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PubMed2003

Field evaluation of capsaicin as a rodent aversion agent for poultry feed.

Developing additional techniques for reducing animal feed contamination by rodents and controlling rodent populations is critical to efforts aimed at reducing the occurrence of Salmonella spp infection on poultry farms. Capsaicin, a compound found in chili peppers of the genus Capsicum, produces a burning sensation in the mouth of mammals and is used effectively as an animal deterrent for some pest species. Applied to poultry feed, capsaicin may be effective as an aversive agent to deter rodent feeding and enhance acceptability of rodenticide baits. We tested capsaicin-treated poultry diets (2000 and 3000 Scoville Heat Units, SHU) in no-choice feeding trials at four active New York farms in the winter of 1997-1998. At all farms, consumption of the 2000 SHU diet by rodents (Norway rats, Rattus norvegicus (Berk), and house mice, Mus musculus L) was significantly less than consumption of a control diet. Consumption of the 3000 SHU diet by rodents was significantly less than consumption of a control diet at three of the four farms. Overall, consumption of treated diets was 58-97% and 55-98% less than consumption of the control diet, for the 2000 and 3000 SHU diets, respectively. These reductions appeared to be related closely to the availability of alternative feed sources at these farms. Two-choice feeding trials involving a rodenticide bait (0.05 g kg(-1) brodifacoum) and the 3000 SHU diet demonstrated that Norway rats preferred the rodenticide to the capsaicin-treated poultry feed. Overall, rodenticide bait acceptance was high (95.6%) when offered simultaneously with capsaicin-treated poultry feed. Although poultry managers must utilize several techniques to manage rodent pests, the use of capsaicin-treated diets to reduce feed losses and increase rodenticide bait acceptance appears promising. Use of capsaicin-treated feed on poultry farms may substantially reduce feed contamination by rodents and ultimately the incidence of Salmonella infection in poultry.

Animal Feed↗
PubMed1999

Clinical pathology and sample collection in the laboratory rodent.

Common laboratory rodents have always been a favorite choice as a pet. Although diagnostic clinical pathology has not been viewed as practical for the rodent patient, current advances in technology make processing of small samples possible. Cultivation of the technical skills necessary for rodent sample collection has the potential to improve the standard of rodent veterinary care. This article provides an overview of rodent sample collection techniques, hematology, clinical biochemistry, serology, and clinical pathology of other tissues and fluids for laboratory rodents. General principles of clinical pathology can be applied across species. This article emphasizes the subtleties of the different rodent species which may impact diagnostic interpretation.

Animals↗
PubMed2003

A community-based surveillance on determinants of rodent infestation.

Rodent infestation is an important factor in the transmission of infectious diseases of public health importance. From October to November 1998, surveillance stations were established in 110 boroughs of Kaohsiung City in southern Taiwan. Boroughs were chosen by random sampling 10 boroughs from each of 11 districts (464 boroughs) in the city. The extent of rodent infestation was determined by cage trapping. The possibility of applying a community-based control program was evaluated by investigating associated demographic and environmental factors as well as related knowledge, attitudes, and behaviors. A total of 90 rodents were trapped in 41% of the 110 boroughs. Using univariate analyses, 17 factors were significantly associated with rodent infestation. A lack of knowledge that rodent control relies on community cooperation was the most important factor among the seven variables associated with the extent of rodent infestation (OR 3.1) by logistic multiple regression. This revealed the importance of community cooperation in controlling rodent infestation. Moreover, improvement of environmental hygiene associated with garbage problems, such as cleanliness of storage rooms and closets, and the hygiene of empty space and resource recycling stations should not be ignored.

Animals↗
PubMed1991

Lyme disease in California: interrelationship of ixodid ticks (Acari), rodents, and Borrelia burgdorferi.

