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1.
Scand J Trauma Resusc Emerg Med ; 29(1): 128, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34461967

RESUMO

BACKGROUND: Metabolic and electrolyte imbalances are some of the reversible causes of cardiac arrest and can be diagnosed even in the pre-hospital setting with a mobile analyser for point-of-care testing (POCT). METHODS: We conducted a retrospective observational study, which included analysing all pre-hospital resuscitations in the study region between October 2015 and December 2016. A mobile POCT analyser (Alere epoc®) was available at the scene of each resuscitation. We analysed the frequency of use of POCT, the incidence of pathological findings, the specific interventions based on POCT as well as every patient's eventual outcome. RESULTS: N = 263 pre-hospital resuscitations were included and in n = 98 of them, the POCT analyser was used. Of these measurements, 64% were performed using venous blood and 36% using arterial blood. The results of POCT showed that 63% of tested patients had severe metabolic acidosis (pH < 7.2 + BE < - 5 mmol/l). Of these patients, 82% received buffering treatment with sodium bicarbonate. Potassium levels were markedly divergent normal (> 6.0 mmol/l/ < 2.5 mmol/l) in 17% of tested patients and 14% of them received a potassium infusion. On average, the pre-hospital treatment time between arrival of the first emergency medical responders and the beginning of transport was 54 (± 20) min without POCT and 60 (± 17) min with POCT (p = 0.07). Overall, 21% of patients survived to hospital discharge (POCT 30% vs no POCT 16%, p = 0.01, Φ = 0.16). CONCLUSIONS: Using a POCT analyser in pre-hospital resuscitation allows rapid detection of pathological acid-base imbalances and potassium concentrations and often leads to specific interventions on scene and could improve the probability of survival.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Serviço Hospitalar de Emergência , Humanos , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/terapia , Testes Imediatos , Estudos Retrospectivos
2.
Haemophilia ; 23(4): 528-537, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28220555

RESUMO

INTRODUCTION: The pharmacokinetics (PK), safety and efficacy of BAY 81-8973, a full-length, unmodified, recombinant human factor VIII (FVIII), were evaluated in the LEOPOLD trials. AIM: The aim of this study was to develop a population PK model based on pooled data from the LEOPOLD trials and to investigate the importance of including samples with FVIII levels below the limit of quantitation (BLQ) to estimate half-life. METHODS: The analysis included 1535 PK observations (measured by the chromogenic assay) from 183 male patients with haemophilia A aged 1-61 years from the 3 LEOPOLD trials. The limit of quantitation was 1.5 IU dL-1 for the majority of samples. Population PK models that included or excluded BLQ samples were used for FVIII half-life estimations, and simulations were performed using both estimates to explore the influence on the time below a determined FVIII threshold. RESULTS: In the data set used, approximately 16.5% of samples were BLQ, which is not uncommon for FVIII PK data sets. The structural model to describe the PK of BAY 81-8973 was a two-compartment model similar to that seen for other FVIII products. If BLQ samples were excluded from the model, FVIII half-life estimations were longer compared with a model that included BLQ samples. CONCLUSIONS: It is essential to assess the importance of BLQ samples when performing population PK estimates of half-life for any FVIII product. Exclusion of BLQ data from half-life estimations based on population PK models may result in an overestimation of half-life and underestimation of time under a predetermined FVIII threshold, resulting in potential underdosing of patients.


Assuntos
Fator VIII/farmacocinética , Limite de Detecção , Proteínas Recombinantes/farmacocinética , Adolescente , Adulto , Criança , Pré-Escolar , Ensaios Clínicos como Assunto , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Distribuição Tecidual , Adulto Jovem
3.
Br J Pharmacol ; 171(22): 5076-92, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24962208

