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PubMed1985

Sensitization or tolerance to morphine effects after repeated stresses.

Rats were subjected to prolonged footshock, intensive acoustic stress, cold water swim and restraint over a period of 10 days. The analgesic and thermoregulatory properties of morphine (2, 4 and 8 mg/kg, sc.) were tested on the 11th day. Analgesia assessment was performed by means of hot-plate (HP) and tail-flick (TF) tests, and body temperature (Tb) changes was measured. Prolonged footshock and acoustic stress increased the sensitivity to morphine, while repeated restraint lessened morphine's effect. Cold water swim caused ambiguous consequences, facilitated the effect of a small dose of morphine, but reduced that of a large dose. It was concluded that the sensory components of the stressful exposure determine the effects of repeated stress on morphine sensitivity. Whereas painful interventions led to sensitization, and non-painful procedures result in tolerance to morphine's effects. The finding that analgesic and thermoregulatory effects of morphine were simultaneously enhanced supports the contention that the mechanism of sensitization to opiates involves a site where pathways mediating opiate analgesia and thermoregulatory effects converge.

Acoustic Stimulation↗
PubMed2003

Different responses of northern and southern ecotypes of Betula pendula to exogenous ABA application.

We investigated responses of northern and southern ecotypes of silver birch (Betula pendula Roth) to exogenous abscisic acid (ABA) under controlled environmental conditions to determine the role of ABA in cold acclimation and dormancy development. Abscisic acid was sprayed on the leaves and changes in freezing tolerance, determined by the electrolyte leakage test, and bud dormancy were monitored. Applied ABA induced cold acclimation but had no effect on growth cessation in seedlings grown in long day conditions (LD, 24-h photoperiod at 18 degrees C). It enhanced freezing tolerance and accelerated growth cessation in seedlings grown in short day conditions (SD, 12-h photoperiod at 18 degrees C), and slightly enhanced freezing tolerance in seedlings grown at low temperature (LT, 24-h photoperiod at 4 degrees C) in both ecotypes. There were distinct ecotypic differences in ABA-induced cold acclimation and dormancy development. The northern ecotype was more responsive to applied ABA than the southern ecotype, resulting in more rapid development of freezing tolerance in all treatments, and earlier dormancy development in SD. When plants were grown in a photoperiod just above the critical photoperiod for the ecotype (defined as the longest photoperiod that induces growth cessation), applied ABA caused growth cessation and dormancy development. Compared with ABA-treated seedlings grown in SD, dormancy development was delayed in ABA-treated seedlings exposed to a near-critical photoperiod, but even in this treatment dormancy developed faster in the northern ecotype than in the southern ecotype.

Abscisic Acid↗
PubMed2004

Temperature and the cold pressor test.

UNLABELLED: As a method of experimental pain induction, the cold pressor test is thought to mimic the effects of chronic conditions effectively. A survey of previous studies using the cold pressor, however, revealed a lack of standardization and control of water temperature, questioning comparability and reliability. This study reports the influence of temperature on pain tolerance and intensity by using a commercially available circulating water bath. Twenty-six participants (12 men, 14 women) underwent 4 cold pressor trials with temperature order counterbalanced across 1 degrees C, 3 degrees C, 5 degrees C, and 7 degrees C, temperatures representative of the range used in previous literature. After each cold immersion participants rated pain intensity on a visual analogue scale and the McGill Pain Questionnaire. Tolerance times were recorded for each trial. Significant main effects of temperature were found for tolerance time, with higher temperatures resulting in longer times, and pain intensity, with lower temperatures resulting in higher intensities. Gender differences were found, with men tolerating the stimulus for significantly longer than women. It was concluded that small differences in water temperature have a significant effect on pain intensity and tolerance time. The use of cold pressor equipment that ensures a precise constant temperature of circulating water is necessary to ensure comparable and reliable results. PERSPECTIVE: The cold pressor method of experimental pain induction has been widely used in the evaluation of psychological and physiological pain treatments. This article highlights the need for clear methodologic guidelines for the technique and demonstrates that very minor changes in experimental protocol can produce significant differences.

