Biokinetic Behaviour Research Articles

Sewage sludge minimisation by OSA-MBR: A pilot plant experiment

This study presents the excess sludge minimisation in a Membrane Bioreactor (MBR) system by an Oxic Settling Anaerobic (OSA) process. The pilot plant was fed with real wastewater and OSA was operated with two different hydraulic retention times (HRT), respectively 4 (Period II) and 6 h (Period III) and compared to an MBR (Period I). Multiple parameters/variables were monitored: sludge minimisation, nitrogen and carbon removal, membrane fouling, and biokinetic behaviour through respirometry. With respect to the current literature, greenhouse gas emissions were also here monitored, often neglected. Results demonstrated that combining MBR and OSA systems can significantly reduce excess sludge production (89.7%, in Period III and 59.7% in Period II, compared to Period I). However, Period III presented better PO4–P removal efficiencies but worse performances in the other parameters (COD, NH4 and Total Nitrogen). No substantial variation in membrane fouling was obtained over the experimental periods. Finally, the HRT increase in the anaerobic reactor promoted a N2O–N increase inside the unaerated reactors, highlighting the need for a trade-off between sludge minimisation and GHG emission.

Respirometric tests in a combined UASB-MBR system treating wastewater containing emerging contaminants at different OLRs and temperatures: Biokinetic analysis

This research focuses on the application of respirometric techniques to provide new insights into the biokinetic behaviour of bacterial species developed in an Upflow Anaerobic Sludge Blanked -UASB reactor combined with a membrane bioreactor -MBR, treating urban wastewater with emerging contaminants frequently found in this kind of effluents. The lab-scale pilot plant was operated at different metabolic and operational conditions by limiting the organic loading rate- OLR of the influent. In a first stage, the MBR was performed with suspended biomass, while in a second stage bio-supports were introduced to operate coexisting suspended and fixed biomass. From the results of the microscopic monitoring of sludge, it was concluded that the decrease in OLR resulted in a greater disintegration of the floc structure, more dispersed growth, and a low presence of inter-floccular bonds. However, no effect of toxicity or inhibition of microorganisms caused by the presence of emerging contaminants -ECs was determined. Kinetic modelling was carried out to study the behaviour of the system. The results showed a slowing down of biomass degradative capacity at low OLR stages and operating at low temperatures of mixed liquor. In addition, a decrease in oxygen consumption was observed with decreasing biodegradable substrate, resulting in lower degradation of organic matter. Mean values of specific oxygen uptake rate and heterotrophic biomass yield at low OLR were SOUR end = 1.49 and 1.15 mg O2· g MLVSS−1 h−1 and YH,MLSSV end = 0.48 and 0.28 mg MLVSS· mg COD−1substrate at stage 1 (suspended biomass) and stage 2 (suspended and supported biomass), respectively. From the analysis of the endogenous decomposition constant (kd), a higher cell lysis was determined operating with suspended biomass (kd = 0.03 d−1) in comparison to the operation coexisting suspended and supported biomass (kd = 0.01 d−1). Heterotrophic biomass yield values (YH, MLVSS = 0.48 ± 0.06, 0.40 ± 0.01 and 0.29 ± 0.01 mg MLVSS· mg COD−1substrate at high, medium and low OLR) showed lower sludge production at low OLR due to the influence of substrate limitation on cell growth.

IDAC-ALPHA: AN ALPHA DOSIMETRY SOFTWARE FOR NORMAL ORGANS AND TISSUES.

Radiopharmaceuticals have been used for the treatment of various forms of cancer since the 1940s. In recent years, the advantages of alpha emitting radionuclides have emerged as a favourable treatment option. However, most alpha emitting radionuclides have long decay chains with long-lived daughter radionuclides. This leads to uncertainties in the dosimetry for normal organs and tissues, when established dosimetry models are employed. The aim of this project is to assign each progeny its own biokinetic behaviour. The novel dosimetry model was applied to 223Ra-dichloride, frequently used for the treatment of patients with metastatic bone disease from castration-resistant prostate cancer. In this dosimetry model, individual biokinetics for each daughter radionuclide was included. This resulted in a decrease in absorbed dose to bone surfaces and red marrow and increased absorbed dose to liver and kidney, when compared with dosimetry models assuming that the daughter nuclides follow the biokinetics of the parent radionuclide.

