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Relationship between cold tolerance and generation of suppressor macrophages during acute cold stress.

Acute cold stress induces suppressor macrophages expressing large numbers of receptors to the crystallizable fragment (Fc) portion of immunoglobulin G (MAC-1+ FcgammaRII/IIIbright cells), resulting in the immunosuppression of splenocyte mitogenesis. The generation of MAC-1+ FcgammaRII/IIIbright cells is mediated by the action of glucocorticoids (GCs) through the GC-receptor. In the present study, the generation of MAC-1+ FcgammaRII/IIIbright cells in peritoneal exudate cells was closely related to the decrease of rectal temperature during 3-day exposure to 5 degrees C. We next investigated the effects of improved cold tolerance on the generation of MAC-1+ FcgammaRII/IIIbright cells during acute cold stress. Mice were adapted to cold by exposure to 5 degrees C for 3 wk (cold-acclimated mice) and then reexposed to 5 degrees C for 3 h (acute cold stress) after living at 25 degrees C for 24 h. The rectal temperature of cold-acclimated mice was not decreased by the acute cold stress. In addition, the proportion of MAC-1+ FcgammaRII/IIIbright cells in peritoneal exudate cell population from cold-acclimated mice was unaffected by the acute cold stress. The cold acclimation significantly attenuated the increases in serum corticosterone levels and the expression of the GC-receptor mRNA on peritoneal exudate cells in response to acute cold stress. These results suggest that the altered GC response to acute cold stress by the improvement of cold tolerance inhibits the generation of suppressor macrophages during acute cold stress.

Acclimatization↗

B-cell neoplasms with homogeneous cold-reacting antibodies (cold agglutinins).

Among 78 patients with persistent cold agglutinins, 31 had lymphoma, 13 had macroglobulinemia of Waldenstrom, six had chronic lymphocytic leukemia and 28 had chronic cold agglutinin disease. The average age was over 60 years. Patients wit chronic cold agglutinin disease had more hemolytic crises, bleeding and Raynaud's phenomena, and less frequently lymphadenopathy or hepatosplenomegaly. The frequency of anemia, positive Coombs test results, cryoglobulinemia and Bence Jones proteinuria was similar in the various groups. Survival time from diagnosis was on average two years in lymphoma, two and a half years in Waldenstrom's macroglobulinemia, more than six years in chronic lymphocytic leukemia and more than five years in chronic cold agglutinin disease. Anti-I were common in chronic cold agglutinin disease (74 percent) and rare in other groups (32 to 33 percent). Anti-I and other cold agglutinins were rare in chronic cold agglutinin disease and common in lymphoma and Waldenstrom's macroglobulinemia. In chronic cold agglutinin disease, and in Waldenstrom's macroglobulinemia, cold agglutinins usually had K light chains--92 percent and 71 percent, respectively--whereas in lymphoma, 71 percent of cold agglutinins had lambda light chains. The type of light chains related to the specifically of cold agglutinins: 58 percent of IgM/K were anti-I, 75 percent of IgM/lambda had other specificities. Cold agglutinins were cytotoxic to autologous and allogeneic cells were killed implying that the former may be precoated in vivo with the antibodies. In conclusion, conditions with persistent cold agglutinins are a spectrum that varies from "benign" autoimmune-like chronic cold agglutinin disease to malignant lymphoma. Marked differences in the light chain type of cold agglutinins, specificity toward membranous antigens and severity of clinical manifestations were noted in benign and malignant varieties.

Adult↗

Heated, humidified air for the common cold.

