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PubMed1986

Somatostatin and oxytocin infusion inhibits the rise of plasma beta-endorphin, beta-lipotrophin and cortisol induced by insulin hypoglycaemia.

The present study investigated the possible effect of somatostatin and oxytocin on the basal and stress-induced rise of beta-endorphin (beta-END), beta-lipotrophin (beta-LPH) and cortisol in the human. For this purpose somatostatin (4.1 micrograms/min for 120 min or oxytocin (0.4 micrograms/min for 120 min) was infused into two different groups of seven healthy subjects; 30 min after the start of the infusion, placebo or insulin (0.1 IU/kg body weight, B.W.) was injected on two different days. In a third experimental step, an insulin tolerance test was performed during saline infusion to evaluate stress-related effects on the different hormonal secretions under basal conditions. Plasma levels of beta-END, beta-LPH and cortisol were measured by radioimmunoassay. Extraction and chromatographic procedures preceded the assay for beta-END and beta-LPH. Neither somatostatin nor oxytocin significantly modified basal plasma levels of beta-END, beta-LPH and cortisol. However these treatments blunted the rise of the three hormones seen at 45 and 60 min during insulin-induced hypoglycaemia (P less than 0.01). These results indicate that somatostatin and oxytocin may influence the beta-END, beta-LPH and cortisol increase induced by stress in humans, without affecting their basal secretion.

Adult↗
PubMed2005

Treatment of local, persistent cutaneous atrophy following corticosteroid injection with normal saline infiltration.

BACKGROUND: Injections of corticosteroids are commonly used for a variety a dermatologic conditions but may cause local, persistent cutaneous atrophy, with few therapeutic options. OBJECTIVE: To determine the effectiveness of bacteriostatic normal saline infiltration on the improvement of corticosteroid-induced cutaneous atrophy. MATERIALS AND METHODS: Four patients with corticosteroid-induced atrophy of the skin, two caused by acneiform cysts and one from intramuscular steroid injection, were treated with weekly injections of normal saline directly into the atrophic site. The patients were seen on weekly follow-up visits, and improvement was documented. RESULTS: All four patients demonstrated complete resolution of skin atrophy and restoration of surface contour within 4 to 8 weeks of initial presentation. Injected volumes of normal saline ranged from 5 to 20 cm(3) per treatment session and three to six weekly treatments. The patients were completely satisfied with these results. CONCLUSION: Normal saline infiltration offers a safe, tolerable, relatively rapid, and effective treatment for local, persistent corticosteroid-induced atrophy.

Adrenal Cortex Hormones↗
PubMed1986

The effect of topical ophthalmic instillation of timolol and betaxolol on lung function in asthmatic subjects.

The propensity of systemic beta-adrenergic blockers to cause bronchoconstriction in patients with reactive airway disease is well recognized. A study was carried out to determine the prevalence of sensitivity to ophthalmic timolol in 24 asthmatic subjects at our institution and to determine the effect of ophthalmic betaxolol, a cardioselective beta-blocker efficacious in the treatment of glaucoma, in 8 subjects who were timolol-sensitive. Subjects received topical timolol 0.5%; ventilatory function, blood pressure, and heart rate were monitored over a 90-min period. The mean FEV1 fell from 2.47 to 1.93 L by 30 min after drug treatment to a minimal value of 1.86 L (-27.8%). There was a corresponding fall in FVC from 3.68 to 3.09 L by 30 min with a minimal value of 3.00 L(-20.7%). FEV1/FVC ratio also fell from 66.9 to 61.0% by 30 min, reaching a minimum of 60.0%. In 14 subjects (58.3%), the fall in FEV1 was greater than or equal to 20%, with a mean fall of 38.7% by 30 min and a maximal fall of 44.9%. The severity of timolol-sensitivity correlated with the extent of reduction in baseline percent predicted FEV1 and FVC and with exercise-induced bronchospasm. In addition, the administration of timolol reduced the bronchodilator response to below the pretimolol value. In 8 of the timolol-sensitive patients who underwent a double-blind crossover challenge with ocular instillation of betaxolol 1% and saline, betaxolol was well-tolerated and did not affect ventilatory function over a 4-h observation period. In addition, it did not prevent the FEV1 response to inhaled bronchodilator.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1979

Salt tolerance of Rhizobium species in broth cultures.

