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Sensory function above lesion level in spinal cord injury patients with and without pain.

Patients with spinal cord injury (SCI) may or may not develop central neuropathic pain despite having cord lesions of apparently the same site, extension and nature. The consequences of the cord lesion in the central nervous system and the mechanisms underlying pain are unclear. In this study, we examined sensory detection and pain thresholds above injury level in 17 SCI patients with central neuropathic pain, in 18 SCI patients without neuropathic pain, and in 20 control subjects without injury and pain. The SCI pain group had significantly higher cold and warm detection thresholds compared with the SCI pain free group and controls and higher tactile detection thresholds compared with the SCI pain free group. No difference in pain or pain tolerance thresholds was seen among pain and pain free SCI patients. These data suggest changes in somatosensory function in dermatomes rostral to the segmental injury level linked to the presence of central neuropathic pain in SCI patients. The results are discussed in relation to current concepts of pain inhibitory and facilitating systems.

Adult↗

Invited review: aging and human temperature regulation.

This mini-review focuses on the effects of aging on human temperature regulation. Although comprehensive reviews have been published on this topic (Kenney WL. Exercise and Sport Sciences Reviews, Baltimore: Williams & Wilkins, 1997, p. 41-76; Pandolf KB. Exp Aging Res 17: 189-204, 1991; Van Someren EJ, Raymann RJ, Scherder EJ, Daanen HA, and Swaab DF. Ageing Res Rev 1: 721-778, 2002; and Young AJ. Exp Aging Res 17: 205-213, 1991), this mini-review concisely summarizes the present state of knowledge about human temperature regulation and aging in thermoneutral conditions, as well as during hypo- and hyperthermic challenges. First, we discuss age-related effects on baseline body core temperature and phasing rhythms of the circadian temperature cycle. We then examine the altered physiological responses to cold stress that result from aging, including attenuated peripheral vasoconstriction and reduced cold-induced metabolic heat production. Finally, we present the age-related changes in sweating and cardiovascular function associated with heat stress. Although epidemiological evidence of increased mortality among older adults from hypo- and hyperthermia exists, this outcome does not reflect an inability to thermoregulate with advanced age. In fact, studies that have attempted to separate the effects of chronological age from concurrent factors, such as fitness level, body composition, and the effects of chronic disease, have shown that thermal tolerance appears to be minimally compromised by age.

Aging↗

Differential effect of cold acclimation on blood composition in rats and hamsters.

Male rats and hamsters were exposed to a progressively lower air temperature and shorter photoperiod to simulate the onset of winter. Normothermic hamsters had a higher haematological oxygen carrying capacity (OCC) and coagulability (shorter prothrombin time and activated partial thromboplastin time) than rats. Cold acclimation significantly increased the OCC of rats, which parallels an increased metabolic rate, while no differences were observed in hamsters. Red cell transit time through filters was faster in the acclimated rats but not in hamsters, reflecting the lower mean cell volume due to a decreased rate of clearance from the circulation. Platelet counts were significantly lower in both cold-acclimated rats and hamsters, and there was a significant leucopenia in rats, which would reduce the degree of microvascular blockade. Whole blood viscosity, plasma viscosity, and serum osmolarity showed little change in either species. However, whole blood viscosity was significantly lower in cold-acclimated hamsters than control hamsters at the lowest shear rate tested (0.95 s(-1)). Interestingly, plasma viscosity and serum osmolarity were significantly lower in hamsters exposed to low temperatures for a shorter period (4 weeks), and may reflect the development of a reduced coagulability. These data suggest that blood composition in hamsters contributes to an innate tolerance of low temperatures, maintaining tissue perfusion under hypothermic conditions and aiding arousal from hibernation.

Acclimatization↗

Lipid composition and thermotropic phase behavior of boar, bull, stallion, and rooster sperm membranes.

