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1.
Arch Dis Child Fetal Neonatal Ed ; 103(1): F55-F58, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28588125

RESUMO

OBJECTIVE: The aims of this study is to measure the ethanol vapours in the isolette after use of hands cleaned with ethanol-based hand sanitiser (EBHS). METHODS: Two squirts (1.5 mL) of hand sanitiser were rubbed on hands for 10 or 20 s before inserting the hands in the isolette for 5 min. Ethanol vapours were measured in the isolette with photoionisation detector and alcohol breathalyser for 30 min. RESULTS: Peak ethanol concentration in the isolette was considerably higher with a 10 s hand rub (381±192 ppm) compared with a 20 s hand rub (99±50 ppm), and dissipated to ≤5 ppm within 30 min. Under routine care, EBHS use by care providers exposes neonates in isolettes to 3.7-7.3 or 1.4-2.8 mg/kg ethanol per day with 10 or 20 s hand rubs, respectively. The expected blood level from average single exposure is 0.036 mg/dL with 10 s hand rub and may increase further with multiple exposures in a short period. CONCLUSION: Preterm neonates in the isolette are at risk of inadvertent exposure to ethanol. The expected blood alcohol level from this exposure is small and below 1 mg/dL level recommended by European Medicines Agency to limit the ethanol exposure in children. The unintended ethanol exposure can be avoided by rubbing hands for at least 20 s after applying EBHS.


Assuntos
Etanol/efeitos adversos , Higienizadores de Mão/efeitos adversos , Incubadoras para Lactentes/normas , Exposição por Inalação , Anti-Infecciosos Locais/efeitos adversos , Anti-Infecciosos Locais/sangue , Anti-Infecciosos Locais/química , Anti-Infecciosos Locais/farmacologia , Etanol/sangue , Etanol/química , Etanol/farmacologia , Desinfecção das Mãos/métodos , Desinfecção das Mãos/normas , Higienizadores de Mão/química , Higienizadores de Mão/farmacologia , Humanos , Recém-Nascido , Exposição por Inalação/efeitos adversos , Exposição por Inalação/análise , Exposição por Inalação/prevenção & controle , Unidades de Terapia Intensiva Neonatal/organização & administração , Unidades de Terapia Intensiva Neonatal/normas , Fatores de Risco , Gestão de Riscos , Estados Unidos , Volatilização
2.
Biochem Med (Zagreb) ; 27(2): 398-403, 2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28694729

RESUMO

INTRODUCTION: This study aimed to establish whether an alcoholic antiseptic, wiped or not before venipuncture, may jeopardize alcohol testing with a commercial enzymatic assay and a reference head-space gas chromatography (GC) technique. MATERIALS AND METHODS: Venous blood was collected from 23 healthy volunteers, with two sequential procedures. In the first blood collection, 2 mL of alcoholic antiseptic (0.5% chlorhexidine, 70% ethanol) were place on a gauge pad, the venipuncture site of right arm was cleaned but the antiseptic was not let to dry before phlebotomy. In the second blood collection, 2 mL of the same alcoholic antiseptic were placed on another gauge pad, the venipuncture site of left harm was cleaned and the antiseptic was accurately cleansed before phlebotomy. Ethanol was measured with a reference GC technique in whole blood and EDTA plasma, and a commercial enzymatic assay in EDTA plasma. RESULTS: No subject complained about feeling a particular itchy sensation when the alcohol was not wiped before puncturing the vein. The concentration of alcohol in all EDTA plasma samples was always lower than the limit of detection of the enzymatic assay (i.e., 2.2 mmol/L; 0.1 g/L). Similarly, alcohol concentration was also undetectable using a reference GC technique (i.e., < 0.22 mmol/L; 0.01 g/L) in EDTA plasma and whole blood. CONCLUSION: It seems reasonable to conclude that using ethanol-containing antiseptics before venipuncture may not be causes of spurious or false positive results of alcohol measurement at least when ideal venipunctures can be performed.


Assuntos
Coleta de Amostras Sanguíneas/métodos , Cromatografia Gasosa/métodos , Ensaios Enzimáticos/métodos , Etanol/administração & dosagem , Etanol/sangue , Flebotomia/métodos , Adulto , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/sangue , Antissepsia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco
3.
Pharm Res ; 34(11): 2260-2269, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28748398

