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Validation of an individualised model of human thermoregulation for predicting responses to cold air.

Most computer models of human thermoregulation are population based. Here, we individualised the Fiala model [Fiala et al. (2001) Int J Biometeorol 45:143-159] with respect to anthropometrics, body fat, and metabolic rate. The predictions of the adapted multisegmental thermoregulatory model were compared with measured skin temperatures of individuals. Data from two experiments, in which reclining subjects were suddenly exposed to mild to moderate cold environmental conditions, were used to study the effect on dynamic skin temperature responses. Body fat was measured by the three-compartment method combining underwater weighing and deuterium dilution. Metabolic rate was determined by indirect calorimetry. In experiment 1, the bias (mean difference) between predicted and measured mean skin temperature decreased from 1.8 degrees C to -0.15 degrees C during cold exposure. The standard deviation of the mean difference remained of the same magnitude (from 0.7 degrees C to 0.9 degrees C). In experiment 2 the bias of the skin temperature changed from 2.0+/-1.09 degrees C using the standard model to 1.3+/-0.93 degrees C using individual characteristics in the model. The inclusion of individual characteristics thus improved the predictions for an individual and led to a significantly smaller systematic error. However, a large part of the discrepancies in individual response to cold remained unexplained. Possible further improvements to the model accomplished by inclusion of more subject characteristics (i.e. body fat distribution, body shape) and model refinements on the level of (skin) blood perfusion, and control functions, are discussed.

Adult↗

The development of the ventilatory response to cold in very young rats.

To assess the range of functional responses of the ventilatory apparatus of developing rats and the degree to which ventilatory function is developed in advance of other functional characteristics, rat pups at five ages (between 4 and 20 days old) were exposed to temperatures of 28, 32 and 36 degrees C while in a flow through metabolic chamber modified to serve as a whole body plethysmograph. Ventilatory frequency, tidal volume and oxygen extraction 'efficiency' (EO2 = VO2/FEO2 x VI) were measured at each age and temperature. Mean breathing frequency at 4 days old was 2.56 breaths per second, decreasing to 1.99 at 20 days old. There was insignificant modification of breathing frequency with temperature. Four day old rat pups at 28 degrees C had mass specific tidal volumes of 0.017 ml/g, 142% of the value at 36 degrees C (0.012 ml/g). Twenty day old pups at 28 degrees C had mass specific tidal volumes of 0.027 ml/g, also 142% of the thermoneutral value (0.019 ml/g at 32 degrees C). At all ages, increases in tidal volumes were similar and increases in tidal volume were the only response to increased metabolic demand. Oxygen extraction 'efficiency' was about half that previously observed in adult rodents. These observations of ventilation during a cold challenge suggest that although structural development is not complete until much later, functional development is sufficient, either at birth or shortly thereafter.

Aging↗

The phosphotransferase system of Lactobacillus casei: regulation of carbon metabolism and connection to cold shock response.

Genome sequencing of two different Lactobacillus casei strains (ATCC334 and BL23) is presently going on and preliminary data revealed that this lactic acid bacterium possesses numerous carbohydrate transport systems probably reflecting its capacity to proliferate under varying environmental conditions. Many carbohydrate transporters belong to the phosphoenolpyruvate:sugar phosphotransferase system (PTS), but all different kinds of non-PTS transporters are present as well and their substrates are known in a few cases. In L. casei regulation of carbohydrate transport and carbon metabolism is mainly achieved by PTS proteins. Carbon catabolite repression (CCR) is mediated via several mechanisms, including the major P-Ser-HPr/catabolite control protein A (CcpA)-dependent mechanism. Catabolite response elements, the target sites for the P-Ser-HPr/CcpA complex, precede numerous genes and operons. PTS regulation domain-containing antiterminators and transcription activators are also present in both L. casei strains. Their activity is usually controlled by two PTS-mediated phosphorylation reactions exerting antagonistic effects on the transcription regulators: P~EIIB-dependent phosphorylation regulates induction of the corresponding genes and P~His-HPr-mediated phosphorylation plays a role in CCR. Carbohydrate transport of L. casei is also regulated via inducer exclusion and inducer expulsion. The presence of glucose, fructose, etc. leads to inhibition of the transport or metabolism of less favorable carbon sources (inducer exclusion) or to the export of accumulated non-metabolizable carbon sources (inducer expulsion). While P-Ser-HPr is essential for inducer exclusion of maltose, it is not necessary for the expulsion of accumulated thio-methyl-beta-D-galactopyranoside. Surprisingly, recent evidence suggests that the PTS of L. casei also plays a role in cold shock response.

Biological Transport↗

Combined evaluation of pupillary and cardiovascular responses to cold pressor test in cluster headache patients.

