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PubMed1975

Contrast media used in cystourethrography. Experimental evaluation.

The effects of five iodinated contrast media and of physiologic saline on bladder capacity were studied. It was found that a significantly greater volume of sodium chloride was tolerated than of Cysto-Conray, Conray 30. Hypaque meglumine 30, Hypaque sodium, and Dimer X. Dimer X was tolerated in the smallest volume. The reason for the difference in volume tolerated is not known. The bladder mucosa showed dehydration changes 6 hr after saline cystogram with no change at 24 hr, 48 hr, 7 days, and 3 months. The contrast media produced dehydration and hydropic and desquamative changes in the bladder mucosa with at least one of these changes persisting up to 3 months. There was no significant difference in the severity of the changes produced by the various contrast media. No evidence of inflammatory changes was seen in the bladder mucosa or wall or in the ureter with any of the agents.

Absorption↗
PubMed1980

No tolerance to antiaggressive effect of d-amphetamine in mice.

Agonistic, locomotor, and stereotyped behavior were measured in male Swiss-Webster mice in their home cage, normally shared with a female, while confronting an intruder mouse. Acute administration of d-amphetamine (2, 4, 8 mg/kg, IP) to resident mice decreased the frequency of attacks toward an untreated intruder, increased the resident's locomotor activity, and induced a small amount of stereotyped behavior. Redetermination of dose-effect functions during chronic treatment (8 or 16 mg/kg/day) indicated that tolerance did not develop to the antiaggressive effect of d-amphetamine. By contrast, the chronically treated mice showed sensitization to amphetamine-induced stereotypies and a diminished sensitivity to the drug's enhancement of locomotor activity. Subsequent tests with cocaine indicated no differences between amphetamine-maintained and saline control animals, providing no evidence for cross-tolerance or cross-sensitization between cocaine's and amphetamine's effects on attack, locomotion, and stereotypies.

Aggression↗
PubMed1991

Alterations in calmodulin content and localization in areas of rat brain after repeated intermittent amphetamine.

To assess whether calmodulin (CaM) could have a role in the behavioral sensitization induced by repeated intermittent amphetamine, CaM content was determined in several brain areas from rats repeatedly administered saline or amphetamine. Rats were treated with amphetamine using an escalating dose paradigm and withdrawn for either 4 weeks (withdrawn group) or 30 min (non-withdrawn group). CaM content was measured in cytosol and 100,000 x g membrane fractions from striatum, limbic forebrain, medial prefrontal cortex, hippocampus and cerebellum. In the withdrawn group, CaM was significantly increased in both striatal membranes and cytosol and in the mesolimbic membranes from amphetamine-treated rats. There were no changes in CaM in the medial prefrontal cortex, hippocampus or cerebellum. In the non-withdrawn group, there was no significant change in CaM in striatal or mesolimbic fractions but CaM was significantly decreased in cytosol of the medial prefrontal cortex and hippocampus as compared to saline controls. This decrease could be related to the tolerance that has developed to the amphetamine after the repeated treatments. In the withdrawn group, challenge with a low dose of amphetamine (1 mg/kg) elicited a translocation of CaM from membranes to cytosol in the striatum and limbic forebrain of rats repeatedly treated with amphetamine, but not in saline-treated rats. Our findings that the change in CaM occurs in striatum and limbic forebrain, requires time after treatment to develop and exhibits persistence after withdrawal correlate with known characteristics of behavioral sensitization to amphetamine. These results suggest that CaM could contribute to neurochemical events underlying behavioral sensitization to amphetamine.

Amphetamine↗
PubMed2002

Genetic architecture of NaCl tolerance in Arabidopsis.

