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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).

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.

It is known that bioscience is perceived to be difficult and causes anxiety within undergraduate nursing students; yet, commencing students' perceptions of bioscience is not known. Therefore, the aim of this study was to ascertain incoming students' perceptions, knowledge and approaches to learning bioscience. Incoming students to the Bachelor of Nursing completed a questionnaire prior to undertaking bioscience. Two hundred and seventy three students completed the questionnaire that explored their expectations, preconceptions of bioscience content, approaches to learning bioscience, and relationship to clinical practice in the context of biosciences. Participant ages ranged from 17 to 53 (mean 23 years), and 78% of students had completed at least one secondary school science subject, of which 60% had studied biology. Overall, students' preconceptions included anxiety about studying bioscience, bioscience being difficult and harder than nursing subjects, and that more content will be required for bioscience than nursing subjects. Analysis using ANOVA revealed the relationships for secondary school science and age on student responses. A significant effect of secondary school science was found for science in school being advantageous for bioscience (p = 0.010), understanding what bioscience entails (p = 0.002), needing to study science prior to the start of the semester (p = 0.009), and that bioscience is considered difficult (p = 0.029). A significant effect of age was found for exams being more difficult than other assessments (p = 0.000) and for being able to see the relevance of nursing when reaching the workplace (p = 0.011). The findings also indicated that perceptions and associated anxieties related to bioscience were present in commencing students, similar to those which have been reported previously in established student groups. This strongly suggests that the faculty should attempt to dispel preconceptions about bioscience and target improved supports to facilitate the transition of students into the commencement of bioscience for nursing students.

Physical restraint of rodents is needed for nose-only exposure to airborne toxicants and is also used as a means of psychological stress. Hyperthermia is often observed in restrained rats, presumably as a result of impairments in heat dissipation. However, such a hyperthermic response should be dependent on the prevailing ambient conditions. To understand how ambient temperature (T(a)) affects the thermoregulatory response to restraint, core temperature (T(c)) and heart rate (HR) were monitored by telemetry in rats subjected to 1 h of physical restraint while T(a) was maintained at 14-30 °C in 2 °C increments. The T(c) of unrestrained rats was unaffected by T(a). During restraint, T(c) was elevated at ambient temperatures with the exception of 14 °C, at which the rats became mildly hypothermic. There was an inverse relationship between T(a) and HR in both unrestrained and restrained rats; however, HR was significantly elevated in restrained rats at all ambient temperatures except 22 and 24 °C. Heat loss from the tail, estimated from T(c) and tail skin temperature, was markedly reduced at all but the highest ambient temperatures in restrained rats. The data suggest that the T(a) limits of normothermia are narrowed in the restrained rat. That is, between 16 and 20 °C, the rat maintains a relatively stable T(c) that is slightly elevated above that of the unrestrained rat. At ambient temperatures above or below this range, the rat shows signs of hyperthermia and hypothermia, respectively. In contrast, the limits of normothermia for unrestrained rats range from 14 (or lower) to 30 °C. Overall, the ideal T(a) for restrained rats appears to be 20 °C and no higher than 22 °C for the thermoregulatory system to maintain a regulated T(c) in rats well adapted to physical restraint.

In laboratories, mice are housed at 20–24°C, which is below their lower critical temperature (≈30°C). This increased thermal stress has the potential to alter scientific outcomes. Nesting material should allow for improved behavioral thermoregulation and thus alleviate this thermal stress. Nesting behavior should change with temperature and material, and the choice between nesting or thermotaxis (movement in response to temperature) should also depend on the balance of these factors, such that mice titrate nesting material against temperature. Naïve CD-1, BALB/c, and C57BL/6 mice (36 male and 36 female/strain in groups of 3) were housed in a set of 2 connected cages, each maintained at a different temperature using a water bath. One cage in each set was 20°C (Nesting cage; NC) while the other was one of 6 temperatures (Temperature cage; TC: 20, 23, 26, 29, 32, or 35°C). The NC contained one of 6 nesting provisions (0, 2, 4, 6, 8, or 10g), changed daily. Food intake and nest scores were measured in both cages. As the difference in temperature between paired cages increased, feed consumption in NC increased. Nesting provision altered differences in nest scores between the 2 paired temperatures. Nest scores in NC increased with increasing provision. In addition, temperature pairings altered the difference in nest scores with the smallest difference between locations at 26°C and 29°C. Mice transferred material from NC to TC but the likelihood of transfer decreased with increasing provision. Overall, mice of different strains and sexes prefer temperatures between 26–29°C and the shift from thermotaxis to nest building is seen between 6 and 10 g of material. Our results suggest that under normal laboratory temperatures, mice should be provided with no less than 6 grams of nesting material, but up to 10 grams may be needed to alleviate thermal distress under typical temperatures.

