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Investigations on-board the biosatellite Cosmos-83.

The program of the 5 day flight of the biosatellite Cosmos-1514 (December 1983) envisaged experimental investigations the purpose of which was to ascertain the effect of short-term microgravity on the physiology, growth and development of various animal and plant species. The study of Rhesus-monkeys has shown in that they are an adequate model for exploring the mechanisms of physiological adaptation to weightlessness of the vestibular apparatus and the cardiovascular system. The rat experiment has demonstrated that mammalian embryos, at least during the last term of pregnancy, can develop in microgravity. This finding has been confirmed by fish studies. The experiment on germinating seeds and adult plants has given evidence that microgravity produces no effect on the metabolism of seedlings and on the flowering stage.

Adaptation, Physiological↗

Investigations onboard the biosatellite Cosmos-1667.

The program of the 7-day flight of the biosatellite Cosmos-1667 launched in July 1985 included experiments on two rhesus monkeys, ten Wistar SPF rats, ten newts, Drosophila flies, maize seedlings, lettuce sprouts, and unicellular organisms--Tetrahymena. The primate study demonstrated that transition to orbital flight was accompanied by a greater excitability of the vestibular apparatus and an increased linear blood flow velocity in the common carotid artery. The rat studies showed that atrophy of antigravity muscles and osteoporosis of limb bones developed even during short-term exposure to microgravity. The experiments on other living systems revealed no microgravity effects on the cell division rate, proliferative activity of cells of regenerating tissues and organs, energy metabolism of developing insects, structure or chemical composition of higher plant seedlings.

Adaptation, Physiological↗

Light microscopic analysis of the gravireceptor in Xenopus larvae developed in hypogravity.

The paper describes an investigation of the influence of gravity on the early differentiation of gravity receptors in Xenopus embryos and larvae. There is evidence that the expression of crystals in the saccus endolymphaticus was statistically greater when the embryos developed in near weightlessness (hypogravity) than on earth. The function of these crystals is unknown but they may contribute to the functioning of the vestibular apparatus.

Animals↗

Development of the otolith organs and semicircular canals in the Japanese red-bellied newt, Cynops pyrrhogaster.

The sequence in which the otoliths and semicircular canals and their associated sensory epithelia appear and develop in the newt are described. Three-dimensional reconstruction of serial sections through the otic vesicle of newt embryos from stages 31 through 58 demonstrate the first appearance, relative position and growth of the otoliths. A single otolith is first seen in stage 33 embryos (approximately 9 days old); this splits into separate utricular and saccular otoliths at stage 40 (13 days). The lateral semicircular canal is the first to appear, at stage 41 (14 days). The anterior and posterior canals appear approximately one week later and the vestibular apparatus is essentially fully formed at stage 58 (approximately 5 weeks). The data reported here will serve as ground-based controls for fertilized newt eggs flown on the International Microgravity Laboratory-2 Space Shuttle flight, to investigate the influence of microgravity on the development of the gravity-sensing organs.

Animals↗

Size and cell number of the utricle in kinetotically swimming fish: a parabolic aircraft flight study.

Humans taking part in parabolic aircraft flights (PAFs) may suffer from space motion sickness (SMS, a kinetosis). Since it has been repeatedly shown earlier that some fish of a given batch also reveal a kinetotic behavior during PAFs (especially so-called spinning movements and looping responses) and due to the homology of the vestibular apparatus among all vertebrates, fish can be used as model systems to investigate the origin of susceptibility to motion sickness. Therefore, we examined the utricular maculae (they are responsible for the internalization of gravity in teleosteans) of fish swimming kinetotically at microgravity in comparison with animals from the same batch who swam normally. On the histological level, it was found that the total number of both sensory and supporting cells of the utricular maculae did not differ between kinetotic animals as compared to normally swimming fish. Cell density (sensory and supporting cells/100 micrometers2), however, was reduced in kinetotic animals (p<0.0001), which seemed to be due to malformed epithelial cells (increase in cell size) of the kinetotic specimens. Susceptibility to kinetoses may therefore originate in malformed sensory epithelia.

