The inflammatory stimulus of a natural latex biomembrane improves healing in mice

The aim of the present study was to compare healing obtained with biomembranes with the natural healing process (sham) using biochemical and immunohistological assays. C57BL/6 mice were divided into 4 groups of 15 mice each and received different subcutaneous implants: natural latex biomembrane (NLB), denatured latex (DL), expanded polytetrafluorethylene (ePTFE), or sham. On the 2nd, 7th, and 14th days post-treatment, 5 mice per group were sacrificed and biopsied for the following measurements: oxidative stress based on malondialdehyde (MDA), myeloperoxidase (MPO) and hydrogen peroxide by the method of ferrous oxidation-xylenol orange (FOX), as well as glutathione and total proteins; histological evaluation to enumerate inflammatory cells, fibroblasts, blood vessels, and collagen, and immunohistochemical staining for inducible nitric oxide synthase, interleukin-1β, vascular endothelial growth factor (VEGF), and transforming growth factor-β1 (TGF-β1). On day 2 post-treatment, NLB stimulated a dense inflammatory infiltrate mainly consisting of polymorphonuclear cells, as indicated by increased MPO (P < 0.05), but oxidative stress due to MDA was not observed until the 7th day (P < 0.05). The number of blood vessels was greater in NLB (P < 0.05) and DL (P < 0.05) mice compared to sham animals on day 14. NLB induced fibroplasia by day 14 (P < 0.05) with low expression of TGF-β1 and collagenesis. Thus, NLB significantly induced the inflammatory phase of healing mediated by oxidative stress, which appeared to influence the subsequent phases such as angiogenesis (with low expression of VEGF) and fibroplasia (independent of TGF-β1) without influencing collagenesis.

Use of anti-PGL-1 antibodies to monitor therapy regimes in leprosy patients

The suitability of IgM antibodies to PGL-1 for monitoring the response to multidrug therapy (MDT) was sequentially tested by ELISA in 105 leprosy patients, and bacterial indexes (BI) were also determined. Patients were divided into 3 groups: group 1, 34 multibacillary (MB) patients treated for 12 months with MDT-MB; group 2, 33 MB patients treated for 24 months with MDT-MB, and group 3, 38 paucibacillary (PB) patients treated for 6 months with MDT-PB. Untreated MB patients exhibited higher antibody levels (mean ± SEM): group 1 (6.95 ± 1.35) and group 2 (12.53 ± 2.02) than untreated PB patients (1.28 ± 0.35). There was a significant difference (P < 0.01) in anti-PGL-1 levels in group 1 patients: untreated (6.95 ± 1.35) and treated for 12 months (2.78 ± 0.69) and in group 2 patients: untreated (12.53 ± 2.02) and treated for 24 months (2.62 ± 0.79). There was no significant difference between untreated (1.28 ± 0.35) and treated (0.62 ± 0.12) PB patients. Antibody levels correlated with BI. The correlation coefficient (Pearson’s r) was 0.72 before and 0.23 (P < 0.05) after treatment in group 1 and 0.67 before and 0.96 (P < 0.05) after treatment in group 2. BI was significantly reduced (P < 0.01) after 12 and 24 months on MDT (group 1: 1.26-0.26; group 2: 1.66-0.36). Our data indicate that monitoring anti-PGL-1 levels during MDT may be a sensitive tool for evaluating treatment efficacy. These data also indicate that the control of leprosy infection can be obtained with 12 months of MDT in MB patients.

