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insulin glargine treatment of a ferret with diabetes mellitus.a 7.5-year-old spayed female ferret was evaluated because of weight loss despite a good appetite. pancreatic insulinoma had been diagnosed at another animal hospital on the basis of detection of low blood glucose concentration on 1 occasion; however, concurrent determination of blood insulin concentration was not performed. the ferret had been treated sc with methylprednisolone acetate (unknown dosage) every 30 days for 2 years. no follow-up data regarding blood glucose concentration were availa ...201223176242
scientific investigations into febrile reactions observed in the paediatric population following vaccination with a 2010 southern hemisphere trivalent influenza vaccine.during the 2010 southern hemisphere (sh) influenza season, there was an unexpected increase in the number of febrile reactions reported in the paediatric population in australia shortly after vaccination with the csl 2010 trivalent influenza vaccine (tiv) compared to previous seasons. a series of scientific investigations were initiated to identify the root cause of these adverse events, including in vitro cytokine/chemokine assays following stimulation of adult and paediatric whole blood, as we ...201223063831
deafferentation-induced plasticity of visual callosal connections: predicting critical periods and analyzing cortical abnormalities using diffusion tensor imaging.callosal connections form elaborate patterns that bear close association with striate and extrastriate visual areas. although it is known that retinal input is required for normal callosal development, there is little information regarding the period during which the retina is critically needed and whether this period correlates with the same developmental stage across species. here we review the timing of this critical period, identified in rodents and ferrets by the effects that timed enucleat ...201223213572
mapping pitch representation in neural ensembles with fmri.functional magnetic resonance imaging (fmri) in humans and macaques allows a test of the hypothesis that there is a specialized neural ensemble for pitch within auditory cortex: a pitch center. fmri measures the blood oxygenation level-dependent (bold) response related to regional synaptic activity (logothetis et al., 2001). the distinction between synaptic activity and spike firing, and species differences encourage caution when comparing bold activity in humans and macaques to recordings from ...201223015424
reference intervals and working ferrets. 201223144096
determination of axonal and dendritic orientation distributions within the developing cerebral cortex by diffusion tensor imaging.as neurons of the developing brain form functional circuits, they undergo morphological differentiation. in immature cerebral cortex, radially-oriented cellular processes of undifferentiated neurons impede water diffusion parallel, but not perpendicular, to the pial surface, as measured via diffusion-weighted magnetic resonance imaging, and give rise to water diffusion anisotropy. as the cerebral cortex matures, the loss of water diffusion anisotropy accompanies cellular morphological differenti ...201221768045
wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the 'runner's high'.humans report a wide range of neurobiological rewards following moderate and intense aerobic activity, popularly referred to as the 'runner's high', which may function to encourage habitual aerobic exercise. endocannabinoids (ecbs) are endogenous neurotransmitters that appear to play a major role in generating these rewards by activating cannabinoid receptors in brain reward regions during and after exercise. other species also regularly engage in endurance exercise (cursorial mammals), and as h ...201222442371
a novel computerized system for thermal stimulation of tooth in ferrets.a dual thermal and electrical stimulator was developed to examine the central pathways that transmit noxious stimuli for intact dentition. this system allows computer-controlled stimulation of the canines of ferrets with either noxious heat or electrical stimuli. a set of in vitro studies demonstrated that the application of thermal stimuli to an intact tooth can produce pulpal temperatures above 43 °c, which is perceived as a painful stimulus in humans. in a set of in vivo studies, it was demon ...201222001221
a new orally active, aminothiol radioprotector-free of nausea and hypotension side effects at its highest radioprotective doses.a new aminothiol, prc-210, was tested for orally conferred radioprotection (rats, mice; 9.0 gy whole-body, which was otherwise lethal to 100% of the animals) and presence of the debilitating side effects (nausea/vomiting, hypotension/fainting) that restrict use of the current aminothiol, amifostine (ethyol, wr-2721).201222330992
endogenous lentiviruses in the ferret genome.by screening 74 chordate genomes for endogenous lentiviruses using pol sequences of exogenous lentiviruses as a reference, we identified a novel endogenous lentivirus in the genome of the ferret (mustela putorius furo). phylogenetic analysis suggested that the ferret endogenous lentivirus, denoted elvmpf, diverged early in the evolution of the mammalian lentiviruses, although with a lack of resolution at key nodes. these data support the notion that lentiviruses have evolved on timescales of mil ...201222238305
echocardiographic and electrocardiographic findings in client-owned ferrets: 95 cases (1994-2009).to characterize echocardiographic and ecg findings in ferrets (mustela putorius furo) evaluated at a clinical practice.201223176241
development of cerebral sulci and gyri in ferrets (mustela putorius).the present study aimed to clarify sulcation and gyration patterns in the developing cerebrum of ferrets. while the brain weight and fronto-occipital length of the cerebral hemisphere reached a plateau by postnatal day (pd) 42, the cerebral width reached a plateau at the rostral region by pd 21, and subsequently at the caudal region by pd 42. the ferret cerebrum already showed a convoluted surface with indentations of coronal and rostral suprasylvian sulci on pd 4. the presylvian and cruciate su ...201222925218
ventricular septal defect in a ferret (mustela putorius furo).a four-year-old, castrated male ferret (mustela putorius furo) was evaluated because of a one-year history of sporadic cough. on physical examination a grade 5 of 6 holosystolic murmur was audible over the right apex of the heart. radiographic findings included the presence of air bronchograms in apical lobes accompanied by pulmonary venous congestion. colour doppler echocardiography revealed a left-to-right shunting compatible with a ventricular septal defect. medical therapy was initiated at t ...201222861049
intramedullary lumbosacral teratoma in a domestic ferret (mustela putorius furo).an 18-month-old, female, spayed domestic ferret (mustela putorius furo) was presented for progressive hind limb paresis of 1 week duration. the ferret was mentally appropriate but cachexic and ataxic with neurological deficits, which localized the lesion to the lumbosacral region. a depression in the lumbosacral spine was associated with discomfort on palpation. results of whole body radiographs were consistent with an abnormal angle between vertebrae l6 and s1, which resulted in hyperflexion of ...201222529139
