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PubMed1992

Mediation of swim-stress antinociception by the opioid delta 2 receptor in the mouse.

The present study has characterized the antinociceptive response to cold water swim-stress (CWSS) in mice using opioid-selective antagonists as well as tolerance and cross-tolerance approaches. Mice subjected to CWSS using water at 5 degrees C for 3 min showed a marked antinociceptive response in the tail-flick test, which reached approximately 90% after +10 min, and which persisted for 15 to 20 min. This antinociceptive response (at +10 min) was antagonized by naloxone or by the delta antagonist ICI 174,864. Additionally, the CWSS response was antagonized by the opioid delta 2 antagonist, naltrindole-5'-isothiocyanate, but not by the delta 1 antagonist, [D-Ala2,Leu5,Cys6]enkephalin, or by the mu antagonist, beta-funaltrexamine or by the kappa antagonist, norbinaltorphimine. Although the CWSS-induced antinociceptive effect was blocked by some delta antagonists and tolerance resulted from the CWSS-induced response, the decrease in body temperature after each CWSS exposure was not affected by the opioid antagonists and reliably occurred in CWSS-tolerant mice, suggesting that the observed antinociception was independent of changes in body temperature. In mice rendered tolerant to the antinociceptive actions of the mu agonist, [D-Ala2,NMPhe4,Gly-ol] enkephalin, or to [D-Pen2,D-Pen5]enkephalin (predominantly a delta 1 agonist), the CWSS-induced antinociceptive response was unaltered. In contrast, in mice tolerant to the delta 2 agonist, [D-Ala2,Glu4]deltorphin, the CWSS-induced antinociceptive response was markedly and significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1977

[The suggestive control of the pain threshold in healthy teeth].

Changes in pain tolerance after administration of differently labelled placebos were studied by measuring the reaction time after a cold stimulus. Significant changes after placebo administration were observed in the morning as well as in the evening. These differed among placebos declared to be analgetics, hyperaesthetics and medications with no effect on pain. The time of day also influenced the results.

Adult↗
PubMed1985

Effect of hypothermia on cell kinetics and response to hyperthermia and X rays.

Hyperthermia is a potent radio enhancer. Studies using hypothermia in combination with irradiation have given confusing results due to lack of uniformity in experimental design. This report shows that hypothermia might have potential significance in the treatment of malignant cells with both thermo- and radiotherapy. Reuber H35 hepatoma cells, clone KRC-7 were used to study the effect of hypothermia on cell kinetics and subsequent response to hyperthermia and/or X rays. Cells were incubated at 8.5 degrees C or between 25 and 37 degrees C for 24 hr prior to hyperthermia or irradiation. Hypothermia caused sensitization to both hyperthermia and X rays. Maximum sensitization was observed between 25 and 30 degrees C and no sensitization was found at 8.5 degrees C. At 25 degrees C maximum sensitization was achieved in approximately 24 hr, cell proliferation was almost completely blocked, and cells gradually accumulated in the G2 phase of the cell cycle. In contrast to the effect of hypothermia on either hyperthermia or X rays alone, thermal radiosensitization was decreased in hypothermically pretreated cells (24 hr at 25 degrees C) compared to control cells (37 degrees C). The expression of thermotolerance and the rate of development at 37 degrees C after an initial heating at 42.5 degrees C were not influenced after preincubation at 25 degrees C for 24 hr. The expression of thermotolerance for heat or heat plus X rays during incubation at 41 degrees C occurred in a significantly smaller number of cells after 24 hr preincubation at 25 degrees C. The enhanced thermo- and radiosensitivity in hypothermically treated cells disappeared in approximately 6 hr after return to 37 degrees C.

Acclimatization↗
PubMed1990

Changes in thermal and mechanical pain thresholds in hand amputees. A clinical and physiological long-term follow-up.

