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PubMed1985

Tolerance to some behavioural effects of lisuride, a dopamine receptor agonist, and reverse tolerance to others, after repeated administration.

To investigate whether prolonged pretreatment with the dopamine (DA) agonist lisuride would result in modification of some of its behavioural effects, food intake, locomotor activity, body temperature or stereotyped and mounting behaviour were evaluated after acute injections of different doses of lisuride into rats, pretreated daily for four weeks with either saline or lisuride. Rats pretreated with lisuride developed tolerance to its anorexigenic and hypothermic effects, and reverse tolerance to its effects on locomotor activity, stereotyped and mounting behaviour. Pretreatment with lisuride did not modify the activity of drug-metabolizing enzymes in the liver. These results, in addition to revealing the pattern of the changes in the behavioural effects of a DA agonist drug, after repeated administration, may be taken as evidence for the existence of different DA receptor systems in different areas of the brain, that mediate different behavioural effects, and that differ markedly in their reactions to prolonged stimulation with an agonist drug.

Animals↗
PubMed2000

Safety assessment of perflenapent emulsion for echocardiographic contrast enhancement in patients with congestive heart failure or chronic obstructive pulmonary disease.

BACKGROUND: Perflenapent injectable emulsion is a newer echocardiographic contrast agent that provides chamber opacification and improved endocardial border delineation. In >1000 patients tested, adverse effects have been minimal. However, previous studies have included few patients with congestive heart failure (CHF) or severe chronic obstructive pulmonary disease (COPD). Because of their reduced cardiopulmonary reserve, these patients might be at greater risk for adverse events. METHODS AND RESULTS: The safety of perflenapent emulsion was evaluated in ambulatory patients with New York Heart Association class III to IV congestive heart failure (CHF) or severe obstructive pulmonary disease (COPD). In 2 separate multicenter, phase II, randomized, double-blind, placebo-controlled, single-administration clinical trials, 146 patients in the CHF study and 134 patients in the COPD study received either perflenapent emulsion or saline placebo during an echocardiographic examination. Perflenapent emulsion was well tolerated in patients with CHF or COPD. The adverse event rates with perflenapent emulsion (15%) were similar to those with saline (11%; P =.43) in the combined groups, and similar findings were seen when analyzed by CHF or COPD groups separately. All adverse events were rated as mild, required no treatment, resolved spontaneously, and left no sequelae. Changes from baseline in vital signs, pulse oximetry, electrocardiography, and laboratory tests were similar between treatment groups. CONCLUSIONS: These data support the safety of perflenapent emulsion for contrast echocardiography in stable ambulatory patients with CHF or COPD.

Aged↗
PubMed1987

Endocrine pancreatic morphology and function in exocrine insufficiency in rats.

Exocrine pancreatic insufficiency was induced in rats by injection of oleic acid into the pancreatic duct. Six weeks after a single injection of 50 microliters oleic acid, the exocrine tissue was reduced by 98%. The islets of Langerhans remained intact and showed no changes in the relative distribution of beta-, alpha-, D-, and PP-cells. In rats fed ad libitum, plasma insulin levels and pancreatic insulin content did not differ between oleic acid-treated animals and controls. The dynamic insulin response was evaluated in the isolated perfused pancreas. The biphasic pattern of insulin release after stimulation by glucose was preserved. The half-maximal (10 mM) glucose-induced insulin release was reduced to 49% after onset of exocrine atrophy. After stimulation of insulin secretion by a maximal glucose load (20 mM), the insulin output from the perfused pancreas was reduced to 56%. A reduction in insulin release to 24% occurred with respect to the arginine (15 + 10 mM glucose)-stimulated secretion. To evaluate the significance of these findings in intact animals, glucose tolerance tests were performed. There were no differences between oleic acid-, saline-, or untreated animals with respect to serum glucose or plasma insulin levels during the oral glucose tolerance test. The insulin response after intravenous glucose in oleic acid-treated rats was not statistically different from controls. Nevertheless, the serum glucose levels in rats with exocrine atrophy were above controls, indicating a slight impairment of glucose tolerance.

