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Age-related fiber order in the ferret's optic nerve and optic chiasm.

Although the mammalian optic tract shows a grouping of fibers by age, with newer fibers nearer the pial surface, the possible rules for fiber ordering in the mammalian optic nerve have not been well defined. In this study, preferential labeling of the older retinal fibers in the ferret, a close relative of the cat, shows that the age-related fiber order in the ferret's optic tract reflects a systematic sorting of fibers by age that occurs in the optic nerve, and that is maintained through the optic chiasm. The older retinofugal fibers, dispersed throughout the nerve near the retina, come to be limited to the perimeter of the nerve as it passes through the optic foramen, while newer fibers come to lie nearest the center of the nerve. These newest fibers approach the ventral surface of the brain nearer the optic chiasm. In the chiasm, as in the tract, the oldest fibers lie furthest from the pial surface of the brain, while newer fibers lie nearer the surface. The age-related fiber ordering in the ferret's optic nerve, with the newest fibers initially being furthest from the surface at the optic foramen, differs from age-related orderings seen in nonmammalian vertebrates, where the newest fibers are always nearest the surface. The changing patterns of fiber ordering along the ferret's optic nerve may relate to changes in the underlying glial structure of the developing nerve.

Age Factors↗

Amrinone effects on electromechanical coupling and depolarization-induced automaticity in ventricular muscle of guinea pigs and ferrets.

The effects of the cardiotonic agent, amrinone (0.05-4 mM), on electrical and mechanical activities of ferret and guinea-pig papillary muscles were studied using current and voltage clamp (single sucrose gap) techniques. In current clamp studies, amrinone increased, in a dose-dependent manner, contractile force elicited by action potential in both species. Depolarization-induced automaticity was facilitated in ferret muscles at all maximum diastolic potentials between -70 and -15 mV. Facilitation of automaticity in guinea-pig muscles occurred only at potentials more negative than -35 mV and was suppressed at more positive potentials. Cimetidine (10 microM) partially reversed the effects of amrinone on automaticity in both species. In voltage clamp studies, amrinone increased the slow inward current. Steady-state outward current was increased in guinea-pig but not in ferret muscles. A dual effect of amrinone on tension was observed. Amrinone was found to increase phasic tension of ferret papillary muscles only for depolarizations lasting less than 250 to 300 msec. For longer depolarizations, amrinone decreased the phasic tension (in a dose-dependent manner), whereas the tonic tension was not modified. The decrease as well as the increase in tension was associated with an increase of the slow inward current. The results suggest that amrinone may be arrhythmogenic and may have an intracellular action at the sarcoplasmic reticulum level (partial inhibition) in addition to its action on the calcium current.

Action Potentials↗

Measles virus encephalitis in ferrets as a model for subacute sclerosing panencephalitis.

Young adult ferrets were used as experimental animals to study subacute sclerosing panencephalitis (SSPE). When cells infected with cell-associated measles virus strains isolated from SSPE patients were inoculated intracerebrally (i.c.) into ferrets, they developed an acute encephalitis and died within 1 to 3 weeks without detectable antibody formation. Immunization with live measles vaccine 5 weeks before i.c. inoculation changed the course of the infection in about 50% of the ferrets. These animals developed a subacute encephalitis within weeks or months after inoculation. Cell-associated measles virus was isolated from their brains and high measles antibody titers were found in their sera, comparable to those in sera of SSPE patients. Measles virus specific immunoglobulins (IgG) were present in their brains and determination of IgG/albumin ratios indicated that antibodies were synthesized in the brain in response to the persistent measles virus infection. Measles specific oligoclonal IgG bands were found in the sera and spinal fluids of these animals. Therefore, subacute ferret encephalitis has virological and immunological characteristics in common with SSPE, indicating that it may serve as a model for the human disease. Other animal models of SSPE are described briefly.

Animals↗

Immunoprophylaxis of respiratory syncytial virus infection in the infant ferret.

