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Intranasally administered atropine methonitrate treatment of experimental rhinovirus colds.

The role of parasympathetic/cholinergic mechanisms in the syndrome of the common cold is not clear. Under double-blind, randomized, placebo-controlled conditions, we intranasally administered the anticholinergic atropine methonitrate (AM) to assess its tolerance in uninfected adults and therapeutic efficacy in volunteers with experimental rhinovirus (RV) colds. Healthy adults given sprays of AM intranasally 250 or 500 micrograms 4 times a day for 5 days developed nasal dryness and systemic side effects more often than did placebo (P) recipients. In 2 separate challenge studies, treatments were begun with AM 125 micrograms 3 times a day (AM = 8, P = 7) or AM 250 micrograms 4 times a day (AM = 9, P = 7) for 5 days, 24 h after intranasal inoculation of RV type 39. The low AM dose was well tolerated but had no effect on nasal mucus weights or nasal symptom scores in persons with RV colds. The higher dose of AM was associated with subjective drying and a reduction in nasal mucus production. These findings suggest that cholinergic mechanisms have a role in the pathogenesis of RV colds but that more work is necessary to determine if anticholinergic compounds will be of practical value in their treatment.

Administration, Intranasal↗

Pea seed mitochondria are endowed with a remarkable tolerance to extreme physiological temperatures.

Most seeds are anhydrobiotes, relying on an array of protective and repair mechanisms, and seed mitochondria have previously been shown to harbor stress proteins probably involved in desiccation tolerance. Since temperature stress is a major issue for germinating seeds, the temperature response of pea (Pisum sativum) seed mitochondria was examined in comparison with that of mitochondria from etiolated epicotyl, a desiccation-sensitive tissue. The functional analysis illustrated the remarkable temperature tolerance of seed mitochondria in response to both cold and heat stress. The mitochondria maintained a well-coupled respiration between -3.5 degrees C and 40 degrees C, while epicotyl mitochondria were not efficient below 0 degrees C and collapsed above 30 degrees C. Both mitochondria exhibited a similar Arrhenius break temperature at 7 degrees C, although they differed in phospholipid composition. Seed mitochondria had a lower phosphatidylethanolamine-to-phosphatidylcholine ratio, fewer unsaturated fatty acids, and appeared less susceptible to lipid peroxidation. They also accumulated large amounts of heat shock protein HSP22 and late-embryogenesis abundant protein PsLEAm. The combination of membrane composition and stress protein accumulation required for desiccation tolerance is expected to lead to an unusually wide temperature tolerance, contributing to the fitness of germinating seeds in adverse conditions. The unique oxidation of external NADH at low temperatures found with several types of mitochondria may play a central role in maintaining energy homeostasis during cold shock, a situation often encountered by sessile and ectothermic higher plants.

Acclimatization↗

Gene expression analysis of cold and freeze stress in Baker's yeast.

We used mRNA differential display to assess yeast gene expression under cold or freeze shock stress conditions. We found both up- and down-regulation of genes, although repression was more common. We identified and sequenced several cold-induced genes exhibiting the largest differences. We confirmed, by Northern blotting, the specificity of the response for TPI1, which encodes triose-phosphate isomerase; ERG10, the gene for acetoacetyl coenzyme A thiolase; and IMH1, which encodes a protein implicated in protein transport. These genes also were induced under other stress conditions, suggesting that this cold response is mediated by a general stress mechanism. We determined the physiological significance of the cold-induced expression change of these genes in two baker's yeast strains with different sensitivities to freeze stress. The mRNA level of TPI1 and ERG10 genes was higher in freeze-stressed than in control samples of the tolerant strain. In contrast, both genes were repressed in frozen cells of the sensitive strain. Next, we examined the effects of ERG10 overexpression on cold and freeze-thaw tolerance. Growth of wild-type cells at 10 degrees C was not affected by high ERG10 expression. However, YEpERG10 transformant cells exhibited increased freezing tolerance. Consistent with this, cells of an erg10 mutant strain showed a clear phenotype of cold and freeze sensitivity. These results give support to the idea that a cause-and-effect relationship between differentially expressed genes and cryoresistance exists in Saccharomyces cerevisiae and open up the possibility of design strategies to improve the freeze tolerance of baker's yeast.

Blotting, Northern↗

Heterology expression of the Arabidopsis C-repeat/dehydration response element binding factor 1 gene confers elevated tolerance to chilling and oxidative stresses in transgenic tomato.

