A Milk-Fat Based Diet Increases Metastasis in the MMTV-PyMT Mouse Model of Breast Cancer.

A high-fat diet (HFD) and obesity are risk factors for many diseases including breast cancer. This is particularly important with close to 40% of the current adult population being overweight or obese. Previous studies have implicated that Mediterranean diets (MDs) partially protect against breast cancer. However, to date, the links between diet and breast cancer progression are not well defined. Therefore, to begin to define and assess this, we used an isocaloric control diet (CD) and two HFDs enriched with either olive oil (OOBD, high in oleate, and unsaturated fatty acid in MDs) or a milk fat-based diet (MFBD, high in palmitate and myristate, saturated fatty acids in Western diets) in a mammary polyomavirus middle T antigen mouse model (MMTV-PyMT) of breast cancer. Our data demonstrate that neither MFBD or OOBD altered the growth of primary tumors in the MMTV-PyMT mice. The examination of lung metastases revealed that OOBD mice exhibited fewer surface nodules and smaller metastases when compared to MFBD and CD mice. These data suggest that different fatty acids found in different sources of HFDs may alter breast cancer metastasis.

Neonatal mortality associated with sodium monofluoracetate in kids fed with colostrum from goats ingesting Amorimia septentrionalis / Mortalidade neonatal associada ao monofluoroacetato de sódio em cabritos alimentados com colostro de cabras ingerindo Amorimia septentrionalis

Sudden deaths after colostrum ingestion in kids and lambs born to mothers grazing in areas with Amorimia septentrionalis have been reported in the Brazilian northeastern semi-arid region, in Paraíba state. This study aimed to determine whether the sodium monofluoracetate (MF) contained in A. septentrionalis is eliminated in milk, causing the death of kids. After confirming gestation on the 25th day after mating, 26 goats were randomly distributed into three groups. In Group 1, eight goats received fresh leaves of A. septentrionalis in daily doses of 1g/kg body weight, administered at three different periods during gestation: from days 91 to 100, 116 to 125, and from day 140 until delivery day. In Group 2, consisting of 10 females, eight goats received 1g/kg body weight of A. septentrionalis dried and milled leaves, fed daily from the 140th day of gestation until delivery. The other two goats of this group did not ingest the plant during gestation and after delivery the colostrum supplied to their kids was replaced by colostrum of goats from that same group that had ingested the plant. Eight goats from Group 3 (control) did not ingest A. septentrionalis. Seven goats from Group 1 showed signs of poisoning from 2nd to 8th days of plant administration, in all periods, and recovered within 7 to 12 days. Another goat presented severe clinical signs and was submitted to euthanasia in extremis. Two goats aborted. Four kids, from two goats, received colostrum and, after 15 minutes, presented depression, breathing wheezing, lateral recumbence, bleating, and death. Two goats gave birth at night; the two kids were found dead and, at necropsy, it was verified that they were born alive. The last goat in this group gave birth to two kids which showed no signs of poisoning after colostrum ingestion. In Group 2, the eight goats that ingested dry leaves of the plant presented tachycardia and engorgement of the jugular veins; six aborted, and the kids of the other two goats died immediately after delivery without ingesting colostrum. The three kids of the two goats that did not ingest the plant during gestation did not show signs of poisoning after ingesting colostrum from the goats that had ingested the plant. In Group 3, all females kidded normally and the kids showed no signs of poisoning. Ten leaf samples of A. septentrionalis contained 0.00074% ±0.00018 MF. These results demonstrate that the MF of A. septentrionalis is eliminated in colostrum and may cause the death of kids. As in previous reports, the plant also caused abortion.(AU)

