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PubMed2005

Nasal rinsing with hypertonic solution: an adjunctive treatment for pediatric seasonal allergic rhinoconjunctivitis.

BACKGROUND: Recent but limited evidence suggests that nasal lavage with hypertonic saline may be useful as an adjunctive treatment modality in the management of pediatric allergic rhinitis. The aim of this study was to clarify whether nasal irrigation with hypertonic solution should be routinely recommended to children with seasonal grass pollen rhinoconjunctivitis. METHODS: Fourty-four children with seasonal grass pollen rhinoconjunctivitis were recruited. Twenty-two patients were randomized to receive three-times daily nasal rinsing with hypertonic saline during the pollen season, which lasted 7 weeks. Twenty-two patients were allocated to receive no nasal irrigation and were used as controls. Twenty patients per group completed the study. A mean daily rhinoconjunctivitis score based on the presence of nasal discharge and obstruction as well as ocular symptoms as reddening and itching were calculated for each week of the pollen season. Patients were allowed to use oral antihistamines when required and the mean number of drugs taken per week was also calculated. RESULTS: The mean weekly rhinoconjunctivitis score in the active group was reduced during the whole pollen period. This difference was statistically significant in week 6 and 7 of therapy. A markedly reduced intake of oral antihistamines was also observed in patients allocated to nasal rinsing, being statistically significant in 5 of the 7 weeks. No adverse effect was reported in the active group. CONCLUSIONS: This study supports the use of nasal rinsing with hypertonic saline in the pediatric patient with seasonal allergic rhinoconjunctivitis. This treatment proved to be tolerable, inexpensive and effective.

Adolescent↗
PubMed1994

Computer simulation of the effect of dDAVP with saline loading on fluid balance after 24-hour head-down tilt.

Fluid loading (FL) before Shuttle reentry is a countermeasure currently in use by NASA to improve the orthostatic tolerance of astronauts during reentry and postflight. The fluid load consists of water and salt tablets equivalent to 32 oz (946 ml) of isotonic saline. However, the effectiveness of this countermeasure has been observed to decrease with the duration of spaceflight. The countermeasure's effectiveness may be improved by enhancing fluid retention using analogs of vasopressin such as lypressin (LVP) and desmopressin (dDAVP). In a computer simulation study reported previously, we attempted to assess the improvement in fluid retention obtained by the use of LVP administered before FL. The present study is concerned with the use of dDAVP. In a recent 24-hour, 6 degree head-down tilt (HDT) study involving seven men, dDAVP was found to improve orthostatic tolerance as assessed by both lower body negative pressure (LBNP) and stand tests. The treatment restored Luft's cumulative stress index (cumulative product of magnitude and duration of LBNP) to nearly pre-bedrest level. The heart rate was lower and stroke volume was marginally higher at the same LBNP levels with administration of dDAVP compared to placebo. Lower heart rates were also observed with dDAVP during stand test, despite the lower level of cardiovascular stress. These improvements were seen with only a small but significant increase in plasma volume of approximately 3 percent. This paper presents a computer simulation analysis of some of the results of this HDT study.

Computer Simulation↗
PubMed2003

A new animal model for testing renal tolerance of contrast agents.

RATIONALE AND OBJECTIVES: To develop a new animal model for the evaluation of the renal tolerance of contrast agent and its application to diatrizoate and iotrolan injections in comparison to saline and mannitol solution. MATERIALS AND METHODS: The nephrotoxic potential of intravenously injected contrast agents in Beagle dogs was determined from the effects on the pharmacokinetics of creatinine injected immediately after these agents in comparison with the kinetics of creatinine injected alone. The kinetic parameters evaluated included plasma half-life, volume of distribution, and clearance. In a series of studies, the experimental conditions were optimized in terms of creatinine dose and the effects of diatrizoate, iotrolan, saline, and mannitol solution on the pharmacokinetic parameters of creatinine were determined. RESULTS: Bolus injection of creatinine into dogs followed a dose-linear pharmacokinetic behavior with a terminal half-life of 90 minutes (10 mg/kg) and 108 minutes (20 mg/kg), respectively, and a clearance of 5 mL/min/kg. Injection of diatrizoate decreased the clearance and the half-life of creatinine significantly. A mannitol solution with the same osmolality as diatrizoate showed the same effect whereas physiological saline did not affect pharmacokinetic parameters of creatinine. The isotonic iotrolan was intermediate between saline and diatrizoate in its effects on creatinine clearance. CONCLUSION: The effect of contrast agents on pharmacokinetic parameters of creatinine injected immediately after the administration of the agents in dogs might be a useful model for the evaluation of renal tolerance. In a cross-over study, iotrolan was not statistically separable from diatrizoate.

