Seemingly Harmless Differentiated Thyroid Carcinoma Presenting as Bone Metastasis.

Thyroid carcinoma is the most common endocrine neoplasia. Differentiated thyroid carcinomas (DTCs) represent the majority of cases, which usually follow an indolent clinical course with low mortality rates. The authors describe two cases of well DTC without classic histological poor prognosis features, presenting as extensive and unresectable osteolytic bone metastases. DTCs are considered harmless tumours, due to their benign and silent behaviour. The authors want to underline the importance of clinical awareness during follow-up in cases of DTC, which can be aggressive in presentation and behaviour. Timely identification and diagnosis of these tumours are essential for prompt treatment initiation and improvement of overall survival.

In silico genotoxicity of coumarins: application of the Phenol-Explorer food database to functional food science.

Coumarins are a group of phytochemicals that may be beneficial or harmful to health depending on their type and dosage and the matrix that contains them. Some of these compounds have been proven to display pro-oxidant and clastogenic activities. Therefore, in the current work, we have studied the coumarins that are present in food sources extracted from the Phenol-Explorer database in order to predict their clastogenic activity and identify the structure-activity relationships and genotoxic structural alerts using alternative methods in the field of computational toxicology. It was necessary to compile information on the type and amount of coumarins in different food sources through the analysis of databases of food composition available online. A virtual screening using a clastogenic model and different software, such as MODESLAB, ChemDraw and STATISTIC, was performed. As a result, a table of food composition was prepared and qualitative information from this data was extracted. The virtual screening showed that the esterified substituents inactivate molecules, while the methoxyl and hydroxyl substituents contribute to their activity and constitute, together with the basic structures of the studied subclasses, clastogenic structural alerts. Chemical subclasses of simple coumarins and furocoumarins were classified as active (xanthotoxin, isopimpinellin, esculin, scopoletin, scopolin and bergapten). In silico genotoxicity was mainly predicted for coumarins found in beer, sherry, dried parsley, fresh parsley and raw celery stalks. The results obtained can be interesting for the future design of functional foods and dietary supplements. These studies constitute a reference for the genotoxic chemoinformatic analysis of bioactive compounds present in databases of food composition.

MAO inhibitory activity of bromo-2-phenylbenzofurans: synthesis, in vitro study, and docking calculations.

Monoamine oxidase (MAO) is an enzyme responsible for metabolism of monoamine neurotransmitters which play an important role in brain development and function. This enzyme exists in two isoforms, and it has been demonstrated that MAO-B activity, but not MAO-A activity, increases with aging. MAO inhibitors show clinical value because besides the monoamine level regulation they reduce the formation of by-products of the MAO catalytic cycle, which are toxic to the brain. A series of 2-phenylbenzofuran derivatives was designed, synthesized and evaluated against hMAO-A and hMAO-B enzymes. A bromine substituent was introduced in the 2-phenyl ring, whereas position 5 or 7 of the benzofuran moiety was substituted with a methyl group. Most of the tested compounds inhibited preferentially MAO-B in a reversible manner, with IC50 values in the low micro or nanomolar range. The 2-(2'-bromophenyl)-5-methylbenzofuran (5) was the most active compound identified (IC50 = 0.20 µM). In addition, none of the studied compounds showed cytotoxic activity against the human neuroblastoma cell line SH-SY5Y. Molecular docking simulations were used to explain the observed hMAO-B structure-activity relationship for this type of compounds.

Adult bronchiolitis--a clinical and pathological interpretative classification.

