Wound healing of diabetic rats treated with Moringa oleifera extract

Purpose: To evaluate if Moringa oleifera leaf aqueous extract (ME) influences the healing of skin wounds of diabetic rats. Methods: Wistar rats were used (6 rats/group). Group 1 received normal saline (NS) v.o. Group 2 received moringa extract (100mg/kg v.o) for 3 weeks. Groups 3 and 4: Streptozotocin (STZ) induced diabetes. Group 3 received NS; Group 4 received aqueous ME (100mg/kg) v.o.The wounds of groups 1 and 3 rats were topically treated with NS; wounds of groups 2 and 4 treated with 200µL of 10% ME. After anesthesia, all rats had skin square excision wounds 1.5cm2. Wound percent contractions were measured. On 10th day, blood glucose and serum cytokines were measured. Histometry of wounds was studied using ImagePro6.0 software. Results: Glycemia was significantly reduced in ME treated rats. These rats had higher percent contraction of the wounds on 2nd, 5th and 10th days, then controls (p<0.05). Diabetic rats treated with NS had TNF-α, IL-1β and IL-6 expression higher than in rats receiving ME. The histopathological score of ME treated diabetic rats (198±13.7) was significantly higher than treatment with NS (145±10.5). Conclusion: ME extract positively influenced healing of wounds in diabetic rats after systemic and topical treatment.(AU)

A curcumin derivative J147 ameliorates diabetic peripheral neuropathy in streptozotocin (STZ)-induced DPN rat models through negative regulation AMPK on TRPA1

Purpose: To investigate the specific molecular mechanisms and effects of curcumin derivative J147 on diabetic peripheral neuropathy (DPN). Methods: We constructed streptozotocin (STZ)-induced DPN rat models to detected mechanical withdrawal threshold (MWT) in vivo using Von Frey filaments. In vitro, we measured cell viability and apoptosis, adenosine 5-monophosphate-activated protein kinase (AMPK) and transient receptor potential A1 (TRPA1) expression using MTT, flow cytometry, qRT-PCR and western blot. Then, TRPA1 expression level and calcium reaction level were assessed in agonist AICAR treated RSC96cells. Results: The results showed that J147reduced MWT in vivo, increased the mRNA and protein level of AMPK, reduced TRPA1 expression and calcium reaction level in AITCR treated RSC96 cells, and had no obvious effect on cell viability and apoptosis. Besides, AMPK negative regulated TRPA1 expression in RSC96 cells. Conclusions: J147 could ameliorate DPN via negative regulation AMPK on TRPA1 in vivo and in vitro. A curcumin derivative J147might be a new therapeutic potential for the treatment of DPN.(AU)

Effect of melatonin on antioxidant capacity, inflammation and apoptotic cell death in lung tissue of diabetic rats

Purpose: To investigate the effects of melatonin on antioxidant capacity, inflammation and apoptotic cell death (through expression of cleaved-caspase 3) in lung tissue samples of diabetic rats. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control group) was made up of healthy rats. Group 2 (diabetes group) received streptozotocin at a dose of 50 mg/kg/day for 5 days.Group 3 (diabetes plus melatonin group) received streptozotocin at a dose of 50 mg/kg/day for 5 days and then they received melatonin at a dose of 20 mg/kg/day between 28th and 35th days of the study. Results: Tissue MDA and MPO levels were found to be significantly higher in diabetes group compared to control group (p< 0.05) whilst administration of melatonin was found to significantly lower this increase down to normal levels (p <0.05). Bronchus associated lymphoid tissue (BALT) was more severe in diabetics whereas administration of melatonin alleviated this hyperplasia. Cleaved caspase 3 activity was severe in hyperplastic BALT in diabetic rats however in lowered down to moderate level when melatonin was administered. Conclusion: The melatonin caused an increase in antioxidant capacity and decreased the expression of cleaved-caspase 3.(AU)

Pathological lesions and global DNA methylation in rat prostate under streptozotocin-induced diabetes and melatonin supplementation.

