NMDA receptors of the vestibular nuclei neurones

Cloning and pharmacological studies have shown that glutamatergic receptors can be divided in two classes (refer to Table 1): ionotropic receptors including N-methyl-D-aspartate (NMDA) and non-NMDA subtypes, and the G-protein-coupled metabotropic receptors (glutamate metabotropic receptor). There are two types of non-NMDA receptors: the AMPA/low-affinity kainate receptor type (the AMPA receptors) activated by a specific agonist, the alpha-amino-3-hydroxy-5-methyl-4-iso-xalone propionate (AMPA), and the high affinity kainate receptors. The vestibular nuclei neurones are endowed with all these types of glutamatergic receptors, which fits well with the fact that various afferents, including the primary vestibular afferents, most probably use glutamate or aspartate as a neurotransmitter. This article is aimed at summarising several past studies of our group and some more recent data obtained in the in vitro whole-brain preparation concerning the NMDA receptors of the central vestibular neurones. In that process, we will detail also many valuable studies of other groups that had been devoted to the same topic.     

Reticular afferents from vestibular nuclei

The purpose of the present study is to observe the electromyogram (EGM) manifestations of the lateral pterygoid muscle (LPM) in monkey during mouth opening and closing movements. The lateral pterygoid muscle of five healthy monkeys (macaques) was exposed by operation under general anesthsia and the electropolar needles were placed into the superior and inferior head of LPM respectively. The EMG manifestations of the superior and inferior head of LPM were recorded by O.T.E. Biomedica EMG Recorder during the natural condition and the movements of opening and closing mouth after complete recovery from anesthesia. It has been found that the two heads acted synergistically only in opening movement and no activity was noted in closing movement. This finding disagrees with the previous viewpoint that the function of the superior and inferior head of LPM is independent.     

Morphometric nerve fiber analysis and aging process of the human abducent nerve

BACKGROUND: Coronary artery disease (CAD) constitutes a considerable financial burden on society in Finland; it is the cause of death of approximately 7,500 men and 6,500 women annually in a population of 5 million. OBJECTIVES: The purpose of this study was to assess the changes in the quality of life (QOL) of patients with CAD treated by medication, percutaneous transluminal coronary angioplasty (PTCA), and coronary artery bypass surgery (CABS) during 1 year. METHOD: The study population consisted of 280 patients with CAD. One hundred patients had been referred to CABS and another 100 to PTCA, whereas 80 patients were on drug therapy. The patients assessed their health status and QOL in terms of functional capacity and aspects of distress using self-completed questionnaires with the Nottingham Health Profile (NHP) instrument before the operation and 6and 12 months afterwards. RESULTS: The QOL of the patients who had undergone CABS and PTCA was significantly better on the dimensions of energy, pain, and mobility 1 year after the intervention. In the medication group, the only improvement took place on the dimension of social isolation, whereas both energy and mobility deteriorated. CONCLUSIONS: The results on QOL obtained in this study support the notion that patients continue to have many problems even after medical treatment with a good outcome. The problems occur in different areas compared with the pretreatment situation as on the dimensions of social isolation and emotional reaction. The rehabilitation of CAD patients is therefore important because the new problems are manifested differently from those seen before the illness or the treatment. The patient's QOL and personal preference for a treatment modality should be important criteria in the choice of treatment.     

Polyamine changes in the vestibular nuclei of guinea pigs following labyrinthectomy

Vestibular compensation is a process of behavioral recovery from ocular, motor and postural disorders following unilateral damage to the vestibular end-organ. Although restoration of the normal resting discharge rate in the ipsilateral vestibular nuclei is important in compensation, the biochemical and molecular mechanisms mediating recovery are largely unknown. The ornithine decarboxylase polyamine pathway is activated in the nervous system following axotomy or denervation. The authors postulate that changes in polyamines mediate vestibular compensation. Within 150-micron brain stem coronal section micropunches analyzed by high performance liquid chromatography techniques, the polyamine spermidine was significantly increased in the ipsilateral lateral vestibular nucleus 8 hours following labyrinthectomy in the guinea pig model. Because naturally occurring polyamines modulate excitatory amino acid receptors (N-methyl-D-aspartate [NMDA]) which in turn mediate neurotransmission between primary afferents and second order vestibular neurons, stimulation of polyamine pathways following neural injury may play a critical role in compensation.     

Convergence of ampullar and macular inputs on vestibular nuclei unit of the rat

181 vestibular nucleus neurons were examined for their responsiveness to rotation about the vertical axis and static tilts in roll and pitch planes in the rat. 68 of these units were sensitive to rotation and tilts (canal-otolith cells). In other words, 41.0% of the neurons responded to rotation (68/166). There was no significant difference in percentage of canal-otolith cells in type I and II neurons, which were 48.6% and 37.0% respectively. Vertical axis rotation when the head was tilted produced a simultaneous stimulation of the canal and otoliths. Using this stimulus method, the bias effect was observed in 72.5% of the canal-otolith cells (29/40). Furthermore, since vertical axis rotation with the head tilted elicited vertical canal responses, the rate of ampullary convergence was estimated by analysing response profiles obtained such rotations. The results obtained in the rat were compared with those in other species.     

