(Table 1) Concentrations of organic pollutants in soil samples from Adélie penguin (Pygoscelis adeliae) colonies and reference sites, Hop Island, Antarctica

Although long-range atmospheric transport has been described as the predominant mechanism for exposing polar regions to persistent organic pollutants (POPs), recent studies have suggested that bird activity can also contribute substantially to contaminant levels in some environments. However, because the species so far reported have all been migratory, it has not been demonstrated conclusively whether locally elevated contamination represents transport from lower latitudes by the migrating birds or, alternatively, redistribution and concentration of contaminants that were already present in the high-latitude environments. The present study demonstrates, for the first time, that several POPs are present in elevated concentrations in an environment frequented by a non-migratory species (Adelie penguins) that spends its entire life in the Antarctic. Levels of POPs, such as p,p'-DDE, hexachlorobenzene (HCB), chlordanes (CHLs) and polychlorinated biphenyls (PCBs), were 10 to 100-fold higher in soil samples from penguin colonies than from reference areas. This significant difference is likely related to local penguin activity, such as a higher abundance of guano and the presence of bird carcasses. This hypothesis is also supported by a higher percentage of persistent congeners (PCB 99, 118, 138 and 153) in the soil from the colonies compared to the reference areas. This profile of PCB congeners closely matched profiles seen in penguin eggs or penguin blood.

(Table 1) Concentration of PCB and other contaminants in blood plasma of polar bears (Ursus maritimus) from Svalbard

Persistent chemicals accumulate in the arctic environment due to their chemical reactivity and physicochemical properties and polychlorinated biphenyls (PCBs) are the most concentrated pollutant class in polar bears (Ursus maritimus). Metabolism of PCB and polybrominated biphenyl ether (PBDE) flame-retardants alter their toxicological properties and these metabolites are known to interfere with the binding of thyroid hormone (TH) to transthyretin (TTR) in rodents and humans. In polar bear plasma samples no binding of [125I]-T4 to TTR was observed after incubation and PAGE separation. Incubation of the plasma samples with [14C]-4-OH-CB107, a compound with a higher binding affinity to TTR than the endogenous ligand T4 resulted in competitive binding as proven by the appearance of a radio labeled TTR peak in the gel. Plasma incubation with T4 up to 1 mM, a concentration that is not physiologically relevant anymore did not result in any visible competition. These results give evidence that the binding sites on TTR for T4 in wild living polar bears are completely saturated. Such saturation of binding sites can explain observed lowered levels of THs and could lead to contaminant transport into the developing fetus.

Exposição a substâncias organocloradas em São Paulo: níveis séricos em doadores de sangue e fatores associados

A utilização de pesticidas organoclorados é motivo de preocupação das entidades ligadas à área de saúde em todo o mundo. Apesar de as formas de contaminação serem bem conhecidas, não há um controle eficaz na fiscalização do seu uso no Brasil. Sabe-se que altos níveis séricos destes compostos nos organismos de seres humanos e animais acarretam sérios problemas de saúde. Tendo em vista essa realidade, foi realizado, em 2009, o Projeto Piloto do I Inquérito Nacional de Populações Expostas a Substâncias Químicas, cujo subprojeto \"doadores de sangue\" teve como objetivo mensurar as concentrações de substâncias químicas no sangue de 547 residentes da região metropolitana de São Paulo, dentre elas os pesticidas organoclorados. Este trabalho teve como objetivos avaliar as concentrações dos pesticidas hexaclorobenzeno (HCB), alfa-HCH, ?-HCH, beta-HCH, beta-HCH, heptacloro, heptacloro epóxido, dieldrin, mirex, o,p\'-DDT, p,p\'-DDT, o,p\'-DDE, p,p\'-DDE, o,p\'-DDD e p,p\'-DDD nesta população e compará-las com as encontradas em outros países e determinar fatores associados aos níveis mais elevados destas substâncias. O método analítico utilizado foi de cromatografia a gás. Os resultados deste estudo indicam que a população adulta de São Paulo não está exposta a níveis preocupantes de pesticidas organoclorados, pois dentre os compostos analisados, apenas o beta-HCH e o p,p\'-DDE tiveram um número significante de amostras acima do limite de quantificação, 10,7% e 31,2% das amostras respectivamente. Quando utilizada a metade do limite de quantificação para substituir os valores abaixo do limite de quantificação do método, o valor médio encontrado para o beta-HCH foi de 0,028 ug/dL e para o p,p\'-DDE foi de 0,045 ug/dL. Este estudo propôs dois modelos multivariados para explicar os fatores associados aos compostos beta-HCH e p,p\'-DDE no sangue dos doadores. Segundo o modelo de Regressão Logística Ordinal Multivariado, os fatores associados a níveis mais altos de beta-HCH foram ter idade entre 26 e 45 anos e ser do sexo feminino. Para o p,p\'-DDE os fatores associados a níveis mais altos foram ter idade entre 26 e 45 anos, ser do sexo feminino e ter trabalhado com pesticidas, enquanto receber renda mensal de 3 a 5 salários mínimos e consumir derivados de origem animal uma ou mais vezes por semana foram associados a níveis mais baixos de p,p\'-DDE. Segundo o modelo de Regressão Linear Múltipla, os fatores associados a níveis mais altos de beta-HCH foram o sexo feminino, ter contato prévio com pesticidas na região agrícola, ter trabalhado com pesticidas em campanhas de saúde pública, ter trabalhado em empresas de capacitores ou transformadores, ter trabalhado em indústrias de solventes clorados, ter renda mensal de 3 a 5 salários mínimos, consumo de carnes uma ou duas vezes por semana e consumo de frutos do mar uma ou duas vezes por semana, enquanto consumo frequente de cerveja e ter renda mensal de 1 a 3 salários mínimos foram associado a níveis menores de beta-HCH. Já para o p,p\'-DDE, os fatores associados a níveis mais elevados foram ser do sexo feminino, ser não branco, ter trabalhado com pesticidas e consumir água de fontes que não sejam minerais ou de rede, enquanto o consumo frequente de bebidas alcoólicas foi associado a níveis mais baixos de p,p\'-DDE

