scholarly journals Allergic Sensitization Increases Contractile Responses to 5-HT in Guinea Pig Aorta

2020 ◽  
pp. 191-197 ◽  
Author(s):  
P. CAMPOS-BEDOLLA ◽  
R. DE-LA-CRUZ-NEGRETE ◽  
M. VARGAS ◽  
E. TORREJÓN-GONZÁLEZ ◽  
D. MENDOZA-MEJÍA ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Western Blot ◽  
Receptor Antagonist ◽  
Clinical Studies ◽  
Guinea Pigs ◽  
Allergic Sensitization ◽  
Area Under The Curve ◽  
Receptor Expression ◽  
Contractile Responses ◽  
Guinea Pig Model

Epidemiological and clinical studies suggest that asthma is associated with adverse cardiovascular outcomes, but its mechanism is uncertain. 5-Hydroxytryptamine (5-HT) is a mediator involved in asthma and in cardiovascular functioning. Thus, in the present study, we explored whether allergic sensitization in guinea pigs modifies 5-HT-induced contractile responses and 5-HT2A receptor expression in thoracic aorta rings. We found that sensitization produced a significant increase of 100 µM 5-HT-induced contractions of aorta rings (~27 % greater contraction than in non-sensitized animals, p<0.05). Preincubation with 10 nM ketanserin (a 5-HT2A receptor antagonist) reduced by ~30 % (p=0.003) and ~36 % (p=0.005) the area under the curve of 5-HT-induced contractions in aortas from non-sensitized and sensitized animals, respectively. There were no differences between sensitized and non-sensitized animals with respect to mRNA (qPCR) and protein (Western blot) expression of 5-HT2A receptor in thoracic aortas. We concluded that in this guinea pig model of asthma, allergic sensitization is not confined to airways, but also affects arterial contractile responses to 5-HT; changes in the expression of the 5-HT2A receptor appear not to be involved in this phenomenon.

scholarly journals Role of 5-HT2 Receptors Family in the Allergy-Induced Increased Aorta Contractile Responses to 5-HT

2021 ◽  
Author(s):  
Patricia Campos-Bedolla ◽  
Emmanuel Gilberto Torrejón-González ◽  
Dinora Mendoza-Mejía ◽  
Mario H. Vargas ◽  
Patricia Segura-Medina ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Protein Expression ◽  
Guinea Pigs ◽  
Allergic Sensitization ◽  
Cardiovascular Disorders ◽  
Contractile Responses ◽  
Asthma Model ◽  
Increased Risk ◽  
Mild Reduction

Abstract Asthma poses an increased risk for cardiovascular disorders, suggesting that allergy, which is an underlying asthma process, causes atypical functioning of organs other than the lungs. A previous study in a guinea-pig asthma model, we concluded that allergic sensitization increased aorta contractile responses to 5-HT. To further characterize these responses, here, we explored the role of the 5-HT2 receptors family. We found that TCB-2 (5-HT2A agonist) and WAY161503 (5-HT2C agonist) induced aorta contractions resembling those elicited by 5-HT but less intense (~43% and ~25%, respectively). In these experiments, aortas from sensitized guinea pigs showed increased contractions to TCB-2 but not to WAY161503. In turn, MDL 100907 (5-HT2A antagonist) and RS-102221 (5-HT2C antagonist) caused a notably and mild reduction of the 5-HT-induced contractions, respectively, with no differences seen between sensitized and non-sensitized tissues. BW723C86 (5-HT2B agonist) did not induce contractile responses, and RS-127445 (5-HT2B antagonist) did not modify the contractile responses to 5-HT. In non-sensitized aortas, the pattern of protein expression of receptors was 5HT2B>5-HT2A=5-HT2C, which did not change in sensitized animals. In conclusion, we found that allergic sensitization increased the aorta contractile responses to 5-HT, partly mediated by enhanced responses of 5-HT2A receptors, which was unrelated to changes in these receptors' expression.

scholarly journals Intravitreal brimonidine inhibits form-deprivation myopia in guinea pigs

