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The term "SOS response" was first coined by Radman in 1974, in an intellectual effort to put together the data suggestive of a concerted gene expression program in cells undergoing DNA damage. A large amount of information about this cellular response has been collected over the following decades. In this review, we will focus on a few of the relevant aspects about the SOS response: its mechanism of control and the stressors which activate it, the diversity of regulated genes in different species, its role in mutagenesis and evolution including the development of antimicrobial resistance, and its relationship with mobile genetic elements.
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BACKGROUND & AIMS: Steatohepatitis drives fibrogenesis in alcohol-related liver disease. Recent studies have suggested that hepatic stellate cells (HSCs) may regulate the parenchymal cell injury and inflammation that precedes liver fibrosis, although the mechanism remains incompletely defined. Neuropilin-1 (NRP-1) and synectin are membrane proteins implicated in HSC activation. In this study, we disrupted NRP-1 and synectin as models to evaluate the role of HSC activation on the development of steatohepatitis in response to alcohol feeding in mice. METHODS: Mice with HSC-selective deletion of NRP (ColCre/Nrp1loxP) or synectin (ColCre/synectinloxP) vs. paired Nrp1loxP or synectinloxP mice were fed a control diet or the chronic/binge alcohol feeding model. Several markers of steatosis and inflammation were evaluated. RESULTS: ColCre/Nrp1loxP mice showed less fibrosis, as expected, but also less inflammation and steatosis, with lower hepatic triglyceride content. Similar results were observed in the synectin model. Hepatocytes treated with supernatant of HSCs from ColCre/Nrp1loxP mice compared to supernatant from Nrp1loxP mice were protected against ethanol-induced lipid droplet formation. An adipokine and inflammatory protein array from the supernatant of HSCs with NRP-1 knockdown showed a significant reduction in Igfbp3 (a major insulin-like growth factor-binding protein with multiple metabolic functions) and an increase in SerpinA12 (a serine-protease inhibitor) secretion compared to wild-type HSCs. Recombinant Igfbp3 induced lipid droplets, triglyceride accumulation, and lipogenic genes in hepatocytes in vitro, while SerpinA12 was protective against ethanol-induced steatosis. Finally, Igfbp3 was increased, and SerpinA12 was decreased in serum and liver tissue from patients with alcoholic hepatitis. CONCLUSION: Selective deletion of NRP-1 from HSCs attenuates alcohol-induced steatohepatitis through regulation of Igfbp3 and SerpinA12 signaling. LAY SUMMARY: Hepatic stellate cells are known for their role in fibrosis (scarring of the liver). In this study, we describe their role in the modulation of fat deposition and inflammation in the liver, which occurs secondary to alcohol damage.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fígado Gorduroso Alcoólico , Células Estreladas do Fígado/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Neuropilina-1/metabolismo , Serpinas/metabolismo , Animais , Modelos Animais de Doenças , Fígado Gorduroso Alcoólico/complicações , Fígado Gorduroso Alcoólico/metabolismo , Fígado Gorduroso Alcoólico/patologia , Fibrose/etiologia , Fibrose/imunologia , Inflamação/metabolismo , Camundongos , Inibidores de Serina Proteinase/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: The Ponseti method has been shown to be the most effective treatment for congenital clubfoot. The current challenge is to establish sustainable national clubfoot treatment programs that utilize the Ponseti method and integrate it within a nation's governmental health system. The Brazilian Ponseti Program (Programa Ponseti Brasil) has increased awareness of the utility of the Ponseti method and has trained >500 Brazilian orthopaedic surgeons in it. METHODS: A group of 18 of those surgeons had been able to reproduce the Ponseti clubfoot treatment, and compiled their initial results through structured spreadsheet. RESULTS: The study compiled 1040 patients for a total of 1621 feet. The average follow-up time was 2.3 years with an average correction time of approximately 3 months. Patients required an average of 6.40 casts to achieve correction. CONCLUSIONS: This study demonstrates that good initial correction rates are reproducible after training; from 1040 patients only 1.4% required a posteromedial release. LEVEL OF EVIDENCE: Level IV.