mechanisms underlying azimuth selectivity in the auditory cortex of the pallid bat.this study focused on mechanisms underlying azimuth selectivity in the primary auditory cortex (a1) of pallid bats. the pallid bat listens to prey-generated noise (5-35 khz) to localize and hunt terrestrial prey. the region of a1 tuned between 5 and 35 khz consists of two clusters of neurons distinguished by interaural intensity difference (iid) selectivity: binaurally inhibited (ei) and peaked. the first aim of this study was to use sequential dichotic/free-field stimulation to test the hypothe ...201222641192
auditory nerve fibre responses in the ferret.the ferret (mustela putorius) is a medium-sized, carnivorous mammal with good low-frequency hearing; it is relatively easy to train, and there is therefore a good body of behavioural data detailing its detection thresholds and localization abilities. however, despite extensive studies of the physiology of the central nervous system of the ferret, even extending to the prefrontal cortex, little is known of the functioning of the auditory periphery. here, we provide an insight into this peripheral ...201222694786
rolapitant (sch 619734): a potent, selective and orally active neurokinin nk1 receptor antagonist with centrally-mediated antiemetic effects in ferrets.nk1 receptor antagonists have been shown to have a variety of physiological and potential therapeutic effects in animal models and in humans. the present studies demonstrate that rolapitant (sch 619734, (5s)-8(s)-[[1(r)-[3,5 bis(trifluoromethyl)phenyl]ethoxy]methyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one) is a selective, bioavailable, cns penetrant neurokinin nk1 receptor antagonist that shows behavioral effects in animals models of emesis. in vitro studies indicate that rolapitant has a high a ...201222497992
man's underground best friend: domestic ferrets, unlike the wild forms, show evidence of dog-like social-cognitive skills.recent research has shown that dogs' possess surprisingly sophisticated human-like social communication skills compared to wolves or chimpanzees. the effects of domestication on the emergence of socio-cognitive skills, however, are still highly debated. one way to investigate this is to compare socialized individuals from closely related domestic and wild species. in the present study we tested domestic ferrets (mustela furo) and compared their performance to a group of wild mustela hybrids and ...201222905244
h5n1 influenza viruses: facts, not fear.the ongoing controversy over publication of two studies involving the transmission in ferrets of h5n1 (h5) subtype influenza viruses and the recommendations of the national science advisory board for biosecurity to redact key details in the manuscripts call for an examination of relevant scientific facts. in addition, there are calls in the media to destroy the viruses, curtail future research in this area, and protect the public from such "frightening" research efforts. fear needs to be put to ...201222308474
thymosin α1 continues to show promise as an enhancer for vaccine response.thymosin α1 (tα1) is an immune-modulating peptide that can be expected to improve response to vaccinations, as stimulated dendritic cells and t cells can act in concert to increase antibody production along with an improved cytotoxic response from the t cells themselves. tα1 demonstrated efficacy in preclinical studies; subsequently, it was shown to enhance response to vaccinations in difficult-to-treat populations, including individuals immune suppressed due to age or hemodialysis, and leading ...201223050813
modification and testing of a pneumatic dispensing device for controlled delivery of injectable materials.vocal fold (vf) injections of viscous materials are typically performed using hand-operated syringes or injection guns; however, these methods can be imprecise due to accumulation of pressure, effort-related tremor, and poor feedback regarding injection volume and rate.201222865123
working safely with h5n1 viruses.research on h5n1 influenza viruses has received much attention recently due to the possible dangers associated with newly developed avian h5n1 viruses that were derived from highly pathogenic avian viruses and are now transmissible among ferrets via respiratory droplets. an appropriate discussion, based on scientific facts about the risks that such viruses pose and on the biocontainment facilities and practices necessary for working safely with these viruses, is needed. selecting the right level ...201222396483
a triclade dna vaccine designed on the basis of a comprehensive serologic study elicits neutralizing antibody responses against all clades and subclades of highly pathogenic avian influenza h5n1 viruses.because of their rapid evolution, genetic diversity, broad host range, ongoing circulation in birds, and potential human-to-human transmission, h5n1 influenza viruses remain a major global health concern. their high degree of genetic diversity also poses enormous burdens and uncertainties in developing effective vaccines. to overcome this, we took a new approach, i.e., the development of immunogens based on a comprehensive serologic study. we constructed dna plasmids encoding codon-optimized hem ...201222496212
the potential of avian h1n1 influenza a viruses to replicate and cause disease in mammalian models.h1n1 viruses in which all gene segments are of avian origin are the most frequent cause of influenza pandemics in humans; therefore, we examined the disease-causing potential of 31 avian h1n1 isolates of american lineage in dba/2j mice. thirty of 31 isolates were very virulent, causing respiratory tract infection; 22 of 31 resulted in fecal shedding; and 10 of 31 were as pathogenic as the pandemic 2009 h1n1 viruses. preliminary studies in balb/cj mice and ferrets showed that 1 of 4 isolates test ...201222848544
pathogenicity and transmissibility of north american triple reassortant swine influenza a viruses in ferrets.north american triple reassortant swine (trs) influenza a viruses have caused sporadic human infections since 2005, but human-to-human transmission has not been documented. these viruses have six gene segments (pb2, pb1, pa, ha, np, and ns) closely related to those of the 2009 h1n1 pandemic viruses. therefore, understanding of these viruses' pathogenicity and transmissibility may help to identify determinants of virulence of the 2009 h1n1 pandemic viruses and to elucidate potential human health ...201222829764
de-novo transcriptome sequencing of a normalized cdna pool from influenza infected ferrets.the ferret is commonly used as a model for studies of infectious diseases. the genomic sequence of this animal model is not yet characterized, and only a limited number of fully annotated cdnas are currently available in genbank. the majority of genes involved in innate or adaptive immune response are still lacking, restricting molecular genetic analysis of host response in the ferret model. to enable de novo identification of transcriptionally active ferret genes in response to infection, we pe ...201222606336