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Yifang Yang ◽  
Junshu Wu ◽  
Defu Wu ◽  
Qi Wei ◽  
Tan Zhong ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Intravitreal Injection ◽  
Guinea Pigs ◽  
Intravitreal Injections ◽  
Eye Drops ◽  
Rna Seq ◽  
Myopia Progression ◽  
Expression Levels ◽  
Guinea Pig Model ◽  
Administration Methods

Abstract Background The use of ocular hypotensive drugs has been reported to attenuate myopia progression. This study explores whether brimonidine can slow myopia progression in the guinea pig form-deprivation (FD) model. Methods Three-week-old pigmented male guinea pigs (Cavia porcellus) underwent monocular FD and were treated with 3 different methods of brimonidine administration (eye drops, subconjunctival or intravitreal injections). Four different concentrations of brimonidine were tested for intravitreal injection (2 μg/μL, 4 μg/μL, 20 μg/μL, 40 μg/μL). All treatments continued for a period of 21 days. Tonometry, retinoscopy, and A-scan ultrasonography were used to monitor intraocular pressure (IOP), refractive error and axial length (AL), respectively. On day 21, guinea pigs were sacrificed for RNA sequencing (RNA-seq) to screen for associated transcriptomic changes. Results The myopia model was successfully established in FD animals (control eye vs. FD eye, respectively: refraction at day 20, 0.97 ± 0.18 D vs. − 0.13 ± 0.38 D, F = 6.921, P = 0.02; AL difference between day 0 and day 21, 0.29 ± 0.04 mm vs. 0.45 ± 0.03 mm, F = 11.655, P = 0.004). Among the 3 different brimonidine administration methods, intravitreal injection was the most effective in slowing myopia progression, and 4 μg/μL was the most effective among the four different concentrations of brimonidine intravitreal injection tested. The AL and the refraction of the brimonidine intravitreal injection group was significantly shorter or more hyperopic than those of other 2 groups. Four μg/μL produced the smallest difference in AL and spherical equivalent difference values. FD treatment significantly increased the IOP. IOP was significantly lower at 1 day after intravitreal injections which was the lowest in FD eye of intravitreal injection of brimonidine. At day 21, gene expression analyses using RNA-seq showed upregulation of Col1a1 and Mmp2 expression levels by intravitreal brimonidine. Conclusions Among the 3 different administration methods, intravitreal injection of brimonidine was the most effective in slowing myopia progression in the FD guinea pig model. Intravitreal brimonidine at 4 μg/μL significantly reduced the development of FD myopia in guinea pigs. Expression levels of the Col1a1 and Mmp2 genes were significantly increased in the retinal tissues of the FD-Inj-Br group.

scholarly journals Use of quantitative real-time PCR for studying the dissemination of Leptospira interrogans in the guinea pig infection model of leptospirosis

2009 ◽  
Vol 58 (5) ◽  
pp. 648-655 ◽  
Author(s):  
Kristel Lourdault ◽  
Florence Aviat ◽  
Mathieu Picardeau
Keyword(s):  
Guinea Pig ◽  
Real Time ◽  
Real Time Pcr ◽  
Guinea Pigs ◽  
Infection Model ◽  
Avirulent Strain ◽  
Leptospira Interrogans ◽  
Quantitative Real Time Pcr ◽  
Guinea Pig Model

The dynamics of leptospirosis infection have been poorly studied. The purpose of this study was to determine the LD50, rate of bacterial dissemination, histopathology and antibody responses against leptospira following inoculation with the highly virulent Leptospira interrogans Fiocruz L1-130 strain in a guinea pig model of leptospirosis. Three routes of infection (intraperitoneal, conjunctival and subcutaneous inoculation) were used to establish disease in guinea pigs. The size and kinetics of leptospiral burdens in the blood and tissues of infected animals were determined over a 1 week course of infection using quantitative real-time PCR (qPCR). Bacteraemia peaked at day 5 post-infection reaching more than 5×104 leptospires ml−1. The highest spirochaetal load was found in the liver and kidneys, and was associated with alterations in organ tissues and a decline in liver and kidney functions. In contrast, lesions and bacteria were not detected in guinea pigs infected with an avirulent strain derived from a high-passage-number in vitro-passaged variant of the Fiocruz L1-130 strain. The use of qPCR supports the findings of earlier studies and provides an easy and reliable method for the quantification of L. interrogans in the tissues of infected animals. qPCR will be used in future studies to evaluate the efficacy of vaccine candidates against leptospirosis and the virulence of selected L. interrogans mutants relative to the parental strain.

