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Exposure of rats to alcohol in utero alters drug sensitivity in adulthood.

Pregnant rats were intubated with alcohol (ethanol, 3 grams per kilogram) twice daily throughout gestation. Control animals received solutions of isocaloric sucrose. At birth, offspring were placed with untreated surrogate dams. Beginning at 6 months of age, the offspring were tested for their thermogenic responsiveness to various drugs and to cold. Prenatal exposure to alcohol resulted in tolerance to alcohol and cross-tolerance to pentobarbital and diazepam but did not affect responsiveness to cold. This pattern of effects suggest that prenatal exposure to alcohol produces specific long-term effects on the neural mechanisms underlying drug tolerance.

Animals↗

Cold legs: a potential indicator of negative outcome in the rehabilitation of patients with patellofemoral pain syndrome.

PURPOSE: The purpose of this paper is to explore the link between a poor outcome in response to an exercise based approach to physiotherapy, in patients with patellofemoral dysfunction and a self-report of legs feeling cold even in warm surroundings. SCOPE: The study was carried out in the physiotherapy outpatients department of Burnley General Hospital, Lancashire, UK with 87 consecutively referred patients with a diagnosis of patellofemoral pain syndrome being assessed for suitability for entry into the study. Of these 77 entered the study with 14 (18%), of these responding 'Yes' to the question 'Do your legs feel cold even in warm surroundings?' All patients were assessed using four outcome measures prior to the commencement of a standardised rehabilitation programme consisting of lower limb biarticular muscle stretching, vastus medialis training and patella taping or biofeedback. The patients were reassessed using the same outcome measures 3 months after completing their course of treatment. CONCLUSIONS: Patients who responded 'Yes' to the question 'Do your legs feel cold even in warm surroundings?' reported higher pain levels and tolerated less physical activity than non-cold sufferers at initial assessment, these differences were statistically significant. The cold sufferers showed less improvement on all of the outcome measures although the differences between the two groups only reached statistical significance for one of the outcome measures. The implications of this in relation to clinical practice are discussed.

Adolescent↗

Accumulation of small heat-shock protein homologs in the endoplasmic reticulum of cortical parenchyma cells in mulberry in association with seasonal cold acclimation.

Cortical parenchyma cells of mulberry (Morus bombycis Koidz.) trees acquire extremely high freezing tolerance in winter as a result of seasonal cold acclimation. The amount of total proteins in endoplasmic reticulum (ER)-enriched fractions isolated from these cells increased in parallel with the process of cold acclimation. Protein compositions in the ER-enriched fraction also changed seasonally, with a prominent accumulation of 20-kD (WAP20) and 27-kD (WAP27) proteins in winter. The N-terminal amino acid sequence of WAP20 exhibited homology to ER-localized small heat-shock proteins (smHSPs), whereas that of WAP27 did not exhibit homology to any known proteins. Like other smHSPs, WAP20 formed a complex of high molecular mass in native-polyacrylamide gel electrophoresis. Furthermore, not only WAP20 but also 21-kD proteins reacted with antibodies against WAP20. Fractionation of the crude microsomes by isopycnic sucrose-gradient centrifugation revealed that both WAP27 and WAP20 were distributed on a density corresponding to the fractions with higher activity of ER marker enzyme, suggesting localization of these proteins in the ER. When ER-enriched fractions were treated with trypsin in the absence of detergent, WAP20 and WAP27 were undigested, suggesting localization of these proteins inside the ER vesicle. The accumulation of a large quantity of smHSPs in the ER in winter as a result of seasonal cold acclimation indicates that these proteins may play a significant role in the acquisition of freezing tolerance in cortical parenchyma cells of mulberry trees.

Acclimatization↗

Efficacy and tolerability of intravenous valproic acid in acute adolescent migraine.