Mortes súbitas, após a ingestão do colostro, em cabritos e cordeiros nascidos de mães que pastejam em áreas com Amorimia septentrionalis são relatadas no semiárido da Paraíba. O objetivo deste trabalho foi determinar se o monofluoracetato de sódio (MF) contido em Amorimia septentrionalis é eliminado pelo leite, causando a morte dos cabritos. Após a confirmação da gestação no 25º dia após a cobertura, 26 cabras foram aleatoriamente distribuídas em três grupos. No Grupo 1, oito cabras receberam folhas frescas de A. septentrionalis em doses diárias de 1g/kg de peso vivo, administradas em três períodos diferentes durante a gestação: entre os dias 91 a 100, 116 a 125 e do 140º dia até o parto. No Grupo 2, composto por 10 fêmeas, oito cabras receberam 1g/kg de peso vivo de folhas secas e trituradas de A. septentrionalis, fornecida diariamente do 140º dia de gestação até o parto. As outras duas cabras desse grupo não ingeriram a planta durante a gestação e, ao parirem, o colostro fornecido aos seus cabritos foi substituído pelo colostro de cabras, desse mesmo grupo, que ingeriram a planta. Oito cabras do Grupo 3 (controle) não ingeriram A. septentrionalis. Sete cabras do Grupo 1 apresentaram sinais de intoxicação entre o 2º e 8º dia de administração da planta, em todos os períodos, e se recuperavam em 7 a 12 dias. Outra apresentou sinais clínicos graves e foi eutanasiada in extremis. Duas cabras abortaram. Quatro cabritos, oriundos de duas cabras, receberam colostro e, após 15 minutos, apresentaram depressão, respiração ofegante, decúbito lateral, berros e morte. Dois cabritos, nascidos de duas cabras que pariram durante a noite, foram encontrados mortos e os achados de necropsia permitem afirmar que nasceram vivos. A outra cabra desse grupo pariu dois cabritos que, mesmo mamando o colostro, não apresentaram sinais de intoxicação. No Grupo 2, as oito cabras que ingeriram a planta seca apresentaram taquicardia e ingurgitamento das veias jugulares; seis abortaram e os cabritos das outras duas morreram imediatamente após o parto, sem ingerir colostro. Os três filhotes das duas cabras que não ingeriram a planta durante a gestação não apresentaram sinais de intoxicação após ter ingerido colostro das cabras que tinham ingerido a planta. No Grupo 3, todas as fêmeas pariram normalmente e os filhotes não apresentaram sinais de intoxicação. Dez amostras de folhas de A. septentrionalis continham 0,00074% ± 0,00018 de MF. Estes resultados demonstram que o MF de A. septentrionalis, além de causar abortos, é eliminado pelo colostro podendo causar a morte dos cabritos.(AU)

Exosomal formulation of anthocyanidins against multiple cancer types.

Over the last two decades, berries and berry bioactives, particularly anthocyanins and their aglycones anthocyanidins (Anthos) have demonstrated excellent anti-oxidant, anti-proliferative, apoptotic and anti-inflammatory properties. However, their physicochemical and pharmacokinetic limitations such as, low permeability, and poor oral bioavailability are considered as unfavorable properties for development as drugs. Therefore there is a need to develop systems for efficient systemic delivery and robust bioavailability. In this study we prepared nano-formulation of bilberry-derived Anthos using exosomes harvested from raw bovine milk. Exosomal formulation of Anthos enhanced antiproliferative and anti-inflammatory effects compared with the free Anthos against various cancer cells in vitro. Our data also showed significantly enhanced therapeutic response of exosomal-Anthos formulation compared with the free Anthos against lung cancer tumor xenograft in nude mice. The Anthos showed no signs of gross or systemic toxicity in wild-type mice. Thus, exosomes provide an effective alternative for oral delivery of Anthos that is efficacious, cost-effective, and safe, and this regimen can be developed as a non-toxic, widely applicable therapeutic agent.

