Resveratrol and lycopene ameliorate contrast-induced nephropathy in a rabbit model.

Oxidative stress appears to possess a central role in CIN pathophysiology. Resveratrol (Res) and lycopene (Lyc) are strong natural antioxidants evaluated in a limited number of CIN animal studies in vivo. The aim of the study was to evaluate the potential renoprotective effects of Res/Lyc in a CIN rabbit model. Twenty-four adult male New Zealand white rabbits were equally assigned into four groups: control (saline), CIN (intravenous iopromide; 7.5 g iodine/kg), Res + CIN (per os Res; 5 mg/kg), and Lyc + CIN (per os Lyc; 4 mg/kg). Serum Cr (sCr); symmetric/asymmetric dimethylarginine (SDMA/ADMA); oxidative stress biomarkers: malondialdehyde; total antioxidant capacity; catalase; glutathione) were evaluated in blood samples at three time points: right after (0 h); 24 h; 48 h after iopromide/saline administration. CD20+/CD3+ lymphocytes were determined (48 h). All animals were sacrificed at 48 h and both kidneys collected. Oxidative stress biomarkers were measured in renal tissue. sCr and SDMA/ADMA levels increased significantly in CIN compared to all groups. Oxidative stress secondary to CIN in blood/kidneys was suppressed by Res/Lyc. B and T lymphocytes decreased significantly in CIN compared to all groups. The present study provides emerging evidence that Res/Lyc ameliorate CIN by modulating oxidant/antioxidant balance in blood/renal tissue and by inhibiting vasoconstriction/blood cytotoxicity.

Cytological diagnosis of unifocal Langerhans cell histiocytosis in the temporomandibular joint.

Unifocal Langerhans cell histiocytosis (LCH) presents as a solitary focal bone lesion characterized by clonal proliferation of CD1a (+) and langerin(+) dendritic cells, derived from the bone marrow. In 38-69% of cases BRAF-V600E mutation is revealed. It gains attention to maxillofacial surgeons due to involvement of the orofacial region and early onset of jaws symptoms. If overlooked, massive deconstruction of tissues, occurs. We present a case of LCH of the temporomandibular joint in a 14 aged child where fine needle aspiration favorably contributed in an accurate diagnosis combined with the appropriate clinicoradioliogical findings. This can overrule unwarranted biopsy and monitor the treatment largely where aproach to histopathology services is restricted.

URINE CYTOLOGY AND AXILLARY TESTING FOR INTERPRETATION AND FOLLOW-UP OF URINARY TUMORS.

Microscopic appearance of cells in urine cytological samples is the formal diagnostic approach adjunct to cystoscopy for the detection and follow-up of urinary tumors. However, cystoscopy is a surgical method and cytology may miss low-grade papillary tumors. Several assays and markers have been developed to assist in this. When combined with conventional cytology, uro-oncological diagnostic performance is improved. We review the value of these non-invasive modalities in comparison with urine cytomorphology in the work-up of urothelial malignancies.

Intraoperative squash Cytology of diffuse glioma not otherwise specified, of the Cerebellum.

OBJECTIVE: Diffuse glioma arises anywhere in the CNS, but most frequent in the cerebral hemispheres. The tumor tends to be seen in children and in younger adults aged 20-30. We report one such case in an older female patient presenting the intraoperative cytology of the tumor. CASE REPORT: A 48-year-old female was diagnosed by MRI with a tumor of cerebellum. Cytologic material was obtained during the resection of the tumor and diagnosed cytologically as glioma. CONCLUSION: This case is presented to focus the ability of the intraoperative cytology in diagnosis of the glioma, using immunocytology and confirmed by histo- immunohistology.

Cerebrospinal fluid and intraoperative squash cytology of childhood ependymoma.

Ependymomas are glial neoplasms of central nervous system originated from the ependymal lining of the brain ventricles and spinal cord central canal, and rarely exfoliated into cerebrospinal fluid (CSF). In this case we report the cytomorphological and immunocytomorphological features of ependymoma in CSF and intraoperative squash preparations, confirmed by histology. Case report. The patient  was a nineteen months old female presented at the University hospital of Heraklion, Crete, in a hemicoma, and was intubated. Computed tomography, scanning and magnetic resonance imaging (MRI), were performed and a mass in the posterior fossa was found. A sample of cerebrospinal fluid (CSF) was sent for cytologic evaluation. A diagnosis of ependymoma was rendered, followed by tumor resection, during which intraoperative squash smears for cytologic interpretation were obtained. Cytological consultation disclosed a grade II ependymoma (WHO grade II), with focally anaplastic features (WHO grade III).

