Airway hyperreactivity modulated by immunotherapy with denatured ovalbumin in ovalbumin-sensitized guinea pigs

Denatured immunogenic peptides have recently been used successfully to treat autoimmune disease in mice. Their effect on airway response is unclear. In this study, we compared the effect of native ovalbumin (OVA) and denatured ovalbumin (DN-OVA) on airway spasm and hyperreactivity in guinea pigs. The effects of immunotherapy using DN-OVA were also investigated. Airway response to antigen was determined in conscious, nose-breathing guinea pigs. Results showed that animals could be sensitized by repeated exposure to OVA, but not DN-OVA. Following OVA exposure in OVA-sensitized guinea pigs, airway resistance was significantly increased in both early (30 min, 118.8% +/- 34.2%) and late (6 h, 91.1% +/- 30.1%) phases. Tidal volumes were reduced in both early (47.5% +/- 12.0%) and late (43.8% +/- 10.3%) phases. This dual-phase airway spasm could not be induced by DN-OVA. In addition, there was no change in pulmonary function noted after DN-OVA exposure in OVA-sensitized guinea pigs. OVA-induced airway response was modulated by immunotherapy with subcutaneous DN-OVA administration for 3 weeks. OVA-specific IgG was also increased after immunotherapy. However, there was no significant change in pulmonary function after oral administration of DN-OVA in OVA-sensitized guinea pigs. We conclude that OVA, but not DN-OVA, can successfully induce dual-phase airway spasm in guinea pigs. These reactions can be modulated by immunotherapy with subcutaneously administered DN-OVA.     

Myopathy in guinea pigs

Myopathy resembling nutritional muscular dystrophy occurred in a colony of 150 guinea pigs. Of 54 animals affected, 27 died. Major clinical signs were depression, conjunctivitis, and reluctance to move. Lesions were widespread throughout skeletal and cardiac musculature. Clinical signs and deaths ceased when the diet was changed to a different commercial ration. A single intramuscular injection of sodium selenite and alphatocopherol brought prompt remission of clinical signs in one group of 20 so treated.     

Airway responses to capsaicin in guinea pigs: role of NK-1 and NK-2 neurokinin receptors

The role of NK-1 and NK-2 receptors on the pulmonary response to capsaicin in guinea pigs was evaluated using intravenous infusion of selective nonpeptide antagonists of NK 1 (CP 96345, 300 nmol/kg, and SR 140333, 300 nmol/kg) and NK-2 (SR 48968, 100 nmol/kg) neurokinin receptors. Maximal values of pulmonary dynamic elastance (Edyn) and pulmonary resistance (RL) after capsaicin infusion were significantly lower in the presence of SR 48968 (p < .005). Morphometric analysis of lungs obtained by quick-freezing showed significant attenuation of airway contraction and peribronchiolar edema formation in the presence of NK-2 antagonist (p < .001). When compared to guinea pigs that received only capsaicin, animals that received SR 140333 or CP 96345 showed lower values of Edyn, RL, airway contraction, and peribronchiolar edema, but only the difference in Edyn values was significant. The combination of NK-1 and NK-2 antagonists was not more effective than NK-2 antagonist alone in attenuating capsaicin effects. The results suggest that airway effects of capsaicin are mainly mediated by activation of NK-2 receptors although NK-1 receptors may also play a role.     

The effect of furosemide on evoked otoacoustic emissions in guinea pigs

After recording transiently evoked otoacoustic emissions (TEOAEs) to a click stimulus in guinea pigs by using the IL088 which was developed by Bray and Kemp (1987) for easy recording and analysis of TEOAE, the changes after intravenous administration of furosemide (30 mg/kg or 50 mg/kg) were examined. The wave of the TEOAE could be detected from 20 of 24 ears (83%). After the i.v. injection of furosemide (30 mg/kg), TEOAE powers (total echo power and highest peak power in FFT pictures) decreased quickly and showed minimum values after 5-10 min. Then they increased rapidly and recovered normally within 60 min after injection. However, no ears showed TEOAEs during the 5- to 10-min period following the injection of the 50-mg/kg dose of furosemide. They then recovered slowly as compared with the group treated with the lower dose of furosemide (30 mg/kg). These changes are similar to those of the endocochlear potential (EP) after furosemide injection. These data support the notion that the EP can contribute to the mechanism of TEOAE generation.     