Infant ferrets can be protected from respiratory syncytical virus challenge at 3 days of age by gestational infection of their mothers. Ferrets acquire their immunity to respiratory syncytial virus postpartum via immunizing products of lactation. The level of protection against viral replication correlates with the maternal serum neutralizing titer or a concomitant factor. Passive administration of adult ferret serum with a neutralizing titer of 1:1024 or greater, either i.p. or orally does not confer immunity. A nonantibody-mediated protective mechanism appears to play an important role in protecting the infant ferret from respiratory syncytial virus replication. Our findings allow the testing of the efficacy of future human vaccines before human clinical trial.

Aging↗

The histochemical localization of cytochrome oxidase in the retina and lateral geniculate nucleus of the ferret, cat, and monkey, with particular reference to retinal mosaics and ON/OFF-center visual channels.

The histochemical localization of cytochrome oxidase within the normal retina and lateral geniculate nucleus (LGN) of cats, ferrets, and monkeys revealed that distinct layers, types of cells, and portions of neurons are more intensely stained than others. The dark staining of photoreceptor inner segments and cone pedicles and the light staining of photoreceptor outer segments, somata, and rod spherules demonstrates that different segments of the same cell may have disparate but distinct levels of oxidative enzyme activity. In tangential sections of retina, regular mosaic arrays were evident for each of several darkly reactive retinal components, such as cone inner segments, cone pedicles, and horizontal cells. In the cat and ferret, regular mosaic arrays were also formed by metabolically distinguishable populations of ganglion cells. Ia and IIa ganglion cells (OFF-; Nelson, R., E. V. Famiglietti, Jr., and H. Kolb (1978) J. Neurophysiol. 41: 472-483) were more darkly reactive than the other classes. The darker staining of sublamina a of the inner plexiform layer (OFF-; Famiglietti, E. V., Jr., and H. Kolb (1976) Science 194: 193-195) in the cat and ferret retina, as well as sublamina A' and A1' of the ferret LGN (OFF-; Stryker, M.P., and K.R. Zahs (1983a) J. Neurosci. 3: 1943-1951) suggest that, under typical rearing conditions, the OFF-channels may be metabolically more active than the ON-channels in these species. In Macaca and Saimiri, darker staining was observed in sublamina b of the inner plexiform layer (ON-; Famiglietti, E.V., Jr., and H. Kolb (1976) Science 194: 193-195) and laminae 1, 2, and 6 of the LGN, implying that, under similar rearing conditions, a different pattern is observed. The dark staining of many large retinal ganglion cells, as well as most of the larger LGN neurons (presumed Y/Y-like), in all species studied is evidence that the Y/Y-like pathway is also highly active.

Animals↗

Pathology of experimental infection with Brugia malayi in ferrets: comparison with occult filariasis in man.

Ferrets experimentally infected with Brugia malayi (subperiodic strain) developed eosinophilia at patency and usually became amicrofilaremic. Ferrets necropsied within 3 months after becoming amicrofilaremic had granulomas and focal reactions to degenerating microfilariae in their livers, lungs and lymph nodes essentially identical to those of tropical eosinophilia. Four of 7 ferrets that received multiple inoculations of larvae, developed edema of the inoculated paw and leg after becoming amicrofilaremic and 6 of these 7 ferrets had granulomatous lymphangitis and lymphadenitis of inoculated limbs but not the lesions of lung and liver characteristic of occult infection.

Animals↗

Antiemetic activity of butorphanol against cisplatin-induced emesis in ferrets and dogs.

