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Influence of cold exposure on plasma triglyceride clearance in humans.

Recent human studies have shown that cold exposure increases lipid oxidation, even when the oxidation of circulating free fatty acid (FFA) is markedly reduced by the ingestion of nicotinic acid, thus seriously questioning the importance of FFA for lipid oxidation in the cold-exposed humans. It was therefore hypothesized that similarly to prolonged exercise, fatty acids from plasma triglycerides (TG) are important energy substrates for oxidation during prolonged cold exposure in man. The goal of this study was to determine the influence of cold exposure on an index of plasma TG utilization, the intravenous fat tolerance test (IVFTT). To evaluate the possibility of a delayed increase in fat tolerance, a second cold exposure and an IVFTT were also performed 24 hours after the first cold exposure. Seven healthy males (fasting, seminude) were subjected to an IVFTT (1 mL/kg 10% Intralipid) on three occasions while resting for 160 minutes: (1) at 29 degrees C, (2) in the cold (10 degrees C, 1 m/s wind), and (3) at 10 degrees C 24 hours after the first cold test. One week separated the warm test from the cold tests. Cold exposure reduced mean body temperature by 3.4 +/- 0.1 degree C and increased energy expenditure 2.5 times in comparison to warm values (P less than .01). It also increased fat oxidation by 70% (P less than .05) and plasma glycerol levels (P less than .05), but did not alter fat tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Habituation and dishabituation to repeated mild cold exposures in C57BL/6J mice.

Every two weeks for 12 weeks four groups of C57BL/6J male mice, initially 12 months old, were subjected to three-hour cold stress tests, which consisted of a partial physical restraint at an ambient temperature of 10 degrees C. The control group experienced six consecutive tests; one experimental group skipped the cold exposure during test No. 4 but was physically restrained at room temperature; the other two experimental groups omitted test No. 4. One of these groups spent the four weeks between test No. 3 and test No. 5 in their home cages, while the other was subjected to daily, 30-minute sessions of electrical stimulation of the hypothalamus through electrodes implanted in the "rewarding" area of the medial forebrain bundle. All animals in this group showed self-stimulating behavior in the test session which preceded cold stress test No. 1. During test No. 3, all four groups showed an improvement of cold tolerance relative to their first tests; body mass and colonic temperature prior to cold exposure remained unchanged. The two experimental groups that were not exposed to cold during test No. 4 and did not receive brain stimulation, demonstrated a significant worsening of cold tolerance during the subsequent test. Their body mass and baseline colonic temperatures did not change. The control group and the group which was subjected to brain stimulation during the interval between tests No. 3 and No. 5 did not demonstrate any changes in cold tolerance. These data demonstrated habituation to repeated mild cold exposures and dishabituation after interruption of cold exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Hepatic cold hypoxia and oxidative stress: implications for ICAM-1 expression and modulation by glutathione during experimental isolated liver preservation.

Cold preservation and reperfusion of liver during transplantation are necessary steps in the procedure but which are also associated with damage to the organ. One aspect of this damage is thought to concern up-regulation of inflammatory markers, such as the adhesion molecule intercellular adhesion molecule 1 (ICAM-1) on target cells in the liver. This aids sequestration of activated leucocytes, which promote inflammation, by a complex sequence of events, including free radical mediated damage. We have studied changes in ICAM-1 in rat liver as a consequence of cold preservation for various times, and also after warm reperfusion during isolated liver perfusion. We have also investigated the effects of the free radical scavenging agent (reduced glutathione-GSH) on the modulation of ICAM-1 expression after cold hypoxia and reperfusion. Livers were subjected to various regimes of cold preservation and reperfusion. Liver biopsies were taken at three time points (initial baseline on liver exposure; after organ flushing and post-storage at 0, 8, 16, and 24h cold hypoxia in University of Wisconsin solution; in the same livers after 1h warm reperfusion). The tissues were processed for frozen biopsy work, and frozen sections were stained using immunohistochemical methods, for blinded scoring by an independent observer. Positive controls were obtained by exposure to endotoxin lipopolysaccharide before liver flushing. ICAM-1 expression was low in control livers (0.33+/-0.21), and increased to near maximal (2.83+/-0.17) after endotoxin exposure. ICAM-1 expression increased progressively with cold preservation, reaching values of 1.17+/-0.31 and 1.83+/-0.31 after 16 and 24h, respectively (P<0.05 and 0.02 versus controls). Warm reperfusuion increased ICAM-1 expression in all flushed groups and with longer cold preservation was close to maximal (2.67+/-0.21 after 16h and 2.98+/-0.02 after 24h; P<0.001 in both cases). Addition of the free radical scavenger GSH prevented up-regulation of ICAM-1 in livers reperfused after flushing and cold storage for up to 8h; beyond this time, ICAM-1 expression still increased, such that by 24h cold preservation and reperfusion absence (2.98+/-0.02) or presence (2.67+/-0.21) made no difference. We conclude that liver ICAM-1 expression is demonstrably increased by progressive cold preservation and reperfusion, and is only marginally affected by addition of GSH during reperfusion. The model can be used to investigate other agents which might be more successful in preventing post-storage inflammatory damage.

