Potential ointment of carica papaya leaf extract against postpartum pe

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Yusmayasari et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-72 2019 543-549 543 IJAMSCR |Volume 7 | Issue 2 | Apr - Jun - 2019 www.ijamscr.com Research article Medical research Potential ointment of carica papaya leaf extract against postpartum perineal wounds healing first: experimental study in galuh wistar mice rattus norvegicus Yusmayasari 1 Noor Pramono 2 Imam Djamaludin Mashoedi 3 1 Poltekkes Kemenkes Semarang / Semarang Indonesia 2 Universitas Diponegoro / Semarang Indonesia 3 Universitas Sultan Agung / Semarang Indonesia Corresponding Author: Yusmayasari Email id: maya_pontiyahoo.com ABSTRACT Background Perineal rupture occurs in about 85 of vaginal deliveries. If the wound is not treated properly it causes pain and infection which prevents wound healing. Perineal wound care in addition to using 10 povidone iodine the use of papaya carica leaf herbs is more effective in accelerating healing with active compounds of flavonoids saponins and tannins which have the potential to be anti-inflammatory and antiseptic so as to stimulate collagen which plays a role in wound healing. Objective Prove the potential of Carica leaf extract ointment for the healing of the first postpartum Galuh Wistar rattus norvegicus wound perineum. Methods True Execution simple random sampling pre post control group design. The subjects of the study were galuh wistar rats after giving birth for the first time as many as 25 divided into 5 groups. The wound healing variable is measured by the REEDA scale. Evaluation is carried out every day for 7 days. Test the hypothesis using Wilcoxon Krussall Wallis Mann Whitney U Test. Results Ointment 10 papaya carica leaf extract EDPC has the potential to accelerate the healing of perineal wounds by achieving a score of 0 which means good wound healing and achieve a minimum score p 0.025 on the fifth day compared to 5 EDPC ointment 15 EDPC ointment Betadine ointment and ointment base. Conclusions and Recommendations EDPC 10 ointment effectively speeds up wound healing before 7 days. It is expected that observation of perineal wounds is further enhanced by microscopic examination. Further researchers can conduct further research on the active ingredient of other Carica papaya leaf extracts that have the potential to inhibit gram-positive and gram- negative bacteria in perineal wounds. Keywords : Ointment of Papaya Carica Leaf Extract Wound Healing REEDA Scale. ISSN:2347-6567 International Journal of Allied Medical Sciences and Clinical Research IJAMSCR

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Yusmayasari et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-72 2019 543-549 544 INTRODUCTION Relative perineal injury occurs in almost all vaginal deliveries with reported rates of around 85 1. Perineal wounds can occur either spontaneously or as a result of episiotomy 2 both in primiparas and multiparas with the highest frequency in primipara 3. As many as 70 of perineal wounds require suturing the broken tissue to be able to reunite 4. Long-term morbidity for women can occur in perineal wounds 5. Some cases experience long-term complications such as perineal pain dyspareunia dysuria and alvi incontinence pelvic organ prolapse long recovery period of the puerperium and psycho-social problems 4 6 7. There are 3 techniques used in the treatment of perineal wounds namely the antiseptic technique a dry clean technique carried out after washing the perineum using water and soap and then drying. As well as in traditional ways with the use of natural plant ingredients 8 9. The use of povidone iodine antiseptic also affects the healing of perineal wounds. Povidon iodine is a bond between iodine and polynyl pyrolidone which has a broad spectrum has antiseptic properties inhibits germs. Topical antiseptics povidone iodine is an effective antiseptic that does not inhibit wound healing. It is bactericidal against gram positive and negative organisms no bacterial resistance or cross resistance helps cure various acute and chronic wounds anti-inflammatory properties 10. Recent research with the results of povidone iodine enhances wound healing through TGF-β not only increases granulation but also increases neurovascularization 11. Other studies have shown that the duration of perineal wound healing using povidone iodine 10 is an average of 8 days 12. Papaya Carica leaves are one of the herbs that can be an alternative choice in wound care. The compounds contained in papaya carica leaves namely flavonoids saponins and tannins which are efficacious as anti-inflammatory and antiseptic in inhibiting the growth of bacteria that can cause infection in wounds. Flavonoids as anti- inflammatory work by inhibiting the arachidonic acid metabolic pathway which is an important inflammatory mediator forming prostaglandin and releasing histamine inflammation 13 14. Saponins and tannins as anti-inflammatory and antiseptic work by increasing the permeability of bacterial cell membranes thereby changing the structure of membranes denaturing membrane proteins and causing damage to bacterial cell membranes 15. Saponins have antiseptic properties and provide a positive influence by stimulating increased collagen which is a protein that plays a role in the process of wound healing 16. The cavity in the area of the wound begins to be filled with granulation tissue neurovaskulerization reaches its peak the collagen fibers multiply and begin to cover the wound 17. Tanin as an antiseptic in wound tissue by depositing protein and having bactericidal properties against staphylococcus bacteria 18. The choice of ointment form is expected so that there is penetration into the top layer of the skin so as to provide a healing effect. Ointment is useful for maintaining medication in an effort to prolong contact with the skin which can increase and slow the release of active substances. ointment protects or treats skin that has both acute and chronic diseases 19. Experimental animals using galuh wistar rats will be carried out at the Animal Laboratory Unit of Diponegoro University Semarang because it has been known as a journal publication in Google Scholar on experimental studies Diponegoro Medical Journal Volume 7 Number 2 May 2018 ISSN Online 2540-8844 about the Effect of Breadfruit and Honey Leaf Extract on the Microscopic Illustration of Dietylnitrisamine- induced Wistar Mice 20. It is necessary to research using 5 10 and 15 papaya carica leaf extract ointment on the healing of perineal wounds in experimental animals galuh wistar rattus norvegicus. Study Objectives To prove the potential of Carica leaf extract ointment for the healing of the first postpartum Galuh Wistar rattus norvegicus wound perineum. METHODS This study was an experimental laboratory with a randomized Pre Post control group design study there was randomization in the subject group

