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2.
Int Wound J ; 8(6): 658-60, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21854546

ABSTRACT

Delayed wound healing in diabetes is a challenging medical and societal problem for which there is currently no efficacious treatment. One of the major contributors of this problem is nitric oxide (NO) deficiency. NO is a critical signalling molecule essential for normal wound repair. Sustained hyperglycaemia in diabetes leads to increased vascular superoxide production, which inactivates NO and causes vascular dysfunction. New therapeutic regiments and strategies to enhance endothelial NO production are a new hope to improve impaired diabetic wound healing. One of the agents that have the ability to improve endothelial NO generation in diabetic patients is folic acid. Folic acid ability to conserve NO bioactivity may be due to homocysteine-lowering effects of folates, antioxidant actions and effects on cofactor availability. Considering these data, we hypothesised that folic acid supplementation may ameliorate delayed diabetic wound healing by increasing NO bioavailability. The potential of exogenous folic acid as an inexpensive and safe oral therapy stimulates ongoing investigations.


Subject(s)
Diabetic Foot/drug therapy , Folic Acid/administration & dosage , Hematinics/administration & dosage , Wound Healing/drug effects , Biological Availability , Diabetic Foot/metabolism , Diabetic Foot/pathology , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Folic Acid/pharmacokinetics , Hematinics/pharmacokinetics , Humans , Nitric Oxide/metabolism , Oxidative Stress/drug effects , Treatment Outcome
3.
Diabetes Res Clin Pract ; 93(2): 228-234, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21632142

ABSTRACT

AIMS: Stem cells are a new hope to ameliorate impaired diabetic wound healing. The purpose of this study was to evaluate the effect of adipose tissue derived mesenchymal stem cells (AD-MSCs) on wound healing in a diabetic rat model. METHODS: Twenty-six rats became diabetic by a single intraperitoneal injection of streptozotocin. Six rats served as non-diabetic (non-DM). Diabetic rats were divided into two equal groups randomly; control and treatment. Six weeks later, a full-thickness circular excisional wound was created on the dorsum of each rat. AD-MSCs were injected intra-dermally around the wounds of treatment group. PBS was applied to control and non-DM groups. The wound area was measured every other day. After wound healing completion, full thickness skin samples were taken from the wound sites for evaluation of volume density of collagen fibers, length and volume density of vessels, and numerical density of fibroblasts by stereological methods. RESULTS: AD-MSCs accelerated wound healing rate in diabetic rats, but did not increase length and volume density of the vessels and volume density of the collagen fibers. AD-MSCs decreased the numerical density of fibroblasts. CONCLUSIONS: We concluded that AD-MSCs enhances diabetic wound healing rate probably by other mechanisms rather than enhancing angiogenesis or accumulating collagen fibers.


Subject(s)
Adipose Tissue/cytology , Diabetes Mellitus, Experimental/pathology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/physiology , Skin/injuries , Wound Healing/physiology , Animals , Collagen , Diabetes Mellitus, Experimental/chemically induced , Fibroblasts , Neovascularization, Physiologic , Rats
4.
J Surg Res ; 169(1): e101-7, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21571319

ABSTRACT

OBJECTIVE: Impaired wound healing in diabetes is associated with decreased nitric oxide (NO) bioavailability in wound tissue. We hypothesized azelnidipine (AZL), a new calcium channel blocker with antioxidant properties, would enhance wound healing in streptozotocin-induced diabetic rats by restoring NO synthesis. METHODS: Twelve male rats were taken as non-diabetic group. Twenty four rats were taken and caused to be diabetic by a single streptozotocin injection. Diabetic rats were divided randomly to two groups: control and treatment. Half of non-diabetic and also diabetic rats (in each group of control and treatment) randomly served as excisional-wound model and the other half as nitrite-measurement model. Six weeks after causing diabetes, the excisional wound model underwent dorsal full-thickness excisional wounds (1 × 1 cm). After wound healing completion, full-thickness skin samples (1 × 1 cm) were taken from the wound sites for evaluation of stereological parameters. The nitrite-measurement model (6 wk after causing diabetes) underwent insertion of subcutaneous polyvinyl alcohol sponges in dorsum. The rats were killed 2 wk post-wounding, and wound fluid was analyzed. In the study, after wounding, the treatment groups were gavaged with AZL (3 mg/kg/d) and control and non-diabetic groups with AZL vehicle till euthanasia. RESULTS: AZL accelerated wound healing rate and also improved wound fluid NO level toward normal value in diabetic rats. Volume density of collagen fibers, numerical density of fibroblasts, and length density of vessels were increased in AZL-treated rats compared with control group. CONCLUSION: AZL administration promotes diabetic wound healing by stimulating NO production and enhancing histologic processes central to normal wound healing.


Subject(s)
Azetidinecarboxylic Acid/analogs & derivatives , Calcium Channel Blockers/pharmacology , Diabetes Mellitus, Experimental/physiopathology , Dihydropyridines/pharmacology , Skin/injuries , Wound Healing/drug effects , Animals , Azetidinecarboxylic Acid/pharmacology , Diabetes Mellitus, Experimental/metabolism , Disease Models, Animal , Male , Nitric Oxide/metabolism , Nitrites/metabolism , Rats , Skin/metabolism , Skin/pathology , Streptozocin , Wound Healing/physiology
5.
Anal Quant Cytol Histol ; 32(4): 186-91, 2010 Aug.
Article in English | MEDLINE | ID: mdl-21434518

ABSTRACT

OBJECTIVE: To determine whether botulinum toxin type A (BTX-A) exerts a lipolytic effect by interfering with acetylcholine transmission at the cholinergic parasympathetic nerve endings. STUDY DESIGN: Fifteen male rabbits were divided into 3 equal groups: 1 control group (A) and 2 case groups (B and C). The abdomens of all rabbits were divided into a 3 x 3-square grid. The groups received 9 subcutaneous injections of 0.9% normal saline, 1 U BTX-A (group B) and 2 U BTX-A (group C), respectively. Four weeks later the entire grid was excised from the abdominal area. Hematoxylin-eosin-stained tissue was used for stereologic analysis to estimate cell surface and volume in 100 randomly selected cells. RESULTS: Gross thinning of subcutaneous fat and shattering and disappearance of fat globules were seen in both case groups. Fat cell volume was reduced by 65% in group B (p = 0.009) and 77% in group C (p = 0.009) compared to control animals. Fat cell surface also decreased by 51% in group B (p = 0.009) and 63% in group C rabbits (p = 0.009) compared to control animals. CONCLUSION: Our pilot animal study revealed a dose-dependent lipolytic effect of subcutaneous BTX-A injection.


Subject(s)
Abdominal Fat/drug effects , Botulinum Toxins, Type A/pharmacology , Cholinergic Fibers/drug effects , Lipolysis/drug effects , Subcutaneous Fat/drug effects , Abdominal Fat/innervation , Acetylcholine/metabolism , Animals , Dose-Response Relationship, Drug , Injections, Subcutaneous , Male , Neuromuscular Agents/pharmacology , Obesity/drug therapy , Pilot Projects , Rabbits , Subcutaneous Fat/innervation
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