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Biomedical subjects

W Schilling

Publications and source records attributed to W Schilling.

At least 19 recordsLinked to original sources
PubMed2005

The hydraulic capacity of deteriorating sewer systems.

Sewer and wastewater systems suffer from insufficient capacity, construction flaws and pipe deterioration. Consequences are structural failures, local floods, surface erosion and pollution of receiving waters bodies. European cities spend in the order of five billion Euro per year for wastewater network rehabilitation. This amount is estimated to increase due to network ageing. The project CARE-S (Computer Aided RE-habilitation of Sewer Networks) deals with sewer and storm water networks. The final project goal is to develop integrated software, which provides the most cost-efficient system of maintenance, repair and rehabilitation of sewer networks. Decisions on investments in rehabilitation often have to be made with uncertain information about the structural condition and the hydraulic performance of a sewer system. Because of this, decision-making involves considerable risks. This paper presents the results of research focused on the study of hydraulic effects caused by failures due to temporal decline of sewer systems. Hydraulic simulations are usually carried out by running commercial models that apply, as input, default values of parameters that strongly influence results. Using CCTV inspections information as dataset to catalogue principal types of failures affecting pipes, a 3D model was used to evaluate their hydraulic consequences. The translation of failures effects in parameters values producing the same hydraulic conditions caused by failures was carried out through the comparison of laboratory experiences and 3D simulations results. Those parameters could be the input of 1D commercial models instead of the default values commonly inserted.

Cities↗
PubMed2003

A software monitor for intermittent bacteria contamination in urban rivers.

Norwegian receiving waters are of such high water quality that authorities consider opening them for bathing. The leading parameter to monitor the quality of bathing waters is fecal coliform bacteria (FC). For this parameter no rapid detection method is available. The main objective of this case study was to find a way to quickly predict bacteria contamination by observing different online parameters such as flow, conductivity or spectral absorption coefficient (SAC). In this study historical data from 1994 to 2000 was analyzed, and over a period of five weeks water samples were taken and analyzed for bacteria. The analysis of the historical data revealed fundamental sampling problems, which made the data useless for the purpose of this study. The analysis of the data collected for this study showed that exceeding the bathing water standard for bacteria can be predicted by evaluating the SAC with an acceptable accuracy. Furthermore a simple river quality model was implemented, including bacteria as a load fraction. With the help of rain data and discharge predictions expected bacteria numbers exceeding the bathing water standard could also be forecast.

Cities↗
PubMed2002

Pollution based real time control of wastewater systems.

Wastewater systems are traditionally built as static systems to handle a design load. The real load varies, though, and hardly ever equals the design load. This implies that wastewater systems hardly ever operate in an optimum way, especially during wet weather. Real time control (RTC) of regulators can improve the operation by better fit of the system to the actual state and load. RTC based on pollutant concentrations together with hydraulic conditions (pollution based real time control, PBRTC) is investigated in this paper to assess the potential pollutant load reduction on receiving waters at wet weather without expansion of transport or storage capacity. Both CSOs and WWTP effluents contribute to the pollutant discharges to receiving waters and both are considered. Three cases are studied to assess the potential benefit of PBRTC. Giving priority to the most polluted wastewater for treatment and storage in branched interceptor systems can reduce CSO discharge loads by more than 20%. Biological WWTPs and especially activated sludge plants are more complex and less stable than chemical precipitation plants during and after high pollutant and hydraulic load. Biological plants can hence profit more from PBRTC than chemical precipitation plants. Receiving waters that are sensitive to acute effects caused by intermittent discharges can benefit more from PBRTC than receiving waters with problems connected to long-term accumulation of pollution.

Chemical Precipitation↗
PubMed2002

Deterministic modelling of integrated urban drainage systems.

Today, the main concepts required for describing the dynamics of drainage in an entire urban area are known and models are available that can reasonably simulate the behaviour of the urban water system. Still, such integrated modelling is a complex exercise not only due to the sheer size of the model, but also due to the different modelling approaches that reflect the history of the sub-models used and of the purpose they were built for. The paper reviews the state of the art in deterministic modelling, outlines experiences and discusses problems and future developments.