Adult↗
PubMed2005

Functional analysis of rice DREB1/CBF-type transcription factors involved in cold-responsive gene expression in transgenic rice.

The transcription factors dehydration-responsive element-binding protein 1s (DREB1s)/C-repeat-binding factors (CBFs) specifically interact with the DRE/CRT cis-acting element and control the expression of many stress-inducible genes in Arabidopsis. The genes for DREB1 orthologs, OsDREB1A and OsDREB1B from rice, are induced by cold stress, and overexpression of DREB1 or OsDREB1 induced strong expression of stress-responsive genes in transgenic Arabidopsis plants, resulting in increased tolerance to high-salt and freezing stresses. In this study, we generated transgenic rice plants overexpressing the OsDREB1 or DREB1 genes. These transgenic rice plants showed not only growth retardation under normal growth conditions but also improved tolerance to drought, high-salt and low-temperature stresses like the transgenic Arabidopsis plants overexpressing OsDREB1 or DREB1. We also detected elevated contents of osmoprotectants such as free proline and various soluble sugars in the transgenic rice as in the transgenic Arabidopsis plants. We identified target stress-inducible genes of OsDREB1A in the transgenic rice using microarray and RNA gel blot analyses. These genes encode proteins that are thought to function in stress tolerance in the plants. These results indicate that the DREB1/CBF cold-responsive pathway is conserved in rice and the DREB1-type genes are quite useful for improvement of stress tolerance to environmental stresses in various kinds of transgenic plants including rice.

Arabidopsis↗
PubMedDate not supplied

Gene expression during cold and heat shock in wheat.

Translatable messenger RNAs expression was compared in cold- and heat-stressed winter wheat (Triticum aestivum L. 'Fredrick' and 'Norstar') and spring wheat (T. aestivum L. 'Glenlea'). Polyadenylated RNA isolated from the crown and leaf tissues was translated in a wheat germ cell free system and the acidic and basic in vitro products were resolved by two-dimensional SDS-PAGE and autoradiography. The results showed that low temperature stress rapidly induced two groups of mRNAs. The first group was transient in nature and consists of 18 mRNAs that reached their highest levels of induction after 24 h of low temperature exposure and then decreased to undetectable levels. The second group consists of 53 mRNAs that were also induced or increased rapidly, but maintained their levels of expression during the 4 weeks required to induce freezing tolerance. Among those, at least 34 were expressed at higher levels in the freezing tolerant winter wheat compared with the less tolerant spring wheat. This suggests a possible relation between the expression of these mRNAs and the capacity of each genotype to develop freezing tolerance. In the case of heat shock, 50 mRNAs were induced or increased after 3 h at 40 degrees C. Among these, the expression of only six mRNAs was altered in a similar manner in the three genotypes by both treatments. The remaining mRNAs code for typical heat shock proteins which are different from those induced by low temperature. None of these mRNAs has been associated with the development of freezing tolerance. These results suggest that heat and cold stress are controlled by different genetic systems.

Autoradiography↗
PubMed1992

Acute exacerbations in severe COLD patients. Treatment using positive pressure ventilation by nasal mask.

We retrospectively evaluated the clinical effectiveness of a treatment schedule with intermittent positive pressure ventilation via nasal mask in 49 patients with acute exacerbations of COLD. According to the ability to successfully tolerate a preliminary trial with NIPPV, patients were submitted either to standard treatment plus NIPPV (25 patients) or to ST alone (24 patients). The ST consisted of medical, oxygen and physical therapy. The NIPPV was delivered by a volume cycled ventilator in control mode at least 4 h a day for five consecutive days a week, for three weeks. Comparison of baseline with measurements performed after 10 and 21 days of treatment respectively showed a significant improvement in PaO2 and in PaCO2 in both groups. After 21 days of treatment, VC, FEV1, inspiratory muscle strength, and dyspnea significantly improved in both groups. No significant difference was found between groups at any time of treatment. We conclude that the treatment schedule of NIPPV used is not more effective than ST alone in acute exacerbations of COLD.