OBJECTIVES: To assess the effects of inhaling heated water vapour with the help of a rhinotherm (an equipment designed to deliver heated water vapour to a person's nasal cavity), in the treatment of the common cold by comparing a. symptoms b. viral shedding c. nasal resistance after a natural or experimentally induced common cold. SEARCH STRATEGY: We searched MEDLINE with MeSH headings: common cold, rhinopharyngitis, inhalation, steam, heated vapour, rhinothermy, till July 1999. EMBASE, Current Contents, review articles, cross references were also searched. Attempts were also made to contact the manufacturers for any unpublished data. SELECTION CRITERIA: Randomized trials using heated water vapour in a standardized way in patients with the common cold or volunteers with experimental induction of rhinovirus infection were included in the review. DATA COLLECTION AND ANALYSIS: All the articles retrieved were initially subjected to a review for inclusion / exclusion criteria. Review articles, editorials, abstracts with inadequate outcome description were excluded. Studies selected for inclusion were subjected to a methodological assessment. MAIN RESULTS: The results of a systematic review of six trials with 319 participants, support the use of warm vapour inhalations in the common cold in terms of relief of symptoms (Odds Ratio with 95 % CI 0.31, 0.16-0.60, Relative risk 0.56, 0.4-0. 79). Results on symptom score indices were equivocal. None of the studies demonstrated a worsening of clinical symptom scores. One study demonstrated increased nasal resistance one week after steam inhalation in contrast to an earlier study which showed improvement in the nasal resistance. There was no evidence of decreased viral shedding measured by virus isolation in the nasal secretions (Tyrrell 1989) or measurement of viral titres in nasal washings among treatment group. The rhinovirus titres in the nasal washings from the treatment group were the same as those of the placebo group on day one prior to the treatment and on all four days after the treatment. The area under curve (Hendley 1994) was also similar in the placebo and treatment groups for titres of virus in the nasal washings as were the average viral titres across five days of follow up, the maximum values after treatment, and viral shedding velocity i.e. amount of virus shed per day (Hendley 1994). Minor side effects due to thermal stress were reported in all the studies. REVIEWER'S CONCLUSIONS: Three trials demonstrated beneficial effects on the symptoms of the common cold. One study from Israel showed a decrease in nasal resistance measured by peak nasal expiratory and inspiratory flow rate. Studies done in North America failed to show any objective improvement in outcome measures with the study intervention. A multi-centre double blind randomised controlled trial testing this therapy with uniform outcome measures is recommended.

Air↗

Infant cold exposure changes Fos expression to acute cold stimulation in adult hypothalamic brain regions.

It is known that cold exposure as an infant results in a permanent cold tolerance which is accompanied by a reduced rate of colonic temperature decline and increased metabolic heat production to cold stimulation. The present study was aimed to elucidate the central mechanism of cold tolerance of adult rats with cold exposure as infants. Newborn infants were exposed to cold ambient (4 degrees C) daily for 2 weeks, and when they were 15-weeks old, Fos expression to acute cold stimulation (10 degrees C) in whole brain regions was investigated using quantitative immunohistochemistry. Acute cold stimulation induced a significant increase of Fos-positive neurons in many nuclei of whole brain areas in adult rats both with and without cold exposure as infants. However, the number of Fos-positive neurons was significantly less in the rats with cold exposure than without cold exposure as infants, particularly in the hypothalamic nuclei such as the lateral septal nucleus (LS), preoptic area (POA), parvocellular paraventricular nucleus (pPVN0, ventromedial hypothalamic nucleus (VMH) and supramammillary nucleus (SuM). However, there was no significant difference in the number of Fos-positive neurons in the extra-hypothalamic regions between the rats with and without cold exposure as infants. These results suggest that the central mechanism of cold tolerance with cold exposure as infants is due to metabolic changes of the hypothalamic brain regions.

Animals↗

Effectiveness of zinc gluconate glycine lozenges (Cold-Eeze) against the common cold in school-aged subjects: a retrospective chart review.

Of the 62 million common colds requiring medical attention in the United States each year, more than 80% affect school-aged children. Controlled clinical trials have demonstrated the effectiveness of zinc gluconate glycine lozenges (Cold-Eeze) in reducing cold duration. The objective of this study was to determine the effectiveness of zinc gluconate glycine lozenges in reducing the duration and severity of colds in school-aged subjects and to identify the benefits of prophylactic administration of zinc gluconate glycine lozenges in reducing the occurrence of colds. The medical charts of subjects enrolled at Utah's Heritage Center before and after the introduction of zinc gluconate glycine lozenges (between January 1998 and August 2001) were reviewed to identify those who experienced cold signs or symptoms. Two or more prespecified signs or symptoms on the same day identified a cold and, along with patient or medical staff reports and use of cold medications, were used to determine cold start and resolution dates. Results from subjects who did or did not take study treatment were compared statistically to determine the prophylactic effects of lozenge use. Effects of zinc gluconate glycine lozenges on the need for antibiotic therapy were also analyzed. The review encompassed 496 records. Treatment with zinc gluconate glycine lozenges significantly decreased cold duration (7.5 versus 9.0 days for nonuse; P < 0.0001). Prophylaxis also significantly reduced the median number of colds per year (0.0 versus 1.3; P < 0.001) and concomitant antibiotic use to manage colds (4.1% versus 36.2%; P < 0.0001). Therapy with zinc gluconate glycine lozenges significantly reduced cold duration and antibiotic use in school-aged subjects. Prophylactic administration also significantly decreased cold frequency.