The little success of breeding approaches toward the improvement of salt tolerance in crop species is thought to be attributable to the quantitative nature of most, if not all the processes implicated. Hence, the identification of some of the quantitative trait loci (QTL) that contribute to natural variation in salt tolerance should be instrumental in eventually manipulating the perception of salinity and the corresponding responses. A good choice to reach this goal is the plant model system Arabidopsis, whose complete genome sequence is now available. Aiming to analyze natural variability in salt tolerance, we have compared the ability of 102 wild-type races (named ecotypes or accessions) of Arabidopsis to germinate on 250 mM NaCl, finding a wide range of variation among them. Accessions displaying extremely different responses to NaCl were intercrossed, and the phenotypes found in their F(2) progenies suggested that natural variation in NaCl tolerance during germination was under polygenic controls. Genetic distances calculated on the basis of variations in repeat number at 22 microsatellites, were analyzed in a group of either extremely salt-tolerant or extremely salt-sensitive accessions. We found that most but not all accessions with similar responses to NaCl are phylogenetically related. NaCl tolerance was also studied in 100 recombinant inbred lines derived from a cross between the Columbia-4 and Landsberg erecta accessions. We detected 11 QTL harboring naturally occurring alleles that contribute to natural variation in NaCl tolerance in Arabidopsis, six at the germination and five at the vegetative growth stages, respectively. At least five of these QTL are likely to represent loci not yet described by their relationship with salt stress.

Adaptation, Physiological↗
PubMed2004

Early growth response of container-grown selected woody boreal seedlings in amended composite tailings and tailings sand.

Successful reclamation of saline-alkaline sites may be enhanced by revegetating with species that are tolerant to factors that limit normal plant growth. Boreal woody plants tested in this study have shown promise for use in saline habitats. This study was conducted to assess the effects of amendment treatments (peat, pulp waste, agriboost, a combination of pulp waste and fly ash, and mineral fertilizer) on the early growth of three hybrid poplar clones and three coniferous species. Twelve-week and 18-week container-grown hybrid poplar clones and coniferous species, respectively, were monitored for 12 weeks in pot culture in both composite tailings (CTs) and tailings sand (TS) materials obtained from the oil sands plant, Syncrude Canada Ltd., Ft. McMurray, Alberta. These substrates with low nutrients, organic matter, and water-holding capacities, were amended with different organic materials at different rates. Growth, as assessed by the volume increment in both substrates, was generally better for the first 6 weeks than for the last 6 weeks. Growth was reduced during the last 6 weeks due to nutrient depletion over time in these impoverished substrates. Overall, for both substrates, the mineral fertilizer, 20%, 40% and 60% peat were the best amendments treatments for poplar clones with NM-6 being the most productive clone. For coniferous species, 20% and 40% pulp or peat appear to be the best amendment treatments, with lodgepole pine being the most productive species. The inflexion point of the regression functions were found around 30% rate of the amendment materials. The results also indicated that peat and pulp waste were the best amendment treatments for both hybrid poplars and coniferous species whereas the agriboost and mix (combination of pulp waste and fly ash) were the worst.

Canada↗
PubMed1991

Role of associative and nonassociative mechanisms in tolerance to morphine "anorexia".

To determine whether tolerance to morphine-induced anorexia involves associative mechanisms, rats were given chronic injections of morphine (Group 1, 10 mg/kg; Group 2, 20 mg/kg) in the presence of one compound cue on alternate days and injections of saline in the presence of another compound cue on the intervening days. After tolerance developed to the initial suppression of intake, three tests of Pavlovian conditioning were conducted. On the compensatory response test, in which saline injections were given in the presence of the morphine cue, only Group 2 showed a significant increase in milk intake. On the explicit unpairing test and the environmental specificity test, in which morphine injections were given in the presence of the saline cue or in an entirely different room, respectively, neither group showed a significant loss of tolerance. The failure to demonstrate cue-dependent tolerance in this paradigm may have been due in part to inadvertent temporal conditioning and in part to the rapid development of nonassociative tolerance.

Animals↗
PubMed2004

Direct evidence that induced nitric oxide production in hepatocytes prevents liver damage during lipopolysaccharide tolerance in rats.

