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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several organic cations are actively transported by proximal renal tubules by mediated processes across both the apical and basolateral cell membranes. In order to evaluate this transport system in a cultured renal epithelium, uptake of 3H-tetraethylammonium (TEA) across the apical membrane was measured in LLCPK1 cells, a cell line with several characteristics of proximal tubules. 3H-TEA progressively entered these cells and reached a near-steady state by 30 min. Three-minute uptake was saturable with an apparent Vmax of 1,669 +/- 129 fmoles/micrograms DNA and apparent Km of 34.0 +/- 3.4 microM. 3H-TEA uptake was inhibited by an excess of nonradioactive TEA, other organic cations, sodium azide, and hypothermia. An alkaline external pH was associated with greater 3H-TEA uptake than an acid pH. However, efflux of 3H-TEA from cells was not appreciably affected by changes in external pH. Preincubation of cells in acid or alkaline media did not affect uptake. Alteration of cell pH by ammonium chloride addition or removal had little effect on 3H-TEA uptake. Finally, uptake of 3H-TEA was not accelerated by preloading cells with an excess of nonradioactive TEA. These results indicate that intact LLCPK1 cells possess a mechanism(s) in their apical membranes for the mediated transport of a prototypic organic cation. The mechanism(s) involved in this transport is uncertain. However, neither organic cation/proton nor organic cation/organic cation exchange appears to be the predominant process.
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PMID:Organic cation uptake by a cultured renal epithelium. 319 30

We used mild hypothermia (34 degrees C) and mild hyperthermia (39 degrees C) to examine aging at the cellular level in relation to DNA damage and repair. With the filter elution technique we monitored spontaneous single-strand breaks (SSBs) and double-strand breaks (DSBs) in DNA during in vitro aging at 34 degrees C, 37 degrees C and 39 degrees C of normal human diploid fibroblasts (HDF). DNA repair was assessed after ionizing and non-ionizing (ultraviolet) radiation of HDF at different population doubling levels (PDLs): the former was assayed by filter elution and the latter by unscheduled DNA synthesis. Survival was assessed by trypan blue dye exclusion and colony formation. Cells at 37 degrees C achieve a higher cumulative PDL (67 +/- 6) than cells at 39 degrees C (60 +/- 5) or at 34 degrees C (55 +/- 6). The level of spontaneous SSBs and DSBs, and radiosensitivity of DNA to either 6 Gy or 100 Gy gamma rays, do not change with in vitro age at any of the three temperatures. Repair of SSBs (induced by 6 Gy) and DSBs (induced by 100 Gy) does not change with in vitro age: rejoining is 86-104% complete by 60 min repair and generally does not differ across temperatures. Response to non-ionizing radiation (254 nm, 75, 150, 300 ergs/mm2) does not change with in vitro age at 37 degrees C or 39 degrees C, whereas excision repair increases with age at 34 degrees C even though cell survival does not. The results do not support the rate of living theory of aging (Pearl, R., The Rate of Living, University of London Press, London, 1928) as applied to temperature effects on HDF aging in vitro (as measured by proliferative lifespan) and on their response to radiation-induced DNA damage.
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PMID:The effect of mild hypothermia (34 degrees C) and mild hyperthermia (39 degrees C) on DNA damage, repair and aging of human diploid fibroblasts. 362 41

