RESUMO
In a natural ecosystem, fish are subjected to a multitude of variable environmental factors. It is important to analyze the impact of combined factors to obtain a realistic understanding of the mixed stress occurring in nature. In this study, the physiological performance of juvenile common carp (Cyprinus carpio) exposed for one week to an environmentally relevant metal mixture (4.8 µg/L of copper; 2.9 µg/L of cadmium and 206.8 µg/L of zinc) and to two temperatures (10 °C and 20 °C), were evaluated. After 1, 3 and 7 days, standard (SMR) and maximum metabolic rate (MMR) were measured and aerobic scope (AS) was calculated. In addition, hematocrit, muscle lactate, histology of the gills and metal accumulation in gills were measured. While SMR, MMR and AS were elevated at the higher temperature, the metal mixture did not have a strong effect on these parameters. At 20 °C, SMR transiently increased, but no significant changes were observed for MMR and AS. During metal exposure, hematocrit levels were elevated in the 20 °C group. The bioaccumulation of Cd in the gills reflected the increased metabolic rate at the higher temperature, with more accumulation at 20 °C than at 10 °C. Anaerobic metabolism was not increased, which corresponds with the lack of significant histopathological damage in the gill tissue. These results show that common carp handled these metal exposures well, although increased temperature led to higher Cd accumulation and necessitated increased hematocrit levels to maintain aerobic performance.
Assuntos
Cádmio/toxicidade , Carpas/fisiologia , Cobre/toxicidade , Brânquias/efeitos dos fármacos , Músculos/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Zinco/toxicidade , Animais , Brânquias/fisiologia , Músculos/fisiologia , Estresse Fisiológico/efeitos dos fármacos , TemperaturaRESUMO
Mitigating the environmental effects of global population growth, climatic change and increasing socio-ecological complexity is a daunting challenge. To tackle this requires synthesis: the integration of disparate information to generate novel insights from heterogeneous, complex situations where there are diverse perspectives. Since 1995, a structured approach to inter-, multi- and trans-disciplinary(1) collaboration around big science questions has been supported through synthesis centres around the world. These centres are finding an expanding role due to ever-accumulating data and the need for more and better opportunities to develop transdisciplinary and holistic approaches to solve real-world problems. The Australian Centre for Ecological Analysis and Synthesis (ACEAS
Assuntos
Conservação dos Recursos Naturais/métodos , Ecologia , Política Ambiental , Austrália , Comportamento Cooperativo , Ecossistema , Monitoramento Ambiental , Comunicação InterdisciplinarRESUMO
The primary goals of this study were to evaluate diurnal patterns of and sex differences in the levels of cortisol, 11-ketotestosterone, testosterone, and 17beta-estradiol in the sex-changing bluebanded goby Lythrypnus dalli. Steroid hormones were collected from water samples and analyzed by enzyme immunoassay. During the breeding season, hormones were sampled from both males and females at seven time points between 0600 and 2000 h. When comparing each time point separately, there were significant overall time effects for cortisol and 17beta-estradiol. Cortisol concentrations were lowest at the 0800-1000 h sampling point and showed a qualitative peak in late morning (1000-1200 h). Concentrations of 17beta-estradiol were elevated at the last sampling point (1800-2000 h). Broader temporal trends were revealed for testosterone and 11-ketotestosterone concentrations, both of which were elevated in the morning. There were no sex differences in overall hormone concentrations or temporal profiles for cortisol, 11-ketotestosterone, or testosterone. Males and females showed similar diurnal patterns of 17beta-estradiol but females had significantly higher water-borne 17beta-estradiol levels than males. The results show the presence of diurnal changes in steroid hormone levels in male and female bluebanded gobies. The lack of sex differences in androgens suggests that males of this species, and perhaps other bi-directional sex-changing species in which males do not exhibit prominent secondary sexual characteristics, do not require persistent elevations in 11-ketotestosterone or testosterone to maintain the male phenotype. Although the role of 17beta-estradiol in maintaining sex differences in sexually plastic species is unclear, our results suggest that, of the hormones measured, 17beta-estradiol has the greatest potential for future studies interested in this question.