Animals↗
PubMed1984

Role of spinal mu opioid receptors in the development of morphine tolerance and dependence.

We previously demonstrated that the spinal cord is a primary site for the development of morphine-induced tolerance and dependence. In the current investigation, we have determined the significance of mu opioid receptors in the spinal cord in tolerance and dependence induced by systemically administered morphine. Rats surgically implanted with intrathecal (i.t.) catheters were injected i.t. with various doses of beta-funaltrexamine (beta-FNA), a specific irreversible mu opioid receptor antagonist. beta-FNA (i.t.) dose-dependently antagonized morphine-induced analgesia (i.p.) with approximately one-half the potency of beta-chlornaltrexamine, a nonselective irreversible opioid receptor antagonist. Rats injected with saline i.t. 24 h before implanting morphine pellets developed a significant degree of tolerance and dependence 72 h after morphine administration. Tolerance did not develop in similarly treated animals that received i.t. injections of 4.5 nmol beta-FNA. Signs of naloxone-precipitated withdrawal were also significantly antagonized in all instances, except weight loss, in animals pretreated with beta-FNA (i.t.). We conclude that i.t. injections of beta-FNA significantly antagonized the development of tolerance and dependence induced by systemically administered morphine. Therefore, our results indicate that mu opioid receptors within the spinal cord, and probably throughout the central nervous system, play a primary role in morphine-induced tolerance and dependence.

Analgesia↗
PubMed1975

The duration of tolerance to the anorexigenic effect of amphetamine in rats.

Rats were given dl-amphetamine 16 mg/kg twice daily for 15 days. Complete tolerance to the anorexigenic effect of amphetamine developed from day 7--11. A single injection of 16 mg/kg amphetamine was given to the amphetamine pretreated rats and to saline pretreated controls at different time-points after withdrawal, and their food intakes were compared. Signs of tolerance were present in 16 but not 20 days after withdrawal.

Amphetamine↗
PubMed1995

Environmental physiology of the mole crab Emerita asiatica, at a power plant discharge area on the east coast of India.

Cage experiments at the discharge area of Madras Atomic Power Station (MAPS) facilitated studies of thermal tolerance in Emerita asiatica. At the laboratory, oxygen consumption at various temperatures and varying salinities was also investigated. In the field 100% mortality of crabs was recorded at the Condenser Cooling Water Pumps (CCWP) discharge site compared to no mortality at the Processed Sea Water Pumps (PSWP) site. This observation implicated temperature as a stress factor at the CCWP outfall, because other factors, including residual chlorine and water velocity, were the same at the PSWP and CCWP sites. Laboratory experiments on tolerance revealed that 38.5 degrees C was lethal to mole crabs. The time taken for 100% mortality decreased as the temperature increased from 35 to 40 degrees C. Oxygen metabolism showed a progressive increase with temperature from 29 to 36 degrees C, and declined at 37 degrees C. The influence of salinity on oxygen consumption was marginal at salinities of 20 to 35 per thousand but, when reduced to 15 per thousand, the oxygen consumption declined. The present study thus indicates that temperature could be the lethal factor, determining the distribution of mole crabs near the power station, where water temperature can exceed 40 degrees C.

Journal Article↗
PubMed1975

Adjuvant effect on maintenance and escape from tolerence.

