Renewable adsorbents from the solid residue of sewage sludge hydrothermal liquefaction for wastewater treatment.

Solid residue from hydrothermal liquefaction (HTL) of nutrient rich feedstock presents a promising source to recover valuable nutrients, such as phosphorus, in the solid form. The present work shows for the first time the potential of utilizing the waste residue remaining after nutrients extraction from HTL of sewage sludge, as renewable adsorbents. A parametric study was undertaken to investigate the influence of chemical activation conditions (temperature, residence time, activation agent loading, washing after activation) on raw and partially demineralized HTL solids. Kinetic and equilibrium adsorption investigation was undertaken for the removal of methylene blue (MB) from aqueous solution. For comparison purposes, a commercial activated charcoal (AC) was used. Demineralization was found to have a significant influence in the adsorption capacity of the resultant adsorbents. Three adsorbents were found to follow the Langmuir adsorption model, while the acid washed demineralized adsorbent had higher adsorption capacity than AC and was found to follow the Freundlich adsorption model. The superior performance of the acid washed demineralized adsorbent was verified from the kinetic study where all adsorbents were found to best fit the pseudo-second order model. Adsorption capacities for MB at equilibrium were 367.1, 332.3, 297.4 and 87.6 mg/g, for acid washed demineralized adsorbent, AC, demineralized adsorbent, and raw adsorbent, respectively. Finally, the most promising adsorbents were assessed for their adsorption capacity to remove pharmaceuticals present in a real wastewater treatment effluent. Results indicated ultimate concentration for all targeted compounds below the detection limits for acid washed demineralized adsorbent, AC and demineralized adsorbent. Future implementation of HTL technology in wastewater treatment facilities, will not only provide an efficient way to valorize sewage sludge into bio-crude and nutrients, but can also enhance technology integration by providing the precursors for renewable adsorbents needed in tertiary treatment of wastewater.

Determination of the catechol-O-methyltransferase inhibitor tolcapone and three of its metabolites in animal and human plasma and urine by reversed-phase high-performance liquid chromatography with ultraviolet detection.

Reversed-phase HPLC procedures were developed for the determination of tolcapone (Ro 40-7592) and its metabolites Ro 40-7591, Ro 61-1448, and Ro 47-1669 in plasma and in urine samples. One of the procedures for plasma involved the determination of tolcapone and its metabolite Ro 40-7591 and the other, the determination of the two other metabolites. The urine assay enabled the simultaneous determination of tolcapone and all metabolites in one run. Sample preparation in plasma involved protein precipitation with acetonitrile. Urine was simply diluted. The compounds of interest were monitored in the UV at 270 nm. The limits of quantification were 0.05 microg/ml for each compound (plasma assay) and 0.2 microg/ml for the urine assay. The mean inter-assay precisions (C.V.) were < or = 6% (plasma assay) and < or = 8% (urine assay). The procedures were successfully applied to the sample analysis of animal pharmacokinetic (rat, dog, mouse, rabbit and cynomolgus monkey) and clinical pharmacology studies.

Animal pharmacokinetics and interspecies scaling from animals to man of lamifiban, a new platelet aggregation inhibitor.

Relating pharmacokinetic information obtained in animal species to man (interspecies scaling) can play an important role in enabling understanding of the differences and similarities between species, and helping to predict the kinetic profile of a new compound in man. Interspecies scaling techniques have been applied to lamifiban (Ro 44-9883), a new selective and potent nonpeptidic inhibitor of human glycoprotein IIb-IIIa intended for use in clinical treatment of, for example, acute coronary syndrome. The pharmacokinetic profile of lamifiban in man was predicted from animal data (in rats, dogs and cynomolgus monkeys) by using allometric scaling and concentration-time transformations. These extrapolations for lamifiban were performed prospectively, to help design the first pharmacokinetic studies in man. The approach based on equivalent time was preferred for our prospective predictions, in view of the high values found for the allometric exponents. Using allometric scaling, clearance (CL), half-life (t1/2) and volume of distribution (Vd) were overestimated by approximately two- to fourfold. Compared with allometric scaling, the transformation based on equivalent time improved the prediction for all human pharmacokinetic parameters. For t1/2 and CL, the observed values for man were within the range predicted from the various animal species. Of the individual animal species, the cynomolgus monkey gave the most reliable predictions of these two parameters, as well as accurately predicting the Vd value.