Osteoclast: like giant cell undiferrentiated pancreatic tumor diagnosed by means of EUS guided FNA.

OBJECTIVE: Osteoclast-like giant cell tumours are rare abdominal malignant neoplasms mainly arising in the pancreas. Because of their rarity, clinical and cytopathology reports are very limited, and sonographic features have not been clearly specified ; these tumors are easily misdiagnosed by ultrasound as mucinous cystic tumors (MCTs)  or solid pseudopapillary neoplasms (SPNs). CASE STUDY: We report a case of osteoclast  like giant cell tumor arising in the pancreas of an 80 year old female patient offered by EUS-FNA cytology on direct and cell block slides. A biphasic pattern composed by a malignant mononuclear cell component and a giant cell component were hallmarks to the diagnosis. CONCLUSION: Our case highlights the performance of EUS-FNA in the diagnostic approach of  abdominal tumours and the significance of cell block method in the interpretation of osteoclast-like giant cell pancreatic tumour.

Determination of prenatal exposure to parabens and triclosan and estimation of maternal and fetal burden.

BACKGROUND: Parabens (PBs) and triclosan (TCS) are generally used as antimicrobials mostly in personal care products. Their wide prevalence in daily products raised an acute need for the biomonitoring of these contaminants and the investigation of possible health impacts. MATERIAL AND METHODS: In this study we aimed to quantitatively determine PBs and TCS levels in urine and amniotic fluid samples using a liquid chromatography - mass spectrometry system (LC-MS). Ninety nine (99) pregnant women took part in this research. The samples were collected during the amniocentesis in the early second trimester of their pregnancy. Women of all ages, education, household income and profession were selected. The exposure and the burden of pregnant women and their infants were also evaluated. RESULTS: The most prevalent compound in urine, among the analyzed, was TCS with 74.7 % positive samples while in amniotic fluid methyl paraben (MePB) with 21.2 % positive samples. MePB was detected at higher concentrations in urine (mean: 378.5 ng/mL) followed by TCS (mean: 55.3 ng/mL), ethyl paraben (EtPB) (mean: 23.2 ng/mL) and butyl paraben (BuPB) (mean: 2.3 ng/mL) while benzyl paraben (BePB) was not detected in any urine sample. Concentrations in amniotic fluid samples were much lower. In particular, the mean concentrations were 6.6 ng/mL for MePB, 9.2 ng/mL for EtPB, 0.4 ng/mL for BuPB, 0.6 ng/mL for BePB and 1.8 ng/mL for TCS. The detected levels of all analytes in urine were correlated with those in amniotic fluid but no statistically significant results arose (p >n0.05). Negative associations were observed between amniotic fluid levels of MePB and maternal age (p = 0.05) while both urinary and amniotic levels of TCS were correlated with maternal BMI (p = 0.04). Somatometric characteristics of the infants showed no statistical significant associations with the detected levels of PBs and TCS. CONCLUSION: This study indicated a strong/possible association between exposure of pregnant women to TCS and higher/lower maternal body weight gain during pregnancy. The same trend was observed between amniotic fluid MePB levels and maternal age. However, no statistically significant associations were observed between neonatal somatometric characteristics or health status and PBs and TCS levels.

Diagnosis and immunocytochemical characterization of an EBV related diffuse B large cell lymphoma of the retroperitoneum from cell block preparations obtained by means of EUS guided FNA.

Diffuse large B cell lymphoma (DLBCL) in the retroperitoneum has been scarcely reported and the diagnostic workup is challenging due to difficulties in access to tissue. A 73-year-old female presented to the gastroenterology clinic, with recent-onset atypical abdominal pain and alternating constipation and diarrhea.

Carcinogenic, ethanol, acetaldehyde and noncarcinogenic higher alcohols, esters, and methanol compounds found in traditional alcoholic beverages. A risk assessment approach.

