scholarly journals Epoetin Alpha and Epoetin Zeta: A Comparative Study on Stimulation of Angiogenesis and Wound Repair in an Experimental Model of Burn Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Natasha Irrera ◽  
Alessandra Bitto ◽  
Gabriele Pizzino ◽  
Mario Vaccaro ◽  
Francesco Squadrito ◽  
...  
Keyword(s):  
Experimental Model ◽  
Wound Repair ◽  
Wound Closure ◽  
Burn Injury ◽  
Conformational Structure ◽  
Epoetin Zeta ◽  
Epoetin Alpha ◽  
To Receive ◽  
Cdk2 Expression ◽  
Stimulation Of

Deep second-degree burns are characterized by delayed formation of granulation tissue and impaired angiogenesis. Erythropoietin (EPO) is able to stimulate angiogenesis and mitosis, activating vascularization and cell cycle. The aim of our study was to investigate whether two biosimilar recombinant human erythropoietins, EPO-αand EPO-Z, may promote these processes in an experimental model of burn injury. A total of 84 mice were used and a scald burn was produced on the back after shaving, in 80°C water for 10 seconds. Mice were then randomized to receive EPO-α(400 units/kg/day/sc) or EPO-Z (400 units/kg/day/sc) or their vehicle (100 μL/day/sc 0.9% NaCl solution). After 12 days, both EPO-αand EPO-Z increased VEGF protein expression. EPO-αcaused an increased cyclin D1/CDK6 and cyclin E/CDK2 expression compared with vehicle and EPO-Z (p<0.001). Our study showed that EPO-αand EPO-Z accelerated wound closure and angiogenesis; however EPO-αresulted more effectively in achieving complete skin regeneration. Our data suggest that EPO-αand EPO-Z are not biosimilars for the wound healing effects. The higher efficacy of EPO-αmight be likely due to its different conformational structure leading to a more efficient cell proliferation and skin remodelling.

scholarly journals Is a diluted seawater-based solution safe and effective on human nasal epithelium?

2021 ◽  
Author(s):  
Song Huang ◽  
Samuel Constant ◽  
Barbara De Servi ◽  
Marisa Meloni ◽  
Amina Saaid ◽  
...  
Keyword(s):  
Wound Repair ◽  
Wound Closure ◽  
Isotonic Saline ◽  
Nasal Epithelium ◽  
Mucin Secretion ◽  
Nasal Irrigation ◽  
Tissue Integrity ◽  
Human Nasal Epithelium ◽  
Pre Treatment

Abstract Purpose Nasal irrigation is an effective method for alleviating several nasal symptoms and regular seawater-based nasal irrigation is useful for maintaining nasal hygiene which is essential for appropriate functioning of the nose and for preventing airborne particles including some pollutants, pathogens, and allergens from moving further in the respiratory system. However, safety studies on seawater-based nasal irrigation are scarce. In this study, the safety and efficacy of a diluted isotonic seawater solution (Stérimar Nasal Hygiene, SNH) in maintaining nasal homeostasis were evaluated in vitro. Methods Safety was assessed by measuring tissue integrity via transepithelial electrical resistance (TEER). Efficacy was measured by mucociliary clearance (MCC), mucin secretion, and tissue re-epithelization (wound repair) assays. All assays were performed using a 3D reconstituted human nasal epithelium model. Results In SNH-treated tissues, TEER values were statistically significantly lower than the untreated tissues; however, the values were above the tissue integrity limit. SNH treatment significantly increased MCC (88 vs. 36 µm/s, p < 0.001) and mucin secretion (1717 vs. 1280 µg/ml, p < 0.001) as compared to untreated cultures. Faster wound closure profile was noted upon pre-SNH treatment as compared to classical isotonic saline solution pre-treatment (90.5 vs. 50.7% wound closure 22 h after wound generation). Conclusion SNH did not compromise the integrity of the nasal epithelium in vitro. Furthermore, SNH was effective for removal of foreign particles through MCC increase and for enhancing wound repair on nasal mucosa.

