Absorption, metabolism and excretion of once-weekly somapacitan, a long-acting growth hormone derivative, after single subcutaneous dosing in human subjects.

Somapacitan is a reversible albumin-binding growth hormone (GH) derivative in clinical development for once-weekly administration in patients with adult GH deficiency (AGHD) and children with GH deficiency (GHD). To date, the use of somapacitan in AGHD or severe AGHD has been approved in the USA and Japan, respectively. This study (ClinicalTrials.gov, NCT02962440) investigated the absorption, metabolism and excretion, as well as the pharmacokinetics (PK), of tritium-labelled somapacitan ([3H]-somapacitan). Seven healthy males received a single subcutaneous dose of 6 mg somapacitan containing [3H]-somapacitan 20 MBq. Blood, serum, plasma, urine, faeces, and expired air were collected for radioactivity assessment. Metabolites were identified and quantified in plasma and urine collected. The PK of plasma components were determined, and the radioactive peaks of the most abundant plasma metabolites and urine metabolites were selected for analysis. Twenty-eight days after dosing, 94.0% of the administered dose was recovered as [3H]-somapacitan-related material, most of which was excreted in urine (80.9%); 12.9% was excreted in faeces, and an insignificant amount (0.2%) was exhaled in expired air. PK properties of [3H]-somapacitan-related material appeared to be consistent across plasma, serum and blood. Three abundant plasma metabolites (P1, M1 and M1B) and two abundant urine metabolites (M4 and M5) were identified. The total exposure of intact somapacitan accounted for 59% of the total exposure of all somapacitan-related material, P1 accounted for 21% and M1 plus M1B accounted for 12%. M4 and M5 were the most abundant urine metabolites and accounted for 37% and 8% of the dosed [3H]-somapacitan radioactivity, respectively. No intact somapacitan was found in excreta. Two subjects had six adverse events (AEs); all were mild in severity and unlikely to be related to trial product. The majority of dosed [3H]-somapacitan (94%) was recovered as excreted metabolites. Urine was the major route for excretion of somapacitan metabolites, followed by faeces, and exhalation in expired air was negligible. The low molecular weights of identified urine metabolites demonstrate that somapacitan was extensively degraded to small residual fragments that were excreted (fully biodegradable). The extensive metabolic degradation and full elimination of metabolites in excreta were the major clearance pathways of somapacitan and the key elements in its biological fate. A single dose of 6 mg somapacitan (containing [3H]-somapacitan) in healthy male subjects was well tolerated with no unexpected safety issues identified.

Optimal Monitoring of Weekly IGF-I Levels During Growth Hormone Therapy With Once-Weekly Somapacitan.

CONTEXT: Somapacitan is a long-acting growth hormone (GH) in development for once-weekly treatment of GH deficiency (GHD). Optimal monitoring of insulin-like growth factor-I (IGF-I) levels must account for weekly IGF-I fluctuations following somapacitan administration. OBJECTIVE: To develop and assess the reliability of linear models for predicting mean and peak IGF-I levels from samples taken on different days after dosing. DESIGN: A pharmacokinetic/pharmacodynamic model was used to simulate IGF-I data in adults and children following weekly somapacitan treatment of GHD. SETTING AND PATIENTS: 39 200 IGF-I profiles were simulated with reference to data from 26 adults and 23 children with GHD. INTERVENTION(S): The simulated dose range was 0.02 to 0.12 mg/kg for adults and 0.02 to 0.16 mg/kg for children. Simulated data with >4 average standard deviation score were excluded. MAIN OUTCOME MEASURE(S): Linear models for predicting mean and peak IGF-I levels based on IGF-I samples from different days after somapacitan dose. RESULTS: Robust linear relationships were found between IGF-I sampled on any day after somapacitan dose and the weekly mean (R2 > 0.94) and peak (R2 > 0.84). Prediction uncertainties were generally low when predicting mean from samples taken on any day (residual standard deviation [RSD] ≤ 0.36) and peak from samples taken on day 1 to 4 (RSD ≤ 0.34). IGF-I monitoring on day 4 and day 2 after dose provided the most accurate estimate of IGF-I mean (RSD < 0.2) and peak (RSD < 0.1), respectively. CONCLUSIONS: Linear models provided a simple and reliable tool to aid optimal monitoring of IGF-I by predicting mean and peak IGF-I levels based on an IGF-I sample following dosing of somapacitan. A short visual summary of our work is available (1).

