scholarly journals Dapsone therapy for the acute inflammatory phase of ocular pemphigoid.

1992 ◽  
Vol 76 (6) ◽  
pp. 332-335 ◽  
Author(s):  
A. I. Fern ◽  
J. L. Jay ◽  
H. Young ◽  
R. MacKie
Keyword(s):  
Inflammatory Phase ◽  
Ocular Pemphigoid

PHENOTYPIC HETEROGENEITY OF CARDIAC MACROPHAGES DURING WOUND HEALING FOLLOWING MYOCARDIAL INFARCTION: PERSPECTIVES IN CLINICAL RESEARCH

2018 ◽  
Vol 33 (2) ◽  
pp. 70-76 ◽  
Author(s):  
A. E. Gombozhapova ◽  
Yu. V. Rogovskaya ◽  
M. S. Rebenkova ◽  
J. G. Kzhyshkowska ◽  
V. V. Ryabov
Keyword(s):  
Myocardial Infarction ◽  
Wound Healing ◽  
Cardiac Remodeling ◽  
Phenotypic Heterogeneity ◽  
Macrophage Infiltration ◽  
Myocardial Regeneration ◽  
Control Group ◽  
M2 Macrophage ◽  
Inflammatory Phase ◽  
Regenerative Phase

Purpose. Myocardial regeneration is one of the most ambitious goals in prevention of adverse cardiac remodeling. Macrophages play a key role in transition from inflammatory to regenerative phase during wound healing following myocardial infarction (MI). We have accumulated data on macrophage properties ex vivo and in cell culture. However, there is no clear information about phenotypic heterogeneity of cardiac macrophages in patients with MI. The purpose of the project was to assess cardiac macrophage infiltration during wound healing following myocardial infarction in clinical settings taking into consideration experimental knowledge.Material and Methods. The study included 41 patients with fatal MI type 1. In addition to routine analysis, macrophages infiltration was assessed by immunohistochemistry. We used CD68 as a marker for the cells of the macrophage lineage, while CD163, CD206, and stabilin-1 were considered as M2 macrophage biomarkers. Nine patients who died from noncardiovascular causes comprised the control group.Results. The intensity of cardiac macrophage infiltration was higher during the regenerative phase than during the inflammatory phase. Results of immunohistochemical analysis demonstrated the presence of phenotypic heterogeneity of cardiac macrophages in patients with MI. We noticed that numbers of CD68+, CD163+, CD206+, and stabilin-1+ macrophages depended on MI phase.Conclusion. Our study supports prospects for implementation of macrophage phenotyping in clinic practice. Improved understanding of phenotypic heterogeneity might become the basis of a method to predict adverse cardiac remodeling and the first step in developing myocardial regeneration target therapy.

Treatment Strategies Against Diabetic Foot Ulcer: Success so far and Road Ahead

2020 ◽  
Vol 16 ◽  
Author(s):  
Ankit Awasthi ◽  
Sachin Kumar Singh ◽  
Bimlesh Kumar ◽  
Monica Gulati ◽  
Rajesh Kumar ◽  
...  
Keyword(s):  
Lower Limb ◽  
Diabetic Foot ◽  
Treatment Strategies ◽  
Foot Ulcer ◽  
Diabetic Foot Ulcer ◽  
Arterial Disease ◽  
Current Status ◽  
Limb Amputation ◽  
Bibliographic Databases ◽  
Inflammatory Phase

Background: Diabetic foot ulcer (DFU) is one of the leading complications of type-2 diabetes mellitus. It isassociated with neuropathy and peripheral arterial disease of the lower limb in patients with diabetes. Basically, there are four stages of wound healing namely hemostasis phase, inflammatory phase, proliferative phase and maturation phase. In case of DFU, all these stages are disturbed which lead to delay in healing and consequently to lower limb amputation. Traditionally the dosage forms like tablets, creams, ointments, gels and capsules have been used for the treatment of diabetic foot ulcer from many years. Introduction: In this review the global prevalence as well as etiopathogenesis related to diabetic foot ulcer has been discussed. Potential role of various synthetic and herbal drugs as well as their conventional dosage form for the effective management of diabetes foot ulcer has been highlighted. Methods: Structured search of bibliographic databases for previously published peer-reviewed research papers was explored and data was culminated in terms of various approaches that are used for the treatment of diabetic foot ulcer. Results: About 142 papers including both, research and review articles, were included in this review in order to produce a comprehensive as well as readily understandable article. A series of herbal and synthetic drugs have been discussed along with their current status of treatment in terms of dose and mechanism of action. Conclusion: DFU has become one of the most common complications in patients having more than ten years of diabetes. Hence, understanding the root cause and its successful treatment is a big challenge because it depends upon multiple factors such as judicious selection of drug as well as proper control of blood sugar level. Most of the drugs that have been used so far either belong to the category of antibiotics, antihyperglycaemics or, they have been repositioned. Moreover, in clinical practice, much focus has been given towards dressings that have been used to cover the ulcer. The complete treatment of DFU is still a farfetched dream to be achieved and it is expected that a combination therapy of herbal and synthetic drug with multiple treatment pathway could be able to overcome the disease.