Composition and thermotropic phase behavior of sperm membrane lipids from species ranging in sensitivity to cold shock were determined. Lipids from whole sperm and sperm plasma membrane were fractionated into neutral lipid, glycolipid, and phospholipid fractions. Compositional analyses were completed for free sterols, phospholipids and phospholipid-bound fatty acids. Phase transition temperatures were determined for phospholipid and glycolipid fractions using differential scanning calorimetry. Cholesterol was the major sterol in sperm lipids of all species. Cholesterol to phospholipid molar ratios were 0.26, 0.30, 0.36, and 0.45 for sperm plasma membrane of the boar, rooster, stallion, and bull, respectively. Choline and ethanolamine phosphoglycerides and sphingomyelin were the major phospholipid classes in sperm and their proportions differed across species. Phospholipid-bound fatty acyl compositions of choline and ethanolamine phosphoglycerides were characterized by a high proportion of docosapentanoyl and docosahexanoyl groups in mammalian sperm and shorter, more saturated groups in rooster sperm. Glycolipids represented less than 10% of total polar lipids for all species. Thin-layer chromatographic analysis indicated that the major glycolipid component of rooster sperm was different from that of mammalian sperm. Peak phase transition temperatures (Tm) for sperm membrane phospholipids were 24.0, 25.4, 20.7 and 24.5, for the boar, stallion, and rooster, respectively. Corresponding Tm's for glycolipids were 36.2, 42.8, and 33.4 with no exotherm for rooster sperm glycolipids. These results demonstrate a difference in both composition and thermotropic phase behavior of glycolipids between rooster and mammalian sperm which may be related to the greater tolerance of rooster sperm to rapid cooling.

Animals↗

cDNA sequence analysis and expression of two cold-regulated genes of Arabidopsis thaliana.

The DNA sequences of cDNAs for two cor (cold-regulated) genes of Arabidopsis thaliana L. (Heyn) were determined. One cDNA (approximately 70% full-length) corresponds to a cor gene, designated cor47, that encodes a 47 kDa hydrophilic polypeptide. The data indicate that COR47 has amino acid sequence homology with Group II LEA (late embryogenesis abundant) proteins, a class of proteins that accumulate late in embryo development. DNA sequence analysis of a second cDNA (containing the complete protein coding sequence) indicates that it represents a cor gene, designated cor6.6, that encodes an alanine-rich 6.6 kDa hydrophilic polypeptide. COR6.6 is almost identical to KIN1, a cold-regulated Arabidopsis gene that has been suggested to have amino acid sequence similarities with type I fish antifreeze proteins (S. Kurkela, M. Franck, Plant Mol Biol 15: 137-144, 1990). Northern analysis indicated that transcripts for cor47 and cor6.6 do not accumulate to high levels in late-developing embryos or fresh mature seeds as is typical of lea gene transcripts. The similarities and differences between COR and LEA proteins are discussed as are their possible roles in freezing and drought tolerance.

Adaptation, Physiological↗

Introduction of specific carbohydrates into Eucalyptus gunnii cells increases their freezing tolerance.

The comparison of soluble sugar content in various cell lines of Eucalyptus gunnii exhibiting different freezing resistances revealed that the most resistant cell line contained the highest soluble sugar content. It was possible to increase the freezing resistance of the sensitive cell line by progressive exposure to low temperatures (acclimation). During the early stage of cold acclimation, an increase of soluble sugar concentration was observed in the cells confirming the correlation between freezing resistance and soluble carbohydrate content in this species. In addition, feeding experiments on the sensitive cell line were performed to introduce specific sugars into the cells. Both electropulsation and long-term incubation in the presence of fructose and raffinose led to an increase in the tolerance of the cells during a freezing programme. Using radioactive fructose, the uptake of the sugar into cells and protoplasts was checked. In the light of these results, hypotheses are presented concerning the possible role of intracellular sugars in cryoprotection.

Adaptation, Physiological↗

The cold pressor test in children: methodological aspects and the analgesic effect of intraoral sucrose.