The marked improvement in outcome following induction of hypothermia after cardiac arrest has spurred the search for better methods to induce cooling. A regulated decrease in core temperature mediated by a drug-induced reduction in the set point for thermoregulation may be an ideal means of inducing hypothermia. To this end, the exploratory drug HBN-1 was assessed as a means to induce mild and prolonged hypothermia.Free moving rats were infused i.v. for 12 hours with: a vehicle at room temperature (normothermia), a vehicle chilled to 4°C (forced hypothermia), or HBN-1 (mixture of ethanol, lidocaine, and vasopressin) at room temperature. Core (intra-abdominal) temperature (Tc) was measured telemetrically, tail skin temperature (Ttail) by infrared thermography, metabolic rate (MR) was estimated with indirect calorimetery, and shivering was scored visually.HBN-1 elicited a reduction in Tc from 37.5°C to 34°C within 80 minutes after initiation of the infusion; Tc was maintained between 33°C and 34°C for more than 13 hours. HBN-1 infusion was associated with a reduction in MR (p=0.0006), a slight reduction in Ttail, and no evidence of shivering (p0.001). The forced hypothermia group displayed shivering (p0.001), a significant increase in MR, and a decrease in Ttail, indicative of peripheral vasoconstriction to reduce heat loss.HBN-1 infusion induced a mild and prolonged hypothermia in free moving, unanesthetized rats characterized by modulation of thermoeffectors to reduce heat gain and increase heat loss. HBN-1 thus appears to elicit regulated hypothermia and may provide a new method for achieving a prolonged state of therapeutic hypothermia.

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 ( T a ) and motor activity (MA) over a 6- to 7-day period. Core temperature ( T c ) and heart rate (HR) were also monitored simultaneously using radiotelemetry. Injection of the peanut oil vehicle led to transient elevations in T c , HR, and MA, but no change in selected T a . 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 T c . The decrease in T c was accompanied by reductions in HR, MA, and selected T a . During the first night after DFP, selected T a remained elevated as T c 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 T c . In conclusion, with the option of using behavioral thermoregulatory responses, the hypothermic effects of acute DFP treatment are mediated by a selection for cooler T a s . An elevation in T c during recovery from acute DFP corroborates the many incidents of fever in humans exposed to anti-ChE 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.

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 envirommental 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 ( T sk ) and core temperature ( T c ) were measured at ambient temperatures ( T a ) of 10, 20, 28, 30, 32, and 34°C. These thermoregulatory variables were essentially unaffected by floor type at T a s of 20 and 28°C. The acrylic floor showed greater increases in M , E , T c , and T sk , but a smaller elevation in C as T a increased from 28 to 34°C. At a T a of 10°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 T a of 20°C. The MDMA caused T c to increase > 2.0°C in rats in the acrylic cage but had no effect on T c 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.

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.

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 ∼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 methylscopolamine 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. The CHLP treated rat exhibits a prolonged elevation in HR, hypersensitivity to noradrenergic stimulation and cholinergic antagonism but hyposensitivity to central cholinergic stimulation.

Physical restraint of rodents is needed for nose-only exposure to airborne toxicants and is also used as a means of psychological stress. Hyperthermia is often observed in restrained rats, presumably as a result of impairments in heat dissipation. However, such a hyperthermic response should be dependent on the prevailing ambient conditions. To understand how ambient temperature (T(a)) affects the thermoregulatory response to restraint, core temperature (T(c)) and heart rate (HR) were monitored by telemetry in rats subjected to 1 h of physical restraint while T(a) was maintained at 14-30 °C in 2 °C increments. The T(c) of unrestrained rats was unaffected by T(a). During restraint, T(c) was elevated at ambient temperatures with the exception of 14 °C, at which the rats became mildly hypothermic. There was an inverse relationship between T(a) and HR in both unrestrained and restrained rats; however, HR was significantly elevated in restrained rats at all ambient temperatures except 22 and 24 °C. Heat loss from the tail, estimated from T(c) and tail skin temperature, was markedly reduced at all but the highest ambient temperatures in restrained rats. The data suggest that the T(a) limits of normothermia are narrowed in the restrained rat. That is, between 16 and 20 °C, the rat maintains a relatively stable T(c) that is slightly elevated above that of the unrestrained rat. At ambient temperatures above or below this range, the rat shows signs of hyperthermia and hypothermia, respectively. In contrast, the limits of normothermia for unrestrained rats range from 14 (or lower) to 30 °C. Overall, the ideal T(a) for restrained rats appears to be 20 °C and no higher than 22 °C for the thermoregulatory system to maintain a regulated T(c) in rats well adapted to physical restraint.