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Yusmayasari et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-72 2019 543-549 545 which used female wistar rats. This study is comparative namely knowing the potency of 5 10 and 15 papaya carica leaf extract ointment for healing perineal wistar postpartum rats after giving birth first. Previously an assessment of perineal wounds of wistar rats pretest was carried out. After that the treatment was given for 7 days. Evaluation of perineal wound healing after 7 days of treatment posttest Assessment of perineal wound healing before and after treatment using the REEDA scale. DATA ANALYSIS Univariate analysis was carried out with the aim of describing each variable studied separately by making a table of mean and standard deviation of each variable and analyzing descriptively the variables studied. To find out the time interval of the measurement Friedman test was carried out followed by the post hoc Wilcoxon test to determine the timing of the difference. To test the differences between groups tested with kruskal-walls. Followed by the Whitney U Test posthoc test to find out which treatment group differences were the most significant among the test groups. Heterogeneous age characteristics so it was continued by multivariate analysis to see whether there was an effect of age on REEDA scores RESULT Univariat Analysis Table 1. Characteristics of Research Samples Characteristics of the study sample Group Salep EDPC 5 Salep EDPC 10 Salep EDPC 15 Basis salep Povidon Iodine Mean SD Mean SD Mean SD Mean SD Mean SD Age month 240 055 260 055 280 045 200 000 260 055 Weight gr 1886 1189 1866 1499 1918 511 1834 1346 1842 978 Number of children 680 217 600 324 620 303 640 230 540 182 Time of wound healing days 480 084 400 071 440 134 600 071 520 045 Based on Table 1 it is known that the characteristics of the study sample were in accordance with the inclusion criteria set by the researcher where the study sample was between 2- 2.8 months with a weight of 183.4-191.8 grams. While the children of rats born first numbered 5-7 tails. Based on observations the wound healing time ranges from 4-6 days. Bivariate Analysis Wound Healing Duration Based on REEDA Total Score Table 2. Total REEDA score REEDA Score measurement day to Group Salep EDPC 5 Salep EDPC 10 Salep EDPC 15 Basis salep Povidon iodine Mean ± SD Mean ± SD Mean ± SD Mean ± SD Mean ± SD 1 1000 ± 000 1000 ± 000 1000 ± 000 1000 ± 000 1000 ± 000 2 800 ± 235 620 ± 217 780 ± 259 980 ± 045 880 ± 084 3 500 ± 141 340 ± 270 380 ± 283 780 ± 164 640 ± 152 4 180 ± 179 020 ± 045 120 ± 164 560 ± 134 420 ± 130