OBJECTIVE: To describe the efficacy and tolerability of rapid intravenous valproic acid (VPA) infusions in children with severe migraine headache. BACKGROUND: Intravenous VPA is an emerging treatment option for acute migraine headache. Adult data suggests both efficacy and tolerability of rapid VPA infusions as abortive therapy, but little data exist in children. METHODS: We conducted a retrospective chart review of all children who received intravenous VPA at The Children's Hospital Headache Clinic during an 18--month study period. Baseline intensity of headache pain, time at which maximum relief was attained, pain reduction following therapy, dose and duration of VPA infusion(s), patient's pulse, blood pressure, respiratory rate, and pulse oximetry were collected. Adverse events were also recorded. RESULTS: Thirty-one children (age=15+/- 2 years; 81% female) requiring 58 clinic visits and 71 VPA infusions were included. Most visits (n=45; 78%) resulted in only one dose of VPA (976+/- 85 mg infused over 12+/- 4 minutes) for desired pain relief. Percent pain reduction in those children was 39.8%, with time to maximum relief of 63+/- 31 minutes. Some children required a second dose of 500 mg (n=13 visits; 22%), that was infused over 14+/- 6 minutes and produced a 57% reduction in pain intensity from baseline. VPA infusions were well tolerated. Adverse events described included cold sensation (1), dizziness (3), nausea (1), possible absence seizure (1), paraesthesia (2), and tachycardia (2). CONCLUSIONS: Rapid infusion of intravenous VPA is generally well tolerated and may play a role in the management of children with acute migraine headache. Prospective, controlled trials to further investigate this treatment in children are warranted.

Acute Disease↗

Emotional stability and facial activity as predictors for pain tolerance.

40 subjects were given the Cold Pressor Test. There were large individual differences in the time subjects were willing to keep their hands immersed in the cold water. Predictors indicated for these differences were sex, emotional stability, and facial activity during the test. Emotional stability was measured by means of questionnaire scales and facial activity by ratings on the basis of videotapes.

Adolescent↗

Expression of a bifunctional fusion of the Escherichia coli genes for trehalose-6-phosphate synthase and trehalose-6-phosphate phosphatase in transgenic rice plants increases trehalose accumulation and abiotic stress tolerance without stunting growth.

Trehalose plays an important role in stress tolerance in plants. Trehalose-producing, transgenic rice (Oryza sativa) plants were generated by the introduction of a gene encoding a bifunctional fusion (TPSP) of the trehalose-6-phosphate (T-6-P) synthase (TPS) and T-6-P phosphatase (TPP) of Escherichia coli, under the control of the maize (Zea mays) ubiquitin promoter (Ubi1). The high catalytic efficiency (Seo et al., 2000) of the fusion enzyme and the single-gene engineering strategy make this an attractive candidate for high-level production of trehalose; it has the added advantage of reducing the accumulation of potentially deleterious T-6-P. The trehalose levels in leaf and seed extracts from Ubi1::TPSP plants were increased up to 1.076 mg g fresh weight(-1). This level was 200-fold higher than that of transgenic tobacco (Nicotiana tabacum) plants transformed independently with either TPS or TPP expression cassettes. The carbohydrate profiles were significantly altered in the seeds, but not in the leaves, of Ubi1::TPSP plants. It has been reported that transgenic plants with E. coli TPS and/or TPP were severely stunted and root morphology was altered. Interestingly, our Ubi1::TPSP plants showed no growth inhibition or visible phenotypic alterations despite the high-level production of trehalose. Moreover, trehalose accumulation in Ubi1::TPSP plants resulted in increased tolerance to drought, salt, and cold, as shown by chlorophyll fluorescence and growth inhibition analyses. Thus, our results suggest that trehalose acts as a global protectant against abiotic stress, and that rice is more tolerant to trehalose synthesis than dicots.

Adaptation, Physiological↗

Physiological responses to freezing in hatchlings of freeze-tolerant and -intolerant turtles.

