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1.
Bull World Health Organ ; 96(8): 540-547, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30104794

RESUMO

OBJECTIVE: To rapidly increase childhood immunization through a preventive, multi-antigen, vaccination campaign in Mambéré-Kadéï prefecture, Central African Republic, where a conflict from 2012 to 2015 reduced vaccination coverage. METHODS: The three-round campaign took place between December 2015 and June 2016 using: (i) oral poliomyelitis vaccine (OPV); (ii) combined diphtheria, tetanus and pertussis (DTP) vaccine, Haemophilus influenza type B (Hib) and hepatitis B (DTP-Hib-hepatitis B) vaccine; (iii) pneumococcal conjugate vaccine (PCV); (iv) measles vaccine; and (v) yellow fever vaccine. Administrative data were collected on vaccines administered by age group and vaccination coverage surveys were carried out before and after the campaign. FINDINGS: Overall, 294 054 vaccine doses were administered. Vaccination coverage for children aged 6 weeks to 59 months increased to over 85% for the first doses of OPV, DTP-Hib-hepatitis B vaccine and PCV and, in children aged 9 weeks to 59 months, to over 70% for the first measles vaccine dose. In children aged 6 weeks to 23 months, coverage of the second doses of OPV, DTP-Hib-hepatitis B vaccine and PCV was over 58% and coverage of the third doses of OPV and DTP-Hib-hepatitis B vaccine was over 20%. Moreover, 61% (5804/9589) of children aged 12 to 23 months had received two PCV doses and 90% (25933/28764) aged 24 to 59 months had received one dose. CONCLUSION: A preventive, multi-antigen, vaccination campaign was effective in rapidly increasing immunization coverage in a post-conflict setting. To sustain high coverage, routine immunization must be reinforced.


Assuntos
Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Programas de Imunização , Esquemas de Imunização , Vigilância da População , Vacinação/estatística & dados numéricos , República Centro-Africana , Criança , Pré-Escolar , Vacinas contra Hepatite B , Humanos , Lactente
2.
J Toxicol Environ Health A ; 77(9-11): 628-49, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24754397

RESUMO

Polychlorinated biphenyls (PCB) are environmental pollutants linked to adverse health effects including endocrine disruption and disturbance of reproductive development. This study aimed to determine whether exposure of pregnant sheep to three different mixtures of PCB 153 and PCB 118 affected fetal testis development. Ewes were treated by oral gavage from mating until euthanasia (d 134), producing three groups of fetuses with distinct adipose tissue PCB levels: high PCB 153/low PCB 118 (n = 13), high PCB 118/low PCB 153 (n = 14), and low PCB 153/low PCB 118 (n = 14). Fetal testes and blood samples were collected for investigation of testosterone, testis morphology, and testis proteome. The body weight of the offspring was lower in the high PCB compared to the low PCB group, but there were no significant differences in testis weight between groups when corrected for body weight. PCB exposure did not markedly affect circulating testosterone. There were no significant differences between groups in number of seminiferous tubules, Sertoli cell only tubules, and ratio between relative areas of seminiferous tubules and interstitium. Two-dimensional (2D) gel-based proteomics was used to screen for proteomic alterations in the high exposed groups relative to low PCB 153/low PCB 118 group. Twenty-six significantly altered spots were identified by liquid chromatography (LC)-mass spectroscopy (MS)/MS. Changes in protein regulation affected cellular processes as stress response, protein synthesis, and cytoskeleton regulation. The study demonstrates that in utero exposure to different environmental relevant PCB mixtures exerted subtle effects on developing fetal testis proteome but did not significantly disturb testis morphology and testosterone production.


Assuntos
Poluentes Ambientais/toxicidade , Exposição Materna/efeitos adversos , Bifenilos Policlorados/toxicidade , Ovinos/embriologia , Testículo/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Determinação de Ponto Final , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Imuno-Histoquímica , Masculino , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Proteômica , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/metabolismo , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Testículo/metabolismo , Testosterona/metabolismo
3.
Environ Toxicol ; 28(3): 164-77, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21544918