RESUMO

PURPOSE: To evaluate the potential of levofloxacin intranasal administration as a promising alternative approach to treat local infections such as chronic rhinosinusitis, by delivering drug concentrations directly to the site of infection. METHODS: Drug concentrations were measured in plasma, olfactory bulb and nasal mucosa of anterior (ANM) and posterior regions after intranasal (0.24 mg/kg) and intravenous (10 mg/kg) administration to rats, and pharmacokinetic parameters were compared between routes. For intranasal administration a thermoreversible in-situ gel was used. RESULTS: Plasma and olfactory bulb exposure to levofloxacin was minimal following intranasal dose, preventing systemic and central nervous system adverse effects. Levofloxacin concentration-time profile in ANM revealed higher concentrations during the first 60 min of the study following intranasal administration than the corresponding ones obtained after intravenous administration. A rapid and continuous decay of levofloxacin concentration in this nasal region was observed after intranasal delivery, resulting in much lower values at the last sampling time-points. CONCLUSION: The higher dose-normalized concentrations and pharmacokinetic exposure parameters of levofloxacin in ANM after intranasal administration, demonstrates that intranasal delivery of the formulated gel is, by itself, advantageous for delivering levofloxacin to biophase and thus an attractive approach in management of chronic rhinosinusitis.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/farmacocinética , Levofloxacino/administração & dosagem , Levofloxacino/farmacocinética , Administração Intranasal , Animais , Anti-Infecciosos Locais/efeitos adversos , Anti-Infecciosos Locais/sangue , Encéfalo/metabolismo , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Géis , Humanos , Levofloxacino/efeitos adversos , Levofloxacino/sangue , Masculino , Mucosa Nasal/metabolismo , Mucosa Olfatória/metabolismo , Estudo de Prova de Conceito , Ratos Wistar
4.
Neurotoxicol Teratol ; 51: 45-51, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26247661

RESUMO

CONTEXT: The developing brain is vulnerable to iodine deficiency (ID) and environmental neuro-toxicants. OBJECTIVES: To assess neurocognitive development of children whose mothers have received (or not) iodine supplementation during pregnancy, in an area of borderline ID, while assessing in utero exposure to environmental neuro-toxicants. DESIGN/PATIENTS: Among 86 children born from normal euthyroid women who participated in our prospective interventional study on iodine supplementation (150 µg/day) started early in pregnancy, 44 (19 with iodine supplementation, 25 controls) were assessed at two years using the Bayley test. Information on parents' education and habits (smoking), and on child development was recorded. Thyroid tests at each trimester of pregnancy and on cord blood (CB) were available, as well as milk concentrations of selected environmental compounds known for their neurotoxicity, including heavy metals and PCBs. RESULTS: There was no difference in Bayley tests for children born to mothers with and without iodine supplementation, but sample size was small. Language and Social-Emotional Scales were negatively correlated with TBG at all times tested, while PCB 118 correlated negatively with all Language scales. Among maternal and CB thyroid tests, only CB thyroglobulin, the best marker of iodine status, correlated (negatively) with neurodevelopment scales (Motor and Expressive Language). CONCLUSIONS: This pilot study suggests that PCB118 has a negative impact on neurocognitive development, possibly mitigating the benefit of iodine supplementation in an area of borderline ID. We propose that exposure to environmental neurotoxicants should be taken into account when designing studies on the benefit of iodine supplementation in pregnancy. The potential interactions between TBG, environmental neurotoxicants and brain development warrant further studies.


Assuntos
Anti-Infecciosos Locais/toxicidade , Deficiências do Desenvolvimento/etiologia , Suplementos Nutricionais/toxicidade , Iodo/toxicidade , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Adulto , Anti-Infecciosos Locais/sangue , Estudos de Coortes , Deficiências do Desenvolvimento/diagnóstico , Feminino , Humanos , Iodo/sangue , Masculino , Testes Neuropsicológicos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Estatística como Assunto , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto Jovem
5.
J Perinatol ; 33(10): 768-71, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23702618

RESUMO

OBJECTIVE: To assess chlorhexidine absorption and skin tolerability in premature infants, following skin antisepsis with 2% aqueous chlorhexidine gluconate (CHG) prior to peripherally inserted central catheter (PICC) placement. STUDY DESIGN: Neonates less than 32 weeks gestation had skin cleansed with CHG prior to PICC placement. CHG concentrations were measured on serial blood samples. Skin integrity was evaluated for 2 weeks after CHG exposure. RESULT: Twenty infants were enrolled; median gestational age was 28 2/7 weeks (range 24 3/7 to 31 4/7). Ten infants had detectable serum chlorhexidine concentrations (range 1.6 to 206 ng ml(-1)). Seven of these infants had their highest serum concentration 2 to 3 days following exposure. No CHG-related skin irritation occurred in any infant. CONCLUSION: CHG was detected in the blood of preterm infants receiving CHG skin antisepsis for PICC insertion. Highest serum concentrations occurred 2 to 3 days after exposure. Further investigation is needed to determine the clinical relevance of CHG absorption in preterm infants.


