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PubMed1979

Diphenylhydantoin induced gingival hyperplasia in ferrets: a precautionary note.

Diphenylhydantoin appears to modify the tissue response in ferrets to a gingival irritant. In the present study, ferrets were tested for the tissue response to a local irritant in their maxillary right quadrant, while their maxillary left quadrant was the control. A low incidence of hyperplasia was induced only in irritated gingival tissue of animals receiving DPH. The problems encountered in comparing the hyperplasia produced in ferrets and humans were also discussed.

Animals↗

PubMed1990

Reduction of calculus accumulation in domestic ferrets with two dentifrices containing pyrophosphate.

Work performed by King et al. in the 1940's and 1950's, as well as recent studies by our group, have shown that the domestic ferret is a suitable model for the study of calculus formation, offering several advantages over the rodent and dog models in current use. We have demonstrated that mineral supplementation of a moist diet accelerates calculus accumulation, and that twice-daily application of a regular dentifrice slows the initial rate of calculus formation, but permits significant accumulation by the eighth week. The present study compared calculus accumulation in female ferrets receiving mineral-supplemented cat food and a twice-daily application of either Regular Crest toothpaste (Crest), Anti-tartar Crest (Crest-AT), or Anti-tartar Colgate Gold toothpaste (Colg-AT). Animals received an ultrasonic prophylaxis, then were fed once daily for eight weeks with moist canned cat food supplemented with sucrose and mineral salts, and were scored for area and extent of calculus accumulation at four and eight weeks after prophylaxis. The data show that the groups treated with the anti-calculus dentifrices produced significantly less calculus than the group treated with regular dentifrice; the Colg-AT group also exhibited lower scores than did the Crest-AT group, especially at four weeks. These results, similar to those seen in human studies, demonstrate that the ferret is a suitable model for the study of anti-calculus dentifrices.

Analysis of Variance↗

PubMed1997

Helicobacter mustelae-associated gastric adenocarcinoma in ferrets (Mustela putorius furo).

Helicobacter pylori in humans is associated with active, chronic gastritis, peptic ulcer disease, and most recently has been linked epidemiologically to gastric adenocarcinoma. A related organism, Helicobacter mustelae, naturally infects ferrets and also causes a persistent gastritis, a precancerous lesion, and focal glandular atrophy of the proximal antrum. In this report, we document the clinical presentation and histopathologic confirmation of H. mustelae-associated gastric adenocarcinoma in two middle-aged male ferrets. The ferret appears to be well suited to study the pathogenesis of naturally occurring Helicobacter sp.-induced gastric adenocarcinoma.

Adenocarcinoma↗

PubMed1997

Immunohistochemistry of pancreatic islet cell tumors in the ferret (Mustela putorius furo).

Twenty-two pancreatic islet cell tumors and normal pancreatic islets from ferrets were evaluated by immunohistochemistry for expression of the peptide hormones insulin, somatostatin, glucagon, and pancreatic polypeptide (PP) and the neuroendocrine markers chromogranin A (CgA) and neuron-specific enolase (NSE). In normal pancreatic islets, the majority of cells stained strongly with CgA and NSE. A cells, B cells, D cells, and PP cells stained strongly with glucagon, insulin, somatostatin, and PP, respectively. All 22 tumors stained with CgA and NSE. The proportion of cells within tumors staining for CgA was variable, but more than half of the cells stained positively in 18 of the tumors. The intensity of staining for CgA was strongly (reactivity equivalent to or greater than normal islet cells in adjacent tissue) in 11 moderate in six, and weak in five of the tumors. All tumors stained for NSE, with > or = 50% of the cells staining in 21 of the tumors, and the intensity of staining was strong in 18 of the tumors. Twenty of 22 tumors stained positively for insulin. with > or = 50% of the cells staining in 19 of them. The intensity of staining for insulin was strong in 12, moderate in seven, and weak in one of the tumors. Approximately < or = 1% of the cells in 15 of 22 tumors stained for somatostatin, five tumors stained for pancreatic polypeptide, and three tumors stained for glucagon. These data indicate that the majority of islet cell tumors of ferrets express immunohistochemically detectable insulin. CgA and NSE are both useful general markers for such tumors, including those that are insulin negatives. Commercially available antisera to CgA, NSE, insulin, glucagon, somatostatin, and PP work well in formalin-fixed, paraffin-embedded tissue for immunophenotyping islet cell tumors in the ferret.

