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Response of nigral dopamine neurons to actue and prolonged morphine treatment: effect of exposure to cold, physostigmine and nicotine.

The effects of morphine and acute exposure to cold on nigral dopamine (DA) neurons and possible interactions with cholinergic systems were studied by histochemical microfluorimetry in normal and partially morphine-tolerant mice. Morphine (40 mg/kg), cold (4 degrees C), nicotine (1 mg/kg) and physiostigmine (0.25 mg/kg) elicited a rapid rise and subsequent decrease in the fluorescence intensity of DA nerve cells with certain differences in time course. Fastest changes with a peak at 5 min, a marked subsequent drop below control levels and return towards control intensity after 40 min were seen after physostigmine. Antagonisms between various treatments were noted. DA responses correlated well with the time course of behavioural effects, especially after physostigmine. After 3 1/2 days of morphine treatment, the locomotor and analgesic effects of the drug were reduced. At this stage, the initial increase in fluorescence intensity after morphine and the biphasic pattern caused by physostigmine were delayed without any change in response magnitude. Responses to cold and nicotine remained unaltered both in magnitude and time course. Thus, partial tolerance affected the response of nigral DA neurons to some but not all funtional conditions and thereby markedly changed the interaction with cholinergic systems. The difference between physostigmine and nicotine suggests that neuronal circuits including mustcarinic mechanisms are possibly more susceptible to alteration.

Analgesia↗

A cluster of 11 CBF transcription factors is located at the frost tolerance locus Fr-Am2 in Triticum monococcum.

Due to the adverse effects of cold temperatures on winter wheat, frost tolerance is an important trait for breeding programs in regions with severe winters. Frost tolerance locus Fr-A(m)2 was recently discovered in diploid wheat (Triticum monococcum L.). This locus was mapped as a QTL on chromosome 5A(m) in the same region as a QTL for the level of transcription of the cold-regulated gene COR14b at 15 degrees C. A CBF transcription factor was mapped in the center of these two overlapping QTLs. However, since the CBF gene family in wheat has numerous members, it was possible that multiple CBF genes were present at Fr-A(m)2. To investigate this possibility we initiated a systematic characterization of the CBF family in T. monococcum. Here we report the molecular characterization of thirteen TmCBF genes. Nine of them were numbered according to the closest barley HvCBF gene, and the other four that have no clear barley orthologues were assigned numbers TmCBF15 to TmCBF18. TmCBF5 and TmCBF18 were mapped on T. monococcum chromosomes 7A(m) and 6A(m), respectively, and are thus not candidates for the Fr-A(m)2 gene. The remaining eleven TmCBF genes are clustered at the Fr-A(m)2 locus within five different Bacterial Artificial Chromosome (BAC) clones. These BACs were mapped using a high-density map and recombination events were found between most BACs. Lines carrying these recombination events will be useful to identify which of the CBF genes is responsible for the differences in frost tolerance between the T. monococcum parental lines at the Fr-A(m)2 locus.

Acclimatization↗

Myocardial LDH isoenzyme patterns in rats exposed to cold and/or hypobaric hypoxia.

Exposure of rats to hypobaric hypoxia (9.5% O2) for 40 days produced cardiac hypertrophy, increases in the total LDH activity and subunit M percentage of LDH and a significant decrease (50%) in H/M ratio when compared to control rats. An equally long exposure to cold (+6 degrees C) did not affect heart weight or total LDH activity, but a significant increase (17.6%) in the H/M ratio developed. Simultaneous exposure to cold (+6 degrees C) and hypoxia (9.5% O2) caused a significant decrease in the H/M ratio, but there was no change in the total LDH-activity when compared to the control group. The poor hypoxic tolerance of the cold-exposed rats could partly be explained by disadvantageous distribution of LDH isoenzymes leading to impaired glycolytic capacity of such an aerobic organ as the heart.

Altitude↗

[Physical urticarias].