Cities↗
PubMed2001

Urban drainage redefined: from stormwater removal to integrated management.

Even though urban drainage has been practised for more than 5000 years, many challenges arising from growing demands on drainage still remain with respect to runoff quantity and quality; landscape aesthetics, ecology and beneficial uses; and operation of existing urban wastewater systems. Further advances can be achieved by adopting an integrated approach, optimal operation of the existing infrastructure, advanced pollution and runoff source controls, improved resilience of receiving waters, and adaptive water management. The specific research needs include new technologies and strategies for stormwater management, advanced treatment of urban wet-weather effluents, and tools for analysis and operation of drainage systems. High diversity of demands on, and region/site specific conditions of, urban drainage shapes the role of urban drainage experts--as mediators among the many stakeholders and fields involved.

Cities↗
PubMed2000

NKP608: a selective NK-1 receptor antagonist with anxiolytic-like effects in the social interaction and social exploration test in rats.

NKP608 is a non-peptidic derivative of 4-aminopiperidine which acts as a selective, specific and potent antagonist at the neurokinin-1 (NK-1) receptor both in vitro and in vivo. In vitro, the binding of NKP608 to bovine retina was characterized by an IC50 of 2.6+/-0.4 nM, whereas the compound's affinity to other receptor binding sites, including NK-2 and NK-3, was much lower. Species differences in IC(50) values with NKP608 were less pronounced than with previously described NK-1 receptor antagonists, being 13+/-2 and 27+/-2 nM in gerbil midbrain and rat striatum, respectively. In vivo, using the hind foot thumping model in gerbils, NKP608 exhibited a potent NK-1 antagonistic activity following oral administration (ID(50)=0.23 mg/kg; 2 h pretreatment), supporting a central activity of NKP608. The compound had a long duration of action with an ID(50) value of 0. 15 mg/kg p.o. and 0.38 mg/kg p.o. following a pretreatment of 5 and 24 h, respectively. Following a subchronic administration for 7 consecutive days (once daily) there was no evidence for the development of tolerance or accumulation. In the social interaction test performed in a highly illuminated, unfamiliar test arena, NKP608 specifically increased the time the two rats spent in social contact, and there was no concomitant increase in parameters reflecting general activity, i.e. ambulation (number of square entries) or the number of rearings. Active social time was maximally increased at a dose range of 0.01-1 mg/kg p.o. NKP608, the effect being weaker or absent at both lower (0.001 mg/kg p.o.) and higher (10 mg/kg p.o.) doses. A comparable bell-shaped dose-response relation was seen in the social exploration test in rats. In this modified resident/intruder paradigm, maximal increase in social contact of the intruder rat directed towards the resident rat was seen at a similar dose range (0.03-3 mg/kg p.o.) The effects observed following an acute oral administration of NKP608 were comparable to those seen following a treatment with the well-known benzodiazepine, chlordiazepoxide, in both these tests. These findings indicate that NKP608 exhibits an anxiolytic-like effect and that this effect, as concluded from the observed antagonism of the hind foot thumping induced by i.c.v. administration of the NK-1 receptor agonist SPOMe, is centrally mediated. This makes this compound a potentially promising candidate for treating anxiety-related disorders in humans.

Administration, Oral↗
PubMed2000

Design, synthesis and SAR of a series of 2-substituted 4-amino-quinazoline neuropeptide Y Y5 receptor antagonists.

The design of a novel series of NPY-Y5 receptor antagonists is described. Key elements for the design were the identification of weak Y5 hits from a Y1 program, results from a combinatorial approach and database mining. This led to the discovery of the quinazoline 4 and the aryl-sulphonamide moiety as major components of the pharmacophore for Y5 affinity. The synthesis and SAR towards CGP71683A is described.

Drug Design↗
PubMed1999

Simultaneous extraction of hepatitis C virus (HCV), hepatitis B virus, and HIV-1 from plasma and detection of HCV RNA by a reverse transcriptase-polymerase chain reaction assay designed for screening pooled units of donated blood.

