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L A Toth

Publications and source records attributed to L A Toth.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of sleep deprivation and other stressors on the immune and inflammatory responses of influenza-infected mice.

Many stressors have well-documented effects on host immune competence. However, two important stressors that have not been extensively characterized in terms of their immune-modulatory properties are sleep deprivation and alterations in light:dark cycles. We therefore evaluated the effects of these stressors on the immune and inflammatory responses of mice inoculated intranasally with influenza virus. In contrast to a previous report, sleep deprivation did not significantly alter viral clearance or antibody titers of either virus-naive or immunized mice. Exposure to constant light also failed to affect these variables. However, repeated overnight restraint, a well-characterized stressor, reduced the pulmonary inflammatory response elicited by influenza virus, as previously reported. The data indicate that sleep deprivation and altered light cycles do not markedly influence selected host defense responses to influenza infection under the conditions tested.

Amyloid↗
PubMed1998

Rodent quarantine programs: purpose, principles, and practice.

In animal research, validity and reproducibility of data are critically influenced by the microbial status of the experimental animals. One of the most crucial aspects of assuring quality in animal research is providing research personnel with confidence that experimental results will not be invalidated due to interference caused by infectious disease. An effective quarantine program is essential to providing this assurance. Quarantine programs are generally instituted to prevent the introduction of rodent pathogens into established specific-pathogen-free colonies in a facility. Therefore, programs should be designed to isolate newly acquired rodents until their health status can be determined and to maximize the probability that microorganisms of interest will be detected before the animals are introduced into (and thus, could potentially contaminate) established colonies. Important principles that are critical to designing an effective quarantine program will be discussed here, as will the practical implementation of these principles. Although quarantine programs may be costly in terms of time and effort, these costs must be balanced against the potential costs of disease outbreaks that could invalidate long-term studies, alter normal biological baselines, and cause the loss or necessitate re-derivation of rare or valuable strains of rodents. Reducing the incidence of quarantine failures through appropriate program design and implementation helps to maintain the confidence of research personnel in the value of quarantine programs and in our competence as specialists in laboratory animal management and as partners in the research process.

Animal Husbandry↗
PubMed1997

EEG delta power and auditory arousal in rested and sleep-deprived rabbits.

Slow-wave activity in the electroencephalogram is thought to reflect the depth or intensity of sleep. This hypothesis is primarily derived from studies of rats or humans. However, some characteristics of sleep of rabbits differ from those of rats or humans. To determine whether slow-wave activity (power density in the delta frequency band of 0.5-5.0 Hz) correlates with arousability in rabbits, we presented auditory stimuli (72-90 dB) to control or sleep-deprived animals during slow-wave sleep. The resulting behavioral responses, defined by changes in eye state and body posture, and the latency to return to sleep were used as measures of arousability. Behavioral responsiveness to auditory stimuli increased with increasing stimulus intensity in both control and sleep-deprived animals. Overall, however, sleep-deprived animals exhibited fewer postural changes and eye openings than did control rabbits. Sleep-deprived rabbits also more rapidly returned to sleep after the stimulus presentation than did control animals. Latency to return to sleep was correlated with delta power before stimulus presentation, but behavioral responsiveness was not. These data suggest that, in this rabbit model, delta power may not be predictive of behavioral arousability but may reflect sleep propensity.

Acoustic Stimulation↗
PubMed1996

Strain differences in the somnogenic effects of interferon inducers in mice.

Increased slow-wave sleep accompanies influenza infection in C57BL/6 mice but not BALB/c mice. These strains of mice possess different alleles of the genetic lucus If-1, which codes for high (If-1h; C57BL/6) and low (If-1(1); BALB/c) production of interferon (IFN), a putative sleep-inducing cytokine. To evaluate the contribution of the If-1 gene to differences in murine sleep propensity, sleep patterns were evaluated in mice treated with the IFN inducers polyinosinic:polycytidilic acid (pIC) or Newcastle disease virus (NDV), with influenza virus, or with murine interferon (IFN-alpha) or IFN-alpha/beta. As compared with baseline values, C57BL/6 mice exhibited increased slow-wave sleep after all three challenges, but BALB/c mice did not. Congenic B6.C-H28c mice, which bear the BALB/c allele for low IFN production on the C57BL/6 genetic background, showed enhanced slow-wave sleep after influenza infection but not after NDV. Exogenous IFN did not enhance slow-wave sleep in either C57BL/6 or BALB/c mice. These data suggest that the If-1 allele may influence the somnogenic responsiveness of mice under some conditions but that additional mechanisms may contribute to sleep enhancement during infectious disease.