LC-MS/MS method for the determination of erianin in rat plasma: Application to a pharmacokinetic study.

Erianin is one of the bibenzyl ingredients isolated from Dctidrobium chrysotoxum Lindl. In recent years, erianin has attracted attention owing to its antitumor activity. In this study, an LC-MS/MS method was established to measure erianin in rat plasma. Gigantol was used as the internal standard. A Waters Acquity UPLC BEH C18 column was employed for chromatographic separation. The mobile phase consisted of water containing 0.1% formic acid and acetonitrile with a gradient elution at the flow rate of 0.4 ml/min. Selective reaction monitoring mode was used for quantitative analysis of erianin in positive electrospray ionization. In the concentration range of 0.1-1200 ng/ml, erianin in rat plasma was linear with correlation coefficient >0.999. The lowest limit of quantification was 0.1 ng/ml. The intra- and inter-day RSDs were <9.69%, while the RE was in the range of -8.59-11.24%. The mean recovery was >85.37%. Erianin was stable in rat plasma after storage under certain conditions. The validated method was demonstrated to be selective, sensitive and reliable, and has been successfully applied to pharmacokinetic study of erianin in rat plasma. Erianin was rapidly eliminated from rat plasma with a short half-life (〜1.5 h) and low oral bioavailability (8.7%).

Development of a Combined In Vitro Physiologically Based Kinetic (PBK) and Monte Carlo Modelling Approach to Predict Interindividual Human Variation in Phenol-Induced Developmental Toxicity.

With our recently developed in vitro physiologically based kinetic (PBK) modelling approach, we could extrapolate in vitro toxicity data to human toxicity values applying PBK-based reverse dosimetry. Ideally information on kinetic differences among human individuals within a population should be considered. In the present study, we demonstrated a modelling approach that integrated in vitro toxicity data, PBK modelling and Monte Carlo simulations to obtain insight in interindividual human kinetic variation and derive chemical specific adjustment factors (CSAFs) for phenol-induced developmental toxicity. The present study revealed that UGT1A6 is the primary enzyme responsible for the glucuronidation of phenol in humans followed by UGT1A9. Monte Carlo simulations were performed taking into account interindividual variation in glucuronidation by these specific UGTs and in the oral absorption coefficient. Linking Monte Carlo simulations with PBK modelling, population variability in the maximum plasma concentration of phenol for the human population could be predicted. This approach provided a CSAF for interindividual variation of 2.0 which covers the 99th percentile of the population, which is lower than the default safety factor of 3.16 for interindividual human kinetic differences. Dividing the dose-response curve data obtained with in vitro PBK-based reverse dosimetry, with the CSAF provided a dose-response curve that reflects the consequences of the interindividual variability in phenol kinetics for the developmental toxicity of phenol. The strength of the presented approach is that it provides insight in the effect of interindividual variation in kinetics for phenol-induced developmental toxicity, based on only in vitro and in silico testing.

Bioremediation of phenol in soil through using a mobile plant-endophyte system.

Plant-endophyte remediation of volatile pollutants in soil is an emerging technology. For more efficient application, plant-endophyte systems were formed through stimulation of transfer of degradative plasmids in plant tissue by co-inoculation of corn, wheat or tomato seedlings with Pseudomonas fluorescens TP13 carrying a self-transmissible degradative plasmid, and P. fluorescens streptomycin-resistant P13 strain. The corn-TP13-P13 (CTP) system had higher degradation activity than other plant-endophyte systems. Transplanting the CTP, from loam to sandy clay loam soil, from greenhouse to field trials, almost completely removed phenol from contaminated soils in 15 d. Intact transplantation of the CTP to contaminated soils was more efficient than co-transplanting of phenol-degrading bacteria and plant in detoxification of phenol. After the experiments the harvested CPT still exhibited remarkable bioremediation activity. The number of degradative plasmid-carrying endophytic bacteria in the CTP system was just slightly more than in the corn seedlings inoculated with TP13 alone, but the former substantially surpassed the latter in phenol-degrading activity, probably due to stimulation of transfer of the degradative plasmids among endophytic bacteria in plant tissues. More degradative plasmid-carrying bacteria colonized bioremediating soil and plant tissues, and higher plasmid transfer frequency and C23O activity of transconjugant were found in soils for the CTP system compared with other treatments. These results showed that the CTP system is a valuable tool to degrade volatile organic pollutants and transfer of degradative plasmids in plant tissues is important for construction of a mobile plant-endophyte system applied in bioremediation of volatile pollutants.

