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PubMed1987

Discriminative stimulus effects of caffeine: tolerance and cross-tolerance with methylphenidate.

Twice daily injection of caffeine (30 mg/kg) for 3-1/2 days shifted the caffeine stimulus generalization curve to the right by 3-fold in rats trained to discriminate saline from 30 mg/kg of caffeine, and by 4-fold in rats trained to discriminate saline from 10 mg/kg of caffeine. The latter group was also tested for cross-tolerance with methylphenidate, a drug that generalizes completely with caffeine. Twice daily injection of caffeine (30 mg/kg) for 3-1/2 days increased the ED50 of methylphenidate for caffeine-appropriate responding from 1.5 to 5.5 mg/kg. Conversely, injections of methylphenidate (3.0 mg/kg) increased the ED50 of caffeine from 5.2 to 15 mg/kg. The development of symmetrical cross-tolerance to the discriminative effects of caffeine and to the caffeine-like discriminative effects of methylphenidate supports previous observations suggesting commonalities in the cellular bases of the stimulus properties of these drugs.

Animals↗
PubMed1975

Effects of chronic administration of heroin on rats trained on two food reinforcement schedules.

The effects on behaviour and growth of rats given heroin s.c. every 8-hr, and during withdrawal (saline q.8.h.) were studied. Performance of rats trained on one food-reinforcement schedule (FR-10 or VI-10) was tested every day after one of the injections of saline or heroin. Doses of 0.25 mg/kg/injection heroin hydrochloride were increased stepwise to 32 mg/kg as "behavioural tolerance" developed. Threshold doses which blocked feeding in the first 30 min of testing ranged from 0.75 to 4.0 mg/kg and "tolerance" to 32 mg/kg/injection required from 18-71 + days. Heroin interrupted growth in heavier rats; lighter rats gained like saline-treated controls. Within 48 hr of withdrawal bar-pressing increased but all rats lost weight, were hyperirritable, and had diarrhoea. Thereafter, performance and body weight rose steadily. Administration of heroin at regular intervals over a prolonged period, and withdrawal from it, cause a disruption in behaviour comparable to that reported for morphine.

Animals↗
PubMed2003

Plasma-enhanced chemical vapor deposited silicon carbide as an implantable dielectric coating.

Amorphous silicon carbide (a-SiC) films, deposited by plasma-enhanced chemical vapor deposition (PECVD), have been evaluated as insulating coatings for implantable microelectrodes. The a-SiC was deposited on platinum or iridium wire for measurement of electrical leakage through the coating in phosphate-buffered saline (PBS, pH 7.4). Low leakage currents of <10(-11) A were observed over a +/-5-V bias. The electronic resistivity of a-SiC was 3 x 10(13) Omega-cm. Dissolution rates of a-SiC in PBS at 37 and 90 degrees C were determined from changes in infrared absorption band intensities and compared with those of silicon nitride formed by low-pressure chemical vapor deposition (LPCVD). Dissolution rates of LPCVD silicon nitride were 2 nm/h and 0.4 nm/day at 90 and 37 degrees C, respectively, while a-SiC had a dissolution rate of 0.1 nm/h at 90 degrees C and no measurable dissolution at 37 degrees C. Biocompatibility was assessed by implanting a-SiC-coated quartz discs in the subcutaneous space of the New Zealand White rabbit. Histological evaluation showed no chronic inflammatory response and capsule thickness was comparable to silicone or uncoated quartz controls. Amorphous SiC-coated microelectrodes were implanted in the parietal cortex for periods up to 150 days and the cortical response evaluated by histological evaluation of neuronal viability at the implant site. The a-SiC was more stable in physiological saline than LPCVD Si(3)N(4) and well tolerated in the cortex.

Animals↗
PubMed1981

Morphine, experimental pain, and psychological reactions.

