Biomedical subjects

C J Gordon

Publications and source records attributed to C J Gordon.

135 records · Page 8Linked to original sources

PubMedDate not supplied

Thermoregulation in mice following acute administration of lead acetate.

Several reports in the literature suggest a relationship between lead intoxication and thermoregulatory capacity. To investigate the effects of lead on the control of body temperature, mice of the BALB/c strain were injected intraperitoneally with lead acetate (0 to 100 mg/kg) while colonic temperature was measured 30, 60, and 90 min post-injection at ambient temperatures (Ta) of 20 and 30 degrees C. Lead acetate caused a transient hypothermia, an effect which was augmented at cooler Ta's. In a second experiment, mice were injected with 100 mg/kg lead acetate and placed in a longitudinal temperature gradient to measure their preferred Ta. Lead acetate significantly reduced the preferred Ta during the first 30 min post-injection which augmented the lead-induced hypothermia. In a third experiment it was found that lead acetate-induced lethality was potentiated with increasing Ta. Hence, the hypothermic response to acute lead acetate treatment may be beneficial to survival.

Animals↗

PubMedDate not supplied

Behavioral and autonomic thermoregulation in the rat following chlordimeform administration.

This study was designed to assess the effects of a single acute injection of chlordimeform (CDM) on some behavioral and autonomic effectors of the thermoregulatory system of the Sprague-Dawley rat. In one experiment rats injected intraperitoneally with 60 mg/kg CDM were placed in an environmental chamber set at an ambient temperature (Ta) of 5, 10, 15, 20, 25 or 30 degrees C for 60 min. Exposure to CDM resulted in hypothermia at Ta's of 5 to 25 degrees C and had no effect on body temperature at a Ta of 30 degrees C. In a second experiment, rats injected with 60 mg/kg CDM were placed in a temperature gradient which permitted the continuous recording of preferred Ta (i.e., behavioral thermoregulation), oxygen consumption (i.e., metabolic rate), and total activity. CDM-treated rats preferred Ta's of 20 degrees C after 60 min in the temperature gradient in spite of a hypothermic body temperature (35.3 degrees C). That is, the animals could have moved to the warm end of the gradient and thereby prevented a fall in body temperature. CDM also led to a significant reduction in oxygen consumption. In a third experiment, foot and tail skin temperature, and heart rate were recorded in anesthetized rats maintained under normothermia while treated with CDM. Tail and foot skin temperature rapidly increased following CDM administration which was indicative of peripheral vasodilation and increased heat loss. The changes in temperature were concomitant with an abrupt drop in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidines↗

PubMedDate not supplied

Effect of nickel chloride on body temperature and behavioral thermoregulation in the rat.

This study was designed to assess the effects of acute nickel chloride administration on behavioral and autonomic thermoregulation in the rat. In one experiment, male rats of the Fischer 344 strain were injected with nickel chloride (IP) at dosages of 0 to 24.0 mg/kg and placed in an environmental chamber maintained at an ambient temperature (Ta) of 10 or 20 degrees C. Colonic temperature was measured 60 min postinjection. Nickel chloride caused a dose-related decrease in colonic temperature, and the hypothermia was accentuated at the cooler Ta. In a second study, rats injected with 0, 6.0, 12.0, or 24.0 mg/kg nickel chloride were placed in a temperature gradient which allowed the rats to select their preferred thermal environment. Nickel chloride at dosages of 12.0 and 24.0 mg/kg caused a significant reduction in the selected Ta. At these dosages the rats were also significantly hypothermic at 60 min postinjection. In a third experiment, whole-body oxygen consumption (i.e., metabolic rate) was measured at Ta's of 10, 20, and 30 degrees C following a 12.0 mg/kg injection of nickel chloride. Nickel chloride caused an initial depression in metabolic rate and hypothermia at Ta's of 10 and 20 degrees C but not at 30 degrees C. In conclusion, (a) nickel chloride affects both behavioral and autonomic control of thermoregulation in the rat and appears to induce a regulated decrease in body temperature and (b) the behavioral thermoregulatory response of the rat is less sensitive to nickel chloride when compared to the mouse.

Animals↗

PubMedDate not supplied

Thermoregulatory effects of methanol in Fischer and Long Evans rats.