Effect of metabolic control on interferon-gamma and interleukin-10 production by peripheral blood mononuclear cells from type 1 and type 2 diabetic patients

The objective of the present study was to evaluate the production of cytokines, interferon-g (INF-g) and interleukin-10 (IL-10), in cultures of peripheral blood mononuclear cells (PBMC) from type 1 and type 2 diabetic patients and to correlate it with inadequate and adequate metabolic control. We studied 11 type 1 and 13 type 2 diabetic patients and 21 healthy individuals divided into two groups (N = 11 and 10) paired by sex and age with type 1 and type 2 diabetic patients. The PBMC cultures were stimulated with concanavalin-A to measure INF-g and IL-10 supernatant concentration by ELISA. For patients with inadequate metabolic control, the cultures were performed on the first day of hospitalization and again after intensive treatment to achieve adequate control. INF-g levels in the supernatants of type 1 diabetic patient cultures were higher compared to type 2 diabetic patients with adequate metabolic control (P < 0.001). Additionally, INF-g and IL-10 tended to increase the liberation of PBMC from type 1 and 2 diabetic patients with adequate metabolic control (P = 0.009 and 0.09, respectively). The increased levels of INF-g and IL-10 released from PBMC of type 1 and 2 diabetic patients with adequate metabolic control suggest that diabetic control improves the capacity of activation and maintenance of the immune response, reducing the susceptibility to infections.

Dermatoses em pacientes com diabetes mellitus / Skin lesions in diabetic patients

Ainda é desconhecida a relação do diabetes com fatores determinantes ou precipitantes de lesões dermatológicas em pacientes diabéticos. Assim, o objetivo do estudo foi investigar a presença de lesões cutâneas, não referidas pelo paciente diabético e sua relação com o controle metabólico da doença. MÉTODOS: Foram examinados 403 pacientes, dos quais 31 por cento eram diabéticos do tipo 1 e 69 por cento do tipo 2. Em ambulatório de um hospital universitário, os pacientes foram atendidos por endocrinologista para a avaliação endócrino-metabólica e por dermatologista para a avaliação dermatológica. O grau de controle metabólico foi documentado em 136 pacientes por meio da dosagem de hemoglobina glicada. RESULTADOS: Houve predomínio de dermatofitoses (82,6 por cento), seguido de grupo de dermatoses como acne e degeneração actínica (66,7 por cento), piodermites (5 por cento), tumores cutâneos (3 por cento) e necrobiose lipoídica (1 por cento). Entre as dermatoses mais comuns em diabéticos, foram confirmados com exame histológico: dois diagnósticos de necrobiose (0,4 por cento), cinco de dermopatia diabética (1,2 por cento) e três casos de mal perfurante plantar (0,7 por cento). Os valores da hemoglobina glicada foram: 7,2 por cento em pacientes com controle metabólico adequado nos dois tipos de diabetes e de 11,9 por cento e 12,7 por cento nos tipos 1 e 2, respectivamente, com controle inadequado. Nos pacientes com controle metabólico inadequado foi observada freqüência maior de dermatofitoses, em ambos os tipos de diabetes. CONCLUSÕES: Os dados revelaram freqüência elevada de lesão dermatológica nos pacientes diabéticos, especialmente dermatofitoses. Dessa forma, o descontrole metabólico do diabético propicia maior suscetibilidade a infecções cutâneas.

Nephrotoxicity attributed to meglumine antimoniate (glucantime) in the treatment of generalized cutaneous leishmaniasis

Antimoniais pentavalentes sao importantes no tratamento da leishmaniose. Seus efeitos mais graves que tem sido relatados sao o aumento do nivel de enzimas hepaticas e anormalidades eletrocardiograficas. Nefrotoxicidade tem sido raramente relatada. Nos relatamos um caso de leishmaniose cutanea generalizada, envolvendo um paciente masculino de 50 anos de idade, que foi submetido ao tratamento com Glucantime. Ele desenvolveu insuficiencia renal devido a necrose tubular aguda e depois veio a obito; apos receber um total de 53 ampolas de Glucantime. O tratamento com o Glucantime foi o responsavel pela necrose tubular aguda diagnosticada em nosso caso