Assuntos
Anti-Infecciosos Locais/farmacocinética , Antissepsia , Cateterismo Periférico , Clorexidina/análogos & derivados , Recém-Nascido Prematuro , Absorção Cutânea/efeitos dos fármacos , Absorção , Anti-Infecciosos Locais/sangue , Antissepsia/métodos , Clorexidina/sangue , Clorexidina/farmacocinética , Cromatografia Líquida , Feminino , Humanos , Cuidado do Lactente , Recém-Nascido , Masculino , Projetos Piloto , Espectrometria de Massas em Tandem
6.
J Clin Periodontol ; 40(2): 155-62, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23305133

RESUMO

AIM: The aim of this randomized controlled clinical trial was to evaluate the clinical effects of chlorhexidine (CHX) application in a full-mouth disinfection (FMD) protocol in poorly controlled type-2 diabetic subjects with generalized chronic periodontitis. MATERIAL AND METHODS: Thirty-eight subjects were randomly assigned into FMD group (n=19): full-mouth scaling and root planing (FMSRP) within 24 h + local application of CHX gel + CHX rinses for 60 days or Control group (n = 19): FMSRP within 24 h + local application of placebo gel + placebo rinses for 60 days. Clinical parameters, glycated haemoglobin and fasting plasma glucose were assessed at baseline, 3, 6 and 12 months post-therapies. RESULTS: All clinical parameters improved significantly at 3, 6 and 12 months post-therapies for both groups (p < 0.05). There were no significant differences between groups for any clinical parameters, and glycemic condition at any time-point (p > 0.05). CONCLUSIONS: The treatments did not differ with respect to clinical parameters, including the primary outcome variable (i.e. changes in clinical attachment level in deep pockets), for up to 12 months post-treatments.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Clorexidina/uso terapêutico , Periodontite Crônica/complicações , Periodontite Crônica/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Adulto , Idoso , Análise de Variância , Anti-Infecciosos Locais/sangue , Raspagem Dentária , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Géis , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Perda da Inserção Periodontal/patologia , Estudos Prospectivos , Método Simples-Cego , Estatísticas não Paramétricas , Resultado do Tratamento
7.
Chemosphere ; 87(7): 825-7, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22273184

RESUMO

The antibacterial triclocarban (TCC) concentrates in the cellular fraction of blood. Consequently, plasma levels are at least two-fold lower than the TCC amount present in blood. Utilizing whole blood sampling, a low but significant absorption of TCC from soap during showering is demonstrated for a small group of human subjects.


Assuntos
Anti-Infecciosos Locais/sangue , Análise Química do Sangue/métodos , Carbanilidas/sangue , Animais , Exposição Ambiental/análise , Masculino , Camundongos
8.
Toxicology ; 286(1-3): 69-74, 2011 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-21635932

RESUMO

3,4,4'-Trichlorocarbanilide (triclocarban, TCC) is widely used as an antimicrobial agent in a variety of consumer and personal care products. TCC is considered a potential endocrine disruptor, but its potential toxic effects in humans are still largely unknown. Because of its widespread uses, the potential for human exposure to TCC is high. In order to identify adequate exposure biomarkers of TCC, we investigated the metabolic profile of TCC in adult female Sprague Dawley rats after administering TCC once (500 mg/kg body weight) by oral gavage. Urine was collected 0-24 h before dosing, and 0-24 h and 24-48 h after dosing. Serum was collected at necropsy 48 h after dosing. We identified several metabolites of TCC in urine and serum by on-line solid phase extraction-high performance liquid chromatography-mass spectrometry. We unambiguously identified two major oxidative metabolites of TCC, 3'-hydroxy-TCC and 2'-hydroxy-TCC, by comparing their chromatographic behavior and mass spectral fragmentation patterns with those of authentic standards. By contrast, compared to these oxidative metabolites, we detected very low levels of TCC in the urine or serum. Taken together these data suggest that in rats, oxidation of TCC is a major metabolic pathway. We also measured TCC and its oxidative metabolites in 50 urine and 16 serum samples collected from adults in the United States. The results suggest differences in the metabolic profile of TCC in rats and in humans; oxidation appears to be a minor metabolic pathway in humans. Total (free plus conjugated) TCC could serve as a potential biomarker for human exposure to TCC.