Adolescent↗

Reversibility of cold-induced hypertension after removal of rats from cold.

Chronic exposure of rats to cold air induces hypertension, including elevation of blood pressure and cardiac hypertrophy. The present study was designed to assess reversibility of these changes after removal from cold. Five groups of six male rats each were exposed to cold (5 +/- 2 degrees C) for 39 days, while six control rats were maintained at 26 +/- 2 degrees C. Systolic blood pressures of the rats in one of the cold-treated groups, as well as the controls, were measured twice weekly throughout the experiment. Blood pressure of the cold-exposed rats (150 +/- 3 mmHg; 1 mmHg = 133.3 Pa) became elevated significantly above that of controls (129 +/- 3 mmHg) within 4 weeks. On day 39 of cold exposure, one group (six rats) of the cold-treated rats was sacrificed while still in the cold. The remaining four groups of cold-treated rats were than removed from cold and kept at 26 +/- 2 degrees C. One group of cold-treated rats was sacrificed weekly thereafter. During the last week, the six control rats were also sacrificed. At death, the heart, kidneys, and adrenal glands were removed and weighed. Mean heart weight of the cold-treated group (346 +/- 7 mg/100 g body weight), sacrificed prior to removal from cold, was significantly (p less than 0.01) greater than that of controls (268 +/- 5 mg/100 g body weight). The increased heart weight of the cold-treated group appeared to result mainly from an increase in left ventricular weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Preferential translation of cold-shock mRNAs during cold adaptation.

Upon temperature downshift below the lower threshold of balanced growth (approximately 20 degrees C), the Escherichia coli translational apparatus undergoes modifications allowing the selective translation of the transcripts of cold shock-induced genes, while bulk protein synthesis is drastically reduced. Here we were able to reproduce this translational bias in E. coli cell-free extracts prepared at various times during cold adaptation which were found to display different capacities to translate different types of mRNAs as a function of temperature. Several causes were found to contribute to the cold-shock translational bias: Cold-shock mRNAs contain cis-elements, making them intrinsically more prone to being translated in the cold, and they are selective targets for trans-acting factors present in increased amounts in the translational apparatus of cold-shocked cells. CspA was found to be among these trans-acting factors. In addition to inducing a higher level of CspA, cold shock was found to cause a strong (two- to threefold) stoichiometric imbalance of the ratio between initiation factors (IF1, IF2, IF3) and ribosomes without altering the stoichiometric ratio between the factors themselves. The most important sources of cold-shock translational bias is IF3, which strongly and selectively favors translation of cold-shock mRNAs in the cold. IF1 and the RNA chaperone CspA, which stimulate translation preferentially in the cold without mRNA selectivity, can also contribute to the translational bias. Finally, in contrast to a previous claim, translation of cold-shock cspA mRNA in the cold was found to be as sensitive as that of a non-cold-shock mRNA to both chloramphenicol and kanamycin inhibition.

Anti-Bacterial Agents↗

Lasting effect of infantile cold experience on cold tolerance in adult rats.

