Intramedullary Metastatic Endometrial Adenocarcinoma in a Goat.

A 7-year-old female goat developed progressive ataxia, which progressed to sternal recumbency. Clinical examination revealed a slight elevation in the sacral spine (S1-S2), tetraparesis, perineal hypoaesthesia and absent tail and anal reflexes. Due to unresponsiveness to treatment with corticosteroids, the goat was euthanized. At necropsy, a 4.0 × 5.7 × 2.5 cm tumour mass was found in the uterine body and right uterine horn. In the cauda equina (L6‒S2), a 3 cm tumour associated with a 2 cm ventral intraosseous sacral haematoma was also found. The tumours were characterized by neoplastic proliferation of columnar epithelial cells with a predominant tubular pattern. Neoplastic cells with glandular cytoplasm stained with acid Alcian blue and periodic acid‒Schiff. Other metastases were found in the lungs, right ovary, dura mater and nerve roots of the medullary cone. Neoplastic cells were immunolabelled for cytokeratin but were negative for vimentin, and the tumour was diagnosed as metastatic endometrial tubular adenocarcinoma. To our knowledge, this is the first report of intramedullary metastasis to the spinal cord of this tumour in any species except humans.

Multibiomarker approach to assess the magnitude of occupational exposure and effects induced by a mixture of metals.

Metals and metalloids including lead (Pb), arsenic (As) and manganese (Mn) can occur as mixtures in occupational contexts, such as mines. These chemicals are all known to be neurotoxic and provoke changes in heme metabolism also known to induce neurotoxicity. The objective of this work was to propose a multi-biomarker (BM) methodology to screen subjects exposed to the mixture of Pb, As and Mn and assess the severity of their exposure/effects, in an individual basis. The urinary levels of the metals, dela-aminolevulinic acid (ALA) and porphyrins were determined in Portuguese miners and in a control group. The combination of Pb and As urinary levels had the highest capability to identify subjects occupationally exposed to this mixture in mines, as evaluated through Receiver Operating Characteristic (ROC) (A = 98.2%; p < 0.05), allowing that 94.2% of 86 studied subjects were properly identified and the generation of an equation indicating the odd of a subject be considered as exposed to the metal mixture. The combination of urinary ALA and porphyrins revealed to be best one to be applied in the assessment of subjects with high, intermediate, and low magnitudes of exposure/effects, with 95.7% of 46 miners classified correctly according to their severity sub-group and allowing to generate equations, which can be applied in new subjects. The proposed methodology showed a satisfactory performance, evaluating in an integrated manner the magnitude of exposure/effects of the exposed workers, may contributing to improve the control of their health.

Assessment of occupational exposures to multiple metals with urinary porphyrin profiles.

Chronic occupational exposures to low levels of metal mixtures necessitates biomonitoring of exposed workers. However, a single biomarker (BM) is rarely sufficient to ascertain the exposure of an individual to a complex mixture, with multiparameter analysis of the same sample considered recently as a preferred approach. Porphyrins are formed as intermediates of heme biosynthesis and different metals can exert their effects at different points of this metabolic pathway, leading to changed urinary porphyrins excretion profiles. The aim of this work was to develop a model that could serve to identify, on an individual basis, multiple metal exposure resulting from mining work, by using urinary porphyrin profiles. Urine samples of workers were obtained from a Portuguese mining company and a non-occupationally exposed group was used as control. The levels of uro-, hepta-, hexa-, penta-, copro- and protoporphyrins were determined by HPLC. It was observed that only heptaporphyrin levels in miners were significantly (p<0.05) different from controls. However, when the concentrations of all porphyrins were combined by binary logistic regression, their ability to discriminate between miners and controls was higher than each one of the porphyrins alone, as indicated by a greater curve' area under a ROC curve. Moreover, when the combined porphyrins were used to calculate the probability of each subject fit in the occupationally exposed group, 83% of 47 individuals were correctly identified with respect to their type of exposure. These results suggest that the integration of the urinary porphyrin profile is a promising tool for the detection of subjects exhibiting biochemical modifications due to occupational exposure to metals in mines.

Lead, Arsenic, and Manganese Metal Mixture Exposures: Focus on Biomarkers of Effect.

The increasing exposure of human populations to excessive levels of metals continues to represent a matter of public health concern. Several biomarkers have been studied and proposed for the detection of adverse health effects induced by lead (Pb), arsenic (As), and manganese (Mn); however, these studies have relied on exposures to each single metal, which fails to replicate real-life exposure scenarios. These three metals are commonly detected in different environmental, occupational, and food contexts and they share common neurotoxic effects, which are progressive and once clinically apparent may be irreversible. Thus, chronic exposure to low levels of a mixture of these metals may represent an additive risk of toxicity. Building upon their shared mechanisms of toxicity, such as oxidative stress, interference with neurotransmitters, and effects on the hematopoietic system, we address putative biomarkers, which may assist in assessing the onset of neurological diseases associated with exposure to this metal mixture.

Arsenic and manganese alter lead deposition in the rat.