Role of platelet-activating factor in long-term potentiation of the rat medial vestibular nuclei

In rat brain stem slices, we investigated the role of platelet activating factor (PAF) in long-term potentiation (LTP) induced in the ventral part of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferent. The synaptosomal PAF receptor antagonist, BN-52021 was administered before and after HFS. BN-52021 did not modify the vestibular potentials under basal conditions, but it reduced the magnitude of potentiation induced by HFS, which completely developed after the drug wash-out. The same effect was obtained by using CV-62091, a more potent PAF antagonist at microsomal binding sites, but with concentrations higher than those of BN-52021. By contrast both BN-52021 and CV-6209 had no effect on the potentiation once induced. This demonstrates that PAF is involved in the induction but not in the maintenance of vestibular long-term effect through activation of synaptosomal PAF receptors. In addition, we analyzed the effect of the PAF analogue, 1-O-hexadecyl-2-O- (methylcarbamyl)-sn-glycero-3-phosphocoline (MC-PAF) and the inactive PAF metabolite, 1-O-hexadecyl-sn-glycero-3-phosphocoline (Lyso-PAF) on vestibular responses. Our results show that MC-PAF, but not Lyso-PAF induced potentiation. This potentiation was prevented by D,L-2-amino 5-phosphonopentanoic acid, suggesting an involvement of N-methyl-D-aspartate receptors. Furthermore, under BN-52021 and CV-6209, the MC-PAF potentiation was reduced or abolished. The dose-effect curve of MC-PAF showed a shift to the right greater under BN-52021 than under CV-6209, confirming the main dependence of MC-PAF potentiation on the activation of synaptosomal PAF receptors. Our results suggest that PAF can be released in the MVN after the activation of postsynaptic mechanisms triggering LTP, and it may act as a retrograde messenger which activates the presynaptic mechanisms facilitating synaptic plasticity.     

Rhinomanometric analysis of vestibular stenoses of the nose

The distinction of the resistance in the nasal vestibule (valve area) and cavity (turbinates, septum deviations, crest, spine) is important for the settlement of the operative course in nasally impaired patients. Collapsed valves, free floating polyps, spines, and other turbulence producing factors in the nose are characterized in active anterior rhinomanometry (AAR) as decreased ?percentage of flow increase? (deltaV150-300). This parameter allows no distinction between underlying anatomical factors. Other patients have increased resistance in the vestibule area that is static; rhinomanometry is unable to document these instances. The aim of this study was to investigate the influence of the vestibule dilator on nasal flow, and to determine if the diagnostic findings of AAR could be improved by the data obtained from the measurement with the dilator. METHODS: To prove the influence of the vestibule dilator on the nasal airflow, we determined typical rhinomanometric parameters in 20 nasally healthy and 40 nasally impaired persons with and without the dilator. For the measurements, we used a computer-aided rhinomanometer (Rhinodat K, Heinemann Medizintechnik, D-Hamburg). Tubular vestibule dilators were produced from silicon guide rails of tracheal tubes (Rüschelit, Fa. Rüsch, D-Kernen) and individually adapted to the patient's vestibule, ensuring dilation between the external ostium and the nasal isthmus. RESULTS: Active interior rhinomanometry revealed a significant effect of the vestibule dilator in repeated application (mean variation 3%). Total nasal flow showed a mean increase of about 48% with the dilator. In AAR, we found 5 patients with decreased deltaV150-300 below 25%. To demonstrate the presence of vestibule stenosis, we compared the changes of deltaV150-300 is AAR with and without dilator. In rhinomanometry with the dilator, deltaV150-300 of patients with vestibule stenosis showed physiological values. In these patients, mean difference of deltaV150-300 between conventional rhinomanometry and rhinomanometry with a vestibule dilator was significantly higher (47,2%) than observed in all other persons (3,8%). The static vestibule resistance in the total nasal resistance was obtained by calculating the difference between nasal flows with and without the dilator. CONCLUSIONS; Stenosis in the nasal vestibule could be proved and measured via active anterior rhinomanometry using a vestibule dilator. Data obtained from this method are helpful in functional assessment of nasally impaired patients, particularly to answer the question of whether the vestibule requires surgical treatment.     

