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Valdez-Perez C.,Instituto Nacional Of Angiologia Y Cirugia Vascular | Savigne-Gutierrez W.,Instituto Nacional Of Angiologia Y Cirugia Vascular | Franco-Perez N.,Instituto Nacional Of Angiologia Y Cirugia Vascular | Vargas-Machiran E.,Instituto Nacional Of Angiologia Y Cirugia Vascular | And 4 more authors.
Biotecnologia Aplicada | Year: 2010

Impaired healing in diabetes affects the resolution of both acute and chronic wounds. The vicious circle between wound chronicity and a deficient control of local infection is the cause that diabetic patients constitute 85% of all non-traumatic lower extremity amputations. From an etiological viewpoint, hyperglycemia is what triggers the onset and progression of biochemical disturbances that lead to systemic complications. In contrast to normal wound healing, physiological apoptotic clearance of inflammatory cells is prevented and the inflammatory phase is abnormally prolonged in diabetic wounds. Pro-inflammatory cytokines as tumor necrosis factor-alpha (TNF-α) and interleukin-1β(IL-1β) are increased in diabetic wounds with negative local and remote consequences. The etiopathogenic network consisting of inflammatory cytokines, local proteases, reactive oxygen and nitrogen species produces a cytotoxic and pro-degradation environment within the wound bed that impairs granulation and re-epithelialization. The nonenzymatic glycation of proteins, generating advanced glycation end-products (AGE), acts as an active pathogenic stream affecting healing. The accumulation of AGE interferes with DNA replication, cell anchoring, migration and proliferation. The binding of AGE to a receptor model (RAGE) may completely hamper the healing process. Diabetes impairs the recruitment and differentiation of bone marrow-derived stem cells, thereby limiting the availability of tissue repair cells. Re-epithelialization is also hindered by incomplete activation and/or differentiation of keratinocytes that impair migration. Novel and revolutionary pharmacological interventions are urgently needed to reduce diabetes complications, such as amputations of the lower extremities. Source


Alvarez H.,Instituto Nacional Of Angiologia Y Cirugia Vascular | Perez C.,Ministerio de Salud Publica de Cuba | Yera I.,Centro Para El Control Of La Farmacoepidemiologia | Padron L.,Ministerio de Salud Publica de Cuba | Llanes J.A.,Instituto Nacional Of Angiologia Y Cirugia Vascular
Biotecnologia Aplicada | Year: 2010

The Cuban product Heberprot-P is indicated for the treatment of complex diabetic foot ulcers (DFU). After its registration in 2006, the product was included into the Cuban List of Medicines and a nationwide program for the integral care of the DFU patient began. To date Heberprot-P is available in more than 85 Cuban health institutions and more than 3 800 diabetic patients with ulcers in their feet have received the benefits of this unique product. An integral program has been established for the attention of the patient with DFU, including the advanced technology of Heberprot-P. This program relies on the closely linked and coordinated interaction between the primary and secondary levels of health, in which prevention and therapy merge each other. The Ministry of Public Health of Cuba has established impact indicators in order to control and assess the performance of the program. Source


Mencherini T.,University of Salerno | Campone L.,University of Salerno | Piccinelli A.L.,University of Salerno | Garcia Mesa M.,Instituto Nacional Of Angiologia Y Cirugia Vascular | And 3 more authors.
Journal of Agricultural and Food Chemistry | Year: 2013

The phytochemical profile of a hydroalcoholic extract of Citrus aurantium var. amara L. peel, used as herbal medicine, was characterized by HPLC-PDA-MS. Two di-C-glycosyl flavones (vincenin II and diosmetin 6,8-di-C-glucoside), a series of flavones (luteolin 7-O-neohesperidoside, rhoifolin, and neodiosmin), and flavanone (neoeriocitrin, naringin, and neohesperidin) 7-O-neohesperidosides and two methoxyflavones (nobiletin and tangeretin), commonly present in Citrus, were identified. Furthermore, brutieridin and melitidin, two 3-hydroxy-3-methylglutaryl flavanone glycosides, were also characterized along with rhoifolin 4′-glucoside and three coumarins (8,3′-β-d- glucopyranosyloxy-2′-hydroxy-3′-methylbutyl-7-methoxycoumarin, merazin hydrate, and isomerazin). A preparative isolation procedure followed by NMR spectroscopy confirmed the proposed structures of the major flavonoids and identified the coumarins. The phenolic content was found to be 14.8 mg mL -1, and naringin and neohesperidin were the compounds present in the highest concentration (3.6 and 2.6 mg mL-1). The extract of C. aurantium peel inhibited significantly (p < 0.05) both histamine- and dextran-induced edema in rats in a concentration-dependent manner (IC 50 = 119.6 and 118.3 mg kg-1, respectively), providing evidence for the therapeutic use of C. aurantium var. amara peel. © 2012 American Chemical Society. Source


