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[Evaluation of treating anemia in patients undergoing chronic dialysis with small doses of human recombinant erythropoietin].

The aim of the study was to assess the efficacy of low dose subcutaneous (sc) recombinant human erythropoietin (rHuEpo) therapy in hemodialysis (hd) patients, with particular emphasis on their quality of life. 25 anemic (Ht < 25%) hd patients with end-stage renal disease were given small sc doses of rHuEpo once or twice weekly for 12 months. During first 4 months of the therapy there was a significant increase of Ht (21.1 +/- 0.5 vs 28.5 +/- 0.6%; p < 0.0001) and serum hb (6.68 +/- 0.12 vs 8.51 +/- 0.18 g/dl; p < 0.0001) at mean induction dose of 52.5 +/- 2.5 IU/kg/week and this was maintained with a mean dose 67.0 +/- 10.5 IU/kg/week. RHuEpo was effective in 24 patients; all of them required no blood transfusions after starting the therapy. In majority of patients an substantial (p < 0.01) improvements in exercise tolerance, well-being, cold tolerance, sexual satisfaction and libido were observed, although sexual hormones profile revealed no significant changes during the treatment. Within first 6 months of the study cardiac index decreased substantially (p < 0.01), mainly because of stroke volume reduction, but after one year this hemodynamic improvement was noted only in patients who maintained a stable blood pressure. Hypertension worsened in 31% of patients. Low-dose s.c. rHuEpo: (1) is effective and safe treatment for anemia in hds patients, sufficient to abolish blood transfusion requirements; (2) produces significant improvements in quality of life; and (3) allows for 50% costs reduction.

Adult↗

Mathematical model of man's tolerance to cold using morphological factors.

A mathematical model has been developed to anticipate the physiological responses and the thermal state of a naked human under exposure to cold, taking into account his morphological characteristics (skinfold, size, weight) and the environmental conditions (air or water temperature and velocity, barometric pressure and hygrometry). The skinfold conditions the body's thermal conductance and the metabolism depends both on rectal (Tre) and mean skin (Tsk) temperatures. After being tested, this model was used to study the evolution of Tre. It shows the influence of the skinfold which accounts for most of the inter-individual differences. It also permits discussion of survival possibilities during immersion and completes data provided by previously established curves.

Body Surface Area↗

[Influence of stress and stress-protecting factors on rat tolerance to cold and efficiency of rat adaptation to cold].

The adaptive characteristics of the body, including the specific features of increased cold resistance upon repeated exposures to cold, are determined not only by the properties of thermogenic structures themselves, but largely depend on the contribution of the central mechanisms which control the processes of habituation and mobilization of functions. The experiments revealed an increase in cold resistance in rats after preexposure to cold. Immobilization stress prior to training cold significantly decreased rapid cold resistance in the animals, but increased the training effect of the first cooling. On the contrary, chlordiazepoxide increased cold resistance during the first cooling. Testing of the untreated animal showed no effect of training. No adaptive changes in cold resistance occurred in rats with impaired amygdaloid complex. Analyzing adrenal catecholamines revealed a significant elevation of dopamine concentrations in the rats exposed to cold. Hypothalamic catecholamines did not change with cold and serotonin in intact rats and 5-hydroxyindoleacetic acid in amygdalectomized rats substantially increased.

Adaptation, Physiological↗

Sperm membrane fatty acid composition in the Eastern grey kangaroo (Macropus giganteus), koala (Phascolarctos cinereus), and common wombat (Vombatus ursinus) and its relationship to cold shock injury and cryopreservation success.