The analgesic agent butorphanol was evaluated for its ability to block cisplatin-induced emesis in ferrets and dogs. In ferrets, butorphanol (0.15, 0.3, or 0.45 mg/kg; expressed in terms of the tartrate salt) administered sc 30 minutes prior to cisplatin (8 mg/kg iv) reduced the number of emetic episodes but did not eliminate them. When these doses of butorphanol were administered 30 minutes before and 30 and 90 minutes after cisplatin, they caused a dose-related reduction in the number of emetic episodes; there was complete protection at a dose of 0.45 mg/kg/injection. In dogs, butorphanol (0.185 or 0.37 mg/kg/injection, expressed in terms of the tartrate salt) was administered sc on the same multiple-dose schedule used in the ferrets; this caused a nearly complete elimination of the emetic response to cisplatin (3 mg/kg iv). Butorphanol caused some sedation in both species at effective antiemetic doses but had no effect on the antitumor activity of cisplatin against murine L1210 leukemia. Naloxone blocked the antiemetic effect of butorphanol in ferrets, indicating the involvement of opiate receptors. The results of these studies suggest that butorphanol may be useful clinically in mitigating the emetic effects of cisplatin.

Animals↗

Aplastic anemia associated with estrus in pet ferrets.

Aplastic anemia in association with estrus was diagnosed in 6 pet ferrets. The ferrets had been examined because of anorexia, depression, and lethargy of 2-5 days' duration. Consistent clinical findings were pale mucous membranes and enlargement of the vulva. Hemorrhages were found in 3 ferrets. Hematologic findings included severe anemia, thrombocytopenia, granulocytopenia, and hypocellularity of the bone marrow. The aplastic anemia was attributed to prolonged estrogenic exposure in ferrets with protracted estrus.

Anemia, Aplastic↗

Cisplatin-induced emesis in the Ferret: a new animal model.

The ferret, a carnivore weighing about 1 kg, was evaluated for its potential use in testing drugs for emetic and antiemetic activity. An acute emetic response to apomorphine indicated that the ferret can respond to emetic stimuli and suggested that the ferret has an emetic chemoreceptor trigger zone. Cisplatin produced a dose-related emetic response. Antagonism with metoclopramide provided complete protection from cisplatin-induced emesis. The results of these initial studies indicate that the ferret may be a useful species in emesis research.

Animals↗

Trial of avermectin B1a, mebendazole and melarsoprol against pre-cardiac Dirofilaria immitis in the ferret (Mustela putorius furo).

Avermectin B1a was found active against the pre-cardiac stage of Dirofilaria immitis in ferrets. The drug was given orally, at 0.2 mg/kg, on days 38--42 of infection. At necropsy, 5 1/2 months after inoculation, worms were almost totally absent from the hearts of these ferrets. The efficacy of melarsoprol against developing Dirofilaria, which has been demonstrated in dogs by other workers, was demonstrated in ferrets given oral doses, at 100 mg/kg, on days 38--42 of infection. The reported efficacy of mebendazole was not evident in the ferret host in this study, probably because the treatment (100 mg/kg, orally, on days 38--42) was shorter and later than that reported for dogs.

Animals↗

[Rabies antibody production in ferrets after immunization with four different rabies vaccines].

The Development of Rabies Antibodies in Ferrets after Injection of Four Different Types of Rabies Vaccines. Experiments aimed at proving the suitability of ferrets in the routine testing of rabies vaccines for human and animal use were carried out. A total of 40 ferrets received four vaccines, two for use in humans and two for use in animals. For the determination of rabies antibodies, blood was taken on days 28 and 56, respectively, after inoculation of the vaccines. All animals developed antibodies of more than [0.5 IE/ml] serum as determined by RFFIT. The antibody titre following injection of the vaccines for animals (A1 and A2) was 4.1 IE/ml on day 28 and 5.86 IE/ml on day 56. The antibody titre following injection of the vaccines for humans was 6.64 IE/ml on day 28 and 8.87 IE/ml on day 56. The suitability of ferrets for the potency assay of rabies vaccines is discussed.

Animals↗

Comparison of twitch force and calcium handling in papillary muscles from right ventricular pressure overload hypertrophy in weanling and juvenile ferrets.