This study examines the effects of morphine (10 mg/70 kg body weight) versus placebo (isotonic saline) on experimentally induced cold pressor pain threshold and tolerance, on self-reports of psychological states and drug effects, observer ratings of psychological states, and performance on timed cognitive-motor tasks in 20 non-drug using, normal male volunteers (21-28 years of age). Morphine increased both threshold and tolerance for cold pressor pain, and also increased "euphoric" and decreased "clear thinking" responses on the respective scales. Morphine, in contrast to placebo, increased scores on depression, fatigue, and cognitive loss-dysfunction scales and decreased scores on carefree and "friendliness" scales. Three sets of psychological variables were observed to covary significantly: Measures of anxiety and hostility; reports of fatigue and cognitive dysfunction; and reports of carefree feelings and perceptions of clear thinking. While measures of hostility, fatigue, and cognitive dysfunction covaried positively, reports of carefree feelings and perception of clear thinking covaried negatively with increased pain threshold and tolerance. Anxiety, contrary to reports in the literature, also covaried positively with the pain measures. The results were interpreted as supporting a relationship between increased arousal of the nervous system and decreased pain sensitivity in conjunction with the known analgesic effects of morphine.

Adult↗
PubMed2004

Halobacterium noricense sp. nov., an archaeal isolate from a bore core of an alpine Permian salt deposit, classification of Halobacterium sp. NRC-1 as a strain of H. salinarum and emended description of H. salinarum.

Two rod-shaped haloarchaeal strains, A1 and A2, were isolated from a bore core from a salt mine in Austria. The deposition of the salt is thought to have occurred during the Permian period (225-280 million years ago). The 16S rDNA sequences of the strains were 97.1% similar to that of the type species of the genus Halobacterium, which was also determined in this work. Polar lipids consisted of C20-C20 derivatives of phosphatidylglycerol, methylated phosphatidylglycerol phosphate, phosphatidylglycerol sulfate, triglycosyl diether and sulfated tetraglycosyl diether. Optimal salinity for growth was 15-17.5% NaCl; Mg++ was tolerated up to a concentration of 1 M. The DNA-DNA reassociation value of strain A1T was 25% with H. salinarum DSM 3754T and 41% with Halobacterium sp. NRC-1, respectively. Based on these results and other properties, e.g. whole cell protein patterns, menaquinone content and restriction patterns of DNA, strains A1 and A2 are members of a single species, for which we propose the name H. noricense. The type strain is A1 (DSM 15987T, ATCC BAA-852T, NCIMB 13967T). Since we present evidence that Halobacterium sp. NRC-1 is a member of H. salinarum, an emended description of H. salinarum is provided.

Archaeal Proteins↗
PubMed2006

Evaluation of methods for the isolation, detection and quantification of cyanobacterial hepatotoxins.

Cyanobacterial hepatotoxins such as microcystins and nodularins have been responsible for the poisoning of both animals and humans who ingest or come into contact with toxic blooms. They are extremely stable in water due to their stable chemical structure and can tolerate radical changes in water chemistry, including pH and salinity. Different methods for the extraction and detection of these compounds have been reported. Extraction methods utilizing both aqueous and organic solvent systems have been reported. The detection methods ranging from immunological or biochemical assays such as enzyme linked immunosorbent assays (ELISA) and enzyme activity assays, to chemicals methods such as high performance liquid chromatography (HPLC) and more sophisticated liquid chromatography-mass spectrometry (LC-MS) have been documented as well. We review some important aspects of cyanobacterial hepatotoxins and methods of analysis for these toxins.

Animals↗
PubMed2005

Acute and chronic continuous methamphetamine have different long-term behavioral and neurochemical consequences.

We compared two different methamphetamine dosing regimens and found distinct long-term behavioral and neurochemical changes. Adult rats were treated with 1-day methamphetamine injection (3x5 mg/kg s.c., 3 h apart) or 7-day methamphetamine minipump (20 mg/kg/day s.c.). The minipump regimen models the sustained methamphetamine plasma levels in some human bingers whereas the 1-day regimen models a naive user overdose. On withdrawal days 7 and 28, rats were acutely challenged with cocaine to test for behavioral sensitization and subsequently sacrificed for caudate and accumbens dopamine tissue content. Other rats were analyzed on withdrawal days 3, 7 or 28 using voltammetry in caudate slices. On withdrawal days 7 and 28, the methamphetamine injection but not the minipump rats showed behavioral cross-sensitization to cocaine. There was no change in baseline dopamine release, reuptake or sensitivity to quinpirole in any treatment group on either withdrawal day. However, consistent with the behavioral sensitization, cocaine had a greater effect in potentiating dopamine release and in blocking dopamine reuptake in methamphetamine injection versus saline irrespective of withdrawal day. The minipump group showed tolerance to the dopamine releasing effect of cocaine on withdrawal day 28 and had lower dopamine tissue content in the caudate versus the methamphetamine injection group. Dopamine turnover as measured by the DOPAC/dopamine ratio tended to be higher in the minipump-treated rats. These data suggest that the behavioral cross-sensitization seen in the methamphetamine injection rats could be in part due to the increased potency of cocaine in blocking dopamine reuptake and in increasing dopamine release. The decreased potency of cocaine in the caudate slices from the minipump-treated group may be related to decreased dopamine tissue content.