Freeze tolerance is a complex cold-hardiness adaptation that has independently evolved in a diverse group of organisms, including several ectothermic vertebrates. Because little is known about the mechanistic basis for freeze tolerance in reptiles, we compared responses to experimental freezing in winter-acclimatized hatchlings representing nine taxa of temperate North American turtles, including ones that tolerated freezing and others that did not. Viability rates of hatchlings frozen to -3 degrees C for 72 h ranged from 0 to 100%. Tolerance to freezing was poor in Sternotherus odoratus, Graptemys geographica and Trachemys scripta, intermediate in Chelydra serpentina, and high in Emydoidea blandingii, Chrysemys picta bellii, C. p. marginata, Malaclemys terrapin, and Terrapene ornata, and generally reflected the winter thermal ecology of each taxon. Plasma activity of lactate dehydrogenase (LDH), a novel in vivo index of freeze/thaw damage, corroborated viability assessments and demonstrated that cryoinjury occurred even in surviving turtles. Irrespective of taxon, cryoinjury tended to be higher in smaller individuals and in those having relatively low water contents; however, bases for these associations were not apparent. Screening for certain organic osmolytes that might promote freezing survival by colligatively reducing ice content and limiting cell dehydration showed that the plasma of unfrozen (control) turtles contained small quantities of glucose (1.3-5.8 mmol l(-1)) and lactate (0.6-3.2 mmol l(-1)) and modest amounts of urea (range of mean values for all taxa 8.2-52.3 mmol l(-1)). Frozen/thawed turtles of all taxa accumulated modest amounts of glucose and lactate that jointly raised the plasma solute concentration by 30-100 mmol l(-1). We conclude that organic osmolytes accumulated both before and during freezing may promote survival in species that have evolved a tolerance to freezing, but are not necessarily accumulated for that purpose.

Adaptation, Physiological↗

Effects of low temperature on egg and larval stages of the lesser appleworm (Lepidoptera: Tortricidae).

Lesser appleworm, Grapholita prunivora (Walsh), eggs were subjected to cold storage conditions at 2.0 degrees C +/- 0.2 degrees C for 0-90 d. The most tolerant embryonic stage was the blackhead stage (96-120-h-old eggs) with an LT90 of 25 d. The four instars of lesser appleworm were subjected to cold storage conditions at 2.0 degrees C +/- 0.2 degrees C for 0-280 d. The fourth instar was the most tolerant to cold storage, with an LT90 of 71.5 d. Exposure to low temperatures such as those commonly used for fruit storage shows promise as an alternative to fumigation for lesser appleworm eggs and larvae on apples and pears after harvest.

Animals↗

Evaluation of live attenuated cold-adapted influenza B/Yamagata/16/88 reassortant virus vaccine in healthy adults.

The safety and immunogenicity of a new cold-adapted reassortant influenza B/Yamagata/10/88 virus vaccine was evaluated in healthy young adults with low levels of preinoculation serum antibody to the vaccine virus, and symptoms and viral shedding after vaccination were compared with those following administration of the homologous B/Yamagata/88 wild-type virus. Administration of the cold-adapted virus was well tolerated and resulted in a significantly lower frequency of respiratory symptoms and viral shedding than did the wild-type virus. Twelve of 14 subjects who received the cold-adapted virus had an antibody response to the vaccine virus following vaccination. These data suggest that the B/Yamagata/88 virus is safe and immunogenic in seronegative adults and support the concept that the attenuation phenotype can be transferred reliably and reproducibly to successive new influenza B wild-type viruses along with the six internal gene segments of the cold-adapted influenza B/Ann Arbor/1/66 master vaccine virus.

Adaptation, Physiological↗

Efficacy and tolerability of ebastine 10 mg plus pseudoephedrine 120 mg in the symptomatic relief of the common cold.

Background: The objective of this multicenter, parallel, double-blind, placebo-controlled clinical trial was to determine the efficacy and tolerability of the combination of ebastine 10 mg plus pseudoephedrine 120 mg once daily after 3 days of treatment in the symptomatic relief of patients with a common cold. Methods: The principal variable studied was the evaluation of overall efficacy and secondary variables were improvement of the patient, evolution of symptoms, disposition of the patient to take the medication again, and variation in nasal peak flow. Results: The percentage of subjects showing a good or excellent treatment efficacy was significantly higher in the group treated with ebastine plus pseudoephedrine (75.8%) than in the group treated with placebo (57.6%; p<0.001). Statistically significant differences were also found in favor of ebastine plus pseudoephedrine when comparing the changes in the sum of scores for nasal and ocular symptoms (p<0.006) or total symptoms (p<0.0016). The tolerability of the active treatment studied was good; that is, no significant differences were found between ebastine 10 mg plus pseudoephedrine 120 mg and placebo. Most adverse events described were slight or moderate in intensity, and no serious adverse events were reported. Conclusions: The combination of ebastine 10 mg immediate release and pseudoephedrine 120 mg sustained release was found effective in the symptomatic treatment of patients suffering from a common cold and as safe as placebo.