Ten percent of chronic urticarias are physical urticarias. Patients suffering from physical urticaria all have a suggestive history with specific eliciting stimuli (cold, heat, water, sun.) and wheals in the areas where the stimulus acts. The involved pathomechanisms are not well known. An unknown allergen (related to a cold or a heat injury, a polar molecule contained in the stratum corneum and soluble into water, a photoallergen) could induce a mast cell mediator release, followed by an infiltration by eosinophil then neutrophils polymorphonuclears. T-cells are not highly involved. Dermographism, the most frequent can be cured by anti-H1. In diagnosing cholinergic urticaria physical exercise has to be done by the patient (jogging, running, riding), anti-H1 are efficient. In other physical urticarias (delayed-pressure, cold, solar, heat, vibratory urticarias) as to be managed as follows: (1) to perform specific tests with respectively (weights; ice cube; UVA, UVB and visible light exposure; hot water contained in a tube; a vortex mixer); (2) to avoid eliciting stimuli; (3) to treat the associated diseases e.g. in secondary cold urticaria; (4) to try to induce a physical tolerance, a review is enclosed concerning cold, solar, heat and aquagenic urticarias; (5) to associate or not non sedative 2(nd) generation antihistamines. All the other alternative treatments are discussed but none of them has been evaluated.

Anti-Allergic Agents↗

Humor as a cognitive technique for increasing pain tolerance.

Substantial research has demonstrated that cognitive psychological techniques including distraction can increase pain tolerance. In recent years, there also have been claims that humor and laughter possess unique characteristics for coping with pain and stress. Theoretically, explanations include the release of endorphins, the lowering of tension, as well as the distraction that results from humor. The question is whether humor is more effective than simple distraction. For this purpose humor was contrasted with a repulsive stimulus and a neutral stimulus controlled for interest level, that would also have distraction capabilities but not the unique aspects of humor. Pain tolerance was tested using cold pressor stimulation. Four groups (20 subjects in each) were tested. Three groups were shown a film: (1) a humorous film, (2) a repulsive film, (3) a neutral film. Group 4 was not shown any film. Results indicated that both the humor and repulsive groups showed a significant increase in pain tolerance as compared to the other groups. The repulsive group yielded the largest increase in pain tolerance although not different from the humor group. Except for sex differences, pain ratings did not show any group effects. Discussion focused on the type of distraction that would be meaningful for increasing pain tolerance and on the place of humor in pain control.

Adolescent↗

Fear of pain, not pain catastrophizing, predicts acute pain intensity, but neither factor predicts tolerance or blood pressure reactivity: an experimental investigation in pain-free individuals.

Previous studies of the Fear-Avoidance Model of Exaggerated Pain Perception have commonly included patients with chronic low back pain, making it difficult to determine which psychological factors led to the development of an "exaggerated pain perception". This study investigated the validity of the Fear-Avoidance Model of Exaggerated Pain Perception by considering the influence of fear of pain and pain catastrophizing on acute pain perception, after considering sex and anxiety. Thirty-two males and 34 females completed the State-Trait Anxiety Inventory, the Fear of Pain Questionnaire, and the Coping Strategies Questionnaire. Subjects underwent a cold pressor procedure and tolerance, pain intensity, and blood pressure reactivity were measured. Sex, anxiety, fear of pain, and pain catastrophizing were simultaneously entered into separate multiple regression models to predict different components of pain perception. Tolerance was not predicted by fear of pain, pain catastrophizing, or anxiety. Pain intensity at threshold and tolerance were significantly predicted by fear of pain, only. Blood pressure reactivity to pain was significantly predicted by anxiety, only. These results suggest that fear of pain may have a stronger influence on acute pain intensity when compared to pain catastrophizing, while neither of the factors predicted tolerance or blood pressure reactivity.

Acute Disease↗

Cold storage of rat skeletal muscle free flaps and pre-ischemic perfusion with modified UW solution.

