Asunto(s)
Cosméticos/efectos adversos , Dermatitis Alérgica por Contacto/etiología , Dermatosis Facial/etiología , Octanoles/efectos adversos , Urticaria/etiología , Dermatitis Alérgica por Contacto/diagnóstico , Dermatosis Facial/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Octanoles/administración & dosificación , Pruebas del Parche , Cuidados de la Piel/efectos adversosRESUMEN
BACKGROUND: Interest in developing physically active pediculicides has identified new active substances. The objective was to evaluate a new treatment for clinical efficacy. METHODS AND FINDINGS: We describe the selection of 1,2-octanediol as a potential pediculicide. Clinical studies were community based. The main outcome measure was no live lice, after two treatments, with follow up visits over 14 days. Study 1 was a proof of concept with 18/20 (90%) participants cured. Study 2 was a multicentre, parallel, randomised, observer-blind study (520 participants) that compared 0.5% malathion liquid with 1,2-octanediol lotion (20% alcohol) applied 2-2.5 hours or 8 hours/overnight. 1,2-octanediol lotion was significantly (p<0.0005) more effective with success for 124/175 (70.9%) RRâ=â1.50 (97.5% CI, 1.22 to 1.85) for 2-2.5 hours, and 153/174 (87.9%) RRâ=â1.86 (97.5% CI, 1.54 to 2.26) for 8 hours/overnight compared with 81/171 (47.4%) for malathion. Study 3, a two centre, parallel, randomised, observer-blind study (121 participants), compared 1,2-octanediol lotion, 2-2.5 hours with 1,2-octanediol alcohol free mousse applied for 2-2.5 hours or 8 hours/overnight. The mousse applied for 8 hours/overnight cured 31/40 (77.5%), compared with 24/40 (60.0%) for lotion (RRâ=â1.29, 95% CI, 0.95 to 1.75; NNTâ=â5.7) but mousse applied for 2-2.5 hours 17/41 (41.5%) was less effective than lotion (RRâ=â0.69, 95% CI, 0.44 to 1.08). Adverse events were more common using 1,2-octanediol lotion at both 2-2.5 hours (12.0%, pâ=â0.001) and 8 hours/overnight (14.9%, p<0.0005), compared with 0.5% malathion (2.3%). Similar reactions were more frequent (p<0.045) using lotion compared with mousse. CONCLUSIONS: 1,2-octanediol was found to eliminate head louse infestation. It is believed to disrupt the insect's cuticular lipid, resulting in dehydration. The alcohol free mousse is more acceptable exhibiting significantly fewer adverse reactions. TRIAL REGISTRATIONS: Controlled-Trials.com ISRCTN66611560, ISRCTN91870666, ISRCTN28722846.
Asunto(s)
Infestaciones por Piojos/tratamiento farmacológico , Octanoles/uso terapéutico , Tensoactivos/uso terapéutico , Adolescente , Adulto , Animales , Niño , Preescolar , Femenino , Humanos , Masculino , Octanoles/administración & dosificación , Octanoles/efectos adversos , Pediculus , Tensoactivos/efectos adversosRESUMEN
Monoamines and neuropeptides interact to modulate behavioral plasticity in both vertebrates and invertebrates. In Caenorhabditis elegans behavioral state or "mood" is dependent on food availability and is translated by both monoaminergic and peptidergic signaling in the fine-tuning of most behaviors. In the present study, we have examined the interaction of monoamines and peptides on C. elegans aversive behavior mediated by a pair of polymodal, nociceptive, ASH sensory neurons. Food or serotonin sensitize the ASHs and stimulate aversive responses through a pathway requiring the release of nlp-3-encoded neuropeptides from the ASHs. Peptides encoded by nlp-3 appear to stimulate ASH-mediated aversive behavior through the neuropeptide receptor-17 (NPR-17) receptor. nlp-3- and npr-17-null animals exhibit identical phenotypes and animals overexpressing either nlp-3 or npr-17 exhibit elevated aversive responses off food that are absent when nlp-3 or npr-17 are overexpressed in npr-17- or nlp-3-null animals, respectively. ASH-mediated aversive responses are increased by activating either Galpha(q) or Galpha(s) in the ASHs, with Galpha(s) signaling specifically stimulating the release of nlp-3-encoded peptides. In contrast, octopamine appears to inhibit 5-HT stimulation by activating Galpha(o) signaling in the ASHs that, in turn, inhibits both Galpha(s) and Galpha(q) signaling and the release of nlp-3-encoded peptides. These results demonstrate that serotonin and octopamine reversibly modulate the activity of the ASHs, and highlight the utility of the C. elegans model for defining interactions between monoamines and peptides in individual neurons of complex sensory-mediated circuits.