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Yusmayasari et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-72 2019 543-549 546 5 020 ± 045 000 ± 000 020 ± 045 320 ± 192 080 ± 179 6 000 ± 000 000 ± 000 000 ± 000 020 ± 045 000 ± 000 7 000 ± 000 000 ± 000 000 ± 000 000 ± 000 000 ± 000 p 0000 0000 0000 0000 0000 Friedman Based on Table 2 it is known that there are significant differences in the first day to the seventh day of the REEDA score in each study group p 0000. Table 3. Post hoc Total REEDA score Measurement Group p The first day The second day Salep EDPC 5 0109 Salep EDPC 10 0059 Salep EDPC 15 0102 Basis salep 0317 Povidon iodine 0063 The first day The third day Salep EDPC 5 0039 Salep EDPC 10 0042 Salep EDPC 15 0041 Basis salep 0038 Povidon iodine 0039 The first day The fourth day Salep EDPC 5 0042 Salep EDPC 10 0034 Salep EDPC 15 0041 Basis salep 0034 Povidon iodine 0039 The first day Fifth day Salep EDPC 5 0034 Salep EDPC 10 0025 Salep EDPC 15 0034 Basis salep 0042 Povidon iodine 0034 The first day Sixth day Salep EDPC 5 0025 Salep EDPC 10 0025 Salep EDPC 15 0025 Basis salep 0034 Povidon iodine 0025 The first day Seventh day Salep EDPC 5 0025 Salep EDPC 10 0025 Salep EDPC 15 0025 Basis salep 0025 Povidon iodine 0025 Post Hoc Wilcoxon Based on the post hoc Wilcoxon results it was found that on the second day there was no significant difference in the REEDA score in each study group p 0.05. While on the third day there was a significant difference in the REEDA score especially in the group given the ointment base p 0.038 5 EDPC and the group given povidone iodine p 0.039. On the sixth day all the study groups achieved a minimum REEDA score except the group given the ointment base which achieved a REEDA score of at least on the seventh day p 0.025.

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Yusmayasari et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-72 2019 543-549 547 Differences in Wound Healing Duration based on REEDA Total Score Figure 1. Comparison of the average REEDA score for each study group Figure 1 shows that the REEDA score of each group has decreased gradually every day. However there was a significant difference on the fourth day where the decline in the REEDA score of the group given the ointment tended to be slower compared to the other groups. While the most stable decrease in REEDA score was seen in the group given 10 EDPC ointment. DISCUSSION In this study the wound healing was fastest in the SEDPC group 5 10 and 15 and the longest in the base group of ointment and betadine ointment 10. Perineal wound care was carried out on the study sample 2 times a day namely in the morning and evening. The treatment of the wound is cleaned and dried then given an ointment according to each group The purpose of wound care is a preventive effort against infection in the wound area in the vulva perineum and in the uterus reducing pain in the wound area accelerating wound healing and bleeding in the perineal suture and maintaining the cleanliness of the perineum and vulva. Cleanse wounds from foreign objects or debris drainage to facilitate the removal of exudates. In addition perineal wound care was also given 10 betadine ointment and EDPC ointment of various concentrations. The administration of papaya leaf extract is due to the compound content of papaya carica leaves namely flavonoids saponins and tannins which are efficacious as anti-inflammatory and antiseptic in inhibiting the growth of bacteria that can cause infection in wounds. The research conducted by Parampasi in 2013 showed that the number of macrophages given by papaya leaf extract was more accelerating the work of macrophages by increasing the production of interleukin in the inflammatory process. Collagen tissue that is formed becomes thicker acts as an antiseptic by destroying germs which inhibits infection and wound healing 18. When experiencing a wound the body responds through several phases in the form of cellular and vascular responses that occur due to tissue damage. The inflammatory phase starts aiming to stop bleeding clean the wound area from foreign objects and dead cells and prepare for the healing process to begin. EDPC 10 ointment was proven to accelerate wound healing by achieving a minimum REEDA score on the fifth day. The most stable decline in REEDA score. This shows that the active ingredient of saponins tannins and flavonoids has proven efficacy in wound healing. Flavonoids as anti-inflammatory work by inhibiting the metabolic pathway of arachidonic acid which is an important inflammatory mediator forming prostaglandin and releasing histamine inflammation13 14. Saponins and tannins as anti-inflammatory and antiseptic work by increasing the permeability of bacterial cell membranes thereby changing the structure of membranes denaturing membrane proteins and causing damage to bacterial cell membranes 15. Saponins have antiseptic properties and provide a positive influence by stimulating increased collagen which is a protein that plays a role in the process of wound healing 16. The cavity in the area of the wound begins to be filled with granulation tissue neurovaskulerization reaches its