Determination of an aldosterone antagonist in urine by high-performance liquid chromatography using automated column switching.

An automated high-performance liquid chromatographic assay for the determination of an aldosterone antagonist (I) is described using column switching for direct injection of urine samples. After dilution with buffered internal standard solution, the sample was injected onto a clean-up column (17 X 4.6 mm I.D.), dry-packed with C18 reversed-phase material (particle size 30 micron). Polar urine components were removed by flushing the clean-up column with water. Retained substances, including I and the internal standard, were desorbed by backflush elution onto a 5-micron ODS-silica analytical column (125 X 4 mm I.D.), separated with water-methanol-tetrahydrofuran, and detected at 295 nm. After backflushing the analytical column and re-equilibrating the clean-up column, the system was ready for the next injection. The limit of quantification was ca. 100 ng/ml, using a 100-microliter specimen of diluted urine. The mean inter-assay precision of the method up to 25.6 micrograms/ml was 2%. Practicability and accuracy of the new method were demonstrated by the application to excretion studies performed with human volunteers.

Effect of diazepam on cerebral 5-hydroxytryptamine synthesis.

In the brains of normal and reserpinized rats both diazepam and amino-oxyacetic acid (AOAA) decreased the 5-hydroxytryptophan (5HTP) accumulation induced by the decarboxylase inhibitor 3-hydroxybenzylhydrazine (NSD 1015). In reserpinized animals, the action of diazepam was antagonized by picrotoxin and bicuculline in doses which did not themselves influence the NSD 1015-induced rise in 5HTP. In conclusion, diazepam probably depresses 5HT synthesis via GABAergic mechanisms and this effect is not dependent on a functionally intact monoaminergic synaptic transmission.

Blood platelets as models for central 5-hydroxytryptaminergic neurons.

Blood platelets resemble 5-hydroxytryptamine (5HT) neurons of the central nervous system (CNS) with regard to uptake kinetics of 5HT at the plasma membrane and potencies of 5HT uptake inhibitors at this membrane. Furthermore, by comparing 5HT uptake in normal and reserpinized platelets the site of action of uptake inhibitors (plasma membrane, intracellular amine storage organelles) may be determined. The specific 5HT receptors of platelets whose stimulation induces a reversible shape change of platelets seem to react to drugs in a similar way as 5HT receptors of some CNS-regions such as spinal cord, cortex and possibly reticular formation. In other CNS areas e.g. those with dense 5HT innervation and the hippocampus the 5HT receptors show a reaction to drugs which is partially different from that of the platelet receptors. In other respects e.g. the synthesis and turnover of 5HT platelets do not resemble 5HT neurons. It is concluded that platelets may be used with caution as models for 5HT-neurons with regard to some aspect of 5HT-dynamics.

The cardiovascular effects of the antihypertensive drug debrisoquin: A contribution to the pharmacology of chronic treatment. II. Eight-week administration to dogs.

Debrisoquin was administered twice daily at the dose of 2.5 mg/kg p.o. to normotensive mongrel dogs for 8 weeks. Weekly measurements of systolic blood pressure in the conscious animals revealed a drug-induced fall by 10 to 12 mm Hg which was fully developed after 2 weeks and was maintained throughout the treatment period. Body weight, blood volume, hematocrit and plasma sodium and potassium did not change significantly under debrisoquin while there was a slight but just significant increase in plasma volume. No adverse effects were observed. Sixteen hours after the last dose, the animals were anesthetized with chloralose-urethane and subjected to several hemodynamic and biochemical measurements. The following results obtained after prolonged treatment with debrisoquin were not different from those after subacute administration (1-week treatment) reported in the preceding paper: decrease in blood pressure and cardiac output, reduction of the pressor response to bilateral carotid occlusion and of the vasoconstrictor effect of sympathetic nerve stimulation in the perfused hind legs and the isolated perfused mesenteric arteries, decrease in sympathetic tone to the vasculature of the hind leg and depletion of norepinephrine from adrenergic nerve endings. The sensitivity of arterial blood vessels to norepinephrine was not altered. However, the bradycardic effects of debrisoquin did fade in the course of the treatment. The results indicate the absence of the development of tolerance to nearly all cardiovascular effects of debrisoquin during a treatment of 8 weeks.

