| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Ceberg, Crister, et al.
(författare)
-
A comparative study on the pharmacokinetics and biodistribution of boronated porphyrin (BOPP) and sulfhydryl boron hydride (BSH) in the RG2 rat glioma model
- 1995
-
Ingår i: Journal of Neurosurgery. - 0022-3085. ; 83:1, s. 86-92
-
Tidskriftsartikel (refereegranskat)abstract
- Boron neutron capture therapy is a treatment modality for cancer that depends on the specific uptake of boron by the tumor cells. The infiltrative growth of malignant gliomas requires that boron reach and accumulate in migrating cells outside the margin of the tumor; thus, it is important that the biodistribution of new boron compounds is also studied in the surrounding healthy brain tissue. This study is undertaken in the present work, in which the biodistribution and pharmacokinetics of sulfhydryl boron hydride (BSH) and boronated porphyrin (BOPP) in the RG2 rat glioma model are investigated. This model mimics the characteristics of human glioma with cells migrating into the surrounding brain. The animals were infused intravenously with either BSH (25 micrograms or 175 micrograms of boron per gram of body weight) or BOPP (12 micrograms of boron per gram body weight). For the low dose of BSH, the maximum tumor-boron content was 8 ppm at approximately 9 hours after the infusion with a tumor-to-blood ratio of 0.6. At the higher dose, the corresponding figures were 15 ppm after 12 hours with a tumor-to-blood ratio of 0.5. For BOPP, a tumor-boron concentration of 81 ppm was achieved 24 hours after the infusion and sustained in that range for at least 72 hours. The tumor-to-blood ratio at 24 hours was slightly above 6, but continued to increase as the blood was cleared. These results indicate that both compounds are spread into the normal brain tissue following the same pathways as the migrating tumor cells and in this way can be taken up even in distant tumor cell foci.
|
|
| 5. |
- Ceberg, Crister, et al.
(författare)
-
A stochastic model for subcellular dosimetry in boron neutron capture therapy
- 1995
-
Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 1361-6560 .- 0031-9155. ; 40:11, s. 1819-1830
-
Tidskriftsartikel (refereegranskat)abstract
- The therapeutic effectiveness of boron neutron capture therapy is highly dependent on the microscopic distribution of the administered boron compound. Two boron compounds with different uptake mechanisms in the tumour cells may thus cause effects of different degrees even if the macroscopic boron concentrations in the tumour tissue are the same. This difference is normally expressed quantitatively by the so-called relative local efficiency (RLE). In this work, a stochastic model for the subcellular dosimetry has been developed. This model can be used to calculate the probability for an energy deposition above a certain threshold level in the cell nucleus due to a single neutron capture reaction. If a threshold cell-kill function is assumed, and if the dose is low enough that multiple energy depositions are rare, the model can also be applied to calculations of the survival probability for a cell population. Subcellular boron distributions in rats carrying RG 2 rat gliomas were measured by subcellular fractionation after administration of two different boron compounds: a sulphydryl boron hydride (BSH) and a boronated porphyrin (BOPP). Based on these data, the RLE factors were then calculated for these compounds using the stochastic model.
|
|
| 6. |
- Ceberg, Crister, et al.
(författare)
-
Performance of sulfhydryl boron hydride in patients with grade III and IV astrocytoma: a basis for boron neutron capture therapy
- 1995
-
Ingår i: Journal of Neurosurgery. - 0022-3085. ; 83:1, s. 79-85
-
Tidskriftsartikel (refereegranskat)abstract
- This study investigated the rationale of boron neutron capture therapy (BNCT) for the treatment of Grade III and IV astrocytoma. The European Community joint research program on BNCT plans to use sulfhydryl boron hydride (BSH) in clinical trials. The work presented here, examines the performance of BSH in eight patients with Grade III and IV astrocytoma using a measurement technique which precisely correlates the boron uptake with the histology of the tumor and the peritumoral brain. Astrocytomas are exceptionally heterogeneous and spread migrating tumor cells into the surrounding brain. The patients were infused with 50 mg BSH per kilogram of body weight at 12, 18, 24 or 48 hours before surgery. At the time of operation, specimens were obtained of the tumor, skin, muscle, dura, blood, urine, and, when surgically possible, the brain adjacent to tumor. In three patients the intracellular boron distribution was investigated by subcellular fractionation. The blood clearance was biphasic with half-lives of 0.6 and 8.2 hours. After 3 days, approximately 70% of the dose injected was excreted in the urine. The maximum boron concentration in the tumor was 20 ppm, 12 hours after the infusion. The tumor-to-blood ratios ranged between 0.2 and 1.4, with the highest values after 18 to 24 hours. In the brain specimens the boron concentration never exceeded 1 ppm. This work confirms a selective uptake of boron in the tumor compared to the surrounding brain and that boron, to some extent, is incorporated in the tumor cells.
|
|
| 7. |
|
|
| 8. |
- Persson, Bertil R, et al.