The association of immature ixodid ticks, several species of rodents, and the Lyme disease spirochete, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, was studied in two habitats in northern California in spring and summer 1985 and year-round in 1986. A total of 428 rodents were collected from ecotonal chaparral and a woodland-grass-rock outcrop; the former habitat yielded six species, the latter three species. The deer mouse, Peromyscus maniculatus (Wagner), and the piñon mouse, P. truei (Shufeldt), were the dominant species year-round and collectively comprised 78% of rodents captured within chaparral and 87% from the rock outcrop in 1986. In both habitats, rodents were trapped most frequently in winter and spring, and least often in summer and fall. A total of 306 rodent blood films from all six species were assayed for spirochetes by direct immunofluorescence; of these, only one film prepared from P. truei (n = 123 films from 53 individual mice) was found to contain spirochetes. Immature western black-legged ticks, Ixodes pacificus Cooley & Kohls, and Pacific Coast ticks, Dermacentor occidentalis Marx, were collected from each species of rodent. Larvae of I. pacificus infested P. maniculatus and P. truei in low numbers year-round, but nymphs of this tick rarely parasitized these rodents. D. occidentalis larvae infested P. maniculatus and P. truei in spring and particularly in summer; nymphal ticks infested these mice primarily in summer. The efficiency of visual inspection for collecting immatures of these ticks from P. maniculatus ranged from 45 to 69% in spring and summer, whereas the efficiency of a drop-off technique appeared to be 100%. Spirochetes were detected in <1% of D. occidentalis larvae (n = 310) and nymphs (n = 120), and in approximately 4% of I. pacificus larvae (n = 75) derived from these hosts. The potential significance od these findings in the enzootiology of B. burgdorferi is discussed.

Animals↗
PubMed1995

Infestation of rodents with larval Ixodes ricinus (Acari: Ixodidae) is an important factor in the transmission cycle of Borrelia burgdorferi s.l. in German woodlands.

The ecology of Borrelia burgdorferi Johnson et al. s.l. was investigated from 1987 to 1993 in a preserved woodland in western Germany near Bonn. In selected biotopes, host-seeking Ixodes ricinus L. were regularly collected by blanket dragging in 1987, 1988, and 1989 and screened for infection with B. burgdorferi. Rodents were trapped monthly between April and October in 1988, 1990, 1991, and in the winter of 1992-1993, examined for antibodies to B. burgdorferi s.l., and inspected for feeding ticks. Ticks collected from rodents were screened for spirochete infection. High numbers of host-seeking nymphs were consistently collected within a biotope characterized by humid and acid soils. The mean number of ticks was significantly lower in biotopes with permeable soils. All small mammals captured belonged to the species Apodemus flavicollis Melchior, A. sylvaticus L., and Clethrionomys glareolus Schreber. Of 11,680 ticks obtained from rodents, 11,674 were I. ricinus, with 97.9% of the ticks being larvae, 2.0% nymphs, and 0.1% females. Mean numbers of feeding ticks ranged from 3.4 to 117 larvae per rodent and from 0.0 to 0.64 nymph per rodent, respectively. High levels of larval infestation on rodents were recorded in the same biotope where high numbers of host-seeking nymphs were present. Members of the genus Apodemus were more heavily infested with I. ricinus larvae than C. glareolus. The mean infection prevalence in host-seeking ticks was found to be 1% for larvae, 5% for nymphs, and 10-20% for adults. The infection prevalence in host-seeking nymphs ranged from 1.1 to 15.4% according to the particular biotope. The values for specific infectivity for the Apodemus populations were positively correlated with the mean larval infestation, but not with nymphal infestation. The respective estimates for C. glareolus were much higher than those for Apodemus spp. in biotopes with low tick densities. However, specific infectivity of C. glareolus was substantially reduced at sites with high tick abundances. In biotopes with high numbers of infected I. ricinus, significantly more rodents were found to have antibodies to B. burgdorferi than in biotopes with low abundances of ticks. The data show that C. glareolus plays a different role as reservoir host species compared with the 2 Apodemus species. This and previous studies suggest that the degree of infestation with larval I. ricinus differentially modulates infectivity of host species for ticks. We conclude that immune processes in natural reservoir hosts induced by B. burgdorferi or I. ricinus bites (or both) are important regulatory factors in the transmission cycle(s) of B. burgdorferi.

Animals↗
PubMed2002

Hantavirus-specific antibodies in rodents and humans living in Kuwait.