Potentiation of the bioavailability of blueberry phenolic compounds by co-ingested grape phenolic compounds in mice, revealed by targeted metabolomic profiling in plasma and feces.

The low bioavailability of dietary phenolic compounds, resulting from poor absorption and high rates of metabolism and excretion, is a concern as it can limit their potential beneficial effects on health. Targeted metabolomic profiling in plasma and feces of mice supplemented for 15 days with a blueberry extract, a grape extract or their combination revealed significantly increased plasma concentrations (3-5 fold) of blueberry phenolic metabolites in the presence of a co-ingested grape extract, associated with an equivalent decrease in their appearance in feces. Additionally, the repeated daily administration of the blueberry-grape combination significantly increased plasma phenolic concentrations (2-3-fold) compared to animals receiving only a single acute dose, with no such increase being observed with individual extracts. These findings highlight a positive interaction between blueberry and grape constituents, in which the grape extract enhanced the absorption of blueberry phenolic compounds. This study provides for the first time in vivo evidence of such an interaction occurring between co-ingested phenolic compounds from fruit extracts leading to their improved bioavailability.

Efectividad de distintas técnicas de activación en la remoción de medicación de hidróxido de calcio de las paredes radiculares / Effectiveness of different activation techniques in the removal of calcium hydroxide medication from root canal walls

Objetivos: Investigar distintos protocolos de irrigación y soluciones para la remoción de hidróxido de calcio de las paredes radiculares mediante Microscopía Electrónica de Barrido (MEB). Metodología: Se seleccionó una muestra de 48 raíces palatinas de molares superiores. Los conductos fueron instrumentados, irrigados, secados y obturados con medicación a base de hidróxido de calcio. Los dientes fueron aleatoriamente asignados en 6 grupos, dependiendo de la técnica utilizada para activar hipoclorito sódico y Smear Clear para la remoción de la medicación intraconducto: Grupo 1, Irrigación positiva con jeringa (P), Grupo 2, Irrigación Ultrasónica (UI), Grupo 3, Irrigación por presión apical negativa (ANP), Grupo 4: Irrigación ultrasónica pasiva e irrigación por presión apical negativa (UI + ANP). Se incluyeron dos grupos control: Grupo 5: Grupo control positivo (C+), que fue obturado con hidróxido de calcio, pero no se eliminó del conducto, y Grupo 6: Grupo control negativo (C-), que no fue obturado con hidróxido de calcio. Todos los conductos fueron observados con microscopio electrónica de barrido (MEB). Se evaluó la presencia de material residual usando un sistema de medición en los tercios apical, medio y coronal. Los resultados fueron analizados estadísticamente mediante los test de Kruskal-Wallis y Bonferroni (p < 0,05). Resultados: Se encontraron diferencias estadísticamente significativas entre todos los grupos en todos los tercios a estudio (p < 0,05). El uso combinado de UI y ANP resultó en una remoción más eficiente de hidróxido de calcio de las paredes radiculares, independientemente del área analizada. Conclusiones: La utilización de irrigación ultrasónica pasiva e irrigación por presión apical negativa como activación final, sugiere una mejor limpieza de los conductos. Ninguna técnica es capaz de remover completamente el hidróxido de calcio de las paredes radiculares

Aim: To investigate different irrigation protocols and solutions to remove Ca(OH)2 from the root canal walls by using Scanning Electron Microscopy (SEM). Methodology. Forty-eight palatal roots from upper molars were selected. The root canals were instrumented, irrigated, dried and filled with a calcium hydroxide medication. Teeth were then randomly assigned to one of 6 groups depending on which technique was used to activate NaOCl and Smear Clear irrigants to remove medication: Group 1, Positive syringe irrigation (P); Group 2, Ultrasonic Irrigation (UI); Group 3, Apical Negative Pressure irrigation (ANP); Group 4, Passive Ultrasonic Irrigation and Apical Negative Pressure irrigation (UI + ANP). 2 control groups were also included: Group 5, positive control (C+), which were filled with calcium hydroxide that was not removed from the canal and Group 6, negative controls (C-), which were not filled with calcium hydroxide. All root canals were observed through SEM. Presence of residual material was evaluated using a score system for the coronal, middle, and apical portions. Data were statistically analysed using the Kruskal-Wallis and Bonferroni tests (P < 0.05). Results. There was a statistically significant difference among all groups at all root levels (P < 0.05). The combined use of UI and ANP irrigation resulted more efficient in the removal of calcium hydroxide from the root canal walls, irrespective of the area analyzed. Conclusions. The use of passive ultrasonic irrigation and apical negative pressure as a final activation is suggested to improve cleaning of the root canals. No technique is able to completely remove calcium hydroxide dressing from the root canal walls

