A conscious-rabbit model to study vardenafil hydrochloride and other agents that influence penile erection.
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Experimental models to study the effect of agents on penile erection usually include electrical stimulation of peripheral nerves in anesthetized animals combined with systemic or intracavernous injection of drugs. The objective of this study was to demonstrate that conscious rabbits can be used as a simple and quantitative model for the assessment of compounds that show potential for the treatment of erectile dysfunction. Erection was assessed by measuring the length of uncovered penile mucosa before and after the intravenous (i.v.) administration of agents. Animals did not require anesthesia during the course of the study. The phosphodiesterase 5 (PDE5) inhibitors vardenafil x HCl (hereafter called vardenafil) and sildenafil were given intravenously, and measurements were taken for 0-5 h. The effects of phentolamine and milrinone were also evaluated. Vardenafil (0.1-3 mg/kg) induced dose-dependent penile erections in conscious rabbits following i.v. administration. The efficacy of vardenafil was potentiated, and the minimal effective dose was reduced significantly to 0.01 mg/kg by simultaneous administration of the nitric oxide (NO) donor sodium nitroprusside (SNP). Administration of the NO-synthase inhibitor L-NAME abolished the effect. Sildenafil was effective in this model after i.v. administration. The alpha-adrenergic receptor antagonist phentolamine (0.1, 0.3 and 1 mg/kg i.v.) induced erections with a slower t(max) compared with vardenafil and sildenafil. Intravenous administration of the PDE3 inhibitor milrinone (1 mg/kg i.v.) was less effective than the PDE5 inhibitor vardenafil. The conscious rabbit is a suitable and reliable model for the evaluation of compounds with potential for the treatment of erectile dysfunction. This was demonstrated using compounds that target different signaling pathways that induce smooth muscle relaxation in the penis. (+info)
Helical structure of hair cell stereocilia tip links in the chinchilla cochlea.
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Outer-hair-cell stereocilia tip-link structure in the chinchilla cochlea was studied by transmission electron microscopy using tannic acid and Ruthenium red/ Alcian blue histochemical procedures. Tannic acid and Ruthenium red/Alcian blue treatments showed the tip link as a compact strand of filaments 9-12 nm thick. Fourier analysis of tip-link images showed that the strand is a three-start helical bundle of fine, coiled filaments which had an axial period of 22.5+/-1.5 nm. Each of three coiled filaments in the strand showed globular structures, 4.3+/-0.3 nm in diameter. The globular structures may correspond to individual protein subunits or they may be repeating identical domains of one polypeptide. The three filaments of the helical array may provide a rigidity to the tip link during stereocilia deflections. Alternatively, changes in the subunit or domain structure of each filament may result in a lengthening or shortening of the tip-link strand. (+info)
Naturally occurring histoplasmosis in the chinchilla (Chinchilla laniger).
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Histoplasmosis was diagnosed histopathologically in a female chinchilla. This animal had originated from a commercial chinchilla ranch in central Missouri. Seventeen of 130 animals in the colony had died within a month's period with a respiratory illness. This animal had a history of fur chewing, but this was not true of all the other animals that had died. Histoplasma capsulatum was cultured from timothy hay used for food. (+info)
Blood capillary distribution correlates with hemodynamic-based functional imaging in cerebral cortex.
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Our study concerns the mechanisms that underlie functional imaging of sensory areas of cortex using hemodynamic-based methods such as optical imaging of intrinsic signals, functional magnetic resonance imaging and positron emission tomography. In temporal cortex of chinchilla, we have used optical imaging of intrinsic signals evoked by acoustic stimulation to define the functionally responsive area and then made (scanning electron microscopy) observations of the corresponding capillary networks prepared by corrosion cast methods. We report that intrinsic signals associated with auditory cortex correlate directly with discrete capillary beds. These capillary beds, within the cortical surface layers, are distributed across the cortex in a non-uniform fashion. Within cortex both the arterial supply and the capillary network contain various flow control structures. Our study suggests a causal relationship between the metabolic demands of local neuronal activity and both the density of the capillary network and the placement of the control structures. Such relationships will affect the ultimate spatial resolution obtainable by hemodynamic-based functional brain imaging studies. These relationships will also affect quantitative comparisons of activity levels in different areas of cortex. (+info)
Elevated fusiform cell activity in the dorsal cochlear nucleus of chinchillas with psychophysical evidence of tinnitus.
