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Biomedical subjects

C J Gordon

Publications and source records attributed to C J Gordon.

At least 19 recordsLinked to original sources
PubMed1995

Temperature regulation and metabolism in rats exposed perinatally to dioxin: permanent change in regulated body temperature?

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been shown to lower thyroxine levels and cause hypothermia in the adult rat; however, there is little known regarding the perinatal effects of TCDD on metabolism and temperature regulation of the offspring. To address this issue, thermoregulatory responses were assessed in adult male rat offspring exposed perinatally to 1.0 micrograms TCDD/kg body wt by gavage on Gestational Day 15. Individual castrated offspring were placed in a gradient-layer calorimeter for 5 hr during their nocturnal period while ambient temperature (Ta) was maintained at 10, 16, 24, or 28 degrees C. Metabolic rate (M), as measured from the total heat loss in the calorimeter, was determined along with evaporative heat loss (EHL), dry thermal conductance, and body core temperature (Tc). Animals exposed to TCDD had a significantly lower body temperature at TaS of 10, 16, and 24 degrees C and a higher thermal conductance. M was unaffected by TCDD, indicating that TCDD did not impair the effector to regulate Tc during cold exposure. EHL was also unaffected by TCDD. Skin blood flow of the interscapular area was measured in anesthetized rats with laser Doppler velocimetry and found to be the same in control and TCDD groups. The reduction in body temperature over a wide range of TaS concomitant with normal thermoregulatory effector function suggests that perinatal exposure to TCDD results in a reduction in the regulated body temperature (i.e., decrease in set-point).

Adipose Tissue, Brown↗
PubMed1995

Strain differences in the laboratory rat: impact on the autonomic, behavioral, and biochemical response to cholinesterase inhibition.

Intraspecies variation has been found to affect the physiological, behavioral, and biochemical responses to a variety of neurotoxicants, including the organophosphate diisopropyl fluorophosphate (DFP). However, there is little information on long-term physiological responses to neurotoxicant exposure using strain as a dependent variable. In the present study, radiotelemetry methodology was used to continuously monitor core temperature, heart rate, and motor activity for 4 d following administration of 1.5 mg/kg DFP (sc) in four common strains of rat: Sprague-Dawley (SD), Long-Evans (LE), Fischer 344 (F344), and Wistar (WST). The F344 rat was least susceptible to DFP in terms of both a minimal hypothermic response and recovery of the day-night difference in core temperature. The SD strain was unusual in that its heart rate was elevated relative to the other strains after DFP, in spite of a marked decrease in core temperature and motor activity. The LE strain exhibited the largest reduction in core temperature and heart rate following DFP. Serum and brain cholinesterase activity (ChE) measured 3 h after administration of 1.0 mg/kg DFP also indicated strain effects. The F344 showed less inhibition in these variables compared to the other strains, a response that may explain its attenuated thermoregulatory response to DFP. Overall, the inbred F344 rat demonstrated better resistance to DFP compared to the outbred strains. Therefore, the impact of genetic differences on sensitivity to neurotoxicants such as DFP could be an important tool in understanding the mechanism of action of these agents.

Analysis of Variance↗
PubMed1995

Trimethyltin-induced neuropathy in the rat: interaction with thermoregulation.

The enhanced production of glial fibrillary acidic protein (GFAP) by astroglia appears to be a general response of the CNS to many types of toxic insult. The organometallic neurotoxicant, trimethyltin (TMT), is one such agent known to increase the production of GFAP as a consequence of widespread neuronal destruction. TMT also leads to transient reductions in body temperature (Tb), a response which may alter the neurotoxic effects of this compound. To study the role of Tb in the neurotoxic effects of TMT, rats were injected (i.v.) with saline or 8.0 mg/kg TMT and maintained at ambient temperatures (Ta) of 16, 22, or 30 degrees C for 72 hr while Tb (core) was measured periodically. Animals were then housed at a Ta of 22 degrees C for 35 days after which time their brains were removed and dissected into hippocampus, cerebral cortex, striatum, midbrain and cerebellum for subsequent analysis of GFAP. TMT led to a significant decrease in Tb of rats housed at 22 degrees C measured 3 hr after treatment. Tb of rats maintained at Ta's of 16 and 30 degrees C was unaffected by TMT initially (i.e., no hypothermia); however, by 72 hr after TMT, rats maintained at 22 and 30 degrees C had a significantly elevated Tb. TMT led to marked elevations in GFAP levels, a response that was affected by Ta. In the hippocampus the elevation in GFAP was significantly greater in rats housed at 16 and 30 degrees C. A similar pattern was seen in the midbrain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Metabolic and thermoregulatory responses of the rat maintained in acrylic or wire-screen cages: implications for pharmacological studies.