Kinetic Evaluation of Two-Phase Anaerobic Treatment of Slaughterhouse Wastewater

Two-phase anaerobic treatment by a continuously stirred tank reactor (CSTR) and an upflow anaerobic sludge blanket (UASB) system was applied to treat slaughterhouse wastewater at ambient temperature, non-pH adjustment, at five different organic loading rates (OLR) of 1.39-2.60 kg COD/m3.d with the hydraulic retention time (HRT) in the range of 14.1-26.4 hr. The kinetic evaluation of the experimental data was carried out using a kinetic model derived from Michaelis-Menten and Monod equation. The maximum substrate utilization rate (kmax) and the half velocity constant (Ks) were 0.252 d−1 and 586.5 mg/l, respectively. The results indicated that the applied kinetic model is capable of explaining the bio-kinetic behaviour of the CSTR-UASB system and can be used as a design criteria for two-phase anaerobic treatment treating other fat-containing wastewater.

Activity estimation and biokinetic analysis of 99mTc-DMSA in renal infant patients using a gamma camera

Biokinetic data from the administration of radiopharmaceuticals is essential in nuclear medicine dosimetry. It has particular significance in children, as their metabolism is very different from adults. Biokinetic models for paediatric patients could therefore need to be adapted to better reflect their absorption, retention and excretion functions, when compared to adults. Obtaining quality in vivo infant or paediatric biokinetic data is then essential to improve the available reference models, which in turn can lead to the optimization of paediatric procedures and protocols in clinical practice.This study analyses the biokinetic behaviour of 99mTc-dimercaptosuccinic acid (DMSA), in 8 infants aged 4 months to 2 years old, through an imaging study using a gamma camera, and compares the obtained values with those obtained with the reference ICRP biokinetic model. The in vivo data was treated using an adapted methodology from the MIRD 16 pamphlet. Activity curves for the liver, the kidney and the whole body, were built, and new effective absorption, retention and excretion half-lives were estimated, and compared with the reference biokinetic parameters of ICRP 128. The obtained residence time in the kidneys of 2.56 h, has a deviation of 30.8% to the ICRP 128 value of 3.70 h. The obtained maximum uptake in the kidneys was of 0.22/A0, which compares to the value of 0.31/A0 for ICRP.The obtained biokinetic parameters were used to estimate the absorbed dose. The obtained dose values are smaller than the reference ICRP 128 ones by 32.1% in the kidneys, and 18.4% in the liver.

IDAC-Dose 2.1, an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms

BackgroundTo date, the estimated radiation-absorbed dose to organs and tissues in patients undergoing diagnostic examinations in nuclear medicine is derived via calculations based on models of the human body and the biokinetic behaviour of the radiopharmaceutical. An internal dosimetry computer program, IDAC-Dose2.1, was developed based on the International Commission on Radiological Protection (ICRP)-specific absorbed fractions and computational framework of internal dose assessment given for reference adults in ICRP Publication 133. The program uses the radionuclide decay database of ICRP Publication 107 and considers 83 different source regions irradiating 47 target tissues, defining the effective dose as presented in ICRP Publications 60 and 103. The computer program was validated against another ICRP dosimetry program, Dose and Risk Calculation (DCAL), that employs the same computational framework in evaluation of occupational and environmental intakes of radionuclides. IDAC-Dose2.1 has a sub-module for absorbed dose calculations in spherical structures of different volumes and composition; this sub-module is intended for absorbed dose estimates in radiopharmaceutical therapy. For nine specific alpha emitters, the absorbed dose contribution from their decay products is also included in the committed absorbed dose calculations.ResultsThe absorbed doses and effective dose of 131I-iodide determined by IDAC-Dose2.1 were validated against the dosimetry program DCAL, showing identical results. IDAC-Dose2.1 was used to calculate absorbed doses for intravenously administered 18F-FDG and orally administered 99mTc-pertechnetate and 131I-iodide, three frequently used radiopharmaceuticals. Using the tissue weighting factors from ICRP Publication 103, the effective dose per administered activity was estimated to be 0.016 mSv/MBq for 18F-FDG, 0.014 mSv/MBq for 99mTc-pertechnetate, and 16 mSv/MBq for 131I-iodide.ConclusionsThe internal dosimetry program IDAC-Dose2.1 was developed and applied to three radiopharmaceuticals for validation against DCAL and to generate improved absorbed dose estimations for diagnostic nuclear medicine using specific absorbed fraction values of the ICRP computational voxel phantoms. The sub-module for absorbed dose calculations in spherical structures 1 mm to 9 cm in diameter and different tissue composition was included to broaden the clinical usefulness of the program. The IDAC-Dose2.1 program is free software for research and available for download at http://www.idac-dose.org.