Animals↗
PubMed1996

Comparison of saline infusion sonography with office hysteroscopy for the evaluation of the endometrium.

OBJECTIVE: Intrauterine infusion of saline solution during transvaginal ultrasonography enhances visualization of the endometrium. We compared the accuracy and pain rating of saline infusion sonography with those of flexible office hysteroscopy. STUDY DESIGN: The uterine cavities of 130 patients with abnormal bleeding were evaluated by two physicians in an office setting. Findings of endometrial polyps, submucous myomas, synechiae, endometrial hyperplasia, or cancer were recorded independently and subsequently compared. Patients rated their pain after each procedure. RESULTS: Both procedures were performed in 113 of 130 patients. With saline infusion sonography pathologic findings were identified in 61 patients (54%). For all findings combined, sensitivity was 0.96 and specificity was 0.88, compared with hysteroscopy. The results of saline infusion sonography and hysteroscopy did not differ significantly (p = 0.18). The former was less painful for patients than hysteroscopy (p < 0.0001). CONCLUSION: Saline infusion sonography is an accurate and well-tolerated method to evaluate abnormal uterine bleeding, compared with hysteroscopy.

Adult↗
PubMed2002

Managing selenium-contaminated agricultural drainage water by the integrated on-farm drainage management system: role of selenium volatilization.

The Integrated on-Farm Drainage Management (IFDM) system was designed to dispose of selenium (Se)-contaminated agricultural irrigation drainage water through the sequential reuse of saline drainage water to grow crops having different salt tolerance. This study quantified the extent of biological volatilization in Se removal from the IFDM system located in the western San Joaquin Valley, California. Selenium volatilization from selected treatment areas, including pickleweed (Salicornia bigelovii Torr.), saltgrass (Distichlis spicata L.), bare soil, and the solar evaporator, was monitored biweekly using an open-flow sampling chamber system during the pickleweed growing season from February to September 1997, and monthly from September 1997 to January 1998. Biological volatilization from the pickleweed section removed 62.0 +/- 3.6 mg Se m(-2) y(-1) to the atmosphere, which was 5.5-fold greater than the Se accumulated in pickleweed tissues (i.e., phytoextraction). The total Se removed by volatilization from the bare soil, saltgrass, and the solar evaporator was 16.7 +/- 1.1, 4.8 +/- 0.3, and 4.3 +/- 0.9mg Se m(-2) y(-1), respectively. Selenium removal by volatilization accounted for 6.5% of the annual total Se input (957.7mg Sem(-2) y(-1)) in the pickleweed field, and about 1% of the total Se input (432.7 mg Se m(-2) y(-1)) in the solar evaporator. We concluded that Se volatilization under naturally occurring field conditions represented a relatively minor, but environmentally important pathway of Se removal from the IFDM system.

Agriculture↗
PubMed1997

Pain and synovial fluid concentration of serotonin in arthritic temporomandibular joints.

The aim of this study was to investigate the relation between serotonin in the synovial fluid (SF-5-HT) and pain of arthritic temporomandibular joints (TMJ). The study comprised 1 male and 10 female patients (22 TM joints) with bilateral TMJ pain or tenderness and a mean age of 42 years. The patients were studied regarding pain from the TMJ at rest and during mandibular movements as well as regarding pressure pain thresholds and tolerance levels over the TMJ. TMJ samples, obtained by saline washing of the joint, and blood serum samples were taken for measurement of the 5-HT content. There was a positive correlation between SF-5-HT and pain in the TMJ upon movement. Maximum voluntary mouth opening ability was negatively correlated to SF-5-HT. In conclusion, the results of this study indicate that 5-HT in the TMJ synovial fluid is related to pain perceived upon movement of the joint and to decreased mandibular mobility.

