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PubMed1994

Variation in tolerance to the antinociceptive, hormonal and thermal effects of morphine after a 5-day pre-treatment of male rats with increasing doses of morphine.

The manifestation of tolerance to the effects of morphine on nociception and the secretion of anterior pituitary hormones, and the correlation of hormonal effects to changes in body temperature and to hypothalamic monoamines were studied in male rats. Morphine (three times a day in increasing doses) or saline (control) were administered intraperitoneally during a 5-day treatment and either saline or morphine was administered as an acute challenge 92 h later. The influence of the thermal environment on the effect of morphine on the body temperature was also studied. The 5-day morphine regimen was sufficient for the development of tolerance to the antinociceptive effect of morphine. After a 92-h lag-time, the tolerance was still complete. Tolerance to the depressant effect of morphine (10-25 mg/kg) on cold-stimulated TSH secretion was seen at 2 h, but was only barely detectable at 1 h, after the injection of a challenge dose. On the other hand, a tolerance to the stimulatory effect of morphine on prolactin secretion was already seen 1 h after the acute dose of morphine. Tolerance to the hypothermic effect of morphine (25 mg/kg) was evident in rats kept at +4 degrees C after the challenge dose. On the contrary, no tolerance to the hyperthermic effect of morphine (15 or 25 mg/kg) was observed in rats kept at +30 degrees C. However, the hyperthermia was reversed when these rats were moved to +4 degrees C for 30 min, irrespective of whether they were morphine pretreated or not. Thus the removal of the hyperthermic stimulus decreased the core temperature of all rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed2006

Experimental heat pain for detecting pregnancy-induced analgesia in humans.

Animal studies suggest that increased circulating estrogen and progesterone, and activation of the endorphin system cause prenancy-induced antinociceptive effects. Human studies have provided inconsistent results and have often lacked a nonpregnant control group. In this study, we compared sensitivity to experimental heat and cold pain in pregnant and nonpregnant women. Nineteen healthy nonpregnant female volunteers and 20 pregnant women at term were enrolled. Pain threshold and tolerance were examined using experimental heat-induced pain and cold pressor pain models. Subjects were evaluated pre- and 1-2 days post-delivery (pregnant), or on consecutive days (nonpregnant). Heat pain tolerance was significantly increased in the pregnant women during pre and postdelivery when compared with nonpregnant controls (50.0 +/- 1.0 vs 49.0 +/- 1.2 and 50.1 +/- 0.7 vs 49.2 +/- 1.2 degrees C; mean +/- sd). However, pain induced by the cold pressor test was endured for a similar amount of time by both study groups. Pregnancy-induced analgesic effects at term can be detected in a model of experimental heat pain. These effects persist during the first 24-48 h after delivery. Experimental heat pain is a suitable modality for further characterizing the phenomenon of pregnancy-induced analgesia in humans.

Adult↗
PubMed2004

Cloning and functional analysis of a novel DREB1/CBF transcription factor involved in cold-responsive gene expression in Zea mays L.

The transcription factors DREB1s/CBFs specifically interact with the DRE/CRT cis-acting element (core motif: G/ACCGAC) and control the expression of many stress-inducible genes in Arabidopsis. We isolated a cDNA for a DREB1/CBF homolog, ZmDREB1A in maize using a yeast one-hybrid system. The ZmDREB1A proteins specifically bound to DRE and the highly conserved valine at the 14th residue in the ERF/AP2 DNA binding domain was a key to determining the specific interaction between this protein and the DRE sequence. Expression of ZmDREB1A was induced by cold stress and slightly increased by high-salinity stress. This gene was also transiently expressed by mechanical attack. ZmDREB1A activated the transcription of the GUS reporter gene driven by DRE in rice protoplasts. Overexpression of ZmDREB1A in transgenic Arabidopsis induced overexpression of target stress-inducible genes of Arabidopsis DREB1A resulting in plants with higher tolerance to drought and freezing stresses. This indicated that ZmDREB1A has functional similarity to DREB1s/CBFs in Arabidopsis. The structure of the ERF/AP2 domain of ZmDREB1A in maize is closely related to DREB1-type ERF/AP2 domains in the monocots as compared with that in the dicots. ZmDREB1A is suggested to be potentially useful for producing transgenic plants that is tolerant to drought, high-salinity and/or cold stresses.

Amino Acid Sequence↗
PubMed1998

Vacuolar membrane lesions induced by a freeze-thaw cycle in protoplasts isolated from deacclimated tubers of Jerusalem artichoke (Helianthus tuberosus L.).

