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1.
Sci Rep ; 7(1): 13112, 2017 10 13.
Article in English | MEDLINE | ID: mdl-29030642

ABSTRACT

Urea cycle enzyme deficiency (UCED) patients with hyperammonemia are treated with sodium benzoate (SB) and sodium phenylacetate (SPA) to induce alternative pathways of nitrogen excretion. The suggested guidelines supporting their use in the management of hyperammonemia are primarily based on non-analytic studies such as case reports and case series. Canine congenital portosystemic shunting (CPSS) is a naturally occurring model for hyperammonemia. Here, we performed cross-over, randomized, placebo-controlled studies in healthy dogs to assess safety and pharmacokinetics of SB and SPA (phase I). As follow-up safety and efficacy of SB was evaluated in CPSS-dogs with hyperammonemia (phase II). Pharmacokinetics of SB and SPA were comparable to those reported in humans. Treatment with SB and SPA was safe and both nitrogen scavengers were converted into their respective metabolites hippuric acid and phenylacetylglutamine or phenylacetylglycine, with a preference for phenylacetylglycine. In CPSS-dogs, treatment with SB resulted in the same effect on plasma ammonia as the control treatment (i.e. saline infusion) suggesting that the decrease is a result of volume expansion and/or forced diuresis rather than increased production of nitrogenous waste. Consequentially, treatment of hyperammonemia justifies additional/placebo-controlled trials in human medicine.


Subject(s)
Hyperammonemia/drug therapy , Nitrogen/blood , Saline Waters/therapeutic use , Animals , Dogs , Female , Hyperammonemia/blood , Male , Phenylacetates/adverse effects , Phenylacetates/pharmacokinetics , Phenylacetates/therapeutic use , Random Allocation , Sodium Benzoate/adverse effects , Sodium Benzoate/pharmacokinetics , Sodium Benzoate/therapeutic use
2.
Vet J ; 204(3): 282-6, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25959128

ABSTRACT

Portosystemic shunting (PSS) often results in hyperammonaemia and, consequently, hepatic encephalopathy. This retrospective study evaluated the sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively) and other test performance metrics for the ammonia tolerance test (ATT), serum fasting bile acids (FBA), serum fasting ammonia concentration (FA), and combinations of these tests for their association with PSS in dogs. Medical records of 271 dogs suspect for PSS (symptomatic group) and 53 dogs returning for evaluation after surgical closure of a congenital PSS (CPSS post-surgical control group) were analysed. In the symptomatic group, ATT at 40 min (T40), and the FBA had the highest sensitivity (100% and 98%, respectively) and NPV (100% and 96%, respectively) for PSS. The combination of increased FBA and FA had the highest specificity (97%), with a PPV of 97%, and a positive likelihood ratio of 29. In the CPSS post-surgical control group, the specificity and PPV of FA and the combination of increased FBA/FA were both 100%. In purebred populations, the NPV of all tests was 100%. Consequently, PSS would be ruled out in a symptomatic dog with normal FBA or ATT (T40) and would be highly probable when both FBA and FA are increased. Increased FA was conclusive for PSS in dogs evaluated for post-surgical closure of a CPSS. FBA was the most suitable test for screening purposes.


Subject(s)
Ammonia/blood , Arteriovenous Malformations/veterinary , Bile Acids and Salts/blood , Dog Diseases/blood , Portal System/abnormalities , Administration, Rectal , Ammonia/administration & dosage , Animals , Arteriovenous Malformations/diagnosis , Dog Diseases/diagnosis , Dog Diseases/metabolism , Dogs , Predictive Value of Tests , Retrospective Studies , Sensitivity and Specificity
3.
Bioresour Technol ; 179: 314-322, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25549905

ABSTRACT

Energy requirements for resource transport of algae cultivation are unknown. This work describes the quantitative analysis of energy requirements for water and CO2 transport. Algae cultivation models were combined with the quantitative logistic decision model 'BeWhere' for the regions Benelux (Northwest Europe), southern France and Sahara. For photobioreactors, the energy consumed for transport of water and CO2 turns out to be a small percentage of the energy contained in the algae biomass (0.1-3.6%). For raceway ponds the share for transport is higher (0.7-38.5%). The energy consumption for transport is the lowest in the Benelux due to good availability of both water and CO2. Analysing transport logistics is still important, despite the low energy consumption for transport. The results demonstrate that resource requirements, resource distribution and availability and transport networks have a profound effect on the location choices for algae cultivation.