RESUMO

BACKGROUND AND PURPOSE: Previously, a systems pharmacology model was developed characterizing drug effects on the interrelationship between mean arterial pressure (MAP), cardiac output (CO) and total peripheral resistance (TPR). The present investigation aims to (i) extend the previously developed model by parsing CO into heart rate (HR) and stroke volume (SV) and (ii) evaluate if the mechanism of action (MoA) of new compounds can be elucidated using only HR and MAP measurements. EXPERIMENTAL APPROACH: Cardiovascular effects of eight drugs with diverse MoAs (amiloride, amlodipine, atropine, enalapril, fasudil, hydrochlorothiazide, prazosin and propranolol) were characterized in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats following single administrations of a range of doses. Rats were instrumented with ascending aortic flow probes and aortic catheters/radiotransmitters for continuous recording of MAP, HR and CO throughout the experiments. Data were analysed in conjunction with independent information on the time course of the drug concentration following a mechanism-based pharmacokinetic-pharmacodynamic modelling approach. KEY RESULTS: The extended model, which quantified changes in TPR, HR and SV with negative feedback through MAP, adequately described the cardiovascular effects of the drugs while accounting for circadian variations and handling effects. CONCLUSIONS AND IMPLICATIONS: A systems pharmacology model characterizing the interrelationship between MAP, CO, HR, SV and TPR was obtained in hypertensive and normotensive rats. This extended model can quantify dynamic changes in the CVS and elucidate the MoA for novel compounds, with one site of action, using only HR and MAP measurements. Whether the model can be applied for compounds with a more complex MoA remains to be established.


Assuntos
Hemodinâmica/efeitos dos fármacos , Hipertensão/metabolismo , Modelos Biológicos , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacocinética , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Amilorida/farmacocinética , Amilorida/farmacologia , Anlodipino/farmacocinética , Anlodipino/farmacologia , Animais , Atropina/farmacocinética , Atropina/farmacologia , Enalapril/farmacocinética , Enalapril/farmacologia , Hidroclorotiazida/farmacocinética , Hidroclorotiazida/farmacologia , Masculino , Prazosina/farmacocinética , Prazosina/farmacologia , Propranolol/farmacocinética , Propranolol/farmacologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
4.
Br J Pharmacol ; 169(7): 1510-24, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23849040

RESUMO

BACKGROUND AND PURPOSE: The homeostatic control of arterial BP is well understood with changes in BP resulting from changes in cardiac output (CO) and/or total peripheral resistance (TPR). A mechanism-based and quantitative analysis of drug effects on this interrelationship could provide a basis for the prediction of drug effects on BP. Hence, we aimed to develop a mechanism-based pharmacokinetic-pharmacodynamic (PKPD) model in rats that could be used to characterize the effects of cardiovascular drugs with different mechanisms of action (MoA) on the interrelationship between BP, CO and TPR. EXPERIMENTAL APPROACH: The cardiovascular effects of six drugs with diverse MoA, (amlodipine, fasudil, enalapril, propranolol, hydrochlorothiazide and prazosin) were characterized in spontaneously hypertensive rats. The rats were chronically instrumented with ascending aortic flow probes and/or aortic catheters/radiotransmitters for continuous recording of CO and/or BP. Data were analysed in conjunction with independent information on the time course of drug concentration using a mechanism-based PKPD modelling approach. KEY RESULTS: By simultaneous analysis of the effects of six different compounds, the dynamics of the interrelationship between BP, CO and TPR were quantified. System-specific parameters could be distinguished from drug-specific parameters indicating that the model developed is drug-independent. CONCLUSIONS AND IMPLICATIONS: A system-specific model characterizing the interrelationship between BP, CO and TPR was obtained, which can be used to quantify and predict the cardiovascular effects of a drug and to elucidate the MoA for novel compounds. Ultimately, the proposed PKPD model could be used to predict the effects of a particular drug on BP in humans based on preclinical data.


Assuntos
Pressão Arterial/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/farmacocinética , Modelos Animais , Ratos Endogâmicos SHR/fisiologia , Resistência Vascular/efeitos dos fármacos , Animais , Estado de Consciência/fisiologia , Masculino , Ratos
5.
J Vet Pharmacol Ther ; 36(2): 174-80, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22568394