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Yusmayasari et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-72 2019 543-549 548 peak the collagen fibers multiply and begin to cover the wound 17. Tanin as an antiseptic in wound tissue by depositing protein and having bactericidal properties against staphylococcus bacteria 18. CONCLUSIONS Based on the results of research on the potential of papaya carica leaf extract ointment for healing perineal wounds after the first birth galca wistar rattus norvegicus rats it can be concluded that carica leaf extract ointment has the potential to cure perineal and ointment wounds. perineal wound healing. Recommendation Future It is expected that observation of perineal wounds is further enhanced by microscopic examination. Further researchers can conduct further research on the active ingredient of other Carica papaya leaf extracts that have the potential to inhibit gram-positive and gram-negative bacteria in perineal wounds REFERENCES 1. Edqvist M Hildingsson I Mollberg M Lundgren I and Lindgren H. Midwives’ Management during the Second Stage of Labor in Relation to Second ‐Degree Tears—An Experimental Study. Birth. 44 2017 86-94. 2. Aasheim V Nilsen ABV Reinar LM and Lukasse M. Perineal techniques during the second stage of labour for reducing perineal trauma. Cochrane Database of Systematic Reviews. 2017. 3. Ott J Gritsch E Pils S et al. A retrospective study on perineal lacerations in vaginal delivery and the individual performance of experienced mifwives. BMC pregnancy and childbirth. 15 2015 270. 4. Webb S Sherburn M and Ismail KM. Managing perineal trauma after childbirth. BMJ. 349 2014. 5. Leeman L Rogers R Borders N Teaf D and Qualls C. The Effect of Perineal Lacerations on Pelvic Floor Function and Anatomy at 6 Months Postpartum in a Prospective Cohort of Nulliparous Women. Birth Berkeley Calif. 43 2016 293-302. 6. Bharathi A Reddy DD and Kote GS. A prospective randomized comparative study of vicryl rapide versus chromic catgut for episiotomy repair. Journal of clinical and diagnostic research: JCDR. 7 2013 326 7. Abdel-Fattah M Familusi A Fielding S Ford J and Bhattacharya S. Primary and repeat surgical treatment for female pelvic organ prolapse and incontinence in parous women in the UK: a register linkage study. BMJ open. 1 2011 000206 . 8. Normal JNPKAP. Buku Panduan Peserta. Jakarta: JNPK 2010 9. Sinclair C. Buku Saku Kebidanan. Jakarta: EGC 2010 10. Bigliardi PL Alsagoff SAL El-Kafrawi HY Pyon J-K Wa CTC and Villa MA. Povidone iodine in wound healing: A review of current concepts and practices. International Journal of Surgery. 44 2017 260-8. 11. Wang L Qin W Zhou Y et al. Transforming growth factor β plays an important role in enhancing wound healing by topical application of Povidone-iodine. Scientific reports. 2017 7: 991. 12. “SSJP. Perbedaan Efektifitas Povidone Iodine Dengan Air Rebusan Daun Binahong Terhadap Penyembuhan Luka Perineum Pada Ibu Postpartum Di Bpm Wilayah Kerja Dinas Kesehatan Kabupaten Lampung Selatan Tahun 2017. 13. “Mardiana LdT. Daun Ajaib Tumpas Penyakit. Jakarta: Penebar Swadaya 2012. 14. ndraswary R. Efek Konsentrasi Ekstrak Buah Adas Foeniculum vulgare Mill. Topikal pada Epitelisasi Penyembuhan Luka Gingiva Labial Tikus Sprague Dawley In Vivo. Majalah Universitas Sultan Agung. 2011. 15. Prasetyo BF Wientarsih I and Priosoeryanto BP. Aktivitas sediaan gel ekstrak batang pohon pisang ambon dalam proses penyembuhan luka pada mencit. Jurnal veteriner. 11 2010 70-3 16. Singer AJ and Dagum AB. Current Management of Acute Cutaneous Wounds. New England Journal of Medicine. 359 2008 1037-46. . 17. Kumar V Abbas AK Fausto N and Aster J. Tissue renewal regeneration and repair. Robbins and Cotran pathologic basis of disease 8th ed Philadelphia: Saunders/Elsevier. 2010 79-110. 18. Parampasi N and Soemarno T. Pengaruh Pemberian Ekstrak Daun Pepaya dalam Etanol 70 pada Proses Penyembuhan Luka Insisi. Majalah Patologi Indonesia. 22 2013. 19. Wardiyah S. Perbandingan sifat fisik sediaan krim gel dan salep yang mengandung etil p-metoksisinamat dari

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Yusmayasari et al / Int. J. of Allied Med. Sci. and Clin. Research Vol-72 2019 543-549 549 ekstrak rimpang kencur kaempferia galanga linn.. UIN Syarif Hidayatullah Jakarta: Fakultas Kedokteran dan Ilmu Kesehatan 2015 2015. 20. Purnamasari P Purnawati RD and Susilaningsih N. Pengaruh Ekstrak Daun Sukun Dan Madu Terhadap Gambaran Mikroskopik Ginjal Tikus Wistar Yang Diinduksi Dietilnitrosamin. Jurnal Kedokteran Diponegoro. 7 2018 1391-405. How to cite this article: Yusmayasari Noor Pramono Imam Djamaludin Mashoedi. Potential ointment of carica papaya leaf extract against postpartum perineal wounds healing first: experimental study in galuh wistar mice rattus norvegicus. Int J of Allied Med Sci and Clin Res 2019 72: 543- 549. Source of Support: Nil. Conflict of Interest: None declared.

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