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PubMed2004

Seasonal changes in metabolic and temperature responses to cold air in humans.

The metabolic and temperature response to mild cold were investigated in summer and winter in a moderate oceanic climate. Subjects were 10 women and 10 men, aged 19-36 years and BMI 17-32 kg/m2. Metabolic rate (MR) and body temperatures were measured continuously in a climate chamber with an ambient temperature of 22 degrees C for 1 h and subsequently 3 h of 15 degrees C. The average metabolic response during cold exposure, measured as the increase in kJ/min over time, was significantly higher in winter (11.5%) compared to summer (7.0%, P < .05). The temperature response was comparable in both seasons. The metabolic response in winter was significantly related to the response in summer (r2 = .47, P < .001). Total heat production during cold exposure was inversely related to the temperature response in both seasons (summer, r2 = .39, P < .01; winter r2 = .32, P < .05). In conclusion, the observed higher metabolic response in winter compared to summer indicates cold adaptation. The magnitude of the cold response varies, but the relative contribution of metabolic and temperature response was subject specific and consistent throughout the seasons, which can have implications for energy balance and body composition.

Acclimatization↗
PubMed2005

A proteomic analysis of cold stress responses in rice seedlings.

Using proteomic analysis, an investigation aimed at a better understanding of the molecular adaptation mechanisms of cold stress was carried out in rice (Oryza sativa). The seedlings were exposed to a progressively low temperature stress treatment from normal temperature to 15, 10, and 5 degrees C. Proteins were extracted from the leaves collected from both control and stressed seedlings. By fractionation, approximately 1700 protein spots were separated and visualized on CBB-stained 2-D gels. Sixty protein spots were found to be up-regulated in responding to the progressively low temperature stress and displayed different dynamic patterns. As an initial work, 41 of these proteins were identified using MALDI-TOF MS or ESI/MS/MS. These cold responsive proteins, besides two proteins of unknown function, include four factors of protein biosynthesis, four molecular chaperones, two proteases, and eight enzymes involved in biosynthesis of cell wall components, seven antioxidative/detoxifying enzymes, and proteins linked to energy pathway, as well as a protein involved in signal transduction. The functional proteomes illuminate the facts, at least in plant cell, that protein quality control mediated by chaperones and proteases and enhancement of cell wall components play important roles in tolerance to cold stress. Using TargetP program, the subcellular localization of the identified proteins was analyzed. Proteins (43.9%) were predicted to be located in the chloroplasts, implying that chloroplast proteome is virtually subjective to cold stress. The physiological implications, revealed from the experimental data, are discussed in context of a complex metabolic network in plant cells responsive to cold stress.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1983

Effect of one year clofazimine therapy on autonomic functions in lepromatous leprosy with lepra (ENL) reaction.

Twenty patients of either sex of Lepromatous leprosy with frequent type II (ENL) reactions were selected for the study after exclusion of autonomic disorders. ANS functions were evaluated before and after Clofazimine therapy at an interval of two months for one year. Sweat function test, valsalva manoeuvre, Histamine triple response, cold pressor test and Homatropine instillation were carried out in twenty normal healthy volunteers (controls) and the (ENL) patients. Clofazimine was administered initially 100 mg three times daily for one month and then gradually reduced to a dose of 100 mg biweekly for the last three months. Before the clofazimine therapy, eighteen patients had abnormal sweat functions, five patients had abnormal valsalva score, five patients had abnormal cold pressor response and all the eighteen patients had abnormal histamine triple response test. Homatropine instillation test was normal in all the patients. ANS functions did not improve significantly with Clofazimine therapy, except in one patients with abnormal cold pressor response who showed slight improvement in pressor response which, however, did not reach the normal value. ANS function tests indicate complete involvement of local axon reflex and hyporeactivity of sympathetic system and cardiac regulatory mechanisms in these patients. Parasympathetic system seems to be normal as seen from Homatropine instillation test.

Autonomic Nervous System↗
PubMed1997

Reproducibility of exercise-induced modulation of cardiovascular responses to cold stress.

