RESUMO
OBJECTIVES: In this study, we aimed to establish a method for quantifying bromide ions (Br- ) in blood and urine using gas chromatograph-mass spectrometer (GC-MS) equipped with a headspace sampler, for biological monitoring of workers exposed to methyl bromide. METHODS: Samples were mixed with dimethyl sulfate, and Br- ions were detected using GC-MS with a headspace sampler. The validity of the proposed method was evaluated based on most of the US FDA guidance. The values obtained were compared with reference values by analysis using SeronormTM Trace Elements Whole Blood L-1 RUO. RESULTS: The calibration curve showed good linearity in the Br- concentration range of 0.1-20.0 mg/L, and the coefficient of determination R2 value was >.999. Intraday and interday accuracy values were 99.3%-103.1% and 97.4%-101.8%, respectively. The measured and reference values of Seronorm were concordant. Herein, eight urine and serum samples of workers were analyzed; the samples' Br- concentrations were known. The correlation coefficients of urine and serum samples were 0.97 and 0.96, respectively, and results were consistent. CONCLUSIONS: This study established a simple and rapid method for the determination of Br- concentration in biological samples using GC-MS with a headspace sampler. Moreover, it can be used for biological monitoring of occupational exposure to methyl bromide and for the determination of Br- concentration in a wide range of biological samples.
Assuntos
Monitoramento Biológico/métodos , Brometos/sangue , Brometos/urina , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Hidrocarbonetos Bromados/análise , Exposição Ocupacional/análise , Valores de Referência , Reprodutibilidade dos TestesRESUMO
A 47 year old woman presented to the emergency department for an intentional overdose of an over the counter cough suppressant. She had been seen multiple times over the last several months with the same presentation. Her work up revealed a significantly elevated chloride level (125 mmol/L, normal 98-107) as well as an anion gap of 1. She denied any other co-ingestions, including other over the counter medications or alcohol, and was otherwise asymptomatic. She was given fluids and supportive care. Ultimately, a significantly elevated bromide level was noted on a send out lab. She was diagnosed with chronic bromide toxicity (bromism) from recurrent over the counter Robitussin HBr use, which was the source of her hyperchloremia and decreased anion gap.
Assuntos
Brometos/sangue , Dextrometorfano/efeitos adversos , Overdose de Drogas/complicações , Feminino , Humanos , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Substâncias/complicaçõesRESUMO
BACKGROUND: Population pharmacokinetic methods were used to characterize the pharmacokinetics of fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) in patients with chronic obstructive pulmonary disease (COPD) when administered as a fixed-dose combination via a single closed inhaler. METHODS: Plasma concentration data from three studies were analyzed using non-linear mixed-effects modeling in NONMEM®. RESULTS: The pooled dataset consisted of 2948, 2589, and 3331 FF, UMEC, and VI observations from 714, 622, and 817 patients with COPD, respectively. There were 41%, 13%, and 21% of observations below the quantification limit for FF, UMEC, and VI, respectively. The pharmacokinetics of FF, UMEC, and VI were all adequately described by a two-compartment model with first-order absorption. The following covariates were statistically significant, but none were considered to be clinically relevant. For FF, Japanese heritage and FF/VI treatment on apparent inhaled clearance (CL/F) with FF CL/F 35% lower in patients of Japanese heritage across all treatments and FF CL/F 42% higher in patients with COPD following FF/VI administration. This is in line with the product label. For UMEC, weight, age, and smoking status on CL/F and weight on apparent volume of distribution (V2/F) with every 10% increase in age from 60 years of age leading to approximately a 6% decrease in UMEC CL/F and every 10% increase in weight from 70 kg leading to approximately a 6% increase in UMEC CL/F and approximately an 8% increase in UMEC V2/F. For a subject with COPD who smoked, UMEC CL/F was 28% higher. For VI, weight on CL/F and smoking status on V2/F with an approximately 4% increase in VI CL/F for every 10% increase in weight from 70 kg, and for a subject with COPD who smoked, VI V2/F was 46% higher. The majority of these covariates have been previously identified in historical analyses. None of these effects were clinically relevant in terms of systemic exposures and do not warrant dose adjustment. CONCLUSIONS: All FF, UMEC, and VI plasma concentrations were well interspersed with historical data and were all adequately described by a two-compartment model with first-order absorption. There were no clinically relevant differences in FF, UMEC, or VI systemic exposures when administered as FF/UMEC/VI, FF/VI + UMEC, or the dual combinations FF/VI and/or UMEC/VI.