To determine whether intraoral sucrose has analgesic-like effects in pre-pubertal children and to explore the utility of an ethical and viable laboratory test of nociceptive stimulation in this age group, 8-11-year-olds (n = 42) underwent the cold pressor test (CPT) at 10 degrees C on each of 2 successive days, while holding either 24% sucrose or water in their months. Outcome measures used were threshold (time at which the arm first started to hurt), tolerance (when children removed their arms because they could not stand it any more) and visual analogue scale (VAS) ratings of the intensity of sensation. To ensure validity of the data obtained in this age group, some responses were rejected according to established decision rules and blind to group assignment. Each measure produced interesting data but also had limitations. Threshold data that did not meet validity criteria occurred more frequently with younger children. Tolerance data was not available for a significant proportion (57%) of children, since they left their arms in the water for the maximum time allowed (4 min). This occurred more frequently on the second day of testing and with younger children. Inability to perform adequately on the VAS also occurred, but was not related to age. Holding sucrose in the mouth was associated with a significant 35% prolongation of the children's threshold times relative to water, but there was no detectable effect on tolerance and intensity ratings. It is concluded that the analgesic properties of intraoral sucrose, seen previously in human newborns and rat pups, may also be present in pre-pubertal children.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Once daily felodipine in patients with primary Raynaud's phenomenon.

The symptomatic effects of felodipine (Plendil) have been assessed in 10 patients with primary Raynaud's phenomenon in a single blind study. After 2 weeks on placebo, the patients were treated for 6 weeks with felodipine, the dose being titrated stepwise every 2 weeks, starting with 5 mg, and increasing to 10 mg and 20 mg once daily if symptoms persisted. After the drug period the patients received placebo for 2 weeks. Objective measurement by cold exposure finger plethysmography did not show any benefit of felodipine in the higher temperature range, taking 33 degrees C as reference point. However, when using 24 degrees C as the reference point, the area under the plethysmography versus temperature curve (AUC) for 5 mg felodipine were significantly larger than the initial placebo area. The AUC during recovery from cold exposure for the maximal accepted dose of felodipine was significantly larger than for the initial placebo period. Subjective judgement by the patients showed a significant reduction in the number of Raynaud attacks and a trend to a shorter duration of attacks with the maximal dose of felodipine. Two patients became free from attacks of Raynaud's phenomenon. Felodipine 10 mg once daily was well tolerated. It was regarded as the optimal dose to treat patients with Raynaud's symptoms.

Adult↗

Antinociceptive and hypothermic crosstolerance between continuous and intermittent cold-water swims in rats.

Antinociceptive responses induced by continuous (CCWS: 2 degrees C, 3 min) and intermittent (ICWS: 2 degrees C, 18 10-s swims, 18 10-s recoveries) cold-water swims differ in their sensitivity to opioid antagonists and crosstolerance with morphine. The present study examined whether CCWS and ICWS antinociception and hypothermia displayed crosstolerance in rats. Jump thresholds were significantly increased following acute exposure to CCWS (30 min) and ICWS (30-60 min). CCWS antinociception displayed tolerance (90% reduction) to CCWS after 14 days and crosstolerance (100% reduction) to ICWS on the fifteenth day. ICWS antinociception displayed tolerance (74% reduction) to ICWS and crosstolerance (81% reduction) to CCWS. Core body temperatures were significantly decreased following acute exposure to CCWS (30 min) and ICWS (30-90 min). Although CCWS and ICWS hypothermia displayed tolerance to the same stressor and crosstolerance to the other stressor, the changes in the antinociceptive and hypothermic effects failed to correlated significantly with each other.

Acclimatization↗

Quantitative analysis of the probability of intracellular ice formation during freezing of isolated protoplasts.