Nicotine-induced hypothermia is well established, but the nicotinic receptor actions underlying this effect are not clear. Nicotine causes activation and desensitization at a variety of nicotinic receptor subtypes. Sazetidine-A [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol] is a novel compound that potently and selectively desensitizes α4β2* nicotinic receptors. The main goal of this study was to investigate the effects of sazetidine-A, on core body temperature (Tc) in mice and rats. Sazetidine-A effects on Tc and the interactions of sazetidine-A with nicotine and selective nicotinic antagonists were investigated to determine the receptor actions underlying nicotine-induced hypothermia. Adult male mice were injected with different dose of nicotine (0.2, 0.4 and 0.8 mg/kg), sazetidine-A (0.3, 1, and 3 mg/kg), a mixture of nicotine (0.4 or 0.8 mg/kg) and sazetidine-A (0.3 or 0.6 mg/kg) or saline and Tc was monitored telemetrically. In another set of experiments, the interaction between sazetidine-A and dihydro-β-erythroidine (DHβE), an α4β2* nicotinic receptors antagonist, and methyllycaconitine (MLA), an α 7 antagonist, was investigated. Tc of mice was monitored following DHβE (1, 3 and 6 mg/kg), a combination of DHβE (3 mg/kg) and sazetidine-A (0.6 mg/kg), MLA (1.5, 3 or 6 mg/kg) or combination of MLA (6 mg/kg) and sazetidine (0.6 mg/kg) or saline. The acute effect of sazetidine-A (1, 3, and 6 mg/kg) on rats Tc was also studied. Acute sazetidine-A caused a pronounced and long-lasting hypothermia in mice; Tc decreased to about 28 °C at 100 min and recovered within 230 min. The hypothermic effect of sazetidine in rats was much less in magnitude (about 3°C) and shorter in duration compared with that in mice. Nicotine co-administration with low doses of sazetidine potentiated the magnitude and duration of hypothermia in mice. The α4β2* nicotinic receptors antagonist DHβE significantly prolonged sazetidine-A-induced hypothermia but did not increase its depth. The α7 antagonist MLA caused a modest degree of hypothermia with relatively short duration in mice. MLA failed to counteract the sazetidine-A-induced hypothermia. Overall, our results show that pharmacological modulation of α4β2* nicotinic receptors elicits changes in body temperature that may involve desensitization of these receptors.

The rodent, specifically the laboratory rat, is the primary experimental animal used in toxicology testing. Despite its popularity, recent studies from our laboratory and others raise a number of questions concerning the rat's appropriateness as an animal model for toxicological studies. While there may be additional areas in which the rat and other small rodents fail to adequately mimic the human response to xenobiotic agents, this article will focus on the area of temperature regulation. Thus, this article will review the thermoregulatory response of the laboratory rat following acute exposure to toxic agents and examine the impact of this response on the extrapolation of toxicological data from experimental animals to humans. In general, the rat responds to acute intoxication by lowering its core temperature via both physiological and behavioral mechanisms, thereby attenuating the induced toxicity. Similar responses have not been reported in humans.

The purpose of this study was to assess intraspecies differences in behavioral and autonomic function in three strains of rat following administration of diisopropyl fluorophosphate (DFP), an irreversible inhibitor of acetylcholinesterase activity. Male rats of the Long-Evans (LE), Fischer 344 (F344), and Sprague-Dawley (SD) strains wer administered DFP at doses of 0-1.5 mg/kg (sc). The animals were placed 60 min later into one of two motor activity chambers and tested for 30 min. Motor activity was measured using either a Doppler-based system or a commercial photocell device. Following measurement of motor activity in the Doppler system, body temperature (Tb) was measured and blood was then withdrawn by cardiac puncture and analyzed for serum cholinesterase activity (ChE). The remaining rats were retested 1 d after DFP administration in the photocell device. The results showed a significant influence of strain on the effects of DFP. Motor activity of LE rats was reduced by DFP at doses of 1.0 and 1.5 mg/kg, whereas the activity of F344 rats was reduced only at 1.5 mg/kg. The relative sensitivity of SD rats depended on the device used to measure motor activity. The SD rats resembled F344 rats in their response to DFP when motor activity was measured in the photocell device, and LE rats when motor activity was measured in the Doppler system. The Tb of F344 rats was unaffected by DFP, while the LE and SD rats became hypothermic at 1.5 mg/kg. The DFP-induced inhibition of serum ChE activity was significantly less in F344 rats. All three strains retested the day after DFP still showed significant decreases in motor activity. Overall, it appears that the F344 strain is relatively resistant to the behavioral and autonomic effects of DFP. This intraspecies variability should be considered in selecting appropriate experimental models for assessing the neurotoxicological hazards of cholinesterase-inhibiting pesticides.

The purpose of this study was to assess the effect of time of day on the behavioral thermoregulatory patterns of nocturnal rodents, the Long-Evans (LE) rat, Fischer 344 (F344) rat, and the golden hamster. Individual animals were placed in a temperature gradient for 4 days while selected ambient temperature (STa) and motor activity (MA) were monitored. Food was provided at the cold and warm ends of the gradient and water was provided ad lib. All animals eventually showed a 24-h rhythm of STa and MA characterized by a preference for cooler TaS during the dark period which coincided with an increase in MA. Both rat strains had STaS of approximately 28 degrees C during the light period that decreased to 22-24 degrees C during the dark period. The F344 rat developed a STa rhythm by the second day in the gradient, whereas the LE strain required 4 days. The hamster exhibited relatively warm STaS of 32-33 degrees C during the light period that decreased to 26-28 degrees C during the dark period. The nocturnal preference for cooler STaS contradicts a current concept of an elevation in set point of the thermoregulatory system. However, the data also suggest that behavioral and autonomic thermoregulatory effectors may operate independently in the control of night time elevations in body temperature.