Hantaviruses are found in widely scattered areas of the world and are transmitted by inhalation of virus-contaminated aerosols of rodent excreta. The present study was undertaken in Kuwait to investigate the serological evidence for hantavirus infection in rodents and humans. Sera were collected from 283 wild rodents and 183 human subjects (46 Kuwaitis and 137 non-Kuwaitis). The rodent sera were investigated for the presence of antibodies against the Seoul and Puumala strains of the hantaviruses by enzyme-linked immunosorbent assay and immunofluorescence technique using the virus-infected Vero E6 cells. The findings showed the presence of anti-hantavirus antibodies in seven out of the 283 (2.8%) rodents. Antibodies against the Seoul strain were present in six (2.1%) and against the Puumala strain in three (1%) rodents. Further, it was observed that three out of 84 (3.6%) of the Rattus norvegicus and four out of 174 (2.3%) Mus musculus had anti-hantavirus antibodies. Two rodents belonging to species Mus musculus had antibodies against both strains of the hantaviruses. Out of 183 human sera, 13 (7%) were positive for hantavirus antibodies. Among the Kuwaitis 5/46 (11%) and among the non-Kuwaitis 8/137 (6%) were positive for the hantavirus antibodies. Antibodies to both Puumala and Hantaan strains were detected in Kuwaitis as well as in non-Kuwaitis. Although no human case of hantavirus illness has yet been reported in Kuwait, the serological evidence of infection suggests a constant vigil.

Adult↗
PubMed1988

Oncogene activation in spontaneous and chemically induced rodent tumors: implications for risk analysis.

The validity of rodent tumor end points in assessing the potential hazards of chemical exposure to humans is a somewhat controversial but very important issue since most chemicals are classified as potentially hazardous to humans on the basis of long-term carcinogenesis studies in rodents. The ability to distinguish between genotoxic, cytotoxic, or receptor-mediated promotion effects of chemical treatment would aid in the interpretation of rodent carcinogenesis data. Activated oncogenes in spontaneously occurring and chemically induced rodent tumors were examined and compared as one approach to determine the mechanism by which chemical treatment caused an increased incidence of rodent tumors. Different patterns of activated oncogenes were found not only in spontaneous versus chemically induced mouse liver tumors but also in a variety of spontaneous rat tumors versus chemically induced rat lung tumors. In the absence of cytotoxic effects, it could be argued that the chemicals in question activated protooncogenes by a direct genotoxic mechanism. These results provided a basis for the analysis of activated oncogenes in spontaneous and chemically induced rodent tumors to provide information at a molecular level to aid in the extrapolation of rodent carcinogenesis data to human risk assessment.

Animals↗
PubMed2001

Detection of rodent parvoviruses by use of fluorogenic nuclease polymerase chain reaction assays.

Polymerase chain reaction (PCR) assays have proven useful for detection of rodent parvoviruses in animals and contaminated biological materials. Fluorogenic nuclease PCR assays combine PCR with an internal fluorogenic hybridization probe, eliminating post-PCR processing and potentially enhancing specificity. Consequently, three fluorogenic nuclease PCR assays were developed, one that detects all rodent parvoviruses, one that specifically detects minute virus of mice (MVM), and one that specifically detects mouse parvovirus 1 (MPV) and hamster parvovirus (HaPV). When rodent parvoviruses and other rodent DNA viruses were evaluated, the rodent parvovirus assay detected only rodent parvovirus isolates, whereas the MVM and MPV/HaPV assays detected only the MVM or MPV/ HaPV isolates, respectively. Each assay detected the equivalent of 10 or fewer copies of target template, and all fluorogenic nuclease PCR assays exceeded the sensitivities associated with previously reported PCR assays and mouse antibody production testing. In addition, each fluorogenic nuclease PCR assay detected the targeted parvovirus DNA in tissues obtained from mice experimentally infected with MVM or MPV. Results of these studies indicate that fluorogenic nuclease PCR assays provide a potentially high-throughput, PCR-based method to detect rodent parvoviruses in infected mice and contaminated biological materials.

Animals↗
PubMed1979

Field and experimental studies of poxvirus infections in rodents.

