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PubMed1990

Superior myocardial preservation with modified UW solution after prolonged ischemia in the rat heart.

Cardiac transplantation remains constrained by poor graft tolerance of prolonged cold ischemia. University of Wisconsin solution has remarkably extended ischemic preservation in pancreas, kidney, and liver transplantation. To assess its efficacy in cardiac preservation, modified University of Wisconsin solution flush and storage were tested against St. Thomas' cardioplegia flush and normal saline solution storage after six hours of ischemia at 0 degrees C in 46 isolated rat hearts. After ischemia, groups were compared before and after reperfusion. After ischemia but before reperfusion, University of Wisconsin solution hearts had significantly less tissue water (3.8%), superior tissue sodium, potassium, calcium, and magnesium profiles, and elevated adenosine and inosine levels, and tended toward better histological preservation. After reperfusion, University of Wisconsin solution more effectively preserved left ventricular compliance (75% versus 35% of baseline), developed pressure (71% versus 45% of baseline), histological integrity, and tissue potassium and calcium profiles than St. Thomas' solution. The University of Wisconsin solution provided superior preservation of systolic and diastolic ventricular function, tissue histology, tissue water, and tissue electrolytes than did St. Thomas' cardioplegia and normal saline solution storage in this experimental model, and might result in improved graft tolerance of ischemia in clinical cardiac transplantation.

Adenine Nucleotides↗
PubMed1980

Task-dependent development of tolerance to scopolamine.

Rats were chronically treated with once daily injections of either 0.5 mg/kg scopolamine hydrochloride or isotonic saline for 21 days. When spontaneous locomotor activity or acquisition of active avoidance in a two-way shuttle box were measured at 48 hours after the cessation of chronic treatment, no differences were observed between the two chronically treated groups. Tolerance to scopolamine's locomotor stimulatory effects was evident as the increase in locomotor activity following acute treatment was smaller in the group which had been chronically treated with scopolamine. On the other hand, acutely administered scopolamine facilitated the acquisition of active avoidance responding to an equal degree in both chronically treated groups. The reasons which may account for this task-dependent tolerance development to scopolamine are discussed.

Animals↗
PubMed1996

Expanded followup of intravesical oxybutynin chloride use in children with neurogenic bladder.

PURPOSE: We evaluated the long-term results of intravesical oxybutynin chloride use in children with neurogenic bladders who could not tolerate or whose conditions were refractory to oral therapy. MATERIALS AND METHODS: We reviewed our experience with 28 children (myelomeningocele in 27 and imperforate anus in 1) who presented with urinary incontinence and/or elevated bladder pressures refractory to intermittent catheterization and oral anticholinergic medication. Intravesical oxybutynin was administered to each child by instillation of 5 mg. crushed oxybutynin chloride in 10 cc sterile saline 2 times daily during catheterization. RESULTS: Seven patients (25%) could not tolerate intravesical oxybutynin secondary to anticholinergic side effects. The remaining 21 children have been followed on intravesical oxybutynin for a mean of 35 months (range 3 to 67). Of these 21 children 12 (57%) became completely dry day and night, 5 (24%) achieved daytime continence between catheterizations and 4 (19%) remained clinically unchanged with 2 in diapers. On urodynamics these 21 patients had increased bladder capacity of up to 1,150% (mean 237%, p < 0.0001) and decreased mean maximum filling pressures of -31% (p = 0.002). CONCLUSIONS: Although a number of patients continued to have anticholinergic side effects, a majority had significant improvement in urodynamic parameters and continence. The response appears to be durable, and it spares many of these children from undergoing bladder augmentation.

Administration, Intravesical↗
PubMed2002

Diversity of azospirillum strains isolated from rice plants grown in saline and nonsaline sites of coastal agricultural ecosystem.

The diversity of indigenous Azospirillum spp. associated with rice cultivated along the coastline of Tamil Nadu was analyzed. Twelve sites with varying soil characteristics such as salinity, texture, and the host variety were chosen. Of the 402 strains isolated using NFB media, 302 were confirmed to be Azospirillum spp. and subjected to DNA polymorphism analysis using PCR-RFLP of 16S rDNA. They were also screened for their salt tolerance and microaerobic N2-fixing-dependent growth. On species identification, all the strains were found to be A. brasilense, A. lipoferum, or unidentified. On comparing the influence of the previously noted variability on the indigenous population, soil salinity was found to play a dominant role. This was revealed by PCR-RFLP studies and salt tolerance studies. A high association between soil salinity and the distribution of Azospirillum genotypes reveals that soil salinity should be taken into consideration while developing biofertilizers specifically for the coastal agricultural ecosystem.

