Local and systemic toxicity of h-R3, an anti-epidermal growth factor receptor monoclonal antibody, labeled with 188osmiun after the intracerebral administration in rats.

h-R3 is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MAb). This receptor is over-expressed in the majority of tumors of epithelial origin, including glioblastomas. 188Rhenium (188Re) constitutes an ideal radionuclide for imagining and radioimmunotherapy, and its toxicity is known, nevertheless, it is unknown if 188Os, as 188Re's daughter, has any local or systemic toxicity effect when it is administered intracerebrally for treating intracranial tumors. For this reason we decided to assess the toxicity of stable 188Os once the complete decay of 188Re has occurred, by administering intracerebrally to rats the h-R3 labeled with 188Os. Forty rats (20 each sex) were distributed randomly into four experimental groups (ten per group): control group received 5microL of glucoheptonate solution vehicle; two other groups were treated with unlabeled or labeled h-R3 with 188Os. The remaining group served as a non-treated control group. A single 5 microL dose (2.5 microL into each lateral ventricle) of neutral solution containing 50 microg of h-R3 labeled initially with 13.25 microCi of 188Re was stereotactically administered into lateral ventricles 8 days after the conjugation with the radionuclide was done. Each animal was observed daily for detection of toxicity signs. Body weights were recorded on days 0, 7 and 14. Blood samples for analysis of hematological and clinical chemistry parameters were taken on days 0 and 14. Necropsy and histopathological studies were carried out at the end of the study. All animals gained weight by day 14. There were no changes in hematological and clinical chemistry, but minimal histopathological changes were observed at the application sites. This study shows that single doses of 188Os-h-R3 is tolerable and causes minimal local and no systemic toxicity effects in rats.

Immunological study in Parkinson's disease patients with intracerebral allografts

Immunological response was characterized in 15 patients with Parkinso's disease intracerebrally transplanted: seven in unilateral and eight in bilateral hemisphere with fetal mesencephalic cells by stereotactical technique. The phenotypic distribution of mononuclear cells in CSF and PB was investigated using monoclonal antibodies. The total protein, albumin and IgG in CSF and albumin, IgA, IgM and IgG Concentration in serum were also analyzed, before and after evolution. A general decrease in CD2+ cells was found in patients with unilateral neurotransplantation during the first semester following trasplant. A small increase in the proportion of CSF CD8+ cells was observed in the first month and in the fourth month in PB. In patients with bilateral intracerebral allografts a decrease in CD2+ and CD4+ cells was found during the first and fourth month. The intrathecal synthesis of IgG during the fourth month was observed in both patients. Results are discussed taking into account the immunosupressor treatment(AU)

Lesion of the nigrostriatal neurons by 6-hydroxydopamine induces changes in rat brain glutathione S-transferase

Wistar rats were lesioned into the nigrostriatal pathway with 6-OHDA. The D-amphetamine-induced circling behavior test was performed to evaluate lesion efficiency. Animals that showed more than 620 turns/90 min were named totally lesioned animals (TLA). The group of rats that performed less than 620 turns/90 min was named partially lesioned animals (PLA). The contents of DA and its catabolites in the striata of these groups, and in the same tissue of the untreated animals, were mearured. Moreover, the striatal gluthatione-S-transferase (GST) specific activity for all groups was tested, and the kinetics parameters for GST ppurified from the whole brain were evaluated from other three similar groups. The striatal DA depletion in TLA was greater than in PLA. Striatal GST activity showed a significant bilateral increase in PLA, whereas TLA exhibited only an ipsilateral augment. There were also differences between groups about the kinetic parameters of the purified brain enzyme. The possible role of GST on the interindividual lesion response difference was analyzed (AU)

Lesion of the nigrostriatal neurons by 6-hydroxydopamine induces changes in rat brain glutathione S-transferase

Wistar rats were lesioned into the nigrostriatal pathway with 6-OHDA. The D-amphetamine-induced circling behavior test was performed to evaluate lesion efficiency. Animals that showed more than 620 turns/90 min were named totally lesioned animals (TLA). The group of rats that performed less than 620 turns/90 min was named partially lesioned animals (PLA). The contents of DA and its catabolites in the striata of these groups, and in the same tissue of the untreated animals, were mearured. Moreover, the striatal gluthatione-S-transferase (GST) specific activity for all groups was tested, and the kinetics parameters for GST ppurified from the whole brain were evaluated from other three similar groups. The striatal DA depletion in TLA was greater than in PLA. Striatal GST activity showed a significant bilateral increase in PLA, whereas TLA exhibited only an ipsilateral augment. There were also differences between groups about the kinetic parameters of the purified brain enzyme. The possible role of GST on the interindividual lesion response difference was analyzed(AU)

Lesion of the nigrostriatal neurons by 6-hydroxydopamine induces changes in rat brain glutathione S-transferase

Wistar rats were lesioned into the nigrostriatal pathway with 6-OHDA. The D-amphetamine-induced circling behavior test was performed to evaluate lesion efficiency. Animals that showed more than 620 turns/90 min were named totally lesioned animals (TLA). The group of rats that performed less than 620 turns/90 min was named partially lesioned animals (PLA). The contents of DA and its catabolites in the striata of these groups, and in the same tissue of the untreated animals, were mearured. Moreover, the striatal gluthatione-S-transferase (GST) specific activity for all groups was tested, and the kinetics parameters for GST ppurified from the whole brain were evaluated from other three similar groups. The striatal DA depletion in TLA was greater than in PLA. Striatal GST activity showed a significant bilateral increase in PLA, whereas TLA exhibited only an ipsilateral augment. There were also differences between groups about the kinetic parameters of the purified brain enzyme. The possible role of GST on the interindividual lesion response difference was analyzed(AU)

Lesion of the nigrostriatal neurons by 6-hydroxydopamine induces changes in rat brain glutathione S-transferase

Wistar rats were lesioned into the nigrostriatal pathway with 6-OHDA. The D-amphetamine-induced circling behavior test was performed to evaluate lesion efficiency. Animals that showed more than 620 turns/90 min were named totally lesioned animals (TLA). The group of rats that performed less than 620 turns/90 min was named partially lesioned animals (PLA). The contents of DA and its catabolites in the striata of these groups, and in the same tissue of the untreated animals, were mearured. Moreover, the striatal gluthatione-S-transferase (GST) specific activity for all groups was tested, and the kinetics parameters for GST ppurified from the whole brain were evaluated from other three similar groups. The striatal DA depletion in TLA was greater than in PLA. Striatal GST activity showed a significant bilateral increase in PLA, whereas TLA exhibited only an ipsilateral augment. There were also differences between groups about the kinetic parameters of the purified brain enzyme. The possible role of GST on the interindividual lesion response difference was analyzed