RESUMO

This study investigated the effects of exposure to the ubiquitous contaminants polychlorinated biphenyls (PCBs) on the fetal adrenal cortex and on plasma cortisol using the domestic sheep (Ovis aries) as a model. Pregnant ewes were intendedly subjected to oral treatment with PCB 153 (98 µg/kg bw/day), PCB 118 (49 µg/kg bw/day) or the vehicle corn oil from mating until euthanasia on gestation day 134 (±0.25 SE). However, because of accidental cross-contamination occurring twice causing a mixed exposure scenario in all three groups, the focus of this paper is to compare three distinct groups of fetuses with different adipose tissue PCB levels (PCB 153high, PCB 118high and low, combined groups) rather than comparing animals exposed to single PCB congeners to those of a control group. When comparing endocrine and anatomical parameters from fetuses in the PCB 153high (n = 13) or PCB 118high (n = 14) groups with the low, combined group (n = 14), there was a significant decrease in fetal body weight (P < 0.05), plasma cortisol concentration (P < 0.001) and adrenal cortex thickness (P < 0.001). Furthermore, adrenal weight was decreased and plasma ACTH was increased only in the PCB 118high group. Expression of several genes encoding enzymes and receptors related to steroid hormone synthesis was also affected and mostly down-regulated in fetuses with high PCB tissue levels. In conclusion, we suggest that mono-and di-ortho PCBs were able to interfere with growth, adrenal development and cortisol production in the fetal sheep model. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/embriologia , Bifenilos Policlorados/toxicidade , Glândulas Suprarrenais/metabolismo , Animais , Feminino , Masculino , Modelos Animais , Gravidez , Ovinos , Carneiro Doméstico
4.
Environ Toxicol ; 27(11): 623-34, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21344607

RESUMO

The effects of in utero and lactational exposure to two structurally different polychlorinated biphenyl (PCB) congeners on follicular dynamics and the pituitary-gonadal axis in female lambs were investigated. Pregnant ewes received corn oil, PCB 118, or PCB 153, and offspring was maintained until 60 days postpartum. Ovarian follicles were quantified using stereology. Plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured using radioimmunoassay before and after administration of a gonadotropin releasing hormone (GnRH) analog. PCB 118 exposure increased numbers of transitional, secondary, and the sum of secondary, early antral, and antral (Σsecondary-antral) follicles, PCB 153 exposure only increased the number of primary follicles. GnRH-induced LH levels were significantly elevated in the PCB 153 exposure group. We conclude that PCB 153 and PCB 118 alter follicular dynamics in lambs and modulate the responsiveness of the pituitary gland to GnRH.


Assuntos
Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Luteinizante/metabolismo , Folículo Ovariano/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Animais , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/metabolismo , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Luteinizante/sangue , Hipófise/efeitos dos fármacos , Gravidez , Ovinos
5.
Epilepsia ; 51(11): 2280-8, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20726872

RESUMO

PURPOSE: Endocrine disruptive effects have been frequently observed in patients using antiepileptic drugs (AEDs). Two different AEDs, valproate (VPA) and levetiracetam (LEV), were tested in forskolin-stimulated human adrenal carcinoma (H295R) cells to explore their effect on steroidogenesis. VPA has a long history as an anticonvulsant and is linked with many of the endocrine disorders associated with AED use. LEV is a newer AED, and no endocrine disruptive effects have been reported in humans to date. METHODS: H295R cells, which are capable of full steroidogenesis, were stimulated with forskolin and exposed to either VPA or LEV for 48 h. Medium was collected and analyzed for hormone production. For the VPA-exposed cells, steroidogenic gene expression analysis was also conducted. RESULTS: VPA exposure resulted in a significant reduction in progesterone and estradiol (E2) production, whereas testosterone (T) levels remained unchanged. There were also significant alterations in expression level for most genes analyzed. LEV exposure resulted in a minor, but statistically significant, reduction in T and E2 production. DISCUSSION: Exposure of forskolin-stimulated H295R cells to VPA led to an increased T/E2 ratio through a significant decrease in estradiol production. Gene analysis suggested that VPA affects NR0B1 expression. NR0B1 inhibits promoters of other genes involved in steroidogenesis, and the altered expression of NR0B1 might explain the observed down-regulation in hormone production. The effects of LEV exposure on hormone secretion were not considered to be biologically significant.


Assuntos
Anticonvulsivantes/farmacologia , Colforsina/farmacologia , Estradiol/metabolismo , Piracetam/análogos & derivados , Progesterona/metabolismo , Testosterona/metabolismo , Ácido Valproico/farmacologia , Neoplasias das Glândulas Suprarrenais/patologia , Aromatase/metabolismo , Linhagem Celular Tumoral , Citocromo P-450 CYP1A1/genética , Receptor Nuclear Órfão DAX-1/genética , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Levetiracetam , Piracetam/farmacologia , Reação em Cadeia da Polimerase , Fator Esteroidogênico 1/genética , Estimulação Química
6.
J Toxicol Environ Health A ; 73(16): 1122-32, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20574914