Polymer-Based Drug Delivery Systems, Development and Pre-Clinical Status.

The nanomedicine is considered as the application of nanotechnology in the medical field where nanoparticles are sized in the nanoscale range. Drug delivery technologies are becoming increasingly important as a scientific area of investigation. Controlled-release systems and drug-targeting systems represents an alternative to traditional delivery nanoparticles, and the use of polymers is increasing nowadays. Although polymers could be classified as excipients, they are capable of modifying the biopharmaceutical and biokinetic behaviour of the transported active molecule increasing its efficacy and stability, and reduced cytotoxicity on healthy peripheral tissues. The goal of this work is to collect and analyse the most current polymeric nanoparticles development as controlledrelease and drug-targeting systems in cancer, infectious diseases and immunomodulation areas, as alternatives to conventional therapies. This review provides an update on the polymeric nanoparticles development analysing the trend of polymeric-based drug delivery systems, future opportunities and challenges of this fast-growing area. With the thorough comprehension of biological effects depending on structure, it is possible to design specific systems for specific diseases, treatments and patients. The ability of polymer- based nanoparticles to modify and improve pharmacokinetics and pharmacodynamics, associated to techniques for enhancement of the therapeutic efficiency with minimal side effects, demonstrate the advantages of these systems.

The Mayak Worker Dosimetry System (MWDS-2013): A Comparison of Intakes Based on Urine Versus Autopsy Data From Mayak Workers Using the Leggett Systemic Model for Plutonium.

The Mayak Worker Dosimetry System-2013 (MWDS-2013) uses a model developed by Leggett and colleagues to represent the biokinetic behaviour of plutonium after uptake to blood. Of particular importance, with regard to estimating intakes (and doses), is the distribution of activity between urine and body organs (particularly liver and skeleton). In this study, measurement data (urine and autopsy) from around 500 Mayak workers have been used to validate use of this model. A robust method has been developed and used to estimate intakes from both urine and autopsy data separately, and the ratio of these estimates has been calculated for each worker. The geometric mean ratio has been shown to lie within a range of 0.92-1.14, depending on assumptions made. Since this range includes 1, the hypothesis that the model is unbiased with regard to estimating intakes either with urine or autopsy data cannot be rejected on the basis of these data. This lends weight to the argument for increasing the MWDS-2013 cohort to include an additional 500 workers for whom only autopsy data are available, and who have previously been excluded from the cohort. Future directions in which this work could be extended are also suggested.

SPECIFIC BLOOD ABSORPTION PARAMETERS FOR 239PUO2 AND 238PUO2 NANOPARTICLES AND IMPACTS ON BIOASSAY INTERPRETATION.

Specific absorption parameters for 239PuO2 and 238PuO2 have been determined based on available biokinetic data from studies in rodents, and the impacts of these parameters on bioassay interpretation and dosimetry after inhalation of nanoPuO2 materials have been evaluated. Calculations of activities after an acute intake of nanoparticles of 239PuO2 and 238PuO2 are compared with the corresponding calculations using standard default absorption parameters using the International Commission on Radiological Protection (ICRP) 66 respiratory tract model. Committed effective doses are also evaluated and compared. In this case, it was found that interpretation of bioassay measurements with the assumption that the biokinetic behaviour of PuO2 nanoparticles is the same as that of micrometre-sized particles can result in an overprediction of the committed effective dose by two orders of magnitude. Although in this case the use of the default assumptions (5 µm AMAD, Type S) for assessing dose following inhalation exposure to airborne PuO2 nanoparticles appears to be conservative, the evaluation of situations involving PuO2 nanoparticles that may have different particle size and solubility properties should prudently follow the ICRP recommendation to obtain and use additional, material-specific information whenever possible.

