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Zinc gluconate lozenges for treating the common cold in children: a randomized controlled trial.

CONTEXT: The common cold is one of the most frequently occurring illnesses and is responsible for substantial morbidity and economic loss. Biochemical evidence suggests that zinc may be an effective treatment, and zinc gluconate glycine (ZGG) lozenges have been shown to reduce the duration of cold symptoms in adults. OBJECTIVE: To determine the efficacy of ZGG treatment of colds in children and adolescents. DESIGN: A randomized, double-masked, placebo-controlled study. SETTING: Two suburban school districts in Cleveland, Ohio. PATIENTS: A total of 249 students in grades 1 through 12 were enrolled within the first 24 hours of experiencing at least 2 of 9 symptoms of the common cold. INTERVENTION: Zinc lozenges, 10 mg, orally dissolved, 5 times a day (in grades 1-6) or 6 times a day (in grades 7-12). MAIN OUTCOME MEASURES: Time to resolution of cold symptoms based on subjective daily symptom scores for cough, headache, hoarseness, muscle ache, nasal congestion, nasal drainage, scratchy throat, sore throat, and sneezing. RESULTS: Time to resolution of all cold symptoms did not differ significantly between students receiving zinc (n = 124) and those receiving placebo (n = 125) (median, 9 days; 95% confidence interval [CI], 8-9 days; median, 9 days, 95% CI, 7-10 days, respectively; P=.71). There were no significant differences in the time to resolution of any of the 9 symptoms studied. Compared with controls, more students in the zinc group reported adverse effects (88.6% vs 79.8%; P=.06); bad taste (60.2% vs 37.9%; P=.001); nausea (29.3% vs 16.1%; P=.01); mouth, tongue, or throat discomfort (36.6% vs 24.2%; P=.03); and diarrhea (10.6% vs 4.0%; P=.05). CONCLUSIONS: In this community-based, randomized controlled trial, ZGG lozenges were not effective in treating cold symptoms in children and adolescents. Further studies with virologic testing are needed to clarify what role, if any, zinc may play in treating cold symptoms.

Adolescent↗

Heated, humidified air for the common cold.

BACKGROUND: Heated, humidified air is used by common cold sufferers since the invention of the steam kettle. There is scientific literature available investigating this mode of therapy using a rhinotherm. The present reviews addresses to the use of hot, humid air in 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: In the initial review published in issue 3, 1999 of The Cochrane Library, we searched MEDLINE with MeSH headings: common cold, rhinopharyngitis, inhalation, steam, heated vapour, rhinothermy (January 1966 to July 1999). EMBASE, Current Contents, review articles, cross references were also searched. Attempts were also made to contact the manufacturers for any unpublished data. In this updated review, we have searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2003), MEDLINE (January 1966 to November Week 2, 2003), EMBASE (January 1990 to November 2003), and Current Contents (current five years). 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 1989a) 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. REVIEWERS' 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↗

Neandertal cold adaptation: physiological and energetic factors.

European Neandertals employed a complex set of physiological cold defenses, homologous to those seen in contemporary humans and nonhuman primates. While Neandertal morphological patterns, such as foreshortened extremities and low relative surface-area, may have explained some of the variance in cold resistance, it is suggested the adaptive package was strongly dependent on a rich array of physiological defenses. A summary of the environmental cold conditions in which the Neandertals lived is presented, and a comparative ethnographic model from Tierra del Fuego is used. Muscle and subcutaneous fat are excellent "passive" insulators. Neandertals were quite muscular, but it is unlikely that they could maintain enough superficial body fat to offer much cold protection. A major, high-energy metabolic adaptation facilitated by modest amounts of highly thermogenic brown adipose tissue (BAT) is proposed. In addition, Neandertals would have been protected by general mammalian cold defenses based on systemic vasoconstriction and intensified by acclimatization, aerobic fitness, and localized cold--induced vasodilation. However, these defenses are energetically expensive. Based on contemporary data from circumpolar peoples, it is estimated that Neandertals required 3,360 to 4,480 kcal per day to support strenuous winter foraging and cold resistance costs. Several specific genetic cold adaptations are also proposed--heat shock protein (actually, stress shock protein), an ACP*1 locus somatic growth factor, and a specialized calcium metabolism not as yet understood.