Mycobacterial infection in guinea pigs

We described published reports of the chaos which exists in research concerning laboratory animal models for assay of tuberculosis (TB) vaccines and proposed a "rational animal model" as a solution to the problem. This animal model, an aerosol challenge model in guinea pigs, was recently applied to the problem of differences in growth characteristics of sputum isolates of low and high virulence. The same model was used to investigate the protective effect of high dose BCG given aerogenically. Based on studies in the guinea pig model of experimental airborne TB, and a review of the literature on pathogenesis of human TB, we described an "integrated model" for the pathogenesis of TB, a model which includes a role for both the endogenous reactivation and the exogenous reinfection pathways. Our hypothesis is that tubercle bacilli must be able to gain access to the "vulnerable region" in the lung apex in order to survive the effects of the CMI response. In endogenous reactivation TB (virulent tubercle bacilli), this access occurs via the bloodstream. Whereas in exogenous reinfection TB, access to the vulnerable region occurs via multiple exposures via the respiratory tract. Central to our perspective is the acceptance of the evidence that during first infection with virulent organisms, tubercle bacilli enter the bloodstream via the efferent lymphatics. We believe the hypotheses we have proposed have the potential to lead to a further increase in our knowledge of these mechanisms and are a prerequisite to studies aimed at the development of new vaccines.     

Biphasic effect of hydrogen peroxide on field potentials in rat hippocampal slices

In the CA1 region of rat hippocampal slices, H2O2 (0.294-2.94 mM) caused initial augmentation, and subsequent long-lasting depression, of population spikes and excitatory postsynaptic potentials. The effect of H2O2 may not be mediated by its degradation product, hydroxyl radicals, because an iron chelator deferoxamine did not block the effect. A catalase inhibitor 3-amino-1,2,4-triazole only modestly attenuated the initial augmentation, suggesting that the effect of H2O2 is not attributable to catalase-dependent O2 generation, either. An N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonovaleric acid had no influence on the effect of H2O2, whereas a gamma-aminobutyric acid type A receptor channel blocker picrotoxin attenuated long-lasting depression, indicating that gamma-aminobutyric acid-mediated inhibition is altered during the depression phase. The initial augmentation but not subsequent depression was attenuated by a phospholipase A2/C inhibitor 4-bromophenacyl bromide, suggesting the involvement of lipid signaling molecule(s) in the enhancement of excitatory synaptic transmission. These results suggest that H2O2 regulates hippocampal synaptic transmission via multiple mechanisms.     

Sulfur mustard-induced microvesication in hairless guinea pigs: effect of short-term niacinamide administration

It has been postulated that sulfur mustard (HD) damage may activate poly(ADP-ribose) polymerase (PADPRP), resulting in depletion of cellular NAD+. This biochemical alteration is postulated to result in blister (vesicle) formation. It has been previously demonstrated that niacinamide (NAM), an inhibitor of PADPRP and a precursor for NAD+ synthesis, may be useful as a pretreatment compound to reduce HD-induced microvesication. The present study was undertaken to determine whether niacinamide's protective action could be extended beyond 24 hr and if the degree of microvesication is related to changes in skin NAD+ content. HD exposures were made by vapor cup to hairless guinea pigs. Niacinamide (750 mg/kg, ip) given as a 30-min pretreatment did not reduce the degree of microvesication 72 hr after HD compared to saline controls. However, niacinamide given as a 30-min pretreatment and at 6-, 24-, and 48-hr after HD, exhibited a 28% reduction in microvesication 72 hr after HD. Skin NAD+ content at 72 hr after HD was depleted by approximately 53% in the saline and NAM-treated groups. Skin NAD+ content was depleted despite NAM administration. Niacinamide did not reduce the degree of erythema at 48 or 72 hr. These results suggest that niacinamide's protective effect against HD-induced microvesication may be extended for at least 72 hr, but NAM levels must be sustained during the post-HD period. The link between maintenance of skin NAD+ and reductions in microvesication is still uncertain.     

The cytochochleogram in atoxyl-treated guinea pigs

The earliest atoxyl induced changes in the cochlea appeared in the upper and medial parts of the 4th coil, whence the changes spread progressively downwards towards the round window, the extent of the changes depending on the amount of atoxyl administered and the duration of the treatment. The inner hair cells were more resistant to the effects of atoxyl than the outer hair cells which were affected first. The sensory cells in the 2nd and 3rd rows appeared more sensitive than the outer hair cells in the first row.     

Trypanosoma cruzi: effect of immunization on the risk of vector-delivered infection in guinea pigs

The protective effect of experimental immunization was studied in guinea pigs exposed to vectorial infection by Trypanosoma cruzi. Immunized animals received an inoculum of live-attenuated T. cruzi epimastigotes into a granuloma previously induced by Freund's complete adjuvant in the hind footpad. Seven days later, a delayed-type hypersensitivity reaction was triggered by reinjection of the parasites in the front footpad. The animals were then placed in Triatoma infestans-colonized corrals and exposed to vectorial T. cruzi transmission of the parasite for up to 200 days. The effectiveness of this immunizing protocol was controlled in terms of the number of bites necessary for infection (NBNI) in immunized as compared with control animals. Periodic entomological census allowed for the determination of vector biting and infection rates and the calculation of NBNI. Although this measurement was quite variable between yards, an overall average of 4,973 bites was enough to infect a control guinea pig in 4 separate experiments. The corresponding figure for the experimental group was 21,307 bites, implying that immunized animals could resist a 4.28-fold increase (range: 1.99-8.32) in the number of vector bites before becoming infected.     