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.

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. These findings suggest that MDMA exerts an inhibitory action on alcohol preference, possibly by enhancing serotonergic and/or dopaminergic systems in the CNS.

The physiological response to environmental toxicants and drugs is modulated by the thermoregulatory system. Environmental and body temperature can affect the entry of toxicants into the body through pulmonary, cutaneous, and gastrointestinal routes. Thermoregulation can ultimately influence the metabolic clearance of chemicals and their toxicity, including lethality. The thermoregulatory response following acute exposure to many toxic chemicals involves a regulated hypothermic response, characterized by activation of autonomic thermoeffectors to raise heat loss and a behavioral preference for cooler temperatures. Moderate hypothermia in rodents improves recovery and survival following toxic exposure. In relatively large mammals, including humans, the hypothermic response is minimal. Fever-like responses are often seen in humans and other large mammals exposed to many toxicants. Fever is also observed in rodents exposed to some toxicants provided that core temperature can be monitored without disturbing the animal (e.g., telemetry). Overall, the universal effects of temperature on chemical toxicity call for researchers to have a better understanding of how body and ambient temperature affect the physiological response to environmental toxicants.

Our understanding of the effects of temperature on toxic response has seen resurgence in the past several decades, with the development of better methods to study the integration of autonomic and behavioural thermoregulatory responses in rodents and other species. Radiotelemetry provides researchers with the best tool to study the thermoregulatory responses in undisturbed rodents exposed chronically or acutely to toxic chemicals. The thermoregulatory response to acute exposure to many toxic chemicals involves a regulated hypothermic response, characterized by an increase in autonomic thermoeffectors to increase heat loss and a behavioural preference for cooler temperatures. This thermoeffector response is quickly manifested by a marked drop in the core temperature in rodents. However, in humans and other large mammals, the hypothermic response is meagre due to their large thermal inertia. A combination of exposure to cool temperatures and a moderate hypothermic response has been found to benefit survival with a variety of toxic agents. Thus, the integrated thermoregulatory response of rodents to lower their core temperature seems to be an adaptive response. On the other hand, fever or hyperthermia is often seen in humans and other large mammals exposed to various toxicants. A fever is also seen in rodents provided that core temperature is monitored without disturbing the animal (e.g. telemetry). The universal effects of temperature on chemical toxicity calls for researchers to have a better understanding of the thermoregulatory effects of environmental toxicants. Keywords: thermoregulation; autonomic; behavioural; radiotelemetry; thermal stress; organophosphate insecticides; fever

Background: Recognition of and early intervention for patients with acutely deteriorating conditions is often the responsibility of medical-surgical nurses. This study examined the effect of simulation on medical-surgical graduate nurses' perceived ability and confidence in responding to patient clinical emergencies. Method: Fifty medical-surgical graduate students participated in high-fidelity immersive simulations. Questionnaires completed before and after simulation asked participants to rate their perceived ability and confidence. Results: After simulation, participants reported increased confidence in their ability to perform both technical and nontechnical aspects of responding to patient clinical emergencies. Ninety-four percent of participants identified formal debriefing as the most useful aspect of the simulation experience. Conclusion: Medical-surgical graduate nurses' confidence and perceived technical and nontechnical skills during patient clinical emergencies are enhanced following simulation. The ability of graduates to transfer the increased confidence and perceived advanced resuscitation skills following simulation to the clinical environment needs to be investigated. J Contin Educ Nurs 2009;40(11):491–498.

Summary Background There is a paucity of evidence regarding the efficacy in preparing medical–surgical nurses to respond to patients with acutely deteriorating conditions. Study aim The aim of this study was to evaluate registered nurses' ability to respond to the deteriorating patient in clinical practise following training using immersive simulation and use of a high fidelity simulator. Methods This study was a follow-up survey of medical–surgical graduate nurses following immersive high fidelity simulation training. Thirty eight registered nurses practising in medical–surgical areas completed the simulation as part of university graduate study. A follow-up survey of the graduate medical–surgical registered nurses conducted three months following completion of a high fidelity simulation-based learning experience. Outcomes consisted of the number of times skills were used in practise and the usefulness of simulation in preparing for actual emergency events. Results Participants reported a total of 164 clinical patient emergencies in the follow-up time period including: 46% cardiac, 32% respiratory, 10% neurological, 7% cardiac arrest and 5% related to electrolyte disturbances. The ability to respond in a systematic way, handover to the emergency team and airway management were identified as the skills most improved during patient emergencies following simulation. The most useful aspects of the simulation experience identified were scenario debriefing and assertiveness training. Participants with less years of clinical experience were more likely to report practising the team leader role and debriefing as the most useful aspects of simulation. Conclusions The skills practised in simulation were highly relevant to participants practise in medical–surgical areas. Non-technical skills, including assertiveness skills should be considered in future emergency training courses for nurses.