Little is known about the structures and mechanisms involved in the pathophysiology of cluster headache (CH). In this study, pupillary and cardiovascular responses to the cold pressor test (CPT) were monitored in CH patients during either an active phase of disease or a remission period in order to evaluate the oculocephalic and cardiovascular functioning of the autonomic nervous system in this form of idiopathic headache. CH patients showed a specific pattern of pupillary response on both sides during both phases of the disease. This response differed from that of controls because of an absent miosis. The pressor response to CPT was more marked in CH patients than in controls. Naloxone pretreatment caused specific and selective changes in both the pupillary and cardiovascular responses of CH patients. These data suggest a systemic sympathetic hyperactivation in response to CPT in CH patients. An oculocephalic sympathetic hypofunction is possibly associated as well as an altered opioid neuromodulation.

Adult↗

fMRI responses to cold pressor challenges in control and obstructive sleep apnea subjects.

Obstructive sleep apnea (OSA) patients exhibit altered sympathetic outflow, which may reveal mechanisms underlying the syndrome. We used functional MRI (fMRI) in 16 control and 10 OSA subjects who were free of cardiovascular or mood-altering drugs to examine neural responses to a forehead cold pressor challenge, which elicits respiratory slowing, bradycardia, and enhanced sympathetic outflow. The magnitude of cold-induced bradycardia was smaller, and respiratory slowing showed greater intersubject variability and reached a nadir later in OSA patients. Both groups showed similar signal changes to cold stimulation in multiple brain sites. However, signal increases emerged in OSA over controls in anterior and posterior cingulate and cerebellar and frontal cortex, whereas signals markedly declined in the ventral thalamus, hippocampus, and insula rather than rising as in controls. Anomalous responses often paralleled changes in breathing and heart rate. Medullary, midbrain areas and lentiform and cerebellar dentate nuclei also showed lower signals in OSA cases. Cold pressor physiological responses are modified in OSA and may result from both diminished and exaggerated responses in multiple brain structures.

Adult↗

Response to cold in the blue fox and raccoon dog as evaluated by metabolism, heart rate and muscular shivering: a re-evaluation.

Oxygen consumption (ml kg-0.75/min) in relation to ambient air temperature at or below the lower critical temperature (Tlc) of the winter-furred raccoon dog (+10 degrees C) and the blue fox (-6 degrees C) is described by the equations y = 14.8-0.28x and y = 7.5-0.20x, respectively. Muscular shivering activity (integrated EMG) of both species increased below thermoneutrality parallel with increasing oxygen uptake and heart rate. Seasonal changes in measured metabolic parameters were evident for both species. The results suggest that the overall body insulation or the metabolic response to cold are not essentially worse in the raccoon dog as compared with the blue fox. It is concluded that earlier speculations of surprisingly wide thermoneutral zone and very low Tlc of the Arctic fox are not evident for the blue fox.

Animals↗

The influence of a genetic change in egg production, body weight, fertility or response to cold stress on semen yield in the turkey.

Egg production and semen yield, sperm concentration and total sperm per ejaculate were positively associated in a line (E) selected for increased egg production. Semen yield was decreased in a line (F) selected for increased 16-week body weight in comparison to a randombred control population (RBC). The effect may be attributable to decreased egg production in this line, as another line (I), developed from the same RBC, which exhibited genetic increases in body weight but no reduction in egg production, did not differ significantly in semen yield from the RBC. Genetic increases in body weight reduced sperm concentration and total sperm per ejaculate. Genetic changes in average clutch length, total days lost from broodiness, fertility, and response to cold stress did not have a major influence on semen production in the turkey.

Animals↗

Cold shock response of yeast cells: induction of a 33 kDa protein and protection against freezing injury.

Cold shock (10 degrees C) treatment to Saccharomyces cerevisiae cells normally grown at 30 degrees C resulted in splitting of vacuoles and retarded membrane fluidity as detected by phase contrast microscopy and in vivo nuclear magnetic resonance (NMR) studies, respectively. The treatment was found to impart protection against subsequent freezing as studied by cell viability and colony forming efficiency. We have earlier reported similar protection and retarded membrane fluidity as a result of heat shock treatment to these cells (Obuchi et al., 1990). This suggests that cold shock and heat shock treatments to yeast cells evoke some analogous responses. However, biochemically a new 33 kDa protein (CSP 33) was detected upon cold shock treatment which is distinct from heat shock induced family of proteins (Kaul et al., 1992). We present here the first report of this kind and its practical implications for protection against freezing.

Cold Temperature↗

The effect of maternal starvation on the metabolic response to cold of the newborn rabbit.

