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M Rutgers

Publications and source records attributed to M Rutgers.

At least 19 recordsLinked to original sources
PubMed2006

Algal-bacterial interactions in metal contaminated floodplain sediments.

The aim of the present study was to investigate algal-bacterial interactions in a gradient of metal contaminated natural sediments. By means of multivariate techniques, we related the genetic structure (denaturing gradient gel electrophoresis, DGGE) and the physiological structure (community-level physiological profiling, CLPP) of the bacterial communities to the species composition of the algal communities and to the abiotic environmental variables, including metal contamination. The results revealed that genetic and physiological structure of the bacterial communities correlated with the species composition of the algal community, but hardly to the level of metal pollution. This must be interpreted as an indication for a strong and species-specific linkage of algal and bacterial species in floodplain sediments. Metals were, however, not proven to affect either the algal or the bacterial communities of the Dutch river floodplains.

Bacteria↗
PubMed2004

[Nutrition and health--safety of new types of food].

In Europe it is currently a statutory requirement that all novel foods must first be tested before they can be put on the market to establish that they pose no hazard to consumers. A novel food is a food or food ingredient which was not used to a significant degree on the European market prior to 1997 and which falls within one of the categories described in a specific European regulation. The procedure used to establish the safety of such a novel food involves a request for authorization. The company compiles a safety dossier containing a comprehensive report on the characteristics of the substance, details of toxicological studies and any other relevant information. The company submits the dossier to the relevant authority in one of the European member states. In the Netherlands, this is the Ministry of Health, Welfare and Sport. The Ministry then arranges for an initial assessment to be carried out. In the Netherlands the Committee on Safety Assessment of Novel Foods (Dutch acronym: VNV), part of the Health Council, conducts the assessment. Following the completion of the assessment, other member states may carry out their own assessments. Finally, the member states make a collective decision on whether or not to authorise the marketing of the product. The VNV assessment takes a case-by-case and step-by-step approach. Each request for authorization is individually examined to determine the types of research data that will be needed to reach a verdict. A short-track procedure or 'notification' is available for products that are substantially equivalent to existing foods. The VNV Committee operates as transparently as possible. All dossiers are available for inspection. The Committee's advisory reports are available to the public and committee members provide details of their personal interests.

Consumer Product Safety↗
PubMed2001

A comparison of targeting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients.

Iodine-131 labelled anti L1-CAM antibody mAb chCE7 was compared with the effective neuroblastoma-seeking agent 131I-labelled metaiodobenzylguanidine (MIBG) with regard to (a) its therapeutic efficacy in treating nude mice with neuroblastoma xenografts and (b) its tumour targeting ability in neuroblastoma patients. The SK-N-SH tumour cells used in the mouse experiments show good MIBG uptake and provide a relatively low number of 6,300 binding sites/cell for mAb chCE7. Tumours were treated with single injections of 131I-MIBG (110 MBq) and with 131I-labelled mAb chCE7 (17 MBq) and both agents showed antitumour activity. After therapy with 131I-chCE7, the subcutaneous tumours nearly disappeared; treatment with 131I-MIBG was somewhat less effective, resulting in a 70% reduction in tumour volume. A calculated tumour regrowth delay of 9 days occurred with a radioactivity dose of 17 MBq of an irrelevant control antibody mAb 35, which does not bind to SK-N-SH cells, compared with a regrowth delay of 34 days with 131I-mAb chCE7 and of 24 days with 131I-MIBG. General toxicity appeared to be mild, as assessed by a transient, approximate 10% maximum decrease in body weight during the treatments. The superior growth inhibition achieved by 131I-chCE7 compared with 131I-MIBG can be explained by its prolonged retention in the tumours, due to slower normal tissue and plasma clearance. Cross-reaction of mAb chCE7 with L1-CAM present in normal human tissues was investigated by direct binding of radioiodinated mAb to frozen tissue sections. Results showed a strong reaction with normal human brain tissue and weak but detectable binding to normal adult kidney sections. Seven patients with recurrent neuroblastoma were sequentially imaged with 131I-MIBG and 131I-chCE7. The results underlined the heterogeneity of neuroblastoma and showed the two imaging modalities to be complementary. 131I-chCE7 scintigraphy may have clinical utility in detecting metastases which do not accumulate 131I-MIBG, and the antibody may hold potential for radioimmunotherapy, either by itself or in combination with 131I-MIBG.