Assuntos
Androstadienos/farmacocinética , Álcoois Benzílicos/farmacocinética , Brometos/farmacocinética , Clorobenzenos/farmacocinética , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinuclidinas/farmacocinética , Administração por Inalação , Idoso , Androstadienos/administração & dosagem , Androstadienos/sangue , Androstadienos/uso terapêutico , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/sangue , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Álcoois Benzílicos/administração & dosagem , Álcoois Benzílicos/sangue , Álcoois Benzílicos/uso terapêutico , Brometos/administração & dosagem , Brometos/sangue , Brometos/uso terapêutico , Clorobenzenos/administração & dosagem , Clorobenzenos/sangue , Clorobenzenos/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/administração & dosagem , Antagonistas Muscarínicos/sangue , Antagonistas Muscarínicos/farmacocinética , Antagonistas Muscarínicos/uso terapêutico , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica/etnologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Quinuclidinas/administração & dosagem , Quinuclidinas/sangue , Quinuclidinas/uso terapêuticoRESUMO
Bromide (Br-) is a bromine atom with a negative charge which is released mainly in the production of pesticides and flame retardants. It is also found naturally in seawater. Br¯ has been associated with many detrimental effects such as respiratory problems, gastric hemorrhages, and dermal burns. The aim of the study was to monitor serum bromide in humans and to correlate its level with genotoxicity and apoptosis in human. The study utilized comet assay, to measure DNA damage in peripheral leukocytes (i.e. T%DNA), enzyme-linked immunosorbent assay were used to determine fortilin level as an apoptosis marker, and spectrophotometry to measure serum Br¯ in two populations at the Dead Sea area, which are located close to and far from a local bromine factory: Ghor As-safi and Deir Alla, respectively. The biomarkers were compared with the correlating serum Br¯. A total of 397 individuals were involved in the study. The serum Br- and the genotoxicity biomarker were significantly higher (p < 0.001) in Ghor As-safi than in Deir Alla. In contrast, serum fortilin did not differ significantly between the two regions (p > 0.05). T%DNA was significantly correlated (r = 0.867, p < 0.01) to serum Br¯. In conclusion, residing near a bromide source site is increasing the bromide body burden, and enhancing genotoxicity with no detectible apoptosis. Furthermore, the selected biomarkers could serve as tools to assess the toxicity of bromide as a consequence of environmental exposure.
Assuntos
Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/genética , Brometos/sangue , Dano ao DNA/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Leucócitos/patologia , Poluentes Químicos da Água/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Brometos/efeitos adversos , Criança , Pré-Escolar , Ensaio Cometa , Feminino , Humanos , Jordânia , Leucócitos/citologia , Masculino , Pessoa de Meia-Idade , Testes de Mutagenicidade , Água do Mar/química , Proteína Tumoral 1 Controlada por Tradução , Poluentes Químicos da Água/efeitos adversos , Adulto JovemRESUMO
Potassium bromide overdose (bromism) in the management of canine epilepsy has been known. However, a protocol to reduce bromide concentrations rapidly has not been previously established. The effects of three infusion fluids with different chloride contents on the steady-state serum concentrations of bromide in beagles were determined. After stabilization of the serum bromide concentrations, seven dogs were infused with saline (Na+ 154 mmol/L; Cl- 154 mmol/L), lactated Ringer's (Na+ 131 mmol/L; Cl- 110 mmol/L), or maintenance solutions (Na+ 35 mmol/L; Cl- 35 mmol/L) at a rate of 2 or 10 ml kg-1 hr-1 for 5 hr. Serum and urine were collected hourly, and the bromide concentrations were measured. When saline and lactated Ringer's solutions were infused at a rate of 10 ml kg-1 hr-1 for 5 hr, serum bromide concentrations were decreased by 14.24% and urine bromide concentrations by 17.63%, respectively. Of all compositions of infusion fluids, only sodium and chloride contents were associated with the decreased serum concentrations and the increased renal clearance of bromide. In summary, saline and lactated Ringer's solutions reduced serum bromide concentrations in a sodium chloride-dependent manner in dogs were found when infused at 10 ml kg-1 hr-1 for 5 hr.
