RESUMEN
The biodegradation of N-alkyl polypropylene polyamines (NAPPs) was studied using pure and mixed cultures to enable read-across of ready biodegradability test results. Two Pseudomonas spp. were isolated from activated sludge with N-oleyl alkyl propylene diamine and N-coco alkyl dipropylene triamine, respectively. Both strains utilized all NAPPs tested as the sole source of carbon, nitrogen and energy for growth. Mineralization of NAPPs was independent of the alkyl chain length and the size of the polyamine moiety. NAPPs degraded in closed bottle tests (CBTs) using both river water and activated sludge. However, ready biodegradability of NAPPs with alkyl chain lengths of 16-18 carbon atoms and polyamine moieties with three and four nitrogen atoms could not be demonstrated. Biodegradation in the CBT was hampered by their limited bioavailability, making assessment of the true ready biodegradability of these highly adsorptive surfactants impossible. All NAPPs are therefore classified as readily biodegradable through read-across. Read-across is justified by the broad substrate specificity of NAPP-degrading microorganisms, their omnipresence and the mineralization of NAPPs.
Asunto(s)
Poliaminas/metabolismo , Polipropilenos/metabolismo , Pseudomonas/metabolismo , Tensoactivos/metabolismo , Biodegradación Ambiental , Agua Dulce/microbiología , Poliaminas/química , Polipropilenos/química , Aguas del Alcantarillado/microbiología , Tensoactivos/químicaRESUMEN
Wastewater from an Akzo Nobel production site contains more than 50 g/l total dissolved salts, mainly chlorides and sulphates, and is currently being treated after 10-20 x dilution. Biological treatment of undiluted or less diluted wastewater is very desirable for environmental and economic reasons. Possibilities were investigated in laboratory scale reactors to treat this highly saline and high strength wastewater aerobically, either after long adaptation or after removing part of the salts by a pretreatment. Adaptation and selection from mixed activated sludge populations took approximately 40 days to finally achieve a COD removal in aerobic treatment of 55-65% at two times dilution (11-16 g/l chloride and 5-7 g/l sulphate). Undiluted wastewater was not treatable. A higher removal percentage (> 80%) was possible at the original high salt concentration only when the sludge load was limited to approximately 0.4-0.5 kg COD/kg sludge/day. A longer adaptation time was required. Nanofiltration (NF) and crystallization could be used as a pretreatment to remove and recover up to 80% of the sulphate in the form of crystallized Glauber salt. Recovery strongly depended on the sulphate and chloride concentration in the NF concentrate and on crystallization temperature. The salt (sulphate) reduction through the NF improved the removal efficiency of a consecutive biotreatment only at a relatively low chloride level, demonstrating that the combination of nanofiltration-crystallization-aerobic biodegradation is less feasible for very saline wastewaters. Anaerobic pretreatment of saline waters turned out to be rather sensitive to high salinities. Only wastewater diluted to 10 g/l chloride could be treated well: sulphate concentration decreased by 80% and COD by 40%. Removal efficiencies of the combined anaerobic-aerobic treatment were approximately 80-85%, proving that this was a feasible route for 2-3 x diluted wastewater. The study has shown that several alternatives are available for treatment of the very saline wastewaters at a much lower degree of dilution than currently practiced.
Asunto(s)
Residuos Industriales , Cloruro de Sodio , Eliminación de Residuos Líquidos/métodos , Reactores Biológicos , Cristalización , Filtración , Concentración de Iones de Hidrógeno , Técnicas de Dilución del Indicador , Nanoestructuras , Oxígeno/farmacologíaRESUMEN
The effect of omitting nickel from the influent on methanol conversion in an Upflow Anaerobic Sludge Bed (UASB) reactor was investigated. The UASB reactor (30 degrees C, pH 7) was operated for 261 days at a 12-h hydraulic retention time (HRT) and at organic loading rates (OLRs) ranging from 2.6 to 7.8 g COD l reactor(-1) day(-1). The nickel content of the sludge decreased by 66% during the 261-day reactor run because of washout and doubling of the sludge bed volume. Nickel deprivation initially had a strong impact on the methanogenic activity of the sludge with methanol; e.g., after 89 days of operation, this activity was doubled by adding 2 micro M nickel. Upon prolonged UASB reactor operation, methanol and VFA effluent concentrations decreased whereas the sludge lost its response to nickel addition in activity tests. This suggests that a less nickel-dependent methanol-converting sludge had developed in the UASB reactor.
