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Biomedical subjects

M Anniko

Publications and source records attributed to M Anniko.

At least 253 records · Page 14Linked to original sources

Cochlear pathology following exposure to mercury.

The sensory and secretory epithelia may become morphologically changed following the exposure to mercury chloride. The earliest and most sever change in the sensory epithelium appeared in the apical part of the cochlea, while the basal coils were only seldom damaged (cytocochleogram studies). Acute intoxication mostly affected both afferent and efferent nerve terminals and the hair cells, while chronic poisoning could also damage the stria vascularis.

Animals↗

The effects of mercurial poisoning on the vestibular system.

The sensory epithelium with adjacent nerve endings and the secretory epithelium may both become damaged following mercury chloride intoxication. Peripheral myelinated nerve fibres in the crista ampullaris showed signs of degeneration following chronic poisonins. Ultrastructural alterations of the vestibular hair cells initially occurred in animals free from clinical signs of intoxication. The sensory epithelium and occasionally the secretory cells were affected before signs of ultrastructural damage could be detected in the myelinated nerves.

Animals↗

Reversible and irreversible changes of the stria vascularis. An evaluation of the effects of ethacrynic acid separately and in combination with atoxyl.

The morphological changes in the cochlea following administration of ethacrynic acid occur initially in the stria vascularis of the basal coils as an increased intracellular vesiculation of the marginal cells followed by inter- and intracellular oedema in the intermediate cell layer. The combined administration of ethacrynic acid and atoxyl (individual doses) can cause irreversible damage to the cochlear hair cells and the stria vascularis, while the administration of each of them separately in the same low dose did not cause hair cell degeneration or persistent morphological changes of the stria vascularis. An increased penetration of atoxyl into the cochlea is likely to occur due to the ethacrynic acid-induced changes in the permeability of the endolymphatic partition so that the earlier known penetration of atoxyl into the cochlea is increased.

Aniline Compounds↗

Organ culture of the 16th gestation day mouse labyrinth. A model suggestion for pre- and post-partum development.

The 16th day mouse embryo inner ear was explanted and cultured "in vitro" for 6 days, which corresponds to 1 day post-partum development "in vivo". A normal development occurred both when the inner ear anlage was divided into a vestibular and a cochlear portion and when it was cultured as a whole. The present model system may provide a helpful tool in the study of both normal development and inner ear pathology.

Animals↗

A physiological and morphological study of the cochlea of the rat following treatment with atoxyl and neomycin.

By means of physiological and morphological techniques the inner ear pathology following exposure to the ototoxic compounds atoxyl and neomycin was analysed in the rat. Primarily a high tone deterioration occurred with a subsequent morphological degeneration pattern among the hair cells in the basal part of the cochlea. The outer hair cells were more frequently affected than the inner hair cells following the administration of both atoxyl and neomycin.

Animals↗

Problems and pitfalls in ototoxicity testing.

A local anaesthetic drug under development, intended for use in ear surgery, was tested with regard to adverse, ototoxic effects. Inner ear damage was not obvious. However, in the guinea pig a massive formation of new bone occurred in the middle ear (bulla tympanica) within 5 weeks after a single local administration of the drug.

Anesthetics, Local↗

Human pituitary tumours in organ culture with correlation to clinical data.

Out of 56 operated pituitary tumours 31 were hypersecreting growth hormone (GH), 12 hypersecreting prolactin (PRL), 2 hypersecreting ACTH and 11 tumours were chromophobe without secretion of hormone. One pituitary revealed normal conditions at the surgical exploration later confirmed at the renewed endocrinological investigation. 36 pituitary tumours have been explanted to in vitro culture: 20 tumours causing acromegaly, 9 porlactinomas, 2 ACTH-producing and 5 chromophobe adenomas. The higher the GH concentration was in vitro, the more active was the degree of acromegaly found clinically. GH hypersecreting tumours also secreted small amounts of PRL in vitro and the countary concerning prolactinomas. The GH/PRL ratio was individual for each tumour, GH or PRL hypersecreting. Tumour tissue revealed approximately the same characteristics in vitro, irrespective of whether taken from different regions of the tumour. A good correlation occurred in the secretion of PRL in vivo and in vitro, i.e. the higher the serum level of PRL the higher concentration of PRL found in the culture medium. Mitosis did not occur in any of the histological sections of more than 400 separate specimens. The increase in PRL in cultured specimens is probably due to the absence of a prolactin-inhibiting factor (PIF) during in vitro culture. On the other hand, the decreasing GH levels may be due to the absence of a GH-releasing factor. The results of the present study suggest an individual biology in each pituitary tumour.

Acromegaly↗

The post-natal mammalian labyrinthine secretory epithelium in vitro.