We used the rat medial gastrocnemius free flap, based on a pedicle of the femoral artery and vein, in order to test the tolerance of skeletal muscle to cold ischemia-reperfusion (IR) injury, and to determine whether tolerance can be enhanced by pre-ischemic perfusion with tissue/organ preservation solutions. Muscle flaps (n = 6 per group) were subjected to variable periods of cold storage (0, 1, 2, 3, or 4 days) and 24-h normothermic reperfusion. Muscle viability, as determined by nitroblue tetrazolium (NBT) histochemical staining of viable mitochondria and supported by histological examination, was 100%, 26%, 11%, 4%, and 1%, respectively. Using 24-h cold storage/24-h reperfusion as the experimental conditions, groups of muscle flaps (n = 5 per group) were perfused immediately before cold storage with either modified, colloid-free University of Wisconsin (UW) solution, a solution described by Kohout et al. (Br J Plast Surg 1995;48:132-144) or normal saline. Perfusion with modified UW solution or Kohout's solution increased survival to 33% (P < 0.05) and 28% (not statistically significant), respectively, compared with the 19% viability of separate groups of nonperfused or saline-perfused controls. These findings indicate that cold-stored skeletal muscle is highly susceptible to cold IR injury and that the viability can be increased by prior perfusion with a tissue preservation solution such as modified UW solution.

Adenosine↗

Naltrexone antagonizes the biobehavioral adaptation to cold water stress in rats.

The reported studies on the development of tolerance to the analgesic effects of stress have been mostly concerned with the involvement of opioid or non-opioid substances in stress-induced analgesia (SIA). To further investigate the processes involved in SIA tolerance, rats were exposed to forced intermittent cold water swim (ICWS, 18 exposures, 3/min, 10 sec each) on 16 consecutive days. On days 15 and 16, they were injected prior to swim with saline and naltrexone (10 mg/kg), respectively. During swim, three types of readily identifiable behaviors were observed. They may be characterized by immobility and horizontal floating (Type I), intensive activity and escape attempts (Type II), and passivity and "behavioral despair" (Type III). In the acute condition, only Type II and Type III appear in sequence. In the chronic condition, the sequence of behaviors is: Type I, Type II, and Type III. Thirty minutes after swim, analgesia, core temperature, and degree of inactivity were measured. With chronic exposure, tolerance developed to the analgesia, core hypothermia and hypoactivity induced by the ICWS. Type I behavior appeared on day 3 or 4 and persisted throughout the chronic treatment. Type II behavior did not adapt. Naltrexone (10 mg/kg) antagonized the adaptive aspect of all those variables where adaptation or tolerance were found (analgesia, hypoactivity, core hypothermia, and Type I behavior) but had no effect on Type II behavior where no adaptation was observed. It is suggested that the endorphins have a functional role in the behavioral and and physiological adaptation to aversive stressful environmental situations.

Adaptation, Physiological↗

The beneficial effect of heparin in preischemic perfusion solutions for cold-stored skin flaps.

Storage of skin flaps in the cold before replantation increases their tolerance to ischemic damage. Rat epigastric skin flaps were perfused immediately before 2 days of cold ischemia with 3 ml of normal saline containing either 10 U per milliliter of heparin (group 1, N = 11) or normal saline (group 2, N = 10), or stored without perfusion (group 3, N = 6), and replanted. Flap viability was assessed 7 days later. The mean flap survival in groups 1, 2, and 3 was 73% (p<0.01 compared with group 2), 10%, and 33% respectively. Intravascular fibrin deposits were detected histochemically 5 minutes before reperfusion in nonperfused flaps and 5 minutes after reperfusion in saline-perfused flaps, but not in flaps perfused with heparinized saline. Angiography revealed evidence of no reflow in the first 5 minutes of reperfusion in saline-perfused flaps, but normal blood flow in heparinized saline-perfused flaps. Tissue water content, myeloperoxidase activity, and hydroperoxide levels after 1 and 24 hours of reperfusion were not significantly different in flaps perfused with heparinized saline and normal saline. These findings indicate that in skin flaps perfused before ischemia, flaps perfused with heparinized saline survive significantly better than flaps perfused with normal saline. They also survive better than nonperfused flaps but the improvement is not significant.

