bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin-2 Affects Cochlear Function Gradually but Reversibly
Authors: Kubo Takeshi , Anniko Matti , Stenqvist Monika , Hsu Wey-Jim 
Published: April 2003

Interleukin-2 (IL-2), one of the chemical mediators produced by helper T cells, activates its target cells via its receptor and induces inflammatory reactions indirectly. In this study, IL-2 was instilled into the round window niche of rats and the electrophysiological effects of inflammation on the inner ear were evaluated by a frequency-specific auditory brainstem response (ABR) technique. ABR threshold curves and intensity-latency (I-L) curves were investigated. In most cases, moderate sensorineural hearing loss (SNHL) was observed in the high-frequency areas (16–31.5 kHz). In the time course investigation of I-L curves, the responses of SNHL type appeared only 1 day after instillation (day 1) gradually becoming more prominent, to become most pronounced on days 5–7. The electrophysiological impairment was reversible within 2 weeks. Differing degrees of responsiveness of effusion production were observed following the instillation of IL-2, varying from pronounced middle ear effusion causing rather severe mixed hearing loss, to complete lack of effusion. Inflammation induced by IL-2 affects cochlear function gradually but reversibly.
Effect of Acoustic Trauma on Cytochrome Oxidase Activity in Stria vascularis
Authors: Hsu Chuan-Jen , Liu Tien-Chen , Lin Kai-Nan 
Published: April 2003

The present study was undertaken to determine the role of metabolic disturbance in noise-induced hearing loss by histochemical studies of cytochrome oxidase activity. Adult normal albino guinea pigs were used. The experimental animals were exposed to broad-band noise at 105 dB SPL for 24 h. The control animals were not exposed to the noise. The thresholds of the auditory brainstem response (ABR) of all guinea pigs were measured 3 times: before noise exposure, 1 day and 1 month later. The difference between the ABR thresholds before and after noise exposure was statistically significant. Vibratome sections of decalcified cochleae of the noise-exposed (n = 8) and control groups (n = 4) were incubated with Spector’s medium and embedded with Epon. Thin sections (2 µm) and ultrathin sections (100 nm) were cut to observe cytochrome oxidase activity in the stria vascularis under light and electron microscopes, respectively. A decreased activity of cytochrome oxidase was consistently shown in the normal-appearing stria vascularis of most noise-exposed ears. Acoustic trauma has an adverse effect on cytochrome oxidase activity in the stria vascularis as well as on hearing. A decrease in the activity of cytochrome oxidase implicates that metabolic damage may play a role in noise-induced hearing loss.
Free Radicals in the Guinea Pig Inner Ear following Gentamicin Exposure
Authors: Takumida Masaya , Popa Raul , Anniko Matti 
Published: April 2003

The purpose of this study was to investigate the occurrence of free radicals, nitric oxide (NO), superoxide (O<sup>–</sup><sub>2</sub>) and peroxynitrite, in the inner ear of the guinea pig following intratympanic injection with 5 mg of gentamicin (GM). Forty-eight hours after GM injection, varying degrees of degeneration of the inner ear were observed. Immunohistochemical study revealed immunoreactivity to NO synthase II (which generates NO) and to xanthine oxidase (which generates O<sup>–</sup><sub>2</sub>) in both the vestibular organ and the organ of Corti. Immunohistochemical investigation, using a specific antinitrotyrosine antibody, also showed intense staining, suggesting formation of peroxynitrite in the inner ear through the reaction of NO with O<sup>–</sup><sub>2</sub>. Scanning electron-microscopic study showed that the ototoxic effects could be blocked with N-nitro-L-arginine methylester, a competitive inhibitor of NO synthase, with superoxide dismutase, an O<sup>–</sup><sub>2</sub> scavenger, and with ebselen, a scavenger of peroxynitrite. On the basis of these findings, it can be concluded that NO together with O<sup>–</sup><sub>2</sub>, which form more reactive peroxynitrite, play an important role in GM ototoxicity in the guinea pig.
Perilymphatic and Endolymphatic Pressure in the Normal Guinea Pig
Authors: Warmerdam T.J. , Schröder F.H.H.J. , Wit H.P. , Albers F.W.J. 
Published: April 2003

