Spiral Modiolar Vein: Its Importance in Viral Load of the Inner Ear

1992 ◽  
Vol 101 (10_suppl) ◽  
pp. 67-71 ◽  
Author(s):  
Satoshi Fukuda ◽  
Jeffrey P. Harris ◽  
Elizabeth M. Keithley ◽  
Kazuo Ishikawa ◽  
Babür Küçük ◽  
...  
Keyword(s):  
Viral Load ◽  
Guinea Pig ◽  
Inner Ear ◽  
Guinea Pigs ◽  
Inflammatory Cell ◽  
Sendai Virus ◽  
Inflammatory Cells ◽  
Systemic Circulation ◽  
Scala Tympani ◽  
Normal Defense

Guinea pig—specific cytomegalovirus and Sendai virus were inoculated into the cochleas of seronegative guinea pigs to study the route of entry of cells participating in inner ear inflammation. Inflammatory cells accumulated around the spiral modiolar vein and appeared to be streaming from this vein into the scala tympani via a collecting venule. Inactivated virus inoculated into the cochlea and normal control cochlea failed to show inflammatory cell infiltrates. The spiral modiolar vein appears to play an important role in the movement of cells from the systemic circulation into the inner ear as part of the host's normal defense against invading pathogens such as viruses.

scholarly journals Vaccination with a Live Attenuated Cytomegalovirus Devoid of a Protein Kinase R Inhibitory Gene Results in Reduced Maternal Viremia and Improved Pregnancy Outcome in a Guinea Pig Congenital Infection Model

2015 ◽  
Vol 89 (19) ◽  
pp. 9727-9738 ◽  
Author(s):  
Mark R. Schleiss ◽  
Craig J. Bierle ◽  
Elizabeth C. Swanson ◽  
Michael A. McVoy ◽  
Jian Ben Wang ◽  
...  
Keyword(s):  
Viral Load ◽  
Protein Kinase ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Congenital Infection ◽  
Virus Genome ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protein Kinase R ◽  
Targeted Deletion ◽  
Pup Mortality

ABSTRACTDevelopment of a vaccine to prevent congenital cytomegalovirus infection is a major public health priority. Live vaccines attenuated through mutations targeting viral mechanisms responsible for evasion of host defense may be both safe and efficacious. Safety and vaccine efficacy were evaluated using a guinea pig cytomegalovirus (GPCMV) model. Recombinant GPCMV with a targeted deletion ofgp145(designated Δ145), a viral protein kinase R (PKR) inhibitor, was generated. Attenuation was evaluated following inoculation of 107PFU of Δ145 or parental virus into guinea pigs immunosuppressed with cyclophosphamide. Efficacy was evaluated by immunizing GPCMV-naive guinea pigs twice with either 105or 106PFU of Δ145, establishing pregnancy, and challenging the guinea pigs with salivary gland-adapted GPCMV. The immune response, maternal viral load, pup mortality, and congenital infection rates in the vaccine and control groups were compared. Δ145 was substantially attenuated for replication in immunocompromised guinea pigs. Vaccination with Δ145 induced enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody levels comparable to those achieved in natural infection. In the higher- and lower-dose vaccine groups, pup mortality was reduced to 1/24 (4%) and 4/29 (14%) pups, respectively, whereas it was 26/31 (81%) in unvaccinated control pups (P< 0.0001 for both groups versus the control group). Congenital infection occurred in 20/31 (65%) control pups but only 8/24 (33%) pups in the group vaccinated with 106PFU (P< 0.05). Significant reductions in the magnitude of maternal DNAemia and pup viral load were noted in the vaccine groups compared to those in the controls. Deletion of a GPCMV genome-encoded PKR inhibitor results in a highly attenuated virus that is immunogenic and protective as a vaccine against transplacental infection.IMPORTANCEPrevious attempts to develop successful immunization against cytomegalovirus have largely centered on subunit vaccination against virion proteins but have yielded disappointing results. The advent of bacterial artificial chromosome technologies has enabled engineering of recombinant cytomegaloviruses (CMVs) from which virus genome-encoded immune modulation genes have been deleted, toward the goal of developing a safe and potentially more efficacious live attenuated vaccine. Here we report the findings of studies of such a vaccine against congenital CMV infection based on a virus with a targeted deletion ingp145, a virus genome-encoded inhibitor of protein kinase R, using the guinea pig model of vertical CMV transmission. The deletion virus was attenuated for dissemination in immunocompromised guinea pigs but elicited ELISA and neutralizing responses. The vaccine conferred protection against maternal DNAemia and congenital transmission and resulted in reduced viral loads in newborn guinea pigs. These results provide support for future studies of attenuated CMV vaccines.