Subject(s)
Cell Culture Techniques/methods , Eukaryota/growth & development , Biomass , Carbon Dioxide/metabolism , Energy Metabolism , Geography , Logistic Models , Thermodynamics , Water/metabolism , Weather
4.
Curr Alzheimer Res ; 7(5): 409-14, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20455868

ABSTRACT

Macrophage colony-stimulating factor (M-CSF) is a hematopoietic growth factor that activates microglial cells, involved in phagocytosis of amyloid-beta (Abeta) in the brain. In the present study, we found in 50 patients with Alzheimer's disease (AD) significantly increased M-CSF plasma levels compared to 22 patients with mild cognitive impairment (MCI) and 35 age-matched healthy controls. In contrast, MCI patients showed significantly decreased M-CSF levels in cerebrospinal fluid (CSF) compared to AD patients and 20 patients with other non-inflammatory neurological disease (NIND). Analyzing the impact of Beta-amyloid 1-42 (Abeta 1-42), tau protein and M-CSF for differentiation between the groups we found that M-CSF, but not Abeta 1-42 and tau-protein is a significant parameter for distinction between MCI and NIND patients with 68.8% sensitivity and 75.0% specificity. M-CSF CSF levels < or = 357.8 pg/ml yielded 73.7% sensitivity and 75.0% specificity for diagnosing MCI patients in comparison with control subjects. In conclusion, our data indicate that M-CSF in CSF could be a putative biomarker for MCI.


Subject(s)
Alzheimer Disease/blood , Alzheimer Disease/cerebrospinal fluid , Cognition Disorders/blood , Cognition Disorders/cerebrospinal fluid , Macrophage Colony-Stimulating Factor/blood , Macrophage Colony-Stimulating Factor/cerebrospinal fluid , Aged , Aged, 80 and over , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Female , Humans , Male , Middle Aged
5.
Biomech Model Mechanobiol ; 8(6): 499-507, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19360445

ABSTRACT

The shear stresses in printed scaffold systems for tissue engineering depend on the flow properties and void volume in the scaffold. In this work, computational fluid dynamics (CFD) is used to simulate flow fields within porous scaffolds used for cell growth. From these models the shear stresses acting on the scaffold fibres are calculated. The results led to the conclusion that the Darcian (k(1)) permeability constant is a good predictor for the shear stresses in scaffold systems for tissue engineering. This permeability constant is easy to calculate from the distance between and thickness of the fibres used in a 3D printed scaffold. As a consequence computational effort and specialists for CFD can be circumvented by using this permeability constant to predict the shear stresses. If the permeability constant is below a critical value, cell growth within the specific scaffold design may cause a significant increase in shear stress. Such a design should therefore be avoided when the shear stress experienced by the cells should remain in the same order of magnitude.


Subject(s)
Tissue Engineering/methods , Algorithms , Animals , Bone and Bones/pathology , Cell Proliferation , Extracellular Matrix , Goats , Mesenchymal Stem Cells/cytology , Models, Statistical , Perfusion , Permeability , Porosity , Reproducibility of Results , Shear Strength , Stress, Mechanical , Tissue Scaffolds/chemistry , Viscosity
6.
J Biotechnol ; 125(2): 252-68, 2006 Sep 01.
Article in English | MEDLINE | ID: mdl-16621094