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Moldes Cirúrgicos , Pé Torto Equinovaro/terapia , Manipulação Ortopédica/métodos , Tenotomia , Tendão do Calcâneo/cirurgia , Pré-Escolar , Países em Desenvolvimento , Feminino , Acessibilidade aos Serviços de Saúde/normas , Humanos , Lactente , Masculino , Avaliação de Programas e Projetos de Saúde , Tenotomia/métodos , Resultado do TratamentoAssuntos
Cloridrato de Fingolimode/efeitos adversos , Hipotireoidismo/induzido quimicamente , Imunossupressores/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adulto , Feminino , Cloridrato de Fingolimode/administração & dosagem , Humanos , Imunossupressores/administração & dosagem , Adulto JovemRESUMO
Korean rose bitterling (Rhodeus uyekii) is a freshwater fish endemic to Korea. Natural populations of this species have experienced severe declines as a result of habitat fragmentation and water pollution. To conserve and restore R. uyekii, the genetic diversity of this species needs to be assessed at the population level. Eighteen novel polymorphic microsatellite loci for R. uyekii were developed using an enriched partial genomic library. Polymorphisms at these loci were studied in 150 individuals collected from three populations. The number of alleles at each locus ranged from 3 to 47 (mean = 17.1). Within the populations, the observed heterozygosity ranged from 0.032 to 1.000, expected heterozygosity from 0.082 to 0.967, and polymorphism information content from 0.078 to 0.950. Six loci showed significant deviation from Hardy-Weinberg equilibrium after Bonferroni's correction, and no significant linkage disequilibrium was detected between most locus pairs, except in three cases. These highly informative microsatellite markers should be useful for genetic population structure analyses of R. uyekii.
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Peixes/genética , Biblioteca Genômica , Repetições de Microssatélites , Alelos , Animais , Genótipo , Polimorfismo GenéticoRESUMO
PURPOSE: To evaluate the efficacy of radiotherapy and factors affecting the prognosis of gliomatosis cerebri. METHODS: Twenty-eight patients with pathologically confirmed gliomatosis cerebri underwent radiotherapy between August 1988 and September 2003. The median age of the patients was 39 years (range 18-67). Performance status was good (ECOG score ≤2) in 23 patients (82 %). The extent of radiotherapy was partial brain in 17 patients, whole brain in 2 patients, and whole brain followed by partial brain in 9 patients. The median radiation dose was 55.8 Gy (range 46.8-70.4). The median duration of follow-up was 136 months for survivors (range 39-191). RESULTS: The median overall and progression-free survival times of all patients were 20 and 11 months, respectively. When initial response to radiotherapy was grouped as improved, stationary, and aggravated, the median overall survival times in patients with improved, stationary, and aggravated responses were 76, 20, and 7 months, respectively (p = 0.0129). However, radiation parameters such as dose and irradiation volume had no impact on overall survival. On multivariate analysis, both performance status and initial response to radiotherapy were significant prognostic factors affecting overall survival (p = 0.0249 and 0.0065, respectively). CONCLUSIONS: This study showed that gliomatosis cerebri could be effectively treated with radiotherapy and that initial response to radiotherapy was a significant prognostic factor affecting the survival.