Assuntos
Anti-Infecciosos Locais/metabolismo , Carbanilidas/metabolismo , Exposição Ambiental/efeitos adversos , Poluentes Químicos da Água/metabolismo , Animais , Anti-Infecciosos Locais/sangue , Anti-Infecciosos Locais/urina , Biomarcadores/sangue , Biomarcadores/urina , Carbanilidas/sangue , Carbanilidas/urina , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Espectrometria de Massas , Oxirredução , Ratos , Ratos Sprague-Dawley , Extração em Fase Sólida , Especificidade da Espécie , Fatores de Tempo , Poluentes Químicos da Água/sangue , Poluentes Químicos da Água/urina
9.
J Dairy Sci ; 94(4): 1738-43, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21426962

RESUMO

Despite the recent growth of the organic dairy industry, organic producers and veterinarians have limited information when choosing mastitis treatments for animals in organic dairy production. Organic producers commonly administer homeopathic or other plant-based products without having research evaluating the efficacy of these products and using estimated or no withholding times to treat mastitis and other health problems in their herds. In this pilot study, we attempted to identify several active ingredients of Phyto-Mast (Penn Dutch Cow Care, Narvon, PA), a plant-based mastitis treatment used on organic dairy farms, and to quantify the product residue in milk and plasma after intramammary administration. We developed an assay to quantify thymol (one of the active ingredients in Phyto-Mast) in milk and plasma using gas chromatography and mass spectrometry (GC-MS). Thymol is a volatile aromatic compound with antiinflammatory properties. As a model for dairy cows, 5 healthy, lactating alpine dairy goats were given 5 mL of Phyto-Mast per udder half. For 10 d following treatment, we analyzed blood and milk samples for thymol residues using GC-MS. The GC-MS assay was very sensitive for thymol detection, to a concentration of 0.01 µg/mL in plasma. Using thymol as a marker, Phyto-Mast was detectable and quantifiable in plasma beginning with the 15-min posttreatment sample, but was no longer detectable in the 4-h posttreatment sample. Thymol residues were only detected in the 12-h posttreatment milk sample. An inflammatory response was not evident in the udder following phytoceutical administration. Although this study provides information about the elimination of thymol, the product contains several other active chemicals, which may have different pharmacokinetic behaviors. Further analysis and additional study animals will help to determine a milk withholding time for Phyto-Mast. Given the recent growth of the organic dairy industry, understanding the pharmacokinetics of therapeutics used in organic production and developing accurate withholding recommendations will help to ensure milk safety.


Assuntos
Anti-Infecciosos Locais/análise , Resíduos de Drogas/análise , Glândulas Mamárias Animais/metabolismo , Mastite/veterinária , Leite/química , Fitoterapia/veterinária , Timol/análise , Angelica sinensis , Animais , Anti-Infecciosos Locais/sangue , Anti-Infecciosos Locais/uso terapêutico , Indústria de Laticínios/métodos , Vias de Administração de Medicamentos , Feminino , Gaultheria , Glycyrrhiza uralensis , Cabras , Mastite/tratamento farmacológico , Mastite/metabolismo , Projetos Piloto , Timol/sangue , Timol/uso terapêutico , Thymus (Planta)
10.
Environ Pollut ; 157(8-9): 2248-54, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19410343

RESUMO

The presence of triclosan, a widely-used antibacterial chemical, is currently unknown in higher trophic-level species such as marine mammals. Blood plasma collected from wild bottlenose dolphins (Tursiops truncatus) in Charleston, SC (CHS) (n = 13) and Indian River Lagoon, FL (IRL) (n = 13) in 2005 was analyzed for triclosan. Plasma concentrations in CHS dolphins ranged from 0.12 to 0.27 ng/g wet weight (mean 0.18 ng/g), with 31% of the sampled individuals having detectable triclosan. The mean IRL dolphin plasma concentrations were 0.072 ng/g wet weight (range 0.025-0.11 ng/g); 23% of the samples having detectable triclosan. In the CHS area, triclosan effluent values from two WWTP were both 190 ng/L and primary influents were 2800 ng/L and 3400 ng/L. Triclosan values in CHS estuarine surface water samples averaged 7.5 ng/L (n = 18) ranging from 4.9 to 14 ng/L. This is the first study to report bioaccumulation of anthropogenic triclosan in a marine mammal highlighting the need for further monitoring and assessment.


Assuntos
Golfinho Nariz-de-Garrafa/sangue , Triclosan/sangue , Poluentes Químicos da Água/sangue , Animais , Anti-Infecciosos Locais/análise , Anti-Infecciosos Locais/sangue , Oceano Atlântico , Monitoramento Ambiental , Feminino , Masculino , South Carolina , Triclosan/análise , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água/análise , Áreas Alagadas
11.
J Anal Toxicol ; 33(2): 85-91, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19239733

