English Shorthair Guinea Pigs Research Articles

Antagonism by NKP608 of substance P-induced plasma protein exudation in a novel preparation of perfused trachea in rats and guinea-pigs in vivo.

To examine whether NKP608, a novel 1-benzoyl-2-benzyl-4-aminopiperidine NK1 receptor antagonist, inhibits substance P (SP)-induced airway plasma protein exudation in vivo. Anaesthetised English shorthair guinea-pigs and Wistar rats. Tachykinin peptides were applied topically onto the trachea and antagonists administered intravenously. Tracheal segments isolated in situ were perfused with saline and plasma-derived protein assayed in the perfusate. SP (1 microM) caused plasma protein exudation, which was abolished by an NK1 antagonist (RP 67580,1.75 micromol/kg) but unaffected by an NK2 antagonist (SR 48968, 1.75 micromol/ kg) indicating the response is NK1-receptor-mediated. This was confirmed with a response to an NK1 agonist ([Sar9, Met(O2)11]-SP, 1 microM) but none to an NK2 agonist ([betaAla8]-neurokinin A(4-10), 1 microM). NKP608 inhibited SP responses with estimated ID50 values (micromol/kg) of 0.0044 (guinea-pigs) and 0.19 (rats). NKP608 is an antagonist in vivo of NK1 receptor-induced tracheal plasma protein exudation and is more potent in guinea-pigs than rats.

Postnatal development of flicker sensitivity in guinea pigs

Background: The retinal response to flickering stimuli (steady state ERG) recruits many retinal elements and is a sensitive indicator of early retinal dysfunction. This study reports the post‐natal maturation of the steady state ERG response in guinea pigs.Methods: The steady state ERG response to flickering stimuli (0.6 to 20 Hz) was recorded from dark adapted (more than 12 hrs) English Shorthair guinea pigs (n = 7) using flashes that produced rod and cone dominated responses. Temporal sensitivity functions and critical fusion frequencies (GFF) were derived over a range of ages from postnatal day (PND) 1 to 45.Results: Guinea pig rod and cone temporal sensitivity functions show shape characteristics and CFF similar to humans. Furthermore, the post‐natal development of the guinea pig temporal characteristics is also similar to that of humans—they are present at birth and mature rapidly post‐natally. The time‐course of CFF maturation is similar for rod and cone mediated responses.Conclusions: These data show that the temporal response and its maturation in the guinea pig retina is similar to that in humans. Therefore, we propose that the guinea pig is a particularly useful animal model to study retinal disease in early childhood.

Strain differences in adrenal CYP2D16 expression in guinea pigs: Relationship to xenobiotic metabolism

Experiments were done to determine the mechanisms responsible for differences in adrenal microsomal xenobiotic metabolism between Strain 13 and English Short-Hair (ESH) guinea pigs. The rates of adrenal xenobiotic metabolism (bufuralol 1′-hydroxylase, benzo[a]pyrene hydroxylase, benzphetamine N-demethylase) were 2–3 times greater in microsomes from the Strain 13 animals. In both strains, xenobiotic-metabolizing activities were far greater in the inner zone (zona reticularis) than in the outer zones (zona fasciculata and zona glomerulosa) of the adrenal cortex. Northern blot analyses of total adrenal RNA with a CYP2D16 cDNA as the probe revealed significantly greater amounts of CYP2D16 mRNA in the Strain 13 guinea pigs. In addition, SDS-PAGE and Western blotting of adrenal microsomes demonstrated higher concentrations of CYP2D16 protein in Strain 13 than in ESH animals. Expression of CYP2D16 was predominantly in the inner zone of the adrenal, coinciding with the major site of xenobiotic metabolism. The results demonstrated higher levels of expression of CYP2D16 in adrenal glands from Strain 13 than from ESH guinea pigs, which may account for the strain differences in adrenal xenobiotic metabolism. Strain 13 guinea pigs should serve as a good experimental model for further studies on the regulation of adrenal CYP2D16.

Differential susceptibility to noise-induced permanent threshold shift between albino and pigmented guinea pigs

Evidence that reduced levels of cochlear melanin are associated with increased auditory sensitivity, increased levels of auditory fatigue and an increased susceptibility to noise-induced hearing loss led us to investigate the effects of noise exposure on the cochlear microphonic (CM) in albino and pigmented English shorthair guinea pigs. CMs were recorded from the round window prior to and at 90 min and 7 days after exposure to 45 min of 126 dB noise. Thresholds for the first detectable elicitation of the CM for four pure tones were determined and the output voltage of each cochlea was measured in 10 dB steps through intensity levels which produced a maximum voltage amplitude in the CM and voltage rollover. This analysis demonstrated that: 1. (1) albino guinea pigs displayed significantly lower auditory thresholds than did pigmented animals before exposure to noise; 2. (2) thresholds were elevated to comparable levels in both groups 90 min after noise exposure; 3. (3) pigmented guinea pigs showed a reliable recovery in CM thresholds 7 days after exposure to noise while thresholds in the albinos remained elevated to the same degree at both 90 min and 7 days after noise; 4. (4) 90 min after noise exposure, the maximum voltage output of albino cochleas was significantly less than that recorded from the cochleas of the pigmented guinea pigs. These results demonstrate that albino guinea pigs are more susceptible to the ototoxic effects of high intensity noise than pigmented guinea pigs. Converging evidence indicates that some aspects of cochlear function involve melanin pigment and that its absence may produce auditory abnormalities. Reduced melanin pigmentation may also contribute to such phenomena as noise-induced threshold shifts and individual differences in noise-induced hearing loss.

Markers of Venezuelan encephalitis virus which distinguish enzootic strains of subtype I-D from those of I-E.