RESUMO

In dogs, activation of the Renin-Angiotensin-Aldosterone System (RAAS) is an important feature of congestive heart failure (CHF). Long-term increases in angiotensin II (AII) and aldosterone (ALD) lead to the progression of heart failure to its end stage. Angiotensin-converting enzyme inhibitors (ACEIs) are the foremost therapeutic option in the management of CHF. Recent literature has challenged the efficacy of ACEIs, based on modest reduction in urinary aldosterone (UALD) excretion despite marked inhibition of ACE activity. This study was designed to heighten the understanding of the effect of benazepril, a potent ACEI, on the RAAS, using a low-sodium diet as an experimental model of RAAS activation. Time course profiles of RAAS peptides and related areas under the curve (AUC) were used for comparison between benazepril and placebo groups. Results indicated substantial changes in the dynamics of these biomarkers. At presumed benazeprilat steady state, significant differences in AUC of plasma renin activity (+90%), angiotensin I (+43%), and AII (-53%) were found between benazepril and placebo-treated dogs. ALD decreased by 73% in plasma but only by 5% in urine. In conclusion, despite modest reduction in UALD excretion, benazepril markedly influences RAAS dynamics in dogs.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Benzazepinas/farmacologia , Cães/sangue , Cães/metabolismo , Regulação da Expressão Gênica/fisiologia , Sistema Renina-Angiotensina/fisiologia , Animais , Área Sob a Curva , Sistema Renina-Angiotensina/genética
6.
J Pharmacokinet Pharmacodyn ; 38(6): 697-711, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21909798

RESUMO

Drug-induced sleep fragmentation can cause sleep disturbances either via their intended pharmacological action or as a side effect. Examples of disturbances include excessive daytime sleepiness, insomnia and nightmares. Developing drugs without these side effects requires insight into the mechanisms leading to sleep disturbance. The characterization of the circadian sleep pattern by EEG following drug exposure has improved our understanding of these mechanisms and their translatability across species. The EEG shows frequent transitions between specific sleep states leading to multiple correlated sojourns in these states. We have developed a Markov model to consider the high correlation in the data and quantitatively compared sleep disturbance in telemetered rats induced by methylphenidate, which is known to disturb sleep, and of a new chemical entity (NCE). It was assumed that these drugs could either accelerate or decelerate the transitions between the sleep states. The difference in sleep disturbance of methylphenidate and the NCE were quantitated and different mechanisms of action on rebound sleep were identified. The estimated effect showed that both compounds induce sleep fragmentation with methylphenidate being fivefold more potent compared to the NCE.


Assuntos
Avaliação Pré-Clínica de Medicamentos/estatística & dados numéricos , Cadeias de Markov , Modelos Estatísticos , Privação do Sono/induzido quimicamente , Telemetria/estatística & dados numéricos , Animais , Drogas em Investigação/efeitos adversos , Drogas em Investigação/farmacocinética , Eletroencefalografia/estatística & dados numéricos , Eletromiografia/estatística & dados numéricos , Masculino , Metilfenidato/efeitos adversos , Metilfenidato/farmacocinética , Ratos , Ratos Sprague-Dawley , Fases do Sono/efeitos dos fármacos , Telemetria/métodos
7.
Clin Pharmacol Ther ; 88(2): 166-82, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20613720

RESUMO

Modeling and simulation in general, and specifically clinical trial simulation (CTS), have been recognized by the (larger) pharmaceutical companies and regulatory authorities as being pivotal to improving the efficiency of the drug development process. This includes the use of CTS to learn about drug effectiveness and safety and to optimize trial designs at the various stages of development. By reviewing papers published during the period January 2000-January 2010, this paper discusses recent developments with respect to methodology, applications, and lessons learned in the use of CTS in the development and clinical use of specific drugs. It is expected that future CTS experiments will be aided by the hybridization of optimal design methods with computationally intensive stochastic simulations. This will take advantage of optimizing the experimental design and leave the task of evaluating the probable real-world performance of a limited number of candidate trial designs and analysis procedures.


Assuntos
Ensaios Clínicos como Assunto , Simulação por Computador , Farmacocinética , Farmacologia Clínica/estatística & dados numéricos , Descoberta de Drogas , Humanos , Modelos Estatísticos , Projetos de Pesquisa , Software
8.
Drug Metab Rev ; 33(2): 125-47, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11495500