3-Iodobenzylguanidine↗
PubMed2000

[(131)I] and [(125)I] metaiodobenzylguanidine therapy in macroscopic and microscopic tumors: a comparative study in SK-N-SH human neuroblastoma and PC12 rat pheochromocytoma xenografts.

[(131)I]Metaiodobenzylguanidine ([(131)I]MIBG) targeted radiotherapy is effective in debulking childhood neuroblastoma. The high-energy beta-emitter [(131)I]MIBG is, however, not very well suited to treat submillimeter tumors. The [(125)I]MIBG emission is more fully absorbed in small target volumes and therefore advocated for treatment of microscopic neuroblastoma. We investigated whether i.v. [(125)I]MIBG can have a therapeutic advantage over i.v. [(131)I]MIBG in realistic animal models. We used BALB/c nu/nu mice, bearing neuroadrenergic xenografts which differ in MIBG handling, i.e., extragranular vs. granular MIBG storage in the SK-N-SH human neuroblastoma and PC12 rat pheochromocytoma, respectively. Groups of 4-9 animals were treated with 10-100 MBq radioiodinated MIBG. Responses were calibrated against the effect of 4-5 Gy of external beam X-rays. SUBCUTANEOUS XENOGRAFTS: Due to the more extensive MIBG accumulation, the estimated MIBG exposure of the PC12 tumor was nearly 20-fold higher compared with the SK-N-SH xenograft which corresponded with a marked, i.e., nine-fold increased tumor growth delay after radioiodinated MIBG therapy. Both xenografts were equally sensitive to high-dose rate local irradiation. In neuroblastoma as well as pheochromocytoma, the therapeutic efficacy of [(131)I]MIBG was 6 times higher compared to the [(125)I]MIBG which is in reasonable agreement with the reported "131-I over 125-I" ratio of approximately 9 for the calculated absorbed radiation doses per unit of radioactivity. Apparently, the neuroblastoma was not relatively more sensitive to the (ultra)short range emitter [(125)I]MIBG than the pheochromocytoma, indicating that its therapeutic efficacy is independent of the intracellular MIBG storage mode. MICROSCOPIC TUMORS: The pheochromocytoma model consisted of widespread disease after i.v. cell injection with survival as endpoint. For the neuroblastoma, we induced focal intrahepatic microscopic tumors by intrasplenic injection and evaluated total liver weights 26 days after therapy. Theoretically, the therapeutic potential of [(125)I]MIBG at the cellular level should be at least as high as [(131)I]MIBG, but we failed to show any effect of [(125)I]MIBG therapy in both models. In contrast, measurable responses were obtained with [(131)I]MIBG, but these were lower than in the s.c. tumors when related to the responses induced by external X-rays. In conclusion, [(131)I]MIBG is decreasingly effective in microscopic disease and can therefore not be curative as a single agent. Our results strongly argue against the clinical use of [(125)I]MIBG and indicate that conventional total body irradiation was superior to [(131)I]MIBG for microscopic neuroblastoma. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 312-325 (2000).

3-Iodobenzylguanidine↗
PubMed2000

Targeting of meta-iodobenzylguanidine to SK-N-SH human neuroblastoma xenografts: tissue distribution, metabolism and therapeutic efficacy.