RESUMO

This paper presents the extraction and analysis of chlorhexidine (CHX) from whole blood using solid-phase extraction (SPE) together with high-performance liquid chromatography (HPLC). Blood samples, spiked with chlorpromazine used as an internal standard, were fortified with sodium acetate buffer and purified with Bakerbond C(18) SPE columns. The columns were washed, dried, and eluted with experimental optimized solvent systems. The HPLC was performed using a Capcell Pak C(18) MG column (4.6 x 250-mm) and monitored at 260 nm, using a UV detector. A mobile phase consisting of acetonitrile/water (40:60 v/v), containing 0.05% trifluoroacetic acid, 0.05% heptafluorobutyric acid, and 0.1% triethylamine, was employed. The assay was linear over the range of 0.05 to 2.0 microg/g and the limit of detection was 0.01 microg/g for CHX in whole blood. At the concentration range of 0.05 to 2.0 microg/g, the recoveries ranged from 72% to 85%, and the intra- and interday precision, expressed as coefficient of variation, were less than 11% and 13%, respectively. Kinetic characteristics following an intravenous infusion of a CHX product, Maskin solution, at a dose of 15 mg/kg in rats were evaluated using the present method. The kinetic profiles of CHX conformed to a two-compartment model with an alpha half-life (of distribution) at 0.05 h and a beta half-life (of elimination) at 0.55 h in rats. The method is simple and reliable for the determination of CHX in blood samples and could be expected to apply to forensic and clinical specimens.


Assuntos
Anti-Infecciosos Locais/sangue , Clorexidina/sangue , Toxicologia Forense/métodos , Animais , Anti-Infecciosos Locais/farmacocinética , Anti-Infecciosos Locais/intoxicação , Área Sob a Curva , Clorexidina/farmacocinética , Clorexidina/intoxicação , Cromatografia Líquida de Alta Pressão , Meia-Vida , Infusões Intravenosas , Masculino , Taxa de Depuração Metabólica , Intoxicação/sangue , Ratos , Ratos Sprague-Dawley , Padrões de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Extração em Fase Sólida
12.
Am J Infect Control ; 37(4): 318-21, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-18945516

RESUMO

BACKGROUND: Alcohol hand gels (AHG) have been used by children in child day care centers (CDCCs) to prevent the transmission of microbes. Because parents and personnel have been concerned about the safety of AHGs, we conducted a trial to assess this. METHODS: A total of 82 children age 3.5 to 7.2 years (mean, 5.7 years) at 2 CDCCs rubbed their hands with AHG. Alcohol concentrations in expiratory air were measured using an official police alcometer after 15 and 60 minutes. We also conducted a questionnaire survey asking how commonly AHGs were used in CDCCs, obtaining 128 answers from 68 CDCCs (with more than 1 person responding in 6 CDCCs). RESULTS: All of the alcometer readings were < 0.01 per thousand, although up to 30 contacts with the mucous membranes (mean, 2.4) occurred during the first 15 minutes. An AHG was used in all 68 CDCCs, but only by adults at 11 of them. The most common occasions for using an AHG were before serving food and after cleaning secretions. One case of fire occurred when a worker lit a fire while his hands were covered with AHG. Personnel were most concerned about situations in which children put their fingers into their mouth or eyes after using an AHG. CONCLUSION: The use of an AHG in CDCCs is safe. Even though children tend to put their hands into their mouth after disinfection, no significant amount of alcohol is absorbed.


Assuntos
Anti-Infecciosos Locais/efeitos adversos , Desinfecção/métodos , Etanol/efeitos adversos , Géis/efeitos adversos , Desinfecção das Mãos/métodos , Anti-Infecciosos Locais/sangue , Anti-Infecciosos Locais/farmacocinética , Testes Respiratórios , Criança , Creches , Pré-Escolar , Qualidade de Produtos para o Consumidor , Etanol/sangue , Etanol/farmacocinética , Feminino , Humanos , Masculino , Fatores de Risco , Absorção Cutânea , Inquéritos e Questionários
13.
Anaesthesist ; 58(2): 149-52, 2009 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-18825351

RESUMO

Isopropanol is an ingredient of commonly used industrial and household agents. Intoxication can occur unintentionally, in suicide attempts or by alcohol abusers when used as a substitute for ethanol. Symptoms involve the gastrointestinal tract, the central nervous system, and the cardiovascular system at higher doses. Mortality is especially high in patients with deep coma and marked hypotension. This report describes a case of life-threatening isopropanol intoxication of a prison inmate successfully treated by haemodialysis.