Marsupial spermatozoa tolerate cold shock well, but differ in cryopreservation tolerance. In an attempt to explain these phenomena, the fatty acid composition of the sperm membrane from caput and cauda epididymides of the Eastern grey kangaroo, koala, and common wombat was measured and membrane sterol levels were measured in cauda epididymidal spermatozoa. While species-related differences in the levels of linolenic acid (18:3, n-6) and arachidonic acid (20:4, n-6) were observed in caput epididymal spermatozoa, these differences failed to significantly alter the ratio of unsaturated/saturated membrane fatty acids. However in cauda epididymidal spermatozoa, the ratio of unsaturated/saturated membrane fatty acids in koala and kangaroo spermatozoa was approximately 7.6 and 5.2, respectively; substantially higher than any other mammalian species so far described. Koala spermatozoal membranes had a higher ratio of unsaturated/saturated membrane fatty acids than that of wombat spermatozoa (t = 3.81; df = 4; p < or = 0.02); however, there was no significant difference between wombat and kangaroo spermatozoa. The highest proportions of DHA (22:6, n-3), the predominant membrane fatty acid in cauda epididymidal spermatozoa, were found in wombat and koala spermatozoa. While species-related differences in membrane sterol levels (cholesterol and desmosterol) were observed in cauda epididymidal spermatozoa, marsupial membrane sterol levels are very low. Marsupial spermatozoal membrane analyses do not support the hypothesis that a high ratio of saturated/unsaturated membrane fatty acids and low membrane sterol levels predisposes spermatozoa to cold shock damage. Instead, cryogenic tolerance appears related to DHA levels.

Animals↗

Cold-pressor pain tolerance in opiate and cocaine abusers: correlates of drug type and use status.

The objective of this study was to describe pain tolerance in drug abusers. Research suggests that drug dependence and pain perception share common neuroanatomical and neurophysiological substrates; thus the abuse of psychoactive drugs was hypothesized to relate to pain tolerance. We examined cold-pressor pain tolerance in 122 male, current and former opioid and cocaine abusers, across use status and primary drug of abuse. Descriptive analyses showed that the ratio of pain-sensitive to pain-tolerant persons was considerably higher than that described in the normative cold-pressor pain literature. Two-way analysis of variance revealed a significant main effect for using status, indicating that current drug use is associated with decreased pain tolerance. The main effect for drug type approached significance, implying that persons who abuse opioids manifest less pain tolerance than cocaine users. The findings emphasize the importance of studying pain tolerance and drug abuse as interrelated phenomena.

Adult↗

Rapid cold-hardening of Drosophila melanogaster (Diptera: Drosophiladae) during ecologically based thermoperiodic cycles.

In contrast to most studies of rapid cold-hardening, in which abrupt transfers to low temperatures are used to induce an acclimatory response, the primary objectives of this study were to determine (i) whether rapid cold-hardening was induced during the cooling phase of an ecologically based thermoperiod, (ii) whether the protection afforded was lost during warming or contributed to increased cold-tolerance during subsequent cycles and (iii) whether the major thermally inducible stress protein (Hsp70) or carbohydrate cryoprotectants contributed to the protection afforded by rapid cold-hardening. During the cooling phase of a single ecologically based thermoperiod, the tolerance of Drosophila melanogaster to 1 h at -7 degrees C increased from 5 +/- 5% survival to 62.5 +/- 7.3% (means +/- S.E.M., N=40-60), while their critical thermal minima (CTmin) decreased by 1.9 degrees C. Cold hardiness increased with the number of thermoperiods to which flies were exposed; i.e. flies exposed to six thermoperiods were more cold-tolerant than those exposed to two. Endogenous levels of Hsp70 and carbohydrate cryoprotectants were unchanged in rapidly cold-hardened adults compared with controls held at a constant 23 degrees C. In nature, rapid cold-hardening probably affords subtle benefits during short-term cooling, such as allowing D. melanogaster to remain active at lower temperatures than they otherwise could.

Acclimatization↗

Rapid cold hardening in the western flower thrips Frankliniella occidentalis.