In an attempt to improve stress tolerance of tomato (Lycopersicon esculentum) plants, an expression vector containing an Arabidopsis C-repeat/dehydration responsive element binding factor 1 (CBF1) cDNA driven by a cauliflower mosaic virus 35S promoter was transferred into tomato plants. Transgenic expression of CBF1 was proved by northern- and western-blot analyses. The degree of chilling tolerance of transgenic T(1) and T(2) plants was found to be significantly greater than that of wild-type tomato plants as measured by survival rate, chlorophyll fluorescence value, and radical elongation. The transgenic tomato plants exhibited patterns of growth retardation; however, they resumed normal growth after GA(3) (gibberellic acid) treatment. More importantly, GA(3)-treated transgenic plants still exhibited a greater degree of chilling tolerance compared with wild-type plants. Subtractive hybridization was performed to isolate the responsive genes of heterologous Arabidopsis CBF1 in transgenic tomato plants. CATALASE1 (CAT1) was obtained and showed activation in transgenic tomato plants. The CAT1 gene and catalase activity were also highly induced in the transgenic tomato plants. The level of H(2)O(2) in the transgenic plants was lower than that in the wild-type plants under either normal or cold conditions. The transgenic plants also exhibited considerable tolerance against oxidative damage induced by methyl viologen. Results from the current study suggest that heterologous CBF1 expression in transgenic tomato plants may induce several oxidative-stress responsive genes to protect from chilling stress.

Acclimatization↗

Physical allergies and exercise. Clinical implications for those engaged in sports activities.

There are several allergic responses that may occur in susceptible individuals as a result of exposure to physical stimuli. Most of these conditions are mediated by vasoactive substances and usually result in symptoms of urticaria and/or angioedema. There are 2 such conditions that may occur as a direct result from exercise. The first of these is cholinergic urticaria. Patients with cholinergic urticaria experience punctate (2 to 4mm) hives which occur reproducibly with exercise or with passive warming, such as might occur in a steam bath or hot pool. Life-threatening hypotension or angioedema usually do not occur with cholinergic urticaria. This condition usually responds well to oral hydroxyzine. Exercise-induced anaphylaxis (EIA) is a form of physical allergy that has been recognised with increasing frequency in recent years. This syndrome typically presents with generalised pruritus, a flushing sensation, a feeling of warmth and the development of conventional (10 to 15mm) urticaria in association with vigorous physical exertion only. Symptoms tend to occur variably with exposure to exercise and do not typically occur with passive warming. During symptomatic attacks, cutaneous mast cells degranulate and serum histamine levels increase. Treatment is problematic. Cessation of exercise with onset of symptoms and self-administration of epinephrine (adrenaline) are recommended. Other physical allergies that may affect exercising individuals include cold urticaria, localised heat urticaria, symptomatic dermatographism (dermographism), delayed pressure urticaria (angioedema), solar urticaria and aquagenic urticaria. Management of these conditions may include patient education, selective avoidance, antihistamines and, in some cases, induction of tolerance.

Anaphylaxis↗

Transcriptome comparison of winter and spring wheat responding to low temperature.

Freezing tolerance in plants is a complex trait that occurs in many plant species during growth at low, nonfreezing temperatures, a process known as cold acclimation. This process is regulated by a multigenic system expressing broad variation in the degree of freezing tolerance among wheat cultivars. Microarray analysis is a powerful and rapid approach to gene discovery. In species such as wheat, for which large scale mutant screening and transgenic studies are not currently practical, genotype comparison by this methodology represents an essential approach to identifying key genes in the acquisition of freezing tolerance. A microarray was constructed with PCR amplified cDNA inserts from 1184 wheat expressed sequence tags (ESTs) that represent 947 genes. Gene expression during cold acclimation was compared in 2 cultivars with marked differences in freezing tolerance. Transcript levels of more than 300 genes were altered by cold. Among these, 65 genes were regulated differently between the 2 cultivars for at least 1 time point. These include genes that encode potential regulatory proteins and proteins that act in plant metabolism, including protein kinases, putative transcription factors, Ca2+ binding proteins, a Golgi localized protein, an inorganic pyrophosphatase, a cell wall associated hydrolase, and proteins involved in photosynthesis.

Acclimatization↗

Hypertolerance to morphine in G(z alpha)-deficient mice.