Llanes J.A.,Instituto Nacional Of Angiologia Y Cirugia Vascular | Bejar J.,Instituto Nacional Of Angiologia Y Cirugia Vascular | Romero M.M.,Policlinico Docente 26 de Julio | Benavides T.,Policlinico Docente Jorge Ruiz Ramirez | And 3 more authors.
Biotecnologia Aplicada | Year: 2010

A model was introduced within the Program of Integral Attention to the Diabetic Patient (PIADP), in each policlinic of the Playa municipality in Havana, Cuba, and implemented under the integral treatment of patients with less complicated diabetic foot ulcers (DFU) and by using Heberprot-P to accelerate wound granulation and healing in an ambulatory manner. Since January of 2010, a strategy was developed in the primary health attention (PHA) of that municipality, constituted by three stages and including organizational elements such as: the elaboration of a Situational Room of the municipality, the qualification theoretical-practice of the human resources, the logistic securing, the redispensarization of diabetic patients, the programmed investigation in consultations and domiciliary visits; as well as elements of implementation: action of communitary promotion and mass media use. The application of the Heberprot-P started with the characterization of patient with DFU in the municipality and the selection of the human resources that would execute the treatment. All the 33 health professionals were prepared at each area, in the PIADP room, a system of filter for a suitable classification of the DFU was implemented. To date, 233 patients were treated, 28 of them (12.1%) requiring treatment with Heberprot-P, and their data being registered in pharmacovigilance models; 65 (27.8%) were sent to the secondary level of health, with complicated DFU and other vascular affections (60.1%). All except two of those patients, who completed treatment at the hospital, completed treatment at the PHA. The feasibility of the model by using Heberprot-P was demonstrated and an integral approach was established under intensive pharmacovigilance. Source


Valdez-Perez C.,Instituto Nacional Of Angiologia Y Cirugia Vascular | Puentes-Madera I.,Instituto Nacional Of Angiologia Y Cirugia Vascular | Savigne-Gutierrez W.,Instituto Nacional Of Angiologia Y Cirugia Vascular | Alvarez-Duarte H.,Instituto Nacional Of Angiologia Y Cirugia Vascular | And 2 more authors.
Biotecnologia Aplicada | Year: 2012

Type 2 diabetes mellitus comprises a group of non-communicable metabolic diseases with an expanding pandemic magnitude. Diabetes predisposes to lower extremities ulceration and impairs the healing process leading to wounds chronifi cation. Diabetes also dismantles innate immunity favoring wound infection. Amputation is therefore acknowledged as one of the disease's complications. Hyperglycemia appears as the proximal detonator of toxic effectors including pro-infl ammation, spillover of reactive oxygen and nitrogen species. The systemic accumulation of advanced glycation end-products irreversibly impairs the entire physiology from cells-to-organs. Insulin axis defi ciency weakens wounds' anabolism and predisposes to infl ammation. These factors converge to hamper fi broblasts and endothelial cells proliferation, migration, homing, secretion and organization of a productive granulation tissue. Diabetic wound bed may turn chronically infl amed, pro-catabolic and a superimposed source of circulating pro-infl ammatory cytokines, establishing a self-perpetuating loop. Diabetic toxicity breadth includes mitochondrial damages in fi broblasts and endothelial cells becoming prone to apoptosis thus hindering granulation. Endothelial progenitor cells recruitment and tubulogenesis are also impaired. Failure of wound reepithelialization remains as a clinical challenge while it appears to be biologically multifactorial. Novel medical interventions as the local intra-ulcer infi ltration of epidermal growth factor have emerged to hopefully reduce the current worldwide amputation rates. Source

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