A rapid cold hardening process is reported in first instar larvae of Frankliniella occidentalis. When larvae are transferred directly from 20 degrees C to -11.5 degrees C for 2h there is 78% mortality, whereas exposure to 0 degrees C for 4h prior to transfer to -11.5 degrees C reduces mortality to 10%. The response can also be induced by exposure to 5 degrees C for 4h or by gradual cooling at rates between 0.1 and 0.5 degrees C min(-1.) The acquired cold tolerance is transient and is rapidly lost (after 1h at 20 degrees C). Rapid cold hardening extends survival times at -11.5 degrees C and depresses lethal temperatures in short (2h) exposures. Rearing at 15 degrees C (12L:12D), (a cold acclimation regime for F. occidentalis), does not protect against the cold shock induced by direct transfer to -11.5 degrees C (which rapid cold hardening does) but does extend survival time at -5 degrees C (i.e. increased chill tolerance) whilst rapid cold hardening does not. The rapid and longer term cold hardening responses in F. occidentalis therefore appear to have different underlying mechanisms.

Journal Article↗

OsCDPK13, a calcium-dependent protein kinase gene from rice, is induced by cold and gibberellin in rice leaf sheath.

Calcium-dependent protein kinases (CDPKs) play an important role in rice signal transduction, but the precise role of each individual CDPK is still largely unknown. Recently, a full-length cDNA encoding OsCDPK13 from rice seedling was isolated. To characterize the function of OsCDPK13, its responses to various stresses and hormones were analyzed in this study. OsCDPK13 accumulated in 2-week-old leaf sheath and callus, and became phosphorylated in response to cold and gibberellin (GA). OsCDPK13 gene expression and protein accumulation were up-regulated in response to GA3 treatment, but suppressed in response to abscisic acid and brassinolide. Antisense OsCDPK13 transgenic rice lines were shorter than the vector control lines, and the expression of OsCDPK13 was lower in dwarf mutants of rice than in wild type. Furthermore, OsCDPK13 gene expression and protein accumulation were enhanced in response to cold, but suppressed under salt and drought stresses. Sense OsCDPK13 transgenic rice lines had higher recovery rates after cold stress than vector control rice. The expression of OsCDPK13 was stronger in cold-tolerant rice varieties than in cold-sensitive ones. The results suggest that OsCDPK13 might be an important signaling component in the response of rice to GA and cold stress.

Abscisic Acid↗

Chilling-induced photoinhibition in nine isolates of Valonia utricularis (Chlorophyta) from different climate regions.

Chilling induced inhibition of photosynthesis was studied in nine isolates of the marine tropical to warm-temperate green macrophyte Valonia utricularis (Roth) C. Agardh. According to their temperature requirements for growth and survival, the isolates belong to a cold-tolerant Atlantic/Mediterranean group and a cold-sensitive Indo-west Pacific group. After 5 hours exposure to 5 degrees C under moderate light, all isolates experienced similar substantial photoinhibition, which approached steady state levels after a decline in Fv/Fm to about 40% of the initial values. After return to optimal temperature and dim light conditions, Fv/Fm values increased with biphasic kinetics. A fast phase with half-life times of less than 30 minutes (dynamic photoinhibition) was followed by a slow phase lasting a few hours, indicating repair of photodamaged PSII reaction centres (chronic photoinhibition). In the Atlantic/Mediterranean isolates the fast phase accounted for more than 80 % of the recovery response, showing that these isolates were able to cope with the applied low temperature stress by down-regulating their PSII reaction centres. In contrast, the two isolates from the Seychelles were predominantly photodamaged. In a second experiment, three isolates (Corsica, Seychelles, Japan) were exposed to a similar relative amount of cold stress (0, 10, 15 degrees C, respectively). The Japanese isolate and the isolate from the Seychelles showed significantly less inhibition compared to 5 degrees C exposure, but no significant difference was found in the Corsican isolate. However, the degree of low temperature stress had no significant influence on the relative contributions of dynamic and chronic photoinhibition. Only two of the seven investigated isolates had a lower final inhibition level when grown at sub-optimal temperatures than at optimal temperatures. However, all sub-optimally grown Atlantic/Mediterranean isolates exhibited faster recovery kinetics from chilling-induced photoinhibition than optimally grown plants. This is related to a faster recovery from chronic photoinhibition than to a higher relative contribution of dynamic photoinhibition. A specific role of the photoprotective pigments of the xanthophyll cycle, leading to an acclimation response in the Atlantic/Mediterranean isolates may be involved. We conclude that ecotypic differentiation in V. utricularis is mirrored in different degrees of susceptibility to low temperature stress.