Climate conditions associated with the occurrence of pyrethroid residues in bulk milk tank / Condições climáticas associadas à ocorrência de resíduos de piretroides em amostras de leite de tanque

The present study attempted to identify climate conditions that are associated with the occurrence of pyrethroid residues using a multivariate principal component analysis (PCA). A total of 132 raw milk samples were collected from dairy farms in Minas Gerais State - Brazil and analyzed for seven analytes using gas chromatography with electron capture detection. Of the 132 milk samples, pyrethroid residues were identified in 14 (10.6%) milk samples, of which 12 (9.1%) and two (1.5%) milk samples had the identification of cypermethrin and deltamethrin, respectively. From those samples, nine (6.8%) milk samples were regarded as non-compliant for cypermethrin with this analyte concentration above the maximum residue limits set by Brazilian legislation. A PCA assessing pyrethroid residues in bulk tank milk demonstrated that the average temperature and the Temperature-Humidity Index were associated with pyrethroids residues in bulk milk tank, although the relative humidity was inversely correlated. Thus, the data analysis indicated that the pyrethrid residues associated with some climate conditions can predict the moments with higher risk of occurrence of pyrethroid residues in bulk tank milk.(AU)

O presente trabalho objetivou identificar fatores climáticos associados à ocorrência de resíduos de piretroides em amostras de leite de tanque por análise multivariada de componentes principais (ACP). Para o presente trabalho, 132 amostras de leite cru foram coletadas em fazendas leiteiras localizadas no estado de Minas Gerais (Brasil) e analisadas por sete analitos por cromatografia gasosa com detector por captura de eletróns para detecção de resíduos de piretroides. Das 132 amostras de leite analisadas, a presença de resíduos de piretroides foi detectada em 14 amostras (10,6%), e em 12 (9,1%) e duas (1,5%) foram detectados cipermetrina e deltametrina, respectivamente. Destas amostras, em nove (6,8%) a concentração de cipermetrina encontrada foi maior que a permitida pela legislação brasileira. A ACP demonstrou que a presença de resíduos de piretroides no leite de tanque ocorreu menos frequentemente nos dias com maior umidade relativa, embora a presença desses resíduos estivesse associada a maior temperatura média e a maior índice de temperatura e umidade. Dessa forma, conclui-se que alguns índices climáticos podem predizer períodos com maior risco de ocorrência de resíduos de piretroides no leite de tanque.(AU)

Bovine milk-derived exosomes for drug delivery.

Exosomes are biological nanovesicles that are involved in cell-cell communication via the functionally-active cargo (such as miRNA, mRNA, DNA and proteins). Because of their nanosize, exosomes are explored as nanodevices for the development of new therapeutic applications. However, bulk, safe and cost-effective production of exosomes is not available. Here, we show that bovine milk can serve as a scalable source of exosomes that can act as a carrier for chemotherapeutic/chemopreventive agents. Drug-loaded exosomes showed significantly higher efficacy compared to free drug in cell culture studies and against lung tumor xenografts in vivo. Moreover, tumor targeting ligands such as folate increased cancer-cell targeting of the exosomes resulting in enhanced tumor reduction. Milk exosomes exhibited cross-species tolerance with no adverse immune and inflammatory response. Thus, we show the versatility of milk exosomes with respect to the cargo it can carry and ability to achieve tumor targetability. This is the first report to identify a biocompatible and cost-effective means of exosomes to enhance oral bioavailability, improve efficacy and safety of drugs.

Analysis of industry-generated data. Part 2: Risk-based sampling plan for efficient self-control of aflatoxin M1 contamination in raw milk.