Journal Article↗

Components of the Arabidopsis C-repeat/dehydration-responsive element binding factor cold-response pathway are conserved in Brassica napus and other plant species.

Many plants increase in freezing tolerance in response to low, nonfreezing temperatures, a phenomenon known as cold acclimation. Cold acclimation in Arabidopsis involves rapid cold-induced expression of the C-repeat/dehydration-responsive element binding factor (CBF) transcriptional activators followed by expression of CBF-targeted genes that increase freezing tolerance. Here, we present evidence for a CBF cold-response pathway in Brassica napus. We show that B. napus encodes CBF-like genes and that transcripts for these genes accumulate rapidly in response to low temperature followed closely by expression of the cold-regulated Bn115 gene, an ortholog of the Arabidopsis CBF-targeted COR15a gene. Moreover, we show that constitutive overexpression of the Arabidopsis CBF genes in transgenic B. napus plants induces expression of orthologs of Arabidopsis CBF-targeted genes and increases the freezing tolerance of both nonacclimated and cold-acclimated plants. Transcripts encoding CBF-like proteins were also found to accumulate rapidly in response to low temperature in wheat (Triticum aestivum L. cv Norstar) and rye (Secale cereale L. cv Puma), which cold acclimate, as well as in tomato (Lycopersicon esculentum var. Bonny Best, Castle Mart, Micro-Tom, and D Huang), a freezing-sensitive plant that does not cold acclimate. An alignment of the CBF proteins from Arabidopsis, B. napus, wheat, rye, and tomato revealed the presence of conserved amino acid sequences, PKK/RPAGRxKFxETRHP and DSAWR, that bracket the AP2/EREBP DNA binding domains of the proteins and distinguish them from other members of the AP2/EREBP protein family. We conclude that components of the CBF cold-response pathway are highly conserved in flowering plants and not limited to those that cold acclimate.

Acclimatization↗

Overexpression of the Arabidopsis CBF3 transcriptional activator mimics multiple biochemical changes associated with cold acclimation.

We further investigated the role of the Arabidopsis CBF regulatory genes in cold acclimation, the process whereby certain plants increase in freezing tolerance upon exposure to low temperature. The CBF genes, which are rapidly induced in response to low temperature, encode transcriptional activators that control the expression of genes containing the C-repeat/dehydration responsive element DNA regulatory element in their promoters. Constitutive expression of either CBF1 or CBF3 (also known as DREB1b and DREB1a, respectively) in transgenic Arabidopsis plants has been shown to induce the expression of target COR (cold-regulated) genes and to enhance freezing tolerance in nonacclimated plants. Here we demonstrate that overexpression of CBF3 in Arabidopsis also increases the freezing tolerance of cold-acclimated plants. Moreover, we show that it results in multiple biochemical changes associated with cold acclimation: CBF3-expressing plants had elevated levels of proline (Pro) and total soluble sugars, including sucrose, raffinose, glucose, and fructose. Plants overexpressing CBF3 also had elevated P5CS transcript levels suggesting that the increase in Pro levels resulted, at least in part, from increased expression of the key Pro biosynthetic enzyme Delta(1)-pyrroline-5-carboxylate synthase. These results lead us to propose that CBF3 integrates the activation of multiple components of the cold acclimation response.

Acclimatization↗

Catastrophizing as a mediator of sex differences in pain: differential effects for daily pain versus laboratory-induced pain.

Sex differences in the experience of pain have been widely reported, with females generally reporting more frequent clinical pain and demonstrating greater pain sensitivity. However, the mechanisms underpinning such differences, while subject to intense speculation, are not well-characterized. Catastrophizing is a cognitive and affective process that relates strongly to enhanced reports of pain and that varies as a function of sex. It is thus a prime candidate to explain sex differences; indeed, several prior studies offer evidence that controlling for catastrophizing eliminates the gap between men and women in reported pain. We recruited 198 healthy young adults (115 female) who took part in laboratory studies of pain responses, including thermal pain, cold pain, and ischemic pain, and who also completed questionnaires assessing catastrophizing, mood, and day-to-day painful symptoms (e.g. headache, backache). Women reported greater levels of catastrophizing, more recent painful symptoms, and demonstrated lower pain thresholds and tolerances for noxious heat and cold relative to men. Mediational analyses suggested that after controlling for negative mood, catastrophizing mediated the sex difference in recent daily pain but did not mediate the much larger sex differences in pain threshold and tolerance. These findings highlight the role of catastrophizing in shaping pain responses, as well as illuminating potentially important differences between experimental pain assessment and the clinical experience of pain.