Adenoma, Islet Cell↗

PubMed1991

Receptor-mediated cAMP production in adult and infant ferret tracheal epithelium.

Tracheal epithelial cells obtained from adult and infant ferrets were grown in primary culture in vitro. Cells from adult animals grew readily, and many ciliated cells were observed in the cultures. Successful cultures were derived from infant animals, but cell number in infant and adult cultures began to decrease after 6 d. Receptor-mediated activation of adenylate cyclase was determined by incubating monolayers of adult or neonatal cells with beta-adrenergic agonists, prostaglandin E2 (PGE2) and vasoactive intestinal peptide and measuring cAMP production. beta-adrenergic agonists and PGE2, but not vasoactive intestinal peptide, stimulated production of cAMP in both cell types. The 50% effective concentration for isoproterenol and PGE2 in neonatal ferret tracheal epithelial (NFTE) cells was nearly 10-fold more than for adult ferret tracheal epithelial (FTE) cells, but maximal agonist-stimulated cAMP production was significantly different between the cell types only for PGE2. Radioligand binding studies were performed using the beta-adrenergic antagonist [125I]iodocyanopindolol on membrane particulates from confluent monolayers and freshly isolated FTE cells. Binding of iodocyanopindolol was saturable, stereoselective, and of high affinity (binding affinity = 26.1 +/- 6.6 pmol/L, adult; 16.5 +/- 5.7 pmol/L, NFTE). Competition studies with the specific beta 2-adrenergic receptor antagonist, ICI 118 551 revealed a predominance of beta 2-adrenergic receptors on both adult FTE and NFTE cells. Receptor density was significantly higher in adult FTE compared with NFTE cells (48.2 +/- 9.1, 18.1 +/- 1.5 fmol/mg, respectively). Basal adenylate cyclase activity was significantly lower in neonatal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

PubMed1996

Digestive lipases of the newborn ferret: compensatory role of milk bile salt-dependent lipase.

The amount of mRNA hybridizing to bile salt-dependent lipase and to colipase-dependent lipase probes as well as their translation into active proteins were quantified in the adult and newborn pancreas and lactating mammary gland from the ferret, a species whose milk, similar to that of the human, has bile salt-dependent lipase. The concentration of colipase-dependent lipase mRNA correlated with the amount of activity found in the adult and newborn pancreas, whereas neither mRNA nor activity of this enzyme was detected in the kit pancreas or in the lactating mammary gland. These data indicate that colipase-dependent lipase is actually expressed in adult pancreas and might represent the main lipolytic system in the adult. mRNA hybridizing to the bile salt-dependent lipase probe used in this study were detected in adult and in newborn ferret pancreas as well as in lactating mammary gland. However, the bile salt-dependent lipase activity expressed in the newborn pancreas was very low when compared with the activity expressed either in the mammary gland or in the adult pancreas. These data argue for a compensatory role of milk bile salt-dependent lipase in lipid digestion in the newborn. The hydrolysis of dietary fat might be initiated by preduodenal lipase, the activity of which is only two times lower in the gastric mucosa of the newborn than in the adult ferret. The high concentration of mRNA hybridizing to the bile salt-dependent lipase probe associated with a very poor bile salt-dependent lipase activity and protein suggests either that these mRNA are very unstable or that they are poorly translated into an active pancreatic bile salt-dependent lipase.

Animals↗

PubMed1982

Plasma concentrations of testosterone and dihydrotestosterone during perinatal development in male and female ferrets.