BACKGROUND: Testing for viral nucleic acids should reduce the residual risk of transmitting viral infections by transfusion of blood components. The AmpliScreen Hepatitis C (HCV) Test, Version 2.0, was designed for screening pools composed of samples from individual units of blood or plasma. STUDY DESIGN AND METHODS: An ultracentrifugation step during sample processing simultaneously extracts and concentrates HCV, HIV type 1, and hepatitis B virus particles from plasma. An HCV internal control RNA serves as an extraction and amplification control for each processed sample. Processed samples are amplified by reverse transcriptase polymerase chain reaction and detected by hybridization of the amplified products to HCV- and internal-control-specific oligonucleotide probes. Plasma samples containing known quantities of HCV were used to evaluate analytical sensitivity and precision. RESULTS: The analytical sensitivity of the test was 25 IU of HCV per mL of pooled plasma; all HCV genotypes were detected with similar efficiency. The test did not react with other blood-borne viruses. The within-run and total coefficients of variation were 1.3-13.0 percent and 1.7-22.0 percent, respectively, with low copy samples producing the more variable results. The test performed well using plasma collected in either EDTA, ACD, or PPT Vacutainer tubes. Plasma samples containing elevated levels of hemoglobin, albumin, triglycerides, or bilirubin did not interfere with the test. The test detected HCV RNA 23 to 32 days prior to seroconversion for four of the five seroconversion panels tested. CONCLUSION: The AmpliScreen HCV Test, Version 2.0 provides a reproducible and specific method for screening pooled blood units for HCV. Theoretically, this test has sufficient sensitivity to detect a single infected unit containing 2.4 x 10(3) IU of HCV per mL in a pool with 95 uninfected units and should reduce the window period by at least 20 to 30 days.

Blood↗
PubMed1999

Sanglifehrins A, B, C and D, novel cyclophilin-binding compounds isolated from Streptomyces sp. A92-308110. I. Taxonomy, fermentation, isolation and biological activity.

A novel class of macrolides for which the name sanglifehrins is proposed, has been discovered from actinomycete strains based on their high affinity binding for cyclophilin A (CypA), an immunophilin originally identified as a cytosolic protein binding cyclosporin A (CsA). The sanglifehrins were produced by Streptomyces sp. A92-308110. They were isolated and purified by extraction and several chromatographic, activity-guided steps. Sanglifehrins A and B exhibit a 10 to approximately 20 fold higher affinity for CypA than CsA, whereas the affinity of sanglifehrins C and D for CypA is comparable to that of CsA. Sanglifehrins exhibit a lower immunosuppressive activity than CsA when tested in the mixed lymphocyte reaction. Their in vitro activity indicates that they belong to a novel class of immunosuppressants.

Animals↗
PubMed1999

Sanglifehrins A, B, C and D, novel cyclophilin-binding compounds isolated from Streptomyces sp. A92-308110. II. Structure elucidation, stereochemistry and physico-chemical properties.

A novel class of macrolides, the sanglifehrins, was discovered by screening of actinomycete strains with a cyclophilin-binding assay. The chemical structures and absolute stereochemistries of the sanglifehrins A, B, C and D were determined unambiguously by NMR-techniques and by X-ray crystallography of the complex with cyclophilin A. Sanglifehrin A consists of a 22-membered macrocycle containing a tripeptide subunit and features in position 23 a chain of nine carbon atoms bearing a spirocyclic substituent. Sanglifehrins A and B are genuine metabolites whereas sanglifehrins C and D are artefacts.

Anti-Bacterial Agents↗
PubMed1998

Food intake in free-feeding and energy-deprived lean rats is mediated by the neuropeptide Y5 receptor.