neuroglobin of seals and whales: evidence for a divergent role in the diving brain.although many physiological adaptations of diving mammals have been reported, little is known about how their brains sustain the high demands for metabolic energy and thus o(2) when submerged. a recent study revealed in the deep-diving hooded seal (cystophora cristata) a unique shift of the oxidative energy metabolism and neuroglobin, a respiratory protein that is involved in neuronal hypoxia tolerance, from neurons to astrocytes. here we have investigated neuroglobin in another pinniped species ...201222864183
rare and new cumaceans (crustacea, peracarida) from the southern margin of the cap ferret canyon (bay of biscay).a new cumacean genus and species, ithyleucon sorbeigen. et sp. n., was described from material collected in the southern margin of the cap ferret canyon (bay of biscay, ne atlantic). although the new genus resembles pseudoleucon zimmer, 1903, in terms of the general aspect of the carapace and the pseudo-rostrum position, it shows important differences in the uropod structure and in the size of the antenna 1 accessory flagellum. in addition, some comments regarding the morphology of certain rare ...201223226964
engineering h5n1 avian influenza viruses to study human adaptation.two studies of h5n1 avian influenza viruses that had been genetically engineered to render them transmissible between ferrets have proved highly controversial. divergent opinions exist about the importance of these studies of influenza transmission and about potential 'dual use' research implications. no consensus has developed yet about how to balance these concerns. after not recommending immediate full publication of earlier, less complete versions of the studies, the united states national s ...201222722191
low pathogenic avian influenza isolates from wild birds replicate and transmit via contact in ferrets without prior adaptation.direct transmission of avian influenza viruses to mammals has become an increasingly investigated topic during the past decade; however, isolates that have been primarily investigated are typically ones originating from human or poultry outbreaks. currently there is minimal comparative information on the behavior of the innumerable viruses that exist in the natural wild bird host. we have previously demonstrated the capacity of numerous north american avian influenza viruses isolated from wild b ...201222675507
sylvatic plague vaccine: a new tool for conservation of threatened and endangered species?plague, a disease caused by yersinia pestis introduced into north america about 100 years ago, is devastating to prairie dogs and the highly endangered black-footed ferret. current attempts to control plague in these species have historically relied on insecticidal dusting of prairie dog burrows to kill the fleas that spread the disease. although successful in curtailing outbreaks in most instances, this method of plague control has significant limitations. alternative approaches to plague manag ...201222846964
mustelidae are natural hosts of staphylococcus delphini group a.according to the current taxonomy, the staphylococcus intermedius group (sig) comprises of at least three distinct species. while s. intermedius and s. pseudintermedius are associated with specific hosts (pigeons and dogs, respectively), the natural host of s. delphini remains unclear. we analysed 158 sig isolates from less studied animal species belonging to the order carnivora, including mink (n=118), fox (n=33), badger (n=6) and ferret (n=1). species identification was performed by nuc pcr in ...201222542523
adaptation of a chinese ferret badger strain of rabies virus to high-titered growth in bhk-21 cells for canine vaccine development.rabies virus strain jx08-45cc was derived from a chinese isolate (jx08-45) by serial passage in the bhk-21 cell line, reaching a titer of 10(8) tcid(50)/ml. jx08-45cc produced rabies in adult mice but was nonpathogenic in dogs after intramuscular injection. a comparison of the entire genomes of jx08-45 and jx08-45cc led to the identification of 17 nucleotide substitutions, resulting in seven amino acid changes in the mature g and l proteins. the immunogenicity of β-propiolactone-inactivated jx08 ...201222886183
transmission routes for nipah virus from malaysia and bangladesh.human infections with nipah virus in malaysia and bangladesh are associated with markedly different patterns of transmission and pathogenicity. to compare the 2 strains, we conducted an in vivo study in which 2 groups of ferrets were oronasally exposed to either the malaysia or bangladesh strain of nipah virus. viral shedding and tissue tropism were compared between the 2 groups. over the course of infection, significantly higher levels of viral rna were recovered from oral secretions of ferrets ...201223171621
canid progesterone receptors lack activation function 3 domain-dependent activity.progesterone regulates multiple behavioral, physiological, and pathological aspects of female reproductive biology through its two progesterone receptors (prs), pr-b and the truncated pr-a. pr-b is necessary for mammary gland development in mice and, compared with pr-a, is overall a stronger transactivator of target genes due to an additional activation function 3 (af3) domain. in dogs, known for their high sensitivity to progesterone-induced mammary cancer, the pr-b function was studied. canine ...201223041671
novel hepatitis e virus in ferrets, the netherlands. 201222840220
mycoplasmosis in ferrets.we report an outbreak of severe respiratory disease associated with a novel mycoplasma species in ferrets. during 2009-2012, a respiratory disease characterized by nonproductive coughing affected ≈8,000 ferrets, 6-8 weeks of age, which had been imported from a breeding facility in canada. almost 95% became ill, but almost none died. treatments temporarily decreased all clinical signs except cough. postmortem examinations of euthanized ferrets revealed bronchointerstitial pneumonia with prominent ...201223092744
complete genome sequence of hepatitis e virus from rabbits in the united states.hepatitis e virus (hev) is a single-strand positive-sense rna virus in the family hepeviridae. the disease caused by hev, hepatitis e, is an important public health problem in developing countries of asia and africa and is also endemic in many industrialized countries, including the united states. hev has been identified from several other animal species in addition to humans, including the pig, chicken, mongoose, deer, rabbit, ferret, bat, and fish. here we report the complete genome sequence o ...201223118454
protective efficacy of in vitro synthesized, specific mrna vaccines against influenza a virus infection.despite substantial improvements, influenza vaccine production-and availability-remain suboptimal. influenza vaccines based on mrna may offer a solution as sequence-matched, clinical-grade material could be produced reliably and rapidly in a scalable process, allowing quick response to the emergence of pandemic strains. here we show that mrna vaccines induce balanced, long-lived and protective immunity to influenza a virus infections in even very young and very old mice and that the vaccine rema ...201223159882