Long-term exercise training selectively alters serum cytokines involved in fever. Chronic exercise training has a number of effects on the immune system that may mimic the physiological response to fever. Female rats that voluntarily exercise on running wheels develop an elevated daytime core temperature after several weeks of training. It remains to be seen whether the elevation in daytime temperature involves inflammatory patterns characteristic of an infectious fever. We assessed whether chronic exercise training in the rat would alter levels of cytokines involved in fever. Female Sprague Dawley rats at 45 days of age weighing 90—110 g were divided into two groups (exercise and sedentary) and housed at an ambient temperature of 22°C. Interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), iron, and zinc levels were analyzed. Rats underwent 8 weeks of exercise on running wheels. Exercise led to altered levels of some key cytokines that are involved in fever. Exercise animals had significantly higher IL-1β levels and lower IL-10 levels compared to sedentary animals. Although IL-6 levels were slightly lower in the exercise animals, these levels were not significantly affected by training. TNF-α activity was similar in the two groups. Training also led to a slight increase in serum zinc and decrease in serum unsaturated iron binding capacity (UIBC). The data suggest that chronic exercise training evokes immune responses that mimic some, but not all, aspects of fever. This may explain why exercise leads to elevated daytime core temperature.

Past studies have found that the laboratory rat placed in a temperature gradient prefers temperatures that are markedly below its lower critical ambient temperature (LCT), whereas other rodents (e.g., mouse, hamster, and guinea pig) generally select thermal environments associated with minimal metabolic expenditure. To further study the rat's thermoregulatory behavior, a temperature gradient was designed to monitor the selected ambient temperature (STa) and motor activity (MA) of food-deprived rats of the Long-Evans (LE), Fischer 344 (F344), and Sprague-Dawley (SD) strains over a 22-h period. All three rat strains selected relatively cool STas of 21-26 degrees C during the first 1-3 h in the temperature gradient. This was followed by a gradual increase in the STa that peaked at 4 (F344) to 6 h (SD and LE) after being placed in the gradient. The LE strain had a significantly lower STa during the initial period in the gradient. There were slight decreases in the STa during the nocturnal phase in the F344 and SD strains concomitant with marked increases in MA. These results indicate that the rat requires a relatively long adjustment period in a temperature gradient before it exhibits STas that are associated with minimal metabolic expenditure. Given adequate time for accommodation, behavioral thermoregulatory responses of the rat appear to be similar to those of other rodents.

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.

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.

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 temperatures (Ta) of 10, 20, and 30°C. MDMA caused an elevation in MR at Ta's of 20 and 30°C but had no effect at 10°C. At a Ta of 30°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°C increase in Tc at 30°C, no change in Tc at 20°C, and a 2.0°C decrease in Tc at 10°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°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 pathway causes an elevation in MR and peripheral vasoconstriction, thus producing life-threatening elevations in Tc. The increase in EWL following MDMA partially attenuates the hyperthermia at warm Ta's, but leads to hypothermia in the rat maintained at a cold Ta of 10°C.

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.

Background: the mortality and morbidity of falls in older people is significant, with recurrent fallers being at an increased risk. The most effective way to reduce falls in this group is not clear. Objective: to determine the effectiveness of two interventions, one based in primary care and the other in secondary care, at preventing further falls in recurrent fallers. Design: cluster randomised controlled trial. Participants: sixty-five years or over, living in the community, two or more falls in the previous year and not presenting to an emergency department with index fall. Setting: Mid Hampshire, UK. Intervention:eighteengeneral practices were randomly allocated to one of three groups.The primary care groupwas assessed by nurses in the community, using a risk factor review and subsequent targeted referral to other professionals. The secondary care group received a multi-disciplinary assessment in a day hospital followed by identified appropriate interventions. The control group received usual care. Follow-up was for 1 year. Results: five hundred and five participants were recruited. Follow-up was completed in 83% (421/505). The proportion of participants who fell again was significantly lower in the secondary care group (75%, 158/210) compared to the control group [84%, 133/159, adjusted odds ratio (OR) 0.52 (95% CI 0.35‐0.79) P = 0.002]. The primary care group showed similar results to the control group [87%, 118/136, adjusted OR 1.17 (95% CI 0.57‐2.37) P = 0.673]. Conclusion: a structured multi-disciplinary assessment of recurrent fallers significantly reduced the number experiencing further falls, but a community-based nurse-led assessment with targeted referral to other professionals did not.

