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The effect of warm ischemia and cold-storage preservation on rat pancreas transplantation.

Pancreatic isografts subjected to preharvest warm ischemia as well as cold-storage preservation in Collins' solution were studied after transplantation into diabetic rats to determine whether warm ischemia will limit the ability to preserve pancreas grafts for transplantation. Warm ischemic periods of up to 2 hr did not alter islet function as measured by daily glucose levels and response to intravenous glucose challenge. Likewise, hypothermic preservation of nonischemic pancreata was also well tolerated for up to 24 hr. However, the combination of preharvest warm ischemia and cold storage was deleterious. Whereas 60 min of warm injury coupled with 12 hr of cold storage resulted in successful transplantation in 86% of recipients, lengthening the duration of either warm or cold ischemia uniformly resulted in nonfunctioning grafts. Thus while islet function in the transplanted pancreas is very tolerant of warm ischemia alone, these studies suggest that it should be kept to a minimum if cold storage preservation is to be used.

Animals↗

Thrombophlebitis following intravenous glucose in the cold.

In an effort to characterize the role of carbohydrate metabolism during the hypermetabolic state associated with whole body cooling, oral (n = 6) and intravenous (iv; n = 3) glucose tolerance tests (GTT) were performed in nude subjects. Unexpectedly, 1-2 wks after the completion of their iv GTT (50% dextrose) in the cold, superficial thrombophlebitis was diagnosed in all 3 subjects. No subject developed thrombophlebitis after the oral GTT in the warm and cold, nor after the iv GTT in the warm. Since this complication was not observed in further testing with isotonic iv solutions under identical conditions in the cold as above, we conclude that the adverse reaction is the result of an interaction between whole body cooling or vasoconstriction and the hypertonicity of the dextrose solution. Environmental physiologists and medical officers should be aware of this complication.

Administration, Oral↗

Paradoxical elevation of threshold to angina pectoris by cold pressor test in men with significant coronary artery disease.

Patients with coronary artery disease (CAD) have angina pectoris at varying levels of myocardial oxygen demand. Fluctuations in coronary blood supply due to dynamic changes in coronary vasomotor tone are believed to be responsible for this variation in angina threshold. Cutaneous cold application produces an inappropriate increase in coronary vascular resistance in patients with CAD. To assess the effect of a coronary vasoconstrictor stimulus during exercise (when there are competitive stimuli for coronary dilatation), 16 men with documented CAD and angina underwent 2 exercise tolerance tests, 1 performed for control purposes and the other during cold application (hand and forearm immersed in ice). The cold pressor test elicited an increase in systolic blood pressure at rest (134 vs 159 mm Hg, p less than 0.02) at the end of stage I (145 vs 165 mm Hg, p less than 0.02) and at peak exercise (154 vs 166 mm Hg, p less than 0.05). The diastolic pressure was similarly increased during cold pressor exercise test, but the heart rate showed little or no change. Most patients (11 of 16) tolerated equal or greater double products (heart rate X systolic pressure X 10(-3) at angina (17 vs 20, p less than 0.02), 1-mm ST-segment depression (16 vs 18, p less than 0.05) and peak exercise (18 vs 20, p less than 0.08) during cold pressor exercise test as compared with the baseline exercise test, without a reduction in exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Antivirals for the common cold.

BACKGROUND: The common cold is a ubiquitous short and usually mild illness for which preventive and treatment interventions have been under development since the mid-40s. As our understanding of the disease has increased, more experimental antivirals have been developed. This review attempts to draw together experimental evidence of the effects of these compounds. OBJECTIVES: To identify, assemble, evaluate and (if possible) synthesise the results of published and unpublished randomised controlled trials of the effects of antivirals to prevent or minimise the impact of the common cold. SEARCH STRATEGY: We searched electronic databases, corresponded with researchers and handsearched the archives of the MRC's Common Cold Unit (CCU). SELECTION CRITERIA: We included original reports of randomised and quasi-randomised trials assessing the effects of antivirals on volunteers artificially infected and in individuals exposed to colds in the community. DATA COLLECTION AND ANALYSIS: We included 241 studies assessing the effects of Interferons, interferon-inducers and other antivirals on experimental and naturally occurring common colds, contained in 230 reports. We structured our comparisons by experimental or community setting. MAIN RESULTS: Although intranasal interferons have high preventive efficacy against experimental colds (protective efficacy 46%, 37% to 54%) and to a lesser extent against natural colds (protective efficacy 24%, 21% to 27%) and are also significantly more effective than placebo in attenuating the course of experimental colds (WMD 15.90, 13.42 to 18.38), their safety profile makes compliance with their use difficult. For example, prolonged prevention of community colds with interferons causes blood-tinged nasal discharge (OR 4.52, 3.78 to 5.41). Dipyridamole (protective efficacy against natural colds 49%, 30% to 62%), ICI 130, 685 (protective efficacy against experimental colds 58%, 35% to 74% ), Impulsin (palmitate) (protective efficacy against natural colds 44%, CI 35% to 52% ) and Pleconaril (protective efficacy against experimental colds 71%, 15% to 90% ) appear to have important antiviral properties and are well-tolerated. The evidence of effectiveness of other compounds in the treatment of experimental or natural colds is sparse. REVIEWER'S CONCLUSIONS: There are no licensed effective antivirals for the common cold. Because prolonged intranasal administration causes a clinical picture which is not distinguishable from the common cold, interferons have no place in everyday use. Further assessment of the effects of dipyridamole, palmitate, ICI 130, 685, Impulsin and Pleconaril in preventing the common cold should be carried out. Given the multi-agent nature of the causes of the common cold, future research efforts should focus on non virus-specific compounds.