INTRODUCTION: Bronchiolitis is a heterogeneous group of diseases of an inflammatory nature, centered on small conducting airways and often associated with other pulmonary disorders. No single classification scheme for bronchiolar diseases has been widely accepted. In this retrospective study, it was decided to apply a new clinical and pathological interpretative classification. OBJECTIVES: To propose a new clinical and pathological interpretative classification for adult bronchiolitis, based on statistical analysis of a population of 193 patients with histopathological diagnosis of bronchiolitis. MATERIALS AND METHODS: A retrospective study analyzed the epidemiological characteristics, co-morbidities and radiological findings present in a group of patients with histopathological diagnosis of bronchiolitis. RESULTS: This trial involved 193 cases collected over a period of eleven years; 48 (24.9%) patients had simultaneous pulmonary disease; non-pulmonary diseases, such as cardiovascular diseases, type II Diabetes mellitus and dyslipidemia were present in 57 cases. The image study was extremely important in order to integrate clinical and pathological aspects. In this study respiratory bronchiolitis related to smoking dominated. The radiological findings confirmed the secondary nature of the histopathological features, with prevalence of ground-glass patterns, pneumothorax and patterns of interstitial involvement, as described in the literature. It was also verified that clinical behavior of different forms of bronchiolitis was important to distinguish the various types, since they could progress without typical anatomopathological aspects. CONCLUSION: This trial showed that the vast majority of diagnosis obtained corresponded to bronchiolitis as secondary to pulmonary pathology. In most cases, morphological findings had to be complemented with clinical and radiological characteristics, in order to obtain the final diagnosis.

Overlap syndrome--Asthma and obstructive sleep apnea.

INTRODUCTION: Asthma is a chronic inflammatory disease with multiple phenotypes. There is still a major gap in the understanding of its complex causality. Obstructive sleep apnea (OSA) is a common condition that has been implicated as a risk factor for asthma exacerbations. OBJECTIVES: This study aims to characterize patients with the diagnosis of asthma and suspected OSA; identify the presence of OSA and review, on the current literature, the association between asthma and OSA, as an overlap syndrome. MATERIALS AND METHODS: The authors present a retrospective study that included patients diagnosed with asthma that underwent sleep study in a 3 year period. Demographic, clinical data, body mass index (BMI), sleep study parameters and treatments were analyzed. RESULTS: The sample consisted of 47 patients. The majority of population was females (68%) and the mean age was 55.65 ± 13.04 years. The most common nighttime symptom was snoring (93.6%). Regarding BMI, values above the normal limit were observed in 89.36% of the patients. 68% underwent polysomnography and the others cardiorespiratory polygraphy. In 57.4% of the patients, OSA was confirmed with a higher prevalence in males (73.3%) compared to females (50%). The therapeutic approach in 81.8% of these patients was home ventilation therapy. CONCLUSION: The combination of asthma and OSA has become increasingly more frequent. In the described study, the prevalence of OSA was 57.4%, value that is in fact higher than in general population. After the therapeutic approach, all patients referred improvement of symptoms. It is therefore essential that OSA is investigated in patients with asthma when there is poor control of symptoms, in order to achieve a better control.

Alternative functional criteria to assess airflow-limitation reversibility in asthma.

INTRODUCTION: International guidelines define significant bronchodilator response as absolute and percentage change from baseline in forced expiratory volume (FEV1) in the first second and/or forced vital capacity (FVC) ≥12% and 200 mL. However, bronchodilator effects on other lung function parameters have also been correlated to some degree of reversible airflow limitation. OBJECTIVES: To determine whether changes in other lung function parameters apart from FEV1 and FVC detect functional responses to bronchodilator in asthmatic patients. MATERIALS AND METHODS: Spirometry and body plethysmography were performed at baseline conditions and after administration of 400 µg of salbutamol by metered-dose inhaler through a space chamber device in asthmatic patients. Paired t-tests were used to compare lung function parameters between those with and without criteria for reversibility of airway obstruction according to ATS/ERS criteria. Cut-off values were obtained from the corresponding ROC curves. Measurements evaluated were FEV1, FVC, maximum mid-forced expiratory flow (FEF25-75%), residual volume (RV), inspiratory capacity (IC), airway resistance (Raw) and specific airway conductance (sGaw). RESULTS: From a total of 100 consecutive asthmatics patients (46% of them men; average age 58.7±14.1 years; 76% with mild to moderate obstruction), 50 patients had a significant bronchodilator response. All of these had noteworthy variations (p<0.004) in PEF, FEF25-75%, RV, Raw and sGaw. The most accurate in predicting a significant bronchodilator response were the absolute and percentage improvements in PEF (≥0.4 L/s and 8%), FEF25-75% (≥0.087 L/s and 27%) and the percentage of sGaw compared with that at baseline (≥25%). Based on these cut-off values, a sizeable number of the patients defined as non-responders had important changes in airway caliber. 17 patients had significant increments in the percentage of PEF and 10 had changes in absolute volume; 6 patients had increments in percentage and 16 in absolute change of FEF25-75%; 22 patients had increments in the percentage change of sGaw. CONCLUSIONS: Changes of FEV1 and/or FVC may underestimate significant functional response to bronchodilators in asthmatic patients with airway obstruction when considering the change in other lung function parameters.