Animals↗

Temporal bone histopathologic findings in partial trisomy 13 and partial trisomy 14.

OBJECTIVE: To describe temporal bone histopathology in an infant with partial trisomies of chromosomes 13 and 14. METHODS: Temporal bones were taken at autopsy from a 7-day-old neonate who has both partial trisomy 13 and partial trisomy 14. The right temporal bone was embedded in celloidin and sections were cut for microscopic examination. The left temporal bone was studied by microdissection. The middle ear was examined and the inner ear sensory organs dissected for study by light microscopy. RESULTS: The external auditory canal was stenotic in both ears. Remnants of mesenchymal tissue were present in the middle ear cavity. The middle ear ossicles were normal except that both stapes were malformed with a single crus and a small footplate. Both facial nerve canals were dehiscent in the region of the oval window. The cochlea was malformed bilaterally; a scala communis was present and the basilar membrane was abnormally short. No loss of sensory cells was observed in either cochlea. Blood vessels were found traversing scala vestibuli and there were cystic lesions in the stria vascularis and spiral ligament. In the middle cochlear turn, the bony wall of scala vestibuli and the osseous spiral lamina were covered by a substantial layer of connective tissue which appeared to be an extension of the spiral ligament. This is an unusual finding which, to the authors' knowledge, has not been previously reported. In the vestibular apparatus a wide communication was present between the saccule and utricle. CONCLUSIONS: As this study demonstrates, abnormalities of the external, middle, and inner ear may occur in cases of partial trisomy 13 and partial trisomy 14. Both temporal bone findings and clinical features in partial trisomy 13 and partial trisomy 14 to some degree overlap with those of trisomy 13, partial trisomy 13 and partial trisomy 14.

Chromosomes, Human, Pair 13↗

KCNQ potassium channels: physiology, pathophysiology, and pharmacology.

KCNQ genes encode a growing family of six transmembrane domains, single pore-loop, K(+) channel alpha-subunits that have a wide range of physiological correlates. KCNQ1 (KvLTQ1) is co-assembled with the product of the KCNE1 (minimal K(+)-channel protein) gene in the heart to form a cardiac-delayed rectifier-like K(+) current. Mutations in this channel can cause one form of inherited long QT syndrome (LQT1), as well as being associated with a form of deafness. KCNQ1 can also co-assemble with KCNE3, and may be the molecular correlate of the cyclic AMP-regulated K(+) current present in colonic crypt cells. KCNQ2 and KCNQ3 heteromultimers are thought to underlie the M-current; mutations in these genes may cause an inherited form of juvenile epilepsy. The KCNQ4 gene is thought to encode the molecular correlate of the I(K,n) in outer hair cells of the cochlea and I(K,L) in Type I hair cells of the vestibular apparatus, mutations in which lead to a form of inherited deafness. The recently identified KCNQ5 gene is expressed in brain and skeletal muscle, and can co-assemble with KCNQ3, suggesting it may also play a role in the M-current heterogeneity. This review will set this family of K(+) channels amongst the other known families. It will highlight the genes, physiology, pharmacology, and pathophysiology of this recently discovered, but important, family of K(+) channels.

Animals↗

Inner ear anomalies in two cases of trisomy 18.

Two cases of trisomy 18 in which temporal bone defects were limited to the inner ears are described. Several abnormalities were present that have not been described previously in this syndrome. The first case involved a 1-month-old female infant who died of congenital heart defects. Cochlear nerve fibers were absent on the left side, with near-normal innervation on the right. Although the organ of Corti was present bilaterally, some of the outer hair cells were deformed, having small rounded cell bodies unsupported by Deiters' cells. On the right, similar abnormal cells were found in the tunnel of Corti. Vestibular defects in this case included reduced nerve supply of the left saccular macula, cysts in the superior and posterior cristae, and absence of the utriculoendolymphatic valve. The second case involved a newborn male infant with multiple congenital anomalies. The major cochlear defect was a deformity of the stria vascularis. In the lower apical turn, the stria was adherent to Reissner's membrane and extended beneath it into scala media. Large capillaries, which ran freely suspended in scala vestibuli, entered the upper portion of the stria. Severe atresia of the lateral and posterior semicircular ducts was found in the vestibular apparatus.