Agriculture↗
PubMed1978

Inhaled antihistamines--bronchodilatation and effects on histamine- and methacholine-induced bronchoconstriction.

To assess further the bronchodilator activity of inhaled antihistamines ten stable asthmatic subjects inhaled aerosols of clemastine, 1 mg/ml, and saline placebo administered double blind. Subjects underwent bronchial challenge with increasing concentrations of histamine and methacholine, and specific airways conductance was measured by whole body plethysmography at each concentration. There was a significant 21.9% increase in specific airways conductance after inhalation of clemastine. Subjects could tolerate significantly higher mean concentrations of histamine when treated with clemastine than with saline. The shift of the cumulative log histamine dose-reponse curve suggests that such protection is due to competitive antagonism to the inhaled clemastine. Clemastine did not protect subjects against methacholine-induced bronchoconstriction, which suggests that its bronchodilator properties are not related to any anticholinergic action.

Adult↗
PubMed2006

Amphetamine and pentylenetetrazole given post-trial 1 enhance one-trial tolerance to the anxiolytic effect of diazepam in the elevated plus-maze in mice.

There are several hypotheses to explain the lack of an anxiolytic effect on animals with previous maze experience (one-trial tolerance). Some of these hypotheses are related to learning and memory, so the reduction of trial 1 duration to 1 min or amnesic drug administration before trial 1 prevents the lack of an anxiolytic effect in trial 2. Amphetamine and pentylenetetrazole have been shown to enhance memory consolidation when administered immediately after training. Thus, the aim of the present study was to evaluate the effect of amphetamine (1.0-3.0 mg/kg) or pentylenetetrazole (30.0 mg/kg), at putative memory-enhancing doses, on the effect of diazepam (2.5 mg/kg) in the elevated plus-maze trial 2 on mice exposed to a 1-min long trial 1. Mice were submitted to 1-min trial 1 in the elevated plus-maze immediately followed by drug treatment (saline, amphetamine, or pentylenetetrazole) and to elevated plus-maze trial 2 after 48 h. Animals were treated with vehicle or diazepam 30 min before trial 2. The results showed that post-trial 1 saline and 1.0 mg/kg amphetamine did not induce one-trial tolerance. On the other hand, 2.0 and 3.0 mg/kg amphetamine and 30 mg/kg pentylenetetrazole induced a lack of anxiolytic effect of diazepam on trial 2 even with 1-min trial 1 length. Furthermore, these data were not due to novelty exposure in trial 1 or to amphetamine treatment so that mice exposed to an activity chamber instead of the plus-maze (trial 1) and then immediately submitted to amphetamine treatment (2.0 mg/kg) did not show one-trial tolerance 48 h after trial 1. Taken as a whole, these data support the hypothesis that memory is involved in the lack of an anxiolytic effect in the elevated plus-maze trial 2.

Amphetamine↗
PubMed1990

Simultaneous development of opioid tolerance and opioid antagonist-induced receptor upregulation.

Mice treated chronically with opioid antagonists have increased receptor density in brain and are supersensitive to the pharmacodynamic action of morphine. In the present study mice were implanted subcutaneously with naltrexone or placebo pellets for 8 days. During implantation mice received daily injections of morphine (100 or 250 mg/kg) or saline. Morphine analgesia was completely blocked in mice that were implanted with naltrexone at the low dose of morphine; while some analgesic action was observed at the higher dose. Mice implanted with placebo were analgesic following the daily morphine treatment. At the end of 8 days the pellets were removed and 24 h later some mice were tested for morphine analgesia while others were examined in binding studies. Naltrexone treatment increased [3H]naloxone, 3H[D-Ala2-D-Leu5]enkephalin (DADLE) and 3H[D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO) binding compared to controls and increased the analgesic potency of morphine. Daily treatment with morphine did not alter brain opioid binding or naltrexone-induced receptor upregulation. Mice injected daily with morphine were significantly less sensitive to morphine (tolerant) than their respective saline control group for both the placebo and the naltrexone-treated groups. However, naltrexone-treated mice were more sensitive to morphine than placebo controls regardless of whether they were injected daily with morphine or not. These results indicate that if naltrexone-induced opioid receptor upregulation occurs in the presence of repeated agonist administration, the new binding sites mediate tolerance via desensitization to morphine.