Transforming growth factor-alpha enhances alveolar epithelial cell repair in a new in vitro model

1994 ◽  
Vol 267 (6) ◽  
pp. L728-L738 ◽  
Author(s):  
F. Kheradmand ◽  
H. G. Folkesson ◽  
L. Shum ◽  
R. Derynk ◽  
R. Pytela ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cell ◽  
Wound Repair ◽  
Wound Closure ◽  
Transforming Growth Factor ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial ◽  
Factor Alpha ◽  
Vitro Model

Alveolar epithelial type II cells are essential for regenerating an intact alveolar barrier after destruction of type I cells in vivo. The first objective of these experimental studies was to develop an in vitro model to quantify alveolar epithelial cell wound repair. The second objective was to investigate mechanisms of alveolar epithelial cell wound healing by studying the effects of serum and transforming growth factor-alpha (TGF-alpha) on wound closure. Primary cultures of rat alveolar type II cells were prepared by standard methods and grown to form confluent monolayers in 48 h. Then a wound was made by denuding an area (mean initial area of 2.1 +/- 0.6 mm2) of the monolayer. Re-epithelialization of the denuded area over time in the presence or absence of serum was measured using quantitative measurements from time-lapse video microscopy. The half time of wound healing was significantly enhanced in the presence of serum compared with serum-free conditions (2.4 +/- 0.2 vs. 17.4 +/- 0.8 h, P < 0.001). We then tested the hypothesis that TGF-alpha is an important growth factor for stimulating wound repair of alveolar epithelial cells. Exogenous addition of TGF-alpha in serum-free medium resulted in a significantly more rapid wound closure, and, furthermore, the addition of a monoclonal antibody to TGF-alpha in the presence of serum significantly decreased fourfold the rate of wound closure. Measurement of internuclear cell distance confirmed that both cell motility and cell spreading were responsible for closure of the wound. These data demonstrate that 1) the mechanisms of alveolar cell repair can be studied in vitro and that 2) TGF-alpha is a potent growth factor that enhances in vitro alveolar epithelial cell wound closure.

Anterior and Posterior Oral Cavity Responsive Neurons Are Differentially Distributed Among Parabrachial Subnuclei in Rat

1997 ◽  
Vol 78 (2) ◽  
pp. 920-938 ◽  
Author(s):  
Christopher B. Halsell ◽  
Susan P. Travers
Keyword(s):  
Oral Cavity ◽  
Taste Receptor ◽  
Hierarchical Cluster ◽  
Response Rates ◽  
Differential Sensitivity ◽  
Response Profiles ◽  
To Receive ◽  
Gustatory Neurons ◽  
Comparable Population ◽  
Stimulation Of

Halsell, Christopher B. and Susan P. Travers. Anterior and posterior oral cavity responsive neurons are differentially distributed among parabrachial subnuclei in rat. J. Neurophysiol. 78: 920–938, 1997. The responses of single parabrachial nucleus (PBN) neurons were recorded extracellularly to characterize their sensitivity to stimulation of individual gustatory receptor subpopulations (G neurons, n = 75) or mechanical stimulation of defined oral regions (M neurons, n = 54) then localized to morphologically defined PBN subdivisions. Convergence from separate oral regions onto single neurons occurred frequently for both G and M neurons, but converging influences were more potent when they arose from nearby locations confined to the anterior (AO) or posterior oral cavity (PO). A greater number of G neurons responded optimally to stimulation of AO than to PO receptor subpopulations, and these AO-best G neurons had higher spontaneous and evoked response rates but were less likely to receive convergent input than PO-best G neurons. In contrast, proportions, response rates, and convergence patterns of AO- and PO-best M neurons were more comparable. The differential sensitivity of taste receptor subpopulations was reflected in PBN responses. AO stimulation with NaCl elicited larger responses than PO stimulation; the converse was true for QHCl stimulation. Within the AO, NaCl elicited a larger response when applied to the anterior tongue than to the nasoincisor duct. Hierarchical cluster analysis of chemosensitive response profiles suggested two groups of PBN G neurons. One group was composed of neurons optimally responsive to NaCl (N cluster); the other to HCl (H cluster). Most N- and H-cluster neurons were AO-best. Although they were more heterogenous, all but one of the remaining G neurons were unique in responding best or second-best to quinine and so were designated as quinine sensitive (Q+). Twice as many Q+ neurons were PO- compared with AO-best. M neurons were scattered across PBN subdivisions, but G neurons were concentrated in two pairs of subdivisions. The central medial and ventral lateral subdivisions contained both G and M neurons but were dominated by AO-best N-cluster G neurons. The distribution of G neurons in these subdivisions appeared similar to distributions in most previous studies of PBN gustatory neurons. In contrast to earlier studies, however, the external medial and external lateral-inner subdivisions also contained G neurons, intermingled with a comparable population of M neurons. Unlike cells in the central medial and ventral lateral subnuclei, nearly every neuron in the external subnuclei was PO best, and only one was an N-cluster cell. In conclusion, the present study supports a functional distinction between sensory input from the AO and PO at the pontine level, which may represent an organizing principle throughout the gustatory neuraxis. Furthermore, two morphologically distinct pontine regions containing orosensory neurons are described.

