Assessment of Labrasol/Labrafil/Transcutol (4/4/2, v/v/v) as a non-clinical vehicle for poorly water-soluble compounds after 4-week oral toxicity study in Wistar rats.

Drug safety research is frequently faced with the challenge of the selection of appropriate vehicles for use in in vivo non-clinical safety assessment studies. Reported here are the results of blend Labrasol, Labrafil and Transcutol, [L/L/T, (4/4/2, v/v/v)], excipients used as bioavailability enhancer and solubilizer for poorly water-soluble compounds and tested daily for 4 weeks by oral route in Wistar rats (10/sex/group) at dose volumes of 5, 10 or 20 mL/kg/day and compared to controls given 20 mL/kg/day of 1% (w/v) hydroxyethylcellulose in purified water. L/L/T was broadly well tolerated at 5 mL/kg/day and lethal at 20 mL/kg/day in 1 of 20 rats treated at this level. Changes in appearance and behaviour were observed from 10 mL/kg/day with volume-related incidence, severity and duration. Reduced feed intake observed from 5 (females) or 10 mL/kg/day (males) resulted in low bodyweights for high volume males only (-11% of controls). There was a volume-related induction of hepatic CYP 1A1/2, 2B1/2 and/or 2E1 subfamilies from 5 mL/kg/day, with high liver weight, centrilobular hepatocellular hypertrophy and high ALT, triglyceride and cholesterol serum values at 20 mL/kg/day. Renal tubular dilation in medulla, cortical cell degeneration/necrosis with granular material in adjacent glomerular spaces, crystal deposits in the inner medulla, papilla and/or renal pelvis, and tubular mineralization, associated with proteinuria and calcium oxalate crystalluria, were observed at 20 mL/kg/day as well as vacuolation in the adrenal cortex, with a sex-dependant localization. According to these results, 5 mL/kg/day was considered as an acceptable volume for further use of L/L/T (4/4/2, v/v/v) blend as a vehicle for poorly water soluble drugs in Wistar rat toxicity studies.

[Assessment of behavioral dependence with the Glover-Nilsson test in smoking cessation treatment]. / Evaluación de la dependencia psicológica mediante el test de Glover-Nilsson en el tratamiento del tabaquismo.

OBJECTIVE: To assess behavioral dependence using the Glover-Nilsson test and determine its association with successful smoking cessation. MATERIAL AND METHODS: An analytical longitudinal study was carried out, the target population of which consisted of smokers who enrolled in a smoking cessation clinic for treatment. The following variables were examined: age, sex, nicotine dependence (Fagerström test), psychoactive drug use, prior attempts at quitting, and behavioral dependence measured with the Glover-Nilsson test. The most recent version of this test is an 11-item questionnaire which classifies behavioral dependence according to the scores obtained: mild (<12), moderate (12-22), severe (23-33), and very severe (>33). Successful cessation was defined as self-reported abstinence confirmed by measurement of expired CO level (< or =10 ppm). Results were expressed as means (SD) for quantitative variables and percentages and absolute frequencies for qualitative variables. RESULTS: The study population consisted of 167 smokers--89 men (53.3%) and 78 women (46.7%)--with a mean age of 43.5 (9.9) years, a nicotine dependence score (Fagerström test) of 6.5 (2.2) points, and a Glover-Nilsson score of 23.3 (6.6). Of the study population, 65.9% (n=110) had made previous attempts at quitting. Abstinence at 3 months was 55.1% (n=92). Differences between the sexes were found for age and previous attempts at quitting. Younger patients had higher scores on the Glover-Nilsson test and the Fagerström test and lower abstinence rates. CONCLUSIONS: Severe behavioral dependence can result in less successful cessation outcome. All aspects related to dependence must be assessed to help select the most adequate pharmacological and psychological treatment for results to be optimized.

Evaluación de la dependencia psicológica mediante el test de Glover-Nilsson en el tratamiento del tabaquismo / Assessment of behavioral dependence with the glover-nilsson test in smoking cessation treatment

Objetivo: Evaluar la dependencia psicológica mediante el test de Glover-Nilsson y establecer su relación con el éxito al finalizar el tratamiento. Material y métodos: Se ha realizado un estudio analítico longitudinal, cuya población objetivo han sido los fumadores que accedieron a una unidad de tabaquismo para deshabituación tabáquica. Se estudiaron las siguientes variables: edad, sexo, dependencia a la nicotina (test de Fagerström), consumo de psicofármacos, intentos previos de cesación y dependencia psicológica mediante el test de Glover-Nilsson. Este cuestionario, en su versión más reciente, consta de 11 ítems y clasifica la dependencia psicológica, según la puntuación obtenida, en leve ( 33). Se consideró éxito la abstinencia autodeclarada confirmada con cooximetría (monóxido de carbono ≤ 10 ppm). Los resultados se expresan como medias ± desviación estándar (variables cuantitativas) y como proporciones y frecuencias absolutas (variables cualitativas). Resultados: La población de estudio estaba compuesta por 167 fumadores --89 varones (53,3%) y 78 mujeres (46,7%)--, con una edad media de 43,5 ± 9,9 años, dependencia a la nicotina (test de Fagerström) de 6,5 ± 2,2 puntos y media en el test de Glover-Nilsson de 23,3 ± 6,6 puntos. El 65,9% (n = 110) había hecho intentos previos para dejar de fumar. El éxito a los 3 meses fue del 55,1% (n = 92). Según el sexo, se observaron diferencias en la edad y en la existencia de intentos previos. Los individuos más jóvenes obtuvieron mayor puntuación en el test de Glover-Nilsson y en el test de Fagerström y presentaron una menor tasa de éxito. Conclusiones: La elevada dependencia psicológica puede condicionar peores resultados en el éxito de la deshabituación. Es necesario valorar todos los aspectos relacionados con la dependencia, ya que puede ayudar a seleccionar el tratamiento farmacológico y psicológico más adecuado para optimizar los resultados