Aflatoxin M1 (AFM1) contamination in 21,969 milk samples taken in Italy during 2005-08 and 2010 provided the basis for designing an early warning self-control plan. Additionally, 4148 AFM1 data points from the mycotoxin crisis (2003-04) represented the worst case. No parametric function provided a good fit for the skewed and scattered AFM1 concentrations. The acceptable reference values, reflecting the combined uncertainty of AFM1 measured in consignments consisting of milk from one to six farms, ranged from 40 to 16.7 ng kg(-1), respectively. Asymmetric control charts with these reference values, 40 and 50 ng kg(-1) warning and action limits are recommended to assess immediately the distribution of AFM1 concentration in incoming consignments. The moving window method, presented as a worked example including 5 days with five samples/day, enabled verification of compliance of production with the legal limit in 98% of the consignments at a 94% probability level. The sampling plan developed assumes consecutive analyses of samples taken from individual farms, which makes early detection of contamination possible and also immediate corrective actions if the AFM1 concentration in a consignment exceeds the reference value. In the latter case different control plans with increased sampling frequency should be applied depending on the level and frequency of contamination. As aflatoxin B1 increases in feed at about the same time, therefore a coordinated sampling programme performed by the milk processing plants operating in a confined geographic area is more effective and economical then the individual ones. The applicability of the sample size calculation based on binomial theorem and the fast response rate resulting from the recommended sampling plan were verified by taking 1000-10,000 random samples with replacement from the experimental databases representing the normal, moderately and highly contaminated periods. The efficiency of the control plan could be substantially enhanced if the dairy farms used feed with a tolerable level of AFB1.

Analysis of industry-generated data. Part 1: a baseline for the development of a tool to assist the milk industry in designing sampling plans for controlling aflatoxin M1 in milk.

The presence of aflatoxin M1 (AFM1) in milk was assessed in Italy in the framework of designing a monitoring plan actuated by the milk industry in the period 2005-10. Overall, 21,969 samples were taken from tankers collecting milk from 690 dairy farms. The milk samples were representative of the consignments of co-mingled milk received from multiple (two to six) farms. Systematic, biweekly sampling of consignments involved each of the 121 districts (70 in the North, 17 in the Central and 34 in the South regions of Italy). AFM1 concentration was measured using an enzyme-linked immunoassay method (validated within the range of 5-100 ng kg(-1)) whereas an HPLC method was used for the quantification of levels in the samples that had concentrations higher than 100 ng kg(-1). Process control charts using data collected in three processing plants illustrate, as an example, the seasonal variation of the contamination. The mean concentration of AFM1 was in the range between 11 and 19 ng kg(-1). The 90th and 99th percentile values were 19-34 and 41-91 ng kg(-1), respectively, and values as high as 280 ng kg(-1) were reached in 2008. The number of non-compliant consignments (those with an AFM1 concentration above the statutory limit of 50 ng kg(-1)) varied between 0.3% and 3.1% per year, with peaks in September, after the maize harvest season. The variability between different regions was not significant. The results show that controlling the aflatoxins in feed at farm level was inadequate, consequently screening of raw milk prior to processing was needed. The evaluation of the AFM1 contamination level observed during a long-term period can provide useful data for defining the frequency of sampling.

Neurochemical and behavioral characteristics of toxic milk mice: an animal model of Wilson's disease.

Toxic milk mice have an inherited defect of copper metabolism. Hepatic phenotype of the toxic milk mice is similar to clinical findings in humans suffering from Wilson's disease (WND). In the present study, neurotransmitter system and locomotor performance in toxic milk mice was examined to verify the feasibility of this animal model for studying neuropathology of WND. Mice aged 2 and 12 months were used in the experiment. The mice were tested according to rotarod and footprint protocols. Monoamine content in brain structures was measured by high performance liquid chromatography. In order to detect neuronal loss, expression of enzymes specific for dopaminergic [tyrosine hydroxylase (TH)], noradrenergic (dopamine beta-hydroxylase) and serotoninergic [tryptophan hydroxylase (TPH)] neurons was analyzed by Western blot. The 12-month-old toxic milk mice demonstrated impaired locomotor performance in behavioral tests. Motor deficits were accompanied by increased copper and serotonin content in different brain regions and slight decrease in dopamine concentration in the striatum. The expression of TH, dopamine beta-hydroxylase and TPH in the various brain structures did not differ between toxic milk mice and control animals. Despite differences in brain pathology between humans and rodents, further exploration of neuronal injury in toxic milk mice is warranted to broaden the understanding of neuropathology in WND.

Four years follow-up of 101 children with melamine-related urinary stones.