Acclimatization↗

Anatomical substrates for the central control of sympathetic outflow to interscapular adipose tissue during cold exposure.

The thermogenic activity of interscapular brown adipose tissue (IBAT) in response to physiologic stimuli, such as cold exposure, is controlled by its sympathetic innervation. To determine which brain regions might be involved in the regulation of cold-evoked increases in sympathetic outflow to IBAT, the present study compared central nervous system (CNS) areas activated by cold exposure with brain regions anatomically linked to the sympathetic innervation of IBAT. Immunocytochemical localization of Fos was examined in the brains of rats exposed to 4 degrees C for 4 hours. In a separate group of rats, the neural circuit involved in IBAT control, including the location of sympathetic preganglionic neurons in the spinal cord, was characterized with pseudorabies virus, a retrograde transynaptic tracer. Central noradrenergic and serotonergic groups related to the sympathetic outflow to IBAT also were identified. Localization of viral antigens at different survival times (66-96 hours) revealed infection in circumscribed CNS populations, but only a subset of the regions comprising this circuitry showed cold-evoked Fos expression. The raphe pallidus and the ventromedial parvicellular subdivision of the paraventricular hypothalamic nucleus (PVH), both infected at early survival times, were the main areas containing sympathetic premotor neurons activated by cold exposure. Major cold-sensitive areas projecting to spinal interneurons or to regions containing sympathetic premotor neurons, which became infected at intermediate intervals, included lateral hypothalamic, perifornical, and retrochiasmatic areas, anterior and posterior PVH, ventrolateral periaqueductal gray, and Barrington's nucleus. Areas infected later, most likely related to reception of cold-related signals, comprised the lateral preoptic area, parastrial nucleus, dorsomedial hypothalamic nucleus, lateral parabrachial nucleus, and nucleus of the solitary tract. These interconnected areas, identified by combining functional and retrograde anatomic approaches, likely constitute the central circuitry responsible for the increase in sympathetic outflow to IBAT during cold-evoked thermogenesis.

Adipose Tissue, Brown↗

The metabolism of supplementary vitamin C during the common cold.

Ascorbic acid concentrations have been measured in leukocytes and plasma following oral administration of 2000 mg vitamin C in the same subjects while they had cold symptoms and after recovery from their colds. Plasma and leukocyte concentrations rose significantly in females, but only plasma concentrations rose in males, after the loading dose during colds. In the postcold tests, only plasma concentrations rose in both sexes. There was a significant difference in plasma leukocyte regression coefficients between the cold and postcold tests in females. Ascorbic acid passes into the plasma for metabolic purposes, and its storage is less in the leukocytes, during colds. Males had worse colds than females because their catarrhal symptoms were more severe. Higher tissue concentrations of ascorbic acid tended to be associated with low total, toxic, and catarrhal symptom values. A rise in tissue ascorbic acid was associated with less severe catarrhal symptoms in females. Ascorbic acid concentrations in the plasma and tongue were significantly higher after the subjects had recovered from their cold symptoms. Increasing the loading dose of vitamin C from 500 to 2000 mg more than doubled the leukocyte concentration of ascorbic acid in females. The higher dose enabled uptake of the vitamin into the leukocytes to take place over a 4-hour period. It did not give rise to increased uptake into male leukocytes. Administration of supplementary vitamin C elevated plasma ascorbic acid. The ascorbic acid then passed into the tissues depleted of vitamin C during the cold syndrome. A single supplementary dose of 2000 mg vitamin C can replete leukocyte ascorbic acid during a 4-hour period in females, but a larger dose may be necessary in males.