[Specific features of the distribution of 2,4- and 2,6-dimethyl derivatives of hydroxybenzene in the body of the warm-blooded animals].

This study was designed to elucidate the specific features of the distribution of 2,4- and 2,6-dimethyl derivatives of hydroxybenzene in the body of the warm-blooded animals (rats) after the intragastric administration of these poisonous substances. It was shown that large amounts of these compounds are present in the unmetabolized form in the blood and internal organs of the experimental animals. Their largest quantities were found in the stomach contents, spleen, and small intestines.

Combining in vitro embryotoxicity data with physiologically based kinetic (PBK) modelling to define in vivo dose-response curves for developmental toxicity of phenol in rat and human.

In vitro assays are often used for the hazard characterisation of compounds, but their application for quantitative risk assessment purposes is limited. This is because in vitro assays cannot provide a complete in vivo dose-response curve from which a point of departure (PoD) for risk assessment can be derived, like the no observed adverse effect level (NOAEL) or the 95 % lower confidence limit of the benchmark dose (BMDL). To overcome this constraint, the present study combined in vitro data with a physiologically based kinetic (PBK) model applying reverse dosimetry. To this end, embryotoxicity of phenol was evaluated in vitro using the embryonic stem cell test (EST), revealing a concentration-dependent inhibition of differentiation into beating cardiomyocytes. In addition, a PBK model was developed on the basis of in vitro and in silico data and data available from the literature only. After evaluating the PBK model performance, effective concentrations (ECx) obtained with the EST served as an input for in vivo plasma concentrations in the PBK model. Applying PBK-based reverse dosimetry provided in vivo external effective dose levels (EDx) from which an in vivo dose-response curve and a PoD for risk assessment were derived. The predicted PoD lies within the variation of the NOAELs obtained from in vivo developmental toxicity data from the literature. In conclusion, the present study showed that it was possible to accurately predict a PoD for the risk assessment of phenol using in vitro toxicity data combined with reverse PBK modelling.

[Specific features of 2-methyl hydroxybenzene and 3-methyl hydroxybenzene distribution in the organism of warm-blooded animals].

The present work was designed to study the specific features of 2-methyl hydroxybezene and 3-methyl hydroxybenzene distribution after intragastric administration of these toxicants to warm-blooded animals (rats). They were detected in the unmetabolized form in the internal organs and blood of the animals. The levels of 2-methyl hydroxybezene were especially high in the stomach and blood whereas the maximum content of 3-methyl hydroxybenzene was found in brain, blood, small intestines of the poisoned rats.

Preparation and valuation of a topical solution containing eutectic mixture of itraconazole and phenol.

The purposes of this study were to prepare a topical solution containing itraconazole (ITR)-phenol eutectic mixture and to evaluate its ex vivo skin permeation, in vivo deposition and in vivo irritation. The eutectic mixture was prepared by agitating ITR and phenol (at a weight ratio of 1:1) together at room temperature. The effects of additives on the skin permeation of ITR were evaluated using excised hairless mouse skin. The in vivo skin deposition and skin irritation studies were performed in Sprague-Dawley rat and New Zealand white rabbit model. The permeability coefficient of ITR increased with addition of oleic acid in the topical solution. Otherwise, the permeability coefficient was inversely proportional to the concentration of the thickening agent, HPMC. The optimized topical solution contained 9 wt% of the ITR-phenol eutectic mixture, 9.0 wt% of oleic acid, 5.4 wt% of hydroxypropylmethyl cellulose and 76.6 wt% of benzyl alcohol. The steady-state flux and permeability coefficient of the optimized topical solution were 0.90 ± 0.20 µg/cm(2)·h and 22.73 ± 5.73 × 10(6) cm/h, respectively. The accumulated of ITR in the epidermis and dermis at 12 h was 49.83 ± 9.02 µg/cm(2). The topical solution did not cause irritation to the skins of New Zealand white rabbits. Therefore, the findings of this study indicate the possibilities for the topical application of ITR via an external preparation.