Assuntos
Brometos/sangue , Solução Salina/farmacocinética , Animais , Anticonvulsivantes/sangue , Anticonvulsivantes/intoxicação , Brometos/intoxicação , Cães/sangue , Cães/metabolismo , Feminino , Infusões Intravenosas/veterinária , Soluções Isotônicas/administração & dosagem , Soluções Isotônicas/farmacocinética , Compostos de Potássio/sangue , Compostos de Potássio/intoxicação , Solução de Ringer/administração & dosagem , Solução de Ringer/farmacocinética , Solução Salina/administração & dosagem , Cloreto de Sódio/administração & dosagem , Cloreto de Sódio/farmacocinéticaAssuntos
Anestesia Geral/métodos , Anticonvulsivantes/uso terapêutico , Brometos/uso terapêutico , Cloretos/sangue , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Compostos de Potássio/uso terapêutico , Adolescente , Anticonvulsivantes/sangue , Brometos/sangue , Criança , Epilepsia Resistente a Medicamentos/sangue , Feminino , Humanos , Masculino , Compostos de Potássio/sangueRESUMO
Bromoderma is a rare skin disorder caused by bromide intake. It presents as single or multiple papillomatous nodules or plaques, and ulcers studded with small pustules on the face or limbs. The clinical features of bromoderma are similar to those of pyoderma gangrenosum. A 41-year-old Japanese woman was diagnosed with pyoderma gangrenosum 11 years prior to presentation. Pyoderma had repeatedly appeared over her entire body despite treatment. She also frequently complained of syncopal episodes. She was admitted to our hospital after loss of consciousness and an episode of generalized convulsion. Laboratory tests revealed a negative serum anion gap and hyperchloremia. Her serum bromide level was significantly elevated, suggesting bromide intoxication. The patient had a 10-year history of high serum bromide levels. After the intake of bromide-containing sedatives was stopped, there was no recurrence of pyoderma in the absence of treatment. In conclusion, this case was diagnosed as bromoderma with commercial sedative-induced bromide intoxication. Although the US Food and Drug Administration have banned the use of bromides, over-the-counter (OTC) treatments containing bromides are still used in Japan and other countries. Long-term use of OTC medicines containing bromvalerylurea may result in the development of bromoderma. If unclarified neurological or psychiatric symptoms are associated with pyoderma, we propose measurement of the patient's serum chloride concentration. Determination of hyperchloremia is helpful for the diagnosis of chronic intoxication with bromides.
Assuntos
Brometos/efeitos adversos , Bromisoval/efeitos adversos , Toxidermias/patologia , Hipnóticos e Sedativos/efeitos adversos , Medicamentos sem Prescrição/efeitos adversos , Pioderma Gangrenoso/patologia , Doenças Raras/patologia , Equilíbrio Ácido-Base , Adulto , Anorexia Nervosa/tratamento farmacológico , Biópsia , Brometos/administração & dosagem , Brometos/sangue , Bromisoval/sangue , Bromisoval/uso terapêutico , Cloretos/sangue , Ciclosporina/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Toxidermias/sangue , Toxidermias/etiologia , Eritema/induzido quimicamente , Eritema/tratamento farmacológico , Eritema/patologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hipnóticos e Sedativos/sangue , Hipnóticos e Sedativos/uso terapêutico , Medicamentos sem Prescrição/análise , Prednisolona/uso terapêutico , Pioderma Gangrenoso/tratamento farmacológico , Doenças Raras/sangue , Doenças Raras/induzido quimicamente , Convulsões/etiologia , Síncope/etiologia , Suspensão de TratamentoAssuntos