scholarly journals Recent advances in understanding NRF2 as a druggable target: development of pro-electrophilic and non-covalent NRF2 activators to overcome systemic side effects of electrophilic drugs like dimethyl fumarate

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2138 ◽  
Author(s):  
Takumi Satoh ◽  
Stuart Lipton
Keyword(s):  
Side Effects ◽  
Specific Interaction ◽  
Dimethyl Fumarate ◽  
Carnosic Acid ◽  
European Medicines Agency ◽  
Related Factor ◽  
Inflammatory Phase ◽  
First Case ◽  
Systemic Side Effects ◽  
Transcriptional Pathway

Dimethyl fumarate (DMF) is an electrophilic compound previously called BG-12 and marketed under the name Tecfidera®. It was approved in 2013 by the US Food and Drug Administration and the European Medicines Agency for the treatment of relapsing multiple sclerosis. One mechanism of action of DMF is stimulation of the nuclear factor erythroid 2-related factor 2 (NRF2) transcriptional pathway that induces anti-oxidant and anti-inflammatory phase II enzymes to prevent chronic neurodegeneration. However, electrophiles such as DMF also produce severe systemic side effects, in part due to non-specific S-alkylation of cysteine thiols and resulting depletion of glutathione. This mini-review presents the present status and future strategy for NRF2 activators designed to avoid these side effects. Two modes of chemical reaction leading to NRF2 activation are considered here. The first mode is S-alkylation (covalent reaction) of thiols in Kelch-like ECH-associated protein 1 (KEAP1), which interacts with NRF2. The second mechanism involves non-covalent pharmacological inhibition of protein-protein interactions, in particular domain-specific interaction between NRF2 and KEAP1 or other repressor proteins involved in this transcriptional pathway. There have been significant advances in drug development using both of these mechanisms that can potentially avoid the systemic side effects of electrophilic compounds. In the first case concerning covalent reaction with KEAP1, monomethyl fumarate and monoethyl fumarate appear to represent safer derivatives of DMF. In a second approach, pro-electrophilic drugs, such as carnosic acid from the herb Rosmarinus officinalis, can be used as a safe pro-drug of an electrophilic compound. Concerning non-covalent activation of NRF2, drugs are being developed that interfere with the direct interaction of KEAP1-NRF2 or inhibit BTB domain and CNC homolog 1 (BACH1), which is a transcriptional repressor of the promoter where NRF2 binds.

scholarly journals Bv8-Like Toxin from the Frog Venom of Amolops jingdongensis Promotes Wound Healing via the Interleukin-1 Signaling Pathway

Toxins ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 15 ◽  
Author(s):  
Jiajia Chang ◽  
Xiaoqin He ◽  
Jingmei Hu ◽  
Peter Muiruri Kamau ◽  
Ren Lai ◽  
...  
Keyword(s):  
Wound Healing ◽  
Signaling Pathway ◽  
Wide Spectrum ◽  
Interleukin 1 ◽  
Full Thickness ◽  
Mice Model ◽  
Small Peptides ◽  
Newborn Mice ◽  
Proliferative Effect ◽  
Inflammatory Phase

Prokineticins are highly conserved small peptides family expressed in all vertebrates, which contain a wide spectrum of functions. In this study, a prokineticin homolog (Bv8-AJ) isolated from the venom of frog Amolops jingdongensis was fully characterized. Bv8-AJ accelerated full-thickness wounds healing of mice model by promoting the initiation and the termination of inflammatory phase. Moreover, Bv8-AJ exerted strong proliferative effect on fibroblasts and keratinocytes isolated from newborn mice by activating interleukin (IL)-1 production. Our findings indicate that Bv8 is a potent wound healing regulator and may reveal the mechanism of rapid wound-healing in amphibian skins.

scholarly journals Inflammatory M1-like macrophages polarized by NK-4 undergo enhanced phenotypic switching to an anti-inflammatory M2-like phenotype upon co-culture with apoptotic cells