The melamine-contaminated milk powder incidence occurred in China in 2008. Many studies have been published regarding the epidemiology, clinical symptoms, diagnosis and treatment of melamine-related urinary stones. The objective of this study is to follow-up the effects of melamine-contaminated milk powder consumption on kidney and body growth in children with melamine-related urinary stones 4 years ago. One hundred and one children with melamine-related urinary stones were followed up by urinalysis, renal function tests and urinary ultrasonography. The data of body weight and height, clinical signs and complications were collected. Eighty normal children without the history of consuming melamine-contaminated milk powder were collected as controls. Eighty-one children with melamine-related urinary stones were successfully followed up. Of 45 cases with melamine-related urinary stones treated conservatively after discharge, 34 disappeared completely, 6 dissolved partially, 1 increased in size and 4 did not change at 4 years follow-up. The percentages of under-height and under-weight infants were significantly higher in melamine-related urinary stones group compared to the controls, respectively (p < 0.05). Routine blood, renal and bladder function tests as well as urinalysis were normal in all children. No urological tumors were detected. No noticeable impact of melamine-related urinary stones on kidney and bladder was found at 4 years follow-up. However, whether or not melamine-related urinary stones had effect on body growth needs follow-up in future.

Toxics, Toyotas, and terrorism: the behavioral economics of fear and stigma.

Economists have traditionally viewed the behavioral response to risk as continuous and proportional. In contrast, psychologists have often contended that people have little control over their response to risk that is dichotomous, nonproportional, visceral, and fear based. In extreme cases, this automatic response results in the stigmatization of a product, technology, or choice, which seemingly cannot be eliminated or reduced. In resolving these contrasting perspectives, we review four recent studies that blend behavioral economics and psychology. Together, they provide evidence for a dual-process decision model for risk that incorporates both reason and fear. They show consumers' responses to perceived risk as a mix of proportional and dichotomous (safe/unsafe) responses that are relatively more continuous in situations where deliberation is possible, and more dichotomous in emotional or stressful circumstances. These findings reconcile mixed results in past studies, and, more importantly, the dual-process model allows a clear definition of stigma, and suggests new ways to mitigate stigma and to help manage potentially damaging overreactions to it.

Estudio sobre plaguicidas organofosforados en leche y en fórmulas infantiles en el noroeste de España / Study of organophosphate pesticides in milk and in foods for infants in north-west Spain

Comentario sobre un estudio que contribuye a detectar la presencia de plaguicidas y prevenir el riesgo que pueda suponer el consumo de leche contaminada

Neuroinflammatory and behavioural changes in the Atp7B mutant mouse model of Wilson's disease.

Wilson's disease (WD) is caused by mutations in the copper transporting ATPase 7B (Atp7b). Patients present with liver pathology or behavioural disturbances. Studies on rodent models for WD so far mainly focussed on liver, not brain. The effect of knockout of atp7b on sensori-motor and cognitive behaviour, as well as neuronal number, inflammatory markers, copper and synaptic proteins in brain were studied in so-called toxic milk mice. Copper accumulated in striatum and hippocampus of toxic milk mice, but not in cerebral cortex. Inflammatory markers were increased in striatum and corpus callosum, but not in cerebral cortex and hippocampus, whereas neuronal numbers were unchanged. Toxic milk mice were mildly impaired in the rotarod and cylinder test and unable to acquire spatial memory in the Morris water maze. Despite the latter observation only synaptophysin of a number of synaptic proteins, was altered in the hippocampus of toxic milk mice. In addition to disturbances in neuronal signalling by increased brain copper, inflammation and inflammatory signalling from the periphery to the brain might add to the behavioural disturbances in the toxic milk mice. These mice can be used to evaluate therapeutic strategies to alleviate behavioural disturbances and cerebral pathology observed in WD.