(i) A quantitative prediction of the temperature and cooling-rate dependence of IIF requires information on the probability distribution for IIF temperature; the super-cooling tolerance; and membrane permeability, initial cell size, Boyle-van't Hoff relation, and other parameters associated with the thermodynamic description of cell volumetric behavior. (ii) A probabilistic analysis of IIF was developed on the basis that IIF occurs if the underlying potential IIF temperature T* falls within the range of temperatures over which the cell is supercooled beyond its tolerance delta T*. The "location" of the transition range of cooling rates, in which the Pr(IIF) increases from 0 to 1, depends on the mean of T* and delta T*. The breadth of the transition range increases strongly with variability in T*. (iii) Cryomicroscopic studies of IIF in rye protoplasts isolated from cold acclimated and nonacclimated leaves showed that the range of IIF temperatures and the incidence of IIF are strongly dependent on the solute used to manipulate osmolality in the suspending medium. The ionic solutes used in this study (NaCl + CaCl2, KCl + CaCl2, KNO3 + CaCl2) generally yielded median IIF temperatures lower than those of the nonionic solutes (sucrose, sorbitol, proline). Cold acclimation reduced the median IIF temperature for all suspending media and reduced the incidence of IIF for KCl + CaCl2, sorbitol, and proline. A Weibull distribution was found to describe adequately the distribution of IIF temperatures at the highest cooling rate. (iv) Estimates of the supercooling tolerance were generally from 1.0 to 1.5 degrees C based on the location of the transition range of cooling rates and on the estimates of Lp and delta E from (6). The breadth of the transition range of cooling rates could mostly be attributed to random variability in the underlying potential IIF temperature. The rise in median IIF temperature with higher cooling rates was correctly predicted by the model when the supercooling tolerance was also assumed to be random. For rye protoplasts, both the model and the data showed that cooling-rate dependence in median IIF temperatures occurs within the transition range of cooling rates.

Edible Grain↗

Barotolerance is inducible by preincubation under hydrostatic pressure, cold-, osmotic- and acid-stress conditions in Lactobacillus sanfranciscensis DSM 20451T.

AIMS: This study addresses the inducibility of barotolerance by preincubation of Lactobacillus sanfranciscensis DSM 20451T under various sublethal stress conditions. METHODS AND RESULTS: Stress conditions which reduce the growth rate of L. sanfranciscensis DSM 20451T to 10% of its maximum were determined. These conditions were met at 43, 12.5 degrees C, a pH value of 3.7, 1.9% NaCl, or 80 MPa respectively. In contrast to heat preincubation, other prestresses, including salt, cold and pressure led to an increase of barotolerance by hydrostatic pressure of 300 MPa for 30 min. Stationary-phase cells also showed an increased barotolerance. Sublethal pressure leads to enhanced heat tolerance. CONCLUSIONS: Stress response to salt, low temperature and acidic pH as well as starvation overlap with that one to high pressure by inducing barotolerance. SIGNIFICANCE AND IMPACT OF THE STUDY: Inactivation of bacteria by high pressure treatment is influenced by their history which modulates barotolerance. Mechanisms of barotolerance appear different from heat shock defence.

Cold Temperature↗

Tolerance by old livers of prolonged periods of preservation in the rat.

To determine the tolerance of old livers to prolonged preservation, livers from aged rats (corresponding to humans in the sixth to seventh decades of life) were transplanted after specific periods of cold preservation. Male BN/BiRij rats received orthotopic, arterialized liver grafts from either young (5 months) or old (25 to 28 month) donor rats after liver storage for 12 (n = 6), 24 (n = 6) or 30 (n = 10) hours in University of Wisconsin solution. Outcome was assessed by survival, liver enzymes after transplantation, and histology of the grafts. There were no significant differences in survival rates between recipients of old and young grafts. All rats survived after 12-hr and 24-hr preservation except one recipient of an old graft preserved for 24 hr. After 30-hr preservation recipients of old and young livers had identical survival rates (60%). There was a strong correlation between the highest postoperative AST and ALT and the duration of preservation in all groups (P < 0.0001), but only in the 24-hr preservation experiments was the ALT significantly higher in recipients of old grafts than in recipients of young livers (P = 0.025). Age of the donor did not significantly affect the peak AST, but there was a correlation between donor age and the highest postoperative ALT (P = 0.007). Although intracellular vacuolization was a prominent histological finding in more than half of the old livers at the end of preservation, it was not associated with an increase in mortality. It is concluded that under the ideal conditions provided in the experiments, old rat livers tolerate long preservation periods with satisfactory graft survival compared with young livers.

Age Factors↗

Evaluation of a cold-adapted influenza B/Texas/84 reassortant virus (CRB-87) vaccine in young children.

