The Effects of Endocrine Disrupters on Fetal Male Rat Testicular and Adrenal Development

Many of the reproductive disorders that emerge in adulthood have their origin during fetal development. Numerous studies have demonstrated that exposure to endocrine disrupting chemicals can permanently affect the reproductive health of experimental animals. In mammals, male sexual differentiation and development are androgen-dependent processes. In rat, the critical programming window for masculinization occurs between embryonic days (EDs) 15.5 and 19.5. Disorders in sex steroid balance during fetal life can disturb the development of the male reproductive tract. In addition to the fetal testis, the adrenal cortex starts to produce steroid hormones before birth. Glucocorticoids produced by the adrenal cortex are essential for preparing the fetus for birth. In the present study, the effects of exposure to endocrine disrupters on fetal male rat testicular and adrenal development were investigated. To differentiate the systemic and direct testicular effects of endocrine disrupters, both in vivo and in vitro experiments were performed. The present study also clarified the role of desert hedgehog signalling (Dhh) in the development of the testis. The results indicate that endocrine disrupters, diethylstilbestrol (DES) and flutamide, are able to induce rapid steroidogenic changes in fetal rat testis under in vitro conditions. Although in utero exposure to these chemicals did not show overt effects in fetal testis, they can induce permanent changes in the developing testis and accessory sex organs later in life. We also reported that exposure to antiandrogens can interfere with testicular Dhh signalling and result in impaired differentiation of the fetal Leydig cells and subsequently lead to abnormal testicular development and sexual differentiation. In utero exposure to tetrachlorodibenzo-p-dioxin (TCDD) caused direct testicular and pituitary effects on the fetal male rat but with different dose responses. In a study in which the effects of developmental exposure to environmental antiandrogens, di-isononylphthalate and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p^’-DDE), on fetal male rat steroidogenesis were investigated, chemicals did not down-regulate testicular or adrenal steroid hormone synthesis or production in 19.5-day-old fetal rats. However, p,p^’-DDE-treatment caused clear histological and ultrastructural changes in the prenatal testis and adrenal gland. These structural alterations can disturb the development and function of fetal testis and adrenal gland that may become evident later in life. Exposure to endocrine disrupters during fetal life can cause morphological abnormalities and alter steroid hormone production by fetal rat Leydig cells and adrenocortical cells. These changes may contribute to the maldevelopment of the testis and the adrenal gland. The present study highlights the importance of the fetal period as a sensitive window for endocrine disruption.

El rompecabezas de aprender a jugar a rugby

La comunicación pretende mostrar la experiencia que hemos vivido en el proceso de construcción y consolidación de un equipo de rugby universitario formado por jugadores y jugadoras mayoritariamente inexpertas en nuestro deporte. Por lo tanto, centraremos nuestra comunicación en el ámbito de las habilidades individuales del jugador y el conocimiento teórico del deporte. Para hacerlo, además del estudio del prototipo de jugador que conforma el equipo, también debemos abordar la problemática propia que surge en la construcción de un equipo novel.

Substâncias tóxicas persistentes (STP) no Brasil

The present article presents an assessment of PTS in Brazil including polychlorinated biphenyls, polycyclic aromatic hydrocarbons, benzene hexachloride, aldrin, dieldrin, endrin, p,p,-DDT, p,p,DDE, p,p,-DDD, hexachlorocyclohexanes (alpha-HCH, beta-HCH, gamma-HCH and delta-HCH), endossulfan, heptachlor and pentachlorophenol. The data presented here are related to a survey of PTS levels in different environmental matrixes (soil, sediment, water, air, biota) and human tissues (milk, blood, human hair), according to the scope of the UNEP-GEF Regionally Based Assessment of PTSs. Potential sources were evaluated considering national products and imports, since most of the literature does not allow source identification. Finally, Brazilian legislation was updated.