Salt tolerance of five rhizobia strains was examined in broth cultures. Five levels of NaCl concentration were used and the optical density was taken as a measure for the vigour of bacterial growth. Rhizobium leguminosarum and R. meliloti were tolerant to high levels of salinity and growth curves in saline broth showed a similar pattern to the control level. Rhizobium japonicum, cowpea Rhizobium, and R. trifolii were intolerant to salt and showed a strong growth retardation with increasing salt concentration. Growth was inhibited at high levels of salinity. It is suggested that rhizobia sensitivity to salts may be partly responsible to the inhibition of nitrogen fixation by legumes growing under salt stress.

Culture Media↗
PubMed1994

The CCK-B receptor antagonist Cl 988 reverses tolerance to morphine in rats.

The ability of the selective cholecystokinin-B (CCK-B) receptor antagonist Cl 988 to reverse tolerance to morphine's antinociceptive effect was investigated with the hot-plate test in Sprague-Dawley rats. Tolerance was induced by subcutaneous (s.c.) injection of 10 mg kg-1 morphine twice daily for four days. On the fifth day rats were administered CI 988 (10 mg kg-1) or saline plus 5 mg kg-1 morphine s.c. Significant antinociception was observed in the group that received the CCK-B antagonist plus morphine, whereas the saline plus morphine group exhibited total tolerance. These results suggest that upregulation of the endogenous CCK system during repeated morphine administration may have an important role in the development of opiate tolerance.

Analgesia↗
PubMed1998

Effect of topical butyrate on rectal epithelial kinetics and mucosal enzyme activities.

1. This study aimed to determine the effect of luminal butyrate on proliferative kinetics, a differentiation marker (alkaline phosphatase), and a molecule that controls cell-substratum adhesion (urokinase) in histologically normal human rectal mucosa. 2. Ten subjects with a colonoscopically normal colon (seven had previous adenomas) were given either butyrate or saline enemas for 4 days in a double-blind cross-over manner. Rectal biopsies were taken before and after each course of enemas. Epithelial proliferative kinetics were measured immunohistochemically using antibodies to proliferating cell nuclear antigen. Urokinase and alkaline phosphatase activities were measured spectrophotometrically in biopsy homogenates. 3. Both saline and butyrate enemas were well tolerated and induced no histological change except for a significant increase in crypt length (P < 0.05). The number of proliferating cells per crypt also increased significantly after butyrate (P = 0.018). 4. Compared with saline enemas, butyrate did not affect kinetic indices nor alkaline phosphatase activities. However, mucosal urokinase activities were significantly lower in butyrate-treated patients (9.5 +/- 2.0 i.u./g) than in saline-treated patients (12.8 +/- 2.0 i.u./g; P = 0.045). 5. Delivering of extra butyrate to the distal colon in healthy subjects may stabilize cell-substratum adhesion in surface epithelium and therefore offer a potential mechanism by which elevating distal colonic luminal butyrate concentrations might be beneficial in patients with colitis or hyperproliferative large bowel epithelium.

Adult↗
PubMed1987

Comparative bronchial responses to hyperosmolar saline and methacholine in asthma.

Airway responsiveness to inhaled methacholine and to ultrasonically nebulised hyperosmolar saline was compared in 20 asthmatic subjects. Each subject had two hyperosmolar inhalation tests and a methacholine challenge in random order at least 48 hours apart over a period of two weeks. Hyperosmolar challenge, carried out with doubling concentrations of saline from 0.9% to 14.4% to obtain a dose-response curve, was well tolerated by all subjects. The response to hyperosmolar saline--expressed as the PO20, the osmolarity inducing a 20% fall in forced expiratory volume in one second (FEV1) was obtained in 16 of the 20 subjects and in each was repeatable to within one doubling concentration of saline. The peak bronchoconstrictor effect of hyperosmolar saline inhalation occurred at 3 minutes and its mean total duration (FEV1 less than 90% of baseline) was 50 minutes. There was no significant correlation between the PO20 and the PC20 methacholine (the concentration inducing a 20% fall in FEV1). Thus by using a new method to obtain a quantitative airway response to inhaled hyperosmolar saline we found that the airway response to hyperosmolar inhalation differs from the airway response to methacholine.

