Influence of Nitrate and Sulfate on the Anaerobic Treatment of Pharmaceutical Wastewater

Anaerobic treatment of wastewater from the pharmaceutical industry, which contained about 3.2 g/L of sulfate, was carried out in an Upflow Anaerobic Sludge Blanket (UASB) reactor. After a startup period of 120 days, a chemical oxygen demand (COD) removal efficiency of more than 90 % was obtained along with an organic loading rate (OLR) of 1.5 g COD/(L day). During the same period, the sulfate removal was about 90 %. However, the performance of the reactor was affected when the loading rate was increased to 2.09 g COD/(L day). It was found that the accumulation of sulfides, combined with a decrease in the pH, affected the reactor performance. In batch reactor studies with pharmaceutical wastewater it was observed that methane production began only after the initiation of nitrate consumption. The denitrification process can inhibit sulfate reduction at high nitrate concentrations, but compared to reactors without nitrate, the sulfate reduction process and sulfide formation were quickly initiated at low nitrate concentrations. The methanogenic activity was however affected by the presence of more than 2 g/L of sulfate.     

Bioactive Sulforaphane from in vitro Propagated Brassica Seedlings

Sulforaphane is a biologically active phytochemical found abundantly in Brassica species. Sulforaphane from eighteen samples of three‐day‐old in vitro seedlings from Brassicas, the Brassica oleracea and Brassica rapa varieties were analyzed by HPLC. San Martino, cavolfiore Alverda, cavolo verza riccio d'Asti and cavolfiore Minaret (4.57; 4.54; 4.53 and 4.53 [mg/g d.w], respectively) seedlings showed the highest level of sulforaphane. The presented data may be applicable to choose sulforaphane‐rich Brassica varieties for functional foods. A higher sulforaphane content in functional foods might offer health benefits or desirable physiological effects.     

Evaluation of carbamazepine uptake and metabolization by Typha spp., a plant with potential use in phytotreatment

Phytoremediation technologies such as constructed wetlands have shown higher efficiencies in removal of pharmaceuticals from wastewaters than conventional wastewater treatment processes, and plants seem to have an important role in the removal of some of those compounds. In this context, a study was conducted to assess tolerance, uptake, and metabolism of the epilepsy drug, carbamazepine, by the macrophyte Typha spp. This evaluation was conducted in hydroponic solutions with 0.5-2.0 mg/L of this pharmaceutical for a maximum period of 21 days. The removal of carbamazepine from nutrient solutions by the plants reached values of 82% of the initial contents. Furthermore, a metabolite (10,11-dihydro-10,11-epoxycarbamazepine) was detected in leaf tissues indicating carbamazepine translocation and metabolism inside plants. Activities of antioxidant enzymes catalase, superoxide dismutase, and guaiacol peroxidase generally increase (after some mild initial inhibition in the case of the latter enzyme) as result of the abiotic stress caused by the exposure to carbamazepine, but ultimately Typha seemed able to cope with its toxicity. The results obtained in this study suggest the ability of Typha spp., to actively participate in the removal of carbamazepine from water when used in phytotreatment systems.     

Solid-phase treatment with the fungus Trametes versicolor substantially reduces pharmaceutical concentrations and toxicity from sewage sludge

For safe biosolid-land-applying, sludge should be contaminant-free. However, it may contain important amounts of micropollutants, not removed in the wastewater-treatment-processes. An alternative treatment with the fungus Trametes versicolor was applied in sterile solid-phase systems consisting of sludge and a lignocellulosic substrate. Fungal colonization and activity were demonstrated during the process, according to monitoring of ergosterol, laccase activity and the naproxen-degradation test (ND24). Fourteen out of 43 analyzed pharmaceuticals were found in the raw sludge. After treatment, phenazone, bezafibrate, fenofibrate, cimetidine, clarithromycin, sulfamethazine and atenolol were completely removed, while removals between 42% and 80% were obtained for the remaining pharmaceuticals. Toxicological analyses (Daphnia magna, Vibrio fischeri and seed germination) showed an important reduction in sludge toxicity after treatment. Results suggest that a solid-phase treatment with T. versicolor may reduce the ecotoxicological impact of micropollutants present in sewage sludge. This is the first report of a fungal-approach for elimination of emerging pollutants from biosolids.     