Adult↗
PubMed1994

The crystal structure of citrate synthase from the thermophilic archaeon, Thermoplasma acidophilum.

BACKGROUND: The Archaea constitute a phylogenetically distinct, evolutionary domain and comprise organisms that live under environmental extremes of temperature, salinity and/or anaerobicity. Different members of the thermophilic Archaea tolerate temperatures in the range 55-110 degrees C, and the comparison of the structures of their enzymes with the structurally homogolous enzymes of mesophilic organisms (optimum growth temperature range 15-45 degrees C) may provide important information on the structural basis of protein thermostability. We have chosen citrate synthase, the first enzyme of the citric acid cycle, as a model enzyme for such studies. RESULTS: We have determined the crystal structure of Thermoplasma acidophilum citrate synthase to 2.5 A and have compared it with the citrate synthase from pig heart, with which it shares a high degree of structural homology, but little sequence identity (20%). CONCLUSIONS: The three-dimensional structural comparison of thermophilic and mesophilic citrate synthases has permitted catalytic and substrate-binding residues to be tentatively assigned in the archaeal, thermophilic enzyme, and has identified structural features that may be responsible for its thermostability.

Amino Acid Sequence↗
PubMed1997

A phase I feasibility and pharmacokinetic study of intrapleural paclitaxel in patients with malignant pleural effusions.

To evaluate the feasibility and pharmacology of intrapleural (IP(L)) administration of paclitaxel, 18 patients with malignant pleural effusions were entered onto a phase I clinical study, 13 were caused by lung cancer. Following an effusion drainage rate of less than 100 ml/24 h and full expansion of the lung, patients were treated with a single instillation of pacilitaxel administered IP(L) in 500 ml of normal saline and retained for a maximum of 96h when tolerated. No systemic chemotherapy or ipsilateral thoracic irradiation was given for 4 weeks before and after the IP(L) treatment. The starting dose was 82.5 mg/m2 with the dose escalation schedule of 125, 175, 225 and 300 mg/m2. There were minimal local or systemic toxicities, such as local chest pain or myelosuppression, even when the paclitaxel dose reached 225 mg/m2. The pharmacological advantages of the IP(L) administration of paclitaxel were demonstrated by the mean exposure of the pleural cavity (area under the concentration time curve) to paclitaxel after IP(L) delivery exceeding that of the plasma by approximately 370-fold (range 55-684) and by the extraordinarily slow IP(L) clearance of paclitaxel (mean +/- SE 0.49 +/- 0.07 l/m2/day; range 0.08-1.16 l/m2/day) with significant concentrations of paclitaxel persisting within the cavity for more than 48-96 h after a single IP(L) instillation. In patients with detectable plasma paclitaxel levels, the plasma levels achieved exceed the minimal concentrations that are required to induce cytotoxic effects in vitro. Four patients had progressive dyspnea during IP(L) retention of paclitaxel solution because of treatment failure and needed drainage of effusion. One of these patients who was at the dose level of 225 mg/m2 originally had severely chronic obstructive lung disease, developed acute respiratory failure, refused mechanical ventilation support and succumbed to respiratory failure. No further patients were included after this event. Antitumor effect was shown by four of the 15 evaluable patients having no recurrence of effusion on chest radiograph at 1 month. Most of these responders had a good performance status, normal pretreatment pleural pH and/or glucose compared with the non-responders. We conclude that paclitaxel at a dose level of 175 or 225 mg/m2 is feasible for use intrapleurally. It could be considered for incorporation into treatment programs for patients with less advanced thoracic tumors with carcinomatous pleuritis or with IP(L) tumors following surgical debulking.

Adenocarcinoma↗
PubMed1978

Mannitol osmolar clearance in diabetes insipidus of children.