The processes of freezing injury in Jerusalem artichoke (Helianthus tuberosus L.) tubers were studied using protoplasts isolated from cold-acclimated and deacclimated tubers. Prior to freezing, protoplasts were preloaded with 10 microM fluorescein diacetate (FDA) in an isotonic sorbitol solution. After freeze-thawing at various temperatures, cell viability was evaluated under a fluorescence microscope. In cold-acclimated tubers, more than 80% of protoplasts survived freezing to -20 degrees C. By contrast, in deacclimated tubers, the cell survival abruptly declined after freezing to temperatures below -5 degrees C. Thus, freezing tolerance differed significantly between protoplasts isolated from cold-acclimated and deacclimated tubers. Two distinct types of cell injury, which were caused by either damage to plasma membrane (cell-lysis type) or by damage to the vacuolar membrane (abnormal-staining type), were observed, depending on the cold hardiness and freezing temperature. In the cells of the abnormal-staining type, shrinkage of the central vacuolar space and simultaneous acidification of the cytoplasmic space were characteristically observed immediately before complete cell-rehydration during thawing. The decrease in freezing tolerance of protoplasts after deacclimation was suggested to be due mainly to destabilization of the vacuolar membrane by freeze-induced dehydration stress.

Freezing↗
PubMed2001

The analgesic effect of codeine as compared to imipramine in different human experimental pain models.

The hypoalgesic effect of single oral doses of 100 mg imipramine and 125 mg codeine was evaluated in a randomised, placebo-controlled, double-blind, 3-way cross-over experiment including 18 healthy volunteers. Pain tests were performed before and 90, 180, 270, 360 and 450 min after medication. The tests included determination of pain tolerance thresholds to pressure, pain detection/tolerance thresholds to single electrical sural nerve stimulation and pain summation at tolerance threshold to repetitive electrical sural nerve stimulation (temporal summation) and pain experienced during the cold pressor test, rated as peak pain intensity, pain average intensity and discomfort. Compared to placebo, imipramine significantly increased pressure pain tolerance threshold (P = 0.03) and increased pain tolerance threshold (P = 0.05) and pain summation threshold (P = 0.03), but not pain detection threshold to electrical stimulation. Imipramine did not cause significant changes in pain perception during the cold pressor test. Codeine significantly increased pressure pain tolerance threshold (P = 0.02), pain detection (P = 0.04) and pain tolerance threshold (P = 0.01) and pain summation threshold (P = 0.02) to electrical stimulation. In addition, codeine reduced the pain experienced during the cold pressor test (P = 0.04-0.003). It is concluded that both imipramine and codeine inhibit temporal pain summation, whereas only codeine reduces cold pressor pain. Pain summation may be a key mechanism in neuropathic pain. Imipramine has a documented effect on such pain conditions on temporal summation. The present study showed that codeine also inhibits temporal summation, which is in line with the clinical observations indicating that opioids relieve neuropathic pain.

Adrenergic Uptake Inhibitors↗
PubMed2003

OsDREB genes in rice, Oryza sativa L., encode transcription activators that function in drought-, high-salt- and cold-responsive gene expression.

The transcription factors DREBs/CBFs specifically interact with the dehydration-responsive element/C-repeat (DRE/CRT) cis-acting element (core motif: G/ACCGAC) and control the expression of many stress-inducible genes in Arabidopsis. In rice, we isolated five cDNAs for DREB homologs: OsDREB1A, OsDREB1B, OsDREB1C, OsDREB1D, and OsDREB2A. Expression of OsDREB1A and OsDREB1B was induced by cold, whereas expression of OsDREB2A was induced by dehydration and high-salt stresses. The OsDREB1A and OsDREB2A proteins specifically bound to DRE and activated the transcription of the GUS reporter gene driven by DRE in rice protoplasts. Over-expression of OsDREB1A in transgenic Arabidopsis induced over-expression of target stress-inducible genes of Arabidopsis DREB1A resulting in plants with higher tolerance to drought, high-salt, and freezing stresses. This indicated that OsDREB1A has functional similarity to DREB1A. However, in microarray and RNA blot analyses, some stress-inducible target genes of the DREB1A proteins that have only ACCGAC as DRE were not over-expressed in the OsDREB1A transgenic Arabidopsis. The OsDREB1A protein bound to GCCGAC more preferentially than to ACCGAC whereas the DREB1A proteins bound to both GCCGAC and ACCGAC efficiently. The structures of DREB1-type ERF/AP2 domains in monocots are closely related to each other as compared with that in the dicots. OsDREB1A is potentially useful for producing transgenic monocots that are tolerant to drought, high-salt, and/or cold stresses.