Ascorbic Acid↗

Cold adaptation of parainfluenza virus type 3: induction of three phenotypic markers.

In order to attenuate parainfluenza type 3 virus, a wild type strain that was isolated from a child with respiratory disease was adapted to replicate in African green monkey kidney cells at 20 degrees C. Replication at 20 degrees C was not a property of the wild type virus. The virus was serially passaged 45 times in the cold, and clones were selected following passage levels 7, 12, 18, and 45. The population of cold-adapted virus was found to be progressively enriched with temperature sensitive (ts) mutants. After 7 passages in the cold, 1 of 9, and after 12 passages in the cold, 3 of 12 clones were temperature sensitive. Following 18 passages in the cold, 80% of the clones were temperature sensitive and after 45 passages in the cold, all clones were temperature sensitive. In addition to being temperature sensitive each ts clone manifested the tiny plaque morphology. Each temperature-sensitive clone was also cold adapted. Some clones were cold adapted but were not temperature sensitive. The mutants were found to be genetically stable when serially passaged at 32 degrees, 35 degrees, or 39 degrees C. The mutants may possess the necessary degree of attenuation for use as live attenuated intranasal vaccines.

Adaptation, Physiological↗

Low temperature-induced systems failure in Escherichia coli: insights from rescue by cold-adapted chaperones.

The growth of Escherichia coli cells is impaired at temperatures below 21 degrees C and stops at 7.5 degrees C; however, growth of a transgenic strain producing the cold-adapted chaperones Cpn60 and Cpn10 from the psychrophilic bacterium Oleispira antarctica is good at low temperatures. The E. coli cpn(+) transgene offers a novel opportunity for examining the essential protein for cell viability at low temperatures. By screening a large-scale protein map (proteome) of cells of K-12 and its Cpn(+) transgene incubated at 4 degrees C, we identified 22 housekeeping proteins involved in systems failure of E. coli when confronted with low temperature. Through co-immunoprecipitation of Cpn60, Northern blot, and in vitro refolding, we systematically identified that protein-chaperone interactions are key determinants of their protein functions at low temperatures. Furthermore, chromosomal gene deletion experiments suggest that the mechanism of cold-induced systems failure in E. coli is cold-induced inactivation of the GroELS chaperonins and the resulting failure to refold cold-inactivated Dps, ClpB, DnaK and RpsB proteins. These findings: (1) indicate the potential importance of chaperones in cold sensitivity, cold adaptation and cold tolerance in cellular systems, and (2) suggest the identity of a few key cold-sensitive chaperone-interacting proteins that get inactivated and ultimately cause systems failure in E. coli cells at low temperatures.

Adaptation, Physiological↗

Activation and apoptosis of murine peritoneal macrophages by acute cold stress.

Effects of acute cold stress (5 degrees C for 24 h) on the functions of peritoneal macrophages and the mechanisms for controlling host homeostasis were investigated in mice. Phagocytic activity and expression of the cell surface adhesion molecule CD11b/CD18 were markedly increased in peritoneal exudate cells by acute cold stress. These alterations were attributable to an increased number and phenotypical changes of adherent cells from acute cold-stressed mice. On the other hand, a lipopolysaccharide-induced activity of src-family tyrosine kinase Fgr, an expression of interleukin-1beta (IL-1 beta) mRNA, and a bioactivity of IL-1 in the culture supernatants of adherent cells from acute cold-stressed mice were markedly lower than those from control mice. A time course study revealed that the number of adherent cells in peritoneal exudate cells was markedly increased in mice exposed to cold for 24 h but returned to normal numbers when mice were exposed to cold for 72 h. DNA fragmentation and Annexin-V(+) cells were observed in peritoneal exudate cells from acute-cold stressed mice. Thus, cold stress activated macrophages but these macrophages were destined to be eliminated by apoptosis.