Assuntos
Ritmo Circadiano/fisiologia , Estradiol/metabolismo , Hidrocortisona/metabolismo , Perciformes/metabolismo , Testosterona/análogos & derivados , Testosterona/metabolismo , Análise de Variância , Animais , Feminino , Masculino , Fatores SexuaisRESUMO
The relationship between androgens and paternal behavior is not straightforward, potentially because of the diversity of tasks a male must undertake to maximize reproductive success, notably alternating between courtship, aggression, and offspring care. In some species, these events are separated in time, but in others they are coincident. The endocrine profiles of species that simultaneously court, parent, and defend a nest, such as male bluebanded gobies (Lythrypnus dalli), are not well understood. We sampled a potent fish androgen, 11-ketotestosterone (KT), at different life history stages (experienced parenting males, experienced males not actively parenting, inexperienced males with their first clutch, and females), to examine this relationship. We found that experienced parenting L. dalli males have the highest KT levels of any group, while none of the other groups differed significantly. Males showed elevated KT levels when they had eggs compared to when they did not. Our data suggest that KT facilitates at least some aspects of parental care in L. dalli.
Assuntos
Organismos Hermafroditas , Comportamento de Nidação/fisiologia , Perciformes/fisiologia , Processos de Determinação Sexual , Comportamento Sexual Animal/fisiologia , Testosterona/análogos & derivados , Animais , Feminino , Larva/crescimento & desenvolvimento , Masculino , Testosterona/sangueRESUMO
A limiting factor in the efficacy of bioartificial liver (BAL) for the treatment of liver failure is the toxicity of the patients' serum to the hepatocytes in the device. This study investigates the interaction of liver cancer patient serum with primary and immortalised rat hepatocytes. Liver cancer serum increased the growth rate of immortalised hepatocytes, without affecting reduced glutathione levels. The activities of DT-diaphorase and pi glutathione-S-transferase (GST), enzymes associated with de-differentiation, were also increased. Exposure of primary hepatocytes to liver cancer serum resulted in a decrease in cytochrome P450 (CYP) content, and in P450 dependent metabolism of testosterone. Formation of 2-alpha- and 6-beta- hydroxy testosterone was decreased. These reactions are predominantly associated with CYP 2C11 and 3A1 respectively in normal rat liver. The activity of total GST was also decreased, although that of the pi isoenzyme of GST was not affected. Our results suggest that exposure of hepatocytes in a bioreactor to liver cancer patient serum will result in overgrowth of cells, if proliferating cells are being used, and in de-differentiation. The serum may have to be pretreated with adsorbants to remove toxins prior to BAL treatment.
Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/enzimologia , Fígado Artificial/normas , Animais , Glutationa/sangue , Ratos , Resultado do TratamentoAssuntos
Perna (Membro) , Dor/etiologia , Pronação , Doenças do Pé/complicações , Doenças do Pé/diagnóstico , Marcha , Humanos , Masculino , PodiatriaAssuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Lactonas/uso terapêutico , Dor/tratamento farmacológico , Sulfonamidas/uso terapêutico , Anti-Inflamatórios não Esteroides/economia , Anti-Inflamatórios não Esteroides/farmacologia , Celecoxib , Inibidores de Ciclo-Oxigenase/economia , Inibidores de Ciclo-Oxigenase/farmacologia , Custos de Medicamentos , Interações Medicamentosas , Feminino , Humanos , Lactonas/economia , Lactonas/farmacologia , Gravidez , Pirazóis , Sulfonamidas/economia , Sulfonamidas/farmacologia , SulfonasRESUMO
Cells of the reticuloendothelial system (RES e.g. macrophages) play an important role in the immunopathogenesis of AIDS. The objective of the present study was to investigate the possibility of specifically targeting antiviral drugs such as azidothymidine (AZT) to macrophages using nanoparticles as colloidal drug carriers. In a first series of experiments the body distribution of 14C-labelled AZT bound to nanoparticles and a similarly prepared control solution with unbound AZT were studied in rats after intravenous injection. In a second series of experiments polysorbate 80-coated nanoparticles and a solution of AZT in saline were tested. 