Data are presented from serological and virological investigations of natural and experimental infections, in rodents, with different poxviruses. The demonstration of poxvirus antibodies (virus neutralizing antibodies, antihaemagglutinins, and precipitins) in the kidneys and/or lungs of rodents from Europe and Africa, and the isolation of poxviruses from them, all indicate that rodents may be poxvirus carriers. Isolates from rodents differed in their properties. Some, from Turkmenistan rodents or from white rats caught near Moscow, appeared to be very close to cowpox virus, while others (from Zaire rodents) were identical to variola-like (whitepox) viruses found earlier in monkeys in the same region. The results suggest that rodents that carry the virus closely similar to cowpox virus might be a source of infection for other animal species.

Animals↗
PubMedDate not supplied

Human relevance of rodent prolactin-induced non-genotoxic mammary carcinogenesis: prolactin involvement in human breast cancer and significance for toxicology risk assessments.

Prolactin-induced mammary carcinogenesis in rodents, particularly rats, is often stated to be of low toxicological relevance to humans. This opinion appears to have developed from a number of lines of cited evidence. Firstly, there had been long experience of use of dopamine antagonists (that increase prolactin) in human medicine and no evidence of an increase in breast cancer incidence or risk had been reported. Secondly, dopamine agonists (that lower prolactin) had been shown to have no effect in human breast cancer treatment. Thirdly, the actions of prolactin were considered different between rodents and humans. However, recent evidence now suggests that prolactin has a major role in human breast cancer, and the similarity of mechanism with the rodent suggests that prolactin-mediated mammary carcinogenesis in rodents could be of much higher toxicological relevance to humans than previously thought. Large epidemiology studies have upgraded a limited database and shown that dopamine antagonists (both antipsychotics and anti-emetics) increase breast cancer risk, that hyperprolactinaemia is consistently associated with human breast cancer growth, development and poor prognosis, and that prolactin is indeed a mitogen in human breast cancer cells that suppresses apoptosis and upregulates BRCA1. It is now clear that initial studies giving dopamine agonists to breast cancer patients had no effect because breast cancer cells also produced prolactin independently of the pituitary, which remained uncontrolled and unrecognized in early clinical studies. The evidence for the role of prolactin in human breast cancer is now strong and consistent, and is discussed and related to the risk assessment of drugs and chemicals. The conclusion is that it is invalid to suggest that prolactin-induced mammary carcinogenesis in rodents is of low relevance to humans because prolactin can induce an adverse response in the mammary tissue of both rodents and humans alike. Drugs and chemicals causing rodent prolactin-induced mammary carcinogenesis may therefore pose a risk to humans via the same mechanism if exposures also increase prolactin secretion in humans.

Animals↗
PubMed2004

Functional morphology of the ear in fossorial rodents, Microtus arvalis and Arvicola terrestris.

Functionally relevant features and parameters of the outer, middle, and inner ear were studied morphologically and morphometrically in two species of voles, smaller Microtus arvalis and larger Arvicola terrestris. The findings in these fossorial (i.e., burrowing) rodents with components of surface activity were compared with respective findings reported for taxonomically related muroid rodents representing the same size classes but different eco-morphotypes: obligate subterranean rodents (Ellobius talpinus and Spalax ehrenbergi superspecies) and generalized rodents (Mus domesticus and Rattus norvegicus). The ear in voles was characterized by traits reported for subterranean rodents. The eardrum was round, without a distinct pars flaccida, and had an area of 5.4 mm2 in M. arvalis and 9 mm2 in A. terrestris. The middle ear exhibited reduced goniale, enlarged incus nearly parallel to the manubrium of the malleus. The malleus-incus lever ratio amounted to 2.1 (M. arvalis) and 2.0 (A. terrestris). The malleus-incus complex weighed about 0.8 mg in both vole species. The stapedial footplate had an area of 0.3 mm2 in M. arvalis and 0.4 mm2 in A. terrestris. The cochlea had 2.3 coils in both vole species; the basilar membrane was 8.5 mm and 10.5 mm long in M. arvalis and A. terrestris, respectively. There were on average 1,030 (M. arvalis) and 1,220 (A. terrestris) inner hair cells, and 3,760 (M. arvalis) and 4,250 (A. terrestris) outer hair cells in the organ of Corti. In quantitative terms, all these (as well as some further) traits and parameters were intermediate (related to body size) between those reported for generalized rodents on the one hand and subterranean ones on the other. The sound transmission system of the ear seems to be best tuned to frequencies of about 8-16 kHz with a high-frequency cut-off at about 50-60 kHz. The ear of A. terrestris seems to be tuned to somewhat lower frequencies than that in M. arvalis. In this aspect as well as regarding hearing sensitivity (as judged from the mechanical transmission parameters), voles can be considered intermediate not only in their lifestyle but also in their hearing abilities between the subterranean rodents (mole-vole and blind mole-rat) and the surface dwellers (house mouse and Norway rat).