Animals↗
PubMed1995

Muscarinic stimulation maintains in vivo insulin secretion in response to glucose after prolonged hyperglycemia.

Prolonged hyperglycemia impairs the in vitro insulin release by islets of Langerhans in response to glucose but exaggerates the in vivo insulin response. We hypothesized that this discrepancy results from increased vagal stimulation of the islets. Conscious chronically cannulated rats were infused with glucose (15 mg/min) or saline for 48 h. Three hours thereafter, an intravenous glucose tolerance test was performed with or without prior injection of atropine (0.2 mg). Atropine markedly (> 70%) reduced the insulin response in glucose-infused, but not in saline-infused, rats. Glucose-infused rats displayed basal hypoglycemia but normal glucose excursions during an intravenous glucose tolerance test. It is concluded that prolonged hyperglycemia produces exaggerated muscarinic activation of the beta-cells that will persist > or = 3 h after the termination of the glucose infusion and normalizes in vivo insulin secretion. It is possible that increased parasympathetic activation of the pancreas might constitute a general mechanism to maintain insulin output when the demand for insulin exceeds the inherent beta-cell responsiveness.

Animals↗
PubMed1998

Pulmonary apoptosis in aged and oxygen-tolerant rats exposed to hyperoxia.

Accumulating evidence demonstrates that genotoxic and oxidant stress can induce programmed cell death or apoptosis in cultured cells. However, little is known about whether oxidative stress resulting from the deleterious effects of hyperoxia can induce apoptosis in vivo and even less is known regarding the functional significance of apoptosis in vivo in response to hyperoxia. Using hyperoxia as a model of oxidant-induced lung injury in the rat, we show that hyperoxic stress results in marked apoptotic signals in the lung. Lung tissue sections obtained from rats exposed to hyperoxia exhibit increased apoptosis in a time-dependent manner by terminal transferase dUTP nick end labeling assays. To examine whether hyperoxia-induced apoptosis in the lung correlated with the extent of lung injury or tolerance (adaptation) to hyperoxia, we investigated the pattern of apoptosis with a rat model of age-dependent tolerance to hyperoxia. We show that apoptosis is associated with increased survival of aged rats to hyperoxia and with decreased levels of lung injury as measured by the volume of pleural effusion, wet-to-dry lung weight, and myeloperoxidase content in aged rats compared with young rats after hyperoxia. We also examined this relationship in an alternate model of tolerance to hyperoxia. Lipopolysaccharide (LPS)-treated young rats not only demonstrated tolerance to hyperoxia but also exhibited a significantly lower apoptotic index compared with saline-treated rats after hyperoxia. To further separate the effects of aging and tolerance, we show that aged rats pretreated with LPS did not exhibit a significant level of tolerance against hyperoxia. Furthermore, similar to the hyperoxia-tolerant LPS-pretreated young rats, the nontolerant LPS-pretreated aged rats also exhibited a significantly reduced apoptotic index compared with aged rats exposed to hyperoxia alone. Taken together, our data suggest that hyperoxia-induced apoptosis in vivo can be modulated by both aging and tolerance effects. We conclude that there is no overall relationship between apoptosis and tolerance.

Aging↗
PubMed1985

[Development of reverse tolerance to the ambulation-increasing effect of ephedrine after repeated administration in mice].

Effects of repeated administration of ephedrine (EPH) 40 and 80 mg/kg sc, and 20, 40, and 80 mg/kg ip on ambulatory activity in adult male mice of the dd strain were investigated. The drug was administered 5 times at intervals of 1 and 7 days. The ambulatory activity of each mouse was measured by a tilting-type round activity cage of 25 cm in diameter for 150-210 min after the drug administration. Repeated administration of EPH 80 mg/kg ip produced a marked augmentation in the sensitivity of the mouse, i.e. reverse tolerance, to the ambulation-increasing effect of the drug regardless of the administration intervals. However, repeated administration of 80 mg/kg sc and 40 mg/kg ip at intervals of 7 days caused a slight reverse tolerance, while 40 mg/kg sc at intervals of 7 days as well as 20 and 40 mg/kg ip at intervals of 1 day did not produce reverse tolerance. In contrast, a poorer development of reverse tolerance to the ambulation-increasing effect of EPH was observed when a mouse was confined in a glass jar of 5 cm in diameter to impede ambulation for 150-180 min after each administration. Mice showing reverse tolerance to EPH demonstrated an increased sensitivity to methamphetamine as compared with the saline-pretreated control mice. The present results suggest that the characteristics of reverse tolerance to ambulation-increasing effect of EPH are almost identical with those after methamphetamine and methylphenidate.

