Relationship among Short and Long Term of Hypoinsulinemia-Hyperglycemia, Dermatophytosis, and Immunobiology of Mononuclear Phagocytes.

Dermatophytes are fungi responsible for causing superficial infections. In patients with diabetes mellitus (DM), dermatophytosis is usually more severe and recurrent. In the present study, we aimed to investigate the influence of short and long term hypoinsulinemia-hyperglycemia (HH) during experimental infection by Trichophyton mentagrophytes as well as alterations in the mononuclear phagocytes. Our results showed two distinct profiles of fungal outcome and immune response. Short term HH induced a discrete impaired proinflammatory response by peritoneal adherent cells (PAC) and a delayed fungal clearance. Moreover, long term HH mice showed low and persistent fungal load and a marked reduction in the production of TNF-α by PAC. Furthermore, while the inoculation of TM in non-HH mice triggered high influx of Gr1(+) monocytes into the peripheral blood, long term HH mice showed low percentage of these cells. Thus, our results demonstrate that the time of exposure of HH interferes with the TM infection outcome as well as the immunobiology of mononuclear phagocytes, including fresh monocyte recruitment from bone marrow and PAC activity.

Continuous electrical current and zinc sulphate administered by transdermal iontophoresis improves skin healing in diabetic rats induced by alloxan: morphological and ultrastructural analysis.

PURPOSE: Evaluated the effects of continuous electrical current (CEC) or zinc administrated by transdermal iontophoresis (Zn+TDI). METHODS: 120 male Wistar rats were submitted to an incision surgery at the anterior region of abdomen and distributed into 6 experimental groups with 40 animals: 3 diabetic groups and 3 normal groups, untreated and treated with CEC alone or with Zn + TDI. Each group was further divided into 4 subgroups with 10 rats each to be evaluated on the 4th, 7th, 14th, and 21st day after surgery. In each period, clinical and laboratory parameters from the animals were analyzed. RESULTS: The analysis by optical and scanning electron microscopy showed a delay in the phases of wound healing in diabetic rats without treatment in all periods of the experiment; breaking strength (BS) was significantly reduced in skin scars of untreated diabetic rats when compared to other groups. In contrast, BS in skin scars of nondiabetic groups and diabetic rats treated with Zn + TDI showed significant increase in those, besides not presenting delayed healing. CONCLUSION: Electrical stimulation of surgical wounds used alone or in association with zinc by TDI is able to consistently improve the morphological and ultrastructural changes observed in the healing of diabetic animals.

Inhibition of δ-aminolevulinate dehydratase is not closely related to the development of hyperglycemia in alloxan-induced diabetic mice.

Alloxan is a compound widely used in models of diabetes mellitus due to its ability for damage insulin-producing ß-cells. The aim of this study was to investigate acute (after 24h) and sub-acute (after seven days) effects of 200mg/kg alloxan administration on mice. Biochemical parameters as liver, kidney, and blood δ-ALA-D activity, total sulfhydryl content of hepatic and renal tissues, and hepatic and renal content of malondialdehyde (MDA) were evaluated. The histopathology of hepatic and renal tissues of alloxan-treated and control animals was carried out. Further, blood glucose levels were determined in an attempt to correlate alloxan-induced hyperglycemia with changes in thiol status. Results showed that mice exhibited a significant inhibition of hepatic and renal δ-ALA-D activity in addition to a significant decrease in total sulfhydryl groups of same tissues in both acute and sub-acute alloxan administrations. Moreover, alloxan-induced inhibition of δ-ALA-D activity was partly suppressed when enzymatic assay was performed in the presence of dithiothreitol, suggesting that inhibitory effect of alloxan on δ-ALA-D activity is, at least partially, related to the oxidation of the enzyme's essential thiol groups. Blood δ-ALA-D activity was significantly inhibited only 24h after alloxan administration; however, at this time, a hyperglycemic status was not observed in animals. In contrast, a significant increase in blood glucose levels was observed seven days after alloxan administration. Despite of alterations in biochemical parameters, histological tissue examination of alloxan-treated mice revealed typical renal and hepatic parenchyma. Therefore, these results showed that acute toxic effects of alloxan are related, at least partially, to depletion of sulfhydryl groups, and do not closely relate to the development of hyperglycemia in mice.

Alloxan-dialuric acid cycling: a complex redox mechanism.

Time-resolved kinetic studies involving the reactions of alloxan (A.H(2)O) with the reducing species superoxide and carbon dioxide radical anions and the reaction of dialuric acid (HA(-)) with sulphate radicals showed that the same radical (AH(.)) was formed either by the one-electron reduction of alloxan or by the one-electron oxidation of dialuric acid. A mechanism including several reversible reactions was proposed and validated. A detailed kinetic analysis yields the following bimolecular rate constants: k(A.H(2)O + [image omitted] ) < 10(5) m ( -1 ) s(-1), k(A.H(2)O + O(2) (-))=(3.4+/-0.5)x10(6) m ( -1 ) s(-1), k(HA(-)+[image omitted] )=(8+/-1)x10(7) m ( -1 ) s(-1) and k(AH(.)+AH(.))=(1.7+/-0.8)x10(8) m ( -1 ) s(-1). From these values, the redox potentials E degrees (A.H(2)O,H(+)/AH(.))=(-290+/-20) mV, E degrees (AH(.)/HA(-))=(277+/-20) mV and E degrees (A.H(2)O,H(+)/HA(-))=(-15+/-20) mV, were obtained.