Aged↗
PubMed1987

Intranasally and orally administered antihistamine treatment of experimental rhinovirus colds.

Although antihistamines are widely used for symptomatic treatment of seasonal (allergic) rhinitis, the role of histamines in the pathogenesis of infectious rhinitis is not clear. Two antihistamines, orally administered chlorpheniramine maleate (CM) and diphenhydramine hydrochloride (DH) administered by intranasal spray, were used under double-blinded, randomized, placebo-controlled conditions to assess both tolerance and efficacy in volunteers with experimental rhinovirus (RV) colds. In the initial trial, CM (4.0 mg per treatment) was ingested 4 times daily for 4 days beginning 24 h after intranasal inoculation of RV type 29 in susceptible volunteers. In the second trial, DH was sprayed intranasally 4 times daily (2 mg per treatment) for 5 days beginning 24 h after inoculation of RV type 39. Clinical colds occurred in 60% of the CM group (n = 13) and 73% of the placebo (n = 15) in the first study, and in 66% of the DH group (n = 12) compared with 81% in the placebo group (n = 11) in the second. Both CM and DH were well tolerated but had no significant effects on nasal symptoms or nasal mucus production. The findings provide additional evidence against an important role for histamine in the pathogenesis of nasal symptomatology in rhinovirus colds.

Administration, Intranasal↗
PubMed2006

R-Ras3/(M-Ras) is involved in thermal adaptation in the critical period of thermal control establishment.

Neuroanatomically, the body temperature is balanced by the preoptic anterior hypothalamus (PO/AH) and controlled by thermosensitive neurons. Hot or cold exposure during the critical period of temperature control development causes a plastic change in the ratio between hot- and cold-sensitive cells and can modulate temperature tolerance. In this project, mRNA fingerprinting was used to identify the proteins involved in thermal adaptation in 3-day-old chicks. Fifteen genes were induced, among which were NADH dehydrogenase, protocadherin, anolase alpha, 14-3-3epsilon, and R-Ras3. The role of each of these genes is potentially interesting and requires detailed evaluation, but since the present working hypothesis assumed neuronal remodeling, we concentrated on the role of R-Ras3/(M-Ras), which is uniquely expressed in the brain and whose physiological role has not been described. In the present study, R-Ras3 expression during thermal conditioning was investigated by several molecular techniques and its mRNA was found to be induced in the PO/AH with a tenfold peak after 12 h of heat conditioning and a fourfold increase after 6 h of cold conditioning. To improve our understanding of thermal adaptation-related signal transduction, we screened for changes in the expression of transcription factors that were implicated with the Ras gene family, and found that both jun mRNA expression and Jun phosphorylation were induced after 30 min of temperature conditioning. Taken together, the present findings correlate the R-Ras3-jun pathway with thermal-control establishment.

Acclimatization↗
PubMed1976

A serum factor in aspirin intolerance disease.

Direct and indirect intradermal serum challenge with aspirin intolerant sera in both aspirin tolerant and intolerant patients demonstrated a heat, cold and storage stable serum factor capable of inducing acute anti-hemostatic effects and in some aspirin intolerant patients exacerbation of brief induced clinical symptoms. The data supports a hypothesis for possible induced, conformationally altered gamma globulin resulting from low molecular weight chemical exposures such as aspirin with ensuing recognition by a genetically determined subpopulation of B-lymphocytes with surface membrane receptors avid for the Fc portion of altered gamma globulin or some conformationally altered gamma globulin fraction leading to immune and/or interprotein complexes with subsequent alterations of adrenergic, cholinergic and/or metabolic pharmacologic pathways.

Aspirin↗
PubMed1992

Cloning, characterization, and expression of a cDNA encoding a 50-kilodalton protein specifically induced by cold acclimation in wheat.