The clinical results of [(131)I]meta-iodobenzylguanidine (MIBG)-targeted radiotherapy in neuroblastoma patients is highly variable. To assess the therapeutic potential of [(131)I]MIBG, we used the SK-N-SH human neuroblastoma, xenografted in nude mice. The model was first characterized for basic parameters of MIBG handling in the host species. This demonstrated the presence of both strain- and nu/nu mutation-related differences in [(131)I]MIBG biodistribution. Fecal and urinary clearance rates of [(131)I]MIBG in mice roughly resemble those in humans, but mice metabolize MIBG more extensively. In both species, enzymatic deiodination in vivo was not an important metabolic route. Therapy with increasing [(131)I]MIBG doses (25-92 MBq) given as single i.v. injections resulted in proportionally increasing specific growth delay values (tumor regrowth delay/doubling time) of 1 to 5. Using gamma-camera scintigraphy for non-invasive dosimetry, the corresponding calculated absorbed tumor radiation doses ranged from 2 to 11 Gy. We also compared the therapeutic effects of a single [(131)I]MIBG administration with those resulting from a more protracted exposure by fractionating the dose in 2 to 6 injections or with high dose rate external-beam irradiation. No therapeutic advantage of a fractionated schedule was observed, and 5.5 Gy delivered by low dose-rate [(131)I]MIBG endo-irradiation was equi-effective with 5.0 Gy X-rays. The SK-N-SH neuroblastoma xenograft model thus appears suitable to evaluate possible treatment improvements to reach full potential of MIBG radiotherapy.

3-Iodobenzylguanidine↗
PubMed2000

Improved effect of 131I-MIBG treatment by predosing with non-radiolabeled MIBG in carcinoid patients, and studies in xenografted mice.

BACKGROUND: 131I-meta-iodobenzylguanidine (MIBG) has been used with success for the palliation of metastatic carcinoid. To qualify more patients for this treatment, we evaluated the effect of predosing with non-radiolabeled MIBG on 131I-MIBG tumour targeting in carcinoid patients and in mice with BON human carcinoid xenografts. PATIENTS AND METHODS: Ten carcinoid patients with a faint tumour imaging on a diagnostic 131I-MIBG scan (1 mCi = 37 MBq, 5 mg MIBG) received non-radiolabeled MIBG prior to a second scintigraphy. In case of improved tumour targeting patients were treated with 200 mCi (7.4 GBq) 131I-MIBG following a pharmacological predose of 20-40 mg/m2 MIBG. RESULTS: In six patients. highly increased 'tumour/non-tumour' ratios were seen due to reduced levels in normal tissues and increased tumour accumulation. The combined treatment applied in five patients, considerably improved symptoms in all (duration 6-12 months), accompanied by biochemical response in three. In BON carcinoid xenografted mice, MIBG was injected intraperitoneally followed by intravenous 125I-MIBG with similar findings: increased 'tumour/non-tumour' radioactivity ratios by 1.5-3-fold. CONCLUSION: Predosing with non-radiolabeled MIBG resulted in improved 131I-MIBG tumour targeting, prolonged palliation and encouragingly often biochemical responses in carcinoid.

3-Iodobenzylguanidine↗
PubMed1999

Carcinoid tumors.

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3-Iodobenzylguanidine↗
PubMed1999

[Carcinoid tumors of the intestines: developments in the Netherlands for diagnosis and palliative treatment].

Carcinoid tumours in the intestine are slowly growing neuroendocrine tumours. Patients as a rule report symptoms of the carcinoid syndrome: attacks of diarrhoea and of flushing. When the earliest symptoms manifest themselves, metastases are already present, virtually always localized in the liver. At a late stage, heart failure may occur, difficult to treat and caused by fibrosis of the tricuspid valve in the presence of protractedly raised blood serotonin levels. To diagnose carcinoid tumours, use is made of radioactive substances binding to hormone receptors such as 131I-MIBG and 111-In-octreotide. When multiple metastases exist, only palliative treatment is possible. The drugs used are the somatostatin analog octreotide, interferon alpha, radioactive MIBG and non-radioactive MIBG; these drugs may also be used in combination. The therapies mentioned have approximately the same effect: symptoms improve in 60-80%, while 30-50% show a biochemical response, i.e. decrease of the number of breakdown products in the urine of the hormones produced by the tumour; tumour size decreases in 0-12%.