RESUMO

Polychlorinated biphenyls (PCB) are ubiquitous environmental pollutants that have been linked to adverse health effects including endocrine disruption. This study compared the mono-ortho-substituted PCB 118 and di-ortho-substituted PCB 153 with the non-ortho-substituted PCB 126, for possible effects on steroid hormone production and on the expression of 10 genes encoding proteins involved in steroidogenesis. The H295R human adenocarcinoma cell line was used as an in vitro model. Cells were exposed for 48 h to solvent control (dimethyl sulfoxide, DMSO) or 6 different concentrations ranging from 40 pM to 4 muM of one of the three test compounds. All three congeners significantly increased the production of estradiol-17beta. PCB 118 produced a rise in progesterone and cortisol in a concentration-dependent manner, similar to PCB 126. Testosterone was significantly reduced in response to PCB 153 but not PCB 118 or PCB 126. All three congeners elevated aldosterone at the highest concentration tested. A significant increase was observed in CYP11B2 mRNA levels in cells exposed to the three congeners. In addition, PCB 126 upregulated CYP19, 3beta-HSD2, StAR, and HMGR mRNA levels at the highest concentration tested, and downregulated CYP21 at 40 nM. In conclusion, all three PCB congeners are capable of modulating steroidogenesis in H295R in a concentration-dependent manner, whereby the hormone profile following PCB 118 exposure resembles that of PCB 126. Where changes in gene expression profile are concerned, exposure to PCB 126 showed the greatest effects.


Assuntos
Neoplasias do Córtex Suprarrenal/patologia , Poluentes Ambientais/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônios/biossíntese , Bifenilos Policlorados/toxicidade , Esteroides/biossíntese , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Poluentes Ambientais/química , Estradiol/biossíntese , Humanos , Bifenilos Policlorados/química , Bifenilos Policlorados/classificação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Tumorais Cultivadas
7.
J Toxicol Environ Health A ; 72(3-4): 164-72, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19184731

RESUMO

Short-term stress exposure is associated with activation of the hypothalamic-pituitary-adrenal (HPA) axis and a consequent rise in blood glucocorticoids and catecholamines, from the adrenal cortex and medulla, respectively. The HPA axis is a potential target for some persistent organic pollutants, among which polychlorinated biphenyls (PCB) were found to be modulators of the mammalian endocrine system. PCB are distributed globally in the environment, in food chains, and are transferred to the fetuses of pregnant animals and via mother's milk to suckling offspring. In the present study it was postulated that intrauterine and lactational exposure to either of two single congeners of PCB (PCB 153 and PCB 126, respectively) might affect basal cortisol concentrations, and also the cortisol response to short-term stress in adulthood. Thus, pregnant goats were orally exposed to one of these PCB congeners from d 60 of gestation until delivery, and their offspring studied. Low-dose exposure to PCB 153 and PCB 126 resulted in significantly lower mean basal cortisol concentrations in goat offspring during certain periods of pubertal development and their first breeding season. Male goat kids exposed to either PCB congener showed a greater and more prolonged rise in plasma cortisol levels than controls when animals were subjected to mild stress at 9 mo of age using frequent blood sampling. Neither the basal maternal cortisol plasma level nor goat kid adrenal masses were affected by PCB exposure.


Assuntos
Cabras/sangue , Hidrocortisona/sangue , Bifenilos Policlorados/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Estresse Fisiológico/efeitos dos fármacos , Administração Oral , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia , Animais , Relação Dose-Resposta a Droga , Feminino , Cabras/fisiologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Lactação/metabolismo , Masculino , Exposição Materna , Troca Materno-Fetal , Tamanho do Órgão/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/patologia , Estresse Fisiológico/fisiologia
8.
J Steroid Biochem Mol Biol ; 111(1-2): 24-8, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18511263

RESUMO

The present study evaluated whether a specific androstenone-binding protein is present in porcine and human serum, and in the cytosolic fraction of porcine testis. The binding of [(3)H]-androstenone to serum and testicular cytosol was measured in the absence (total binding) and presence (non-specific binding) of unlabelled androstenone. The optimization of the assay is described. As a part of the assay validation, the binding of [(3)H]-dihydrotestosterone ([(3)H]-DHT) to porcine and human serum was also examined. As expected, specific binding of [(3)H]-DHT was detected in human serum, but not in porcine serum. No specific androstenone-binding protein was detected, either in porcine or human serum, or in the cytosolic fraction of porcine testis. The amount of non-specific binding of [(3)H]-androstenone was slightly lower in porcine serum compared to human serum. Between-animal variations in [(3)H]-androstenone binding were studied in plasma samples from 15 animals with androstenone concentrations ranging from 1.1 to 23.1 ng/mL. Mean values+/-standard deviations of binding in these samples were 15.2+/-0.9% for total binding and 15.9+/-0.8% for non-specific bindings. Low between-animal variations indicate that androstenone binding does not affect androstenone accumulation in fat.