Reduction of Inner Ear Inflammation by Treatment with Anti-ICAM-1 Antibody

1997 ◽  
Vol 106 (12) ◽  
pp. 1070-1075 ◽  
Author(s):  
Tsuyoshi Takasu ◽  
Jeffrey P. Harris
Keyword(s):  
Monoclonal Antibody ◽  
Inner Ear ◽  
Therapeutic Approach ◽  
Inflammatory Cell ◽  
Inflammatory Cell Infiltration ◽  
Endolymphatic Sac ◽  
Experimental Paradigm ◽  
Scala Tympani ◽  
Immune Mediated

The in vivo effect of systemic administration of monoclonal antibody (mAb) against ICAM-1 (αICAM-1) in experimental immune-mediated labyrinthitis was evaluated. The αICAM-1–treated rats showed reduced inflammatory cell infiltration in the scala tympani and the perisaccular tissue of the endolymphatic sac. However, with this experimental paradigm, labyrinthitis could not be completely abolished. These findings suggest that ICAM-1–dependent pathways play an important role in the series of immunologic events occurring in the inner ear, and that the use of ICAM-1 antagonist may be a possible therapeutic approach to labyrinthitis.

Effects of interleukin 5-induced pulmonary eosinophilia on airway reactivity in the guinea pig

1996 ◽  
Vol 270 (3) ◽  
pp. L368-L375 ◽  
Author(s):  
C. M. Lilly ◽  
R. W. Chapman ◽  
S. J. Sehring ◽  
P. J. Mauser ◽  
R. W. Egan ◽  
...  
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Airway Hyperresponsiveness ◽  
Histological Grade ◽  
Platelet Activating Factor ◽  
Inflammatory Cells ◽  
Dependent Manner ◽  
Interleukin 5 ◽  
Dose Dependent

Administration of interleukin 5 (IL-5) to guinea pigs by tracheal injection was associated with increased recovery of eosinophils and neutrophils from bronchoalveolar lavage (BAL) fluid. The number of eosinophils recovered from BAL fluid increased in a dose-dependent manner from 9 +/- 2 X 10(3)/ml to a plateau of 143 +/- 29 X 10(3)/ml after the administration of recombinant human IL-5 (rhIL-5). Tracheal administration of recombinant guinea pig IL-5 (gpIL-5) also increased eosinophil recovery but was less potent than rhIL-5. Histological analysis confirmed the presence of inflammatory cells in the lung; there were higher grades of inflammation in airway than in parenchymal tissue after gpIL-5 administration. In addition, the histological grade of airway inflammation was greater 24 and 72 h after gpIL-5 administration than it was 6 days after administration. Airway hyperresponsiveness is reported to occur in guinea pigs exposed to rhIL-5 by intraperitoneal cellular production. It is surprising that airway infiltration with eosinophils induced by the topical application of IL-5 was not associated with hyperresponsiveness to substance P, histamine, or platelet-activating factor in intact animals or to methacholine in tracheally perfused lungs. Furthermore, the microvascular leakage induced by substance P was not altered by rhIL-5 administration. These findings indicate that the presence of eosinophils alone is not sufficient for the expression of airway hyperresponsiveness. Our ability to separate eosinophil recruitment and retention in the tissues from airway hyperresponsiveness indicates that these two processes are distinct and that the presence of eosinophils in lung tissue, by itself, is not sufficient to alter airway contractile responses.

Perilymph Displacement by Cerebrospinal Fluid in the Cochlea

1973 ◽  
Vol 82 (1) ◽  
pp. 53-61 ◽  
Author(s):  
D. H. Moscovitch ◽  
R. P. Gannon ◽  
C. A. Laszlo
Keyword(s):  
Cerebrospinal Fluid ◽  
Guinea Pig ◽  
Respiratory Depression ◽  
Subarachnoid Space ◽  
Guinea Pigs ◽  
Test Substance ◽  
Scala Tympani ◽  
Cochlear Aqueduct ◽  
Single Opening ◽  
Continuous Displacement