Concentrations of brominated and chlorinated contaminants in adipose tissue of polar bears (Ursus maritimus) between 1991-2007

Adipose tissue was sampled from the western Hudson Bay (WHB) subpopulation of polar bears at intervals from 1991 to 2007 to examine temporal trends of PCB and OCP levels both on an individual and sum-contaminant basis. We also determined levels and temporal trends of emerging polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), polybrominated biphenyls (PBBs) and other current-use brominated flame retardants. Over the 17-year period, sum DDT (and p,p'-DDE, p,p'-DDD, p,p'-DDT) decreased (-8.4%/year); alpha-hexachlorocyclohexane (alpha-HCH) decreased (-11%/year); beta-HCH increased ( + 8.3%/year); and sum PCB and sum chlordane (CHL), both contaminants at highest concentrations in all years (>1 ppm), showed no distinct trends even when compared to previous data for this subpopulation dating back to 1968. Some of the less persistent PCB congeners decreased significantly (-1.6%/year to -6.3%/year), whereas CB153 levels tended to increase (+ 3.3%/year). Parent CHLs (c-nonachlor, t-nonachlor) declined, whereas non-monotonic trends were detected for metabolites (heptachlor epoxide, oxychlordane). sum chlorobenzene, octachlorostyrene, sum mirex, sum MeSO2-PCB and dieldrin did not significantly change. Increasing sum PBDE levels (+13%/year) matched increases in the four consistently detected congeners, BDE47, BDE99, BDE100 and BDE153. Although no trend was observed, total-(alpha)-HBCD was only detected post-2000. Levels of the highest concentration brominated contaminant, BB153, showed no temporal change. As long-term ecosystem changes affecting contaminant levels may also affect contaminant patterns, we examined the influence of year (i.e., aging or "weathering" of the contaminant pattern), dietary tracers (carbon stable isotope ratios, fatty acid patterns) and biological (age/sex) group on congener/metabolite profiles. Patterns of PCBs, CHLs and PBDEs were correlated with dietary tracers and biological group, but only PCB and CHL patterns were correlated with year. DDT patterns were not associated with any explanatory variables, possibly related to local DDT sources. Contaminant pattern trends may be useful in distinguishing the possible role of ecological/diet changes on contaminant burdens from expected dynamics due to atmospheric sources and weathering.

Enantioselective transformation of alpha-hexachlorocyclohexane by the dehydrochlorinases LinA1 and LinA2 from the soil bacterium Sphingomonas paucimobilis B90A.