When mice are injected with deaggregated human gamma globulin (HGG), and HGG-tolerant state ordinarily is produced and persists despite subsequent challenges with an immunizing dose of HGG in saline or with an immunizing dose of HGG in Mycobacterium adjuvant. Subsequent administration of an immune elimination dose of radiolabeled HGG, at 27 days and 47 days does not break the tolerant state. Of special interest is the observation that when complete adjuvant containing increasing amounts of mycobacterial components was administered in conjunction with antigen very early in the tolerance induction phase 5 days after TID, it appears to prevent tolerance production. Mice challenged 5 and 17 days after the tolerance-inducing inoculation exhibit a statistically significant increase in circumvention of tolerance when compared with individuals challenged on the 7 and 17 day schedule. This increased circumvention of tolerance, as evidenced by 5 day challenge mice, seems to be related both to the mycobacterial content of the adjuvant and murine strain.

Animals↗
PubMed2005

Nontoxic suramin treatments enhance docetaxel activity in chemotherapy-pretreated non-small cell lung xenograft tumors.

PURPOSE: We reported that nontoxic suramin treatments enhance the activity of chemotherapy in preclinical models, a finding supported by the results of subsequent phase I/II trials in chemotherapy-naive non-small cell lung cancer (NSCLC) patients who received/carboplatin (P/C) combination therapy. The present study evaluated whether suramin enhances the activity of docetaxel in human NSCLC xenografts. METHODS: The in vitro effect of suramin on docetaxel activity was evaluated using 3-D histocultures of chemotherapy-naive A549 tumors. For in vivo activity evaluation, we first established the P/C pretreatment schedule that produced tumor growth inhibition, but not tumor eradication, and established the maximally tolerated docetaxel/suramin regimens. In the second study, P/C-treated animals received physiological saline, single-agent suramin (10 mg/kg), docetaxel (10 mg/kg), or the combination twice weekly for 3 weeks. RESULTS: The in vitro results showed that 20 microM suramin, which had no activity as single agent, enhanced the docetaxel activity (measured as 50% inhibition of DNA synthesis) by more than 10-fold. The in vivo studies showed reduced tumor growth by P/C (30% growth in 14 days vs. 75% in control). In contrast, docetaxel produced tumor regression (15% reduction) in P/C-treated animals, significantly reduced, on a cellular level, the viable cell density and the proliferating fraction (40% reduction for both measurements), and enhanced the apoptotic fraction 4-fold (p < 0.05 for all effects). Suramin had no activity or toxicity (measured as body weight loss) but significantly enhanced the docetaxel activity. Compared to docetaxel alone, the combination showed earlier onset of tumor size reduction, greater extent of tumor regression (31 vs. 15%), greater reduction of viable cell density and proliferating fraction (additional 15-25% reduction), and greater apoptotic fraction (additional 2.5-fold increase) (p < 0.05 for all parameters). CONCLUSIONS: Results of the present study indicate that nontoxic suramin treatments enhanced the activity of docetaxel in P/C-pretreated A549 xenograft tumors in mice without enhancing host toxicity. These encouraging results provided the basis for phase I/II trials of docetaxel plus low-dose suramin in patients with NSCLC in second-/third-line settings.

Animals↗
PubMed1993

A method for third ventricular cannulation of small passerine birds.

This paper describes a method for chronically cannulating the third ventricle of the white-crowned sparrow, a small passerine bird, without damaging the midsagittal sinus. The method is reliable and chronic over at least 1 month. The technique was verified by assessing the effects of angiotensin II (ANG II) on inducing drinking behavior. All birds rapidly recovered from the surgery and tolerated repeated injections spaced over 1 month. Animals were injected with saline or 0.01, 0.5, 1.0, and 10.0 micrograms of ANG II, respectively. The intermediate dose of 1.0 microgram was maximally effective and caused a significant increase of water intake over the test hour. Lower and higher doses were less effective. This method for cannulating the third ventricle of small passerine birds should prove beneficial in future neurobiological applications.

Angiotensin II↗
PubMed1981

The effect of hematin on the development of microsomal enzyme induction and physical dependence in mice following repeated oral propoxyphene administration.

