scholarly journals Efficacy of Combined Rifampicin Formulations Delivered by the Pulmonary Route to Treat Tuberculosis in the Guinea Pig Model

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1309
Author(s):  
Lucila Garcia-Contreras ◽  
Vasu Sethuraman ◽  
Masha Kazantseva ◽  
Anthony Hickey
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Pig Model ◽  
Spleen Weight ◽  
Bacterial Burden ◽  
Solvent Evaporation Method ◽  
Projected Area ◽  
Evaporation Method ◽  
Polypropylene Membrane ◽  
Guinea Pig Model

Liposomes, as vehicles alone or in combination with rifampicin (RIF) microparticles (RMs), were evaluated as vehicles to enhance the permeation of RIF into granulomas. RIF liposomes (RLs) were extruded through a 0.1 µm polypropylene membrane. RMs were prepared by the solvent evaporation method. Four weeks after infection, guinea pigs (GPs) were assigned to groups treated with a combination of RM-RLs or RLs alone. RLs were nebulized after extrusion whereas RMs were suspended in saline and nebulized to GPs in a nose-only inhalation chamber. Necropsy was performed after the treatment; the lungs and spleen were resected for bacteriology. RLs had mean diameters of 137.1 ± 33.7 nm whereas RMs had a projected area diameter of 2.48 µm. The volume diameter of RMs was 64 ± 1 µm, indicating that RMs were aggregated. The treatment of TB-infected GPs with RLs significantly reduced their lung bacterial burden and wet spleen weight compared with those treated with blank liposomes. The treatment of TB-infected animals with RM-RLs also reduced their lung bacterial burden and wet spleen weight even though these reductions were not statistically different. Based on these results, the permeation of RIF into granulomas appears to be enhanced when encapsulated into liposomes delivered by the pulmonary route.

scholarly journals Listeriosis in the Pregnant Guinea Pig: a Model of Vertical Transmission

2004 ◽  
Vol 72 (1) ◽  
pp. 489-497 ◽  
Author(s):  
Anna I. Bakardjiev ◽  
Brian A. Stacy ◽  
Susan J. Fisher ◽  
Daniel A. Portnoy
Keyword(s):  
Guinea Pig ◽  
Vertical Transmission ◽  
Guinea Pigs ◽  
Effective Means ◽  
Clinical Manifestations ◽  
Pig Model ◽  
Cellular Mechanisms ◽  
Guinea Pig Model ◽  
Internalin A

ABSTRACT Feto-placental infections represent a major cause of pregnancy complications, and yet the underlying molecular and cellular mechanisms of vertical transmission are poorly understood. Listeria monocytogenes, a facultative intracellular pathogen, is one of a group of pathogens that are known to cause feto-placental infections in humans and other mammals. The purpose of this study was to evaluate possible mechanisms of vertical transmission of L. monocytogenes. Humans and guinea pigs have a hemochorial placenta, where a single layer of fetally derived trophoblasts separates maternal from fetal circulation. We characterized L. monocytogenes infection of the feto-placental unit in a pregnant guinea pig model and in primary human trophoblasts and trophoblast-derived cell lines. The clinical manifestations of listeriosis in the pregnant guinea pigs and the tropism of L. monocytogenes to the guinea pig placenta resembled those in humans. Trophoblast cell culture systems were permissive for listerial growth and cell-to-cell spread and revealed that L. monocytogenes deficient in internalin A, a virulence factor that mediates invasion of nonphagocytic cells, was 100-fold defective in invasion. However, crossing of the feto-placental barrier in the guinea pig model was independent of internalin A, suggesting a negligible role for internalin-mediated direct invasion of trophoblasts in vivo. Further understanding of vertical transmission of L. monocytogenes will help in designing more effective means of treatment and disease prevention.

Iron Does Not Cause Arrhythmias in the Guinea Pig Model of Transfusional Iron Overload.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3724-3724
Author(s):  
Lana Kaiser ◽  
John Davis ◽  
Jon Patterson ◽  
N. Bari Olivier ◽  
George Bohart ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Iron Overload ◽  
Cardiac Arrhythmias ◽  
Guinea Pigs ◽  
Pig Model ◽  
Cardiac Events ◽  
Liver Iron ◽  
Secondary Iron Overload ◽  
Life Threatening ◽  
Guinea Pig Model

