39 resultados para Arsenic tolerance
em University of Queensland eSpace - Australia
Resumo:
The extent of exposure of residents of Changqing (Guizhou, PR China) to arsenic through coal-burning was investigated. Despite the low coal-arsenic content (56.3 +/- 42.5 mg As kg(-1)) when compared with coals collected at different location and times from the same province, more than 30% of the study subjects have shown symptoms of arsenicosis. Coal, urine, hair, and water samples were collected in mid-September 2001 and analysed for arsenic. The average urinary and hair-arsenic concentrations in the exposed subjects were 71.4 +/- 37.1 mug As g(-1) creatinine (control 41.6 +/- 12.1) and 7.99 +/- 8.16 mg kg(-1), respectively. A positive correlation between the hair and urinary-arsenic concentration (R-2 = 0.601) was found. There was no significant difference between females and males for both urinary and hair-arsenic concentrations. Females were found to have a higher dimethylarsinic acid but lower percentages of inorganic arsenic and monomethylarsonic acid in their urine than males. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
Induction and transmission of Bacillus thuringiensis tolerance in the flour moth Ephestia kuehniella
Resumo:
The use of Bacillus thuringiensis (Bt) endotoxins to control insect vectors of human diseases and agricultural pests is threatened by the possible evolution of resistance in major pest species. In addition to high levels of resistance produced by receptor insensitivity (5, 16, 17), several cases of tolerance to low to medium levels of toxin have been reported in laboratory colonies of lepidopteran species (3, 18). Because the molecular basis of some of these cases of tolerance to the toxin are not known, we explored alternative mechanisms. Here, we present evidence that tolerance to a Bt formulation in a laboratory colony of the flour moth Ephestia kuehniella can be induced by preexposure to a low concentration of the Bt formulation and that the tolerance correlates with an elevated immune response. The data also indicate that both immune induction and Bt tolerance can be transmitted to offspring by a maternal effect and that their magnitudes are determined by more than one gene.
Resumo:
The Mechanism Underlying the development of tolerance to morphine, is still incompletely understood. Morphine binds to opioid receptors, Which in turn activates downstream second messenger cascades through heterotrimeric guanine nucleotide binding proteins (G proteins). In this paper, we show that G(z), a member of the inhibitory G protein family, plays an important role in mediating the analgesic and lethality effects of morphine after tolerance development. We blocked signaling through the G(z) second messenger cascade by genetic ablation of the alpha subunit of the G protein in mice. The Galpha(z) knockout Mouse develops significantly increased tolerance to morphine. which depends oil Galpha(z), gene dosage. Further experiments demonstrate that the enhanced morphine tolerance is not caused by pharmacokinetic and behavioural learning mechanisms. The results suggest that G(z) signaling pathways are involved ill transducing the analgesic and lethality effects of morphine following chronic morphine treatment. (C) 2004 Elsevier Ltd. All rights reserved.
Resumo:
Objectives: To describe the glycaemic status (assessed by an oral glucose tolerance test (OGTT)) and associated comorbidities in a cohort of Australian children and adolescents at risk of insulin resistance and impaired glucose homeostasis (IGH). Methods: Twenty-one children and adolescents (three male, 18 female) (18 Caucasian, one Indigenous, two Asian) (20 obese, one lipodystrophy) referred to the Paediatric Endocrinology and Diabetes Clinic underwent a 2-h OGTT with plasma glucose and insulin measured at baseline, + 60 and + 120 min. If abnormal, the OGTT was repeated. Results: The mean (SD) age was 14.2 (1.6) years, BMI 38.8 (7.0) kg/m(2) and BMI-SDS 3.6 (0.6). Fourteen patients had fasting insulin levels >21 mU/L. Type 2 diabetes mellitus was diagnosed in one patient, impaired glucose tolerance (IGT) in four patients and impaired fasting glycaemia (IFG) in one patient. Despite no weight loss, only one patient had a persistently abnormal OGTT on repeat testing. Three patients with IGH were medicated with risperidone at the time of the initial OGTT. One patient who had persistent IGT had continued risperidone. The other two patients had initial OGTT results of IGT and diabetes mellitus type 2. They both ceased risperidone between tests and repeat OGTT showed normal glycaemic status. Conclusions: Use of fasting glucose alone may miss cases of IGH. Diagnosis of IGT should not be made on one test alone. Interpretation of glucose and insulin responses in young people is limited by lack of normative data. Larger studies are needed to generate Australian screening recommendations. Further assessment of the potential adverse effects of atypical antipsychotic medication on glucose homeostasis in this at-risk group is important.