Tem veneno na pecuária: riscos associados ao uso de carrapaticidas na pecuária leiteira / It has poison in cattle: risks associated with the use of acaricides in dairy farming

O presente trabalho teve por objetivo caracterizar os riscos relacionados ao uso de pesticidas na pecuária leiteira, em questões relacionadas à legislação, à saúde e à percepção de riscos de trabalhadores dessa atividade, baseando-se em articulaçãometodológica que incluiu: a) revisão sistemática da literatura de referência sobre o objeto da pesquisa; b) análise da legislação correlata (produtos veterinários e agrotóxicos); c) identificação de perigos relacionados a produtos veterinários formulados à base de princípios ativos regulados como agrotóxicos; e d) análise da percepção de riscos de um grupo de trabalhadores da pecuária leiteira. A análise dosresultados do estudo apontou uma situação de especial interesse para o campo da Saúde Coletiva. No que diz respeito aos trabalhadores da pecuária leiteira, a invisibilidade de riscos associados ao manejo de agrotóxicos de uso veterinário aumenta sua exposição epode estar relacionada a diversos problemas de saúde. Esta mesma invisibilidade leva a um negligenciamento do respeito ao período de carência, o que pode indicar risco decontaminação aos consumidores de leite. Parte dos problemas pode estar associado à não-classificação dos inseticidas de uso veterinários como agrotóxicos, o que torna necessária e urgente a discussão do tema.

Selective oxidative stress in brain areas of neonate rats exposed to 2,4-Dichlorophenoxyacetic acid through mother's milk.

2,4-Dichlorophenoxyacetic acid (2,4-D) induced disparate alterations on enzymatic activities of the defensive mechanism and/or modifications of the reactive oxygen species levels in specific neonate rat brain regions. The midbrain, striatum, and prefrontal cortex were the areas where the alterations were more remarkable and with similar tendency. The hippocampus did not suffer many alterations, and the hypothalamus was the area where no changes were observed. The current results suggest that the developing brain areas have different susceptibilities to the adverse effect of the herbicide, especially those areas related to the dopaminergic system, and that oxidative stress is one 2,4-D mechanism of toxicity.

Developmental dental toxicity of dioxin and related compounds--a review.

Non-halogenated polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons such as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs, or dioxins), and polychlorinated biphenyls (PCBs) are wide-spread environmental pollutants that have unequivocal adverse effects on different species, including humans. Accidental exposure of children to high amounts of PCDD/Fs has been found to be associated with developmental enamel defects and missing permanent teeth. An association between dioxin exposure via mother's milk and developmental mineralisation defects in permanent first molars was also found in otherwise healthy Finnish children born in the late 1980s but not in those born in the late 1990s. Results of experimental animal studies in vivo and in vitro are compatible with findings in human teeth. In addition to the dose, dental effects of the most toxic dioxin congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), essentially depend on the stage of tooth development at the time of exposure. Accordingly, TCDD arrests early rat and mouse molar tooth development and in more advanced teeth it interferes with mineralisation of enamel and dentine and arrests root development. Expression of the specific dioxin receptor (AhR) in dental cells at TCDD-sensitive stages of tooth development suggests that the dental, like other developmental effects of TCDD, are mediated by the AhR. Early effects also depend on the epidermal growth factor receptor and involve enhanced apoptosis. The lowest TCDD dose (30ng/kg) causing adverse dental effects in rats has been estimated to result in maternal tissue levels approaching the high end of human background range and human milk PCDD/F levels that were associated with enamel defects in children. However, because of the uniform and clear decline in background dioxin and PCB levels in mother's milk during the last twenty years, dioxins are currently likely to be of small or no account as regards developmental dental defects in children. Even so, this is not the case after heavy exposure and little is known about the possible synergistic effects of these toxicants with other chemicals interfering with tooth development.

