RESUMO
Patterns of wildlife visitation and interaction with cyanide-bearing tailings slurry and solutions at the Fimiston tailings storage facility (TSF) have been reported in a previously published ecological study. The above-mentioned findings are extended in this paper by the examination of additional wildlife survey data, along with process water chemistry data collected during the same study period. Analysis of the combined results revealed that the primary wildlife protective mechanism in operation was effective management of tailings cyanide concentration. Nevertheless, tailings discharge concentration exceeded the industry standard wildlife protective limit of 50mg/L weak acid dissociable (WAD) cyanide episodically during the study period. Wildlife that interacted with habitats close to the spigot outlet during brief periods of increased discharge concentration were likely to have been exposed to bioavailable cyanide at concentrations greater than the industry standard protective limit. However, no wildlife deaths were recorded. These results appear to support the hypothesis that hypersalinity of process solutions (unique to the Kalgoorlie district of Western Australia) and a lack of aquatic food resources represent secondary protective mechanisms that operated to prevent cyanide-related wildlife mortality during the project. The proposed protective mechanisms are discussed in the context of their potential application as proactive management procedures to minimise wildlife exposure to cyanide.
Assuntos
Aves , Cianetos/intoxicação , Ouro , Resíduos Industriais/efeitos adversos , Mineração , Poluentes Químicos da Água/intoxicação , Animais , Disponibilidade Biológica , Cianetos/metabolismo , Coleta de Dados , Monitoramento Ambiental/métodos , Cadeia Alimentar , Água Doce/química , Invertebrados/efeitos dos fármacos , Medição de Risco , Fatores de Risco , Salinidade , Poluentes Químicos da Água/metabolismo , Austrália OcidentalRESUMO
Chiral immunoaffinity microbore columns were directly interfaced with MS detection, and the effect of column length and temperature on the enantiomer separation of a number of underivatized aromatic and aliphatic amino acids was investigated utilizing an antibody chiral stationary phase that had been prepared by immobilizing a monoclonal anti-D-amino acid antibody onto silica. The stronger affinity of the antibody towards aromatic and bulky amino acids allowed separation of such analytes in a 0.75 x 150 mm column, while an increase in column length enabled separation of more weakly bound compounds. The strength of interaction between chiral selector and analytes could be modulated conveniently by lowering the temperature. For the first time, simultaneous enantiomer separation of mixtures of amino acids was achieved on antibody-based chiral stationary phases using extracted ion chromatograms.
Assuntos
Aminoácidos/isolamento & purificação , Cromatografia de Afinidade/métodos , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Aminoácidos/análise , Aminoácidos/química , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Bicarbonatos/química , Soluções Tampão , Cromatografia de Afinidade/instrumentação , Cromatografia Líquida/instrumentação , Concentração de Íons de Hidrogênio , Miniaturização , Estrutura Molecular , Concentração Osmolar , Proteínas/química , Proteínas/imunologia , EstereoisomerismoRESUMO
OBJECTIVES: To evaluate the response rate and progression free and overall survival of patients with advanced endometrial cancer treated with paclitaxel, carboplatin and amifostine. To evaluate the toxicity of amifostine when used in combination with carboplatin and paclitaxel. METHODS: Forty-seven eligible patients (median age: 66; range 45-82) with bidimensionally measurable advanced, recurrent, or refractory endometrial cancer were treated with carboplatin (AUC = 6), paclitaxel (175 mg/M2) and amifostine (740 mg/M2) every 4 weeks for 6 cycles or until disease progression or unacceptable toxicity. RESULTS: There were 4 CRs (8%) (2 confirmed, 2 unconfirmed) and 15 PRs (32%) (9 confirmed, 6 unconfirmed) for a total response rate of 40% (95% confidence interval [CI], 26% to 56%). The median progression-free survival (PFS) was 7 months (95% CI, 6-9 months) and a 6-month PFS rate of 64% (95% CI, 50% to 78%). The median overall survival was 14 months (95% CI, 12 to 17 months). Toxicity was tolerable. While 79% of patients developed Grade 3/4 neutropenia (30% Grade 3, 49% Grade 4), there were no episodes of Grade 4 febrile neutropenia and one episode of infection with grades 3-4 neutropenia. CONCLUSION: The combination of paclitaxel and carboplatin with amifostine was well reasonably tolerated in this cohort. The regimen demonstrated significant activity in endometrial cancer, comparable to other multi-agent chemotherapy programs in terms of response rate and survival, and with a favorable toxicity profile.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Amifostina/administração & dosagem , Amifostina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversosRESUMO
This article describes the production of stereoselective antibodies using both classical immunological and modern molecular biological techniques. Stereoselective antibodies against alpha-hydroxy acids were raised in rabbits and mice and compared with previously produced anti-alpha-amino acid antibodies. It was found that both types of antibodies combine stereoselectivity with class-specificity. Sequence analyses revealed that antibodies with opposing stereoselectivities can be formed during the affinity maturation process from a common progenitor or independently using nonhomologous binding sites. For the first time, phage display was employed to obtain stereoselective antibody fragments. The versatility of stereoselective antibodies as chiral selectors was demonstrated by applying them in several immunosensors and in chiral chromatography. A simple, membrane-based optical sensor allowed detection of enantiomeric impurities at the 1/2,000 level (99.9% ee). Silica-based antibody chiral stationary phases could be used for enantiomer separation of aliphatic amino acids in standard-sized columns, while miniaturized columns allowed interfacing with an MS-detector.