Animals↗

Effect of cold shock on protein synthesis and on cryotolerance of cells frozen for long periods in Lactococcus lactis.

Aspects of the cold-shock response in Lactococcus lactis subsp. lactis LL41-1 were investigated. First, it was determined whether new proteins were synthesized in response to cold shock. Cell-free extracts were prepared from a cold-shocked (exposed to 10 degreesC for 5 h) culture (cfe-cs) and from a non-cold-shocked (held at 30 degreesC continuously) culture (cfe-non), and were subjected to sodium dodecyl sulphate-polyacrylamide gel electrophoresis. A protein of approximately 6.3 kDa was present in the cfe-cs and appeared not to be present in the cfe-non. No other changes were evident. Second, the effect of cold shock on cryotolerance of cells that have been frozen at -20 degreesC for up to 1 year was examined. Without the cold-shock treatment prior to freezing the cell viability following freezing for 1 day was 34%, 14 days 32%, 182 days 7%, and 364 days 0.2%. However, with the cold shock treatment it was 83%, 82%, 12%, and 0.8%, respectively. It appears that cold shock significantly improves cryotolerance of the cells for short periods of freezing, but the protective effect was less marked following longer storage periods.

Bacterial Proteins↗

Extended alternating-temperature cold acclimation and culture duration improve pear shoot cryopreservation.

Meristems of many pear genotypes can be successfully cryopreserved following 1 week of cold acclimation, but an equal number do not survive the process or have very little regrowth. This study compared commonly used cold acclimation protocols to determine whether the cold acclimation technique used affected the cold hardiness of shoots or the regrowth of cryopreserved meristems. In vitro-grown pear (Pyrus L.) shoots were cold acclimated for up to 16 weeks, then either the shoot tips were tested for cold hardiness or the meristems were cryopreserved by controlled freezing. Cold acclimation consisted of alternating temperatures (22 degrees C with light/-1 degrees C darkness with various photo- and thermoperiods) or a constant temperature (4 degrees C with an 8-h photoperiod or darkness). Compared with nonacclimated controls, both alternating- and constant-temperature acclimation significantly improved postcryopreservation regrowth of P. cordata Desv. and P. pashia Buch. -Ham. ex D. Don meristems. Alternating-temperature acclimation combined with either an 8-h photoperiod or darkness was significantly better than constant-temperature acclimation. Alternating-temperature shoot acclimation for 2 to 5 weeks significantly increased postcryopreservation meristem regrowth, and recovery remained high for up to 15 weeks acclimation. Postcryopreservation meristem regrowth increased with 1 to 5 weeks of constant-temperature acclimation and then declined with longer acclimation. Shoot cold hardiness varied with the acclimation procedure. The LT(50) of shoots acclimated for 10 weeks with alternating temperatures was -25 degrees C; that with constant temperature was -14.7 degrees C; and that of the nonacclimated control was -10 degrees C. Less frequent transfer of cultures also improved acclimation of shoots. Shoots grown without transfer to fresh medium for 6-12 weeks had higher postcryopreservation recovery with shorter periods of acclimation than shoots with a 3-week transfer cycle.

Acclimatization↗

The American bullfrog (Rana catesbeiana) exhibits differential cardiovascular responses to LTC4 after short- and long-term cold exposure.

Mean arterial pressure (MAP) and heart rate (HR) responses to leukotriene (LT)C4 have been studied in warm (W-A) and cold-acclimated (C-A) America bullfrogs, Rana catesbeiana, but nothing is known about how the length of cold treatment affects the response to LTC4 or how responses are affected by return to room temperature following cold exposure. In this study, two groups of frogs were placed at 5 degrees either for 30 days (C-A) or for 1 day (W-C) and LTC4 dose-response curves obtained at 5 degrees. After the frogs were removed from cold, the baseline MAP and HR were monitored for 120 min, and dose-response curves were repeated at 2, 24, and 48 hr. The LTC4 dose-response curves were also obtained during the three experimental days on frogs which had never been placed at cold temperature (W-A). C-A frogs showed greater MAP response than W-C frogs at 5 degrees, and also showed the greatest MAP response of the three groups 48 hr after the animals were removed from cold temperature. These data suggest that up regulation of LTC4 receptors may have occurred in C-A frogs. Cold exposure alone eliminated reflex HR response to LTC4 in both C-A and W-C groups. Longer duration of action was also observed in these groups. The results demonstrate that short-term cold exposure can affect the response to LTC4 in frogs, but that physiological adjustments occur in frogs undergoing long-term exposure.