Administration, Inhalation↗
PubMed2000

The dopamine D2/D3 antagonist DS121 potentiates the effect of cocaine on locomotion and reduces tolerance in cocaine tolerant rats.

To explore the significance of dopamine (DA) autoreceptors in cocaine tolerance and cocaine induced locomotor activity rats were treated with saline and cocaine (40 mg/kg per day via osmotic minipump; normal and cocaine tolerant rats, respectively). Injections of DS121 (0-7 mg/kg, i.p.; S(-)-3-(3-(cyanophenyl)-N-n-propylpiperidine), a DA D2/3 and autoreceptor preferring antagonist, either alone (i.e. DS121 + saline injection) or in combination with cocaine (7.5 mg/kg, i.p.) were also given. DS121 (+ saline) increased locomotor activity in both saline and cocaine pump (CP) treated animals. DS121 also potentiated the effect of cocaine on locomotor activity; this effect was greatest in CP (tolerant) animals. It is concluded that DS121 can increase locomotor activity and that this effect is greatest when the DA tone is high, that is when cocaine is present, suggestive of a presynaptic mechanism. Furthermore, because DS121 potentiation of cocaine induced locomotor activity is greatest in tolerant animals it is concluded that supersensitive DA autoreceptors underlie this effect. These data further support our previous data, which show that DA autoreceptors are sensitized after continuous cocaine (minipump) treatment.

Animals↗
PubMed1990

Butorphanol's efficacy at mu and kappa opioid receptors: inferences based on the schedule-controlled behavior of nontolerant and morphine-tolerant rats and on the responding of rats under a drug discrimination procedure.

The purpose of the present investigation was to characterize the mu agonist and kappa antagonist effects of the mixed opioid agonist/antagonist butorphanol. To this end, the effects of butorphanol were examined: 1) alone and in combination with the kappa agonist bremazocine in nontolerant and morphine-tolerant rats responding under a fixed-ratio 30 (FR30) schedule of food presentation, and 2) in rats trained to discriminate 10 mg/kg morphine from saline. Prior to the induction of morphine tolerance, morphine, bremazocine and butorphanol produced dose-dependent decreases in rate of responding under the FR30. In these nontolerant rats, butorphanol failed to antagonize bremazocine's rate-decreasing effects. During the chronic morphine regimen, the dose-effect curve for morphine was shifted to the right of its prechronic position by approximately 0.9 log units, whereas the bremazocine curve was not altered substantially. The butorphanol dose-effect curve, in contrast, was shifted to the right and flattened such that doses which eliminated responding in nontolerant rats, as well as doses approximately 1.0 log unit higher, had no effect on responding. In these morphine-tolerant rats, butorphanol produced a dose-dependent antagonism of bremazocine's rate-decreasing effects. In rats trained to discriminate morphine from saline, butorphanol substituted completely for the morphine stimulus. Unlike morphine, which produced its stimulus effects only at doses that decreased rate of responding, butorphanol substituted for the morphine stimulus at doses that had little or no effect on rate of responding.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1986

Angina pectoris-like pain provoked by intravenous adenosine in healthy volunteers.

In a study to characterise the chest pain induced by adenosine this agent was given as a bolus into a peripheral vein to six healthy volunteers (five men) aged 30-44. On the first day the maximum tolerable dose was determined in each case. On the second day three doses of adenosine (one third, two thirds, and the full maximum tolerable dose) and three doses of saline were given single blind in randomised order. Thereafter aminophylline 5 mg/kg was given and the procedure repeated in a different randomised order. On the third day between two thirds and the full maximum tolerable dose was given followed by 10 mg dipyridamole intravenously and a second injection of the same dose of adenosine. Heart rate and atrioventricular blocks were recorded by electrocardiography. One minute after each dose of adenosine the chest pain was scored. The maximum tolerable dose of adenosine ranged from 10.6 to 37.1 mg. All subjects experienced uneasy central chest pain provoking anxiety. The pain radiated to the shoulders, ulnar aspect of the arms, epigastric area, back, and into the throat. The pain began about 20 seconds after the injection and lasted 10-15 seconds. Increasing the dose of adenosine increased the intensity of the pain. Administration of aminophylline reduced the pain significantly. Second degree heart block was recorded in five of the six subjects during the time that the pain was experienced. After aminophylline no block was observed. Dipyridamole increased the intensity of pain. The duration of second degree heart block increased in four of the subjects, and in two of these third degree heart block occurred. These findings suggest that adenosine released from the myocardium during ischaemia induces angina pectoris by stimulating theophylline sensitive receptors.