Animals↗
PubMed1994

The effect of dDAVP with saline loading on fluid balance during LBNP and standing after 24-hr head-down bedrest.

Shuttle astronauts currently drink approximately a quart of water with eight salt tablets before reentry to restore lost body fluid and thereby reduce the likelihood of cardiovascular instability and syncope during reentry and after landing. However, the saline loading countermeasure is not entirely effective in restoring orthostatic tolerance to preflight levels. We tested the hypothesis that the effectiveness of this countermeasure could be improved with the use of a vasopressin analog, 1-deamino-8-D-arginine vasopressin (dDAVP). The rationale for this approach is that reducing urine formation with exogenous vasopressin should increase the magnitude and duration of the vascular volume expansion produced by the saline load, and in so doing improve orthostatic tolerance during reentry and postflight.

Adult↗
PubMed2006

Introgression of a novel salt-tolerant L-myo-inositol 1-phosphate synthase from Porteresia coarctata (Roxb.) Tateoka (PcINO1) confers salt tolerance to evolutionary diverse organisms.

We have previously demonstrated that introgression of PcINO1 gene from Porteresia coarctata (Roxb.) Tateoka, coding for a novel salt-tolerant L-myo-inositol 1-phosphate synthase (MIPS) protein, confers salt tolerance to transgenic tobacco plants (Majee, M., Maitra, S., Dastidar, K.G., Pattnaik, S., Chatterjee, A., Hait, N.C., Das, K.P. and Majumder, A.L. (2004) A novel salt-tolerant L-myo-inositol-1-phosphate synthase from Porteresia coarctata (Roxb.) Tateoka, a halophytic wild rice: molecular cloning, bacterial overexpression, characterization, and functional introgression into tobacco-conferring salt-tolerance phenotype. J. Biol. Chem. 279, 28539-28552). In this communication we have shown that functional introgression of the PcINO1 gene confers salt-tolerance to evolutionary diverse organisms from prokaryotes to eukaryotes including crop plants albeit to a variable extent. A direct correlation between unabated increased synthesis of inositol under salinity stress by the PcINO1 gene product and salt tolerance has been demonstrated for all the systems pointing towards the universality of the application across evolutionary divergent taxa.

Adaptation, Physiological↗
PubMed2002

[Extraction of the salt-tolerant cDNA in mangrove Avicennia marina by mRNA differential display].

RNAs of the leaves in Avicennia marina, which cultured in 50@1000 and 0@1000 salinity condition respectively, were isolated for mRNA differential display analysis. Screened by OligodT12 GC and eight 10-oligonucleotide arbitrary primers, differential cDNA fragments-csrg1(600 bp), csrg2(550 bp), csrg3(480 bp), only appeared in the leaves of Avicennia marina cultured in 50@1000 salinity condition. After detected by RNA dot hybridization, only csrg1 appeared the difference between the RNAs of the leaves in Avicennia marina cultured in 50@1000 and 0@1000 salinity condition respectively, and csrg1 was confirmed as the salt-tolerant cDNA. csrg1 was cloned and sequenced. After searching in Genbank, there were no similar sequences reported.

Base Sequence↗
PubMed1997

The osmotic hypersensitivity of the yeast Saccharomyces cerevisiae is strain and growth media dependent: quantitative aspects of the phenomenon.