BACKGROUND: The role of nitric oxide (NO) in lipopolysaccharide (LPS) tolerance in the liver has been investigated in a number of previous studies, but it is still not clear whether NO is cytotoxic or cytoprotective. The aims of this study were to investigate whether low-dose LPS (LLPS)-induced hepatic production of NO is beneficial and to clarify the origins of cytoprotective NO-producing cells in the liver during LPS tolerance. MATERIALS AND METHODS: Male Wistar rats received saline or LLPS intraperitoneally (i.p.; 0.01-1000 microg/kg) followed by a high dose of LPS (HLPS, 5 mg/kg) at various time intervals (4-16 h). NG-nitro-L-arginine methyl ester (L-NAME) was used to investigate the effects of inhibition of NOS. 4,5-Diaminofluorescein (DAF-2) was used to identify NO-producing cells in isolated liver cells in vitro. At various time points (4-16 h) after saline or LLPS (1 microg/kg, i.p.) injection, hepatocytes and Kupffer cells were isolated, incubated in 7 microm DAF-2 diacetate, and perfused with Krebs solution. Illumination at 495 nm revealed DAF-fluorescence (515 nm) in isolated cells under confocal laser fluorescence microscopy. The NO production in hepatocytes and Kupffer cells was assessed by the number of labeled cells per 1000 cells or per 100 cells, respectively. RESULTS: Pretreatment with LLPS (0.1-100 microg/kg) resulted in a significant reduction (maximal at 8 h) of the HLPS-induced liver damage. L-NAME abolished the LLPS-induced protection. The NO production in hepatocytes was significantly increased and reached a maximum of 84% of all cells 8 h after LLPS administration. By contrast, the NO production in Kupffer cells remained constant at 95%, even following preinjection of LLPS. CONCLUSION: LLPS-induced NO in hepatocytes, but not in Kupffer cells, exhibits cytoprotective effects on HLPS-induced liver damage, suggesting that NO has a beneficial role in the induction of the early phase of LPS tolerance.

Animals↗
PubMed1994

The effect of chronic naltrexone pretreatment on associative vs. non-associative morphine tolerance.

The purpose of this study was to examine the effect of chronic naltrexone on associative and non-associative morphine tolerance. Rats were given nine injections of either naltrexone (5 mg/kg) or saline during a 5 day period. Following this pretreatment, all rats received 6 morphine injections (5 mg/kg) during the next 14 days. For half the rats in each pretreatment condition, morphine was injected in a distinctive room (paired) while the other half received morphine in the home cage (unpaired). All rats were given the seventh morphine injection (5 mg/kg) in the distinctive room and tested for analgesia. Context-specific tolerance was found in both pretreatment conditions. Compared to pretreatment with saline, naltrexone pretreatment produced more analgesia in the unpaired condition but had no effect in the paired condition. These results suggest that antagonist pretreatment attenuated tolerance that was not mediated by explicit environmental cues but had no effect on context-specific analgesic tolerance.

Animals↗
PubMed1984

Learning and cross drug effects: thermic effects of pentobarbital and amphetamine.

The effects of environmental cues explicitly paired or unpaired with pentobarbital on the thermic effects of pentobarbital and amphetamine were investigated. Rats received 19 injections of pentobarbital in a distinctive environment and were subsequently tested for the thermic effects of pentobarbital and amphetamine in the distinctive environment, another environment previously associated only with saline, or in the colony room not previously associated with injections. Rats tested in the context of the environmental cues previously associated with pentobarbital were tolerant to the hypothermic effect of pentobarbital, but rats tested in the environment previously associated only with saline or in the colony room were not tolerant. Pentobarbital-experienced rats administered amphetamine in the context of the usual pentobarbital cues exhibited an exaggerated hyperthermic reaction compared to previously drug-naive rats administered amphetamine. Pentobarbital-experienced rats injected with amphetamine in the homeroom exhibited a smaller hyperthermic response than previously drug-naive rats administered amphetamine in the home room. These results demonstrate that an animal's response to a drug can be affected by cues paired and unpaired with drug administration.