The cardiovascular effects of the antihypertensive drug debrisoquin: a contribution to the pharmacology of chronic treatment. I. One-week administration to dogs.

Debrisoquin (5 mg/kg/day) was administered to mongrel dogs on 7 consecutive days either i.v. or p.o. Sixteen hours after the last dose, the animals were anesthetized with chloralose-urethane and subjected to several hemodynamic and biochemical measurements which serve for a comparison with the results of the chronic treatment in a subsequent paper. Aortic blood pressure, cardiac output, heart rate (after vagotomy) and pressor responses to bilateral carotid occlusion were decreased by debrisoquin; cardiac contractility and left ventricular end-diastolic pressure remained unaffected. The fall in vascular resistance of the perfused hind legs which occurred after cutting the lumbar sympathetic chain was smaller after debrisoquin than in controls. Increases in perfusion pressure elicited in the hind legs by electrical stimulation of the peripheral end of the sectioned lumbar sympathetic chain or by i.a. injection of tyramine were inhibited by treatment with debrisoquin. The vascular responses to i.a. injections of norepinephrine, angiotensin and acetylcholine remained unchanged. Isolated perfused mesenteric artery preparations obtained from dogs pretreated with debrisoquin showed reduced pressor responses to periarterial nerve stimulation. Dose-response curves for the pressor effect of norepinephrine were not altered by debrisoquin. Debrisoquin administered i.v. or p.o. depleted to a similar extent the stores of norepinephrine in the heart, spleen, mesenteric and femoral arteries.

Increase of striatal dopamine turnover by drugs: interference with granular storage or receptor blackade?

Apomorphine completely antagonized the reserpine-induced enhancement of the striatal 3,4-dihydroxyphenylalanine (dopa) accumulation seen after administration of the decarboxylase inhibitor 3-hydroxybenzylhydrazine (NSD 1015). Reserpine-like drugs, e.g. Ro 4-1284 and Ro 4-9040, markedly enhanced the striatal dopa accumulation (due to NSD 1015) in normal animals but not in rats treated with reserpine plus apomorphine. Haloperidol enhanced the striatal dopa accumulation to a similar extent in normal and in reserpine-apomorphine-treated animals. Chlorpromazine also caused an enhancement of striatal dopa accumulation in both types of animals, but its potency was somewhat higher in normal rats than in those treated with reserpine plus apomorphine. In conclusion, reserpinized animals treated with apomorphine appear to be useful models for differentiating whether a drug enhances striatal DA turnover by interference with granular DA storage or by blockade of DA receptors. The latter seems to be the main mechanism of action of neuroleptic drugs.

Accumulation of 5-HT in non-terminal axons after p-chloro-N-methylamphetamine without degeneration of identified 5-HT nerve terminals.