OBJECTIVE: The aim was to compare differences in peak twitch force occurring despite similar degrees of right ventricular hypertrophy in ferrets with pulmonary artery banding at either weanling or juvenile age. METHODS: After inducing pressure overload hypertrophy by banding the pulmonary artery of weanling and juvenile age ferrets, mechanical function (that is, isometric twitch force and passive stiffness), intracellular [Ca2+] using the calcium indicator aequorin, markers of myocardial energy supply, and quantified connective tissue content were studied. RESULTS: It was previously found that there was a reduced peak isometric twitch force despite normal [Ca2+]i in juvenile banded ferrets age 10-12 weeks with right ventricular pressure overload hypertrophy (POHj). In the present study we report findings in banded weanling ferrets (POHw) age 7 weeks. POHw animals showed a similar degree of hypertrophy to that found in the POHj. However, there was a greater peak twitch force in hypertrophied muscles at higher [Ca2+]o. There was no difference in peak [Ca2+]i: -3.1(SEM 0.1) v -3.1(0.3) (log fractional luminescence) at 16 mM [Ca2+]o for control and POHw, respectively. Connective tissue content for control animals was 10(1)% versus 10(2)% in POHw. Despite a lack of quantitative change in connective tissue content or resting [Ca2+]i in POHw, passive stiffness in papillary muscles was increased. Retrospective analysis of tissue from POHj revealed a connective tissue content of 24(6.8)% (P << 0.001). Thus the decreased peak twitch force reported in POHj might in part be due to an increase in fibrous connective tissue. In this study, lactate dehydrogenase was significantly higher (38%) in POHw animals. In contradistinction, total creatine kinase activity and total creatine content were significantly less (22%) in hearts from POHj animals, indicating differences in myocyte remodelling despite similar degrees and durations of hypertrophy. CONCLUSIONS: Comparison of POHw and POHj showed that, when there is restructuring of the extracellular space in terms of increased fibrosis, there is also molecular remodelling in the myocyte, as demonstrated by a decrease in the creatine kinase system.

Animals↗

Ultrasonographic detection of adrenal gland tumors in two ferrets.

Hyperadrenocorticism is recognized as a common medical condition in middle- to old-aged ferrets. Because diagnosis of adrenocortical tumors in ferrets, using results of adrenocorticotropic hormone stimulation or dexamethasone suppression tests, is unreliable, ultrasonography was used as an alternative to laparotomy for the detection of tumors in 2 ferrets. The diagnosis was confirmed by surgical excision and histologic examination of the adrenal gland. In a typical manifestation of the condition, clinical signs in 1 ferret included vulvar swelling and serous to mucopurulent vaginal discharge, which resolved after the adrenalectomy.

Adenocarcinoma↗

A cluster of cases of juvenile mediastinal lymphoma in a ferret colony.

Three cases of juvenile mediastinal lymphoma developed in a laboratory colony of ferrets. Two ferrets became acutely moribund, and one was found dead with no preceding signs of illness. Splenomegaly, hepatomegaly, and a large thoracic mass were the primary features in each case. All three ferrets had multiorgan metastasis of the tumor. Two ferrets were tested for feline leukemia virus and Aleutian disease virus with negative results.

Animals↗

Pathogenicity, immunogenicity and genetic stability in mice and ferrets of a cold inhibitor-resistant mutant of influenza H3N2 virus.

A cold inhibitor-resistant mutant was derived from MRC-2 virus by means of serial passages in the presence of rabbit serum and at gradually decreasing temperatures. This virus, denoted MRC-2 IRc, grew well at both 26 and 37 degree C. The pathogenicity and immunogenicity of the virus was examined in mice and ferrets. No clinical reactions were detected in either species. Both mice and ferrets developed high levels of hemagglutination inhibition and neuraminidase inhibition antibodies. The virus was reisolated from the lungs of intranasally inoculated mice; in ferrets it was recovered from nasal washing and trachea but not from lungs. The properties of the isolated viruses were examined. The viruses reisolated from mice lost their reproductive capacity at 26 degree C and were less resistant to inhibitors than the original virus. The virus isolated from the ferret nose was identical with the original virus, however the tracheal isolate exhibited a certain degree of reversion in both the markers tested.

