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PubMed1986

Effect of exercise training on the disappearance of cold adaptability in rats.

Following the transfer of cold-adapted rats to a warm environment at 25 degrees C, enhanced nonshivering thermogenesis and enlarged interscapular brown adipose tissue (BAT) decreased gradually and reached a steady state after 4 weeks of de-adaptation. Animals that were exercised in the process of de-adaptation, however, showed no decrease in enhanced nonshivering thermogenesis, but did show a decrease in BAT weight as compared with sedentarily de-adapted animals. Triiodothyronine (T3), the physiologically most active thyroid hormone, was at a higher plasma level in cold-adapted rats than in de-adapted animals with or without exercise loads. Although the resting level of T3 in running-trained rats was not higher than that in sedentary rats, some fluctuations of T3 level were observed during running.

Adaptation, Physiological↗

PubMed1994

A randomized controlled trial of cold-adapted and inactivated vaccines for the prevention of influenza A disease.

A double-blind, randomized controlled trial over 5 years compared the safety, immunogenicity, and efficacy of cold-adapted and inactivated influenza A vaccines in 5210 normal subjects. Both vaccines were well tolerated. Inactivated vaccine significantly increased hemagglutination inhibition antibody titers. Significant titer rises were also noted after cold-adapted vaccine but of lesser magnitude than with inactivated vaccine. The efficacy of inactivated vaccine in preventing culture-positive influenza was 76% (95% confidence interval [CI], 58%-87%) for H1N1 disease and 74% (95% CI, 52%-86%) for H3N2; for cold-adapted vaccine, 85% (95% CI, 70%-92%) and 58% (95% CI, 29%-75%), respectively. The efficacy of inactivated vaccine in preventing a four-fold rise in antibody titer over the influenza season was 69% (95% CI, 61%-76%) for H1N1 and 73% (95% CI, 65%-79%) for H3N2; for cold-adapted vaccine, 54% (95% CI, 44%-62%) and 32% (95% CI, 17%-44%), respectively. Cold-adapted and inactivated influenza vaccines are safe and effective for preventing influenza A disease.

Administration, Intranasal↗

PubMed1999

Haemodynamic responses and changes of haemostatic risk factors in cold-adapted humans.

Epidemiological studies have shown an increase in acute myocardial infarctions or deaths due to myocardial infarction in colder weather; the mechanisms most likely involve increased blood levels of haemostatic risk factors, and increases in arterial blood pressure and heart rate. We studied the relationship between cold adaptation, haemostatic risk factors and haemodynamic variables. Cold adaptation was obtained by a programme of immersion of the whole body up to the neck in a water-filled bath, the temperature of which was gradually decreased from 22 degrees C to 14 degrees C, time of exposure being increased from 5 to 20 min over a period of 90 days. We studied 428 patients (44% men) and measured blood levels of fibrinogen, plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator antigen (t-PA), plasma viscosity, von Willebrand factor, D-dimer and platelet count, both at baseline and after 90 days of daily immersion. There were significant reductions in von Willebrand factor (-3%; p < 0.001), and plasma viscosity (-3.0 s; p < 0.001), and a mild but significant increase in PAI-1 (+0.3 IU/ml; p = 0.02). The pressure rate product (systolic blood pressure x heart rate) was also significantly lower after cold adaptation (-310; p = 0.004). Cold adaptation, compared with exposure to cold weather, induces different haemodynamic responses and changes of blood levels of haemostatic risk factors.

Acclimatization↗

PubMed1984

[Sensitivity of skin cold receptors to noradrenaline in control and cold-adapted rats].

I. a. administration of noradrenaline (NA) activated cold receptors both in control and in cold-adapted rats. Various doses of NA induced the receptors reaction of different duration. After adaptation to cold the sensitivity of receptors to NA increased. The data obtained suggest that the sympathetic systems and the receptors sensitivity to NA play an important role in static activity of the skin cold receptors.