Our laboratory has generated a mouse deficient in the alpha (alpha) subunit of the G protein, G(z), (G(z alpha)) gene and we have examined the involvement of G(z alpha) in spinal and supraspinal analgesia and tolerance mechanisms. Spinal analgesia was tested by the response times to heat or cold tail flick times in a water bath at 50 degrees C or -5 degrees C and supraspinal analgesia was tested by the times for paw licking and jumping from a plate at 52 degrees C or 0.5 degrees C. Tolerance to morphine was induced in wild type and G(z alpha)-deficient mice over a 5 day period and the behavioral tests were performed daily. The tail flick reaction times to both hot and cold stimuli did not differ between the wild type and G(z alpha)-deficient mice. Analysis of the reaction times from the hot and cold plate tests showed the G(z alpha)-deficient mice developed tolerance to morphine to a greater degree and at a faster rate than wild type mice. Opioid binding assays were performed on synaptic membranes prepared from naive and morphine tolerant wild type and G(z alpha)-deficient brains. No changes in the affinity of morphine for its receptor or in the density of mu and delta opioid receptors were found between the two groups of mice in the naive or morphine tolerant state. This indicates that the absence of G(z alpha) does not affect opioid receptor affinity or receptor up or down regulation. Our results suggest that the presence of G(z alpha) delays the development of morphine tolerance and represents a possible therapeutic target for improving the clinical use of morphine.

Analgesia↗

Ipratropium bromide treatment of experimental rhinovirus infection.

The importance of parasympathetic-cholinergic mechanisms in the production of common cold symptoms is not clear. The quaternary ammonium anticholinergic antagonist ipratropium bromide was intranasally administered under double-blind, randomized, placebo-controlled conditions to assess its tolerance and efficacy in reducing nasal hypersecretion in adult volunteers with experimental rhinovirus colds. Ipratropium was sprayed intranasally three times daily (80 micrograms per treatment) for 5 days beginning 24 h after intranasal inoculation of rhinovirus type 39. Clinical colds occurred in 50% of 30 infected ipratropium recipients and in 76% of 33 infected placebo recipients (P = 0.04). The nasal mucus weights tended to be lower for ipratropium-treated persons (mean +/- standard deviation, 14.7 +/- 15.1 g/5 days) than for placebo-treated recipients (24.7 +/- 28.0 g/5 days; P = 0.076). Whereas total nasal symptom scores were similar between the two groups, the rhinorrhea score analyzed for each day of treatment showed nonsignificant trends favoring the ipratropium group over the last 4 days of treatment. Ipratropium was generally well tolerated. The results suggest that cholinergic mechanisms are at least partially responsible for nasal mucus production in rhinovirus colds but that the effect of anticholinergic compounds alone is insufficient to be of practical use in treatment, although they may have value as components of multi-ingredient preparations.

Administration, Intranasal↗

The tridimensional personality theory and pain: harm avoidance and reward dependence traits correlate with pain perception in healthy volunteers.

The aim of the present study was to examine the possible role of personality traits in determining the variability of pain perception among individuals. More specifically, it was intended to test whether or not the three personality dimensions suggested by Cloninger in 1987 - mainly harm avoidance (HA), but also reward dependence (RD), and novelty seeking (NS), can predict interpersonal differences in responsiveness to experimental pain. Seventy healthy volunteers participated in the study. Their personality traits were evaluated through Cloninger's tridimensional personality questionnaire (TPQ). Pain threshold (latency to pain onset), pain magnitude (VAS), and pain tolerance (time to withdrawal) were measured by using the cold pressor test. Bonferroni-adjusted correlations were found between HA and the pain parameters as follows: a negative correlation between HA and threshold (rho=-0.297, P(adj)=0.039); no significant correlation between HA and tolerance (rho=-0.219, P(adj)=0.207); and a trend for a positive correlation between HA and VAS (rho=0.266, P(adj)=0.081). Possible correlations between pain perception and the various possible combinations of high and low scoring for each of the three traits were also investigated. Correlations were found only for the combinations of high/low HA and high/low RD. The low HA/low RD combination demonstrated the lowest responsiveness to pain (VAS 65.2+/-21.4; tolerance 107.6+/-71.8 s), whereas the high HA/low RD combination was correlated with the highest responsiveness (VAS 83.3+/-10.8; tolerance 30.8+/-28.4 s). The results indicate that HA personality trait correlates best with pain responsiveness. As such, a high HA are likely to predict a heightened pain response. RD may modify this pattern. The possible relevant behavioral and neuro-chemical mechanisms are discussed.

Adult↗

The MKK2 pathway mediates cold and salt stress signaling in Arabidopsis.