Abstract Cardiac events, including heart failure and arrhythmias, are the major cause of death in patients with b-thalassemia. Although cardiac arrhythmias in humans are believed to result from iron overload, excluding confounding factors in the human population is difficult. The purpose of these studies was to evaluate the development of cardiac arrhythmias using the guinea pig model of secondary iron overload. Electrocardiograms were recorded via surgically implanted telemetry devices in guinea pigs loaded intraperitoneally with iron dextran and controls. Cardiac and liver iron concentrations were significantly elevated in the iron loaded animals when compared to control, and were in the range of those reported for humans with thalassemia. Arrhythmias were noted infrequently in both iron loaded and control guinea pigs. No life threatening arrhythmias were detected in either group. These data suggest that iron alone may be insufficient to cause cardiac arrhythmias, and that arrhythmias detected in individuals with iron overload may be the result of a complex interplay of factors.

scholarly journals The ascorbate-deficient guinea pig model of shigellosis allows the study of the entire Shigella life cycle

2020 ◽  
Author(s):  
Antonin C André ◽  
Céline Mulet ◽  
Mark C Anderson ◽  
Louise Injarabian ◽  
Achim Buch ◽  
...  
Keyword(s):  
Animal Model ◽  
Life Cycle ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Colonic Mucosa ◽  
Extended Period ◽  
Pig Model ◽  
Suitable Animal Model ◽  
Guinea Pig Model

AbstractShigella spp. are the causative agents of bacillary dysentery or shigellosis, mainly in children living in developing countries. The study of Shigella entire life cycle in vivo and the evaluation of vaccine candidates’ protection efficacy have been hampered by the lack of a suitable animal model of infection (1). None of the ones evaluated so far (mouse, rabbit, guinea pig) allows to recapitulate shigellosis symptoms upon Shigella oral challenge. Historical reports suggest that dysentery and scurvy are both metabolic diseases associated with ascorbate-deficiency. Mammals which are susceptible to Shigella infection (humans, non-human primates and guinea pigs) are the lonely ones which are unable to synthesize ascorbate. We optimized a low-ascorbate diet to induce moderate ascorbate-deficiency but not scurvy in guinea pigs (Ascplasma conc.=1.6 μM vs 36 μM with optimal ascorbate supply). We demonstrated that moderate ascorbate-deficiency increases shigellosis severity during extended period of time (up to 48h) with all strains tested (Shigella flexneri 5a and 2a, Shigella sonnei). At late time-points, a massive influx of neutrophils was observed both within the disrupted colonic mucosa and in the luminal compartment, although Shigella remains able to disseminate deep into the organ to reach the sub-mucosal layer and the bloodstream. This new model of shigellosis opens new doors for the study both of Shigella infection strategy and innate and adaptive immune responses to Shigella infection. It may be also of a great interest to study the virulence of other pathogen for which no suitable animal model of infection is available (Vibrio cholerae, Yersinia pestis, Mycobacterium tuberculosis or Campylobacter jejuni, among others).SignificanceThe study of Shigella virulence cycle in vivo has been hampered by the lack of a suitable animal model, which would allow the colonic mucosa infection upon oral challenge. Based on historical reports and physiological aspects, it was suggested that ascorbate-deficiency may stand as a new dysentery risk-factor. To test this hypothesis, we set up a new ascorbate-deficient guinea pig model and demonstrated for the first time that the Shigella infectious process occurred for extended period of time (up to 48h) and demonstrated that shigellosis severity was higher in ascorbate-deficient animal. Ascorbate-deficient guinea pig model of infection may be used to assess the virulence of other pathogens for which no suitable animal model of infection is still lacking.

scholarly journals The Novel TRPA1 Antagonist BI01305834 Inhibits Ovalbumin-Induced Bronchoconstriction in Guinea Pigs

2020 ◽  
Author(s):  
Mariska van den Berg ◽  
Susan Nijboer - Brinksma ◽  
Sophie Bos ◽  
Maarten van den Berge ◽  
David Lamb ◽  
...  
Keyword(s):  
Pilot Study ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Ex Vivo ◽  
Optimal Dose ◽  
Pig Model ◽  
The Novel ◽  
Airway Narrowing ◽  
Guinea Pig Model