A cold-adapted (ca) influenza B reassortant virus vaccine that contained the six internal RNA segments from influenza B/Ann Arbor/1/66 ca virus and the neuraminidase and hemagglutinin genes from wild-type influenza B/Texas/1/84 virus was evaluated in children ranging in age from 8 months to 14 years. The children were vaccinated intranasally with doses ranging from 10(3.2) to 10(6.2) 50% tissue culture infective doses (TCID50). Thirty children were seropositive, and 26 were seronegative. Thirty-three children participated as unvaccinated controls. The vaccine was well tolerated by both seronegative and seropositive children. The amount of virus required to infect 50% of seronegative children was approximately 10(4.5) TCID50. Vaccine viruses recovered from airway secretions retained temperature-sensitive and cold-adapted characteristics. The results of this study indicate that the vaccine virus, influenza B/Texas/84 ca reassortant virus, is attenuated, immunogenic, and phenotypically stable when given to young seronegative children.

Adaptation, Biological↗

Antidiabetic activities of aqueous and ethanolic extracts of Piper betle leaves in rats.

Leaves of Piper betle (Piperaceae) possess several bioactivities and are used in traditional medicinal systems. However, its antidiabetic activity has not been scientifically investigated so far. The aim of this study therefore, was to investigate the antidiabetic activity of Piper betle leaves. This was tested in normoglycaemic and strepozotocin (STZ)-induced diabetic rats using oral administration of hot water extract (HWE) and cold ethanolic extract (CEE). In normoglycaemic rats, both HWE and CEE significantly lowered the blood glucose level in a dose-dependent manner. In glucose tolerance test, both extracts markedly reduced the external glucose load. The antidiabetic activity of HWE is comparable to that of CEE. Moreover, HWE failed to inhibit the glucose absorption from the small intestine of rats. Both extracts were found to be non-toxic and well tolerated after following chronic oral administration (no overt signs of toxicity, hepatotoxicity or renotoxicity). However, the weight of the spleen had increased in treated groups possibly indicating lymphoproliferative activity. It is concluded that HWE and CEE of Piper betle leaves possess safe and strong antidiabetic activity.

Animals↗

Glucose effectiveness and insulin sensitivity from the minimal models: consequences of undermodeling assessed by Monte Carlo simulation.

The unlabeled (cold) minimal model (MM) and the labeled (hot) minimal model (HMM) are a powerful tool to investigate in vivo metabolism from a standard intravenous glucose tolerance test (IVGTT) or hot IVGTT (HIVGTT). They allow to estimate metabolic indexes of the glucose-insulin system, namely glucose effectiveness (GE) and insulin sensitivity (IS) (of uptake and production those of MM, and of uptake only those of HMM). Here, the consequences of the single-compartment glucose kinetics approximation used in the MM's are investigated via Monte Carlo simulation, using a physiologic reference model (RM) of the system. RM allows to generate noisy synthetic plasma concentrations of glucose, tracer glucose, and insulin during IVGTT and HIVGTT, which are then analyzed with MM and HMM. The MM and HMM GE and IS are then compared with the RM ones. Results of 400 runs show that: 1) correlation of MM GE with the RM index is weak; 2) MM IS is well correlated with the RM index, but severely underestimates it; 3) HMM clearance rate is correlated with RM clearance; and 4) HMM IS is well correlated and only slightly overestimates the RM index. These results demonstrate that GE of MM is most affected by the single-compartment approximation and the indexes of HMM are more robust than those of MM.

Blood Glucose↗

Endogenous and exogenous ice-nucleating agents constrain supercooling in the hatchling painted turtle.