Osmotic hypersensitivity is manifested as cellular death at magnitudes of osmotic stress that can support growth. Cellular capacity for survival when plated onto high NaCl media was examined for a number of laboratory and industrial strains of Saccharomyces cerevisiae. During respiro-fermentative growth in rich medium with glucose as energy and carbon source, the hypersensitivity phenomenon was fairly strain invariant with a threshold value of about 1 M-NaCl; most strains fell within a 300 mM range in LD10 values (lethal dose yielding 10% survival). Furthermore, all but one of the strains displayed similar differential death responses above the threshold value, i.e. ten-fold decreased viability for every 250 mM increase in salinity. Addition of small amounts of salt to the growth medium drastically improved tolerance and shifted the hypersensitivity threshold to higher NaCl concentrations. This salt-instigated tolerance could partly be reversed by washing in water. The washing procedure depleted cells of the glycerol that they had accumulated under saline growth, and the contribution from glycerol to the improved tolerance was about 50% in the two strains examined. Growth on derepressing carbon sources like galactose, ethanol or glycerol gave strain-dependent responses. The laboratory strain X2180-1A drastically improved tolerance while the bakers' yeast strain Y41 did so only marginally. It was concluded that all strains of S. cerevisiae display the osmotic hypersensitivity phenomenon in qualitative terms while the quantitative values differ. It was also proposed that growth rate does not dictate the level of osmotic hypersensitivity of S. cerevisiae.

Culture Media↗
PubMed1986

Tolypocladium cylindrosporum (Deuteromycotina: Moniliales), a fungal pathogen of the mosquito Aedes australis. I. Influence of temperature, pH and salinity on the growth and sporulation of the fungus in the laboratory.

The New Zealand strain of Tolypocladium cylindrosporum was cultured on Sabouraud dextrose agar medium under varying regimes of growth conditions. The isolate exhibited good tolerances to temperature (4-35 degrees C), pH (3-10) and salinity (0-7% NaCl). Optimal vegetative growth and sporulation were recorded between a temperature range of 20-30 degrees C, pH of 5-6 and a salinity level of 0-2% NaCl. The North American isolate of the fungus showed similar tolerances, while the European isolate was less tolerant.

Aedes↗
PubMed2003

Uptake of an endocytic marker by rice cells: variations related to osmotic and saline stress.

Saline and osmotic stress are the main abiotic factors limiting the productivity of rice and other crop plants. Although both coincide in generating water deficit and affect many aspects of plant growth and development similarly, some effects of salinity are distinctively related to the ionic component of salt stress. At the cellular level, dessication tolerance is largely dependent on the cell's ability for osmotic adjustment. Here, we have studied the effects of saline and osmotic stress on endocytosis by rice cells, to investigate the common and distinctive effects of saline-generated stress and osmotically generated stress, and the possible involvement of endocytosis in tolerance mechanisms. For this purpose, we have used rice cell lines with different levels of tolerance and biotinylated bovine serum albumin (bBSA) as an endocytic marker, which in our previous experiments has been shown to enter rice cells by a process with the characteristics of receptor-mediated endocytosis. Our results indicate that the pattern of uptake is common to both types of stress. Thus, when rice cells were subjected to saline or osmotic stress there was an initial dose-dependent inhibition of uptake. However, after more extended stress periods, there was an activation of uptake in the stressed cells. This late activation appears mainly related to the inhibition of growth commonly caused by the different stress agents used in this study. When using cell lines with different degrees of tolerance, the level of uptake activation varied as a function of the type of stress. Thus, under osmotic stress, a higher stress tolerance was directly related to a higher bBSA uptake, while the opposite occurred under saline stress. The possible role of endocytosis in the cellular responses to osmotic and saline stress is discussed.

Biological Transport↗
PubMed2006

[Differential reversal effect of intrathecal bovine adrenal medulla peptide 22 on morphine tolerance in rats].