Assuntos
2-Propanol/intoxicação , Anti-Infecciosos Locais/intoxicação , 2-Propanol/sangue , Anti-Infecciosos Locais/sangue , Cuidados Críticos , Serviços Médicos de Emergência , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Intoxicação/diagnóstico , Intoxicação/terapia
14.
PLoS Med ; 5(8): e157; discussion e157, 2008 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-18684007

RESUMO

BACKGROUND: The rectum is particularly vulnerable to HIV transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. In the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (ARV) drugs. To prevent mucosal transmission of HIV, a microbicide/ARV should ideally act locally at and near the virus portal of entry. As part of an integrated rectal microbicide development programme, we have evaluated rectal application of the nucleotide reverse transcriptase (RT) inhibitor tenofovir (PMPA, 9-[(R)-2-(phosphonomethoxy) propyl] adenine monohydrate), a drug licensed for therapeutic use, for protective efficacy against rectal challenge with simian immunodeficiency virus (SIV) in a well-established and standardised macaque model. METHODS AND FINDINGS: A total of 20 purpose-bred Indian rhesus macaques were used to evaluate the protective efficacy of topical tenofovir. Nine animals received 1% tenofovir gel per rectum up to 2 h prior to virus challenge, four macaques received placebo gel, and four macaques remained untreated. In addition, three macaques were given tenofovir gel 2 h after virus challenge. Following intrarectal instillation of 20 median rectal infectious doses (MID50) of a noncloned, virulent stock of SIVmac251/32H, all animals were analysed for virus infection, by virus isolation from peripheral blood mononuclear cells (PBMC), quantitative proviral DNA load in PBMC, plasma viral RNA (vRNA) load by sensitive quantitative competitive (qc) RT-PCR, and presence of SIV-specific serum antibodies by ELISA. We report here a significant protective effect (p = 0.003; Fisher exact probability test) wherein eight of nine macaques given tenofovir per rectum up to 2 h prior to virus challenge were protected from infection (n = 6) or had modified virus outcomes (n = 2), while all untreated macaques and three of four macaques given placebo gel were infected, as were two of three animals receiving tenofovir gel after challenge. Moreover, analysis of lymphoid tissues post mortem failed to reveal sequestration of SIV in the protected animals. We found a strong positive association between the concentration of tenofovir in the plasma 15 min after rectal application of gel and the degree of protection in the six animals challenged with virus at this time point. Moreover, colorectal explants from non-SIV challenged tenofovir-treated macaques were resistant to infection ex vivo, whereas no inhibition was seen in explants from the small intestine. Tissue-specific inhibition of infection was associated with the intracellular detection of tenofovir. Intriguingly, in the absence of seroconversion, Gag-specific gamma interferon (IFN-gamma)-secreting T cells were detected in the blood of four of seven protected animals tested, with frequencies ranging from 144 spot forming cells (SFC)/10(6) PBMC to 261 spot forming cells (SFC)/10(6) PBMC. CONCLUSIONS: These results indicate that colorectal pretreatment with ARV drugs, such as tenofovir, has potential as a clinically relevant strategy for the prevention of HIV transmission. We conclude that plasma tenofovir concentration measured 15 min after rectal administration may serve as a surrogate indicator of protective efficacy. This may prove to be useful in the design of clinical studies. Furthermore, in vitro intestinal explants served as a model for drug distribution in vivo and susceptibility to virus infection. The finding of T cell priming following exposure to virus in the absence of overt infection is provocative. Further studies would reveal if a combined modality microbicide and vaccination strategy is feasible by determining the full extent of local immune responses induced and their protective potential.


Assuntos
Adenina/análogos & derivados , Apresentação Cruzada/efeitos dos fármacos , Macaca/virologia , Organofosfonatos/farmacologia , Reto/virologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Linfócitos T/imunologia , Adenina/administração & dosagem , Adenina/sangue , Adenina/farmacologia , Animais , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/sangue , Anti-Infecciosos Locais/farmacologia , Formação de Anticorpos/efeitos dos fármacos , Géis , HIV-1/efeitos dos fármacos , HIV-1/isolamento & purificação , HIV-1/fisiologia , Células HeLa , Humanos , Interferon gama/metabolismo , Macaca/imunologia , Organofosfonatos/administração & dosagem , Organofosfonatos/sangue , Reto/efeitos dos fármacos , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vírus da Imunodeficiência Símia/fisiologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Linfócitos T/virologia , Tenofovir , Resultado do Tratamento , Replicação Viral/efeitos dos fármacos
15.
Pediatr Infect Dis J ; 27(6): 505-11, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18449064