Greek fermentation and distillation industries produce traditional spirit beverages, such as tsipouro and tsikoudia, consumed both in bottles and bulk quantities by the general population or tourists. The same spirits are also produced by individuals at home since previous centuries, as a part of the local culture but mainly due to the Greek agricultural sector unique characteristics (small cultivation areas with great number of farmers). In this study, the concentrations of carcinogenic compounds: ethanol and acetaldehyde; and noncarcinogenic: higher alcohols (1-propanol, isobutanol, and isoamyl alcohol), esters (ethyl acetate), and methanol were measured to estimate the potential cancer risk and daily intake of these compounds. The margin of exposure (MOE) of carcinogenic compounds was found to be less than 500 (mean value), well below the toxic threshold of 10,000, above which there is not public concern, as suggested by the European Food Safety Authority. Additionally, through risk assessment of noncarcinogenic compounds, we identified two specific compounds in-bulk spirits (produced by individuals), namely ethyl acetate and isobutanol, with health risk index (HRI) greater than 1 (indicating a possibility to induce side effects by consumption of high amounts). Our results indicate that bottled spirits, which are produced in a controlled environment (alcohol industries), showed higher human safety level in terms of both carcinogenic and noncarcinogenic risk assessment studies, comparing to bulk beverages produced by individuals (with out strict regulations).

Current and Future Trends in Molecular Biomarkers for Diagnostic, Prognostic, and Predictive Purposes in Non-Melanoma Skin Cancer.

Skin cancer represents the most common type of cancer among Caucasians and presents in two main forms: melanoma and non-melanoma skin cancer (NMSC). NMSC is an umbrella term, under which basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Merkel cell carcinoma (MCC) are found along with the pre-neoplastic lesions, Bowen disease (BD) and actinic keratosis (AK). Due to the mild nature of the majority of NMSC cases, research regarding their biology has attracted much less attention. Nonetheless, NMSC can bear unfavorable characteristics for the patient, such as invasiveness, local recurrence and distant metastases. In addition, late diagnosis is relatively common for a number of cases of NMSC due to the inability to recognize such cases. Recognizing the need for clinically and economically efficient modes of diagnosis, staging, and prognosis, the present review discusses the main etiological and pathological features of NMSC as well as the new and promising molecular biomarkers available including telomere length (TL), telomerase activity (TA), CpG island methylation (CIM), histone methylation and acetylation, microRNAs (miRNAs), and micronuclei frequency (MNf). The evaluation of all these aspects is important for the correct management of NMSC; therefore, the current review aims to assist future studies interested in exploring the diagnostic and prognostic potential of molecular biomarkers for these entities.

The toxic influence and biodegradation of carbon nanofibers in freshwater invertebrates of the families Gammaridae, Ephemerellidae, and Chironomidae.

Carbon nanofibers (CNFs) are widely used in consumer products today. In this study, we assessed the effects of CNFs on the digestive system of three freshwater invertebrate species (Gammaridae, Ephemerellidae, and Chironomidae). The aquatic insects Diamesa sp., Drunella cryptomeria, and Gammarus suifunensis were incubated with the CNFs at the concentration of 100 mg/L during the 7-days period. Histological examination of the whole specimens and the longitudinal sections revealed no toxic effects of CNFs. However, a noticeable change in the structure of the CNFs accumulated in the intestines of the aquatic insects was found by Raman spectroscopy. The registered decrease in the relative proportion of amorphous carbon included in the CNF sample was found in the intestines of Diamesa sp. and D. cryptomeria. The registered effect can indicate a biodegradation of amorphous carbon in the digestive tract of these two insect species. In contrast, the decrease of highly structured carbons and the decrease of G-bonds intensity were registered in the digestive tract of G. suifunensis. This observation demonstrates the partial biodegradation of CNFs in the digestive tract of G. suifunensis.

Translational Application of Circulating DNA in Oncology: Review of the Last Decades Achievements.