The modulation of cardiovascular responses to the cold pressor test (CPT) as produced by exercise was studied in 13 volunteers. The reproducibility of the measurements selected for the study, i.e. heart rate (HR), blood pressure (BP), blood flow (BF) and skin temperature (ST), was investigated through repeat experiments in the fall of 1994 and the winter of 1995. HR was monitored before, during and after a 10-min period of bicycling at 70% of reserve HR. BP, cutaneous BF and ST were measured before and after exercise. Two CPTs (hand into ice-cold water for 1 min) were performed: one preceding exercise and another at 3 min after exercise. The results obtained allow us to conclude that in non-hypertensive volunteers (1) the pronounced cardiovascular responses (ST, BF and BP) induced by CPT are reproducible (p > 0.2) when compared to basal level values and (2) cardiovascular responses to cold stress are significantly attenuated by exercise (p < 0.03). Our study, therefore, supports and validates the use of our coupled exercise-CPT method in ongoing epidemiological studies attempting to identify individuals at risk for the development of hypertension as well as those most likely to benefit from preventative exercise programs.

Adolescent↗
PubMed1994

Abnormal responses to cold stress in Charcot-Marie-Tooth I syndrome.

In Charcot-Marie-Tooth syndrome (CMT, Hereditary Motor Sensory Neuropathy), patient complaints of cold intolerance are common but their peripheral responses to cold have not been documented. Using digital plethysmography, a simple test of vascular reactivity with 1 minute cold stress, 20 unrelated adult CMT patients showed a significantly increased average heart rate and decreased average arterial oxygen saturation following cold when compared to 50 age-matched normal controls. There did not appear to be a unique or characteristic CMT vascular reaction to cold stress in CMT patients because their abnormal peripheral vascular responses were variable. Variability in CMT neuropathic responses to cold is consistent with the known irregular segmental demyelination of CMT peripheral nerves as well as abnormal CMT sweating patterns. Though understanding the precise patterns of CMT patient peripheral nerve disturbances remains difficult, awareness of CMT patient's abnormal responses to cold may facilitate CMT patient care and rehabilitation.

Adult↗
PubMed1984

The relationship of airways responsiveness to cold air, cigarette smoking, and atopy to respiratory symptoms and pulmonary function in adults.

The response to eucapnic hyperventilation with subfreezing air was studied in a population based sample of 171 adults, all of whom also completed a respiratory questionnaire, spirometry, and skin testing. A positive response to the cold air challenge was defined as [initial FEV1-post-challenge FEV1)/initial FVC) X 100) greater than or equal to 9%. Cigarette smoking was with a positive cold air response: 12 of 128 current and ex-smokers (9.4%) versus 1 of 43 nonsmokers (2.3%) (p = 0.095). Among current and ex-smokers, a positive response to the cold air challenge was significantly associated with asthma (p = 0.046). Using a logistic regression model, both current smoking and response to cold air were significant predictors of the presence of "persistent wheeze" or asthma. A positive skin test to any of the 4 environmental antigens used (ragweed, housedust, trees, and grasses) was significantly associated with cigarette smoking (p = 0.018) and hay fever (p = 0.003 among current and ex-smokers) but not with wheezing or asthma. Though not statistically significant, cold air responders had a lower percentage of positive skin test reactivity than nonreactors. The findings of this cross-sectional analysis suggest that in adults, both airways responsiveness and cigarette smoking are important predictors of wheezing and asthma. Furthermore, the data suggest that airway hyperresponsiveness and atopy are independent traits. However, in adults, these traits are associated with cigarette smoking, a common environmental exposure.

Child↗
PubMed1996

Effect of alpha 1-adrenoceptor antagonists, prazosin and urapidil, on a finger skin vasoconstrictor response to cold stimulation.