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Neoplasias Encefálicas/radioterapia , Neoplasias Neuroepiteliomatosas/radioterapia , Radioterapia/métodos , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias Neuroepiteliomatosas/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemAssuntos
Amitriptilina/efeitos adversos , Antidepressivos/efeitos adversos , Citocromo P-450 CYP2D6/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Fluoxetina/efeitos adversos , Amitriptilina/sangue , Antidepressivos/sangue , Citocromo P-450 CYP2D6/genética , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/genética , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Fluoxetina/sangue , Seguimentos , Humanos , Masculino , México , Polimorfismo Genético , Fatores de TempoRESUMO
AIMS: In an international prospective cohort study we assessed the relationship between glucose levels and incident cardiovascular events and death. METHODS AND RESULTS: 18,990 men and women were screened for entry into the DREAM clinical trial from 21 different countries. All had clinical and biochemical information collected at baseline, including an oral glucose tolerance test (OGTT), and were prospectively followed over a median (IQR) of 3.5 (3.0-4.0) years for incident cardiovascular (CV) events including coronary artery disease (CAD), stroke, congestive heart failure (CHF) requiring hospitalization, and death. After OGTT screening, 8000 subjects were classified as normoglycaemic, 8427 had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and 2563 subjects had newly diagnosed type 2 diabetes mellitus (DM). There were incident events in 491 individuals: 282 CAD, 54 strokes, 19 CHF, and 164 died. The annualized CV or death event rate was 0.79/100 person-years in the overall cohort, 0.51/100 person-years in normoglycaemics, 0.92/100 person-years among subjects with IFG and/or IGT at baseline, and 1.27/100 person-years among those with DM (p for trend <0.0001). Among all subjects, a 1 mmol/l increase in fasting plasma glucose (FPG) or a 2.52 mmol/l increase in the 2-h post-OGTT glucose was associated with a hazard ratio increase in the risk of CV events or death of 1.17 (95% CI 1.13-1.22). CONCLUSIONS: In this large multiethnic cohort, the risk of CV events or death increased progressively among individuals who were normoglycaemic, IFG or IGT, and newly diagnosed diabetics. A 1 mmol/l increase in FPG was associated with a 17% increase in the risk of future CV events or death. Therapeutic or behavioural interventions designed to either prevent glucose levels from rising, or lower glucose among individuals with dysglycaemia should be evaluated.
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Glicemia/análise , Doenças Cardiovasculares/epidemiologia , Transtornos do Metabolismo de Glucose/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Ásia/epidemiologia , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/diagnóstico , Intolerância à Glucose/epidemiologia , Transtornos do Metabolismo de Glucose/sangue , Transtornos do Metabolismo de Glucose/diagnóstico , Transtornos do Metabolismo de Glucose/mortalidade , Teste de Tolerância a Glucose , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologia , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , América do Sul/epidemiologia , Fatores de Tempo , Regulação para CimaRESUMO
AIMS: In an international prospective cohort study we assessed the relationship between glucose levels and incident cardiovascular events and death.METHODS AND RESULTS: 18,990 men and women were screened for entry into the DREAM clinical trial from 21 different countries. All had clinical and biochemical information collected at baseline, including an oral glucose tolerance test (OGTT), and were prospectively followed over a median (IQR) of 3.5 (3.0-4.0) years for incident cardiovascular (CV) events including coronary artery disease (CAD), stroke, congestive heart failure (CHF) requiring hospitalization, and death. After OGTT screening, 8000 subjects were classified as normoglycaemic, 8427 had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and 2563 subjects had newly diagnosed type 2 diabetes mellitus (DM). There were incident events in 491 individuals: 282 CAD, 54 strokes, 19 CHF, and 164 died. The annualized CV or death event rate was 0.79/100 person-years in the overall cohort, 0.51/100 person-years in normoglycaemics, 0.92/100 person-years among subjects with IFG and/or IGT at baseline, and 1.27/100 person-years among those with DM (p for trend <0.0001). Among all subjects, a 1 mmol/l increase in fasting plasma glucose (FPG) or a 2.52 mmol/l increase in the 2-h post-OGTT glucose was associated with a hazard ratio increase in the risk of CV events or death of 1.17 (95% CI 1.13-1.22).CONCLUSIONS: In this large multiethnic cohort, the risk of CV events or death increased progressively among individuals who were normoglycaemic, IFG or IGT, and newly diagnosed diabetics. A 1 mmol/l increase in FPG was associated with a 17% increase in the risk of future CV events or death. Therapeutic or behavioural interventions designed to either prevent glucose levels from rising, or lower glucose among individuals with dysglycaemia should be evaluated.
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Epidemiologia , Glucose , Infarto do MiocárdioRESUMO
Dopamine (DA) D2 receptors expressed in DA neurons (D2 autoreceptors) exert a negative feedback regulation that reduces DA neuron firing, DA synthesis and DA release. As D2 receptors are mostly expressed in postsynaptic neurons, pharmacological and genetic approaches have been unable to definitively address the in vivo contribution of D2 autoreceptors to DA-mediated behaviors. We found that midbrain DA neurons from mice deficient in D2 autoreceptors (Drd2(loxP/loxP); Dat(+/IRES-cre), referred to as autoDrd2KO mice) lacked DA-mediated somatodendritic synaptic responses and inhibition of DA release. AutoDrd2KO mice displayed elevated DA synthesis and release, hyperlocomotion and supersensitivity to the psychomotor effects of cocaine. The mice also exhibited increased place preference for cocaine and enhanced motivation for food reward. Our results highlight the importance of D2 autoreceptors in the regulation of DA neurotransmission and demonstrate that D2 autoreceptors are important for normal motor function, food-seeking behavior, and sensitivity to the locomotor and rewarding properties of cocaine.
