signaling pathway after 1 week were shown in comparison to Fx. CONCLUSIONS Hemorrhagic shock has a retarding effect on fracture healing in the early phase of fracture healing and leads to activation of the IL6 and RANKL/OPG signaling pathways.
    Type of Medium: Online Resource
    ISSN: 2163-0763 , 2163-0755
    URL: Article
    DOI: 10.1097/TA.0000000000001952
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2651313-4
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  • 3
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    Online Resource
    Acute Intoxication With Alcohol Reduces Trauma-Induced Proinflammatory Response and Barrier Breakdown in the Lung via the Wnt/β-Catenin Signaling Pathway
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-5-18)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-5-18)
    Abstract: Trauma is the third leading cause of mortality worldwide. Upon admission, up to 50% of traumatized patients are acutely intoxicated with alcohol, which might lead to aberrant immune responses. An excessive and uncontrolled inflammatory response to injury is associated with damage to trauma-distant organs. We hypothesize that, along with inflammation-induced apoptosis, the activation of the Wnt/β-catenin signaling pathway would cause breakdown of the lung barrier and the development of lung injury after trauma. It remains unclear whether ethanol intoxication (EI) prior to trauma and hemorrhagic shock will attenuate inflammation and organ injury. Methods In this study, 14 male C57BL/6J mice were randomly assigned to two groups and exposed either to EtOH or to NaCl as a control by an oral gavage before receiving a femur fracture (Fx) and hemorrhagic shock, followed by resuscitation (THFx). Fourteen sham animals received either EtOH or NaCl and underwent surgical procedures without THFx induction. After 24 h, oil red O staining of fatty vacuoles in the liver was performed. Histological lung injury score (LIS) was assessed to analyze the trauma-induced RLI. Gene expression of Cxcl1 , Il-1β , Muc5ac , Tnf , and Tnfrsf10b as well as CXCL1, IL-1β, and TNF protein levels in the lung tissue and bronchoalveolar lavage fluid were determined by RT-qPCR, ELISA, and immunohistological analyses. Infiltrating polymorphonuclear leukocytes (PMNLs) were examined via immunostaining. Apoptosis was detected by activated caspase-3 expression in the lung tissue. To confirm active Wnt signaling after trauma, gene expression of Wnt3a and its inhibitor sclerostin ( Sost ) was determined. Protein expression of A20 and RIPK4 as possible modulators of the Wnt signaling pathway was analyzed via immunofluorescence. Results Significant fatty changes in the liver confirmed the acute EI. Histopathology and decreased Muc5ac expression revealed an increased lung barrier breakdown and concomitant lung injury after THFx versus sham. EI prior trauma decreased lung injury. THFx increased not only the gene expression of pro-inflammatory markers but also the pulmonary infiltration with PMNL and apoptosis versus sham, while EI prior to THFx reduced those changes significantly. EI increased the THFx-reduced gene expression of Sost and reduced the THFx-induced expression of Wnt3a . While A20, RIPK4, and membranous β-catenin were significantly reduced after trauma, they were enhanced upon EI. Conclusion These findings suggest that acute EI alleviates the uncontrolled inflammatory response and lung barrier breakdown after trauma by suppressing the Wnt/β-catenin signaling pathway.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2022.866925
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 4
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    Online Resource
    Fracture Healing in Elderly Mice and the Effect of an Additional Severe Blood Loss: A Radiographic and Biomechanical Murine Study
    MDPI AG ; 2023
    In:  Bioengineering Vol. 10, No. 1 ( 2023-01-05), p. 70-
    Details
    In: Bioengineering, MDPI AG, Vol. 10, No. 1 ( 2023-01-05), p. 70-
    Abstract: Femoral fractures and severe bleeding frequently occur in old patients showing a delayed healing. As there are no studies investigating the combined effect of high age and severe blood loss on fracture healing, this was examined radiographically and biomechanically in this study. Therefore, young and old male mice were randomly assigned to three operation groups. In the fracture group (Fx), external fixator and osteotomy were applied to the femur. The combined trauma group (THFx) additionally received a pressure-controlled hemorrhage. Sham animals were only implanted with arterial catheter and external fixator. Sacrifice was performed after three weeks and bone healing was evaluated radiologically via µCT, as well as biomechanically using a three-point bending test. A decreased share of callus/total bone volume was observed in old mice with blood loss compared to old Fx. Hemorrhagic shock also reduced the trabecular number in old mice compared to Fx and young THFx. Moreover, a lower elastic limit in old Sham mice without fracture was revealed. Fracture combined with a high loss of blood further reduced the elastic limit in old mice compared to isolated Fx in old animals. In conclusion, this study showed that severe blood loss has a higher negative effect in old mice compared to young ones.