Hatchlings of the painted turtle (Chrysemys picta) commonly hibernate in their shallow, natal nests. Survival at temperatures below the limit of freeze tolerance (approximately -4 degrees C) apparently depends on their ability to remain supercooled, and, whereas previous studies have reported that supercooling capacity improves markedly with cold acclimation, the mechanistic basis for this change is incompletely understood. We report that the crystallization temperature (T(c)) of recently hatched (summer) turtles acclimated to 22 degrees C and reared on a substratum of vermiculite or nesting soil was approximately 5 degrees C higher than the T(c) determined for turtles acclimated to 4 degrees C and tested in winter. This increase in supercooling capacity coincided with elimination of substratum (and, in fewer cases, eggshell) that the hatchlings had ingested; however, this association was not necessarily causal because turtles reared on a paper-covered substratum did not ingest exogenous matter but nevertheless showed a similar increase in supercooling capacity. Our results for turtles reared on paper revealed that seasonal development of supercooling capacity fundamentally requires elimination of ice-nucleating agents (INA) of endogenous origin: summer turtles, but not winter turtles, produced feces (perhaps derived from residual yolk) that expressed ice-nucleating activity. Ingestion of vermiculite or eggshell, which had modest ice-nucleating activity, had no effect on the T(c), whereas ingestion of nesting soil, which contained two classes of potent INA, markedly reduced the supercooling capacity of summer turtles. This effect persisted long after the turtles had purged their guts of soil particles, because the T(c) of winter turtles reared on nesting soil (mean +/- S.E.M.=-11.6+/-1.4 degrees C) was approximately 6 degrees C higher than the T(c) of winter turtles reared on vermiculite or paper. Experiments in which winter turtles were fed INA commonly found in nesting soil showed that water-soluble, organic agents can remain fully active for at least one month. Such INA may account for the limited supercooling capacity (T(c) approximately -7.5 degrees C) we found in turtles overwintering in natural nests and may therefore pose a formidable challenge to the winter survival of hatchling C. picta.

Acclimatization↗

Treatment of vascular disease caused by vibration.

Vascular diseases caused by vibration are treated by different methods. We ourselves applied in our patients subcutaneous injections of hot-spring gas, per os prazosin (postsynaptic blocker of alpha-sympathetic receptors) which except for its vasodilatory effect improves the rheologic qualities of blood). Subcutaneous injections of hot-spring gas were administered to 31 males aged 32 to 67 years (average 50.58 years) for 15 days, Prazosin VUFB to 12 males aged 33 to 64 years (average 47.8 years) for 28 days and pentoxifylline (Agapurin SPOFA) to 20 males aged 29 to 69 years (average 46.35 years) for 28 days. Simultaneous nervous disease caused by vibration was present in 12 patients, articular affections caused by vibration in 10 patients, and disease of peripheral nerves and joints in 16 patients. The subjective complaints were influenced mostly by hotspring gas, the cold water test by prazosin, the skin temperature and plethysmogram by pentoxifylline. When evaluating the number of favourably influenced indicators pentoxifylline is the most successful. Tolerance of all three methods proved to be good.

Adrenergic alpha-Antagonists↗

Cholecystokinin-octapeptide-induced hypothermia in rats: dose-effect and structure-effect relationships, effect of ambient temperature, pharmacological interactions and tolerance.

Subcutaneous injection of cholecystokinin octapeptide (CCK-8) (0.005-1.25 mg/kg) elicited dose-dependent hypothermia in rats. The threshold of the response was between 0.01 and 0.05 mg/kg and the dose-response curve levelled off at doses larger than 0.2-0.5 mg/kg. Warm and cold ambient temperatures decreased and increased the response, respectively. Pretreatment with capsaicin, morphine, naloxone, atropine, haloperidol or propranolol did not affect the response to CCK-8, whereas pretreatment with phenoxybenzamine and a large dose of proglumide, an antagonist for CCK-receptors, attenuated the hypothermia. It seems that neither capsaicin-sensitive thermal and non-thermal afferents, nor opiate mechanisms are involved in the response, but alpha-adrenoceptors might be of some importance in the hypothermia. Non-sulphated-CCK-8, the C-terminal tetrapeptide and hexapeptide, [D-Ala4]-CCK-8 and [D-Met6]-CCK-8 were ineffective. Chronic treatment with CCK-8 resulted in the development of tolerance to the thermoregulatory effect, while the hypothermic responses to apomorphine and capsaicin were not affected. It seems that the tolerance cannot be attributed to conditioned homeostatic reactions.

Animals↗