Concentrations of testosterone (T) and 5 alpha-dihydrotestosterone (DHT) were measured in plasma collected from male and female ferrets at eight perinatal ages, spanning the period when behavioral sexual differentiation occurs in this species. Concentrations of T were significantly higher in males than in females 5 days before birth (day -5) and on postnatal days 10, 15, and 40. Plasma concentrations of DHT were equivalent in both sexes at all ages. In males, mean plasma T (2,278 pg/ml) and DHT (1,989 pg/ml) concentrations were highest on day -5, and declined significantly by postnatal day 5. In females, plasma concentrations of T (1,220 pg/ml) were highest on the day of birth, whereas concentrations of DHT (1,896 pg/ml) were highest on day -5; both declined significantly by postnatal day 5. The mean concentrations of T and DHT in sera from reproductively active adult male ferrets were 26,019 and 888 pg/ml, respectively, whereas sera from seasonally quiescent males contained 2,976 pg/ml T and 252 pg/ml DHT. The results demonstrate that circulating concentrations of T are significantly higher in male than in female ferrets at those neonatal ages when, in other experiments, T administration to females permanently augmented their ability to display masculine coital behavior in adulthood.

Age Factors↗

PubMed1988

Effect of birth on plasma testosterone, brain aromatase activity, and hypothalamic estradiol in male and female ferrets.

The present studies examined the patterns of circulating testosterone (T) within 0-24 h after birth in male and female ferrets along with concomitant changes in neural aromatase activity and hypothalamic concentrations of estradiol (E2). Plasma and brain samples were obtained 0 and 2 h (cesarean delivery) or 0, 2, 12, and 24 h (natural delivery) after birth. Plasma T levels were significantly higher in male neonates 2 h after birth than at 0 h in both cesarean-delivered (9.48 +/- 1.25 vs. 3.37 +/- 0.60 ng/ml) and naturally delivered (19.28 +/- 2.94 vs. 5.13 +/- 1.93 ng/ml) ferrets, while female neonates showed no significant changes in T over these sampling times. T levels had returned to 0 h levels by 12 h in naturally delivered males. T was significantly lower in females than in males 0, 2, and 24 h after natural delivery, whereas T levels were equivalent in males and females immediately after cesarean delivery. Male kits kept on a heating pad for 2 h after natural delivery had lower plasma T levels than males that were left with their mothers over this same period. Brain aromatase activity in anterior hypothalamus-preoptic area, medial basal hypothalamus (MBH), temporal lobe, and cerebral cortex was equivalent in males and females at all postpartum ages, regardless of whether delivery occurred by cesarean section or naturally. However, in naturally delivered kits of both sexes significant elevations in aromatase activity occurred in MBH and temporal lobe 24 h postpartum. Finally, E2 concentrations in anterior hypothalamus-preoptic area and MBH were equivalent 0 and 2 h postpartum in males and females, regardless of whether they were delivered naturally or by cesarean section. The observed postnatal elevation in T may contribute to brain and behavioral sexual differentiation of male ferrets. It is unclear, however, whether such an effect of T depends on its neural aromatization to E2.

Animals↗

PubMed1991

Differential regulation of brain aromatase by androgen in adult and fetal ferrets.

The contribution of androgens to the regulation of aromatase activity (AA), measured by quantifying the in vitro formation of [3H]estrone from 19-[3H]hydroxyandrostenedione precursor, was studied in equivalent microdissected brain regions of adult and fetal ferrets. In adulthood, AA was similar in the bed nucleus of the stria terminalis, medial (M) and lateral (L) preoptic area (POA), medial (MA) and lateral amygdala (LA), ventromedial hypothalamus (VMH), and parietal cortex of gonadectomized males and females given no concurrent steroid treatment. Daily sc injections of the androgen dihydrotestosterone propionate significantly stimulated AA in MPOA, MA, and VMH of adult males and in MA of females; a similar trend was seen in MPOA and VMH of females. By contrast, no evidence of androgenic regulation of AA was obtained in these three brain regions microdissected from fetuses killed on embryonic day 35 (E35; 41-day gestation). Transplacental administration of the antiandrogen flutamide beginning on day E24 failed to affect AA in MPOA, LPOA, MA, LA, or parietal cortex, although this treatment significantly reduced AA in bed nucleus of the stria terminalis of fetal males. The results suggest that the responsiveness of aromatizing enzymes to androgenic induction is similar in several subcortical brain regions of adult ferrets of both sexes. In breeding males such an action of androgen may augment the neural production of estrogen, which has previously been implicated in the control of sexual behavior and the feedback regulation of LH secretion. By contrast, androgen apparently contributes minimally to the regulation of AA in brain regions of fetal ferrets, particularly in the MPOA, in which a sexually dimorphic nucleus differentiates in males around E37 in response to estrogen produced locally.

