scholarly journals Clostridium Collagenase Impact on Zone of Stasis Stabilization and Transition to Healthy Tissue in Burns

2021 ◽  
Vol 22 (16) ◽  
pp. 8643
Author(s):  
Rosanne E. Frederick ◽  
Robert Bearden ◽  
Aleksa Jovanovic ◽  
Nasreen Jacobson ◽  
Rajiv Sood ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cellular Response ◽  
Burn Injury ◽  
Macrophage Polarization ◽  
Clinical Results ◽  
Burn Wounds ◽  
Inflammatory Microenvironment ◽  
Collagenase Treatment ◽  
Dermal Collagen ◽  
The Impact

Clostridium collagenase has provided superior clinical results in achieving digestion of immediate and accumulating devitalized collagen tissue. Recent studies suggest that debridement via Clostridium collagenase modulates a cellular response to foster an anti-inflammatory microenvironment milieu, allowing for a more coordinated healing response. In an effort to better understand its role in burn wounds, we evaluated Clostridium collagenase’s ability to effectively minimize burn progression using the classic burn comb model in pigs. Following burn injury, wounds were treated with Clostridium collagenase or control vehicle daily and biopsied at various time points. Biopsies were evaluated for factors associated with progressing necrosis as well as inflammatory response associated with treatment. Data presented herein showed that Clostridium collagenase treatment prevented destruction of dermal collagen. Additionally, treatment with collagenase reduced necrosis (HMGB1) and apoptosis (CC3a) early in burn injuries, allowing for increased infiltration of cells and protecting tissue from conversion. Furthermore, early epidermal separation and epidermal loss with a clearly defined basement membrane was observed in the treated wounds. We also show that collagenase treatment provided an early and improved inflammatory response followed by faster resolution in neutrophils. In assessing the inflammatory response, collagenase-treated wounds exhibited significantly greater neutrophil influx at day 1, with macrophage recruitment throughout days 2 and 4. In further evaluation, macrophage polarization to MHC II and vascular network maintenance were significantly increased in collagenase-treated wounds, indicative of a pro-resolving macrophage environment. Taken together, these data validate the impact of clostridial collagenases in the pathophysiology of burn wounds and that they complement patient outcomes in the clinical scenario.

EP.WE.629The effect of different anaesthetic agents in postsurgical inflammatory response in thoracic surgery: a systematic review

2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Julian Aquilina ◽  
Georgios Geropoulos ◽  
Ioannis Loufopoulos ◽  
Anaya Gupte ◽  
Sofoklis Mitsos ◽  
...  
Keyword(s):  
Systematic Review ◽  
Inflammatory Response ◽  
Thoracic Surgery ◽  
Cellular Response ◽  
Interferon Γ ◽  
Anaesthetic Agents ◽  
Systemic Inflammatory Reaction ◽  
Immunological Effects ◽  
Immune Changes ◽  
The Impact

Abstract Aims Post-operative systemic inflammatory reaction is part of the stress response caused by major thoracic surgery. Different anaesthetic agents used affect different immunological phenomena. This systematic review evaluates the impact of anaesthetic agents on the immunological profile and the associated clinical significance. Methods A systematic review of MEDLINE, EMBASE and Cohrane databases to explore how different anaesthetic agents affect post-operative inflammatory response. Results A total of nine studies were included in our analysis. Peri-operative use of dexmedetomidine, propofol, sevoflurane, isoflurane, ropivacaine, sufentanil, naloxone and clonidine were compared, based on their effect on the systemic release of inflammatory markers. Variance on the levels of the circulating inflammatory molecules such as interleukins, interferon-γ, tumor necrosis factor a and on the cellular response including natural killer, CD4 and CD8 T cells, were observed among different anaesthetic agents. Conclusions Inflammation improves immunity and regenerative cell recruitment, however excessive responses can lead to delayed wound healing, organ dysfunction and increased morbidity and mortality. There is still uncertainty regarding the role of immune changes on clinical outcomes of patients undergoing thoracic surgery, and more research is needed to explore other immunological effects related to anaesthetic agents.

scholarly journals Harmine Alleviates Titanium Particle-Induced Inflammatory Bone Destruction by Immunomodulatory Effect on the Macrophage Polarization and Subsequent Osteogenic Differentiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Liangliang Wang ◽  
Qing Wang ◽  
Wei Wang ◽  
Gaoran Ge ◽  
Nanwei Xu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Osteogenic Differentiation ◽  
Macrophage Polarization ◽  
Polarization State ◽  
Bone Destruction ◽  
Wear Particle ◽  
Central Nervous Systems ◽  
The Impact