Because of differences in thermal conductivity, it is likely that a rodent's thermoregulatory requirements and their response to drugs and other stimuli will vary in metal and acrylic cages. To address these issues, thermoregulatory responses were measured in rats housed in an environmental chamber with a floor made of either solid metal (aluminum) or acrylic materials (Plexiglas). Metabolic rate (M), evaporative water loss (E), thermal conductance (C), and tail skin (Tsk) and core temperature (Tc) were measured at ambient temperatures (Ta) of 10, 20, 28, 30, 32, and 34 degrees C. These thermoregulatory variables were essentially unaffected by floor type at Tas of 20 and 28 degrees C. The acrylic floor showed greater increases in M, E, Tc, and Tsk, but a smaller elevation in C as Ta increased from 28 to 34 degrees C. At a Ta of 10 degrees C, rats on the acrylic floor had a smaller M compared to that measured on the metal floor. Rats were then injected with saline or 30 mg/kg (SC) of 3,4-methylenedioxymethamphetamine (MDMA) and placed in an acrylic cage with wood chip bedding or a wire-screen cage at a Ta of 20 degrees C. The MDMA caused Tc to increase > 2.0 degrees C in rats in the acrylic cage but had no effect on Tc of rats in the wire-screen cage. The marked effect of cage type on basal thermoregulatory processes and thermogenic response to MDMA should be useful in the design and interpretation of many pharmacological studies.

3,4-Methylenedioxyamphetamine↗
PubMed1994

24-hour control of body temperature in the rat: II. Diisopropyl fluorophosphate-induced hypothermia and hyperthermia.

Diisopropyl fluorophosphate (DFP) and other anticholinesterase (antiChE) agents have been found to induce marked hypothermic responses in laboratory rodents. To characterize the effects of DFP on autonomic and behavioral thermoregulation, rats of the Long-Evans strain were injected with DFP while housed in a temperature gradient. The gradient allowed for the measurement of selected ambient temperature (Ta) and motor activity (MA) over a 6- to 7-day period. Core temperature (Tc) and heart rate (HR) were also monitored simultaneously using radiotelemetry. Injection of the peanut oil vehicle led to transient elevations in Tc, HR, and MA, but no change in selected Ta. The next day animals were injected with 0.25, 1.0, or 1.5 mg/kg DFP. DFP (1.0 AND 1.5 mg/kg) led to a marked reduction in Tc. The decrease in Tc was accompanied by reductions in HR, MA, and selected Ta. During the first night after DFP, selected Ta remained elevated as Tc recovered to its preinjection level. The second 24-h period after 1.0 and 1.5 mg/kg DFP was associated with a significant elevation in the daytime Tc. In conclusion, with the option of using behavioral thermoregulatory responses, the hypothermic effects of acute DFP treatment are mediated by a selection for cooler TaS. An elevation in Tc during recovery from acute DFP corroborates the many incidents of fever in humans exposed to anti-ChE agents.

Animals↗
PubMed1994

Autonomic and behavioral responses of selectively bred hypercholinergic rats to oxotremorine and diisopropyl fluorophosphate.