Carcinoid Heart Disease↗
PubMed1999

Bioavailability and toxicity after oral administration of m-iodobenzylguanidine (MIBG).

meta-iodobenzylguanidine (MIBG) radiolabelled with iodine-131 is used for diagnosis and treatment of neuroadrenergic neoplasms such as phaeochromocytoma and neuroblastoma. In addition, non-radiolabelled MIBG, administered i.v., is used in several clinical studies. These include palliation of the carcinoid syndrome, in which MIBG proved to be effective in 60% of the patients. Oral MIBG administration might be convenient to maintain palliation and possibly improve the percentage of responders. We have, therefore, investigated the feasibility of oral administration of MIBG in an animal model. Orally administered MIBG demonstrated a bioavailability of 59%, with a maximal tolerated dose of 60 mg kg(-1). The first and only toxicity encountered was a decrease in renal function, measured by a reduced clearance of [51Cr]EDTA and accompanied by histological tubular damage. Repeated MIBG administration of 40 mg kg(-1) for 5 sequential days or of 20 mg kg(-1) for two courses of 5 sequential days with a 2-day interval did not affect renal clearance and was not accompanied by histological abnormalities in kidney, stomach, intestines, liver, heart, lungs, thymus, salivary glands and testes. Because of a sufficient bioavailability in absence of gastrointestinal toxicity, MIBG is considered suitable for further clinical investigation of repeated oral administration in patients.

3-Iodobenzylguanidine↗
PubMed1997

Chemical characterization and comparative cellular effects of meta-iodobenzyl guanidine and benzyl guanidine.

meta-Iodobenzyl guanidine (MIBG) combines the structural properties of the neuron-blocking agents bretylium and guanethidine and is being used increasingly for various clinical applications. Different samples of MIBG were assayed for possible contamination with benzyl guanidine (BG). Fast-atom-bombardment mass spectrometry (FAB-MS) analysis showed a prominent but variable m/z 150 signal, corresponding to a protonated BG. The MS/MS fragmentation pattern of these [M + H]+ ions was similar to that obtained from FAB-MS-generated, protonated BG, confirming the proposed molecule and associated structures. RP-HPLC analysis of both guanidines, however, excluded the possibility of contamination of MIBG with BG. It was therefore concluded that the BG signal was an artifact of the FAB-MS procedure. In addition, the importance of the meta-substituted iodine for the biological activity of MIBG was investigated. Three different biochemical and cell-biological properties of MIBG were compared with those of its precursor MIBA and BG. The assays used were: inhibition of the catecholamine "Uptake I" system in SK-N-SH neuroblastoma and PC-12 pheochromocytoma cells, inhibition of mitochondrial respiration, and general cytotoxicity in L1210 leukemia cells. Of the drugs tested, MIBG was the most efficient in Uptake I inhibition and was more toxic in survival assays, but as compared with BG it was almost equipotent in inhibiting mitochondrial respiration. These findings contribute to a further elucidation of the mechanism by which MIBG exerts its various actions.

3-Iodobenzylguanidine↗
PubMed1996

Assessment of inhibition kinetics of the growth of strain P5 on pentachlorophenol under steady-state conditions in a nutristat.