Bovine adrenal medulla 22 (BAM22), an endogenous opioid peptide, is one of the cleavage products of proenkephalin A. It potently activates opioid receptors and sensory neuron-specific receptor (SNSR). The present study was aimed at investigating the effect of BAM22 on morphine tolerance. Intrathecal (i.t.) administration of morphine for 7 d produced morphine tolerance in rats. Then the rats were divided into three groups in which morphine, saline or BAM22 were administered i.t., respectively, on day 8, and morphine was given to all of the animals on day 9. It was found that morphine administered on day 9 resumed antinociceptive effects in BAM22 group, but not in saline or morphine group. The potency of morphine in BAM22 group was 48.5% of the maximal possible effect (MPE) detected by paw withdrawal test and the antinociception persisted for approximately 1 h. Following the similar treatment, morphine administered on day 9 reduced nocifensive behaviors by 3.2 min and 24 min in BAM22 group in the first and second phases, in the formalin test, respectively. The decreases were 45% and 82% of the corresponding values observed in saline group. Furthermore, following the treatment with BAM22 (10 nmol) on day 8 in morphine-tolerance rats, morphine administered on day 9 decreased the expressions of the heat-evoked c-Fos-like immunoreactivity (FLI) protein by approximately 80% in laminae I-II, III-IV and V-VI in the spinal cord at L4-L5 compared with that in saline or morphine group. The present study provided evidence at behavioral and cellular levels showing that BAM22 resumed antinociception of morphine. The results that the reversal effect of BAM22 on morphine tolerance was more efficient in persistent pain model than in acute pain may indicate that BAM22 differentially modulates morphine tolerance. The present study suggests that SNSR is involved in the modulation of morphine tolerance.

Animals↗
PubMed1988

Evidence for crosstolerance to the analgesic effects between morphine and selective alpha 2-adrenoceptor agonists.

Rats were injected subcutaneously (s.c.) with morphine (5 mg/kg) until tolerance developed to its antinociceptive action, or with 0.9% saline which was used as vehicle for morphine. Subsequently, both groups of animals were given an intrathecal (i.th.) dose of either noradrenaline (2 micrograms), clonidine (12.5 micrograms) or guanfacine (12.5 micrograms), that had been found previously to be reliably antinociceptive. In the saline-treated animals, these doses of noradrenaline, clonidine or guanfacine induced clear antinociceptive effects, but not in the morphine-group. It is therefore concluded that cross-tolerance to the antinociceptive effects of systemic morphine and the alpha-adrenoceptor agonists was obtained. The cross-tolerance between morphine on one hand, and noradrenaline, clonidine and guanfacine on the other, implies that a substantial opiate-adrenoceptor interaction exists in antinociceptive processes.

Adrenergic alpha-Agonists↗
PubMed1990

Tolerance to morphine stimulus control: role of morphine maintenance dose.

Experiments assessed the development of tolerance to morphine stimulus control during treatment with selected maintenance doses of morphine. Separate groups of rats were trained to discriminate saline and either 3.2 mg/kg or 5.6 mg/kg morphine under fixed-ratio schedules of food delivery. Dose-response functions for generalization of morphine stimulus control were determined before, during, and after repeated treatment with selected doses of morphine. Similar experiments were performed with repeated pentobarbital treatment in order to assess the pharmacological selectivity of tolerance. Repeated treatment with saline, 3.2 mg/kg morphine, or twice daily injections of 17.8 mg/kg pentobarbital produced no tolerance to morphine stimulus control. In contrast, treatment with daily injections of 10 mg/kg or twice daily injections of 10 or 17.8 mg/kg morphine produced a dose-dependent increase in the dose of morphine required for stimulus control. The magnitude of tolerance to morphine stimulus control varied directly with the maintenance dose of morphine and was slightly greater for a lower than a higher morphine training dose. Termination of repeated treatment was followed by a return to initial sensitivity, without additional training. Tolerance to morphine stimulus control was not necessarily accompanied by tolerance to its rate-suppressing effects.

Animals↗
PubMed2005

Influence of host cultivars and Rhizobium species on the growth and symbiotic performance of Phaseolus vulgaris under salt stress.

