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Ozone-induced epithelial injury in the ferret is similar to nonhuman primates.

Extrapolation to humans from rodent ozone exposure is limited by the anatomic differences between the species. Ferrets have similar pulmonary structures to humans, with well developed respiratory bronchioles and submucosal glands. We exposed adult ferrets, monkeys, and rats to 1 ppm ozone (O(3)) or filtered air for 8 h followed by 1 h in filtered air. Bronchoalveolar lavage (BAL) analysis, histopathology, and confocal microscopy were used to evaluate ozone-induced epithelial injury and inflammation. BAL showed significantly increased numbers of neutrophils in ozone-exposed as compared with filtered air ferrets, monkeys, and rats. However, there were 3- to 4-fold more neutrophils in monkeys and ferrets per milliliter of BAL than in rats. Ozone-exposed lungs showed a severe, acute infiltration of neutrophils in regions with necrotic epithelial cells, especially in the centriacinar region that was more severe in ferrets and monkeys than rats. We conclude that acute ozone exposure in ferrets induce severe epithelial necrosis and inflammation, results in similar epithelial injury compared with monkeys, and represents a better model of humans than rodents.

Animals↗

Androgen aromatization and 5 alpha-reduction in ferret brain during perinatal development: effects of sex and testosterone manipulation.

Ferrets of both sexes were killed 8 or 5 days before expected parturition as well as 7, 15, 30, or 51 days after birth, and the activities of aromatase (using 19-[3H]hydroxyandrostenedione as substrate) and of 5 alpha-reductase (using [3H] testosterone as substrate) were assayed in whole homogenates of preoptic area plus anterior hypothalamus (POA), mediobasal hypothalamus (MBH), temporal lobe (TL), and cerebral cortex. Aromatase and testosterone 5 alpha-reductase activities were also measured in these regions in adult gonadectomized male and female ferrets. Compared with adults of both sexes in which aromatase activity was low in all brain regions studied, fetal ferrets had high levels of aromatase activity in POA plus MBH and in TL. At these prenatal ages, aromatase activity in POA plus MBH was significantly higher in males than in females. Aromatase activity in POA, MBH, and TL remained high in both sexes on postnatal days 7, 15, and 30, before declining by postnatal day 51. Cortical aromatase activity was uniformly low across all perinatal ages. The existence of a sex difference in aromatase activity in fetal POA plus MBH cannot be explained by a concurrent sex difference in circulating testosterone. Administration of testosterone to pregnant female ferrets over days 30-41 of gestation caused 150- to 350-fold increases in maternal plasma concentrations of testosterone and 2- to 5-fold increases in fetal plasma testosterone. However, aromatase activity was not affected in the POA and MBH of fetuses or mothers, although activity was significantly increased in the TL of mothers given testosterone. Furthermore, castration of neonatal or adult breeding males decreased plasma androgen levels by factors of 8 and 480, respectively, but resulted in only modest reductions in POA, MBH, and TL aromatase activity (a significant reduction occurred only in the adult male TL). Relatively high levels of testosterone 5 alpha-reductase activity were found in all brain regions across all perinatal ages, as well as in gonadectomized adult ferrets; there was no sex differences at any postnatal age studied. Prenatally, males had higher levels of 5 alpha-reductase activity than females only on day -8 in the POA plus MBH. The results show that estrogen and 5 alpha-reduced androgens can be synthesized in the brains of ferrets of both sexes during the perinatal period of sexual differentiation. A functional role for this neural metabolism of androgen remains to be demonstrated in this carnivorous species.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Sex difference in the effect of mating on the pulsatile secretion of luteinizing hormone in a reflex ovulator, the ferret.

