Prestin as an Otologic Biomarker of Cisplatin Ototoxicity in a Guinea Pig Model

2017 ◽  
Vol 158 (3) ◽  
pp. 541-546 ◽  
Author(s):  
James Naples ◽  
Robert Cox ◽  
Gregory Bonaiuto ◽  
Kourosh Parham
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Auditory Brainstem ◽  
Therapeutic Interventions ◽  
Saline Injection ◽  
Brainstem Response ◽  
Experimental Animal Study ◽  
Guinea Pig Model ◽  
The Relationship

Objective To evaluate (1) whether changes in serum prestin aid in early detection of cisplatin ototoxicity, (2) the role of diltiazem as an otoprotectant, and (3) whether prestin levels are sensitive to effects of diltiazem. Study Design Experimental animal study. Setting Translational research laboratory. Subjects Twenty female guinea pigs. Methods Two groups of 10 guinea pigs were used. The relationship between serum prestin levels and auditory brainstem response (ABR) thresholds was compared between the groups. All animals had baseline blood draws and ABR thresholds recorded prior to cisplatin administration. Intraperitoneal cisplatin bolus (8 mg/kg) was administered followed by 5 consecutive days of intratympanic (IT) diltiazem (2 mg/kg) or sham IT-saline injection. Serum prestin levels and ABR thresholds were measured at days 1, 2, 3, 7, and 14 postcisplatin. Results In sham, IT-saline–treated animals, mean prestin levels were elevated above baseline on days 1 to 7. The prestin levels were significantly elevated from baseline on day 1 ( P < .001), while significant ABR threshold elevations did not occur until day 2 ( P = .028) for click-evoked ABRs and day 3 ( P = .041) for tones. In diltiazem-treated animals, prestin levels were not elevated above baseline but ABR thresholds were elevated on days 1 to 3. However, the thresholds returned toward baseline on days 7 and 14. Conclusion Changes in serum prestin levels were detectable prior to shifts in ABR thresholds in a guinea pig cisplatin ototoxicity model. These changes did not occur in diltiazem-treated animals. Prestin may serve as a biomarker of cochlear injury that is sensitive to therapeutic interventions in cisplatin ototoxicity.

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.

scholarly journals The release of an endogenous pyrogen from guinea pig leukocytes in vitro: a new model for investigating the role of lymphocytes in fevers induced by antigen in hosts with delayed hypersensitivity.

1977 ◽  
Vol 145 (5) ◽  
pp. 1288-1298 ◽  
Author(s):  
P Chao ◽  
L Francis ◽  
E Atkins
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Polymorphonuclear Leukocytes ◽  
Delayed Hypersensitivity ◽  
Endogenous Pyrogen ◽  
Phagocytic Cells ◽  
Relationship Of ◽  
The Relationship

Guinea pig periotoneal exudate (PE) cells incubated overnight in vitro with heat-killed Staphylococci released an endogenous pyrogen (EP) that could be assayed by intravenous injection in rabbits. The febrile responses were linearly related to the dosage of EP over an eightfold range. PE cells derived from guinea pigs with delayed hypersensitivity (DH) to bovine gamma globulin (BGG), also released EP when incubated with antigen in vitro. This reaction was specific and did not occur withe PE cells from normal or complete Freund's adjuvant-sensitized guinea pigs. Studies indicated that monos and/or polymorphonuclear leukocytes rather than lymphocytes were the source of EP. However, when incubated with BGG and sufficient dosages of BGG-sensitized lymphocytes, normal PE cells released EP over a 42 h period. These results suggest that antigen stimulates specifically sensitized lymphocytes to release an agent (perhaps a lymphokine) that activates phagocytic cells to release EP. This model offers unique advantages for investigating in vitro the role of the lymphocyte in antigen-induced fever in DH as well as the relationship of this lymphocyte-induced activity to other known biologic activities mediated by antigen stimulated lymphocytes.

Second Place — Resident Clinical Science Award 1993: Effect of Otologic Drill Noise on ABR Thresholds in a Guinea Pig Model

1993 ◽  
Vol 109 (4) ◽  
pp. 660-667 ◽  
Author(s):  
Gregg W. Suits ◽  
Robert E. Brummett ◽  
Jim Nunley
Keyword(s):  
Guinea Pig ◽  
Auditory Brainstem Response ◽  
Auditory Brainstem ◽  
Pig Model ◽  
Threshold Shift ◽  
Ear Surgery ◽  
Sound Exposure ◽  
Brainstem Response ◽  
Guinea Pig Model ◽  
Mastoid Surgery