decoding the distribution of glycan receptors for human-adapted influenza a viruses in ferret respiratory tract.ferrets are widely used as animal models for studying influenza a viral pathogenesis and transmissibility. human-adapted influenza a viruses primarily target the upper respiratory tract in humans (infection of the lower respiratory tract is observed less frequently), while in ferrets, upon intranasal inoculation both upper and lower respiratory tract are targeted. viral tropism is governed by distribution of complex sialylated glycan receptors in various cells/tissues of the host that are specif ...201222359533
the multibasic cleavage site in h5n1 virus is critical for systemic spread along the olfactory and hematogenous routes in ferrets.the route by which highly pathogenic avian influenza (hpai) h5n1 virus spreads systemically, including the central nervous system (cns), is largely unknown in mammals. especially, the olfactory route, which could be a route of entry into the cns, has not been studied in detail. although the multibasic cleavage site (mbcs) in the hemagglutinin (ha) of hpai h5n1 viruses is a major determinant of systemic spread in poultry, the association between the mbcs and systemic spread in mammals is less cle ...201222278228
laboratory creation of a highly transmissible h5n1 influenza virus: balancing substantial risks and real benefits.controversy erupted when influenza researchers announced that they had created an h5n1 influenza virus that was transmissible between ferrets. the controversy escalated when the national science advisory board for biosecurity (nsabb) recommended that the work be published but recommended significant voluntary redactions. the responses to the nsabb action and to the research itself have been polarized. a readily transmitted h5n1 virus could be extraordinarily lethal; therefore, the risk for accid ...201222282172
engineered h5n1: a rare time for restraint in science.two scientific teams have recently engineered the h5n1 virus to make it readily transmissible between ferrets. given that ferrets are considered the most reliable animal surrogate for human influenza infection, the newly engineered h5n1 strain is probably transmissible between humans as well. the potential consequences of an engineered human-transmissible h5n1 strain are stunning. although seasonal flu infects as much as 20% of the world's population-more than 1 billion persons-each year, only a ...201222282173
science should be in the public domain.variants of avian influenza h5n1 virus that are transmitted by the airborne route among ferrets have been identified. the national science advisory board for biosecurity has advised against publication of the details of the methods used to obtain these viruses and the amino acid changes that lead to transmission in ferrets. this decision is not based on sound scientific principles and risks setting a precedent that will make it easier to put in place highly restrictive regulations on scientific ...201222294675
oligomeric recombinant h5 ha1 vaccine produced in bacteria protects ferrets from homologous and heterologous wild-type h5n1 influenza challenge and controls viral loads better than subunit h5n1 vaccine by eliciting high-affinity antibodies.recombinant hemagglutinin from influenza viruses with pandemic potential can be produced rapidly in various cell substrates. in this study, we compared the functionality and immunogenicity of bacterially produced oligomeric or monomeric ha1 proteins from h5n1 (a/vietnam/1203/04) with those of the egg-based licensed subunit h5n1 (su-h5n1) vaccine in ferrets challenged with homologous or heterologous h5n1 highly pathogenic influenza strains. ferrets were vaccinated twice with the oligomeric or mon ...201222951833
cedar virus: a novel henipavirus isolated from australian bats.the genus henipavirus in the family paramyxoviridae contains two viruses, hendra virus (hev) and nipah virus (niv) for which pteropid bats act as the main natural reservoir. each virus also causes serious and commonly lethal infection of people as well as various species of domestic animals, however little is known about the associated mechanisms of pathogenesis. here, we report the isolation and characterization of a new paramyxovirus from pteropid bats, cedar virus (cedpv), which shares signif ...201222879820
animal challenge models of henipavirus infection and pathogenesis.the henipaviruses, hendra virus (hev), and nipah virus (niv), are enigmatic emerging pathogens that causes severe and often fatal neurologic and/or respiratory disease in both animals and humans. amongst people, case fatality rates range between 40 and 75% and there are no vaccines or treatments approved for human use. a number of species of animals including guinea pigs, hamsters, cats, ferrets, pigs, and african green monkeys have been employed as animal models of human henipavirus infection. ...201222476556
gastric helicobacter spp. in animal models: pathogenesis and modulation by extragastric coinfections.animal models are used to study complex host, microbial, and environmental influences associated with gastric helicobacter infection. evidence that gastric helicobacters are pathogenic in animals first came from ferrets. felids, nonhuman primates, and many other species also harbor stomach helicobacters. today, mice are preferred by most researchers for scientific investigation because of cost-efficiencies, rapid reproduction, choice of laboratory reagents, and availability of genetically engine ...201223015504
multiple routes of invasion of wild-type clade 1 highly pathogenic avian influenza h5n1 virus into the central nervous system (cns) after intranasal exposure in ferrets.human infections with highly pathogenic avian influenza (hpai) h5n1 have been associated with central nervous system involvement. the purpose of this study was to examine the route of invasion of wild-type hpai h5n1 virus into the central nervous system (cns) using a ferret model of infection. sixteen ferrets were exposed by the intranasal route to 10(6) tcid(50) of a/vietnam/1203/04, a clade 1 strain originally isolated from a fatal human case. the ferrets were euthanased for histological and v ...201222763823
airborne transmission of influenza a/h5n1 virus between ferrets.highly pathogenic avian influenza a/h5n1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet ("airborne transmission") between humans. to address the concern that the virus could acquire this ability under natural conditions, we genetically modified a/h5n1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. the genetically modified a/h5n1 virus acquired mutations during passage in ...201222723413
the current state of h5n1 vaccines and the use of the ferret model for influenza therapeutic and prophylactic development.highly pathogenic avian influenza h5n1 is a threat to global public health as a natural pandemic causing agent but has recently been considered a bioterrorism concern.  the evolving view of the h5n1 virus necessitates the re-evaluation of the current status of h5n1 therapeutics and prophylactics, in particular the preparation of viable h5n1 vaccination strategies as well as the use of ferrets in influenza research.  here the highly pathogenic h5n1 virus dilemma is discussed in context with the c ...201222706187