Perilymphatic and endolymphatic pressures were measured consecutively in the normal guinea pig using a WPI 900A micropressure system. The mean (n = 10) perilymphatic and endolymphatic pressures were 2.26 and 2.31 cm H<sub>2</sub>O, respectively. There was no statistically significant difference between the pressures of the endolymphatic and perilymphatic compartments. The measured values were within the range of pressures found in the literature.
Intraoperative Mitomycin C in Endolymphatic Sac Surgery for Ménière’s Disease: A Pilot Study
Authors: Yazawa Yoshiro , Suzuki Mikio , Kitano Hiroya , Kitajima Kazutomo 
Published: April 2003

The long-term results of endolymphatic sac (ES) shunt surgery in Ménière’s disease have been reported to be unsatisfactory compared to the short-term results, probably because of fibrosis and/or reclosure of the incised ES. To solve this problem, we tried to apply mitomycin C (MMC) intraoperatively to the incised ES as used in trabeculectomy for glaucoma. MMC has an antiproliferative effect as well as an antineoplastic effect. Thus, it is expected that MMC would have a benefit to prevent rapid fibrosis and/or reclosure of the ES. MMC did not show any ototoxicity in our animal study and we started a clinical trial after being approved by the Ethics Committee for Human Research at our university. Fourteen patients with Ménière’s disease underwent ES mastoid shunt surgery with intraoperative application of MMC and they were followed up more than 6 months. No patients experienced vertigo, although some complained of slight dizziness. Five patients out of 14 showed remarkable hearing improvement by more than 10 dB, accompanied with decrease of tinnitus.
A Possible Case of Saccular Endolymphatic Hydrops
Authors: Seo Toru , Yoshida Keiko , Shibano Akiko , Sakagami Masafumi 
Published: April 2003

The vestibular-evoked myogenic potential (VEMP) is expected to be one of the examinations for saccular function. We report a case of dysequilibrium possibly due to a saccular disorder. A 27-year-old female came to our clinic complaining of severe recurrent dysequilibrium spells for few hours on September 21, 1998. The first attack was only vertigo with bilateral tinnitus for 8 days before. She did not show possible vestibular findings on a routine vestibular test. An electrochochleogram showed the dominant negative summating potential (SP) on both sides, and the furosemide test showed negative findings on both sides. A VEMP test indicated a low amplitude in the right ear, which improved to the normal response after furosemide injection. The amplitude was increased by furosemide administration even in the left ear. These findings suggested bilateral endolymphatic hydrops in the cochlea and saccule especially on the right side. The VEMP test may reveal saccular hydrops, which differs from the conventional Ménière type vertigo.
Ultrastructural Evidence for Protection of the Outer Hair Cells of the Inner Ear during Intense Noise Exposure by Application of the Organic Calcium Channel Blocker Diltiazem
Authors: Heinrich Ulf-Rüdiger , Maurer Jan , Mann Wolf 
Published: April 2003

Outer hair cells could be protected during intense noise exposure by the application of the calcium channel blocker diltiazem given before and after noise treatment. After various experimental approaches, the ultrastructural morphology was analysed for the different animal populations in the basal part of the second turn of the cochlea, which was the most destroyed area after an acute noise trauma caused by a gun shot (sound pressure at the ear drum 156 dB, frequency maximum between 4 and 6 kHz). Compared to untreated control specimens (experimental animal group I), the outer hair cells in the basal part of the second turn of the cochlea were mostly destroyed without any diltiazem application but after intense noise exposure (group II) or when the calcium channel blocker was given only before (group III) or only after an intense noise exposure (group IV). Only cellular debris of these receptor cells could be identified within this region of the cochlea at the electron-microscopic level. After diltiazem application before and after the intensive noise exposure (group V), the general morphology of the tissue was much better conserved and almost no destroyed outer hair cells were found. But nevertheless, the electron-microscopic analysis revealed that the cellular fine structure was altered. Compared to untreated control specimens, small invaginations were sometimes seen in the basolateral membranes of outer hair cells, and also the cuticular structures of the Deiters cells forming the lamina reticularis bulged into the outer hair cells. To get more information about possible physiological alterations, the amounts of precipitable calcium within the outer hair cells were determined by an image-processing system for the five different populations (groups I–V). The values obtained were compared to the calcium content in specimens which had received diltiazem without any additional noise exposure (group VI) and with an animal population which was exposed to a pure tone for 5 min at 90 dB (group VII). The results are discussed in respect of outer hair cell protection preventing morphological damage and/or physiological alterations.
Real-Ear to Coupler Difference in Patients with Ear Drum Perforation
Authors: Liu Tien-Chen , Lin Kai-Nan 
Published: April 2003

