Biodegradation of magnetite dextran nanoparticles in the rat. A histologic and biophysical study.

BACKGROUND: Superparamagnetic iron oxide particles represent a new class of contrast agents that increase the detectability of hepatic and splenic tumors by magnetic resonance imaging (MRI). Magnetite dextran nanoparticles, a preparation with a small mean particle diameter in solution and null zêta potential present high safety margin and efficacy. The purpose of this investigation was to define the main steps of the metabolism of the iron oxide crystals. EXPERIMENTAL DESIGN: Rats were intravenously administered a single small dose of 59Fe-labeled MD3 (3 mg Fe/kg), and the biodistribution of 59Fe was investigated in the different organs from 2 hours to 25 days postinjection. Magnetic susceptibility studies were conducted in parallel to light microscopy and immunohistochemistry from day 1 to day 14 after administration. RESULTS: Most of the dose accumulated in the carcass (45%), liver (7%), and spleen (7%) in the first 2 hours. In the spleen, a continuously iron uptake was observed up to 48 hours (44%), then decreased to 25 days (22%). The splenic magnetic susceptibility dropped sharply during the first days and then more slightly until day 14. In the liver and blood, the 59Fe-level decreased at 24 hours and then increased until day 25 (11% and 27%, respectively). Histochemistry features essentially confirmed the radiotracer data and showed that iron oxide cores were accumulated into the Kupffer cells and the macrophages of the splenic marginal zone. With time, the number of the granules was decreased whereas the fine iron granules appeared in the cytoplasm. Immunopositive staining for ferritin was markedly increased in the liver hepatocytes to 3 days after injection, and in the splenic marginal zone macrophages to 14 days after injection. CONCLUSIONS: The data point to the early biodegradation of the iron oxide crystals. MD3 thus appear as an interesting biodegradable new contrast agent first devoted to magnetic resonance imaging of liver and spleen diseases that could be further extended to heart, kidneys, and other organs.

[The metasympathetic mechanisms supporting the constancy and stability of the internal environment in vertebrates]. / Nekotorye metasimpaticheskie mekhanizmy podderzhaniia postoianstva i ustoichivosti vnutrennei sredy pozvonochnykh.

The data were obtained with the aid of extracellular recording of unit activity in the cardial, enteral and respiratory parts of the metasympathetic nervous system, staining of the neural tissue preparations of atrial walls, intestine and lower part of the guinea pig trachea. The neurons were shown to be very sensitive to the main homeostatic contants: pH of the perfusion solution, its temperature and the grade of oxygenation. These structures were shown to take a direct part in maintenance of the constancy and stability of the organism inner milieu. Sympathetic nervous system differs from the above system in that the former is the system of transmission, defence, mobilisation of resources which is necessary for active interaction of the organism with ambient milieu.

[Seasonal changes in adrenoreactivity and a modification in the fractional phospholipid composition of the frog bladder]. / Sezonnye izmeneniia adrenoreaktivnosti i modifikatsiia fraktsionnogo sostava fosfolipidov mochevogo puzyria liagushki.

The study has shown seasonal changes in the responses of the frog bladder isolated preparation to exogenous adrenalin. The finding is explained by heterogeneity of the smooth muscle adrenoreceptors and alteration of functionally domineering populations during the winter-spring cycle. The changes corresponded to modifications of the fraction composition of phospholipids, the modifications being, probably, one of the ways of regulation of the smooth muscle adrenoreceptor apparatus' activity.

[The mechanisms regulating the activity of the longitudinal layer of the intestinal smooth muscle in the Dolly Varden trout]. / Mekhanizmy reguliatsii aktivnosti prodol'nogo sloia gladkikh myshts kishki mal'my.

Spontaneous myogenic rhythmic motility of the Salvelinus malma curilus smooth muscle structures was studied. The findings suggested presence of a general tonic inhibitory action of the enteral part of the metasympathetic nervous system on myogenic motility of intestinal longitudinal layer. The splanchnic nerve effect on intestinal motor activity was revealed. Dependence of obvious components of visceromotor response on the stimulation frequency, was shown. Possible origin of these components was discussed on the basis of experimentally obtained characteristics of effects of the transmitter substances on the smooth muscle structure. Functioning of neural muscular structures was compared in the mammalian and fish intestines.

[The mechanographic and biochemical characteristics of induced contractile activity in the frog bladder]. / Mekhanograficheskie i biokhimicheskie kharakteristiki vyzvannoi sokratitel'noi aktivnosti mochevogo puzyria liagushek.

Contractile activity of the frog bladder induced by electrical stimulation of the IX spinal nerve was shown to have a tubocurarine-resistant component. Two main components of the induced motor response were revealed differing from each other in latency, duration and sensitivity to tubocurarine. One of the components seems to be maintained by the activity of cholinergic fibres of the pelvic nerve and ganglion apparatus of the bladder plexus whereas the other component seems to be due to the results of efferent action of sensory terminals on the smooth muscle cells.

[Neurocyte reaction of the kinesthetic analyzer of rats to the action of vibration]. / Reaktsiia neirotsitov kinestezicheskogo analizatora krys na deistvie vibratsii.

By neurohistological, morphometric and electron-microscopic methods the effect of vibration of 80 Hz applied at an acceleration of 8 m/sec2 on the nerve cell and conduction components of the kinesthetic analyzer was investigated. After a single exposure to vibration nerve cells of the sensorimotor cortex showed some changes. Exposure to vibration for as long as a week caused reactive changes in every structure of the kinesthetic analyzer investigated. After 1-month exposure the changes were more disseminated and became destructive, after 2-month exposure the process developed at a slower rate, and after 3-month exposure it remained at the same level. However, after 3-month exposure the morphological equivalent of compensatory-adaptive reactions was seen.

[Background activity of neurons of the tracheal plexus in the rat]. / Fonovaia aktivnost' neironov trakheal'nogo spleteniia krysy.

Morphological structure of the nerve plexus of the rat tracheal dorsal muscle wall is described and electrophysiological data on neuronal activity of this plexus are presented. Extracellular recording revealed two types of spontaneous activity including a single-spike type and a serial-spike type. The presence of excitatory and inhibitory interaction between neurons of a single ganglion is shown. Characteristic features of the tracheal part are discussed in comparison with other parts of the metasympathetic system.

[Activity of the cortical neurons during paroxysmal after-discharge]. / Aktivnost' kortikal'nykh neironov v protsesse sudorozhnogo posledeistviia.

Features of electrographic and neuronal activities of occipital region of the cortex following repetitive electrical stimulation with the threshold intensity for triggering the electrographic paroxysmal after--discharges in the region of stimulation and for triggering the spreading motor paroxysmal after--discharge in the cortex, were studied in chronic experiments on unanesthetized rabbits. The frequency of paroxysmal potentials was 8 1/s in the focus of the local paroxysmal after--discharge and 15 1/s in the focus of spreading after-discharge. In the focus of spreading paroxysmal after--discharge the "epileptic" neurons in deep layers of cortex were observed; neurons in deep layers of the local paroxysmal after--discharge discharged mainly with single impulses or with trains of 2--3 impulses in the rhythm of paroxysmal potentials. The primary paroxysmal activity focus in upper cell layers is supposed to exist during local after--discharge. The changes in activity of deep cell layer neurons are discussed as the necessary condition for the spreading of paroxysmal after--discharge.