Animals↗

Measles antibodies and immunoglobulins in sera from patients with subacute sclerosing panencephalitis (SSPE) and from an infected ferret.

Cellulose acetate electrophoresis of sera from 2 patients with SSPE revealed a slow-moving and a fast-moving gamma-globulin band. The IgG fractions from sera were isolated by the combination of starch block electrophoresis, Sephadex gel filtration and isoelectric focusing techniques. The purity of each protein was tested by immunoelectrophoresis using a potent goat anti-whole human serum. The isolated IgG preparations were tested in HI, CF and N tests against measles virus envelope, measles virus nucleocapsid and whole measles virus, respectively. The results showed that isolated IgG fractions, having different electrophoretic mobilities, contained high titers of HI, CF and N antibodies, and these titers were proportional to the protein concentration of IgG. Although both IgG fractions appeared to show an increase of K-type chain, neither fraction was devoid of L-type chain. These results indicate that the homogeneous IgG bands observed in the SSPE serum were not monoclonal as they failed to show selective increase of one type of light chain and uneven distribution of measles antibody activity. These findings were compared with the results from a ferret, which developed encephalitis 2 months after intracerebral inoculation with cell-associated measles virus derived from the brain of an SSPE patient. The electrophoretic pattern of the ferret serum was similar to that of the human. High titers of measles HI and N antibodies were seen in the isolated slow- and fast-moving IgG's. The similarities observed in the human and ferret IgG's, with respect to homogeneous bands in electrophoresis and measles HI and H antibody activities, suggest that the ferret may be a useful animal model for studying the immune mechanism of SSPE.

Animals↗

Immunity to influenza in ferrets. XI. Cross-immunity between A/Hong Kong/68 and A/England/72 viruses: serum antibodies produced by infection or immunization.

The degree of immunity due to cross-reactions between antibody to influenza virus A/Hong Kong/1/68 and A/England/42/72 was studied in ferrets. Ferrets were immunized with the viruses by either live infection or by inoculation with inactivated virus vaccines. The vaccines were given with Freund's incomplete adjuvant or were given to ferrets previously infected with influenza virus A/PR/8/34. As a result of these immunizations the animals all produced similar titres of serum HI antibody to the immunizing virus, although the degree of cross-reaction with the other virus strain was variable. After immunization the animals were challenged by infection with an A/Eng/42/72-like virus and their degree of immunity was measured. It was found that the greatest immunity was in ferrets previously infected with the homologous A/Eng/42/72 virus. Animals previously infected with A/HK/68 virus also showed a measurable degree of immunity to A/Eng/42/72 infection, and this was greater than that found in animals given inactivated virus vaccines. The immunity produced by the vaccines was approximately equal, regardless of which vaccine or method of immunization was used. Thus, live infection produced a more effective, broader immunity than did the use of inactivated virus vaccines.

Animals↗

An outbreak of post-vaccinal suspected distemper-like encephalitis in farmed ferrets (Mustela putorius furo).

Two outbreaks of an encephalitis apparently induced by an attenuated live distemper vaccine occurred in a large ferret breeding establishment in New Zealand. Approximately 350 of 6,000 young ferrets 16-22 weeks old died. Many were found dead with no premonitory signs, others showed severe neurological signs. Some with central nervous system (C.N.S.) signs recovered. Pathological examination showed no gross abnormalities except for a few with mild conjunctivitis, rhinitis and lung emphysema. Microscopically there was a moderate to massive non-inflammatory necrosis of hippocampal nerve cell bodies. In those animals which survived for several days with CNS signs there was also a mild to moderately severe non-supportive encephalitis, and in some of these distinct neuronal intranuclear and intracytoplasmic eosinophilic inclusion bodies were seen. Some ferrets also had a bronchiolitis with intracytoplasmic eosinophilic inclusion bodies in bronchiolar epithelium. All these lesions suggest that a distemper like condition was involved. About half of the ferrets also had a mild to severe inflammatory myocardial necrosis.

Journal Article↗