Assuntos
Androstenos/metabolismo , Citosol/metabolismo , Plasma/metabolismo , Soro/metabolismo , Testículo/metabolismo , Androstenos/sangue , Animais , Bioensaio , Fracionamento Celular , Di-Hidrotestosterona/metabolismo , Feminino , Humanos , Masculino , Sus scrofa
9.
Seizure ; 17(2): 203-9, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18155931

RESUMO

PURPOSE: Several antiepileptic drugs (AEDs) induce changes in endocrine function in women with epilepsy. Levetiracetam (LEV) is one of the newer AEDs, and to date no endocrine side-effects have been reported in humans. However, a recent study on ovarian follicular cells from prepubertal pigs showed that LEV affected basal steroid hormone secretion. The aim of the present study was to investigate possible effects of the drug on endocrine function and ovarian morphology in non-epileptic rats. METHODS: Thirty female Wistar rats were fed per-orally with either 50mg/kg LEV (n=15) or 150 mg/kg LEV (n=15) twice daily for 90-95 days. Twenty rats received a control solution. The rats were killed in the dioestrus phase of the oestrous cycle. Serum concentrations of testosterone, 17beta-oestradiol, progesterone, follicle stimulating hormone (FSH), luteinizing hormone (LH) and LEV were measured, and the ovaries examined histologically. RESULTS: Mean ovarian weight showed a significant, dose-dependent increase after LEV treatment. Mean numbers of ovarian follicular cysts were not changed, but the numbers of corpora lutea and secondary follicles were significantly higher in the treated animals. Serum testosterone was significantly increased in treated animals (0.50 nmol/l versus 0.16 nmol/l in controls, p<0.05), while oestradiol was reduced (67.4 compared to 257.5 pmol/l in controls, p<0.05). The low-dose group had significantly lower serum progesterone concentrations than the control group (56.8 nmol/l versus 34.7 nmol/l, respectively, p<0.05). FSH was reduced in the treated animals (3.3 ng/ml versus 5.5 ng/ml, p<0.05) while LH was unaffected. CONCLUSION: Our findings indicate a possible effect of LEV on the hypothalamic-pituitary-gonadal (HPG) axis and ovarian morphology in non-epileptic rats. The effects differ from those previously described for other AEDs. Caution must be taken before these results can be applied to humans.


Assuntos
Anticonvulsivantes/farmacologia , Sistema Endócrino/efeitos dos fármacos , Piracetam/análogos & derivados , Administração Oral , Análise de Variância , Animais , Corpo Lúteo/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Gonadotropinas Hipofisárias/metabolismo , Levetiracetam , Ciclo Menstrual/efeitos dos fármacos , Ovário/efeitos dos fármacos , Piracetam/farmacologia , Radioimunoensaio , Ratos , Ratos Wistar , Estatísticas não Paramétricas , Fatores de Tempo
10.
Environ Pollut ; 145(1): 138-45, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16713050

RESUMO

Exposure to organohalogens in endotherms has been suggested to impose chemically induced stress by affecting functions related to maintenance energy requirements. Effects on basal metabolic rate (BMR) have been suggested to be, in part, mediated through interactions with the thyroid hormones (THs). We investigated the relationships between plasma concentrations of major organochlorines, PBDEs, hydroxylated (OH)- and methoxylated (MeO)-PBDEs and OH-PCBs, circulating TH levels and BMR in breeding glaucous gulls (Larus hyperboreus) from the Norwegian Arctic. Negative associations were found between BMR and concentrations of sigma PCB, Sigma DDT and particularly Sigma chlordane, which combined made up 91% of the total contaminant burden. Levels of THs (thyroxine and triiodothyronine) were not associated significantly with variation of BMR or concentrations of any of the compounds determined. The present study suggests that BMR may be altered in glaucous gulls exposed to high loadings of persistent contaminants in the Norwegian Arctic environment.