The Noise Generated By The Otologic Drill Has Been Implicated As A Cause Of Sensorineural Hearing Loss After Ear Surgery. However, Clinical Studies On This Subject Are Contradictory And Difficult To Interpret. Therefore A Guinea Pig Model Was Used To Study Whether The Level Of Noise Generated By The Otologic Drill Can Cause Threshold Shifts In The Auditory Brainstem Response (Abr). The Source Noise Was A Recording Obtained During A Human Cadaver Mastoidectomy Using A Microphone And An Accelerometer. Ten Female Topeka-Strain Guinea Pigs Were Exposed To The Recorded Drill Noise For A Period Of 55 Minutes. Exposure Included Both Air-Conducted Energy From A Speaker And Bone-Conducted Energy From A Bone Vibrator Applied Directly To The Skull. Abr Threshold Measurements Were Taken Pre-Exposure (Baseline), Immediately After Exposure, And At Weekly Intervals Thereafter For 3 Weeks. Three Control Animals Were Subjected To The Same Procedure Without The Sound Exposure. A Significant Threshold Shift ( P > 0.0001) Was Seen For Each Frequency Tested (2, 4, 8, 16, 20, And 32 Khz) Immediately After Exposure To Noise In All Experimental Animals. Thresholds Returned To Baseline Within 3 Weeks. We Conclude That The Level Of Noise Generated By The Otologic Drill In Mastoid Surgery Can Cause A Temporary Threshold Shift In This Guinea Pig Model

scholarly journals Regulatory Roles of Differentially Expressed MicroRNAs in Metabolic Processes in Negative Lens-Induced Myopia Guinea Pigs

2019 ◽  
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 Myopia is one of the most common vision defects worldwide. microRNAs can regulate the target gene expression, influencing the development of diseases. In order 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. In summary, 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.

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.

Antioxidant Enzyme Levels Inversely Covary with Hearing Loss After Amikacin Treatment

2003 ◽  
Vol 14 (03) ◽  
pp. 134-143 ◽  
Author(s):  
James J. Klemens ◽  
Robert P. Meech ◽  
Larry F. Hughes ◽  
Satu Somani ◽  
Kathleen C.M. Campbell
Keyword(s):  
Hearing Loss ◽  
Enzyme Activity ◽  
Antioxidant Enzyme ◽  
Guinea Pigs ◽  
Auditory Brainstem ◽  
Antioxidant Enzyme Activity ◽  
Control Group ◽  
Glutathione S Transferase ◽  
Brainstem Response ◽  
The Difference

This study's purpose was to determine if a correlation exists between cochlear antioxidant activity changes and auditory function after induction of aminoglycoside (AG) ototoxicity. Two groups of five 250-350 g albino guinea pigs served as subjects. For 28 days, albino guinea pigs were administered either 200 mg/kg/day amikacin, or saline subcutaneously. Auditory brainstem response testing was performed prior to the first injection and again before sacrifice, 28 days later. Cochleae were harvested and superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase activities and malondialdehyde levels were measured. All antioxidant enzymes had significantly lower activity in the amikacin group (p ≤ 0.05) than in the control group. The difference in cochlear antioxidant enzyme activity between groups inversely correlated significantly with the change in ABR thresholds. The greatest correlation was for the high frequencies, which are most affected by aminoglycosides. This study demonstrates that antioxidant enzyme activity and amikacin-induced hearing loss significantly covary.

scholarly journals Key Role of Capsular Polysaccharide in the Induction of Systemic Infection and Abortion by Hypervirulent Campylobacter jejuni

2017 ◽  
Vol 85 (6) ◽  
Author(s):  
Orhan Sahin ◽  
Samantha A. Terhorst ◽  
Eric R. Burrough ◽  
Zhangqi Shen ◽  
Zuowei Wu ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Campylobacter Jejuni ◽  
Capsular Polysaccharide ◽  
Systemic Infection ◽  
The United States ◽  
Content Type ◽  
Model Following ◽  
Capsule Production ◽  
Guinea Pig Model

ABSTRACT Campylobacter jejuni is a zoonotic pathogen, and a hypervirulent clone, named clone SA, has recently emerged as the predominant cause of ovine abortion in the United States. To induce abortion, orally ingested Campylobacter must translocate across the intestinal epithelium, spread systemically in the circulation, and reach the fetoplacental tissue. Bacterial factors involved in these steps are not well understood. C. jejuni is known to produce capsular polysaccharide (CPS), but the specific role that CPS plays in systemic infection and particularly abortion in animals remains to be determined. In this study, we evaluated the role of CPS in bacteremia using a mouse model and in abortion using a pregnant guinea pig model following oral challenge. Compared with C. jejuni NCTC 11168 and 81-176, a clone SA isolate (IA3902) resulted in significantly higher bacterial counts and a significantly longer duration of bacteremia in mice. The loss of capsule production via gene-specific mutagenesis in IA3902 led to the complete abolishment of bacteremia in mice and abortion in pregnant guinea pigs, while complementation of capsule expression almost fully restored these phenotypes. The capsule mutant strain was also impaired for survival in guinea pig sera and sheep blood. Sequence-based analyses revealed that clone SA possesses a unique CPS locus with a mosaic structure, which has been stably maintained in all clone SA isolates derived from various hosts and times. These findings establish CPS as a key virulence factor for the induction of systemic infection and abortion in pregnant animals and provide a viable candidate for the development of vaccines against hypervirulent C. jejuni.

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