A modified technique of amnnitol-induced diuresis is described, in order to assess renal concentrating ability in infants and children. The infusion of 10% mannitol in 0.9% saline avoided the hypertonic saline overload and the fluid restriction period, both badly tolerated by infants and small children. In a control group of children aged from two months to seven years, the values of T(H2O) plotted against C(OSM) allowed to calculate the adjustment curve y=0.80x0.75, r=0.98 (p is less than 0.0001). In six patients with pituitary diabetes insipidus (PDI), the test was used in order to quantify the degree of ADH deficiency and evaluate the carbamazepine and clofibrate effect, in the renal concentrating mechanism. The test was tolerated perfectly in every case, obtaining qualitative and quantitative data and avoiding the hyponatremia and hypokalemia produced by the mannitol.

Carbamazepine↗
PubMed1975

Sensitivity changes to morphine and other drugs induced by cholinergic blockade.

Mice were given several atropine injections at a high dosage level. After 2 to 5 days of cessation of treatment the effects of morphine, arecoline, amphetamine, pentylenetetrazol, reserpine, and hexobarbital were determined and compared with those found in saline injected controls. The influence of atropine treatment on tolerance development to morphine was also studied. After withdrawal of atropine a reduction of the analgesic responses to morphine and arecoline was observed. A decrease in hexobarbital sleeping time was also found. There was no significant influence on the analgesic effect of amphetamine, on the depressant action of reserpine, and on the convulsant effect of pentylenetetrazol. The influence of the administration and further withdrawal of atropine on tolerance development to morphine was masked by the concomitant reduction of morphine analgesia. It was impossible to observe a supersensitivity to the pharmacological agents studied.

Amphetamine↗
PubMed2004

Nitrogenase and antioxidant enzyme activities in Phaseolus vulgaris nodules formed by Rhizobium tropici isogenic strains with varying tolerance to salt stress.

Common bean plants inoculated with salt-tolerant Rhizobium tropici wild-type strain CIAT899 formed a more active symbiosis than did its decreased salt-tolerance (DST) mutant derivatives (HB8, HB10, HB12 and HB13). The mutants formed partially effective (HB10, HB12) or almost ineffective (HB8, HB13) nodules (Fix(d)) under non-saline conditions. The DST mutant formed nodules that accumulated more proline than did the wild-type nodules, while soluble sugars were accumulated mainly in ineffective nodules. Under salt stress, plant growth, nitrogen fixation, and the activities of the antioxidant defense enzymes of nodules were affected in all symbioses tested. Overall, mutant nodules showed lower antioxidant enzyme activities than wild-type nodules. Levels of nodule catalase appeared to correlate with symbiotic nitrogen-fixing efficiency. Superoxide dismutase and dehydroascorbate reductase seem to function in the molecular mechanisms underlying the tolerance of nodules to salinity.

Antioxidants↗
PubMed2004

Insulin infusion induces endothelin-1-dependent hypertension in rats.

We previously showed that chronic insulin infusion induces insulin resistance, hyperendothelinemia, and hypertension in rats (C. C. Juan, V. S. Fang, C. F. Kwok, J. C. Perng, Y. C. Chou, and L. T. Ho. Metabolism 48: 465-471, 1999). Endothelin-1 (ET-1), a potent vasoconstrictor, is suggested to play an important role in maintaining vascular tone and regulating blood pressure, and insulin increases ET-1 production in vivo and in vitro. In the present study, BQ-610, a selective endothelin A receptor antagonist, was used to examine the role of ET-1 in insulin-induced hypertension in rats. BQ-610 (0.7 mg/ml; 0.5 ml/kg body wt) or normal saline was given intraperitoneally two times daily for 25 days to groups of rats infused with either saline or insulin (2 U/day via sc-implanted osmotic pumps), and changes in plasma levels of insulin, glucose, and ET-1 and the systolic blood pressure were measured over the experimental period, whereas changes in insulin sensitivity were examined at the end of the experimental period. Plasma insulin and ET-1 levels were measured by RIA, plasma glucose levels using a glucose analyzer, systolic blood pressure by the tail-cuff method, and insulin sensitivity by an oral glucose tolerance test. Our studies showed that insulin infusion caused sustained hyperinsulinemia in both saline- and BQ-610-injected rats over the infusion period. After pump implantation (2 wk), the systolic blood pressure was significantly higher in insulin-infused rats than in saline-infused rats in the saline-injected group (133 +/- 3.1 vs. 113 +/- 1.1 mmHg, P < 0.05) but not in the BQ-610-injected group (117 +/- 1.2 vs. 117 +/- 1.8 mmHg). Plasma ET-1 levels in both sets of insulin-infused rats were higher than in saline-infused controls (2.5 +/- 0.6 and 2.5 +/- 0.8 vs. 1.8 +/- 0.4 and 1.7 +/- 0.3 pmol/l, P < 0.05). Oral glucose tolerance tests showed that BQ-610 treatment did not prevent the insulin resistance caused by chronic insulin infusion. No significant changes were found in insulin sensitivity and blood pressure in saline-infused rats treated with BQ-610. In a separate experiment, insulin infusion induced the increase in arterial ET-1 content, hypertension, and subsequent plasma ET-1 elevation in rats. These results suggest that, in the insulin infusion rat model, ET-1 plays a mediating role in the development of hypertension, but not of insulin resistance.