RESUMO

BACKGROUND: Chlorhexidine skin cleansing might substantially reduce neonatal infection and mortality in developing countries. Few data exist on the impact of chlorhexidine cleansing on skin colonization of infants during the first day of life or on the absorption potential of chlorhexidine during newborn skin cleansing. METHODS: Hospital-born newborns in Kathmandu, Nepal were randomly allocated to full-body skin cleansing with 0.25%, 0.50%, or 1.00% chlorhexidine solution. Skin swabs were collected from the axilla, inguinal, and peri-umbilical areas before cleansing (baseline), and at 2 and 24 hours after treatment. Skin flora was quantified and organisms identified. In a subsample, heel prick blood was collected 24 hours after the cleansing and percutaneous absorption of chlorhexidine was assessed. RESULTS: Among 286 enrolled newborns, no adverse effects on skin were reported and body temperature was minimally reduced (mean reduction, 0.33 degrees C). In all groups, positive skin culture rates were significantly reduced at 2 hours but generally not at 24 hours; greater reductions were observed with higher concentrations of chlorhexidine. Effect at 24 hours was highest in the 1.00% group (37% lower positive skin culture rate). For 15 of 75 infants with heel pricks, chlorhexidine was detected at trace concentrations (<8 ng/mL, n = 14; 25.8 ng/mL, n = 1). CONCLUSIONS: Chlorhexidine skin cleansing seemed safe and reduced skin flora in newborns in a dose-dependent manner 2 hours after treatment. Greater residual effect at the highest concentration (1%) might provide broader benefit and may simplify combined maternal and neonatal regimens by matching the concentration used for vaginal cleansing during labor.


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Bactérias/isolamento & purificação , Clorexidina/uso terapêutico , Dermatopatias Bacterianas/prevenção & controle , Pele/microbiologia , Anti-Infecciosos Locais/efeitos adversos , Anti-Infecciosos Locais/sangue , Bactérias/classificação , Análise Química do Sangue , Clorexidina/efeitos adversos , Clorexidina/sangue , Contagem de Colônia Microbiana , Feminino , Hospitais , Humanos , Recém-Nascido , Masculino , Mães , Nepal
16.
Sci Total Environ ; 393(1): 162-7, 2008 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-18207219

RESUMO

The bactericide triclosan has found wide-spread use in e.g. soaps, deodorants and toothpastes. Recent in vitro and in vivo studies indicate that triclosan might exert adverse effects in humans. Triclosan has previously been shown to be present in human plasma and milk at concentrations that are well correlated to the use of personal care products containing triclosan. In this study we investigated the influence of age, gender, and the region of residence on triclosan concentrations in pooled samples of Australian human blood serum. The results showed no influence of region of residence on the concentrations of triclosan. There was a small but significant influence of age and gender on the serum triclosan concentrations, which were higher in males than in females, and highest in the group of 31-45 year old males and females. However, overall there was a lack of pronounced differences in the triclosan concentrations within the dataset, which suggests that the exposure to triclosan among different groups of the Australian population is relatively homogenous. A selection of the dataset was compared with previous measurements of triclosan concentrations in human plasma from Sweden, where the use of triclosan is expected to be low due to consumer advisories. The triclosan concentrations were a factor of 2 higher in Australian serum than in Swedish plasma.


Assuntos
Anti-Infecciosos Locais/sangue , Triclosan/sangue , Adolescente , Adulto , Austrália , Criança , Pré-Escolar , Monitoramento Ambiental , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Suécia
17.
BMC Infect Dis ; 7: 117, 2007 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-17927841

RESUMO

BACKGROUND: Despite the increasing promotion of alcohol-based hand rubs and the worldwide use of ethanol-based hand rubs in hospitals only few studies have specifically addressed the issue of ethanol absorption when repeatedly applied to human skin. The aim of this study was to assess if ethanol absorption occurs during hygienic and surgical hand disinfection using three different alcohol-based hand-rubs, and to quantify absorption levels in humans. METHODS: Twelve volunteers applied three hand-rubs containing 95% (hand-rub A), 85% (hand-rub B) and 55% ethanol (hand-rub C; all w/w). For hygienic hand disinfection, 4 mL were applied 20 times for 30 s, with 1 minute break between applications. For surgical hand disinfection, 20 mL of each hand rub was applied to hands and arms up to the level of the elbow 10 times for 3 minutes, with a break of 5 minutes between applications. Blood concentrations of ethanol and acetaldehyde were determined immediately prior and up to 90 minutes after application using head space gas chromatography. RESULTS: The median of absorbed ethanol after hygienic hand disinfection was 1365 mg (A), 630 mg (B), and 358 mg (C). The proportion of absorbed ethanol was 2.3% (A), 1.1% (B), and 0.9% (C). After surgical hand disinfection, the median of absorbed ethanol was 1067 mg (A), 1542 mg (B), and 477 mg (C). The proportion of absorbed ethanol was 0.7% (A), 1.1% (B), and 0.5% (C). The highest median acetaldehyde concentration after 20 hygienic hand disinfections was 0.57 mg/L (hand-rub C, after 30 min), after 10 surgical hand disinfections 3.99 mg/L (hand-rub A, after 20 minutes). CONCLUSION: The overall dermal and pulmonary absorption of ethanol was below toxic levels in humans and allows the conclusion that the use of the evaluated ethanol-based hand-rubs is safe.