A 5-HT4 agonist mosapride enhances rectorectal and rectoanal reflexes in guinea pigs

2003 ◽  
Vol 285 (2) ◽  
pp. G389-G395 ◽  
Author(s):  
Hidehiko Shimatani ◽  
Yu Kojima ◽  
Makoto Kadowaki ◽  
Tadashi Nakagawa ◽  
Hisao Fujii ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Receptor Antagonist ◽  
Strain Gauge ◽  
Guinea Pigs ◽  
Internal Anal Sphincter ◽  
Pressure Transducer ◽  
Force Transducer ◽  
Rectal Distension ◽  
Pelvic Nerves ◽  
Strain Gauge Force Transducer

The rectal distension-evoked reflex rectal (R-R) contractions and internal anal sphincter (R-IAS) relaxations in guinea pigs were generated through the extrinsic sacral excitatory nerve pathway (pelvic nerves) and the intrinsic cholinergic excitatory and nitrergic inhibitory nerve pathways. The aim of the present study was to evaluate whether a prokinetic benzamide, mosapride, enhances the R-R and R-IAS reflexes mediated via 5-HT4 receptors in the guinea pig. The mechanical activities of the R and IAS were recorded with a balloon connected to a pressure transducer and a strain gauge force transducer in the anesthetized guinea pig with intact spinal-intestinal pathways. Gradual and sustained rectal distension evoked R-R contractions and synchronous R-IAS relaxations. Mosapride (0.1–1.0 mg/kg iv) dose-dependently enhanced both R-R and R-IAS reflex responses. Reflex indexes for R-R and R-IAS maximally increased from 1.0 (control) to 1.92 and 1.88, respectively. A specific 5-HT4 receptor antagonist, GR 113808 (1.0 mg/kg iv), antagonized the enhancement of the R-R and R-IAS reflexes induced by mosapride 1.0 mg/kg iv. The present results indicate that mosapride enhanced the R-R and R-IAS reflexes mediated through 5-HT4 receptors.

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.

scholarly journals Serological evidence of rotavirus infection in guinea pig colony

1988 ◽  
Vol 83 (4) ◽  
pp. 411-413 ◽  
Author(s):  
L. de Castro ◽  
H. P. de Araújo ◽  
A. M. Fialho ◽  
V. S. Gouvea ◽  
H. G. Pereira
Keyword(s):  
Guinea Pig ◽  
Western Blot ◽  
Enzyme Immunoassay ◽  
Guinea Pigs ◽  
Serological Evidence ◽  
Western Blot Assay ◽  
Antibody Titres ◽  
Group A Rotaviruses ◽  
Group A ◽  
Experimental Use

Antibodies reacting with simian rotavirus SAII were detected by enzyme immunoassay (EIA) and Western blot assay (WBA) in sera from guinea pigs bred for experimental use at the Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. The proportion of antibody-positive animals and the antibody titres rose sharply in 1985, were maintained at a high levels in 1986 and declined in 1987. There were no obvious signs of disease coinciding with serological evidence of infection. Results of WBA suggest that the virus involved belongs to subgroup 1 of group A rotaviruses.

scholarly journals Regulatory roles of differentially expressed MicroRNAs in metabolic processes in negative Lens-induced myopia Guinea pigs

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Dadong Guo ◽  
Meihua Ding ◽  
Xiaoli Song ◽  
Yuanyuan Sun ◽  
Guoping Li ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Signaling Pathways ◽  
Guinea Pigs ◽  
Messenger Rna ◽  
Differentially Expressed ◽  
Metabolic Processes ◽  
Ppar Signaling ◽  
Vision Defects ◽  
Guinea Pig Model

