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      Evaluation of wound healing activity of cow urine ark in diabetic Wistar albino rats

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          Abstract

          Aim:

          To evaluate wound healing activity of cow urine ark in diabetic rats.

          Materials and Methods:

          Streptozotocin-induced diabetic Wistar albino rats were randomly divided into six groups ( n = 6). Three groups - diabetic control, active control (glibenclamide), and treatment (cow urine ark) were operated for excision wounds (EWs). Rats in these groups received distilled water 1 ml/day, glibenclamide 0.5 mg/kg body weight/day, and cow urine ark 5.5 ml/kg body weight/day orally till complete healing of the EWs. EWs were evaluated for wound contraction on 3 rd, 7 th, and 11 th day and for reepithelization on 11 th day. The other three groups were operated for incision wounds (IW) as well as dead space wounds (DW) in the same animal which received the above agents orally for 11 days. IWs were analyzed for wound breaking strength and DWs were analyzed for dry weight, hydroxyproline content, and histology of granulation tissue.

          Results:

          EWs showed significantly increased wound closure in the treatment group as compared to the diabetic as well as active control groups at 3 rd ( P < 0.001) and 11 th ( P < 0.05) post-wounding day and to the only diabetic control group at 7 th ( P < 0.01) post-wounding day. IWs showed significant improvement in wound breaking strength in the treatment as compared to diabetic ( P < 0.001) and active control ( P < 0.01) groups. DWs showed significant increase in hydroxyproline content of granulation tissue in the treatment as compared to diabetic control ( P < 0.001) and active control ( P < 0.001) groups. Wound breaking strength and hydroxyproline content also significantly increased in the active control group compared to diabetic control ( P < 0.001 and P < 0.05, respectively). Granulation tissue dry weight was significantly increased in treatment and active control groups as compared to diabetic control ( P < 0.001).

          Conclusion:

          Cow urine ark increases granulation tissue formation as well as collagen content. Wound contraction was also significantly improved. The cow urine ark could be potentially effective in promoting healing of diabetic wounds by increasing granulation tissue formation and collagen content, however, further studies are required for its clinical application.

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          Most cited references27

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          Incidence, outcomes, and cost of foot ulcers in patients with diabetes.

          To determine the incidence of foot ulcers in a large cohort of patients with diabetes, the risk of developing serious complications after diagnosis, and the attributable cost of care compared with that in patients without foot ulcers. Retrospective cohort study of patients with diabetes in a large staff-model health maintenance organization from 1993 to 1995. Patients with diabetes were identified by algorithm using administrative, laboratory, and pharmacy records. The data were used to calculate incidence of foot ulcers, risk of osteomyelitis, amputation, and death after diagnosis of foot ulcer, and attributable costs in foot ulcer patients compared with patients without foot ulcers. Among 8,905 patients identified with type 1 or type 2 diabetes, 514 developed a foot ulcer over 3 years of observation (cumulative incidence 5.8%). On or after the time of diagnosis, 77 (15%) patients developed osteomyelitis and 80 (15.6%) required amputation. Survival at 3 years was 72% for the foot ulcer patients versus 87% for a group of age- and sex-matched diabetic patients without foot ulcers (P < 0.001). The attributable cost for a 40- to 65-year-old male with a new foot ulcer was $27,987 for the 2 years after diagnosis. The incidence of foot ulcers in this cohort of patients with diabetes was nearly 2.0% per year. For those who developed ulcers, morbidity, mortality, and excess care costs were substantial compared with those for patients without foot ulcers. The results appear to support the value of foot-ulcer prevention programs for patients with diabetes.
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            High-Glucose Environment Enhanced Oxidative Stress and Increased Interleukin-8 Secretion From Keratinocytes

            Impaired wound healing frequently occurs in patients with diabetes. Interleukin (IL)-8 production by keratinocyte is responsible for recruiting neutrophils during healing. Intense inflammation is associated with diabetic wounds, while reduction of neutrophil infiltration is associated with enhanced healing. We hypothesized that increased neutrophil recruitment by keratinocytes may contribute to the delayed healing of diabetic wounds. Using cultured human keratinocytes and a diabetic rat model, the current study shows that a high-glucose environment enhanced IL-8 production via epidermal growth factor receptor (EGFR)–extracellular signal–regulated kinase (ERK) pathway in a reactive oxygen species (ROS)-dependent manner in keratinocytes. In addition, diabetic rat skin showed enhanced EGFR, ERK, and IL-8 expression compared with control rats. The dermal neutrophil infiltration of the wound, as represented by expression of myeloperoxidase level, was also significantly higher in diabetic rats. Treating diabetic rats with dapsone, an agent known to inhibit neutrophil function, was associated with improved healing. In conclusion, IL-8 production and neutrophil infiltration are increased in a high-glucose environment due to elevated ROS level and contributed to impaired wound healing in diabetic skin. Targeting these dysfunctions may present novel therapeutic approaches.
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              Histologic characterization of vaginal vs. abdominal surgical wound healing in a rabbit model.

              We aimed to compare the histologic characteristics of vaginal vs. abdominal surgical wound healing in the rabbit. Bilateral 6 mm full-thickness circular segments were excised from the vagina and abdominal skin in 34 New Zealand white female rabbits. Animals were euthanized on the day of and 4, 7, 10, 14, 21, 28, and 35 days after wounding, and their wounds were evaluated using a modified scoring system. The inter- and intraobserver agreements of the scoring system were good (weighted kappa 0.63 and 0.71, respectively). A transient fibrinous crust was evident in 75% of the abdominal and in none of the vaginal wound specimens on days 4-7 after wounding (p=0.01). Acute inflammation peaked at day 4 in both the vaginal and abdominal wounds, while chronic inflammation peaked at days 4-7 and 14-21 in the abdomen and vagina, respectively. Both neovascularization and the amount of granulation tissue peaked at days 4 and 7 in the vagina and abdomen, respectively. Maturation of granulation tissue and collagen deposition increased persistently in both tissues until postwounding day 35. Reepithelialization increased after wounding, and was completed by day 14 in both tissues. The surgical wound-healing process in both the vagina and abdomen includes transient acute and chronic inflammation, fibroblast proliferation, and neovascularization, as well as progressive maturation of granulation tissue, reepithelialization, and collagen deposition. A transient fibrinous crust forms in the abdomen but not in the vagina 4-7 days after wounding. The modified histologic scoring system described here was found to be reliable and reproducible.
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                Author and article information

                Journal
                J Intercult Ethnopharmacol
                J Intercult Ethnopharmacol
                Journal of Intercultural Ethnopharmacology
                SAGEYA (Turkey )
                2146-8397
                Sep-Dec 2016
                25 September 2016
                : 5
                : 4
                : 434-438
                Affiliations
                [1 ]Department of Pharmacology, GMERS Medical College, Junagadh, Gujarat, India
                [2 ]Department of Pharmacology, Billev Pharma East, Ljubljana, Slovenia
                [3 ]Department of Pharmacology, Government Medical College, Bhavnagar, Gujarat, India
                Author notes
                Address for Correspondence: Hiren N. Hirapara, GMERS Medical College, Junagadh, Gujarat, India. E-mail: dr.hirenhirpara@ 123456gmail.com
                Article
                JIE-5-434
                10.5455/jice.20160923100135
                5061489
                c4d71ac6-868e-4697-b851-b01358b72142
                Copyright: © SAGEYA

                This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, noncommercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 25 July 2016
                : 02 September 2016
                Categories
                Original Research

                collagen,cow urine ark,granulation tissue,streptozotocin-induced diabetes

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