Sex differences in the pulsatile secretion of LH were examined in male and female ferrets after mating. Female ferrets which were either gonadally intact and in estrus or gonadectomized and maintained on a pulsed regimen of daily estradiol (E2) injections exhibited a prolonged rise in plasma LH, characterized by an elevation in mean LH levels and an increase in the number of LH pulses after receiving an intromission from a stud male. By contrast, no such increase in LH secretion occurred in males which achieved an intromission with a female, regardless of whether they were gonadally intact and in breeding condition or gonadectomized and given pulsed estrogen. In fact, intact breeding males which achieved an intromission had significantly fewer LH pulses 1-5 h later than unmated males bled serially over the same time period. This decrease in LH pulse frequency was followed by a significant rise in mean plasma levels of androgen 5-12 h later. When a sexually dimorphic LH response to intromission was observed in gonadectomized E2-treated ferrets, we asked whether this could reflect a sex difference in pituitary responsiveness to the endogenous release of GnRH. Thus, plasma LH levels were measured in gonadectomized and gonadectomized E2-treated ferrets for 2 h after iv injection of GnRH. In the absence of gonadal steroids, ferrets exhibited a sex-specific difference in LH responsiveness to GnRH; however, no sex difference was apparent under the influence of E2. These findings demonstrate that ferrets' sexually dimorphic LH responses to intromission probably reflect a sex difference in the processing of somatosensory inputs from the genitalia or in the neural control of GnRH release into the pituitary portal vessels.

Androgens↗

Pathogenesis of two strains of lion (Panthera leo) morbillivirus in ferrets (Mustela putorius furo).

Canine distemper virus (CDV) was previously considered to have a host range restricted to the canid family. In 1994, the virus was associated with sporadic outbreaks of distemper in captive felids. However, after severe mortality occurred in the Serengeti lions (Panthera leo), attention became focused on the pathogenesis of the virus and a concerted effort was made to identify the virus as CDV or a closely related feline morbillivirus. The present study was designed to explore the susceptibility of ferrets to challenge with two morbilliviruses isolated from lions and the protective effects of a modified-live mink distemper vaccine. Because mortality in ferrets infected with pathogenic CDV approaches 100%, the ferret was selected as a test animal. Two strains of lion morbillivirus were used as a challenge, A92-27/20 (California lion isolate) and A94-11/13 (Serengeti lion isolate). The two strains of lion morbillivirus were antigenically related to CDV (Rockborn strain), and ferrets were susceptible to both of the viruses when inoculated intraperitoneally. The inoculated ferrets were anorectic at 5-6 days postinoculation (PI), exhibited oculonasal discharge at 9-12 days PI, and became moribund at 12-22 days PI. Severe bilateral conjunctivitis was the typical clinical sign. Inclusion bodies characteristic of morbillivirus (eosinophilic, intranuclear, and intracytoplasmic) were distributed in many epithelial cells, including those of the skin, conjunctiva, gallbladder, liver, pancreas, stomach, trachea, lung, urinary bladder, and kidney. Virus was reisolated from selected lung tissues collected at necropsy and identified by CDV-specific immunofluorescence. Ferrets vaccinated with the mink distemper vaccine (Onderstepoort strain) were protected from challenge with the two lion strains, adding further support to the premise that the viruses are closely related to CDV.

Animals↗

Cats differ from mink and ferrets in their response to commercial vaccines: a histologic comparison of early vaccine reactions.

Early histologic changes in lesions at vaccine sites were compared in cats, mink, and ferrets. Twenty-four 4-month-old cats, 20 4-month-old mink, and 20 12-month-old ferrets were vaccinated with three rabies virus vaccines, two feline leukemia virus vaccines, alum adjuvant, and saline. Injection sites were excised at selected time points up to 21 days postvaccination. Histologic examination of the tissue revealed significant differences among the cats, mink, and ferrets in the local response to the commercial vaccines. When compared with ferrets and mink, cats had more lymphocytes in response to all three rabies vaccines. Production of fibroblasts, collagen, and macrophages differed among the three killed aluminum-adjuvanted vaccines in cats but did not differ significantly in mink or ferrets. Cats produced fewer binucleate cells than did mink or ferrets in response to the two adjuvanted leukemia virus vaccines. Differences seen in early tissue response of cats to commercial vaccines may be related to the increased predisposition of cats to vaccine-associated sarcomas.