Animals↗

Effect of cold-induced hyperthyroidism on H2O2 production and susceptibility to stress conditions of rat liver mitochondria.

Previous studies have shown that T3 treatment and cold exposure induce similar biochemical changes predisposing rat liver to oxidative stress. This suggests that the liver oxidative damage observed in experimental and functional hyperthyroidism is mediated by thyroid hormone. To support this hypothesis we investigated whether middle-term cold exposure (2 and 10 days), like T3 treatment, also increases H2O2 release by liver mitochondria. We found that the rate of H2O2 release increased only during State 4 respiration, but faster flow of reactive oxygen species (ROS) from mitochondria to the cytosolic compartment was ensured by the concomitant increase in tissue mitochondrial proteins. Cold exposure also increased the capacity of mitochondria to remove H2O2. This indicates that cold causes accelerated H2O2 production, which might depend on enhanced autoxidizable carrier content and should lead to increased mitochondrial damage. Accordingly, mitochondrial levels of hydroperoxides and protein-bound carbonyls were higher after cold exposure. Levels of low-molecular weight antioxidants were not related to the extent of oxidative damage, but susceptibility to both in vitro oxidative challenge and Ca2+-induced swelling increased in mitochondria from cold exposed rats. The cold-induced changes in several parameters, including susceptibility to swelling, were time dependent, because they were apparent or greater after 10 days cold exposure. The cold-induced increase in swelling may be a feedback mechanism to limit tissue oxidative stress, purifying the mitochondrial population from ROS-overproducing mitochondria, and the time course for such change is consistent with the gradual development of cold adaptation.

Animals↗

Changes in membrane lipid composition following rapid cold hardening in Drosophila melanogaster.

Naturally occurring diurnal variations in temperature are sufficient to induce a rapid cold hardening (RCH) response in insects. RCH can increase cold tolerance by 1-2 degrees C and extend the temperature interval at which insects can remain active. While the benefits of RCH are well established, the underlying physiological mechanisms remain unresolved. In this study we investigated the role of RCH on expression of heat shock proteins (Hsp70) after a cold shock, and the effect of RCH on the composition of phospholipid fatty acids (PLFAs) in membranes of Drosophila melanogaster. These experiments were performed on both "control" flies and flies selected for cold resistance in order to additionally examine a possible target for selection for cold tolerance. RCH improved survival following cold shock at -4, -6 and -8 degrees C. No induction of Hsp70 was found following cold shock irrespective of the pre-treatment. In contrast, a 5h RCH treatment was sufficient to induce small, but significant, changes in the composition of PLFAs. Here, the polyunsaturated linoleic acid, 18:2(n-6), increased while monounsaturated (18:1) and saturated (14:0) PLFAs decreased in abundance. These changes were observed in both selection groups and caused a significant increase in the overall degree of unsaturation. This response is consistent with the membrane response typically found during cold acclimation in ectothermic animals and it is likely adaptive to maintain membrane function during cold. Cold selection resulted in PLFA changes (decrease of 18:0 and 18:1 and increase of 14:0 and 16:1), which may improve the ability to harden during RCH.

Acclimatization↗

Increased susceptibility to transcriptional changes with novel stressor in adrenal medulla of rats exposed to prolonged cold stress.