    Type of Medium: Online Resource
    ISSN: 2306-5354
    URL: Article
    DOI: 10.3390/bioengineering10010070
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2746191-9
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  • 5
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    Characteristics of Mesenchymal Stem Cells Are Independent of Bone Marrow Storage Temperatures
    Hindawi Limited ; 2021
    In:  Stem Cells International Vol. 2021 ( 2021-10-19), p. 1-8
    Details
    In: Stem Cells International, Hindawi Limited, Vol. 2021 ( 2021-10-19), p. 1-8
    Abstract: Mesenchymal stem cells play an important role in regenerative medicine due to their capability of self-renewal and multipotent differentiation. For research or clinical application, bone marrow aspirates are harvested during elective surgeries to isolate MSCs. If an immediate purification of the MSCs is not possible, the bone marrow must be stored. Therefore, the aim of this study was to investigate possible differences of stem cell characteristics regarding the self-renewal capability, the adipogenic, chondrogenic, and osteogenic differentiation, and the expression of surface antigens after different storage conditions of the bone marrow aspirates. Three groups were analysed: the first group was purified immediately after harvesting, the other two groups were processed after they were stored 18 to 24 hours at 22°C (room temperature) or at 4°C. Comparisons between the groups were performed using the Kruskal-Wallis test for nonparametric data. The final results showed no significant difference between the different storage conditions. Therefore, storage of bone marrow aspirates for 18 to 24 hours at room temperature or 4°C is possible without loss of stem cell characteristics.
    Type of Medium: Online Resource
    ISSN: 1687-9678 , 1687-966X
    URL: Article
    DOI: 10.1155/2021/6864988
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2573856-2
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  • 6
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    Online Resource
    Selective Inhibition of IL-6 Trans-Signaling Has No Beneficial Effect on the Posttraumatic Cytokine Release after Multiple Trauma in Mice
    MDPI AG ; 2021
    In:  Life Vol. 11, No. 11 ( 2021-11-17), p. 1252-
    Details
    In: Life, MDPI AG, Vol. 11, No. 11 ( 2021-11-17), p. 1252-
    Abstract: While improvements in pre-hospital and in-hospital care allow more multiple trauma patients to advance to intensive care, the incidence of posttraumatic multiple organ dysfunction syndrome (MODS) is on the rise. Herein, the influence of a selective IL-6 trans-signaling inhibition on posttraumatic cytokine levels was investigated as an approach to prevent MODS caused by a dysbalanced posttraumatic immune reaction. Therefore, the artificial IL-6 trans-signaling inhibitor sgp130Fc was deployed in a murine multiple trauma model (femoral fracture plus bilateral chest trauma). The traumatized mice were treated with sgp130Fc (FP) and compared to untreated mice (WT) and IL-6 receptor knockout mice (RKO), which received the same traumas. The overall trauma mortality was 4.4%. Microscopic pulmonary changes were apparent after multiple trauma and after isolated bilateral chest trauma. Elevated IL-6, MCP-3 and RANTES plasma levels were measured after trauma, indicating a successful induction of a systemic inflammatory reaction. Significantly reduced IL-6 and RANTES plasma levels were visible in RKO compared to WT. Only a little effect was visible in FP compared to WT. Comparable cytokine levels in WT and FP indicate neither a protective nor an adverse effect of sgp130Fc on the cytokine release after femoral fracture and bilateral chest trauma.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    URL: Article
    DOI: 10.3390/life11111252
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662250-6
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  • 7
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    Online Resource
    Impact of age on liver damage, inflammation, and molecular signaling pathways in response to femoral fracture and hemorrhage
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-8-24)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-8-24)
    Abstract: Trauma causes disability and mortality globally, leading to fractures and hemorrhagic shock. This can trigger an irregular inflammatory response that damages remote organs, including liver. Aging increases the susceptibility to dysregulated immune responses following trauma, raising the risk of organ damage, infections, and higher morbidity and mortality in elderly patients. This study investigates how aging affects liver inflammation and damage post-trauma. Methods 24 male C57BL/6J mice were randomly divided into four groups. Twelve young (17-26 weeks) and 12 aged (64-72 weeks) mice were included. Mice further underwent either hemorrhagic shock (trauma/hemorrhage, TH), and femoral fracture (osteotomy) with external fixation (Fx) (THFx, n=6) or sham procedures (n=6). After 24 hours, mice were sacrificed. Liver injury and apoptosis were evaluated using hematoxylin-eosin staining and activated caspase-3 immunostaining. CXCL1 and infiltrating polymorphonuclear leukocytes (PMNL) in the liver were assessed by immunostaining, and concentrations of CXCL1, TNF, IL-1β, and