Biomedical subjects

S Kent

Publications and source records attributed to S Kent.

At least 19 recordsLinked to original sources

PubMed1992

Different receptor mechanisms mediate the pyrogenic and behavioral effects of interleukin 1.

Interleukin 1 (IL-1) is a cytokine released during immune activation that mediates the host's response to infection and inflammation. Peripheral and central injections of IL-1 induce fever and sickness behavior, including decreased food motivation and reduced interest in social activities. To determine the receptor mechanisms responsible for these effects, rats were injected with IL-1 receptor antagonist (IL-1ra), an endogenous cytokine that acts as a pure antagonist of IL-1 receptors. IL-1ra blocked the increased body temperature and oxygen consumption induced by injection of recombinant human IL-1 only when both cytokines were administered i.p. In contrast, i.p. or intracerebroventricular administration of IL-1ra blocked the depressive effect of IL-1 beta on food-motivated behavior and social exploration when this cytokine was administered by the same route as the antagonist. In addition, intracerebroventricular IL-1ra blocked the reduction in social exploration produced by i.p. IL-1 beta but had only partial antagonist effects on the decrease in food-motivated behavior induced by i.p. IL-1 beta. In each case, the dose of IL-1ra was 100- to 1000-fold in excess of the biologically active dose of IL-1. These results suggest that the receptor mechanisms that mediate the behavioral and pyrogenic effects of IL-1 are heterogeneous.

Animals↗

PubMed1992

Effects of lipopolysaccharide on food-motivated behavior in the rat are not blocked by an interleukin-1 receptor antagonist.

To investigate the role of interleukin-1 (IL-1) in the decrease in food-motivated behavior after peripheral administration of lipopolysaccharide (LPS), rats trained to press a lever for food on a fixed ratio 10 schedule were pre-treated with a recombinant human IL-1 receptor antagonist (IL-1ra). This endogenous cytokine has been shown to block most of the inflammatory and immune effects of IL-1 both in vitro and in vivo. Intraperitoneal (i.p.) injection of LPS (400 micrograms/kg) decreased operant responding for food to 30-60% of baseline for 1-4 h. Response rates gradually recovered, but were still below control levels 8 and 24 h post-injection. Neither i.p. (8 mg/kg) nor intracerebroventricular (288 micrograms/kg) administration of IL-1ra blocked the effects of peripherally administered LPS on food-motivated behavior. These results suggest that the effects of LPS on this behavior are not mediated by the release of IL-1.

Animals↗

PubMed1992

Sickness behavior as a new target for drug development.

Sickness behavior refers to the nonspecific symptoms (anorexia, depressed activity, loss of interest in usual activities, disappearance of body-care activities) that accompany the response to infection. Increasing evidence suggests that these symptoms are part of an organized defense response to antigenic challenge and that they are mediated by the neural effects of cytokines such as interleukin 1. An understanding of the mechanisms involved in these effects should permit development of new drugs aimed at decreasing sickness or promoting recovery processes.

Cytokines↗

PubMed1992

A multicenter evaluation of lipid profiling with a compact analyzer (Miles Clinistat).

We evaluated the Clinistat Analyzer (Miles Inc., Diagnostics Division, Elkhart, IN) for measuring cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol at three medical centers. The system, based on multilayer film technology, uses precalibrated, dry film reagent disks. Ten microliters of serum is applied to the dry film reagent disk in the test procedure. For HDL-cholesterol measurement, serum is pretreated by precipitation with phosphotungstic acid and magnesium chloride. Total precision (CVs) of each of the three assays was less than or equal to 5%. The assay ranges were linear and satisfactory for clinical use. Patients' results compared well with established methods. No significant interferences were found with hemolysis, icterus, and lipemia.

Chemistry, Clinical↗

PubMed1991

Phentolamine and thermoregulation in rats.

Phentolamine (PHEN), a nonselective alpha-adrenoceptor antagonist, causes a dose and ambient temperature (Ta)-dependent fall in body temperature (Tb) when injected intraperitoneally. In this paper, we investigated whether this was caused by integrated behavioral and autonomic thermoregulatory responses and whether it was due to a central action of the drug. Male rats were trained to press a bar for warm air in the cold or cold air in the heat. Rats were tested in both conditions near their Tb peaks and troughs after injections of saline or PHEN (5 and 10 mg/kg, IP). Tb fell significantly within the first 30 min post-PHEN, and after that, in the cold, the rats worked to increase Ta. In the heat they did not change Ta. To determine what was responsible for the Tb fall, we measured heat loss and heat production after saline or PHEN (10 mg/kg; IP) at Ta 2, 20, and 30 degrees C. Decreases in Tb at 2 and 20 degrees C were caused by increased heat loss during the first 15-30 min post-PHEN. At 2 degrees C, heat production increased after the drop in Tb. We conclude that the main reason the rats do not start to work immediately to prevent their core temperature from falling is that skin temperature is high, due to peripheral vasodilation, and that skin temperature is the major stimulus for regulating preferred Ta. We believe these effects are mediated by peripheral mechanisms because intracerebro-ventricular injections of PHEN did not cause a fall in Tb.

Animals↗

PubMed1991

Circadian rhythms of body temperature and drinking and responses to thermal challenge in rats after PCPA.

Body temperature (Tb) and drinking were measured for five days in male and female rats. On day 6 (S1) the rats were injected with saline. On day 7 (P1) they were injected with PCPA (300 mg/kg IP). Measurements continued for 12 days. Immediately after PCPA Tb dropped. After that, the amplitude of the daily Tb rhythm was significantly decreased from days P2-P5. Females were more affected than males. Nocturnality of drinking was decreased on days P2-P4. Because the peak of the Tb rhythm advanced after PCPA, while the peak of the drinking rhythm was delayed, we conclude that the attenuation of the Tb rhythm was a direct result of PCPA treatment rather than a masking effect due to the attenuation of other rhythms. Other rats were thermally challenged during the first week post-PCPA. There were no differences in ability to regulate Tb in the cold, and the small variations in the heat were overshadowed by gender differences.

Animals↗

PubMed1991

Elevated body temperature in female rats after exercise.

Female Sprague-Dawley rats living in basin cages (sedentary rats) under a 12:12 light-dark cycle normally have body temperatures (Tb; measured via telemetry) that vary from a mean peak of 38.1 +/- 0.1 degrees C in the dark to a mean trough of 36.0 +/- 0.1 degrees C C in the light. We have found that if rats are housed in activity wheels, their mean peak Tb in the dark, when they run in the wheels, rises to about 39.5 degrees C. Mean trough Tb in the light also rises, to about 36.5 degrees C, although they never or very rarely run in the wheels in the light. Other rats were rotated through two cycles of wheel-open (WO) and wheel-locked (WL) conditions. During the first WO cycle their mean Tb in the dark gradually rose over the first 2 wk, and their mean Tb in the light gradually fell. In the first WL, mean Tb in the dark fell immediately to sedentary levels, and mean Tb in the light fell more gradually. In the second WO condition, both dark and light Tb rose almost immediately. Since rats in locked wheels have Tb similar to sedentary controls, these results support the hypothesis that steady exercise at night results in an upward resetting of a thermoregulatory set-point during the day.

Animals↗

PubMed1979