ABSTRACT

Monitoring and control of production processes for biopharmaceuticals have become standard requirements to support consistency and quality. In this paper, a constant specific growth rate in fed-batch cultivation of Bordetella pertussis is achieved by a newly designed specific growth rate controller. The performance of standard control methods is limited because of the time-varying characteristics due to the exponentially increasing biomass and volume. To cope with the changing dynamics, a stable model reference adaptive controller is designed which adapts the controller settings as volume and biomass increase. An important asset of the design is that dissolved oxygen is the only required online measurement. An original design without considering the dissolved oxygen dynamics resulted experimentally in oscillatory behaviour. Hence, in contrast to common believes, it is essential to include dissolved oxygen dynamics. The robustness of this novel design was tested in simulation. The validity of the design was confirmed by laboratory experiments for small-scale production of B. pertussis. The controller was able to regulate the specific growth rate at the desired set point, even during a long fed-batch cultivation time with exponentially increasing demands for substrates and oxygen.


Subject(s)
Bioreactors/microbiology , Bordetella pertussis/growth & development , Industrial Microbiology/methods , Algorithms , Bacteriological Techniques/methods , Biomass , Computer Simulation , Reproducibility of Results
7.
J Vet Intern Med ; 19(3): 321-4, 2005.
Article in English | MEDLINE | ID: mdl-15954545

ABSTRACT

The pathogenesis of congenital portosystemic shunt (CPSS) in dogs still is incompletely understood. In Irish Wolfhounds and Yorkshire Terriers, CPSS is reported to be hereditary. The aim of this study was to investigate a possible genetic basis and the mode of inheritance of CPSS in Cairn Terriers. Between July 1990 and July 2001, 6-week-old pups of the Dutch Cairn Terrier population were screened by measuring venous ammonia concentrations and in the presence of hyperammonemia by ultrasonography, autopsy, portal vein angiography, or exploratory celiotomy. The same successfully operated female was used 3 times in test matings with an unrelated affected male, her unaffected sire, and an affected offspring. The prevalence of CPSS in the general Cairn Terrier population, the direct progeny of frequently used males, and the offspring of the test matings were tested for significant differences. In total, 6,367 Cairn Terriers were screened; 32 males and 26 females had CPSS. In 3 large family groups, significantly higher prevalences were found compared with the general population (P < .0001, P < .0001, and P < .044). The prevalence of CPSS in the offspring of the test matings was significantly higher (P < .002) than in the general population. No sex predisposition occurred among the affected dogs. The higher prevalence of CPSS in the test matings and the 3 family groups compared with the general population indicates that CPSS in Cairn Terriers is a genetic disease. The inheritance is autosomal and most likely polygenic or monogenic with variable expression.


Subject(s)
Dog Diseases/congenital , Dog Diseases/genetics , Portal System/abnormalities , Animals , Breeding , Dogs , Female , Genetic Predisposition to Disease , Male , Pedigree
8.
Water Res ; 37(2): 429-35, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12502071

ABSTRACT

In the field of water technology, forward uncertainty propagation is frequently used, whereas backward uncertainty propagation is rarely used. In forward uncertainty analysis, one moves from a given (or assumed) parameter subspace towards the corresponding distribution of the output or objective function. However, in the backward uncertainty propagation, one moves in the reverse direction, from the distribution function towards the parameter subspace. Backward uncertainty propagation, which is a generalisation of parameter estimation error analysis, gives information essential for designing experimental or monitoring programmes, and for tighter bounding of parameter uncertainty intervals. The procedure of carrying out backward uncertainty propagation is illustrated in this technical note by working example for an oxidation ditch wastewater treatment plant. Results obtained have demonstrated that essential information can be achieved by carrying out backward uncertainty propagation analysis.