The effect of short and repetitive exposure to cold (5 degrees C, 4 hr/day for 2 weeks) from the birth up to the 14th day of newborn rats onthe thermal regulation in adulthood and on the tolerance to cold was investigated. After being exposed to cold, they were transferred to a room at 25 degrees C (N-CA). The control rats were raised at 25 degrees C (N-WA). An acute cold exposure test was performed by placing the animals in a room at 5 degrees C under urethane anesthesia. Electrical activity of neck muscles as an index of shivering was recorded. The colonic temperature fell at a significantly slower rate in N-CA rats with less shivering than in N-WA ones. Nonshivering thermogenesis tested by norepinephrine was significantly greater in N-CA rats than in N-WA ones. These results suggest that N-CA rats developed improved cold tolerance accompanied by greater nonshivering thermogenesis. Such a phenomenon in N-CA lasted for 18 weeks after the termination of cold exposure. Adult rats subjected to the same scheme of cold exposure (A-CA) (5 degrees C, 4 hr/day, 2 weeks) showed essentially the same results as seen in N-CA, but its improved cold tolerance and elevated nonshivering thermogenesis disappeared 4 weeks after the termination of cold exposure. Extirpation of interscapular brown adipose tissue immediately before the cold test did not appreciably affect the cold tolerance in N-CA and A-CA rats. The colonic temperature at the onset of shivering was significantly lower in N-CA as well as A-CA rats than in each of the corresponding control rats, indicating a shift of the shivering threshold to lower temperature values in the animals exposed intermittently to cold. These results indicate that an infantile experience with cold results in a greater and longer sustained ability to tolerate cold in adulthood, characterized by enhanced nonshivering thermogenesis.

Acclimatization↗

Cold-acclimation improves cold-tolerance of diabetic rats.

1. The aim of these experiments was to study the extent to which previous cold-acclimation improves the cold-tolerance of diabetic rats. 2. Alloxan diabetic rats (fasting blood glucose higher than 200 mg/dl) were used in the experiments. 3. In Expt. 1, non-cold-acclimated control and diabetic rats were exposed to cold environment (7-9 degrees C), and the percentage of survival calculated during a 12-day experimental period. In Expt. 2, the rats were previously cold-acclimated before alloxan or saline injection (diabetic and control cold-acclimated rats) and the survival rate was also assessed during a 12-day period in the cold. 4. The percentage of survival of the non-cold-acclimated diabetic rats (Expt.1) was 19% compared with 79% of the diabetic cold-acclimated animals (Expt. 2). There were no deaths in the control groups. 5. Cold-acclimated diabetic rats maintained a near-normal thermogenic response after noradrenaline injection. This response was impaired in non-cold-acclimated diabetic rats. 6. The results of these experiments suggest that the enhanced cold-tolerance of diabetic cold-acclimated rats could be related to the increased sympathetic activity and enhanced insulin sensitivity in thermogenic tissues, such as brown fat.

Acclimatization↗

Cold acclimation, diapause, and geographic origin affect cold hardiness in eggs of Aedes albopictus (Diptera: Culicidae).

Eggs of five strains of Aedes albopictus (Skuse) were obtained in both diapause and nondiapause conditions and exposed to various cold acclimation regimes in the laboratory, after which they were subjected to diverse chilling treatments. Larvae that survived chilling as eggs survived to the pupal stage. Eggs of Aedes aegypti (L.) and Aedes triseriatus (Say) were included as control species. Eggs of temperate Ae. albopictus were more cold-hardy than eggs of Ae. aegypti but less cold-hardy than the eggs of Ae. triseriatus. Cold acclimation and diapause enhanced cold hardiness of only temperate Ae. albopictus. Cold acclimation had a greater influence on cold hardiness than did diapause. Both the temperature and the duration of cold acclimation modulated cold hardiness. Cold hardiness induced in the laboratory was similar to cold hardiness induced in the field in northern Indiana. The cold hardiness of Ae. albopictus from central Florida was intermediate in comparison with temperate and tropical strains. Tropical Brazilian Ae. albopictus and tropical Asian Ae. albopictus were similar in cold hardiness.

Acclimatization↗

Improved cold tolerance and its mechanism in cold-acclimated rats by high fat diet feeding.

