scholarly journals Validation of Сhoice of Laboratory Model for Preclinical Estimation of Medical Protectors Against Bolivian Hemorrhagic Fever

2019 ◽  
Vol 3 (4) ◽  
pp. 319-328
Keyword(s):  
Animal Models ◽  
Guinea Pigs ◽  
Macaca Fascicularis ◽  
Hemorrhagic Fever ◽  
Laboratory Animals ◽  
Laboratory Model ◽  
Small Laboratory ◽  
Quantitative Indices ◽  
Machupo Virus

Th is review is dedicated to the peculiarities of pathogenesis of the experimental Bolivian hemorrhagic fever (BHF) – the disease, caused by Machupo virus (Arenaviridae family). Th e authors come to the conclusion that for carrying out preclinical researches of the medical means of protection (MMP) in vivo on small laboratory animals it is expedient to use guinea pigs, infected with a strain of Chicava or with a variant of Carvallo strain, adapted for these animals. Th e use of guinea pigs as small laboratory animals when studying pathogenesis of the disease caused by Machupo virus allows to carry out statistically reliable defi nition of quantitative indices of an experimental infection and to select medicines for the fi nal stage of preclinical assessment. As arenaviruses block the process of formation of interferon (IFN) in the infected organism, mice, defective by IFN formation, are the perspective animal models for the study of BHF pathogenesis and may be used for the study of attenuated variants of Machupo virus. Th e Javanese macaques (Macaca fascicularis) are the laboratory animals, modeling the pathogenetic manifestations of BHF in humans. Th ey can be used when carrying out the fi nal stages of preclinical assessment of means of medical protection

Nasal cavity dimensions in guinea pig and rat measured by acoustic rhinometry and fluid-displacement method

2004 ◽  
Vol 96 (6) ◽  
pp. 2109-2114 ◽  
Author(s):  
Sune P. Straszek ◽  
Ole F. Pedersen
Keyword(s):  
Nasal Cavity ◽  
Guinea Pigs ◽  
Acoustic Rhinometry ◽  
Laboratory Animals ◽  
Small Laboratory ◽  
Acoustic Measurements ◽  
Displacement Method ◽  
Fluid Displacement ◽  
Custom Made

The purpose of the study was to measure nasal passageway dimensions in guinea pigs and rats by use of acoustic rhinometry (AR) and by a previously described fluid-displacement method (FDM) (Straszek SP, Taagehoej F, Graff S, and Pedersen OF. J Appl Physiol 95: 635–642, 2003) to investigate the potential of AR in pharmacological research with these animals. We measured the area-distance relationships by AR of nasal cavities postmortem in five guinea pigs (Duncan Hartley, 400 g) and five rats (Wistar, 250 g) by using custom-made equipment scaled for the purpose. Nosepieces were made from plastic pipette tips and either inserted into or glued onto the nostrils. We used liquid perfluorocarbon in the fluid-displacement study, and it was carried out subsequent to the acoustic measurements. We found for guinea pigs that AR measured a mean volume of 98 mm3 (95–100 mm3) (mean and 95% confidence interval) of the first 2 cm of the cavity. FDM measured a mean volume of 146 mm3 (117–175 mm3), meaning that AR only measured 70% (50–90) of the volume by FDM. For rats, the volume from 0 to 2 cm was 58 mm3 (55–61 mm3) by AR and 73 mm3 (60–87 mm3) by FDM, resulting in AR only measuring 83% (66–100%) of volume by FDM (see Table 2 ). We conclude that absolute nasal cavity dimensions are underestimated by AR in guinea pigs and rats. This does not preclude that relative changes may be correctly measured. In vivo trials with AR using rats have not yet been published. The FDM is possibly the most accurate alternative to AR for measurements of the nasal cavity geometry in small laboratory animals, but it can only be used postmortem.

scholarly journals Machupo virus with mutations in the transmembrane domain and glycosylation sites is attenuated and immunogenic in animal models of Bolivian Hemorrhagic Fever