Chromosomes, Human, 16-18↗

Vestibular decompensation in labyrinthectomized rats placed in weightlessness during parabolic flight.

The purpose of this study was to determine whether the absence of gravitational cues during weightlessness could alter the posture and static eye deviation of Earth compensated rats with peripheral vestibular lesions. The responses of bilaterally (BL) and unilaterally (UL) labyrinthectomized rats at a compensated stage (40-43 days after lesion) during parabolic flight were compared with those at an acute stage (2-7 h after lesion) on Earth. When free-floating in 0 g, UL animals showed the same postural pattern as during water immersion just after surgery. The most striking observation was a continuous roll body motion at about 4 Hz, and a skewed asymmetric posture. When restrained in 0 g, static eye deviation was also comparable to that observed at an acute stage. A return to a compensated posture and gaze was observed within a few seconds following the end of the weightlessness conditions. BL animals were less affected. These results suggest that vestibular compensation after unilateral lesion can be disrupted momentarily and is a fragile state during which the otolith system in the remaining vestibular apparatus presumably plays a continuous role.

Animals↗

Exploring dinosaur neuropaleobiology: viewpoint computed tomography scanning and analysis of an Allosaurus fragilis endocast.

The unique opportunity to examine an exceptionally well-preserved natural endocranial cast (endocast) from a carnivorous dinosaur of the late Jurassic period, Allosaurus fragilis, was afforded this neurobiologist. The endocast exhibits numerous surface features including the complete vestibular apparatus. Spiral computed tomography scanning revealed multiple internal features including putative blood vessels, connective tissue-like arrays, and a prominent symmetrical density consistent with the putative brain or its cast. The evidence suggests that this organism's neurobiology resembled closely that of modern crocodylian species and should be included for consideration when examining ideas of Allosaurus evolution, behavior, and eventual extinction.

Animals↗

Gentamicin ototoxicity in continuous ambulatory peritoneal dialysis.

A prospective study was undertaken of 10 chronic renal failure patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) complicated by repeated bouts of peritonitis treated with gentamicin. Each 10-day treatment course consisted of a 120 mg loading dose, followed by 16 mg in 21 of peritoneal dialysate, given four times a day. Serum gentamicin analysed by enzyme immunoassay showed a mean level of 5.2 micrograms/ml, (range 3.7 to 6.6 mg/ml) four hours after the loading dose. Similar levels, well within the therapeutic range, were maintained on the 3rd, 5th, 7th and 9th days of intraperitoneal gentamicin therapy, suggesting no accumulation of gentamicin in the serum. Pure tone audiometry, electronystagmography and clinical assessment were performed during each course of treatment. Although no evidence of ototoxicity was found during the first two courses of gentamicin, but disequilibrium and bobbing oscillopsia were present during the third and fourth courses of gentamicin. These findings could be explained by cumulative injury to the vestibular apparatus caused by repeated therapeutic insults.

Adult↗

Neuroanatomy of flying reptiles and implications for flight, posture and behaviour.

Comparison of birds and pterosaurs, the two archosaurian flyers, sheds light on adaptation to an aerial lifestyle. The neurological basis of control holds particular interest in that flight demands on sensory integration, equilibrium, and muscular coordination are acute. Here we compare the brain and vestibular apparatus in two pterosaurs based on high-resolution computed tomographic (CT) scans from which we constructed digital endocasts. Although general neural organization resembles birds, pterosaurs had smaller brains relative to body mass than do birds. This difference probably has more to do with phylogeny than flight, in that birds evolved from nonavian theropods that had already established trends for greater encephalization. Orientation of the osseous labyrinth relative to the long axis of the skull was different in these two pterosaur species, suggesting very different head postures and reflecting differing behaviours. Their enlarged semicircular canals reflect a highly refined organ of equilibrium, which is concordant with pterosaurs being visually based, aerial predators. Their enormous cerebellar floccular lobes may suggest neural integration of extensive sensory information from the wing, further enhancing eye- and neck-based reflex mechanisms for stabilizing gaze.