Anticonvulsivantes/uso terapêutico , Brometos/uso terapêutico , Epilepsias Mioclônicas/tratamento farmacológico , Compostos de Potássio/uso terapêutico , Adolescente , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/sangue , Brometos/efeitos adversos , Brometos/sangue , Criança , Pré-Escolar , Avaliação de Medicamentos , Quimioterapia Combinada , Epilepsias Parciais/tratamento farmacológico , Epilepsia Tônico-Clônica/tratamento farmacológico , Humanos , Masculino , Compostos de Potássio/efeitos adversos , Compostos de Potássio/sangue , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Despite appropriate antiepileptic drug treatment, approximately one-third of humans and dogs with epilepsy continue experiencing seizures, emphasising the importance for new treatment strategies to improve the quality of life of people or dogs with epilepsy. A 6-month prospective, randomised, double-blinded, placebo-controlled cross-over dietary trial was designed to compare a ketogenic medium-chain TAG diet (MCTD) with a standardised placebo diet in chronically antiepileptic drug-treated dogs with idiopathic epilepsy. Dogs were fed either MCTD or placebo diet for 3 months followed by a subsequent respective switch of diet for a further 3 months. Seizure frequency, clinical and laboratory data were collected and evaluated for twenty-one dogs completing the study. Seizure frequency was significantly lower when dogs were fed the MCTD (2·31/month, 0-9·89/month) in comparison with the placebo diet (2·67/month, 0·33-22·92/month, P=0·020); three dogs achieved seizure freedom, seven additional dogs had ≥50 % reduction in seizure frequency, five had an overall <50 % reduction in seizures (38·87 %, 35·68-43·27 %) and six showed no response. Seizure day frequency were also significantly lower when dogs were fed the MCTD (1·63/month, 0-7·58/month) in comparison with the placebo diet (1·69/month, 0·33-13·82/month, P=0·022). Consumption of the MCTD also resulted in significant elevation of blood ß-hydroxybutyrate concentrations in comparison with placebo diet (0·071 (sd 0·035) v. 0·053 (sd 0·028) mmol/l, P=0·028). There were no significant changes in serum concentrations of glucose (P=0·903), phenobarbital (P=0·422), potassium bromide (P=0·404) and weight (P=0·300) between diet groups. In conclusion, the data show antiepileptic properties associated with ketogenic diets and provide evidence for the efficacy of the MCTD used in this study as a therapeutic option for epilepsy treatment.
Assuntos
Dieta Cetogênica/veterinária , Epilepsia/dietoterapia , Epilepsia/veterinária , Convulsões/dietoterapia , Convulsões/veterinária , Triglicerídeos/administração & dosagem , Ácido 3-Hidroxibutírico/sangue , Animais , Anticonvulsivantes/administração & dosagem , Glicemia/metabolismo , Brometos/sangue , Estudos Cross-Over , Cães , Método Duplo-Cego , Feminino , Masculino , Fenobarbital/sangue , Compostos de Potássio/sangue , Estudos Prospectivos , Qualidade de Vida , Resultado do TratamentoRESUMO
OBJECTIVE: To determine the pharmacokinetics of bromide in sheep after single intravenous (IV) and oral (PO) doses. PROCEDURE: Sixteen Merino sheep were randomly assigned to two treatment groups and given 120 mg/kg bromide, as sodium bromide IV or potassium bromide PO. Serum bromide concentrations were determined by colorimetric spectrophotometry. RESULTS: After IV administration the maximum concentration (Cmax ) was 822.11 ± 93.61 mg/L, volume of distribution (Vd ) was 0.286 ± 0.031 L/kg and the clearance (Cl) was 0.836 ± 0.255 mL/h/kg. After PO administration the Cmax was 453.86 ± 43.37 mg/L and the time of maximum concentration (Tmax ) was 108 ± 125 h. The terminal half-life (t½ ) of bromide after IV and PO administration was 387.93 ± 115.35 h and 346.72 ± 94.05 h, respectively. The oral bioavailability (F) of bromide was 92%. No adverse reactions were noted in either treatment group during this study. The concentration versus time profiles exhibited secondary peaks, suggestive of gastrointestinal cyclic redistribution of the drug. CONCLUSIONS AND CLINICAL RELEVANCE: When administered PO, bromide in sheep has a long half-life (t½ ) of approximately 14 days, with good bioavailability. Potassium bromide is a readily available, affordable salt with a long history of medical use as an anxiolytic, sedative and antiseizure therapy in other species. There are a number of husbandry activities and flock level neurological conditions, including perennial ryegrass toxicosis, in which bromide may have therapeutic or prophylactic application.