Biotransformation and endocrine disruptive effects of contaminants in ringed seals - implications for monitoring and risk assessment

Marine mammals are exposed to persistent organic pollutants (POPs), which may be biotransformed to metabolites some of which are highly toxic. Both POPs and their metabolites may lead to adverse health effects, which have been studied using various biomarkers. Changes in endocrine homeostasis have been suggested to be sensitive biomarkers for contaminant-related effects. The overall objective of this doctoral thesis was to investigate biotransformation capacity of POPs and their potential endocrine disruptive effects in two contrasting ringed seal populations from the low contaminated Svalbard area and from the highly contaminated Baltic Sea. Biotransformation capacity was studied by determining the relationships between congener-specific patterns and concentrations of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs) and their hydroxyl (OH)- and/or methylsulfonyl (MeSO₂)-metabolites, and catalytic activities of hepatic xenobiotic-metabolizing phase I and II enzymes. The results suggest that the biotransformation of PCBs, PBDEs and toxaphenes in ringed seals depends on the congener-specific halogen-substitution pattern. Biotransformation products detected in the seals included OH-PCBs, MeSO₂-PCBs and –DDE, pentachlorophenol, 4-OHheptachlorostyrene, and to a minor extent OH-PBDEs. The effects of life history state (moulting and fasting) on contaminant status and potential biomarkers for endocrine disruption, including hormone and vitamin homeostasis, were investigated in the low contaminated ringed seal population from Svalbard. Moulting/fasting status strongly affected thyroid, vitamin A and calcitriol homeostasis, body condition and concentrations of POPs and their OH-metabolites. In contrast, moulting/fasting status was not associated with variations in vitamin E levels. Endocrine disruptive effects on multiple endpoints were investigated in the two contrasting ringed seal populations. The results suggest that thyroid, vitamin A and calcitriol homeostasis may be affected by the exposure of contaminants and/or their metabolites in the Baltic ringed seals. Complex and non-linear relationships were observed between the contaminant levels and the endocrine variables. Positive relationships between circulating free and total thyroid hormone concentration ratios and OH-PCBs suggest that OH-PCBs may mediate the disruption of thyroid hormone transport in plasma. Species differences in thyroid and bone-related effects of contaminants were studied in ringed and grey seals from low contaminated references areas and from the highly contaminated Baltic Sea. The results indicate that these two species living at the same environment approximately at the same trophic level respond in a very different way to contaminant exposure. The results of this thesis suggest that the health status of the Baltic ringed seals has still improved during the last decade. PCB and DDE levels have decreased in these seals and the contaminant-related effects are different today than a decade ago. The health of the Baltic ringed seals is still suggested to be affected by the contaminant exposure. At the present level of the contaminant exposure the Baltic ringed seals seem to be at a zone where their body is able to compensate for the contaminant-mediated endocrine disruption. Based on the results of this thesis, several recommendations that could be applied on monitoring and assessing risk for contaminant effects are provided. Circulating OH-metabolites should be included in monitoring and risk assessment programs due to their high toxic potential. It should be noted that endogenous variables may have complex and highly variable responses to contaminant exposure including non-linear responses. These relationships may be further confounded by life history status. Therefore, it is highly recommended that when using variables related to endocrine homeostasis to investigate/monitor or assess the risk of contaminant effects in seals, the life history status of the animal should be carefully taken into consideration. This applies especially when using thyroid, vitamin A or calcitriolrelated parameters during moulting/fasting period. Extrapolations between species for assessing risk for contaminant effects in phocid seals should be avoided.

Avaliação dos parâmetros de solubilidade de Hildebrand/Hansen na seleção de solventes para a extração de pesticidas organoclorados do solo

This work evaluated the use of the Hildebrand/Hansen solubility parameters for selection of solvents for extraction of the organochlorine pesticides pp' DDT, pp' DDE, Aldrin and a-Endossulfan from soil using columns packed with Al2O3. The mixtures hexane:dichloromethane (7:3; v/v), hexane:acetonitrile (1:1; v/v), hexane:acetone (1:1; v/v) and pure hexane were chosen as extracting solutions. In the addition and recovery tests, different extraction solutions provided high recoveries percentages (>75%) with coefficients of variation below 15%. The recoveries are in agreement with the Hildebrand/Hansen parameters, demonstrating its applicability in the selection of extracting solution and in the replacement of toxic solvents, as dichloromethane