Abstract Background: We hypothesized that TRPA1 channels contribute to airway hyperresponsiveness (AHR) and inflammation in asthma. We evaluated the efficacy of the novel TRPA1 antagonist BI01305834 in a guinea pig model of asthma. Methods: First a pilot study was performed in a guinea pig model of allergic asthma to find the optimal dose of BI01305834. Next, the effect of BI01305834 on AHR to inhaled histamine after the early and late asthmatic reaction (EAR and LAR), magnitude of EAR and LAR and airway inflammation was assessed. Precision-cut lung slices and trachea strips were used to investigate the bronchoprotective and bronchodilating effect of BI01305834. Statistical evaluation of differences of in vivo data was performed using a Mann-Whitney U test or One-way nonparametric Kruskal-Wallis ANOVA, for ex vivo data One- or Two-way ANOVA was used, all with Dunnett’s post-hoc test where appropriate.Results: A dose of 1 mg/kg BI01305834 was selected based on AHR and exposure data in blood samples from the pilot study. In the subsequent study 1 mg/kg BI01305834 inhibited AHR after the EAR, and the development of EAR and LAR elicited by ovalbumin in ovalbumin-sensitized guinea pigs. BI01305834 did not inhibit allergen-induced total and differential cells in the lavage fluid and interleukin-13 gene expression in lung homogenates. Furthermore, BI01305834 was able to inhibit allergen and histamine-induced airway narrowing in guinea pig lung slices, without affecting histamine release, and reverse allergen-induced bronchoconstriction in guinea pig trachea strips.Conclusions: TRPA1 inhibition protects against AHR and the EAR and LAR in vivo and allergen and histamine-induced airway narrowing ex vivo, and reverses allergen-induced bronchoconstriction, independently of inflammation. This effect was partially dependent upon histamine, suggesting a neuronal and possible non-neuronal role for TRPA1 in allergen-induced bronchoconstriction.

scholarly journals A new candidate vaccine for human brucellosis based on influenza viral vectors: development of immunization schedule in guinea pig model

2020 ◽  
Author(s):  
Dina Bugybayeva ◽  
Zhailaubay Kydyrbayev ◽  
Nadezhda Zinina ◽  
Nurika Assanzhanova ◽  
Bolat Yespembetov ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Viral Vectors ◽  
Virulent Strain ◽  
Pig Model ◽  
Effective Vaccine ◽  
Human Brucellosis ◽  
Sublingual Administration ◽  
Vector Vaccine ◽  
Guinea Pig Model

Abstract Background: A new candidate vector vaccine against human brucellosis based on recombinant influenza viral vectors (rIVV) subtypes H5N1 expressing Brucella Omp16, L7/L12, Omp19 or Cu-Zn SOD proteins has been developed. This paper presents the results of the study of protection of the vaccine with various options of administering, dosing and frequency of use on guinea pigs.Methods: General states of guinea pigs was assessed based on , behavior and dynamics of a guinea pig weight-gain test. The effectiveness of the new anti-brucellosis vector vaccine was determined by studying its protective effect after conjunctival, intranasal and sublingual administration in doses 105 EID50, 106 EID50 and 107 EID50 during prime and boost vaccinations of animals, followed by challenge with a virulent strain of B. mellitensis 16M infection. For sake of comparison, the commercial B. melitensis Rev.1 vaccine was used as a control. The protective properties of vaccines were assessed by quantitation of Brucella colonization in organs and tissues of infected animals and compared to the control groups.Results: It was observed a gradual increase in body weight of guinea pigs after prime and booster immunization with the vaccine using conjunctival, intranasal and sublingual routes of administration, as well as after using various doses of vaccine. . The most optimal way of using the vaccine has been established: double intranasal immunization of guinea pigs at a dose of 106 EID50, which provides 80% protection of guinea pigs from B. melitensis 16M infection (P < 0.05), which is comparable to the results of the effectiveness of the commercial B. melitensis Rev.1 vaccine.Conclusions: We developed effective vaccine candidate against brucellosis and developed its immunization protocol in guinea pig model. We believe that this study is a substantial step for using the vaccine for future pre-clinical and clinical trials in human.

scholarly journals A new candidate vaccine for human brucellosis based on influenza viral vectors: development of immunization schedule in guinea pig model

2020 ◽  
Author(s):  
Dina Bugybayeva ◽  
Zhailaubay Kydyrbayev ◽  
Nadezhda Zinina ◽  
Nurika Assanzhanova ◽  
Bolat Yespembetov ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Viral Vectors ◽  
Pig Model ◽  
Effective Vaccine ◽  
Human Brucellosis ◽  
Sublingual Administration ◽  
Protective Properties ◽  
Vector Vaccine ◽  
Guinea Pig Model