2021 ◽  
Author(s):  
Emily K Mantlo ◽  
Junki Maruyama ◽  
John T Manning ◽  
Timothy G Wanninger ◽  
Cheng Huang ◽  
...  
Keyword(s):  
Animal Models ◽  
Mouse Model ◽  
Guinea Pigs ◽  
Rational Design ◽  
Transmembrane Domain ◽  
Vaccine Development ◽  
Hemorrhagic Fever ◽  
Highly Pathogenic ◽  
Glycosylation Sites ◽  
Machupo Virus

AbstractSeveral highly pathogenic mammarenaviruses cause severe hemorrhagic and neurologic disease in humans, for which vaccines and antivirals are limited or unavailable. New World (NW) mammarenavirus Machupo virus (MACV) infection causes Bolivian hemorrhagic fever in humans. We previously reported that the disruption of specific N-linked glycan sites on the glycoprotein (GPC) partially attenuate MACV in an IFN-αβ/γ receptor knockout mouse model. However, some capability to induce neurological pathology still remained. Highly pathogenic Junin virus (JUNV) is another NW arenavirus closely related to MACV. A F427I substitution in the GPC transmembrane domain (TMD) rendered JUNV attenuated in a lethal mouse model after intracranial inoculation. In this study, we rationally designed and rescued a MACV containing mutations at two glycosylation sites and the corresponding F438I substitution in GPC TMD. The MACV mutant is fully attenuated in IFN-αβ/γ receptor knockout mice and outbred guinea pigs. Furthermore, inoculation with this mutant MACV fully protected guinea pigs from wild-type MACV lethal challenge. Lastly, we found the GPC TMD F438I substitution greatly impaired MACV growth in neuronal cell lines of mouse and human origins. Our results highlight the critical roles of the glycans and the TMD on the GPC in arenavirus virulence, which informs the rational design of potential vaccine candidates for highly pathogenic arenaviruses.ImportanceFor arenaviruses, the only vaccine available is the live-attenuated Candid#1 vaccine, a JUNV vaccine approved in Argentina. We and others have found that the glycans on GPC and the F427 residue in the GPC TMD are important for virulence of JUNV. Nevertheless, mutating either of them is not sufficient for full and stable attenuation of JUNV. Using reverse genetics, we disrupted specific glycosylation sites on MACV GPC, and also introduced the corresponding F438I substitution in the GPC TMD. This MACV mutant is fully attenuated in two animal models and protects animals from lethal infection. Thus, our studies highlight the feasibility of rational attenuation of highly pathogenic arenaviruses for vaccine development. Another important finding from this study is that the F438I substitution in GPC TMD could substantially affect MACV replication in neurons. Future studies are warranted to elucidate the underlying mechanism and the implication of this mutation in arenavirus neural tropism.

In-vitro and in-vivo Evaluation of Anti-asthmatic Activity of Eugenia jambolana bark

2021 ◽  
pp. 3337-3342
Author(s):  
Bhong Prabha N. ◽  
Naikawade Nilofar. S. ◽  
Mali Pratibha. R. ◽  
Bindu Madhavi. S.
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Animal Models ◽  
Aqueous Extract ◽  
Guinea Pigs ◽  
Bark Extract ◽  
Eugenia Jambolana ◽  
In Vivo Animal Models

Objectives: The present study designed to evaluate the Antiasthmatic activity of aqueous extract of bark of Eugenia Jambolana (AEEJ) on in vitro and in vivo animal models. Materials and methods: Different in vitro and in vivo animal models was used to study the anti asthmatic activity as isolated goat tracheal chain preparation, Acetylcholine and Histamine induced bronconstriction in guinea pigs, effect of drug extract on histamine release from mast cell was checked by clonidine-induced mast cell degranulation, and milk-induced eosinophilia and leukocytosis. Results: In-vitro study on goat tracheal chain preparation revealed that aqueous extract of Eugenia jambolana (AEEJ)bark exerted antagonistic effect on the histamine induced contraction. (P<0.05) The guinea pigs when exposed to 0.2% histamine aerosol showed signs of progressive dyspnoea leading to convulsions. AEEJ significantly prolonged the latent period of convulsions (PCT) as compared to control following the exposure of histamine (0.2%) aerosol (P<0.01). The observation of present study indicates aqueous extract of Eugenia jambolana shows significant inhibition of milk induced eosinophilia and leukocytosis. Group of animals pretreated with aqueous Eugenia jambolana bark extract showed significant reduction in degranulation of mast cells when challenged with clonidine. The prevention of degranulation process by the aqueous Eugenia jambolana bark extract (P<0.01) indicates a possible stabilizing effect on the mast cells, indicating mast cell stabilizing activity. Conclusions: Thus, AEEJ showed antihistaminic, mast cell stabilizing and protective in guinea pigs against histamine induced PCD, reduced eosinophilia and leukocytosis and hence possesses potential role in the treatment of asthma.