Hydrozoa e Scyphozoa existentes no instituto paulista de oceanografia

Continuing the inventory of the Coelenterate Fauna of the Brazilian coast, 23 species of Hydrozoa and a Scyphomedusa are recorded from different points of the coast aproximately between 22º and 24º lat. S. Of these, 14 species were already known from other points of the coast and the remaining 10 were unknown from this latitude. Two species are here listed as new, they are: Halocordyle fragHis and Calicella gabriellae. 1. - Halocordyle fragilis, Stechow's (1923) correction of the generic name Pennaria has been followed, shows remarkable distinctive specific characters such as: alternate distribution of the cladii which do not lie all in the same plane, they are inserted at random on the hydrocaulus with a tendency towards a spiral dexiotropic distribution, sparse distribution of the pedicels which are alternate and not all located on the same side of the hydrocladium, and, finally, the long, wiry aspect of the colony which is as brittle as light glass. This characteristics are not sufficient, to my belief, to establish a new genus, since the polyps and the gonophores are entirely of the Halocordyle type, but they confer upon the species a very peculiar habitus. 2. - Calicella gabriellae forms erect hydrocauli which are extremely soft and flexuose, with hydrothecate and intermediate internodes. The thecae are deep, cylindrical, with a conical base, there are 10-12 long and narrow opercular valves. The gonangia are small, conical, with a short distal digitiform process. The included sporosac exhibits maturing ova. Dynamena heteroclonta described by Jarvis (1922) as a new species, is here considered as a new form of the very variable species Dynamena quadridentata. Schizotricha billardi nom. nov., is specifically separated from Sch. diaphana (Heller) to which it had been identified up to know. The Brazilian colonies agree with the French Somaliland specimens described by Billard (1904) and they are reunited in a new species named after the French worker. The main difference, between the two mentioned species are: shape and size of the gonothecae, of the thecae and of the nematophores. A description is given of all the species not previously recorded from the Brazilian coast as well as biological observations on Olindias sambaquiensis whose shoals during winter months are very large and may entangle partially the fishermen's nets. Its feeding and swimming habits are described and the species proves to be an excellent laboratory animal both for class and research purposes, for it easily endures long transportation (even up to 12 hours during summer months) as well as unoxygenized acquaria and nevertheless greadily feeds on any animal food.

Pseudomonas syringae pv. tabaci in papaya seedlings

The natural occurrence of Pseudomonas syringae pv. tabaci causing leaf spot symptoms in papaya seedlings is reported. The pathogen was identified through biochemical, physiological, serological, and molecular assays and artificial inoculations in papaya plants. It was also shown that the strains were pathogenic to bean and tobacco plants. The restriction patterns obtained with Afa I, Alu I, Dde I, Hae III, Hpa II, Hinf I, Sau 3A I and Taq I of the PCR-RFLP of 16S-23S DNAr were identical to the P. s. pv. tabaci patterns. Primers corresponding to hrpL gene of P. syringae were also tested and the results grouped the papaya strains with P s. pv. tabaci. Bacterial strains were deposited at Coleção de Culturas IBSBF, Instituto Biológico, Campinas, Brazil, under access numbers 1687 and 1822.