Adaptation, Physiological↗
PubMed2004

A prominent role for the CBF cold response pathway in configuring the low-temperature metabolome of Arabidopsis.

The Arabidopsis CBF cold response pathway has a central role in cold acclimation, the process whereby plants increase in freezing tolerance in response to low nonfreezing temperatures. Here we examined the changes that occur in the Arabidopsis metabolome in response to low temperature and assessed the role of the CBF cold response pathway in bringing about these modifications. Of 434 metabolites monitored by GC-time-of-flight MS, 325 (75%) were found to increase in Arabidopsis Wassilewskija-2 (Ws-2) plants in response to low temperature. Of these 325 metabolites, 256 (79%) also increased in nonacclimated Ws-2 plants in response to overexpression of C-repeat/dehydration responsive element-binding factor (CBF)3. Extensive cold-induced changes also occurred in the metabolome of Arabidopsis Cape Verde Islands-1 (Cvi-1) plants, which were found to be less freezing tolerant than Ws-2 plants. However, low-temperature-induced expression of CBF1, CBF2, CBF3, and CBF-targeted genes was much lower in Cvi-1 than in Ws-2 plants, and the low-temperature metabolome of Cvi-1 plants was depleted in metabolites affected by CBF3 overexpression. Taken together, the results indicate that the metabolome of Arabidopsis is extensively reconfigured in response to low temperature, and that the CBF cold response pathway has a prominent role in this process.

Acclimatization↗
PubMed1983

Evidence against involvement of beta-endorphin in thermoregulation in the cat.

In the cat naloxone has little, if any, effect on temperature under usual laboratory conditions and does not reduce febrile responses to leukocytic pyrogen. Hence, endogenous opioid peptides that are antagonized by naloxone are not essential for induction of fever or for maintenance of normal temperature in the absence of appreciable thermal stress. The purpose of this study was to assess the contribution of such endogenous opioids to thermoregulation in cats exposed to more severe thermal and non-thermal stresses. Changes in temperature of unanesthetized cats were determined after third cerebral ventricular injections of large doses (100, 250 micrograms) of naloxone or saline vehicle. Naloxone had no appreciable effect on the temperature of cats acutely exposed to hot (34 degrees C) or cold (4 degrees C) environments, either before or after tolerance to morphine had been induced by progressively greater daily or twice-daily intraventricular doses of 10-70 micrograms morphine sulfate. Naloxone also did not significantly affect the temperature of cats subjected to neck-restraint or forced to stand on a small platform if they were to avoid contact with ice water. These results provide no indication that an endogenous opioid peptide, such as beta-endorphin, that is antagonized by naloxone contributes appreciably to thermoregulation in cats. They do not rule out the possibility that endogenous opioids, such as Met-enkephalin, that are not readily antagonized by naloxone are important for normal thermoregulation.

Animals↗
PubMed1977

Responses to temperate, cold, and hot environments and the effect of physical training.

Ten young men underwent several tests before and after a training program: a bicycle ergometer test and 60 min of moderate exercise performed at a temperate 24 degrees C; the same work load performed in heat (40.0 degrees C DB, 30.4 degrees C WB) for 3 h; and cold (10 degrees C) exposure for 60 min. Training consisted of 13 1-h sessions of hard, strenuous, and exhaustive work performed in temperate conditions four times a week. Training resulted in substantial decreases in heart rate and rectal temperature responses to exercise in temperate, minor increases in hot, and no significant changes in cold conditions. Subjects who showed good responses to heat, also showed good responses at 24 degrees C, and poor compensatory responses to cold, which were indicated by relatively low heat production and rectal temperature values, and relatively high body heat loss and extremities temperature values. Subjects who showed poor heat tolerance also showed poor responses in temperate and good compensatory responses in cold conditions. Positive correlation coefficients were found between rectal temperatures in the three environments, and between heart rate and sweat rate responses in temperate and hot conditions. The results indicated that moderately severe training causes minor tolerance improvements in heat and no changes in cold, and that responses in temperate, cold, and hot environments are interdependent.

Acclimatization↗
PubMed1984

Efficiency of cold hardiness induction by desiccation stress in four winter cereals.

A number of defined desiccation treatments without low temperature exposure were able to induce freezing tolerance in 20 cultivars of winter cereals. A maximal degree of freezing tolerance was induced in epicotyls at 24 degrees C in 24 hours at 40% relative humidity in rye and wheat, 7 days at 54% RH in barley, and 4 days at 70% RH in oats. Freezing tolerance was not correlated to water content of the plants after desiccation treatment but was related to the genetic capacity of the cultivars to frost harden. Levels of freezing tolerance induced by desiccation were similar to those induced by cold acclimation in rye and wheat, but considerably less in barley and oats. This is associated with a more rapid desiccation injury in barley and oats, precluding the completion of the hardening process.