The Eastern pipistrelle (Pipistrellus subflavus) is typical of exceptionally small bats capable of a 30-fold range in aerobic metabolism as they arouse from hypothermia and sustain foraging flight. This report describes their basic lung structure and the extent to which this organ is protected from protein depletion during hibernation. Bats were collected at the beginning (Fall), middle (Winter), and end (Spring) of hibernation from a permanent overwintering cave, and analyzed within several days of capture. Regardless of whether bats were examined in the Fall (average body weight = 6.22 g) or in the Spring (4.58 g) no significant differences existed for total lung volume (237 microliter), alveolar surface area (338 cm2), harmonic mean septal thickness, tau ht (0.221 micron), or membrane diffusing capacity (4.13 microliter O2/sec/mbar). These parameters exceed predictions based on body weights for either season, and resemble published data for another highly active mammalian group, the insectivorous shrews. Both tau ht and the minimal septal thickness of 0.083 micron approach the anatomical limits for thinning of alveolar septa without loss of epithelial continuity. Although both the heart and lungs lost 13% of their fresh weights during hibernation, compared to 25% for the liver, the lung contents of DNA (0.14 mg) and blood-free protein (7.38 mg) were not altered significantly. These small bats possess lungs which are well suited for the high aerobic cost of flight. Those lungs are resistant to hibernation-induced proteolysis, and also resistant to the deterioration of alveolar membranes which occurs in nonhibernators subjected to starvation-induced weight losses of similar magnitude.
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PMID:Pulmonary design in a microchiropteran bat (Pipistrellus subflavus) during hibernation. 399 64

The development of myocardial ischemia is known to elicit the formation and enlargement of collateral vessels. The stimulus for these events is unknown. We have investigated the possibility that cardiac tissue releases a factor that can stimulate endothelial cell proliferation. Hearts from New Zealand rabbits were made progressively ischemic by differential hypothermia. Extracts from these hearts were tested for their growth-stimulating ability and were found to increase the proliferation of fetal bovine aortic endothelial cells as well as DNA synthesis by 3T3 cells. The level of activity in the extracts appears to be related to the degree of ischemia as measured by creatine phosphokinase levels. The liberation of an endothelial cell growth factor by ischemic cardiac tissue may function in the initiation and/or potentiation of coronary collateral formation.
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PMID:Do ischemic hearts stimulate endothelial cell growth? 646 72

A short test (DSI test) in vivo for the identification of environmental mutagens and carcinogens was recently published by Friedman and Staub (1976), and Seiler (1977). The test is based on the measurements of [3H]thymidine incorporation into murine testicular DNA. This incorporation was inhibited by a number of mutagens and carcinogens when given at high doses. However, under such conditions, many chemicals are known to cause hypothermia in mice, which may itself lead to a reduced [3H]thymidine incorporation. We therefore investigated the effect of a few non-mutagenic and mutagenic test substances on the incorporation of [3H]thymidine into testicular DNA and on changes in body temperature. We also studied the effect of reduced testicular temperature, caused by physical means, on the incorporation of [3H]thymidine into DNA. 3 mutagens out of 4, and 6 non-mutagens out of 6, caused hypothermia in mice, and at the same time inhibited [3H]thymidine incorporation. This parameter also changed as the testicular temperature was reduced, indicating an obvious correlation between the 2 effects. Furthermore, we found that, with some of the test substances, a reduction of [3H]thymidine incorporation into DNA can be compensated under isothermal conditions. We believe that the DSI test is not reliable as a screening system for the identification of potential mutagens and cancerogens because of the unspecificity of the parameter measured.
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PMID:Critical appraisal of the 'mouse testicular DNA-synthesis inhibition test' for the detection of mutagens and carcinogens. 708 7