Intoxicação experimental por Baccharis coridifolia (Compositae) em bovinos

Treze terneiros receberam Baccharis coridifolia recém-colhida ou dessecada, em doses únicas que variaram entre 0,5 e 5g/kg. Um terneiro recebeu quatro administrações diárias de 0,5g/kg da planta dessecada. Dois terneiros não receberam a planta e serviram como controles. A planta foi colhida mensalmente de julho de 1991 a maio de 1992 e em março de 1993, e foi analisada para seu conteúdo em tricotecenos macrocíclicos. Quando em floração, as amostras dos espécimes macho e fêmea da planta foram analisadas e administradas aos terneiros separadamente. Os níveis de tricotecenos macrocíclicos e seus glicosídeos foram muito maiores nas plantas fêmeas em floração do que os níveis observados nas plantas não em floração e nas plantas machos em floração. Dez bovinos morreram espontaneamente ou foram sacrificados devido à toxicose. Dois terneiros que receberam a planta fêmea em floração, adoeceram e morreram, enquanto que três terneiros que receberam a planta macho em floração não adoeceram. Os sinais clínicos nos terneiros intoxicados foram anorexia, desidratação, atonia ruminal, tensão e dores abdominais, diarréia líquida, focinho seco, instabilidade dos membros posteriores e decúbito esternal. Os achados patológicos incluiram lesões necróticas no tubo gastrintestinal, particularmente nos pré-estômagos, e nos tecidos linfóides com exceção do timo. Esse último achado sugere um efeito sobre as células B do tecido linfóide. A distribuição das lesões nos sistemas digestivo e linfóide foi sistematicamente determinada. Conclui-se que os tricotecenos macrocíclicos presentes na planta são responsáveis pelas lesões observadas na toxicose e que a planta fêmea em floração é substâncialmente mais tóxica que a planta macho em floração ou das plantas que não estão em floração. Essa diferença em toxicidade é devida à diferença no conteúdo de tricotecenos macrocíclicos.

Eritrograma, metabolismo do ferro e concentração sérica de eritropoetina em fêmeas caprinas da raça Saanen nos períodos de gestação, parto e pós-parto

As alterações hematológicas durante o período de gestação, parto e pós-parto são de grande importância em humanos e têm sido estudadas em várias espécies de animais domésticos. O objetivo do trabalho foi determinar as alterações no eritrograma, no metabolismo do ferro e na concentração sérica de eritropoetina durante os períodos de gestação, parto e pós-parto em fêmeas nulíparas Saanen. Foram colhidas amostras de sangue de 20 fêmeas, clinicamente sadias, aos 49 (M1), 42 (M2), 35 (M3), 28 (M4), 21 (M5), 14 (M6), sete (M7), três (M8) dias antes do parto, no dia do parto (M9), três (M10) e sete (M11) dias após o parto, para a realização do eritrograma, proteína plasmática total, e dosagens séricas de eritropoetina, ferro, capacidade total de ligação do ferro, índice de saturação da transferrina e ferritina. Os dados foram analisados pelo teste de análise de variância (ANOVA) ao nível de 5% de significância (P<0,05). Houve diferença significativa (P<0,05) entre alguns momentos para as variáveis, número de eritrócitos, concentração de hemoglobina, volume globular, proteína total plasmática, concentração de ferro sérico, capacidade total de ligação do ferro (CLTF) e índice de saturação da transferrina (IST). Não houve diferença significativa (P<0,05) para as variáveis eritropoetina, volume corpuscular médio (VCM), hemoglobina corpuscular média (HCM), concentração de hemoglobina corpuscular média (CHCM), distribuição do diâmetro dos eritrócitos (DDE) e ferritina. Concluiu-se que não há aumento do estímulo para a produção de eritrócitos durante os períodos de gestação, parto e pós-parto em fêmeas Saanen e as alterações encontradas no eritrograma e no metabolismo do ferro não possuem significado clínico.

Clinical results of the use of mitotane for adrenocortical carcinoma

Mitotane (o,p'-DDD) acts mainly as an inhibitor of intramitochondrial pregnenolone and cortisol synthesis. Its adrenolytic effect depends on metabolic activation due to conversion to o,p'-DDA and o,p'-DDE. The drug has been used for 40 years in the treatment of adrenocortical carcinoma, mainly its regional and metastatic stage, as an adjuvant to surgical resection of the tumor. In the medical literature there are controversial opinions about its efficacy for the treatment of adrenocortical carcinoma. In our experience, mitotane administered immediately after surgery appeared to be much more efficient than when administered later. We have administered this drug in all cases of microscopically confirmed adrenocortical carcinoma, irrespectively of stage at the time of surgery, for fear of a false too optimistic classification. In our series of 82 patients with adrenocortical carcinoma, 59 patients have been treated with mitotane, 32 of them immediately after surgery, and 27 with a delay of 2 to 24 months. Today there are 18 survivors in the group of patients treated with mitotane soon after the operation and only 6 survivors in the group receiving mitotane with a delay. All patients were simultaneously given replacement therapy. Undesired effects of mitotane administration included increased aminotransferase and alkaline phosphatase activity, decreased white cell, platelet or red cell number, and myasthenia. Furthermore, we used mitotane with good results in Cushing's syndrome of non-malignant origin as pre-treatment before surgery or in long-term treatment for patients with poor tolerance of other adrenal inhibitors.