Male ICR mice (25 - 30 g) were pretreated with bovine hematin (20, 40 or 50 mumoles per kg per day, i.p.) for three days. During the next six-day period, animals received either 50 mg per kg per day propoxyphene-HCl or saline, p.o., in addition to the daily hematin injections. Only the highest hematin regimen depressed the induction of propoxyphene-N-demethylase activity significantly in the drug-treated animals. A similar depression below control levels was noted in the animals receiving only saline (p.o.) and hematin (i.p.). While hematin treatment abolished the metabolic tolerance to propoxyphene analgesia such treatment failed to generate any appreciable degree of physical dependence to propoxyphene as assessed by a challenge with naloxone. These findings may be helpful in assessing the risk factors associated with the widespread use of propoxyphene.

Analgesia↗
PubMed2004

Malaria vectors in the changing environment of the southern Punjab, Pakistan.

The Pakistani Punjab experienced several devastating malaria epidemics during the twentieth century. Since the 1980s, however, malaria has been at a low ebb, while in other areas of Pakistan and neighbouring India malaria is on the increase. This raises the question of whether transmission in the Pakistani Punjab may have been influenced by a change in vector species abundance or composition, possibly induced by environmental changes. To investigate this question, routinely-collected government entomological data for the period 1970 to 1999 for the district of Bahawalnagar, in the Indus Basin irrigation system in the southern Punjab, was analysed. Our findings suggest that Anopheles stephensi has increased in prevalence and became more common than A. culicifacies during the 1980s. This shift in species dominance may be due to the large-scale ecological changes that have taken place in the Punjab, where irrigation-induced waterlogging of soil with related salinization has created an environment favourable for the more salt-tolerant A. stephensi. Some biotypes of A. stephensi are suspected of being less efficient vectors and, therefore, the shift in species dominance might have played a role in the reduced transmission in the Punjab, although further research is needed to investigate the effect of other transmission-influencing factors.

Animals↗
PubMed2001

Lipopolysaccharide-induced ischemic tolerance is associated with increased levels of ceramide in brain and in plasma.

Intravenous administration of lipopolysaccharide (LPS) (0.9 mg/kg) has been shown to induce ischemic tolerance in spontaneously hypertensive rats (SHR). TNF-alpha is believed to play a crucial role in preconditioning as its inhibition with TNF-alpha-binding protein abolished tolerance. Our recent studies (Liu et al., Am. J. Physiol. 278 C144, 2000) have demonstrated that ceramide, a downstream messenger in TNF-alpha signaling, is a mediator of hypoxia-induced tolerance in neuronal cells. To test the hypothesis that ceramide contributes to LPS-induced tolerance in vivo, SHR were injected intravenously with either LPS or saline and the levels of ceramide in brain and in plasma were determined by reversed phase HPLC. LPS injection resulted in a significant increase of ceramide in plasma with a maximum at 24 h (8.32+/-1.14 pmol/microl (LPS) vs. 2.65+/-0.62 pmol/microl (saline)). LPS also induced ceramide upregulation in brain cortex, which started between 6 and 12 h and remained elevated up to 48 h after LPS injection. Fluorescent NBD-C6 ceramide was able to cross blood-brain barrier and was found in brain vessels, perivascular cells and in brain parenchyma 30 min after intravenous injection. These findings demonstrate that LPS preconditioning leads to elevation of ceramide in brain and plasma and, in conjunction with previous work, suggests that ceramide plays a role in LPS-induced protection against brain ischemic injury in vivo.

4-Chloro-7-nitrobenzofurazan↗
PubMed1998

Comparative study of enzymes related to proline metabolism in tepary bean (Phaseolus acutifolius) and common bean (Phaseolus vulgaris) under drought and irrigated conditions, and various urea concentrations.

There are several mechanisms used by plants for survival in adverse environments such as drought, high temperature and salinity. The objective of this study was to evaluate the drought tolerance of tepary bean as a function of biochemical processes linked to isozyme synthesis and changes in enzymatic activity related to proline metabolism. Mature seeds of common beans var. flor de mayo, Phoseolus vulgaris and tepary beans Phaseolus acutifolius were grown under two water conditions (irrigation and drought), and four levels of urea. Vertical electrophoresis and spectrophotometric techniques were used to evaluate protein patterns, glutamate dehydrogenase (GDH), proline oxidase (PO) and pyrroline-5-carboxylate reductase (P5C reductase) enzyme activities. These enzymes were studied because they are directly related to protein synthesis. Electrophoretic patterns showed more proteins in tepary beans than in common beans with limited irrigation. GDH showed only one isozyme, with a molecular weight between 240) to 270 kDa. A decrease in PO activity was observed in common beans under drought stress with a value of 237 micromol/min, in comparison to irrigation conditions of 580 micromol/min. GDH and P5C reductase enzymes have had higher activity in common beans than in tepary beans under water stress. There was a significant difference only in glutamate dehydrogenase enzyme with respect to urea level. The results suggest that drought tolerance of tepary beans is due to biochemical processes related to proline metabolic enzymes.