14C-labelled AZT was bound to nanoparticles using the surfactant bis(2-ethylhexyl) sulphosuccinate sodium (DOSS). The radioactivity in several organs, including those containing large numbers of macrophages, was measured after intravenous injection of the AZT-nanoparticles and the AZT-control solutions. AZT concentrations were up to 18 times higher in organs belonging to the RES if the drug was bound to nanoparticles compared with unbound AZT. These results demonstrate that nanoparticles are a potential drug targeting system for anti-AIDS drugs. The increase in drug concentration at the sites containing abundant macrophages may allow a reduction in dosage to reduce systemic toxicity.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Cianoacrilatos/administração & dosagem , Zidovudina/administração & dosagem , Animais , Feminino , Injeções Intravenosas , Masculino , Sistema Fagocitário Mononuclear/metabolismo , Ratos , Ratos Wistar , Distribuição Tecidual , Zidovudina/farmacocinéticaRESUMO
This experiment determined the amount of leptin required to correct different abnormalities in leptin-deficient ob/ob mice. Baseline food intakes and body weights of lean (+/?) and obese (ob/ob) C57B1/6J
Assuntos
Obesidade/tratamento farmacológico , Proteínas/farmacologia , Animais , Monoaminas Biogênicas/análise , Temperatura Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Insulina/sangue , Leptina , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , Ovário/efeitos dos fármacosRESUMO
Humans ingest about 1 g of flavonoids daily in their diet, and they are increasingly being associated with cytoprotective antitumour properties. The mechanism(s) responsible for these effects have not yet been elucidated but may involve interaction with xenobiotic metabolising enzymes to alter the metabolic activation of potential carcinogens. We have investigated the effect of the flavonoids, quercetin (Q), myricetin (M) and epicatechin (E) on the growth, morphology and enzyme activities of MCF7 human breast cancer cells. Of the three flavonoids studied only Q caused a decrease in cell protein content and decreased the reduction of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium). It also inhibited protein, DNA and RNA synthesis to the greatest extent. Q and M increased intracellular reduced glutathione (GSH) content, and Q altered the morphology of the cells after 24 h exposure to 25 microM. E and Q inhibited the O-deethylation of ethoxyresorufin (EROD) catalysed by cytochrome P450 CYPIA. In contrast, M increased the EROD reaction 2-fold. Q increased the activity of DT-diaphorase, NADPH cytochrome c reductase and glutathione reductase, while E increased only NADPH cytochrome c reductase activity. The effects on enzyme activities in vitro suggest that there is not only the potential for flavonoids to alter metabolic activation of carcinogens but also of therapeutically administered drugs in vivo. We are at present investigating the synergy between anti-cancer drugs and flavonoids in terms of anti-tumour efficacy.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Flavonoides/farmacologia , Neoplasias da Mama/patologia , Catequina/farmacologia , Divisão Celular/efeitos dos fármacos , Glutationa/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Proteínas de Neoplasias/metabolismo , Oxirredução , Quercetina/farmacologia , Sais de Tetrazólio/metabolismo , Tiazóis/metabolismo , Células Tumorais CultivadasRESUMO
When studying the biocompatibility of orthopaedic biomaterials it is often necessary to discriminate between responses which show mild cytotoxicity. It is therefore essential to use a very sensitive index of toxicity. We have compared the sensitivity of four well-established indices of toxicity: total cell protein content, leakage of lactate dehydrogenase (LDH), reduced glutathione content and the MTT assay, with that of a novel index, alkaline phosphatase (ALP) activity. Comparisons were made by detecting nickel chloride toxicity in osteoblasts. ALP activity, the novel method, proved the most sensitive index of toxicity and it provides a convenient automated assay for assessing the interactions of materials with osteoblasts. The responses to nickel chloride and to aqueous extracts prepared from carbon fibre reinforced epoxy and polyetheretherketone (peek), two candidate materials for orthopaedic implants, were compared in primary and immortalized rat osteoblasts, and in primary human osteoblasts. Although the immortalized rat osteoblast cell line, FFC, was consistently the most sensitive cell type, the responses of the human cells and the FFC cell line were similar in terms of ALP activity throughout the range of nickel concentrations studied. Neither peek nor epoxy material extracts showed a significant decrease in the MTT or ALP responses in any of the three cell types. Our data suggest that immortalized rat osteoblasts may provide an in vitro model system for screening the biocompatibility of orthopaedic polymers.