Androgens↗

PubMed1999

Changes in mediobasal hypothalamic gonadotropin-releasing hormone messenger ribonucleic acid levels induced by mating or ovariectomy in a reflex ovulator, the ferret.

The ferret is a reflex-ovulating species in which receipt of an intromission induces a prolonged (+/- 12 h) preovulatory LH surge in the estrous female. This LH surge is probably stimulated by a large release of GnRH from the mediobasal hypothalamus (MBH). In Exp 1 we asked whether GnRH messenger RNA (mRNA) levels increase in response to mating so as to replenish the MBH GnRH stores needed to sustain the preovulatory LH surge. Estrous females were killed 0, 0.25, 0.5, 1, 3, 6, 14, or 24 h after the onset of a 10-min intromission from a male. Coronal brain sections ranging from the rostral preoptic area caudally to the posterior hypothalamus were processed for in situ hybridization using a 35S-labeled oligoprobe complementary to the human GnRH-coding region. We found no evidence of increased MBH GnRH mRNA levels during the ferret's mating-induced preovulatory LH surge. Instead, the number of GnRH mRNA-expressing cells dropped significantly in the arcuate region beginning 6 h after onset of intromission and remained low thereafter. Furthermore, cellular GnRH mRNA levels decreased in the arcuate region toward the end of the preovulatory LH surge. In Exp 2 we asked whether ovarian hormones regulate MBH GnRH mRNA levels in the female ferret. Ovariectomy of estrous females significantly reduced the number of GnRH mRNA-expressing cells in the arcuate region. This decrease was probably not due to the absence of circulating estradiol. Gonadally intact anestrous females had levels of MBH GnRH mRNA similar to those in estrous females even though plasma estradiol levels were equally low in anestrous females and ovariectomized females. Ovarian hormones other than estradiol may stimulate MBH GnRH mRNA levels in anestrous and estrous females.

Animals↗

PubMed1991

Antiemetic effects of YM060, a potent and selective serotonin (5HT)3-receptor antagonist, in ferrets and dogs.

YM060, (R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole hydrochloride, is a new serotonin (5HT)3-receptor antagonist. We examined the effects of YM060 on chemotherapeutic agent-, apomorphine- and copper sulfate-induced emesis. Intravenous YM060 potently prevented cisplatin (10 mg/kg, i.v.)-induced emesis with ED50 values of 0.06 (0.05-0.07) micrograms/kg, i.v. in ferrets. Based on the ED50 values, YM060 was 300, 20 and 100 times more potent than ondansetron, granisetron and the S-isomer of YM060, respectively. The relative potencies of these drugs described above were similar to those in the previously reported 5HT3-receptor antagonism. YM060 given orally also potently inhibited cisplatin (10 mg/kg, i.p.)- and cyclophosphamide (200 mg/kg, i.p.)-induced emesis in ferrets with ED50 values of 0.1 (0.09-0.11) and 0.02 (0.16-0.27) micrograms/kg, p.o., respectively. All tested 5HT3-receptor antagonists including YM060 failed to prevent apomorphine (0.1 mg/kg, s.c.)-induced emesis in dogs and copper sulfate (1%, 10 ml, p.o.)-induced emesis in ferrets. Our data indicate that YM060 is a highly potent inhibitor of chemotherapeutic agent-induced emesis and that the antiemetic effect of YM060 may be depend on 5HT3-receptor antagonism.