Newborn and mature inner ears from the guinea pig and the CBA/CBA mouse were explanted to an in vitro system. Special attention was paid to the secretory regions of the labyrinth showing surviving cells during the investigated period of 1 week on organ culture. Cells comprising the stria vascularis and the dark cells of the vestibular organs were both morphologically rather well preserved. Degenerative cytological alterations became apparent towards the end of the culture period.

Animals↗

Elemental composition of the mature inner ear.

An X-ray energy dispersive analysis was performed on the mature serial sectioned freeze-dried mammalian labyrinth (CBA/CBA mouse). The elemental distribution in the endolymphatic and perilymphatic spaces revealed similar results as have been reported in the literature when withdrawing fluid for microanalysis. The cupulae of the vestibular organs showed only minimal relative peak intensities of chlorine and potassium in contrast to the tectorial membrane in the cochlea with elemental identification also of sodium, sulphur and calcium. A difference in structural composition is therefore likely between these two tissues.

Animals↗

The human acoustic neurinoma in organ culture. II. Tissue changes after gamma irradiation.

Acoustic neurinoma tissue in organ culture was exposed to gamma irradiation (60CO) 30-150 Gy single dose. Schwann cell degeneration occurred from the first week onward in vitro following irradiation. After 3 weeks only a limited number of surviving cells were observed in the specimens, as compared with controls. The in vitro changes in tissue morphology indicate an irreversible course even after irradiation with the lowest dose, 30 Gy single dose. As a comparison with the in vitro experimental material it has also been possible to analyse the light and electron microscopic morphology of a tumour from a patient previously treated with stereotactic radiosurgery. An similar substantial Schwann cell loss was found in the centre of the tumour treated with stereotactic irradiation prior to surgery, as compared with the in vitro material.

Adult↗

Gamma irradiation effects on human growth hormone producing pituitary adenoma tissue. An analysis of morphology and hormone secretion in an in vitro model system.

Irradiation-induced effects on pituitary cell morphology and secretion of growth hormone (GH) and prolactin (PRL) have been analysed using an in vitro system. Specimens for organ culture were obtained from three patients with pituitary tumours causing acromegaly but with different clinical activity of disease. Specimens were followed in vitro 1 h - 6 days after single-dose gamma irradiations (60Co) with 70, 100 and 150 Gy, respectively. These doses are used in clinical work for the stereotactic radiosurgery of pituitary adenomas. Considerable fluctuations in hormone secretion/release occurred during the first 24 h after irradiation. Following 70 Gy single dose, the GH secretion increased slightly a few days after irradiation, having been at a minimum level 24 h after exposure. When using dose of 100 and 150 Gy, however, no such increased secretion with time after irradiation was indicated. All three tumors showed individual differences concerning irradiation-induced morphological damage. Only a minor variation occurred between specimens from the same tumour. In specimens from all tumours, irrespective of dose, minor morphological changes were observed 3-5 h after irradiation. Thereafter an individual response to irradiation became apparent. One tumour displayed maximum cell damage 24 h after irradiation with 70 Gy, showing severe oedema and damage to cell organelles. The other two adenomas were only slightly damaged following irradiation with 70, 100 and 150 Gy. Numerous morphologically normal or near-normal cells were found in all specimens from the three tumours 6 days after irradation. An individual sensitivity to irradiation of pituitary tumours in vitro is documented. The great number of surviving pituitary tumour cells one week after irradiation--many with an intact ultrastructure and containing hormone granules--indicated an initial high degree of radioresistance.

Acromegaly↗

Early development and maturation of the spiral ganglion.

The maturation of the spiral ganglion and its peripheral pathways to the cochlea has been morphologically analysed from birth to the 14th day postnatally, i.e. to the time from the onset and during the maturation of cochlear potentials (mouse). The spiral ganglion cells and the neurons between the ganglion and habenula perforata must attain myelination before action potentials can be elicited. Earlier observations that a certain maturation of the organ of Corti is a prerequisite for the development of electrophysiological potentials is probably only coincidental in time with the structural development of the ganglion and the neurons.

Animals↗

Embryonic development of the specific vestibular hair cell pathology in a strain of the waltzing guinea pig.

The cytodifferentiation and maturation of vestibular hair cells, and the pathological development of vestibular type I hair cells, were followed in a strain of the waltzing guinea pig. The hair cells are first identified on the 30th gestational day. During the next 7-10 days the number of hair cells increases considerably in parallel with cytodifferentiation: the development of stereocilia, the cuticular plate, the afferent nerve terminals and the formation of synaptic contacts. On the 48th gestational day efferent nerve terminals are identified as are also a large number of fully developed nerve calyces. Differentiation into hair cells type I and type II was clearly evident at this stage. The first pathological finding appeared on the 38th gestational day as fusion of stereocilia. Actin filament rods in type I hair cells are identified with certainty on the 60th gestational day. In parallel with the in vivo development, inner ear explants (30-50th gestational days) were cultured in vitro. In this material actin filament rods were found already in 30th gestational day explants cultured 8 days in vitro. At this stage also hair cell protrusion and sensory hair fusion occurred.

