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      Trans-Cinnamaldehyde Increases Random Pattern Flap Survival Through Activation of the Nitric Oxide Pathway

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          Abstract

          Background

          The application of random pattern skin flaps is limited in plastic surgery reconstruction due to necrosis. Trans-cinnamaldehyde has antibacterial, anticancer, and antioxidant properties. In this study, we aimed to investigate the effect of trans-cinnamaldehyde on skin flap survival and its possible mechanism regarding nitric oxide.

          Materials and Methods

          One hundred forty male Sprague-Dawley rats were randomly divided into seven groups (n = 20 each group). After the dorsal flap was raised, different doses of trans-cinnamaldehyde (10, 20, and 30 mg/kg) were immediately given by oral gavage in the three different groups. To assess the possible involvement of the nitric oxide system, N G-nitro-L-arginine methyl ester (L-NAME, a nonselective nitric oxide synthase inhibitor) was used in this study. All flap samples were incised on postoperative day 7.

          Results

          Our results showed that flap survival was increased significantly in the 20 mg/kg (P < 0.001) trans-cinnamaldehyde (TC) group compared to the control group or 30 mg/kg TC group. This protective function was restrained by coadministration of L-NAME with 20 mg/kg TC. The results of histopathology, laser Doppler, arteriography mediated with oxide–gelatine, and fluorescent staining all showed a significant increase in capillary count, collagen deposition, angiogenesis, and flap perfusion. Immunohistochemistry results revealed a significant increase in the expression of CD34, eNOS, and VEGF.

          Conclusion

          Trans-cinnamaldehyde increased flap survival through the nitric oxide synthase pathway and contributed to angiogenesis. A concentration of 20 mg/kg trans-cinnamaldehyde was recommended in this study.

          Most cited references37

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          Skin Wound Healing: An Update on the Current Knowledge and Concepts.

          The integrity of healthy skin plays a crucial role in maintaining physiological homeostasis of the human body. The skin is the largest organ system of the body. As such, it plays pivotal roles in the protection against mechanical forces and infections, fluid imbalance, and thermal dysregulation. At the same time, it allows for flexibility to enable joint function in some areas of the body and more rigid fixation to hinder shifting of the palm or foot sole. Many instances lead to inadequate wound healing which necessitates medical intervention. Chronic conditions such as diabetes mellitus or peripheral vascular disease can lead to impaired wound healing. Acute trauma such as degloving or large-scale thermal injuries are followed by a loss of skin organ function rendering the organism vulnerable to infections, thermal dysregulation, and fluid loss.
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            A comparison of chemical, antioxidant and antimicrobial studies of cinnamon leaf and bark volatile oils, oleoresins and their constituents.

            The antioxidant, antifungal and antibacterial potentials of volatile oils and oleoresin of Cinnamomum zeylanicum Blume (leaf and bark) were investigated in the present study. The oleoresins have shown excellent activity for the inhibition of primary and secondary oxidation products in mustard oil added at the concentration of 0.02% which were evaluated using peroxide, thiobarbituric acid, p-anisidine and carbonyl values. Moreover, it was further supported by other complementary antioxidant assays such as ferric thiocyanate method in linoleic acid system, reducing power, chelating and scavenging effects on 1,1'-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals. In antimicrobial investigations, using inverted petriplate and food poison techniques, the leaf and bark volatile oils has been found to be highly effective against all the tested fungi except Aspergillus ochraceus. However, leaf oleoresin has shown inhibition only for Penicillium citrinum whereas bark oleoresin has caused complete mycelial zone inhibition for Aspergillus flavus and A. ochraceus along with Aspergillus niger, Aspergillus terreus, P. citrinum and Penicillium viridicatum at 6 microL. Using agar well diffusion method, leaf volatile oil and oleoresin have shown better results in comparison with bark volatile oil, oleoresin and commercial bactericide, i.e., ampicillin. Gas chromatographic-mass spectroscopy studies on leaf volatile oil and oleoresin resulted in the identification of 19 and 25 components, which accounts for the 99.4% and 97.1%, respectively of the total amount and the major component was eugenol with 87.3% and 87.2%, respectively. The analysis of cinnamon bark volatile oil showed the presence of 13 components accounting for 100% of the total amount. (E)-cinnamaldehyde was found as the major component along with delta-cadinene (0.9%), whereas its bark oleoresin showed the presence of 17 components accounting for 92.3% of the total amount. The major components were (E)-cinnamaldehyde (49.9%), along with several other components.
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              The vascular territories (angiosomes) of the body: experimental study and clinical applications.

              The blood supply to the skin and underlying tissues was investigated by ink injection studies, dissection, perforator mapping and radiographic analysis of fresh cadavers and isolated limbs. The results were correlated with previous regional studies done in this department. The blood supply is shown to be a continuous three-dimensional network of vessels not only in the skin but in all tissue layers. The anatomical territory of a source artery in the skin and deep tissues was found to correspond in most cases, giving rise to the angiosome concept. Arteries follow closely the connective tissue framework of the body. The primary supply to the skin is by direct cutaneous arteries which vary in calibre, length and density in different regions. This primary supply is reinforced by numerous small indirect vessels, which are "spent" terminal branches of arteries supplying the deep tissues. An average of 374 major perforators was plotted in each subject, revealing that there are still many more potential skin flaps. Our arterial roadmap of the body provides the basis for the logical planning of incisions and flaps. The angiosomes defined the tissues available for composite transfer.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                18 February 2021
                2021
                : 15
                : 679-688
                Affiliations
                [1 ]Department of Orthopedics (Division of Hand Surgery), The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Key Laboratory of Orthopedics of Zhejiang Province, The Second School of Medicine, Wenzhou Medical University , Wenzhou, Zhejiang, 325027, People’s Republic of China
                [2 ]Department of Post Anaesthesia Care Unit, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, The Second School of Medicine, Wenzhou Medical University , Wenzhou, 325027, Zhejiang, People’s Republic of China
                Author notes
                Correspondence: Hede Yan Department of Orthopaedics (Division of Hand Surgery), The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University , West Xueyuan Road 109#, Wenzhou, 325027, Zhejiang Province, People’s Republic of China Email yanhede@hotmail.com
                Author information
                http://orcid.org/0000-0003-1276-3059
                Article
                297458
                10.2147/DDDT.S297458
                7899309
                951e8cb4-bad3-477d-a760-9a9b06cdf09b
                © 2021 Luo et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 15 December 2020
                : 30 January 2021
                Page count
                Figures: 0, Tables: 4, References: 37, Pages: 10
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                random pattern flap,flap necrosis,trans-cinnamaldehyde,angiogenesis,flap perfusion

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