Assuntos
Brometos/farmacocinética , Compostos de Potássio/farmacocinética , Ovinos/metabolismo , Compostos de Sódio/farmacocinética , Administração Intravenosa/veterinária , Administração Oral , Animais , Brometos/administração & dosagem , Brometos/sangue , Feminino , Meia-Vida , Compostos de Potássio/administração & dosagem , Compostos de Potássio/sangue , Distribuição Aleatória , Compostos de Sódio/administração & dosagem , Compostos de Sódio/sangue , Espectrofotometria/métodos , Espectrofotometria/veterináriaRESUMO
OBJECTIVE: To compare estimates by bioimpedance spectroscopy analysis (BIS) of extracellular water (ECW), fat mass (FM), and fat-free mass (FFM) against standard techniques of bromide dilution and dual energy X-ray absorptiometry (DXA) during intervention that causes significant changes in water compartments and body composition. METHODS: Body composition analysis using BIS, bromide dilution, and DXA was performed in 71 healthy recreational athletes (43 men, 28 women; aged 18-40 years; BMI 24 ± 0.4 kg/m(2)) who participated in a double-blinded, randomized, placebo-controlled study of GH and testosterone treatment. The comparison of BIS with bromide dilution and DXA was analyzed using linear regression and the Bland-Altman method. RESULTS: At baseline, there was a significant correlation between BIS and bromide dilution-derived estimates for ECW, and DXA for FM and FFM (P<0.001). ECW by BIS was 3.5 ± 8.1% lower compared with bromide dilution, while FM was 22.4 ± 26.8% lower and FFM 13.7 ± 7.5% higher compared with DXA (P<0.01). During treatment, the change in ECW was similar between BIS and bromide dilution, whereas BIS gave a significantly greater reduction in FM (19.4 ± 44.8%) and a greater increase in FFM (5.6 ± 3.0%) compared with DXA (P<0.01). Significant differences in body composition estimates between the BIS and DXA were observed only in men, particularly during the treatment that caused greatest change in water compartments and body composition. CONCLUSION: In healthy adults, bioimpedance spectroscopy is an acceptable tool for measuring ECW; however, BIS overestimates FFM and substantially underestimates FM compared with DXA.
Assuntos
Absorciometria de Fóton/normas , Composição Corporal/fisiologia , Brometos/sangue , Espectroscopia Dielétrica/normas , Hormônio do Crescimento Humano/uso terapêutico , Absorciometria de Fóton/métodos , Adolescente , Adulto , Espectroscopia Dielétrica/métodos , Método Duplo-Cego , Feminino , Humanos , Masculino , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To determine serum bromide concentrations following an oral loading dose in dogs. METHODS: Retrospective review of clinical records of dogs suffering from seizures that were treated with bromide. A loading dose of 600 mg/kg potassium bromide was administered orally in 17 to 48 hours together with a maintenance dose of 30 mg/kg/day. Blood samples were collected within 24 hours after completing the protocol and serum bromide concentrations were determined by ultra-violet gold chloride colorimetric assay. RESULTS: Thirty-eight dogs were included in the study. The median age was 3 (range, 0 · 2 to 10) years and bodyweight 21 · 8 (3 · 45 to 46 · 2) kg. The median serum bromide concentration was 1 · 26 (0 · 74 to 3 · 6) mg/mL. Thirty-two dogs (84 · 2%) had serum bromide concentrations within the therapeutic interval (1 to 3 mg/mL). The serum concentration in five dogs (13 · 2%) was just under the minimal therapeutic value and in one dog (2 · 6%) it exceeded the maximal therapeutic value (3 · 6 mg/mL). CLINICAL RELEVANCE: Following this oral loading dose protocol, serum bromide concentrations reach the therapeutic range in the majority of dogs. This indicates that the suggested protocol is effective in achieving therapeutic concentrations rapidly in epileptic dogs.
Assuntos
Anticonvulsivantes/sangue , Brometos/sangue , Doenças do Cão/tratamento farmacológico , Epilepsia/veterinária , Compostos de Potássio/sangue , Administração Oral , Animais , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Brometos/administração & dosagem , Brometos/uso terapêutico , Doenças do Cão/sangue , Cães , Epilepsia/sangue , Epilepsia/tratamento farmacológico , Compostos de Potássio/administração & dosagem , Compostos de Potássio/uso terapêutico , Estudos RetrospectivosRESUMO
Two cases that involve drug compounding errors are described. One dog exhibited increased seizure activity due to a compounded, flavored phenobarbital solution that deteriorated before the expiration date provided by the compounder. The other dog developed clinical signs of hyperkalemia and bromine toxicity following a 5-fold compounding error in the concentration of potassium bromide (KBr).