Administration, Intranasal↗

Endogenous opiates increase pain tolerance after stress in humans.

This study investigates the role of endogenous opioids in the regulation of pain in humans. Two groups of healthy volunteers were subjected to different stress situations (cold pressor and arithmetic). In a double-blind design the changes in pain tolerance after stress were measured after an injection of either 0.8 mg naloxone or placebo. The cold pressor test raised the pain threshold in the placebo-treated group, but not in the naloxone-treated group. Mental arithmetic had no effect on pain perception. One can conclude therefore that physical stress may change pain perception depending upon the secretion of endogenous opioids.

Adult↗

Natural freeze-tolerance in hatchling painted turtles?

Hatchlings of the North American painted turtle (Family Emydidae: Chrysemys picta) typically spend their first winter of life inside a shallow, subterranean hibernaculum (the natal nest) where life-threatening conditions of ice and cold commonly occur. Although a popular opinion holds that neonates exploit a tolerance for freezing to survive the rigors of winter, hatchlings are more likely to withstand exposure to ice and cold by avoiding freezing altogether-and to do so without the benefit of an antifreeze. In the interval between hatching by turtles in late summer and the onset of wintery weather in November or December, the integument of the animals becomes highly resistant to the penetration of ice into body compartments from surrounding soil, and the turtles also purge their bodies of catalysts for the formation of ice. These two adjustments, taken together, enable the animals to supercool to temperatures below those that they routinely experience in nature. However, cardiac function in hatchlings is diminished at subzero temperatures, thereby compromising the delivery of oxygen to peripheral tissues and eliciting an increase in reliance by those tissues on anaerobic metabolism for the provision of ATP. The resulting increase in production of lactic acid may disrupt acid/base balance and lead to death even in animals that remain unfrozen. Although an ability to undergo supercooling may be key to survival by overwintering turtles in northerly populations, a similar capacity to resist inoculation and undergo supercooling characterizes animals from a population near the southern limit of distribution, where winters are relatively benign. Thus, the suite of characters enabling hatchlings to withstand exposure to ice and cold may have been acquired prior to the northward dispersal of the species at the end of the Pleistocene, and the characters may not have originated as adaptations specifically to the challenges of winter.

Acclimatization↗

Beta-adrenoceptor blockers and terbutaline in patients with chronic obstructive lung disease. Effects and interaction after oral administration.

We studied the effects of a combined treatment with beta 2-stimulating and beta-blocking drugs in 35 patients suffering from chronic obstructive lung disease (COLD) and ischemic heart disease, and/or arterial hypertension. The drugs used were equipotent repeated oral doses of metoprolol (100 mg twice daily [bid]), propranolol (80 mg bid), and a matching placebo for beta-adrenoceptor blockade given in a double-blind and crossover fashion. The intake period of each beta-blocker was two days with consecutive two-day-washout period; 2.5 mg terbutaline and beta-stimulator placebo, respectively, were given throughout the whole trial three times daily (tid). Propranolol alone caused severe deterioration of lung function. After 18 patients had been studied, this drug had to be excluded from the trial. When compared with placebo, metoprolol provoked increasing obstruction, too, but to a significantly lesser degree than propranolol. These negative effects on FEV1 and FRC were completely equalized by terbutaline. Predictive factors for the tolerability of beta-blockers in patients with COLD could not be found. Therefore, careful observations in the initial phase of the treatment with beta-selective blockers are necessary.

Administration, Oral↗

LEA proteins prevent protein aggregation due to water stress.