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Keizo Kohno ◽  
Satomi Koya-Miyata ◽  
Akira Harashima ◽  
Takahiko Tsukuda ◽  
Masataka Katakami ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Macrophage Polarization ◽  
Phenotypic Switching ◽  
Apoptotic Cells ◽  
Phenotypic Switch ◽  
Inflammatory Phase ◽  
M1 Macrophage ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Background NK-4 has been used to promote wound healing since the early-1950s; however, the mechanism of action of NK-4 is unknown. In this study, we examined whether NK-4 exerts a regulatory effect on macrophages, which play multiple roles during wound healing from the initial inflammatory phase until the tissue regeneration phase. Results NK-4 treatment of THP-1 macrophages induced morphological features characteristic of classically-activated M1 macrophages, an inflammatory cytokine profile, and increased expression of the M1 macrophage-associated molecules CD38 and CD86. Interestingly, NK-4 augmented TNF-α production by THP-1 macrophages in combination with LPS, Pam3CSK4, or poly(I:C). Furthermore, NK-4 treatment enhanced THP-1 macrophage phagocytosis of latex beads. These results indicate that NK-4 drives macrophage polarization toward an inflammatory M1-like phenotype with increased phagocytic activity. Efferocytosis is a crucial event for resolution of the inflammatory phase in wound healing. NK-4-treated THP-1 macrophages co-cultured with apoptotic Jurkat E6.1 (Apo-J) cells switched from an M1-like phenotype to an M2-like phenotype, as seen in the inverted ratio of TNF-α to IL-10 produced in response to LPS. We identified two separate mechanisms that are involved in this phenotypic switch. First, recognition of phosphatidylserine molecules on Apo-J cells by THP-1 macrophages downregulates TNF-α production. Second, phagocytosis of Apo-J cells by THP-1 macrophages and activation of PI3K/Akt signaling pathway upregulates IL-10 production. Conclusion It is postulated that the phenotypic switch from a proinflammatory M1-like phenotype to an anti-inflammatory M2-like phenotype is dysregulated due to impaired efferocytosis of apoptotic neutrophils at the wound site. Our results demonstrate that NK-4 improves phagocytosis of apoptotic cells, suggesting its potential as a therapeutic strategy to resolve sustained inflammation in chronic wounds.

Flaxseed Protects Against the Inflammatory Phase of Lung Ischemia Reperfusion Injury in a Murine Model

2010 ◽  
Vol 158 (2) ◽  
pp. 358
Author(s):  
S.S. Razi ◽  
G. Schwartz ◽  
D. Boone ◽  
X. Li ◽  
S. Belsley ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Murine Model ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inflammatory Phase

Nanofiber Wound Dressing Materials—A Comparative Study of Wound Healing on a Porcine Model

2021 ◽  
Author(s):  
Katerina Menclová ◽  
Petr Svoboda ◽  
Jan Hadač ◽  
Štefan Juhás ◽  
Jana Juhásová ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Dressing ◽  
Blood Count ◽  
Serum Amyloid A ◽  
Porcine Model ◽  
Serum Amyloid ◽  
Wound Dressings ◽  
Amyloid A ◽  
Inflammatory Phase ◽  
Dressing Materials

ABSTRACT Background Nanofiber wound dressings remain the domain of in vitro studies. The purpose of our study was to verify the benefits of chitosan (CTS) and polylactide (PLA)-based nanofiber wound dressings on a porcine model of a naturally contaminated standardized wound and compare them with the conventional dressings, i.e., gauze and Inadine. Material and Methods The study group included 32 pigs randomized into four homogeneous groups according to the wound dressing type. Standardized wounds were created on their backs, and wound dressings were regularly changed. We evaluated difficulty of handling individual dressing materials and macroscopic appearance of the wounds. Wound swabs were taken for bacteriological examination. Blood samples were obtained to determine blood count values and serum levels of acute phase proteins (serum amyloid A, C-reactive protein, and haptoglobin). The crucial point of the study was histological analysis. Microscopic evaluation was focused on the defect depth and tissue reactions, including formation of the fibrin exudate with neutrophil granulocytes, the layer of granulation and cellular connective tissue, and the reepithelialization. Statistical analysis was performed by using SPSS software. The analysis was based on the Kruskal–Wallis H test and Mann–Whitney U test followed by Bonferroni correction. Significance was set at P < .05. Results Macroscopic examination did not show any difference in wound healing among the groups. However, evaluation of histological findings demonstrated that PLA-based nanofiber dressing accelerated the proliferative (P = .025) and reepithelialization (P < .001) healing phases, while chitosan-based nanofiber dressing potentiated and accelerated the inflammatory phase (P = .006). No statistically significant changes were observed in the blood count or acute inflammatory phase proteins during the trial. Different dynamics were noted in serum amyloid A values in the group treated with PLA-based nanofiber dressing (P = .006). Conclusion Based on the microscopic examination, we have documented a positive effect of nanofiber wound dressings on acceleration of individual phases of the healing process. Nanofiber wound dressings have a potential to become in future part of the common wound care practice.

scholarly journals Vaginal dilator therapy to prevent stenosis from radiotherapy: A systematic review