Administration, Oral↗

PubMed1993

Practical venipuncture techniques for the ferret.

As the number of ferrets (Mustela putorius furo) used in research and kept as pets continues to rise, so does the need for simple, humane research and diagnostic techniques. We have developed venipuncture methods for the ferret utilizing the jugular and cephalic veins. Using these methods it is possible to repeatedly sample moderate volumes of blood and to perform intravenous injections in both conscious and sedated ferrets.

Animals↗

PubMed1994

A technique for catheterization of the urinary bladder in the ferret.

The technique of catheterization of the urinary bladder, an important clinical skill for the diagnosis of urinary tract disorders, has not been described for the ferret. The bladder was catheterized in 23 ferrets (10 intact females; 11 spayed females; and 2 intact males) using a 3 1/2 French, red rubber urethral catheter fitted with a steel wire stylet. Ferrets were anaesthetized with isoflurane or ketamine (30 mg/kg IM) and xylazine (3 mg/kg IM). Females were positioned in ventral recumbency with the rear quarters elevated by a rolled surgical towel. The urethra was catheterized by direct visualization of the external urethral orifice using a vaginal speculum. The orifice was approximately 1 cm cranial to the clitoral fossa on the ventral floor of the vestibule. Blind passage was used in several spayed females. In males, the distal end of the penis was exteriorized from the prepuce and the external urethral orifice cannulated without stylet. No difficulty was encountered in advancing the catheter past the os penis. This catheterization technique allows urinary tract access for urine collection, pneumocystography, contrast cystography, double contrast cystography, and urine output determination in pharmacologic studies or in critical care of debilitated animals.

Anesthesia↗

PubMed2003

Adrenal cortical carcinomas with myxoid differentiation in the domestic ferret (Mustela putorius furo).

A total of 15 adrenocortical carcinomas with myxoid differentiation from 15 ferrets were evaluated in this retrospective study. Six of these ferrets (40%) either were euthanatized or died due to invasive and/or metastatic disease. The myxoid component was a variable part (between 5% and 95%) of the adrenal cortical neoplasm and consisted of sheets and cords of small, polygonal neoplastic cells that formed lumenlike spaces. Such spaces contained a variable amount of alcian blue (pH 2.5)-positive mucinous product (i.e., acidic mucopolysaccharides). Neoplastic cells were negative for the argentaffin reaction, but immunohistochemically they were strongly positive for vimentin and alpha-inhibin and lightly positive for synaptophysin. Proliferating cell nuclear antigen (PCNA)-labeling indices (LI) of adrenal cortical neoplastic cells within the myxoid component of the neoplasm were significantly elevated (P < 0.05) compared with those of typical neoplastic adrenal cortical cells or the adjacent nonneoplastic zona reticularis. Ultrastructurally, cells in the myxoid component exhibited a typical adrenocortical phenotype characterized by cytoplasmic lipid vacuoles, prominent rough and smooth endoplasmic reticulum, and zonula adherens. This lesion was interpreted as an adrenal cortical carcinoma with myxoid differentiation and appeared to be highly malignant based on PCNA LI, rate of invasion into adjacent tissue, and metastasis (6/15). This report is the first description of this histologic variant in the ferret, which morphologically resembled the rare myxoid variant of adrenocortical carcinoma described in humans.

Adrenal Cortex Neoplasms↗

PubMed2006

Renal tubular-cell neoplasms in black-footed ferrets (Mustela nigripes)--38 cases.

Thirty-eight cases of renal tubular cell neoplasms were diagnosed in 184 captive, adult (>1-year-old), black-footed ferrets (Mustela nigripes) examined from 1985 to 1996. This prevalence (20.7%) is one of the highest reported for this neoplasm in a population of animals. These tumors rarely metastasized (1/38), and usually were incidental postmortem findings, associated clinical disease being present in only 3 (8%) of the 38 cases. The prevalence of renal tubular cell neoplasms found at postmortem examination increased linearly with age, up to 67% in ferrets >8 years old. Both males (prevalence = 19%) and females (prevalence = 24%) were affected. Multiple renal tumors were common, and seven ferrets (18.4% of affected animals) had bilateral tumors. The cause of this neoplastic syndrome could not be determined. Since most of the animals affected by this condition were in their postreproductive years of life, the impact of this neoplastic syndrome on the captive propagation of this species is negligible.