an optimized real-time pcr to avoid species-/tissue-associated inhibition for h5n1 detection in ferret and monkey tissues.the real-time pcr diagnostics for avian influenza virus h5n1 in tissue specimens are often suboptimal, since naturally occurring pcr inhibitors present in samples, or unanticipated match of primer to unsequenced species' genome. with the principal aim of optimizing the sybr green real-time pcr method for detecting h5n1 in ferret and monkey (chinese rhesus macaque) tissue specimens, we screened various h5n1 gene-specific primer pairs and tested their ability to sensitively and specifically detect ...201222645461
the future of research and publication on altered h5n1 viruses.recently, we and others obtained experimental evidence that highly pathogenic avian influenza virus subtype h5 can acquire the ability to transmit via aerosols between ferrets. upon submission of manuscripts describing the results of these studies, the us national science advisory board for biosecurity was consulted and recommended that the main conclusions of the work be published but without the experimental details and mutation data that would enable replication of the experiments. over the p ...201222454474
influenza virus respiratory infection and transmission following ocular inoculation in ferrets.while influenza viruses are a common respiratory pathogen, sporadic reports of conjunctivitis following human infection demonstrates the ability of this virus to cause disease outside of the respiratory tract. the ocular surface represents both a potential site of virus replication and a portal of entry for establishment of a respiratory infection. however, the properties which govern ocular tropism of influenza viruses, the mechanisms of virus spread from ocular to respiratory tissue, and the p ...201222396651
ferret-transmissible influenza a(h5n1) virus: let us err on the side of caution. 201222396481
mammalian-transmissible h5n1 influenza: facts and perspective.two recently submitted (but as yet unpublished) studies describe success in creating mutant isolates of h5n1 influenza a virus that can be transmitted via the respiratory route between ferrets; concern has been raised regarding human-to-human transmissibility of these or similar laboratory-generated influenza viruses. furthermore, the potential release of methods used in these studies has engendered a great deal of controversy around publishing potential dual-use data and also has served as a ca ...201222366820
adjuvant solution for pandemic influenza vaccine production.extensive preparation is underway to mitigate the next pandemic influenza outbreak. new vaccine technologies intended to supplant egg-based production methods are being developed, with recombinant hemagglutinin (rha) as the most advanced program for preventing seasonal and avian h5n1 influenza. increased efforts are being focused on adjuvants that can broaden vaccine immunogenicity against emerging viruses and maximize vaccine supply on a worldwide scale. here, we test protection against avian f ...201223045649
spread of influenza virus a (h5n1) clade 2.3.2.1 to bulgaria in common buzzards.on march 15, 2010, a highly pathogenic avian influenza virus was isolated from the carcass of a common buzzard (buteo buteo) in bulgaria. phylogenetic analyses of the virus showed a close genetic relationship with influenza virus a (h5n1) clade 2.3.2.1 viruses isolated from wild birds in the tyva republic and mongolia during 2009-2010. designated a/common buzzard/bulgaria/38wb/2010, this strain was highly pathogenic in chickens but had low pathogenicity in mice and ferrets and no molecular marke ...201223017273
avian influenza a h5n1 virus: a continuous threat to humans.we report the first case of severe pneumonia due to co-infection with the emerging avian influenza a (h5n1) virus subclade 2.3.2.1 and mycoplasma pneumoniae. the patient was a returning traveller who had visited a poultry market in south china. we then review the epidemiology, virology, interspecies barrier limiting poultry-to-human transmission, clinical manifestation, laboratory diagnosis, treatment and control measures of h5n1 clades that can be transmitted to humans. the recent controversy r ...201226038430
early indicators of disease in ferrets infected with a high dose of avian influenza h5n1.avian influenza viruses are widespread in birds, contagious in humans, and are categorized as low pathogenicity avian influenza or highly pathogenic avian influenza. ferrets are susceptible to infection with avian and human influenza a and b viruses and have been widely used as a model to study pathogenicity and vaccine efficacy. in this report, the natural history of the h5n1 influenza virus a/vietnam/1203/04 influenza infection in ferrets was examined to determine clinical and laboratory param ...201223240077
isolation and characterization of microsatellite markers in the domestic ferret (mustela putorius furo).the domestic ferret (mustela putorius furo) is an important model organism for the study of avian influenza and other diseases of humans and animals, as well as a popular pet animal. in order to evaluate genetic diversity and study disease relationships in ferrets, 22 nuclear microsatellite loci (17 dinucleotide and 5 tetranucleotide) were developed from ferret genomic libraries and organized into seven multiplex sets. polymorphism was preliminarily assessed in one population in australia and on ...201223443120
campylobacter polysaccharide capsules: virulence and vaccines.campylobacter jejuni remains a major cause of bacterial diarrhea worldwide and is associated with numerous sequelae, including guillain barré syndrome, inflammatory bowel disease, reactive arthritis, and irritable bowel syndrome. c. jejuni is unusual for an intestinal pathogen in its ability to coat its surface with a polysaccharide capsule (cps). these capsular polysaccharides vary in sugar composition and linkage, especially those involving heptoses of unusual configuration and o-methyl phosph ...201222919599
Vaccine-specific antibody secreting cells are a robust early marker of LAIV-induced B-cell response in ferrets.Currently, a robust set of immune correlates for live attenuated influenza vaccine (LAIV) efficacy in humans has not been fully elucidated. The serum hemagglutination inhibition (HAI) assay has been historically used to measure humoral immune responses to injectable inactivated influenza vaccination. However, serum antibody titers do not reliably reflect the complete mechanism of action of LAIV, which is an intranasally delivered vaccine and is expected to induce local mucosal and cellular immun ...201222080173
experimental adaptation of an influenza h5ha strain confers respiratory droplet transmission to reassortant h5h/h1n1 virus strain in ferrets.an evaluation of the role - if any - of censorship in scientific papers, based on the publishing of the article that shows it is possible to modify the genetics of the h5n1 aviary influenza virus, enhancing its transmission among mammals, which was followed by much ado and ethical discussion.201223386026
in vivo genetic manipulation of cortical progenitors in gyrencephalic carnivores using in utero electroporation.brain structures such as the outer subventricular zone (osvz) and the inner fiber layer (ifl) in the developing cerebral cortex are especially prominent in higher mammals. however, the molecular mechanisms underlying the formation of the osvz are still largely unknown, mainly because genetic manipulations that can be applied to the osvz in higher mammals had been poorly available. here we developed and validated a rapid and efficient genetic manipulation technique for germinal zones including th ...201223336081
