Assessment of Hydroxyproline Levels in Non-Ischemic Diabetic Foot Ulcers During Recovery. A Prospective Case-Control Study

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Background and aims: Proline hydroxylation is essential for collagen synthesis in wound healing. Therefore, hydroxyproline quantification may be a suitable marker of wound healing in diabetic tissue. Material and method: This is a prospective casecontrol clinical study including 90 referral patients from our clinics in Golestan hospital affiliated to Jundishapour Medical University, Ahwaz-Iran, during a period of 18 months. Three groups were recruited: intervening diabetics with non-ischemic foot ulcers, diabetics without foot ulcers (normal diabetics) and non-diabetics without foot ulcers (normal non-diabetics) as control groups (n=30 per group). 500 mg of granulation tissue from ulcers after treatment and 500 mg of normal skin from both control groups were taken for the measurement of hydroxyproline levels. Results: 13 (43.3%) males and 17 (56.7%) females in trial group were analysed. There was no significant differences in age, gender, and BMI between groups. Mean hydroxyproline concentration in wound granulation tissue (140.44 μg/g) was statistically different from the mean concentration in the skin content of normal diabetics (173.22 g/g,) and the skin content of nondiabetics (178.83 μg/g) (p=0.001). There were no statistically significant differences between the mean values of normal diabetics and non-diabetics (p=0.63). Conclusion: Our results showed the presence of a lower quantity of hydroxyproline in diabetic patients with foot ulcers compared to control groups. This raises the issue of its effectiveness in delaying the repair process in diabetics. Therefore, compensating for tissue hydroxyproline deficit can be a clue in improving diabetic tissue repair.

1. Bentley J, Foster A. Multidisciplinary management of the diabetic foot ulcer. Br J Community Nurs 12: S6, S8, S10 passim, 2007.

2. Jason H, Calvoun, Jon T, Mader. Diabetic foot care. In: Chapman’s Orthopedic Surgery, 3th edition. Michael W Chapman (ed). Lippincott Williams &Wilkins, Philadelphia, pp 3073-76, 2001.

3. Koltuksuz U, Mutus HM, Kutlu R, et al. Effects of caffeic acid phenethyl ester and epidermal growth factor on the development of caustic esophageal stricture in rats. J Pediatr Surg 36: 1504-1509, 2001.

4. Williams JZ, Abumrad N, Barbul A. Effect of a specialized amino acid mixture on human collagen deposition. Ann Surg 236: 369-374, 2002.

5. Zheng XP, Ding Y, Zheng MZ. Effect of zhuhuang frost on wound hydroxyl-proline level after anal operation. Zhongguo Zhong Xi Yi Jie He Za Zhi. 21: 272-273, 2001.

6. Sakallioglu AE, Yagmurlu A, Dindar H, Hasirci N, Renda N, Deveci MS. Sustained local application of low-dose epidermal growth factor on steroid-inhibited colonic wound healing. J Pediatr Surg 39: 591-595, 2004.

7. Fernandez-Montequin JI, Infante-Cristia E, Valenzuela-Silva C, et al. Intralesional injections of Citoprot-P (recombinant human epidermal growth factor) in advanced diabetic foot ulcers with risk of amputation. Int Wound J 4: 333-343, 2007.

8. Witte MB, Kiyama T, Barbul A. Nitric oxide enhances experimental wound healing in diabetes. Br J Surg 89: 1594-1601, 2002.

9. Shi HP, Most D, Efron DT, Witte MB, Barbul A. Supplemental L-arginine enhances wound healing in diabetic rats. Wound Repair Regen 11: 198-203, 2003.

10. Bakker K, Schaper NC. New developments in the treatment of diabetic foot ulcers. Ned Tijdschr Geneeskd 144 : 409-412, 2000.

11. Ong M. Hyperbaric oxygen therapy in the management of diabetic lower limb wounds. Singapore Med J 49: 105-109, 2008.

12. Bakker DJ. Hyperbaric oxygen therapy and the diabetic foot. Diabetes Metab Res Rev 16(Suppl 1): S55- S58, 2000.

13. Niinikoski J. Hyperbaric oxygen therapy of diabetic foot ulcers, transcutaneous oxymetry in clinical decision making. Wound Repair Regen 11: 458-461, 2003.

14. Petrofsky JS, Lawson D, Suh HJ, et al. The influence of local versus global heat on the healing of chronic wounds in patients with diabetes. Diabetes Technol Ther 9: 535-544, 2007.

15. Falanga V. Wound healing and its impairment in the diabetic foot. Lancet 366(9498): 1736-1743, 2005.

16. Jeffcoate WJ, Price P, Harding KG; International Working Group on Wound Healing and Treatments for People with Diabetic Foot Ulcers. Wound healing and treatments for diabetic foot ulcers. Diabetes Metab Res Rev 20(Suppl 1): S78-S89, 2004.

17. Edwards CA, O'Brien WD Jr. Modified assay for determination of hydroxyproline in a tissue hydrolyzate. Clin Chim Acta 104: 161-167, 1980.

18. Ribu L, Birkeland K, Hanestad BR, Moum T, Rustoen T. A longitudinal study of patients with diabetes and foot ulcers and their health-related quality of life: wound healing and quality-of- life changes. J Diabetes Complications 22: 400-407, 2008.

19. Muller M, Trocme C, Lardy B, Morel F, Halimi S, Benhamou PY. Matrix metalloproteinases and diabetic foot ulcers: the ratio of MMP-1 to TIMP-1 is a predictor of wound healing. Diabet Med 25: 419-426, 2008.

20. Lobmann R, Zemlin C, Motzkau M, Reschke K, Lehnert H. Expression of matrix mtalloproteinases and growth factors in diabetic foot wounds treated with a protease absorbent dressing. J Diabetes Complications 20: 329-335, 2006.

21. Black E, Vibe-Petersen J, Jorgensen LN et al. Decrease of collagen deposition in wound repair in type 1 diabetes independent of glycemic control. Arch Surg 138: 34-40, 2003.

22. Prompers L, Schaper N, Apelqvist J, et al. Prediction of outcome in individuals with diabetic foot ulcers: focus on the differences between individuals with and without peripheral arterial disease. The EURODIALE Study. Diabetologia 51: 747-755, 2008.

23. Ramamuthy NS, Kucine AJ, McClain SA, McNamara TF, Golub LM. Topically applied CMT-2 enhances wound healing in streptozotocin diabetic rat skin. Adv Dent Res 12: 144-148, 1998.

24. Monami M, Longo R, Desideri CM, Masotti G, Marchionni N, Mannucci E. The diabetic person beyond a foot ulcer: healing, recurrence, and depressive symptoms. J Am Podiatr Med Assoc 98: 130-136, 2008.

Romanian Journal of Diabetes Nutrition and Metabolic Diseases

The Journal of Romanian Society of Diabetes Nutrition and Metabolic Diseases

Journal Information

CiteScore 2017: 0.11

SCImago Journal Rank (SJR) 2017: 0.122
Source Normalized Impact per Paper (SNIP) 2017: 0.077


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