Patterns of dendritic cell and monocyte subsets are associated with disease severity and mortality in liver cirrhosis patients.

Liver cirrhosis is often complicated by an immunological imbalance known as cirrhosis-associated immune dysfunction. This study aimed to investigate disturbances in circulating monocytes and dendritic cells in patients with acute decompensation (AD) of cirrhosis. The sample included 39 adult cirrhotic patients hospitalized for AD, 29 patients with stable cirrhosis (SC), and 30 healthy controls (CTR). Flow cytometry was used to analyze monocyte and dendritic cell subsets in whole blood and quantify cytokines in plasma samples. Cirrhotic groups showed higher frequencies of intermediate monocytes (iMo) than CTR. AD patients had lower percentages of nonclassical monocytes than CTR and SC. Cirrhotic patients had a profound reduction in absolute and relative dendritic cell numbers compared with CTR and showed higher plasmacytoid/classical dendritic cell ratios. Increased plasma levels of IL-6, IL-10, and IL-17A, elevated percentages of CD62L+ monocytes, and reduced HLA-DR expression on classical monocytes (cMo) were also observed in cirrhotic patients. Patients with more advanced liver disease showed increased cMo and reduced tissue macrophages (TiMas) frequencies. It was found that cMo percentages greater than 90.0% within the monocyte compartment and iMo and TiMas percentages lower than 5.7% and 8.6%, respectively, were associated with increased 90-day mortality. Monocytes and dendritic cells are deeply altered in cirrhotic patients, and subset profiles differ between stable and advanced liver disease. High cMo and low TiMas frequencies may be useful biomarkers of disease severity and mortality in liver cirrhosis.

Psychopharmacological effects and safety of styryl-2-pyrones and dihydrostyryl-2-pyrones-rich fraction from Polygala sabulosa: absence of withdrawal syndrome and tolerance to anxiolytic-like and anticonvulsant effects.

OBJECTIVES: To investigate whether mice develop tolerance to the anxiolytic-like and anticonvulsant effects of subchronic treatment with EA (the styryl-2-pyrones and dihydrostyryl-2-pyrones-rich fraction of Polygala sabulosa), as well as any withdrawal symptoms after abrupt discontinuation; to compare the effects of EA with those of diazepam (DZP) on withdrawal-induced anxiety; and to evaluate the toxicity of EA according to OECD guidelines. METHODS: Male or female mice were acutely or subchronically treated with EA or DZP, and their tolerance to anxiolytic (evaluated in the elevated plus maze, EPM) and anticonvulsant effects (measured against pentylenetetrazole (PTZ)-induced convulsions) were investigated. Other groups received EA or DZP for 28 days followed by withdrawal, being the anxiety-like behaviour evaluated in the EPM. KEY FINDINGS: Both acute and subchronic treatments with EA induced an anxiolytic effect in the EPM. The anticonvulsant activity of DZP, but not EA, was reduced by protracted treatment. EA withdrawal retained the anxiolytic profile, while DZP withdrawal induced anxiogenesis. EA counteracted the anxiogenic-like actions of DZP withdrawal. EA has low toxicity as it did not cause any changes in the biochemical, haematological and histopathological markers. CONCLUSIONS: EA avoids the development of tolerance to its anxiolytic-like and anticonvulsant actions, and does not promote withdrawal syndrome. EA does not cause relevant toxic effects in rodents.

Markers of genotoxicity and oxidative stress in farmers exposed to pesticides.

The effects of chronic exposure to pesticides can lead to the development of several diseases, including different types of cancer, since the genotoxic and mutagenic capacity of these substances can be observed. The objective of this study is to investigate the relation between the occupational exposure to various pesticides and the presence of DNA damage and oxidative stress. Blood samples from 50 rural workers (41 men and 9 women) exposed to pesticides, 46 controls (20 men and 26 women) from the same city (Antônio Carlos, Santa Catarina state, Brazil) and 29 controls (15 men and 14 women) from another city (Florianópolis, Santa Catarina state, Brazil), were evaluated using the comet assay and the cytokinesis-block micronucleus (CBMN) technique for genetic damage, and the test of thiobarbituric acid reactive substances (TBARS) and catalase (CAT) activity for the oxidative stress. Cholinesterase activities were also determined, but there was no statistical difference among exposed workers and controls. Significant differences were found in DNA damage among groups. The comet assay performed on peripheral blood lymphocytes of these individuals had a significantly higher DNA damage index in the exposed group comparing to controls (p < 0.0001). MNi (p < 0.001), NBUDs (p < 0.005) and NPBs (p < 0.0001) were also found to be significantly higher in the exposed group. The TBARS values were significantly higher comparing to the Florianopolis control group (p < 0.0001). Even though CAT values were higher than controls, there was no statistical difference. Thus, it is concluded that the exposed individuals, participants of this study, are more subject to suffer genetic damage and, consequently, more susceptible to diseases resulting from such damages.

