'Wanted-standard guinea pigs': standardisation and the experimental animal market in Britain ca. 1919-1947.
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ABSTRACT:
SUBMITTER: Kirk RG
PROVIDER: S-EPMC3302564 | biostudies-other | 2008 Sep
REPOSITORIES: biostudies-other
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Project description:ObjectiveTo develop an animal model of intraocular tuberculosis (TB) with features of pulmonary TB and extrapulmonary dissemination to the eye.MethodsHartley strain guinea pigs were infected via an aerosol route with virulent Mycobacterium tuberculosis. One group of guinea pigs was infected with a relatively low bacterial inoculum and received no treatment. A second group of guinea pigs received high-dose infection and were treated with the first-line anti-TB drugs isoniazid, rifampin, and pyrazinamide. Development of ocular TB lesions was documented by histological analysis, acid-fast staining, and real-time polymerase chain reaction for M tuberculosis DNA.ResultsUntreated guinea pigs developed pulmonary and extrapulmonary TB. Ocular TB, primarily involving the uvea, developed in 5 of 12 eyes (42%). Uveal granulomatous lesions showed the presence of acid-fast organisms and M tuberculosis DNA. In treated animals, none of the 8 eyes examined revealed the presence of acid-fast organisms; however, there was mild nongranulomatous uveitis in 4 eyes.ConclusionsMycobacterium tuberculosis delivered via aerosol to guinea pigs results in extrapulmonary dissemination to the eye. Of significance, intraocular changes in this model include granulomatous inflammation and the presence of acid-fast organisms, as seen in human cases of ocular TB. Clinical Relevance The guinea pig model may provide greater insight into the pathogenesis of intraocular TB and assist in the development of novel modalities to treat this global infectious disease.
| S-EPMC3062475 | biostudies-literature
Project description:Ebola virus (EBOV) transmission is currently poorly characterized and is thought to occur primarily by direct contact with infectious material; however transmission from swine to nonhuman primates via the respiratory tract has been documented. To establish an EBOV transmission model for performing studies with statistical significance, groups of six guinea pigs (gps) were challenged intranasally (i.n.) or intraperitoneally (i.p.) with 10,000 times the 50% lethal dose (LD50) of gp-adapted EBOV, and naive gps were then introduced as cage mates for contact exposure at 1 day postinfection (p.i.). The animals were monitored for survival and clinical signs of disease and quantitated for virus shedding postexposure. Changes in the duration of contact of naive gps with infected animals were evaluated for their impact on transmission efficiency. Transmission was more efficient from i.n.- than from i.p.-challenged gps, with 17% versus 83% of naive gps surviving exposure, respectively. Virus shedding was detected beginning at 3 days p.i. from both i.n.- and i.p.-challenged animals. Contact duration positively correlated with transmission efficiency, and the abrogation of direct contact between infected and naive animals through the erection of a steel mesh was effective at stopping virus spread, provided that infectious animal bedding was absent from the cages. Histopathological and immunohistochemical findings show that i.n.-infected gps display enhanced lung pathology and EBOV antigen in the trachea, which supports increased virus transmission from these animals. The results suggest that i.n.-challenged gps are more infectious to naive animals than their systemically infected counterparts and that transmission occurs through direct contact with infectious materials, including those transported through air movement over short distances.Ebola is generally thought to be spread between humans though infectious bodily fluids. However, a study has shown that Ebola can be spread from pigs to monkeys without direct contact. Further studies have been hampered, because an economical animal model for Ebola transmission is not available. To address this, we established a transmission model in guinea pigs and determined the mechanisms behind virus spread. The survival data, in addition to microscopic examination of lung and trachea sections, show that mucosal infection of guinea pigs is an efficient model for Ebola transmission. Virus spread is increased with longer contact times with an infected animal and is possible without direct contact between an infected and a naive host but can be stopped if infectious materials are absent. These results warrant consideration for the development of future strategies against Ebola transmission and for a better understanding of the parameters involved in virus spread.
| S-EPMC4300644 | biostudies-literature
Project description:HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.
| S-EPMC4494233 | biostudies-literature
Project description:Biomarker discovery using plasma obtained from exposed guinea pigs (N=6) exposed to VX.
2020-08-03 | PXD017254 | Pride
Project description:BACKGROUND:Leishmaniasis is a human and animal disease caused by parasites of the genus Leishmania, which is now divided into four subgenera, Leishmania, Viannia, Sauroleishmania and Mundinia. Subgenus Mundinia, established in 2016, is geographically widely dispersed, its distribution covers all continents, except Antarctica. It consists of 5 species; L. enriettii and L. macropodum are parasites of wild mammals while L. martiniquensis, L. orientalis and an unnamed Leishmania sp. from Ghana are infectious to humans. There is very little information on natural reservoir hosts and vectors for any Mundinia species. METHODS:Experimental infections of guinea pigs with all five Mundinia species were performed. Animals were injected intradermally with 107 culture-derived promastigotes into both ear pinnae. The courses of infections were monitored weekly; xenodiagnoses were performed at weeks 4 and 8 post-infection using Lutzomyia migonei. The distribution of parasites in different tissues was determined post-mortem by conventional PCR. RESULTS:No significant differences in weight were observed between infected animals and the control group. Animals infected with L. enriettii developed temporary lesions at the site of inoculation and were infectious to Lu. migonei in xenodiagnoses. Animals infected with L. martiniquensis and L. orientalis developed temporary erythema and dry lesions at the site of inoculation, respectively, but were not infectious to sand flies. Guinea pigs infected by L. macropodum and Leishmania sp. from Ghana showed no signs of infection during experiments, were not infectious to sand flies and leishmanial DNA was not detected in their tissue samples at the end of experiments at week 12 post-inoculation. CONCLUSIONS:According to our results, guinea pigs are not an appropriate model organism for studying Mundinia species other than L. enriettii. We suggest that for better understanding of L. (Mundinia) biology it is necessary to focus on other model organisms.