Animals↗

Comparison of the effects of physical exercise, cold acclimation and repeated injections of isoprenaline on rat muscle enzymes.

The metabolic effects on rat cardiac and skeletal muscle of a strenous program of swimming, of cold acclimation and of isoprenaline treatment (0.3 mg/kg daily for 5 five-day weeks) were compared. Exercised and cold-exposed rats gained less body weight than did controls or isoprenaline-treated rats. In all treated groups the heart and the intercapular brown adipose tissue hypertrophied. The size of the adrenals increased only in isoprenaline-treated animals. Cold-acclimation and physical training increased and isoprenaline treatment reduced or did not affect the activities of succinate dehydrogenase, malate dehydrogenase and citrate synthase of cardiac muscle. In the skeletal muscle all treatments resulted in increased activities of these enzymes. Of the anaerobic enzymes analysed, only the activity of hexokinase increased in response to the treatements used. This increase was the same in cardiac as in skeletal muscle, but it was significantly greater with isoprenaline-treatment than with training or with cold-acclimation. The activities of lactate dehydrogenase and phosphofructokinase did not differ significantly. All treatments improved cold resistance, but only swimming exercise and cold acclimation significantly increased tolerance to exercise. It is concluded that prolonged stimulation of adrenergic beta-receptors by catecholamines is responsible for the metabolic changes observed.

Acclimatization↗

Eskimo1 mutants of Arabidopsis are constitutively freezing-tolerant.

Temperate plants develop a greater ability to withstand freezing in response to a period of low but nonfreezing temperatures through a complex, adaptive process of cold acclimation. Very little is known about the signaling processes by which plants perceive the low temperature stimulus and transduce it into the nucleus to activate genes needed for increased freezing tolerance. To help understand the signaling processes, we have isolated mutants of Arabidopsis that are constitutively freezing-tolerant in the absence of cold acclimation. Freezing tolerance of wild-type Arabidopsis was increased from -5.5 degreesC to -12.6 degreesC by cold acclimation whereas the freezing tolerance of 26 mutant lines ranged from -6.8 degreesC to -10.6 degreesC in the absence of acclimation. Plants with mutations at the eskimo1 (esk1) locus accumulated high levels of proline, a compatible osmolyte, but did not exhibit constitutively increased expression of several cold-regulated genes involved in freezing tolerance. RNA gel blot analysis suggested that proline accumulation in esk1 plants was mediated by regulation of transcript levels of genes involved in proline synthesis and degradation. The characterization of esk1 mutants and results from other mutants suggest that distinct signaling pathways activate different aspects of cold acclimation and that activation of one pathway can result in considerable freezing tolerance without activation of other pathways.

Acclimatization↗

Glycine betaine involvement in freezing tolerance and water stress in Arabidopsis thaliana.

Levels of endogenous glycine betaine in the leaves were measured in response to cold acclimation, water stress and exogenous ABA application in Arabidopsis thaliana. The endogenous glycine betaine level in the leaves increased sharply during cold acclimation treatment as plants gained freezing tolerance. When glycine betaine (10 mM) was applied exogenously to the plants as a foliar spray, the freezing tolerance increased from -3.1 to -4.5 degrees C. In addition, when ABA (1 mM) was applied exogenously, the endogenous glycine betaine level and the freezing tolerance in the leaves increased. However, the increase in the leaf glycine betaine level induced by ABA was only about half of that by the cold acclimation treatment. Furthermore, when plants were subjected to water stress (leaf water potential of approximately -1.6 MPa), the endogenous leaf glycine betaine level increased by about 18-fold over that in the control plants. Water stress lead to significant increase in the freezing tolerance, which was slightly less than that induced by the cold acclimation treatment. The results suggest that glycine betaine is involved in the induction of freezing tolerance in response to cold acclimation, ABA, and water stress in Arabidopsis plants.