WITHDRAWN: Alternative functional criteria to assess airflow-limitation reversibility in asthma.

This article has been withdrawn for editorial reasons because the journal will be published only in English. In order to avoid duplicated records, this article can be found at http://dx.doi.org/10.1016/j.rppnen.2014.08.002. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Graphene­boron nitride superlattices: the role of point defects at the BN layer.

We investigate, by means of first-principles calculations, the role of hBN point defects on the energetical stability and electronic structure of heterostructures composed of graphene atop hBN, rotated at angles of 13.17°, 9.43° and 7.34°. We consider, as possible point defects, boron and nitrogen vacancies and antisites, substitutional oxygen at the nitrogen site ON, substitutional carbon dimers, and nitrogen interstitials. The electronic and structural properties of all defects were analyzed. Among these, the most stable is ON, with negative formation energies at several possible rotation angles and chemical environments. Under such conditions, ON doping can raise the Fermi level of the neutral system by as much as 1 eV relative to graphene's Dirac point, reaching the band crossing between adjacent Dirac cones at the M point of the heterostructure Brillouin zone. This could lead to interesting electronic transport properties without the need for electrostatic doping.

Chronic obstructive pulmonary disease in Portugal: Pneumobil (1995) and 2002 prevalence studies revisited.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) has been a leading cause of morbidity and mortality worldwide, over the years. In 1995, the implementation of a respiratory function survey seemed to be an adequate way to draw attention to neglected respiratory symptoms and increase the awareness of spirometry surveys. By 2002 there were new consensual guidelines in place and the awareness that prevalence of COPD depended on the criteria used for airway obstruction definition. The purpose of this study is to revisit the two studies and to turn public some of the data and respective methodologies. METHODS: From Pneumobil study database of 12,684 subjects, only the individuals with 40+ years old (n = 9.061) were selected. The 2002 study included a randomized representative sample of 1,384 individuals with 35-69 years old. RESULTS: The prevalence of COPD was 8.96% in Pneumobil and 5.34% in the 2002 study. In both studies, presence of COPD was greater in males and there was a positive association between presence of COPD and older age groups. Smokers and ex-smokers showed a higher proportion of cases of COPD. CONCLUSIONS: Prevalence in Portugal is lower than in other European countries. This may be related to lower smokers' prevalence. Globally, the most important risk factors associated with COPD were age over 60 years, male gender and smoking exposure. All aspects and limitations regarding different recruitment methodologies and different criteria for defining COPD cases highlight the need of a standardized method to evaluate COPD prevalence and associated risks factors, whose results can be compared across countries, as it is the case of BOLD project.

Chronic obstructive pulmonary disease prevalence in Lisbon, Portugal: the burden of obstructive lung disease study.

BACKGROUND: There is a great heterogeneity in the prevalence of Chronic Obstructive Pulmonary Disease (COPD) demonstrates a great heterogeneity across the world. The Burden of Obstructive Lung Disease (BOLD) initiative was started to measure the prevalence of COPD in a standardized way. We aimed to estimate the prevalence of COPD in Portuguese adults aged 40 years or older of a target population of 2,700 000 in the Lisbon region, in accordance with BOLD protocol. METHODS: A stratified, multi-stage random sampling procedure was used which included 12 districts. The survey included a questionnaire with information on risk factors for COPD and reported respiratory disease and a post-bronchodilator spirometry performed at survey centres. RESULTS: For the 710 participants with questionnaires and acceptable spirometry, the overall weighted prevalence of GOLD stage I+ COPD was 14.2% (95% C.I. 11.1, 18.1), and stage II+ was 7.3% (95% C.I. 4.7, 11.3). Unweighted prevalence was 20.2% (95% C.I.17.4, 23.3) for stage I+ and 9.5% (95% C.I. 7.6, 11.9) for stage II+. Prevalence of COPD in GOLD stage II+ increased with age and was higher in men. The prevalence of GOLD stage I+ COPD was 9.2% (95% C.I. 5.9, 14.0) in never smokers versus 27.4% (95% C.I. 18.5, 38.5) in those who had smoked >20 pack-years. The agreement between previous doctor diagnosis and spirometric diagnosis was low, with 86.8% of underdiagnosed individuals. CONCLUSIONS: The 14.2% of COPD estimated prevalence indicates that COPD is a common disease in the Lisbon region. In addition, a large proportion of underdiagnosed disease was detected. The high prevalence of COPD with a high level of underdiagnosis, points to the need of raising awareness of COPD among health professionals, and requires more use of spirometry in the primary care setting.