overexpression of serum response factor in astrocytes improves neuronal plasticity in a model of early alcohol exposure.neuronal plasticity deficits underlie many of the cognitive problems seen in fetal alcohol spectrum disorders (fasd). we have developed a ferret model showing that early alcohol exposure leads to a persistent disruption in ocular dominance (od) plasticity. recently, we showed that this deficit could be reversed by overexpression of serum response factor (srf) in the primary visual cortex during the period of monocular deprivation (md). surprisingly, this restoration was observed throughout the e ...201222742904
Characterization and scanning electron microscopic investigation of crosslinked freeze dried gelatin matrices for study of drug diffusivity and release kinetics.Drug delivery is a promising technique to enhance the therapeutic efficacy of the drug. However, properties of carrier materials require intense improvement for effective transport of drug molecules. In the current study, attempts have been made to develop freeze dried gelatin matrices cross linked with genipin at various temperatures (5°C, 15°C and 25°C) prior to freeze-drying (-80°C). The freeze dried matrices thus obtained at the said temperatures are characterized for crosslinking density, c ...201222172346
Usefulness of Olanzapine as an Adjunct to Opioid Treatment and for the Treatment of Neuropathic Pain.BACKGROUND:: The use of opioids for pain management is often associated with nausea and vomiting. Although conventional antipsychotics are often used to counter emesis, they can be associated with extrapyramidal symptoms. However, chronic pain can induce sleep disturbance. The authors investigated the effects of the atypical antipsychotic olanzapine on morphine-induced emesis and the sleep dysregulation associated with chronic pain. METHODS:: A receptor binding assay was performed using mouse wh ...201222126917
comparative analysis of the subventricular zone in rat, ferret and macaque: evidence for an outer subventricular zone in rodents.the mammalian cerebral cortex arises from precursor cells that reside in a proliferative region surrounding the lateral ventricles of the developing brain. recent work has shown that precursor cells in the subventricular zone (svz) provide a major contribution to prenatal cortical neurogenesis, and that the svz is significantly thicker in gyrencephalic mammals such as primates than it is in lissencephalic mammals including rodents. identifying characteristics that are shared by or that distingui ...201222272298
in vitro evolution of h5n1 avian influenza virus toward human-type receptor specificity.acquisition of α2-6 sialoside receptor specificity by α2-3 specific highly-pathogenic avian influenza viruses (h5n1) is thought to be a prerequisite for efficient transmission in humans. by in vitro selection for binding α2-6 sialosides, we identified four variant viruses with amino acid substitutions in the hemagglutinin (s227n, d187g, e190g, and q196r) that revealed modestly increased α2-6 and minimally decreased α2-3 binding by glycan array analysis. however, a mutant virus combining q196r wi ...201222056389
evidence for distinct chronic wasting disease (cwd) strains in experimental cwd in ferrets.chronic wasting disease (cwd) is an evolving prion disease of cervids (deer, elk and moose) that has been recognized in north america and korea. infection of non-cervid reservoir or transport species in nature is not reported. however, the ferret (mustela putorius furo) is susceptible to cwd after experimental inoculation. here, we report that infection of ferrets with either of two ferret cwd isolates by various routes of exposure has revealed biologically distinct strain-like properties distin ...201221918005
evaluation of the efficacy of a pre-pandemic h5n1 vaccine (mg1109) in mouse and ferret models.the threat of a highly pathogenic avian influenza (hpai) h5n1 virus causing the next pandemic remains a major concern. in this study, we evaluated the immunogenicity and efficacy of an inactivated whole-virus h5n1 pre-pandemic vaccine (mg1109) formulated by green cross co., ltd containing the hemagglutinin (ha) and neuraminidase (na) genes of the clade 1 a/vietnam/1194/04 virus in the backbone of a/puerto rico/8/34 (rgvietnam/04xpr8/34). administration of the mg1109 vaccine (2-doses) in mice and ...201222752912
surface glycoproteins of influenza a h3n2 virus modulate virus replication in the respiratory tract of ferrets.the hemagglutinin (ha) genes of the influenza a h3n2 subtype viruses isolated from 1968 to 2010 have evolved substantially but their neuraminidase (na) genes have been relatively less divergent. the h3n2 viruses isolated since 1995 were found to replicate in the lower respiratory tract of ferrets less efficiently than the earlier isolates. to evaluate whether the ha or/and na or the internal protein gene segments of the h3n2 virus affected viral replication in the respiratory tract of ferrets, r ...201222743127
evaluation of influenza virus a/h3n2 and b vaccines on the basis of cross-reactivity of postvaccination human serum antibodies against influenza viruses a/h3n2 and b isolated in mdck cells and embryonated hen eggs.the vaccine strains against influenza virus a/h3n2 for the 2010-2011 season and influenza virus b for the 2009-2010 and 2010-2011 seasons in japan are a high-growth reassortant a/victoria/210/2009 (x-187) strain and an egg-adapted b/brisbane/60/2008 (victoria lineage) strain, respectively. hemagglutination inhibition (hi) tests with postinfection ferret antisera indicated that the antisera raised against the x-187 and egg-adapted b/brisbane/60/2008 vaccine production strains poorly inhibited rec ...201222492743
pathogenesis and transmission of swine origin a(h3n2)v influenza viruses in ferrets.recent isolation of a novel swine-origin influenza a h3n2 variant virus [a(h3n2)v] from humans in the united states has raised concern over the pandemic potential of these viruses. here, we analyzed the virulence, transmissibility, and receptor-binding preference of four a(h3n2)v influenza viruses isolated from humans in 2009, 2010, and 2011. high titers of infectious virus were detected in nasal turbinates and nasal wash samples of a(h3n2)v-inoculated ferrets. all four a(h3n2)v viruses possesse ...201222355116
comparable fitness and transmissibility between oseltamivir-resistant pandemic 2009 and seasonal h1n1 influenza viruses with the h275y neuraminidase mutation.limited antiviral compounds are available for the control of influenza, and the emergence of resistant variants would further narrow the options for defense. the h275y neuraminidase (na) mutation, which confers resistance to oseltamivir carboxylate, has been identified among the seasonal h1n1 and 2009 pandemic influenza viruses; however, those h275y resistant variants demonstrated distinct epidemiological outcomes in humans. specifically, dominance of the h275y variant over the oseltamivir-sensi ...201222811535