Acute starvation of the pregnant rabbit before delivery leads to lipid mobilization, the circulating concentrations of free fatty acids (FFA) increase, and more fatty acids cross the placenta and are stored as triglyceride in fetal tissues, particularly the liver and adipose tissue. Thus the newborns from these unfed does are born with larger fat stores than normal. In this investigation the responses of newborns of unfed and fed does were compared with respect to aspects of the metabolic responses to birth and subsequent cold exposure. It was found that at 2 hr of age the newborns of unfed does had higher circulating concentrations of FFA and triglycerides. The glucose and glycerol concentrations were similar in the two groups, but after 2 hr of cold exposure the newborns of fed does had much higher blood concentrations of both glucose and glycerol. In both, a large increase in FFA concentration was seen. The newborns of unfed and fed does had similar minimal metabolic rates, but the maximal rate of heat production was greater on average by 15% in the newborns of unfed does over the first 3 days of life. Maternal nutrition immediately before delivery has considerable effect on the circulating concentrations of metabolites and the responses to cold of the newborn.

Acute Disease↗

Laryngeal afferents activated by phenyldiguanide and their response to cold air or helium-oxygen.

In anesthetized cats, sensory neurons in the superior laryngeal nerves (SLN) were identified with respect to their response to (1) phenyldiguanide (PDG) i.v., (2) mechanical stimulation and (3) lowering temperature in an isolated tracheolaryngeal segment. The activity originating from 107 SLN afferent units activated by PDG was recorded using glass microelectrodes advanced in the nodose ganglion. All tested afferent units increased their discharge rate during direct touching of the airway mucosa. None showed flow or pressure related activity during abrupt changes in constant laryngeal flow or transmural pressure in the isolated segment. Fifteen units were inhibited by cold air. Sixty-two units significantly increased their firing rate when the temperature approached 18 degrees C, reached a peak discharge near 15 degrees C, then their activity decreased or stopped. The response to cold air was compared to cold heliox (79% He-21% O2), which enhanced the respiratory heat loss by conduction. The peak firing rate was significantly higher with heliox (+356% compared to +246% with air), the temperature threshold higher (25 degrees C +/- 1.0 degree C) and the temperature range broader (25-11.5 degrees C). Present results show that a large proportion (58%) of afferent SLN fibres activated by PDG are likely non-proprioceptive units, which are stimulated by cooling the inspired gas. Thermosensitive units in the upper airways may act as sensors of the thermal flux through the airway wall more than as detectors of the absolute value of temperature in the airway lumen.

Action Potentials↗

Gene expression profiling of potato responses to cold, heat, and salt stress.

In order to identify genes involved in abiotic stress responses in potato, seedlings were grown under controlled conditions and subjected to cold (4 degrees C), heat (35 degrees C), or salt (100 mM NaCl) stress for up to 27 h. Using an approximately 12,000 clone potato cDNA microarray, expression profiles were captured at three time points following initiation of the stress (3, 9, and 27 h) from two different tissues, roots and leaves. A total of 3,314 clones could be identified as significantly up- or down-regulated in response to at least one stress condition. The genes represented by these clones encode transcription factors, signal transduction factors, and heat-shock proteins which have been associated with abiotic stress responses in Arabidopsis and rice, suggesting similar response pathways function in potato. These stress-regulated clones could be separated into either stress-specific or shared-response clones, suggesting the existence of general response pathways as well as more stress-specific pathways. In addition, we identified expression profiles which are indicative for the type of stress applied to the plants.

Cold Temperature↗

Static and dynamic response characteristics, receptive fields, and interaction with noxious input of midline medullary thermoresponsive neurons in the rat.

Thermal clamping of deep-body temperature and 16 fields covering the total truncal skin surface enabled characterization of thermal transmission neurons distributed in a midline medullary location. The total data set comprised 136 neurons from 54 female rats. Relative abundance of neuronal types was 27 to 34 to 75 for cold-responsive, warm-responsive, and thermally unresponsive neurons. Response maxima of thermoresponsive neurons to static thermal stimulation of the total truncal surface were 55 +/- 4 ips (mean +/- SE) at 5 degrees C for cold-responsive neurons and 6.0 +/- 1.6 ips at 35 degrees C for warm-responsive neurons. Dynamic thermal stimulation of the total truncal surface at rates up to +/- 1.6 degrees C/s failed to reveal a clear dynamic thermosensitivity in either cold- or warm-responsive neuronal pools. Instead, the data suggest a preferential passing of the static response relative to the dynamic response. Cutaneous thermal receptive fields were diffuse, occupying most of the truncal surface. Subparts of these fields drove thermoresponsive neurons to variable extents, suggesting convergence from unequally represented multiple cutaneous sources. Noxious stimulation at widely distributed body sites consistently augmented activity in cold-responsive neurons. A thermoregulatory rather than somatesthetic role is proposed for the midline medullary neurons studied here.

Animals↗

Direct effects of endogenous pyrogen on medullary temperature-responsive neurons in rabbits.