RESUMO

Glycyrrhizic acid is widely applied as a sweetener in food products and chewing tobacco. In addition, it is of clinical interest for possible treatment of chronic hepatitis C. In some highly exposed subjects, side effects such as hypertension and symptoms associated with electrolyte disturbances have been reported. To analyze the relationship between the pharmacokinetics of glycyrrhizic acid in its toxicity, the kinetics of glycyrrhizic acid and its biologically active metabolite glycyrrhetic acid were evaluated. Glycyrrhizic acid is mainly absorbed after presystemic hydrolysis as glycyrrhetic acid. Because glycyrrhetic acid is a 200-1000 times more potent inhibitor of 11-beta-hydroxysteroid dehydrogenase compared to glycyrrhizic acid, the kinetics of glycyrrhetic acid are relevant in a toxicological perspective. Once absorbed, glycyrrhetic acid is transported, mainly taken up into the liver by capacity-limited carriers, where it is metabolized into glucuronide and sulfate conjugates. These conjugates are transported efficiently into the bile. After outflow of the bile into the duodenum, the conjugates are hydrolyzed to glycyrrhetic acid by commensal bacteria; glycyrrhetic acid is subsequently reabsorbed, causing a pronounced delay in the terminal plasma clearance. Physiologically based pharmacokinetic modeling indicated that, in humans, the transit rate of gastrointestinal contents through the small and large intestines predominantly determines to what extent glycyrrhetic acid conjugates will be reabsorbed. This parameter, which can be estimated noninvasively, may serve as a useful risk estimator for glycyrrhizic-acid-induced adverse effects, because in subjects with prolonged gastrointestinal transit times, glycyrrhetic acid might accumulate after repeated intake.


Assuntos
Glycyrrhiza/química , Ácido Glicirrízico/farmacocinética , Modelos Biológicos , Administração Tópica , Animais , Antibacterianos/sangue , Antibacterianos/metabolismo , Antibacterianos/farmacocinética , Antibacterianos/toxicidade , Anti-Inflamatórios/sangue , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/toxicidade , Sistema Digestório/metabolismo , Sistema Digestório/microbiologia , Ácido Glicirretínico/sangue , Ácido Glicirretínico/metabolismo , Ácido Glicirretínico/toxicidade , Ácido Glicirrízico/sangue , Ácido Glicirrízico/metabolismo , Ácido Glicirrízico/uso terapêutico , Ácido Glicirrízico/toxicidade , Hepatite C Crônica/tratamento farmacológico , Humanos , Fígado/metabolismo , Estrutura Molecular
9.
Toxicol Appl Pharmacol ; 170(1): 46-55, 2001 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-11141355

RESUMO

Glycyrrhizic acid is widely applied as a sweetener in food products and chewing tobacco. Habitual consumption of this compound may lead to hypertension and electrolyte disturbances due to inhibition of 11-beta-hydroxysteroid dehydrogenase by the metabolite glycyrrhetic acid. The effect of 130 mg glycyrrhetic acid/day for 5 days on 11-beta-hydroxysteroid dehydrogenase activity was studied by measuring the cortisol-cortisone ratio in 24-h urine. A twofold increase in this ratio was observed. It took 4 days for the elevated urinary cortisol-cortisone ratio to return to the baseline ratio after cessation of the treatment. The pharmacokinetics of glycyrrhetic acid were studied after the first and last dose. Using data from a previously performed single-dose study and present multiple-dose treatment, a physiologically based pharmacokinetic model for glycyrrhetic acid was developed. The variability of the pharmacokinetics of glycyrrhetic acid in the population studied could be explained for a considerable part by interindividual differences in gastrointestinal transit of glycyrrhetic acid metabolites. The relationship between glycyrrhetic acid exposure and changes in urinary cortisol-cortisone ratio was described by a pharmacodynamic model, using nonlinear mixed-effect modeling. Literature data on the inhibitory effect of glycyrrhetic acid on 11-beta-hydroxysteroid dehydrogenase activity under various exposure scenarios could be adequately described by the model. Due to the relationship between the pharmacokinetics of glycyrrhetic acid and its inhibitory effect on 11-beta-hydroxysteroid dehydrogenase activity, reflected by a change in the urinary cortisol-cortisone ratio, this ratio might serve as a noninvasive marker to identify individuals at risk for glycyrrhizic acid over-consumption.