In recent years, the introduction of new molecular techniques in experimental and clinical settings has allowed researchers and clinicians to propose circulating-tumor DNA (ctDNA) analysis and liquid biopsy as novel promising strategies for the early diagnosis of cancer and for the definition of patients' prognosis. It was widely demonstrated that through the non-invasive analysis of ctDNA, it is possible to identify and characterize the mutational status of tumors while avoiding invasive diagnostic strategies. Although a number of studies on ctDNA in patients' samples significantly contributed to the improvement of oncology practice, some investigations generated conflicting data about the diagnostic and prognostic significance of ctDNA. Hence, to highlight the relevant achievements obtained so far in this field, a clearer description of the current methodologies used, as well as the obtained results, are strongly needed. On these bases, this review discusses the most relevant studies on ctDNA analysis in cancer, as well as the future directions and applications of liquid biopsy. In particular, special attention was paid to the early diagnosis of primary cancer, to the diagnosis of tumors with an unknown primary location, and finally to the prognosis of cancer patients. Furthermore, the current limitations of ctDNA-based approaches and possible strategies to overcome these limitations are presented.

Genotoxic, cytotoxic, and cytopathological effects in rats exposed for 18 months to a mixture of 13 chemicals in doses below NOAEL levels.

The present study investigates the genotoxic and cytotoxic effects of long term exposure to low doses of a mixture consisting of methomyl, triadimefon, dimethoate, glyphosate, carbaryl, methyl parathion, aspartame, sodium benzoate, EDTA, ethylparaben, buthylparaben, bisphenol A and acacia gum in rats. Four groups of ten Sprangue Dawley rats (5 males and 5 females per group) were exposed for 18 months to the mixture in doses of 0xNOAEL, 0.0025xNOAEL, 0.01xNOAEL and 0.05xNOAEL (mg/kg bw/day). After 18 months of exposure, the rats were sacrificed and their organs were harvested. Micronuclei frequency was evaluated in bone marrow erythrocytes whereas the organs were cytopathologically examined by the touch preparation technique. The exposure to the mixture caused a genotoxic effect identified only in females. Cytopathological examination showed specific alterations of tissue organization in a tissue-type dependent manner. The observed effects were dose-dependent and correlated to various tissue parameters. Specifically, testes samples revealed degenerative and cellularity disorders, liver hepatocytes exhibited decreased glycogen deposition whereas degenerative changes were present in gastric cells. Lung tissue presented increased inflammatory cells infiltration and alveolar macrophages with enhanced phagocytic activity, whereas brain tissue exhibited changes in glial and astrocyte cells' numbers. In conclusion, exposure to very low doses of the tested mixture for 18 months induces genotoxic effects as well as monotonic cytotoxic effects in a tissue-dependent manner.

Contrast-induced nephropathy in an animal model: Evaluation of novel biomarkers in blood and tissue samples.

Identification of novel biomarkers of contrast-induced nephropathy (CIN) that may more accurately detect renal function changes; reflect kidney damage; assist monitoring; and elucidate pathophysiology attract considerable scientific attention nowadays. To evaluate novel biomarkers of nephrotoxicity in blood/tissue samples of a CIN model, 10 New Zealand white rabbits were divided into group 1 (n = 5; iopromide) and group 2 (n = 5; control). Blood was drawn at 0 h (immediately), 24 h and 48 h after contrast medium (CM) administration. Animals were euthanized at 48 h and kidneys were removed. Serum creatinine (sCr)/symmetric-asymmetric dimethylarginine (SDMA-ADMA) levels were measured. CM genotoxic/cytotoxic effect was investigated 48 h post-CM exposure using micronucleus assay in lymphocytes. Cytological examination was conducted using touch preparation technique (TPT). All animals in group 1 developed CIN: mean sCr levels increased by 68.2% within 48 h. Significant SDMA-ADMA level elevation was observed at 0 h and 24 h with insignificant drop at 48 h in group 1, remaining normal in group 2 at all time-points. Significant increase in bi-nucleated cells with micronuclei and micronuclei frequency was detected in group 1. Cytokinesis block proliferation index was reduced insignificantly in group 1. TPT revealed degenerative lesions/inflammation, cell degeneration, abnormal uterine tubular casts and rubella in kidneys of all animals in group 1. Group 2 presented normal cells.

Adverse and hormetic effects in rats exposed for 12 months to low dose mixture of 13 chemicals: RLRS part III.