2016 ◽  
Author(s):  
Nupur Bansal ◽  
Abhishek Soni ◽  
Anil Khurana ◽  
Yashpal Verma ◽  
Paramjeet Kaur ◽  
...  
Keyword(s):  
Large Population ◽  
Good Evidence ◽  
Control Group ◽  
Cochrane Central Register ◽  
Psychological Consequences ◽  
Pelvic Radiotherapy ◽  
Inflammatory Phase ◽  
Vaginal Stenosis ◽  
Vaginal Length ◽  
Central Register

Background: Pelvic radiotherapy may damage the vagina and cause vaginal stenosis. Its incidence in the literature ranges from 1.2% to 88%. To prevent vaginal stenosis, routine vaginal dilation is recommended during and after pelvic radiotherapy. Materials and Methods: The objective was to examine critically the evidence behind this guideline. Searches included the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Google scholarly articles. All the relevant articles were included in the study. Discussion: Various studies gave recommendations on dilation during or immediately after radiotherapy. Literature does not support routine vaginal dilatation during or immediately after pelvic radiotherapy. Occasional penetration might prevent the sides of the vagina adhering to each other, and dilation might be valuable once the inflammatory and psychological scarring has settled. Two trials demonstrated that encouraging vaginal dilation increased patient compliance, but no difference was found in sexual function scores in the first trial. One retrospective study reported that dilation lowered stenosis rates, but the control group is not comparable. One study involving 89 women revealed that the median vaginal length was 6 cm, six to ten weeks after radiation therapy, but women tolerated a 9-cm dilator/measurer after 4 months of dilation experience. One trial showed no significant advantage by inserting mitomycin C. A study of five women reported that vaginal stenosis can be treated by dilation even many years after radiotherapy. Dilation during or immediately after radiotherapy can cause damage, and there is no evidence that it prevents stenosis. Dilation might stretch the vagina if commenced after the inflammatory phase. Dilation has been associated with traumatic rectovaginal fistulae and psychological consequences. Conclusion: Vaginal dilation might help treat the late effects of radiotherapy, but it must not be assumed that this applies to the acute toxicity phase. Routine dilation during treatment is not supported by good evidence. Prophylactic and therapeutic dilation therapy needs to be considered separately and research is needed to determine when dilation therapy should start on a large population.

Abstract 315: Efficacy and Safety of Rivaroxaban in in vitro Experiments With the Endothelial Cells

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Kaname Seki ◽  
Yosuke Mizuno ◽  
Toku Sakashita ◽  
Jun Tanno ◽  
Shintaro Nakano ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Time Course ◽  
Umbilical Vein ◽  
Endothelial Damage ◽  
Coagulation Cascade ◽  
Elisa Assay ◽  
Mrna Levels ◽  
Factor X ◽  
Clotting Factors ◽  
Inflammatory Phase

Aim: Activated factor X (FXa) plays important roles in the thrombin generation and in inflammation, which is evoked during the endothelial damage. Although rivaroxaban is a selective FXa antagonist, it is one of the key therapies in ischemic heart disease, and yet its function in the state of inactivated coagulation cascade is uncertain. Rivaroxaban blocks FXa in the blood but not the tissue, while factor X is converted to FXa only when glutamic acid is changed to γ-carboxyglutamic acid by vitamin K following the intrinsic clotting factors and/or cellular injury activation. To uncover this aspect, we performed the following experiments. Methods and results: Human umbilical vein endothelial cells (HUVECs) were obtained from Lonza Co., Ltd. The cells were grown to 80% confluence and were treated with rivaroxaban (100nM, 500nM, 1000nM, 2000nM respectively) without FXa stimulation for 4 h, 10 h or 24 h. Cells and medium were collected and then their RNA was extracted from the cells. The qPCR of MCP-1, PAR1-4 and the DNA micro arrays (The GeneChip Human Gene 2.0 ST Array, Affymetrix) were performed. There was neither increased nor decreased gene expression significantly in either experimental time course of the qPCRs or the the DNA micro arrays. The ELISA assay of MCP-1 with medium showed non-activated MCP-1. As a next step, cells were treated with 100nM FXa and with/without rivaroxaban in same time course, and cells and medium were collected for further experiments. FXa evoked induction of mRNA levels for several pro-inflammatory cytokines including MCP-1 maximally at 4h, whereas MCP-1 was maximally evoked at 24 h in ELISA assay. Interestingly rivaroxaban inhibited both in all time course, at 4 hour inflammatory phase and at 24 hour inflammatory phase. Conclusion: Collectively, these results suggest that rivaroxaban may be safe in the inactivated coagulation state, and has the efficacy to attenuate the endothelial damage evoked by FXa and by pro-inflammatory cytokine genes.

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