On histological examination, the cochlear aqueduct of guinea pigs has a large open lumen, unlike the tissue-filled periotic duct of primates. Hence, the guinea pig's large patent periotic duct appears capable of accommodating a bulk flow of cerebrospinal fluid from the subarachnoid space into the scala tympani if an egress for this fluid was provided by experimentally perforating the cochlea. In order to measure this flow the cochlea in anesthetized guinea pigs was surgically exposed and a single opening was drilled in the basal turn of the scala tympani. All of the displaced perilymph was collected in a calibrated, silicone-coated micropipette sealed into this hole, and; was measured directly by recording the advance of the meniscus in the micropipette. The displacement rates were typically 0.8 to 1 μliter/min, but could be temporarily increased by short periods of respiratory depression and changes in body orientation. From a consideration of anatomical and hydrodynamic relationships, it is concluded that a major source of the fluid which displaces perilymph in the opened guinea pig cochlea is cerebrospinal fluid which enters the scala tympani via the cochlear aqueduct. These results indicate that if a single opening is made into the cochlea at the apex, all of the perilymph in scala tympani (8.0 utters) would be displaced in approximately 10 min. Furthermore, these results have important implications for the technique of intracochlear injection used to study the effects of ions and drugs on the cochlea, because the continuous displacement of perilymph from the opened cochlea consequently removes the test substance previously injected into the scala tympani.

scholarly journals Inflammatory cell distribution in guinea pig airways and its relationship to airway reactivity

2001 ◽  
Vol 10 (3) ◽  
pp. 143-154 ◽  
Author(s):  
Fiona Westerhof ◽  
Wim Timens ◽  
Annemiek van Oosten ◽  
Annet B. Zuidhof ◽  
Nathalie Nauta ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Inflammatory Cell ◽  
Allergen Challenge ◽  
Inflammatory Cells ◽  
Airway Hyperreactivity ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Airway Reactivity ◽  
Allergen Provocation ◽  
Time Point

Although airway inflammation and airway hyperreactivity are observed after allergen inhalation both in allergic humans and animals, little is known about the mechanisms by which inflammatory cells can contribute to allergen-induced airway hyperreactivity. To understand how inflammatory cell infiltration can contribute to airway hyperreactivity, the location of these cells within the airways may be crucial.Using a guinea pig model of acute allergic asthma, we investigated the inflammatory cell infiltration in different airway compartments at 6 and 24 h (i.e. after the early and the late asthmatic reaction, respectively) after allergen or saline challenge in relation to changes in airway reactivity (AR) to histamine.At 6 h after allergen challenge, a threefold(p<0.01)increase in the AR to histamine was observed. At 24 h after challenge, the AR to histamine was lower, but still significantly enhanced (1.6-fold,p<0.05).Adventitial eosinophil and neutrophil numbers in both bronchi and bronchioli were significantly increased at 6 h post-allergen provocation as compared with saline (p<0.01for all), while there was a strong tendency to enhanced eosinophils in the bronchial submucosa at this time point(p=0.08). At 24 h after allergen challenge, the eosinophilic and neutrophilic cell infiltration was reduced. CD3+T lymphocytes were increased in the adventitial compartment of the large airways(p<0.05)and in the parenchyma(p<0.05)at 24h post-allergen, while numbers of CD8+cells did not differ from saline treatment at any time point post-provocation.The results indicate that, after allergen provocation, inflammatory cell numbers in the airways are mainly elevated in the adventitial compartment. The adventitial inflammation could be important for the development of allergen-induced airway hyperreactivity.

scholarly journals Successful transplantation of guinea pig gut microbiota in mice and its effect on pneumonic plague sensitivity

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5637
Author(s):  
Xiang Li ◽  
Zhengchao Li ◽  
Yuxiao Chang ◽  
Fengyi Hou ◽  
Zongyu Huang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Guinea Pig ◽  
Yersinia Pestis ◽  
Intestinal Microbiota ◽  
Guinea Pigs ◽  
Survival Rates ◽  
Systemic Circulation ◽  
Large Mammals ◽  
Pneumonic Plague ◽  
Fecal Suspension

Microbiota-driven variations in the inflammatory response are predicted to regulate host responses to infection. Increasing evidence indicates that the gastrointestinal and respiratory tracts have an intimate relationship with each other. Gut microbiota can influence lung immunity whereby gut-derived injurious factors can reach the lungs and systemic circulation via the intestinal lymphatics. The intestinal microbiota’s ability to resist colonization can be extended to systemic infections or to pathogens infecting distant sites such as the lungs. Unlike the situation with large mammals, the microtusYersinia pestis201 strain exhibits strong virulence in mice, but nearly no virulence to large mammals (such as guinea pigs). Hence, to assess whether the intestinal microbiota from guinea pigs was able to affect the sensitivity of mice to challenge infection with theY. pestis201 strain, we fed mice with guinea pig diets for two months, after which they were administered 0.5 ml of guinea pig fecal suspension for 30 days by oral gavage. The stools from each mouse were collected on days 0, 15, and 30, DNA was extracted from them, and 16S rRNA sequencing was performed to assess the diversity and composition of the gut microbiota. We found that the intestinal microbiota transplants from the guinea pigs were able to colonize the mouse intestines. The mice were then infected withYersinia pestis201 by lung invasion, but no statistical difference was found in the survival rates of the mice that were colonized with the guinea pig’s gut microbiota and the control mice. This indicates that the intestinal microbiota transplantation from the guinea pigs did not affect the sensitivity of the mice to pneumonic plague.