Asunto(s)
Monoaminas Biogénicas/fisiología , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiología , Neuropéptidos/metabolismo , Nociceptores/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Reacción de Prevención/efectos de los fármacos , Reacción de Prevención/fisiología , Monoaminas Biogénicas/metabolismo , Caenorhabditis elegans/citología , Caenorhabditis elegans/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gs/metabolismo , Nociceptores/efectos de los fármacos , Octanoles/efectos adversos , Octopamina/farmacología , Serotonina/farmacologíaRESUMEN
OBJECTIVES: The study examined acute neurobehavioral effects provoked by controlled exposure to 1-octanol and isopropanol among male volunteers. METHODS: In a 29-m3 exposure laboratory, 24 male students (mean age 25.8 years) were exposed to 1-octanol and isopropanol. Each substance was used in two concentrations (0.1 and 6.4 ppm for 1-octanol; 34.9 and 189.9 ppm for isopropanol:). In a crossover design, each subject was exposed for 4 hours to the conditions. Twelve subjects reported enhanced chemical sensitivity; the other 12 were age-matched controls. At the onset and end of the exposures neurobehavioral tests were administered and symptoms were rated. RESULTS: At the end of the high and low isopropanol exposures the tiredness ratings were elevated, but no dose-dependence could be confirmed. For both substances and concentrations, the annoyance ratings increased during the exposure, but only for isopropanol did the increase show a dose-response relation. The subjects reported olfactory symptoms during the exposure to the high isopropanol and both 1-octanol concentrations. Isopropanol provoked no sensory irritation, whereas high 1-octanol exposure slightly enhanced it. Only among the subjects with enhanced chemical sensitivity were both 1-octanol concentrations associated with a stronger increase in annoyance, and lower detection rates were observed in a divided attention task. CONCLUSIONS: Previous studies reporting no neurobehavioral effects for isopropanol (up to 400 ppm) were confirmed. The results obtained for 1-octanol lacked dose-dependency, and their evaluation, is difficult. The annoying odor of 1-octanol may mask sensory irritation and prevent subjects with enhanced chemical sensitivity from concentrating on performance in a demanding task.
Asunto(s)
2-Propanol/efectos adversos , Contaminantes Ocupacionales del Aire/efectos adversos , Síntomas Conductuales/inducido químicamente , Síndromes de Neurotoxicidad/etiología , Octanoles/efectos adversos , 2-Propanol/farmacología , Adulto , Atención , Técnicas de Laboratorio Clínico , Estudios de Cohortes , Humanos , Masculino , Modelos Teóricos , Sensibilidad Química Múltiple , Análisis Multivariante , Pruebas Neuropsicológicas , Síndromes de Neurotoxicidad/fisiopatología , Octanoles/farmacología , Valores de Referencia , Medición de Riesgo , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Halothane more so than isoflurane potentiates an alpha1-adrenoceptor (alpha1-AR)-mediated action of epinephrine that abnormally slows conduction in Purkinje fibers and may facilitate reentrant arrhythmias. This adverse drug interaction was further evaluated by examining conduction responses to epinephrine in combination with thiopental and propofol, which "sensitize" or reduce the dose of epinephrine required to induce arrhythmias in the heart, and with etomidate, which does not, and responses to epinephrine with verapamil, lidocaine, and l-palmitoyl carnitine, a potential ischemic metabolite. METHODS: Action potentials and conduction times were measured in vitro using two microelectrodes in groups of canine Purkinje fibers stimulated at 150 pulses/min. Conduction was evaluated each minute after exposure to 5 microm epinephrine (or phenylephrine) alone or with the test drugs. Changes in the rate of phase 0 depolarization (Vmax) and the electrotonic spread of intracellular current were measured during exposure to epinephrine with octanol to evaluate the role of inhibition of active and passive (intercellular coupling) membrane properties in the transient depression of conduction velocity. RESULTS: Lidocaine (20 microm) and octanol (0.2 mm) potentiated alpha1-AR-induced conduction depression like halothane (0.4 mm), with maximum depression at 3-5 min of agonist exposure, no decrease of Vmax, and little accentuation at a rapid (250 vs. 150 pulses/min) stimulation rate. Thiopental (95 microm), propofol (50 microm), and verapamil (2 microm) similarly potentiated epinephrine responses, whereas etomidate (10 microm) did not. Between groups, the decrease of velocity induced by epinephrine in the presence of (10 microm) l-palmitoyl carnitine (-18%) was significantly greater than that resulting from epinephrine alone (-6%; 0.05 = P = 0.10). Current injection experiments were consistent with marked transient inhibition of cell-to-cell coupling correlating with alpha1-AR conduction depression in fibers exposed to octanol. CONCLUSIONS: Anesthetic "sensitization" to the arrhythmogenic effects of catecholamines may be a special case of a more general phenomenon by which not only some anesthetics and antiarrhythmic drugs but also possible ischemic fatty acid metabolites potentiate conduction depression due to acute alpha1-AR-mediated cell-to-cell uncoupling.