OBJECTIVES: Cold stimulation causes a finger skin vasoconstrictor response, which is regulated by stimulation of alpha-adrenergic receptors and is reduced by administration of prazosin. The purpose of this study was to investigate, using a laser Doppler flowmeter, whether the decrease in the finger skin vasoconstrictor response to cold stimulation produced by administration of two different alpha 1-adrenoceptor antagonists, prazosin and urapidil, was correlated with the corresponding plasma drug concentration, and whether this method could be used to evaluate the relative potency of these alpha 1-adrenoceptor antagonists in human subjects. METHOD: In thirteen healthy male subjects (20-42 y), finger tip skin blood flow was measured during cold stimulation before and 1, 2, 3, 6, and 9 h after administration of placebo, prazosin (1 mg) or urapidil (60 mg). RESULTS: Both prazosin and urapidil significantly decreased the vasoconstrictor response to cold stimulation. The degree of the decrement in the response indicated by the reduction ratio was significantly correlated with the plasma concentration of prazosin and urapidil. The alpha 1-adrenoceptor blocking activity of prazosin estimated by the regression lines was about 130-times more potent than that of urapidil. CONCLUSION: These findings suggest that the cold stimulation response of finger skin vasoconstriction may be used to evaluate the relative alpha 1-adrenoceptor blocking potency of drugs.

Administration, Oral↗
PubMed2000

Physiological and haematological responses to cold exposure in the elderly.

Throughout Europe, including Norway, increased winter mortality from cardiovascular diseases (CVD) is well described. However, while there are associations between high CVD mortality and cold climate, the reason for the excess deaths is not entirely known. Recent epidemiological evidence suggests that brief outdoor exposure to cold conditions may be linked to increased winter mortality in the elderly. However, the question as to whether alterations in the haemostatic system following exposure to cold could be responsible for the increased winter risk has been little investigated in elderly subjects. In this study, we have compared the effect of exposing lightly clothed healthy elderly men and women (60-70 years) for 90 minutes to either a mild cold stress (16 degrees C) or thermoneutral conditions (28 degrees C). Measurements of a variety of autonomic and haematological parameters were made in order to compare to what extent exposure to cold stress affects production of thrombogenic risk factors. The overall autonomic responses clearly showed that the subjects were mildly cold exposed. The main changes in the blood system were a cold exposure increase in hemoconcentration and an increase in the fibrinolytic parameter, t-PA. This coupled with other changes support previous findings and it is concluded that short term mild cold exposure in the elderly initiates a mild inflammatory reaction and a tendency for an increased state of hypercoagulability.

Aged↗
PubMed2026

Genome-wide identification and cold-stress-responsive expression analysis of the NOX gene family in Cucumis melo.

NADPH oxidases (NOXs) are crucial enzymes for reactive oxygen species (ROS) generation in plants and play vital roles in growth, development, and stress responses. To elucidate the sequence characteristics of the NOX gene family and its low-temperature response patterns in melon (Cucumis melo L.), this study conducted genome-wide identification and expression profiling of NOX family members using bioinformatics analysis, RNA-seq transcriptome sequencing, and real-time quantitative PCR (RT-qPCR). The results revealed that eight NOX members were identified in the melon genome, distributed across six chromosomes. All members harbored conserved domains including Ferric_reductase, FAD_binding_8, NAD_binding_6, and NADPH_Ox, and the encoded proteins were generally basic and hydrophilic. Phylogenetic analysis classified the NOX proteins into five subgroups. Synteny analysis indicated the presence of only one pair of intraspecific duplicated genes in melon, which was under purifying selection. The promoter regions contained multiple hormone- and stress-responsive cis-acting elements, with CmNOX2 and CmNOX4 harboring low-temperature responsive elements. Following treatment at 4&#x2103; for 24 h and 48 h, leaf relative electrolyte leakage (REL) increased from 28.33% to 42.67% and 52.67%, respectively; transcriptome analysis identified 5,633 and 6,882 differentially expressed genes (DEGs), respectively. Cold-responsive genes exhibited significant differential expression, with SLAC1 and CPK19 showing sustained upregulation. RT-qPCR results demonstrated that the expression of CmNOX2, CmNOX5, CmNOX6, and CmNOX7 was significantly downregulated after low-temperature treatment, whereas CmNOX4 expression was significantly upregulated at 48 h. Integrating promoter elements and expression characteristics, CmNOX4 may represent an important candidate gene involved in melon low-temperature response. This study systematically characterized the structure, evolution, and expression patterns of the melon NOX gene family, identified candidate genes responsive to low temperature, and provides a reference for further investigation into the mechanisms underlying melon cold adaptation.