Chronic hyperglycemia increases production of reactive oxygen species, which favors carcinogenesis. The association between diabetes and prostate cancer is controversial. Melatonin has antioxidant, anti-inflammatory, and antiproliferative properties. We investigated whether low doses of melatonin prevent the tissue alterations caused by diabetes and alter prostate histology of healthy rats. We also investigated whether experimental diabetes promoted the development of pathological lesions in the ventral prostate of rats. Melatonin was provided in drinking water (10 µg/kg/day) from age 5 weeks until the end of experiment. Diabetes was induced at 13 weeks by administration of streptozotocin (40 mg/kg, ip). Rats were euthanized at 14 or 21 weeks. Histological and stereological analyses were carried out and the incidence and density of malignant and pre-malignant lesions were assessed. Immunohistochemical assays of α-actin, cell proliferation (PCNA), Bcl-2, glutathione S-transferase (GSTPI), and DNA methylation (5-methylcytidine) were performed. Melatonin did not elicit conspicuous changes in the prostate of healthy animals; in diabetic animals there was a higher incidence of atrophy (93%), microinvasive carcinoma (10%), proliferative inflammatory atrophy, PIA (13%), prostatitis (26%), and prostate intraepithelial neoplasia, PIN (20%) associated with an increase of 40% in global DNA methylation. Melatonin attenuated epithelial and smooth muscle cell (smc) atrophy, especially at short-term diabetes-and normalized incidence of PIN (11%), inflammatory cells infiltrates, prostatitis (0%) and PIA (0%) at long-term diabetes. MLT was effective in preventing inflammatory disorders and PIN under diabetic condition. Although MLT has antioxidant action, it did not influence DNA methylation and not avoid carcinogenesis at low doses.

Modelo de sistema basado en conocimiento para apoyo en la investigación y p'roceso clínico de la diabetes / Knowledge-based system model to support diabetes research and clinical process

Due to the great amount of information generated and supported by the explosive evolution of computer science systems since the end of the last century, the expansion and transference of scientific knowledge has caused a rapid transformation of scientific discoveries in products and applications that have positive effects in the life quality of societies. Today, a great amount of data in medicine is obtained by the application of biotechnological methods that constantly evolve. Thus, scientific research related to diabetes keeps improving. In this context, productivity and competitiveness must be sustained on knowledge which facilitates and encourages organizational innovation capacity. For this reason, knowledge based systems emerge as a useful tool to help organizations solve difficult assignments or improve their processes. In this work, derivate from known diabetes group of symptoms and interactions that diabetes research maintains with the biotechnological processes, the authors carried out a brief analysis of the knowledge involved as well as the role that knowledge-based systems have played, and keep playing in support of them. Additionally, with the systemic perspective obtained by the authors regarding aspects like knowledge, practices and resources needed in clinical and laboratory practices, they propose a systemic model that can support diabetes research and clinical process.

Debido a la gran cantidad de información generada y apoyada por la evolución explosiva de sistemas de la ciencia computacional, desde finales del siglo pasado, la expansión y transferencia de conocimiento científico ha provocado una rápida transformación de los descubrimientos científicos en productos y aplicaciones que afectan positivamente la calidad de vida de las sociedades. Actualmente, una gran cantidad de datos en medicina se obtiene por la aplicación de métodos biotecnológicos que constantemente evolucionan. De igual manera, la investigación científica sobre diabetes mantiene una mejora constante. En este contexto, tanto la productividad como la competitividad se deben apoyar con conocimiento que facilite y promueva la capacidad de innovación organizacional. Por esta razón, los sistemas basados en conocimiento emergen como una herramienta útil para coadyuvar con las organizaciones en la solución de situaciones difíciles o en la mejora de sus procesos. En este trabajo, derivado del conocido grupo de síntomas y de las interacciones que la investigación en diabetes mantiene con los procesos biotecnológicos, los autores realizan un breve análisis del conocimiento implicado y del rol que los sistemas basados en el conocimiento han desempeñado, -y continúan desempeñando, en apoyo a tales procesos. Adicionalmente, con la perspectiva sistémica obtenida por los autores respecto al conocimiento y recursos necesarios en prácticas clínicas y de laboratorio, proponen un modelo sistémico capaz de apoyar la investigación y el proceso clínico de la diabetes.

Myoglobin-H2O2 catalyzes the oxidation of ß-ketoacids to α-dicarbonyls: mechanism and implications in ketosis.