Analgesia↗
PubMed1998

Lacrimal system obstruction treated with lacrimal polyurethane stents: outcome of removal of occluded stents.

PURPOSE: To describe the short- and long-term outcomes of the removal of occluded stents. MATERIALS AND METHODS: With fluoroscopic guidance, 571 lacrimal polyurethane stents were placed in 502 patients with epiphora due to obstruction of the lacrimal system. Of the 571 stents, 142 were removed 2 weeks to 42 months (mean, 7 months) after placement because of recurrent epiphora, and the lacrimal system was irrigated with saline solution through the lacrimal point. RESULTS: Stent removal was well tolerated. Mild epistaxis occurred in one patient and was controlled with a nasal pack. Recurrent epiphora was due to obstruction of the stent with mucoid material in 49 (35%) of 142 systems and granulation tissue in 93 (65%) systems. After stent removal, 73 (51%) of the 142 lacrimal systems showed improvement of epiphora, with a patent lacrimal system at 7-day follow-up dacryocystography. During the follow-up of 2 weeks to 49 months (mean, 22 months) after stent removal, patency was maintained in 24 (33%) of the 73 lacrimal systems. CONCLUSION: Removal of an occluded lacrimal plastic stent was easy and safe. Recurrent epiphora after placement of lacrimal plastic stents can be treated with removal of the occluded stents an irrigation with saline solution through the lacrimal point, which resulted in a patent lacrimal system in 33% of cases in this study.

Adult↗
PubMed2000

Complete prevention but stimulus-dependent reversion of morphine tolerance by the glycine/NMDA receptor antagonist (+)-HA966 in neuropathic rats.

BACKGROUND: Tolerance to the analgesic effect of morphine complicates the management of chronic pain states. The authors studied the ability of the glycine/N-methyl-D-aspartate receptor antagonist (+)-HA966 to modify morphine tolerance in a rat model of neuropathic pain. METHODS: Mononeuropathy was induced by placing four ligatures around the common sciatic nerve. The 4-day pretreatment regimens with two daily subcutaneous injections of saline and saline, saline and morphine (10 mg/kg), (+)-HA966 (2.5 mg/kg) and morphine, or (+)-HA966 and saline were begun on post-operative day 12 to test the ability of (+)-HA966 to prevent the development of tolerance. Behavioral experiments were performed on postoperative day 16, when the pain-related behavior reached a stable maximum. The effect of an acute dose of morphine (1 mg/kg intravenously) was tested against both mechanical (vocalization threshold to paw pressure) and thermal (struggle latency to hind paw immersion into a 46 degrees C hot-water bath) stimuli. In addition, to test the ability of a single injection of (+)-HA966 to reverse established morphine tolerance, groups of morphine-pretreated rats received injections of either (+)-HA966 (2.5 mg/kg subcutaneously) and morphine (1 mg/kg intravenously), saline and morphine, or (+)-HA966 and saline. RESULTS: Baseline vocalization thresholds and struggle latencies did not differ in the various pretreatment groups, indicating that the pretreatments had no effect on pain-related behavior. Coadministration of (+)-HA966 prevented the reduction of the effect observed with morphine alone in both the mechanical test and the thermal test. (+)-HA966 reversed morphine tolerance in the thermal but not in the mechanical test. CONCLUSION: (+)-HA966 prevented morphine tolerance in both mechanical and thermal tests but reversed established morphine tolerance in the thermal test only.

Analgesics, Opioid↗
PubMed1992

Prevention of development of tolerance and dependence to opiate in mice by BR-16A (Mentat), a herbal psychotropic preparation.

