Surface-modified ZrO2 nanoparticles with caffeic acid: Characterization and in vitro evaluation of biosafety for placental cells.

The toxicity of hybrid nanoparticles, consisting of non-toxic components, zirconium dioxide nanoparticles (ZrO2 NPs), and caffeic acid (CA), was examined against four different cell lines (HTR-8 SV/Neo, JEG-3, JAR, and HeLa). Stable aqueous ZrO2 sol, synthesized by forced hydrolysis, consists of 3-4 nm in size primary particles organized in 30-60 nm in size snowflake-like particles, as determined by transmission electron microscopy and direct light scattering measurements. The surface modification of ZrO2 NPs with CA leads to the formation of an interfacial charge transfer (ICT) complex followed by the appearance of absorption in the visible spectral range. The spectroscopic observations are complemented with the density functional theory calculations using a cluster model. The ZrO2 NPs and CA are non-toxic against four different cell lines in investigated concentration range. Also, ZrO2 NPs promote the proliferation of HTR-8 SV/Neo, JAR, and HeLa cells. On the other hand, hybrid ZrO2/CA NPs induced a significant reduction of the viability of the JEG-3 cells (39 %) for the high concentration of components (1.6 mM ZrO2 and 0.4 mM CA).

Massive Relief: Papillary Adenoma of the Lung in Asymptomatic Former Smoker Patient.

Benign epithelial tumors of the lung are uncommon and can represent a diagnostic challenge. Herein, we describe one such emblematic case. A 59-year-old former smoker male was admitted to the hospital complaining of cough for a long time. A radiological examination showed a centrally excavated mass strictly connected to the visceral pleura. The patient underwent tumorectomy. At gross examination, the tumor was composed of solid and cystic areas containing clear liquid. Histological examination highlighted a sub-pleural encapsulated tumor, with foci of capsular invasion, characterized by a single layer of columnar and cuboidal epithelial cells lining moderately cellular fibro-vascular cores. A wide spectrum of immunohistochemical markers was performed. The final diagnosis was suggestive of a peripheral pulmonary papillary tumor of undetermined malignant potential. At the last follow-up, six years after surgery, no recurrence or metastases were described. Reporting this case, we would like to point out the existence of these rare entities that should be taken into account in the diagnostic process, thus avoiding potential misdiagnosis. Moreover, the presence of capsular invasion should be better investigated in order to reconsider the exact terminology of the tumor and the classification of its malignant potential.

Correlation of genomic alterations and PD-L1 expression in thymoma.

Thymic epithelial tumors (TETs) include several anterior mediastinal malignant tumours: thymomas, thymic carcinomas and thymic neuroendocrine cancers. There is significant variety in the biologic features and clinical course of TETs and many attempts have been made to identify target genes for successful therapy of TETs. Next generation sequencing (NGS) represents a huge advancement in diagnostics and these new molecular technologies revealed that thymic neoplasms have the lowest tumor mutation burden among all adult malignant tumours with a different pattern of molecular aberrations in thymomas and thymic carcinomas. As for the PD-L1 expression in tumor cells in thymoma and thymic carcinoma, it varies a lot in published studies, with findings of PD-L1 expression from 23% to 92% in thymoma and 36% to 100% in thymic carcinoma. When correlated PD-L1 expression with disease stage some controversial results were obtained, with no association with tumor stage in most studies. This is, at least in part, explained by the fact that several diverse PD-L1 immunohistochemical tests were used in each trial, with four different antibodies (SP142, SP263, 22C3, and 28-8), different definition of PD-L1 positivity and cutoff values throughout the studies as well. There is a huge interest in using genomic features to produce predictive genomic-based immunotherapy biomarkers, particularly since recent data suggest that certain tumor-specific genomic alterations, either individually or in combination, appear to influence immune checkpoint activity and better responses as the outcome, so as such in some cancer types they may complement existing biomarkers to improve the selection criteria for immunotherapy.

Cadmium retention and distribution in contaminated soil: effects and interactions of soil properties, contamination level, aging time and in situ immobilization agents.

