Intrathecal Catheterization and Drug Delivery in Guinea Pigs

2016 ◽  
Vol 125 (2) ◽  
pp. 378-394 ◽  
Author(s):  
Kelly A. Eddinger ◽  
Eric S. Rondon ◽  
Veronica I. Shubayev ◽  
Marjorie R. Grafe ◽  
Miriam Scadeng ◽  
...  
Keyword(s):  
Animal Model ◽  
Guinea Pigs ◽  
Ex Vivo ◽  
Intrathecal Morphine ◽  
Small Animal ◽  
Thermal Stimulus ◽  
Small Animal Model ◽  
Morphine Infusion ◽  
Catheter Tip ◽  
Intrathecal Infusion

Abstract Background Intrathecal infusion of opioids in dogs, sheep, and humans produces local space-occupying masses. To develop a small-animal model, the authors examined effects of intrathecal catheterization and morphine infusion in guinea pigs. Methods Under isoflurane, polyethylene or polyurethane catheters were advanced from the cisterna magna to the lumbar enlargement. Drugs were delivered as a bolus through the externalized catheter or continuously by subcutaneous minipumps. Hind paw withdrawal to a thermal stimulus was assessed. Spinal histopathology was systematically assessed in a blinded fashion. To assist in determining catheter placement, ex vivo images were obtained using magnetic resonance imaging in several animals. Canine spinal tissue from previous intrathecal morphine studies was analyzed in parallel. Results (1) Polyethylene (n = 30) and polyurethane (n = 25) catheters were implanted in the lumbar intrathecal space. (2) Bolus intrathecal morphine produced a dose-dependent (20 to 40 μg/10 μl) increase in thermal escape latencies. (3) Absent infusion, a catheter-associated distortion of the spinal cord and a fibrotic investment were noted along the catheter tract (polyethylene > polyurethane). (4) Intrathecal morphine infusion (25 mg/ml/0.5 μl/h for 14 days) resulted in intrathecal masses (fibroblasts, interspersed collagen, lymphocytes, and macrophages) arising from meninges proximal to the catheter tip in both polyethylene- and polyurethane-catheterized animals. This closely resembles mass histopathology from intrathecal morphine canine studies. Conclusions Continuous intrathecal infusion of morphine leads to pericatheter masses that morphologically resemble those observed in dogs and humans. This small-animal model may be useful for studying spinal drug toxicology in general and the biology of intrathecal granuloma formation in particular.

scholarly journals Development and Characterization of a Guinea Pig-Adapted Sudan Virus

2015 ◽  
Vol 90 (1) ◽  
pp. 392-399 ◽  
Author(s):  
Gary Wong ◽  
Shihua He ◽  
Haiyan Wei ◽  
Andrea Kroeker ◽  
Jonathan Audet ◽  
...  
Keyword(s):  
Animal Model ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Lethal Dose ◽  
Fatal Outcome ◽  
Small Animal ◽  
Disease Outbreak ◽  
Small Animal Model ◽  
Content Type

ABSTRACT Infections with Sudan virus (SUDV), a member of the genus Ebolavirus , result in a severe hemorrhagic fever with a fatal outcome in over 50% of human cases. The paucity of prophylactics and therapeutics against SUDV is attributed to the lack of a small-animal model to screen promising compounds. By repeatedly passaging SUDV within the livers and spleens of guinea pigs in vivo , a guinea pig-adapted SUDV variant (SUDV-GA) uniformly lethal to these animals, with a 50% lethal dose (LD 50 ) of 5.3 × 10 −2 50% tissue culture infective doses (TCID 50 ), was developed. Animals infected with SUDV-GA developed high viremia and died between 9 and 14 days postinfection. Several hallmarks of SUDV infection, including lymphadenopathy, increased liver enzyme activities, and coagulation abnormalities, were observed. Virological analyses and gross pathology, histopathology, and immunohistochemistry findings indicate that SUDV-GA replicates in the livers and spleens of infected animals similarly to SUDV infections in nonhuman primates. These developments will accelerate the development of specific medical countermeasures in preparation for a future disease outbreak due to SUDV. IMPORTANCE A disease outbreak due to Ebola virus (EBOV), suspected to have emerged during December 2013 in Guinea, with over 11,000 dead and 28,000 infected, is finally winding down. Experimental EBOV vaccines and treatments were administered to patients under compassionate circumstances with promising results, and availability of an approved countermeasure appears to be close. However, the same range of experimental candidates against a potential disease outbreak caused by other members of the genus Ebolavirus , such as Sudan virus (SUDV), is not readily available. One bottleneck contributing to this situation is the lack of a small-animal model to screen promising drugs in an efficient and economical manner. To address this, we have generated a SUDV variant (SUDV-GA) that is uniformly lethal to guinea pigs. Animals infected with SUDV-GA develop disease similar to that of SUDV-infected humans and monkeys. We believe that this model will significantly accelerate the development of life-saving measures against SUDV infections.