Cucumis melo↗
PubMed1992

The appearance of Fos protein-like immunoreactivity in the hypothalamus of developing rats in response to cold ambient temperatures.

This study examined cellular activity in the hypothalamus of developing rats in response to cold environmental temperatures. The appearance of the nuclear protein, Fos, in response to cold ambient temperatures in rats three to 35 days of age was used as a marker of neuronal activation. Fos-positive nuclei were first seen in response to cold ambient temperatures in the ventromedial nucleus at three days of age, the paraventricular nucleus at eight days of age, the preoptic-anterior hypothalamus at 10 days of age and the anterior hypothalamic nucleus at 21 days of age. The rectal temperature of the 10-day-old pups dropped by less than half that measured in the nine-day-old pups after 1 h in the cold. It is possible that the activation of neurons in the preoptic-anterior hypothalamus in the 10-day-old animal may contribute to the decreased hypothermia observed in the 10-day-old after 1 h in the cold. The high density of Fos-like immunoreactive-labeled nuclei in the preoptic-anterior hypothalamus in the 10-day-old rats that were exposed to the cold environment indicates increased neuronal activity at this site. The results suggest that, at least in the preoptic-anterior hypothalamus, the appearance of the cellular response to cold ambient temperatures is coincidental with a thermogenic response.

Acclimatization↗
PubMed1987

Human vascular fluid responses to cold stress are not altered by cold acclimation.

Repeated cold water immersion can induce the development of an insulative type of cold acclimation in man. This investigation determined if repeated cold water immersion produced changes in vascular fluid responses to cold stress in addition to the previously reported changes in thermoregulation. Seven male subjects performed a standardized cold air and cold water exposure before and again after a cold acclimation program. The cold acclimation program consisted of daily immersion (90 min) in cold water (18 degrees C, stirred) repeated 5 times/wk for 5 consecutive wk. Cold acclimation did not alter the responses of plasma volume or electrolyte concentrations, nor urinary flow or electrolyte excretion during either cold air or cold water exposure. The percent reduction in plasma volume was larger (P less than 0.01) in cold water (-17%) than in cold air (-12%). Cold water immersion resulted in greater (P less than 0.01) diuresis than cold air exposure. Plasma K+ concentration increased (P less than 0.01) during cold (both air and water) exposure, whereas plasma Na+ concentration was unchanged. Calculated renal clearance and urinary excretion rate of both Na+ and K+ increased during cold (both air and water) exposure. The magnitude of plasma volume reduction during cold exposure was not correlated with either the degree of body cooling or diuresis. It is concluded that a) insulative cold acclimation does not influence vascular fluid responses to cold stress, and b) although vascular fluid shifts, body cooling and diuresis are all greater in cold water than in air, a consistent relationship among these parameters could not be established for an individual's response.

Acclimatization↗
PubMed1997

Race, family history of hypertension, and sympathetic response to cold pressor testing.

This laboratory recently reported that the blood pressure and muscle sympathetic nerve activity (MSNA) responses to cold pressor testing are greater in normotensive blacks than in age- and weight-matched normotensive whites. The present study was designed to determine the relationship between race, family history of hypertension, and sympathetic response to cold pressor testing. The study used microneurography to measure MSNA responses to cold pressor testing in normotensive blacks with (n = 8) and without (n = 8) and normotensive white subjects with (n = 8) and without (n = 10) a positive family history of hypertension. Resting blood pressure was lower in black subjects without a positive family history of hypertension but otherwise resting blood pressure, heart rate, and MSNA were similar in the four groups. Black subjects with a family history of hypertension manifested a greater increase in blood pressure and MSNA than both white groups. Blood pressure and sympathetic responses of black subjects with a negative family history of hypertension tended to be intermediate and were not statistically different from the other three groups. These results indicate that the greater sympathetic response to cold stress observed in normotensive African-Americans is true only of black subjects with a positive family history of hypertension.