Subject(s)
Models, Theoretical , Water Movements , Water Supply , Forecasting , Oxidation-Reduction , Waste Disposal, Fluid
9.
Soc Sci Med ; 55(2): 227-34, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12144137

ABSTRACT

This article describes the development of a valid and reliable instrument to measure different dimensions of public trust in health care in the Netherlands. This instrument is needed because the concept was not well developed, or operationalized in earlier research. The new instrument will be used in a research project to monitor trust and to predict behaviour of people such as consulting "alternative practitioners". The idea for the research was suggested by economic research into public trust. In the study, a phased design was used to overcome the operationalization problem. In the first phase, a qualitative study was conducted; and, in the second, a quantitative study. In the first phase, more than 100 people were interviewed to gain insight into the issues they associated with trust. Eight categories of issues that were derived from the interviews were assumed to be possible dimensions of trust. On the basis of these eight categories and the interviews, a questionnaire was developed that was used in the second phase. In this phase, the questionnaire was sent to 1500 members of a consumer panel; the response was 70 percent. The analysis reveals that six of the eight possible dimensions appear in factor analysis. These dimensions are trust in: the patient-focus of health care providers; macro policies level will have no consequences for patients; expertise of health care providers; quality of care; information supply and communication by care providers and the quality of cooperation. The reliability of most scales is higher than 0.8. The validity of the dimensions is assessed by determining the correlation between the scales on the one hand, and people's experience and a general mark they would assign on the other. We conclude that public trust is a multi-dimensional concept, including not only issues that relate to the patient-doctor relationship, but also issues that relate to health care institutions. The instrument appears to be reliable and valid.


Subject(s)
Attitude to Health , Health Care Surveys/methods , Professional-Patient Relations , Public Opinion , Communication , Evaluation Studies as Topic , Humans , Interpersonal Relations , Interviews as Topic , Netherlands , Patient Education as Topic , Patient-Centered Care , Quality Indicators, Health Care , Quality of Health Care , Reproducibility of Results , Research Design
10.
Water Sci Technol ; 45(4-5): 151-8, 2002.
Article in English | MEDLINE | ID: mdl-11936628

ABSTRACT

This paper presents validation and implementation results of a benchmark developed for a specific full-scale oxidation ditch wastewater treatment plant. A benchmark is a standard simulation procedure that can be used as a tool in evaluating various control strategies proposed for wastewater treatment plants. It is based on model and performance criteria development. Testing of this benchmark, by comparing benchmark predictions to real measurements of the electrical energy consumptions and amounts of disposed sludge for a specific oxidation ditch WWTP, has shown that it can (reasonably) be used for evaluating the performance of this WWTP. Subsequently, the validated benchmark was then used in evaluating some basic and advanced control strategies. Some of the interesting results obtained are the following: (i) influent flow splitting ratio, between the first and the fourth aerated compartments of the ditch, has no significant effect on the TN concentrations in the effluent, and (ii) for evaluation of long-term control strategies, future benchmarks need to be able to assess settlers' performance.


Subject(s)
Benchmarking , Water Purification/methods , Water Purification/standards , Netherlands , Oxidation-Reduction , Oxygen/metabolism , Reproducibility of Results , Time Factors , Water Pollutants/analysis
11.
Water Sci Technol ; 43(7): 357-65, 2001.
Article in English | MEDLINE | ID: mdl-11385868

ABSTRACT

When applied to large simulation models, the process of parameter estimation is also called calibration. Calibration of complex non-linear systems, such as activated sludge plants, is often not an easy task. On the one hand, manual calibration of such complex systems is usually time-consuming, and its results are often not reproducible. On the other hand, conventional automatic calibration methods are not always straightforward and often hampered by local minima problems. In this paper a new straightforward and automatic procedure, which is based on the response surface method (RSM) for selecting the best identifiable parameters, is proposed. In RSM, the process response (output) is related to the levels of the input variables in terms of a first- or second-order regression model. Usually, RSM is used to relate measured process output quantities to process conditions. However, in this paper RSM is used for selecting the dominant parameters, by evaluating parameters sensitivity in a predefined region. Good results obtained in calibration of ASM No. 1 for N-removal in a full-scale oxidation ditch proved that the proposed procedure is successful and reliable.