The new neuropeptide Y (NPY) Y5 receptor antagonist CGP 71683A displayed high affinity for the cloned rat NPY Y5 subtype, but > 1, 000-fold lower affinity for the cloned rat NPY Y1, Y2, and Y4 subtypes. In LMTK cells transfected with the human NPY Y5 receptor, CGP 71683A was without intrinsic activity and antagonized NPY-induced Ca2+ transients. CGP 71683A was given intraperitoneally (dose range 1-100 mg/kg) to a series of animal models of high hypothalamic NPY levels. In lean satiated rats CGP 71683A significantly antagonized the increase in food intake induced by intracerebroventricular injection of NPY. In 24-h fasted and streptozotocin diabetic rats CGP 71683A dose-dependently inhibited food intake. During the dark phase, CGP 71683A dose-dependently inhibited food intake in free-feeding lean rats without affecting the normal pattern of food intake or inducing taste aversion. In free-feeding lean rats, intraperitoneal administration of CGP 71683A for 28 d inhibited food intake dose-dependently with a maximum reduction observed on days 3 and 4. Despite the return of food intake to control levels, body weight and the peripheral fat mass remained significantly reduced. The data demonstrate that the NPY Y5 receptor subtype plays a role in NPY-induced food intake, but also suggest that, with chronic blockade, counterregulatory mechanisms are induced to restore appetite.

Animals↗
PubMed1997

Cymbimicin A and B, two novel cyclophilin-binding structures isolated from actinomycetes.

Two novel metabolites, cymbimicins A and B, were isolated from the culture broth of a strain of Micromonospora sp. by screening for cyclophilin binding metabolites from actinomycete strains. Cymbimicin A binds to cyclophilin A with a high affinity six fold lower than to that of cyclosporin A. The binding affinity of cymbimicin B is about 100 times lower. The taxonomy of the producing strain, fermentation, isolation, physical and biological properties and structure elucidation are described.

Binding, Competitive↗
PubMed1996

Antascomicins A, B, C, D and E. Novel FKBP12 binding compounds from a Micromonospora strain.

5 novel ascomycin-like compounds, antascomicins A, B, C, D and E were isolated from a strain of Micromonospora. The antascomicins bind strongly to the FK506-binding protein FKBP12 and antagonize the immunosuppressive activity of FK506 and rapamycin. The strain description, fermentation, structure elucidation and biological activity of these compounds are described.

Animals↗
PubMed1992

Endothelium-dependent relaxant effect of neurokinins on rabbit aorta is mediated by the NK1 receptor.

Several neurokinins, namely substance P, neurokinin A, neurokinin B, [beta-Ala8]neurokinin A-(4-10) and senktide, were tested on noradrenaline-precontracted rabbit aortic rings to characterize the receptor mediating their endothelium-dependent relaxant effect in this preparation. CP-96,345, the new nonpeptide antagonist selective for the NK1 receptor, was also studied. Substance P, neurokinin A and neurokinin B, in that order of potency, were effective in relaxing precontracted rings, indicating the involvement of the NK1 receptor; [beta-Ala8]neurokinin A-(4-10) and senktide, which are selective agonists for NK2 and NK3 receptors, respectively, had no significant relaxant effect. The relaxant effects of substance P, neurokinin A and neurokinin B were competitively antagonized by nanomolar concentrations of CP-96,345. These findings support the view that the NK1 receptor mediates the endothelium-dependent relaxant effect of the neurokinins in rabbit aorta.

Animals↗
PubMed1992

Bradykinin and other inflammatory mediators in BAL-fluid from patients with active pulmonary inflammation.

We evaluated the levels of bradykinin, albumin, TAME-esterase activity, histamine, PGD2 and LTC4 in bronchoalveolar lavage fluid from asthmatics and from patients with pneumonia, sarcoidosis, fibrosis, and chronic bronchitis. Compared with the results of healthy volunteers and atopic asymptomatic asthmatics the bradykinin levels and TAME-esterase activity were significantly elevated. In all other groups, histamine was additionally elevated in asymptomatic asthmatics, whereas albumin was elevated in symptomatic asthmatics and fibrosis patients, and decreased in chronic bronchitis and pneumonia patients. Following local intrabronchial allergen challenge of mild grass pollen asthmatics out of season bradykinin levels increased significantly, correlated with albumin, histamine and TAME-esterase activity. In contrast to the increased mediator concentrations in the early phase reaction there was no change of BAL cells in asthmatics compared to baseline and healthy volunteers. The presence of bradykinin in the bronchoalveolar space of patients with active pulmonary inflammations and bradykinin generation in asthmatics as a result of intrabronchial allergen challenge provides strong evidence that kinins are involved in inflammatory disorders of the lower airways.

Asthma↗