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The pathogenesis of respiratory syncytial virus infection in infant ferrets.

The infant ferret is susceptible to respiratory syncytial virus infection in both the upper and lower respiratory tracts. In the nose, viral replication is restricted to the surface respiratory epithelium in the nasal passages and turbinates. In the lungs, viral replication is of a lower order of magnitude and is localized in the alveolar cells. The pattern of viral replication in nasal tissues is independent of the age of the animal at infection, whereas the pattern in lung tissues shows a striking age dependence, with viral replication progressively decreasing as a function of age. Thes age dependence appears to be due to an intrinsic age-related mechanism yet to be defined. We feel that the infant ferret is an acceptable model for the study of respiratory syncytial virus disease and that the study of age dependence observed in ferrets may allow elucidation of the mechanisms involved in the age dependence seen in humans.

Aging↗

Cyclic GMP inhibits the inotropic response to alpha 1-adrenoceptors in the papillary muscle of the ferret.

The physiological role of cyclic GMP in the heart remains controversial. In the present study we investigated the interaction between a number of agents known to increase the level of cyclic GMP in the myocardium and alpha 1-adrenergic stimulation in isolated preparations of cardiac papillary muscle in the ferret. Inotropic responses to the cumulative addition of phenylephrine were measured in papillary muscles of the ferret in the absence and presence of 1 microM sodium nitroprusside, 1 microM atrial natriuretic peptide, 0.1 microM substance P (which stimulates the release of nitric oxide from endocardial endothelium) or 1 microM 8-bromo-cyclic GMP. In parallel experiments using similar preparations, alpha 1-induced hydrolysis of phosphatidylinositol was assessed by measuring changes in the levels of inositol 1,4,5-trisphosphate in response to 10 microM phenylephrine in the absence and presence of the same agents that increase the level of cyclic GMP. Phenylephrine (0.001-10 microM) induced a concentration-dependent positive inotropic effect that was significantly inhibited by each of the agents that increase cyclic GMP. Phenylephrine (10 microM) induced an approximately three-fold rise in the level of inositol trisphosphate in the myocardium, which was likewise significantly inhibited by each of the agents that increase cyclic GMP. These data show that agents that increase the level of cyclic GMP in the myocardium inhibit both the positive inotropic and phosphatidylinositol response to alpha 1-stimulation in isolated preparations of papillary muscle in the ferret.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗

FEEDING OF FERRETS WITH THE RAW MEAT AND LIVER OF CHICKENS CHRONICALLY POISONED WITH TOXIC GROUNDNUT MEAL.

Chickens were fed a ration containing 30 per cent of toxic groundnut meal for up to six weeks. The concentration of aflatoxin (toxic metabolites of Aspergillus flavus) in the above ration was 3.06 p.p.m. At the end of 2nd, 4th or 6th week the birds were killed. The meat was removed from the bones and put through a meat grinder. The livers of three groups were pooled together. Three control groups of birds kept on commercial pellets were treated similarly. Female ferrets, two years of age, were used in the present study. They were divided into four groups. The first three groups were given for one month meat from chickens fed the toxic ration for 2, 4, and 6 weeks, respectively. Each of these three groups contained one control ferret that was fed with the meat of chickens fed a commercial ration for a similar period of time. One half of the 4th group was fed pooled liver from intoxicated birds and one half was fed liver from control birds. No significant changes in the ferret tissues were observed as a consequence of feeding them with the meat or liver from the chickens chronically poisoned with toxic groundnut meal.

Aflatoxins↗

Age-related differences in vascular effects of pentoxifylline in isolated perfused ferret lungs.

We have determined the magnitude and sites of action of pentoxifylline (PTX), a methylxanthine derivative, in the adult and 3- to 4-week old ferret pulmonary circulation. Lungs of 8 ferrets, four 3- to 4-week-old and 4 adult, were isolated and perfused with blood. During perfusion, blood flow was kept constant, as were airway and left atrial pressures (6 and 8 cm H2O respectively, zone 3 conditions). In all lungs, pulmonary artery pressure was measured continuously and the circulation was partitioned into arteries, microvessels and veins, by measurement of pressures in 20-50 microns diameter subpleural arterioles and venules using the micropipette-servonulling method. Pressures were obtained in each lung during baseline, after vasoconstriction with hypoxia, and again after the infusion of PTX, 20 mg/kg, during hypoxia. We found that with hypoxia, total vascular resistance increased by approximately 90% in both adult and neonatal lungs; arterial and venous resistances increased by 100-180% in both age groups, with little change in microvascular resistance. PTX resulted in a significant decrease in total vascular resistance, due to a decrease in resistance in both arteries and veins. The decrease in resistance with PTX was greater in adult lungs (of the increase in resistance induced by hypoxia, 80% was eliminated by PTX) than in 3- to 4-week old lungs (51% elimination of tone induced by hypoxia). This difference was mainly due to a smaller reduction in arterial resistance with PTX in 3- to 4-week-old lungs. We conclude that PTX is a powerful pulmonary vasodilator in ferrets and that its effectiveness as a vasodilator depends on the age of the animal, the older animal showing greater responsiveness.