Adaptation, Physiological↗

PubMed1982

Studies on pathogenicity and immunogenicity of cold adapted variants of influenza virus.

Cold adapted variants of influenza virus, replicated at 37, 35, 33 and 30 degrees C, were tested for capability to multiply in ferrets and to induce H and N antibodies. Virus grown at 30 degrees C differed from the other in electrophoretic mobility of its polypeptides in PAGE, in inducing higher level of N antibodies, and in higher intensity of immunofluorescence reaction in the respiratory tract.

Adaptation, Physiological↗

PubMed2000

Use of gel electrophoresis for the study of enzymatic activities of cold-adapted bacteria.

Glutamate dehydrogenase (GDH) and lactate dehydrogenase (LDH) activity of 13 cold-adapted strains, isolated from cold soils and showing GDH and/or LDH activity in spectrophotometric assays, were revealed by the use of electrophoresis on a nondenaturing acrylamide gel (zymogram). Psychrophilic strains were grown at 4 degrees C and 10 degrees C and the psychrotolerant strains at 4 degrees, 20 degrees and 28 degrees C. Incubation with the specific substrate and staining were done at 4, 28 or 37 degrees C. In the most cold-adapted strains, LDH and GDH production was high at 4 degrees C. In psychrotrophic strains, enzyme production and activity were greater at 20 or 28 degrees C than at lower temperatures. LDH remained active up to 37 degrees C while GDH activity was more thermolabile. GDH activity was NAD-dependent in some psychrophilic strains. In other strains, it was dependent on NAD(P) only or on both NAD and NAD(P). Two bands were seen for GDH or LDH activity in some strains. This method, which does not require a dialysis step, can be used to study the influence of temperature on enzyme production and activity, and the co-factor dependence. It detects phenotypic differences between isozymes, providing data for systematics.

Adaptation, Physiological↗

PubMed1992

General and local cold adaptation after a ski journey in a severe arctic environment.

It is hypothesized that some of the variability in the conclusions of several human cold adaptation studies could be explained if not only were the changes in core and shell temperatures taken into account, before and after cold adaptation, but also the absolute temperatures and metabolic rate in both thermally neutral environments and in the cold. Such an approach was used in a group of volunteers before and after a ski journey (3 weeks at -20 to -30 degrees C) across Greenland. Eight subjects were submitted to cold tests (Tdb = 1 degree C, r.h. = 40%, wind speed = 0.8 m.s-1) for 2 hours. Thermoregulatory changes were also monitored in a neutral environment (Tdb = 30 degrees C). In the neutral environment, the arctic journey increased metabolic rate (11.2%; P less than 0.05) and mean skin temperature [Tsk: 33.5 (SEM 0.2) degrees C vs 32.9 (SEM 0.2) degrees C, P less than 0.05]. During the cold test, the arctic journey was associated with a lower final rectal temperature [36.8 (SEM 0.2) degrees C vs 37.3 (SEM 0.2) degrees C, P less than 0.01], a lower final Tsk [20.7 (SEM 0.4) degrees C vs 21.2 (SEM 0.3) degrees C, P less than 0.01] with no change in metabolic heat production. These observations are indicative of an hypothermic insulative isometabolic general cold adaptation, which was associated with a local cold adaptation of the extremities, as shown by warmer foot temperatures [12.3 (SEM 0.9) degrees C vs 9.8 (SEM 0.9) degrees C, P less than 0.001].

Adaptation, Physiological↗

PubMed1997

Cold-adapted live attenuated influenza vaccines developed in Russia: can they contribute to meeting the needs for influenza control in other countries?