The aim of the current study was to evaluate the effects of a mixture of thirteen common chemicals on rats, after a one-year exposure to doses around the acceptable daily intake (ADIs), using blood and urinary tests. The influence of low doses of the mixture on weight gain, water consumption, feed consumption and feed efficiency, biochemistry parameters, haematological parameters, blood lymphocytes subsets, serum inflammation profile and urine parameters was evaluated. Our mixture caused a moderate monotonic increase of the males' appetite and a non-monotonic increase of anabolism and a monotonic increase of appetite for the females. Regarding biochemical parameters, the exposure to the test mixture caused non-monotonic increases of AST and ALT, a decrease of PChE in males and plausibly a monotonic biliary obstruction in both sexes. Monocytes significantly increased in low dose groups of both sexes. A significant decrease of all the lymphocytes subclasses and an increased expression of TNF-α protein associated with an increased expression of IFN-γ protein observed in various groups. It became apparent that after twelve months of exposure very low doses of the tested mixture had both non-monotonic and monotonic harmful effects on different levels on rats.

An imazamox-based herbicide causes apoptotic changes in rat liver and pancreas.

We studied the acute toxicity of an imazamox-based herbicide at 12, 24 and 36 mg/kg body (bw) weight imazamox equivalent dose on the liver and pancreatic tissue in Sprague Dawley rats. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, glucose, calcium as well as creatinine, were determined in blood samples, which were collected after 24, 48 and 72 h exposure. Caspase 3 and anti-insulin expression and immunopositivity were evaluated using in situ hybridization and immunohistochemistry, respectively. The imazamox-based herbicide evaluated in this study induced toxic effects even from the lowest dose tested (12 mg/kg bw). The two highest doses caused a statistically significant cytotoxicity on the Langerhans islet cells. Necrotic and degenerative changes were detected in hepatocytes at the two highest doses. Imazamox is considered to be poorly toxic to the liver. Nevertheless, the imazamox-based herbicide formulation tested here reduced the size of the ß-islet cells, induced an elevation in serum glucose and calcium. Our data shows that commercial formulations of imazamox containing various co-formulants can have hepatic and pancreatic toxic effects.

Schwannoma of right cerebellopontine angle. A cytologic diagnosis.

Schwannomas affect mainly head and neck peripheral nerves, are benign tumors and derive from Schwann cells. Schwannoma of right cerebellopontine angle is extremely rare to diagnose by cytology. We report one such rare case presenting the cytological features in material obtained during the resection of the tumor. Case report: A 47-year-old female was diagnosed by MRI with a tumor of right cerebellopontine angle.. Cytologic material from the tumor was obtained intraoperatively and diagnosed cytologically as a neurilemoma. Conclusion: This case is presented here to focus the ability of cytology in diagnosis of schwannoma in intraoperative material of the tumor, using immunohistochemistry and confirmed by histology- immunohistochemistry.

The immunotoxicological pattern of subchronic and chronic benzene exposure in rats.

Exposure to benzene and its inevitable metabolites can result in deleterious effects on human health, including lymphocytopenia, hematotoxicity and cancer. However, the duration of exposure might alter the effects including immune consequences. The aim of this study was to determine whether benzene could modulate lymphocyte proliferation induced by the T cell mitogen concanavalin A, in rats, at different exposure durations. 386 Wistar rats were assigned into control and treatment groups which were subdivided into groups for 45, 90 and 135days for 0,6mL/kg of drinking water mixed benzene treatment. The percentage of CD3+, CD4+, CD8+ spleen lymphocytes was defined using the flow cytometer. Interleukin (IL)-4, IL-6, IL-10 and interferon-gamma, in supernatants of splenocyte cultures stimulated with Concanavalin A, were assessed by enzyme-linked immunosorbent assay (ELISA) technique. The decrease in the total lymphocyte and T cell counts were associated with increased benzene exposure duration. Th2-type cytokine, IL-4 significantly increased, whereas IL-6, CD4+T cells, CD4+/CD8+ ratio and CD3+ T cells decreased. Despite the positive correlation between benzene toxicity and indicated increased immune responses, 45-day exposure to benzene appeared to be the most sensitive time point for evaluating benzene cytotoxicity.