Amphetamine↗
PubMed1986

Evidence for a role of conditioning in the development of tolerance to morphine-induced inhibition of gastrointestinal transit in rats.

Groups of rats were administered s.c. saline or morphine for 14 consecutive days and received morphine, saline or no treatment on day 15. Significant and consistent environmental cues were established through the treatment and test periods. Transit of a charcoal meal along the gastrointestinal tract, measured on day 15, was significantly greater in rats conditioned to daily morphine, followed by saline on day 15, than in any other group. This enhanced transit was approximately equal in magnitude to the amount of developed tolerance to morphine. These results support the hypothesis that tolerance to opiates may be partly explained by a compensatory conditioned physiological response opposing the acute effect.

Animals↗
PubMed1971

Induction of liver acetaldehyde dehydrogenase: possible role in ethanol tolerance after exposure tobarbiturates.

Mice were injected twice a day for 4 days with saline or phenobarbital or ethanol. Treatment with phenobarbital, but not ethanol, increased the amount of liver acetaldehyde dehydrogenase activity. More rapid removal of acetaldehyde, which is a toxic metabolic intermediate of ethanol, may contribute to the alcohol tolerance exhibited by persons who use barbiturates regularly.

Acetaldehyde↗
PubMed1988

[Tolerance of intraoperative, intraperitoneal chemotherapy in advanced gynecologic malignancies].

Assuming that cells and portions of tumor may remain in the abdominal cavity after surgery to reduce tumor size in cases of ovarian carcinoma, and that a change in cell kinetics could result in accelerated growth in the event of a recurrence, 23 patients with advanced tumors were given local (intraperitoneal) treatment intraoperatively. The treatment consisted of 15 mg Mitomycin C or 30 or 40 mg of Mitoxantron, in 1000 ml normal saline. Since the observation time was so short, the tolerance and side effects of this form of treatment were of primary interest, rather than remission quotas and survival times. The principal abdominal complaints included two subileus conditions which responded well to therapy and the problem of postoperative nausea. Four patients reacted to the treatment described with temperatures of over 38 degrees C. Chemical changes detected in the laboratory included 18 cases of leukopenia, which in one case reached WHO Grade 4. Intermittent changes in liver values and electrolytes were observed in isolated cases. Wound-healing impairments occurred in three cases. In one of them, a patient who sustained a prolapse of the small intestine with tumor growth into the abdominal wall, reoperation was necessary. Taken overall, the side effects of the intraoperative, intraperitoneal cytostatic therapy were acceptable. In view of the courses observed and with the idea of employing a form of therapy to combat aggressive growth of tumor cells remaining after surgery, it appears justified to continue with this form of treatment.

Adolescent↗
PubMed1974

Growth hormone release inhibiting hormone in acromegaly.

Growth hormone release inhibiting hormone (GHRIH) was administered by constant infusion over 75 minutes to eight acromegalic patients at different doses. 100 to 1,000 mug were equally effective in reducing circulating growth hormone (GH) levels; 25 mug lowered GH levels in only five patients, and at this dose the extent of the fall was smaller than from doses of 100 mug or more. 10 mug was ineffective. Injection of single doses of 500 mug by intravenous, subcutaneous, and intramuscular routes caused only small and transient reductions in GH levels, though the effect was improved by injecting the hormone intramuscularly in 2 ml of 16% gelatin. Injection of a suspension of 4 mg GHRIH in 1 ml of arachis oil lowered growth hormone levels for between three and four hours.In four acromegalic patients an oral 50-g glucose tolerance test was performed during a continuous infusion of either saline or 1,000 mug GHRIH. The "paradoxical" rise in growth hormone seen in these patients during the saline infusion was suppressed by GHRIH. The blood glucose responses were, moreover, modified by GHRIH in that the peak was delayed and occurred at the end of the infusion in each case. A "normal" glucose tolerance curve was converted to a "diabetic" type of response in two patients. This effect could be accounted for by the inhibition of insulin secretion known to occur with large doses of GHRIH.We speculate that acromegaly may be primarily a hypothalmic disease due to deficiency of GHRIH resulting in excessive secretion of growth hormone from the pituitary and adenoma formation due to inappropriate and prolonged stimulation of the pituitary.