Aging↗

DAT-582, a novel serotonin3 receptor antagonist, is a potent and long-lasting antiemetic agent in the ferret and dog.

The antiemetic effects of a novel serotonin3 receptor antagonist, DAT-582 [(6R)-(-)-N-[1-methyl-4-(3-methylbenzyl)hexahydro-1H-1,4- diazepin-6-yl]-1H-indazole-3-carboxamide dihydrochloride] were compared with those of the existing serotonin3 receptor antagonists, ondansetron and granisetron, in experimental animals. In ferrets, DAT-582 (0.003-0.1 mg/kg i.v. twice) dose-relatedly prolonged the latency to the first emetic episode and decreased the number of emetic episodes induced by cisplatin (10 mg/kg i.v.). DAT-582 was more potent than ondansetron or granisetron in inhibiting the emesis. The emesis induced by cyclophosphamide (150 mg/kg i.v.), doxorubicin (15 mg/kg i.v.) or combination of cisplatin (3.3 mg/kg i.v.), cyclophosphamide (50 mg/kg i.v.) and doxorubicin (5 mg/kg i.v.) was also inhibited by DAT-582 (0.1 mg/kg i.v., twice). When administered 2 hr before cisplatin in ferrets, DAT-582 decreased markedly the number of emetic episodes induced by cisplatin at 0.1 mg/kg i.v., whereas ondansetron and granisetron were without effect even at 0.3 mg/kg i.v. DAT-582 (0.1 mg/kg i.v.), when administered in the ferrets which were vomiting after cisplatin, immediately and almost completely blocked the subsequent emesis. Furthermore, DAT-582 (0.1 mg/kg i.v.) completely inhibited the cisplatin (3 mg/kg i.v.)-induced emesis for 24 hr after cisplatin in three of five dogs. In addition, DAT-582, at 0.3 and 1 mg/kg, p.o., inhibited the cisplatin-induced emesis in dogs. However, DAT-582, even at 3 mg/kg s.c., did not inhibit the apomorphine (0.3 mg/kg,, s.c.)-induced emesis in dogs, or the nicotine-, copper sulfate- or motion stimulus-induced emesis in the house musk shrew, Suncus Murinus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Endogenous arachidonic acid metabolism by calcium ionophore stimulated ferret lungs. Effect of age, hypoxia.

We have studied the metabolism of endogenous arachidonic acid by isolated perfused lungs of ferrets when stimulated with calcium ionophore A23187 at two ages, neonatal (2- to 3-week-old) and adult (greater than 6 months). We have also determined the effect of hypoxia on lung metabolism of arachidonic acid in the two age groups. Lungs were perfused with Kreb's bicarbonate buffer in a recirculating system and eicosanoid production was stimulated by addition of A23187 (5 microM). Eicosanoids produced were measured in perfusate and lung homogenate supernatant. Cyclooxygenase metabolites; PGE2, TxB2 and 6-keto-PGF1 alpha were measured by radioimmunoassay and 5-lipoxygenase metabolites, leukotrienes; LTB4, LTC4, LTD4 and LTE4 by high performance liquid chromatography. During normoxia, leukotriene production, LTC4 and LTB4, was 10- to 20-fold higher in neonatal than in adult lungs, but total amount of cyclooxygenase products measured was similar. Compared with adult lungs, neonatal lungs produced more 6-keto-PGF1 alpha, but produced less PGE2. There was no difference in TxB2 production by neonatal and adult lungs. Hypoxia increased the production of 5-lipoxygenase metabolites in adult lungs, with production of cyclooxygenase metabolites remaining unchanged, whereas hypoxia decreased all eicosanoid production in neonatal lungs. In summary, there are age-related differences in endogenous arachidonic acid metabolism by isolated ferret lungs when stimulated with calcium ionophore A23187 as well as age related differences in the effect of hypoxia on endogenous arachidonic acid metabolism in ferret lungs.

Aging↗

Pyloric adenocarcinoma in a ferret.

Pyloric adenocarcinoma was diagnosed in a ferret with clinical signs of gastric distention. The development of this tumor may be related to Helicobacter mustelae infection in the gastric mucosa of ferrets. Pyloric adenocarcinoma has only recently been reported in ferrets and should be considered as a differential diagnosis for gastric distention in this species.