Journal Article↗

[Maximization of pleasure, the answer to a conflict of motivations].

An experiment has been set up to explore the hypothesis according to which behaviour is determined by the trend to maximize pleasure. Twelve subjects were placed individually in a situation of conflict where the pleasure of playing a videogame clashed with the increasing discomfort of a cold environment. The time lapse tolerated could be predicted from the algebraic sum of the rating of displeasure aroused by the cold environment and the rating of pleasure aroused by the videogame, obtained in other sessions. This result supports the working hypothesis and allows to conclude that pleasure is the common currency of tradeoffs among various motivations.

Cold Temperature↗

Modulation of aversively motivated learning in rats adapted to a cold stressor.

Two experiments studied effects of adaptation to cold water stress upon learning in two aversively motivated (shock) tasks. Experiment 1 found animals previously experiencing cold water stress exhibited more tolerance to shock, having shorter latencies, in an approach-avoidance conflict situation than non-treated controls. In Experiment 2, animals with previous cold water stress experience exhibited longer response latencies than controls in an active-avoidance task. These findings provide evidence that adaptation to a noncontingent stressor can modulate behavioral responses which suggest increased tolerance.

Adaptation, Physiological↗

Detection of polypeptides associated with the cold acclimation process in spinach.

Exposure of spinach (Spinacia oleracea) seedlings to 5 degrees C for several days has previously been shown to induce a greater tolerance to the stresses of extracellular freezing. Associated with this response to low temperature, termed cold acclimation, was a subtle shift in protein synthesis and altered polypeptide composition. Two-dimensional gel electrophoresis was used to study the changes in spinach leaf tissue protein synthesis in an effort to identify polypeptides that may play a central role in the induction of greater freezing tolerance. Through a combination of silver staining, in vivo labeling, and in vitro translation of mRNAs, we identified several high molecular weight polypeptides whose synthesis and presence in spinach leaf tissue were highly correlated with freezing tolerance. Synthesis of these polypeptides was elevated or induced during cold acclimation when freezing tolerance increases, but was rapidly reduced or halted during deacclimation when freezing tolerance declines. The close association of the synthesis of these polypeptides with the induction and loss of freezing tolerance suggested that they could play a role in cold tolerance mechanisms of spinach.

Acclimatization↗

Transcriptome changes for Arabidopsis in response to salt, osmotic, and cold stress.

To identify genes of potential importance to cold, salt, and drought tolerance, global expression profiling was performed on Arabidopsis plants subjected to stress treatments of 4 degrees C, 100 mM NaCl, or 200 mM mannitol, respectively. RNA samples were collected separately from leaves and roots after 3- and 27-h stress treatments. Profiling was conducted with a GeneChip microarray with probe sets for approximately 8,100 genes. Combined results from all three stresses identified 2,409 genes with a greater than 2-fold change over control. This suggests that about 30% of the transcriptome is sensitive to regulation by common stress conditions. The majority of changes were stimulus specific. At the 3-h time point, less than 5% (118 genes) of the changes were observed as shared by all three stress responses. By 27 h, the number of shared responses was reduced more than 10-fold (< 0.5%), consistent with a progression toward more stimulus-specific responses. Roots and leaves displayed very different changes. For example, less than 14% of the cold-specific changes were shared between root and leaves at both 3 and 27 h. The gene with the largest induction under all three stress treatments was At5g52310 (LTI/COR78), with induction levels in roots greater than 250-fold for cold, 40-fold for mannitol, and 57-fold for NaCl. A stress response was observed for 306 (68%) of the known circadian controlled genes, supporting the hypothesis that an important function of the circadian clock is to "anticipate" predictable stresses such as cold nights. Although these results identify hundreds of potentially important transcriptome changes, the biochemical functions of many stress-regulated genes remain unknown.

Adaptation, Physiological↗