cloned defective interfering influenza virus protects ferrets from pandemic 2009 influenza a virus and allows protective immunity to be established.influenza a viruses are a major cause of morbidity and mortality in the human population, causing epidemics in the winter, and occasional worldwide pandemics. in addition there are periodic outbreaks in domestic poultry, horses, pigs, dogs, and cats. infections of domestic birds can be fatal for the birds and their human contacts. control in man operates through vaccines and antivirals, but both have their limitations. in the search for an alternative treatment we have focussed on defective inte ...201223251341
immunogenic and protective properties of the first kazakhstan vaccine against pandemic influenza a (h1n1) pdm09 in ferrets.this paper presents the results of a pre-clinical study of the immunogenicity and efficacy of an egg-derived, inactivated, whole-virion adjuvanted vaccine (refluvac®) on ferret models. for this purpose, groups of eight ferrets (6 to 7 months old) were injected with 0.5 ml of vaccine specimens containing 3.75, 7.5 or 15.0 μg of virus hemagglutinin. administration was intramuscular and given either as a single dose or as two doses 14 days apart. all vaccine specimens manifested immunogenicity in f ...201223180289
endogenous lentiviral elements in the weasel family (mustelidae).endogenous retroviruses provide molecular fossils for studying the ancient evolutionary history of retroviruses. here, we report our independent discovery and analysis of endogenous lentiviral insertions (mustelidae endogenous lentivirus [melv]) within the genomes of weasel family (mustelidae). genome-scale screening identified melv elements in the domestic ferret (mustela putorius furo) genome (melvmpf). melvmpf exhibits a typical lentiviral genomic organization. phylogenetic analyses position ...201222522310
consecutive ct in vivo lung imaging as quantitative parameter of influenza vaccine efficacy in the ferret model.preclinical vaccine efficacy studies are generally limited to certain read out parameters such as assessment of virus titers in swabs and organs, clinical signs, serum antibody titers, and pathological changes. these parameters are not always routinely applied and not always scheduled in a logical standardized way. we used computed tomography (ct) imaging as additional and novel read out parameter in a vaccine efficacy study by quantifying alterations in aerated lung volumes in ferrets challenge ...201223085360
differential pathological and immune responses in newly weaned ferrets are associated with a mild clinical outcome of pandemic 2009 h1n1 infection.young children are typically considered a high-risk group for disease associated with influenza virus infection. interestingly, recent clinical reports suggested that young children were the smallest group of cases with severe pandemic 2009 h1n1 (h1n1pdm) influenza virus infection. here we established a newly weaned ferret model for the investigation of h1n1pdm infection in young age groups compared to adults. we found that young ferrets had a significantly milder fever and less weight loss than ...201223055557
characterization of the 2009 pandemic a/beijing/501/2009 h1n1 influenza strain in human airway epithelial cells and ferrets.a novel 2009 swine-origin influenza a h1n1 virus (s-oiv h1n1) has been transmitted among humans worldwide. however, the pathogenesis of this virus in human airway epithelial cells and mammals is not well understood.201223049974
comparison of the protection of ferrets against pandemic 2009 influenza a virus (h1n1) by 244 di influenza virus and oseltamivir.the main antivirals employed to combat seasonal and pandemic influenza are oseltamivir and zanamivir which act by inhibiting the virus-encoded neuraminidase. these have to be deployed close to the time of infection and antiviral resistance to the more widely used oseltamivir has arisen relatively rapidly. defective interfering (di) influenza virus is a natural antiviral that works in a different way to oseltamivir and zanamivir, and a cloned version (segment 1 244 di rna in a cloned a/pr/8/34 vi ...201223041142
virulence and transmissibility of h1n2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses.efficient worldwide swine surveillance for influenza a viruses is urgently needed; the emergence of a novel reassortant pandemic h1n1 (ph1n1) virus in 2009 demonstrated that swine can be the direct source of pandemic influenza and that the pandemic potential of viruses prevalent in swine populations must be monitored. we used the ferret model to assess the pathogenicity and transmissibility of predominant korean triple-reassortant swine (trsw) h1n2 and h3n2 influenza viruses genetically related ...201223019374
flagellin-ha vaccines protect ferrets and mice against h5n1 highly pathogenic avian influenza virus (hpaiv) infections.in order to meet the global demand for rapid production of pandemic influenza vaccines, we have developed a recombinant fusion vaccine platform in which the globular head of hemagglutinin (ha) antigen is genetically fused to bacterial flagellin (a tlr5 ligand). these flagellin-ha fusion vaccine candidates elicit highly protective immunity against a lethal challenge with 2009 pandemic h1n1 (liu, et al. plos one 2011; 6:e20928) or h5n1 influenza a/vietnam/1203/04 (a/vn) infections in mice (song, e ...201223000130
transmission of a 2009 h1n1 pandemic influenza virus occurs before fever is detected, in the ferret model.during the early phase of the 2009 influenza pandemic, attempts were made to contain the spread of the virus. success of reactive control measures may be compromised if the proportion of transmission that occurs before overt clinical symptoms develop is high. in this study we investigated the timing of transmission of an early prototypic strain of pandemic h1n1 2009 influenza virus in the ferret model. ferrets are the only animal model in which this can be assessed because they display typical i ...201222952661
pentamers not found in the universal proteome can enhance antigen specific immune responses and adjuvant vaccines.certain short peptides do not occur in humans and are rare or non-existent in the universal proteome. antigens that contain rare amino acid sequences are in general highly immunogenic and may activate different arms of the immune system. we first generated a list of rare, semi-common, and common 5-mer peptides using bioinformatics tools to analyze the uniprotkb database. experimental observations indicated that rare and semi-common 5-mers generated stronger cellular responses in comparison with ...201222937099
molecular imaging reveals a progressive pulmonary inflammation in lower airways in ferrets infected with 2009 h1n1 pandemic influenza virus.molecular imaging has gained attention as a possible approach for the study of the progression of inflammation and disease dynamics. herein we used [(18)f]-2-deoxy-2-fluoro-d-glucose ([(18)f]-fdg) as a radiotracer for pet imaging coupled with ct (fdg-pet/ct) to gain insight into the spatiotemporal progression of the inflammatory response of ferrets infected with a clinical isolate of a pandemic influenza virus, h1n1 (h1n1pdm). the thoracic regions of mock- and h1n1pdm-infected ferrets were image ...201222911695