Adult↗
PubMed1981

Acute metabolic response to cold exposure in unipolar and bipolar II patients.

The thermoregulatory response to cold exposure was examined in 11 unipolar and 5 bipolar II drug-free outpatients and 12 healthy controls. Subjects were studied in an environmental chamber at 10 C for 60 min. The heat production response was derived from the rate of oxygen consumption measured at 15-min intervals. Rectal and mean skin temperatures were continuously recorded from thermistor probes. Responses of the controls were used to establish a standard range against which the responses of the patients were compared. Six unipolar patients (54.5%) fell outside the standard range (chi 2 = 8.86, df = 1, p less than 0.005). Four of these patients showed a paradoxical decrease in heat production. Responses of the bipolar II patients fell within a narrow segment of the standard range, such that 10 of 12 controls (83.3%) responded outside the segment (chi 2 = 10.12, df = 1, p less than 0.005). These findings indicate that unipolar patients show greater variability and bipolar II patients less variability than controls in thermoregulatory response to cold. These observations extend previous suggestions of hypothalamic-limbic system dysfunction in patients with depression.

Adult↗
PubMed1991

Central role of brown adipose tissue thyroxine 5'-deiodinase on thyroid hormone-dependent thermogenic response to cold.

As judged by the response of uncoupling protein and key enzymes, brown adipose tissue (BAT) is highly dependent upon the local generation of T3 catalyzed by the tissue type II T4 5'-deiodinase (5'-D-II). In hypothyroid rats treated with T3 or T4, the capacity to withstand cold seems better correlated with the normalization of BAT responses than with the liver thyroid status. 5'D-II is activated by cold via sympathetic nervous system (SNS) stimulation, and the activation generates enough T3 to nearly saturate BAT nuclear T3 receptor (NTR) in euthyroid rats. In hypothyroidism, 5'D-II is highly stimulated by the SNS and hypothyroxinemia. In the present studies we have taken advantage of this situation to test 1) the capacity of 5'D-II to maintain nuclear T3 in rats with various degrees of hypothyroxinemia, and 2) the hypothesis that thyroid hormone-dependent BAT-facultative thermogenesis, rather than the effect of thyroid hormone on obligatory thermogenesis (basal metabolic rate), is the basic mechanism by which thyroid hormone confers protection against acute cold exposure. We treated methimazole-blocked rats (undetectable plasma T4 and T3) for a week with either subreplacement doses of T4 (0.5, 1, 2, and 4 micrograms/kg.day) or replacement doses of T4 or T3 (8 or 3 micrograms/kg.day, respectively). Sources and content of BAT nuclear T3 were studied at 25 C and after 48 h at 4 C by labeling the plasmaborne T3 (T3[T3]) with [131I]T3 and the locally generated T3 (T3[T4]) with [125I]T4. Neither the kinetics of nuclear-plasma exchange of T3[T3], the time of appearance of T3[T4] in BAT nuclei, nor NTR maximal binding capacity (0.71 ng T3/mg DNA) was affected by hypothyroidism. Kinetic analyses indicated a maximal BAT NTR occupancy of 40% at euthyroid serum T3 concentrations if T4 is not present. Replacement with T4 normalized both serum T4 and T3, while replacement with T3 normalized serum T3; for all other doses of T4, serum T4 and T3 concentrations were predictably related to the dose. 5'D-II activity decreased with increasing doses of T4, but for each dose of T4, this activity was 2-4 times greater at 4 C than at 25 C. BAT NTR occupancy normalized with 2 micrograms T4/kg in rats maintained at 25 C and with 4 micrograms T4/kg in cold-exposed rats, although in neither condition were serum T4 and T3 normalized nor more than 30% of NTR occupied by plasma T3.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue, Brown↗
PubMed1986

Human thermoregulatory responses to cold air are altered by repeated cold water immersion.