Acromegaly↗
PubMed1993

Treatment with an interleukin-1 receptor antagonist protein prolongs mouse islet allograft survival.

An interleukin-1 receptor antagonist protein was evaluated with regard to its efficacy in allogeneic and xenogeneic islet transplantation. Alloxan-induced diabetic C57BL/6 (H-2b) mice were transplanted under the kidney capsule with 500 C57BL/Ks (H-2d) mouse islets. Alzet osmotic pumps, which release their content over an 11- to 13-day period, were implanted subcutaneously for continuous infusion of interleukin-1 receptor antagonist protein (1.0, 5.0, 8.0 mg.kg-1 x day-1) or phosphate-buffered saline. Blood glucose determinations were performed every second or third day; at death, the islet-bearing kidneys were morphologically evaluated. Mice treated initially with the higher interleukin-1 receptor antagonist protein concentrations were followed for an additional period after cessation of the drug release to evaluate whether a transitory interleukin-1 receptor antagonist protein treatment would induce tolerance to the graft. All phosphate-buffered saline-treated mice were hyperglycemic 11 days after islet allotransplantation. Most of their grafts were heavily infiltrated with mononuclear cells. In the various interleukin-1 receptor antagonist protein-treated groups, 60-80% of the mice were normoglycemic after 11 days. Moreover, light microscopic examinations showed that most mice treated with interleukin-1 receptor antagonist protein had normal islet grafts or grafts infiltrated with only a few mononuclear cells. After interruption of interleukin-1 receptor antagonist protein infusion (8.0 mg.kg-1 x day-1), all animals developed hyperglycemia within 2-9 days. In xenogeneic experiments, 500-750 fetal porcine islet-like cell clusters were transplanted under the kidney capsule of normoglycemic C57BL/6 mice. These animals were treated either with interleukin-1 receptor antagonist protein (8.0 mg.kg-1 x day-1) or phosphate-buffered saline.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Prophylactic treatment of endotoxic shock with monophosphoryl lipid A in newborn rats.

Mortality due to gram-negative septic shock remains high despite advances in medical care. Induction of endotoxin tolerance might be a new treatment strategy to prevent septic shock in the newborn. The present study was performed to show that an injection in pregnant rats of monophosphoryl lipid A (MPL), a nontoxic derivative of lipopolysaccharide (LPS), induces tolerance to Salmonella enteritidis LPS and tumor necrosis factor alpha (TNF-alpha) in their offspring. MPL at a dose of 2 mg/kg was injected into pregnant rats on the 19th day of gestation. Their 0-day-old offspring later received an intraperitoneal injection of S. enteritidis LPS or TNF-alpha. Newborn rats of MPL-treated dams exhibited a higher survival rate, absence of lactacidemia and lower plasma TNF-alpha concentration in response to S. enteritidis LPS when compared to the newborn rats of saline-treated dams. Newborn rats of MPL-treated dams were more tolerant to TNF-alpha than those of saline-treated dams. MPL injection into pregnant rats did not increase plasma endotoxin concentration in the fetuses, suggesting no placental passage took place, but it did increase plasma TNF-alpha concentration. We concluded that an injection of MPL into pregnant rats induced tolerance to LPS in their offspring, which might be due to TNF-alpha-induced TNF-alpha tolerance.

Adjuvants, Immunologic↗
PubMed2006

The Na+, K+, 2Cl- cotransporter of estuarine pufferfishes (Sphoeroides testudineus and S. greeleyi) in hypo- and hyper-regulation of plasma osmolality.