LEA (late embryogenesis abundant) proteins in both plants and animals are associated with tolerance to water stress resulting from desiccation and cold shock. However, although various functions of LEA proteins have been proposed, their precise role has not been defined. Recent bioinformatics studies suggest that LEA proteins might behave as molecular chaperones, and the current study was undertaken to test this hypothesis. Recombinant forms of AavLEA1, a group 3 LEA protein from the anhydrobiotic nematode Aphelenchus avenae, and Em, a group 1 LEA protein from wheat, have been subjected to functional analysis. Heat-stress experiments with citrate synthase, which is susceptible to aggregation at high temperatures, suggest that LEA proteins do not behave as classical molecular chaperones, but they do exhibit a protective, synergistic effect in the presence of the so-called chemical chaperone, trehalose. In contrast, both LEA proteins can independently protect citrate synthase from aggregation due to desiccation and freezing, in keeping with a role in water-stress tolerance; similar results were obtained with lactate dehydrogenase. This is the first evidence of anti-aggregation activity of LEA proteins due to water stress. Again, a synergistic effect of LEA and trehalose was observed, which is significant given that non-reducing disaccharides are known to accumulate during dehydration in plants and nematodes. A model is proposed whereby LEA proteins might act as a novel form of molecular chaperone, or 'molecular shield', to help prevent the formation of damaging protein aggregates during water stress.

Animals↗

Seasonal changes in physiology and development of cold hardiness in the hatchling painted turtle Chrysemys picta.

Hatchling painted turtles (Chrysemys picta) commonly hibernate in shallow, natal nests where winter temperatures may fall below -10 degrees C. Although hatchlings are moderately freeze-tolerant, they apparently rely on supercooling to survive exposure to severe cold. We investigated seasonal changes in physiology and in the development of supercooling capacity and resistance to inoculative freezing in hatchling Chrysemys picta exposed in the laboratory to temperatures that decreased from 22 to 4 degrees C over a 5.5 month period. For comparison, we also studied hatchling snapping turtles (Chelydra serpentina), a less cold-hardy species that usually overwinters under water. Although Chrysemys picta and Chelydra serpentina differed in some physiological responses, both species lost dry mass, catabolized lipid and tended to gain body water during the acclimation regimen. Recently hatched, 22 degrees C-acclimated Chrysemys picta supercooled only modestly (mean temperature of crystallization -6.3+/-0.2 degrees C; N=6) and were susceptible to inoculation by ice nuclei in a frozen substratum (mean temperature of crystallization -1.1+/-0.1 degrees C; N=6) (means +/- s.e.m.). In contrast, cold-acclimated turtles exhibited pronounced capacities for supercooling and resistance to inoculative freezing. The development of cold hardiness reflected the elimination or deactivation of potent endogenous ice nuclei and an elevation of blood osmolality that was due primarily to the retention of urea, but was not associated with accumulation of the polyols, sugars or amino acids commonly found in the cryoprotection systems of other animals. Also, Chrysemys picta (and Chelydra serpentina) lacked both antifreeze proteins and ice-nucleating proteins, which are used by some animals to promote supercooling and to initiate freezing at the high temperatures conducive to freezing survival, respectively.

Acclimatization↗

The effects of experimenter characteristics on pain reports in women and men.

The present study investigated the effects of two attributes of the experimenter (gender and professional status) on the report and tolerance of pain in male and female subjects. 160 non-psychology students (80 male and 80 female, aged 17-59 years) participated in a cold-pressor task. Subjects were assigned to one of 8 groups: male (M) and female (F) experimenters tested male (m) and female (f) students. In each combination (Mm, Mf, Fm, Ff), the cold-pressor task was conducted by either one of two faculty members (high professional) or one of two students (low professional). Subjects were asked to immerse their non-dominant hand as long as possible in cold water (-1 degrees C). Dependent variables were pain threshold, pain tolerance, and pain intensity. Results indicated a significant main effect for professional status of the experimenter on pain tolerance. Subjects tolerated pain longer when they were tested by a professional experimenter. Further, a significant interaction of experimenter gender and subject gender on pain tolerance indicated that subjects also tolerated pain longer when they were tested by an experimenter of the opposite sex. Additionally, a significant main effect for experimenter gender showed higher pain intensities for subjects tested by female experimenters. The observation that pain responsivity is influenced by the professional status of the experimenter might have implications for the study of pain in general and should be addressed in more detail in future experiments.

Adolescent↗

Human morphology and temperature regulation.