Age-related changes in [3H]strychnine binding in the vestibular nuclei of rats

Glycine plays an important role as a neurotransmitter in the four vestibular nuclei (VN). The objective of this study was to determine if the levels of glycine-receptor binding in the VN change as a function of age. Quantitative receptor autoradiography was performed on brainstem sections from three age groups (3, 18 and 26 months) of Fischer 344 rats to assess binding in the VN. Glycine receptors were localized using [3H]strychnine binding. Strychnine binding declined monotonically with increasing age, such that the level of strychnine binding in each of the VN in the 28-month-old animals was approximately one-half that in the 3-month-olds. The age-related decrease in levels of strychnine binding suggest altered glycinergic function in the VN, which may in turn contribute to disturbances in equilibrium observed in the elderly.     

Morphometric video analysis of the engine-driven nickel-titanium Lightspeed instrument system

Two hundred and sixteen Lightspeed instruments were evaluated microscopically for the presence of corrosion, surface debris, and alloy defects. The instruments were assessed morphometrically for consistency of physical design and dimensions by measuring and analyzing eight parameters of the instrument pilot tips, heads, and shafts. Results from visual inspection showed that none of the instruments were corroded; 23 presented surface porosities, and 17 had sharp strips of alloy. Data obtained by morphometric analysis indicated the mean diameter of the head of only 7 of 18 sizes met the +/- 0.02 mm allowable tolerance set forth by the American Dental Association (ADA) Specification No. 28. Observation and video analysis indicated that instruments of the same size adhere to the same basic design, but that morphometric variations do exist. The visual and intersize analysis indicated that the Lightspeed is not an instrument of any one determined shape that changes only in diameter. Rather, it is a series of instruments that show gradual shifts in both size and shape as the instrument size increases. Lightspeed instruments are a new type of nickel-titanium endodontic instrument that cannot be evaluated using the standards proposed by the American National Standards Institute/ADA Specification No. 28 for files and reamers.     

Apoptosis of neurons in the vestibular nuclei of adult mice results from prolonged change in the external environment

Five patients with non-cytotoxic drug-induced agranulocytosis were treated with recombinant human granulocyte-colony-stimulating factor (rh-G-CSF). The drugs involved were dipyrone, captopril, clozapine and carbimazole. Bone marrow examination revealed a depleted granulopoiesis with normal erythro- and megakaryocytopoiesis. After discontinuation of the suspected drug, rh-G-CSF was administered daily at 5 microg/kg subcutaneously. The neutrophil counts were recovered between day 6 and 12 and patients were discharged from hospital shortly afterwards. Compared to data from the literature, the neutrophil recovery appeared to be faster than expected without the use of haematopoietic growth factors. In conclusion, rh-G-CSF at a standard dose of 5 microg/kg seems to be an effective treatment for drug-induced agranulocytosis.     

The variational anatomy of the external aperture of the human vestibular aqueduct

A study was undertaken to demonstrate the variational anatomy of the external aperture of the vestibular aqueduct in 90 human temporal bones obtained from 58 cadavers. Topographic landmarks of the posterior surface of the petrous bone are useful for general orientation and include the external aperture of the vestibular aqueduct, internal auditory meatus, sigmoid sinus, subarcuate fossa, superior petrosal sinus and cochlear canaliculus. We determined the mean distances from the external aperture of vestibular aqueduct to the above structures to be 10.98, 11.21, 9.42, 10.27 and 13.90 mm, respectively. Furthermore, the length of the external aperture of the vestibular aqueduct revealed significant differences between the right and left sides. The distances between the EAVA and certain anatomical structures on the posterior surface of the temporal bone should be taken into consideration during surgery. Knowing the variability of the position of the external aperture of the vestibular aqueduct may help surgeons avoid traumatizing, and thus producing inadvertent lesions to the hearing mechanism.     

Morphometric analysis of heparin coated versus standard intra-aortic balloons

The adverse effects of systemic heparin administration has led to the development of heparin coated devices. Intra-aortic balloons are frequently used in clinical settings in which complications of systemic heparin, especially bleeding, are feared. The current study evaluated the thromboresistance of heparin coated intra-aortic balloons. Six bovine calves were chosen for the experiment. In each animal, three intra-aortic balloons were inserted, and set to the automatic mode: two in the vena cava for 15 min and 45 min, respectively, and one in the aorta for 6 hr. There were nine standard and nine heparin coated intra-aortic balloons. At the end of the procedures, three samples of each intra-aortic balloon were analyzed with scanning electron microscopy for computed analysis of the balloon surface covered with fibrin and cells. The scanning electron microscopy analysis showed no deposit at any time interval on the heparin coated sample surfaces, whereas 3.6% +/- 9.2% (mean +/- SD) of the standard sample surfaces were covered with deposits at 15 min (p = 0.06), 14.8% +/- 24.3% at 45 min (p = 0.01), and 4.4% +/- 12.4% at 6 hr (p = 0.06). Strikingly, none of the 27 heparin coated samples showed any microscopic deposits, whereas 11 of the 27 standard samples did (p < 0.002). Heparin coated intra-aortic balloons appear to be a promising strategy, especially for patients with absolute or relative contraindications to systemic heparinization.     