In a previous study, allodynia to cold and vibratory stimuli was found in the finger stumps of 24 patients with amputations, control values being obtained from fingers of the intact contralateral hand. When treated with regional intravenous guanethidine block (RGB), some of the patients only had short-lasting relief of symptoms, whereas others experienced a more long-lasting beneficial effect. In the present long-term follow-up study the patients were re-examined 6 years after the RGB treatment. The aim was to investigate whether the earlier symptoms and signs persisted, and whether there were any differences in these respects, between patients with long-lasting (group 1) and short-lasting relief of symptoms after RGB (group 2). All 24 patients were asked to answer a questionnaire concerning their clinical symptoms. In addition, 14 of them visited the laboratory for determination of thermal and vibration-induced pain thresholds. Comparisons were made with values obtained at the first examination before RGB treatment and with values from 14 healthy subjects tested in a similar way on 2 occasions with an interval of 8 years. Twenty of 23 patients reported that cold exposure still evoked stump pain. However, the threshold measurements showed that with time the patients had become more tolerant to thermal stimuli not only in the injured but also in the uninjured hand. A rise in pain threshold was also observed when vibration-induced pain was tested in the injured hand. There was no significant difference between groups 1 and 2. Similar changes in pain thresholds with time were not observed in the group of healthy control subjects.

Adult↗
PubMed2004

Heart rate and blood pressure responses of left-handers and right-handers to autonomic stressors.

We hypothesized that cerebral dominance may contribute to differences in cardio-vascular responses of right-handers (RH) and left-handers (LH) to autonomic stressors. We tested this hypothesis by exposing 14 RH, and 14 LH males to category I tests in which the hand and cerebral cortex were involved in performing the test viz.--i) Cold pressor test (CPT), ii) Handgrip dynamometry (HGD) and; category II (no use of hand)--i) Orthostatic Tolerance Test (OTT), ii) Valsalva Manuever (VM), iii) Controlled Breathing Test for sinus arrhythmia (SA) in a random sequence, and measured their heart rate (HR/min) and blood pressure (MAP mmHg). All subjects had similar resting HR and MAP values, and responded to the category I interventions with increased HR and BP. The absolute HR values of LH and RH did not differ significantly during the interventions. However, the increase in HR from control induced by the CPT, and the HGD was greater for LH (P<0.05). Also, LH showed a greater decrease in HR and MAP in the recovery phase (P<0.05). The VAS scores for degree of discomfort during the CPT were similar for both the groups. During the OTT, the increase in HR was more in RH (P<0.05). The Valsalva ratios for LH and RH were similar. Our findings suggest that the autonomic control over the cardio-vascular system may be different in LH and RH, and that this imbalance could be attributable to a variation in cerebral dominance.

Adult↗
PubMed2006

Transcriptional profiling implicates novel interactions between abiotic stress and hormonal responses in Thellungiella, a close relative of Arabidopsis.

Thellungiella, an Arabidopsis (Arabidopsis thaliana)-related halophyte, is an emerging model species for studies designed to elucidate molecular mechanisms of abiotic stress tolerance. Using a cDNA microarray containing 3,628 unique sequences derived from previously described libraries of stress-induced cDNAs of the Yukon ecotype of Thellungiella salsuginea, we obtained transcript profiles of its response to cold, salinity, simulated drought, and rewatering after simulated drought. A total of 154 transcripts were differentially regulated under the conditions studied. Only six of these genes responded to all three stresses of drought, cold, and salinity, indicating a divergence among the end responses triggered by each of these stresses. Unlike in Arabidopsis, there were relatively few transcript changes in response to high salinity in this halophyte. Furthermore, the gene products represented among drought-responsive transcripts in Thellungiella associate a down-regulation of defense-related transcripts with exposure to water deficits. This antagonistic interaction between drought and biotic stress response may demonstrate Thellungiella's ability to respond precisely to environmental stresses, thereby conserving energy and resources and maximizing its survival potential. Intriguingly, changes of transcript abundance in response to cold implicate the involvement of jasmonic acid. While transcripts associated with photosynthetic processes were repressed by cold, physiological responses in plants developed at low temperature suggest a novel mechanism for photosynthetic acclimation. Taken together, our results provide useful starting points for more in-depth analyses of Thellungiella's extreme stress tolerance.