Animals↗

Heterologous anti-progesterone monoclonal antibody arrests early embryonic development and implantation in the ferret (Mustela putorius).

Early embryo development and implantation were arrested in ferrets passively immunized with a mouse monoclonal anti-progesterone antibody injected intraperitoneally at 72 and 96 h post coitum (p.c.) or at 72 h p.c. only. In control ferrets injected with mouse serum or 0.9% NaCl, implantation sites were found in all mated females; autopsies were carried out at Day 14 p.c. A total of 34 unimplanted embryos were recovered from the reproductive tract of antibody-treated ferrets and none of these had progressed to the blastocyst stage. When ferrets were treated with antibody at 72 h p.c. and autopsies were carried out at Day 6 p.c., only 1 of 29 embryos recovered had progressed beyond the 4-cell stage in 4 females. In 4 control animals most embryos recovered at Day 6 were at the morula (32%) or blastocyst (28%) stage. Embryos from ferrets treated with antibody were therefore developmentally arrested when recovered 72 h after antibody administration. Plasma progesterone concentrations were approximately 6-fold higher in antibody-treated ferrets with unimplanted embryos (711 +/- 132 nmol/l; 223 ng/ml) compared with control pregnant females (102 +/- 4 nmol/l; 32 ng/ml) at Day 14 p.c. The results are consistent with the hypothesis that the normal course of pregnancy is arrested as a result of antibody binding of progesterone in the circulation, presumably causing a decrease in the amount of progesterone available to target cell receptors, and that heterologous anti-progesterone antibody blocks normal cleavage and embryonic development at an early stage before cavitation.

Animals↗

Recombinant F1-V fusion protein protects black-footed ferrets (Mustela nigripes) against virulent Yersinia pestis infection.

Black-footed ferrets (Mustela nigripes) are highly susceptible to sylvatic plague, caused by the bacterium Yersinia pestis, and this disease has severely hampered efforts to restore ferrets to their historic range. A study was conducted to assess the efficacy of vaccination of black-footed ferrets against plague using a recombinant protein vaccine, designated F1-V, developed by personnel at the U.S. Army Medical Research Institute of Infectious Diseases. Seven postreproductive black-footed ferrets were immunized with the vaccine, followed by two booster immunizations on days 23 and 154; three control black-footed ferrets received a placebo. After the second immunization, antibody titers to both F1 and V antigen were found to be significantly higher in vaccinates than controls. On challenge with 7,800 colony-forming units of virulent plague by s.c. injection, the three control animals died within 3 days, but six of seven vaccinates survived with no ill effects. The seventh vaccinate died on day 8. These results indicate that black-footed ferrets can be immunized against plague induced by the s.c. route, similar to fleabite injection.

Animals↗

Study of prolactin levels in the ferret.

A radioimmunoassay for canine prolactin has been used to measure prolactin in the ferret. Serial dilutions of extracts of ferret pituitary glands and of ferret plasma yielded curves that were parallel with the canine prolactin standard curve. The sensitivity, accuracy, reproducibility and precision of the assay were within acceptable limits. Plasma prolactin levels increased after the administration of thyrotrophin releasing hormone (TRH) or chlorpromazine, but not after giving luteinizing hormone releasing hormone. Female ferrets, which were anoestrous, oestrous or spayed, and male ferrets had similar basal prolactin levels when sampled under sodium pentobarbitone anaesthesia. These basal levels were higher than in conscious males and the latter also showed a lesser response to TRH. Hypophysectomy significantly reduced basal prolactin levels in female ferrets by 2 h postoperatively and abolished the response to TRH.

