Leandro Rodrigues

New method for evaluation of cutaneous sensibility in diabetic feet: preliminary report

UNLABELLED Diabetic neuropathy is an important complication of the disease, responsible for ulceration and amputation of the foot. Prevention of these problems is difficult mainly because there is no method to correctly access sensibility on the skin of the foot. The introduction of the Pressure-Specified Sensory Device (PSSD) in the last decade made possible the measurement of pressure thresholds sensed by the patient, such as touch, both static and in movement, on a continuous scale. This paper is the first in Brazil to report the use of this device to measure cutaneous sensibility in 3 areas of the foot: the hallux pulp, the calcaneus, and the dorsum, which are territories of the tibial and fibular nerves. METHOD Non-diabetic patients were measured as controls, and 2 groups of diabetic patients - with and without ulcers - were compared. The PSSD was used to test the 3 areas described above. The following were evaluated: 1 PS (1-point static), 1 PD (1-point dynamic), 2 PS (2-points static), 2 PD (2-points dynamic). RESULTS The diabetic group had poorer sensibility compared to controls and diabetics with ulcers had poorer sensibility when compared to diabetics without ulcers. The differences were statistically significant (P <.001). CONCLUSION Due to the small number of patients compared, the results should be taken as a preliminary report.

Protective effects of exogenous and endogenous hydrogen sulfide in mast cell-mediated pruritus and cutaneous acute inflammation in mice

Graphical abstract Figure. No caption available. ABSTRACT The recently described ‘gasomediator’ hydrogen sulfide (H2S) has been involved in pain mechanisms, but its effect on pruritus, a sensory modality that similarly to pain acts as a protective mechanism, is poorly known and controversial. The effects of the slow‐releasing (GYY4137) and spontaneous H2S donors (Na2S and Lawessons reagent, LR) were evaluated in histamine and compound 48/80 (C48/80)‐dependent dorsal skin pruritus and inflammation in male BALB/c mice. Animals were intradermally (i.d.) injected with C48/80 (3 &mgr;g/site) or histamine (1 &mgr;mol/site) alone or co‐injected with Na2S, LR or GYY4137 (within the 0.3–100 nmol range). The involvement of endogenous H2S and KATP channel‐dependent mechanism were also evaluated. Pruritus was assessed by the number of scratching bouts, whilst skin inflammation was evaluated by the extravascular accumulation of intravenously injected 125I‐albumin (plasma extravasation) and myeloperoxidase (MPO) activity (neutrophil recruitment). Histamine or C48/80 significantly evoked itching behavior paralleled by plasma extravasation and increased MPO activity. Na2S and LR significantly ameliorated histamine or C48/80‐induced pruritus and inflammation, although these effects were less pronounced or absent with GYY4137. Inhibition of endogenous H2S synthesis increased both Tyrode and C48/80‐induced responses in the skin, whereas the blockade of KATP channels by glibenclamide did not. H2S‐releasing donors significantly attenuate C48/80‐induced mast cell degranulation either in vivo or in vitro. We provide first evidences that H2S donors confer protective effect against histamine‐mediated acute pruritus and cutaneous inflammation. These effects can be mediated, at least in part, by stabilizing mast cells, known to contain multiple mediators and to be primary initiators of allergic processes, thus making of H2S donors a potential alternative/complementary therapy for treating inflammatory allergic skin diseases and related pruritus.

Retalho ósseo pré-fabricado com osso homógeno: estudo da maturação óssea em um modelo experimental

As conventional options for bone repair are not satisfactory, a new flap category was developed, the prefabricated flap (RPF). 42 metatarsic-I bone were obtained from 21 Wistar rats, and divided in two groups: group I (n=21) the bones were freeze- dryed and decalcified and group II (n=21) was frozen to - 70o C. After 3 weeks the bones were grafted in 21 rats, onto the left na right inferior epigastric vessels wrapped in silicon sheet. Groups I and II were subdivided in 3 groups each, following the period of permanence (1,2 or 4 weeks). In macroscopic histologic study, group I revealed loss of bone architecture and group II manteined its concistency and shape. In quantitative analysis, alterations were observed in group I, mainly inthe 2 weeks group. There is a histologic difference in prefabricated bone flaps betwenn groups I and II. Gradual bone reabsorption suggests that the flap should be rotated early. This study shows the applicability of homogenous bone for flap prefabrication.

Hydrogen sulfide donors alleviate itch secondary to the activation of type-2 protease activated receptors (PAR-2) in mice.

Hydrogen sulfide (H2S) has been highlighted as an endogenous signaling molecule and we have previously found that it can inhibit histamine-mediated itching. Pruritus is the most common symptom of cutaneous diseases and anti-histamines are the usual treatment; however, anti-histamine-resistant pruritus is common in some clinical settings. In this way, the involvement of mediators other than histamine in the context of pruritus requires new therapeutic targets. Considering that the activation of proteinase-activated receptor 2 (PAR-2) is involved in pruritus both in rodents and humans, in this study we investigated the effect of H2S donors on the acute scratching behavior mediated by PAR-2 activation in mice, as well as some of the possible pharmacological mechanisms involved. The intradermal injection of the PAR-2 peptide agonist SLIGRL-NH2 (8-80nmol) caused a dose-dependent scratching that was unaffected by intraperitoneal pre-treatment with the histamine H1 antagonist pyrilamine (30mg/kg). Co-injection of SLIGRL-NH2 (40nmol) with either the slow-release H2S donor GYY4137 (1 and 3nmol) or the spontaneous donor NaHS (1 and 0.3nmol) significantly reduced pruritus. Co-treatment with the KATP channel blocker glibenclamide (200nmol) or the nitric oxide (NO) donor sodium nitroprusside (10nmol) abolished the antipruritic effects of NaHS; however, the specific soluble guanylyl cyclase inhibitor ODQ (30μg) had no significant effects. The transient receptor potential ankyrin type 1 (TRPA1) antagonist HC-030031 (20μg) significantly reduced SLIGRL-NH2-induced pruritus; however pruritus induced by the TRPA1 agonist AITC (1000nmol) was unaffected by NaHS. Based on these data, we conclude that pruritus secondary to PAR-2 activation can be reduced by H2S, which acts through KATP channel opening and involves NO in a cyclic guanosine monophosphate (cGMP)-independent manner. Furthermore, TRPA1 receptors mediate the pruritus induced by activation of PAR-2, but H2S does not interfere with this pathway. These results provide additional support for the development of new therapeutical alternatives, mainly intended for treatment of pruritus in patients unresponsive to anti-histamines.

Alterações histológicas em enxerto de osso homógeno preparado e armazenado com duas técnicas diferentes

This research analyzes histologic alterations in allogenic bone graft from rats wich were prepared in two different ways. In one group (n=6), metatarsic-l bones not descalcified were stored at -70°C. In the other (n=6), the bones were desminerlised and freeze-drying. The bones were grafted into the groin region of rats and studied 30 days after. In the macroscopic evaluation, the bones not descalcified and stored at -70°C were surrounded by a thin capsule with consistency of cortical bone. Microscopically, it was observed reabsorption of endostal area with a decrease in the cortical thickness, and increase in the intracortical cavity. The bones descalcified and freeze-drying, in a macroscopic evaluation, were surrounded by a thick capsule and the consistency of the bone was softened. Microscopically, the bone showed a tissue without cells and vases, wich was very similar to cartilage; and a thick and fibrous capsule with inflamatory cells. Therefore, there were histologic differences in the allogenic bone grafts, and these differences depend on the way the bone was prepared and stored.