Assuntos
Charadriiformes/metabolismo , Poluentes Ambientais/sangue , Hormônios Tireóideos/sangue , Animais , Regiões Árticas , Metabolismo Basal , Cruzamento , Charadriiformes/sangue , Clordano/sangue , DDT/sangue , Feminino , Masculino , Noruega , Éteres Fenílicos/sangue , Bifenil Polibromatos/sangue , Bifenilos Policlorados/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
11.
J Toxicol Environ Health A ; 69(1-2): 53-76, 2006 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-16291562

RESUMO

Long-range transport of persistent organic compounds by air and ocean currents from industrialized areas resulted in high levels of these pollutants in food webs in the Svalbard area. With the aim to test if organochlorine (OC) exposure in free-living polar bears from Svalbard affected their plasma steroid hormone concentrations, it was found that polychlorinated biphenyls (PCBs) were associated with increased progesterone levels in females. The sum of pesticides (sigma pesticides) and sigma PCBs contributed significantly negative to the variation of the plasma testosterone in males, and the overall contribution of the OCs to the plasma cortisol variation was negative. A second objective was to study the effects of selected OCs (i.e., PCB 153 and PCB 126) on animal health as a consequence of effects on endocrine-regulated functions such as reproduction and immunity in a goat model focusing on long-term and low-level exposure during the periods of fetal development and in the neonatal period. Additionally, acute exposure was studied in adult mice. The results indicated that exposure to low doses of PCB 153 in utero and in the suckling period influenced reproductive functions and both PCB 153 and PCB 126 exerted immunomodulatory effects on the offspring, whereas acute exposure of adult mice had minor effects on male reproductive function.


Assuntos
Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Hidrocarbonetos Clorados/toxicidade , Animais , Disruptores Endócrinos/sangue , Disruptores Endócrinos/farmacocinética , Poluentes Ambientais/sangue , Poluentes Ambientais/farmacocinética , Feminino , Cabras , Hormônios/sangue , Hidrocarbonetos Clorados/sangue , Hidrocarbonetos Clorados/farmacocinética , Contagem de Leucócitos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Masculino , Exposição Materna , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Reprodução/efeitos dos fármacos , Ursidae
12.
Environ Toxicol Chem ; 25(11): 2990-6, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17089723

RESUMO

Organohalogen contaminants detected globally in avian wildlife, including populations from the Arctic, have been related to various reproductive hormone potencies, and altered hormonal balance and functions. Besides legacy organochlorine (OC) substances, that is, polychlorinated biphenyls (PCBs) and OC pesticides and by-products, endocrine-disruptive properties have been defined for chemicals of new and emerging environmental concern, such as polybrominated diphenyl ethers (PBDEs) and metabolically derived products like methylsulfonyl (MeSO2)- and hydroxyl (OH)-PCBs. We investigated the relationships between plasma concentrations of selected legacy OCs, PBDEs, and MeSO2- and OH-PCB metabolites and the circulating reproductive hormones testosterone (T), 17beta-estradiol (E2), and progesterone (P4) in incubating male and female glaucous gulls (Larus hyperboreus) from the Norwegian Arctic. Principal component and regression analyses demonstrated that P4 levels in male glaucous gulls were associated positively with variations of sum (Y) PCB, dichloro-diphenyl-trichloroethane (sigmaDDT), chlordane (sigmaCHL), and sigmaPBDE concentrations, which were the most recalcitrant organohalogens determined in glaucous gulls. No such relationship was found for female glaucous gulls as well as between concentrations of any of the selected organohalogens and levels of T for both sexes. The E2 was not detected in any plasma samples. Present results were highly suggestive that exposure to high organohalogen concentrations in glaucous gulls, particularly the most persistent compound classes, may have the potential to interfere with steroidogenesis and impinge on circulating P4 homeostasis. Because significant effects were found in males exclusively, it cannot be completely ruled out that male glaucous gulls are more sensitive than females to organohalogen-mediated alteration of P4 synthesis and breakdown.


Assuntos
Charadriiformes/sangue , Poluentes Ambientais/sangue , Hidrocarbonetos Clorados/sangue , Éteres Fenílicos/sangue , Bifenil Polibromatos/sangue , Progesterona/sangue , Animais , Monitoramento Ambiental , Estradiol/sangue , Feminino , Masculino , Noruega , Testosterona/sangue
13.
Environ Health Perspect ; 111(4): 431-6, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12676595

RESUMO

High concentrations of polychlorinated biphenyls (PCBs) in polar bears from Svalbard have increased concern for that population's reproductive health. We examined whether there were associations between the plasma concentrations of PCBs and reproductive hormones [progesterone (P4)] and 17 beta-estradiol (E2)] in free-living female polar bears from Svalbard. Concentrations of P4 depended on reproductive status, and concentrations were lowest in females with offspring--females with cubs and females with yearlings. In these females, the P4 concentrations were positively correlated with plasma sigma PCBs (sum of all analyzed polychlorinated biphenyl congeners) concentrations. The sigma PCBs concentrations explained 27% of the variation in the P4 concentrations. There were no correlations between sigma PCBs and E2 and cortisol in any of the groups of polar bears, or between sigma PCBs and P4 in single polar bears. Although the sigma PCBs-P4 relationship in female polar bears with offspring is not evidence per se of a direct cause-effect association, the results indicate that PCBs may affect levels of P4 in polar bear females. There is a clear need to further assess the hormone balance and population health of polar bears at Svalbard.