The in vitro biokinetics of chlorpromazine and diazepam in aggregating rat brain cell cultures after repeated exposure

Neurotoxic effects of compounds can be tested in vitro using cell systems. One example is aggregating rat brain cell cultures. For the extrapolation of in vitro data to the in vivo situation, it is important to take the biokinetics of the test compound into account. In addition, the exposure in vivo is often for a longer period of time; therefore, it is crucial to incorporate this into in vitro assays as well. In this study, aggregating rat brain cell cultures were exposed to chlorpromazine (CPZ) and diazepam (DZP) for 12-days with repeated exposure. Samples were taken from the stocks, test media, cell culture media and cells at specific time points on the first and last exposure day. These samples were analysed by HPLC-UV. The amount of CPZ in the medium decreased over time, whereas the amount in the cells showed an increase. Accumulation of CPZ in the cells was seen over the 12-day repeated exposure. The amount of DZP in the medium remained stable over time and only up to 2% of DZP added was found in the cells. Different biokinetic behaviour was found for CPZ and DZP. Possible explanations are differences in uptake into the cells or efflux out of the cells. The decrease of CPZ in the medium versus the stable amount of DZP results in differences in exposure concentrations over time, which should be taken into account when interpreting in vitro effect data.

Skull counting in late stages after internal contamination by actinides.

Monitoring preparation for internal contamination with actinides (e.g. Pu and Am) is required to assess internal doses at nuclear fuel cycle-related facilities. In this paper, the authors focus on skull counting in case of single-incident inhalation of (241)Am and propose an effective procedure for skull counting with an existing system, taking into account the biokinetic behaviour of (241)Am in the human body. The predicted response of the system to skull counting under a certain counting geometry was found to be only ∼1.0 × 10(-5) cps Bq(-1) 1y after intake. However, this disadvantage could be remedied by repeated measurements of the skull during the late stage of the intake due to the predicted response reaching a plateau at about the 1000th day after exposure and exceeding that in the lung counting. Further studies are needed for the development of a new detection system with higher sensitivity to perform reliable internal dose estimations based on direct measurements.

Assesment of Kinetic Parameters for Thermophilic Anaerobic Contact Reactor Treating Food-Processing Wastewater

A thermophilic anaerobic contact reactor for the treatment of potato-processing wastewaterswas designed as a continuous-flow, completely-mixed homogeneous system. The reactor was operated at ten different organic loading rates ranging from 0.84 g COD/L·d to 7.00 g COD/L·d for a duration of approximately 250 days. The fundamental way to maintain optimum operating conditions of anaerobic digestion systems is to have a well acquaintance with the dynamic behaviours of the process. For this purpose, different types of kinetic models were used in this study, namely the substrate balance, the maximum / specific substrate utilization rate and the methane production rate models. The experimental data obtained indicated that the models used were all applicable for the description of bio-kinetic behaviour of the thermophilic anaerobic contact reactor.

Efficiency correction factors of an ACCUSCAN whole-body counter due to the biodistribution of 134Cs, 137Cs and 60Co

The efficiency calibration of whole-body counters (WBCs) for monitoring of internal contaminations is usually performed with anthropomorphic physical phantoms assuming homogeneous activity distribution. Besides the inherent limitations of these phantoms in resembling the human anatomy, they do not represent a realistic activity distribution, since in real situations each incorporated radionuclide has its particular biodistribution after entering the systemic circulation. Moreover, the activity content in the different organs and tissues comprising the biokinetics is time dependent. This work aims at assessing the whole-body counting efficiency deviations arising from considering a detailed voxel phantom instead of a standard physical phantom (BOMAB) and at evaluating the effect of the anatomical differences between both phantoms. It also aims at studying the efficiency considering the biodistribution of a set of radionuclides of interest incorporated in the scope of environmental and occupational exposures (inhalation and ingestion) and at computing the time-dependent efficiency correction factors to account for the biodistribution variation over time. For the purpose, Monte Carlo (MC) simulations were performed to simulate the whole-body counting efficiencies and biokinetic models were used to estimate the radionuclides' biokinetic behaviour in the human body after intake. The comparison between the efficiencies obtained with BOMAB and the voxel phantom showed deviations between 1.8 and 11.7 %, proving the adequacy of the BOMAB for WBC calibration. The obtained correction factors show that the effect of the biodistribution in the whole-body counting efficiency is more pronounced in cases of acute activity uptake and long-term retention in certain organs than in cases of homogeneous distribution in body tissues, for which the biokinetics influence can be neglected. This work further proves the powerful combination of MC simulation methods using voxel phantoms and biokinetic models for internal dosimetry studies.