Macrophage function in vitamin C-deficient guinea pigs

Guinea pigs were fed a vitamin C-deficient diet and at various time periods thereafter their peritoneal cells were tested for biological activity. The serum levels of vitamin C in the deficient animals indicated a progressive state of ascorbic acid deficiency with time and this correlated well with clinical signs and symptoms of scurvy. Fewer macrophages were obtained from the peritoneal cavities of deficient animals and in structural appearance under the phase contrast and light microscope they were smaller in size. They showed no significant impairment in phagocytosis of bacterial cells. The macrophages, however, exhibited significantly reduced migration on glass as compared to the normal cells. In vitro addition of vitamin C partially reversed this reduced migration.     

Mechanisms of gallbladder hypomotility in pregnant guinea pigs

BACKGROUND & AIMS: Gallbladder muscle contraction becomes impaired during pregnancy. This study was designed to investigate the mechanisms of gallbladder hypomotility induced by pregnancy in guinea pigs. METHODS: Gallbladder muscle cells were obtained by enzymatic digestion. Cell contraction was expressed as percent shortening of initial control cell length. RESULTS: Contraction induced by cholecystokinin (CCK)-8 or guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) was reduced in muscle cells from pregnant guinea pigs. The response to KCl or D-myo-inositol 1,4, 5-trisphosphate was not different between controls and pregnant animals. These findings suggest that impaired contraction in pregnancy might be caused by defective G protein activation. The function and content of G proteins were examined by using [35S]GTPgammaS binding and G protein subunit quantitation. In female controls, CCK-8 at 1 micromol/L caused increased [35S]GTPgammaS binding to Galphai3 but not to Galphaq/11, Galphai1-2, or Galphas. GTPgammaS binding to Galphai3 induced by CCK-8 was reduced in gallbladder muscle from pregnant guinea pigs. Measurements of basal G proteins showed that the content of Galphai3 was significantly lower and the Galphas content was higher in muscles from pregnant guinea pigs than in controls. CONCLUSIONS: Pregnancy may cause down-regulation of contractile G proteins such as Galphai3 and up-regulation of Galphas that mediates relaxation, resulting in impaired gallbladder muscle contraction.     

Investigation of topical ciprofloxacin ototoxicity in guinea pigs

Antibiotic eardrops mostly contain potentially ototoxic aminoglycosides. Ciprofloxacin is an alternative, and there is limited experience in its topical use. To investigate the topical ototoxicity of ciprofloxacin, 11 guinea pigs have been operated on. Transbullae silicone drug delivery tubes were placed to both ears of the animals. After the operation the guinea pigs were divided into two groups. The first group of animals received 0.2 ml of 4% gentamicin in one ear and 0.2 ml of 0.9% sodium chloride solution in the other. The second group received 0.2 ml of 0.2% ciprofloxacin in the test ear and 0.2 ml of 0.9% sodium chloride solution in the control ear. All drugs were given once a day on 7 consecutive days. Auditory brainstem response thresholds were recorded using click, 4 and 8 kHz logon stimuli before and after the operation, and after topical drug application. Results were statistically compared using Wilcoxon matched pairs signed-ranks test. Comparison of the thresholds before and after the operation, physiological saline application, as well as ciprofloxacin application yielded no statistically significant differences, whereas application of gentamicin resulted in total hearing loss. The results indicate that topical use of 0.2% ciprofloxacin is not ototoxic in guinea pigs.     

Experimentally-induced osteoarthritis in guinea pigs: effect of surgical procedure and dietary intake of vitamin C

The effect of variation in dietary ascorbic acid on surgically induced osteoarthritis was examined in the stifle joints of guniea pigs. Two different surgical procedures were used to induce osteoarthritis in the right stifle joint of these animals. Guinea pigs were maintained either on a high (150 mg/day) or low (2.4 mg/day) dietary intake of vitamin C. Regardless of the surgical procedure used to induce osteoarthritis, the animals maintained on the high level of vitamin C consistently showed severe joint damage than animals on the low level of the vitamin.     

The protective effect of Clostridium novyi type B alpha-toxoid against challenge with spores in guinea pigs

Acute renal failure continues to be a difficult clinical problem despite developments in dialysis and critical care. Diagnosis of the etiology frequently determines treatment. Urinalysis remains an essential diagnostic tool in the approach to acute renal failure, particularly with the current emphasis on cost-containment and evidence-based medicine. This review focuses on some of the characteristic features in the urinalysis found in different forms of acute renal failure, current developments into the molecular basis for these urinary abnormalities, and new markers on the horizon.