Assuntos
Exposição Ambiental , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/sangue , Estradiol/sangue , Bifenilos Policlorados/efeitos adversos , Bifenilos Policlorados/sangue , Progesterona/sangue , Ursidae/fisiologia , Animais , Regiões Árticas , Relação Dose-Resposta a Droga , Sistema Endócrino/efeitos dos fármacos , Feminino , Nível de Saúde , Noruega , Reprodução
14.
Reprod Toxicol ; 19(1): 87-95, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15336716

RESUMO

The aim of the present study was to investigate if environmental doses of PCB 153 and PCB 126 could produce effects in a controlled animal model. Possible adverse effects on the hypothalamic-pitutitary-gonadal axis were examined by measuring gonadotrophins and gonadal steroid hormone concentrations in goat kids exposed during gestation and lactation. The concentrations of PCB 153 and PCB 126 in adipose tissue in the goat kids 9 months post-partum were 5800 ng/g (fat-weight, range; 2900-12700 ng/g) and 0.49 ng/g (fat-weight, range; 0.28-0.80 ng/g), respectively. The pre- and post-pubertal plasma concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (Prl) and progesterone (P4) were analysed. LH, FSH, Prl, and P4 were also measured during an induced oestrus cycle. The prepubertal LH concentration was significantly lower, the puberty was delayed and the P4 level during the luteal phase of an estrous cycle was higher in the group exposed to PCB 153. No significant effect of PCB 153 exposure was found on Prl and FSH. PCB 126 did not produce any effects at the exposure level tested in this study. In conclusion, perinatal exposure to PCB 153 affected the reproductive function and the puberty maturation in goats.


Assuntos
Poluentes Ambientais/toxicidade , Gonadotropinas Hipofisárias/sangue , Lactação/efeitos dos fármacos , Exposição Materna , Adeno-Hipófise/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Maturidade Sexual/efeitos dos fármacos , Administração Oral , Animais , Animais Recém-Nascidos , Poluentes Ambientais/administração & dosagem , Antagonistas de Estrogênios/administração & dosagem , Antagonistas de Estrogênios/toxicidade , Ciclo Estral/efeitos dos fármacos , Feminino , Cabras , Masculino , Troca Materno-Fetal , Modelos Animais , Adeno-Hipófise/metabolismo , Bifenilos Policlorados/administração & dosagem , Gravidez
15.
J Toxicol Environ Health A ; 67(11): 889-904, 2004 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-15205043

RESUMO

Pregnant does (10 goats/group) were dosed orally with either PCB 153 or PCB 126 dissolved in corn oil or only corn oil (control group) from day 60 of gestation until delivery. Effects on in vitro mitogen-induced lymphocyte proliferation and blood cell counts in their goat kids exposed to low levels of PCB 153 and PCB 126 during gestation and lactation were assessed. The concentrations of PCB 153 and PCB 126 in adipose tissue in the goat kids 9 mo postpartum were 5800 ng/g (fat weight) and 0.49 ng/g (fat weight), respectively. Kids exposed to PCB 153 had a significantly higher number of white blood cells, neutrophils, and lymphocytes at 2 wk of age compared to controls. In the kids exposed to PCB 126 there was a significantly lower concentration of monocytes at 2, 4, and 8 wk of age. The mean lymphocyte response to phytohemagglutinin (PHA) and to concanavalin A (Con A) was significant lower in the PCB 153 compared to the control group at wk 2, 4, and 8 postnatally. The results of the present study support previous reports on immunotoxic effects of PCB exposure in animals. However, this is the first report to demonstrate immunotoxicity in animals by using low doses of PCB 153. The difference in results between PCB 126 and PCB 153 treatment groups may strengthen the hypothesis that PCBs mediate immunotoxic effects through both AhR-dependent and -independent mechanisms.