Objective: To assess behavioral dependence using the Glover-Nilsson test and determine its association with successful smoking cessation. Material and Methods: An analytical longitudinal study was carried out, the target population of which consisted of smokers who enrolled in a smoking cessation clinic for treatment. The following variables were examined: age, sex, nicotine dependence (Fagerström test), psychoactive drug use, prior attempts at quitting, and behavioral dependence measured with the Glover-Nilsson test. The most recent version of this test is an 11-item questionnaire which classifies behavioral dependence according to the scores obtained: mild (33). Successful cessation was defined as self-reported abstinence confirmed by measurement of expired CO level (≤10 ppm). Results were expressed as means (SD) for quantitative variables and percentages and absolute frequencies for qualitative variables. Results: The study population consisted of 167 smokers --89 men (53.3%) and 78 women (46.7%)--with a mean age of 43.5 (9.9) years, a nicotine dependence score (Fagerström test) of 6.5 (2.2) points, and a Glover-Nilsson score of 23.3 (6.6). Of the study population, 65.9% (n=110) had made previous attempts at quitting. Abstinence at 3 months was 55.1% (n=92). Differences between the sexes were found for age and previous attempts at quitting. Younger patients had higher scores on the Glover-Nilsson test and the Fagerström test and lower abstinence rates. Conclusions: Severe behavioral dependence can result in less successful cessation outcome. All aspects related to dependence must be assessed to help select the most adequate pharmacological and psychological treatment for results to be optimized

[Predictors of success at 6-month follow-up for smokers treated at a smoking cessation clinic]. / Factores predictores de éxito a los 6 meses en fumadores tratados en una unidad de tabaquismo.

OBJECTIVE: To identify the predictors of successful outcome in a smoking cessation program at 6-month follow-up. MATERIAL AND METHODS: Cross-sectional descriptive study of a sample of smokers who attended a smoking cessation clinic for combined medical and cognitive-behavioral group therapy. The independent variables assessed included age, sex, level of education, nicotine dependence (Fagerström test), prior attempts to quit smoking, medication prescribed, compliance with group therapy regimen, and success at one week and 3 months. Success was defined as self-reported abstinence, confirmed by CO-oximetry (carbon monoxide <10 ppm). Odds ratios (with 95% confidence intervals) were calculated for the categorical variables and a test of statistical significance of differences between means was performed for quantitative variables. Univariate logistic regression analysis was performed and significant variables were entered into a multivariate logistic regression model. RESULTS: The study population comprised 248 individuals, 67.7% male and 32.3% female, with a mean (SD) age of 43.1 (10.5) years. The mean score on the Fagerström test was 6.3 (2.1) points and 84.7% of the individuals complied with the treatment regimen. Success rates were as follows: 77% at one week, 30.2% at 3 months, and 31.9% at 6 months. Three variables--success at 3 months, age, and nicotine dependence--were entered into the multivariate logistic regression model; the only variable predictive of successful smoking cessation at 6 months was success at 3 months. CONCLUSIONS: Individuals who fully comply with treatment and abstain from smoking during the first weeks are more likely to be successful at 6 months.

[Apropos of clinical manifestations suggestive of a pheochromocytoma with dominant dopaminergic secretion: tumor or metabolic abnormality?]. / A propos d'un tableau évocateur de phéochromocytome à sécrétion dopaminergique dominante: tumeur ou déviation métabolique?

The case of a young woman with clinical and biological manifestations suggestive of a pheochromocytoma primarily producing dopamine is reported. Whether endogenous production of dopamine was due to a tumor or to a metabolic abnormality remained unclear.

[Application of derivative spectrophotometry for determining plasma hemoglobin and semi-quantitative evaluation of urinary porphyrins]. / Application de la spectrophotométrie dérivée au dosage de l'hémoglobine plasmatique et a l'évaluation semi-quantitative des porphyrines urinaires.

We described a method using second-derivative spectrophotometry with a spectrophotometer Uvikon (Kontron) for the assay of plasma hemoglobin and urinary porphyrins. We evaluated the procedure for sensitivity, linearity, analytical recovery. Non specific interference is not significant and reproductibility is excellent. This simple, rapid, sensitive, not expansive method can be adapted for use in a clinical laboratory.

[Assay of vanilmandelic acid (VMA) by gas chromatography using a capillary tube]. / Dosage de l'acide vanilmandélique (VMA) par chromatographie en phase gazeuse avec colonne capillaire.

The authors describe a method for the determination of urinary VMA as trimethylsilyl derivative by gas-chromatography with a capillary column (OV1 phase). They evaluated the procedure for sensitivity, linearity, analytical recovery and they studied correlation with a spectrophotometric method. The results obtained for normal adults and children are reported. This rapid, sensitive, not expansive method can be adapted for use in a clinical laboratory.