The development of high throughput biochemical screens could be useful to assess the broad spectrum of physiological effects of environmental toxicants. To explore the prospect of using a screen in an in vivo exposure scenario, we applied a commercially available multianalyte profile (MAP) of 58 serum biomarkers to rats exposed acutely to two anticholinesterase insecticides, chlorpyrifos (CHP) and carbaryl (CAR). Male, Long-Evans rats were dosed orally with 30 mg/kg CHP, 75 mg/kg CAR or the corn oil vehicle. Doses were selected based on their equivalent physiological effects (hypothermia and reduced motor activity). The animals were terminated 24h or 7 days after dosing. Serum was collected and analyzed for 58 biomarkers consisting primarily of cytokines, chemokines, and a few hormones. There were changes in six analytes (four up, two down) following CHP and eight analytes (five up, three down) following CAR at 24h. There were significant changes in only two biomarkers when measured 7 days after dosing with CHP. Overall, the MAP detected a broad spectrum of unique effects for CHP and CAR. It is concluded that the MAP is a useful tool to screen for in vivo effects of environmental toxicants and its use could lead to the discovery of novel mechanisms of action.

Ciguatoxins (CTX) are polyether neurotoxins that target voltage-gated sodium channels and are responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post-exposure 2.4% of features on a 44K whole genome array were differentially expressed (por = 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure. Data were filtered (/fold change/or = 1.5 and por = 0.0001 in at least one time point) and a trend set of 1550 genes were used for further analysis. Early gene expression was likely influenced prominently by an acute 4 degrees C decline in core body temperature by 1 h, which resolved by 8 h following exposure. An initial downregulation of 32 different solute carriers, many involved in sodium transport, was observed. Differential gene expression in pathways involving eicosanoid biosynthesis and cholesterol homeostasis was also noted. Cytochrome P450s (Cyps) were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial downregulation at 1 h but were quickly and strongly upregulated at 4 and 24 h post-exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice.

Practice managers are often involved in the employment of practice nurses and are likely to have a significant role in future transition programs in general practice. Therefore, the aim of the study was to explore practice managers’ expectations of new graduate registered nurses working in general practice. A nation-wide web-based electronic survey distributed by the Australian Association of Practice Management was used to collect demographic data and practice managers’ expectations of new graduate nurses directly transitioning into general practice in their first year of practice. The sample was broadly representative of the Australian state and territory population numbers. Respondents were predominantly female with postgraduate qualifications. The findings of this study highlight that practice managers who currently work with practice nurses would be supportive of graduate registered nurses in general practice in their first year with preceptor support. The results of this study have important implications for nursing workforce development and it is recommended that such initiatives are widely introduced with appropriate financial support.

This study was designed to assess the thermoregulatory mechanisms responsible for the elevation in body temperature following ethanol administration when exposed to a high ambient temperature (Ta). Male rats of the Fischer 344 strain were gavaged with 20% ethanol at doses of 0, 2.0, 4.0, 6.0, or 8.0 g/kg and were then placed in an environmental chamber set at a Ta of 37°C. Metabolic rate normalized to body mass0.75 (MR), evaporative water loss (EWL), and motor activity were recorded for 60 min. Ethanol elicited a significant increase in colonic temperature and decrease in MR, EWL, and motor activity. Ethanol also significantly reduced the quantity of evaporated water per milliliter of oxygen consumed (E/M). Multiple linear regression analysis indicated that the two major factors which were associated with the ethanol-induced elevation in body temperature were an increase in MR and a decrease in E/M. Visual observation of behavior indicated that the normal grooming of saliva onto the fur during heat stress was impaired in ethanol-treated animals. Thus, during exposure to a high Ta, the acute ethanol-induced elevation in body temperature appears to be attributed to a suppression in both autonomic and behavioral mechanisms of heat dissipation.

To measure the effect of methanol on autonomic thermoregulation, male Fischer rats were injected intraperitoneally with saline or 1 or 3 g/kg methanol (20% w/v in saline). The rats were then placed in a chamber, set at an ambient temperature (Ta) of 5, 15, 25, or 35 degrees C, for 60 min while total activity, metabolic rate (MR), evaporative water loss (EWL), and dry thermal conductance were measured. After 60 min, the rat was removed from the chamber and colonic temperature (Tc) was measured. The rats developed a significant hypothermia following the 3 g/kg dosage of methanol at Ta's from 5 to 25 degrees C, while the change in Tc at 35 degrees C was not significant. Total activity decreased following 3 g/kg methanol at Ta's from 15 to 35 degrees C. At a Ta of 25 degrees C, MR was at basal levels and methanol had no effect, but at the other Ta's, where MR was elevated, methanol caused a significant reduction in MR. EWL and thermal conductance were elevated at 35 degrees C in control rats, and methanol reduced EWL at this Ta while it had no effect on conductance at this or any other Ta. These data suggest that the methanol-induced hypothermia and its depressive effect on activity and MR were related. The effect of methanol on the heat loss effectors (EWL, conductance) was not significant or was in the direction of heat conservation. Thus, methanol exposure leads to a significant hypothermia in rats by an inhibitory action on heat production pathways.