As soil cadmium (Cd) contamination becomes a serious concern and one of the significant environmental pollution issues all over the world, knowledge of the basic chemistry, origin, inputs, sources, quantity, chemical forms, reactions, as well as the fate and transport of Cd in different types of soil is crucial for better understanding Cd bioavailability, health risks and remedial options. This study aimed to increase the current knowledge on the complex interdependence between the factors affecting behavior, transport and fate of Cd in the soil and to test and compare the performance of the stabilization agents in different soil types. Soils demonstrated various sorption affinity and capacity for Cd accumulation, which proved to be positively correlated with soil pH and the cation exchange capacity (CEC). With increasing levels of contamination, sequential extraction analysis showed the highest increase of relative Cd amounts in the exchangeable fraction regardless of the soil properties, suggesting that added Cd is principally associated with the easily accessible and mobile fraction. For different initial Cd concentrations and soil types, Cd sorption reached the quasi-equilibrium within 24 h of contact. Prolonged aging (two months) influenced the natural stabilization of Cd in all types of soil, but only at low contamination level. The application of both, conventional (slaked lime Ca(OH)2) and alternative phosphate-rich (annealed bovine bones B400) amendments, resulted in Cd relocation and reduction of exchangeable Cd content. Although the effect was smaller when apatite amendment was utilized, observed re-distribution of Cd to more stable soil fractions is preferable for achieving long-term stabilization. Cd concentrations extracted in exchangeable and acid soluble fractions after the treatments of contaminated soil samples suggest that the practical applicability of in situ immobilization depends on the soil properties and the level of contamination, as well as that effect, should be monitored for the possible re-mobilization of Cd.

Rare histological subtype of pulmonary artery intimal sarcoma diagnosed by multidisciplinary approach.

Pulmonary artery intimal sarcoma (PAS) is a rare mesenchymal tumor mostly diagnosed in middle-aged women. In a 63-year-old female, the radiological findings showed cavitation in the left upper lobe of the lung and infiltrative tumor mass around the left pulmonary artery. PAS consisted of small, round tumor cells with about 80% of mitotic activity and with myxoid background and specific immunoprofile and diagnosed as undifferentiated sarcoma with round cell features type. The final diagnosis of PAS was established according to the pathohistological, chest computed tomography scan, and surgery finding.

Membrane PD-L1 expression and soluble PD-L1 plasma levels in idiopathic pulmonary fibrosis-a pilot study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) has common risk factors with cancer and significant similarities in the pathobiology process, both diseases having poor outcomes. Immune checkpoint PD-L1 has become the target of checkpoint inhibitory therapy that unleashes antitumor T cells and has revolutionized cancer treatment. This is a pilot study exploring membrane immune checkpoint PD-L1 expression in human IPF lung tissue samples and its soluble form, soluble PD-L1 (sPD-L1) plasma concentrations in IPF patients, in order to investigate potential role of PD-L1 as an IPF biomarker. METHODS: Twelve human IPF lung tissue samples (formalin-fixed, paraffin-embedded) obtained by surgical biopsy, have been tested for PD-L1 expression by PD-L1 IHC 22C3 pharmDx assay, while plasma samples for examination of sPD-L1 forms, PD-L1 (B7-H1/CD274) blood concentration, originated from 23 patients with IPF who did not undergo surgical biopsy. RESULTS: Membrane PD-L1 expression in IPF lung tissue samples was positive to overexpression of PD-L1 in 9 samples out of 12. Only very few cells in the interstitium have shown a discrete PD-L1 expression, but not of a membrane type. As for sPD-L1 forms, we have found elevated concentrations of sPD-L1 in the serum of IPF patients 314.3 ng/L (117.7-483.1 ng/L), significantly higher compared with healthy control group 91.0 ng/L (52.4-119.7 ng/L), P<0.01. CONCLUSIONS: For IPF with PD-L1 expression on alveolar macrophages, further studies are necessary to elucidate this phenomenon. Serum sPD-1/PD-L1 is easily detected in clinical practice and should be further evaluated as a potential prognostic or/and predictive biomarker in IPF.