Animals↗

Composition of cerebrospinal fluid in clinically normal adult ferrets.

OBJECTIVE: To determine the protein and cellular composition of CSF in healthy adult ferrets. ANIMALS: 42 clinically normal adult ferrets. PROCEDURE: CSF samples were collected from the cerebellomedullary cistern of anesthetized ferrets by use of disposable 25-gauge, 1.6-cm-long hypodermic needles. Samples were processed within 20 minutes after collection. The number of WBCs and RBCs per microliter of CSF was counted by use of a hemacytometer. The total protein concentration was determined by use of an automated chemistry analyzer. RESULTS: Total WBC counts (range, 0 to 8 cells/microL; mean, 1.59 cells/microL) in CSF of ferrets were similar to reference range values obtained for CSF from other species. Twenty-seven CSF samples had <100 RBCs/microL (mean, 20.3 RBCs/microL). A small but significant effect of blood contamination on WBC counts was found between the 27 CSF samples with <100 RBCs/microL and the remaining samples. Protein concentrations in CSF of ferrets (range, 28.0 to 68.0 mg/dL; mean, 31.4 mg/dL) were higher than has been reported for the CSF of dogs and cats. A significant effect of blood contamination on the CSF protein concentration was not found. CONCLUSION AND CLINICAL RELEVANCE: We have established reference range values for WBC counts and protein concentrations in CSF from healthy adult ferrets that may be useful in the clinical investigation of CNS disease. Results of our study indicate that the WBC count is significantly affected by blood contamination of the CSF sample.

Animals↗

The induction of hepatic and extrahepatic xenobiotic metabolism in the rat and ferret by a polychlorinated biphenyl mixture (Aroclor 1254).

1. The effect of a single i.p. dose (500 mg/kg) of a polychlorinated biphenyl mixture (Aroclor 1254) on hepatic and extrahepatic xenobiotic metabolism in male rat, and male and female ferret, was studied. 2. Aroclor 1254 treatment induced hepatic microsomal N-demethylase activities, and cytochrome P-450 and protein content in both rat and ferret. Liver size and aniline 4-hydroxylase were also increased in rat, but not ferret. The polychlorinated biphenyl mixture appeared to be a mixed-type inducer of hepatic xenobiotic metabolism in both species. 3. Aroclor 1254 treatment produced large increases in activities of benzo(a)pyrene hydroxylase and 7-ethoxycoumarin O-deethylase in whole homogenates of the liver, small intestinal mucosa, kidneys and lungs of both species. Maximal stimulation of xenobiotic metabolism occurred in the kidney of both the rat and ferret. In contrast, UDP-glucuronyltransferase activity was only stimulated in liver, intestine and kidney of the rat and in liver and intestine of the ferret. 4. These results suggest a general species similarity in the response to the polychlorinated biphenyl mixture between the rat and ferret.

Animals↗

The ferret (Mustela putorius furo) as an experimental host for Brugia malayi and Brugia pahangi.

Ferrets inoculated subcutaneously with 150--200 infective larvae of Brugia malayi (subperiodic strain) usually developed patent infection during the 3rd month post inoculation. Microfilaremia was transient, and most animals became amicrofilaremic after the 6th month of infection. Ferrets developed a persistent eosinophilia at the time of patency. At necropsy, 5--8 months post infection, adult worms were recovered principally from lymphatic vessels and recovery ranged from 0.5--13% of the inoculated larvae. The inflammatory response of ferrets to microfilariae was characterized by nodules 1--5 mm in diameter in the liver, lungs, spleen, and submucosa of the gastrointestinal tract. The center of these lesions contained a degenerated microfilaria or the cast of a microfilaria embedded in Splendore-Hoeppli substance. The Splendore-Hoeppli substance was surrounded by eosinophils and/or foreign body giant cells. Identical lesions were observed in ferrets experimentally infected with Brugia pahangi. Sera from ferrets infected with B. malayi demonstrated a 3- to 5-fold increase in IgG by the 4th month of infection and these sera produced 2--3 precipitin bands in double gel diffusion assays with an extract of B. malayi microfilarial antigen. Skin tests with B. malayi microfilarial antigen showed that the majority of the infected ferrets had immediate hypersensitivity responses, but none had Arthus or delayed hypersensitivity responses.