Mice with a disruption of the IFN-gamma receptor alpha-chain gene (IFN-gamma R alpha o/o mice) were found to be significantly more sensitive than their wild-type counterparts to induction of the anti-CD3-induced disease syndrome. Specifically, when given a selected dose of anti-CD3 Ab, IFN-gamma R alpha o/o mice developed severe hypothermia and hypoglycemia, leading to 100% mortality within 72 h. In contrast, wild-type mice failed to develop overt pathologic manifestations and survived. Histologic examination revealed apoptosis in thymuses and spleens, which were significantly more pronounced in the mutant than in the wild-type mice, as confirmed by flow cytometric and DNA electrophoretic analysis. Apoptosis affected mainly CD4+CD8+ and CD4+CD8- thymocytes. Other histologic alterations were steatosis in livers, and erythrocyte extravasation and infiltration of apoptotic cells in lungs, all of which were exclusively observed in IFN-gamma R alpha o/o mice. Blood levels of TNF, IL-2, IL-6, and IL-10 were slightly more elevated in IFN-gamma R alpha o/o mice, but insufficiently so to explain increased disease severity. Thus, even more elevated cytokine levels in wild-type mice receiving high doses of anti-CD3 Ab were not associated with morbidity or apoptosis. Blood levels of IFN-gamma were barely detectable in anti-CD3-challenged wild-type mice, but were relatively high in the mutant mice. Increased susceptibility of IFN-gamma R alpha o/o mice was associated with impaired nitric oxide (NO) production, as indicated by significantly lower plasma nitrite levels and by more transient expression of spleen inducible NO synthase mRNA. Moreover, treatment of wild-type mice with the NO synthase inhibitor N-nitro-L-arginine methylester resulted in increased anti-CD3-induced morbidity and mortality. The data indicate that IFN-gamma R alpha o/o mice produce less NO and are therefore more sensitive than wild-type mice to the deleterious effect of anti-CD3 Ab.
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PMID:IFN-gamma receptor-deficient mice are hypersensitive to the anti-CD3-induced cytokine release syndrome and thymocyte apoptosis. Protective role of endogenous nitric oxide. 756 Oct 88

To study the responses of thermogenic activity in brown adipose tissue (BAT) to creatine depletion, male Wistar rats were fed creatine analogue beta-guanidinopropionic acid (beta-GPA) for about 10 weeks. Compared to control rats, a marked decrease in the levels of high-energy phosphates, such as phosphocreatine and ATP, was noted in BAT of beta-GPA rats. Conversely, upward trends in other chemical components (DNA, glycogen, and total protein) in BAT as well as an increase in BAT mass were observed in beta-GPA rats, suggesting a tendency to hyperplasia of the BAT. The thermogenic activity (which was assessed by guanosine 5'-diphosphate binding to BAT mitochondria) in the mitochondria recovered from BAT of beta-GPA rats, however, was not increased in response to such changes but rather decreased. Moreover, uncoupling protein (UCP) content in the mitochondrial fraction of beta-GPA rats was significantly lower than that in control rats (the relative amounts were 77 +/- 6 and 100 +/- 4%, respectively). Nevertheless, surprisingly, the level of UCP mRNA was remarkably greater in beta-GPA rats than in control rats. These observations indicate that there is a discordance between BAT growth and activity in beta-GPA rats, thereby suggesting that a failure on and after UCP translation may be involved in the impairment of BAT thermogenic activity with creatine depletion. The impairment of BAT thermogenic activity, that is, UCP activity may indicate that uncoupling or heat production was inhibited in order to increase the ATP synthesis in BAT of beta-GPA rats in compensation for a reduction in the levels of high-energy phosphates (including ATP), with resultant hypothermia.
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PMID:Increased growth of brown adipose tissue but its reduced thermogenic activity in creatine-depleted rats fed beta-guanidinopropionic acid. 761 43

Donor lungs for transplantation are susceptible to "preservation" injury during both storage and postimplantation reperfusion. We investigated whether lung dysfunction seen after storage and reperfusion was associated with any biochemical hallmarks of direct cellular oxidant injury to lipid, protein, or DNA. Heart/lung blocks were extracted from adult rats following pulmonary vascular flush. Lungs were either perfused immediately ex vivo for 2 h with deoxygenated venous rat blood or were stored at 10 degrees C for 13 h before perfusion. Stored lungs had increased airway pressure, pulmonary vascular shunt fraction, wet/dry weight ratio, and parenchymal hemorrhage after perfusion but no change in pulmonary artery pressure compared with immediately perfused lungs. Hypothermic storage caused no biochemical changes in lung tissue. Perfusion of fresh or stored lungs resulted in lipid peroxidation and loss of nonprotein reduced sulfhydryls; sulfhydryl loss was threefold higher in lungs stored before perfusion compared with freshly perfused lungs. Reperfusion of stored, not fresh, lungs was associated with DNA damage. No loss of protein sulfhydryls occurred following lung perfusion. We conclude that DNA damage, loss of reduced nonprotein sulfhydryls, and lipid peroxidation during reperfusion of stored lungs may be responsible for physiologic lung dysfunction.
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PMID:Lung oxidant injury in a model of lung storage and extended reperfusion. 792 33