Animals↗
PubMed2006

Behavioral models of Parkinson's disease in rodents: a new look at an old problem.

The circuitry important for voluntary movement is influenced by dopamine from the substantia nigra and regulated by the nigrostriatal system. The basal ganglia influence the pyramidal tract and other motor systems, such as the mesopontine nuclei and the rubrospinal tract. Although the neuroanatomical substrates underlying motor control are similar for humans and rodents, the behavioral repertoire mediated by those circuits is not. The principal aim of this review is to evaluate how injury to dopamine-mediated pathways in rodents gives rise to motor dysfunction that mimics human Parkinsonism. We will examine the behavioral tests in common use with rodent models of Parkinson's disease and critically evaluate the appropriateness of each test for detecting motor impairment. We will show how tests of motor performance must be guided by a thorough understanding of the clinical symptoms accompanying the disease, the circuitry mediating dopamine deficits in rodents, and familiarity with the rodent behavioral repertoire. We will explain how investigations in rodents of skilled forepaw actions, including placing, grooming, or foot faults, have clear correlates in Parkinson's disease, and are, therefore, the most sensitive ways of detecting motor impairment following dopamine loss from the basal ganglia of rodents.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMedDate not supplied

Neogene paleobiogeography and East African paleoenvironments: contributions from the Tugen Hills rodents and lagomorphs.

A minimum of 28 genera of rodents and one genus of lagomorph were recovered from the Tugen Hills, Baringo District, Kenya, from localities dating from over 15.5 to about 4.4 Ma. The middle Miocene (sites dated between 15.8 and 15.3 Ma) rodent fauna recovered primarily from the Kipsaramon site complex, Muruyur Formation, includes a mixture of characteristically early Miocene taxa, and more derived forms. Composition of the African rodent fauna changes dramatically with the introduction of myocricetodontines, democricetodontines, and dendromurines, immigrants primarily from southern Asia. In the Tugen Hills, these taxa are first found in the Kabasero localities, Ngorora Formation, at sites dating from 12.5-12.33 Ma. A second major change in the African rodent fauna reflects the introduction of murines, immigrants from southern Asia. In the Tugen Hills murines are first encountered at Kapcheberek, Lukeino Formation, dated to 5.9-5.7 Ma. One rodent genus from the Lukeino Formation (Arvicanthis), and two from the Tabarin locality, Chemeron Formation (Heliosciurus, Paraxerus; 4.5-4.4 Ma), represent the earliest records of these extant African genera. A cricetomyine from the Ngorora Formation (12.5 Ma) is likely the earliest report of this exclusively African group. One of the earliest African records of porcupines (Hystricide) is from the Lukeino Formation. Lagomorphs are poorly represented, but include one of the earliest African occurrences of the family Leporidae from the Mpesida Beds (bracketed by dates of 7-6.2 Ma), and possibly a new genus of leporid from the Kapcheberek locality. Analysis of the Tugen Hills small mammals in association with other African records suggests several episodes of dispersal between Africa and Eurasia during the middle and late Miocene. Rodents from Kipsaramon are indicative of forests in conjunction with more open habitats. Those from the Kapcheberek locality are suggestive of a savanna habitat. The rodents from the Tabarin locality suggest a woodland environment.