Importância do Staphylococcus aureus nas mastites subclínicas: pesquisa de enterotoxinas e toxina do choque tóxico, e a relação com a contagem de células somáticas / Importance of Staphylococcus aureus in bovine subclinical mastitis: presence of enterotoxins, shock syndrome toxin and relationship with somatic cell count

O Staphylococcus aureus é um dos principais agentes das mastites consideradas contagiosas, apresentando elevada incidência na maioria dos rebanhos leiteiros em vários países. Além de perdas econômicas é importante salientar o aspecto de saúde pública para cepas produtoras de enterotoxinas e da toxina do choque tóxico. A enterotoxina A, relacionada com maior ênfase nos casos de toxinfecções alimentares, pode ser veiculada pelo leite cru, pasteurizado e subprodutos lácteos. A síndrome do choque tóxico é determinada mais freqüentemente pela toxina do choque tóxico, porém as enterotoxinas do tipo B e C também podem ser implicadas. O objetivo deste estudo foi verificar a ocorrência de S.aureus produtores de enteroxinas e da toxina do choque tóxico em amostras de leite de animais com mastite subclínica, e correlacionar estes resultados com a contagem de células somáticas; utilizando a técnica de "celofane over agar" para detecção da TNAase, kit comercial para identificação das enterotxinas e contagem eletrônica de células somáticas. Avaliou-se 209 amostras de leite oriundas de vacas com mastite subclínica por S.aureus, e dentre estas, 209 (98,86 por cento) produziram TNAse, nove amostras (4,39 por cento) foram produtoras de enterotoxinas, sendo que uma (0,49 por cento) dentre elas foi produtora de EED, três (1,46 por cento) de EEC, e três (1,46 por cento) de EEB. Em uma amostra (0,49 por cento), detectou-se concomitantemente EEA e EEB e em outra EEB e EEC. A toxina do choque tóxico não foi encontrada nas cepas avaliadas neste estudo, assim como não houve aumento estatisticamente significativo, na contagem de células somáticas, das amostras de cepas produtoras de enteroxinas.

Monitoramento de resíduos de agrotóxicos em leite consumido pela população do estado de São Paulo, Brasil, 2000 e 2002 / Monitoring of pesticide residues in milk consumed by the population of the State of São Paulo, Brazil, 2000 and 2002

O leite é um importante constituinte da dieta alimentar do homem e apresenta um consumo elevado, principalmente pela população infantil. Os resíduos de agrotóxicos não intencionais e seus metabólitos podem ser encontrados no leite em decorrência do consumo de água, pastagens e rações com resíduos pelo gado ou pelo uso de agrotóxicos para controle de ectoparasitas. Com o objetivo de avaliar os níveis desses resíduos foram analisadas 73 amostras de leite, coletadas pela Vigilância Sanitária em diversos estabelecimentos comerciais do Estado de São Paulo nos anos de 2000 a 2002. A análise dos agrotóxicos foi efetuada por cromatografia a gás e cromatografia a líquido de alta eficiência. Para verificar a exatidão e precisão do método foram realizados estudos de recuperaçoes cujos resultados variaram de 71 a 105%, todos dentro dos limites aceitáveis, com coeficientes de variações entre 1,2 e 17,8%. O limite de quantificação do método foi de 0,01 mg/kg para hexaclorobenzeno, a HCH, B HCH, y HCH, aldrin, heptacloro, heptacloro epóxido, endosulfan I, endosulfan II, sulfato de endosulfan, dieldrin, endrin, pp'DDE, pp'DDD, op'DDT, pp'DDT; 0,02 mg/kg para cialotrina, a cipermetrina, deltametrina e 0,10 mg/kg para carbendazim e tiabendazol. Nenhum dos agrotóxicos avaliados foram encontrados na amostras de leite analisadas

Effect of the toxic milk mutation (tx) on the function and intracellular localization of Wnd, the murine homologue of the Wilson copper ATPase.