Journal Article↗
PubMed2006

Reptile freeze tolerance: metabolism and gene expression.

Terrestrially hibernating reptiles that live in seasonally cold climates need effective strategies of cold hardiness to survive the winter. Use of thermally buffered hibernacula is very important but when exposure to temperatures below 0 degrees C cannot be avoided, either freeze avoidance (supercooling) or freeze tolerance strategies can be employed, sometimes by the same species depending on environmental conditions. Several reptile species display ecologically relevant freeze tolerance, surviving for extended times with 50% or more of their total body water frozen. The use of colligative cryoprotectants by reptiles is poorly developed but metabolic and enzymatic adaptations providing anoxia tolerance and antioxidant defense are important aids to freezing survival. New studies using DNA array screening are examining the role of freeze-responsive gene expression. Three categories of freeze responsive genes have been identified from recent screenings of liver and heart from freeze-exposed (5h post-nucleation at -2.5 degrees C) hatchling painted turtles, Chrysemys picta marginata. These genes encode (a) proteins involved in iron binding, (b) enzymes of antioxidant defense, and (c) serine protease inhibitors. The same genes were up-regulated by anoxia exposure (4 h of N2 gas exposure at 5 degrees C) of the hatchlings which suggests that these defenses for freeze tolerance are aimed at counteracting the injurious effects of the ischemia imposed by plasma freezing.

Animals↗
PubMed2002

Influence of attention focus and trait anxiety on tolerance of acute pain.

OBJECTIVES: In light of inconsistencies in the reported effects of attention and anxiety on pain tolerance, this study examined the separate and combined effects of attention focus and trait anxiety on tolerance of acute experimental pain. DESIGN: Participants with 'high' and 'low' trait anxiety were assigned to three attention-focus conditions: pain-focused attention, 'undirected' (no experimenter-induced attempts to influence attention focus) and distraction. METHODS: Several indices of autonomic arousal (systolic and diastolic blood pressure, heart rate and EMG) were measured before and during, and several self-report inventories were completed before and after, each of two administrations of the cold pressor test. RESULTS: In general, pain tolerance was greater when participants were distracted and in low- rather than high-anxiety participants. However, attention and anxiety interacted such that low-anxiety participants were most pain tolerant, and high-anxiety participants were least pain tolerant, in the undirected condition. CONCLUSION: The results are consistent with the notion that anxiety fosters attentiveness to possible environmental threats, and might have implications for the clinical management of acute pain.

Journal Article↗
PubMed2003

Bile salts and cholesterol induce changes in the lipid cell membrane of Lactobacillus reuteri.

AIMS: The objective of this study was to evaluate the effect of bile salts and cholesterol in the lipid profile of Lactobacillus reuteri CRL 1098 and to determine the relationship existing between these changes: the in vitro removal of cholesterol and the tolerance of the cells to acid and cold stress. METHODS AND RESULTS: Lactobacillus reuteri CRL 1098 was grown in the following media: MRS (deMan Rogosa Sharpe; MC, control medium), MB (MC with bile salts), MCH (MC with sterile cholesterol) and MBCH (MC with bile salts and cholesterol). Fatty acids were determined by analytical gas-liquid chromatography, and phospholipids and glycolipids by colorimetric techniques. The cells from different culture media were subjected to cold and acid stress. The MB cultures displayed a decrease in phospholipids and a low ratio of saturated : unsaturated fatty acids. The presence of the unusual C18 : 0,10-OH and C18 : 0,10-oxo fatty acids was the prominent characteristic of the bile salts growing cells. The relative increase in glycolipids and the changes in the fatty acids profiles of the MB cells would be responsible for the cholesterol remotion. The changes induced by bile salts in the lipid profile did not improve the tolerance of L. reuteri CRL 1098 to freezing and acid stress. CONCLUSIONS: The changes in lipid profiles reported in this study would play a key role in the response of Lactobacilli to environmental stress. SIGNIFICANCE AND IMPACT OF THE STUDY: This work provides useful information about the effect of bile salts on the cell membrane of L. reuteri, a probiotic enterolactobacillus. The steady-state response of the cells subjected to bile stress seems to be the appropriate model for evaluating the bacterial behaviour in detergent-containing gastrointestinal tracts, where the bile salts stress would presumably be continuous.

Bile Acids and Salts↗
PubMed2004

A genetic link between cold responses and flowering time through FVE in Arabidopsis thaliana.