A bacterium degrading pentachlorophenol (PCP) as the only source of carbon and energy was grown in a nutristat , i.e., a continuous culture with on-line measurement and control of the substrate concentration. We improved the PCP nutristat by incorporation of a personal computer with a proportional integral derivative (PID) algorithm for controlling the medium feed pump. The controlled value deviated from the average (set-point) value by 1% maximally. In the PCP nutristat (30 degrees C), the steady-state dilution rate, and hence, specific growth rate, showed a maximum value of 0.142 +/- 0.004 h-1 at set-point PCP concentrations between 37 and 168 microM. At PCP concentrations above 168 microM, the steady-state growth rate decreased because of inhibition. The growth yield coefficient was not seriously affected by the PCP concentration, suggesting that uncoupling was not the inhibitory mechanism. It was concluded that the PCP nutristat is very useful for establishing steady-state conditions that maintain growth-inhibitory PCP concentrations and high cell concentrations, conditions for which the chemostat is not suitable.

Bacteriological Techniques↗
PubMed1996

In vitro evaluation of N-(fluoro)isopropyl norephedrine as potential cardiac imaging agents for PET.

N-Isopropylnorephedrine (INE) and N-fluoroisopropylnorephedrine (FINE) were found to have a poor affinity for either beta-adrenoceptors and the norepinephrine carrier protein. The low affinity of both compounds for Uptake-1 is probably due to the introduction of a bulky substituent on the nitrogen atom. It is concluded that INE and FINE cannot be used for cardiac imaging with PET.

3-Iodobenzylguanidine↗
PubMed1995

Meta-iodobenzylguanidine uptake in platelets, megakaryoblastic leukaemia cell lines MKPL-1 and CHRF-28-11 and erythroleukaemic cell line HEL.

The major toxicity encountered with [131I]-Meta-iodobenzylguanidine (MIBG) therapy in neuroblastoma patients is an often isolated thrombocytopenia. We believe that this results from MIBG-induced radiotoxicity of the megakaryocytes. Since it is difficult to obtain enough human megakaryocytes for uptake studies, we investigated whether the megakaryocytic cell lines, MKPL-1, CHRF-288-11 and HEL, are good models to study serotonin and MIBG accumulation in human megakaryocytes. Compared with platelets, low levels of specific MIBG accumulation (imipramine-sensitive) were shown in all cell lines, but that of serotonin was negligible in MKPL-1 and CHRF-288-11. Furthermore, the proportion of specific uptake of both MIBG and serotonin appeared greatest in the HEL cells. Although these cells seem to be good candidates to study serotonin and MIBG uptake, they are not a good model to investigate MIBG and serotonin accumulation in human megakaryocytes since they have no functional storage granules.

3-Iodobenzylguanidine↗
PubMed1993

Uptake of the neuron-blocking agent meta-iodobenzylguanidine and serotonin by human platelets and neuro-adrenergic tumour cells.

The adrenomedulla-imaging agent meta-iodobenzylguanidine (MIBG) is concentrated by various tumours of neuroectodermal origin. Radio-iodinated [131I]MIBG is therefore increasingly used for diagnosis and therapy of these disorders. To study the cause of thrombocytopenia associated with [131I]MIBG therapy, we investigated the uptake of MIBG in human platelets in comparison with that of serotonin. Specific imipramine-sensitive uptake of [131I]MIBG was much slower than of [3H]serotonin, but after prolonged incubation high and serotonin-equivalent uptake levels were observed. Accumulation of MIBG saturated at 10- to 100-fold higher concentration than serotonin, and the affinity for uptake and intracellular storage in platelets was much higher for serotonin than for MIBG. Conversely, serotonin was not detectably concentrated by neuroadrenergic Uptake-I in SK-N-SH neuroblastoma and PC12 pheochromocytoma cells. Fluvoxamine inhibited the uptake of norepinephrine and MIBG in PC12 cells, similarly to that of serotonin in platelets. However, the drug was 100-fold more effective in inhibiting platelet transport of MIBG than of serotonin. The results indicate that MIBG uptake in platelets is not mediated by a neuro-adrenergic Uptake-I, but probably proceeds via the serotonin transport system. MIBG concentration by platelets was at least as efficient as in neuro-adrenergic tumour cells and has therefore (radio)biological potential for injuring these cells or precursor megakaryocytes. Platelet uptake of MIBG could be selectively blocked by fluvoxamine in concentrations which minimally affected its accumulation in neuro-adrenergic target cells.