Wilson disease is an autosomal recessive copper transport disorder resulting from defective biliary excretion of copper and subsequent hepatic copper accumulation and liver failure if not treated. The disease is caused by mutations in the ATP7B (WND) gene, which is expressed predominantly in the liver and encodes a copper-transporting P-type ATPase that is structurally and functionally similar to the Menkes protein (MNK), which is defective in the X-linked copper transport disorder Menkes disease. The toxic milk (tx) mouse has a clinical phenotype similar to Wilson disease patients and, recently, the tx mutation within the murine WND homologue (WND:) of this mouse was identified, establishing it as an animal model for Wilson disease. In this study, cDNA constructs encoding the wild-type (Wnd-wt) and mutant (Wnd-tx) Wilson proteins (Wnd) were generated and expressed in Chinese hamster ovary (CHO) cells. The tx mutation disrupted the copper-induced relocalization of Wnd in CHO cells and abrogated Wnd-mediated copper resistance of transfected CHO cells. In addition, co-localization experiments demonstrated that while Wnd and MNK are located in the trans-Golgi network in basal copper conditions, with elevated copper, these proteins are sorted to different destinations within the same cell. Ultrastructural studies showed that with elevated copper levels, Wnd accumulated in large multi-vesicular structures resembling late endosomes that may represent a novel compartment for copper transport. The data presented provide further support for a relationship between copper transport activity and the copper-induced relocalization response of mammalian copper ATPases, and an explanation at a molecular level for the observed phenotype of tx mice.

Pyrrolizidine alkaloids in human diet.

Pyrrolizidine alkaloids are the leading plant toxins associated with disease in humans and animals. Upon ingestion, metabolic activation in liver converts the parent compounds into highly reactive electrophiles capable of reacting with cellular macromolecules forming adducts which may initiate acute or chronic toxicity. The pyrrolizidine alkaloids present a serious health risk to human populations that may be exposed to them through contamination of foodstuffs or when plants containing them are consumed as medicinal herbs. Some pyrrolizidine alkaloids (PA) adducts are persistent in animal tissue and the metabolites may be re-released and cause damage long after the initial period of ingestion. PAs are also known to act as teratogens and abortifacients. Chronic ingestion of plants containing PAs has also led to cancer in experimental animals and metabolites of several PAs have been shown to be mutagenic in the Salmonella typhimurium/mammalian microsome system. However, no clinical association has yet been found between human cancer and exposure to PAs. Based on the extensive reports on the outcome of human exposure available in the literature, we conclude that while humans face the risk of veno-occlusive disease and childhood cirrhosis PAs are not carcinogenic to humans.

Bracken carcinogens in the human diet.

The ubiquitous bracken fern (genus Pteridium) is the only higher plant known to cause cancer naturally in animals. In addition to the well-recognized syndromes of thiamine deficiency, acute haemorrhage associated with myeloid aplasia and blindness due to retinal degeneration, it causes neoplasia of the urinary bladder and in some circumstances, of the upper gut. In addition, it has been shown to cause neoplasia in a wide range of tissues in many experimental species. The major carcinogen (and the cause of the retinal degeneration and the myeloid aplasia) has been shown to be ptaquiloside (PT), a norsesquiterpene glucoside that can be present in bracken in extraordinary concentrations, up to 13 000 ppm. The highest concentrations were found in the crosiers and young unfolding fronds. The mutagenicity, clastogenicity, teratogenicity and carcinogenicity have been convincingly demonstrated. Under alkaline conditions the loss of the glucose gives rise to the formation of a dienone intermediate which possesses a highly reactive cyclopropyl ring capable of reacting with cellular macromolecules. PT has been shown to alkylate DNA at N3 of adenines in the minor groove, preferentially in 5'-TAG and 3'-A in 5'-AA-3' sequences. It also alkylates N7 guanines in the major groove occurring in 5'-TG sequences. It is believed that these alkylations lead to mismatch repair and subsequent mutations in particular proto-oncogenes. Recently a rat model of carcinogenesis has been established using intravenously (iv) administered PT. Some epidemiological evidence has indicated higher risk of cancer in people who consume bracken crosiers, people who consume milk of cows feeding on bracken and those who live in bracken-infested areas. PT has been found in the milk of cows fed on bracken fern experimentally and the milk of bracken-fed cows has been shown to cause cancer in rats. PT carcinogenesis presents an excellent model of environmental and experimental carcinogenesis.