Adenosine↗
PubMed1997

Enhancement of morphine actions in morphine-naive and morphine-tolerant mice by LY 235959, a competitive antagonist of the NMDA receptor.

1. The effects of LY 235959, a competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, on the analgesic and hypothermic actions of morphine, were determined in nontolerant and morphine-tolerant mice. 2. LY 235959 enhanced the analgesic and hypothermic action of morphine in nontolerant mice. 3. LY 235959 also enhanced the analgesic and hypothermic actions of morphine in morphine-tolerant mice. LY 235959, injected before saline injection, had no effect on the antinociception or the body temperature. 4. It is concluded that competitive antagonism of the NMDA receptor enhances the pharmacologic actions of morphine both in morphine-naive and morphine-tolerant mice and that these actions differ from the noncompetitive antagonism of the NMDA receptors.

Analgesics, Opioid↗
PubMed1994

Persistence of tolerance to effects of cocaine on schedule-controlled behavior in pigeons.

Keypecking by seven pigeons, maintained by a fixed-ratio 30 schedule of food presentation, was decreased in rate by acute pre-session administration of cocaine. In Part 1 (four pigeons), tolerance to the rate-suppressing effects of cocaine developed during daily administration conditions. Tolerance persisted (1) when daily cocaine injections were replaced by conditions in which cocaine was administered every other day, then every fourth day, then every eighth day, then every 16th day, with all intervening sessions preceded by saline injections and (2) when daily cocaine administration was replaced abruptly by a condition in which cocaine injections were spaced 16 days apart, with all intervening sessions preceded by saline. In Part 2 (three pigeons), tolerance developed during intermittent administration conditions (e.g. cocaine injected every eighth day) for two subjects, and during daily administration for the third subject. As in Part 1, tolerance persisted when cocaine was administered only once every 16 days. These results are consistent with an interpretation of tolerance based upon operant compensatory reactions to drug-induced behavioral disruptions and suggest that a simple associationist model of tolerance to cocaine-induced response-rate suppression may be inadequate. The data also have practical implications regarding tolerance development during intermittent administration conditions similar to conventional acute dose-effect determination procedures.

Journal Article↗
PubMed2005

Sorghum bicolor's transcriptome response to dehydration, high salinity and ABA.

Genome wide changes in gene expression were monitored in the drought tolerant C4 cereal Sorghum bicolor, following exposure of seedlings to high salinity (150 mM NaCl), osmotic stress (20% polyethylene glycol) or abscisic acid (125 microM ABA). A sorghum cDNA microarray providing data on 12,982 unique gene clusters was used to examine gene expression in roots and shoots at 3- and 27-h post-treatment. Expression of approximately 2200 genes, including 174 genes with currently unknown functions, of which a subset appear unique to monocots and/or sorghum, was altered in response to dehydration, high salinity or ABA. The modulated sorghum genes had homology to proteins involved in regulation, growth, transport, membrane/protein turnover/repair, metabolism, dehydration protection, reactive oxygen scavenging, and plant defense. Real-time PCR was used to quantify changes in relative mRNA abundance for 333 genes that responded to ABA, NaCl or osmotic stress. Osmotic stress inducible sorghum genes identified for the first time included a beta-expansin expressed in shoots, actin depolymerization factor, inositol-3-phosphate synthase, a non-C4 NADP-malic enzyme, oleosin, and three genes homologous to 9-cis-epoxycarotenoid dioxygenase that may be involved in ABA biosynthesis. Analysis of response profiles demonstrated the existence of a complex gene regulatory network that differentially modulates gene expression in a tissue- and kinetic-specific manner in response to ABA, high salinity and water deficit. Modulation of genes involved in signal transduction, chromatin structure, transcription, translation and RNA metabolism contributes to sorghum's overlapping but nonetheless distinct responses to ABA, high salinity, and osmotic stress. Overall, this study provides a foundation of information on sorghum's osmotic stress responsive gene complement that will accelerate follow up biochemical, QTL and comparative studies.