The hypercholinergic Flinders Sensitive Line (FSL) rat was significantly more sensitive than the Flinders Resistant Line (FRL) rat to the biotelemetrically recorded hypothermic effects of oxotremorine, a direct-acting muscarinic agonist, and diisopropyl fluorophosphate (DFP), an anticholinesterase agent. The effects of these agents on heart rate and motor activity, also recorded biotelemetrically, indicate either small differences (DFP) or no significant effect (oxotremorine) between the lines. These findings confirm the dramatic differences in temperature responses to cholinergic compounds between FSL and FRL rats, for which they were selectively bred, but suggest that a general increase in the sensitivity of the FSL rats to all muscarinic-mediated responses may not occur.

Animals↗
PubMed1994

Autonomic and behavioral thermoregulation in the golden hamster during subchronic administration of clorgyline.

Chronic administration of clorgyline, a type-A monoamine oxidase inhibitor, leads to a decrease in peritoneal (i.e., core) temperature of golden hamsters. To better understand the mechanisms of clorgyline's thermoregulatory effects, autonomic and behavioral thermoregulatory effectors were measured in Syrian hamsters following chronic infusion of clorgyline via a minipump (2 mg/kg/day). Metabolic rate, evaporative water loss, motor activity, and core temperature were measured after 60 min of exposure to ambient temperatures (Ta) of 5, 20, 30, and 35 degrees C. Behavioral thermoregulatory responses were assessed by measuring selected Ta and motor activity of the same animals in a temperature gradient over the course of 23 h. Metabolic rate and motor activity were significantly elevated in clorgyline-treated hamsters exposed to a Ta of 5 degrees C. There were no effects of clorgyline on evaporative water loss. In the temperature gradient the mean selected Ta of clorgyline-treated hamsters was nearly equal to that of the saline-treated hamsters, 30.7 and 31.2 degrees C, respectively. On the other hand, the mode of selected Ta in the clorgyline group was 2.8 degrees C higher than that of the saline group. Motor activity in the gradient was significantly elevated and food consumption was depressed by clorgyline treatment. Overall, these findings indicate that chronic clorgyline treatment in the golden hamster results in novel autonomic and behavioral modification; it stimulates metabolic thermogenesis during cold exposure, but appears to increase the behavioral zone of thermoneutrality. This latter effect may mean an improvement in heat tolerance, suggesting that this drug might assist in the adaptation to warm temperatures.

Animals↗
PubMed1994

24-hour control of body temperature in rats. I. Integration of behavioral and autonomic effectors.

Some studies suggest that the nocturnal elevation in core temperature (Tc) of the rat is mediated by an elevation in the set point. The role of set point can be assessed if behavioral effectors are measured simultaneously with other thermoregulatory effectors and Tc over a 24-h period. Selected ambient temperature (STa) and motor activity (MA) were measured in rats housed in a temperature gradient system with a 12:12-h photoperiod (lights on 0600 h). Tc and heart rate (HR) were monitored by telemetry. During the light phase, STa, Tc, HR, and MA were relatively stable with values 29.0 degrees C, 37.1 degrees C, 310 beats/min, and 1-2 m/h, respectively. During the light-to-dark transition there were abrupt elevations in Tc, HR, and MA but no change in STa. STa decreased during the dark phase and reached a nadir of 23 degrees C at 0500 h. All variables recovered to basal levels within 3-4 h after the onset of the light phase. Overall, autonomic effectors control the elevation in Tc during the onset of the dark phase while behavioral effectors have little if any role. Behavioral thermoregulation is important in two ways: 1) the selection of cooler Ta values at night to prevent an excess elevation in Tc and 2) a preference for cooler Ta values before the light phase to facilitate the recovery of Tc.

Animals↗
PubMed1992

Attenuation of alcohol consumption by MDMA (ecstasy) in two strains of alcohol-preferring rats.