Arabidopsis↗
PubMed2006

Stress- and development-induced expression of spliced and unspliced transcripts from two highly similar dehydrin 1 genes in V. riparia and V. vinifera.

Dehydrins are proteins that accumulate in vegetative tissues subjected to various dehydrating stress conditions such as cold, drought, and salinity and in seeds at later stages of embryogenesis. Here, we report on two highly identical dehydrin genes, DHN1a and DHN1b, in wild and cultivated grapes, Vitis riparia and Vitis vinifera, and their expression in different tissues and under different environmental conditions. The two genes and their transcripts can easily be distinguished by RT-PCR because DHN1b has an 18 bp deletion compared to DHN1a. V. riparia expressed only DHN1a; V. vinifera expressed both DHN1a and DHN1b. Spliced transcripts, DHN1-S, encoding a putative YSK(2)-type dehydrin were present in low amounts in control leaves, but in high amounts in buds and seeds. Unspliced transcripts, DHN1-U, accumulated to high levels in buds and seeds. Cold, drought, and ABA treatment increased accumulation of both DHN1-S and DHN1-U in leaves, whereas short-day treatment increased only DHN1-S. The possible relation of these results with the difference in freezing stress tolerance between V. riparia and V. vinifera is discussed.

Abscisic Acid↗
PubMed2004

The pancreas of the naked mole-rat (Heterocephalus glaber): an ultrastructural and immunocytochemical study of the endocrine component of thermoneutral and cold acclimated animals.

Endocrine cell distribution within the islets of Langerhans may vary both between species and under different energetically demanding conditions such as cold acclimation. The naked mole-rat, Heterocephalus glaber, lacking an effective insulatory pelage, is effectively a poikilotherm, yet it shows a typical mammalian cold-acclimation response by substantially increasing food intake to meet higher energy requirements when housed at lower temperatures. The endocrine component of the pancreas of thermoneutral and cold-acclimated naked mole-rats was thus characterized using immunocytochemistry and ultrastructural analyses. Four distinct endocrine cells were identified: alpha (glucagon-producing), beta (insulin-producing), delta (somatostatin-producing), and PP (pancreatic polypeptide-producing) cells. Distribution of these cells differed from that of other rodents, in that beta cells formed the mantle while alpha cells formed the core of the islets. This distribution may contribute to the observed insulin insensitivity of this species, as indicated in abnormal responses to glucose tolerance tests. Insulin-producing cells, however, were more numerous than glucagon-producing cells. This ratio was unchanged with cold acclimation. Immunoreactivity of alpha and beta cells was more intense in cold-acclimated than in thermoneutral animals, possibly indicative of a change in hormonal production in animals housed at a lower temperature.

Acclimatization↗
PubMed1998

ATP-sensitive K+ channels in cardiac muscle from cold-acclimated goldfish: characterization and altered response to ATP.

ATP-sensitive potassium channels (K(ATP)) play an important, if incompletely defined, role in myocardial function in mammals. With the discovery that K(ATP) channels are also present at high densities in the hearts of vertebrate ectotherms, speculation arises as to their function during periods of cold-acclimation and depressed ATP synthesis. We used single-channel and intracellular recording techniques to examine the possibility that channel activity would be altered in cardiac muscle from goldfish (Carassius auratus) acclimated at 7+/-1 degrees C relative to control (21+/-1 degrees C). As previously observed in mammals, K(ATP) channels in isolated ventricular myocytes were inwardly rectified with slope conductances of 63 pS. However, channel mean open-time and overall open-state probability (Po) were significantly increased in cells from the cold-acclimated animals. In addition, K(ATP) channels in cells from fish acclimated at 7 degrees were nearly insensitive to the inhibitory effects of 2 mM ATP, whether studied at 7 or at 21 degrees C. Transmembrane action potential duration (APD) in hearts of cold-acclimated fish studied at 21 degrees was significantly shorter than that observed in hearts of warm-acclimated fish at the same temperature; this difference was eliminated by the K(ATP) channel antagonist glibenclamide (5 microM). These data suggest that K(ATP) channels in the hearts of cold-acclimated animals are more active and less sensitive to ATP-inhibition than those in warm-acclimated fish, possibly reflecting a functional adaptation to promote tolerance of low temperatures in this species.