Asunto(s)
Reactores Biológicos , Metanol/metabolismo , Níquel/farmacología , Aguas del Alcantarillado , Anaerobiosis , Biodegradación AmbientalRESUMEN
Nitrogen losses from plants may occur through a variety of pathways, but so far, most studies have only quantified losses of nutrients by above-ground litter production. We used 15N pulse labelling to quantify total nitrogen losses from above- and below-ground plant parts. Using this method we were able to include also pathways other than above-ground litter production. To test the hypothesis that species from nutrient-poor habitats lose less nitrogen than species from more fertile soils, six perennial grasses from habitats with a wide range of nutrient availability were investigated: Lolium perenne, Arrhenatherum elatius, Anthoxanthum odoratum, Festuca rubra, F. ovina and Molinia caerulea. The results of an experiment carried out in pots in a green-house at two fertility levels show that statistically significant losses occur through pathways other than above-ground litter production. In the low fertility treatment, most (70%) losses from L. perenne occurred by litter production, but in Ar. elatius, F. rubra, F. ovina and M. caerulea, more than 50% of labelled N losses took place by root turn-over, leaching or exudation from roots. When nutrient supply increased, the 15N losses in above-ground dead material increased in all species and in Ar. elatius, A. odoratum and F. rubra the 15N losses via other pathways decreased. Ranked according to decreasing turnover coefficient the sequence of species was: L. perenne, A. odoratum, F. rubra, F. ovina, Ar. elatius, M. caerulea. These results suggest that species adapted to sites with low availability of nutrients lose less nitrogen (including above- and below-ground losses) than species adapted to more fertile soils.
RESUMEN
Loperamide oxide is a prodrug of the effective antidiarrheal loperamide. Administration of this prodrug improves efficacy and tolerability. For better understanding of these effects, the absorption and gastrointestinal distribution of loperamide oxide and of its active drug loperamide were studied. Beagle dogs received a single oral dose of loperamide oxide or loperamide at 0.16 mg/kg. Plasma, gastrointestinal contents and tissues, and some other organs were obtained. Concentrations were determined by specific radioimmunoassays. Loperamide oxide was gradually converted to loperamide in the gastrointestinal tract. After administration of the prodrug, the systemic absorption of the active drug was lower and more delayed than after administration of loperamide itself. As a consequence, more loperamide was available in the contents and the mucosa of the gut, in particular in the lower part of the small intestine and in the large intestine. The higher levels of loperamide in mucosa may cause more pronounced and longer lasting antisecretory effects after administration of loperamide oxide. The results of this study are in line with the hypothesis that loperamide oxide is a site-specific prodrug that acts as a chemically designed controlled-release form of loperamide keeping a higher amount of the active drug for a longer time at the site of action in the gut wall.
