Quantitative evaluation of the pulmonary microdistribution of TiO2 nanoparticles using X‐ray fluorescence microscopy after intratracheal administration with a microsprayer in rats

The unevenness of pulmonary nanoparticle (NP) distribution, which hinders the establishment of an absolute dose–response relationship, has been described as one of the limitations of intratracheal administration techniques for toxicological assessment of inhaled NPs. Quantification of the NP microdistribution would facilitate the establishment of a concentration–response relationship in localized regions of the lung; however, such quantitative methods have not been reported. Here, we established a quantitative method for evaluating pulmonary TiO₂ NP microdistribution in rats using X‐ray fluorescence microscopy. Ti intensity in lung sections from rats intratracheally administered 10 mg kg^–1 TiO₂ NPs with a microsprayer was measured using X‐ray fluorescence with a 100 µm beam size. Ti reference samples were prepared by dropping different concentrations of Ti solutions on glass slide or lung sections of untreated rat. Ti intensity increased linearly with Ti content in the reference samples on both substrates. The detection limit of TiO₂ was estimated to be 6.3 ng mm^–2. The reproducibility was confirmed for measurements done in the short‐ (2 weeks) and long‐term (6 months). The quantitative results of TiO₂ NP microdistribution suggested that more TiO₂ NPs were distributed in the right caudal and accessory lobes, which are located downstream of the administration direction of the NP suspension, and the lower portion of each lobe. The detection rates of TiO₂ NPs were 16.6–25.0%, 5.19–15.6%, 28.6–39.2%, 21.4–38.7% and 10.6–23.2% for lung sections from the right cranial, middle, caudal, accessory and left lobes, respectively. Copyright © 2015 John Wiley & Sons, Ltd.     

Sarcoidosis presenting as an osteolytic skull lesion: a case report and review of literature on skull sarcoidosis

Bone sarcoidosis of the skull is an infrequent presentation of sarcoidosis. We describe a 51-year-old man who consulted due to inflammatory-appearing nodulation in the right supraorbital region. Images showed a solitary osteolytic lesion extending to soft tissues with increased scintigraphic uptake. The anatomopathological study revealed the presence of non-caseating epithelioid granulomas, compatible with sarcoidosis. Steroid treatment led to a marked remission of the lesion, without evidence of relapse during a follow-up period of 1 year. The literature dealing with skull sarcoidosis is reviewed.     

Biological and clinical significance of MMP-2, MMP-9, TIMP-1 and TIMP-2 in non-small cell lung cancer

Our main aim consists of investigating the clinical usefulness of gelatinases and their tissue inhibitors in non-small cell lung cancer (NSCLC). Thus, we have analysed in 111 NSCLCs, levels and activity of MMP-2, MMP-9, TIMP-1 and TIMP-2, by Enzymoimmunoassay and Gelatine zymography, respectively. Our data revealed higher MMP-2 net activity in the NSCLC population analyzed in this study, this parameter showing a significant association with the TNM stage of tumours (P=0.002). Moreover, MMP-9 levels were significantly associated with poor clinical evolution of patients (P=0.02). Also, disease-free survival time was higher for patients whose tumours showed TIMP-1 increased levels (P=0.04). Of interest, Cox multivariate analysis revealed that TIMP-1 levels can be considered as an independent prognostic factor in NSCLC. Relative Risk (RR) to tumour relapse was more than two times lower for patients showing high TIMP-1 levels (RR=0.420, P=0.041). Therefore, according to our results, we conclude that MMP-9 and TIMP-1 levels of synthesis could be useful for the selection of patients with potentially unfavourable clinical evolution in order to establish adjuvant therapy protocols. Among these parameters, TIMP-1 level evaluation emerges as the main factor to predict the clinical outcome of patients.     

Anetoderma developing in juvenile xanthogranuloma

Anetoderma is characterized by circumscribed oval macules with overlying wrinkled skin that is slightly depressed or bulges outwards. Skin biopsy shows a decrease of elastic dermal fibers. It may not be associated with an underlying disease (primary anetoderma) or may be related to many dermatoses (secondary anetoderma).
We report a 7-year-old girl who presented at birth with yellowish brown papules on the upper trunk, neck and head, which within days evolved to yellowish orange papules. A skin biopsy was carried out and the presence of an histiocytic infiltrate with foam cells and Touton cells in the dermis that were CD68+, factor XIII+ and S-100−, confirmed the diagnosis of Juvenile Xanthogranuloma (JXG). After 4 years the lesions began to evolve to asymptomatic oval and round atrophic skin areas. Histopathologic evaluation showed decrease of elastic fibers in the dermis, diagnostic of anetoderma.
The mechanisms of anetoderma are unknown. Although many different dermatoses have been associated with anetoderma we have only found two reported cases of anetoderma and JXG.     

A new genetic variant involved in genetic susceptibility to alcoholic liver cirrhosis: -330T>G polymorphism of the interleukin-2 gene

OBJECTIVE: Genetic factors may determine susceptibility to develop alcoholic liver cirrhosis, although it remains uncertain why only a minority of alcoholics suffers from this disease. A decrease in serum levels of interleukin-2 (IL-2) is usually found in alcoholic cirrhotics. In this study we examined the relationship between the -330T>G IL-2 gene (IL2) polymorphism and alcoholic liver cirrhosis. METHODS: Genotyping of the aforementioned polymorphism was done by polymerase chain reaction and digestion with restriction enzymes in 257 male alcoholics (161 without liver disease and 96 with alcoholic liver cirrhosis) and 101 healthy controls. A logistic regression analysis was performed to adjust for potential confounders and to analyze the model of inheritance. RESULTS: We found an association between the -330T>G IL2 polymorphism and alcoholic liver cirrhosis: the frequency of the allele T carriers (genotype TT and GT) was significantly higher in alcoholics with cirrhosis (96.9%) than in those without liver disease (89.4%, P=0.043). CONCLUSION: We report for the first time that the possession of the -330T allele of the IL2 is associated with a higher risk of developing alcoholic liver cirrhosis and this fact may favor the progression of alcoholic liver disease.     

Outcome according to cytogenetic abnormalities and DNA ploidy in myeloma patients receiving short induction with weekly bortezomib followed by maintenance

Cytogenetic abnormalities (CAs) such as t(4;14), t(14;16) or del(17p), and nonhyperdiploidy are associated with poor prognosis in multiple myeloma. We evaluated the influence of CAs by FISH and DNA ploidy by flow cytometry on response and survival in 232 elderly, newly diagnosed multiple myeloma patients receiving an induction with weekly bortezomib followed by maintenance therapy with bortezomib-based combinations. Response was similar in the high-risk and standard-risk CA groups, both after induction (21% vs 27% complete responses [CRs]) and maintenance (39% vs 45% CR). However, high-risk patients showed shorter progression-free survival (PFS) than standard-risk patients, both from the first (24 vs 33 months; P = .04) and second randomization (17 vs 27 months; P = .01). This also translated into shorter overall survival (OS) for high-risk patients (3-year OS: 55% vs 77%; P = .001). This adverse prognosis applied to either t(4;14) or del(17p). Concerning DNA ploidy, hyperdiploid patients showed longer OS than nonhyperdiploid patients (77% vs 63% at 3 years; P = .04), and this was more evident in patients treated with bortezomib, thalidomide, and prednisone (77% vs 53% at 3 years; P = .02). The present schema does not overcome the negative prognosis of high-risk CAs and nonhyperdiploidy. This trial was registered with www.ClinicalTrials.gov as NCT00443235.