Assuntos
Ativação Linfocitária/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Tecido Adiposo/metabolismo , Administração Oral , Animais , Animais Recém-Nascidos , Contagem de Células Sanguíneas , Relação Dose-Resposta a Droga , Feminino , Cabras , Linfócitos/classificação , Linfócitos/efeitos dos fármacos , Exposição Materna , Bifenilos Policlorados/administração & dosagem , Bifenilos Policlorados/farmacocinética , Gravidez
16.
J Toxicol Environ Health A ; 67(12): 959-77, 2004 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-15205038

RESUMO

Since the polar bear (Ursus maritimus) is among the most highly organochlorine-contaminated species of the Arctic mammals, there is growing concern that in addition to the natural stressors in the polar bear's environment, several organochlorines (OCs) may be able to change basic endocrine pathways. Alterations in the hypothalamic-pituitary-adrenal (HPA) axis may affect plasma cortisol concentrations and inhibit physiological processes involved in the maintenance of homeostasis in a way that may endanger the animal's health. Between 1995 and 1998, samples were collected from 121 male and 130 female free-ranging polar bears from the Svalbard area. The aim of the study was to investigate relationships between plasma cortisol concentrations, biological factors, and OCs. The variation in plasma cortisol concentrations was determined for the total sample. Axillary girth and body mass together with their interactions explained more than 50% of the variation in the plasma cortisol concentration. The sum of pesticides (Sigma pesticides) combined with the sum of polychlorinated biphenyls (Sigma PCBs) and their interactions explained over 25% of the variation in the cortisol concentration. Although Sigma pesticides contributed negatively and Sigma PCBs contributed positively to the variation in the plasma cortisol, the over-all contribution of the OCs to the plasma cortisol variation was negative. Despite the complexity on stress responses and the interactions with environmental factors, this study demonstrated that high concentrations of OCs in polar bears might alter plasma cortisol concentrations.


Assuntos
Poluentes Ambientais/toxicidade , Hidrocarbonetos Clorados , Hidrocortisona/sangue , Inseticidas/toxicidade , Ursidae/fisiologia , Animais , Animais Selvagens , Poluentes Ambientais/sangue , Feminino , Inseticidas/sangue , Masculino , Sistema Hipófise-Suprarrenal/efeitos dos fármacos
17.
J Toxicol Environ Health A ; 66(22): 2119-39, 2003 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-14710596

RESUMO

Normal sexual development and subsequent reproductive function are dependent on appropriate testosterone production and action. The regulation of steroid hormones, including androgens, can be influenced by both biological and environmental factors, including environmental chemicals. Concentrations of organochlorines are considerably greater in Svalbard polar bears than in polar bears from other regions. Between 1995 and 1998, samples were collected from 121 male polar bears (Ursus maritimus) from the Svalbard area. In this study, testosterone concentration variations were described for male polar bears during different seasons and for all age groups. To study possible relationships between plasma testosterone concentrations and biological factors, such as age, axial girth, and extractable plasma fat, and organochlorine contaminants including hexachlorocyclohexanes, hexachlorobenzene, chlordanes, p,p'-DDE, and 16 individual polychlorinated biphenyl (PCB) congeners, identical statistical analyses were performed on the total population and a subsample of reproductively active adults. Of the biological factors, axial girth showed a significant positive relationship and percentage extractable fat and a significant negative relationship with the testosterone concentrations. Both the epsilon pesticides and epsilon PCBs made significant negative contributions to the variation of the plasma testosterone concentration. The continuous presence of high concentrations of organochlorines in male polar bears throughout their life could possibly aggravate any reproductive toxicity that may have occurred during fetal and early postnatal development.


Assuntos
Exposição Ambiental , Poluentes Ambientais/toxicidade , Inseticidas/toxicidade , Bifenilos Policlorados/toxicidade , Testosterona/sangue , Ursidae/fisiologia , Fatores Etários , Animais , Masculino , Reprodução/efeitos dos fármacos , Estações do Ano , Maturidade Sexual
18.
Theriogenology ; 61(4): 785-95, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14698066

RESUMO

Transrectal or transabdominal examinations of 13 pluriparous reindeer (Rangifer tarandus tarandus) by ultrasonography from the start of mating until week 20 of gestation were conducted to find out when pregnancy could first be detected and to describe fetal development in early pregnancy. The examinations (n=35 per animal) were performed with a 5 MHz linear transducer from 7th October until 1st January and with a 3 MHz sector transducer from that time until 24th February. Time of pregnancy diagnosis by ultrasonography, the first fetal heartbeat and measurements of crown-rump length, chest width and chest depth were recorded during the examinations. Pregnancy was diagnosed by transrectal ultrasonography between the weeks 3 and 7 of gestation. The accuracy of the pregnancy diagnosis, defined as the proportion of females correctly detected to be pregnant, was 15% at week 3, 46% at week 4, 77% at week 5, and 92% at week 6 of gestation. Fetal heartbeat was first detected between the weeks 5 and 8 of gestation. The first measurements of crown-rump length were made on week 3 of gestation, of chest width on week 4 and of chest depth on week 5 of gestation. Chest width and depth were detectable until the end of the study at week 20 of gestation. Transrectal ultrasonography is an efficient tool in early pregnancy diagnosis of reindeer. The fetal growth curves obtained by ultrasonography resembled those obtained in previous morphological studies.