Animals↗

Training and aging modulate the loss-of-balance phenotype observed in a new ENU-induced allele of Otopetrin1.

BACKGROUND INFORMATION: The sensing of head movement in mammals depends upon the vestibular endorgan of the inner ear, a complex structure made up of the semicircular canals and otoliths. Due to the similarity between the human and mouse vestibular apparatus, the analysis of mutant mouse is a valuable strategy aiming to identify genes involved in the control of balance and movement. RESULTS: In the course of a genome-wide chemical-mutagenesis programme, we isolated a recessive mutation, named ied (inner ear defect), which induced a severe loss-of-balance. A detailed phenotypic analysis of the mutant mice demonstrates that the balance impairment does not affect the motor activity and can be rescued, in part, by training, despite a complete agenesis of otoconia in the utricule and the saccule of the inner ear. Molecular characterization of the ied mutation revealed a transversion that affects the splicing of the second exon of the Otopetrin1 gene located on mouse chromosome 5. The consequence of such a mutation leads to a disruption of the transcription of the gene. CONCLUSIONS: The identification of the ied knock-down allele strengthens the role of the Otopetrin1 in the sensing of balance. Moreover, the rescue of the ied mutant phenotype in specific behavioural tasks confirmed that other sensory inputs or neural plasticity can compensate, to some extent, for the loss-of-balance. In the future, the ied mutant mice might be helpful to study the genetic control of the compensation strategies developed by organisms to counteract balance defects.

Acoustic Maculae↗

A systematic approach to the management of postoperative nausea and vomiting.

Postoperative nausea and vomiting (PONV), a common complication after anesthesia and surgery, often results in delayed discharge with the patient's unpleasant symptoms continuing at home. To effectively prevent and treat PONV, it is important to understand the factors implicated in PONV, the mechanisms of PONV, the pharmacology of the antiemetic agents, and the nonpharmacologic measures that have been shown to be effective. The cause of PONV is likely to be multifactorial, with important predictors being female gender, history of PONV, and history of motion sickness. The vomiting center can be triggered by activation of dopamine, serotonin (type 3), histamine (type 1), and muscarinic cholingergic receptors in the chemoreceptor trigger zone and the nucleus tractus solitarus, as well as acetylcholine receptors in the vestibular apparatus, vagal afferents from the periphery, and the endocrine environment. Antiemetic agents such as the serotonin antagonists (eg, ondansetron, dolasetron), droperidol, antihistamines (eg, diphenhydramine, dimenhydrinate), and promethazine can prevent and treat PONV effectively. Transdermal scopolamine and dexamethasone have a role in the prevention of PONV, particularly for certain high-risk patients. Nonpharmacologic measures and alternative treatments such as hydration, maintaining blood pressure, acupressure techniques, trancutaneous acupoint stimulation, and isopropyl alcohol must not be overlooked. Finally, an evidence-based algorithm for the prevention and treatment of PONV in adults is presented.

Algorithms↗

Cholinergic influence on vestibular stimulation-induced locus coeruleus inhibition in rats.

In our previous study, caloric stimulation (CS) of the vestibular apparatus inhibited noradrenergic neuronal activity in the locus coeruleus (LC) in urethane-anaesthetized rats. Therefore, the inhibition of LC noradrenergic neurons is involved in vestibulo-autonomic responses. Since motion sickness can be cured by scopolamine, cholinergic neuron system may also be involved in vestibulo-autonomic responses. The present study examined the effects of intracerebroventricular injection of ethylcholine mustard aziridinium ion (AF64A), a presynaptic cholinergic neurotoxin, on CS-induced LC inhibition. In AF64A-treated rats, the CS-induced LC inhibition was less pronounced than in normal rats. In a subsequent series of experiments, the intravenous injection of scopolamine blocked the CS-induced LC inhibition. These findings suggest that central cholinergic neurons are associated with noradrenergic neuronal inhibition during the vestibulo-autonomic reflex.

Animals↗