Middle ear fluid cytokine and inflammatory cell kinetics in the chinchilla otitis media model.
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Streptococcus pneumoniae is the most frequent microbe causing middle ear infection. The pathophysiology of pneumococcal otitis media has been characterized by measurement of local inflammatory mediators such as inflammatory cells, lysozyme, oxidative metabolic products, and inflammatory cytokines. The role of cytokines in bacterial infection has been elucidated with animal models, and interleukin (IL)-1beta, IL-6, and IL-8 and tumor necrosis factor alpha (TNF-alpha) are recognized as being important local mediators in acute inflammation. We characterized middle ear inflammatory responses in the chinchilla otitis media model after injecting a very small number of viable pneumococci into the middle ear, similar to the natural course of infection. Middle ear fluid (MEF) concentrations of IL-1beta, IL-6, IL-8, and TNF-alpha were measured by using anti-human cytokine enzyme-linked immunosorbent assay reagents. IL-1beta showed the earliest peak, at 6 h after inoculation, whereas IL-6, IL-8, and TNF-alpha concentrations were increasing 72 h after pneumococcal inoculation. IL-6, IL-8, and TNF-alpha but not IL-1beta concentrations correlated significantly with total inflammatory cell numbers in MEF, and all four cytokines correlated significantly with MEF neutrophil concentration. Several intercytokine correlations were significant. Cytokines, therefore, participate in the early middle ear inflammatory response to S. pneumoniae. (+info)
Some observations on the ultrastructure of the adenohypophysis of the Plains viscacha (Lagostomus maximus).
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The ultrastructural appearance of the pars distalis of the Plains viscacha is described. Of particular interest are the prolactin cells and stellate cells and the intercellular cysts or channels which may be part of a transport system for hormones. (+info)
Protection against development of otitis media induced by nontypeable Haemophilus influenzae by both active and passive immunization in a chinchilla model of virus-bacterium superinfection.
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Three separate studies, two involving active-immunization regimens and one involving a passive-transfer protocol, were conducted to initially screen and ultimately more fully assess several nontypeable Haemophilus influenzae outer membrane proteins or their derivatives for their relative protective efficacy in chinchilla models of otitis media. Initial screening of these antigens (P5-fimbrin, lipoprotein D, and P6), delivered singly or in combination with either Freund's adjuvant or alum, indicated that augmented bacterial clearance from the nasopharynx, the middle ears, or both anatomical sites could be induced by parenteral immunization with P5-fimbrin combined with lipoprotein D, lipoprotein D alone, or the synthetic chimeric peptide LB1 (derived from P5-fimbrin), respectively. Data from a second study, wherein chinchillas were immunized with LB1 or lipoprotein D, each delivered with alum, again indicated that clearance of nontypeable H. influenzae could be augmented by immunization with either of these immunogens; however, when this adjuvant was used, both antibody titers in serum and efficacy were reduced. A third study was performed to investigate passive delivery of antisera directed against either LB1, lipoprotein D, nonacylated lipoprotein D, or a unique recombinant peptide designated LPD-LB1(f)2,1,3. The last three antiserum pools were generated by using the combined adjuvant of alum plus monophosphoryl lipid A. Passive transfer of sera specific for LB1 or LPD-LB1(f)2,1,3 to adenovirus-compromised chinchillas, prior to intranasal challenge with nontypeable H. influenzae, significantly reduced the severity of signs and incidence of otitis media which developed (P +info)
Blood-borne, albumin-bound prostaglandin E2 may be involved in fever.
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Although the involvement of blood-borne PGE2 in fever has been hypothesized by several authors and has substantial experimental support, the current literature often rejects this hypothesis because several attempts to induce fever by a peripheral PGE2 failed. However, it is usually ignored that the amphipathic molecules of PGE2 are readily self-associating and that such an aggregation could have prevented the peripherally administered PGE2 (free form) from expressing its pyrogenic activity, thus leading to false negative results. To ensure disaggregation of PGE2, we prepared its complex within a carrier protein, human serum albumin (HSA). HSA was purified with activated charcoal and polymixin B-polyacrylamide gel and incubated with PGE2 for 1 h at 37 degrees C. Adult Chinchilla rabbits were injected intravenously with PGE2-HSA complex in either the higher (75 micrograms/kg PGE2:30 mg/kg HSA) or the lower (15 micrograms/kg:6 mg/kg) dose, and the rectal temperature (Tr) was measured. In the controls, either the ligand alone or the carrier alone was administered. At the higher dose, neither free PGE2 nor albumin alone was pyrogenic, whereas the PGE2-HSA complex produced a fever characterized by a short latency (<10 min) and a maximal Tr rise of 0.7 +/- 0.2 degrees C. At the lower dose, none of the substances affected the Tr. This study demonstrates a marked pyrogenic activity of the intravenous PGE2-HSA, but not of the free PGE2. Administration of a preformed complex may be more physiologically relevant than administration of the free ligand because of the ligand's disaggregation, protection from enzymatic degradation, and facilitated delivery to targets. Our study supports the hypothesis that peripheral PGE2 is involved in fever genesis. (+info)
Responses of cochlear nucleus units in the chinchilla to iterated rippled noises: analysis of neural autocorrelograms.