The response to stress is influenced by prior experience with the same or different stressor. For example, exposure of cold pre-stressed rats to heterotypic (novel) stressors, such as immobilization (IMO), triggers an exaggerated release of catecholamines and increase in gene expression for adrenomedullary tyrosine hydroxylase (TH), the rate limiting catecholamine biosynthetic enzyme. To study the mechanism, we examined induction or phosphorylation of several transcription factors, which are implicated in IMO-triggered regulation of TH transcription, in rats exposed to cold (4 degrees C) for up to 28 days and then subjected to IMO. Levels of c-fos increased transiently after 2-6 h and returned to basal levels after 1-28 days cold stress. Fra-2, was unaffected by short term cold, but was induced about 2-fold by 28 days continual cold. In contrast, there were no significant changes in CREB phosphorylation or Egr1 induction. Rats, with and without pre-exposure to 28 days cold, were subjected to single IMO for up to 2 h. Phosphorylation of CREB after 30 min IMO was greater in cold pre-exposed rats. Induction of Egr1 was three times higher in cold pre-exposed rats and remained significantly elevated even 3 h after cessation of IMO. Exposure to IMO triggered a 10-20-fold elevation in Fra-2 in both groups, which was even higher 3 h after the IMO. However, Fra-2 was more heavily phosphorylated following IMO stress in cold pre-exposed animals. The results reveal that sensitization to novel stress in cold pre-exposed animals is manifested by exaggerated response of several transcription factors.

Adrenal Medulla↗

Analysis of the cold-water restraint procedure in gastric ulceration and body temperature.

Gastric mucosal injury induced by body restraint can be enhanced when combined with cold-water immersion. Based on this fact, the present study had two main purposes: (i) to examine the contribution of each of these two forms of stress on the development of gastric ulceration and regulation of body temperature and (ii) to investigate the importance of the animal's consciousness on gastric ulceration induced by the cold-water restraint. Independent groups of animals were exposed for 3 h to one of the following stressful treatments: body restraint plus cold-water (20+1 degrees C) immersion, body restraint alone or cold-water immersion alone. Control animals were not exposed to any form of stress. Half of the animals submitted to each of the four treatments were anesthetized with thionembutal (35 mg/kg), whereas the other half was injected with saline. Results indicated that body restraint alone was not sufficient to induce gastric ulceration or changes in body temperature. On the other hand, cold-water exposure, either alone or in conjunction with body restraint, induced the same amount of stomach erosions and hypothermia. Therefore, it appears that body restraint does not play an important role on gastric ulceration induced by the cold-water restraint procedure. Present results also indicated that conscious and anesthetized animals immersed in cold water presented robust gastric ulceration and a marked drop in body temperature. However, conscious animals developed more severe gastric damage in comparison to anesthetized animals although both groups presented the same degree of hypothermia. These findings suggest that hypothermia resulting from cold-water exposure has a deleterious effect on gastric ulceration but the animal's conscious activity during the cold-water immersion increases the severity of gastric mucosal damage. It is concluded that cold-water restraint is a useful procedure for the study of the underlying mechanisms involved in stress-induced ulceration.

Analysis of Variance↗

AP-1 transcription factor binding activity in rat adrenal medulla and hypothalamus with age and cold exposure.

The AP-1 regulatory element has been implicated in the cold-induced expression of tyrosine hydroxylase in the adrenal medulla. Since in this tissue, the cold-induced increase in tyrosine hydroxylase expression is impaired with age and in other tissues, there is some evidence that AP-1 transcription factor binding is diminished with age, we examined the cold-stimulated AP-1 transcription factor binding to an oligonucleotide with the consensus sequence of the AP-1 response element in nuclear extracts from adrenal medulla and hypothalamus of young and senescent rats. AP-1 transcription factor binding activity diminished by 38% with age in unstimulated adrenal medulla. Following cold stimulation, the AP-1 binding activity increased by 21-25% in the adrenal medulla of both young and senescent rats. However, the level of AP-1 binding in cold-stimulated senescent rats was still less than in cold-stimulated younger rats. There were no changes in AP-3 binding activity with either age or cold exposure in the adrenal medulla. Similarly, in the hypothalamus, there was a 25% decrease with age and a 25% increase following cold stimulation in the level of AP-1 binding. There was a 62% age-related increase in AP-3 binding activity but no change with cold exposure. These data indicate that there is reduced AP-1 binding activity in senescent control rats. Moreover, the demonstration that cold stimulus evokes similar increases in AP-1 binding activity in both young and old rats suggests that the stimulation pathway that increases AP-1 transcription factor is maintained in the senescent animal.