Estimation of Cadmium uptake by tobacco plants from laboratory leaching tests.

The objective of the present study was to determine the impact of cadmium (Cd) concentration in the soil on its uptake by tobacco plants, and to compare the ability of diverse extraction procedures for determining Cd bioavailability and predicting soil-to-plant transfer and Cd plant concentrations. The pseudo-total digestion procedure, modified Tessier sequential extraction and six standard single-extraction tests for estimation of metal mobility and bioavailability were used for the leaching of Cd from a native soil, as well as samples artificially contaminated over a wide range of Cd concentrations. The results of various leaching tests were compared between each other, as well as with the amounts of Cd taken up by tobacco plants in pot experiments. In the native soil sample, most of the Cd was found in fractions not readily available under natural conditions, but with increasing pollution level, Cd amounts in readily available forms increased. With increasing concentrations of Cd in the soil, the quantity of pollutant taken up in tobacco also increased, while the transfer factor (TF) decreased. Linear and non-linear empirical models were developed for predicting the uptake of Cd by tobacco plants based on the results of selected leaching tests. The non-linear equations for ISO 14870 (diethylenetriaminepentaacetic acid extraction - DTPA), ISO/TS 21268-2 (CaCl2 leaching procedure), US EPA 1311 (toxicity characteristic leaching procedure - TCLP) single step extractions, and the sum of the first two fractions of the sequential extraction, exhibited the best correlation with the experimentally determined concentrations of Cd in plants over the entire range of pollutant concentrations. This approach can improve and facilitate the assessment of human exposure to Cd by tobacco smoking, but may also have wider applicability in predicting soil-to-plant transfer.

Comparison of mediastinal lymph node status and relapse pattern in clinical stage IIIA non-small cell lung cancer patients treated with neoadjuvant chemotherapy versus upfront surgery: A single center experience.

BACKGROUND: In spite of the progress made in neoadjuvant therapy for operable non small-cell lung cancer (NSCLC), many issues remain unsolved, especially in locally advanced stage IIIA. METHODS: Retrospective data of 163 patients diagnosed with stage IIIA NSCLC after surgery was analyzed. The patients were divided into two groups: a preoperative chemotherapy group including 59 patients who received platinum-etoposide doublet treatment before surgery, and an upfront surgery group including 104 patients for whom surgical resection was the first treatment step. Adjuvant chemotherapy or/and radiotherapy was administered to 139 patients (85.3%), while 24 patients (14.7%) were followed-up only. RESULTS: The rate of N2 disease was significantly higher in the upfront surgery group ( P < 0.001). The one-year relapse rate was 49.5% in the preoperative chemotherapy group compared to 65.4% in the upfront surgery group. There was a significant difference in relapse rate in relation to adjuvant chemotheraphy treatment ( P = 0.007). The probability of relapse was equal whether radiotherapy was applied or not ( P = 0.142). There was no statistically significant difference in two-year mortality ( P = 0.577). The median survival duration after two years of follow-up was 19.6 months in the preoperative chemotherapy group versus 18.8 months in the upfront surgery group ( P = 0.608 > 0.05). CONCLUSION: There was significant difference in preoperative chemotherapy group regarding relapse rate and treatment outcomes related to the lymph node status comparing to the upfront surgery group. Neoadjuvant/adjuvant chemo-therapy is a part of treatment for patients with stage IIIA NSCLC, but further investigation is required to determine optimal treatment.

Identification of transcription factors involved in the transcriptional regulation of the CXCL12 gene in rat pancreatic insulinoma Rin-5F cell line.