Correlation between (in)commensurate domains of multilayer epitaxial graphene grown on SiC(0001) and single layer electronic behavior.

A systematic study of the evolution of the electronic behavior and atomic structure of multilayer epitaxial graphene (MEG) as a function of growth time was performed. MEG was obtained by sublimation of a 4H-SiC(0001(-)) substrate in an argon atmosphere. Raman spectroscopy and x-ray diffraction were carried out in samples grown for different times. For 30 min of growth the sample Raman signal is similar to that of graphite, while for 60 min the spectrum becomes equivalent to that of exfoliated graphene. Conventional x-ray diffraction reveals that all the samples have two different (0001) lattice spacings. Grazing incidence x-ray diffraction shows that thin films are composed of rotated (commensurate) structures formed by adjacent graphene layers. Thick films are almost completely disordered. This result can be directly correlated to the single layer electronic behavior of the films as observed by Raman spectroscopy. Finally, to understand the change in lattice spacings as a result of layer rotation, we have carried out first principles calculations (using density functional theory) of the observed commensurate structures.

Anomalous response of supported few-layer hexagonal boron nitride to DC electric fields: a confined water effect?

We use electric force microscopy (EFM) to study the response of supported few-layer hexagonal boron nitride (h-BN) to an electric field applied by the EFM tip. Our results show an anomalous behavior in the dielectric response of h-BN atop Si oxide for different bias polarities: for a positive bias applied to the tip, h-BN layers respond with a larger dielectric constant than the dielectric constant of the substrate, while for a negative bias, the h-BN dielectric constant appears to be smaller. Based on ab initio calculations, we propose that this behavior is due to a water layer confined between the Si oxide substrate and h-BN layers. This hypothesis was experimentally confirmed by sample annealing and also by a comparative analysis with h-BN on a non-polar substrate.

Prevalence of obesity and its relationship to clinical lipodystrophy in HIV-infected adults on anti-retroviral therapy.

BACKGROUND: Combination antiretroviral therapy (cART) is associated with lipodystrophy (lipoatrophy and lipoaccumulation) and several metabolic abnormalities that together can contribute to an increased cardiovascular risk. The aim of this study was to evaluate the prevalence of obesity in patients on cART according to the presence of clinical lipodystrophy (CL) and to analyze factors associated with obesity. METHODS: We evaluated 368 HIV-infected adults on cART. RESULTS: CL was present in 59.0%. Independently of gender, patients with CL were more frequently underweight [5.7% (21/368)] and of normal weight [47.3% (174/368)], and less frequently overweight [33.2% (122/368)] or obese [13.9% (51/368)]. Mean body mass index was higher in patients with abdominal prominence regardless of the presence of clinical lipoatrophy. Patients with CL had lower waist circumference, higher waist/hip and fat mass ratio and lower total and subcutaneous fat, without significant difference in visceral fat but with a higher visceral/subcutaneous fat ratio, as evaluated by CT at abdominal level. CL was significantly less frequent in overweight [odds ratio (OR)=0.21, 95% confidence interval (CI): 0.05-0.92] and obese (OR=0.05, 95%CI: 0.01-0.26) patients, when compared to underweight ones, independent of age, gender, duration of infection, cART regimen, virological suppression, and HIV-infection risk factor. CONCLUSIONS: Being overweight or obese is highly prevalent in HIV-infected patients on cART. Patients with CL were more frequently under- or normal weight, and less frequently overweight or obese. Obesity is a condition that should be considered in HIV patients on cART.