Assuntos
Anticonvulsivantes/efeitos adversos , Doenças do Cão/induzido quimicamente , Composição de Medicamentos/veterinária , Erros de Medicação/veterinária , Convulsões/veterinária , Animais , Anticonvulsivantes/uso terapêutico , Brometos/sangue , Brometos/uso terapêutico , Doenças do Cão/sangue , Doenças do Cão/tratamento farmacológico , Cães , Composição de Medicamentos/efeitos adversos , Masculino , Fenobarbital/efeitos adversos , Fenobarbital/uso terapêutico , Compostos de Potássio/sangue , Compostos de Potássio/uso terapêutico , Convulsões/tratamento farmacológicoRESUMO
The aim of this study was to evaluate the relationships between carapace parameters as indicators of age and plasma elements in 25 captive hawksbill sea turtles. Particle-induced X-ray emission allowed detection of 23 trace and major elements. There were significant but weak correlations between the virtual carapace surface area and plasma bromide (r = -0.552, P<0.01), phosphorus (r = 0.547, P<0.01), lead (r =-0.434, P<0.05) and strontium (r = 0.599, P<0.01), while there were no significant correlations with other elements. These results suggest that major and trace plasma elements in captive sea turtles show almost no variation with carapace parameters, suggesting that the increase in plasma elements seen in wild sea turtles might be the result of marine pollution.
Assuntos
Exoesqueleto/anatomia & histologia , Monitoramento Ambiental/estatística & dados numéricos , Oligoelementos/sangue , Tartarugas/anatomia & histologia , Tartarugas/sangue , Poluentes Químicos da Água/sangue , Fatores Etários , Animais , Brometos/sangue , Monitoramento Ambiental/métodos , Chumbo/sangue , Fósforo/sangue , Espectrometria por Raios X , Estrôncio/sangueRESUMO
Although bromide (Br) is used to treat intractable epilepsy, serum Br concentrations are not routinely analyzed. The present study measured serum Br(-) and Cl(-) concentrations in Br-treated epileptic patients, showing a significant correlation between Br(-) and imprecise Cl(-) concentrations, which suggested the use of a unique correlating equation for each diagnostic tool. Results indicated that imprecise Cl(-) concentrations are useful markers for measuring appropriate serum Br(-) levels in epileptic patients.
Assuntos
Brometos/sangue , Brometos/uso terapêutico , Cloretos/sangue , Processamento Eletrônico de Dados , Epilepsia/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Eletrodos Seletivos de Íons , Modelos Lineares , Masculino , Potenciometria , Valor Preditivo dos Testes , Adulto JovemRESUMO
Bromide is a sedative hypnotic. Due to its potential use as a sedative or calmative agent in competition horses, a method to control bromide is needed. Colorimetric method had been employed in the authors' laboratory from 2003 for the semi-quantification of bromide in equine plasma samples. However, the method was found to be highly susceptible to matrix interference, and was replaced in 2008 with a more reliable inductively coupled plasma-mass spectrometry (ICP/MS) method. Equine plasma was protein-precipitated using trichloroacetic acid, diluted with nitric acid, and then submitted directly to ICP/MS analysis. Since bromide is naturally occurring in equine plasma, a threshold is necessary to control its misuse in horses. Based on population studies (n = 325), a threshold of 90 µg/mL was proposed (with a risk factor of less than 1 in 10 000). Using the ICP/MS screening method, equine plasma samples with bromide greater than 85 µg/mL would be further quantified using the more accurate ICP/MS standard addition method. Confirmation of bromide was achieved by gas chromatography-mass spectrometry (GC-MS), with the bromide detected as its pentafluorobenzyl derivative. A sample is considered positive if its plasma bromide concentration exceeds the threshold (90 µg/mL) plus the measurement uncertainty of the quantification method (8 µg/mL at 99% 1-tailed confidence level) and its presence is confirmed using the GC-MS method. Following oral administration of potassium bromide (60 g each) to two geldings, plasma bromide levels peaked after approximately 2 hours at about 300 µg/mL, and then remained above the threshold for 8 and 13 days respectively.