Peri-prosthetic osteolysis (PPO) and following aseptic loosening are regarded as the prime reasons for implant failure after joint replacement. Increasing evidence indicated that wear-debris-irritated inflammatory response and macrophage polarization state play essential roles in this osteolytic process. Harmine, a β-carboline alkaloid primitively extracted from the Peganum harmala seeds, has been reported to have various pharmacological effects on monoamine oxidase action, insulin intake, vasodilatation and central nervous systems. However, the impact of harmine on debris-induced osteolysis has not been demonstrated, and whether harmine participates in regulating macrophage polarization and subsequent osteogenic differentiation in particle-irritated osteolysis remains unknown. In the present study, we investigated the effect of harmine on titanium (Ti) particle-induced osteolysis in vivo and in vitro. The results suggested harmine notably alleviated Ti particle-induced bone resorption in a murine PPO model. Harmine was also found to suppress the particle-induced inflammatory response and shift the polarization of macrophages from M1 phenotypes to M2 phenotypes in vivo and in vitro, which improved anti-inflammatory and bone-related cytokines levels. In the conditioned medium from Ti particle-stimulated murine macrophage RAW264.7 cells treated with harmine, the osteoblast differentiation ability of mouse pre-osteoblastic MC3T3-E1 cells was greatly increased. And we also provided evidences that the immunomodulatory capacity of harmine might be attributed to the inhibition of the c-Jun N-terminal kinase (JNK) in wear particle-treated macrophages. All the results strongly show that harmine might be a promising therapeutic agent to treat PPO.

The Learning Curve in Arthroscopic ACL Reconstruction. The impact on the Surgical Time and Postoperative Clinical Results

2018 ◽  
Vol 69 (10) ◽  
pp. 2874-2876
Author(s):  
Teodor Negru ◽  
Stefan Mogos ◽  
Ioan Cristian Stoica
Keyword(s):  
Anterior Cruciate Ligament ◽  
Learning Curve ◽  
Clinical Outcomes ◽  
Positive Impact ◽  
Cruciate Ligament ◽  
Clinical Results ◽  
Single Bundle ◽  
Surgical Time ◽  
Anterior Cruciate ◽  
The Impact

Rupture of the anterior cruciate ligament (ACL) is a common injury. The objective of the current study was to evaluate if the learning curve has an impact on surgical time and postoperative clinical outcomes after anatomic single-bundle anterior cruciate ligament reconstruction (ACLR) using an outside-in tunnel drilling hamstrings technique. The learning curve has a positive impact on surgical time but has no influence on postoperative clinical outcomes at short time follow-up.

scholarly journals Uremic toxin indoxyl sulfate promotes proinflammatory macrophage activation by regulation of β-catenin and YAP pathways

2021 ◽  
Author(s):  
Ying Li ◽  
Jing Yan ◽  
Minjia Wang ◽  
Jing Lv ◽  
Fei Yan ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Inflammatory Response ◽  
Macrophage Polarization ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Lps Challenge ◽  
Hla Dr ◽  
M1 Macrophage

AbstractEvidence has been shown that indoxyl sulfate (IS) could impair kidney and cardiac functions. Moreover, macrophage polarization played important roles in chronic kidney disease and cardiovascular disease. IS acts as a nephron-vascular toxin, whereas its effect on macrophage polarization during inflammation is still not fully elucidated. In this study, we aimed to investigate the effect of IS on macrophage polarization during lipopolysaccharide (LPS) challenge. THP-1 monocytes were incubated with phorbol 12-myristate-13-acetate (PMA) to differentiate into macrophages, and then incubated with LPS and IS for 24 h. ELISA was used to detect the levels of TNFα, IL-6, IL-1β in THP-1-derived macrophages. Western blot assay was used to detect the levels of arginase1 and iNOS in THP-1-derived macrophages. Percentages of HLA-DR-positive cells (M1 macrophages) and CD206-positive cells (M2 macrophages) were detected by flow cytometry. IS markedly increased the production of the pro-inflammatory factors TNFα, IL-6, IL-1β in LPS-stimulated THP-1-derived macrophages. In addition, IS induced M1 macrophage polarization in response to LPS, as evidenced by the increased expression of iNOS and the increased proportion of HLA-DR+ macrophages. Moreover, IS downregulated the level of β-catenin, and upregulated the level of YAP in LPS-stimulated macrophages. Activating β-catenin signaling or inhibiting YAP signaling suppressed the IS-induced inflammatory response in LPS-stimulated macrophages by inhibiting M1 polarization. IS induced M1 macrophage polarization in LPS-stimulated macrophages via inhibiting β-catenin and activating YAP signaling. In addition, this study provided evidences that activation of β-catenin or inhibition of YAP could alleviate IS-induced inflammatory response in LPS-stimulated macrophages. This finding may contribute to the understanding of immune dysfunction observed in chronic kidney disease and cardiovascular disease.