Acclimatization↗
PubMed2001

Cold preservation of rat pancreatic islets just above the freezing point using University of Wisconsin solution.

AIMS: To confirm whether rat islets stored at a temperature just above the freezing point using University of Wisconsin (UW) solution would remain viable for the short term. METHODOLOGY: Rat islets were stored for 24 hours in UW solution, either at 4 degrees C or at -0.6 degrees C (just above the specific freezing point of the UW solution). After cold storage, the islets were assessed for in vitro viability by static incubation and for in vivo viability by a transplantation study. One thousand islets preserved under different conditions were injected intraportally into a streptozotocin-induced diabetic rat as an isograft. Four weeks after the transplantation, an intravenous glucose tolerance test was performed. RESULTS: Islets stored at -0.6 degrees C showed higher insulin secretion rates than those stored at 4 degrees C on a static challenge. The interval from transplantation to the achievement of normoglycemia was also shorter in the -0.6 degrees C group than in the 4 degrees C group. After islet transplantation, the daily nonfasting plasma glucose concentration was higher in the 4 degrees C group than in the -0.6 degrees C group. When compared with the 4 degrees C group, the -0.6 degrees C group showed lower blood glucose values during all investigational periods on an intravenous glucose tolerance test. CONCLUSION: Islet preservation at -0.6 degrees C using UW solution is more advantageous for short term.

Animals↗
PubMed2026

Physiological sub-typing of cold and freezing injury in Triticum turgidum subspecies with bioinformatic and expression characterization of glutathione reductase.

BACKGROUND: This study examined how different subspecies of Triticum turgidum (T. durum, T. polonicum, T. turanicum) respond to cold and freezing, assessing their water status, stress responses, and antioxidant system, with particular focus on the structure and function of glutathione reductase (TtGR). METHODS: TtGR genes were first identified from the T. turgidum genome using publicly available genomic resources such as Ensembl Plants. Promoter regions (~2 kb upstream) were analyzed to identify cis-regulatory elements using PlantCARE. Gene classification was performed based on predicted subcellular localization and conserved domain features. Plants were subjected to cold acclimation and freezing treatments, and physiological, biochemical, and enzymatic parameters were measured. RESULTS: Bioinformatics analyses identified four TtGR genes in the T. turgidum genome. The genes in two groups: cytosolic (Class I) and chloroplastic (Class II). Gene structure analysis showed a conserved exon-intron organization, while motif analysis confirmed the presence of Nicotinamide Adenine Dinucleotide Phosphate (NADPH)-binding and redox-active domains across all TtGR proteins. Several regulatory sequences in the promoters are involved in cold (DRE), abscisic acid (ABRE), and stress (STRE) responses, indicating that TtGR genes are dynamically regulated in response to environmental changes. Physiological analyses showed that freezing treatment reduces leaf water content in all genotypes, leading to turgor loss, hydrogen peroxide (H2O2) accumulation, and increased malondealdehyte (MDA) levels. However, tolerance mechanisms addressing water stress and membrane damage differ among genotypes. At the biochemical level, activation of the antioxidant defense system occurs in all genotypes. T. turanicum displays strong defense by significantly increasing enzyme activities, ensuring that the ascorbate-glutathione cycle continues under stress. By contrast, T. polonicum, although showing increased overall enzyme activities, experiences a dramatic drop in glutathione reductase (GR) activity at freezing temperatures, which restricts reduced glutathione (GSH) regeneration and creates a functional bottleneck in the antioxidant cycle. T. durum fails to sustain enzyme activities over the stress period, leading to an intermediate-sensitive response. Thus, whereas T. turanicum effectively maintains antioxidant function during freezing, T. polonicum and T. durum exhibit less efficient stress responses, either through enzymatic bottlenecks or a lack of sustained defense. CONCLUSIONS: One of the most striking findings of this study is the observed dissociation between TtGR gene expression levels and enzyme activities. Low temperature limits the link between transcription and enzyme function. The primary determinant of low-temperature tolerance in T. turgidum subspecies is the sustainability of GR enzyme activity and GSH regeneration under freezing conditions.