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Chinchillas with psychophysical evidence of chronic tinnitus were shown to have significantly elevated spontaneous activity and stimulus-evoked responses in putative fusiform cells of the dorsal cochlear nuclei (DCN). Chinchillas were psychophysically trained and tested before and after exposure to a traumatic unilateral 80 dB (sound pressure level) 4 kHz tone. Before exposure, two groups were matched in terms of auditory discrimination performance (noise, and 1, 4, 6, and 10 kHz tones). After exposure, a single psychophysical difference emerged between groups. The exposed group displayed enhanced discrimination of 1 kHz tones (p = 0.00027). Postexposure discrimination of other stimuli was unaffected. It was hypothesized that exposed animals experienced a chronic subjective tone (i.e., tinnitus), resulting from their trauma, and that features of this subjective tone were similar enough to 1 kHz to affect discrimination of 1 kHz objective signals. After psychophysical testing, single-unit recordings were obtained from each animal's DCN fusiform cell layer. Putative fusiform cells of exposed animals showed significantly (p = 0.0136) elevated spontaneous activity, compared with cells of unexposed animals. Putative fusiform cells of exposed animals showed a greater stimulus-evoked response to tones at 1 kHz (p = 0.0000006) and at characteristic-frequency (p = 0.0000009). This increased activity was more pronounced on the exposed side. No increase in stimulus-evoked responses was observed to other frequencies or noise. These parallel psychophysical and electrophysiological results are consistent with the hypothesis that chronic tonal tinnitus is associated with, and may result from, trauma-induced elevation of activity of DCN fusiform cells. (+info)
Malocclusions in guinea pigs, chinchillas and rabbits.
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The types of malocclusions encountered in rodents and lagomorphs are classified. Diagnosis, treatment, and prognosis are reviewed. Some malocclusions are curable, whereas others can only be controlled. The need to perform a complete oral examination and to find a cause for the condition is stressed, as it will seriously affect the prognosis. (+info)
Influence of extracorporeal shock-wave application on normal bone in an animal model in vivo. Scintigraphy, MRI and histopathology.
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There is little information about the effects of extracorporeal shock-wave application (ESWA) on normal bone physiology. We have therefore investigated the effects of ESWA on intact distal rabbit femora in vivo. The animals received 1500 shock-wave pulses each of different energy flux densities (EFD) on either the left or right femur or remained untreated. The effects were studied by bone scintigraphy, MRI and histopathological examination. Ten days after ESWA (0.5 mJ/mm2 and 0.9 mJ/mm2 EFD), local blood flow and bone metabolism were decreased, but were increased 28 days after ESWA (0.9 mJ/mm2). One day after ESWA with 0.9 mJ/mm2 EFD but not with 0.5 mJ/mm2, there were signs of soft-tissue oedema, epiperiosteal fluid and bone-marrow oedema on MRI. In addition, deposits of haemosiderin were found epiperiosteally and within the marrow cavity ten days after ESWA. We conclude that ESWA with both 0.5 mJ/mm2 and 0.9 mJ/mm2 EFD affected the normal bone physiology in the distal rabbit femur. Considerable damaging side-effects were observed with 0.9 mJ/mm2 EFD on periosteal soft tissue and tissue within the bone-marrow cavity. (+info)
Experimental acute otitis media due to nontypeable Haemophilus influenzae: comparison of high and low azithromycin doses with placebo.
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Treatment of acute otitis media (AOM) with azithromycin results in apparent clinical success, but tympanocentesis performed 4 to 6 days after initiation of therapy in children with nontypeable Haemophilus influenzae (NTHI) recovered from initial middle ear cultures demonstrates persistence of infection in more than 50% of episodes. We sought to determine the effect of azithromycin at different doses on the density of middle ear infection due to NTHI to provide additional understanding of this dichotomy between clinical and microbiologic outcome measures in AOM. In a chinchilla model of experimental otitis media (EOM), animals treated with placebo were compared to animals receiving a single daily dose 30 or 120 mg of azithromycin per kg of body weight per day for 5 days. Microbiologic outcome was assessed by obtaining quantitative cultures from the middle ear during a 5-day course and for 1 week following therapy. Azithromycin concentrations were measured to ascertain whether a concentration-dependent effect was present. Azithromycin at 30 and 120 mg/kg/day demonstrated a dose-dependent effect on the quantitative assessment of middle ear infection due to NTHI. A 30-mg/kg dose of azithromycin daily resulted in levels in serum and areas under the serum concentration-time curve at 24 h comparable to published data obtained with children given azithromycin at 5 to 10 mg/kg in multiday regimens. Increased doses of azithromycin (120 mg/kg) achieved 2.5- to 4-fold-higher levels in serum and 3- to 6-fold-higher total levels and levels in extracellular middle ear fluid as well as more rapid reduction in bacterial density and a greater proportion of middle ears with complete sterilization than either placebo or the 30-mg/kg/day regimen. (+info)