Acclimatization↗

NFkappaB expression during cold ischemia correlates with postreperfusion graft function.

In liver transplantation, activation of NFkappaB occurs upon reperfusion, yet few data exist regarding NFkappaB activation during cold ischemia. We hypothesized that activation of NFkappaB may initially occur during cold ischemia, prior to reperfusion, and serve as an important determinant of postreperfusion function. To test this hypothesis, serial biopsies during porcine liver harvest were obtained immediately upon laparotomy, upon completion of dissection, after 45 and 120 min of cold ischemia, and 60 and 180 min after reperfusion. Nuclear extracts were isolated for Western blot analysis of NFkappaB. Hepatic function was assessed through bile output and sorbitol dehydrogenase (SDH) activity. NFkappaB expression was maximal at 45 min of cold ischemia and decreased by 120 min. The expression at 120 min of cold ischemia correlated with markers of postreperfusion function, namely bile flow and SDH activity. During reperfusion a second distinct peak occurred at 180 min. Increased expression of NFkappaB at 180 min of reperfusion correlated directly with prior expression at 120 min during cold ischemia and with increased SDH activity. These data indicate that nuclear expression of NFkappaB demonstrate two distinct peaks of activity, one during cold ischemia and one after reperfusion. Enhanced expression of NFkappaB during cold ischemia not only correlates directly with NFkappaB expression during reperfusion, but also correlates inversely with postreperfusion graft function.

Animals↗

Soluble acid invertase determines the hexose-to-sucrose ratio in cold-stored potato tubers.

Cold storage of potato (Solanum tuberosum L.) tubers is known to cause accumulation of reducing sugars. Hexose accumulation has been shown to be cultivar-dependent and proposed to be the result of sucrose hydrolysis via invertase. To study whether hexose accumulation is indeed related to the amount of invertase activities, two different approaches were used: (i) neutral and acidic invertase activities as well as soluble sugars were measured in cold-stored tubers of 24 potato cultivars differing in the cold-induced accumulation of reducing sugars and (ii) antisense potato plants with reduced soluble acid invertase activities were created and the soluble sugar accumulation in cold-stored tubers was studied. The cold-induced hexose accumulation in tubers from the different potato cultivars varied strongly (up to eightfold). Large differences were also detected with respect to soluble acid (50-fold) and neutral (5-fold) invertase activities among the different cultivars. Although there was almost no correlation between the total amount of invertase activity and the accumulation of reducing sugars there was a striking correlation between the hexose/sucrose ratio and the extractable soluble invertase activity. To exclude the possibility that other cultivar-specific features could account for the obtained results, the antisense approach was used to decrease the amount of soluble acid invertase activity in a uniform genetic background. To this end the cDNA of a cold-inducible soluble acid invertase (EMBL nucleic-acid database accession no. X70368) was cloned from the cultivar Desirée, and transgenic potato plants were created expressing this cDNA in the antisense orientation under control of the constitutive 35S cauliflower mosaic virus promotor. Analysis of the harvested and cold-stored tubers showed that inhibition of the soluble acid invertase activity leads to a decreased hexose and an increased sucrose content compared with controls. As was already found for the different potato cultivars the hexose/sucrose ratio decreased with decreasing invertase activities but the total amount of soluble sugars did not significantly change. From these data we conclude that invertases do not control the total amount of soluble sugars in cold-stored potato tubers but are involved in the regulation of the ratio of hexose to sucrose.