DFT studies of the phenol adsorption on boron nitride sheets.

We perform first principles total energy calculations to investigate the atomic structures of the adsorption of phenol (C(6)H(5)OH) on hexagonal boron nitride (BN) sheets. Calculations are done within the density functional theory as implemented in the DMOL code. Electron-ion interactions are modeled according to the local-spin-density-approximation (LSDA) method with the Perdew-Wang parametrization. Our studies take into account the hexagonal h-BN sheets and the modified by defects d-BN sheets. The d-BN sheets are composed of one hexagon, three pentagons and three heptagons. Five different atomic structures are investigated: parallel to the sheet, perpendicular to the sheet at the B site, perpendicular to the sheet at the N site, perpendicular to the central hexagon and perpendicular to the B-N bond (bridge site). To determine the structural stability we apply the criteria of minimum energy and vibration frequency. After the structural relaxation phenol molecules adsorb on both h-BN and d-BN sheets. Results of the binding energies indicate that phenol is chemisorbed. The polarity of the system increases as a consequence of the defects presence which induces transformation from an ionic to covalent bonding. The elastic properties on the BN structure present similar behavior to those reported in the literature for graphene.

Evaluation of phenol detoxification by Brassica napus hairy roots, using Allium cepa test.

INTRODUCTION: Meristematic mitotic cells of Allium cepa constitute an adequate material for cytotoxicity and genotoxicity evaluation of environmental pollutants, such as phenol, which is a contaminant frequently found in several industrial effluents. RESULTS AND DISCUSSION: In the present work, Brassica napus hairy roots (HR) were used for phenol removal assays. The toxicity of post-removal solutions (PRS) and phenol solutions was analyzed. These HR removed the contaminant with high efficiency (100-80% for phenol solutions containing 10-250 mg/L, respectively). Phenol solutions treated with B. napus HR showed a significant reduction of general toxicity compared to untreated phenol solutions, since the IC50 values were 318.39 and 229.02 mg/L, respectively. Moreover, PRS presented lower cytotoxicity and genotoxicity than that found in phenol solutions untreated. The mitotic index (MI) observed in meristematic cells treated with PRS (100 and 250 mg/L of phenol) showed an increase of 35% and 42%, whereas the chromosome aberrations showed a significant decrease. According to these results, B. napus HR cultures could be used for the treatment of solutions contaminated with phenol, since we observed not only high removal efficiency, but also an important reduction of the general toxicity, cytotoxicity, and genotoxicity.

[Indoor air guide values for phenol]. / Richtwerte für Phenol in der Innenraumluft. Mitteilung der Ad-hoc-Arbeits-gruppe Innenraumrichtwerte der Innenraumlufthygiene-Kommission des Umweltbundesamtes und der Obersten Landesgesundheitsbehörden.

The German Working Group on Indoor Guidelines of the Federal Environment Agency and the States´ Health Authorities is issuing indoor air guide values to protect public health. For health evaluation of phenol in indoor air a qualified working-place study emphasizing the POD hemo- and hepatotoxicity as well as results of a limited inhalation-study which underline neurological effects on rats were used. The Working Group assessed a lowest observed adverse effect level of 21 mg Phenol/m3 in the working-place study and 100 mg Phenol/m3 in the animal-based study. Both toxicological derivatives come to the same result but the working-place study was preferred. By applying a factor of 10 for interindividual variability, a factor of 4.2 for the different exposing-time of workers and usual population and a modifying factor of 2 regarding children a health hazard guide value (RW II) of 0.2 mg phenol/m3 is obtained. A health precaution guide value of 0.02 mg phenol/m3 is recommended.