Assuntos
Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/farmacocinética , Ácido Glicirretínico/farmacologia , Ácido Glicirretínico/farmacocinética , Hidroxiesteroide Desidrogenases/antagonistas & inibidores , 11-beta-Hidroxiesteroide Desidrogenases , Adulto , Algoritmos , Cortisona/urina , Humanos , Hidrocortisona/urina , Masculino , Dinâmica não Linear , População , Reprodutibilidade dos Testes
10.
Compend Contin Educ Dent ; 22(11A): 996-1002, 1004-7; quiz 1044, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11915646

RESUMO

Occlusal dental caries often is not apparent using traditional diagnostic techniques. The clinical significance of pit-and-fissure discoloration in the absence of dietary and habit substances was examined. The study included 462 extracted teeth (216 with obvious pit-and-fissure discoloration, 216 with subtle discoloration, and 30 with no discoloration); 130 clinical teeth with varying degrees of pit-and-fissure discoloration; and 159 teeth in young adults, which had sealants placed > or = 10 years. All teeth studied were excavated very conservatively using air abrasion and/or the uniquely small H1 004 carbide bur. Presence of caries and its depth and extent were recorded, photographed, and measured with a custom made calibrated probe. Of the 721 teeth with discolored pits and fissures studied (432 extracted teeth and 289 clinical teeth), 660 (92%) had two or more of the four clinical criteria used to define dental caries in this study. Sixty-four percent of the lesions were > 2 mm in depth and 27% were > 3 mm in depth. Of the 159 teeth sealed for > or = 10 years, 47 (92%) were carious, and 26% had large, deep carious lesions penetrating > 3 mm. These data indicate: more effective methods are needed to diagnose pit-and-fissure caries and presence of pit-and-fissure discoloration in the absence of substances causing extrinsic staining should be a strong warning for clinicians to examine carefully for dental caries.


Assuntos
Cárie Dentária/diagnóstico , Fissuras Dentárias/patologia , Descoloração de Dente/etiologia , Adulto , Cárie Dentária/complicações , Cárie Dentária/etiologia , Fissuras Dentárias/complicações , Humanos , Selantes de Fossas e Fissuras
11.
Toxicol Appl Pharmacol ; 162(3): 177-88, 2000 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-10652246

RESUMO

Glycyrrhizic acid is currently of clinical interest for treatment of chronic hepatitis. It is also applied as a sweetener in food products and chewing tobacco. In some highly exposed subgroups of the population, serious side effects such as hypertension and electrolyte disturbances have been reported. In order to analyze the health risks of exposure to this compound, the kinetics of glycyrrhizic acid and its active metabolites were evaluated quantitatively. Glycyrrhizic acid and its metabolites are subject to complex kinetic processes, including enterohepatic cycling and presystemic metabolism. In humans, detailed information on these processes is often difficult to obtain. Therefore, a model was developed that describes the systemic and gastrointestinal tract kinetics of glycyrrhizic acid and its active metabolite glycyrrhetic acid in rats. Due to the physiologically based structure of the model, data from earlier in vitro and in vivo studies on absorption, enterohepatic cycling, and presystemic metabolism could be incorporated directly. The model demonstrates that glycyrrhizic acid and metabolites are transported efficiently from plasma to the bile, possibly by the hepatic transfer protein 3-alpha-hydroxysteroid dehydrogenase. Bacterial hydrolysis of the biliary excreted metabolites following reuptake of glycyrrhetic acid causes the observed delay in the terminal plasma clearance of glycyrrhetic acid. These mechanistic findings, derived from analysis of experimental data through physiologically based pharmacokinetic modeling, can eventually be used for a quantitative health risk assessment of human exposure to glycyrrhizic acid containing products.


Assuntos
Circulação Êntero-Hepática/fisiologia , Ácido Glicirrízico/farmacocinética , Modelos Biológicos , Animais , Bile/metabolismo , Sistema Biliar/metabolismo , Sistema Digestório/metabolismo , Ácido Glicirretínico/sangue , Ácido Glicirretínico/metabolismo , Ácido Glicirretínico/farmacocinética , Ácido Glicirrízico/sangue , Ácido Glicirrízico/metabolismo , Humanos , Fígado/metabolismo , Computação Matemática , Ratos
12.
Pharm Res ; 17(12): 1516-25, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11303962