It is now more than 30 years since the first cold-adapted influenza viruses were developed in Russia as potential live, attenuated vaccines. In the past 15-20 years considerable experience has been gained from Russian and joint Russian-US laboratory and clinical studies with type A monovalent and bivalent vaccines prepared with genetic reassortant viruses derived from one of these cold-adapted viruses in particular. A/Leningrad/134/57. More recent experiences include use of trivalent cold-adapted vaccines with a type B component. The overall high level of safety of individual and combined vaccines in pre-school and school-aged children, with illness reductions in open field trials equivalent to that seen with inactivated vaccines, is such as to suggest that practical measures might now be justified to facilitate expansion of the use of these vaccines to other countries. It is proposed that further experimentation with the Russian cold-adapted live attenuated vaccines should be focused on issues that will relate to the public health perspective, i.e. selection of the single best candidate type A and B vaccines for intense study using as criteria their potential for meeting licensing requirements outside Russia, and documenting the clinical protective efficacy of a single vaccine dose compared to two doses as studied until now. Resolution of these issues is important to ensure that costs for future live vaccine production, control, and utilization will be kept at lowest levels so that expanded use of live vaccines will have maximum cost-benefit and afford-ability. To guide those interested in these issues, examples are given of populations for whom a licensed live cold-adapted vaccine might be considered, together with indications of extra data needed to fully validate each suggested use.

Cold Temperature↗

PubMed1984

Serological evaluation of an influenza A virus cold-adapted reassortant live vaccine, CR-37 (H1N1), in Japanese adult volunteers.

A cold-adapted influenza A virus, CR-37 (H1N1), derived from genetic reassortment between A/Ann Arbor/6/60 (H2N2) cold-adapted variant virus and A/California/10/78 (H1N1) wild-type virus, was tested in Japanese adult volunteer. The CR-37 live virus preparation induced only low-grade clinical reactions in volunteers for the first 3-4 days after inoculation. Two vaccinees who did not show any antibody changes became febrile (over 38.0 degrees C). Skin tests using the vaccine preparation and uninfected allantoic fluid were performed, and indicated that one of these two vaccines was positive for the CR-37 vaccine preparation. A high proportion of the vaccinees whose sera had a haemagglutination-inhibition (HI) antibody titre against the vaccine strain of less than or equal to 64 before inoculation, seroconverted in both HI and neuraminidase-inhibition (NAI) antibody titrations, and only a few seroconverted in the titration of antibody against type-specific internal antigens. The serological examinations against heterotypic H1N1 variants indicated that the cold-adapted live influenza virus vaccine could induce a broad spectrum of HI antibody reactivity and immunity of long duration.

Adult↗

PubMed1987

Stimulatory effect of cold adaptation on glucose utilization by brown adipose tissue. Relationship with changes in the glucose transporter system.

The effect of cold adaptation (4 degrees C) on the in vivo glucose utilization and on the number and properties of the glucose transporters has been studied in brown adipose tissue of normal rats. Glucose utilization was assessed in vivo by the 2-deoxyglucose method. Glucose transporters in plasma and microsomal membranes were quantified by the [3H]cytochalasin B-binding assay. After cold adaptation the in vivo glucose utilization by brown adipose tissue increased 21-fold compared to controls (22 degrees C). The number of glucose transporters in plasma membranes of brown adipose tissue increased from 75 to 436 pmol/g tissue and that of total glucose transporters (plasma + microsomal membranes) from 438 to 754 pmol/g tissue. In addition, cold adaptation increased the Hill coefficient of the plasma membrane transporter for cytochalasin B from 0.90 to 2.03 and decreased the Kd from 100 to 54 nM. This study shows that cold adaptation promotes: a translocation of glucose transporters from an intracellular pool to plasma membranes; an increased number of plasma membrane glucose transporters unaccounted for by the translocation process (e.g. "de novo" synthesis); an increase in the Hill coefficient for cytochalasin B that could also represent changes in the properties of the transporters vis-à-vis glucose, (e.g. positive cooperativity); and a decrease in the Kd value for cytochalasin B.

Acclimatization↗

PubMed2000

Structural comparison of psychrophilic and mesophilic trypsins. Elucidating the molecular basis of cold-adaptation.