Triticum↗
PubMed1993

Comparative evaluation of laser Doppler flux metering, bulbar conjunctival angioscopy, and nail fold capillaroscopy in sickle cell disease.

Eleven adult patients with stable sickle cell disease (SCD) were investigated twice at a 15-day interval by nail fold capillaroscopy (NFC), bulbar conjunctival angioscopy (BCA), and laser Doppler flux metering (LDF). NFC and BCA are essentially descriptive. NFC revealed, in some patients, network patterns similar to those observed in vasculitis. BCA provides a reproducible method for the visual assessment of the microcirculation. When using a rating scale with five criteria it identified abnormalities related to both altered red blood cells and vascular morphology but failed to discriminate between patients. LDF, in contrast, is quantifiable and showed reproducible characteristic reactive alterations of vasomotion in response to ischemia after 3 min of occlusion. The SCD patients had a delayed response, best measured by the recovery half time, which was four to five times longer than that of normal subjects. In addition, the cold provocative test was always abnormal, as evidenced by a significant drop in the contralateral flux, and was often poorly tolerated. The observed trends suggest that BCA and LDF should be performed in a large cohort of patients, both in the steady state and during vasoocclusive crises. These methods seem to be useful complementary noninvasive procedures to cellular and clinical evaluation monitoring for therapeutic trials.

Adult↗
PubMed1975

Autoimmune hemolytic anemia.

Warm-type autoantibodies of autoimmune hemolytic anemia (AIHA) are usually IgG but may be IgM or IgA. They are usual Rh specific. Cold-type antibodies are IgM or IgG (Donath-Landsteiner [DL] antibody). IgM antibodies are usually anit-l (occasionally anti-i) and DL antibodies anti-P. The warm IgG antibodies do not fix complement (C); they cause red blood cell (RBC) destruction predominantly in the spleen as the result of interaction between fixing; they cause RBC destruction either by intravascular lysis (complement sequence completed) or by interaction between C3-coated RBCs and phagocytes in liver and spleen. Gentic factors, immunoglobulin deficiency, somatic mutation, viral infections and drugs, and failure of T-lymphocyte function, all probably play a part in breaking immunological tolerance and the development of AIHA.

Anemia, Hemolytic, Autoimmune↗
PubMed1989

Seasonal variation in freeze tolerance and ice content of the tree frog Hyla versicolor.

Freeze tolerance and ice content of Hyla versicolor showed pronounced variation between summer (June) and winter (December). Summer frogs survived freezing at -3 degrees C for up to 9 hr and ice accumulation up to 50% of their total body water. A time course of ice formation indicated that an equilibrium level was reached in approximately 15 hr. Thus, the lethal ice content was less than the equilibrium ice content for these conditions (63.1%). A second group was induced to enter an overwintering condition by holding them through the summer and then subjecting them to a progressive reduction in temperature and photoperiod for 2 months. These frogs survived freezing for 48 hr at -3 degrees C. Their equilibrium ice content at this temperature was significantly lower (52.5%) than comparably treated summer animals. In the winter acclimatized group, frozen frogs had substantially higher blood glucose levels than unfrozen frogs (22.7 mumol/ml vs. 1.33 mumol/ml), but glycerol levels were not elevated after freezing. Freezing frogs conditioned for overwintering at -7 degrees C resulted in a higher equilibrium ice content (62.6%), but none survived. It is evident that in preparation for overwintering, frogs reduce the amount of ice formed at a given subzero temperature, but there is little indication of a substantial change in the total amount of ice tolerated.

Animals↗