Amifostine (WR-2721, S-2 [3-aminopropylamino]-ethylphosphorothioic acid; Ethyol, US Bioscience, Inc. West Conshohocken, PA), developed as a radiation protector, has exhibited activity as a chemoprotector. The compound requires activation by dephosphorylation to produce the free thiol, WR-1065. This process is catalyzed by capillary alkaline phosphatase that is close to the desired site of protection. Additionally, the neutral pH of normal tissues, compared with the slightly acidic pH of tumors, favors selective activation. The protective mechanism against radiation damage is produced, and is, most probably, different from that of chemotherapy. The most likely mechanism for radioprotection involves free radical scavenging and hydrogen donation to repair damaged DNA. The hydrogen ion donation by the thiol group is required for both chemoprotection and radioprotection. Chemoprotection is presumed to be mediated by inactivation of the charged carbonium ions of activated alkylating agents through a nucleophilic attack, thereby protecting the nucleic acids from alkylation. Amifostine is able to reduce DNA platination when preincubated or coincubated with cisplatin, but this effect is much weaker when given postincubation. Observations show that maximum protection can only be obtained if amifostine is given before the administration of cytotoxic therapy. Amifostine side effects, as seen in mice, are dose dependent. A dose of 200 mg/kg has been found to be relatively nontoxic, although some hypothermia was observed.
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PMID:Protection of normal tissues from the cytotoxic effects of chemotherapy and radiation by amifostine (Ethyol): preclinical aspects. 797 74

Ca2+ accumulates in the nucleus and DNA undergoes enzymatic cleavage into internucleosome-length fragments before acetaminophen and dimethylnitrosamine produce hepatic necrosis in vivo and toxic cell death in vitro. However, Ca(2+)-endonuclease fragmentation of DNA is characteristic of apoptosis, a type of cell death considered biochemically and functionally distinct from toxic cell death. The present studies investigate DNA fragmentation as a critical event in toxic cell death by testing whether the Ca(2+)-calmodulin antagonist chlorpromazine and the Ca2+ channel blocker verapamil prevent acetaminophen-induced hepatic necrosis by inhibiting Ca2+ deregulation and DNA damage. Acetaminophen overdose in mice produced accumulation of Ca2+ in the nucleus (358% of control) and fragmentation of DNA (250% of control) by 6 h, with peak release of ALT occurring at 12-24 h (38,000 U/l). Pretreatment with chlorpromazine prevented increases in nuclear Ca2+ and DNA fragmentation and nearly abolished biochemical evidence of toxic cell death. Verapamil pretreatment also decreased Ca2+ accumulation and DNA damage while attenuating liver injury. The Ca2+ antagonists did not protect against toxic cell death through hypothermia because neither produced the delay in toxicity that is customarily associated with hypothermia. Nor did chlorpromazine or verapamil protect through inhibiting acetaminophen bioactivation. Chlorpromazine failed to diminish glutathione depletion in whole liver and isolated nuclei. Verapamil (250 microM) also failed to alter glutathione depletion in whole liver and had no effect on acetaminophen-glutathione adduct formation by mouse liver microsomes and by cultured mouse hepatocytes. Collectively, these results support the hypothesis that Ca(2+)-induced DNA fragmentation plays a significant role in cell necrosis produced by acetaminophen and may contribute to toxic cell death caused by other alkylating hepatotoxins.
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PMID:Ca2+ antagonists inhibit DNA fragmentation and toxic cell death induced by acetaminophen. 846 87


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