The effect of endogenous pyrogen (E.P.) injected directly into the tissue near the recording site were examined on the activities of the medullary temperature-responsive (TR) neurons in rabbits anesthetized with urethane. Endogenous pyrogen prepared from rabbit's whole blood was administered by a fine glass cannula (100-200 micrometer in diameter) in a fluid volume of 1 to 4 microliter. The cannula was fixed to the manipulator in parallel with a microelectrode and their tips were less than 0.05 mm apart. In rabbits with the intact preoptic/anterior hypothalamic (PO/AH) region, 4 warm-responsive neurons out of 7 were inhibited and 6 cold-responsive neuron out of 7 were excited by the direct administration of the E.P. In rabbits with lesions of the PO/AH, 5 warm-responsive neurons out of 9 were inhibited and 6 cold-responsive neurons out of 8 were facilitated by E.P. Antipyretics administered locally after the E.P. antagonized the pyretic effect, causing a return of the discharge of TR neuron to the control rate within 2.4 +/- 1.2 (mean +/- S.D.) min. The medullary TR neuron itself has the ability to respond to the E.P. and contributes to the development of fever.

Animals↗

Metabolic and endocrine responses to cold air in women differing in aerobic capacity.

PURPOSE: The purpose of this study was to measure resting metabolic rate, plasma norepinephrine, and plasma immunoreactive beta endorphin during exposures to cold air during two consecutive 5-d periods, separated by 2 weekend days, in two groups of women differing in aerobic fitness. METHODS: Plasma norepinephrine (NE), plasma immunoreactive beta-endorphin (IBE), and resting metabolic response (RMR) were measured during repeated exposures to 3.5 degrees C air in two groups of women differing in aerobic fitness. Ten women, separated into highly fit (HFW) and less fit (LFW) groups, sat in 22 degrees C air for 45 min followed by 45 min in 3.5 degrees C air each day during two consecutive 5-d periods separated by two weekend days. RESULTS: Norepinephrine was not different between groups during warm air exposure; however, following 45 min of cold air, NE was two times higher in HFW compared with that in LFW (P < 0.001). Plasma IBE was elevated (P < 0.02) in HFW compared with that in LFW but was not affected by exposure to cold on any test day. Warm RMR was not different between groups and remained unchanged during the study period. Cold RMR was significantly higher in LFW compared with that in HFW (P < 0.01). Resting metabolic rate peaked at 30% of VO2peak in LFW by the 5th minute of cold exposure on day 1 before declining to 21% and remaining steady. In contrast, RMR in HFW peaked at about 13% and then fell to 9.4% before slowly increasing to 14% by the end of 45 min. On other test days HFW RMR increased to 14% of VO2peak and rose slowly through 45 min of cold exposure while LFW RMR peaked at 24% of VO2peak before declining to 20% and remaining steady. CONCLUSIONS: Our findings suggest that, in women, aerobic fitness alters the endocrine and metabolic responses to acute cold air exposure. The norepinephrine response is exaggerated in highly fit women exposed to cold but not the metabolic response. Immunoreactive beta endorphin was not affected by exposure to cold but was elevated in highly fit women. We further conclude that the temperature threshold for acclimation to cold air by women may be higher than the air temperature used in this study.

Acclimatization↗

Clinical response to cold insoluble globulin replacement in a patient with sepsis and thermal injury.

Cold insoluble globulin (fibronectin, alpha 2-surface binding glycoprotein) is a naturally occurring substance necessary for optimal stimulation of the reticuloendothelial system. While this globulin depends on macrophages as the effector cells for its opsonic function, as is true of both antibody and complement, it is neither part of nor dependent on these systems for its opsonic activity. A relatively simple bioassay developed at the Medical College of Georgia substantiated that cold insoluble globulin is severely depleted in sepsis. Cryoprecipitate, properly processed and stored, is an exogenous source of cold insoluble globulin. Infused into septic patients 10 units thawed at 2 degrees C and reconstituted to 250 ml with saline solution can temporarily restore cold insoluble globulin levels and enhance activity of the reticuloendothelial system. Proper current use dictates measurement of cold insoluble globulin levels in the infusate as well as levels in the patient and the clinical response to infusion. Our bioassay and a septic patient's response to infusion of cold insoluble globulin are reported herein.

Burns↗

Steroid-responsive idiopathic cold agglutinin disease: a case report.

We report a case of idiopathic cold agglutinin disease (ICAD) that responded well to corticosteroid therapy, though generally these patients show no response to such therapy. The cold agglutinins in this patient were found to be of low titer (1:32) and wide thermal range (4-37 degrees C). Three patients with ICAD were previously reported, also responsive to corticosteroid therapy and having the same characteristics of their autoantibodies. are likely to respond to corticosteroid therapy and that a therapeutic trial with such agents is warranted in these patients.

Adrenal Cortex Hormones↗