While methanol neurotoxicity has been studied for decades, there are very few data available on the thermoregulatory effects of methanol exposure. This paper will present the results of three studies designed to assess the effects of methanol on body temperature and behavioral thermoregulation in Fischer and Long Evans rats. The first study measured the onset of body temperature changes following methanol exposure. Following gavage of 3 g/kg methanol (20% w/v in saline), brain temperature (Tbr) of Fischer rats decreased 1.5 degrees C within 35 min. A similar volume of saline led to transient increases in Tbr. A second study assessed the time course of changes in body temperature by measuring colonic temperature (Tc) hourly following IP injection of saline or 1 or 3 g/kg methanol. The highest dosage of methanol caused a significant hypothermia in both Fischer and Long Evans rats. The hypothermia reached its nadir in both strains at 1-2 hours and partially recovered within the 6 hour experiment. The third study measured the effects of methanol on behavioral thermoregulation. Fischer and Long Evans rats were gavaged with saline or 1-3 g/kg methanol and placed in a temperature gradient. After 90 min in the gradient, rats of both strains which received 2 or 3 g/kg methanol had a significantly lower Tc than control rats. However, the methanol-treated rats remained in the cool end of the gradient and did not prevent the hypothermic effect of the alcohol. The absence of an observed effect on behavioral temperature selection suggests that methanol may interfere with thermal sensation.

Animals↗

PubMedDate not supplied

Relationship between serum cholinesterase activity and the change in body temperature and motor activity in the rat: a dose-response study of diisopropyl fluorophosphate.

Risk assessment of the neurotoxicology of organophosphate (OP) pesticides calls for a thorough understanding of the relationship between tissue cholinesterase (ChE) activity and changes in behavioral and autonomic responses to OP treatment. To address this issue, motor activity, core and skin temperature, and serum ChE activity were measured 2 h after rats of the Long-Evans strain were treated with the OP, diisopropyl fluorophosphate (DFP) at a dose of 0, 0.1, 0.25, 0.5, 0.75, 1.0, 1.25, and 1.5 mg/kg (SC). DFP doses > or = 0.25 mg/kg led to significant decreases in serum ChE activity, whereas doses of > or = 0.5 mg/kg caused reductions in motor activity and body temperature. The highest dose of DFP caused an increase in tail skin temperature, indicating an elevation in skin blood flow. A hockey stick regression analysis was used to determine threshold inhibition in ChE activity associated with depressions in motor activity and colonic temperature. The threshold serum ChE activity, relative to controls for inhibition of motor activity and reduction in body temperature was 46%. A wide range in individual motor activity and colonic temperature responses was noted when the inhibition in ChE activity exceeded threshold levels. This may be indicative of marked genetic variability to ChE inhibition. That is, rats appear to be either responsive or unresponsive when subjected to extreme inhibition in ChE activity. This pattern has been reported in other rodents and may represent a fundamental aspect of ChE toxicity.

Animals↗

PubMedDate not supplied

Thermoregulatory effects of chlorpyrifos in the rat: long-term changes in cholinergic and noradrenergic sensitivity.

Subcutaneous injection of a sublethal dose of chlorpyrifos (CHLP), an organophosphate (OP) pesticide, causes long-term inhibition in cholinesterase activity (ChE) of brain, blood, and other tissues. Such prolonged inhibition in ChE should lead to marked behavioral and autonomic thermoregulatory patterns, especially in terms of altered noradrenergic and cholinergic sensitivity. To evaluate the behavioral and autonomic effects of long-term ChE inhibition, Long-Evans rats were implanted with radiotelemetry transmitters that continuously monitored core temperature (Tc), heart rate (HR), and motor activity (MA). These parameters were monitored for 7 days following a single injection of peanut oil (vehicle control) or 280 mg/kg CHLP. CHLP led to a significant reduction in Tc during the first night after treatment but had no other effects on Tc. CHLP also resulted in a significant elevation in HR which lasted for approximately 72 h. Motor activity was unaffected by CHLP. Cholinergic and noradrenergic drug sensitivity was assessed between 7 and 25 days after CHLP. CHLP-treated rats were more sensitive to norepinephrine as based on a greater hyperthermic response. MA of CHLP-treated rats was more sensitive to scopolamine. On the other hand, the hypothermic effects of oxotremorine (0.4 mg/kg) were nearly abolished by CHLP treatment, indicating tolerance to cholinergic stimulation. The tachycardic effects of methyscopolamine were also greater in the CHLP group. Overall, the acute effects of CHLP are unusual compared to other OP's in that there is no hypothermic response, an attenuated nocturnal elevation in Tc and a prolonged elevation in HR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Thermoregulation in laboratory mammals and humans exposed to anticholinesterase agents.