Asunto(s)
Sistema Digestivo/metabolismo , Loperamida/análogos & derivados , Loperamida/farmacocinética , Profármacos/farmacocinética , Animales , Disponibilidad Biológica , Perros , Vías de Administración de Medicamentos , Femenino , Absorción Intestinal , Intubación Gastrointestinal , Loperamida/sangre , Masculino , Profármacos/metabolismo , Distribución TisularRESUMEN
Risperidone is a new benzisoxazole antipsychotic. 9-Hydroxy-risperidone is the major plasma metabolite of risperidone. The pharmacological properties of 9-hydroxy-risperidone were studied and appeared to be comparable to those of risperidone itself, both in respect of the profile of interactions with various neurotransmitters and its potency, activity, and onset and duration of action. The absorption, plasma levels and regional brain distribution of risperidone, metabolically formed 9-hydroxy-risperidone and total radioactivity were studied in the male Wistar rat after single subcutaneous administration of radiolabelled risperidone at 0.02 mg/kg. Concentrations were determined by HPLC separation, and off-line determination of the radioactivity with liquid scintillation counting. Risperidone was well absorbed. Maximum plasma concentrations were reached at 0.5-1 h after subcutaneous administration. Plasma concentrations of 9-hydroxy-risperidone were higher than those of risperidone from 2h after dosing. In plasma, the apparent elimination half-life of risperidone was 1.0 h, and mean residence times were 1.5 h for risperidone and 2.5 h for its 9-hydroxy metabolite. Plasma levels of the radioactivity increased dose proportionally between 0.02 and 1.3 mg/kg. Risperidone was rapidly distributed to brain tissues. The elimination of the radioactivity from the frontal cortex and striatum--brain regions with high concentrations of 5-HT2 or dopamine-D2 receptors--became more gradual with decreasing dose levels. After a subcutaneous dose of 0.02 mg/kg, the ED50 for central 5-HT2 antagonism in male rats, half-lives in frontal cortex and striatum were 3-4 h for risperidone, whereas mean residence times were 4-6 h for risperidone and about 12 h for 9-hydroxy-risperidone. These half-lives and mean residence times were 3-5 times longer than in plasma and in cerebellum, a region with very low concentrations of 5-HT2 and D2 receptors. Frontal cortex and striatum to plasma concentration ratios increased during the experiment. The distribution of 9-hydroxy-risperidone to the different brain regions, including frontal cortex and striatum, was more limited than that of risperidone itself. This indicated that 9-hydroxy-risperidone contributes to the in vivo activity of risperidone, but to a smaller extent than would be predicted from plasma levels. AUCs of both active compounds in frontal cortex and striatum were 10-18 times higher than those in cerebellum. No retention of metabolites other than 9-hydroxy-risperidone was observed in any of the brain regions investigated.
Asunto(s)
Antipsicóticos/farmacocinética , Encéfalo/metabolismo , Isoxazoles/farmacocinética , Piperidinas/farmacocinética , Pirimidinas/farmacocinética , Animales , Antieméticos/farmacología , Antipsicóticos/administración & dosificación , Antipsicóticos/farmacología , Apomorfina/antagonistas & inhibidores , Apomorfina/farmacología , Perros , Semivida , Inyecciones Subcutáneas , Isoxazoles/administración & dosificación , Isoxazoles/farmacología , Masculino , Inhibidores de la Captación de Neurotransmisores/farmacología , Norepinefrina/farmacología , Tamaño de los Órganos/efectos de los fármacos , Palmitato de Paliperidona , Piperidinas/administración & dosificación , Piperidinas/farmacología , Ratas , Ratas Wistar , Receptores de Neurotransmisores/efectos de los fármacos , Risperidona , Espectrofotometría Ultravioleta , Triptaminas/farmacologíaRESUMEN
The plasma kinetics and tissue distribution of ketanserin [+)-3-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl]-2,4(1H,3H)- quinazolinedione, R 41 468) were studied in the rat, rabbit and dog. The studies were performed utilizing 3H- and 14C-labelled ketanserin and appropriate techniques to measure levels of radioactivity, unchanged drug and a major metabolite ketanserin-ol in plasma and tissues. Following intravenous administration to male rats and dogs (10 mg/kg), plasma levels could be described by a two-compartment model. The plasma clearance (C1) averaged 3.8 and 19.2 ml/min/kg and the volume of distribution (Vdss) 0.67 and 4.7 l/kg in male rats and in dogs, respectively. Following oral administration (10-40 mg/kg), ketanserin was rapidly and completely absorbed in all species