Estudo comparativo entre aplicação de ATAa 90% e fenol a 88% com a técnica de CROSSnas cicatrizes da acne / Chemical reconstruction of skin scars with 90% trichloroacetic acid or 88% phenol: a comparative study

Introdução: Acne é uma doença comum que afeta a unidade pilosebácea e produz várias sequelas cosméticas, como as cicatrizes. Pacientes e métodos: Este estudo foi realizado para se avaliar o benefício do tratamento das cicatrizes de acne utilizando a técnica de “CROSS”(reconstrução química de cicatrizes de acne) e para se comparar o uso de duas substâncias nesta técnica- o ácido tricloroacetico (ATA) a 90% e o fenola 88% . Foram tratadas cicatrizes de acne em oito pacientes, aplicando-se as substâncias químicas nas cicatrizes. Foram utilizados aplicadores de madeira para aplicar fenol a 88% nas cicatrizes da hemiface direita e ATA a 90% nas cicatrizes da hemiface esquerda. O procedimento foi repetido emintervalos mensais em um total de cinco meses. Resultados: Foi observado que a sensação de queimação que ocorre no momento da aplicação das substâncias é mais intensa quando se usa ATA. Oeritema que surge no local da aplicação é mais é mais evidente e duradouro com uso de ATA. A reepitelização da pele tratada é mais demorada comATA. A maior parte dos pacientes mostrou melhores resultados cosméticos na hemiface onde foi usado o fenol a 88%.Discussão: Neste estudo, a técnica de “CROSS” teve bons resultados, mas foi necessário um longo tempo para que se produzisse resultados clínicosvisíveis. Quando as duas substâncias foram comparadas, o fenol a 88% se mostrou mais satisfatório do que o ATA, pois ocasionou menos dor, tevemelhores resultados cosméticos e reepitelização mais rápida (AU)

Introduction: Acne is a comon disease that affects the pilosebaceous unit and produces many cosmetic sequels, like scarring. Patients and methods: This study has been performed to evaluate the benefit of treating depressed acne scars with CROSS ( chemical reconstruction of skin scars ) technique versus 90% trichloroacetic acid (90% TCA) and 88% phenol. Acne scars in eight patients were treated by applying the chemical substances directly to the scars. We used wooden applicators to apply 88% phenol to the scars of the right hemiface and 90% TCA to the scars of the left hemiface. The procedure was repeated at monthly intervals for a total of five treatments. Results: The burning sensation that occurs at the time of application of both substances was more intense when using TCA. The erythema area that surges at the site of application is more evident and lasts longer with TCA. The reepithelization of the skin treated was slower with TCA. The majority of patients showed best cosmetic results at the hemiface where 88% phenol has been used. Discussion: In this study, the CROSS technique had good results but it required long time to produce clinical visible results. When both substances were compared, 88% phenol seemed to be more satisfactory than 90% TCA since it produced less pain, showed best cosmetic results and had faster reepithelization. (AU)

Effects of preparation and experimental conditions on removal of phenol by surfactant-modified zeolites.

The removal of phenol from aqueous solutions using surfactant-modified clinoptilolite-rich tuffs (SMZ) prepared from two Mexican zeolitic tuffs (Chihuahua and Oaxaca) was investigated. Sodium homoionization of the zeolitic rocks was performed before they were modified with the surfactants: hexadecyltrimethylammonium chloride or bromide and bencylcetildimethylammonium chloride. The surfactants in the modified zeolitic materials were determined considering the total carbon in the samples. The phenol removal was determined in a batch system taking into consideration the different quantities of surfactants in the zeolitic tuffs, contact time, pH and initial phenol concentration. The phenol was determined in the aqueous solutions by UV/Vis spectroscopy. Results showed that the formation of a hemimicelle or admicelle on the zeolites depended on the initial surfactant concentration and they were responsible for the type of interactions between the phenol and the surfactant-modified zeolites. Phenol adsorption by the surfactant-modified zeolites was carried out in approximately three hours. Phenol adsorption data was best adjusted to the pseudo-second order kinetic model. Both, surface properties of the surfactant-modified zeolites and pH of solution play an important role in the removal of this pollutant from aqueous solutions and they are responsible for the type of mechanism involved.

Use of online microdialysis sampling to determine the in vivo rate of phenol glucuronidation in rainbow trout.