Alcohol preference and manifestation of alcoholism are thought by many to be associated with serotonin (5-HT) dysfunction in the brain. Thus, experiments were performed to determine the effect of acute and subchronic administration of (+/-) 3,4-methylenedioxymethamphetamine (MDMA), an amphetamine analog that stimulates 5-HT release, on alcohol preference in two strains of alcohol-preferring rats, the Fawn-Hooded (FH) and alcohol-preferring (P) rats. Rats were individually housed and provided free access to a solution of 10% ethanol, food, and water. Ethanol, food, and water intakes were measured daily. After establishing a stable baseline for ethanol and water intake, each rat was injected SC with a dose of 5.0 mg/kg MDMA or an equal volume of saline for 1 or 3 consecutive days. Body temperature was recorded immediately before and 120, 240, and 360 min after MDMA treatment. Ethanol, food, and water intake were measured for the preceding 24 h. Further, to determine the effect of MDMA on alcohol metabolism rats were injected with 5.0 mg/kg MDMA or saline and 15 min later with 2.5 g/kg alcohol. Then, blood alcohol levels were determined at 1, 3, and 5 h after alcohol administration. Our results show that a single administration of 5.0 mg/kg MDMA significantly decreased ethanol intake in both FH and P rats and increased water intake. Subchronic administration of 5.0 mg/kg MDMA for 3 consecutive days significantly attenuated alcohol intake in both strains but only increased water intake in P rats. Administration of MDMA induced hyper- and hypothermia in FH and P rats, respectively. This drug failed to exert any significant effect on the pharmacokinetics of alcohol, indicating a central effect.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Methylenedioxyamphetamine↗
PubMed1991

Pneumocystis carinii pneumonia in patients with solid tumors without acquired immune deficiency syndrome.

Pneumocystis carinii pneumonia (PCP) developed in two patients with solid tumors without acquired immune deficiency syndrome (AIDS). In patients with neoplastic solid tumors, as in those with hematologic malignancies, Pneumocystis is a possible cause of pneumonia. Management protocols evaluating pulmonary infiltrates in this patient population must include tests for PCP.

AIDS Serodiagnosis↗
PubMed1991

Acute effects of diisopropyl fluorophosphate (DFP) on autonomic and behavioral thermoregulatory responses in the Long-Evans rat.

Experiments were designed to assess the mechanisms of diisopropyl fluorophosphate (DFP)-induced changes in thermoregulation of the rat. In one study, male rats of the Long-Evans strain were injected with DFP (s.c.) at doses ranging from 0 to 2.0 mg/kg while maintained at an ambient temperature (Ta) of 20--24 degrees C. Body (Tb) and tail skin (Tt) temperatures were recorded for 5 h post-injection. DFP doses of greater than or equal to 1.0 mg/kg resulted in significant decreases in Tb lasting up to 5 h and increases in Tt lasting up to 1 h post-injection. In a second study, metabolic rate (MR), evaporative water loss (EWL), motor activity (MA), Tb, and Tt were measured at 2 h post-injection of 0, 0.5, 1.0, and 1.5 mg/kg DFP (s.c.) at Ta values of 10, 20, and 30 degrees C. DFP treatment resulted in hypothermia at all three Ta values, but the effect was attenuated at 30 degrees C. MR was significantly reduced at a Ta of 20 degrees C following 1.5 mg/kg, unaffected by DFP at a Ta of 30 degrees C, and stimulated at 10 degrees C following 0.5 mg/kg DFP. EWL was significantly elevated at 30 degrees C following 1.5 mg/kg DFP. MA was significantly reduced following greater than or equal to 1.0 mg/kg DFP at 20 and 30 degrees C and 1.5 mg/kg at 10 degrees C. Tt was elevated and reduced by DFP at Ta values of 30 and 10 degrees C, respectively. In a third study, rats were injected with DFP and placed in a temperature gradient for 1 to 2 h post-injection while selected Ta and Tb were monitored. While both control and DFP-treated rats remained in the cool end of the gradient, rats administered DFP at doses of 1.0 and 1.5 mg/kg were significantly hypothermic. It was also found that Ta values of 10, 20, and 30 degrees C had no effect on DFP-induced inhibition of cholinesterase activity of plasma and erythrocyte fractions of whole blood. Overall, these data support the hypothesis that acute DFP may lower the set-point for the control of body temperature in the rat and demonstrates that the toxicity of DFP is modified by changes in Ta.