11 Vitamin D Deficiency on Admission and the Association with Length of Stay in Patients with Thermal Injury: A Multi-center Analysis

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S13-S14
Author(s):  
Sarah Zavala ◽  
Kate Pape ◽  
Todd A Walroth ◽  
Melissa A Reger ◽  
Katelyn Garner ◽  
...  
Keyword(s):  
Vitamin D ◽  
Length Of Stay ◽  
Vitamin D Deficiency ◽  
Burn Injury ◽  
Total Body Surface Area ◽  
Inhalation Injury ◽  
Hospital Length Of Stay ◽  
Burn Patients ◽  
Comfort Care ◽  
The Impact

Abstract Introduction In burn patients, vitamin D deficiency has been associated with increased incidence of sepsis. The objective of this study was to assess the impact of vitamin D deficiency in adult burn patients on hospital length of stay (LOS). Methods This was a multi-center retrospective study of adult patients at 7 burn centers admitted between January 1, 2016 and July 25, 2019 who had a 25-hydroxyvitamin D (25OHD) concentration drawn within the first 7 days of injury. Patients were excluded if admitted for a non-burn injury, total body surface area (TBSA) burn less than 5%, pregnant, incarcerated, or made comfort care or expired within 48 hours of admission. The primary endpoint was to compare hospital LOS between burn patients with vitamin D deficiency (defined as 25OHD < 20 ng/mL) and sufficiency (25OHD ≥ 20 ng/mL). Secondary endpoints include in-hospital mortality, ventilator-free days of the first 28, renal replacement therapy (RRT), length of ICU stay, and days requiring vasopressors. Additional data collected included demographics, Charlson Comorbidity Index, injury characteristics, form of vitamin D received (ergocalciferol or cholecalciferol) and dosing during admission, timing of vitamin D initiation, and form of nutrition provided. Dichotomous variables were compared via Chi-square test. Continuous data were compared via student t-test or Mann-Whitney U test. Univariable linear regression was utilized to identify variables associated with LOS (p < 0.05) to analyze further. Cox Proportional Hazard Model was utilized to analyze association with LOS, while censoring for death, and controlling for TBSA, age, presence of inhalation injury, and potential for a center effect. Results Of 1,147 patients screened, 412 were included. Fifty-seven percent were vitamin D deficient. Patients with vitamin D deficiency had longer LOS (18.0 vs 12.0 days, p < 0.001), acute kidney injury (AKI) requiring RRT (7.3 vs 1.7%, p = 0.009), more days requiring vasopressors (mean 1.24 vs 0.58 days, p = 0.008), and fewer ventilator free days of the first 28 days (mean 22.9 vs 25.1, p < 0.001). Univariable analysis identified burn center, AKI, TBSA, inhalation injury, admission concentration, days until concentration drawn, days until initiating supplementation, and dose as significantly associated with LOS. After controlling for center, TBSA, age, and inhalation injury, the best fit model included only deficiency and days until vitamin D initiation. Conclusions Patients with thermal injuries and vitamin D deficiency on admission have increased length of stay and worsened clinical outcomes as compared to patients with sufficient vitamin D concentrations.

scholarly journals Effect of Lipopolysaccharides (LPS) and Lipoteichoic acid (LTA) on the Inflammatory Response in Rumen Epithelial Cells (REC) and the Impact of LPS on Claw Explants

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2058
Author(s):  
Nicole Reisinger ◽  
Dominik Wendner ◽  
Nora Schauerhuber ◽  
Elisabeth Mayer
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Structural Integrity ◽  
Animal Health ◽  
Lipoteichoic Acid ◽  
Local Inflammatory Response ◽  
Tissue Integrity ◽  
Separation Force ◽  
The Impact ◽  
Rumen Epithelial Cells

Endotoxins play a crucial role in ruminant health due to their deleterious effects on animal health. The study aimed to evaluate whether LPS and LTA can induce an inflammatory response in rumen epithelial cells. For this purpose, epithelial cells isolated from rumen tissue (RECs) were stimulated with LPS and LTA for 1, 2, 4, and 24 h. Thereafter, the expression of selected genes of the LPS and LTA pathway and inflammatory response were evaluated. Furthermore, it was assessed whether LPS affects inflammatory response and structural integrity of claw explants. Therefore, claw explants were incubated with LPS for 4 h to assess the expression of selected genes and for 24 h to evaluate tissue integrity via separation force. LPS strongly affected the expression of genes related to inflammation (NFkB, TNF-α, IL1B, IL6, CXCL8, MMP9) in RECs. LTA induced a delayed and weaker inflammatory response than LPS. In claw explants, LPS affected tissue integrity, as there was a concentration-dependent decrease of separation force. Incubation time had a strong effect on inflammatory genes in claw explants. Our data suggest that endotoxins can induce a local inflammatory response in the rumen epithelium. Furthermore, translocation of LPS might negatively impact claw health.