RESUMO

PURPOSE: To analyze the role of the kinetics of glycyrrhizic acid (GD) in its toxicity. A physiologically-based pharmacokinetic (PBPK) model that has been developed for humans. METHODS: The kinetics of GD, which is absorbed as glycyrrhetic acid (GA), were described by a human PBPK model, which is based on a rat model. After rat to human extrapolation, the model was validated on plasma concentration data after ingestion of GA and GD solutions or licorice confectionery, and an additional data derived from the literature. Observed interindividual variability in kinetics was quantified by deriving an optimal set of parameters for each individual. RESULTS: The a-priori defined model successfully forecasted GA kinetics in humans, which is characterized by a second absorption peak in the terminal elimination phase. This peak is subscribed to enterohepatic cycling of GA metabolites. The optimized model explained most of the interindividual variance, observed in the clinical study, and adequately described data from the literature. CONCLUSIONS: Preclinical information on GD kinetics could be incorporated in the human PBPK model. Model simulations demonstrate that especially in subjects with prolonged gastrointestinal residence times, GA may accumulate after repeated licorice consumption, thus increasing the health risk of this specific subgroup of individuals.


Assuntos
Anti-Infecciosos/farmacocinética , Circulação Êntero-Hepática/fisiologia , Ácido Glicirrízico/farmacocinética , Adulto , Algoritmos , Anti-Infecciosos/efeitos adversos , Área Sob a Curva , Biotransformação , Simulação por Computador , Estudos Cross-Over , Feminino , Ácido Glicirrízico/efeitos adversos , Humanos , Masculino , Modelos Biológicos , Reprodutibilidade dos Testes
13.
Toxicol Appl Pharmacol ; 158(3): 261-8, 1999 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-10438659

RESUMO

Neurodegenerative properties of acrylamide were studied in vitro by exposure of differentiated SH-SY5Y human neuroblastoma cells for 72 h. The number of neurites per cell and the total cellular protein content were determined every 24 h throughout the exposure and the subsequent 96-h recovery period. Using kinetic data on the metabolism of acrylamide in rat, a biokinetic model was constructed in which the in vitro toxicity data were integrated. Using this model, we estimated the acute and subchronic toxicity of acrylamide for the rat in vivo. These estimations were compared to experimentally derived lowest observed effect doses (LOEDs) for daily intraperitoneal exposure (1, 10, 30, and 90 days) to acrylamide. The estimated LOEDs differed maximally twofold from the experimental LOEDs, and the nonlinear response to acrylamide exposure over time was simulated correctly. It is concluded that the integration of the present in vitro toxicity data with kinetic data gives adequate estimates of acute and subchronic neurotoxicity resulting from acrylamide exposure.


Assuntos
Acrilamida/farmacocinética , Acrilamida/toxicidade , Algoritmos , Animais , Contagem de Células/efeitos dos fármacos , Simulação por Computador , Humanos , Cinética , Modelos Biológicos , Neuritos/efeitos dos fármacos , Neuroblastoma , Ratos , Células Tumorais Cultivadas
14.
Compend Contin Educ Dent Suppl ; (25): S42-54; quiz S74, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-11908396

RESUMO

Negative effects of rapid, high-intensity resin curing have been predicted for both argon lasers and plasma-arc curing lights. To address these questions, six different resin restorative materials were cured with 14 different resin curing lights representing differences in intensities ranging from 400 mW/cm2 to 1,900 mW/cm2; delivery modes using constant, ramped, and stepped methods; cure times ranging from 1 second to 40 seconds; and spot sizes of 6.7 mm to 10.9 mm. Two lasers, five plasma-arc lights, and seven halogen lights were used. Shrinkage, modulus, heat generation, strain, and physical changes on the teeth and resins during strain testing were documented. Results showed effects associated with lights were not statistically significant, but resin formulation was highly significant. Microfill resins had the least shrinkage and the lowest modulus. An autocure resin had shrinkage and modulus as high as or higher than the light-cured hybrid resins. Lasers and plasma-arc lights produced the highest heat increases on the surface (up to 21 degrees C) and within the resin restorations (up to 14 degrees C), and the halogen lights produced the most heat within the pulp chamber (up to 2 degrees C). Strain within the tooth was least with Heliomolar and greatest with Z100 Restorative and BISFIL II autocure resin. Clinical effects of strain relief were evident as white lines at the tooth-resin interface and cracks in enamel adjacent to the margins. This work implicates resin formulation, rather than light type or curing mode, as the important factor in polymerization problems. Lower light intensity and use of ramped and stepped curing modes did not provide significant lowering of shrinkage, modulus, or strain, and did not prevent enamel cracking adjacent to margins and formation of "white line" defects at the margins. Until materials with lower shrinkage and modulus are available, use of low-viscosity surface sealants as a final step in resin placement is suggested to seal defects.