Diabetes is characterized by a deficit in the number of functional pancreatic ß-cells. Understanding the mechanisms that stimulate neogenesis of ß-cells should contribute to improved maintenance of ß-cell mass. Chemokine CXCL12 has recently become established as a novel ß-cell growth factor, however the mechanisms controlling its expression require clarification. We investigated the proteins involved in the transcriptional regulation of the rat ß-cell CXCL12 gene (Cxcl12). Using the electrophoretic mobility shift assay and chromatin immunoprecipitation, we established the in vitro and in vivo binding of C/EBPß, C/EBPα, STAT3, p53, FOXO3a, and HMG I/Y to the Cxcl12 promoter. Co-immunoprecipitation experiments revealed protein-protein interactions between YY1 and PARP-1, FOXO3a and PARP-1, Sp1 and PARP-1, p53 and PARP-1, C/EBPß and PARP-1, YY1 and p53, YY1 and FOXO3a, p53 and FOXO3a, Sp1 and FOXO3a, C/EBPß and FOXO3a, C/EBPα and FOXO3a, Sp1 and STAT3. Our data lay the foundation for research into the interplay of signaling pathways that determine the ß-cell Cxcl12 expression profile.

Oxidative stress and mitochondrial dysfunction in Kindler syndrome.

BACKGROUND: Kindler Syndrome (KS) is an autosomal recessive skin disorder characterized by skin blistering, photosensitivity, premature aging, and propensity to skin cancer. In spite of the knowledge underlying cause of this disease involving mutations of FERMT1 (fermitin family member 1), and efforts to characterize genotype-phenotype correlations, the clinical variability of this genodermatosis is still poorly understood. In addition, several pathognomonic features of KS, not related to skin fragility such as aging, inflammation and cancer predisposition have been strongly associated with oxidative stress. Alterations of the cellular redox status have not been previously studied in KS. Here we explored the role of oxidative stress in the pathogenesis of this rare cutaneous disease. METHODS: Patient-derived keratinocytes and their respective controls were cultured and classified according to their different mutations by PCR and western blot, the oxidative stress biomarkers were analyzed by spectrophotometry and qPCR and additionally redox biosensors experiments were also performed. The mitochondrial structure and functionality were analyzed by confocal microscopy and electron microscopy. RESULTS: Patient-derived keratinocytes showed altered levels of several oxidative stress biomarkers including MDA (malondialdehyde), GSSG/GSH ratio (oxidized and reduced glutathione) and GCL (gamma-glutamyl cysteine ligase) subunits. Electron microscopy analysis of both, KS skin biopsies and keratinocytes showed marked morphological mitochondrial abnormalities. Consistently, confocal microscopy studies of mitochondrial fluorescent probes confirmed the mitochondrial derangement. Imbalance of oxidative stress biomarkers together with abnormalities in the mitochondrial network and function are consistent with a pro-oxidant state. CONCLUSIONS: This is the first study to describe mitochondrial dysfunction and oxidative stress involvement in KS.

Spontaneous regression of multiple melanocytic nevi after melanoma: report of 3 cases.

Complete spontaneous regression of multiple melanocytic nevi after melanoma is an extremely rare phenomenon. We report 3 cases of patients with a history of melanoma that showed regression of almost all melanocytic nevi over time. One of the patients had 2 simultaneous primary cutaneous melanomas without metastasis. In the other 2 patients, regression of the melanocytic nevi was seen after the development of metastasis in lymph nodes. These patients had spontaneously developed an efficient immune response against melanocytes, and they would represent paradigmatic examples of the spontaneous immune responses in melanoma patients. Better understanding of the mechanisms involved in the complete regression of melanocytic lesions would lead to a better selection of melanoma patients for immunotherapy.

In situ antioxidant and antimicrobial activities of naturally occurring caffeic acid, p-coumaric acid and rutin, using food systems.