Analysis of Variance↗
PubMed1996

Evaluation of anaesthetic regimens in guineapigs.

To establish reliable methods of chemical restraint and anaesthesia for mildly painful procedures in guineapigs, we compared the effects of the following anaesthetics and combinations of anaesthetics: tiletamine-zolazepam (two dosages), pentobarbital, methoxyflurane, ketamine-xylazine (three dosages), and ketamine-xylazine with methoxyflurane. Tiletamine-zolazepam induced a short period of chemical restraint but lacked analgesic effects at the doses tested. Although pentobarbital induced prolonged chemical restraint, the loss of responsiveness to painful stimuli was brief. Methoxyflurane alone induced transient anaesthesia and analgesia. Ketamine-xylazine combinations induced analgesia and chemical restraint of comparable durations, and some dosages were suitable for mildly painful procedures. The addition of methoxyflurane significantly potentiated the anaesthetic and analgesic properties of the high dosage ketamine-xylazine combination.

Anesthesia↗
PubMed1995

Immune-modulatory drugs alter Candida albicans-induced sleep patterns in rabbits.

To evaluate the influences of immune responsiveness on sleep alteration during infectious disease, sleep was monitored during Candida albicans infection in rabbits treated with immune-modulating drugs. Intravenous administration of C. albicans to normal rabbits initially increased and subsequently decreased both the amount of slow-wave sleep (SWS) and delta-wave amplitudes (DWA) during SWS. Cortisone treatment attenuated these effects. The immunosuppressive drug cyclosporine did not alter the initial enhancement of SWS, but did attenuate the C. albicans-induced reduction in SWS time and potentiate the reduction in DWA. In contrast, administration of incomplete Freund's adjuvant and prior immunization with killed C. albicans, which were expected to enhance immune responsiveness, did not markedly alter C. albicans-induced alterations in SWS. However, the immune stimulant levamisole potentiated the effects of C. albicans on SWS. These data indicate that pharmacologic treatments expected to alter immune responsiveness modulate microbially induced sleep, and are consistent with the hypothesis that facets of the immune response mediate sleep changes during infectious disease.

Adjuvants, Immunologic↗
PubMed1995

Strain differences in sleep and other pathophysiological sequelae of influenza virus infection in naive and immunized mice.

To characterize behavioral and physiological alterations induced by viral respiratory infection, C57BL/6 and BALB/c strains of mice were monitored for 2 days before and 4 days after intranasal inoculation with influenza virus. Both strains developed hypothermia, decrease locomotor activity, and decreased delta-wave amplitude during sleep within 24 h after inoculation. However, infected C57BL/6 mice also spent more time in slow-wave sleep, but infected BALB/c mice did not. The increased SWS in C57BL/6 mice occurred during the lights-off phase of the circadian cycle, and resulted in loss of the normal circadian rhythmicity of sleep. Increased sleep also occurred after viral challenge of immunized C57BL/6 mice, but was not observed after secondary challenge of immunized BALB/c mice. These data indicate that sleep alterations may accompany viral infections in some, but not all, strains of mice. The dissimilar sleep patterns seen in C57BL/6 and BALB/c mice after influenza infection may reflect differences in their immune response to influenza virus.

Animals↗
PubMed1995

Sleep, sleep deprivation and infectious disease: studies in animals.

Common perceptions that the desire for sleep is increased during mild infectious diseases like colds and 'the flu' have fostered beliefs that sleep promotes recovery from infectious disease and that lack of sleep increases susceptibility to infections. However, until recently, the relationship between infectious disease and vigilance received relatively little systematic study. At present, several model systems provide evidence that infectious disease is accompanied by alterations in sleep. Indeed, increased sleepiness, like fever and anorexia, may be viewed as a facet of the acute phase response to infectious challenge. Recent studies also suggest that sleep, sleep deprivation and infectious disease may be related via mechanisms of the immune system (Fig. 1). Data are now accumulating to address questions such as whether immune processes alter sleep, whether sleep or sleep deprivation influences immune competence, and whether sleep facilitates recovery from infectious disease.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1995

Lighting conditions alter Candida albicans-induced sleep responses in rabbits.