In order to study the effect of salt stress on the Rhizobium-common bean symbiosis, we investigated the response of both partners, separately and in symbiosis. The comparison of the behaviour of five cultivars of Phaseolus vulgaris differing in seed colour, growing on nitrates and different concentrations of NaCl, showed genotypic variation with respect to salt tolerance. Coco Blanc was the most sensitive cultivar, whereas SMV 29-21 was the most tolerant one. At the Rhizobium level, two strains previously selected for their salt tolerance were used: Rhizobium tropici strain RP163 and Rhizobium giardinii strain RP161. Their relative growth was moderately decreased at 250mM NaCl, but they were able to grow at a low rate in the presence of 342 mM NaCl. Their viability at the minimal inhibitory concentration was slightly affected. The effect of salinity on Rhizobium-plant association was studied by using the tolerant variety SMV 29-21 and the sensitive one Coco Blanc inoculated separately with both strains. In the absence of salinity, the strains induced a significantly higher number of nodules on the roots of the cultivar SMV 29-21 compared to those of Coco Blanc. Concerning effectiveness, both strains were similarly effective with SMV 29-21, but not with Coco Blanc. In the presence of salinity, Coco Blanc was more severely affected when associated with RP163 than with RP161. Salinity affected the nodulation development more than it affected the infection steps. Neither of the two strains was able to nodulate SMV 29-21 under saline conditions, in spite of the fact that this was considered the most salt-tolerant variety. The unsuccessful nodulation of SMV 29-21 could be related to the inhibition by salt of one or more steps of the early events of the infection process. In conclusion, N-fixing plants were found to be more sensitive to salt stress than those depending on mineral nitrogen. Evidence presented here suggests that a best symbiotic N2 fixation under salinity conditions could be achieved if both symbiotic partners, as well as the different steps of their interaction (early events, nodule formation, activity, etc.), are all tolerant to this stress.

Adaptation, Physiological↗
PubMed1993

Salt tolerance and methionine biosynthesis in Saccharomyces cerevisiae involve a putative phosphatase gene.

The progressive salinization of irrigated land poses a threat to the future of agriculture in arid regions. The identification of crucial metabolic steps in salt tolerance is important for the understanding of stress physiology and may provide the tools for its genetic engineering. In the yeast Saccharomyces cerevisiae we have isolated a gene, HAL2, which upon increase in gene dosage improves growth under NaCl and LiCl stresses. The HAL2 protein is homologous to inositol phosphatases, enzymes known to be inhibited by lithium salts. Complementation analysis demonstrated that HAL2 is identical to MET22, a gene involved in methionine biosynthesis. Accordingly, methionine supplementation improves the tolerance of yeast to NaCl and LiCl. These results demonstrate an unsuspected interplay between methionine biosynthesis and salt tolerance.

Adaptation, Physiological↗
PubMed1990

A phase I clinical trial of intraperitoneal thiotepa for refractory ovarian cancer.

Treatment options for patients with ovarian cancer who have failed systemic and intraperitoneal (ip) cisplatin-based chemotherapy are limited. We conducted a phase I clinical study of ip thiotepa in patients with refractory ovarian cancer to determine the maximum tolerated dose (MTD). Ten patients were given 39 courses of thiotepa (median number of courses per patient, 3.5; range, 1-10+). All patients had received prior ip cisplatin; 7 also had received iv cisplatin, and 5 had three or more prior regimens. Thiotepa (30-80 mg/m2) was given ip in 2 liters normal saline every 4 weeks. The therapy was well tolerated. There was no vomiting, stomatitis, alopecia, or peritonitis. The dose-limiting toxicity was myelosuppression. With repeated doses, patients had a delayed marrow recovery and required a 1- to 2-week delay in treatment. Six patients had stable disease (duration 2-14+ months; median duration 5 months); 1 patient had a 50% decrease in CA-125 level, and 1 patient with no measurable disease remained clinically disease-free. In summary, ip thiotepa had clinical activity in heavily pretreated patients with refractory ovarian cancer with disease stabilization seen in 6 of 9 evaluable patients and a partial response seen in 1 patient. Myelosuppression was the only toxicity encountered. A dose of 60 mg/m2 ip is recommended for phase II studies.

Adult↗