BACKGROUND: Three pure compounds that naturally occur in plants were of particular interest to our study regarding the possibility of using them as food preservatives: p-coumaric acid (found in peanuts, tomatoes, carrots, garlic, wine, vinegar, etc.), caffeic acid (found in argan oil, oats, wheat, rice and olive oil) and rutin (found in asparagus, citrus fruits, berries, apple, apricot, asparagus, beef and beer). In the following study we investigated in situ antioxidant and antimicrobial activities of three pure compounds, namely caffeic acid, p-coumaric acid and rutin, naturally occurring in plants. RESULTS: Two food systems were used in order to obtain information on how these compounds react in actual food systems rather than microbiological media. The results indicated good antioxidant activity in in situ food systems. For tested phenolic compounds it was further shown that they successively inhibited the development of the isolated food contaminant Staphylococcus aureus in chicken soup. Panelist found that organoleptic characteristics of chicken soup and pork meat improved after treatment with phenolics. CONCLUSION: Our findings alone, along with the potential use of phenolic compounds that are widespread in nature, may imply their potential use as preservatives in the food industry.

PARP-1 and YY1 are important novel regulators of CXCL12 gene transcription in rat pancreatic beta cells.

Despite significant progress, the molecular mechanisms responsible for pancreatic beta cell depletion and development of diabetes remain poorly defined. At present, there is no preventive measure against diabetes. The positive impact of CXCL12 expression on the pancreatic beta cell prosurvival phenotype initiated this study. Our aim was to provide novel insight into the regulation of rat CXCL12 gene (Cxcl12) transcription. The roles of poly(ADP-ribose) polymerase-1 (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation. The regulatory activities of PARP-1 and YY1 were assessed in transfection experiments using a reporter vector with a Cxcl12 promoter sequence driving luciferase gene expression. Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription. Streptozotocin (STZ)-induced general toxicity in pancreatic beta cells was followed by changes in Cxcl12 promoter regulation. PARP-1 binding to the Cxcl12 promoter during basal and in STZ-compromised conditions led us to conclude that PARP-1 regulates constitutive Cxcl12 expression. During the early stage of oxidative stress, YY1 exhibited less affinity toward the Cxcl12 promoter while PARP-1 displayed strong binding. These interactions were accompanied by Cxcl12 downregulation. In the later stages of oxidative stress and intensive pancreatic beta cell injury, YY1 was highly expressed and firmly bound to Cxcl12 promoter in contrast to PARP-1. These interactions resulted in higher Cxcl12 expression. The observed ability of PARP-1 to downregulate, and of YY1 to upregulate Cxcl12 promoter activity anticipates corresponding effects in the natural context where the functional interplay of these proteins could finely balance Cxcl12 transcription.

Histone h3 glutathionylation in proliferating mammalian cells destabilizes nucleosomal structure.

AIMS: Here we report that chromatin, the complex and dynamic eukaryotic DNA packaging structure, is able to sense cellular redox changes. Histone H3, the only nucleosomal protein that possesses cysteine(s), can be modified by glutathione (GSH). RESULTS: Using Biotin labeled glutathione ethyl ester (BioGEE) treatment of nucleosomes in vitro, we show that GSH, the most abundant antioxidant in mammals, binds to histone H3. BioGEE treatment of NIH3T3 cells indicates that glutathionylation of H3 is maximal in fast proliferating cells, correlating well with enhanced levels of H3 glutathionylation in different tumor cell lines. Furthermore, glutathionylation of H3 in vivo decreases in livers from aged SAMP8 and C57BL/6J mice. We demonstrate biochemically and by mass spectrometry that histone variants H3.2/H3.3 are glutathionylated on their cysteine residue 110. Furthermore, circular dichroism, thermal denaturation of reconstituted nucleosomes, and molecular modeling indicate that glutathionylation of histone H3 produces structural changes affecting nucleosomal stability. INNOVATION: We characterize the implications of histone H3 glutathionylation in cell physiology and the modulation of core histone proteins structure affected by this modification. CONCLUSION: Histone H3 senses cellular redox changes through glutathionylation of Cys, which increases during cell proliferation and decreases during aging. Glutathionylation of histone H3 affects nucleosome stability structure leading to a more open chromatin structure.

Decreased O-GlcNAcylation of the key proteins in kinase and redox signalling pathways is a novel mechanism of the beneficial effect of α-lipoic acid in diabetic liver.