Cold induces expression of a number of genes that encode proteins that enhance tolerance to freezing temperatures in plants. A cis-acting element responsive to cold and drought, the C-repeat/dehydration-responsive element (C/DRE), was identified in the Arabidopsis thaliana stress-inducible genes RD29A and COR15a and found in other cold-inducible genes in various plants. C/DRE-binding factor/DRE-binding protein (CBF/DREB) is an essential component of the cold-acclimation response, but the signaling pathways and networks are mostly unknown. Here we used targeted genetic approach to isolate A. thaliana mutants with altered cold-responsive gene expression (acg) and identify ACG1 as a negative regulator of the CBF/DREB pathway. acg1 flowered late and had elevated expression of FLOWERING LOCUS C (FLC), a repressor of flowering encoding a MADS-box protein. We showed that acg1 is a null allele of the autonomous pathway gene FVE. FVE encodes a homolog of the mammalian retinoblastoma-associated protein, a component of a histone deacetylase (HDAC) complex involved in transcriptional repression. We also showed that plants sense intermittent cold stress through FVE and delay flowering with increasing expression of FLC. Dual roles of FVE in regulating the flowering time and the cold response may have an evolutionary advantage for plants by increasing their survival rates.

Arabidopsis↗
PubMedDate not supplied

The tolerance of the field slug Deroceras reticulatum to freezing temperatures.

Cold hardiness of ectotherms has been widely studied in arthropods, but there is a more limited literature on the survival of molluscs at low temperatures. A number of intertidal species have been examined in detail, but terrestrial molluscs have largely been overlooked until recently. This paper reports results of laboratory experiments to evaluate the cold hardiness of the terrestrial slug, Deroceras reticulatum. The mean supercooling point (SCP) rose from -4.2 degree C in summer to -3.6 degree C in winter. The SCP that caused 50 percent mortality (LSCP50) remained constant at -4.7 to -4.8 degree C in both seasons, but slugs were able to survive the frozen state for longer in winter (LD50 of 31.8 minutes compared with 17.0 minutes in summer). Slug survival at freezing temperatures was prolonged to at least five hours when placed on a moist, absorbent substrate. D. reticulatum exhibits partial freeze tolerance, with an increased survival in winter. The results are discussed in relation to the natural environment of slugs.

Adaptation, Physiological↗
PubMedDate not supplied

Preventing the common cold with a vitamin C supplement: a double-blind, placebo-controlled survey.

One hundred sixty-eight volunteers were randomized to receive a placebo or a vitamin C supplement, two tablets daily, over a 60-day period between November and February. They used a five-point scale to assess their health and recorded any common cold infections and symptoms in a daily diary. Compared with the placebo group, the active-treatment group had significantly fewer colds (37 vs 50, P<.05), fewer days challenged virally (85 vs 178), and a significantly shorter duration of severe symptoms (1.8 vs 3.1 days, P<.03). Consequently, volunteers in the active group were less likely to get a cold and recovered faster if infected. Few side effects occurred with the active treatment, and volunteers reported greatly increased satisfaction with the study supplement compared with any previous form of vitamin C. This well-tolerated vitamin C supplement may prevent the common cold and shorten the duration of symptoms. Volunteers were generally impressed by the protection afforded them during the winter months and the general acceptability of the study medication.

Ascorbic Acid↗
PubMed1990

Antinociception in the rat induced by a cold environment.

Rats placed in a cold environment (4 degrees C) for 2 h had a sustained increase in tail flick latency (TFL) as well as an increase in tail pinch latency (TPch) that was often biphasic with an early peak response at 15 min and a later, often higher, peak at 2 h. Plasma beta-endorphin levels after a modest increase at 5 min (24%) declined throughout the remaining time in the cold. The long-acting opioid antagonist naltrexone had no effect on TFL increases but led to greater increases in TPch (P less than 0.04). In morphine-tolerant rats TFL response was the same as in controls but TPch increases were greater (P less than 0.04). Rats exposed to 2 h of cold for 17 or 18 consecutive days generally developed tolerance to the analgesia of cold, i.e. TFL and TPch increases were diminished; however, the response to morphine on day 18 was the same as in rats never exposed to cold. Adrenalectomy and hypophysectomy led to significantly smaller increases in TFL (P less than 0.02 and P less than 0.001, respectively). The TPch response in contrast, was greater in adrenalectomized (P less than 0.001) and the same in hypophysectomized rats compared to sham controls. An opioid kappa receptor antagonist (Mr 1452) given prior to cold reduced both TFL and TPch response during the first hour. Thus the analgesia induced by cold appeared to shift from an early possibly kappa opioid to a later non-opioid form. The TFL effects seemed to be under hormonal influence while the TPch were not.

Adrenal Glands↗