Lead (Pb) continues to be a major toxic metal in the environment. Pb exposure frequently occurs in the presence of other metals, such as arsenic (As) and manganese (Mn). Continued exposure to low levels of these metals may lead to long-term toxic effects due to their accumulation in several organs. Despite the recognition that metals in a mixture may alter each other's toxicity by affecting deposition, there is dearth of information on their interactions in vivo. In this work, we investigated the effect of As and Mn on Pb tissue deposition, focusing on the kidney, brain, and liver. Wistar rats were treated with eight doses of each single metal, Pb (5 mg/Kg bw), As (60 mg/L), and Mn 10 mg/Kg bw), or the same doses in a triple metal mixture. The kidney, brain, liver, blood, and urine Pb, As, and Mn concentrations were determined by graphite furnace atomic absorption spectrophotometry. The Pb kidney, brain, and liver concentrations in the metal-mixture-treated group were significantly increased compared to the Pb-alone-treated group, being more pronounced in the kidney (5.4-fold), brain (2.5-fold), and liver (1.6-fold). Urinary excretion of Pb in the metal-mixture-treated rats significantly increased compared with the Pb-treated group, although blood Pb concentrations were analogous to the Pb-treated group. Co-treatment with As, Mn, and Pb alters Pb deposition compared to Pb alone treatment, increasing Pb accumulation predominantly in the kidney and brain. Blood Pb levels, unlike urine, do not reflect the increased Pb deposition in the kidney and brain. Taken together, the results suggest that the nephro- and neurotoxicity of "real-life" Pb exposure scenarios should be considered within the context of metal mixture exposures.

High-fish consumption and risk prevention: assessment of exposure to methylmercury in Portugal.

The aim of this study was to evaluate the exposure to methylmercury (MeHg) of potential populations at risk living in Portugal. To ascertain youth exposure, a questionnaire was distributed to 300 students of a middle secondary school in Sesimbra and to 429 students studying in Canecas, selected as the control population. The average number of fish meals consumed by person was 4.1 and 3 per week in Sesimbra and Canecas, respectively. The subpopulations of high intake (PHI) corresponding to those ingesting 7 or more fish meals per week were also analyzed separately, with 17% of the students belonging to the PHI of Sesimbra versus 6.1% in Canecas. Socioeconomic aspects such as relative's professional involvement with fisheries correlated with the higher intakes in Sesimbra. Fish samples were collected in the dock of Sesimbra and total mercury (Hg) was determined by flow injection cold vapor atomic fluorescence spectroscopy (FI-CV-AFS). The mean value found for nonpredators was 0.035 microg/g. Dogfish specimens surpassed the legislated limit for predator species and increased the predators mean to 1 microg/g. The cross-sectional data were integrated with the fish analysis results to estimate the population exposure to MeHg. The indices of risk calculated for youth reached values of 4.5, demonstrating the existence of risk to a part of the population exceeding the provisional tolerable weekly intake (PTWI) level mandated by WHO (1.6 microg/kg bw). The results indicate that monitoring of Hg levels in fish is mandatory and counseling should be provided to populations at risk, encouraging them to prevent the risk.

Interaction of zinc on biomarker responses in rats exposed to 2,5-hexanedione by two routes of exposure.

The interaction of zinc(II) on the toxicokinetics of 2,5-hexanedione (2,5-HD), the ultimate toxic metabolite of n-hexane, was performed by quantifying the changes of two urinary biomarkers, free 2,5-HD and pyrrole derivatives, in rats exposed to 2,5-HD and to 2,5-HD plus zinc acetate. Eight groups of Wistar rats were exposed for 4 days (dietary and intraperitoneally) to 2,5-HD, zinc acetate and 2,5-HD plus zinc acetate and the 24 h urine was used to determine the excretion of these biomarkers. On comparing the results obtained by the two routes of exposure with different doses of 2,5-HD and zinc acetate, it was observed that there was a significant decrease (P<0.05) in the excretion of free 2,5-HD and pyrroles derivatives in rats exposed to the chemical mixture, when compared with the excretion of these biomarkers in rats exposed to 2,5-HD alone. To evaluate the mechanism of this interaction, further experiments were performed using one group of rat dietary pre-exposed to zinc acetate followed by 2,5-HD exposure. The results of our experiment suggest that zinc protect proteins of pyrrolization by coordination to amino groups, with the subsequent inhibition of protein cross-linking responsible by 2,5-HD neurotoxicity.

Evidence for zinc protection against 2,5-hexanedione toxicity by co-exposure of rats to zinc chloride.

The protective role of zinc against the toxic effects of 2, 5-hexanedione (2,5-HD), the main neurotoxic metabolite of n-hexane, was investigated by studying the interference of zinc on the toxicokinetics of 2,5-HD. Six groups of Wistar rats were exposed for 3 days to diets containing 2,5-HD, zinc chloride and 2,5-HD+zinc chloride. The amounts of pyrroles and free and total 2,5-HD in urine were determined using Ehrlichs's reagent and gas chromatography/flame ionization detection, respectively. The results show that after the first day of co-exposure (ZnCl(2)+2,5-HD) there was a significant decrease in the excretion of pyrroles and free 2, 5-HD in rats exposed to the chemical mixture when compared to the pyrroles and free 2,5-HD excreted in rats exposed to 2,5-HD alone. However, no significant decrease was observed in the urinary excretion of total 2,5-HD (free 2,5-HD + preformed 2,5-HD). Suggestions are made about the role played by this metal ion in inhibiting pyrrole formation.