Adrenal Medulla↗

Opposite regulation of brain angiotensin type 1 and type 2 receptors in cold-induced hypertension.

Rats exposed chronically to mild cold (5 degrees C/41 degrees F) develop hypertension. This cold-induced hypertension (CIH) is an environmentally induced, non-surgical, non-pharmacological and non-genetic model for studying hypertension in rats. The blood renin angiotensin system (RAS) appears to play a role in both initiating and maintaining the high blood pressure in CIH. The goal of the present study was to evaluate the role of brain angiotensin type 1 and type 2 receptors (AT1R and AT2R) in CIH. Sprague-Dawley adult male rats were used. Thirty-six rats were kept in a cold room at 5 degrees C and the other 36 were kept at 24 degrees C as controls. Systolic blood pressure (SBP) was recorded by tail cuff. The SBP was elevated in rats exposed to cold within 1 week (n=12, P>0.05), significantly increased at 3 weeks (P<0.05) and reached a maximum (125%) at 5 weeks (P<0.01). Three subgroups of the cold-treated and the controls were sacrificed at 1, 3 and 5 weeks. Specific brain sections were removed, either for reverse transcription polymerase chain reaction (RT-PCR) to measure mRNA, or for autoradiography to measure receptor binding for AT1R and AT2R. The AT1R mRNA was increased significantly in hypothalamus and brainstem after the first week in cold-treated rats and was maintained throughout the time of exposure to cold (n=6, P<0.01). AT1R binding significantly increased initially in hypothalamus and thereafter in brainstem. The mRNA and the receptor binding for AT2R decreased significantly (P<0.01, n=6) in nucleus of inferior olive and locus coeruleus of brainstem in cold-treated rats after exposure to cold. The experiments show differential regulation of RAS components, AT1R and AT2R, in different brain areas in cold-exposed rats and provide evidence that up-regulated AT1R and down-regulated AT2R in different brain areas are involved in CIH. The opposing directions of expression of AT1R and AT2R suggest that they play counterbalancing roles in brain function.

Angiotensin I↗

Prevention by nifedipine of cold pressor-induced decrease in left ventricular ejection fraction.

To examine the effects of nifedipine on changes in ventricular function produced by cold, the cold pressor test was administered to eight patients with angiographically documented coronary artery disease. Radionuclide ventriculograms were obtained at baseline and during the cold pressor stimulus both before and after administration of nifedipine, 10 mg buccally; thus, four serial radionuclide ventriculograms were obtained per patient. The cold pressor stimulus did not produce any significant difference in the mean (+/- standard deviation) peak rate-pressure product during the control or nifedipine test (10,900 +/- 3,390 versus 10,600 +/- 3,700). However, the increase in systolic blood pressure (p = 0.05) and the peak systolic blood pressure achieved (p less than 0.001) were greater during the control (134 +/- 19 to 160 +/- 25 mm Hg) than during the nifedipine (125 +/- 18 to 145 +/- 21 mm Hg) cold pressor test. The mean global left ventricular ejection fraction decreased during the control cold pressor test from a baseline value of 0.60 +/- 0.08 to 0.52 +/- 0.08 (p = 0.004). After nifedipine, this variable did not change during the repeat cold pressor test (0.63 +/- 0.09) compared with the repeat baseline value (0.63 +/- 0.11). Therefore, the difference in left ventricular ejection fraction response during control versus nifedipine cold pressor testing was highly significant (p less than 0.0001). In patients with obstructive coronary artery disease, nifedipine abolished the decrease in left ventricular ejection fraction observed during the control cold pressor test and may be of value to protect patients from cold-induced left ventricular dysfunction. The mechanism may be a combination of coronary artery vasodilation and systolic unloading of the left ventricle.

Adult↗

Active and passive smoking and risk of colds in women.