3-Iodobenzylguanidine↗
PubMed1993

Control and regulation of metabolic fluxes in microbes by substrates and enzymes.

The control of enzymes and substrates on the flux through microbial metabolic pathways can be quantified in terms of flux control coefficients. In pathways involving group transfer, the summation theorem for flux control by the enzymes has to be modified: the sum of control by all enzymes is between 1 and 2. The phosphoenolpyruvate:glucose phosphotransferase system is such a pathway. Experimental determination of the control by the enzymes in this pathway is under way. The control of the enzymes on the glycolytic flux in yeast is low, with the possible exception of the uptake step. In Klebsiella pneumoniae potassium and ammonium ions can simultaneously be 'limiting', (i.e. have significant control on growth) at pH6, but not at pH8. This may be due to the fact that at pH8 the high-affinity potassium uptake system is absent.

Ammonia↗
PubMed1993

Growth and enrichment of pentachlorophenol-degrading microorganisms in the nutristat, a substrate concentration-controlled continuous culture.

The nutristat, a substrate concentration-controlled continuous culture, was used to grow pentachlorophenol (PCP)-degrading microorganisms. The PCP concentration control system consisted of on-line measurement of the PCP concentration in the culture vessel with a tangential filter and a flowthrough spectrophotometer. With PCP concentrations between 45 and 77 microM, a stable situation was established in the nutristat, with an average dilution rate of 0.035 +/- 0.003 h-1. Compared with those of fed-batch cultures and chemostat cultures, the growth rates of microorganisms in the PCP nutristat were significantly higher, leading to considerable time savings in the enrichment procedure. In addition, PCP accumulation to severe inhibitory levels in the culture is prevented because the set point determines the (maximum) PCP concentration in the culture. The use of the nutristat as a tool for the growth of bacteria that degrade toxic compounds is discussed.

Biodegradation, Environmental↗
PubMed1991

Pharmacokinetics and intracellular distribution of the tumor-targeted radiopharmaceutical m-iodo-benzylguanidine in SK-N-SH neuroblastoma and PC-12 pheochromocytoma cells.

Radiodinated meta-iodobenzylguandine (MIBG) is increasingly used for the diagnosis and targeted radiotherapy of neuro-adrenergic tumors. We have investigated various conditions for specific tumor loading and prolonged retention of this radiopharmaceutical in poorly differentiated SK-N-SH neuroblastoma and highly differentiated PC-12 pheochromocytoma cells. At a constant value of drug concentration x incubation time, short incubations were superior to protracted incubations for maximal cell loading. This effect was most pronounced in the SH-N-SH neuroblastoma cells. In highly differentiated pheochromocytoma cells, the levels of MIBG storage remained high and unchanged during incubations up to 46 hr in label-free medium, while primitive SK-N-SH cells lost 40-50% of accumulated drug by diffusion. In PC-12 cells, susceptibility of stored MIBG to exocytotic release induced by acetylcholine or K+ was similar to that of natural norepinephrine (NE) and prevented by the Ca(++)-channel blockers verapamil and nifedipine. Conversely, granule-poor SK-N-SH cells were insensitive to exocytotic release of MIBG. Uptake and retention capacities were minimally impaired by an externally delivered radiation dose of 5 Gy to mimic the radiobiological effect of 131I-MIBG in tumors. In pre-irradiated cultures, drug uptake was even stimulated, probably due to enrichment in non-proliferating cells. An autoradiographic comparison of the (sub)cellular distributions of 3H-norepinephrine and 125I-MIBG showed that routine conditions of cell fixation and sample processing do not yield reliable results regarding localization of MIBG.

3-Iodobenzylguanidine↗