scholarly journals Enhancement of wound closure in diabetic mice by ex vivo expanded cord blood CD34+ cells

2013 ◽  
Vol 18 (2) ◽  
Author(s):  
Kamonnaree Chotinantakul ◽  
Chavaboon Dechsukhum ◽  
Duangnapa Dejjuy ◽  
Wilairat Leeanansaksiri
Keyword(s):  
Cord Blood ◽  
Wound Repair ◽  
Wound Closure ◽  
Ex Vivo ◽  
Autologous Transplantation ◽  
Diabetic Patients ◽  
Isolated Cells ◽  
Cytokine Cocktail ◽  
Cd34 Cells ◽  
Cord Blood Cd34

AbstractDiabetes can impair wound closure, which can give rise to major clinical problems. Most treatments for wound repair in diabetes remain ineffective. This study aimed to investigate the influence on wound closure of treatments using expanded human cord blood CD34+ cells (CB-CD34+ cells), freshly isolated CB-CD34+ cells and a cytokine cocktail. The test subjects were mice with streptozotocin-induced diabetes. Wounds treated with fresh CB-CD34+ cells showed more rapid repair than mice given the PBS control. Injection of expanded CB-CD34+ cells improved wound closure significantly, whereas the injection of the cytokine cocktail alone did not improve wound repair. The results also demonstrated a significant decrease in epithelial gaps and advanced re-epithelialization over the wound bed area after treatment with either expanded CB-CD34+ cells or freshly isolated cells compared with the control. In addition, treatments with both CB-CD34+ cells and the cytokine cocktail were shown to promote recruitment of CD31+-endothelial cells in the wounds. Both the CB-CD34+ cell population and the cytokine treatments also enhanced the recruitment of CD68-positive cells in the early stages (day 3) of treatment compared with PBS control, although the degree of this enhancement was found to decline in the later stages (day 9). These results demonstrated that expanded CB-CD34+ cells or freshly isolated CB-CD34+ cells could accelerate wound repair by increasing the recruitment of macrophages and capillaries and the reepithelialization over the wound bed area. Our data suggest an effective role in wound closure for both ex vivo expanded CB-CD34+ cells and freshly isolated cells, and these may serve as therapeutic options for wound treatment for diabetic patients. Wound closure acceleration by expanded CB-CD34+ cells also breaks the insufficient quantity obstacle of stem cells per unit of cord blood and other stem cell sources, which indicates a broader potential for autologous transplantation.

Fronto-striatal network activation leads to less fatigue in multiple sclerosis

2017 ◽  
Vol 24 (9) ◽  
pp. 1174-1182 ◽  
Author(s):  
Ekaterina Dobryakova ◽  
Hanneke E Hulst ◽  
Angela Spirou ◽  
Nancy D Chiaravalloti ◽  
Helen M Genova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Goal Attainment ◽  
Functional Neuroimaging ◽  
Network Activation ◽  
Healthy Control ◽  
Neuroimaging Study ◽  
To Receive ◽  
Monetary Gain ◽  
Healthy Participants ◽  
Stimulation Of

Background: The fronto-striatal network has been implicated in both fatigue, a common multiple sclerosis (MS) symptom, and goal attainment, which has been shown to reduce fatigue in healthy individuals. Objectives: To investigate whether stimulation of the fronto-striatal network through goal attainment (potential monetary gain) leads to fatigue reduction in MS and healthy control (HC) participants. Methods: In all, 14 healthy and 19 MS participants performed a gambling task during functional magnetic resonance imaging (fMRI). Participants were presented with an opportunity to receive monetary reward during the outcome condition of the task but not during the no outcome condition. Self-reported fatigue measures were obtained after each condition and outside of the scanner. Structural alterations were also examined. Results: A significant decrease in fatigue was observed after the outcome condition compared to the no outcome condition in both groups. Significantly greater activation was observed in the ventral striatum in association with the outcome condition compared to the no outcome condition in both groups. Ventromedial prefrontal cortex showed significantly greater activation during the no outcome condition compared to the outcome condition with greater difference between conditions in the HC group. Conclusion: This is the first functional neuroimaging study showing that stimulation of the fronto-striatal network through goal attainment leads to decreased on-task fatigue in MS and healthy participants.