Asunto(s)
Anestésicos/farmacología , Corazón/inervación , Conducción Nerviosa/efectos de los fármacos , Ramos Subendocárdicos/efectos de los fármacos , Receptores Adrenérgicos alfa 1/efectos de los fármacos , Potenciales de Acción , Agonistas alfa-Adrenérgicos/efectos adversos , Agonistas alfa-Adrenérgicos/farmacología , Anestésicos/efectos adversos , Animales , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/fisiopatología , Perros , Sinergismo Farmacológico , Epinefrina/efectos adversos , Epinefrina/farmacología , Etomidato/efectos adversos , Etomidato/farmacología , Ácidos Grasos/metabolismo , Halotano/efectos adversos , Halotano/farmacología , Técnicas In Vitro , Lidocaína/efectos adversos , Lidocaína/farmacología , Conducción Nerviosa/fisiología , Octanoles/efectos adversos , Octanoles/farmacología , Palmitoilcarnitina/farmacología , Propofol/efectos adversos , Propofol/farmacología , Ramos Subendocárdicos/fisiología , Receptores Adrenérgicos alfa 1/fisiología , Tiopental/efectos adversos , Tiopental/farmacología , Verapamilo/efectos adversos , Verapamilo/farmacologíaRESUMEN
The authors investigated the ability/potencies of 3 microbial volatile organic compounds and a mixture of 5 microbial volatile organic compounds to cause eye and upper respiratory tract irritation (i.e., sensory irritation), with an animal bioassay. The authors estimated potencies by determining the concentration capable of decreasing the respiratory frequency of mice by 50% (i.e., the RD50 value). The RD50 values for 1-octen-3-ol, 3-octanol, and 3-octanone were 182 mg/m3 (35 ppm), 1359 mg/m3 (256 ppm), and 17586 mg/m3 (3360 ppm), respectively. Recommended indoor air levels calculated from the individual RD50 values for 1-octen-3-ol, 3-octanol, and 3-octanone were 100, 1000, and 13000 microg/m3, respectively-values considerably higher than the reported measured indoor air levels for these compounds. The RD50 value for a mixture of 5 microbial volatile organic compounds was also determined and found to be 3.6 times lower than estimated from the fractional concentrations and the respective RD50s of the individual components. The data support the conclusion that a variety of microbial volatile organic compounds may have some synergistic effects for the sensory irritation response, which constrains the interpretation and application of recommended indoor air levels of individual microbial volatile organic compounds. The results also showed that if a particular component of a mixture was much more potent than the other components, it may dominate the sensory irritation effect. With respect to irritation symptoms reported in moldy houses, the results of this study indicate that the contribution of microbial volatile organic compounds to these symptoms seems less than previously supposed.
Asunto(s)
Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire Interior , Oftalmopatías/inducido químicamente , Respiración/efectos de los fármacos , Enfermedades Respiratorias/inducido químicamente , Microbiología del Aire , Animales , Bioensayo , Relación Dosis-Respuesta a Droga , Hongos/metabolismo , Irritantes/efectos adversos , Cetonas/efectos adversos , Masculino , Ratones , Octanoles/efectos adversosRESUMEN
A patient with chronic constipation developed liver injury and leukopenia following the ingestion of Doxidan, a combination drug consisting of danthron and dioctyl calcium sulfosuccinate. Evidence is presented that dioctyl calcium sulfosuccinate may have potentiated the toxicity. The liver injury was associated with deposition of IgE in the Kupffer cells. The mechanism of toxicity remains unclear.