Chronic treatment with BR-16A (20-500 mg/kg) followed by saline on days 1 to 9 failed to produce any significant change in tail-flick latency from the saline-pretreated group in mice. Repeated administration of BR-16A(20-500 mg/kg) for 9 days however, attenuated the development of tolerance to the analgesic effect of morphine (10 mg/kg). BR-16A (20-500 mg/kg) also suppressed, in a dose-dependent manner, the development of morphine dependence as assessed by naloxone (2 mg/kg)-precipitated withdrawal on day 10 of testing.

Analysis of Variance↗
PubMed1989

Pharmacokinetics of single-dose cefmetazole following intramuscular administration of cefmetazole sodium to healthy male volunteers.

The tolerance and pharmacokinetics of cefmetazole were studied in healthy male volunteers who received a placebo (sterile saline) or a single dose of cefmetazole sodium intramuscularly. Drug-treated volunteers received one of four doses, 0.375, 0.750, 1, or 2 g. The drug was well tolerated, with no adverse medical events or laboratory changes observed during the study that could affect the pharmacokinetic interpretation of the data. Cefmetazole concentrations were determined by using a specific high-performance liquid chromatographic method. Serum cefmetazole concentrations were well described by a one-compartment open model with first-order absorption and elimination. Cefmetazole was rapidly absorbed in most volunteers, with a mean time to maximum concentration in serum of 1.24 +/- 0.12 h (+/- standard error of the mean), and the mean maximum concentration in serum increased from 17.0 +/- 1.6 to 74.2 +/- 9.5 micrograms/ml over the 0.375- to 2-g dose range. Maximum concentrations in serum, areas under serum concentration-time curve, and urinary excretion of intact drug increased in proportion to cefmetazole sodium dose. Times at which maximum concentrations in serum occurred, apparent volumes of distribution, steady-state volumes of distribution, absorption and elimination half-lives, and systemic clearances did not change significantly (P greater than 0.05) with drug dose. Although absorption and elimination half-lives were not significantly different in 10 of 40 volunteers (P greater than 0.05), in a majority of subjects elimination half-lives were approximately 10 times longer than absorption half-lives. The mean recovery of intact drug in urine ranged from 68.8 to 86.0% over the dose range studied, with a mean recovery over all doses of 77.1 +/- 2.4%. Rental clearances were significantly lower (P < 0.05) for the two lowest doses (93.0 and 84.3 versus 115.0 and 118.0 ml/min); these differences are not considered clinically important. The results of this study indicate that cefmetazole pharmacokinetics are linear after administration of single intramuscular doses ranging from 0.375 to 2 g, that clinically relevant concentrations of cefmetazole in serum (1 to 2 micrograms/ml) persist in a majority of volunteers for more than 8 h after administration of 0.750-g or higher doses, and that clinically relevant concentrations of cefmetazole continue to be excreted in urine 8 to 12 h after administration of 0.375- to 2-g doses.

Adolescent↗
PubMed1993

Naloxone does not prevent vasovagal syncope during simulated orthostasis in humans.

The mechanism of vasovagal syncope during orthostasis in humans is unknown. Opioid receptors have been implicated in the vasovagal-like responses to hemorrhagic hypotension in conscious animals. We sought to determine if opioid receptor blockade with naloxone (mu receptor antagonist) would prevent or delay the onset of vasovagal syncope in humans. Three protocols were performed in which heart rate, arterial pressure, sympathetic nerve activity, thoracic impedance and forearm vascular resistance were measured during stepwise steady-state increments of lower body negative pressure (LBNP) in nine healthy volunteers. In protocol 1, duplicate trials of LBNP to syncope or -60 mmHg were performed with a 30-45 minute rest period separating the trials. No significant differences in any physiologic responses or cumulative stress tolerance were found. In protocol 2, graded LBNP was repeated after administration of saline or naloxone (0.1 mg/kg) in six subjects in which vasovagal syncope occurred prior to -60 mmHg LBNP. The peak increase of sympathetic nerve activity during LBNP was augmented after naloxone (P = 0.02), but the occurrence of vasovagal syncope was not prevented nor was the cumulative stress tolerated affected (P = 0.42). The heart rate and arterial pressure responses to LBNP were not affected by naloxone. Similarly, in protocol 3, naloxone given just prior to the onset of pre-syncopal symptoms did not alter the physiologic response or the occurrence of vasovagal syncope. These data show that naloxone does not prevent or delay the onset of vasovagal syncope in humans which suggests that mu opioid receptors do not mediate the vasovagal response.