Adenocarcinoma↗

Comparison of sevoflurane and isoflurane in domestic ferrets (Mustela putorius furo).

Isoflurane anesthesia is commonly used in ferrets for routine examinations and diagnostics. Sevoflurane is now being used as well, but there have been no studies to date directly comparing these agents in domestic ferrets. A prospective study was designed to evaluate the quality and speed of anesthetic induction and recovery using isoflurane and sevoflurane in ferrets. In addition effects on heart rate, blood pressure and packed cell volume were also recorded. No significant differences were noted between anesthetic agents.

Anesthetics, Inhalation↗

Further studies on the neonatal ferret model of infection and immunity to and attenuation of human parainfluenza viruses.

Earlier we reported on the susceptibility via the intranasal route of inoculation of newborn ferrets to infection by wild and serially egg passaged parainfluenza type 3 virus. The wild type consistently induced fatal infection whereas with serial egg passage, mortality rate decreased while the degree of infectivity remained the same. This attenuation was accompanied by a change in capacity to induce interferon and decreased growth in human and primate cell cultures. The present work reports, similarly, on the susceptibility of newborn ferrets to wild and serially egg passaged parainfluenza types 1 and 2. Wild type infections caused significantly greater mortality than did egg passaged materials, although infectivity rates were approximately the same. Wild and egg passaged strains produced silent infections in adult ferrets and induced specific circulating hemagglutinin inhibiting antibodies. Newborn offspring of dams inoculated with wild or egg passaged viruses resisted challenge with wild virus. The apparent attenuation of the wild type virus with serial egg passage viruses resisted challenge with wild virus. The apparent attenuation of the wild type virus with serial egg passage was correlated with alteration in cell culture host range and capacity to induce interferon. The low and mid level passages of types 1 and 3 were the subject of clinical vaccination trials in man in four age groups: 18-35 years, 14-16 years and 6-12 years. The clinical and serologic results of these studies will be reported elsewhere.

Animals↗

Delayed neurotoxic effects of bis (1-methylethyl) phosphorofluoridate (DFP) in the European ferret: a possible mammalian model for organophosphorus-induced delayed neurotoxicity.

This study examined the effects of the organophosphorus delayed neurotoxicant bis (1-methylethyl) phosphorofluoridate (DFP) on the central nervous system of the European ferret. Animals received subcutaneous injections of either 2 or 4 mg DFP/kg b.w. The extent of neuropathology was determined by the Fink-Heimer method, the activities of neuropathy target esterase (NTE) and cholinesterase (ChE) by enzyme assay methods, and the severity of clinical signs by a graded scale. In ferrets injected with 4 mg DFP/kg b.w., dense axonal and terminal degeneration were noted at 21 and 28 days post-DFP in the gracile, inferior vestibular, and lateral reticular nuclei, medial and dorsal accessory nuclei of the inferior olive, and in cerebellar folia I-IV. Degeneration was also noted in laminae VI-VII throughout most of the spinal cord and in the ventral motor nucleus at the level of the cervical enlargement. Both NTE and ChE activities were maximally inhibited at 6 hr post-dosing. NTE activity returned to control levels by 4 days while ChE activities reached control levels at 21 days. Clinical signs at 21 and 28 days post-DFP ranged from slight hindlimb weakness to severe ataxia or hindlimb paralysis. Less severe degeneration and clinical signs were noted in the animals exposed to 2 mg DFP/kg b.w. These findings indicate that the European ferret may be a model species for assessing the effects of organophosphorus delayed neurotoxicants.

Animals↗

Experimental infectious bovine rhinotracheitis virus infections of English ferrets (Mustela putorius furo L).

Intranasal and intraperitoneal exposure of English ferrets (Mustela putorius furo L) to infectious bovine rhinotracheitis virus caused acute and chronic infections of the respiratory tract. The clinical syndrome was characterized by sneezing, coughing, and anorexia from postexposure days (PED) 3 to 7. Mucopurulent exudate was observed in the posterior nares and pharyngeal area of ferrets euthanatized on PED 4 and 8. The virus was readily recovered from the turbinates, respiratory tract epithelium of the pharynx, retropharyngeal lymph nodes, trachea, lungs, and spleen of animals euthanatized on PED 4, but only from the respiratory tract epithelium of the pharynx in ferrets euthanatized on PED 8 and 12. Results of histopathologic studies revealed an acute suppurative pharyngitis in animals euthanatized on PED 4 and 8. Recrudescence of chronic infection could be elicited by daily intraperitoneal injections of 4.0 mg of dexamethasone. However, daily administration of 2.0 mg of dexamethasone intraperitoneally did not cause more severe clinical disease. Results of serologic studies revealed serum antibody profiles comparable with those expected in experimentally exposed cattle.