studied. The absolute bioavailability of oral ketanserin was more than 80% in both rats and dogs. Due to the high clearance of the metabolites in rats, ketanserin was the main component of the plasma radioactivity. In dogs, the fraction of the metabolite ketanserin-ol was more pronounced than that of ketanserin. The apparent elimination half-life of ketanserin was 1.5 h in rabbits, 2-5 h in rats and 3-15 in dogs. The pharmacokinetics of ketanserin were dose-related after single and chronic intravenous and oral dosing. Distribution studies in rats after intravenous and oral administration (10 mg/kg) demonstrated an almost immediate equilibrium between plasma and tissues, resulting in slightly higher tissue than plasma concentrations in the well perfused tissues, and similar or slightly lower levels in the remaining tissues. Ketanserin was the main component of tissue radioactivity. The drug crossed the blood-brain barrier only to a slight extent, brain levels of the unchanged drug being similar to the free fraction in plasma. Ketanserin disappeared from tissues with a similar half-life to that in plasma. On repeated dosing, a small fraction of metabolites was more slowly eliminated. The excretion of the urinary and faecal metabolites after repeated dosing was very similar to that after a single dose. Placental transfer of ketanserin in the rat was limited. On average 0.3% of the maternal radioactive dose, preferentially metabolites, was recovered from the combined foetuses. In dogs orally treated with doses of up to 40 mg/kg/d for 12 months, no undue accumulation or retention of ketanserin or ketanserin-ol was found in any tissue. In lactating dogs orally dosed at 10 mg/kg, preferentially metabolites were excreted in the milk. Concentrations of ketanserin and ketanserin-ol in the milk were respectively 2 and 4 times higher than plasma levels.
Asunto(s)
Ketanserina/farmacocinética , Animales , Autorradiografía , Perros , Heces/análisis , Femenino , Masculino , Intercambio Materno-Fetal , Leche/metabolismo , Embarazo , Conejos , Ratas , Ratas Endogámicas , Especificidad de la Especie , Distribución TisularRESUMEN
The plasma kinetics and tissue distribution of the gastrokinetic (+/-)-cis-4-amino-5-chloro-N-[1-(3-(4-fluorophenoxy)propyl]-3-methoxy-4- piperidinyl]-2-methoxybenzamide monohydrate (cisapride, R 51 619) have been studied in the rat, rabbit and dog. After intravenous administration to rats (5 mg/kg) and dogs (0.63 mg/kg) plasma level-time curves were adequately fitted to a two-compartmental model. The plasma clearance (ClT) and volume of distribution (Vdss) averaged 91 ml/min.kg and 4.7 l/kg in the rat and 4.2 ml/min.kg and 0.82 l/kg in the dog, respectively. Following oral administration, cisapride was rapidly and almost completely absorbed from the gastrointestinal tract in rats and rabbits. The absorption was somewhat slower in the dog. In male rats the plasma radioactivity was mainly due to metabolites, unaltered cisapride representing on average 10% of the total radioactivity. A markedly larger proportion of the parent drug was seen in female rats. Linear plasma kinetics were observed for cisapride in the dose range of 10 to 160 mg/kg. Similarly in the dog, linearity was observed after oral administration in the range of 0.31 to 10 mg/kg. The plasma kinetics remained unaltered on repeated oral doses of 10 mg/kg to rats and subchronic intravenous administration at 0.63 mg/kg to dogs. Compared with intravenous administration, the absolute bioavailability of oral cisapride was 23% in rats and 53% in the dog for the drug given in solution. The terminal plasma half-life of cisapride was about 1-2 h in the rat and about 4-10 h in the rabbit and dog.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Piperidinas/farmacocinética , Animales , Autorradiografía , Cisaprida , Perros , Femenino , Masculino , Leche/metabolismo , Piperidinas/sangre , Placenta/metabolismo , Embarazo , Conejos , Ratas , Ratas Endogámicas , Especificidad de la Especie , Distribución TisularRESUMEN
The frequency and the severity of skin lesions were studied in patients with chronic venous insufficiency compared to the function of the muscle pump measured with plethysmography. The study showed that the frequency of skin symptoms parallels the muscle pump dysfunction. Measuring the ambulatory volume change on the calf level and the refilling time required for the normalisation of the calf volume after dorsiflexions of the foot gives suitable parameters for the evaluation of the muscle pump. The plethysmography is a valuable method to quantify the grade of venous insufficiency.