Aging↗

PubMed2004

Molecular organization of the ferret visual thalamus.

The visual system encodes and deciphers information using parallel, anatomically segregated, processing streams. To reveal patterns of gene expression in the visual thalamus correlated with physiological processing streams, we designed a custom ferret cDNA microarray. By isolating specific subregions and layers of the thalamus, we identified a set of transcription factors, including Zic2, Islet1, and Six3, the unique distribution profiles of which differentiated the lateral geniculate nucleus (LGN) from the associated perigeniculate nucleus. Within the LGN, odd homeobox1 differentiated the A layers, which contain X cells and Y cells, from the C layers. One neuron-specific protein, Purkinje cell protein 4 (PCP4), was strongly expressed in Y cells in the ferret LGN and in the magnocellular layers of the primate LGN. In the ferret LGN, PCP4 expression began as early as postnatal day 7 (P7), suggesting that Y cells are already specified by P7. These results reveal a rich molecular repertoire that correlates with functional divisions of the LGN.

Animals↗

PubMed1986

Acute effects of GnRF-induced gonadotrophin secretion upon ovarian steroid secretion in the ferret.

The effects of an increase in endogenous gonadotrophin secretion on the production of oestradiol, progesterone, androstenedione and testosterone by the ovaries of anaesthetized anoestrous and oestrous ferrets were followed. Gonadotrophin secretion was enhanced by the injection of gonadotrophin releasing factor (GnRF), and serial blood samples were collected over 9 h for hormone assay. Thyrotrophic hormone releasing factor (TRF) or acetic acid were injected for control purposes. The plasma content of oestradiol in oestrous females was significantly higher than during anoestrus, but secretion of this steroid was not increased by any means. The plasma concentration of progesterone in anoestrous females was significantly higher than during oestrus. It was increased by GnRF in anoestrous ferrets and less markedly in oestrous females. The plasma concentration of androstenedione was raised by GnRF to a greater extent during anoestrus than during oestrus. Testosterone was present in higher concentration in the plasma during anoestrus than during oestrus, and the level was increased by GnRF administration. These findings indicate that the ovaries of the anoestrous ferret secrete significant quantities of steroid hormones, and that they respond readily to gonadotrophic hormone.

Androstenedione↗

PubMed1993

Reference values for organ weight, hematology and serum chemistry in the female ferret (Mustela putrius furo).

Organ Weight, hematologic and blood chemistry values were determined to establish reference values in the female ferret. Organ weight per kg body weight was calculated for various organs. Body surface area (BSA) was also determined by the direct method, and K values (constant) were calculated. The K value was 3.48 in the Dubois and Dubois equation, and 9.69 in the Meeh-Rubner equation. Blood samples were used to record 10 hematologic and 57 serum (plasma) chemistry values, and 7 immunological parameters. Among hematologic values, values whose coefficient of variation (cv) exceeded 30% were RBC, WBC and PLT. In blood chemistry, the CV of gamma-G, UA, ZTT, GPT, gamma-GTP, MAO, ALD and IgG exceeded 30%. In the total amino acid analysis, only the CV of TAU exceeded 30%. Electrophoretograms of amylase and CPK isozyme were quite different from those of humans. Although 1-MEHIS, 3-MEHIS and CAR have not been detected or are present in trace amounts in human plasma, concrete values were detected in female ferret plasma. Hematologic and serum chemistry values were in general agreement with normal values seen in cats and dogs. However, the alpha 1-G percentage, and ALP and amylase activities were lower than the corresponding values in cats and dogs. The RBC count, RET-C percentage and LDH activities were higher than in cats and dogs. Since there have been no comprehensive articles on reference values for the female ferret, the present report contributes to studies that involve this animal as an experimental model.

Alanine Transaminase↗