Abscisic Acid↗
PubMed1990

Dissociation of the apparent relationship between nicotine tolerance and up-regulation of nicotinic receptors.

Saline or nicotine (0.8 mg/kg/hr) was administered chronically to rats via subcutaneous infusion for 7 days. After chronic treatment, the effects of a challenge dose of nicotine, injected subcutaneously, on open-field activity and body temperature were measured. Nicotine responses were measured 2 hours after infusion had been stopped (day 0) or 1, 2, 4, 8, or 21 days after cessation of treatment. Brain nicotinic receptors were measured using nicotine binding or bungarotoxin binding in six brain regions. Tolerance to nicotine's effects on open-field activity and body temperature were observed; this tolerance was lost before the fourth day of withdrawal. Both nicotine and BTX binding were increased after chronic nicotine treatment. The return of the receptors to control values was dependent on brain region, but in general receptors were still increased at 4 days after withdrawal. The half-lives for receptors returning to normal were greater for nicotine binding compared to BTX binding. These results suggest that a relatively short-lived tolerance results from chronic nicotine infusion and that alterations in nicotinic receptors can be dissociated from behavioral tolerance.

Animals↗
PubMed2004

Natural protein engineering: a uniquely salt-tolerant, but not halophilic, alpha-type carbonic anhydrase from algae proliferating in low- to hyper-saline environments.

Dunaliella salina is a unicellular green alga thriving in environments ranging from fresh water to hyper-saline lakes, such as the Dead Sea. An unusual, internally duplicated, 60 kDa alpha-type carbonic anhydrase (dCA I), located on the surface of this alga, is expected to function over a broad range of salinities. It would therefore differ from other carbonic anhydrases that already lose activity at low salinities and also from halophilic proteins that require high salinities for conformational stability. Enzymatic analyses indeed indicated that dCA I retained activity at salt concentrations ranging from low salt to at least 1.5 M NaCl or KCl for CO(2) hydration, 2.0 M NaCl for esterase activity and 0.5 M for bicarbonate dehydration. Although measurements at higher salinities were constrained by the interference of salt in the respective assayed reactions, activity was noticeable even at 4.0 M NaCl. Comparisons of the internally duplicated dCA I to single-domain derivatives indicated that inter-domain interactions played a decisive role in the stability, activity, salt tolerance and pH responses of dCA I. Hence dCA I is a uniquely salt- tolerant protein, retaining an active conformation over a large range of salinities and, as a Zn metalloenzyme, largely immune to the specific inhibitory effects of anions. Its unique features make dCA I a useful model to understand the physico-chemical basis of halotolerance and protein-salt interactions in general.

Amino Acid Sequence↗
PubMed1987

Effect of salinity on leaf gas exchange in two populations of a c(4) nonhalophyte.

Gas exchange measurements were made on plants from two natural populations differing in salt tolerance of Andropogon glomeratus, a C(4) nonhalophyte, to examine the effect of salinity on components responsible for differences in photosynthetic capacity. Net CO(2) uptake and stomatal conductance decreased with increasing salinity in both populations, but to a greater extent in the inland (nontolerant) population. The intercellular CO(2) concentrations increased with increasing salinity in the inland population, but decreased in the marsh (tolerant) population. Water use efficiency decreased as salinity increased in the inland population, and remained unchanged in the marsh population. Carboxylation efficiency decreased and CO(2) compensation points increased with increasing salinity in both populations, but to a lesser extent in the marsh population. Carboxylation efficiencies were higher with 2% relative to 21% atmospheric O(2) in salt stressed plants, suggesting that a decrease in the carboxylation:oxygenation ratio of ribulose 1,5-bisphosphate carboxylase/oxygenase was partly responsible for the decrease in photosynthetic capacity. Populational differences in photosynthetic capacity were the result of greater salinity-induced changes in carboxylation efficiency in the inland population, and not due to differences in the stomatal limitation to CO(2) diffusion.