Adult↗
PubMed2000

A fluctuating salinity regime mitigates the negative effects of reduced salinity on the estuarine macroalga, Enteromorpha intestinalis (L.) link.

We tested the response of Enteromorpha intestinalis to fluctuating reduced salinity regimes which may occur in coastal estuaries due to both natural and anthropogenic influences. In a fully crossed two factor experiment, we subjected E. intestinalis to 0, 5, 15 and 25 psu water enriched with nutrients for 1-, 5-, 11- and 23-day periods. Each period was followed by 24 h of exposure to 25 psu (ambient) water that was not nutrient enriched. Following 24 h in ambient salinity water, algae were returned to reduced salinity conditions for the appropriate period and the cycle continued over the 24 days for which all treatments were maintained. Exposure to 0 psu for 5 days or longer resulted in loss of pigmentation, decreased wet and dry biomass, increased wet wt:dry wt ratios, decreased removal of nitrogen (N) and phosphorus (P) from the water column and an accumulation of NH(4) in the water column. More frequent exposure to ambient salinity in the 1-day treatment mitigated these effects. Across all salinity levels tested, biomass increased as frequency of exposure to ambient salinity increased. At all durations of exposure to low salinity tested, biomass increased as salinity level increased. We conclude that growth of E. intestinalis is decreased by reduced salinity. E. intestinalis is able to withstand exposure to 0 psu but there is a temporal limit to this tolerance that is somewhere between 1 and 5 days. Populations of E. intestinalis in coastal estuaries may suffer from freshwater inputs if salinity conditions are persistently reduced.

Journal Article↗
PubMed1996

Endothelin-1 induces insulin resistance in conscious rats.

Since endothelin-1 (ET-1) might regulate insulin secretion and glucose metabolism, we carried out experiments to study the effect of ET-1 in conscious rats by injecting ET-1 (0.5 or 1.0 microgram/100 g body weight, i.p.) and examining the plasma glucose (PG) and insulin (PI) concentrations and PG/PI ratios continuously for 3 hours after the injection. Compared to the saline controls, ET-1 increased PG and PG/ P1 ratios in a dose-dependent manner. Oral glucose tolerance test (OGTT) performed at 30 min after the injection showed that PG levels stayed significantly higher in rats preinjected with ET-1 than rats with saline injection, although the change in PI levels was not different. Simultaneous infusion of glucose and insulin to somatostatin-primed rats with ET-1 or saline injection resulted in significantly higher steady state plasma glucose (SSPG) levels and SSPG/PI ratios in rats injected with ET-1 than control rats with saline. These results unequivocally indicated that intraperitoneally administered ET-1 induces insulin resistance in conscious rats.

Animals↗
PubMed2003

A standardisation of Ciona intestinalis (Chordata, Ascidiacea) embryo-larval bioassay for ecotoxicological studies.

A standardisation of the ascidian Ciona intestinalis embryo-larval bioassay for marine pollution assessment has been developed. The minimum percentage of embryogenesis success was established to assess the quality of the biological material used; minimum sample size and number of replicates per treatment were also estimated. The suitability of artificial and natural seawater for the incubation of ascidian embryos and larvae was compared, and the optimum conditions of temperature, salinity, pH, density of embryos in the vials and the sperm/egg ratio were investigated. On the basis of the 10th percentile of the distribution of larval abnormalities, we proposed a threshold of 50% normal larvae in the control in order to consider the test of acceptable biological quality. According to our results n=5 is a sufficiently high replication to detect 5% differences among treatment means with a power of P=90% and alpha=0.05, and a sampling size >/=222 allows a 95% confidence in the estimate with an error of 0.05. Egg density did not affect larval development within the range 1-20 eggs/ml, and the optimum sperm/egg ratio which fertilise 100% of the eggs was 3000-30,000 sperm/egg (i.e. 10(8)-10(7) sperm/ml). There were not significant differences between the two water types tested, and the optimum tolerance ranges were 18-23 degrees C temperature, 34-42 ppt salinity (42 ppt was the highest salinity tested), and 7.4-8.8 pH. The median effective concentration (EC(50)) of copper (Cu) causing a 50% reduction of normal hatched larvae was 54.2 microg/l (0.85 microM), which shows a sensitivity of this species similar to the commonly used bivalve and sea-urchin tests. The ascidian embryo-larval bioassay is an accurate, reliable, simple and rapid method that can be used in ecotoxicological studies.