Diagnosis of respiratory bronchiolitis associated interstitial lung disease.

BACKGROUND: Respiratory Bronchiolitis (RB), described by Niewoehner et al in 1974, is a common finding in heavy smokers and is characterised by the presence of pigmented macrophages within respiratory bronchioles and adjacent alveoli. In the 1980s, Myers et al described RB associated with interstitial lung disease (RBILD), which is a rare entity expressed as an amplified respiratory bronchiolitis in response to cigarette smoke. METHODS: The authors studied a group of 8 patients with biopsy-proven RBILD diagnosed within the last five years, and assessed epidemiological data, clinical and imaging features, lung function tests, bronchoalveolar lavage findings, therapeutic approaches and clinical evolution. RESULTS AND CONCLUSIONS: The most difficult differential diagnosis is between RBILD and Desquamative Interstitial Pneumonia (DIP), which seems to suggest that these disorders are either end of the same spectrum, although the authors claim that there are some clinical, morphological and prognostic distinctions. The diagnosis of RBILD requires an appropriate clinical setting (including smoking habits), characteristic image findings (like ground glass shadowing and centrilobular nodules), and Bronchoalveolar Lavage (BAL) data to exclude other diagnosis. Pathological confirmation may also be important, not only to exclude more adverse interstitial lung disease, such as idiopathic pulmonary fibrosis, but also, as in the eight cases presented, to illustrate some specific features such as the prevalence of lymphocytosis in BAL.

Surgery for bronchiectasis.

OBJECTIVE: The incidence of bronchiectasis has declined markedly in developed countries. However, a reasonable number of patients still need surgery, despite aggressive physiotherapy and antibiotic therapy. We have reviewed our patients to clarify the benefits from surgery and to analyse the complications. MATERIAL AND METHODS: Between 1988 and 1999, we have operated on 119 patients with bronchiectasis, 71 female and 48 male, with a mean age of 42.2 years (range 11--77 years). Surgery was indicated because of unsuccessful medical therapy in 66 patients (55%), 31 (26%) had haemoptysis, 11 (9.2%) had lung abscess, 10 (8.4%) had lung masses, and three (2.5%) had pneumothorax. The most common manifestations were cough with sputum in 90 patients (76%), haemoptysis in 45 (38%) and recurrent infections in 57 (48%). The mean duration of the symptoms was 4 years (range 1--40 years). The lower lobes were diseased in 61 patients and bilateral disease was found in ten. The mean number of involved pulmonary segments was five (range 1-15). A lobectomy was performed in 75 patients (62%), a segmentectomy in 12 (10%), a pneumonectomy in nine (7.4%) and a bilobectomy in four (3.3%). Complete resection of the disease was achieved in 108 cases (91%). RESULTS: There was no operative mortality and perioperative morbidity occurred in 15 patients (15%), including temporary broncho-pleural fistulae in 7 (5.8%), and post-operative haemorrhage and atrial arrhythmias in four (3.3%) each. After a mean follow-up was 4.5 years, 73 patients (68%) of this group were asymptomatic, and 31 (29%) had meaningful clinical improvement, while only four (3.7%) maintained or worsened prior symptoms. The best clinical improvement occurred in patients with complete resection of the disease (P=0.008). There were no differences in the respiratory function, comparing pre- and post-operative data, with a 2-year of minimum interval. The VC was 91 and 89% and the FEV1 was 83% and 81% of expected, respectively before and after surgery, (P=NS). CONCLUSION: Surgery of pulmonary bronchiectasis has few complications and markedly improves symptoms in the great majority of patients, especially when complete resection of the disease is achieved. Pulmonary resection of bronchiectasis does not alter respiratory function.

Synaptosomes isolated from Goto-Kakizaki diabetic rat brain exhibit increased resistance to oxidative stress: role of vitamin E.