PURPOSE: To evaluate the association between active and passive smoking and frequency of colds in women. METHODS: Data on cigarette smoking and frequency and duration of colds were analyzed in the Women's Health Study (WHS), a randomized, double-blind, placebo-controlled trial of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer among 39,876 female health professionals. RESULTS: After adjustment for age, body-mass index, prevalence of asthma and chronic lung diseases, alcohol intake, physical activity, and multivitamin use, current heavy smokers had no appreciable increase in the frequency of colds (relative risk (RR) for >or= 3 versus no colds in the past year, 1.05; 95% confidence interval (CI), 0.80-1.39), but a significantly increased risk of prolonged colds (RR for colds of > 7 vs. 1-3 days, 2.53; 95% CI, 1.95-3.29). There was no difference in the number of days confined to home. Nonsmoking women passively exposed to cigarette smoke had a slightly increased risk of both more frequent colds (RR, 1.33; 95% CI, 1.18-1.51) and more prolonged colds during the previous year (RR, 1.12; 95% CI, 0.99-1.27). CONCLUSIONS: Women who are currently heavy smokers are at increased risk of having colds with longer duration compared with nonsmokers. Nonsmoking women passively exposed to cigarette smoking are at slightly increased risk of having more frequent and longer colds than nonsmoking women not exposed to passive smoke.

Common Cold↗

Cold denaturation and heat denaturation of Streptomyces subtilisin inhibitor. 1. CD and DSC studies.

Cold denaturation and heat denaturation of the protein Streptomyces subtilisin inhibitor (SSI) were studied in the pH range 1.84-3.21 and in the temperature range -3-70 degrees C by circular dichroism and scanning microcalorimetry. The native structure of the protein was apparently most stabilized at about 20 degrees C and was denatured upon heating and cooling from this temperature. Each denaturation was reversible and cooperative, proceeding in two-state transitions, that is, from the native state to the cold-denatured state or from the native state to the heat-denatured state. The two denatured states, however, were not perfect random-coiled structures, and they differed from each other, indicating that there exist three states in this temperature range, i.e., cold denatured, native, and heat denatured. The difference between the cold and heat denaturations was indicated first by circular dichroism. The isodichroic point for the transition from the native state to the cold-denatured state was different from that from the native state to the heat-denatured state in the pH range between 3.21 and 2.45. Moreover, molar ellipticity for the cold-denatured state was different from that of the heat-denatured state, and the transition from the former to the latter was observed at pH values below 2. Values of van't Hoff enthalpies from the native state to the heat-denatured state at pH values between 3.21 and 2.45 were obtained by curve fitting of the CD data, and delta Cp = 1.82 (+/- 0.11) [kcal/(mol.K)] was obtained from the linear plot of the enthalpies against temperature. The parameters obtained from the heat denaturation studies gave curves for delta G zero which were not in agreement with the experimental data in the cold denaturation region when extrapolated to the low temperature. Moreover, the value of the apparent delta Cp for the cold denaturation in the pH range 3.03-2.45 was estimated to be different from that for the heat denaturation, indicating that the mechanism of the cold denaturation of SSI is different from a simple cold denaturation.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Proteins↗

Wild and cultivated barleys show differences in the expression pattern of a cold-regulated gene family under different light and temperature conditions.

Cold acclimation in plants involves the expression of many genes and gene families. The present study reports the expression analysis of three members of the blt14 gene family in barley. Gene-specific antisense oligonucleotides were used as probes in northern experiments so as to follow independently the expression of individual members of the gene family. Each clone revealed different accumulation kinetics when a spring and a winter cultivar were compared, suggesting that the different regulatory mechanisms leading to mRNA accumulation of an individual member of the blt14 gene family are genotype-dependent. In a collection of Hordeum spontaneum genotypes both qualitative and quantitative polymorphisms were found for the accumulation of blt14-related mRNAs, although no clear relationships were found between blt14 expression and frost resistance. The accumulation of the blt14-related mRNAs was also modulated by light and by the albino mutation a(n). The effects of light on the accumulation of the transcripts corresponding to the blt14 gene family were evaluated by comparing etiolated and green plants. Etiolated plants accumulate the blt14-related mRNAs at a detectable level already at 22 degrees C. When the same plants are exposed to cold in absence of light an increased mRNA accumulation above the level present in green cold-treated plants can be detected. On the contrary, etiolated plants showed a reduced blt14 accumulation when exposed to cold in the presence of light. Cold-induced expression of the blt14 gene family was strongly reduced in plants carrying the albino mutation a(n). This mutant showed a defective molecular response to cold even when probed with a cDNA coding for LEA type protein (paf93). The albino mutant a(n) was not able to harden when exposed to low temperature providing a direct evidence of the relationship between expression of cold-regulated (COR) genes and the development of cold hardening. Failure of cold acclimation in the mutant cannot be merely ascribed to the absence of photosynthetic activity, since etiolated wild-type plants accumulated COR mRNAs and improved frost resistance when exposed to cold.