Neuroleptanalgesic drug combinations in the anaesthetic management of small laboratory animals

1975 ◽  
Vol 9 (3) ◽  
pp. 161-178 ◽  
Author(s):  
C. J. Green
Keyword(s):  
Guinea Pigs ◽  
Anaesthetic Management ◽  
Drug Combinations ◽  
Laboratory Animals ◽  
Small Laboratory ◽  
Fentanyl Citrate

Trials of different drug combinations for use in rabbits, guinea-pigs, rats, hamsters and mice are described in detail and experience over a 5-year period evaluated. Combinations of fentanyl citrate, fluanisone and diazepam provided exceptionally good anaesthesia in each species and were considered superior to other injectable agents.

Slow Clearance of Acylated, Hybrid Thrombolytic Enzymes

1988 ◽  
Vol 59 (03) ◽  
pp. 421-425 ◽  
Author(s):  
Jeff H Robinson ◽  
Ian Dodd ◽  
Ashiq Esmail ◽  
Harry Ferres ◽  
Barbara Nunn
Keyword(s):  
Half Life ◽  
Guinea Pigs ◽  
Pharmacokinetic Profile ◽  
Plasminogen Activators ◽  
Laboratory Animals ◽  
Small Laboratory ◽  
Active Centre ◽  
A Chain ◽  
Two Hybrid ◽  
Hybrid Enzymes

SummaryTwo hybrid plasminogen activators, plasmin A-chair/t-PA Bchain and plasmin A-chain/u-PA B-chain have been synthestzed and purified in sufficient yield to permit measurement of clearance in small laboratory animals. Each hybrid enzyme was reversibly acylated at the active centre to allow the pharmacokinetic profile to be followed using an activity-based method without interference from plasma inhibitors. The acylated plasmin/u-PA hybrid had a clearance half-life (t½) in guinea pigs of approximately 80 min, whereas acyl u-PA had a t½ of 3 min. The pharmacokinetic profile of the acylated plasmin/t-PA hybrid was measured in guinea pigs, rats and rabbits; the half-lives in all three species were 60–80 min compared to half-lives of acylated, native t-PA that were in the range 0.5–1.0 min. Thus, plasmin A-chaincontaining, acylated hybrid enzymes are cleared some 30- to 100-fold more slowly than the acylated parent activators.

scholarly journals Prospects for the use of a drug based on a complex of fatty acid esters in models of laboratory animals in vivo

2021 ◽  
Vol 37 ◽  
pp. 00175
Author(s):  
K.Yu. Smirnova ◽  
A.V. Bannikova ◽  
S.V. Kozlov ◽  
O.V. Romanova
Keyword(s):  
Fatty Acid ◽  
Guinea Pigs ◽  
Fatal Outcome ◽  
Fatty Acid Esters ◽  
Laboratory Animals ◽  
Control Group ◽  
Burn Wound ◽  
Complicated Course ◽  
Acid Esters

In this work we carried out studies of the first obtained micellar composition of fatty acid esters with allantoin on a water basis to determine its local irritant effect and therapeutic efficacy in the treatment of burns. It was found that there was a sequential change in the phases of the burn wound process in all groups. During the observation period, wound suppuration was not observed; there were 4 cases of a complicated course of the wound process and a fatal outcome in the control group. When conducting studies of local irritant effects, the assessment was carried out in points, in the experimental group it was on average 2 points as for the animals of the control group. The conducted studies allow us to conclude that the drug, when applied to the skin according to the interstate standard GOST ISO 10993-10—2011, has a weak degree of response to irritation in guinea pigs. The application of a permissive dose of the drug to sensitized guinea pigs does not cause a response from the skin, which indicates the absence of allergenic properties in this composition.