The purpose of this paper is to thoroughly review the literature and present a data base of the basic thermoregulatory parameters of the laboratory rat. This review surveys the pertinent papers dealing with various aspects of the thermal biology of the laboratory rat, including: metabolism, thermoneutrality, core and brain temperature, thermal tolerance, thermal conductance and insulation, thermoregulatory effectors (i.e., thermogenesis, peripheral vasomotor tone, evaporation, and behavior), thermal acclimation, growth and reproduction, ontogeny, aging, motor activity and exercise, circadian rhythm and sleep, gender differences, and other parameters. It is shown that many facets of the thermoregulatory system of the laboratory rat are typical to that of most homeothermic species. However, is several instances the rat exhibits unique thermoregulatory responses which are not comparable to other species.

In the first experiment, mice were placed in a temperature gradient and were permitted to select their ambient temperature ( T a ). After 1 h, the animals were removed from the gradient, injected with mouse urine at doses of 0, 6, 12 or 18 ml/kg (i.p.) and were placed quickly back in the gradient. The 18 ml/kg dose elicited a decrease in the selected T a along with a significant reduction in body temperature measurement at 60 and 120 min post-injection. In a second experiment it was found that urine collected from mice maintained at T a 's of 20, 30 or 35°C overnight had similar effects on the behavioral thermoregulatory response. In the third experiment, mouse urine was dialyzed against saline using dialysis tubing with a molecular cutoff of 1000 Da. The dialyzed urine had no effect on behavioral thermoregulation but did elicit a significant drop in body temperature; however, the decrease in temperature was not as great as that following administration of undialyzed urine. These studies indicate that mouse urine contains toxic substances that evoke a decrease in the set-point (i.e. anapyrexia). Interestingly, the response to urine is similar to that following acute exposure to xenobiotic chemical substances.

To investigate the practicality of hypothermia and hypometabolism as sensitive indices of toxicity in the mouse, oxygen consumption was monitored continuously and body temperature was measured at 30 min postinjection following the intraperitoneal administration of various metal salts. Eleven metal ions were tested: Al3+, Cd2+, Co2+, Cr2+, Cu2+, Hg2+, Mg2+, Mn2+, Ni2+, Pb2+, and Zn2+. All metals induced dose-dependent reductions in both oxygen consumption (hypometabolism) and deep body (colonic) temperature. Comparative toxicity of the metal ions was evaluated by calculating the dose of metal ion in dimensions of mmol/kg body mass needed to reduce colonic temperature to 35 degrees C. The order of toxicity from lowest to highest was as follows: Cr less than Al less than Pb less than Mn less than Mg less than Zn less than Cu less than Co less than Ni less than Hg less than Cd. The threshold doses for reducing body temperature were less than 5% of the LD50 in 6 of the metals studied. Metal salts with relatively low LD50 doses such as Hg, Cd, and Ni were most efficacious in inducing hypothermia and hypometabolism. Moreover, there was a direct linear relationship between dose for inducing hypothermia or hypometabolism and the reported LD50. Hence, the hypothermia and hypometabolism test may prove to be a sensitive and rapid test for the evaluation of toxicity of environmental contaminants.

The thermoregulatory system of laboratory rodents is susceptible to a variety of chemical toxicants. Because temperature directly affects the reaction of virtually all biological processes, it is critical to consider how changes in the thermoregulatory response to a toxicant may affect physiological, behavioral, and pathological endpoints. Researchers in industry and government laboratories are often faced with addressing how changes in body temperature of their experimental subjects may affect the outcome of a particular toxicity test and/or screening panel. However, many toxicologists are either unaware of the importance or ignore the potential impact of a toxic-induced change in body temperature. This paper endeavors to summarize the importance of thermoregulation in the study of toxicology and propose recommendations for thermometry that researchers may utilize in their toxicological studies.

Ciguatera is a common illness in tropical and subtropical regions that manifests in complex and long-lived symptoms which are more severe in subsequent exposures. This study measures central and peripheral neurologic signs, in parallel with blood toxin levels, in mice exposed once or twice (at 3 days interval) to a sublethal dose of ciguatoxin P-CTX-1 (0.26ng/g via i.p.). Mice were implanted with radiotransmitters to monitor motor activity and core temperature. A single exposure to ciguatoxin elicited an immediate and transient decrease in motor activity and temperature, and subsequent long-lasting thermoregulatory dysfunction resulting in stabilized body temperature around 36.0 degrees C with no observable circadian rhythm. The hypothermic response and the reduced activity were enhanced with a second exposure with 30% of the mice dying within 7h. Measurement of the peripheral nervous system by the tail flick assay revealed increased latency with a single ciguatoxin exposure, and a greater effect following the second exposure. Toxin was measurable in blood up to 3 days following the first exposure; at the 1h time point the concentrations were significantly elevated after a second exposure. These findings indicate an early response to ciguatoxin manifest in a central response to lower body temperature and reduce motor activity and a more persistent effect on the peripheral system leading to spinal heat antinociception and delayed fever-like response. The greater neurological response to a second ciguatoxin exposure was associated with elevated concentrations of ciguatoxin in the blood solely over the first hour of exposure. In conclusion, a single exposure to toxin exerts a significant neurological response which may be enhanced with subsequent exposure.

