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Biomedical subjects

B Arvidson

Publications and source records attributed to B Arvidson.

29 records · Page 2Linked to original sources

Cytofluorescence localization of adriamycin in the nervous system. I. Distribution of the drug in the central nervous system of normal adult mice after intravenous injection.

By a fluorescence-microscopic technique the distribution of the antineoplastic glycoside, adriamycin (doxorubicin), was studied in the CNS of normal adult mice after i.v. injection. Doses comparable to those used in patients for the treatment of malignant diseases were used. The drug did not have access to areas of the brain within the blood-brain barrier but, except for the subcommissural organ, it was consistently localized in the nuclei of neurons and/or glial cells of the circumventricular organs (postremal area, subfornical organ, median eminence, neurohypophysis) as well as in cells of the choroid plexus and lamina cribrosa of the optic nerve. The nuclear fluorescence was accompanied by a less intense extracellular fluorescence when the survival time was shorter than 1 min after the injection. The fluorescence emitted by adriamycin was seen as early as 15 s after injection and showed its highest intensity at 1 and 15 min later. After 24 h fluorescence was no longer observed except for the ependymal zone of the median eminence. Our study thus shows that adriamycin passes from the blood into the nervous parenchyma in those areas of the brain located outside the blood-brain barrier. This finding raises the question whether in such regions there are any neurotoxicologic effects produced by the drug which have not yet been detected.

Animals↗

Cytofluorescence localization of adriamycin in the nervous system. II. Distribution of the drug in the somatic and autonomic peripheral nervous systems of normal adult mice after intravenous injection.

By a fluorescence-microscopic technique, the distribution of the antineoplastic glycoside adriamycin (doxorubicin) was studied in the peripheral nervous system (PNS) of normal adult mice after i.v. injection. Doses comparable to those used in patients for treatment of malignant diseases were used. The orange-red fluorescence of the drug was observed in dorsal root ganglia, in the trigeminal ganglia, and in the superior cervical sympathetic ganglia where it was preferentially accumulated in the nuclei of satellite cells. This nuclear labeling was a very quick process which occurred in the superior cervical ganglion within 15 s after the injection. Adriamycin-fluorescent nuclei were also observed in the suprarenal medulla. Fluorescent nuclei were present within the pre- and postganglionic sympathetic nerve trunks close to the superior cervical ganglion but not in the endoneurium of the trigeminal and the sciatic nerves or in the spinal nerve roots. In such structures labeled cells appeared in the connective tissue sheaths covering the nerves and the roots. No adriamycin-induced fluorescence was detected in the myenteric plexus of the intestine. Our study thus shows that i.v. injected adriamycin is distributed preferentially within areas of the PNS where the blood vessels are known to be highly permeable.

Adrenal Medulla↗

Morbidity and mortality in the commitment process.

This study reports a prospective evaluation of 189 patients who entered the commitment process in Oregon. Patients were assessed for commitment status, morbidity, and mortality at six and 19 months. Twenty-nine percent were formally committed. The committed group consisted largely of violence-prone, psychotic patients plus a small number of elderly, demented subjects with serious medical illness. A mortality of 10% included the elderly who died of medical causes and young adult patients who completed suicide. The findings justify psychiatry's concern for patient welfare in commitment systems, especially for the group that is released and not committed. The study is compared with six additional commitment studies, with emphasis on methodology and implications for further research.

Adult↗

A study of the perineurial diffusion barrier of a peripheral ganglion.

The perineurial diffusion barrier to horseradish peroxidase (HRP) and ferritin was investigated in superior cervical ganglia of rats and mice. The ganglion was surrounded by a delicate epineurium and 2-5 perineurial lamellae joined by zonulae occludentes and desmosomes. Following local application of tracers the animals were killed after 5, 30, and 60 min and the distribution of HRP and ferritin was studied by light and electron microscopy. The inner layers of the ganglionic perineurium prevented diffusion of both HRP and ferritin perineurial lamellae investing the ganglion. HRP had often extended to the innermost lamella 60 min after application. HRP and ferritin were present in vesicles of ganglionic perineurial cells. There was no passage of tracers via intercellular junctions.