Animals↗
PubMed1984

Relationship between the development of behavioral tolerance and the biodisposition of phencyclidine in mice.

Mice trained on a differential reinforcement of low rate 10-sec schedule (DRL 10) were treated daily with either IP saline or 10 mg/kg of phencyclidine hydrochloride (PCP). After 21 consecutive days of treatment, dose-effect determinations for PCP were obtained in both groups. Chronic treatment with PCP resulted in approximately 1.5-fold development of tolerance to the PCP-induced reduction of reinforcement rate. Following completion of the dose-effect determinations, the mice were treated for an additional 13 days with either saline or PCP (10 mg/kg, IP). On the fourteenth day, the biodisposition of 3H-PCP-HCl (10 mg/kg, IP) was studied in both groups. The ratio of the brain levels of PCP in the saline-trained animals to that in the PCP-trained animals was 1.3 to 1 which accounted in large part for the development of tolerance. It appears that dispositional factors are involved in the development of tolerance of mice to the disruptive effects of PCP on DRL performance.

Animals↗
PubMed1990

Acute effects of nicotine injection into the nucleus accumbens on locomotor activity in nicotine-naive and nicotine-tolerant rats.

To assess the role of nicotine receptors in the nucleus accumbens on locomotor activity we bilaterally implanted guide cannulae for later injection of (-)-nicotine into the nucleus accumbens of Wistar rats. Motor activity was tested in a complex tunnel maze equipped with photocells for automatic recording. This system of dark tunnels elicits spontaneous exploration even after repeated exposure. Half of the rats were made nicotine-tolerant by daily systemic injections of (-)-nicotine for 15 days (nicotine pretreatment); the other half remained nicotine-naive (saline pretreatment). Whereas (-)-nicotine (40 nmol/0.3 microliter) bilaterally injected into the nucleus accumbens of nicotine-naive animals suppressed locomotor activity, the same amount injected into the nucleus accumbens of nicotine-tolerant rats had no effect on locomotor activity. Systemic injections of nicotine (0.4 mg/kg) induced a depression and stimulation of locomotor activity in saline-pretreated and nicotine-pretreated rats, respectively. Our results support a dual role for nicotine in locomotor activity with the initial depressant effect in nicotine-naive animals due to stimulation of the nucleus accumbens and perhaps other structures.

Animals↗
PubMed1998

[Dexpanthenol nasal spray as an effective therapeutic principle for treatment of rhinitis sicca anterior].

BACKGROUND: Controlled clinical studies on medical treatment of rhinitis sicca anterior have not yet been published. Therapy recommendations are based on experiences but not on results of controlled clinical studies. The aim of this study was to examine the efficacy and tolerance of a new form of application of Dexpanthenol in physiologic saline solution (Nasicur). PATIENTS AND METHODS: A randomized comparison of parallel groups was performed. One group was treated with the nasal spray while the control group received a placebo. The assessment of nasal breathing resistance and the extent of crust formation according to scores were defined as target parameters. Statistical analysis was carried out according to Wilcoxon at alpha < or = 0.05. RESULTS: Forty-eight outpatients diagnosed with rhinitis sicca anterior were included in this study. Twenty-four received the medication, and 29 were treated with a placebo. The superiority of the dexpanthenol nasal spray in comparison to the placebo medication was demonstrated for both target parameters as clinically relevant and statistically significant. The placebo spray showed clinical improvement of the other treatment outcome parameters. Dexpanthenol nasal spray showed no statistically significant difference in comparison to placebo. The clinically proven efficacy is emphasized by good tolerance of both treatments which was validated by the objective rhinoscopy findings. Good compliance was confirmed. CONCLUSION: The result of the controlled clinical study confirms that the dexpanthenol nasal spray is an effective medicinal treatment of rhinitis sicca anterior and is more effective than common medications.

Administration, Intranasal↗