Animals↗

Insulinoma in the ferret: clinical findings and treatment comparison of 66 cases.

The clinical signs and surgical findings were reported for 66 ferrets with insulinomas confirmed histologically. All of the ferrets were treated with one of three modalities, and disease-free intervals and survival times were gathered to determine the most effective treatment. The three treatment groups included 10 ferrets treated medically, 27 ferrets treated with pancreatic nodulectomy, and 29 ferrets treated with pancreatic nodulectomy combined with a partial pancreatectomy. The mean disease-free intervals for each group were 22, 234, and 365 days, respectively. The mean survival times for each group were 186, 456, and 668 days, respectively. Based upon the data, recommendations were made for treating insulinoma in the ferret.

Animals↗

Lack of relay toxicity in ferret hybrids fed carbaryl-treated prairie dogs.

Carbaryl (1-napthol methylcarbamate) is being considered for control of fleas on prairie dogs (Cynomys spp.) used in black-footed ferret (Mustela nigripes) recovery in the western United States. The potential for relay toxicity in ferrets was determined by feeding carbaryl treated prairie dogs to black-footed ferret x Siberian polecat (M. eversmanni) hybrids. Adult prairie dogs were treated topically with 2.5 g of commercial 5% carbaryl dust sold as flea powder. After 14 days prairie dogs were killed and fed to ferrets. Potential for relay toxicity was evaluated by analyzing ferret blood cholinesterase (CHe), prairie dog brain Che, and hepatic carbamate concentration. There was no difference between pre- and post-exposure blood CHe activity, nor did treated prairie dog brain CHe differ significantly from controls. Post-exposure blood CHe did not exhibit reactivation after dilution in aqueous buffer. Hepatic carbaryl concentrations were less than detection limits (50 ppb). Based on these results, we conclude that short-term use of carbaryl for flea control on prairie dogs does not pose a hazard of relay toxicity in black-footed ferrets.

Administration, Topical↗

Evaluation of epidural morphine for postoperative analgesia in ferrets (Mustela putorius furo).

We evaluated the analgesic efficacy of epidural morphine for relieving postoperative pain in domestic ferrets by evaluating behavior and fecal cortisol concentrations. The 12 laboratory-reared, intact, female, domestic ferrets were anesthetized then underwent ovariohysterectomy and bilateral anal sacculectomy. Using a double-blind procedure, we provided epidural morphine (0.1 mg/kg) to six ferrets and epidural saline (0.1 mL/ferret) to the remaining animals prior to surgery. Compared to the animals that received saline, the morphine-treated ferrets were more likely to have attenuated pain responses, and they returned more rapidly to preoperative behavior. Although fecal cortisol concentrations during the first 24 h after surgery increased in all animals, the increase was statistically significant only in the ferrets that received saline epidurals. These data suggest that morphine epidurals administered to ferrets prior to surgery may attenuate both the physiologic and behavioral manifestations of surgically induced pain.

Analgesics, Opioid↗

Alopecia attributed to neoplastic ovarian tissue in two ferrets.