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Cocaína/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Motivação/fisiologia , Receptores de Dopamina D2/deficiência , Recompensa , Análise de Variância , Animais , Autorradiografia , Baclofeno/farmacologia , Comportamento de Escolha/fisiologia , Condicionamento Operante , Di-Hidroxifenilalanina/metabolismo , Dopamina/metabolismo , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Comportamento Exploratório/fisiologia , Alimentos , Agonistas dos Receptores de GABA-B/farmacologia , Hidrazinas/farmacologia , Hipercinese/tratamento farmacológico , Hipercinese/fisiopatologia , Técnicas In Vitro , Aprendizagem em Labirinto/fisiologia , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/genética , Mesencéfalo/citologia , Camundongos , Camundongos Knockout , Atividade Motora/genética , Neurônios/fisiologia , Quimpirol/farmacologia , Esquema de Reforço , Sulpirida/farmacologiaRESUMO
AIMS/HYPOTHESIS: The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial reported that 3 years of therapy with rosiglitazone reduced the primary outcome of diabetes or death by 60%. Here we investigated whether an effect on diabetes prevention persists more than 1.5 years after therapy has been discontinued. METHODS: The DREAM On passive follow-up study was conducted at 49 of the 191 DREAM sites. Consenting participants were invited to have a repeat OGTT 1-2 years after active therapy ended. A diagnosis of diabetes at that time was based on either a fasting or 2 h plasma glucose level of ¡Ý7.0 mmol/l or ¡Ý11.1 mmol/l, respectively, or a confirmed diagnosis by a non-study physician. Regression to normoglycaemia was defined as a fasting and 2 h plasma glucose level of <6.1 mmol/l and <7.8 mmol/l, respectively. RESULTS: After a median of 1.6 years after the end of the trial and 4.3 years after randomisation, rosiglitazone participants had a 39% lower incidence of the primary outcome (hazard ratio [HR] 0.61, 95% CI 0.53-0.70; p < 0.0001) and 17% more regression to normoglycaemia (95% CI 1.01-1.34; p = 0.034). When the analysis was restricted to the passive follow-up period, a similar incidence of both the primary outcome and regression was observed in people from both treatment groups (HR 1.00, 95% CI 0.81-1.24 and HR 1.14, 95% CI 0.97-1.32, respectively). Similar effects were noted when new diabetes was analysed separately from death. Ramipril did not have any significant long-term effect. CONCLUSIONS/INTERPRETATION: Time-limited exposure to rosiglitazone reduces the longer term incidence of diabetes by delaying but not reversing the underlying disease process.
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Complicações do Diabetes , RamiprilRESUMO
OBJECTIVES: To determine a population pharmacokinetic model of the antihelmintic drug, albendazole, and identify the factors influencing the pharmacokinetic parameters in patients with neurocysticercosis. METHODS: A prospective study was performed in 90 patients receiving 30 mg/kg/day of albendazole for 8 days. Blood samples were collected at steady state. Plasma concentrations of albendazole sulfoxide, the main active metabolite of albendazole, were determined by HPLC. The population pharmacokinetics analysis was performed using non-linear mixed-effect modeling (NONMEM). A one-compartment model with first order absorption and elimination was used. RESULTS: Body weight was included empirically on CL/F and V/F using an allometric relationship. Although none of the investigated covariates had a significant influence on the pharmacokinetic parameters of albendazole, the final model identified two subpopulations on the bioavailability parameter. One subpopulation comprising of 27% of the total population had a bioavailability of 28%, with the remaining subpopulation defined to have complete bioavailability. The CL/F and V/F for a standard 70 kg individual was determined to be 51.6 l/h and 4560 l, respectively. Interindividual variability in CL/F was 32%; the residual unexplained variability was 32%. CONCLUSIONS: The considerable variability reported in albendazole pharmacokinetics and plasma concentrations is likely due to issues related to bioavailability. With one-fourth of the population absorbing as little as 30% of the drug relative to others, low drug exposures might be responsible for treatment failures. Therapeutic drug monitoring may be warranted to optimize the eradication of the infecting parasite.