To evaluate the influence of light on sleep patterns after microbial challenge, we studied rabbits housed in 12:12-h light-dark (LD), constant light (LL), or constant darkness (DD) before and after intravenous Candida albicans inoculation. Compared with the LD group, uninoculated LL rabbits sporadically increased slow-wave sleep and delta-wave amplitudes during the circadian period previously associated with the dark phase. In contrast, uninfected DD rabbits showed reduced sleep during the circadian period previously associated with the light phase. Inoculation of LD rabbits with Candida approximately 2 h after light onset increased slow-wave sleep and delta-wave amplitudes during hours 4-8 postinoculation and reduced these parameters during hours 20-46. In contrast, Candida-inoculated LL rabbits demonstrated increased slow-wave sleep for up to 28 h after inoculation, with little subsequent reduction; delta-wave amplitudes were similar to those of LD rabbits. Candida-inoculated DD rabbits demonstrated attenuated increases in slow-wave sleep and delta-wave amplitudes, but the suppression phase was not altered. We conclude that lighting conditions modulate microbially induced sleep alterations.

Animals↗
PubMed1994

Somnogenic effects of rabbit and recombinant human interferons in rabbits.

Interferons (IFNs) are antiviral cytokines that possess several central nervous system activities. IFN therapy is associated with sleepiness, and the IFNs expressed during viral infection may be involved in the excess sleep associated with these infections. Most viruses stimulate the production of both IFN-alpha and IFN-beta. Although large doses of human IFN-alpha 2 are somnogenic in rabbits, the effects of species-specific IFNs on sleep in the rabbit have not been documented. We compared the somnogenic and antiviral effects of IFNs derived from rabbits to the effects of recombinant human (rh) IFN-alpha and IFN-beta. When injected intracerebroventricularly, rhIFN-alpha A/D, rabbit IFN-alpha/beta, and rabbit reference IFN induced non-rapid-eye-movement sleep and fever in a dose-dependent manner. However, the doses of rabbit IFNs required to induce sleep were much lower than those of human IFNs. Heat treatment of both rabbit IFNs and human IFNs greatly reduced their in vitro antiviral effects. The in vivo activities of rabbit IFNs and rhIFN-alpha A/D were significantly attenuated after heat treatment. However, rhIFN-beta retained its sleep-promoting action after heat treatment, suggesting that microbial contaminants were responsible for its somnogenic and pyrogenic activities. We conclude that IFN-alpha is somnogenic.

Animals↗
PubMed1994

Comparison of acute phase responses induced in rabbits by lipopolysaccharide and double-stranded RNA.

Infection of injury results in several systemic and central reactions termed the acute phase response (APR). Substantial evidence suggests that cytokines induced by microbes initiate the APR. We compared the APR induced in rabbits by a model bacterial stimulus, lipopolysaccharide (LPS), to that induced by a model viral stimulus, polyriboinosinic:polyribocytidylic acid (poly I:C). The cytokine mRNA responses in a mouse macrophage cell line (RAW 264.7) to LPS or poly I:C were also determined. Rabbits were injected intravenously or intracerebroventricularly with different doses of LPS or poly I:C. Colonic temperatures (Tco) and blood samples were taken at the time of injection and at 3, 6, and 24 h after injection. Leukocyte numbers, serum antiviral activity, serum ceruloplasmin, and plasma fibrinogen were analyzed. Both intravenously injected LPS and poly I:C increased Tco, decreased leukocytes, and increased ceruloplasmin. Only LPS by the intravenous route increased fibrinogen, whereas only intravenously injected poly I:C induced antiviral activity. Intracerebroventricular injections of LPS and poly I:C also elicited dose-dependent febrile responses but did not change the hematologic APR significantly except for fibrinogen. The primary distinctions between LPS and poly I:C with respect to cytokine induction in the RAW 264.7 macrophage cell line were that LPS failed to induce interferon (IFN)-alpha, poly I:C induced interleukin (IL)-6 mRNA minimally and for a shorter time period than did LPS, and LPS induced IL-1 alpha and IFN-beta more rapidly than did poly I:C.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction↗
PubMed1994

Sleep during experimental trypanosomiasis in rabbits.