Strains of Venezuelan encephalitis virus isolated from enzootic habitats during interepizootic periods in Middle America and northern South America can be distinguished from each other antigenically by hemagglutination inhibition. This test has provided the basis for the classification of these virus strains into subtypes I-E and I-D, respectively. Virus strains of these two subtypes have been found to differ profoundly with respect to virulence for English short hair guinea pigs. Studies are described which confirm that virus strains of the I-D subtype are guinea pig virulent, and that virulence is not the result of cocycling subpopulations of epizootic subtype I-AB or I-C virions. Two additional markers were found which distinguish subtype I-D and I-E Venezuelan encephalitis virus strains. Firstly, hydroxylapatite chromatography of intact virions at pH 6.5 showed differential elution of I-D and I-E prototype strains. Virions of subtype I-D strains eluted at 0.08 to 0.11 M phosphate, while those of subtype I-E strains eluted at 0.15 to 0.20 M phosphate. Secondly, the isoelectric points of the E1 envelope glycoproteins of the I-D and I-E prototype strains were significantly different; pH 6.85 to 7.00 and pH 7.25 to 7.30, respectively. There was no significant difference in the isoelectric points of the E2 envelope glycoproteins. These distinguishing characteristics most likely reflect a fundamental difference in virion surface structure.

Marker characteristics of Venezuelan encephalitis virus strains isolated before and after epidemics and equine epizootics in Middle America.

Ninety-four strains of Venezuelan encephalitis (VE) virus isolated from sentinel hamsters exposed in the Middle American countries of Mexico, Guatemala, Belize, and Honduras were examined for the presence of virions with marker characteristics of strains that cause large epidemics and equine epizootics. Thirty-four strains came from before and 60 strains came from after the Middle American epidemics and equine epizootics of 1966 and 1969-1972. Twenty-three virion clones that resembled epizootic strains by hydroxylapatite chromatography and Vero monkey kidney cell plaque size determinations were characterized further. However, the predominant virions in these clones were like enzootic strains from Middle America north of the Panama Canal region, and not like Middle American epizootic VE strains, since they were in hemagglutination-inhibition antigenic subtype IE, usually had optimal pH of hemagglutination at 6.2, and were avirulent for English shorthair guinea pigs inoculated subcutaneously. These results provide evidence against the theory of origin of epidemic-equine epizootic VE virus strains that posits that epizootic virions emerge in Middle America from strains containing mixtures of enzootic and epizootic virions in enzootic habitats.

IgE antibody production in guinea pigs treated with cyclophosphamide.

Guinea pig anaphylactic responses usually involve IgG1 antibodies. Although IgE antibody production has been accomplished, a reliable and sustained method for production has not been described. We have investigated a method of enhancing IgE antibody production in guinea pigs. The criteria for IgE production were homologous passive cutaneous anaphylaxis (PCA) antibody activity that passed an affinity column of rabbit anti-guinea pig IgG1, heat lability (56 degrees C for 3 hr), and a long sensitization period in skin (7 days). Hartley guinea pigs were primed and boosted monthly with 1 microgram Picryl-Ascaris plus 1 mg of alum i.p. Some Hartley guinea pigs also received cyclophosphamide (250 mg/kg) before the first boost. English short-hair guinea pigs (previously shown to be good IgE producers) were immunized similarly but received no cyclophosphamide. Hartley animals receiving no cyclophosphamide inconsistently made low titered IgE anti-hapten antibody (1:100). Fifteen of 15 Hartley animals that received cyclophosphamide had high titers (1:2000) of IgE anti-hapten antibody. English short-hair animals had moderate titers (1:400), and not all animals responded. Thus, cyclophosphamide converted IgE nonresponder Hartley guinea pigs to uniformly high responders. This method provides material to study the biologic properties of IgE in this species, and also provides a model to study the apparent suppression of IgE responses in Hartley guinea pigs.

16-Hydroxylation of Estrone-3-Sulfate and Estrone in the Guinea Pig in Vivo*

[6,7-3H]Estrone-3-sulfate or [6,7-3H]-estrone of high specific activity was injected into adult female English Shorthair guinea pigs. Blood, liver, kidney, gall bladder bile, and urine were obtained and investigated for metabolites. Chromatographic procedures followed by enzymatic or solvolytic cleavage of conjugates and subsequent crystallization with appropriate carrier steroids revealed the pattern of metabolites formed. Injected estrone sulfate was partially hydrolyzed and reconjugated, resulting in the production of estrone and estradiol glucuronides. The main metabolites, however, were monosulfates of 16alpha-hydroxyestrone, 16-keto-17beta-estradiol, and estriol as well as disulfates of 16alpha-hydroxyestrone, estriol, and 16beta-hydroxyestrone. Particularly high amounts of these were found in urine. By far the main metabolites of injected estrone were glucuronides of estrone and estradiol, although the pattern of mono- and disulfated steroids was qualitatively similar to that found after estrone sulfate injection. It is concluded that the guinea pigs employed in the study hydroxylated estrogen in the 16alpha- and 16beta-configurations and that this activity was much more pronounced after injection of estrone sulfate than after estrone.

Tissue Composition of Lactating Guinea Pia Mammary Glands

Fourteen mammary glands from eight English shorthair guinea pigs were used to determine the fractional contributions (f) to total tissue by secretory epithelial tissue (E) and supportive tissue (S). The blood plasma (B) component was determined with an additional eight animals with 125I-human serum albumin as the label for plasma volume. Means and standard deviations were fE = .557±.023, fS = .398±.023 and fB = .045±.010. Therefore, lactating guinea pig mammary glands (excluding milk) were 55.7% secretory epithelial tissue, 39.8% supportive tisue, and 4.5% blood plasma.