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Albendazol/farmacocinética , Anti-Helmínticos/farmacocinética , Modelos Biológicos , Neurocisticercose/tratamento farmacológico , Adolescente , Adulto , Idoso , Albendazol/análogos & derivados , Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dinâmica não Linear , Estudos Prospectivos , Adulto JovemAssuntos
Neurocisticercose/tratamento farmacológico , Praziquantel/administração & dosagem , Adolescente , Adulto , Cimetidina/administração & dosagem , Cimetidina/efeitos adversos , Carboidratos da Dieta/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Interações Alimento-Droga , Humanos , Masculino , Pessoa de Meia-Idade , Neurocisticercose/diagnóstico , Praziquantel/efeitos adversosRESUMO
In the present study we found that after a single oral dose of 1,800 mg of praziquantel, following a high-lipid diet and a high-carbohydrate diet, the maximum levels in plasma increased 243 and 515% and the area under the plasma concentration curve from 0 to 8 h increased 180 and 271%, respectively.
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Antiplatelmínticos/farmacocinética , Interações Alimento-Droga , Praziquantel/farmacocinética , Adulto , Antiplatelmínticos/administração & dosagem , Área Sob a Curva , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Dieta , Carboidratos da Dieta/farmacologia , Gorduras na Dieta/farmacologia , Meia-Vida , Humanos , Pessoa de Meia-Idade , Praziquantel/administração & dosagem , ComprimidosRESUMO
Neurocysticercosis is the most important parasitic infection of the nervous system. It is common in communities living in conditions with poor hygiene. Until the last 2 decades, there was no specific pharmacological treatment: surgery and corticosteroids were the only medical alternatives. The recent introduction of anticysticercal drugs, an isoquinoline (praziquantel) and a benzimidazole (albendazole), has dramatically changed the medical management of neurocysticercosis. Praziquantel is taken orally and undergoes extensive first pass hepatic biotransformation. Peak concentration in serum is reached after 1 to 2 hours and the elimination half-life is between 1 and 3 hours. Praziquantel permeates the blood-brain barrier, thus explaining its effectiveness on parenchymal brain cysticercosis. Plasma concentrations of the drug are increased when a high carbohydrate diet is administered. Cimetidine also increases the plasma concentration of praziquantel by inhibition of cytochrome P450. Bioavailability of the drug is markedly reduced when given jointly with antiepileptics or corticosteroids, specially carbamazepine, phenytoin or dexamethasone. The current schedule for neurocysticercosis treatment lasts 2 weeks at daily doses of 50 mg/kg. Recently, a new therapeutic scheme has been proposed that considers the pharmacokinetics of the drug. This regime lasts only 1 day and includes 3 dosages of 25 mg/kg at 2-hour intervals. This increases the time that the parasite is exposed to high drug concentrations. This therapeutic scheme has produced similar results to longer schemes, with the additional advantages of cost, length of usual treatments and reduction in total dose received (being one-tenth of the total dosage). Albendazole is considered by many as the drug of choice for treatment of neurocysticercosis. It is given orally and is rapidly and extensively metabolised to albendazole sulfoxide (ALBSO), which is considered to be the metabolite directly or indirectly responsible for both toxicity and efficacy outside the gastrointestinal tract. Concentrations of ALBSO are highly variable between individuals and it has a half-life of between 6 and 15 hours. It also crosses the blood-brain barrier. In patients with extrahepatic obstruction, the elimination process is prolonged and plasma concentration is increased. Fatty meals improve absorption. Concomitant administration of albendazole with dexamethasone or with praziquantel increases plasma concentration of ALBSO. Albendazole is administered in an 8 day course of 15 mg/kg per day in 2 divided doses 12 hours apart. This scheme, based on drug pharmacokinetics, has proven to be highly effective. Inflammation is a common accompaniment of neurocysticercosis; in many cases it is the aetiopathogen responsible for histological damage. Corticosteroid therapy is useful for preventing further tissue injury. Long term corticosteroid therapy can be accomplished with 50 mg of oral prednisone 3 times a week. Acute corticosteroid therapy includes brief courses with high dosages of intramuscular dexamethasone or intravenous methylprednisolone. Clinical decisions on cysticidal and anti-inflammatory treatments must be made with the information gathered by neuroimaging studies, either computed tomography or magnetic resonance, and by the analysis of cerebrospinal fluid.