Management of Acute Wounds

2019 ◽  
Author(s):  
Lee D. Faucher ◽  
Angela L. Gibson
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Wound Closure ◽  
Wound Care ◽  
Connective Tissue Diseases ◽  
Skin Grafting ◽  
Adjunctive Treatment ◽  
Local Trauma ◽  
Life Threatening ◽  
Acute Wound

Acute wounds are the result of local trauma and may be associated with severe life-threatening injuries. All patients with acute wounds should be assessed for comorbidities such as malnutrition, diabetes, peripheral vascular disease, neuropathy, obesity, immune deficiency, autoimmune disorders, connective tissue diseases, coagulopathy, hepatic dysfunction, malignancy, smoking practices, medication use that could interfere with healing, and allergies. The authors address the key considerations in management of the acute wound, including anesthesia, location of wound repair (e.g. operating room or emergency department), hemostasis, irrigation, débridement, closure materials, timing and methods of closure, adjunctive treatment (e.g. tetanus and rabies prophylaxis, antibiotics, and nutritional supplementation), appropriate closure methods for specific wound types, dressings, postoperative wound care, and potential disturbances of wound healing.  This review contains 11 figures, 31 tables, and 92 references. Keywords: wound, wound infection, burns, suture, staple, wound closure, wound healing, dehiscence, skin grafting

scholarly journals Agonist binding to β-adrenergic receptors on human airway epithelial cells inhibits migration and wound repair

2015 ◽  
Vol 309 (12) ◽  
pp. C847-C855 ◽  
Author(s):  
Elizabeth R. Peitzman ◽  
Nathan A. Zaidman ◽  
Peter J. Maniak ◽  
Scott M. O'Grady
Keyword(s):  
Epithelial Cells ◽  
Protein Phosphatase ◽  
Adrenergic Receptors ◽  
Wound Repair ◽  
Wound Closure ◽  
Basal Membrane ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Phosphatase 2A ◽  
Β Adrenergic Receptors

Human airway epithelial cells express β-adrenergic receptors (β-ARs), which regulate mucociliary clearance by stimulating transepithelial anion transport and ciliary beat frequency. Previous studies using airway epithelial cells showed that stimulation with isoproterenol increased cell migration and wound repair by a cAMP-dependent mechanism. In the present study, impedance-sensing arrays were used to measure cell migration and epithelial restitution following wounding of confluent normal human bronchial epithelial (NHBE) and Calu-3 cells by electroporation. Stimulation with epinephrine or the β2-AR-selective agonist salbutamol significantly delayed wound closure and reduced the mean surface area of lamellipodia protruding into the wound. Treatment with the β-AR bias agonist carvedilol or isoetharine also produced a delay in epithelial restitution similar in magnitude to epinephrine and salbutamol. Measurements of extracellular signal-regulated kinase phosphorylation following salbutamol or carvedilol stimulation showed no significant change in the level of phosphorylation compared with untreated control cells. However, inhibition of protein phosphatase 2A activity completely blocked the delay in wound closure produced by β-AR agonists. In Calu-3 cells, where CFTR expression was inhibited by RNAi, salbutamol did not inhibit wound repair, suggesting that β-AR agonist stimulation and loss of CFTR function share a common pathway leading to inhibition of epithelial repair. Confocal images of the basal membrane of Calu-3 cells labeled with anti-β1-integrin (clone HUTS-4) antibody showed that treatment with epinephrine or carvedilol reduced the level of activated integrin in the membrane. These findings suggest that treatment with β-AR agonists delays airway epithelial repair by a G protein- and cAMP-independent mechanism involving protein phosphatase 2A and a reduction in β1-integrin activation in the basal membrane.

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