Development and application of a brain-specific cDNA microarray for effect evaluation of neuro-active pharmaceuticals in zebrafish (Danio rerio)

The environmental fate and ecotoxicological effect of pharmaceuticals are poorly understood, and standardized tests to detect and evaluate their potential effects in the environment are not available. We developed a zebrafish brain-specific microarray containing 682 neurologically relevant cDNA-fragments. To investigate the applicability of this microarray for studying neurotoxic modes-of-action and impact assessment of neuro-active pharmaceuticals in zebrafish, chlorpromazine was used as a model compound. After exposure to chlorpromazine (75 μg/L) for 2, 4, 14 and 28 days or control treatment RNA was extracted from brains of males and females. Fluorescently labeled cDNA was prepared and hybridized to the custom microarray. In total, 56 genes were differentially expressed in brains of male and/or female zebrafish, of which most genes were down-regulated. A clear difference in response to chlorpromazine exposure between males and females was observed with exposure time as well as in functional classes of affected genes. The presented study is one of the first reports on molecular effects of human neuro-active pharmaceuticals in aquatic non-target organisms. This new genomic tool successfully detected gene expression effects of exposure to chlorpromazine in the brain of zebrafish. Reported gene expression effects are found to be consistent with literature data for other laboratory animals.     

Heterologous production of secondary metabolites as pharmaceuticals in <Emphasis Type="Italic">Saccharomyces</Emphasis> <Emphasis Type="Italic">cerevisiae</Emphasis>

Heterologous expression of genes involved in the biosynthesis of various products is of increasing interest in biotechnology and in drug research and development. Microbial cells are most appropriate for this purpose. Availability of more microbial genomic sequences in recent years has greatly facilitated the elucidation of metabolic and regulatory networks and helped gain overproduction of desired metabolites or create novel production of commercially important compounds. Saccharomyces cerevisiae, as one of the most intensely studied eukaryotic model organisms with a rich density of knowledge detailing its genetics, biochemistry, physiology, and large-scale fermentation performance, can be capitalized upon to enable a substantial increase in the industrial application of this yeast. In this review, we describe recent efforts made to produce commercial secondary metabolites in Saccharomyces cerevisiae as pharmaceuticals. As natural products are increasingly becoming the center of attention of the pharmaceutical and nutraceutical industries, such as naringenin, coumarate, artemisinin, taxol, amorphadiene and vitamin C, the use of S. cerevisiae for their production is only expected to expand in the future, further allowing the biosynthesis of novel molecular structures with unique properties.     

Biocatalysis for the synthesis of pharmaceuticals and pharmaceutical intermediates

Biocatalysis has been increasingly used for pharmaceutical synthesis in an effort to make manufacturing processes greener and more sustainable. Biocatalysts that possess excellent activity, specificity, thermostability and solvent-tolerance are highly sought after to meet the requirements of practical applications. Generating biocatalysts with these specific properties can be achieved by either discovery of novel biocatalysts or protein engineering. Meanwhile, chemoenzymatic routes have also been designed and developed for pharmaceutical synthesis on an industrial scale. This review discusses the recent discoveries, engineering, and applications of biocatalysts for the synthesis of pharmaceuticals and pharmaceutical intermediates. Key classes of biocatalysts include reductases, oxidases, hydrolases, lyases, isomerases, and transaminases.     

Peptide therapeutics for the treatment of gastrointestinal disorders

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Hightech aus der grünen Apotheke. Biopharmazeutika aus Pflanzen

Hightech from Natures Pharmacy Plants produce a plethora of valuable natural products, many of which are used as pharmaceuticals. Today, a large fraction of the novel pharmaceuticals entering the market are biomolecules of proteinaceous nature (antibodies, hormones, cytokines, vaccines) and they are produced in transgenic organisms like bacteria, yeast, or mammalian cell cultures. Plants are also capable to serve as a production host for novel therapeutics like monoclonal antibodies, hormones like insulin, or subunit vaccines. Transgenic plants and plant cell cultures are already modified to produce protein biopharmaceuticals and vaccines on a large scale basis and in some aspects they have clear advantages over conventional production hosts (e.g. cost of goods, speed of production, or posttranslational modification of therapeutic proteins). Therefore, plant biotechnology could create entirely novel medicinal plants with applications not known before.