Granzyme B Produced by Natural Killer Cells Enhances Inflammatory Response and Contributes to the Immunopathology of Cutaneous Leishmaniasis.

BACKGROUND: Skin lesions from patients infected with Leishmania braziliensis has been associated with inflammation induced by cytotoxic CD8+ T cells. In addition, CD8+ T cell-mediated cytotoxicity has not been linked to parasite killing. Meanwhile, the cytotoxic role played by natural killer (NK) cells in cutaneous leishmaniasis (CL) remains poorly understood. METHODS: In this study, we observed higher frequencies of NK cells in the peripheral blood of CL patients compared with healthy subjects, and that NK cells expressed more interferon-γ, tumor necrosis factor (TNF), granzyme B, and perforin than CD8+ T cells. RESULTS: We also found that most of the cytotoxic activity in CL lesions was triggered by NK cells, and that the high levels of granzyme B produced in CL lesions was associated with larger lesion size. Furthermore, an in vitro blockade of granzyme B was observed to decrease TNF production. CONCCLUSIONS: Our data, taken together, suggest an important role by NK cells in inducing inflammation in CL, thereby contributing to disease immunopathology.

Key topics for making decisions on decorporation terapies.

Decorporation therapies increase the excretion of the incorporated material and therefore may reduce the probability of the occurrence of stochastic effects and may avoid deterministic effects in persons internally contaminated with radionuclides. The decision to initiate decorporation therapy should consider the effects of treatment in relation to the benefit provided. The literature presents threshold values above which treatment is recommended. The objective of this work is to collect and summarize recommendations on decorporation therapy. Ten key topics are presented for consideration by a multidisciplinary team when assessing the risk-benefit balance for performing decorporation therapy.

Analysis of recommended thresholds for medical evaluation in cases of radionuclide intakes.

Literature presents different thresholds for evaluation intended for screening people who may need additional medical assistance in cases of radionuclide intakes. There are thresholds based on the committed effective dose (CED), as well as thresholds based on the relative biological effectiveness-weighted absorbed dose (ADT) in the bone marrow and lungs. As in some emergency exposure scenarios with radionuclide intakes the risk for stochastic effects may be low whereas the threshold for deterministic effects may be exceeded, the aim of this analysis was to evaluate and to present the most appropriated threshold for each exposure scenario of interest. The results show that even adopting CED of 100 mSv as threshold for medical evaluation, it is important to screen for tissue reactions because in some scenarios the adopted threshold for deterministic effects is reached whilst the CED is below the adopted threshold value for stochastic effects.

Diabetes Modifies the Clinic Presentation of Cutaneous Leishmaniasis.

BACKGROUND: Cutaneous leishmaniasis (CL) caused by L. braziliensis is characterized by 1 or multiple well-limited ulcerated lesions. Diabetes mellitus (DM) impairs neutrophil and monocyte function, and there is a report of vegetative lesions in a patient with both diseases in Morocco. Here we evaluate the influence of DM on clinical manifestations, immune response, and in the treatment of CL. METHODS: The participants were 36 DM patients with CL and 36 patients with CL without DM, matched by age and gender. The diagnosis of CL was performed by documentation of DNA of L. braziliensis by polymerase chain reaction in the lesion biopsy and histopathologic findings. All patients were treated with Glucantime (Sanofi-Aventis) 20 mg/kg of weight per day for 20 days. RESULTS: There was no difference in the majority of the clinical variables between the groups, and the cure rate in patients with CL and DM (67%) was similar to that observed in CL patients (56%; P ˃ .05). The most important finding was the documentation that 36% of the patients with DM and CL had atypical cutaneous lesions characterized by large superficial ulcers without defined borders. High levels of interferon-γ, tumor necrosis facor, and interleukin-1ß were detected in the supernatants of mononuclear cells stimulated with Leishmania antigen in patients with DM and atypical CL. Moreover, while cure was observed in only 33% of the patients with DM and atypical CL lesions, it was observed in 85% of patients with typical lesions (P < .05). CONCLUSIONS: DM modifies the clinical presentation of CL, enhances pro-inflammatory cytokine production, and impairs response to antimony therapy.

Internal dosimetry of nuclear medicine workers through the analysis of (131)I in aerosols.

(131)I is widely used in nuclear medicine for diagnostic and therapy of thyroid diseases. Depending of workplace safety conditions, routine handling of this radionuclide may result in a significant risk of exposure of the workers subject to chronic intake by inhalation of aerosols. A previous study including in vivo and in vitro measurements performed recently among nuclear medicine personnel in Brazil showed the occurrence of (131)I incorporation by workers involved in the handling of solutions used for radioiodine therapy. The present work describes the development, optimization and application of a methodology to collect and analyze aerosol samples aiming to assess internal doses based on the activity of (131)I present in a radiopharmacy laboratory. Portable samplers were positioned at one meter distant from the place where non-sealed liquid sources of (131)I are handled. Samples were collected over 1h using high-efficiency filters containing activated carbon and analyzed by gamma spectrometry with a high-purity germanium detection system. Results have shown that, although a fume hood is available in the laboratory, (131)I in the form of vapor was detected in the workplace. The average activity concentration was found to be of 7.4Bq/m(3). This value is about three orders of magnitude below the Derived Air Concentration (DAC) of 8.4kBq/m(3). Assuming that the worker is exposed by inhalation of iodine vapor during 1h, (131)I concentration detected corresponds to an intake of 3.6Bq which results in a committed effective dose of 7.13×10(-5)mSv. These results show that the radiopharmacy laboratory evaluated is safe in terms of internal exposure of the workers. However it is recommended that the presence of (131)I should be periodically re-assessed since it may increase individual effective doses. It should also be pointed out that the results obtained so far reflect a survey carried out in a specific workplace. Thus, it is suggested to apply the methodology developed in this work to other nuclear medicine services where significant activities of (131)I are routinely handled as an effective means to optimize individual exposures and improve occupational radiation protection safety.