Emulsified perfluorochemicals as respiratory gas carriers: recovery of perfluorodecalin emulsion droplets from rat tissues.

To further understand the in-vivo biokinetic behaviour of perfluorochemical (PFC) emulsions, male rats were injected (10 mL kg-1) with 30% (w/v) emulsified perfluorodecalin (FDC) and uptake into tissues assessed. At 72 h after injection, the mean (+/- s.e.m.) diameters of FDC droplets recovered from liver and spleen were 2.24 +/- 0.04 and 2.78 +/- 0.10 microns, respectively; droplets recovered from lung after 72 h (mean: 1.73 +/- 0.13 micron) were significantly smaller (P < 0.01). After 7 days, FDC droplet diameters in liver had increased to 3.31 +/- 0.13 microns (P < 0.01) and those in lung to 2.71 +/- 0.14 microns (P < 0.01); droplets in spleen after 7 days (2.22 +/- 0.09 microns) were similar to those at 72 h. These data support the hypothesis that significant initial coalescence of FDC droplets occurs in the rat liver and spleen, with further coalescence in the liver up to 7 days. The mean percentage of the injected FDC dose recovered from the liver after 72 h was 2.2 +/- 0.4%, and after 7 days was 0.07 +/- 0.05% (P < 0.01). A smaller decrease in the percent injected FDC in spleen also occurred over the same period (72 h: 1.9 +/- 0.3%; 7 days: 0.8 +/- 0.5%; P < 0.01). The percent injected FDC in lung was similar at 72 h (0.007 +/- 0.004%) and 7 days (0.005 +/- 0.001%). FDC was undetectable (< 0.001%) in all blood samples. The greater rate of FDC elimination from the liver than from the spleen may be related to differences in the rates of reticuloendothelial system processing between these organs.

Absorption of red clover isoflavones in human subjects: results from a pilot study

In addition to soya-derived preparations, red clover-based dietary supplements have gained considerable interest as an alternative isoflavone (IF) source. While metabolism and bioavailability of the main IF from both sources have already been investigated, studies are still lacking on the biokinetic behaviour of IF, which are present in red clover in minor amounts. In the present pilot study, in which seven volunteers ingested a single dose of a commercial red clover dietary supplement, we focused on the absorption of three such IF, irilone (IRI), prunetin (PRUN) and pseudobaptigenin (PBAP). The compounds were measured as aglycones after enzymatic hydrolysis. A single intake of an amount of as low as 3.8 mg IRI (out of 38.8 mg IF in total) resulted in an IRI plasma concentration of 0.35 (sd 0.16) mum at 6.5 h post-ingestion. Compared to the plasma concentrations found for daidzein (0.39 mum) and genistein (0.06 mum), expected to be the main IF metabolites in plasma, the present findings indicate that IRI might possess a relatively high bioavailability. Furthermore, PRUN and PBAP were detected in human plasma for the first time.

Background information about polonium-210 – considerations on its biokinetics and internal dosimetry

Abstract The mysterious death of the former secret service agent Alexander Litvinenko on 23 November 2006 suddenly attracted the attention of the public to the rather unknown radionuclide 210Po. In this respect, this paper presents some general background information about this radionuclide as well as some details about its biokinetic behaviour and internal dosimetry. The results are discussed in the context of the Litvinenko case with regard to possible health effects on people from Germany being potentially contaminated. However, no evidence for contamination with 210Po could be found for any people tested at the GSF-National Research Center for Environment and Health (since 01.01.2008 Helmholtz Zentrum München).