A quantitative microdialysis (MD) sampling method was used to study phenol (PH) glucuronidation in vivo in rainbow trout. The method employs internal calibrators to account for changes in MD probe performance (in vitro-to-in vivo and sample-to-sample) and yields data of high temporal resolution that are well suited for developing kinetic models. Initially, trout were dosed with phenyl glucuronide (PG) by intravascular infusion for 24 h and then depurated for 48 h. Measured concentrations of PG in blood were well described by a one-compartment clearance-volume model. Massbalance calculations showed that 93% of infused PG was eliminated in urine during the depuration period. Peak concentrations of PG in urine averaged 3.4 times higher than those in blood, and the fitted PG clearance constant (15.7 ml/kg/h) was about 2.6 times higher than the reported glomerular filtration rate for trout. These findings confirm earlier work suggesting that PG is actively secreted by the trout kidney. In a second set of experiments, trout were exposed continuously to PH in water. In vivo rate constants for PH glucuronidation were estimated using a pair of linked (PH and PG) one-compartment clearance-volume models. Expressed on a whole-fish basis, the glucuronidation rate averaged 0.049/h, which was about 7% of the total rate of PH elimination. This study demonstrates the utility of quantitative MD sampling for kinetic studies of xenobiotic metabolism in fish.

Toxicity, bioaccumulation and metabolism of phenol in the freshwater fish Oreochromis mossambicus.

The acute toxicity of phenol was determined to be 35.0 mg/l in Oreochromis mossambicus. The fish were exposed to two sublethal concentrations of phenol (2.3 and 3.5 mg/l) for 30 days. The effects of exposure were studied on the bioaccumulation and elimination of phenol from the kidney and biochemical parameters of liver, gill, and muscle at intervals of 10, 20, and 30 days. A statistically significant increase in phenol concentration was noted in tissues from all treated fish groups. Bioaccumulation and biochemical changes were dose and duration dependant. Recovery in fish after post exposure was observed after transferring these fish to normal tap water for 30 days. Elimination of phenol was noted, although the concentration of phenol remained significantly higher than the control after 30 days of the experiment. Total protein, total carbohydrate, and total lipids in the tissues of liver, gill, and muscle of fish decreased greatly. The longer the exposure time, the greater was the percentage reduction of organic matter of the fish exposed to the sublethal concentration of phenol.

Rejuvenescimento facial: peeling de fenol atenuado / Face anti-ageing: profound phenolmethod

O objetivo do presente estudo é descrever a técnica de peeling de fenol pré-oxidado, os principais cuidados pré e pós-operatórios e a avaliação dos resultados obtidos em quatro pacientes submetidos ao método, breve comparação com o método de fenol profundo tradicional de Backer e Gordon.Apresenta-se, ainda.Ao final, conclui-se que o método de peeling de fenol pré-oxidado, sem a necessidade de máscaras oclusivas, é seguro, reprodutível e demonstra um alto grau de aceitação no grupo submetido ao tratamento.

The objective of the present work is to describe the techniques of phenol peeling, the main pre-peeling and post-peeling care and the evaluation from this method of the results obtained by four patients. Comparison with Backer and Gordon traditional profound phenol method. Finally, the conclusion is that the profound phenol peeling method which doesn't use occlusive mascara is secure, reproducible and shows a real acceptance in the group submitted to the treatment.

Removal of high phenol concentrations with adapted activated sludge in suspended form and entrapped in calcium alginate /cross-linked poly(N-vinyl pyrrolidone) hydrogels.

The present work evaluates the aerobic removal of 0.25-2 g/L of phenol by adapted activated sludge in batch and continuous reactors, in suspended form and trapped in polymeric hydrogel beads of calcium alginate(1%) and cross-linked poly(N-vinyl pyrrolidone), x-PVP (4%). The mechanical and chemical resistance of the entrapping hydrogel was also evaluated in three different media: (I) rich in phosphate and ammonium ions; (II) using alternate P and N sources, and (III) without nutrients. The adapted consortium removed phenol concentrations up to 2 g/L more efficiently in the immobilized systems. A decrease in phenol removal rate was observed as the food/microorganisms (F/M) ratio increased. A zero-order kinetics was observed with phenol concentrations > 1 g/L and a first-order kinetics at concentrations < 1 g/L. The best response (100% removal) was in the continuous reactors using type II medium, with a hydraulic residence time (HRT) of 12.5 h, an influent pH = 5, and an F/M ratio below 0.25. The immobilizing matrix deteriorated after 170 h of use in continuous reactors, especially with media I and II, probably due to the attrition forces, to chemical weakness of the material, and to the pressure of the bacterial growth inside the bead.