Adaptation, Psychological↗

Prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges.

Following a tolerance study, double-blind placebo controlled trials were conducted to determine the prophylactic effect of zinc gluconate lozenges on rhinovirus challenge and, in a third study, their therapeutic efficacy when given at the start of colds caused by virus inoculation was tested. In the prophylaxis study a total of 57 volunteers received lozenges of either zinc gluconate (23 mg) (29 volunteers) or matched placebo (28 volunteers) every 2 h while awake during a period of four and a half days. They were challenged with 10(2) tissue culture infecting dose (TCID50) of human rhinovirus 2 (HRV-2) on the second day of medication, and were monitored daily for symptoms and signs of colds and laboratory evidence of infection. Zinc reduced the total mean clinical score from 8.2 in the placebo group to 5.7 and the reduction of the mean clinical score was statistically significant on the second day after virus challenge. In the therapeutic study 69 volunteers were inoculated with 10(2) TCID50 of HRV-2 and those who developed cold symptoms were randomly allocated to receive either zinc gluconate lozenges (six volunteers) or matched placebo lozenges (six volunteers) every two hours they were awake for six days. Treatment of colds with zinc reduced the mean daily clinical score and this was statistically significant on the fourth and fifth day of medication. Similarly, medication also reduced the mean daily nasal secretion weight and total tissue count and these reductions were statistically significant on days two and six for nasal secretion weights and days four to six of medication for tissue counts when compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The history of cold hardiness research in terrestrial arthropods.

R.A.F. Reaumur in 1736 was the first entomologist to observe that some insects can tolerate freezing, while others cannot. The first reviews on insect cold hardiness were published by P. Bachmetjew who also discovered supercooling in insects. Authors like W. Robinson realised that piercing the cuticle changed the supercooling capacity and N.M. Payne pointed out that there are great seasonal variations in insect cold hardiness. In the early literature, references were frequently made to plant cold hardiness, in which theories on tolerance to freezing were more elaborated. A modern approach to the studies of insect cold hardiness was initiated by R.W. Salt. The number of reports increased enormously in the 1960's and 1970's. During the last 20 to 30 years new insight has appeared from studies on ice nucleators, antifreeze proteins, ice-nucleating bacteria, desiccation and biochemistry of cryoprotectants.

Journal Article↗

Effect of humor and tragedy on discomfort tolerance.

Following exposure to comedy, tragedy, or control stimuli, respondents took the cold pressor test. Men, but not women (ns = 36), tolerated icy water for longer periods of time after comedy and tragedy than after control stimuli.

Adult↗

A survey of genes differentially expressed during long-term heat-induced chilling tolerance in citrus fruit.

Long-term storage at low, non-freezing, temperature (1.5 degrees C) induces chilling injury in fruit of Fortune mandarin (Citrus clementina Hort. Ex Tanaka x Citrus reticulata, Blanco), manifested as pitting and brown depressed areas that may end up with local cell death. Pre-conditioning of fruit for 3 days at 37 degrees C prevented chilling injury. The use of suppression subtractive hybridization permitted the isolation of genes differentially expressed in heat-conditioned fruit exposed to chilling conditions, which may be candidates for heat-induced chilling tolerance. Northern blot analysis revealed that some genes were up-regulated by prolonged heat (3 days/37 degrees C) and their expression persisted in fruit cells upon subsequent chilling exposure. The expression of other genes was specifically induced by the combination of heat and cold. Among the putative tolerance-associated genes, we identified two transcription factors of the WRKY family and one TFIIB factor. Heat conditioning also altered the expression of genes encoding proteins involved in secondary metabolism, cell wall modification, oxidative damage and other stress-responsive proteins. These results illustrate the complexity of molecular mechanisms operating during heat-induced chilling tolerance in citrus fruit.

Acclimatization↗