This chapter focuses on the effects of hyperthermia on drug and chemical toxicity. In general, hyperthermia exacerbates the toxicity of many types of drugs and environmental toxicants. Using rodents to model the potential responses of humans to hyperthermic drugs is hampered by the unique differences in thermoregulatory ability and body mass. Because of their relatively large surface area:mass ratio, ambient temperature has a more profound influence on the potential hyperthermic effect of a drug in rodents. The relative increase in heat production (i.e., as a percentage of their basal metabolic rate) required to raise core temperature by 1 degrees C will increase with a decrease in body mass. The thermoregulatory response to methylenedioxymethamphetamine (MDMA) is used to illustrate the differences in thermoregulatory responses of rats and humans to a hyperthermic drug. Overall, the interaction between ambient temperature and drug-induced changes in body temperature is critical in the evaluation of hyperthermic-induced toxicity in rodent models.

This chapter focuses on the effects of hyperthermia on drug and chemical toxicity. In general, hyperthermia exacerbates the toxicity of many types of drugs and environmental toxicants. Using rodents to model the potential responses of humans to hyperthermic drugs is hampered by the unique differences in thermoregulatory ability and body mass. Because of their relatively large surface area:mass ratio, ambient temperature has a more profound influence on the potential hyperthermic effect of a drug in rodents. The relative increase in heat production (i.e., as a percentage of their basal metabolic rate) required to raise core temperature by 1 degrees C will increase with a decrease in body mass. The thermoregulatory response to methylenedioxymethamphetamine (MDMA) is used to illustrate the differences in thermoregulatory responses of rats and humans to a hyperthermic drug. Overall, the interaction between ambient temperature and drug-induced changes in body temperature is critical in the evaluation of hyperthermic-induced toxicity in rodent models.

OBJECTIVES:The aim of this preliminary study was to evaluate if Sleep Restriction Therapy for insomnia is associated with modifications to physiological arousal, indexed through overnight measures of plasma cortisol concentrations and core body temperature. METHODS:In a pre-to-post open label study design, eleven patients with chronic and severe Psychophysiological Insomnia underwent 5 weeks of Sleep Restriction Therapy. RESULTS:Eight (73%) patients out of 11 consented completed therapy and showed a decrease in insomnia severity pre-to-post treatment (mean (SD): 18.1 (2.8) versus 8.4 (4.8); p = .001). Six patients were analyzed with pre-to-post overnight measures of temperature and cortisol. Contrary to our hypothesis, significantly higher levels of plasma cortisol concentrations were found during the early morning at post-treatment compared to baseline (p < .01), while no change was observed in the pre-sleep phase or early part of the night. Core body temperature during sleep was however reduced significantly (overall mean [95% CI]: 36.54 (°C) [36.3, 36.8] versus 36.45 [36.2, 36.7]; p < .05). CONCLUSIONS:Sleep Restriction Therapy therefore was associated with increased early morning cortisol concentrations and decreased core body temperature, supporting the premise of physiological changes in functioning after effective therapy. Future work should evaluate change in physiological variables associated with clinical treatment response. TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry ANZCTR 12612000049875.

Purpose: Simulation in physiotherapy education is increasing, but a standardised assessment tool for student performance in simulation has not been developed. The Assessment of Physiotherapy Practice (APP) is a validated tool for student performance in the clinical workplace, and has been used recently for simulation despite its relevance for this context being unknown. The purpose of the study was to gain consensus about which APP items should be included in a tool to assess physiotherapy students’ performance in simulation. The relevance of items was considered for both single patient encounters, and longitudinal (multiple) encounters. Methods: An online Delphi approach used a custom designed survey. A purposive sample of physiotherapists with simulation experience was recruited via email. Two rounds were undertaken with consensus being reached when at least 80% of the panel agreed on inclusion or exclusion of an item. Results: Twenty participants responded in the first round and fourteen in the second (70% retention). For longitudinal simulations, all APP items reached consensus in the first round. For single patient simulation encounters, consensus was not reached in the first round for the following items: commitment to learning (61%), teamwork (76%) and discharge planning (72%). In the second round, consensus for ‘teamwork’ remained the only item below eighty percent agreement (78.6%). Conclusions: The APP was deemed to be an appropriate measure for longitudinal clinical simulations, and with the exclusion of teamwork, for a single patient simulation encounter.