Sphingomonas paucimobilis B90A contains two variants, LinA1 and LinA2, of a dehydrochlorinase that catalyzes the first and second steps in the metabolism of hexachlorocyclohexanes (R. Kumari, S. Subudhi, M. Suar, G. Dhingra, V. Raina, C. Dogra, S. Lal, J. R. van der Meer, C. Holliger, and R. Lal, Appl. Environ. Microbiol. 68:6021-6028, 2002). On the amino acid level, LinA1 and LinA2 were 88% identical to each other, and LinA2 was 100% identical to LinA of S. paucimobilis UT26. Incubation of chiral alpha-hexachlorocyclohexane (alpha-HCH) with Escherichia coli BL21 expressing functional LinA1 and LinA2 S-glutathione transferase fusion proteins showed that LinA1 preferentially converted the (+) enantiomer, whereas LinA2 preferred the (-) enantiomer. Concurrent formation and subsequent dissipation of beta-pentachlorocyclohexene enantiomers was also observed in these experiments, indicating that there was enantioselective formation and/or dissipation of these enantiomers. LinA1 preferentially formed (3S,4S,5R,6R)-1,3,4,5,6-pentachlorocyclohexene, and LinA2 preferentially formed (3R,4R,5S,6S)-1,3,4,5,6-pentachlorocyclohexene. Because enantioselectivity was not observed in incubations with whole cells of S. paucimobilis B90A, we concluded that LinA1 and LinA2 are equally active in this organism. The enantioselective transformation of chiral alpha-HCH by LinA1 and LinA2 provides the first evidence of the molecular basis for the changed enantiomer composition of alpha-HCH in many natural environments. Enantioselective degradation may be one of the key processes determining enantiomer composition, especially when strains that contain only one of the linA genes, such as S. paucimobilis UT26, prevail.

Dynamics of multiple lin gene expression in Sphingomonas paucimobilis B90A in response to different hexachlorocyclohexane isomers.

Sphingomonas paucimobilis B90A is able to degrade the alpha-, beta-, gamma-, and delta-isomers of hexachlorocyclohexane (HCH). It contains the genes linA, linB, linC, linD, linE, and linR, which have been implicated in HCH degradation. In this study, dynamic expression of the lin genes was measured in chemostat-grown S. paucimobilis B90A by RNA dot blot hybridization and real-time reverse transcriptase PCR upon exposure to a pulse of different HCH isomers. Irrespective of the addition of HCH, linA, linB, and linC were all expressed constitutively. In contrast, linD and linE were induced with alpha-HCH (2 mg/liter) and gamma-HCH (7 mg/liter). A sharp increase in mRNA levels for linD and linE was observed from 10 to 45 min after the addition of alpha- or gamma-HCH. Induction of linD and linE was not detectable upon the addition of 0.7 mg of gamma-HCH per liter, although the compound was degraded by the cells. The addition of beta-HCH (5 mg/liter) or delta-HCH (20 mg/liter) did not lead to linE and linD induction, despite the fact that 50% of the compounds were degraded. This suggests that degradation of beta- and delta-HCH proceeds by a different pathway than that of alpha- and gamma-HCH.

Impaired Compensatory Beta-cell Function And Growth In Response To High-fat Diet In Ldl Receptor Knockout Mice.

In this study, we investigated the effect of low density lipoprotein receptor (LDLr) deficiency on gap junctional connexin 36 (Cx36) islet content and on the functional and growth response of pancreatic beta-cells in C57BL/6 mice fed a high-fat (HF) diet. After 60 days on regular or HF diet, the metabolic state and morphometric islet parameters of wild-type (WT) and LDLr-/- mice were assessed. HF diet-fed WT animals became obese and hypercholesterolaemic as well as hyperglycaemic, hyperinsulinaemic, glucose intolerant and insulin resistant, characterizing them as prediabetic. Also they showed a significant decrease in beta-cell secretory response to glucose. Overall, LDLr-/- mice displayed greater susceptibility to HF diet as judged by their marked cholesterolaemia, intolerance to glucose and pronounced decrease in glucose-stimulated insulin secretion. HF diet induced similarly in WT and LDLr-/- mice, a significant decrease in Cx36 beta-cell content as revealed by immunoblotting. Prediabetic WT mice displayed marked increase in beta-cell mass mainly due to beta-cell hypertrophy/replication. Nevertheless, HF diet-fed LDLr-/- mice showed no significant changes in beta-cell mass, but lower islet-duct association (neogenesis) and higher beta-cell apoptosis index were seen as compared to controls. The higher metabolic susceptibility to HF diet of LDLr-/- mice may be explained by a deficiency in insulin secretory response to glucose associated with lack of compensatory beta-cell expansion.

Macrophage Cell Activation With Acute Apical Abscess Contents Determined By Interleukin-1 Beta And Tumor Necrosis Factor Alpha Production.