Assuntos
Brometos/sangue , Hipnóticos e Sedativos/sangue , Espectrometria de Massas/métodos , Compostos de Potássio/sangue , Administração Oral , Animais , Brometos/administração & dosagem , Dopagem Esportivo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Cavalos , Hipnóticos e Sedativos/administração & dosagem , Masculino , Compostos de Potássio/administração & dosagem , Detecção do Abuso de Substâncias/métodos , Fatores de TempoRESUMO
Perchlorate, ClO(4)(-), interferes with iodide (I(-)) uptake by the sodium-iodide symporter (NIS) and thereby affects thyroid hormone production in the body. Studies have reported human exposures to perchlorate based on measurements in urine, but little is known about the levels in blood. In this study, we determined concentrations of perchlorate, iodide, and other anions (e.g., chlorate [ClO(3)(-)], bromate [BrO(3)(-)], bromide [Br(-)]) in 131 whole blood samples collected from Chinese donors aged 0.4 to 90 yr, in Nanchang, China. Perchlorate, iodide, and bromide were detected in all of the samples analyzed, whereas chlorate was found in only 27% of the samples and bromate was found in only 2%. The mean (range) concentrations of perchlorate, iodide, and bromide were 2.68 (0.51-10.5), 42.6 (1.58-812), and 2120 (1050-4850) ng/mL, respectively. Perchlorate levels in blood from Nanchang adults were 10-fold greater than levels that have been previously reported for U.S. adults. The iodide/perchlorate molar ratio ranged from 3.05 to 15.3 for all age groups, and the ratio increased with age (r = 0.732, p < 0.01). Perchlorate and bromide concentrations decreased significantly with age, whereas iodide concentrations increased with age. No significant gender-related differences in blood perchlorate, iodide, or bromide levels were found. A significant negative correlation was found between the concentrations of perchlorate and iodide in blood. Exposure doses of perchlorate were estimated for infants, toddlers, children, adolescents, and adults based on the measured concentrations in blood, using a simple pharmacokinetic model. The mean exposure doses of perchlorate for our age groups ranged from 1.12 (adults) to 2.22 µg/kg bw/day (infants), values higher than the United States Environmental Protection Agency's (USEPA) reference dose (RfD: 0.7 µg/kg bw/day). This is the first study on perchlorate and iodide levels in whole blood from infants, toddlers, children, adolescents, and adults from a city in China with known high perchlorate levels.
Assuntos
Monitoramento Ambiental , Iodetos/sangue , Percloratos/sangue , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Brometos/sangue , Criança , China , Feminino , Humanos , Lactente , Recém-Nascido , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Adulto JovemRESUMO
Energy dispersive X-ray fluorescence spectrometry (EDX) enables rapid, non-destructive, multi-elemental analysis. Using EDX, bromide was detected in seawater but not in freshwater. We applied EDX to the detection of bromide in cardiac blood from medico-legal autopsy cases to obtain additional evidence supportive of seawater drowning. Bromide was detected in the blood of 4 out of 10 victims drowned in seawater. In contrast, bromide concentrations were below the quantification limit in both victims from freshwater drowning and non-drowning controls. No postmortem invasion of bromide was observed in animal experiments of postmortem immersion in seawater. These results indicate that the detection of bromide in blood by EDX could be a chemical marker supportive of drowning in seawater.
Assuntos
Brometos/sangue , Afogamento/diagnóstico , Água do Mar , Idoso , Animais , Biomarcadores/sangue , Feminino , Patologia Legal , Água Doce , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Ratos Wistar , Sensibilidade e Especificidade , Manejo de Espécimes , Espectrometria por Raios XRESUMO
A 5-year-old neutered male Cavalier King Charles Spaniel was evaluated for a 3-week history of progressive paresis. The dog had been receiving potassium citrate capsules to acidify urine for the past 2 years because of an earlier history of urolithiasis. Results of neurologic examination, spinal cord radiography, and magnetic resonance imaging of the skull and spinal cord revealed no lesions that could have accounted for the neurologic signs. The main abnormalities on a clinical chemistry profile were marked hyperchloremia (179 mmol/L, reference interval 108-122 mmol/L) and an anion gap of -50.4 mmol/L (reference interval 16.3-28.6 mmol/L). Because of the severe hyperchloremia, serum bromide concentration was measured (400 mg/dL; toxic concentration >150 mg/dL; some dogs may tolerate up to 300 mg/dL). Analysis of the potassium citrate capsules, which had been compounded at a local pharmacy, yielded a mean bromide concentration of 239 mg/capsule. Administration of the capsules was discontinued and there was rapid resolution of the dog's neurologic signs. This case of extreme bromide toxicity, which apparently resulted from inadvertent use of bromide instead of citrate at the pharmacy, illustrates the importance of knowing common interferents with analyte methodologies and of pursing logical additional diagnostic tests based on clinical and laboratory evidence, even when a patient's history appears to rule out a potential etiology.