Assuntos
Resinas Compostas/química , Resinas Compostas/efeitos da radiação , Resinas Acrílicas/química , Resinas Acrílicas/efeitos da radiação , Análise de Variância , Esmalte Dentário/lesões , Equipamentos Odontológicos , Análise do Estresse Dentário , Elasticidade , Dureza , Temperatura Alta , Humanos , Lasers , Luz , Modelos Logísticos , Polímeros/química , Polímeros/efeitos da radiação , Poliuretanos/química , Poliuretanos/efeitos da radiação , Cimentos de Resina/química , Cimentos de Resina/efeitos da radiação , Dióxido de Silício/química , Dióxido de Silício/efeitos da radiação , Estatísticas não Paramétricas , Estresse Mecânico , Tecnologia Odontológica/instrumentação , Zircônio/química , Zircônio/efeitos da radiação
17.
Neth J Med ; 38(3-4): 122-5, 1991 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1881498

RESUMO

A woman is reported with a ten-year history of nonspecific chest pain. Bone scintigraphy showed increased local uptake, suggesting isolated sternal osteomyelitis. Radiographic investigations were positive 18 months later. Cultures of needle aspirations of the sternal bone marrow isolated Mycobacterium fortuitum as well as Mycobacterium simiae. Due to its indolent nature, nontuberculous mycobacterial disease is easily missed, especially in non-compromised hosts.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Osteomielite/microbiologia , Adulto , Doença Crônica , Quimioterapia Combinada , Feminino , Ácido Fusídico/uso terapêutico , Humanos , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Osteomielite/tratamento farmacológico , Pirazinamida/uso terapêutico , Esterno
18.
J Am Dent Assoc ; 119(4): 493-505, 1989 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-2507609

RESUMO

Thirty-nine products representing six categories of disinfectants (alcohols, chlorines, dilute glutaraldehydes, iodophors, phenolics, and quaternary ammonium compounds) were first tested in the absence of bioburden, using four test methods with five test organisms. Products that performed best were retested with the same methods and organisms in the presence of both serum and whole blood, using 3- and 10-minute contact times. Only products containing high ethyl alcohol had consistently high antimicrobial activity regardless of the test method, test organism, or contact time used both in the absence and presence of bioburden. Although these specific formulations demonstrated ability to penetrate and inactivate high concentrations of microorganisms within heavy bioburden, optimum disinfection of environmental surfaces is highly formulation dependent. Other products tested showed deficiencies that contraindicate their use as environmental surface disinfectants in clinical dental settings.


Assuntos
Bactérias/efeitos dos fármacos , Desinfetantes/farmacologia , Álcoois/farmacologia , Sangue , Contagem de Colônia Microbiana , Equipamentos Odontológicos , Desinfecção/métodos , Estudos de Avaliação como Assunto , Glutaral/farmacologia , Humanos , Iodóforos/farmacologia , Testes de Sensibilidade Microbiana/métodos , Fenóis/farmacologia , Compostos de Amônio Quaternário/farmacologia , Reprodutibilidade dos Testes , Projetos de Pesquisa , Hipoclorito de Sódio/farmacologia , Ensaio de Placa Viral
19.
Plant Physiol ; 72(4): 964-70, 1983 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16663147

RESUMO

A search for source leaf sucrose pools that differed in their relation to export was carried out in photosynthesizing leaves of Beta vulgaris L. The time course of depletion of [(14)C]sucrose in a leaf in unlabeled CO(2) following steady state labeling provided evidence for two distinct sucrose pools. After the start of the light period, leaf blade sucrose remained constant although it exchanged between the two pools. Newly synthesized sucrose destined for export passed through one pool more rapidly than through the other. All of the leaf blade sucrose appeared to exchange with export sucrose. Modeling and regression analysis of [(14)C]sucrose data provided a means for estimating the size of the two pools. From 20 to 40% of the sucrose was calculated to be present in the pool that provided the less direct path to export; this was likely vacuolar sucrose. The remainder of the sucrose in the blade was probably in the cytoplasm and veins. Added amounts of leaf blade sucrose, produced in response to elevated CO(2), appeared to be stored mainly in the vacuolar compartment.

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