Animals↗

Retrograde transport of horseradish peroxidase in sensory and adrenergic neurons following injection into the anterior eye chamber.

Horseradish peroxidase (HRP) was injected into the anterior eye chamber of rats and mice and frozen sections from both superior cervical and trigeminal ganglia were incubated to demonstrate neurons accumulating the tracer by retrograde axonal transport. Labelled cells were observed only in ganglia ipsilateral to the HRP injection. Within the trigeminal ganglion, peroxidase-containing neurons were restricted to the medial ophthalmic area, whereas labelled cells in the superior cervical ganglion were more widely distributed. With the use of a new and more sensitive technique for the demonstration of HRP in neurons, it was possible to show retrograde transport also of small amounts of peroxidase injected into the anterior eye chamber. In addition, this technique enabled identification of the central and peripheral processes of neurons in the trigeminal ganglion and the dendrites and axons of sympathetic ganglion cells. The rate of retrograde HRP transport in rats was calculated to approximately 4--5 mm/h for both sensory and adrenergic nerves, which is consistent with previous estimates for this protein. It differs from the transport rate reported for nerve growth factor (NGF) and macromolecular toxins in sensory and adrenergic nerves of the same species. These rates were, however, obtained with a different method and in a different population of sensory neurons and are, therefore, not directly comparable. After treatment with 6-hydroxydopamine the number of HRP-labelled cells in the superior cervical ganglion was significantly reduced compared to controls. Cell counts from trigeminal ganglia showed no significant difference between controls and treated animals.

Animals↗

Retrograde axonal transport of horseradish peroxidase from cornea to trigeminal ganglion.

Horseradish peroxidase (HRP) was dripped on the scarified left cornea of adult mice. Twenty-four hours later the animals were fixed by vascular perfusion and frozen sections cut from both trigeminal ganglia. After incubation for peroxidase activity labelled nerve cells were restricted to the medial ophthalmic part of the ganglion ipsilateral to HRP administration. If the scarification was omitted no neuronal labelling was observed. This labelling of the neurons is most probably the result from axonal uptake and subsequent retrograde axonal transport of the tracer. The similarity in distribution of peroxidase labelled nerve cells and the first ganglionic lesions occurring after instillation of herpes simplex virus in the cornea is pointed out.

Animals↗

Cellular uptake of exogenous horseradish peroxidase in mouse peripheral nerve.

Horseradish peroxidase (HRP) was given to adult normal mice either intravenously or locally around the sciatic nerve. After varying time intervals the animals were sacrificed and fixed by whole body perfusion. The sciatic nerve was sampled and the distribution of peroxidatic activity was studied by light and electron microscopy. After both types of HRP administration the tracer was rapidly taken up by epi- and endoneurial cells with the ultrastructural features of macrophages. When increasing doses of HRP were injected intravenously a diffuse endoneurial extravasation was observed 30 min after the injection. It is concluded that a passage of HRP takes place over some endoneurial vessels. The nature and significance of endoneurial macrophages are discussed.

Animals↗

Distribution of 109Cd in the nervous system of rats after intravenous injection.

The distribution of intravenously injected 109Cd in the nervous system was studied in rats twenty-four hr and one week after the injection. Measurements by gamma scintillation showed a high uptake of cadmium in peripheral sensory and autonomic ganglia whereas the uptake was low in the brain, cerebellum and spinal cord. The accumulation of cadmium in the sciatic nerve was significantly higher than in the brain and spinal nerve roots but lower than in ganglia. Autoradiography confirmed that there was no uptake of cadmium in the major part of the brain parenchyma, but showed an accumulation of the metal in areas outside the blood-brain barrier such as the hypophysis, meninges, choroid plexus and pineal gland. Within the peripheral nervous system, the autoradiography showed a localization of cadmium to dorsal root ganglia and, in addition, an uptake was seen in the connective tissue sheaths surrounding the sciatic nerve. The results indicate that the uptake of cadmium is correlated to regional variations in the permeability of blood vessels. The accumulation of cadmium in certain nervous structures may explain some of the neurotoxicological effects which have been demonstrated in animal experiments.

Animals↗