The Arabidopsis mitogen-activated protein kinase (MAPK) kinase 2 (MKK2) and the downstream MAPKs MPK4 and MPK6 were isolated by functional complementation of osmosensitive yeast mutants. In Arabidopsis protoplasts, MKK2 was specifically activated by cold and salt stress and by the stress-induced MAPK kinase kinase MEKK1. Yeast two-hybrid, in vitro, and in vivo protein kinase assays revealed that MKK2 directly targets MPK4 and MPK6. Accordingly, plants overexpressing MKK2 exhibited constitutive MPK4 and MPK6 activity, constitutively upregulated expression of stress-induced marker genes, and increased freezing and salt tolerance. In contrast, mkk2 null plants were impaired in MPK4 and MPK6 activation and were hypersensitive to salt and cold stress. Full genome transcriptome analysis of MKK2-overexpressing plants demonstrated altered expression of 152 genes involved in transcriptional regulation, signal transduction, cellular defense, and stress metabolism. These data identify a MAP kinase signaling cascade mediating cold and salt stress tolerance in plants.

Arabidopsis↗

Cold air analgesia in photodynamic therapy of basal cell carcinomas and Bowen's disease: an effective addition to treatment: a pilot study.

BACKGROUND: There is considerable interpatient variability in pain tolerance during and after treatment of skin cancer with photodynamic therapy (PDT). Additionally, erythema and edema are common, with mild crusting and healing over 1 to 2 weeks. OBJECTIVE: To determine whether concurrent cold air analgesia improves the tolerability of PDT. METHOD: Twenty-six patients with two similar superficial skin cancers were treated with PDT. One lesion was treated with cold air analgesia and the other without. Patients rated their pain during treatment using the Wong Baker Faces Pain Scale and detailed duration of posttreatment pain. At week 2, the inflammatory response was assessed. RESULT: A statistically significant difference in the analgesia group was shown with respect to the mean duration of pain and the level of erythema after the first treatment as well as pain scores during the second treatment. CONCLUSION: Patient acceptance of PDT for treatment of nonmelanoma skin cancer is improved with lessened morbidity assessed with concurrent use of cold air analgesia to the treatment field.

Analgesia↗

Cold storage of the pancreas with a view to preservation of islet cell function following transplantation.

Three solutions, hyperosmolar citrate, modified Collins' C2, and Sacks' II solutions were compared as media for cold storage preservation (arterial infusion and subsequent cold storage in the same medium at 0-4 C) of the rat pancreas with a view to preservation of endocrine function. Pancreatic isotransplantation was performed following cold ischemic intervals of 0, 24, 30, and 36 hr, into streptozotocin-induced diabetic recipients. Results were assessed by normoglycemic survival and insulin response, together with K values following i.v. glucose tolerance tests at 3 months postoperatively; 24-hr preservation was achieved with equal success using modified Collins' C2 solution or hyperosmolar citrate-but not with Sacks' II solution. Preservation for 30 hr was consistently successful using modified Collins C2 solution only, but the period could not be extended with success to 36 hr. Hypoglycemia and hyperinsulinemia occurred 24 hr postoperatively in the majority of animals receiving grafts stored in Sacks' II solution, but to a much lesser extent using modified Collins' C2 and hyperosmolar citrate. This was also temporarily seen in grafts stored for 36 hr in modified Collins C2 solution. At 3 months postoperatively after 30 hr cold ischemia, i.v. glucose tolerance tests showed the hyperosmolar citrate cold-stored grafts had lower K values and significantly reduced insulin responses compared with grafts stored in modified Collins' C2 solution. The modified Collins' C2 solution proved to be the most effective of the three solutions tested.

Animals↗

The prophylactic and therapeutic effectiveness of zinc sulphate on common cold in children.

AIM: To determine the efficacy of prophylactic administration of zinc sulphate in reducing the occurrence of the common cold in children, and to evaluate the efficacy of zinc sulphate in reducing the duration and severity of cold symptoms. METHODS: A total of 200 healthy children were randomly assigned to receive oral zinc sulphate (zinc group, n=100) or placebo (placebo group, n=100). Zinc sulphate (15 mg of zinc) or placebo syrup were administered for prophylaxis once daily during a 7-mo study period. The dose was increased to two times per day (30 mg of zinc) at the onset of cold, until symptoms resolved. RESULTS: The mean number of colds in the zinc group was significantly less than in the placebo group (1.2 vs 1.7 colds per child; p=0.003). The mean cold-related school absence was 0.9 d per child in the zinc group versus 1.3 d in the placebo group (p=0.04). Compared to the placebo group, the zinc group had shorter mean duration of cold symptoms and decreased total severity scores for cold symptoms (p<0.0001). Adverse effects were mild and similar in both groups. CONCLUSION: Zinc sulphate appears to be an easily administered, safe and well-tolerated alternative for the prevention and treatment of the common cold in children.

Antiviral Agents↗

Cold exposure attenuates effects of secretagogues on serum prolactin and growth hormone levels in male rats.