Structural rationalizations for differences in catalytic efficiency and stability between mesophilic and cold-adapted trypsins have been suggested from a detailed comparison of eight trypsin structures. Two trypsins, from Antarctic fish and Atlantic cod, have been constructed by homology modeling techniques and compared with six existing X-ray structures of both cold-adapted and mesophilic trypsins. The structural analysis focuses on the cold trypsin residue determinants found in a more extensive comparison of 27 trypsin sequences, and reveals a number of structural features unique to the cold-adapted trypsins. The increased substrate affinity of the psychrophilic trypsins is probably achieved by a lower electrostatic potential of the S1 binding pocket particularly arising from Glu221B, and from the lack of five hydrogen bonds adjacent to the catalytic triad. The reduced stability of the cold trypsins is expected to arise from reduced packing in two distinct core regions, fewer interdomain hydrogen bonds and from a destabilized C-terminal alpha-helix. The helices of the cold trypsins lack four hydrogen bonds and two salt-bridges, and they have poorer van der Waals packing interactions to the body of the molecule, compared to the mesophilic counterparts.

Adaptation, Physiological↗

PubMed2006

Novel cold-adaptive Penicillium strain FS010 secreting thermo-labile xylanase isolated from Yellow Sea.

A novel cold-adaptive xylanolytic Penicillium strain FS010 was isolated from Yellow sea sediments. The marine fungus grew well from 4 to 20 degrees; a lower (0 degrees) or higher (37 degrees) temperature limits its growth. The strain was identified as Penicillium chrysogenum. Compared with mesophilic P. chrysogenum, the cold-adaptive fungus secreted the cold-active xylanase (XYL) showing high hydrolytic activities at low temperature (2-15 degrees) and high sensitivity to high temperature (>50 degrees). The XYL gene was isolated from the cold-adaptive P. chrysogenum FS010 and designated as xyl. The deduced amino acid sequence of the protein encoded by xyl showed high homology with the sequence of glycoside hydrolase family 10. The gene was subcloned into an expression vector pGEX-4T-1 and the encoded protein was overexpressed as a fusion protein with glutathione-S-transferase in Escherichia coli BL21. The expression product was purified and subjected to enzymatic characterization. The optimal temperature and pH for recombinant XYL was 25 degrees and 5.5, respectively. Recombinant XYL showed nearly 80% of its maximal activity at 4 degrees and was active in the pH range 3.0-9.5.

Adaptation, Physiological↗

PubMed2001

Cold adaptation of the thermophilic enzyme 3-isopropylmalate dehydrogenase.

We have performed random mutagenesis coupled with selection to isolate mutant enzymes with high catalytic activities at low temperature from thermophilic 3-isopropylmalate dehydrogenase (IPMDH) originally isolated from Thermus thermophilus. Five cold-adapted mutant IPMDHs with single-amino-acid substitutions were obtained and analyzed. Kinetic analysis revealed that there are two types of cold-adapted mutant IPMDH: k(cat)-improved (improved in k(cat)) and K(m)-improved (improved in k(cat)/K(m)) types. To determine the mechanisms of cold adaptation of these mutants, thermodynamic parameters were estimated and compared with those of the Escherichia coli wild-type IPMDH. The Delta G(m) values for Michaelis intermediate formation of the k(cat)-improved-type enzymes were larger than that of the T. thermophilus wild-type IPMDH and similar to that of the E. coli wild-type IPMDH. The Delta G(m) values of K(m)-improved-type enzymes were smaller than that of the T. thermophilus wild-type IPMDH. Fitting of NAD(+) binding was improved in the K(m)-improved-type enzymes. The two types of cold-adapted mutants employed one of the two strategies of E. coli wild-type IPMDH: relative destabilization of the Michaelis complex in k(cat)-improved-type, and destabilization of the rate-limiting step in K(m)-improved type mutants. Some cold-adapted mutant IPMDHs retained thermostability similar to that of the T. thermophilus wild-type IPMDH.