The present study aimed to investigate the effects of the treatment with a-lipoic acid (LA), a naturally occurring compound possessing antioxidant activity, on liver oxidant stress in a rat model of streptozotocin (STZ)-induced diabetes by examining potential mechanistic points that influence changes in the expression of antioxidant enzymes such as catalase (CAT) and CuZn/Mn superoxide dismutase(s) (SOD). LA was administered for 4 weeks by daily intraperitoneal injections (10 mg/kg) to STZ-induced diabetic rats, starting from the last STZ treatment. LA administration practically normalised the activities of the indicators of hepatocellular injury, alanine and aspartate aminotransferases, and lowered oxidative stress, as observed by the thiobarbituric acid-reactive substance assay, restored the reduced glutathione:glutathione disulphide ratio and increased the protein sulfhydryl group content. The lower level of DNA damage detected by the comet assay revealed that LA reduced cytotoxic signalling, exerting a hepatoprotective effect. The LA-treated diabetic rats displayed restored specific enzymatic activities of CAT, CuZnSOD and MnSOD. Quantitative real-time PCR analysis showed that LA restored CAT gene expression to its physiological level and increased CuZnSOD gene expression, but the gene expression of MnSOD remained at the diabetic level. Although the amounts of CAT and CuZnSOD protein expression returned to the control levels, the protein expression of MnSOD was elevated. These results suggested that LA administration affected CAT and CuZnSOD expression mainly at the transcriptional level, and MnSOD expression at the post-transcriptional level. The observed LA-promoted decrease in the O-GlcNAcylation of extracellular signal-regulated kinase, protein 38 kinase, NF-kB, CCAAT/enhancer-binding protein and the antioxidative enzymes themselves in diabetic rats suggests that the regulatory mechanisms that supported the changes in antioxidative enzyme expression were also influenced by post-translational mechanisms.

Alpha-lipoic acid upregulates antioxidant enzyme gene expression and enzymatic activity in diabetic rat kidneys through an O-GlcNAc-dependent mechanism.

PURPOSE: The combined hyperglycemia lowering and antioxidant actions of α-lipoic acid (LA) contribute to its usefulness in preventing renal injury and other diabetic complications. The precise mechanisms by which LA alters diabetic oxidative renal injury are not known. We hypothesized that LA through its hypoglycemic effect lowers O-GlcNAcylation which influences the expression and activities of antioxidant enzymes which assume important roles in preventing diabetes-induced oxidative renal injury. METHODS: An experimental model of diabetes was induced in rats by the administration of 40 mg/kg streptozotocin (STZ) intraperitoneally (i.p.) for five consecutive days. LA was applied at a dose of 10 mg/kg i.p. for 4 weeks, starting from the last day of STZ administration. RESULTS: An improved glycemic status of LA-treated diabetic rats was accompanied by a significant suppression of oxidative stress and a reduction of oxidative damage of lipids, proteins and DNA. LA treatment normalized CuZn-superoxide dismutase (SOD) and catalase activities in renal tissue of diabetic rats. These changes were allied with upregulated gene expression and lower levels of O-GlcNA glycosylation. The accompanying increase in MnSOD activity was only linked with upregulated gene expression. The observed antioxidant enzyme gene regulation was accompanied by nuclear translocation of Nuclear factor-erythroid-2-related factor 2 (Nrf2), enhanced expression of heat shock proteins (HSPs) and by reduction in O-GlcNAcylation of HSP90, HSP70, and extracellular regulated kinase and p38. CONCLUSION: α-Lipoic acid administration activates a coordinated cytoprotective response against diabetes-induced oxidative injury in kidney tissue through an O-GlcNAc-dependent mechanism.

Nuclear glutathione.