Influencia de habitos alimentarios sobre las concentraciones de pesticidas organoclorados en tejido adiposo

Fueron evaluados los niveles de residuos de pesticidas organoclorados (p,p'-DDE, HCB, gamma-HCH, aldrín) presentes en 123 muestras de tejido adiposo mamario obtenidas de mujeres residentes en Córdoba (España). Además, se investigó la influencia de hábitos alimentarios y edad de las donantes sobre los niveles de organoclorados encontrados en el tejido. El p,p'-DDE fue el compuesto encontrado en concentraciones más altas (1,848myg/g), seguido de HCB (0,235mg/g), aldrín (0,005myg/g) y gamma-HCH (0,003myg/g). Las donantes mayores presentaron niveles de p,p'-DDE, aldrín y HCB superiores que las más jóvenes. Sin embargo, la edad no influyó en los niveles de gamma-HCH. La mayoría de las donantes (40,65%) indicaron las frutas como el alimento más consumido, seguido de la alimentación variada (34,15%), los legumbres (6,50%), los guisos y potajes (6,50%), las verduras (4,88%), la leche (3,25%), el pescado (2,44%) y la carne (1,63%). Una correlación no significativa fue observada entre los niveles de organoclorados en el tejido adiposo y los hábitos alimentarios de las donantes.

Implementação da técnica de extração de dispersão da matriz em fase sólida ("MSPD") para determinação de resíduos de agrotóxicos em laranjas

Um método de extração de multiresíduos baseado na técnica de dispersão da matriz em fase sólida ("MSPD"), foi otimizado e validado para a extração e análise cromatográfica de 27 agrotóxicos (isômeros a, b, g, d do hexaclorociclohexano (HCH), dieldrin, endrin, heptacloro e seu epóxido (HE), a e b-endosulfan, o,p'-DDD, p,p'-DDD, o,p'-DDE, p,p'-DDE, o,p'-DDT, p,p'-DDT, dicofol, metoxicloro, mirex, hexaclorobenzeno (HCB), clorotalonil, parationa metílica, fenitrotiona, malationa, folpete, diazinona, cis e trans-permetrina em laranjas. A amostra macerada é inicialmente homogeneizada com C18, o homogeneizado é transferido para uma coluna de vidro contendo sílica gel onde se adiciona 10mL de acetato de etila como solvente de eluição. O eluente é concentrado, diluído em isooctano e 1mL deste é injetado no cromatógrafo a gás. Para a separação e quantificação dos 27 agrotóxicos, foi utilizado um CG/DCE. A confirmação dos mesmos foi feita por espectrometria de massas. Para a quantificação dos 27 agrotóxicos utilizou-se a padronização externa. As recuperações dos mesmos variaram de 70 a 120%, considerando-se os níveis de adição agrotóxicos/amostra de 0,02 e 2,0mg/kg. Os limites de quantificação variaram de 0,01 a 0,5mg/kg.