The effect of a single injection of d,1-p-chloro-N-methylamphetamine (PCMA) on 5-hydroxytryptamine (5-HT)- containing neurons in rat brain was investigated using fluorescence histochemical, electron microscopic and biochemical methods. PCMA caused in a dose-dependent manner (from 4.3 mg/kg), an increase of formaldehyde-induced indoleamine (IA) fluorescence in swollen non-terminal axons during the first 6 days and, in contrast, a diminution of IA fluorescence in nerve terminal regions for up to 42 days after treatment. These changes did not appear to be the result of destruction of 5-HT nerve terminals since at all time intervals investigated (12 h to 42 days), the fine structure and frequency of supra-ependymal 5-HT nerve terminals were unaffected. Moreover, no degenerating nerve terminals were observed in the suprachiasmatic nucleus. A marked transient decrease of IA fluorescence on day 2 in the 5-HT cell bodies B3-B9 was not followed by obvious morphological changes up to 42 days after PCMA. Therefore, the reduced 5-HT content of brain up to 42 days after treatment seems not to be due to a destruction of 5-HT neurons. Moreover, the damage to non-terminal 5-HT axons, as indicated by the 5-HT accumulation, seems not to be severe, at least not to those axons projecting to the cerebral ventricles and suprachiasmatic nucleus, since no degeneration of 5-HT nerve terminals was observed at any of the times investigated.

Cerebral monoamine metabolism in guinea-pigs with ascorbic acid deficiency.

Guinea-pigs kept on a diet deficient in vitamin C showed, after 3 weeks, a marked decrease of ascorbic acid in brain and blood leucocytes as well as of the activity of alkaline phosphatase in blood plasma. Pair-fed animals did not exhibit these changes. The alpha-methyl-p-tyrosine (alpha MpT)-induced diminution of noradrenaline in the hypothalamus and the rest of the brain was attenuated in pair-fed animals, but restored in guinea-pigs deficient in ascorbic acid. The cerebral noradrenaline content (without administration of alpha MpT) showed a decrease in both pair-fed and ascorbic acid deficient animals. The noradrenaline of the heart exhibited a similar tendency. The alpha MpT-induced dopamine decrease in the striatum of ascorbic acid deficient animals was attenuated and the dopamine content (without alpha MpT administration) decreased. Pair-fed animals showed a similar tendency. The striatal concentration of homovanillic acid (HVA) was diminished in both pair-fed and ascorbic acid deficient guinea-pigs. The cerebral content of 5-hydroxyindoleacetic acid showed a decrease in pair-fed as well as in ascorbic acid deficient animals. It is concluded that ascorbic acid deficiency enhances the turnover of brain noradrenaline, whereas under-nutrition without ascorbic acid deficiency (pair-feeding) diminishes the turnover of cerebral noradrenaline, 5-hydroxytryptamine and striatal dopamine.

A comparison of drug-induced rotation in rats lesioned in the medial forebrain bundle with 5,6-dihydroxytryptamine or 6-hydroxydopamine.

Drug-induced rotational behaviour was studied in two groups of rats with differing chemical lesion of the right medial forebrain bundle (MFB). 6-hydroxydopamine (6-OH-DA), 3.5 mug, injected in one group, induced a marked lowering of dopamine (DA) and noradrenaline (NA) in the right hemiforebrain. 5,6-Dihydroxytryptamine (5,6-HT), 10 mug, injected in a second group, produced a profound and long-lasting depletion of 5-hydroxytryptamine (5-HT) and DA, but not of NA. Rotational behaviour induced in both groups by DA receptor agonists (apomorphine, piribedil, L-DOPA, ergometrine, ergocornine, 2-bromo-alpha-ergocryptine, ergocristine, methylergometrine) and agents releasing DA (d-methamphetamine, methylphenidate) were qualitatively identical and quantitatively very similar, suggesting a minor role of 5-HT striatal terminals in these experimental conditions. LSD induced contralateral rotation by direct stimulation of the DA receptor, while L-5-hydroxy-tryptophan (L-5HTP) was inactive.

Lysergic acid diethylamide: evidence for stimulation of cerebral dopamine receptors.

In the rat, lysergic acid diethylamide (LSD) decreased the striatal and retinal content of homovanillic acid. LSD did not change the level of dopamine (DA), but delayed the a-methyl-p-tyrosine-induced disappearance of this amine in the teldiencephalon. In the cat, LSD diminished the DA output into the perfusate of the caudate nucleus. Furthermore, LSD increased the activity of adenylate cyclase in striatal homogenates of rat. These and other findings indicate that in the central nervous system LSD stimulates DA receptors which may be involved in LSD-induced phychosis.