Cold tolerance and metabolic responses to cold were studied in cold-acclimated rats on high fat diet (CAHF). Cold tolerance at-5 degrees C was assessed by fall of colonic temperature of clipped rats after 18 h of fasting. Rate of fall in colonic temperature was greatest in warm-acclimated control rats (WAST), slowest in cold-acclimated rats on standard diet (CAST), and remained unchanged in CAHF during cold exposure for 240 min. Increment in blood free fatty acid (FFA) concentration 80 min after cold exposure was greatest in WAST, less in CAST, and least in CAHF. Blood glucose decreased similarly in WAST and CAST after cold exposure, while it remained unchanged in CAHF. Blood beta-hydroxybutyrate also increased similarly in WAST and CAST, while it did not change in CAHF. Nonshivering thermogenesis tested by noradrenaline was greatest in CAHF, followed by CAST and WAST. Shivering induced by cold exposure was less pronounced in CAST than in WAST and did not develop in CAHF; changes in colonic temperature were inversely related to the extent of shivering during cold exposure for 90 min. These results suggest that an integrating effect of cold and high fat diet could improve cold tolerance much more than cold acclimation itself, possibly through enhanced nonshivering thermogenesis caused by metabolic modifications such as increased lipid use and gluconeogenesis.

Acclimatization↗

Metabolic cold acclimation after repetitive intermittent cold exposure in rat.

Repetitive intermittent cold exposure (5 degrees C, 6 h/day, 4 weeks) (ICE) resulted in the same cold adaptability as assessed by an enhanced cold tolerance (less drop of colonic temperature at -5 degrees C) and nonshivering thermogenesis (NST) (greater noradrenaline-induced heat production) as that elicited by continuous cold exposure (5 degrees C, 4 weeks) (CA) in rats. Although shorter intermittent (5 degrees C, 2 h/day, 4 weeks) (ICE-2 hr) as well as shorter continuous (5 degrees C, 1 week) (CA-1 wk) cold exposure effected an improved cold adaptability, the magnitude of cold tolerance and NST was smaller as compared with that in CA and ICE. The cold deacclimation process as reflected on the decreased NST did not differ between CA and ICE. Food intake was less in ICE than CA, while increase in body weight during the acclimation period was greater in the former. Increase in adrenal weight was greater in CA than ICE, but plasma corticosterone level did not differ among warm controls (WC), CA, and ICE in resting state (after 18-20 h at warm control temperature of 25 degrees C). Weights of interscapular and dorsocervical brown adipose tissue (BAT) increased to the same degree in CA and ICE. Plasma glucagon level in resting state did not differ among groups, while BAT glucagon levels significantly increased in CA and ICE, but they were higher in dorsocervical site than interscapular site in all acclimated states. Acute cold exposure (-5 degrees C, 15 min) caused increases in plasma corticosterone, glucagon levels, and in BAT glucagon levels in all acclimated groups. The extent of increase was significantly less for plasma glucagon in CA, while plasma corticosterone increased similarly in all groups. These results indicate that repetitive short-term cold exposure could elicit the same cold adaptability as that induced by continuous exposure, but requiring only one-fourth of the time of continuous cold exposure. Moreover, it is suggested that glucagon is involved in both CA and ICE, but the same extent of cold adaptability can be obtained in the less energy-requiring and less stressful state in ICE.

Acclimatization↗

The effect of cold acclimation and deacclimation on cold tolerance, trehalose and free amino acid levels in Sitophilus granarius and Cryptolestes ferrugineus (Coleoptera).

Canadian and French laboratory strains of Sitophilus granarius (L.) and Cryptolestes ferrugineus (Stephens) were cold acclimated by placing adults at 15, 10 and 5 degrees C successively for 2wk at each temperature before deacclimating them for 1wk at 30 degrees C. Unacclimated S. granarius had an LT(50) (lethal time for 50% of the population) of 12days at 0 degrees C compared with 40days after the full cold acclimation. At -10 degrees C, unacclimated C. ferrugineus had an LT(50) of 1.4days compared with 24days after the full acclimation. Cold acclimation was lost within a week after returning insects to 30 degrees C. Trehalose, as well as the amino acids proline, asparagine, glutamic acid and lysine were higher in cold acclimated insects for both species. For S. granarius, glutamine was higher in cold acclimated insects and isoleucine, ethanolamine and phosphoethanolamine, a precursor of phospholipids, were lower in cold acclimated insects. For C. ferrugineus, alanine, aspartic acid, threonine, valine, isoleucine, leucine, phenylalanine and phosphoethanolamine were higher in cold acclimated insects. For both species tyrosine was lower in cold acclimated insects. There were small but significant differences between Canadian and French strains of S. granarius, with the Canadian strain being more cold hardy and having higher levels of trehalose. There were small but significant differences between male and female S. granarius, with males being more cold hardy and having higher levels of proline, asparagine and glutamic acid. In conclusion, high levels of trehalose and proline were correlated with cold tolerance, as seen in several other insects. However, correlation does not prove that these compounds are responsible for cold tolerance, and we outline further tests that could demonstrate a causal relationship between trehalose and proline and cold tolerance.