For nearly a century individuals have believed that there is a link between human morphology and one's thermoregulatory response in adverse environments. Most early research was focussed on the rate of core cooling in a male adult population and the role of subcutaneous adipose tissue, surface area and the surface-area-to-mass ratio in one's ability to withstand varying degrees of cold stress. More recently research has addressed heat tolerance in various populations, exploring the role of subcutaneous adipose tissue, surface area and the surface-area-to-mass ratio in one's ability to maintain thermal equilibrium in warm and hot, dry and humid environments. Since the late 1970s an emphasis has been placed on the role of muscle and muscle perfusion in total-body thermal insulation. Yet, despite the history of research pertaining to human morphology and temperature regulation there is little consensus as to the impact of variations in human morphology on thermoregulatory responses. Individuals differing in body size, shape and composition appear to respond quantitatively differently to variations in both ambient and core temperatures but the interrelations between morphological components and temperature regulation are complex. It is the purpose of this paper to examine the literature pertaining to the impact of variations in muscularity, adipose tissue thickness and patterning, surface area and the surface-area-to-mass ratio on thermoregulation and thermal stability in response to both heat and cold stress.

Adipose Tissue↗

Catecholamine responses to environmental stressors in trained and untrained men after 3-day bed rest.

INTRODUCTION: The effect of decreased physical activity with reduced gravitational stress on activity, sensitivity, and reactivity of the sympathetic nervous system (SNS) is not fully recognized. We hypothesized that the effect is most pronounced in physically active subjects. Thus, basal plasma norepinephrine [NE] and epinephrine [E], and catecholamine responses to physiological stimuli were determined after 3 d of horizontal bed rest (BR) in subjects differing in level and kind of habitual activity. METHODS: Before and after BR, 11 untrained students, 8 endurance athletes, and 10 power/strength athletes were submitted to oral glucose tolerance test (OGTT) and orthostatic stand test (OST). Another 32 men (12 untrained, 10 endurance athletes, and 10 power/strength athletes) underwent cold pressor test (CPT) and graded exercise test (GET) performed until volitional exhaustion. RESULTS: After BR, basal [NE] was decreased only in athletes (p < 0.01). Increases in both catecholamines during OGTT were diminished (p < 0.05), particularly in endurance athletes. Plasma [NE] response to standing was not affected by BR in individual groups, but it was diminished in the whole group (p < 0.05). Bed rest did not affect the increases in catecholamines induced by CPT and GET. Heart rate response to OST, and BP responses to OST, CPT, and glucose ingestion were enhanced. CONCLUSIONS: Basal sympathetic activity is diminished after 3 d of BR in physically active men. Although catecholamine responses to glucose load and standing were reduced, the general reactivity and sensitivity of SNS were not attenuated since catecholamine responses to the most (exercise) and least (CPT) powerful stimuli were unchanged.

Adult↗

Improvement of freezing tolerance in transgenic tobacco leaves by expressing the hiC6 gene.

A cryoprotective protein, HIC6, was expressed transgenically in tobacco, a cold-sensitive plant, and the localization of the protein within the cell as well as freezing tolerance of the transgenic tobacco was investigated. For constitutive expression of HIC6 in tobacco, its corresponding gene was subcloned into pBI121. Through the transformation with pBI121/hiC6, fifteen transgenic tobacco lines were acquired, out of which twelve lines expressed the HIC6 protein. None of the transgenic tobacco lines, however, showed significant differences in freezing tolerance from the control plants (wild-type and transformed with pBI121) at -1, -3, and -4 degrees C, with the exception that their freezing temperature was -2 degrees C. In order to increase the accumulation level of HIC6, pBE2113 with a stronger promoter was used. Eight lines expressed the protein out of thirteen lines transformed with pBE2113/hiC6. The accumulation levels of the protein were clearly higher in the tobacco plants transformed with pBE2113/hiC6 than in those with pBI121/hiC6. The HIC6 protein seemed to be localized in mitochondria of the transgenic tobacco plants. Freezing-tolerance tests at -1 - -4 degrees C showed that the degree of electrolyte leakage was significantly lower in the plants with pBE2113/hiC6 than in the control plants. A leaf browning observation also showed that high accumulation of HIC6 significantly suppressed injury caused by freezing to the transgenic tobacco at -3 degrees C.

Algal Proteins↗

Facial expression during induced pain.