Animals↗
PubMed1993

Relative utilization of reptiles and rodents as hosts by immature Ixodes scapularis (Acari: Ixodidae) in the coastal plain of North Carolina, USA.

The interaction of immature black-legged ticks, Ixodes scapularis, with reptiles and rodents was investigated in various woodland habitats in the coastal plain of North Carolina. Reptiles were sampled from April 1 to September 30, 1991. No ticks were found on 95 specimens representing 16 species of snakes. Ticks were found on 54 (36.7%) of 147 lizards. I. scapularis was the only tick recovered from lizards. Some lizards were collected in drift fence traps each month of the study except August. Capture rates averaged one lizard per 16 trap-days. Larvae and nymphs of I. scapularis were removed from the southeastern five-lined skink (Eumeces inexpectatus), the ground skink (Scincella lateralis), the broad-headed skink (E. laticeps) and the eastern glass lizard (Ophisaurus ventralis), but ticks were not found on three other lizard species. Tick infestation rates and loads for parasitized species are presented. Ticks were almost exclusively attached at the base or in the axils of forelimbs of skinks and in the lateral grooves of eastern glass lizards. Rodents were live-trapped at sites where lizards were sampled and at other sites from 1 July, 1990 to 30 January, 1992. Capture rates averaged one rodent per 47 trap-nights. Ticks were found on 23 (17.8%) of 129 animals inspected. Five species of rodents were examined but only four species were found to be tick-infested. In contrast to lizards, few I. scapularis were collected. Rodents, principally the white-footed mouse (Peromyscus leucopus) and cotton mouse (P. gossypinus) were most frequently infested with immature American dog ticks, Dermacentor variabilis, during winter and early spring months. Burdens of D. variabilis on these rodents averaged 0.3 ticks per rodent. Effects of the diversion of ticks from feeding on Peromyscus mice on the transmission of the Lyme disease spirochete are discussed.

Animals↗
PubMed1993

The influence of chemical structure on the extent and sites of carcinogenesis for 522 rodent carcinogens and 55 different human carcinogen exposures.

Gold and her colleagues have tabulated the results of rodent bioassays on 522 chemicals and have analysed the data. The present study complements those analyses by providing a perspective from the viewpoint of the chemical structure of the carcinogens. The chemical structure of each of the carcinogens is displayed and the Gold database is represented with the test agents as the primary variable. The carcinogens are gathered into six chemical classes and each chemical is assessed for structural alerts to DNA reactivity. The database is then analysed using an integration of the following parameters: bioassay in rat, mouse or both; structural alert status; chemical class; sites and multiplicity of carcinogenesis, and trans-species carcinogenicity. A series of Figures is presented that enables rapid acquaintance with what represents the core database of rodent carcinogenicity. The several analyses presented combine in endorsing the reality of two broad classes of rodent carcinogen--presumed DNA-reactive and others (putative genotoxic and non-genotoxic carcinogens, but semantics have been largely avoided). Vainio and his colleagues have tabulated 55 situations in which humans have succumbed to chemically induced cancer, and have listed the tissues affected. This database of human carcinogens has been analysed in the present study as done for the rodent carcinogen database, and comparisons made between the two. The predominance of putative genotoxic carcinogens in the human database was confirmed, as was the reality of putative non-genotoxic carcinogenicity in humans. It is concluded that putative genotoxic rodent carcinogenesis can be correlated both with chemical structure and the extent and nature of the induced effect, and that it is of clear relevance to humans. In contrast, it is concluded that putative non-genotoxic rodent carcinogenesis is more closely related to the test species than to the test chemical, and that it is essentially unpredictable in the absence of mechanistic models. In the absence of such models nongenotoxic carcinogenic effects should be extrapolated to humans with caution. Progress in the accurate prediction and extrapolation of rodent carcinogenicity will be helped by a common, if only temporary, enabling acceptance that not all carcinogens are intrinsically genotoxic.

Alkylating Agents↗
PubMed2006

Temporal dynamics of a T-cell mediated immune response in desert rodents.