Morphometric analysis of rat hepatocytes after total billary obstruction

Using light and electron microscopic morphometric techniques, the effects of 48 hr of extrahepatic biliary obstruction on hepatocyte structure were examined in the rat. Liver cells near the portal area were compared to those in the centrilobular regions of the hepatic lobule. Observations on the normal animals confirm earlier evidence of quantitative differences in the surface density of organelles in hepatocytes located within different regions of the lobule. A striking difference in the quantity of the Golgi complex in the two areas of the lobule was noted for the first time, with the portal cells containing a significantly greater quantity of this organelle than centrolobular hepatocytes. After 48 hr of total obstruction, most of the previously reported qualitative changes in the canalicular and pericanalicular regions were confirmed. Morphometric analysis at the light-microscopic level showed an increase in the number of cells and a decrease in cell size in those cells near the portal area were compared to those in the centrolobular regions of the helar level demonstrated a significant decrease in both rough and smooth surfaced endoplasmic reticulum in cells of both zones, a finding in marked contrast to the hypertrophy of smooth endoplasmic reticulum suggested by other investigators on the basis of qualitative assessments. There was also a striking decrease in the amount of the Golgi complex, limited to cells in the portal regions. In addition, in all zones a decrease in the volume density of mitochondria and lysosomes was noted, whereas the volume of microbodies was increased. It is suggested that this loss in total membrane material within the cell may be secondary to the degranulation and decrease in total surface area of rough surfaced endoplasmic reticulum, an organelle thought to be responsible in part for the synthesis of new cellular membranes. These observations suggest that present concepts concerning the pathogenesis of cholestatic liver disease require reappraisal.     

Morphometric analysis of the effect of chloroquine on rat foetal lung maturation

The penetration of ofloxacin into prostatic fluid, ejaculate and seminal fluid was measured by a high-pressure liquid chromatography (HPLC) method after intravenous infusion (60 min) of 400 mg in six healthy male volunteers. The median concentration of ofloxacin in prostatic fluid was about one-third and that in ejaculate and seminal fluid about twice that in corresponding plasma. The results of the study indicate good penetration of ofloxacin into prostatic fluid, ejaculate and seminal fluid. Ofloxacin should thus be of value for the treatment of chronic bacterial prostatitis and vesiculitis.     

Morphometric analysis of the extramacular retina from postmortem eyes with retinitis pigmentosa

Desmosomes are highly organized intercellular adhesive junctions that are particularly prominent in epidermis and other tissues experiencing mechanical stress. Desmoplakin, a constitutive component of the desmosomal plaque, is the most abundant protein present in such junctions and plays a critical role in linking the intermediate filament network to the plasma membrane in these tissues. Here we report the first mutation in the gene encoding desmoplakin. The identified mutation, resulting in a null allele and haploinsufficiency, was observed in genomic DNA from a kindred with the dominantly inherited skin disorder, striate palmoplantar keratoderma. Affected individuals had a linear pattern of skin thickening on the fingers and palms and circumscribed areas of skin thickening on the soles. Affected skin demonstrated loosening of intercellular connections, disruption of desmosome-keratin intermediate filament interactions and a proportion of rudimentary desmosomal structures. The disorder mapped to chromosome 6p21 with a maximum lod score of 10.67. The mutation was a heterozygous C-->T transition in exon 4 of the desmoplakin gene and predicted a premature termination codon in the N-terminal region of the peptide. This is the first reported mutation of desmo-plakin and also the first inherited skin disorder in which haploinsufficiency of a structural component has been implicated. It identifies dosage of desmoplakin as critical in maintaining epidermal integrity.     

Microwave irradiation influences on the state of human cell nuclei

Changes of electrokinetic properties of cell nuclei and the quantity of granules of heterochromatin located near the nuclear envelope in nuclei of human buccal epithelium cells were studied under the influence of electromagnetic fields in vitro. Irradiation of cells was realized by means of a semiconductor generator of millimeter radiation (wavelength 7.1 mm, frequency 42.2 GHz), the Yav-1 apparatus for extremely high frequency therapy. It was shown that irradiation of cells induced a decrease in electric charge of native human buccal epithelium cell nuclei and an increase in chromatin condensation in nuclei. The observed effects depend on irradiation dose and individual peculiarities of donors.     

DNA-dependent RNA-polymerase II from human placental nuclei

The procedure for isolation and purification of RNA polymerase II from human placenta nuclei is described. The sensitivity of the enzyme to alpha-amanitin, bivalent cations, ionic strength and glycerol concentration in vitro has been studied. Eleven subunits of the RNA polymerase II molecule have been identified by gel electrophoresis. An optimal RNA polymerase II assay mixture has been developed.