The stimulatory effect of morphine, dexmedetomidine (an alpha 2-adrenoceptor agonist), 1-(3-chlorophenyl)-piperazine (m-CPP, a 5-HT1B agonist), U-50488H (a kappa-opioid receptor agonist), pimozide (a dopamine antagonist), and restraint stress on prolactin and growth hormone (GH) secretion was compared during cold exposure (4 degrees C) and under basal conditions (30 degrees C) in male rats. Rectal temperature was also measured. The stimulatory effect of morphine, dexmedetomidine, m-CPP, and partially U-50488H on prolactin secretion was attenuated in rats kept at 4 degrees C. Cold exposure did not abolish prolactin release induced by pimozide and restraint stress. Cold exposure also antagonized the effect of morphine and dexmedetomidine on GH secretion. The stimulatory effect of morphine on prolactin and GH secretion was restored in the warm environment despite the sustained hypothermia. Cold exposure blocked the stimulatory effect of morphine on prolactin secretion in rats that were tolerant to the hypothermic effect of morphine. Thus hypothermia caused by morphine, dexmedetomidine, and m-CPP during cold exposure is not the sole factor in the antagonistic effect of cold. We suggest that cold exposure releases some compound(s) modulating hypothalamic neural pathways.

Animals↗

Ineffectiveness of recombinant interferon-beta serine nasal drops for prophylaxis of natural colds.

Two randomized, double-blind, placebo-controlled trials during early autumn of 1986 and 1987 evaluated the efficacy and tolerance of recombinant interferon-beta serine (rIFN-beta ser) nasal drops for prevention of natural rhinovirus colds. In 1986, 9 X 10(6) units of rIFN-beta ser (139 subjects) or placebo (157) were administered once daily except Sundays for 4 w. Rhinovirus colds occurred in 2.8% of rIFN-beta ser recipients and 6.0% of placebo recipients during the treatment period (52% reduction, P = .3). In 1987, 24 X 10(6) units of rIFN-beta ser (186) or placebo (197) were given daily for 25 consecutive days. Rhinovirus colds developed in 6.3% of rIFN-beta ser recipients and 5.3% of placebo recipients. In each study, illness frequency and number of days with subjective colds did not differ between the groups. Recipients of nasal drops of rIFN-beta ser at either dosage did not differ in tolerance from placebo recipients. The lack of both prophylactic efficacy and nasal toxicity are in contrast to prior observations with nasal sprays of rIFN-alpha 2b.

Administration, Intranasal↗

Transformation of Arabidopsis with the codA gene for choline oxidase enhances freezing tolerance of plants.

Arabidopsis thaliana was transformed with the codA gene from Arthrobacter globiformis, which encodes choline oxidase, the enzyme that synthesizes glycinebetaine from choline. The transformation enabled the plants to accumulate glycinebetaine in chloroplasts, and significantly enhanced the freezing tolerance of plants. Furthermore, the photosynthetic machinery of transformed plants was more tolerant to freezing stress than that of wild-type plants. Exogenous application of glycinebetaine also increased the freezing tolerance of wild-type plants, suggesting that the presence of glycinebetaine in transformed plants had enhanced their ability to tolerate freezing stress. Northern blotting analysis revealed that the enhancement of freezing tolerance was not related to the expression of four cold-regulated genes. These results suggest that engineering of the biosynthesis of glycinebetaine by transformation with the codA gene might be an effective method for enhancing the freezing tolerance of plants.

Adaptation, Physiological↗

Labor room and laboratory: clinical validation of the cold pressor as a means of testing preparation for childbirth strategies.

Annually, numerous couples prepare for childbirth through Lamaze childbirth education classes. Research on various portions of the Lamaze method has used the cold pressor as an analogue for labor. In this experiment, pregnant women who had attended either (a) Lamaze classes which taught pain control methods (n = 22), or (b) Red Cross parenting classes which did not teach pain control methods (n = 7), and students who received either (c) brief Lamaze training (n = 10), or (d) no training (n = 10), were tested on the cold pressor. Pregnant women were also interviewed after the delivery of their children. On the cold pressor, clinically trained Lamaze women were superior (longer tolerance, less pain and/or distress) to clinical control (Red Cross) women, which were equal to student Lamaze trained women. All groups performed better than student controls. Post hoc analyses showed that women who managed labor pain well performed better on the cold pressor task than women who did not manage labor pain well. This experiment established some limits for applying analogue results to childbirth. Moreover, it showed that women who attended Lamaze classes received less medication during labor than women who attended Red Cross classes; however, it was not clear whether this difference was due to the Lamaze classes per se, or to other uncontrolled variables.

Adaptation, Psychological↗