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.

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.

In vivo activity of pyrimidine-dispirotripiperaziniumin in the male guinea pig model of genital herpes

2020 ◽  
Vol 09 (01) ◽  
Author(s):  
Novoselova EA ◽  
Alimbarova LM ◽  
Monakhova NS ◽  
Lepioshkin AY ◽  
Ekins S ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Genital Herpes ◽  
Pig Model ◽  
Guinea Pig Model

scholarly journals Effects of an antiplatelet glycoprotein Ib antibody on hemostatic function in the guinea pig

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 690-694 ◽  
Author(s):  
BH Becker ◽  
JL Miller
Keyword(s):  
Animal Model ◽  
Platelet Count ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Bleeding Time ◽  
Model System ◽  
Platelet Counts ◽  
Equal Dose ◽  
Guinea Pig Model

Abstract Previous studies in the guinea pig model system have established a close structural homology between human and guinea pig glycoproteins Ib (GPIb) and IIb/IIIa (GPIIb/IIIa). Moreover, the murine monoclonal antibody (MoAb) PG-1, which recognizes GPIb in guinea pig platelets and megakaryocytes, exerted full inhibition on von Willebrand factor (vWF)- dependent platelet agglutination without inhibiting aggregation induced by ADP, collagen, or thrombin. The present research extends this animal model system to study of the effects on hemostatic function following the in vivo injection of MoAb PG-1 or its F(ab')2 fragments. A hind limb template bleeding time methodology was developed for use in guinea pigs. Normal bleeding time was determined to be 2.7 +/- 0.5 minutes (mean +/- SD), with an observed range of two to four minutes. Platelet counts in these same animals were 501 +/- 82 x 10(3)/microL. After intraperitoneal (IP) injection of busulfan, guinea pigs became increasingly thrombocytopenic. As long as the platelet count remained above approximately 150 x 10(3)/microL, the bleeding time was not more than five minutes; however, further decrease in the platelet count was accompanied by more marked prolongations of the bleeding time. For 14 to 72 hours after IP injection of 1.3 mg/kg intact PG-1 MoAb, a hemorrhagic state was produced with a bleeding time greater than 20 minutes. The platelet count concurrently decreased to approximately 50% of its baseline value but could not be further decreased either by raising the initial PG-1 dosage tenfold or by administering a second, equal dose 24 hours after the initial injection. This finding may reflect a heterogeneity of circulating platelets with respect to GPIb, to Fc receptors, or to an interaction between them. After IP injection of 0.63 to 2.5 mg/kg PG-1 F(ab')2 fragment, platelet counts did not decrease more than 21% below baseline levels in a 72-hour period, and bleeding times never increased by more than one minute over baseline values. Nevertheless, platelets obtained from animals 24 hours after injection of 2.5 mg/kg PG-1 F(ab')2 showed full inhibition of agglutination induced by ristocetin. The response of these platelets to aggregation by asialo-vWF was also severely inhibited as compared with control platelets. PG-1 F(ab')2 produced no effect on aggregation induced by ADP. These studies show that virtually complete functional block of the vWF receptor by F(ab')2 fragments of the anti-GPIb MoAb PG- 1 is not sufficient to produce a hemorrhagic state in the guinea pig animal model system.

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 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 672. Activity of Ibrexafungerp (Formerly SCY-078) Against Candida auris: In vitro, In Vivo, and Clinical Case Studies of Candidemia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S307-S307
Author(s):  
Stephen Barat ◽  
Katyna Borroto-Esoda ◽  
Mahmoud Ghannoum ◽  
Elizabeth Berkow ◽  
David A Angulo
Keyword(s):  
Guinea Pig ◽  
Murine Model ◽  
The United States ◽  
In Vitro Studies ◽  
Pig Model ◽  
Cutaneous Infection ◽  
Candida Auris ◽  
Guinea Pig Model

Abstract Background Candida auris is a growing global threat; a pathogen associated with high mortality (up to 60%), multidrug resistance, the ability to spread from person-to-person and surface-to-person, presenting high risk for outbreaks in healthcare facilities. Ibrexafungerp is a novel IV/oral glucan synthase inhibitor (triterpenoid) antifungal with activity against Candida, Aspergillus, and Pneumocystis spp., in Phase 3 development. Methods In vitro studies tested ibrexafungerp against >100 clinical isolates of C. auris. Other in vitro studies evaluated the effects of ibrexafungerp against C. auris biofilms. In vivo activity against C. auris was evaluated using a disseminated murine model and a cutaneous infection guinea pig model. In humans, an ongoing open-label trial of ibrexafungerp for treatment of patients with infections caused by C. auris (the CARES study) has been initiated in the United States and India. Results In vitro and in vivo studies demonstrated that ibrexafungerp is active against C. auris, including MDR strains. The MIC mode for ibrexafungerp was 1 μg/mL and the MIC50 and MIC90 were 0.5 and 1 μg/mL, respectively. Many echinocandin-resistant C. auris isolates have shown susceptibility to ibrexafungerp. Furthermore, ibrexafungerp has been shown to reduce biofilm thickness. In animal models of C. auris infection, treatment with ibrexafungerp resulted in improved survival and reduced fungal burden in both the murine model of disseminated infection and the guinea pig model of cutaneous infection as compared with untreated controls. In humans, two patients with difficult to treat C. auris candidemias were enrolled in the CARES study and responded positively to oral ibrexafungerp with eradication of the infection. Conclusion These data demonstrate that ibrexafungerp possess potent in vitro and in vivo activity as well as promising clinical activity. Therefore, continued clinical evaluation of ibrexafungerp as an option to treat C. auris infections is warranted. Disclosures All authors: No reported disclosures.

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