3-Isopropylmalate Dehydrogenase↗

PubMedDate not supplied

[Mutations in the genes coding for hemagglutinin and neuraminidase in cold-adapted variants of the influenza virus A/Leningrad/134/57 (H2N2)].

An analysis of ts-mutations in the genomes of native and cold-adapted variants of influenza A/Leningrad/134/57 (H2N2) virus based on the use of fowl plague virus ts mutants was carried out. The recombination test was done by the conventional method in chick embryo fibroblast culture (genes PB2, PB1, PA, NP, NA, M and NS) or cell systems permissive for reproduction of human influenza virus (gene HA). The cold-adapted strain A/Len/17 used for preparation of live influenza vaccine (LIV) for adults was shown to have 4 ts mutations: three in "internal" genes (PB2, NP, and M) and one in gene 4 coding for hemagglutinin (HA). The more attenuated cold-adapted donor A/Len/47 for preparation of similar LIV for children acquired three additional ts mutations: two (PB1 and NS) in "internal" genes and one in gene 6 coding for neuraminidase (NA). The accumulation of ts mutations in the genome of cold-adapter strains was found to be accompanied by a decrease in their pneumotropicity for mice as well as their detectability in different organs of these animals.

Adaptation, Physiological↗

PubMed1981

Analysis of genome composition and reactogenicity of recombinants of cold-adapted and virulent virus strains.

Temperature-sensitive (ts) mutations occurring in three genes, 1, 2, and 7, and 1, 5 and 7 were found in two cold-adapted (ts) attenuated influenza virus strains A/Leningrad/9/37/46 (H0N1) and A/Leningrad/134/17/57 (H2N2) respectively. The recombinants, obtained by crossing these cold-adapted strains with virulent influenza virus strains, had different genome structures and inherited from one to six genes from the cold-adapted parents. Tests of reactogenicity of recombinants in volunteers showed all the recombinants to be non-reactogenic irrespective of the number of genes inherited from the cold-adapted parent.

Adult↗

PubMedDate not supplied

[Importance of thyroid hormones in the realization of the protective effects of cold adaptation].

The possibility of limitation of stress-induced changes of lipid peroxidation (LP) and myocardial antioxidant activity (AA) caused by the combined influence of immobilization and cold during 3 hours was studied in experiments on 128 male rats. Cold adaptation was found to reduce death rates up to 10%, the degree of hypothermia, LP activation and myocardial AA depression under combined stress, significantly elevating the concentration of serum thyroid hormones. Hypothyroidism causes a 2.5-fold decrease in thyroid hormones. It also decreased the concentration of LP products and cardiac AA, and stress in hypothyroid rats resulted in as high as 50% increase in death rates and enhanced hypothermia. This also led to less marked LP stimulation and myocardial AA depression. 50% death of animals, lower hypothermia and the same changes in the content of LP products and cardiac AA, as in non-adapted rats were found in cold-adapter hypothyroid rats during combined stress. It is concluded that thyroid hormones determine the efficiency of cold adaptation to a greater extent.

Adaptation, Physiological↗

PubMed1985

[Homocarnosine in the brain of rats during cold adaptation].

24-hr effect of 2 degrees C-cold decreased the content of homocarnosin by 47.5% in the rat brain. 3-day effect decreased it by 51.2% and 7-day action decreased it by 62.2%. In cold-adapted rats (45 days) the homocarnosin content in the brain remains decreased by 56.5% and practically does not differ from the control level on the 7th day of cold-adaptation.

Adaptation, Physiological↗

PubMed1999

Hyperphagia in cold-adapted rats: a possible role for neuropeptide Y.

The feeding response to intracerebroventricular injection of neuropeptide Y or to starvation is greater in cold-adapted than in non-adapted rats, suggesting that with cold-adaptation the central sensitivity to this peptide is increased. Hypometabolism and hypothermia (which usually follow the administration of neuropeptide Y) cannot, however, be demonstrated in the course of cold-adaptation per se.

Adaptation, Physiological↗