The effects of repeated cold water immersion on thermoregulatory responses to cold air were studied in seven males. A cold air stress test (CAST) was performed before and after completion of an acclimation program consisting of daily 90-min cold (18 degrees C) water immersion, repeated 5 times/wk for 5 consecutive wk. The CAST consisted of resting 30 min in a comfortable [24 degrees C, 30% relative humidity (rh)] environment followed by 90 min in cold (5 degrees C, 30% rh) air. Pre- and postacclimation, metabolism (M) increased (P less than 0.01) by 85% during the first 10 min of CAST and thereafter rose slowly. After acclimation, M was lower (P less than 0.02) at 10 min of CAST compared with before, but by 30 min M was the same. Therefore, shivering onset may have been delayed following acclimation. After acclimation, rectal temperature (Tre) was lower (P less than 0.01) before and during CAST, and the drop in Tre during CAST was greater (P less than 0.01) than before. Mean weighted skin temperature (Tsk) was lower (P less than 0.01) following acclimation than before, and acclimation resulted in a larger (P less than 0.02) Tre-to-Tsk gradient. Plasma norepinephrine increased during both CAST (P less than 0.002), but the increase was larger (P less than 0.004) following acclimation. These findings suggest that repeated cold water immersion stimulates development of true cold acclimation in humans as opposed to habituation. The cold acclimation produced appears to be of the insulative type.

Acclimatization↗
PubMed2026

Genome-wide identification and evolutionary analysis of the ERF-VII gene family in the tea plant (Camellia sinensis) and functional characterization of CsRAP2.2 in response to cold stress.

The ERF-VII gene family, a critical branch of the AP2/ERF superfamily, is central to plant stress adaptation. However, its evolutionary history and function in tea plant (Camellia sinensis) remain unclear. Here, we performed integrated evolutionary, genomic, and functional analyses of ERF-VII genes across 14 plant lineages and 20 tea plant cultivars. The phylogenetic analysis revealed that ERF-VII proteins originated after vascular plant divergence, coinciding with the emergence of the N-terminal MCGGA/I motif linked to the oxygen-dependent N-degron pathway. Gymnosperms retained few conserved members, whereas angiosperms exhibited lineage-specific expansion-extensive in monocots via whole-genome duplication, moderate in eudicots with functional diversification. Pan-genome analysis across 20 tea plant cultivars further revealed varietal differences in ERF-VII gene distribution. Transcriptome profiling via the Tea Plant Information Archive identified CsRAP2.2 as a cold-inducible ERF-VII member with sustained expression under low-temperature stress. Functional assays demonstrated that silencing CsRAP2.2 reduced cold tolerance, while overexpression in tea leaves and heterologous expression in Arabidopsis thaliana enhanced cold tolerance by maintaining photosystem II efficiency, reducing membrane lipid peroxidation, and improving antioxidant capacity. Weighted gene co-expression network analysis positioned CsRAP2.2 as a regulatory hub integrating cold, hormone, and oxygen-sensing pathways. These results clarify the evolutionary trajectory of ERF-VII genes and establish CsRAP2.2 as a core cold-tolerance regulator in tea plant. These findings may inform future breeding of cold-resilient tea cultivars.

Camellia sinensis↗
PubMed1989

Paradoxical social effects on response to cold during ontogeny of the common white-toothed shrew, Crocidura russula.

Postnatal development of thermoregulatory responses to cold differs between shrews measured singly or in groups as a litter. Single shrews increase their metabolic response to cold within 14 days to maintain normothermia. Shrews measured in groups show little or no metabolic response to cold and do not reach normothermia before the 19th day. Lower body temperatures in groups are explained by torpor, which obviously needs the prerequisite of forming a group. Oxygen consumption of the singly measured shrews depends upon body mass.

Animals↗