Subject(s)
Computer Simulation , Sewage , Waste Disposal, Fluid/methods , Automation , Calibration , Models, Statistical , Regression Analysis
12.
Water Res ; 35(8): 2058-64, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11337854

ABSTRACT

Standard methods for the determination of oxygen transfer rate are based on assumptions that are not valid for oxidation ditches. This paper presents a realistic and simple new method to be used in the estimation of oxygen transfer rate in oxidation ditches from clean water measurements. The new method uses a loop-of-CSTRs model, which can be easily incorporated within control algorithms, for modelling oxidation ditches. Further, this method assumes zero oxygen transfer rates (KLa) in the unaerated CSTRs. Application of a formal estimation procedure to real data revealed that the aeration constant (k = KLaVA, where VA is the volume of the aerated CSTR) can be determined significantly more accurately than KLa and VA. Therefore, the new method estimates k instead of KLa. From application to real data, this method proved to be more accurate than the commonly used Dutch standard method (STORA, 1980).


Subject(s)
Fresh Water/analysis , Oxygen/analysis , Kinetics , Models, Theoretical , Netherlands , Oxidation-Reduction , Sewage/analysis , Water/standards
13.
Cell Death Differ ; 7(9): 815-24, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11042676

ABSTRACT

The inhibition of neuronal apoptosis in acute traumatic and ischemic injuries as well as in long term neurodegenerative disorders like spinal muscular atrophy and possibly Alzheimer's disease is a fundamental requirement for a therapeutic strategy. In this study we used an established in vivo model system of induction of neuronal apoptosis in the CNS to evaluate the properties of the X-linked inhibitor of apoptosis protein (XIAP) to inhibit secondary cell death after axonal lesions. We used adenoviral vectors to transduce retinal ganglion cells after axotomy of the optic nerve of adult rats. Vector application was performed at the optic nerve stump so that only the lesioned retinal neurons could be transduced. We found XIAP to be as effective as the viral broad spectrum caspase inhibitor protein p35. These findings suggest that axotomized RGCs degenerate through class II caspase activity and furthermore offer the possibility of using mammalian XIAP protein to inhibit neuronal apoptosis as a basis for a regenerative therapy in the CNS.


Subject(s)
Apoptosis , Axotomy , Neurons/physiology , Proteins/metabolism , Retinal Ganglion Cells/metabolism , Animals , Cell Survival , Genes, Reporter , Genetic Vectors/genetics , Genetic Vectors/metabolism , Immunohistochemistry , Optic Nerve , Proteins/genetics , RNA/metabolism , Rats , Retina/anatomy & histology , Retina/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transgenes/genetics , X-Linked Inhibitor of Apoptosis Protein
14.
Biotechnol Bioeng ; 57(2): 155-63, 1998 Jan 20.
Article in English | MEDLINE | ID: mdl-10099190

ABSTRACT

In this article, an autonomous four-compartment model that describes the endogenous respiration in an aerobic biodegradation process is proposed and analyzed theoretically. First, the multi-time scale of the system's behavior, to be taken into account in subsequent analyses, is emphasized. Then, an identifiability and observability study, given measurements of MLVSS (mixed liquor volatile suspended solids) and respiration rate, is performed for use under practical circumstances, such as in state and parameter estimation. It appears that the process is observable, but not fully identifiable. Hence, for the identification of some of the model parameters, additional measurements or experiments, also indicated here, have to be performed. Furthermore, it is shown that, under quasi-steady state conditions which, in general, appear shortly after initialization of an endogenous respiration experiment, the model can be reduced significantly. Finally, results of parameter estimation from available data are presented and discussed.


Subject(s)
Sewage , Aerobiosis , Biodegradation, Environmental , Bioreactors , Biotechnology , Models, Biological , Oxygen Consumption , Water Microbiology
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