Assuntos
Anti-Infecciosos Locais/química , Etanol/química , Absorção , Acetaldeído/sangue , Administração Cutânea , Adulto , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/sangue , Desinfecção , Etanol/administração & dosagem , Etanol/sangue , Feminino , Mãos , Desinfecção das Mãos , Humanos , Masculino , Pele
18.
J Vet Pharmacol Ther ; 30(4): 358-65, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17610410

RESUMO

The recently recognized potential of sodium chlorate as a possible preharvest food safety tool for pathogen reduction in meat animals has spurred interest in the pharmacokinetics of intraruminally dosed chlorate. Six Loala cattle were assigned (one heifer and one steer per treatment) to one of three intraruminal doses of radiolabeled sodium [36Cl]chlorate (21, 42, or 63 mg/kg body weight) administered in four equal aliquots over a 24-h period. Blood and serum were collected (29 samples in 48 h). Total radioactive residues were measured and the radioactive moieties were speciated. Chlorate appeared rapidly in blood and serum after dosing. For animals administered a dose of 42 or 63 mg/kg, the half-life of absorption was estimated at 0.6-0.9 h. Serum chlorate concentrations progressively increased with aliquot administration until peaking at 6-21 parts per million at 26 h. Between aliquot administrations, serum chlorate levels typically peaked in 3.5 h or less. The half-life of chlorate elimination ranged between 6.9 and 11 h, depending on the dose. Ultimately, absorption of chlorate removes it from its desired site of action, the lower gastrointestinal tract, thereby reducing its efficacy. Further research is needed to develop a chlorate formulation that will allow passage to the lower gastrointestinal tract.


Assuntos
Anti-Infecciosos Locais/farmacocinética , Bovinos/metabolismo , Cloratos/farmacocinética , Administração Oral , Animais , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/sangue , Área Sob a Curva , Cloratos/administração & dosagem , Cloratos/sangue , Cloro/administração & dosagem , Cloro/sangue , Cloro/farmacocinética , Feminino , Masculino , Carne , Radioisótopos/administração & dosagem , Radioisótopos/sangue , Radioisótopos/farmacocinética , Rúmen
19.
Antimicrob Agents Chemother ; 51(3): 1107-8, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17194820

RESUMO

We assessed cutaneous ethanol (ETOH) and isopropanol (ISOP) absorption after intensive (30 times per h) use of alcohol-based hand-rub solutions by healthcare workers (HCWs). ETOH was detectable in the breath of 6/20 HCWs (0.001 to 0.0025%) at 1 to 2 min postexposure and in the serum of 2/20 HCWs at 5 to 7 min postexposure. Serum ISOP levels were unrecordable at all time points.


Assuntos
Anti-Infecciosos Locais/sangue , Anti-Infecciosos Locais/farmacocinética , Etanol/sangue , Etanol/farmacocinética , 2-Propanol/farmacocinética , Administração Tópica , Adulto , Idoso , Anti-Infecciosos Locais/administração & dosagem , Cromatografia Gasosa , Etanol/administração & dosagem , Feminino , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Absorção Cutânea
20.
Am J Emerg Med ; 24(7): 815-7, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17098103

RESUMO

BACKGROUND: Ethanol-based hand sanitizers (EBHSs) are used in most health care facilities in the United States. Infection control personnel advocate the use of generous quantities of EBHS before and after contact with patients. Although it is assumed that little systemic absorption of ethanol occurs during EBHS use, many alcohols are absorbed to varying degrees via the transdermal route. Ethanol intoxication by employees in the medical workplace is a potentially serious finding, and it is of forensic and medical-legal importance to elucidate the effects of frequent use of EBHS upon serum blood ethanol levels (BELs). To investigate the effect of frequent use of EBHS upon serum blood ethanol concentrations, we prospectively studied 5 volunteers undergoing frequent application of EBHS. METHODS: Enrolled subjects applied 5 mL of the product (62% denatured ethyl alcohol manufactured by Kimberley-Clark, Roswell, GA) to both hands and rubbed until dry. This activity was repeated 50 times over 4 hours. Participants had their blood drawn before as well as after completing the study. Each participant was without alcohol exposure during the 12 hours preceding the study. RESULTS: Five volunteers were enrolled. All had an initial blood ethanol level of less than 5 mg/dL. All 5 participants completed the 4-hour study. There were no noted adverse reactions during the study. Blood ethanol level upon completion of the 50 applications of EBHS was less than 5 mg/dL in all 5 study participants. CONCLUSION: The results of this study demonstrate that use of ethanol-based hand sanitizers, when frequently used in accordance with labeling, do not raise serum blood ethanol levels.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/sangue , Etanol/administração & dosagem , Etanol/sangue , Desinfecção das Mãos , Administração Cutânea , Adulto , Esquema de Medicação , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
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