Acetoacetate (AA) and 2-methylacetoacetate (MAA) are accumulated in metabolic disorders such as diabetes and isoleucinemia. Here we examine the mechanism of AA and MAA aerobic oxidation initiated by myoglobin (Mb)/H(2)O(2). We propose a chemiluminescent route involving a dioxetanone intermediate whose thermolysis yields triplet α-dicarbonyl species (methylglyoxal and diacetyl). The observed ultraweak chemiluminescence increased linearly on raising the concentration of either Mb (10-500 µM) or AA (10-100 mM). Oxygen uptake studies revealed that MAA is almost a 100-fold more reactive than AA. EPR spin-trapping studies with MNP/MAA revealed the intermediacy of an α-carbon-centered radical and acetyl radical. The latter radical, probably derived from triplet diacetyl, is totally suppressed by sorbate, a well-known quencher of triplet carbonyls. Furthermore, an EPR signal assignable to MNP-AA(•) adduct was observed and confirmed by isotope effects. Oxygen consumption and α-dicarbonyl yield were shown to be dependent on AA or MAA concentrations (1-50 mM) and on H(2)O(2) or tert-butOOH added to the Mb-containing reaction mixtures. That ferrylMb is involved in a peroxidase cycle acting on the substrates is suggested by the reaction pH profiles and immunospin-trapping experiments. The generation of radicals and triplet dicarbonyl products by Mb/H(2)O(2)/ß-ketoacids may contribute to the adverse health effects of ketogenic unbalance.

Glibenclamide action on myocardial function and arrhythmia incidence in the healthy and diabetic heart.

Myocardial sarcolemmal ATP-dependent potassium (KATP) channels, which are normally closed by high ATP concentration, open during ischemia when ATP generation decreases favoring K(+) efflux. This reduces action potential duration (APD) decreasing the time of Ca(2+) influx and Ca(2+) overload. This behavior suggested that they might be involved in the protection against stunning and arrhythmias and in the mechanism of ischemic preconditioning. Sulfonylureas, used as hypoglycemic agents for the treatment of type 2 diabetes also block myocardial KATP channels prolonging APD during ischemia, which by allowing Ca(2+) entry for a longer period of time, is potentially harmful to the heart. Controversial findings have been reported regarding the protective effect of sulfonylureas. Due to their importance in the clinical setting, their action on the heart of large conscious animal models is relevant. The effect of glibenclamide, a representative sulfonylurea, has been studied in a conscious sheep model submitted to regional 12 min ischemia. Glibenclamide (0.4 mg/kg) completely blocked KATP channels, as assessed by monophasic APD, producing a deleterious effect on reperfusion-induced arrhythmias and myocardial recovery from stunning in normal animals. This adverse effect was more noticeable in alloxan-induced diabetic sheep, where a lower dose (0.1 mg/kg) inhibited KATP channel opening worsening mechanical recovery and arrhythmia incidence. However, glibenclamide did not abolish ischemic late preconditioning against stunning and arrhythmias in normal animals. Because diabetic sheep do not develop this cardioprotective phenomenon, probably due to KATP channel dysfunction, it was not possible to assess glibenclamide effect on preconditioning in this pathological condition. In conclusion, in large conscious animals, glibenclamide interferes with the beneficial action of KATP channel opening during acute ischemia-reperfusion events both in normal and diabetic animals. Therefore, despite some studies claiming no added cardiovascular risk due to glibenclamide treatment, this pharmacological agent should be further investigated to ensure its safe administration in patients with concurrent heart disease.

Comparison between wound healing in induced diabetic and nondiabetic rats after low-level laser therapy.

OBJECTIVE: The aim of this work was to compare the effect of low-level laser therapy (LLLT) on the wound healing process in nondiabetic and diabetic rats. BACKGROUND DATA: Among the clinical symptoms caused by diabetes mellitus, a delay in wound healing is a potential risk for patients. It is suggested that LLLT can improve wound healing. METHODS: The tissue used for this study was extracted from animals suffering from diabetes, which was induced by Streptozotocin, and from nondiabetic rats. Animals were assembled into two groups of 25 rats each (treated and control) and further subdivided into two groups: diabetic (n = 15) and nondiabetic (n = 10). A full-thickness skin wound was made on the dorsum area, with a round 8-mm holepunch. The treated group was irradiated by a HeNe laser at 632.8 nm, with the following parameters: 15 mW, exposition time of 17 sec, 0.025 cm2 irradiated area, and energy density of 10 J/cm2. Square full-thickness skin samples (18 mm each side, including both injured and noninjured tissues) were obtained at 4, 7, and 15 days after surgery and analyzed by qualitative and quantitative histological methods. RESULTS: Quantitative histopathological analysis confirmed the results of the qualitative analysis through histological microscope slides. When comparing tissue components (inflammatory cells, vessels and fibroblast/area), we found that treated animals had a less intense inflammatory process than controls. CONCLUSION: Results obtained by both qualitative and quantitative analyses suggested that irradiation of rats with HeNe (632.8 nm), at the tested dose, promoted efficient wound healing in both nondiabetic and diabetic rats as, compared to the control group.