Glutathione (GSH) is a linchpin of cellular defences in plants and animals with physiologically-important roles in the protection of cells from biotic and abiotic stresses. Moreover, glutathione participates in numerous metabolic and cell signalling processes including protein synthesis and amino acid transport, DNA repair and the control of cell division and cell suicide programmes. While it is has long been appreciated that cellular glutathione homeostasis is regulated by factors such as synthesis, degradation, transport, and redox turnover, relatively little attention has been paid to the influence of the intracellular partitioning on glutathione and its implications for the regulation of cell functions and signalling. We focus here on the functions of glutathione in the nucleus, particularly in relation to physiological processes such as the cell cycle and cell death. The sequestration of GSH in the nucleus of proliferating animal and plant cells suggests that common redox mechanisms exist for DNA regulation in G1 and mitosis in all eukaryotes. We propose that glutathione acts as "redox sensor" at the onset of DNA synthesis with roles in maintaining the nuclear architecture by providing the appropriate redox environment for the DNA replication and safeguarding DNA integrity. In addition, nuclear GSH may be involved in epigenetic phenomena and in the control of nuclear protein degradation by nuclear proteasome. Moreover, by increasing the nuclear GSH pool and reducing disulfide bonds on nuclear proteins at the onset of cell proliferation, an appropriate redox environment is generated for the stimulation of chromatin decompaction. This article is part of a Special Issue entitled Cellular functions of glutathione.

Histological types and age distribution of lung cancer operated patients over a 20-year period: a pathohistological based study.

INTRODUCTION: Lung cancer is the leading cause of death from malignancy in Serbia. OBJECTIVE: This is a retrospective analysis of lung cancer epidemiological changes regarding to its histological type and patients' age of both genders. Data were based on surgically treated lung cancer patients from 1985 to 2005. METHODS: Data were collected from 972 pathohistological reports of operated patients of both genders divided into age groups. Histological types of lung cancer were distributed in four major groups: squamous cell cancer (SCC), adenocarcinoma (AC), small cell cancer (SCLC) and other rare histological types. Both genders together and separately were analysed. Chi-square with the level of significance p<0.05 and chi-square test for trends were used as statistical methods. RESULTS: SCC predominated in both genders; in 44.7% females and 68.0% males. AC was less frequently diagnosed (21.8%) than SCC (64.0%) in both genders and all age groups. The most frequently operated patients were aged between 51 and 60 years (36.6%) with SCC and AC predominance. Three patients with SCLC were operated in 61-70 age-group. In age-group up to 30 years, three (0.5%) patients were operated on for SCC and other rare lung tumours, respectively. Predominance of other rare lung tumours was established in 51-60 age-group, 25% of patients of both genders. CONCLUSION: SCC is the most frequent histological type of lung cancer found in all age groups and in both genders of surgically treated patients.

Extract of the plant Cotinus coggygria Scop. attenuates pyrogallol-induced hepatic oxidative stress in Wistar rats.

To examine the protective potential of the Cotinus coggygria Scop. methanol extract, Wistar rats were treated with the hepatotoxic compound pyrogallol, which possesses a potent ability to generate free radicals and induce oxidative stress. The ability of the extract to counteract the oxidative stress was examined in rats that were injected with the extract intraperitoneally (500 mg·(kg body weight)(-1)) either 2 or 12 h before the pyrogallol treatment. The extract possesses a reducing activity in vitro and an ability to chelate the ferrous ion both in vivo and in vitro. Application of the extract prior to pyrogallol treatment led to a decrease in the levels of thiobarbituric acid-reactive substances, aspartate aminotransferase, and alanine aminotransferase, increased activities of antioxidant enzymes and attenuation of DNA damage, as well as increased Akt activity and inhibition of NF-κB protein expression. Treatment with the extract 12 h prior to pyrogallol administration was more effective in suppressing pyrogallol-induced oxidative damage than the 2 h pretreatment. Extract administration promoted an increase in acute phase reactants haptoglobin and α(2)-macroglobulin that was short of a full-fledged acute phase response. Administration of the extract considerably improved the markers of oxidative stress, thus revealing a potential hepatoprotective activity. Our results suggest that Akt activation, NF-κB inhibition, and induction of the acute phase play important roles in mediating hepatic protection by the extract. The greater effectiveness of the 12 h pretreatment with extract points to the important role that preconditioning assumes in improving resistance to subsequent exposure to oxidative stress.