This clinical study has investigated the antigenic activity of bacterial contents from exudates of acute apical abscesses (AAAs) and their paired root canal contents regarding the stimulation capacity by levels of interleukin (IL)-1 beta and tumor necrosis factor alpha (TNF-α) throughout the root canal treatment against macrophage cells. Paired samples of infected root canals and exudates of AAAs were collected from 10 subjects. Endodontic contents were sampled before (root canal sample [RCS] 1) and after chemomechanical preparation (RCS2) and after 30 days of intracanal medication with calcium hydroxide + chlorhexidine gel (Ca[OH]2 + CHX gel) (RCS3). Polymerase chain reaction (16S rDNA) was used for detection of the target bacteria, whereas limulus amebocyte lysate was used to measure endotoxin levels. Raw 264.7 macrophages were stimulated with AAA exudates from endodontic contents sampled in different moments of root canal treatment. Enzyme-linked immunosorbent assays were used to measure the levels of TNF-α and IL-1 beta. Parvimonas micra, Porphyromonas endodontalis, Dialister pneumosintes, and Prevotella nigrescens were the most frequently detected species. Higher levels of endotoxins were found in samples from periapical exudates at RCS1 (P < .005). In fact, samples collected from periapical exudates showed a higher stimulation capacity at RCS1 (P < .05). A positive correlation was found between endotoxins from exudates with IL-1 beta (r = 0.97) and TNF-α (r = 0.88) production (P < .01). The significant reduction of endotoxins and bacterial species achieved by chemomechanical procedures (RCS2) resulted in a lower capacity of root canal contents to stimulate the cells compared with that at RCS1 (P < .05). The use of Ca(OH)2 + CHX gel as an intracanal medication (RCS3) improved the removal of endotoxins and bacteria from infected root canals (P < .05) whose contents induced a lower stimulation capacity against macrophages cells at RCS1, RCS2, and RCS3 (P < .05). AAA exudates showed higher levels of endotoxins and showed a greater capacity of macrophage stimulation than the paired root canal samples. Moreover, the use of intracanal medication improved the removal of bacteria and endotoxins from infected root canals, which may have resulted in the reduction of the inflammatory potential of the root canal content.

Enhanced Glucose-induced Intracellular Signaling Promotes Insulin Hypersecretion: Pancreatic Beta-cell Functional Adaptations In A Model Of Genetic Obesity And Prediabetes.

Obesity is associated with insulin resistance and is known to be a risk factor for type-2 diabetes. In obese individuals, pancreatic beta-cells try to compensate for the increased insulin demand in order to maintain euglycemia. Most studies have reported that this adaptation is due to morphological changes. However, the involvement of beta-cell functional adaptations in this process needs to be clarified. For this purpose, we evaluated different key steps in the glucose-stimulated insulin secretion (GSIS) in intact islets from female ob/ob obese mice and lean controls. Obese mice showed increased body weight, insulin resistance, hyperinsulinemia, glucose intolerance and fed hyperglycemia. Islets from ob/ob mice exhibited increased glucose-induced mitochondrial activity, reflected by enhanced NAD(P)H production and mitochondrial membrane potential hyperpolarization. Perforated patch-clamp examination of beta-cells within intact islets revealed several alterations in the electrical activity such as increased firing frequency and higher sensitivity to low glucose concentrations. A higher intracellular Ca(2+) mobilization in response to glucose was also found in ob/ob islets. Additionally, they displayed a change in the oscillatory pattern and Ca(2+) signals at low glucose levels. Capacitance experiments in intact islets revealed increased exocytosis in individual ob/ob beta-cells. All these up-regulated processes led to increased GSIS. In contrast, we found a lack of beta-cell Ca(2+) signal coupling, which could be a manifestation of early defects that lead to beta-cell malfunction in the progression to diabetes. These findings indicate that beta-cell functional adaptations are an important process in the compensatory response to obesity.

Partial-hepatectomized (70%) Model Shows A Correlation Between Hepatocyte Growth Factor Levels And Beta-cell Mass.

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Caracterização do complexo de inclusão ropivacaína: beta-ciclodextrina

Characteriza of the inclusion complex ropivacaine: beta-cyclodextrin. Ropivacaine (RVC) is a widely used local anesthetic. The complexation of RVC with beta-cyclodextrin (beta-CD) is of great interest for the development of more efficient local anesthetic formulations. The present work focuses on the characterization of the RVC:beta-CD complex by nuclear magnetic resonance (NMR). The stoichiometry of the complex is 1:2 RVC:beta-CD. DOSY-NMR shows that the association constant is 55.5 M-1. Longitudinal relaxation time results show that RVC changes its mobility in the presence of beta-CD. This study is focused on the physicochemical characterization of inclusion complexes that are potentials options for pain treatment.