Abstract Background Myopia is one of the most common vision defects worldwide. microRNAs can regulate the target gene expression, influencing the development of diseases. Results To investigate the alterations of microRNA profiling in negative lens-induced myopia (NLIM) guinea pigs and to explore the regulatory role of microRNAs in the occurrence and the development of myopia, we first established the NLIM guinea pig model after induction for 2 weeks. Further, we isolated sclera to purify total messenger RNA (mRNA) in both NLIM and NLIM fellow sclera. Using next generation sequencing technique and bioinformatics analysis, we identified the differentially expressed microRNAs in NLIM guinea pigs, performed the bioinformatics annotation for the differentially expressed microRNAs, and validated the expression of differentially expressed microRNAs. As a result, we successfully established an NLIM model in guinea pigs, identified 27 differentially expressed microRNAs in NLIM guinea pig sclera, including 10 upregulated and 17 downregulated microRNAs. The KEGG annotation showed the main signaling pathways were closely associated with PPAR signaling, pyruvate and propanoate metabolisms, and TGF-beta signaling pathways. Conclusions Our findings indicate that the development of myopia is mainly involved in the disorder of metabolic processes in NLIM guinea pigs. The PPAR signaling, pyruvate and propanoate metabolism pathways may play roles in the development of myopia.

Pharmacology of L-660,711 (MK-571): a novel potent and selective leukotriene D4 receptor antagonist

1989 ◽  
Vol 67 (1) ◽  
pp. 17-28 ◽  
Author(s):  
T. R. Jones ◽  
R. Zamboni ◽  
M. Belley ◽  
E. Champion ◽  
L. Charette ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Receptor Antagonist ◽  
Guinea Pigs ◽  
Competitive Inhibitor ◽  
Dose Ratio ◽  
Leukotriene D4 ◽  
Small Component ◽  
Human Trachea ◽  
D4 Receptor ◽  
Orally Active

L-660,711 (3-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl) ((3-dimethyl amino-3-oxo propyl)thio)methyl)thio)propanoic acid is a potent and selective competitive inhibitor of [3H]leukotriene D4 binding in guinea pig (Ki value, 0.22 nM) and human (Ki value, 2.1 nM) lung membranes but is essentially inactive versus [3H]leukotriene C4 binding (IC50 value in guinea pig lung, 23 μM). Functionally it competitively antagonized contractions of guinea pig trachea and ileum induced by leukotriene (LT) D4 (respective pA2 values, 9.4 and 10.5) and LTE4 (respective pA2 values, 9.1 and 10.4) and contractions of human trachea induced by LTD4 (pA2 value, 8.5). L-660,711 (5.8 × 10−8 M) antagonized contractions of guinea pig trachea induced by LTC4 in the absence (dose ratio = 28) but not in the presence of 45 mM L-serine borate (dose ratio <2). L-660,711 (1.9 × 10−5 M) did not block contractions of guinea pig trachea induced by histamine, acetylcholine, 5-hydroxytryptamine, PGF2α, U-44069, or PGD2. In the presence of atropine, mepyramine, and indomethacin, L-660,711 (1.9 × 10−5 M) inhibited a small component of the response to antigen on guinea pig trachea but completely blocked anti-IgE-induced contractions of human trachea. L-660,711 (i.v.) antagonized bronchoconstriction induced in anesthetized guinea pigs by i.v. LTC4, LTD4, and LTE4 but did not block bronchoconstriction to arachidonic acid, U-44069, 5-hydroxytryptamine, histamine, or acetylcholine. Intraduodenal L-660,711 antagonized LTD4 (0.2–12.8 μg/kg) -induced bronchoconstriction in guinea pigs, and p. o. L-660,711 blocked LTD4- and Ascaris-induced bronchoconstriction in conscious squirrel monkeys and ovalbumin-induced bronchoconstriction in conscious sensitized rats treated with methysergide (3 μg/kg). The pharmacological profile of L-660,711 indicates that it is a potent, selective, orally active leukotriene receptor antagonist which is well suited to determine the role played by LTD4 and LTE4 in asthma and other pathophysiologic conditions.

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.

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