comparison of temporal and spatial dynamics of seasonal h3n2, pandemic h1n1 and highly pathogenic avian influenza h5n1 virus infections in ferrets.humans may be infected by different influenza a viruses--seasonal, pandemic, and zoonotic--which differ in presentation from mild upper respiratory tract disease to severe and sometimes fatal pneumonia with extra-respiratory spread. differences in spatial and temporal dynamics of these infections are poorly understood. therefore, we inoculated ferrets with seasonal h3n2, pandemic h1n1 (ph1n1), and highly pathogenic avian h5n1 influenza virus and performed detailed virological and pathological an ...201222905124
elicitation of broadly neutralizing influenza antibodies in animals with previous influenza exposure.the immune system responds to influenza infection by producing neutralizing antibodies to the viral surface protein, hemagglutinin (ha), which regularly changes its antigenic structure. antibodies that target the highly conserved stem region of ha neutralize diverse influenza viruses and can be elicited through vaccination in animals and humans. efforts to develop universal influenza vaccines have focused on strategies to elicit such antibodies; however, the concern has been raised that previous ...201222896678
pathogenicity and transmissibility of reassortant h9 influenza viruses with genes from pandemic h1n1 virus.both h9n2 avian influenza and 2009 pandemic h1n1 viruses (ph1n1) are able to infect humans and swine, which has raised concerns that novel reassortant h9 viruses with ph1n1 genes might be generated in these hosts by reassortment. although previous studies have demonstrated that reassortant h9 viruses with ph1n1 genes show increased virulence in mice and transmissibility in ferrets, the virulence and transmissibility of reassortant h9 viruses in natural hosts such as chickens and swine remain unk ...201222875253
the h275y neuraminidase mutation of the pandemic a/h1n1 influenza virus lengthens the eclipse phase and reduces viral output of infected cells, potentially compromising fitness in ferrets.the h275y amino acid substitution of the neuraminidase gene is the most common mutation conferring oseltamivir resistance in the n1 subtype of the influenza virus. using a mathematical model to analyze a set of in vitro experiments that allow for the full characterization of the viral replication cycle, we show that the primary effects of the h275y substitution on the pandemic h1n1 (h1n1pdm09) strain are to lengthen the mean eclipse phase of infected cells (from 6.6 to 9.1 h) and decrease (by 7- ...201222837199
in vivo evaluation of pathogenicity and transmissibility of influenza a(h1n1)pdm09 hemagglutinin receptor binding domain 222 intrahost variants isolated from a single immunocompromised patient.the influenza a(h1n1)pdm09 virus has circulated worldwide and continued to cause complicated infections and deaths. reports have identified an increased prevalence of the hemagglutinin receptor binding domain d222g mutation in viruses isolated from individuals who have suffered such severe infections, but this association is still unclear. virus isolated from a nasopharyngeal wash of a severely ill immunocompromised patient at the time of diagnosis contained the d222, but isolates collected late ...201222575875
seasonal trivalent inactivated influenza vaccine protects against 1918 spanish influenza virus infection in ferrets.the influenza virus h1n1 pandemic of 1918 was one of the worst medical catastrophes in human history. recent studies have demonstrated that the hemagglutinin (ha) protein of the 1918 virus and 2009 h1n1 pandemic virus [a(h1n1)pdm09], the latter now a component of the seasonal trivalent inactivated influenza vaccine (tiv), share cross-reactive antigenic determinants. in this study, we demonstrate that immunization with the 2010-2011 seasonal tiv induces neutralizing antibodies that cross-react wi ...201222553323
exhaled aerosol transmission of pandemic and seasonal h1n1 influenza viruses in the ferret.person-to-person transmission of influenza viruses occurs by contact (direct and fomites) and non-contact (droplet and small particle aerosol) routes, but the quantitative dynamics and relative contributions of these routes are incompletely understood. the transmissibility of influenza strains estimated from secondary attack rates in closed human populations is confounded by large variations in population susceptibilities. an experimental method to phenotype strains for transmissibility in an an ...201222509254
control of pandemic (h1n1) 2009 influenza virus infection of ferret lungs by non-adjuvant-containing pandemic and seasonal vaccines.the pandemic h1n1 2009 influenza virus caused relatively mild disease in most infected people but some suffered extensively from primary lung infection, many more than would have occurred with seasonal influenza infection. early commercially available pandemic h1n1 vaccines did not contain adjuvant, as did many of the subsequent vaccines, and could not stop infection with the pandemic virus in vaccinated ferrets. nevertheless, we showed that virus loads in the lungs were greatly diminished in fe ...201222464969
influenza virus h1n1pdm09 infections in the young and old: evidence of greater antibody diversity and affinity for the hemagglutinin globular head domain (ha1 domain) in the elderly than in young adults and children.the h1n1 2009 influenza virus (h1n1pdm09) pandemic had several unexpected features, including low morbidity and mortality in older populations. we performed in-depth evaluation of antibody responses generated following h1n1pdm09 infection of naïve ferrets and of 130 humans ranging from the very young (0 to 9 years old) to the very old (70 to 89 years old). in addition to hemagglutination inhibition (hi) titers, we used h1n1pdm09 whole-genome-fragment phage display libraries (gfpdl) to evaluate t ...201222379097
the 2009 pandemic h1n1 virus induces anti-neuraminidase (na) antibodies that cross-react with the na of h5n1 viruses in ferrets.a miniaturized neuraminidase inhibition (ni) assay using ha-mismatched h6 reassortant viruses was performed to examine the neuraminidase (na)-specific antibody response in ferrets immunized with live-attenuated influenza vaccine (laiv) strains. the strains tested possessed different nas derived from seasonal h1n1 and h3n2, 2009 pandemic h1n1, and the highly pathogenic influenza h5n1 virus. the anti-na antibodies from the 2009 pandemic strain (a/california/7/2009) immunized ferrets cross-reacted ...201222330124
pb1-f2 modulates early host responses but does not affect the pathogenesis of h1n1 seasonal influenza virus.in the context of infections with highly pathogenic influenza a viruses, the pb1-f2 protein contributes to virulence and enhances lung inflammation. in contrast, its role in the pathogenesis of seasonal influenza viral strains is less clear, especially in the h1n1 subtype, where strains can have a full-length 87- to 90-amino-acid protein, a truncated 57-amino-acid version, or lack the protein altogether. toward this, we introduced the full-length 1918 pb1-f2, or prevented pb1-f2 expression, in h ...201222318139
pandemic (h1n1) 2009 in captive cheetah.we describe virus isolation, full genome sequence analysis, and clinical pathology in ferrets experimentally inoculated with pandemic (h1n1) 2009 virus recovered from a clinically ill captive cheetah that had minimal human contact. evidence of reverse zoonotic transmission by fomites underscores the substantial animal and human health implications of this virus.201222305505
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