Resumo:
We investigated whether the protection from graft-versus-host disease (GVHD) afforded by donor treatment with granulocyte colony-stimulating factor (G-CSF) could be enhanced by dose escalation. Donor treatment with human G-CSIF prevented GVHD in the B6 --> B6D2F1 murine model in a dose-dependent fashion, and murine G-CSF provided equivalent protection from GVHD at 10-fold lower doses. Donor pretreatment with a single dose of pegylated G-CSF (peg-G-CSF) prevented GVHD to a significantly greater extent than standard G-CSIF (survival, 75% versus 11%, P < .001). Donor T cells from peg-G-CSF-treated donors failed to proliferate to alloantigen and inhibited the responses of control T cells in an interleukin 10 (IL-10)-dependent-fashion in vitro. T cells from peg-GCSF-treated IL-10(-/-) donors induced lethal GVHD; T cells from peg-G-CSF-treated wild-type (wt) donors promoted long-term survival. Whereas T cells from peg-G-CSF wt donors were able to regulate GVHD induced by T cells from control-treated donors, T cells from G-CSF-treated wt donors and peg-G-CSF-treated IL-10(-/-) donors did not prevent mortality. Thus, peg-G-CSF is markedly superior to standard G-CSF for the prevention of GVHD following allogeneic stem cell transplantation (SCT), due to the generation of IL-10-producing regulatory T cells. These data support prospective clinical trials of peg-G-CSF-mobilized allogeneic blood SCT. (C) 2004 by The American Society of Hematology.
Resumo:
Arsenic has been classified as a human carcinogen based on epidemiological data however the mechanism of its carcinogenicity is still unclear. Urinary biomarkers for chronic arsenic exposure would be valuable as an early warning indicator for timely interventions. In this study, young female C57BI/6J mice were given drinking water containing 0, 100, 250 and 500 mug As-v/L as sodium arsenate ad libitum for 12 months. Urine was collected bimonthly for urinary arsenic methylation assay and porphyrin analysis. All detectable arsenic species showed strong linear correlation with administered dosage and the arsenic methylation patterns were similar in all three treatment groups. No significant changes of methylation patterns were observed over time for either the control or test groups. Urinary coproporphyrin III was significantly increased in the 8th month in 250 and 500 mug/L groups and remained significantly dose-related after 10 and 12 months. Coproporphyrin I also showed a significant dose-response relationship after 12 months. Our results confirm that urinary arsenic is a useful biomarker for internal dose. The alteration of porphyrin profile suggests that arsenic can affect the heme metabolism and this may occur prior to the onset of arsenic induced carcinogenesis. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
Resumo:
Objective. To investigate the efficacy and tolerability of a course of 5 injections of hyaluronan (HA) given at intervals of one week in patients with symptomatic, mild to moderate osteoarthritis (OA) of the knee. Methods: A double blind, randomized, parallel group, multicenter (17 centers), saline vehicle-controlled study was conducted over 18 weeks. Patients received either 25 mg (2.5 ml) HA in a phosphate buffered solution or 2.5 ml vehicle containing only the buffer by intraarticular injection. Five injections were given at one week intervals and the patients were followed for a further 13 weeks. The Western Ontario McMaster (WOMAC) OA instrument was used as the primary efficacy variable and repeated measures analysis of covariance was used to compare the 2 treatments over Weeks 6, 10, 14, and 18. Results. Of 240 patients randomized for inclusion in the study, 223 were evaluable for the modified intention to treat analysis. The active treatment and control groups were comparable for demographic details, OA history, and previous treatments. Scores for the pain and stiffness subscales of the WOMAC were modestly but significantly lower in the HA-treated group overall (Weeks 6 to 18; p < 0.05) and the statistically significant difference from the control was not apparent until after the series of injections was complete. The physical function subscale did not reach statistical significance (p = 0.064). Tolerability of the procedure was good and there were no serious adverse events that were considered to have a possible causal relationship with the study treatment. Conclusion. Intraarticular HA treatment was significantly more effective than saline vehicle in mild to moderate OA of the knee for the 13 week postinjection period of the study.