Salivary evaluation in radioactive I131 treated patients with thyroid carcinoma.

BACKGROUND AND OBJECTIVE: radioiodine treatment (I131) used to treat thyroid carcinomas produces side effects (sialadenitis, xerostomia, dysphagia and caries susceptibility) reflecting in a poor patient quality of life. This study aimed to evaluate the effect of I131 on salivary function and possible oral impairment. MATERIAL AND METHODS: Thirty-seven patients undergoing I131 were submitted to oral examination, answer questions regarding xerostomia/hyposalivation and collect saliva at three moments (M1: 30-45 days before I131, M2: 1-2 days after I131 and M3: 7-10 days after treatment). Saliva was assayed for flow rate and calcium/phosphate concentrations. RESULTS AND CONCLUSIONS: significant difference in calcium/phosphate concentration was shown between M1 and M2, with evident decrease at M2. Flow rate reduced right after treatment with 41% of patients returning to previous rate at M3 (no statistical difference). A higher number of patients related xerostomia and difficulty in swallowing food at M2. The results showed that xerostomia/hyposalivation, dysphagia and calcium/phosphate concentration decrease may be considered early radioiodine side effects.

Assessment of exposure to cadmium, lead, manganese, and nickel in workers from foundries.

OBJECTIVES: In this study, biological exposure indicators were used to assess the exposure of workers to cadmium (Cd), lead (Pb), manganese (Mn), and nickel (Ni) in nonferrous metal smelters. METHODS: A total of 273 male participants (178 exposed and 95 nonexposed control group), working in nonferrous metal foundries located in southern Brazil, were evaluated based on biological indicators, environmental levels, and different types of work performed by the participants. Blood Pb (BPb), urinary Cd (UCd), urinary Mn (UMn), and urinary Ni (UNi) levels were quantified by graphite furnace atomic absorption spectrometry with Zeeman background correction. RESULTS: Significant differences between the exposed and nonexposed groups were observed for all of the analyzed elements. The average levels of BPb were higher than the recommended occupational exposure level. Relatively low concentrations were found for UCd, UMn, and UNi. CONCLUSIONS: Although metal production is an important segment of the Brazilian economy, information related to employee health in this sector is scarce. The environmental levels are determinant in occupational exposure in foundries. In companies where air levels of Pb, Cd, and Mn were above the established limits, the different types of activity did not represent an important influence on the biological levels found among workers. In situations with low air levels of these metals, the workers from the "melting" sector were actually more vulnerable.

Evaluation of 2,5-hexanedione in urine of workers exposed to n-hexane in Brazilian shoe factories.

Urinary 2,5-hexanedione (2,5-HD) is used as a biomarker for biological monitoring of workers exposed to n-hexane. The purpose of this study was to compare two types of treatment of urine samples during clean-up (with and without acidic hydrolysis) and to study the exposure situation of workers exposed to n-hexane during shoe manufacturing. There, various glues containing n-hexane are used. Quantification of 2,5-HD was carried out by gas chromatography and flame ionization detection (GC-FID). Fifty-two urine samples taken from workers of seven shoe factories were analyzed. Thirty-four persons from the administrative staff of the same factories served as controls. They were not known to be exposed to n-hexane. The samples treated with acidic hydrolysis showed levels (average 0.94 mg/l) approximately 10 times higher than samples without acidic hydrolysis (0.09 mg/l). The difference is predominantly caused by the conversion of other metabolites of n-hexane (e.g. 4,5-dihydroxy-2-hexanone) to 2,5-HD in the presence of acids. Our results also show, that exposure to n-hexane is different between various industries. Levels of 2,5-HD in urine are predominantly dependent on the type of operation (how the glue is applied on the leather during shoe manufacturing). Simple measures, e.g. using a glue handgun instead of a paintbrush significantly decreased exposure to n-hexane.