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Albendazol/farmacocinética , Anti-Helmínticos/farmacocinética , Encefalopatias/metabolismo , Cisticercose/metabolismo , Praziquantel/farmacocinética , Absorção , Albendazol/efeitos adversos , Albendazol/uso terapêutico , Animais , Anti-Helmínticos/efeitos adversos , Anti-Helmínticos/uso terapêutico , Disponibilidade Biológica , Encefalopatias/tratamento farmacológico , Encefalopatias/parasitologia , Cisticercose/tratamento farmacológico , Cisticercose/parasitologia , Interações Medicamentosas , Glucocorticoides/efeitos adversos , Glucocorticoides/farmacocinética , Glucocorticoides/uso terapêutico , Meia-Vida , Humanos , Praziquantel/efeitos adversos , Praziquantel/uso terapêuticoRESUMO
To evaluate two different dosage regimens for albendazole (7.5 mg/kg twice a day or 5.0 mg/kg three times a day), a study was performed in 10 patients with a diagnosis of parenchymal brain cysticercosis. Each patient received both regimens sequentially according to a randomized, crossover design. Blood and urine samples were taken once the drug steady state had been reached. Plasma levels of albendazole sulfoxide at steady state were determined using a HPLC method. In spite of a great intersubject variability observed with both regimens in the area under the curve (AUC) and in the minimum steady-state plasma concentration (Cp min ss), no statistically significant differences were found in these parameters. We suggest that a regimen of 7.5 mg/kg every 12 h can favorably replace the currently used regimen of 5 mg/kg every 8 h.
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Albendazol/administração & dosagem , Encefalopatias/tratamento farmacológico , Cisticercose/tratamento farmacológico , Adolescente , Adulto , Albendazol/farmacocinética , Encefalopatias/parasitologia , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Albendazole pharmacokinetics were studied in eight patients who were receiving albendazole in doses of 15 mg/kg per day for 8 days as treatment of brain cysticercosis. Albendazole was not detected in plasma, but its main metabolite albendazole sulphoxide could be measured. Maximum plasma levels for albendazole sulphoxide ranged from 0.45 to 2.96 micrograms/mL. The half-life of albendazole sulphoxide was between 10 and 15 hours. A double peak was found in three patients. Mean residence time values were from 14 to 20 hours. Plasma levels of albendazole sulphoxide at the steady state showed great intraindividual variability. The results suggest that albendazole can be administered twice daily rather than three times as is currently done.
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Albendazol/farmacocinética , Encefalopatias/metabolismo , Cisticercose/metabolismo , Administração Oral , Adulto , Idoso , Albendazol/administração & dosagem , Albendazol/análogos & derivados , Albendazol/sangue , Albendazol/uso terapêutico , Anti-Helmínticos/sangue , Encefalopatias/tratamento farmacológico , Encefalopatias/parasitologia , Cisticercose/tratamento farmacológico , Cisticercose/parasitologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
A rapid, sensitive and specific method useful in monitoring diazepam in patients receiving multiple therapy is presented. Plasma was extracted in the presence of borate buffer with hexane and the drug was quantified by HPLC in a Novapak C 18 column. The limit of detection in plasma was about 30 ng/mL. Analytical recovery of the drug added to plasma was about 70%. Within-day variation and between-day variation ranged from 5.9 to 8.3 and 5.9 to 10.7%, respectively. The method was applied in the determination of diazepam levels in patients treated with this drug in combination with other drugs commonly used in our hospital. The concentrations found in most of the patients were in the therapeutic range. It was not possible to detect the drug in one patient with concomitant administration of magnesium hydroxide, which can be attributed to a reduced absorption of diazepam in presence of the antiacid. Average steady-state concentrations of diazepam in psychiatric patients, submitted to 5 mg doses t.i.d. during four weeks, were in the range of 200 to 450 ng/mL.