The aim of this study is to investigate the effects of ear drum perforation on real-ear to coupler difference (RECD) in adults. RECD was measured using a probe tube microphone system in 22 patients with ear drum perforations. Twenty-two normal subjects served as controls. For normal subjects, RECD was in good agreement with the values reported in the literature. For the perforated ears, the RECD was up to 8 dB smaller in the frequency range from 0.5 to 1 kHz. There was no significant difference at frequencies below 0.25 kHz and above 1 kHz. A much larger intersubject variability was found in the experimental group. The mean intersubject standard deviation was 4.4 dB in the experimental group as contrasted with 2.2 dB in the control group. Neither the equivalent ear canal volume nor the perforation size appeared to be correlated with the degree of RECD reduction over lower frequencies. These results strongly suggest the need for individual RECD measurements, rather than using the average normal RECD, to appropriately compensate for the reduced transmission of lower-frequency sounds in fitting hearing aids for patients with ear drum perforations.
The Effects of Chronic Electrical Stimulation on Laryngeal Muscle Physiology and Histochemistry
Authors: Zealear David L. , Billante Cheryl R. , Chongkolwatana Cheerasook , Rho Young S. , Hamdan Abdul-Latif , Herzon Garrett D. 
Published: April 2003

The present study examined the effects of functional neuromuscular stimulation (FNS) on posterior cricoarytenoid (PCA) muscle physiology and histochemistry. In 4 canines, 10 cm of the recurrent laryngeal nerve was resected. A patch electrode array was implanted for PCA stimulation. FNS was applied to 2 canines for a period of 4 weeks with 2 additional animals serving as nonstimulated controls. Results indicated that FNS increased PCA muscle contractility over the period of intervention but had no effect on contraction speed. FNS also protected the muscle from atrophy by preventing muscle weight loss and type 2 fiber deterioration. Finally, it rescued muscle fibers from ensuing fibrosis.
Intratympanic and Systemic Dexamethasone for Ménière’s Disease
Authors: Hirvonen T.P. , Peltomaa M. , Ylikoski J. 
Published: April 2003

Intratympanic and systemic dexamethasone treatment of Ménière’s disease (MD) was evaluated in a prospective study. Seventeen patients (6 men and 11 women) with MD (5 right-sided, 11 left-sided and 1 bilateral) were treated with three 0.2- to 0.4-ml injections of intratympanic dexamethasone hyaluronate (16 mg/ml) during a week and with an initial intramuscular dexamethasone injection of 15 mg. Most of patients were in stage 3, and the mean duration of MD was 5.3 years. Pure-tone and speech audiometry and the symptom scale of the patients were followed up for 1 year after the treatment. Symptoms of aural fullness, hearing loss, tinnitus and vertigo did not improve significantly. However, sufficient control of vertigo was achieved in 76% of the patients. In conclusion, no definite treatment effect has yet been shown for intratympanic and systemic dexamethasone treatment. Therefore, the clinical use of dexamethasone in MD needs further investigation.
Immunoreactivity of Adventitial Matrix Fibrils of Normal and Aneurysmal Abdominal Aorta with Antibodies against Vitronectin and Fibrinogen
Authors: Hirose Hitoshi , Ozsvath Kathleen J. , Xia Shichao , Gaetz Harold P. , Tilson M. David 
Published: April 2003