IL-10 in the liver tissue were determined by ELISA. Gene expression of Tnf , Cxcl1 , Il-1β , and Cxcl2 in the liver tissue was determined by qRT-PCR. Finally, western blot was used to determine protein expression levels of IκBα, Akt, and their phosphorylated forms. Results THFx caused liver damage and increased presence of active caspase-3-positive cells compared to the corresponding sham group. THFx aged group had more severe liver injury than the young group. CXCL1 and PMNL levels were significantly higher in both aged groups, and THFx caused a greater increase in CXCL and PMNL levels in aged compared to the young group. Pro-inflammatory TNF and IL-1β levels were elevated in aged groups, further intensified by THFx. Anti-inflammatory IL-10 levels were lower in aged groups. Tnf and Cxcl1 gene expression was enhanced in the aged sham group. Phosphorylation ratio of IκBα was significantly increased in the aged sham group versus young sham group. THFx-induced IκBα phosphorylation in the young group was significantly reduced in the aged THFx group. Akt phosphorylation was significantly reduced in the THFx aged group compared to the THFx young group. Conclusion The findings indicate that aging may lead to increased vulnerability to liver injury and inflammation following trauma due to dysregulated immune responses.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2023.1239145
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 8
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    Online Resource
    Towards the development of osteochondral allografts with reduced immunogenicity
    Elsevier BV ; 2022
    In:  Journal of the Mechanical Behavior of Biomedical Materials Vol. 133 ( 2022-09), p. 105359-
    Details
    In: Journal of the Mechanical Behavior of Biomedical Materials, Elsevier BV, Vol. 133 ( 2022-09), p. 105359-
    Type of Medium: Online Resource
    ISSN: 1751-6161
    URL: Article
    DOI: 10.1016/j.jmbbm.2022.105359
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2378381-3
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  • 9
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    Online Resource
    Severe Hemorrhagic Shock Leads to a Delayed Fracture Healing and Decreased Bone Callus Strength in a Mouse Model
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Clinical Orthopaedics & Related Research Vol. 475, No. 11 ( 2017-11), p. 2783-2794
    Details
    In: Clinical Orthopaedics & Related Research, Ovid Technologies (Wolters Kluwer Health), Vol. 475, No. 11 ( 2017-11), p. 2783-2794
    Type of Medium: Online Resource
    ISSN: 0009-921X
    URL: Article
    DOI: 10.1007/s11999-017-5473-8
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2018318-5
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  • 10
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    Online Resource
    Cytological Effects of Serum Isolated from Polytraumatized Patients on Human Bone Marrow-Derived Mesenchymal Stem Cells
    Hindawi Limited ; 2021
    In:  Stem Cells International Vol. 2021 ( 2021-11-28), p. 1-18
    Details
    In: Stem Cells International, Hindawi Limited, Vol. 2021 ( 2021-11-28), p. 1-18
    Abstract: Due to their immunomodulatory and regenerative capacity, human bone marrow-derived mesenchymal stem cells (hBMSCs) are promising in the treatment of patients suffering from polytrauma. However, few studies look at the effects of sera from polytraumatized patients on hBMSCs. The aim of this study was to explore changes in hBMSC properties in response to serum from polytrauma patients taken at different time points after the trauma incident. For this, sera from 84 patients with polytrauma (collected between 2010 and 2020 in our department) were used. In order to test the differential influence on hBMSC, sera from the 1st (D1), 5th (D5), and 10th day (D10) after polytrauma were pooled, respectively. As a control, sera from three healthy donors (HS), matched with respect to age and gender to the polytrauma group, were collected. Furthermore, hBMSCs from four healthy donors were used in the experiments. The pooled sera of HS, D1, D5, and D10 were analyzed by multicytokine array for pro-/anti-inflammatory cytokines. Furthermore, the influence of the different sera on hBMSCs with respect to cell proliferation, colony forming unit-fibroblast (CFU-F) assay, cell viability, cytotoxicity, cell migration, and osteogenic and chondrogenic differentiation was analyzed. The results showed that D5 serum significantly reduced hBMSC cell proliferation capacity compared with HS and increased the proportion of dead cells compared with D1. However, the frequency of CFU-F was not reduced in polytrauma groups compared with HS, as well as the other parameters. The serological effect of polytrauma on hBMSCs was related to the time after trauma. It is disadvantageous to use BMSCs in polytraumatized patients at least until the fifth day after polytrauma as obvious cytological changes could be found at that time point. However, it is promising to use hBMSCs to treat polytrauma after five days, combined with the concept of “Damage Control Orthopedics” (DCO).
    Type of Medium: Online Resource
    ISSN: 1687-9678 , 1687-966X
    URL: Article
    DOI: 10.1155/2021/2612480
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2573856-2
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