We have isolated, sequenced, and expressed a cold-specific cDNA clone, Wcs120, that specifically hybridizes to a major mRNA species of approximately 1650 nucleotides from cold-acclimated wheat (Triticum aestivum L.). The accumulation of this mRNA was induced in less than 24 hours of cold treatment, and remained at a high steady-state level during the entire period of cold acclimation in the two freezing-tolerant genotypes of wheat tested. The expression of Wcs120 was transient in a less-tolerant genotype even though the genomic organization of the Wcs120 and the relative copy number were the same in the three genotypes. The mRNA level decreased rapidly during deacclimation and was not induced by heat shock, drought, or abscisic acid. The Wcs120 cDNA contains a long open reading frame encoding a protein of 390 amino acids. The encoded protein is boiling stable, highly hydrophilic, and has a compositional bias for glycine (26.7%), threonine (16.7%), and histidine (10.8%), although cysteine, phenylalanine, and tryptophan were absent. The WCS120 protein contains two repeated domains. Domain A has the consensus amino acid sequence GEKKGVMENIKEKLPGGHGDHQQ, which is repeated 6 times, whereas domain B has the sequence TGGTYGQQGHTGTT, which is repeated 11 times. The two domains were also found in barley dehydrins and rice abscisic acid-induced protein families. The expression of this cDNA in Escherichia coli, using the T(7) RNA polymerase promoter, produced a protein of 50 kilodaltons with an isoelectric point of 7.3, and this product comigrated with a major protein synthesized in vivo and in vitro during cold acclimation.

Journal Article↗
PubMed1998

Characterization of a gene for spinach CAP160 and expression of two spinach cold-acclimation proteins in tobacco.

The cDNA sequence for CAP160, an acidic protein previously linked with cold acclimation in spinach (Spinacia oleracea L.), was characterized and found to encode a novel acidic protein of 780 amino acids having very limited homology to a pair of Arabidopsis thaliana stress-regulated proteins, rd29A and rd29B. The lack of similarity in the structural organization of the spinach and Arabidopsis genes highlights the absence of a high degree of conservation of this cold-stress gene across taxonomic boundaries. The protein has several unique motifs that may relate to its function during cold stress. Expression of the CAP160 mRNA was increased by low-temperature exposure and water stress in a manner consistent with a probable function during stresses that involve dehydration. The coding sequences for CAP160 and CAP85, another spinach cold-stress protein, were introduced into tobacco (Nicotiana tabacum) under the control of the 35S promoter using Agrobacterium tumefaciens-based transformation. Tobacco plants expressing the proteins individually or coexpressing both proteins were evaluated for relative freezing-stress tolerance. The killing temperature for 50% of the cells of the transgenic plants was not different from that of the wild-type plants. As determined by a more sensitive time/temperature kinetic study, plants expressing the spinach proteins had slightly lower levels of electrolyte leakage than wild-type plants, indicative of a small reduction of freezing-stress injury. Clearly, the heterologous expression of two cold-stress proteins had no profound influence on stress tolerance, a result that is consistent with the quantitative nature of cold-stress-tolerance traits.

Adaptation, Physiological↗
PubMed2001

Hyperalgesic responses in methadone maintenance patients.