Animals↗
PubMed1991

Effects of 3,4-methylenedioxymethamphetamine on autonomic thermoregulatory responses of the rat.

3,4-Methylenedioxymethamphetamine (MDMA), a substituted amphetamine analogue which stimulates serotonin release in the CNS, has been shown to induce near lethal elevations in core temperature in the rat. To characterize the effects of MDMA on temperature regulation, we measured metabolic rate (MR), evaporative water loss (EWL), motor activity (MA), and colonic temperature (Tc) in male, Long-Evans rats at 60 min following 30 mg/kg (SC) MDMA or saline at ambient temperature (Ta) of 10, 20 and 30 degrees C. MDMA caused an elevation in MR at Ta's of 20 and 30 degrees C but had no effect at 10 degrees C. At a Ta of 30 degrees C, MR of the MDMA group was double that of the saline group. EWL was elevated by MDMA, an effect which was potentiated with increasing Ta. MDMA also elicited an increase in MA at all three Ta's. MDMA led to a 3.2 degrees C increase in Tc at 30 degrees C, no change in Tc at 20 degrees C, and a 2.0 degrees C decrease in Tc at 10 degrees C. A second study found that treatment with 20 mg/kg MDMA failed to elicit an increase in blood flow to the tail in spite of a hyperthermic core temperature of 41.4 degrees C. Preliminary studies using radiotelemetry methodology suggested that MDMA lethality is preceded by precipitous elevations in heart rate and core temperature. The data suggest that, at relatively warm Ta's. MDMA-induced stimulation of serotonergic pathways causes an elevation in MR and peripheral vasoconstriction, thus producing life-threatening elevations in Tc.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Methylenedioxyamphetamine↗
PubMed1991

Relationship between cholinesterase inhibition and thermoregulation following exposure to diisopropyl fluorophosphate in the rat.

This study examined the relationship between inhibition of cholinesterase activity (CA) and thermoregulatory response in the rat following exposure to the organophosphate (OP), diisopropyl fluorophosphate (DFP). Male Long-Evans rats were injected with DFP dissolved in peanut oil in doses ranging from 0 to 1.5 mg/kg (s.c.). Colonic (Tcol) and tail skin temperature (Ttail) were recorded at 0, 1, 2 and 3 h post-injection. At 3 h post-injection the rat was sacrificed and a blood sample was taken by cardiac puncture and analyzed for CA. There was a biphasic dose effect of DFP on Tcol with slight but significant elevation in Tcol in the dose range of 0.01-0.5 mg/kg and a significant depression in Tcol at doses of 1.0 and 1.5 mg/kg. There was a dose-dependent fall in CA with DFP administration in the erythrocyte, plasma, and whole blood fractions. Hypothermia was associated with 80-87% inhibition in CA, whereas the elevation in Tcol was associated with 20-70% inhibition in CA. DFP also elicited significant elevations in Ttail. Overall, the data fail to demonstrate any clear relationship between inhibition of blood CA and thermoregulatory response following exposure to DFP. However, the elevation in Tcol following relatively low doses of DFP may be of relevance to the frequently reported symptom of fever in humans exposed to OP agents.

Animals↗
PubMed1991

Toxic-induced hypothermia and hypometabolism: do they increase uncertainty in the extrapolation of toxicological data from experimental animals to humans?

Commonly used experimental mammals, such as the rat and mouse, exhibit hypothermia and hypometabolism when exposed acutely to many drugs and other chemical substances. This toxic-induced hypothermic/hypometabolic state may be an inherently protective response that can reduce the lethality of a toxic insult. However, as body mass increases, the ability to lower body temperature in response to toxic insult is diminished. Hence, the presence of a protective hypothermic/hypometabolic response in small laboratory mammals and apparent lack thereof in larger species, such as humans, may represent an additional physiological dissimilarity which may underestimate the risk assessment of acute toxicological data. It is proposed that acute toxicological studies in rodents be performed at relatively warm ambient temperatures (ca. 28 to 32 degrees C) to prevent toxic-induced hypothermia. This would assure a more uniform internal thermal environment between species, thus reducing a major physiological variable in species-to-species extrapolation.