Cold Temperature↗

Responses of sympathetic nervous system to cold exposure in vibration syndrome subjects and age-matched healthy controls.

Plasma norepinephrine and epinephrine in vibration syndrome subjects and age-matched healthy controls were measured for the purpose of estimating the responsibility of the sympathetic nervous system to cold exposure. In preliminary experiment, it was confirmed that cold air exposure of the whole body was more suitable than one-hand immersion in cold water. In the main experiment, 195 subjects were examined. Sixty-five subjects had vibration syndrome with vibration-induced white finger (VWF + group) and 65 subjects had vibration syndrome without VWF (VWF- group) and 65 controls had no symptoms (control group). In the three groups, plasma norepinephrine levels increased during cold air exposure of whole body at 7 degrees +/- 1.5 degrees C. Blood pressure increased and skin temperature decreased during cold exposure. Percent increase of norepinephrine in the VWF+ group was the highest while that in VWF- group followed and that in the control group was the lowest. This whole-body response of the sympathetic nervous system to cold conditions reflected the VWF which are characteristic symptoms of vibration syndrome. Excluding the effects of shivering and a cold feeling under cold conditions, it was confirmed that the sympathetic nervous system in vibration syndrome is activated more than in the controls. These results suggest that vibration exposure to hand and arm affects the sympathetic nervous system.

Adult↗

Effect of cold stress on gallbladder contractility in humans.

The effect of cold stress in the form of repeated hand immersion in ice cold water or repeated application to a hand of extremely cold - nitrogen gas, at a temperature of -180 degrees C (93 K), on the emptying of a meal-stimulated gallbladder was examined in seven healthy volunteers of both sexes. The control procedure consisted of repeated application to a hand of air at neutral temperatures (+35 degrees(-)+37 degrees C). Each subject underwent three examinations on separate days, the procedures being applied in random order. Gallbladder volume was measured by means of real-time ultrasonography. Measurements of volumes of the fasted gallbladder were also made on the three study days and gave similar values: 20.3 cm3, SEM 2.7 (control), 22.1 cm3, SEM 2.5 (cryotherapy), and 20.0 cm3, SEM 2.5 (cold immersion), F(2, 12) = 2.47, P greater than 0.1. A significant delaying effect of cold stress on postprandial gallbladder contractility was observed: F(2, 72) = 7.44, P less than 0.005, and F(2, 72) = 4.45, P less than 0.025 for gallbladder volume and ejection fraction, respectively. A significant difference was detected between the local application of cold gas and the control procedure (P less than 0.005) and local cryotherapy and the cold pressor test (P less than 0.05) in the case of the postprandial gallbladder volume, as well as between the local application of cold gas and the control procedure (P less than 0.025) for the ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Increased contribution of brown adipose tissue to nonshivering thermogenesis in the Djungarian hamster during cold-adaptation.

The effect of cold-adaptation was investigated on the brown adipose tissue of Djungarian hamsters. Animals maintained at 23 degrees C and 16 hours light per day (controls) were exposed to 5 degrees C. The wet weight of the total brown fat is reduced by some 40% within 4 days of cold-exposure, as a result of extensive triacylglycerol depletion of the tissue with no reduction in DNA; the tissue mass remains constant under persistent cold influence. The total amount of tissue mitochondria is doubled by 24 h and increases by a factor of 3 under persistent cold-stimulus, the specific respiratory capacity of the organelles remaining unchanged. The amount of 32 kDa regulatory protein per mg mitochondrial protein quantified from high-affinity GDP-binding, is increased by a factor of 2.7 after 21 days of cold-adaptation; a 9-fold increment is found of the total mitochondrial GDB-binding capacity. Comparison of nonshivering thermogenesis and the maximal thermogenic capacity of brown fat, estimated from the maximal respiration of the isolated mitochondria and the total amount of mitochondria in the tissue, suggests that brown fat may contribute about 20% to the whole-body nonshivering thermogenesis in warm-adapted controls and 45% in cold-adapted hamsters. The estimated increase in thermogenic capacity of the tissue in response to 21 days of cold-adaptation corresponds to the increase in nonshivering thermogenesis, suggesting a central thermoregulatory role of brown fat during cold-adaptation.