(författare)
-
Blood-brain barrier permeability in rats exposed to electromagnetic fields used in wireless communication
- 1997
-
Ingår i: Wireless Networks. - 1022-0038. ; 3, s. 455-461
-
Tidskriftsartikel (refereegranskat)abstract
- iological effects of radio frequency electromagnetic fields (EMF) on the blood-brain barrier (BBB) have been studied in Fischer 344 rats of both sexes. The rats were not anaesthetised during the exposure. All animals were sacrificed by perfusion–fixation of the brains under chloralhydrate anaesthesia after the exposure. The brains were perfused with saline for 3–4 minutes, and thereafter perfusion fixed with 4% formaldehyde for 5–6 minutes. Whole coronal sections of the brains were dehydrated and embedded in paraffin and sectioned at 5 m. Albumin and fibrinogen were demonstrated immunohistochemically and classified as normal versus pathological leakage. In the present investigation we exposed male and female Fischer 344 rats in a Transverse Electromagnetic Transmission line chamber to microwaves of 915 MHz as continuous wave (CW) and pulse-modulated with different pulse power and at various time intervals. The CW-pulse power varied from 0.001 W to 10 W and the exposure time from 2 min to 960 min. In each experiment we exposed 4–6 rats with 2–4 controls randomly placed in excited and non-excited TEM-cells respectively. We have in total investigated 630 exposed rats at various modulation frequencies and 372 controls. The frequency of pathological rats is significantly increased (p < 0:0001) from 62=372 (ratio: 0:170:02) for control rats to 244=630 (ratio: 0:390:03) in all exposed rats. Grouping the exposed animals according to the level of specific absorbed energy (J/kg) give significant difference in all levels above 1.5 J/kg. The exposure was 915 MHz microwaves either pulse modulated (PW) at 217 Hz with 0.57 ms pulse width, at 50 Hz with 6.6 ms pulse width or continuous wave (CW). The frequency of pathological rats (0:17) among controls in the various groups is not significantly different. The frequency of pathological rats was 170=481 (0:350:03) among rats exposed to pulse modulated (PW) and 74=149 (0:500:07) among rats exposed to continuous wave exposure (CW). These results are both highly significantly different to their corresponding controls (p < 0:0001) and the frequency of pathological rats after exposure to pulsed radiation (PW) is significantly less (p < 0:002) than after exposure to continuous radiation (CW).
|
|
| 9. |
- Salford, Leif, et al.
(författare)
-
Brain tumour development in rats exposed to electromagnetic fields used in wireless cellular communication
- 1997
-
Ingår i: Wireless Networks. - 1022-0038. ; 3, s. 463-468
-
Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that electromagnetic fields (EMF) act as promoters late in the carcinogenesis process. To date, however, there is no convincing laboratory evidence that EMFs cause tumour promotion at non-thermal exposure levels. Therefore the effects of exposure to electromagnetic fields were investigated in a rat brain glioma model. Some of the exposures correspond to electromagnetic fields used in wireless communication. Microwaves at 915 MHz were used both as continuous waves (1 W), and pulse-modulated at 4, 8, 16 and 217 Hz in 0.57 ms pulses and 50 Hz in 6.67 ms pulses (2 W per pulse). Fischer 344 rats of both sexes were used in the experiments. By stereotaxic technique rat glioma cells (RG2 and N32) were injected into the head of the right caudate nucleus in 154 pairs of rats, exposed and matched controls. Starting on day 5 after inoculation, the animals were exposed for 7 hours a day, 5 days a week during 2–3 weeks. Exposed animals were kept unanaesthetized in well-ventilated TEM cells producing 915 MHz continuous or modulated microwaves. Their matched controls were kept in identical TEM cells without EMF exposure. All brains were examined histopathologically and the tumour size was estimated as the volume of an ellipsoid. Our study of 154 matched pairs of rats does not show any significant difference in tumour size between animals exposed to 915 MHz, and those not exposed. Thus our results do not support that even an extensive daily exposure to EMF promotes tumour growth when given from the fifth day after the start of tumour growth in the rat brain until the sacrifice of the animal after about 16 days.
|
|
| 10. |
- Vingsbo, Carina, et al.
(författare)
-
Pristance-induced arthritis in rats: a new model for rheumatoid arthritis with a chronic disease course influenced by MHC and non-MHC genes
- 1996
-
Ingår i: American Journal of Pathology. - 1525-2191. ; 149:5, s. 1675-1683
-
Tidskriftsartikel (refereegranskat)abstract
- We present a novel animal model for rheumatoid arthritis induced with a well defined synthetic adjuvant oil, pristane. Two weeks after a single intradermal injection of 150 microliters of pristane, the rats developed severe and chronic arthritis. The inflammation was restricted to the joints and involved pannus formation, major histocompatibility complex (MHC) class II expression, and T lymphocyte infiltration. The initial development as well as the chronic stage of pristane-induced arthritis was ameliorated by treatment with antibodies to the alpha beta-T-cell receptor showing that the disease is T cell dependent. Increased levels of interleukin in serum was seen after pristane injection but not during the chronic stage of arthritis. Joint erosions were accompanied by elevated serum levels of cartilage oligomeric matrix protein. Comparison of MHC congenic LEW strains showed that the severity and chronicity of arthritis varied among the different MHC haplotypes. Rats with RT1f haplotype showed a significantly higher susceptibility to pristane-induced arthritis. A strong influence of non-MHC genes was also suggested by the variability of arthritis susceptibility among different strains with the same MHC haplotype; the most susceptible background was the DA and the least susceptible was the E3. Arthritis induced with a well defined nonimmunogenic adjuvant, with a disease course that closely resembles that of rheumatoid arthritis, makes a suitable animal model for future studies of the pathology and genetics of rheumatoid arthritis
|
|