Animals↗
PubMed1999

Tolerance to shock: an exploration of mechanism.

OBJECTIVE: To determine if cross-tolerance to septic shock could be induced by a previous insult with sublethal hemorrhage (SLH) and to characterize the mechanisms involved in this induced protective response. BACKGROUND DATA: It is possible to condition animals by prior SLH such that they tolerate an otherwise lethal hemorrhage. It is also possible to condition animals with low doses of lipopolysaccharide (LPS) so that they survive a "lethal" septic insult. However, a paucity of information exists on cross-tolerance between hemorrhage and sepsis. METHODS: Rats were made tolerant by conditioning SLH or sham operation. Twenty-four hours later, tolerant and sham rats were exposed to a lethal dose of LPS. To explore the mechanism of tolerance induction, rats were given the macrophage (Mphi) inhibitor CNI-1493 or saline carrier before SLH. Survival and pulmonary vascular injury were determined after LPS. Serum tumor necrosis factor (TNF) levels and splenic Mphi TNF gene expression were measured at several time points. RESULTS: Prior SLH indeed made rats tolerant and imparted a significant survival benefit and reduction in pulmonary vascular injury after LPS. The tolerance induced by SLH was reversed by Mphi inhibition. Tolerant animals had low serum TNF levels immediately after SLH and reduced circulating TNF levels after LPS. SLH, however, did not inhibit the augmentation of TNF gene expression after LPS. CONCLUSIONS: Sublethal hemorrhage bestows protection against a lethal LPS challenge. Inhibition of the Mphi attenuated the benefit of the tolerance induced by SLH. Circulating TNF but not TNF gene after LPS is lessened by SLH. This implicates changes in Mphi intracellular signaling in induction of the tolerant state.

Animals↗
PubMed1978

Effect of High Cation Concentrations on Photosystem II Activities.

The effects of wide concentration ranges of NaCl, KCl, and MgCl(2) on ferricyanide reduction and the fluorescence induction curve of isolated spinach (Spinacia oleracea) chloroplasts were investigated. Concentrations of the monovalent salts above 100 mm and MgCl(2) above 25 mm produced a decrease in the rate of ferricyanide reduction by thylakoids uncoupled with 2.5 mm NH(4)Cl which cannot be attributed to changes in the primary photochemical capacity of photosystem II. Salt-induced decreases in the effective concentration of the secondary electron acceptor of photosystem II, plastoquinone, reduce the capacity for secondary photochemistry of photosystem II and this could contribute to the reduction in ferricyanide reduction by uncoupled thylakoids at high salinities. The rate of ferricyanide reduction by coupled thylakoids is little affected by salinity changes, indicating that the rate-limiting phosphorylation mechanism in electron flow from water to ferricyanide in coupled thylakoids is salt-tolerant, whereas the rate-limiting reaction in uncoupled ferricyanide reduction is considerably affected by salinity changes. Salt-induced changes in the fluorescence induction curve are interpreted in terms of changes in the rate constants for excitation decay by radiationless transitions, exciton transfer from photosystem II chlorophylls to other associated chlorophyll species, and photochemistry.

Journal Article↗