Trypanosoma brucei subspecies cause the human condition known as "sleeping sickness." In rabbits, these organisms induce a chronic and ultimately fatal disease characterized by periodic parasitemia. To characterize sleep alterations during a chronic infectious condition and to determine how immune stimulation of the host, as reflected by cyclic parasitemia, is related to altered somnolence, we monitored sleep and other clinical indices in rabbits inoculated subcutaneously with Trypanosoma brucei brucei. Within four days, infected rabbits developed fever, reduced food intake, and other signs of infectious illness concurrent with the onset of parasitemia were evident. The initial febrile episodes were transient, recurring in temporal correlation with parasitemia. Time spent in slow-wave sleep and delta-wave amplitude during slow-wave sleep increased significantly in association with the onset of febrile episodes, despite an overall trend toward decreases in these parameters. Because each episode of parasitemia presents an immune stimulus to the infected host, the periodic enhancement of sleep observed in this model is consistent with the hypothesis that immune stimulation is correlated with increased somnolence. The data further indicate that sleep alterations occur not only during acute infections, as previously reported, but during chronic infections as well.

Animals↗
PubMed1993

Sleep as a prognostic indicator during infectious disease in rabbits.

Infectious disease alters sleep patterns in rabbits, but the recuperative value of enhanced sleep during infectious disease has not been experimentally verified. To evaluate the relationship between specific sleep patterns and the clinical response to infectious disease, we classified sleep patterns in rabbits inoculated with E. coli, S. aureus, or C. albicans on the basis of the duration of the period of enhanced sleep. Patterns characterized by a long period of enhanced sleep were associated with a more favorable prognosis and less severe clinical signs than were patterns characterized by relatively short periods of enhanced sleep followed by prolonged sleep suppression. A contrasting analysis of these data indicated that animals that eventually died demonstrated reduced sleep compared to rabbits that survived the infection. These observations are consistent with the hypothesis that dynamic changes in sleep over the course of an infectious disease aid in recuperation.

Animals↗
PubMed1992

The role of double-stranded RNA in induction of the acute-phase response in an abortive influenza virus infection model.

The inducer of the acute-phase response in "flu-like" viral infections is not defined. The hypothesis that virus-associated double-stranded (ds) RNA serves this function was investigated by comparison of several acute-phase responses (fever and sleep patterns, white and nucleated red blood cell levels, serum antiviral activity and ceruloplasmin) induced by the synthetic dsRNA polyriboinosinic:polyribocytidylic acid (poly[rI:rC]) with those induced by influenza virus in rabbits. The capacity of either dsRNA or influenza virus to induce hyporesponsiveness with respect to these acute-phase parameters upon rechallenge with the same agent or cross-challenge 24 h later was also examined. Poly(rI:rC) induced only minimal hyporesponsiveness to itself but was a potent inducer of hyporesponsiveness to virus with respect to fever, sleep, leukograms, and antiviral activity. Therefore, poly(rI:rC) can substitute for virus in terms of induction of acute-phase hyporesponsiveness, suggesting that dsRNA of viral origin triggers the acute-phase response in this model of influenza.

Acute-Phase Reaction↗
PubMed1992

Influenza virus-induced changes in rabbit sleep and acute phase responses.

Systematic investigations of sleep after viral inoculation have not previously been described. In the present study, rabbits were inoculated intravenously (iv) with control allantoic fluid followed by two sequential inoculations of influenza virus at intervals of 24 h. After each i.v. inoculation, sleep and brain temperature (Tbr), as well as leukocyte distributions and serum levels of antiviral activity and ceruloplasmin, were monitored. The first viral inoculation elicited several acute phase responses, including increased non-rapid-eye-movement sleep (NREMS), Tbr, serum antiviral activity, and serum ceruloplasmin levels, as well as neutrophilia and lymphopenia. In contrast to the effects of the first inoculation, after the second inoculation of virus, all these acute phase parameters were diminished or absent (the hyporesponsive state). Inoculation of naive rabbits with heat-inactivated virus was similarly ineffective; however, inoculation of this group of rabbits with viable virus 24 h later did induce full-scale acute phase responses. The possible role of cytokines in mediating the acute phase response after influenza viral challenge is discussed. Results support the hypothesis that sleep is a facet of the acute phase response involved in host defense mechanisms.

Acute-Phase Reaction↗