Facial expressions contribute substantially to judgments of sufferer's pain but have not been rigorously described. We obtained a detailed description of 72 female volunteers' facial reactions to the cold pressor experience, using Ekman and Friesen's (1978a) objective, anatomically based Facial Action Coding System. In addition, we examined the impact of exposure to social models tolerant or intolerant to pain. The facial actions systematically provoked by cold pressor exposure comprised a narrowing of the eye aperture from below, raising the upper lip, pulling the lip corners, parting of the lips, or dropping the jaw, and eyes closing or frequently blinking; however, there was rich individual variation in the facial displays. The reactions were most salient at onset, indicating blends of startle, adaptive reaction, emotional expression, and pain, but they declined in vigor over time, although self-report of pain continued to mount. The relation between subjective distress and facial expression was greatest at the beginning of noxious stimulation. The social models had a potent impact on verbal report and pain tolerance but not on facial expression, indicating relative independence of components within the rich range of expressive reactions of painful experience.

Adolescent↗

Long-term preservation of segmental pancreas autografts.

Clinical pancreas transplantation is logistically difficult because of uncertainty concerning how long pancreas grafts can be preserved. We studied the viability of canine segmental (tail) pancreatic autografts transplanted after 24 to 72 hours of hypothermic preservation in either modified Collins' solution or modified silica gel filtered dog plasma (SGF). All grafts stored for 24 to 48 hours functioned immediately (plasma glucose less than 140 mg/dl in recipients). Grafts that failed did so between 2 and 7 days, and five dogs died with functioning grafts. The long-term functional success rate was 80% for fresh transplants; 67% and 40% for grafts stored in Collins' solution for 24 and 48 hours, respectively; and 75%, 75%, and 30% for grafts stored in SGF for 24, 48, and 72 hours, respectively. If technical failures are excluded. 50% of grafts stored in Collins' solution and 100% of grafts stored in SGF for 48 hours functioned long term. K values for the intravenous glucose tolerance test at 2 weeks in dogs with functioning grafts ranged from -1.44% to -1.78% and were similar in all groups. In conclusion, pancreatic grafts can be preserved for 48 hours by simple cold storage, but SGF is more reliable than Collins' solution (P = 0.015). Four human pancreas grafts were stored in SGF for 7 to 22 hours, one with and three without prior warm ischemia, and all three of the latter functioned after transplantation.

Animals↗

Freezing tolerance of citrus, spinach, and petunia leaf tissue : osmotic adjustment and sensitivity to freeze induced cellular dehydration.

Seasonal variations in freezing tolerance, water content, water and osmotic potential, and levels of soluble sugars of leaves of field-grown Valencia orange (Citrus sinensis) trees were studied to determine the ability of citrus trees to cold acclimate under natural conditions. Controlled environmental studies of young potted citrus trees, spinach (Spinacia pleracea), and petunia (Petunia hybrids) were carried out to study the water relations during cold acclimation under less variable conditions. During the coolest weeks of the winter, leaf water content and osmotic potential of field-grown trees decreased about 20 to 25%, while soluble sugars increased by 100%. At the same time, freezing tolerance increased from lethal temperature for 50% (LT(50)) of -2.8 to -3.8 degrees C. In contrast, citrus leaves cold acclimated at a constant 10 degrees C in growth chambers were freezing tolerant to about -6 degrees C. The calculated freezing induced cellular dehydration at the LT(50) remained relatively constant for field-grown leaves throughout the year, but increased for leaves of plants cold acclimated at 10 degrees C in a controlled environment. Spinach leaves cold acclimated at 5 degrees C tolerated increased cellular dehydration compared to nonacclimated leaves. Cold acclimated petunia leaves increased in freezing tolerance by decreasing osmotic potential, but had no capacity to change cellular dehydration sensitivity. The result suggest that two cold acclimation mechanisms are involved in both citrus and spinach leaves and only one in petunia leaves. The common mechanism in all three species tested was a minor increase in tolerance (about -1 degrees C) resulting from low temperature induced osmotic adjustment, and the second in citrus and spinach was a noncolligative mechanism that increased the cellular resistance to freeze hydration.

Journal Article↗

Arabidopsis CBF1 overexpression induces COR genes and enhances freezing tolerance.

Many plants, including Arabidopsis, show increased resistance to freezing after they have been exposed to low nonfreezing temperatures. This response, termed cold acclimation, is associated with the induction of COR (cold-regulated) genes mediated by the C-repeat/drought-responsive element (CRT/DRE) DNA regulatory element. Increased expression of Arabidopsis CBF1, a transcriptional activator that binds to the CRT/DRE sequence, induced COR gene expression and increased the freezing tolerance of nonacclimated Arabidopsis plants. We conclude that CBF1 is a likely regulator of the cold acclimation response, controlling the level of COR gene expression, which in turn promotes tolerance to freezing.

Acclimatization↗