Acclimatization↗

Water relations of the freeze-tolerant New Zealand alpine cockroach Celatoblatta quinquemaculata (Dictyoptera: Blattidae).

Celatoblatta quinquemaculata is a freeze-tolerant alpine cockroach found on the Rock and Pillar Range, Central Otago, New Zealand. This study investigated seasonal changes in water content, as well as desiccation tolerance, and the relationship between desiccation and cold tolerance. Whole body water contents from field-fresh cockroaches collected over a 20 month period ranged from 69.9+/-1.0% fresh weight (FW) in February 1998 to 60.3+/-1.1% FW in July 1998. Water contents were significantly lower in winter than summer, and were positively correlated to microhabitat temperatures over the week preceding collection. Cockroaches survived the loss of up to 82% (mean: 56.7%+/-10.2) of their initial body water content, and the amount of water loss sustained was not dependent on the rate of water loss. Cockroaches did not suffer further mortality due to desiccation after removal to 99% relative humidity, but only regained lost water if given access to liquid water. Experimental dehydration did not enhance freeze-tolerance, but did slightly lower the supercooling point. It is concluded that reduction of body water content in winter may be a consequence of cold hardening responses, but desiccation does not constitute the cold hardening mechanism itself.

Journal Article↗

Cold-hardiness of a laboratory colony of lone star ticks (Acari: Ixodidae).

The cold-hardiness of a lone star tick, Amblyomma americanum (L.), laboratory colony was characterized. Fed and unfed larvae, fed and unfed nymphs, and unfed adults did not survive exposure to -17 degrees C for 7 d. After an 8-d exposure to -10 degrees C, adults tolerated cold better than immatures and unfed specimens fared better than fed ticks. Exposing unfed 6-wk-old (postmolt) adult males and females to -15 degrees C for increasing intervals up to 2 h suggests that males were more tolerant to cold than were females. Half of all adults were alive 3 d after the 2-h low-temperature treatment. Males may have survived because of a significantly higher hemolymph osmotic pressure, although the solute concentration increased for both sexes after a 2-h exposure to 0 degree C. Acclimation to 5 degrees C for 7 d had no influence on supercooling points for unfed males and females, engorged nymphs and larvae, and eggs. None of the life stages survived supercooling, which strongly suggests that this species is freeze intolerant. Intolerance of immature stages to chilling may be a limiting factor in the northern distribution of lone star ticks in North America.

Animals↗

Desiccation stress at sub-zero temperatures in polar terrestrial arthropods.