Journal Article↗
PubMed2005

Changes in the biogenic amine content of the prefrontal cortex, amygdala, dorsal hippocampus, and nucleus accumbens of rats submitted to single and repeated sessions of the elevated plus-maze test.

It has been demonstrated that exposure to a variety of stressful experiences enhances fearful reactions when behavior is tested in current animal models of anxiety. Until now, no study has examined the neurochemical changes during the test and retest sessions of rats submitted to the elevated plus maze (EPM). The present study uses a new approach (HPLC) by looking at the changes in dopamine and serotonin levels in the prefrontal cortex, amygdala, dorsal hippocampus, and nucleus accumbens in animals upon single or double exposure to the EPM (one-trial tolerance). The study involved two experiments: i) saline or midazolam (0.5 mg/kg) before the first trial, and ii) saline or midazolam before the second trial. For the biochemical analysis a control group injected with saline and not tested in the EPM was included. Stressful stimuli in the EPM were able to elicit one-trial tolerance to midazolam on re-exposure (61.01%). Significant decreases in serotonin contents occurred in the prefrontal cortex (38.74%), amygdala (78.96%), dorsal hippocampus (70.33%), and nucleus accumbens (73.58%) of the animals tested in the EPM (P < 0.05 in all cases in relation to controls not exposed to the EPM). A significant decrease in dopamine content was also observed in the amygdala (54.74%, P < 0.05). These changes were maintained across trials. There was no change in the turnover rates of these monoamines. We suggest that exposure to the EPM causes reduced monoaminergic neurotransmission activity in limbic structures, which appears to underlie the "one-trial tolerance" phenomenon.

Amygdala↗
PubMed2002

Comparative study of the endotoxemia and endotoxin tolerance on the production of Th cytokines and macrophage interleukin-6: differential regulation of indomethacin.

Endotoxin tolerance reduces the capacity of monocytes to produce proinflammatory cytokines, results in cellular immune paralysis, and down-regulates the production of helper T (Th)1 type cytokines with a shift toward a Th2 cytokine response. Prostaglandin (PG)E2 in the immune system also results in macrophage inactivation and the suppression of Th1 activation and the enhancement of Th2 activation. However, the inhibitory effects of PGE2 on the altered polarization of the Th cell and macrophage interleukin (IL)-6 production characterized in part by cellular immune paralysis in a state of endotoxin tolerance is unclear. This study was undertaken, using indomethacin, to investigate the role of endogenous PGE2 on the Th cytokines and macrophage IL-6 production in a state of endotoxin tolerance compared to those with endotoxemia mice, wherein, in this latter case, the increased production of proinflammatory cytokines and PGE2 is exhibited. Endotoxemia was induced by injection of lipopolysaccharide (LPS; 10 mg/kg in saline) ip. once in BALB/c mice, and endotoxin tolerance was induced by pretreatment with LPS (1 mg/kg in saline) injected i.p. daily for two consecutive days and then with LPS 10 mg/kg on day 4. Splenocytes or macrophages were obtained from endotoxemia and endotoxin tolerance models pretreated with indomethacin, and then cytokine production was induced by Con A-stimulated splenocytes for the Th cytokine assays and LPS-stimulated macrophages for the IL-6 assay. Our results showed that endotoxemia led to significantly reduced IL-2 and IL-4 production, to significantly increased IL-6 production, whereas interferon (IFN)-gamma production was not affected. Indomethacin in the case of endotoxemia markedly attenuated IFN-gamma and IL-6 production and didnt reverse IL-2 and IL-4 production. Endotoxin tolerance resulted in the significantly reduced production of IL-2 and IFN-gamma and the significantly increased production of IL-4 and IL-6. Indomethacin in endotoxin tolerance greatly augmented IL-2 production, significantly decreased IL-4 production, and slightly attenuated IL-6 production. These findings indicate that endogenous PGE2 may mediate the suppressed Th1 type immune response, with a shift toward a Th2 cytokine response in a state of endotoxin tolerance, whereas endotoxemia may be regulated differentially. Also, endogenous PGE2 may mediate macrophage IL-6 production in the case of endotoxemia to a greater extent than in the case of endotoxin tolerance.

Animals↗