Animals↗
PubMed1991

Hypothermic effects of a homologous series of short-chain alcohols in rats.

The purpose of this study was to assess the utility of the thermoregulatory system as an end point in predicting the toxicity of various short-chain alcohols. Male Fischer rats developed significant hypothermia following acute administration (ip) of methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, or 2-butanol. The hypothermic responses to the six alcohols all showed similar segmented responses characterized by a threshold dose below which no change in body temperature occurred, and a suprathreshold regression with increasing dose causing greater hypothermia. Relative potency of the alcohols was assessed using both the threshold dose to cause hypothermia and the dose that would cause body temperature to decrease by 1 degree C. Both measures gave the progression of toxicity from least to most potent of methanol less than ethanol less than 2-propanol less than 1-propanol less than 2-butanol less than 1-butanol. The effective dose of each alcohol was compared to its membrane/buffer partition coefficient (Pm/b), and there was a high inverse correlation between the hypothermic dose of an alcohol and its lipid solubility. That the potency of an alcohol was strongly correlated with its Pm/b suggests that the membrane disordering theory of narcosis may also be used to explain the hypothermic action of alcohols.

Alcohols↗
PubMed1991

Comparison of rats of the Fischer 344 and Long-Evans strains in their autonomic thermoregulatory response to trimethyltin administration.

The purpose of this study was to assess the effect of genetic strain on the acute and long-term thermoregulatory response to the neurotoxicant trimethyltin (TMT) in rats of the Long-Evans (LE) and Fischer 344 (FCH) strains. In one study basic thermoregulatory responses including colonic temperature (Tc), metabolic rate (MR), evaporative water loss (EWL), motor activity (MA), and thermal conductance (Cd) were measured in both rat strains at ambient temperatures (Ta) of 10, 28, and 37 degrees C. It was found that the LE rat has a significantly higher Tc when it is measured in their home cage. Because of its smaller body mass the FCH rat has a higher MR at all Ta values. The FCH rat also has a greater rate of EWL during exposure to a Ta of 37 degrees C. Following iv administration of 8.0 mg/kg TMT both rat strains become significantly hypothermic; however, the effect differed significantly between the strains. At 26-34 d after TMT exposure thermoregulatory responses at Ta values of 10-37 degrees C were generally similar to that of the saline controls. Overall, the LE and FCH strains of rat exhibit some distinct thermoregulatory differences in response to changes in Ta.

Animals↗
PubMed1991

Comparative effects of hypoxia on behavioral thermoregulation in rats, hamsters, and mice.

Recent studies using reptiles and other ectothermic species have shown that hypoxia lowers the set point for the control of body temperature. This is characterized by a preference for cooler ambient (Ta) and deep body temperatures (Tb) when placed in a temperature gradient. To elucidate the presence of this effect in mammals, the selected Ta and Tb of three rodent species (mouse, hamster, and rat) were measured while subjected to graded hypoxia in a temperature gradient. Individual animals were placed in the gradient for 30 min. Oxygen content of air entering the gradient was then reduced to a constant level for a period of 60 min by dilution with nitrogen. Tb was significantly reduced in all species at %O2 levels of 5.5-10%. Selected Ta was significantly reduced in the mouse at %O2 levels of 5.5 and 7.3%. Selected Ta of the hamster and rat were reduced slightly at %O2 levels of 5.8 and 7.4%, respectively; however, the effect was not statistically significant. To clarify the effects of hypoxia in these two species, the sample size of rat and hamster was increased to strengthen statistical analysis, and the animals were exposed for 60 min to %O2 levels of 7.4 and 6.7%, respectively. Both species exhibited a significant reduction in selected Ta during hypoxia concomitant with hypothermia. These data support the hypothesis that hypoxia lowers the set point for the control of body temperature in rodents.

Animals↗