RESUMO
This study investigated the effect of inducers on the major enzymes responsible for metabolising the quinone antitumor agent mitoxantrone, and on its cytotoxicity in MCF 7 human breast cancer cells. Four inducers were used: 1,2-benzanthracene (BA), phenobarbitone (PB); rifampicin (R) and dexamethasone (DEX). Of these, BA was the most effective, increasing cytochrome P450 dependent metabolism 64-fold and DT-diaphorase activity 1.6-fold. R did not cause an increase in any of the enzyme activities measured and, in fact inhibited glutathione peroxidase activity. PB and DEX increased NADPH cytochrome c reductase activity but had no effect on either DT-diaphorase or cytochrome P450 dependent activities. BA potentiated the cytotoxicity of mitoxantrone in terms of leakage of lactate dehydrogenase (LDH) activity and loss of reduced glutathione (GSH) and protein from cultures. PB had a smaller potentiating effect on cytotoxicity and DEX had no effect. Studies with the enzyme inhibitors, dicoumarol (inhibits DT-diaphorase) and metyrapone (inhibits cytochrome P450), indicate that at least two reactive species are involved in mitoxantrone cytotoxicity. One intermediate, formed by cytochrome P450, caused LDH leakage and GSH depletion. Formation of the second intermediate was catalysed by DT-diaphorase and this hydroquinone caused loss of intracellular protein and GSH. We propose that autooxidation of the hydroquinone resulting in generation of reactive oxygen species contributes to mitoxantrone cytotoxicity. Concomitant exposure to inducing agents may alter the cytotoxicity associated with many cytotoxic drugs, not just mitoxantrone, and this is an important consideration as many cytotoxics have a narrow therapeutic index.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Mitoxantrona/uso terapêutico , Xenobióticos/metabolismo , Benzo(a)Antracenos/farmacologia , Neoplasias da Mama/enzimologia , Morte Celular/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/metabolismo , Dexametasona/farmacologia , Dicumarol/farmacologia , Indução Enzimática , Feminino , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Metirapona/farmacologia , NAD(P)H Desidrogenase (Quinona)/metabolismo , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Fenobarbital/farmacologia , Rifampina/farmacologia , Células Tumorais CultivadasRESUMO
The issue of violence and potential violence against Approved Social Workers (ASWs) cannot be discussed in isolation from its occurrence in mainstream social work. The contents of this article highlight some key issues, raise areas of concern and offer some constructive ideas regarding the planning of a strategy and policy for Approved Social Workers.
Assuntos
Saúde Ocupacional , Serviço Social , Violência , Feminino , Humanos , Responsabilidade Legal , Relações Profissional-Paciente , Reino UnidoRESUMO
OBJECTIVES: To evaluate our experience with renal autotransplantation in the management of loin pain-hematuria (LPH) syndrome after relatively long follow-up (30 to 35 months). METHODS: Four patients with LPH syndrome of 3 to 18 years' duration underwent technically successful autotransplantation. All patients preoperatively had normal radiologic investigations, including renal arteriography and biopsy. All required narcotic analgesia for pain control. Patients were followed for 30 to 35 months. RESULTS: All 4 patients were pain and narcotic free for 6 months postoperatively. At 18 months after surgery, 3 of the 4 had recurrence of the pain and at 30 months, 2 required nephrectomy. Only 1 patient of 4 had sustained pain relief at 35 months. CONCLUSIONS: Renal autotransplantation certainly offers temporary relief from LPH syndrome, but in our experience this was not durable in the majority of our patients.