Opioid substitution treatment for dependence may alter sensitivity to pain. Previous studies on pain sensitivity in methadone maintenance patients have yielded contradictory results. This study compared nociceptive responses between 16 patients on stable, once daily, doses of methadone and 16 matched control subjects. Two types of nociceptive stimuli were used: (1) electrical stimulation; and (2) a cold pressor test. Two parameters were measured: detection for onset of pain, and pain tolerance. Methadone patients were tested over an inter-dosing period: at the time of trough plasma methadone concentration (0 h), and 3 h after their daily dose. Control subjects were tested twice 3 h apart. Blood samples were collected to determine plasma methadone concentration. In methadone patients, trough to peak increases in mean R-(-)- and S-(+)-methadone concentrations (118 and 138 ng/ml to 185 and 259 ng/ml, respectively) resulted in significant increases in pain detection and tolerance values for both nociceptive stimuli. Using electrical stimulation, methadone patients' pain tolerance values were lower than controls at 0 h, but higher than controls at 3 h; no significant differences in pain detection values were found. For the cold pressor test, methadone patients detected pain significantly earlier than controls at 0 h, and were also substantially less pain tolerant than controls at both 0 and 3 h. There were no significant differences in pain detection values between the two groups at 3 h. Pain tolerance to pain detection ratios for methadone patients were significantly lower than controls for the cold pressor test at 0 and 3 h, and for electrical stimulation at 0 h only. In summary, the relative pain sensitivity of methadone maintenance patients is determined by the nature of the nociceptive stimulus (e.g. cold pressor test versus electrical stimulation), the plasma methadone concentration (trough versus peak plasma concentration), and whether thresholds are determined for detection of pain or pain tolerance. Although responding to changes in plasma methadone concentration, maintenance patients are markedly hyperalgesic to pain induced by the cold pressor test.

Adult↗
PubMed1989

The effect of pH on the viability of hypothermically stored rat hepatocytes.

Hepatocytes isolated from the rat liver were stored for up to 72 hr at 4 degrees C in a tissue culture medium (Liebovitz-15) at different pH values to determine how pH affects hepatocyte viability. This is a model to simulate cold storage of livers for transplantation and determine the optimal pH for maintenance of liver cell function. The cells were stored in the absence of oxygen. At the end of cold storage the percentage of the total cellular LDH released into the extracellular medium was used as a measure of hepatocyte viability. Also, lactate dehydrogenase (LDH) release was determined in hepatocytes incubated at normothermia (37 degrees C) for 90 min following 72 hr of cold storage. The results demonstrate that hepatocytes tolerate a wide range of pH values in the storage medium and that only about 10% of the total LDH was released from hepatocytes stored up to 72 hr at pH's from 5.0 to 8.0. Normothermic incubation, however, demonstrated that the pH of the storage medium affected viability. After 48 hr of storage only hepatocytes stored at pH values from 7.0 to 8.0 remained viable (LDH release similar to that of freshly incubated hepatocytes = 28 +/- 7.2%). After 72 hr of storage and 90 min of normothermic incubation, hepatocytes incubated at all pH values studied were nonviable (greater than 60% release of LDH). These results suggest that the optimal pH for storage of hepatocytes at 4 degrees C is near neutrality (7.0 to 7.4).

Animals↗
PubMed2006

The analgesic effect of tramadol after intravenous injection in healthy volunteers in relation to CYP2D6.

Tramadol analgesia results from a monoaminergic effect by tramadol itself and an opioid effect of its metabolite (+)-M1 formed by O-demethylation of tramadol by CYP2D6. In this study we sought to determine the impact of (+)-M1 on the analgesic effect of tramadol evaluated by experimental pain models. The effect of an IV injection of 100 mg tramadol on experimental pain was studied 15-90 min after dosing in volunteers, 10 extensive metabolizers with CYP2D6 and 10 poor metabolizers without CYP2D6 in 2 placebo-controlled trials. The pain tests included detection and tolerance threshold to single electrical sural nerve stimulation, pain summation threshold to repetitive electrical sural nerve stimulation (temporal summation), and the cold pressor test. In extensive metabolizers, tramadol reduced discomfort experienced during the cold pressor test (P = 0.002). In poor metabolizers, the pain tolerance thresholds to sural nerve stimulation were increased (P = 0.04). (+)-M1 could be detected in the serum samples from all extensive metabolizers except one, but (+)-M1 was below the limit of determination in all poor metabolizers. The opioid effect of (+)-M1 appears to contribute to the analgesic effect of tramadol, but the monoaminergic effect of tramadol itself seems to create an analgesic effect.

Adult↗
PubMed1992

Development of tolerance to the hormonal effects of morphine without changes in the aminergic functions in the brain of the rat.