Immunocompetence, the general capacity of an individual host to mount an immune response against pathogens, is commonly assessed by the response to a challenge of the immune system by injection of phytohaemagglutinin (PHA). The response to PHA is commonly considered a reliable estimate of the T-cell mediated immune response. We investigated the temporal pattern of the PHA response in 10 rodent species from the Negev desert, Israel. We hypothesized that the temporal dynamics of the PHA response would differ among species with different natural patterns of flea parasitism. We injected PHA subcutaneously in the footpad of each rodent and measured its PHA response 6, 24 and 48 h after injection. Rodent species showed two types of PHA response. One type was rapid and characteristic of rodents that had either species-poor flea assemblages, or that are rarely attacked by fleas. This response peaked approximately 6 h after PHA injection. The second type of response was delayed and was typical of rodents that have either species-rich flea assemblages or high abundance and prevalence of fleas or both. Their response to PHA peaked 24 h after injection. Furthermore, rodents that responded promptly had a lower maximum response than rodents with a delayed response. Our results suggest the occurrence of a trade-off between intensity and latency of the PHA response and, therefore, the necessity to account for the relationship between maximum PHA response and time after injection when making interspecific comparisons of immunocompetence.

Animals↗
PubMed1999

The profiles of human and primate [3H]Nalpha-methylhistamine binding differ from that of rodents.

Characterization of the histamine H3 receptor in rodent species has been extensive but limited characterization has been done with primate or human tissue. We have characterized the binding of [3H]Nalpha-methylhistamine to cynomolgus monkey and human brain membranes to determine whether there are any significant differences among species' pharmacology. In monkey, [3H]Nalpha-methylhistamine bound, in a guanine nucleotide-sensitive fashion, to an apparently homogeneous class of sites at equilibrium (K(D) = 1.4 nM, Bmax = 34 fmol/mg protein). The profile of binding was broadly similar to that of rodents, with a couple of significant differences. Most notably, the potency of the histamine H3-receptor-specific antagonist thioperamide (Ki = 240 nM) was substantially less than reported for rodents and under assay conditions that yield a two-site curve fit in rodents only a single class of thioperamide binding sites was detected in monkey. Burimamide, however, yielded a two-site curve fit (KiH = 6.7 nM, KiL = 1100 nM) independent of the presence of sodium in the assay, as it does in rodents. Characterization of the human brain histamine H3 receptor showed that it was similar to the monkey and not rodent receptor. Our findings indicate that differences between primate and rodent histamine H3 receptors of potentially serious importance for the discovery of antagonists active in humans do exist.

Animals↗
PubMed1999

Two related G protein-coupled receptors: the distribution of GPR7 in rat brain and the absence of GPR8 in rodents.

GPR7 and GPR8, orphan G protein-coupled receptor (GPCR) genes, expressed in the brain and periphery share highest sequence identity to each other and significant similarity with opioid and somatostatin receptors. To further our knowledge of GPR7's physiological function, we performed in situ hybridization analyses of rat brain to reveal specific patterns of expression in the brain. GPR7 mRNA was found to be discretely localized in areas of the amygdala, hippocampus, hypothalamus and cortex. We previously reported that GPR7 was highly conserved in both human and rodent orthologs while GPR8 was not found in the rodent [9]. We speculated that GPR8 originated after the divergence of the human and rodent. Using primers designed from human GPR8, we isolated lemur GPR8 and subsequently aligned human, monkey, and lemur GPR8 orthologs to design primers recognizing highly conserved regions of GPR8. Using these primers, orthologs of GPR7 and GPR8 were isolated by the PCR from rabbit, tree shrew, and flying lemur, as well as GPR7 in the rat. Subsequent analysis of the clones obtained demonstrated that both GPR7 and GPR8 sequences were highly conserved amongst the species studied, but a rodent GPR8 was not isolated. The absence of a GPR8 gene in the rodent suggests that GPR8 originated from gene duplication of GPR7 after the rodent line diverged from the rabbit, tree shrew, flying lemur, lemur, monkey and human lines. In addition, the taxonomic distribution of GPR8 is consistent with molecular studies grouping rabbits with primates, tree shrews and flying lemurs rather than with rodents.

Amino Acid Sequence↗