Acclimatization↗

Verapamil normalizes the response of left ventricular early diastolic filling to cold pressor test in asymptomatic and mildly symptomatic patients with hypertrophic cardiomyopathy.

The aim of the study was to assess the left ventricular (LV) diastolic filling response to the cold pressor test in asymptomatic or mildly symptomatic patients with nonobstructive hypertrophic cardiomyopathy (HC) before and after verapamil therapy. The cold pressor test-induced alterations in LV filling pattern were additionally compared between HC patients and healthy control subjects. The cold pressor test, producing alpha- and beta-adrenergic stimulation, differentiates paradoxical coronary vasoconstriction due to endothelial dysfunction from the normal endothelium-dependent vasodilation. Such opposite coronary vasomotion at cold pressor test may be reflected by different responses of LV diastolic filling to the cold pressor test. Doppler echocardiography was performed in 10 asymptomatic or mildly symptomatic patients with nonobstructive HC as well as in 10 age- and sex-matched healthy subjects before and immediately after the cold pressor test. In HC patients before verapamil therapy, the cold pressor test induced a significant decrease in LV early filling parameters, contrary to healthy subjects, in whom the cold pressor test improved early filling [changes in early diastolic LV velocity -6.2 +/- 7.3 (-11.4 to -0.98) vs. 7.5 +/- 8.9 (1.13-13.86) cm/s, P = 0.0014, and changes in its acceleration rate -136 +/- 119 (-221 to -51) vs. 252 +/- 181 (122-381) cm/s2, P = 0.0001, respectively]. Verapamil therapy restored the normal pattern of the LV early filling response to the cold pressor test [changes in early diastolic LV velocity -6.2 +/- 7.3 (-11.4 to -0.98) vs. 5.3 +/- 3.4 (2.86 to 7.73) cm/s, P = 0.0003, and changes in its acceleration rate -136 +/- 119 (-221 to -51) vs. 328 +/- 185 (196 to 460) cm/s2, P = 0.0001, respectively]. Verapamil normalizes the LV early filling response to the cold pressor test in asymptomatic or mildly symptomatic patents with HC.

Adult↗

Cold storage induces time-dependent F2-isoprostane formation in renal tubular cells and rat kidneys.

BACKGROUND: Previous findings suggest a possible role for free radicals in cold-storage-associated tissue injury. Because free radical-induced lipid peroxidation catalyzes the cyclooxygenase-independent formation of vasoconstrictive F2-isoprostanes, the hypothesis that isoprostanes are produced during cold storage was tested in this study. METHODS: Total isoprostanes (free and esterified) in renal tubular epithelial (LLC-PK1) cells or whole kidneys, subjected to cold storage, were quantitated employing the gas chromatographic-mass spectroscopic method. LLC-PK1 cells were stored at 4 degrees C in a University of Wisconsin (UW) solution for 0, 24, 48, and 72 hours or 48 hours with desferrioxamine (DFO) or the lazaroid compound 2-methyl aminochroman (2-MAC). In the rat model, kidneys were perfused and stored for 48 hours in the UW solution with or without added DFO or 2-MAC. RESULTS: Isoprostanes in LLC-PK1 cells increased by fivefold following 24 hours of cold storage (36 +/- 2 pg/well to 185 +/- 6, mean +/- SE, following 24 hours of cold storage, P < 0.0001), and the levels continued to increase significantly at 48 and 72 hours. DFO and 2-MAC caused significant suppression of isoprostane formation. Cold storage of the kidneys in UW solution for 48 hours was accompanied by an eightfold increase in isoprostanes compared with control kidneys not subjected to cold storage (25.0 +/- 3.0 vs. 2.9 +/- 0.1 ng/g, P < 0.0001). The addition of 2-MAC or DFO to the UW solution was associated with a near complete suppression of 48-hour cold-induced isoprostane formation. CONCLUSION: Our findings provide evidence for the formation of large quantities of antioxidant-suppressible isoprostanes in kidney cells and whole kidney during cold-preservation. Based on this, it is hypothesized that (a) isoprostanes, which are potent renal vasoconstrictors, may contribute to immediate post-transplant vasoconstriction and dysfunction in kidneys subjected to extended cold storage, and that (b) the addition of 2-MAC or DFO to a UW solution in such circumstances may attenuate these alterations partly by suppressing isoprostane formation.