Assuntos
Desenvolvimento Embrionário e Fetal , Idade Gestacional , Rena/fisiologia , Ultrassonografia Pré-Natal , Animais , Estatura Cabeça-Cóccix , Feminino , Glicoproteínas/sangue , Gravidez , Testes de Gravidez , Progesterona/sangue , Rena/embriologia
19.
Theriogenology ; 79(6): 986-94, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23434359

RESUMO

Androstenone and testosterone levels in Duroc boars with an estimated breeding value for androstenone (EBV(androstenone)) were followed in the period from birth to sexual maturity. The breeding value for androstenone had been estimated based on androstenone levels in 1202 Duroc boars at an age of 24 weeks. Testosterone and androstenone levels in plasma were recorded in 19 boars at 1 week of age and in their 15 respective litter-siblings at 3 weeks of age. Between 12 and 27 weeks of age, plasma levels were recorded weekly in a third set of 16 litter-siblings. In the last group, histomorphology was performed at 12, 16, 20, and 27 weeks of age to determine sexual maturity status. The EBV(androstenone) was positively related to plasma androstenone in animals 12 to 27 weeks of age and to plasma testosterone levels in 1- and 3-week-old animals. The EBV(androstenone) was not related to testis morphology. The concentration of fat androstenone was positively correlated to the percentage of immature seminiferous tubules and negatively correlated to the percentage of mature seminiferous tubules at 20 weeks. Testosterone in plasma showed no relationship with testis morphology. Most individuals reached puberty at 20 weeks of age, which indicates that Duroc mature later than crossbred boars. The results indicated that breeding value based on the single trait boar taint parameter EBV(androstenone) was not related to testicular development.


Assuntos
Androsterona/metabolismo , Suínos/fisiologia , Testículo/anatomia & histologia , Testosterona/metabolismo , Tecido Adiposo/metabolismo , Androsterona/sangue , Animais , Estudos Longitudinais , Masculino , Maturidade Sexual , Suínos/anatomia & histologia , Testículo/crescimento & desenvolvimento , Testosterona/sangue
20.
Sci Total Environ ; 409(11): 2040-8, 2011 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-21420147

RESUMO

This study investigated the effects of two mixtures of persistent organic pollutants (POPs) on steroidogenesis in the H295R cell line. The two mixtures were obtained from the livers of burbot (Lota lota) caught in two Norwegian lakes (Mjøsa and Losna) with different contaminant profiles. Steroid hormone levels in the cell culture medium and mRNA levels of 16 genes involved in steroidogenesis were investigated. The crude Lake Mjøsa extract had to be diluted ten times more than the Lake Losna extract in order to prevent cytotoxicity. The ten times diluted Lake Mjøsa mixture had higher levels of DDT and derivates (∑DDTs, 1.7 times) and brominated flame retardants (∑BDEs and HBCD, 15-25 times) than the Lake Losna mixture, which, on the other hand, had higher concentrations of ∑PCBs (1.5 times higher) and also of HCB, ∑HCH isomers and ∑chlordane isomers (5-20 times higher). In the cell culture media, only cortisol levels were increased at the highest exposure concentration to the Lake Mjøsa mixture, while both cortisol and estradiol levels were increased following exposure to the two highest Lake Losna mixture exposure concentrations. Testosterone levels decreased only at the highest exposure concentration of the Lake Losna mixture. Multivariate models suggested that ∑PCBs, and to a lesser extent ∑DDTs, were responsible for the cortisol responses, while estradiol and testosterone alterations were best explained by HCB and ∑PCBs, respectively. Exposure to the mixtures generally increased mRNA levels, with smaller effects exerted by the Lake Mjøsa mixture than the Lake Losna mixture. It was concluded that both mixtures affected steroidogenesis in the H295R cells. Small differences in mixture composition, rather than the high content of brominated flame retardants in the Lake Mjøsa mixture, were suggested to be the most probable reason for the apparent differences in potencies of the two mixtures.


Assuntos
Disruptores Endócrinos/metabolismo , Água Doce/química , Gadiformes/metabolismo , Hormônios Esteroides Gonadais/sangue , Poluentes Químicos da Água/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , DDT/metabolismo , Disruptores Endócrinos/toxicidade , Monitoramento Ambiental , Retardadores de Chama/metabolismo , Gadiformes/sangue , Gadiformes/fisiologia , Expressão Gênica/efeitos dos fármacos , Éteres Difenil Halogenados/metabolismo , Hidrocarbonetos Bromados/metabolismo , Noruega , Poluentes Químicos da Água/toxicidade
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