Factors that elevate the internal radionuclide and chemical retention, dose and health risks to infants and children in a radiological-nuclear emergency

The factors that influence the dose and risk to vulnerable population groups from exposure and internal uptake of chemicals are examined and, in particular, the radionuclides released in chemical, biological, radiological, nuclear and explosive events. The paper seeks to identify the areas that would benefit from further research. The intake and body burdens of carbon and calcium were assessed as surrogates for contaminants that either act like or bind to hydrocarbons (e.g. tritium and (14)C) or bone-seeking radionuclides (e.g. (90)Sr and (239)Pu). The shortest turnover times for such materials in the whole body were evaluated for the newborn: 11 d and 0.5 y for carbon and calcium, respectively. However, their biokinetic behaviour is complicated by a particularly high percentage of the gut-absorbed dietary intake of carbon (approximately 16%) and calcium (approximately 100%) that is incorporated into the soft tissue and skeleton of the growing neonate. The International Commission on Radiological Protection dose coefficients (Sv Bq(-1)) were examined for 14 radionuclides, including 9 of concern because of their potential use in radiological dispersal devices. The dose coefficients for a 3-month-old are greater than those for adults (2-56 times more for ingestion and 2-12 times for inhalation). The age-dependent dose and exposure assessment of contaminant intakes would improve by accounting for gender and growth where it is currently neglected. Health risk is evaluated as the product of the exposure and hazard factors, the latter being about 10-fold greater in infants than in adults. The exposure factor is also approximately 10-fold higher for ingestion by infants than by adults, and unity for inhalation varying with the contaminant. Qualitative and quantitative physiological and epidemiological evidence supports infants being more vulnerable to cancer and neurological deficit than older children.

Peptides for Tumour Therapy and Diagnosis: Current Status and Future Directions

The use of peptides as targeting tools has been validated in different applications. In particular radiolabelled peptides with adequate stability, receptor-binding properties and biokinetic behaviour have been investigated as an important class of radiopharmaceuticals for cancer pathology imaging and therapy. This review focuses on recent progress in design and synthetic modifications of small biologically active peptides used in diagnosis and therapy. In particular, we report the current development and optimization of suitable peptides for targeting three relevant biological receptors (CCK, somatostatin, and integrin receptors) involved in specific tumour diseases.

Assessing internal exposure in the absence of an appropriate model: two cases involving an incidental inhalation of transuranic elements

Two incidents involving internal exposure by inhalation of transuranic compounds are presented herein. The results of the measurements of urinary and faecal excretions of the two individuals involved do not concur with the values predicted by the ICRP models that should be applied by default, according to the circumstances of the incidents and the chemical form of the products involved: oxide in the first case and nitrate in the second. These cases are remarkable in the similarity of their biokinetic behaviour even though they occurred in different situations and involved different chemical compounds. Both situations provide an illustration of the management of internal contamination events. The precautions to be taken and the questions that the physician should ask himself in the estimation of the internal dose are listed as follows: What type of examinations should be prescribed and at what frequency? What analysis results should be used in assessing the dose? How can the effect of the Ca-DTPA treatment be assessed? How long is it necessary to perform radiotoxicological exams before assessing the dose? What should be done if the ICRP model corresponding to the initial circumstances does not fit the measurement data? Finally, our selected hypotheses, used to explain specific biokinetic behaviour and to estimate its intake in both cases, are detailed. These incidental contaminations suggest that further studies should be carried out to develop a new model for inhalation of transuranic compounds that would follow neither the S nor the M absorption type of the respiratory tract model of ICRP publication 66.

A simple method for assessing that internal doses are below action levels

The accidental or deliberate dispersal of radioactive aerosols into the public environment may require urgent assessments of radiation dose to be made to aid decisions on whether treatment should be implemented, or to reassure the public that doses are acceptably low. However, rapid assessments will be difficult due to lack of information on factors such as the particle size distribution and biokinetic characteristics of the aerosol. A procedure is described that relates the amount of activity of a radionuclide in the body and excreta to time after intake for a specified dose, taking into account the likely variations in aerosol size and differences in the biokinetic behaviour of the same or different chemical forms of the radionuclide. The implementation of the procedure for an intake of caesium-137 and a dose level of 1 mSv is described and the information presented graphically. Figures for other specified dose levels can be produced by simply scaling the data by an appropriate factor. The figures can also be used to assess the most appropriate monitoring procedure and indicate the uncertainty in the assessed dose according to the parameter and parameter values used. This approach is proposed for rapid decisions on public reassurance when potentially large numbers of people are involved. It is not intended as a substitute for individual dose assessment.