scholarly journals The Cotton Rat (Sigmodon hispidus) Is a Permissive Small Animal Model of Human Metapneumovirus Infection, Pathogenesis, and Protective Immunity

2005 ◽  
Vol 79 (17) ◽  
pp. 10944-10951 ◽  
Author(s):  
John V. Williams ◽  
Sharon J. Tollefson ◽  
Joyce E. Johnson ◽  
James E. Crowe
Keyword(s):  
Animal Model ◽  
Respiratory Tract ◽  
Guinea Pigs ◽  
Small Animal ◽  
Human Metapneumovirus ◽  
Small Animal Model ◽  
Cotton Rat ◽  
Nasal Tissue ◽  
Hmpv Infection ◽  
Cotton Rats

ABSTRACT Human metapneumovirus (hMPV) is a newly described paramyxovirus that is an important cause of acute respiratory tract disease. We undertook to develop a small animal model of hMPV infection, pathogenesis, and protection. Hamsters, guinea pigs, cotton rats, and nine inbred strains of mice were inoculated intranasally with hMPV. The animals were sacrificed, and nasal and lung tissue virus yields were determined by plaque titration. None of the animals exhibited respiratory symptoms. The quantity of virus present in the nasal tissue ranged from 4.6 × 102 PFU/gram tissue (C3H mice) to greater than 105 PFU/gram (hamster). The amount of virus in the lungs was considerably less than in nasal tissue in each species tested, ranging from undetectable (<5 PFU/g; guinea pigs) to 1.8 × 105 PFU/gram (cotton rat). The peak virus titer in cotton rat lungs occurred on day 4 postinfection. hMPV-infected cotton rat lungs examined on day 4 postinfection exhibited histopathological changes consisting of peribronchial inflammatory infiltrates. Immunohistochemical staining detected virus only at the luminal surfaces of respiratory epithelial cells throughout the respiratory tract. hMPV-infected cotton rats mounted virus-neutralizing antibody responses and were partially protected against virus shedding and lung pathology on subsequent rechallenge with hMPV. Viral antigen was undetectable in the lungs on challenge of previously infected animals. This study demonstrates that the cotton rat is a permissive small animal model of hMPV infection that exhibits lung histopathology associated with infection and that primary infection protected animals against subsequent infection. This model will allow further in vivo studies of hMPV pathogenesis and evaluation of vaccine candidates.

scholarly journals Virulent infection of outbred Hartley guinea pigs with recombinant Pichinde virus as a surrogate small animal model for human Lassa fever

Virulence ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 1131-1141
Author(s):  
Shuiyun Lan ◽  
Wun-Ju Shieh ◽  
Qinfeng Huang ◽  
Sherif R. Zaki ◽  
Yuying Liang ◽  
...  
Keyword(s):  
Animal Model ◽  
Guinea Pigs ◽  
Small Animal ◽  
Lassa Fever ◽  
Small Animal Model ◽  
Pichinde Virus

scholarly journals A Small Animal Model of Ex Vivo Normothermic Liver Perfusion

10.3791/57541 ◽  
2018 ◽  
Author(s):  
Eliza W. Beal ◽  
Curtis Dumond ◽  
Jung-Lye Kim ◽  
Clifford Akateh ◽  
Emre Eren ◽  
...  
Keyword(s):  
Animal Model ◽  
Ex Vivo ◽  
Liver Perfusion ◽  
Small Animal ◽  
Small Animal Model

scholarly journals Rat model of smoke inhalation-induced acute lung injury

2021 ◽  
Vol 8 (1) ◽  
pp. e000879
Author(s):  
Premila Devi Leiphrakpam ◽  
Hannah R Weber ◽  
Tobi Ogun ◽  
Keely L Buesing
Keyword(s):  
Animal Model ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Caspase 3 ◽  
Small Animal ◽  
Therapeutic Options ◽  
Smoke Inhalation ◽  
Small Animal Model ◽  
Injury Score ◽  
Confounding Variables