Animals↗

Chlorphentermine-induced changes of the peripheral vestibular sense organ of the rat.

Chronic feeding of chlorphentermine to young rats induces an accumulation of electron dense conglomerates and vacuoles in intraepithelial afferent nerve fibres of maculae and cristae in the vestibular part of the inner ear. In spite of the fact that preterminal parts of axons are severely swollen due to this accumulation, the nerve terminals maintain their normal size but can sometimes contain inclusions. Efferent fibres always remain free of these changes. Sensory cells, vestibular ganglion cells and occasionally supporting cells contain lamellar and crystalloid-like inclusions which disappear when the treatment is interrupted. After a long-term feeding break the nerve fibre inclusions disappear. A few swollen distended morphologically empty preterminals remain. The preference of inclusion body accumulation in afferent neurons may indicate an especially high lipid turnover in this part of the hair cell innervation.

Acoustic Maculae↗

Organ culture of the late embryonic inner ear as a model for ototoxicity studies.

The 16th gestational day inner ear of the CBA/CBA mouse was used in an organ culture system as a model for ototoxicity studies. The specimens in culture were exposed to 1, 10, 100 and 1 000 micrograms/ml of gentamicin base during 1-5 days in culture. Minor changes were found after only one day of exposure. Pathological changes of vestibular hair cells characteristic for aminoglycoside antibiotics occurred after exposure to 1 and 10 micrograms/ml. Concentrations of 100 and 1 000 micrograms/ml caused a general toxicity with destruction of the whole morphology of the crista ampullaris. Hair cells were, however, more affected than were supporting cells. Initially, variation of hair cell damage occurred within each crista and between different cristae but this became less apparent after 5 days in culture. The 16th gestational day organ culture system can serve as a useful model system with many controlled experimental parameters in the testing of ototoxic drugs.

Animals↗

Effects of perilymphatically perfused gentamicin on microphonic potential, lipid labeling and morphology of cochlear tissues.

The perilymphatic space of the guinea pig was perfused in situ with artificial perilymph containing [32P] orthophosphate and 3H-glycerol while cochlear microphonic potentials (CM) were monitored. The perfusion of 10 mM gentamicin suppressed CM by 62% within 30 min. 32P-incorporation into phosphatidylinositol bisphosphate in the organ of Corti was decreased but distribution of 3H-glycerol in neutral lipids and phospholipids was not affected by gentamicin. The morphological evaluation included all structures lining the scala media, the spiral ligament, the basal membrane and the vestibular organs. Hair cells sometimes contained small intracellular 'precipitation' lines but, in general, ultrastructure of all tissues was essentially normal and no overt histopathological changes were evident. The observed biochemical changes should, therefore, represent early and primary actions of the drug. This confirms the hypothesis that an interaction with the acidic phospholipid, phosphatidylinositol bisphosphate, is an important step in the ototoxic mechanism of amino-glycoside antibiotics.

Animals↗

Aspects on the ototoxic potential of netilmicin.

The organ culture system using the 16th gestational day inner ear explant from fetal mice was used for ototoxicity screening of netilmicin. Organ cultures were incubated in 1, 10, 100 and 1000 micrograms/ml, respectively, of netilmicin base in the nutrient solution. After constant exposure to the drug during 5 days, the inner ears (N = 56) were analyzed morphologically at the light and electron microscopic levels. All specimens were serially sectioned. Exposure to 1 and 10 micrograms/ml of netilmicin base, doses that are reached during in vivo conditions in man, did not cause morphological damage to hair cells as observed in the light microscope at the end of the 5-day period. At the ultrastructural level, minor changes characteristic for aminoglycosides occurred in hair cell mitochondria. Incubation with 100 and 1000 micrograms/ml of netilmicin base caused morphological changes in many types of epithelia and not only in vestibular hair cells. This indicates a general sign of toxicity of netilmicin in these doses. The dose response relationship with regard to inner ear pathology was obvious in the vestibular part of the labyrinth. In the cochlea, however, few cytological changes occurred independent of dose. As compared with gentamicin, exposure in the same concentrations as in the present study and under similar experimental conditions, the less ototoxic effect of netilmicin was obvious. The results of the present study indicate that the less ototoxic potential of netilmicin as compared with other aminoglycosides is probably due to the drug itself and not primarily due to a poor penetration of netilmicin into the inner ear.

Animals↗