scholarly journals Ototoxic effect of 3’,4’-Dideoxy Kanamycin B (DKB) on the inner ear in the intrauterine guinea pig embryos and newborn guinea pigs

1976 ◽  
Vol 26 ◽  
pp. 90
Author(s):  
Masayuki Yokota ◽  
Masuzo Odaki ◽  
Takemi Koeda ◽  
Kiichi Sato ◽  
Masatoyo Akiyoshi
Keyword(s):  
Guinea Pig ◽  
Inner Ear ◽  
Guinea Pigs

Glycogen in guinea pig neutrophils: Ultrastructural study of neutrophils at the intradermal site of BCG injection

1983 ◽  
Vol 41 ◽  
pp. 726-727
Author(s):  
Corazon D. Bucana
Keyword(s):  
Bone Marrow ◽  
Guinea Pig ◽  
Electron Density ◽  
Peritoneal Cavity ◽  
Ultrastructural Study ◽  
Guinea Pigs ◽  
Random Distribution ◽  
Glycogen Content ◽  
Polymorphonuclear Neutrophils ◽  
Ultrastructural Studies

In the circulating blood of man and guinea pigs, glycogen occurs primarily in polymorphonuclear neutrophils and platelets. The amount of glycogen in neutrophils increases with time after the cells leave the bone marrow, and the distribution of glycogen in neutrophils changes from an apparently random distribution to large clumps when these cells move out of the circulation to the site of inflammation in the peritoneal cavity. The objective of this study was to further investigate changes in glycogen content and distribution in neutrophils. I chose an intradermal site because it allows study of neutrophils at various stages of extravasation.Initially, osmium ferrocyanide and osmium ferricyanide were used to fix glycogen in the neutrophils for ultrastructural studies. My findings confirmed previous reports that showed that glycogen is well preserved by both these fixatives and that osmium ferricyanide protects glycogen from solubilization by uranyl acetate.I found that osmium ferrocyanide similarly protected glycogen. My studies showed, however, that the electron density of mitochondria and other cytoplasmic organelles was lower in samples fixed with osmium ferrocyanide than in samples fixed with osmium ferricyanide.

Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu
Keyword(s):  
Guinea Pig ◽  
Acetylsalicylic Acid ◽  
Guinea Pigs ◽  
Glass Bead ◽  
Animal Species ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

INCORPORATION OF IODIDE INTO ORGANIC COMPOUNDS IN THE GUINEA PIG THYROID

1963 ◽  
Vol 43 (1) ◽  
pp. 110-118 ◽  
Author(s):  
R. Ekholm ◽  
T. Zelander ◽  
P.-S. Agrell
Keyword(s):  
Guinea Pig ◽  
Protein Binding ◽  
Organic Compounds ◽  
Guinea Pigs ◽  
Microsomal Fraction ◽  
Thyroid Tissue ◽  
Particulate Fraction ◽  
Supernatant Fraction ◽  
Hydrolysis Of

ABSTRACT Guinea pigs, kept on a iodine-sufficient diet, were injected with Na131I and the thyroids excised from 45 seconds to 5 days later. The thyroid tissue was homogenized and separated into a combined nuclear-mitochondrial-microsomal fraction and a supernatant fraction by centrifugation at 140 000 g for one hour. Protein bound 131iodine (PB131I) and free 131iodide were determined in the fractions and the PB131I was analysed for monoiodotyrosine (MIT), diiodotyrosine (DIT) and thyroxine after hydrolysis of PB131I. As early as only 20 minutes after the Na131I-injection almost 100% of the particulate fraction 131I was protein bound. In the supernatant fraction the protein binding was somewhat less rapid and PB131I values above 90% of total supernatant 131I were not found until 3 hours after the injection. In all experiments the total amount of PB131I was higher in the supernatant than in the corresponding particulate fraction. The ratio between supernatant PB131I and pellet PB131I was lower in experiments up to 3 minutes and from 2 to 5 days than in experiments of 6 minutes to 20 hours. Hydrolysis of PB131I yielded, even in the shortest experiments, both MIT and DIT. The DIT/MIT ratio was lower in the experiments up to 2 hours than in those of 3 hours and over.

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