Journal Article↗

The role of the 5'-end untranslated region of the mRNA for CspA, the major cold-shock protein of Escherichia coli, in cold-shock adaptation.

During cellular adaptation to low temperature, Escherichia coli transiently synthesizes the major cold-shock protein CspA. It was found that adaptation to cold shock is blocked when the 143-base sequence of the 5' untranslated region (5' UTR) of the cspA mRNA is overproduced. The overproduction of this UTR at 15 degrees C caused the synthesis of not only CspA but also other cold-shock proteins such as CspB and CsdA to be no longer transient but rather prolonged. In addition, inhibition of both the synthesis of cellular proteins other than cold-shock proteins and cell growth was observed. Interestingly, when CspA was also overproduced together with the 5' UTR, normal cold-shock adaptive response was resumed without a prolonged lag period of cell growth. This indicates that the 5' UTR of the cspA mRNA and its gene product CspA play a critical role in the regulation of the expression of cold-shock genes and cold-shock adaptation. An 11-base common sequence (cold box) was found in the 5' UTRs of cspA, cspB, and csdA mRNAs. Indeed, the 25-base sequence within the 5' UTR of the cspA mRNA containing the cold-box sequence was able to prolong CspA production at 15 degrees C. We propose that a putative repressor binds to the cold-box sequence of the cold-shock mRNAs during the adaptive process and this binding in turn blocks the transcription of the cold-shock genes or destabilizes their mRNAs. CspA appears to promote either directly or indirectly the repressor function.

Adaptation, Physiological↗

Effects of diets on cold tolerance and metabolic responses to cold in fasted rats.

Effects of high-fat and high-protein diets on cold tolerance in fasted rats were investigated. High-fat diets caused significant increases in body weight, blood-free fatty acids (FFA), ketone bodies and glucose, while high-protein diet did not modify any of these parameters. Rats on high-fat diets that were exposed to cold after clipping exhibited an intermediate cold tolerance as assessed by the rate of fall in colonic temperature between control rats on a standard diet and cold-acclimated rats. The extent of increase of blood FFA and decrease of blood glucose due to cold exposure was less in the high-fat diet group than in control group, but greater than in cold-acclimated group. The lower fall in colonic temperature due to cold exposure was signifcantly associated with less increase in blood FFA and less decrease in blood glucose. In this relation the high-fat diet group was also intermediate between the control and cold-acclimated groups. The high-protein diet did not make any difference in cold tolerance and cold-induced changes in blood metabolites as compared with those in control standard diet, although it resulted in a marked increase in urinary nitrogen excretion. These results indicate that a high-fat diet could exert a significant favorable effect on cold tolerance in fasted rats, but the effect would not be as much as as in cold acclimated rats.

Adaptation, Physiological↗

Blood pressure and heart rate responses in men exposed to arm and leg cold pressor tests and whole-body cold exposure.

OBJECTIVES: Comparison of the effects of different types of cold exposure on blood pressure and heart rate. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty healthy men were exposed to three different types of cold exposure: cold pressor tests for hands and feet, and a 2-h cold air exposure at an ambient temperature of +10 degrees C. RESULTS: All types of cold exposure caused a rise in systolic and diastolic blood pressures. Heart rate increased in the foot cold pressor test. In the cold chamber test, heart rate fell, causing a decrease in the rate:pressure product. No statistically significant correlations were found between the blood pressure responses to cold pressor and cold chamber tests. The increased rate:pressure product observed in the cold pressor tests is indicative of an increased oxygen consumption in the heart muscle. CONCLUSIONS: The measured cardiovascular responses indicate that a sudden local exposure to severe cold would be more stressful than a long lasting, milder exposure to cold, even when the latter is applied to the whole body

Adult↗