Acclimatization↗

Blood flow and muscle bio-energetics by 31P-nuclear magnetic resonance after local cold acclimation.

To clarify the origin of local cold adaptation and to define precisely its influence on muscle bio-energetics during local exercise, five subjects were subjected to repeated 5 degrees C cold water immersion of the right hand and forearm. The first aim of our investigation was therefore carried out by measuring local skin temperatures and peripheral blood flow during a cold hand test (5 degrees C, 5 min) followed by a 10-min recovery period. The 31P by nuclear magnetic resonance (31PNMR) muscle bio-energetic changes, indicating possible heat production changes, were measured during the recovery period. The second aim of our investigation was carried out by measuring 31PNMR muscle bioenergetics during handgrip exercise (10% of the maximal voluntary contraction for 5 min followed by a 10-min recovery period) performed both at a comfortable ambient temperature (22 degrees C; E) and after a cold hand test (EC), before and after local cold adaptation. Local cold adaptation, confirmed by warmer skin temperatures of the extremities (+30%, P less than 0.05), was related more to an increased peripheral blood flow, as shown by the smaller decrease in systolic peak [-245 (SEM 30) Hz vs -382 (SEM 95) Hz, P less than 0.05] than to a change in local heat production, because muscle bioenergetics did not vary. Acute local cold immersion decreased the inorganic phosphate:phosphocreatine (PC) ratio during EC compared to E [+0.006 (SEM 0.010) vs +0.078 (SEM 0.002) before acclimation and +0.029 (SEM 0.002) vs +0.090 (SEM 0.002) after acclimation respectively, P less than 0.05] without significant change in the PC:beta-adenosine triphosphate ratio and pH. Local adaptation did not modify these results statistically. The recovery of PC during E increased after acclimation [9.0 (SEM 0.2) min vs 3.0 (SEM 0.4) min, P less than 0.05]. These results suggested that local cold adaptation is related more to peripheral blood flow changes than to increased metabolic heat production in the muscle.

Acclimatization↗

Liver alcohol oxidizing systems and gluconeogenic enzyme activities after long term ethanol application in cold exposed guinea pigs.

The effects of 4-weeks ethanol application (20% ethanol, w/w, 2 g X kg-1 on the alcohol oxidizing systems and gluconeogenic enzyme activities of the liver in guinea pigs kept in the cold (+4 degrees C) and at room temperature (+20 degrees C) were studied. The controls were guinea pigs reared at room temperature or in a cold environment without ethanol. The study showed a significant increase (1.5-fold) in liver microsomal cytochrome P-450 after chronic ethanol treatment at room temperature, but not in a cold environment. Microsomal NADPH oxidase activity did not significantly change in any group. Ethanol treatment in a cold environment resulted in a significant increase in liver mitochondrial cytochromes, aa3 and c+c1, and at room temperature in cyt aa3. The activities of total liver homogenate alcohol dehydrogenase or catalase did not change after chronic ethanol treatment. The activity of liver fructose-1.6-diphosphatase showed a significant ethanol induced decrease at room temperature, an effect not observed in the cold environment. Ethanol increased glucose-6-phosphatase activity in the cold, but not at room temperature. In conclusion, the stimulation of liver mitochondrial cytochromes and microsomal cyt P-450 as a consequence of chronic ethanol treatment indicated an increased oxidation capacity for ethanol. The stimulation of glucose-6-phosphatase in a cold environment might be responsible for increasing glucose for heat production after chronic ethanol treatment in cold adapted animals.

Alcohol Oxidoreductases↗