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Temporal encoding of stimulus features related to the pitch of iterated rippled noises was studied for single units in the chinchilla cochlear nucleus. Unlike other periodic complex sounds that produce pitch, iterated rippled noises have neither periodic waveforms nor highly modulated envelopes. Infinitely iterated rippled noise (IIRN) is generated when wideband noise (WBN) is delayed (tau), attenuated, and then added to (+) or subtracted from (-) the undelayed WBN through positive feedback. The pitch of IIRN[+, tau, -1 dB] is at 1/tau, whereas the pitch of IIRN[-, tau, -1 dB] is at 1/2tau. Temporal responses of cochlear nucleus units were measured using neural autocorrelograms. Synchronous responses as shown by peaks in neural autocorrelograms that occur at time lags corresponding to the IIRN tau can be observed for both primarylike and chopper unit types. Comparison of the neural autocorrelograms in response to IIRN[+, tau, -1 dB] and IIRN[-, tau, -1 dB] indicates that the temporal discharge of primarylike units reflects the stimulus waveform fine structure, whereas the temporal discharge patterns of chopper units reflect the stimulus envelope. The pitch of IIRN[+/-, tau, -1 dB] can be accounted for by the temporal discharge patterns of primarylike units but not by the temporal discharge of chopper units. To quantify the temporal responses, the height of the peak in the neural autocorrelogram at a given time lag was measured as normalized rate. Although it is well documented that chopper units give larger synchronous responses than primarylike units to the fundamental frequency of periodic complex stimuli, the largest normalized rates in response to IIRN[+, tau, -1 dB] were obtained for primarylike units, not chopper units. The results suggest that if temporal encoding is important in pitch processing, then primarylike units are likely to be an important cochlear nucleus subsystem that carries the pitch-related information to higher auditory centers. (+info)
Peripherin immunoreactivity labels small diameter vestibular 'bouton' afferents in rodents.
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Recent morphophysiological studies have described three different subpopulations of vestibular afferents. The purpose of this study was to determine whether peripherin, a 56-kDa type III intermediate filament protein present in small sensory neurons in dorsal root ganglion and spiral ganglion cells, would also label thin vestibular afferents. Peripherin immunohistochemistry was done on vestibular sensory organs (cristae ampullares, utriculi and sacculi) of chinchillas, rats, and mice. In these sensory organs, immunoreactivity was confined to the extrastriolar region of the utriculus and the peripheral region of the crista. The labelled terminals were all boutons, except for an occasional calyx. In vestibular ganglia, immunoreactivity was restricted to small vestibular ganglion cells with thin axons. The immunoreactive central axons of vestibular ganglion cells form narrow bundles as they pass through the caudal spinal trigeminal tract. As they exit this tract, several bundles coalesce to form a single, narrow bundle passing caudally through the ventral part of the lateral vestibular nucleus. Finally, we conclude that all labelled axons and terminals were vestibular afferents rather than efferents, as no immunoreactivity in the vestibular efferent nucleus of the brainstem was observed. (+info)
High-frequency dynamics of regularly discharging canal afferents provide a linear signal for angular vestibuloocular reflexes.
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Regularly discharging vestibular-nerve afferents innervating the semicircular canals were recorded extracellularly in anesthetized chinchillas undergoing high-frequency, high-velocity sinusoidal rotations. In the range from 2 to 20 Hz, with peak velocities of 151 degrees/s at 6 Hz and 52 degrees/s at 20 Hz, 67/70 (96%) maintained modulated discharge throughout the sinusoidal stimulus cycle without inhibitory cutoff or excitatory saturation. These afferents showed little harmonic distortion, no dependence of sensitivity on peak amplitude of stimulation, and no measurable half-cycle asymmetry. A transfer function fitting the data predicts no change in sensitivity (gain) of regularly discharging afferents over the frequencies tested but shows a phase lead with regard to head velocity increasing from 0 degrees at 2 Hz to 30 degrees at 20 Hz. These results indicate that regularly discharging afferents provide a plausible signal to drive the angular vestibuloocular reflex (VOR) even during high-frequency head motion but are not a likely source for nonlinearities present in the VOR. (+info)
Evaluation of the virulence of a Streptococcus pneumoniae neuraminidase-deficient mutant in nasopharyngeal colonization and development of otitis media in the chinchilla model.
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Considerable evidence has implicated Streptococcus pneumoniae neuraminidase in the pathogenesis of otitis media (OM); however, its exact role has not been conclusively established. Recently, an S. pneumoniae neuraminidase-deficient mutant, DeltaNA1, has been constructed by insertion-duplication mutagenesis of the nanA gene of S. pneumoniae strain D39. The relative ability of DeltaNA1 and the D39 parent strain to colonize the nasopharynx and to induce OM subsequent to intranasal inoculation and to survive in the middle ear cleft after direct challenge of the middle ear were evaluated in the chinchilla model. Nasopharyngeal colonization data indicate a significant difference in the ability of the DeltaNA1 mutant to colonize as well as to persist in the nasopharynx. The neuraminidase-deficient mutant was eliminated from the nasopharynx 2 weeks earlier than the D39 parent strain. Both the parent and the mutant exhibited similar virulence levels and kinetics during the first week after direct inoculation of the middle ear. The DeltaNA1 neuraminidase-deficient mutant, however, was then completely eliminated from the middle ear by day 10 postchallenge, 11 days before the D39 parent strain. Data from this study indicate that products of the nanA gene have an impact on the ability of S. pneumoniae to colonize and persist in the nasopharynx as well as the middle ear. (+info)