scholarly journals Visualization capabilities of experimental oncological models in small laboratory animals

2018 ◽  
Vol 9 (4) ◽  
pp. 105-112 ◽  
Author(s):  
Valeria A. Pechatnikova ◽  
Alexander P. Trashkov ◽  
Maria A. Zelenenko ◽  
Nikolay A. Verlov ◽  
Grigorii A. Chizh ◽  
...  
Keyword(s):  
Soft Tissues ◽  
Pathological Process ◽  
Nerve Fibers ◽  
Laboratory Animals ◽  
Small Laboratory ◽  
Internal Organs ◽  
Imaging Methods ◽  
Non Invasive ◽  
Long Time

For a long time non-invasive imaging methods have been inaccessible in preclinical practice; their introduction lately has broadened the boundaries of relevant studies and felicitated new approaches to solving fundamental problems. Up-to-date imaging methods constitute an essential component of preclinical and translational biomedical research allowing quick and non-invasive extended representation of structural organization and functional characteristics of pathological processes in vivo. Methods of radiation diagnosis and nuclear magnetic resonance allow to assess the state of bones, soft tissues, internal organs, blood vessels and peripheral nerve fibers in various animals, not only mammals, but also fish, amphibians, reptiles and insects. Multiparametric studies can uniquely localize any anatomical structure or pathological process. However, not all existing techniques are applicable to various oncological models of small laboratory animals.

High-resolution light microscopy of living organs in situ

1995 ◽  
Vol 53 ◽  
pp. 790-791
Author(s):  
R. S. McCuskey
Keyword(s):  
High Resolution ◽  
Light Microscopy ◽  
Laboratory Animals ◽  
Small Laboratory ◽  
Abdominal Incision ◽  
Standard Compound ◽  
Working Distance ◽  
Microscope Stage

Most organs in anesthetized small laboratory animals can be studied in vivo by light microscopy of relatively thin (3-5mm), transilluminated areas of the organ. Thicker areas of the organs in these species, as well as thicker organs of larger animals can be examined only by epi-ilumination. However, the resolution obtainable with epi-ilumination usually is inferior to that realized with transillumination. This paper reviews these methods using the liver as an example of the organ of study. A standard compound trinocular microscope is used which is modified for in vivo microscopy and is equipped for both transillumination and epi-illumination. After the animal is anesthetized, the liver is gently exteriorized through a subcostal, abdominal incision and positioned over a window of optical grade mica or glass on a specially designed, heated microscope stage having provisions for draining irrigation fluids. The window overlies a long working distance condenser. The liver is covered by a piece of Saran or Mylar film which holds it in position and limits movements induced by respiration, the heart and the intestines.

Attempts to establish infections with Strongyloides stercoralis in mice and other laboratory animals

1982 ◽  
Vol 56 (1) ◽  
pp. 23-26 ◽  
Author(s):  
H. J. S. Dawkins ◽  
D. I. Grove
Keyword(s):  
Immune Response ◽  
Small Intestine ◽  
Guinea Pigs ◽  
Strongyloides Stercoralis ◽  
Inbred Strains ◽  
Laboratory Animals ◽  
Complete Development ◽  
Outbred Strain ◽  
Age And Sex

ABSTRACTInfection of a dog with Strongyloides stercoralis filariform larvae resulted in a persistent infection. Patent infections were not seen in rabbits, guinea-pigs, rats and 11 inbred strains and one outbred strain of mice. Manipulation of factors known to influence S. ratti infections in mice, such as age and sex of the host and the route of larval presentation, did not facilitate the appearance of rhabditiform larvae in the stools. Administration of immunosuppressive doses of corticosterioids to rabbits, guinea-pigs and C57B1/6 mice did not permit complete development. Similarly, the course of infection was not altered in T cell-deficient hypothymic (nu/nu) mice. The fate of filariform larvae applied to the skin of mice was ascertained; filariform larvae were observed to migrate from the skin via the lungs to the muscles within several days of infection. Although S. stercoralis does not develop to maturity in the small intestine of mice, this system does allow in vivo studies of the actions of anthelmintics against filariform larvae as well as a number of aspects of the immune response to this parasite.

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