Abstract Background: A new candidate vector vaccine against human brucellosis based on recombinant influenza viral vectors (rIVV) subtypes H5N1 expressing Brucella Omp16, L7/L12, Omp19 or Cu-Zn SOD proteins has been developed. This paper presents the results of the study of the safety and protective properties of the vaccine with various options of administering, dosing and frequency of use on guinea pigs.Methods: The safety of the vaccine was assessed based on the general condition, behavior and dynamics of a guinea pig weight-gain test. The effectiveness of the new anti-brucellosis vector vaccine was determined by studying its protective effect after conjunctival, intranasal and sublingual administration in doses 105 EID50, 106 EID50 and 107 EID50 during prime and boost vaccinations of animals, followed by challenge with a virulent strain of B. mellitensis 16M infection. For sake of comparison, the commercial B. melitensis Rev.1 vaccine was used as a control. The protective properties of vaccines were assessed by quantitation of Brucella colonization in organs and tissues of infected animals and compared to the control groups.Results: It was found that the vaccine after prime and booster immunization using conjunctival, intranasal and sublingual routes of administration, as well as after using various doses of vaccine were safe for guinea pigs. The most optimal way of using the vaccine has been established: double intranasal immunization of guinea pigs at a dose of 106 EID50, which provides 80% protection of guinea pigs from B. melitensis 16M infection (P < 0.05), which is comparable to the results of the effectiveness of the commercial B. melitensis Rev.1 vaccine.Conclusions: We developed effective vaccine candidate against brucellosis and developed its immunization protocol in guinea pig model. We believe that this study is a substantial step for using the vaccine for future pre-clinical and clinical trials in human.

scholarly journals Evaluation of Peripheral Blood Markers as Early Endpoint Criteria in Guinea Pigs (Cavia porcellus) when Testing Tuberculosis Vaccine Candidates

2020 ◽  
Vol 70 (1) ◽  
pp. 45-55
Author(s):  
Wendy R Williams ◽  
JoLynn Troudt ◽  
Elizabeth Creissen ◽  
Helle Bielefeldt-Ohmann ◽  
Matthew S Johnston ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Virulent Strain ◽  
Pig Model ◽  
Starting Point ◽  
Science Community ◽  
Serum Biochemical ◽  
Guinea Pig Model ◽  
Hematology Parameters ◽  
Experimental Disease

The guinea pig model of tuberculosis is used extensively to assess the efficacy of novel tuberculosis vaccines. There are established parameters to determine vaccine efficacy in this model, but the science community currently lacks established biomarkers for early detection and monitoring of experimental disease in guinea pigs. To define a set of biomarkers that could be used as benchmarks for disease progression and early endpoint criteria, we assessed serum biochemical and hematology parameters in 2 groups of guinea pigs—one vaccinated with the attenuated Mycobacterium bovis vaccine strain (BCG) and one sham-vaccinated with saline—and then experimentally infected with a virulent strain of Mycobacterium tuberculosis. After infection, WBC showed the strongest differences between saline-inoculated and vaccinated animals, with more subtle changes in other serum biochemical parameters, including ALT and ALP. Therefore, this study provides a starting point for evaluating the utility of blood values as possible early endpoint criteria in the guinea pig model of tuberculosis.

scholarly journals Efficacy of the Investigational Echinocandin ASP9726 in a Guinea Pig Model of Invasive Pulmonary Aspergillosis

2015 ◽  
Vol 59 (5) ◽  
pp. 2875-2881 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Satoru Matsumoto ◽  
Rosie A. Bocanegra ◽  
Monica L. Herrera ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Quantitative Pcr ◽  
Guinea Pigs ◽  
Plasma Concentrations ◽  
Invasive Pulmonary Aspergillosis ◽  
Pig Model ◽  
Pulmonary Aspergillosis ◽  
Content Type ◽  
Fungal Burden ◽  
Guinea Pig Model

