bromochloroacetic-acid and Diabetic-Foot

Diabetic foot is one of the most common long term complications of diabetes. The risk of developing a foot ulcer is significantly increased when a patient presents with a callus. Callus develops due to various reasons, of which, the most important in people with diabetes is peripheral neuropathy. Motor neuropathy leads to deformity and sensory neuropathy causes lack of sensation, which results in persistent abnormal pressure on the foot. The cells of skin react to it by increasing keratinization and turns into a callus, which predisposes to foot ulceration. However, there is a lack of research in the field of callus. The link between hyperkeratosis, insulin and hyperglycaemia is not fully explored. There is also a lack of research on the relationship between genetic defects of hyperkeratosis, and the risk of developing a diabetic foot ulcer. There is scope for further research in this area, such as exploring whether development of callus is an individual risk factor, and whether glycaemic control or its treatment has any relationship with callus formation. The research around the genetic defects of hyperkeratosis may lead to identification of those, with diabetes, who may have increased risk of developing a foot ulcer.

Topics: Bony Callus; Diabetic Foot; Diabetic Neuropathies; Foot Ulcer; Humans; Keratins; Skin; Skin Diseases

The aim of this study is to explore the localization of human mesenchymal stem cells from umbilical cord matrix (hMSCs-UC) and the role of these cells in the repair of foot ulcerate tissue in diabetic foot ulcers in rats. A diabetic rat model was established by administering Streptozotocin. Diabetic foot ulceration was defined as non-healing or delayed-healing of empyrosis on the dorsal hind foot after 14 weeks. hMSCs-UC were delivered through the left femoral artery. We evaluated the localization of hMSCs-UC and their role in tissue repair in diabetic foot ulcers by histological analysis, PCR, and immunohistochemical staining. A model for diabetes was established in 54 out of 60 rats (90% success rate) and 27 of these rats were treated with hMSCs-UC. The area of ulceration was significantly and progressively reduced at 7 and 14 days following treatment with hMSCs-UC. This gross observation was strongly supported by the histological changes, including newly developed blood vessels and proliferation of inflammatory cells at 3 days post-treatment, significant increase in granulation tissue at 7 days post-treatment and squamous epithelium or stratified squamous epithelium at 14 days post-treatment. Importantly, human leukocyte antigen type-I (HLA-1) was confirmed in ulcerated tissue by RT-PCR. The expression of cytokeratin 19 was significantly increased in diabetic model rats, with no detectable change in cytokeratin 10. Additionally, both collagens I and III increased in model rats treated with hMSCs-UC, but the ratio of collagen I/III was less significant in treated rats compared with control rats. These results suggest that hMSCs-UC specifically localize to the target ulcerated tissue and may promote the epithelialization of ulcerated tissue by stimulating the release of cytokeratin 19 from keratinocytes and extracellular matrix formation.

Topics: Animals; Base Sequence; Collagen; Diabetic Foot; DNA Primers; Fetal Blood; Keratins; Male; Mesenchymal Stem Cells; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Streptozocin; Umbilical Cord

Epithelialization of cutaneous ulcers is a long-lasting process. To study the pathomechanism of impaired epithelialization, we evaluated the role of cell cycle- and apoptosis-related proteins in the regenerating epidermis. We characterized immunohistochemically the expression of cell cycle regulators p63, CD29, PCNA, p53, pro- and antiapoptotic proteins bcl2, bax, caspase 3 and DNA breaks, as well as keratin 10, 16 and 17.. Studies were carried out in 12 patients with diabetic foot, and 10 patients with varicose ulcers of the calf. Skin biopsy specimens were obtained from the border area of ulcers and the topographically corresponding sites of normal skin of patients undergoing orthopedic surgery. Biopsy specimens were stained by use of specific primary antibodies, a kit based on biotin-avidin-peroxidase complex technique, and DAB substrate. Results were expressed as a mean staining intensity.. At the edge of both types of ulcers, keratinocytes were p63+, CD29+, PCNA+ and p53-. The mean intensity of p63 and CD29 staining was slightly higher than in controls. The intensity of bcl2 staining was higher at the edge of diabetic ulcers compared with venous ulcers, whereas the intensity of bax staining was similar. The expression of caspase 3 was lower at the edge of venous ulcers and higher in diabetic ulcers and the intensity of TUNEL staining was lower at the edge of both types of ulcers compared with controls. Keratinocytes at the edge and distally to both types of ulcers expressed cytokeratin 16 and 17. There was no expression of cytokeratin 10 at the edge of ulcers. Together, there was a slight tendency for higher expression of cell cycle-related proteins in venous and of apoptosis-related proteins in diabetic ulcers epidermis; however, the differences were minor.. The impaired epithelialization of chronic leg ulcers is not caused by an inadequate epidermal stem cell proliferation, differentiation, or apoptosis. It may rather reflect the distorted organization of wound bed, caused by infection and impaired nutrition supply, altering keratinocyte migration. To accelerate healing of an ulcer, modeling of the granulation tissue by regulatory cytokines but not stimulation of keratinocyte growth seems to be indicated.

Topics: Aged; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Caspases; Cell Cycle Proteins; Diabetic Foot; DNA Damage; Epidermis; Humans; Keratin-10; Keratins; Middle Aged; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Varicose Ulcer