scholarly journals Pro-Inflammatory Microenvironment Modulates the Transfer of Mutated TP53 Mediated by Tumor Exosomes

2021 ◽  
Vol 22 (12) ◽  
pp. 6258
Author(s):  
Rossana Domenis ◽  
Adriana Cifù ◽  
Catia Mio ◽  
Martina Fabris ◽  
Francesco Curcio
Keyword(s):  
Cancer Progression ◽  
Rare Event ◽  
Tp53 Gene ◽  
Mrna Levels ◽  
Inflammatory Microenvironment ◽  
Hepatic Cells ◽  
Mutational Status ◽  
Sw480 Cells ◽  
Tumor Exosomes ◽  
The Impact

Exosomes released from tumor cells are instrumental in shaping the local tumor microenvironment to allow cancer progression. Recently, it has been shown that tumor exosomes carry large fragments of dsDNA, which may reflect the mutational status of parental cells. Although it has been described that a stressful microenvironment can influence exosomal cargo, the effects on DNA packing and its transfer into recipient cells have yet to be investigated. Here, we report that exosomes derived from SW480 (human colorectal adenocarcinoma cell line) cells can carry dsDNA fragments containing the entire coding sequence of both TP53 and KRAS genes, harboring the SW480-related TP53 c.818G > A and KRAS c.35G > T typical mutations. We also report the following: that cell stimulation with lipopolysaccharides (LPS) promotes the selective packaging of the TP53 gene, but not the KRAS gene; that exosomes secreted by SW480 cells efficiently transfer the mutated sequences into normal CCD841-CoN colon epithelial and THLE-2 hepatic cells; that this mechanism is more efficient when the cells had been previously incubated with pro-inflammatory cytokines; that the TP53 gene appears actively transcribed in both recipient cells; and that mutated mRNA levels are not influenced by cytokine treatment. Our data strongly suggest that pro-inflammatory stimulation promotes the horizontal transfer of an oncogene by exosomes, although this remains a rare event. Further studies are needed to assess the impact of the oncogenic transfer by exosomes in malignant transformation and its role in tumor progression.

scholarly journals Spinal Cord Injury Increases Pro-inflammatory Cytokine Expression in Kidney at Acute and Sub-chronic Stages

Inflammation ◽  
2021 ◽  
Author(s):  
Shangrila Parvin ◽  
Clintoria R. Williams ◽  
Simone A. Jarrett ◽  
Sandra M. Garraway
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Inflammatory Cytokine ◽  
Cardiovascular Health ◽  
Mrna Levels ◽  
Post Injury ◽  
Cord Injury ◽  
And Function ◽  
The Impact

Abstract— Accumulating evidence supports that spinal cord injury (SCI) produces robust inflammatory plasticity. We previously showed that the pro-inflammatory cytokine tumor necrosis factor (TNF)α is increased in the spinal cord after SCI. SCI also induces a systemic inflammatory response that can impact peripheral organ functions. The kidney plays an important role in maintaining cardiovascular health. However, SCI-induced inflammatory response in the kidney and the subsequent effect on renal function have not been well characterized. This study investigated the impact of high and low thoracic (T) SCI on C-fos, TNFα, interleukin (IL)-1β, and IL-6 expression in the kidney at acute and sub-chronic timepoints. Adult C57BL/6 mice received a moderate contusion SCI or sham procedures at T4 or T10. Uninjured mice served as naïve controls. mRNA levels of the proinflammatory cytokines IL-1β, IL-6, TNFα, and C-fos, and TNFα and C-fos protein expression were assessed in the kidney and spinal cord 1 day and 14 days post-injury. The mRNA levels of all targets were robustly increased in the kidney and spinal cord, 1 day after both injuries. Whereas IL-6 and TNFα remained elevated in the spinal cord at 14 days after SCI, C-fos, IL-6, and TNFα levels were sustained in the kidney only after T10 SCI. TNFα protein was significantly upregulated in the kidney 1 day after both T4 and T10 SCI. Overall, these results clearly demonstrate that SCI induces robust systemic inflammation that extends to the kidney. Hence, the presence of renal inflammation can substantially impact renal pathophysiology and function after SCI.

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