Ferrets with adrenal gland dysfunction have alopecia as their most common clinical sign of disease. Two cases of alopecia in neutered female ferrets are reported that were associated instead with neoplastic tissue found at the site of an ovarian pedicle. Androstenedione and 17-hydroxyprogesterone, but not estradiol, concentrations were high in both ferrets. Following surgical resection of the abnormal tissue in one ferret, the high hormone values decreased quickly and hair regrowth ensued. In both cases, histologic examination revealed features consistent with classical sex cord-stromal (gonadostromal) tumors: prominent spindle cells, along with polyhedral epithelial cells and cells with vacuolated cytoplasm. Although similiar cell types have been described in the adrenal glands of ferrets with adrenal-associated endocrinopathy, an ovarian origin for the current neoplasms is considered likely on the basis of their anatomic location; accessory adrenal tissue has only been described close to an adrenal gland or in the cranial perirenal fat of ferrets. Immunohistochemical analysis, using an antibody against Mullerian-inhibiting substance, failed to prove definitively the source of the steroidogenic cells.

17-alpha-Hydroxyprogesterone↗

Pancreatic adenocarcinoma with metastasis in two ferrets.

Exocrine pancreatic adenocarcinoma with carcinomatosis was diagnosed in 2 ferrets. Clinical signs included abdominal distention and hind limb weakness. Ultrasonography revealed moderate ascites in both ferrets, an irregular abdominal mass in 1 ferret, and multiple abdominal masses in the other ferret. The ferrets were euthanatized, and necropsy of 1 ferret revealed carcinomatosis without visceral metastasis.

Adenocarcinoma↗

Interactions of the exchange inhibitory peptide with Na-Ca exchange in bovine cardiac sarcolemmal vesicles and ferret red cells.

The Na-Ca exchange inhibitory peptide (XIP), which corresponds to residues 251-270 of the Na-Ca exchange protein, specifically inhibits exchange activity (Li, Z., Nicoll, D. A, Collins, A., Hilgemann, D. W., Filoteo, A. G., Penniston, J. T., Weiss, J. N., Tomich, J. M., and Philipson, K. D. (1991) J. Biol. Chem. 266, 1014-1020). We have found that XIP decreased Na+i-dependent Ca2+ uptake to 46 and 20% of control in mixed and inside-out bovine sarcolemmal (SL) vesicles, respectively, and to 22% of control in ferret red cell vesicles. XIP inhibited uptake in bovine SL vesicles after proteolytic digestion. XIP also inhibited Na+o-dependent Ca2+ efflux in bovine SL vesicles but did not inhibit Ca2+ uptake in reconstituted proteoliposomes. Extracellular XIP did not inhibit Ca2+ uptake into intact ferret red cells. Inhibition of uptake in bovine SL vesicles was reduced as the ionic strength was increased. 125I-labeled XIP (1 microM) was cross-linked to proteins of bovine SL vesicles, ferret red cell vesicles, and intact ferret red cells. Labeling of bands at approximately 75, 120, and 220 kDa (in bovine SL vesicles) and bands at 55 and 85 kDa (in ferret red cell vesicles) was detected. No cross-linking was detected in intact ferret red cells. We conclude that XIP inhibition is insensitive to proteolytic digestion and is partially dependent on charge association and conformation of the exchanger. XIP binds to and interacts with the intracellular side of the Na-Ca exchanger.

Animals↗

Comparison of the lesions of Aleutian disease in mink and hypergammaglobulinemia in ferrets.

Gross and microscopic lesions of Aleutian disease (AD) in mink and hypergammaglobulinemia in ferrets were compared. Both conditions were characterized by widespread proliferation of plasma cells, but proliferation was more prominent in mink infected with AD. Arteritis did not occur in hypergammaglobulinemic ferrets. Minimal or no glomerular alterations occurred in infected ferrets, but were severe in mink infected with AD. Bile duct proliferation was more prominent in diseased mink. Tissue alterations suggested that AD in Aleutian genotype mink is more rapidly progressive than is AD in ferrets, causing overt clinical disease and death. In contrast, hypergammaglobulinemia in ferrets appeared to progress more slowly, with little clinical evidence of disease. This is probably the result of a paucity of glomerular lesions in ferrets. Possible mechanisms to explain the differences in the development of lesions are discussed.

Aleutian Mink Disease↗