Animals↗

Dracunculus insignis in ferrets: comparison of inoculation routes.

Three routes of inoculation were compared to determine the best method to infect ferrets with Dracunculus insignis. The traditional method of administering infected cyclops containing L3s through gavage was compared to intraperitoneal (i.p.) and subcutaneous (s.c.) inoculation of L3s. Ten of 18 (56%) gavaged ferrets became infected after receiving copepods containing approximately 100 L3s each; 44 adult worms were recovered from these 10 animals. Twenty-one of 28 (75%) animals inoculated with 50 L3s each became infected i.p.; 92 adult worms were recovered from the positive animals. Four of 5 (80%) ferrets given subcutaneous inoculations of 50 L3s became infected; only 6 worms were recovered from these 4 animals. Inoculation of larvae via the i.p. or s.c. route greatly simplifies the infection procedure and produces more consistent results. A simple procedure is described, which permits rapid recovery of L3s to be used in the i.p. or s.c. inoculations.

Animals↗

Derivation of gnotobiotic ferrets: perinatal diet and hand-rearing requirements.

A procedure is described which has resulted in successful gnotobiotic derivation of the domestic ferret. The most critical element of this hand-rearing procedure was found to be diet, with ferret milk being required for at least the first 7 days. Puppy milk replacer was phased in during the next 10 days, and enriched cow's milk sufficed thereafter. Around-the-clock sip-feeding with fire-polished Pasteur pipettes was necessary at intervals gradually increasing from 1 to 1.5 hours at birth to 3 hours by day 21. Temperature regulation was accomplished with an electric heating pad placed eccentrically under towel bedding to provide a 30 degrees-40 degrees C gradient, along which the kits positioned themselves to their own comfort. Techniques are described for minimizing fatalities due to dehydration, milk-aspiration pneumonia, underfeeding, overfeeding, gut stasis and obstipation. Internal hemorrhage, the greatest single cause of mortality in this study, manifested at day 13 and involved all kits by day 17. Despite immediate vitamin K1 dietary supplementation, five of the seven remaining kits died of hemorrhage by day 19. Around day 50, the two surviving kits were weaned from milk to dry commercial cat and ferret diets supplemented with vitamins K, C, A, D, E and B-complex and were reared to adulthood on this diet.

Animal Nutritional Physiological Phenomena↗

Hyperinsulinism and hypoglycemia associated with pancreatic islet cell tumor in a ferret.

Pancreatic islet cell tumor causing hypoglycemia and hyperinsulinism was diagnosed in a ferret with a history of progressive neurologic dysfunction. The diagnosis was suspected by the findings of hypoglycemia when the ferret was not fed, hyperinsulinism, and an amended insulin/glucose ratio approaching infinity. A focal pancreatic mass was removed by partial pancreatectomy, resulting in euglycemia and the resolution of clinical signs. Histologic diagnosis of the pancreatic mass was consistent with islet cell tumor (insulinoma). The ferret remained clinically normal for 8 months, but died after recurring episodes of hyperglycemia and glucosuria. Necropsy revealed no evidence of islet cell neoplasia involving the pancreas or other structures.

Adenoma, Islet Cell↗

Alterations in the course of and histopathologic response to influenza virus infections produced by enflurane, halothane, and diethyl ether anesthesia in ferrets.

Alterations in the course of and histopathologic response to influenza viral infections by halothane, enflurane, and diethyl ether anesthesia were evaluated in ferrets. There were no significant differences in the incidence and duration of lethargy, pyrexia, rhinorrhea, or sneezing in infected animals given one of the three anesthetic agents under investigation, compared with those receiving no anesthesia. There were no differences in lung pathology in infected animals given one of the three anesthetic agents, or no anesthesia, though histopathologic changes in the nasal turbinates were significantly greater in ferrets given enflurane. This study suggests that general anesthesia administered to ferrets infected with influenza virus carries minimal morbidity, although enflurane anesthesia was found to produce greater histopathologic changes than the other agents.

Anesthesia, Inhalation↗

Insulinoma in a ferret.

Insulinoma was diagnosed in a 7-year-old female ferret examined because of generalized seizures, intermittent paraplegia, and abnormal behavior. Low serum glucose, high serum insulin, and infinite amended insulin/glucose ratio values in this ferret supported the clinical diagnosis of insulinoma. Histologic examination of the pancreas confirmed the diagnosis of insulinoma. The clinical signs and laboratory evaluations in this case and in a previously reported case of insulinoma in a ferret were consistent with variations reported in dogs with insulinoma.

Adenoma, Islet Cell↗