Anti-PGL1 levels in leprosy patients and their contacts

1. We determined the anti-PGL1 levels of 402 individuals from the Ribeir ao Preto region since the phenolic glycolipid (PGL1) is a specific Mycobacterium leprae antigen. This group consisted of 47 leprosy patients (26 with the lepromatous form, 16 with the tuberculoid form and 5 with the borderline form), 12 tuberculosis patients, 19 leprosy contacts, and 324 healthy blood donors from the Hemocenter of the University Hospital, Faculty of Medicine of Ribeir ao Preto, University of S ao Paulo. Anti-PGL1 levels were detected by ELISA. 2. Anti-PGL1 levels were normal in patients with tuberculoid and borderline leprosy, in tuberculosis patients and in almost all of the healthy blood donors. Patients with untreated lepromatous leprosy had elevated anti-PGL1 levels while most patients under treatment (9/16) had normal anti-PGL1 levels. Only 3 per cent of blood donors (10/324) had elevated anti-PGL1 levels, but when these individuals were submitted to clinical and bacilloscopic examination no signs of disease were found. To complete the clinical investigation, these 10 subjects were submitted to the Mitsuda reaction which was negative in 3 of them. All of these 10 subjects are being monitored, since they may be at risk to develop leprosy. 3. On the basis of the present data, it seems that ELISA is a potentially important assay for the detection and chemotherapy of subclinical leprosy, permitting the control of epidemic centers of the disease

Serum levels of tumor necrosis factor in insulin-dependent diabetic patients

We determined the serum concentrations of tumor necrosis factor (TNF) in 15 nondiabetic healthy subjects and in 36 insulin-dependent (Type I) diabetic outpatients. The mean (ñ SD) annual fasting plasma glucose, urine glucose and HbA, levels of the diabetic group were 179 ñ 71 mg/dl, 13.0 ñ 13.2 g/day and 12.3 ñ 1.3%, respectively. The mean serum TNF concentration measured by immunoradiometric assay of the diabetic group *8.6 ñ 1.9 pg/ml) was significantly higher than healthy controls (6.9 ñ 0.9 pg/ml). Within the diabetic group, there was no correlation between serum TNF levels and either duration of diabetes or indices of metabolic control. However, serum TNF levels progressively increased from the well to the poorly controlled diabetic groups: 8.1 ñ 1.5 (G), 8.2 ñ 1.4 %): 8.4 ñ 2.4, 11.7 ñ 1.8 and 14.6 ñ 1.2, respectively. Serum TNF levels of the diabetic patients with chronic complications (N=7, 9.5 ñ 2.3 pg/ml) and without complications (N=29, 8.4 ñ 1.7 pg/ml) were statistically higher than control subjects. The progressive increase of the serum TNF levels from the the poorly controlled diabetic groups suggest a relationship between levels of this cytokine glycosylation

Inflammation induced by a glycolipid fraction from Mycobacterium leprae

1. The inflammatory properties of a glycolipid fraction isolated from human recovered Mycobacterium leprae were investigated. The inflammatory reaction induced in mouse lung by the inoculation of the glycolipid fraction adsorbed to charcoal particles was characterized by a large influx of macrophages at various stages of maturation and of epithelioid cells around the particles. 2. When injected as aqueous emulsion into the footpad of mice, the same fraction evoked a dose-dependent massive influx of mononuclear (MN) cells. The inflammatory reaction reached a peak at 6 days. The minimal effective dose of glycolipid was 0.1 microng. 3. The kinetics of inflammatory cell migration was studied by total and differential counts of leucocytes that migrated to the peritoneal cavity of mice inoculated intraperitoneally with the glycolipid fraction. This fraction initially induced intense polymorphonuclear (PMN) migration, which was later reduced, with a simultaneous increase in MN cells. 4. Adherent peritoneal cells (APC) incubated with glycolipid released one or more soluble factor9s) which induce active PMN and MN cell chemotaxis in vivo as well as in vitro. Thus, the MN cells may be atracted to the site of glycolipid incolulation by factor(s) released through the interaction of macrophages with the glycolipid fraction. 5. the present results demonstrate that a glycolipid containing trehalose and mycolic acid isolated from M. leprae reproduces some aspects of the fundamental lesion of leprosy