Cold tolerant polar terrestrial arthropods have evolved a range of survival strategies which enable them to survive the most extreme environmental conditions (cold and drought) they are likely to encounter. Some species are classified as being freeze tolerant but the majority of those found in the Antarctic survive sub-zero temperatures by avoiding freezing by supercooling. For many arthropods, not just polar species, survival of desiccating conditions is equally important to survival of low temperatures. At sub-zero temperatures freeze avoiding arthropods are susceptible to desiccation and may lose water due to a vapour diffusion gradient between their supercooled body fluids and ice in their surroundings. This process ceases once the body fluids are frozen and so is not a problem for freeze tolerant species. This paper compares five polar arthropods, which have evolved different low temperature survival strategies, and the effects of exposure to sub-zero temperatures on their supercooling points (SCP) and water contents. The Antarctic oribatid mite (Alaskozetes antarcticus) reduced its supercooling point temperature from -6 to -30 degrees C, when exposed to decreasing sub-zero temperatures (cooled from 5 to -10 degrees C over 42 days) with little loss of body water during that period. However, Cryptopygus antarcticus, a springtail which occupies similar habitats in the Antarctic, showed a decrease in both water content and supercooling ability when exposed to the same experimental protocol. Both these Antarctic arthropods have evolved a freeze avoiding survival strategy. The Arctic springtail (Onychiurus arcticus), which is also freeze avoiding, dehydrated (from 2.4 to 0.7 g water g(-1) dry weight) at sub-zero temperatures and its SCP was lowered from c. -3 to below -15 degrees C in direct response to temperature (5 to -5.5 degrees C). In contrast, the freeze tolerant larvae of an Arctic fly (Heleomyza borealis) froze at c. -7 degrees C with little change in water content or SCP during further cold exposure and survived frozen to -60 degrees C. The partially freeze tolerant sub-Antarctic beetle Hydromedion sparsutum froze at c. -2 degrees C and is known to survive frozen to -8 degrees C. During the sub-zero temperature treatment, its water content reduced until it froze and then remained constant. The survival strategies of such freeze tolerant and freeze avoiding arthropods are discussed in relation to desiccation at sub-zero temperatures and the evolution of strategies of cold tolerance.

Acclimatization↗

Water or ice?--the challenge for invertebrate cold survival.

The ecophysiology of cold tolerance in many terrestrial invertebrate animals is based on water and its activity at low temperatures, affecting cell, tissue and whole organism functions. The normal body water content of invertebrates varies from 40 to 90% of their live weight, which is influenced by water in their immediate environment, especially in species with a water vapour permeable cuticle. Water gain from, or loss to, the surrounding atmosphere may affect animal survival, but under sub-zero conditions body water status becomes more critical for overwinter survival in many species. Water content influences the supercooling capacity of many insects and other arthropods. Trehalose is known to maintain membrane integrity during desiccation stress in several taxa. Dehydration affects potential ice nucleators by reducing or masking their activity and a desiccation protection strategy has been detected in some species. When water crystallises to ice in an animal it greatly influences the physiology of nearby cells, even if the cells remain unfrozen. A proportion of body water remains unfrozen in many cold hardened invertebrates when they are frozen, which allows basal metabolism to continue at a low level and aids recovery to normal function when thawing occurs. About 22% of total body water remains unfrozen from calculations using differential scanning calorimetry (compared with ca 19% in food materials). The ratio of unfrozen to frozen water components in insects is 1:4 (1:6 for foods). Such unfrozen water may aid recovery of freezing tolerant species after a freezing exposure. Rapid changes in cold hardiness of some arthropods may be brought about by subtle shifts in body water management. It is recognised that cold tolerance strategies of many invertebrates are related to desiccation resistance, and possibly to mechanisms inherent in insect diapause, but the role of water is fundamental to them all. Detailed experimental studies are needed to provide information which will allow a more complete and coherent understanding of the behaviour of water in biological systems and aid the cryopreservation of a wide range of biological material.

Animals↗

Parasites and low temperatures.

Low temperatures affect the rate of growth, development and metabolism of parasites and when temperatures fall below 0 degrees C may expose the parasite to the potentially lethal risk of freezing. Some parasites have mechanisms, such as diapause, which synchronise their life cycle with favourable seasons and the availability of hosts. Parasites of endothermic hosts are protected from low temperatures by the thermoregulatory abilities of their host. Free-living and off-host stages, however, may be exposed to subzero temperatures and both freezing-tolerant and freeze-avoiding strategies of cold hardiness are found. Parasites of ectothermic hosts may be exposed to subzero temperatures within their hosts. They can rely on the cold tolerance adaptations of their host or they may develop their own mechanisms. Exposure to low temperatures may occur within the carcass of the host and this may be of epidemiological significance if the parasite can be transmitted via the consumption of the carcass.

Adaptation, Physiological↗