The effect of morphine on cold-stimulated secretion of TSH and prolactin was studied in male rats, both in acute studies and after the chronic administration of morphine for 14 days (twice a day with increasing doses). The duration of the stimulatory effect of a single dose of morphine on secretion of prolactin was shorter (less than 2 hr) than its inhibitory effect on cold-stimulated secretion of TSH (over 2 hr). In the rats pretreated with morphine, a tolerance to the depressant effect of TSH of the challenge dose of morphine was seen at 2 hr but not at 1 hr after the injection. In contrast, a tolerance to the stimulatory effect of morphine on prolactin was seen at 1 hr after the acute dose of morphine. The minor alterations of the hypothalamic amine neurotransmitters and their metabolites did not correlate with the hormonal responses or to the development of tolerance.

Animals↗
PubMed2006

Deciphering the regulatory mechanisms of abiotic stress tolerance in plants by genomic approaches.

Environmental constraints that include abiotic stress factors such as salt, drought, cold and extreme temperatures severely limit crop productivity. Improvement of crop plants with traits that confer tolerance to these stresses was practiced using traditional and modern breeding methods. Molecular breeding and genetic engineering contributed substantially to our understanding of the complexity of stress response. Mechanisms that operate signal perception, transduction and downstream regulatory factors are now being examined and an understanding of cellular pathways involved in abiotic stress responses provide valuable information on such responses. This review presents genomic-assisted methods which have helped to reveal complex regulatory networks controlling abiotic stress tolerance mechanisms by high-throughput expression profiling and gene inactivation techniques. Further, an account of stress-inducible regulatory genes which have been transferred into crop plants to enhance stress tolerance is discussed as possible modes of integrating information gained from functional genomics into knowledge-based breeding programs. In addition, we envision an integrative genomic and breeding approach to reveal developmental programs that enhance yield stability and improve grain quality under unfavorable environmental conditions of abiotic stresses.

Adaptation, Physiological↗
PubMedDate not supplied

Metabolic adaptations of overwintering European common lizards (Lacerta vivipara).

The European common lizard Lacerta vivipara, a reptile of cold-temperate climates, provides us an interesting model of low-temperature adaptation. Indeed its unique cold-hardiness strategy, which employs both freeze tolerance and freeze avoidance, may be seen as the primary reason for its large distribution, which extends from Spain to beyond the Arctic circle. To study the metabolism supporting this capacity, we used three techniques: two techniques of calorimetry (oxygen consumption and thermogenesis) and nuclear magnetic resonance spectroscopy. These techniques were used to examine the metabolic balance and the different molecular pathways used between three different periods through the year (September, January, and May). The results show a significant 20% augmentation of winter anaerobic metabolism compared to other periods of the year. This is mainly because of an activation of the lactic fermentation pathway leading to an increase of lactate concentration (>34% in winter). Furthermore, glucose, which increases some 245% in winter, is used as antifreeze and metabolic substrate. Furthermore, this study provides evidence that the physiological adaptations of the common lizard differ from those of other ectotherms such as Rana sylvatica. Concentrations of alanine and glycerol, commonly used as antifreeze by many overwintering ectotherms, do not increase during winter.

Adaptation, Physiological↗
PubMed1995

Effect of cold anoxia and cryopreservation on metabolic and contractile functions of human mammary artery.

The ability of human internal mammary artery smooth muscle cells to maintain histoenzymatic activity and contractile response after various times of cold anoxia prior to and following cryostorage was evaluated. The results showed that the enzyme histochemical status of human mammary arteries was largely unchanged after both cold anoxia and cryopreservation. Neither in fresh nor in cryopreserved mammary arteries did cold anoxia for up to 24 h change maximal contractile responses to potassium depolarization and norepinephrine. However, compared to unfrozen controls, the contractile responses were significantly reduced in cryopreserved mammary arteries. In conclusion, after cryopreservation of human mammary arteries, the enzyme activities were globally maintained, whereas the contractile responses were reduced. For up to 24 h after harvesting cold anoxia at 4 degrees C is well tolerated and allows preservation of metabolic and functional properties of these arteries.

Cell Hypoxia↗