<b>Purpose:</b> We have reported that immunoglobulin G (IgG) harvested from specimens of aneurysmal abdominal aorta (AAA) is immunoreactive with a fibrillar component of the matrix of the aortic adventitia. In further studies we have reported the partial amino acid sequence of a 40-kDa protein, purified from the adventitia of the human aorta, which we have called aortic aneurysm antigenic protein-40 kDa (AAAP-40). AAAP-40 has homologies with bovine microfibril-associated glycoprotein-36 kDa (MAGP-36). Both AAAP-40 and MAGP-36 have homologies to fibrinogen beta (FB-b) and vitronectin (VN). The purposes of the present experiments were (1) to determine whether antibodies against VN and fibrinogen are immunoreactive with elements of the normal and/or aneurysmal aortic wall, and (2) to determine whether these antibodies are immunoreactive with soluble extracts of aortic proteins. <b>Methods:</b> Paraffin-embedded tissue sections of normal and aneurysmal aorta were probed with polyclonal rabbit antihuman VN and antihuman FB-b antibodies. Immunoblots of soluble aortic proteins were evaluated with the same antibodies. Histochemical preparations with Gomori’s aldehyde fuchsin and elastin-von-Gieson solutions were also performed. <b>Results:</b> Anti-VN and FB-b antibodies reacted with matrix fibrils in the aortic adventitia in both normal and aneurysmal specimens, with a distribution that resembles the appearance of fibrils that are stained by Gomori’s reaction. By comparison to normal adventitial fibrils, fibrils in the specimens from AAA appeared fragmented, coiled, and frayed. Antibodies against VN and FB-b were immunoreactive in immunoblots with a soluble aortic protein of molecular weight ∼40 kDa, consistent with the migration of AAAP-40. <b>Conclusions:</b> There appear to be immunodeterminants in AAAP-40 that are recognized by polyclonal antibodies against VN and FB-b.
Divergent Selection for Pentobarbital-Induced Sedation Times in Mice
Authors: Stino Farid K.R. , Samaan Saber S. , Kolta Malak G. , Mizinga Kemmy M. , Soliman Karam F.A. 
Published: April 2003

Divergent selection for pentobarbital sedation-time response was practiced in mice for 9 generations. At the end of 9 generations of selection, the long-sedation-time line (LST) slept an average of 433 min; the short sedation time line (SST) slept an average of 29 min. The control line (C) slept an average of 71 min. These differences represent an almost 15-fold increase in sedation time for the LST compared to the SST line and a 6-fold increase compared to the C line. The SST line slept about 40% less than the C line after 9 generations of selection (measured in tenth generation progeny). Analysis of selection differentials and realized heritabilities indicated that selection response did not diminish after 9 generations of selection. Realized heritabilities for sedation time ranged from 0.43 to 0.83 for the LST line and from 0.55 to 0.81 for the SST line. Realized heritabilities did not decrease in magnitude due to selection progress, indicating that more progress can still be achieved. Comparing corrected (for environmental factors) to uncorrected heritabilities showed the importance of including a control line in selection experiments. Crossing of lines to study gene action responsible for this trait revealed that this trait was controlled by a number of genes with additive gene action without dominance, overdominance, epistasis, or maternal effects.
Physiological Effects of Macrocycle 1 on the Rabbit Corpus cavernosum
Authors: Liu Shih-Ping , Hass Martha A. , Horan Patrick , Levin Robert M. 
Published: April 2003

When the penis is in the flaccid state, the corpus cavernosum smooth muscle is under adrenergic control in order to maintain the sinusoids in a contracted condition (primarily via α-adrenergic stimulation). Penile erection is mediated by relaxation of corporal smooth muscle through a variety of direct and indirect mechanisms. Pharmacological agents that either inhibit α-adrenergic transmission or facilitate corporal smooth muscle relaxation will be beneficial for penile erection. Preliminary studies on macrocycle 1, a novel bioactive agent, demonstrated that this compound inhibits receptor-stimulated contraction without significantly altering field-stimulated contraction. The current study was designed to determine the physiological effects of macrocycle 1 on the response of the rabbit corpus cavernosum to various forms of stimulation. Sexually mature male New Zealand White rabbits were used in this study. The corpus cavernosum was dissected sharply from the removed penis and two longitudinal strips were prepared for isometric tension studies. Each strip was prestimulated with 200 µmol/l phenylephrine to produce a maximal contraction. The influences of macrocycle 1 (15.6, 62.5, 250, 1,000 µmol/l) on both the contractile response to phenylephrine and the relaxant effects of field stimulation, carbachol, ATP and nitroprusside were determined. The results demonstrated that although basal tension was not altered, the contractile response to phenylephrine was decreased by 5, 18, 47 and 57%, respectively, by the different concentrations of macrocycle 1. The degree of relaxation induced by field stimulation of various frequencies was significantly enhanced by macrocycle 1 in a concentration-dependent manner. Similarly, the degrees of relaxation induced by bethanechol, ATP and nitroprusside were all significantly enhanced in a concentration-dependent manner. The conclusion from this study is that macrocycle 1 significantly inhibits phenylephrine-stimulated contraction and significantly enhances field-stimulated and pharmacologically induced relaxation. Although the mechanisms of action are not clear, its physiological effects on the rabbit corpus cavernosum implicate a potential for the treatment of erectile dysfunction.
Antiprogestin-Mediated Inactivation of Cytochrome P450 3A4
Authors: Jang Graham R. , Benet Leslie Z. 
Published: April 2003