Animals↗

Influence of lesion of the limbic-hypothalamic system on metabolic responses of acetate to daily repeated cold exposures in rabbits.

The effects of the lesions of basal medial hypothalamus and limbic structure on the acetate metabolic responses to daily repeated cold exposures in rabbit's liver has been investigated. The results obtained were summarized as follows: (1) The lesions of periventricular arcuate nucleus (ARC) had no effects on the acetate metabolism and on the acetate metabolic responses to the 1st cold exposure (cold exposure on the 1st day). (2) The metabolic pattern of acetate and the acetate metabolic responses to the 1st cold exposure were altered by the lesions of ventromedial hypothalamus (VMH), stria terminalis (ST) and dorsal fornix (FX). (3) The effects of cold exposure on the acetate metabolism were completely abolished by the seven times repetition of cold exposures in the rabbits with the lesions of ARC, VMH or ST, as the same as in each sham-operated group. (4) The acetate metabolic responses to cold exposure remained after the seven times repetition of cold exposure in the rabbits with the lesions of FX, but those disappeared completely in sham-operated animals. (5) From these results, it might be suggested that the VMH, amygdala(AMYG)-ST system, dorsal hippocampus(HPC)-FX system played some roles in the metabolic regulation of acetate and in the mechanisms of acetate metabolic responses to the 1st cold exposure, but the ARC did not participate in those mechanisms. And it was suggested that the HPC-FX system participated in the acetate metabolic adaptation to daily cold exposures, but the basal medial hypothalamus and AMYG-ST system did not participate in this process.

Acetates↗

One-year occupational exposure to a cold environment alters lung function.

Numerous observations have shown that breathing cold air causes bronchospasm and increases respiratory tract secretions in asthmatic patients and normal individuals. However, few studies have been conducted on the respiratory effects of protracted daily exposures to a cold environment. In this 1-yr study, the authors examined individuals who spent 6 hr a day in cold stores (+3 degrees C to + 10 degrees C) and spent approximately 25% of that time at +3 degrees C. The protocol included a questionnaire about clinical symptoms, with measurements of baseline pulmonary function and airway responses to carbachol and to nasal inhalation of cold air (-5 degrees C). Eleven subjects were examined prior to their first occupational exposure to cold, and again following 6 mo and 12 mo of work in the cold environment. Compared with a control group of 6 subjects engaged at the same time but who did not work in cold stores, 6 of 11 individuals who worked 12 mo in a cold environment experienced increased symptoms of rhinitis, sore throat, and cough. Physiological measurements at 6 mo and 12 mo showed a progressive decrease in forced expiratory volume in 1 sec and a progressive increase in the baseline value of central airway resistance. Forced expiratory flow measured between 25% and 75% of vital capacity had decreased at 6 mo, but showed no further change at 12 mo. A progressive enhancement of bronchial reactivity to carbachol was noted at 6 mo and again at 12 mo, but airway response to nasal breathing of cold air did not vary. The authors concluded that 1 yr of daily exposure to a cold occupational environment elicits a modest--but significant--airflow limitation, accompanied by bronchial hyperresponsiveness, with the effects beginning within 6 mo of exposure.

Adult↗

The effect of exercise training on cold tolerance in adult and old C57BL/6J mice.

In order to ascertain the effect of aging on cross-adaptation between exercise training and cold tolerance, we studied cold tolerance in adult and old C57BL/6J male mice before and after 6 weeks of an exercise regimen of moderate intensity. There were two age groups of 32 mice each, including 12-month-old (adult) and 24-month-old (aged) mice equally divided into control and exercise groups. The exercise consisted of daily runs on a treadmill (1 hr/day, 5 days/week) for 6 weeks, while the control mice spent the same time on a stationary treadmill. All mice were subjected to a cold stress test (3-hr partial restraint at 6 degrees C) prior to and following the designated regimen. The results revealed a statistically significant interaction between age and exercise training. In adult mice, exercise resulted in a reduction of cold-induced heat production and weakening of cold tolerance, while in aged mice, the opposite effect was observed; i.e., an increase in cold-induced heat production accompanied by greater cold tolerance. However, only the attenuating effect on cold tolerance of adults was statistically significant. The results of our experiments do not support the existence of cross-adaptation between exercise training and cold tolerance. They indicate, however, that exercise training affects the cold tolerance in adult and old mice through different physiological mechanisms.

Adaptation, Physiological↗