| S-EPMC7140393 | biostudies-literature
Project description:BackgroundThe treatment of cough is a significant clinical unmet need because there is little evidence that current therapies are effective. Based on evidence supporting a role for N-methyl D-aspartate receptors (NMDARs) in cough, we hypothesized that memantine, a low-affinity, uncompetitive NMDAR channel blocker in routine use for the treatment of Alzheimer disease, could be an effective, well-tolerated, antitussive therapy. The aim of this study was to establish preclinical evidence that memantine has antitussive effects.MethodsWe studied the influence of memantine on experimentally induced coughing in response to citric acid and bradykinin inhalation in guinea pigs. We also compared the potency and efficacy of memantine as an antitussive to other NMDAR antagonists, dextromethorphan and ketamine, and to the γ-aminobutyric acid class B receptor agonist baclofen.ResultsCompared with control subjects, 10 mg/kg memantine significantly reduced the cumulative number of coughs evoked by both citric acid (median, 24.0 [interquartile range (IQR), 13.0-25.5] vs 1.5 [IQR, 0.3-10.3] coughs; P = .012) and bradykinin aerosols (median, 16.0 [IQR, 9.5-18.5] vs 0.0 [IQR, 0-0.75] coughs; P = .002). Memantine 10 mg/kg produced a similar reduction in the cumulative number of coughs to baclofen 3 mg/kg and demonstrated comparatively greater cough suppression than 30 mg/kg dextromethorphan or 30 mg/kg ketamine. This dose of memantine produced no sedative or respiratory depressive effects.ConclusionsThis study illustrates that memantine has marked antitussive effects in guinea pigs, most likely mediated through NMDAR channel blockade. Memantine, therefore, has the potential to be a safe, effective, and well-tolerated antitussive agent.
| S-EPMC3318948 | biostudies-literature
Project description:RNA-seq gene expression analysis of guinea pig and mouse skin after tick bites
2023-04-20 | GSE148967 | GEO
Project description:Drug-induced torsades de pointes (TdP), a life-threatening arrhythmia associated with prolongation of the QT interval, has been a significant reason for withdrawal of several medicines from the market. Prolongation of the QT interval is considered as the best biomarker for predicting the torsadogenic risk of a new chemical entity. Because of the difficulty assessing the risk for TdP during drug development, we evaluated the metabolic phenotype for predicting QT prolongation induced by sparfloxacin, and elucidated the metabolic pathway related to the QT prolongation. We performed electrocardiography analysis and liquid chromatography-mass spectroscopy-based metabolic profiling of plasma samples obtained from 15 guinea pigs after administration of sparfloxacin at doses of 33.3, 100, and 300 mg/kg. Principal component analysis and partial least squares modelling were conducted to select the metabolites that substantially contributed to the prediction of QT prolongation. QTc increased significantly with increasing dose (r?=?0.93). From the PLS analysis, the key metabolites that showed the highest variable importance in the projection values (>1.5) were selected, identified, and used to determine the metabolic network. In particular, cytidine-5'-diphosphate (CDP), deoxycorticosterone, L-aspartic acid and stearic acid were found to be final metabolomic phenotypes for the prediction of QT prolongation. Metabolomic phenotypes for predicting drug-induced QT prolongation of sparfloxacin were developed and can be applied to cardiac toxicity screening of other drugs. In addition, this integrative pharmacometabolomic approach would serve as a good tool for predicting pharmacodynamic or toxicological effects caused by changes in dose.
| S-EPMC3617128 | biostudies-literature
Project description:Background/aimsColonic peristalsis is mainly regulated via intrinsic neurons in guinea pigs. However, autonomic regulation of colonic motility is poorly understood. We explored a guinea pig model for the study of extrinsic nerve effects on the distal colon.MethodsGuinea pigs were sacrificed, their distal colons isolated, preserving pelvic nerves (PN) and inferior mesenteric ganglia (IMG), and placed in a tissue bath. Fecal pellet propagation was conducted during PN and IMG stimulation at 10 Hz, 0.5 ms and 5 V. Distal colon was connected to a closed circuit system, and colonic motor responses were measured during PN and IMG stimulation.ResultsPN stimulation increased pellet velocity to 24.6 ± 0.7 mm/sec (n = 20), while IMG stimulation decreased it to 2.0 ± 0.2 mm/sec (n = 12), compared to controls (13.0 ± 0.7 mm/sec, P ? 0.01). In closed circuit experiments, PN stimulation in-creased the intraluminal pressure, which was abolished by atropine (10(-6) M) and hexamethonium (10(-4) M). PN stimulation reduced the incidence of non-coordinated contractions induced by NG-nitro-L-arginine methyl ester (L-NAME; 10(-4) M). IMG stimulation attenuated intraluminal pressure increase, which was partially reversed by alpha-2 adrenoceptor antagonist (yohimbine; 10(-6) M).ConclusionsPN and IMG input determine speed of pellet progression and peristaltic reflex of the guinea pig distal colon. The stimulatory effects of PN involve nicotinic, muscarinic and nitrergic pathways. The inhibitory effects of IMG stimulation involve alpha-2 adrenoceptors.
| S-EPMC4015210 | biostudies-literature
Project description:Streptococcus equi subsp. zooepidemicus is a known zoonotic pathogen. In this public health investigation conducted in Virginia, USA, in 2013, we identified a probable family cluster of S. zooepidemicus cases linked epidemiologically and genetically to infected guinea pigs. S. zooepidemicus infections should be considered in patients who have severe clinical illness and report guinea pig exposure.
| S-EPMC4285269 | biostudies-literature