BackgroundAcute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a lethal disease with limited therapeutic options and an unacceptably high mortality rate. Understanding the complex pathophysiological processes involved in the development of ALI/ARDS is critical for developing novel therapeutic strategies. Smoke inhalation (SI) injury is the leading cause of morbidity and mortality in patients with burn-associated ALI/ARDS; however, to our knowledge few reliable, reproducible models are available for pure SI animal model to investigate therapeutic options for ALI/ARDS without the confounding variables introduced by cutaneous burn or other pathology.ObjectiveTo develop a small animal model of pure SI-induced ALI and to use this model for eventual testing of novel therapeutics for ALI.MethodsRats were exposed to smoke using a custom-made smoke generator. Peripheral oxygen saturation (SpO2), heart rate, arterial blood gas, and chest X-ray (CXR) were measured before and after SI. Wet/dry weight (W/D) ratio, lung injury score and immunohistochemical staining of cleaved caspase 3 were performed on harvested lung tissues of healthy and SI animals.ResultsThe current study demonstrates the induction of ALI in rats after SI as reflected by a significant, sustained decrease in SpO2 and the development of diffuse bilateral pulmonary infiltrates on CXR. Lung tissue of animals exposed to SI showed increased inflammation, oedema and apoptosis as reflected by the increase in W/D ratio, injury score and cleaved caspase 3 level of the harvested tissues compared with healthy animals.ConclusionWe have successfully developed a small animal model of pure SI-induced ALI. This model is offered to the scientific community as a reliable model of isolated pulmonary SI-induced injury without the confounding variables of cutaneous injury or other systemic pathology to be used for study of novel therapeutics or other investigation.

scholarly journals Rat-to-Chinese tree shrew heart transplantation is a novel small animal model to study non-Gal-mediated discordant xenograft humoral rejection

2015 ◽  
Vol 22 (6) ◽  
pp. 468-475 ◽  
Author(s):  
WeiLi Chen ◽  
Yuan Wu ◽  
Akira Shimizu ◽  
YinLong Lian ◽  
Masayuki Tasaki ◽  
...  
Keyword(s):  
Animal Model ◽  
Heart Transplantation ◽  
Tree Shrew ◽  
Small Animal ◽  
Humoral Rejection ◽  
Small Animal Model

scholarly journals Longitudinal Raman Spectroscopic Observation of Skin Biochemical Changes due to Chemotherapeutic Treatment for Breast Cancer in Small Animal Model

2017 ◽  
Vol 2017 ◽  
pp. 1-9
Author(s):  
Myeongsu Seong ◽  
NoSoung Myoung ◽  
Songhyun Lee ◽  
Hyeryun Jeong ◽  
Sang-Youp Yim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Animal Model ◽  
Raman Spectra ◽  
Fiber Optic ◽  
Animal Experiments ◽  
Small Animal ◽  
Fiber Optic Probe ◽  
Small Animal Model ◽  
Biochemical Compositions ◽  
Optic Probe

The cancer field effect (CFE) has been highlighted as one of indirect indications for tissue variations that are insensitive to conventional diagnostic techniques. In this research, we had a hypothesis that chemotherapy for breast cancer would affect skin biochemical compositions that would be reflected by Raman spectral changes. We used a fiber-optic probe-based Raman spectroscopy to perform preliminary animal experiments to validate the hypothesis. Firstly, we verified the probing depth of the fiber-optic probe (~800 μm) using a simple intravenous fat emulsion-filled phantom having a silicon wafer at the bottom inside a cuvette. Then, we obtained Raman spectra during breast cancer treatment by chemotherapy from a small animal model in longitudinal manner. Our results showed that the treatment causes variations of biochemical compositions in the skin. For further validation, the Raman spectra will have to be collected from more populations and spectra will need to be compared with immunohistochemistry of the breast tissue.

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