Based on previous observations of very short periods of linearity for antiprogestin metabolite formation and the presence of a common tertiary amine moiety in each compound as the principal site of their metabolism, we hypothesized that mifepristone, lilopristone and onapristone are oxidized by cytochrome P450 (CYP) 3A4 to reactive nitroso species that complex the heme of the enzyme, thereby inactivating it. Upon preincubation with human liver microsomes in the presence (but not the absence) of NADPH, mifepristone inhibited midazolam 1′-hydroxylation, a marker of CYP3A4 catalytic activity, very potently (IC<sub>50</sub> ∼3.5 µmol/l) and extensively (by ∼87%). Lilopristone and onapristone also displayed NADPH and time-dependent inactivation of CYP3A4 with characteristics very similar to mifepristone. These data support antiprogestin-mediated inactivation of CYP3A4 and suggest the potential for drug-drug interactions and time-dependent nonlinearities in pharmacokinetics upon their long-term administration.
Digital Analysis of the Pharmacological Effects of in vitro Ischemia on Rabbit Corpus cavernosum
Authors: Liu Shih-Ping , Horan Patrick , Levin Robert M. 
Published: April 2003

<b>Purpose:</b> Regulation of corporal smooth muscle tone is essential for the initiation of penile erection. In recent years, in vitro isometric tension studies using isolated corpus cavernosal tissue have been used extensively to investigate the mechanisms regulating corporal smooth muscle tone and tension. In the present study, we utilized digital analysis of contractile data generated from investigation of contractile and relaxation responses of isolated rabbit corpus cavenosum to various forms of stimulation. Digital analysis of the contractile and relaxation data allows quantitation of both maximal and mean rates of tension change, and time elapsed to maximal response. Rates of tension changes may provide additional important information regarding cellular events that mediate corporal tone and tension changes. <b>Methods:</b> Sexually mature male New Zealand White rabbits were used. Each corpus cavernosum was dissected sharply from the removed penis, then two longitudinal strips were prepared for isometric tension studies and placed in individual baths. Tension was monitored continually using an 8-channel Grass Polygraph. The Grass PolyVIEW system simultaneously converted analog signals to digital information and stored data using a 486 PC computer. Each corporal strip was prestimulated with 300 µmol/l phenylephrine to produce a maximal contraction, then field stimulation (FS), carbachol and nitroprusside were applied consecutively to determine relaxation effects. This procedure was repeated after strips were deprived of glucose and oxygen (in vitro ischemia) for 1 h. The following parameters were quantitated for all responses: maximal tension change; maximal and mean rates of tension change, and time to maximal response. <b>Results:</b> Effects of 1-hour in vitro ischemia on rabbit corporal tissue were as follows: (1) an 85% decrease in contractile response to phenylephrine, and (2) a marked increase in rate of contractile response to phenylephrine. Phenylephrine precontracted strips exhibited: (3) no change in relaxant response to FS; (4) increased relaxant responses to carbachol and nitroprusside; (5) no change in rates of relaxation in response to FS; (6) increased rates of relaxation in response to carbachol and nitroprusside, (7) no change in elapsed time to maximal relaxation in response to FS, and (8) decreased elapsed time to maximal relaxation in response to carbachol and nitroprusside. <b>Conclusion:</b> Digital analysis of the data generated facilitates recording, reviewing and analyzing of in vitro isometric tension studies on rabbit corpus cavernosum. Digital analysis allows quantification of additional parameters that have important implications for determination of mechanisms by which specific pathological processes occur.