Increased oxidative stress is believed to be an important factor in the development of diabetic complications. In this study, the effect of diabetes on the susceptibility of synaptosomes to oxidative stress, induced by the oxidizing system ascorbate/Fe2+, on the activity of antioxidant enzymes and on the levels of glutathione and vitamin E was investigated. Synaptosomes were isolated from brain of 29-weeks-old Goto-Kakizaki (GK) rats, a model of non-insulin dependent diabetes mellitus and from normal Wistar rats. Synaptosomes isolated from GK rats displayed a lower susceptibility to lipid peroxidation, as assessed by quantifying thiobarbituric acid reactive substances (TBARS), than normal rats (5.33 +/- 0.79 and 7.58 +/- 0.7 nmol TBARS/mg protein, respectively). In the absence of oxidants, no significant differences were found between the levels of peroxidation in synaptosomes of diabetic or control rats. Superoxide dismutase (SOD), glutathione peroxidase and glutathione reductase activities were unaltered in the brain of diabetic rats. There were no statistically significant differences in fatty acid composition of total lipids and reduced glutathione levels in synaptosomes of diabetic and control rats. The decreased susceptibility to membrane lipid peroxidation of diabetic rats synaptosomes correlated with a 1.3-fold increase in synaptosomal vitamin E levels. Vitamin E levels in plasma were also higher in diabetic rats (21.32 micromol/l) as compared to normal rats (15.13 micromol/l). We conclude that the increased resistance to lipid peroxidation in GK rat brain synaptosomes may be due to the increased vitamin E content, suggesting that diabetic animals might develop enhanced defense systems against brain oxidative stress.

Lipid composition and dynamics of cell membranes of Bacillus stearothermophilus adapted to amiodarone.

Bacillus stearothermophilus, a useful model to evaluate membrane interactions of lipophilic drugs, adapts to the presence of amiodarone in the growth medium. Drug concentrations in the range of 1-2 microM depress growth and 3 microM completely suppresses growth. Adaptation to the presence of amiodarone is reflected in lipid composition changes either in the phospholipid classes or in the acyl chain moieties. Significant changes are observed at 2 microM and expressed by a decrease of phosphatidylethanolamine (relative decrease of 23.3%) and phosphatidylglycerol (17.9%) and by the increase of phosphoglycolipid (162%). The changes in phospholipid acyl chains are expressed by a decrease of straight-chain saturated fatty acids (relative decrease of 12.2%) and anteiso-acids (22%) with a parallel increase of the iso-acids (9.8%). Consequently, the ratio straight-chain/branched iso-chain fatty acids decreases from 0. 38 (control cultures) to 0.30 (cultures adapted to 2 microM amiodarone). The physical consequences of the lipid composition changes induced by the drug were studied by fluorescence polarization of diphenylhexatriene and diphenylhexatriene-propionic acid, and by differential scanning calorimetry. The thermotropic profiles of polar lipid dispersions of amiodarone-adapted cells are more similar to control cultures (without amiodarone) than those resulting from a direct interaction of the drug with lipids, i.e., when amiodarone was added directly to liposome suspensions. It is suggested that lipid composition changes promoted by amiodarone occur as adaptations to drug tolerance, providing the membrane with physico-chemical properties compatible with membrane function, counteracting the effects of the drug.

Decreased susceptibility to lipid peroxidation of Goto-Kakizaki rats: relationship to mitochondrial antioxidant capacity.

The respiratory function and the antioxidant capacity of liver mitochondrial preparations isolated from Goto-Kakizaki non-insulin dependent diabetic rats and from Wistar control rats, with the age of 6 months, were compared. It was found that Goto-Kakizaki mitochondrial preparations presented a higher coupling between oxidative and phosphorylative systems, compared to non-diabetic preparations. Goto-Kakizaki mitochondria presented a lower susceptibility to lipid peroxidation induced by ADP/Fe2+, as evaluated by the formation of thiobarbituric acid substances. The decreased susceptibility to peroxidation in diabetic rats was correlated with an increase in mitochondrial vitamin E (alpha-tocopherol) content and GSH/GSSG ratio. Moreover, the glutathione reductase activity was significantly increased, whereas the glutathione peroxidase was decreased. Superoxide dismutase activity was unchanged in diabetic rats. Fatty acid analyses showed that the content in polyunsaturated fatty acids of Goto-Kakizaki mitochondrial membranes was significantly higher compared to controls. These results indicate that the lower susceptibility to lipid peroxidation of mitochondria from diabetic rats was related to their antioxidant defense systems, and may correspond to an adaptative response of the cells against oxidative stress in the early phase of diabetes.