The regulation of body temperature is one of many homeostatic functions affected by exposure to anticholinesterase (antiChE) pesticides, and related compounds. In the study of antiChE neurotoxicity, thermoregulatory variables are often used as sensitive physiological indices. Hence, a review on the thermoregulatory aspects of antiChE agents would be useful to researchers in a variety of fields. A reduction in body temperature is a commonly used indicator of antiChE poisoning in laboratory rodents. On the other hand, humans and some other species often shown an elevation in body temperature when exposed to antiChE agents. Hyperthermia has also been noted in animals treated with either low levels of antiChEs or during recovery from high doses of antiChEs. In this review, the literature dealing with the central and peripheral effects of cholinergic agonists and antagonists is reassessed because the thermoregulatory effects of antiChEs are thought to be linked to the activation of cholinergic pathways. This is followed by a thorough review of the studies reporting thermoregulatory responses in laboratory rodents and humans exposed to low and high doses of a variety of antiChE agents, including the organophosphate- (OP) and carbamate- (CB) based pesticides and related drugs. Attention is given to the possible mechanism of action of OPs on thermoregulation in the laboratory rodent including the involvement of behavioral and autonomic processes. The incidence of antiChE-induced hyperthermia (fever) in humans exposed to antiChEs is also addressed. Other topics of antiChE-induced thermoregulatory dysfunction discussed in this review include the role of exercise, heat, and cold stress, tolerance to antiChE agents, and genetic variability. Overall, the mechanism of antiChE-induced changes in body temperature cannot always be explained solely by the immediate consequences of ChE inhibition.

Acclimatization↗

PubMedDate not supplied

Factors influencing diisopropyl fluorophosphate-induced hypothermia and hyperthermia in the rat.

Exposing rats to the anticholinesterase (anti-ChE) diisopropyl fluorophosphate (DFP) causes a transient period of hypothermia followed by a period of hyperthermia lasting approximately 48 h. Because a fever is a predominant thermoregulatory response in humans exposed to anti-ChE pesticides, the hyperthermic response in the rat may be important to understanding the central neural mechanisms of anti-ChEs. The purpose of the present study was to assess the dependence of DFP-induced thermoregulatory changes on basal behavioral and autonomic activity in the rat. Core temperature (Tc), heart rate (HR), and motor activity (MA) were monitored via radiotelemetry in unrestrained rats 24 h prior to and 72 h after administration of the peanut oil vehicle or 1.5 mg/kg DFP. Mean Tc decreased by approximately 4 degrees C by 4 h after DFP, returned to baseline by 27 h, and then remained approximately 0.8 degrees C above control daytime levels during the second day after DFP injection. Correlations of DFP-induced hypothermia and hyperthermia with baseline Tc, HR, and MA were performed. The baseline Tc was inversely correlated with the magnitude of DFP-induced hyperthermia (r2 = 0.6). DFP-induced hyperthermia was also inversely correlated with baseline HR and MA. The minimum core temperature during DFP-induced hypothermia was directly correlated with the baseline Tc. The inverse pattern between baseline Tc and DFP-induced hyperthermia is similar to that of rats administered endotoxin and other pyrogenic agents. Sixty percent of the variation in DFP-induced hyperthermia, a toxic response seen > 48 h after exposure, can be explained by individual differences in baseline Tc. This relationship may be important in understanding the thermoregulatory and metabolic effects of anti-ChE agents.

Animals↗

PubMedDate not supplied

Thermoregulatory aspects of environmental exposure to anticholinesterase agents.

Anticholinesterase (antiChE) agents can be highly toxic to birds and mammals and constitute a major proportion of the pesticides used throughout the world. AntiChEs consist of the organophosphates (OP), which irreversibly inhibit the enzyme acetylcholinesterase (AChE), and the carbamates (CB), which reversibly inhibit AChE. AChE inhibition elicits cholinergic stimulation in the central nervous system and in peripheral tissues and organs, which can lead to marked dysfunction of homeostatic systems, including temperature regulation. The control of body temperature uses cholinergic pathways in the integration and central processing of thermal information, as well as in the control of thermoeffector responses. Hence, the cholinergic stimulation elicited from exposure to antiChEs has profound effects on body temperature at rest as well as during exercise. Ambient heat and cold stress can also modulate the animal's sensitivity to antiChE exposure. After exposure to most OPs, rodents and other small species undergo a marked hypothermic response lasting up to 24 hours. On the other hand, humans exposed to OP pesticides rarely become hypothermic but rather experience a fever that may last many days. Recent studies monitoring body temperature in OP-exposed, telemetered rats demonstrated that the initial hypothermic response is followed by a period of hyperthermia lasting several days. That the hyperthermia can be blocked with administration of sodium salicylate suggests that the hyperthermia is a fever. Thus, the antiChE-induced effects on body temperature and other physiological systems cannot be explained solely by the immediate consequences of AChE inhibition and stimulation of cholinergic systems. Research into the mechanisms of action of antiChE toxicity will be improved with a better understanding of their effects on temperature regulation.

Acclimatization↗