The pufferfishes Sphoeroides testudineus and Sphoeroides greeleyi are estuarine species that osmoregulate efficiently, but S. testudineus tolerates seawater dilution to a much higher degree than S. greeleyi. This study aimed at testing whether NKCC is involved with their differential tolerance of seawater dilution, through the analysis of in vivo furosemide (NKCC inhibitor) injection both on hypo-regulation (in 35 per thousand salinity) and hyper-regulation (in 5 per thousand salinity). After exposure for 6 h or 5 days to both salinities, blood samples were obtained for determination of plasma osmolality, chloride, sodium and hematocrit, and muscle samples for determination of water content. Furosemide injection led to increased plasma osmolality and sodium in 35 per thousand and decreased osmolality and chloride in 5 per thousand, when compared to saline-injected controls. Furosemide injection led to hematocrit reduction in both salinities, and muscle water content increase in 5 per thousand and decrease in 35 per thousand in S. testudineus. The results are compatible with NKCC working in branchial NaCl secretion in 35 per thousand, in both species, and a higher role in cell volume regulation in blood and muscle cells of S. testudineus, in both salinities, which could partially explain the stronger capacity of S. testudineus to tolerate seawater dilution during low tide.

Animals↗
PubMed1985

Indomethacin facilitates acute tolerance to and dependence upon morphine as measured by changes in fixed-ratio behavior and rectal temperature in rats.

The effects of indomethacin, a prostaglandin (PG) synthetase inhibitor, on acute tolerance to and dependence on morphine were investigated. Twelve mature, male Long-Evans rats were trained to lever press for food reinforcement on a fixed-ratio 30 schedule (FR 30 behavior) and have their rectal temperature taken. The experimental protocol began with taking the rat's temperature followed by a 30 minute behavioral session. Immediately after this session the animal was injected with indomethacin or its vehicle. Two-and-a-half hours later this procedure was repeated, except that morphine or saline was administered. After an additional 2.5 hours had elapsed, a 60 minute behavioral session occurred. Half-way through the session the rat was injected with morphine (tolerance), naloxone (dependence), or saline. Immediately after the session the rat's temperature was recorded. Indomethacin potentiated the acute tolerance to the behavioral suppressant and hyperthermic effects of morphine. Indomethacin pretreatment also greatly enhanced the capacity of naloxone to decrease temperature and suppress FR 30 behavior in morphine-treated rats. These effects were not due to indomethacin altering the acute effects of morphine or the amount of morphine in the brain. These data suggest that indomethacin is inhibiting synthesis of PGs which are important in morphine tolerance and dependence.

Animals↗
PubMed1993

Single-dose ceftriaxone, ornidazole, and povidone-iodine enema in elective left colectomy. A randomized multicenter controlled trial. The French Association for Surgical Research.

Patients undergoing elective left colectomy for colonic carcinoma or diverticulosis (n = 341) were randomly assigned to three groups. Patients in groups 1 (102 patients) and 2 (122 patients) had two 5% povidone-iodine enemas whereas those in group 3 (117 patients) had saline enemas. Groups 1 and 3 received 24-hour intravenous cefotaxime sodium and metronidazole hydrochloride. Group 2 received single injections of ceftriaxone sodium (1 g) and ornidazole (1 g). Senna concentrate was administered the evening before surgery. There was no statistically significant difference found between groups 1 and 2 concerning the number of infected patients (eight vs 11), anastomotic leakages (four vs four), extra-abdominal complications (32 vs 29), or infection-related deaths (one vs zero). Despite poorer tolerance, povidone-iodine enema was more effective than saline enemas, as there were less infected patients in group 1 (8%) or groups 1 + 2 (8.5%) than in group 3 (13%). Single-dose ceftriaxone-ornidazole combined with povidone-iodine enemas is effective against infective complications in elective left colonic surgery for carcinoma or diverticular disease. Single-dose antibiotic prophylaxis reduces costs and work for the nursing staff.

Adult↗