An investigation into some mechanistic aspects of estrogen biosynthesis

The mechanistic aspects of the 19-hydroxy1ation and aromatization of androgens were investigated. Fungal, bacterial and mammalian enzymatic activities were studied in this regard . The fungus Pell i cular~ fi1amentosa metabolized androst-4-ene-3 , 17-dione to the corresponding 110<' , 11 f and 14 0( hydroxylated derivatives. No ~19- hydroxylated products were isolated, although this transformation was previously observed for the C21-steroids . The intestinal bacterium Clostridi um paraputrific~ had been reported to aromatize androsten-4-ene-3,17-dione. In the present study, however, only the ring A reduced products , 17(3 - hydroxy-5f -andro8tane- 3-one and 5f-androstane-3,17-dione , were recovered . Human placental microsomes contain substantial aromatase activity and were employed in an effort to elucidate some of the mechanistic details of aromatization. Selectively deuterated steroidal substrates were employed as a probe in order to distinguish b'!tween certain of the mechanisms proposed for aromatization . Retention of deuterium at C4 and C6 was observed. It was concluded that no free intermediates allowing for loss of hydrogen from either of these two positions are implicated in this process . The involvement of a Schiff base enzyme-sup strate complex in aromatization was examined using the substrate 17f - hydroxyandrost-4-ene-3-one- 3_ 1BO. Since no loss of label was ob~erved, the implication of a Schiff base was discounted . Mixed label1ir~ studies were performed in order to determine if hydroxylation at C19 is a rate-determining process in aromatization . Isotope effects of 2 .1 and 1.7 were determined for the conversion of 17f - hydroxyandrost-4-ene-J-one-19,19,19-dJ and -19-dl respectively to estrogens. It was concluded from this that 19-hydroxylation is at l east a partially rate-determinjng process in aromatization. A homoenb~ation mechanism for 19-hydroxylation was not supported by the data obtained in this s tudy. In vitro 1JC NMR monitoring using l7f-hydroxyandrost-4-ene-Jone- 19-l3C was found not to be a successful approach in the study of steroid transformations, owing in part t o their low solubility in the incubation medium.

Linking community variables to parenting behaviours and youth risk behaviours

The puq)ose of this thesis is to test a model Hnking community disadvantage and urbanicity factors to parenting variables (i.e., monitoring, warmth, and knowledge) and to youth risk behavior (i.e., substance use and delinquency), measured both concurrently and one year after the assessment of parenting variables. The model builds on the work of Fletcher, Steinberg, and Williams-Wheeler (2004) but a) includes a more comprehensive measure of SES than that conceptualized by Fletcher et al.; b) considers whether the role of community disadvantage is indirectly as well as directly linked to youth risk behavior, by way of its association with parenting variables; c) considers whether level of community urbanicity plays a direct role in predicting both parenting variables and risk behaviors, or whether its influence on risk behaviours is primarily indirect through parenting variables. Both community disadvantage and urbanicity had virtually no relation to parenting and risk behaviour variables. Results found for relations of parenting variables and risk behaviour were similar to Fletcher et al. Although urban youth are typically perceived as being more at risk for substance use and delinquency, no evidence was found for a distinction between urban and rural youth within this sample. Targeting risk behaviour prevention/reduction programs toward only urban youth, therefore, is not supported by these findings.

Woodruff Family fonds, 1784 – 1983, (non-inclusive)

The Woodruff Family Collection: From the time the Woodruff Family came to Canada from the United States in 1795, they took an active role in the forming of their communities both in a civic and social manner. This is evident through the documents contained in this collection. The Woodruffs played an active role in the battles fought in Upper Canada and they were an integral part of the Village of St. Davids. They were educated, business-minded and socially engaged. They accumulated much of their fortune through land dealings. Much of this collection focuses on Samuel DeVeaux Woodruff who was principally a businessman. His dedication to his work is shown through his numerous undertakings. He made his mark on the Niagara Peninsula through his work on the railways, roads, marsh land revisions, canals and the paper industry. He was also involved with the founding of the Long Point Company and he took control of building DeVeaux Hall down to the last detail. His offspring inherited his work ethic and his business acumen. The people who married into the Woodruff Family also possessed key social, political and business ties. Anne and Margaret Clement were from a staunch Loyalist background. Samuel Zimmerman was instrumental to the founding of Niagara Falls and Judge Samuel DeVeaux left behind a legacy for poor and homeless boys in Niagara Falls, New York. The Woodruff Family undoubtedly left a mark on the Niagara Peninsula. This collection brings to light many endeavours of the family and their varied contributions.