ABSTRACTASP9726 is an investigational echinocandin within vitroactivity againstAspergillusspecies. We evaluated the pharmacokinetics and efficacy of this agent in an established guinea pig model of invasive pulmonary aspergillosis. ASP9726 plasma concentrations were measured in guinea pigs administered either a single dose or multiple doses of this agent at 2.5, 5, and 10 mg/kg of body weight/day by subcutaneous injection. Immunosuppressed guinea pigs were inoculated withA. fumigatusAF293, and ASP9726 (2.5, 5, and 10 mg/kg/day), voriconazole (10 mg/kg by oral gavage twice daily), or caspofungin (3 mg/kg/day by intraperitoneal injection) was administered for 8 days. Changes in fungal burden were measured by enumerating CFU and by quantitative PCR of specimens from within the lungs, as well as by analysis of serum (1→3)-β-d-glucan and galactomannan. Lung histopathology was also evaluated. ASP9726 plasma concentrations increased in a dose-proportional manner, and the drug was well tolerated at each dose. Each dose of ASP9726, voriconazole, and caspofungin significantly reduced pulmonary fungal burden as measured by quantitative PCR and by determining (1→3)-β-d-glucan and galactomannan levels, but only voriconazole significantly reduced numbers of CFU. ASP9726 at 5 mg/kg also significantly improved survival. Histopathology demonstrated morphological changes in hyphae in animals exposed to ASP9726 and caspofungin, consistent with the activities of the echinocandins. These results suggest that ASP9726 may be efficacious for the treatment of invasive pulmonary aspergillosis.

scholarly journals Three Protein Cocktails Mediate Delayed-Type Hypersensitivity Responses Indistinguishable from That Elicited by Purified Protein Derivative in the Guinea Pig Model ofMycobacterium tuberculosisInfection

2010 ◽  
Vol 79 (2) ◽  
pp. 716-723 ◽  
Author(s):  
Hongliang Yang ◽  
JoLynn Troudt ◽  
Ajay Grover ◽  
Kimberly Arnett ◽  
Megan Lucas ◽  
...  
Keyword(s):  
T Cells ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Ex Vivo ◽  
Interleukin 10 ◽  
Pig Model ◽  
Delayed Type Hypersensitivity ◽  
Necrosis Factor Alpha ◽  
Purified Protein Derivative ◽  
Guinea Pig Model

ABSTRACTPurified protein derivative (PPD) is a widely used reagent for the diagnosis ofMycobacterium tuberculosisinfection. Recently, the molecular composition of PPD was defined, with hundreds of mycobacterial protein representatives making up PPD. Which, if any, of these specific products drive the potency of PPD remains in question. In this study, two proteins (DnaK and GroEL2) previously identified as dominant proteins in PPD were tested for the capacity to induce delayed-type hypersensitivity (DTH) responses in H37Rv-infected or BCG-vaccinated guinea pigs. These two proteins were used in pull-down assays to identify interacting PPD products. Six proteins were identified as interacting partners with DnaK and GroEL2, i.e., Rv0009, Rv0475, Rv0569, Rv0685, Rv2626c, and Rv2632c. These six proteins were tested alone and in combination with DnaK and GroEL2 for the capacity to induce a DTH response in the guinea pig model. From these studies, two cocktails, DnaK/GroEL2/Rv0009 and DnaK/GroEL2/Rv0685, were found to induce DTH responses in H37Rv-infected or BCG-vaccinated guinea pigs that were indistinguishable from DTH responses driven by a PPD injection. The mechanism by which DTH responses were induced was elucidated by histologic examination, analysis of activated CD4+/CD8+T cells, and cytokine mRNA expression at the site of the DTH response. PPD and the protein cocktails tested induced strong DTH responses in H37Rv-infected guinea pigs. Ex vivo phenotyping of T cells at the DTH site indicated that this response is mediated by activated CD4+and CD8+T cells, with increases in gamma interferon and tumor necrosis factor alpha, but not interleukin-10, at the site of the DTH response. Our results demonstrate for the first time that the PPD response can be mimicked at the molecular level with defined protein cocktails. The use of this defined product will allow a more thorough understanding of the DTH response and may provide a platform for more rapid and sensitive second-generation skin test reagents for the diagnosis ofM. tuberculosisinfection.

scholarly journals Efficacy of Voriconazole in a Guinea Pig Model of Invasive Trichosporonosis

2006 ◽  
Vol 50 (6) ◽  
pp. 2240-2243 ◽  
Author(s):  
Carolina Serena ◽  
Félix Gilgado ◽  
Marçal Mariné ◽  
F. Javier Pastor ◽  
Josep Guarro
Keyword(s):  
Body Weight ◽  
Guinea Pig ◽  
Amphotericin B ◽  
Guinea Pigs ◽  
Systemic Infection ◽  
Pig Model ◽  
Trichosporon Asahii ◽  
Tissue Burden ◽  
Guinea Pig Model

ABSTRACT We have evaluated the efficacy of voriconazole (VRC) in a systemic infection by Trichosporon asahii in immunosuppressed guinea pigs. VRC was more effective than amphotericin B in prolonging survival and reducing tissue burden. The best results were obtained with VRC at 10 mg/kg of body weight/day.

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