1-Pyrroline-5-Carboxylate Dehydrogenase↗
PubMed1997

Is an alkalinized lignocaine solution a better topical anaesthetic for intratracheal application?

Topical anaesthesia of the trachea is used to avoid coughing during emergence from anaesthesia. This study was designed to compare the effects of an alkalinized lignocaine and plain lignocaine solution given intratracheally. After institutional approval and written informed consent, 30 patients were randomized into three groups and received in a double-blind fashion: lignocaine, alkalinized lignocaine and normal saline for control. After application of normal or alkalinized lignocaine the tolerance to the tube was significantly better during extubation (P = 0.001). Noradrenaline levels were significantly diminished in the lignocaine groups (P < 0.05). Plain and alkalinized lignocaine solutions for topical anaesthesia significantly improved tolerance to the tracheal tube during emergence from anaesthesia. Plain and alkalinized lignocaine given directly before intubation reduced the sympathomimetic stress response resulting in a lower noradrenaline concentration and a reduced heart rate.

Adolescent↗
PubMed2001

Efficacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis. ORTHOVISC Study Group.

A prospective, multicenter, randomized, double-blind, controlled trial was conducted in 226 patients with knee osteoarthritis to evaluate the safety and efficacy of intraarticular injections of sodium hyaluronate. Patients were randomized to three weekly injections of 30 mg sodium hyaluronate or physiologic saline (control) and were observed for an additional 25 weeks. In comparison with the control group, among patients who completed at least 15 weeks of the study and whose Western Ontario and McMaster Universities Osteoarthritis Index pain score for the contralateral knee was less than 12 at baseline, sodium hyaluronate injection resulted in improvement in Western Ontario and McMaster Universities Osteoarthritis Index pain score, patient and investigator global assessments, and pain on standing from Weeks 7 to 27. Fifty-eight percent of patients treated with sodium hyaluronate achieved a 5-unit or greater improvement in mean pain score from Weeks 7 through 27, compared with 40% of control patients. In addition, nearly twice as many patients treated with sodium hyaluronate as with saline (30% versus 17%, respectively) achieved a net improvement of at least 7 units. In contrast to treatment with saline, Western Ontario and McMaster Universities Osteoarthritis Index pain score for the contralateral knee was inversely related to the magnitude of improvement after treatment with sodium hyaluronate. Few side effects were attributed to treatment, and no differences between treatment groups were seen in this respect (sodium hyaluronate, nine [8%]; saline, 11 [10%]). The incidence of injection site reactions was low (sodium hyaluronate, 1.2 %; saline, 1.5%). The results indicate that sodium hyaluronate treatment is well tolerated and produces statistically and clinically significant improvement of symptoms in patients with mild to moderate knee osteoarthritis in whom pain in the contralateral knee is relatively modest.

Adjuvants, Immunologic↗
PubMed2000

Effect of adjunctive intracoronary adenosine on myocardial ischemia, hemodynamic function and left ventricular performance during percutaneous transluminal coronary angioplasty: clinical access to ischemic preconditioning?

BACKGROUND: Ischemic preconditioning has been defined as a mechanism that renders the heart more resistant to subsequent ischemia. Adenosine plays an important role in the pathogenesis of ischemic preconditioning. OBJECTIVE: To assess whether intracoronary administration of adenosine prevents the deterioration of left ventricular performance and hemodynamic function by allowing adaptation to myocardial ischemia in the setting of percutaneous transluminal coronary angioplasty (PTCA). DESIGN: This was a prospectively randomized doubly blinded trial. METHODS: We investigated 20 patients undergoing PTCA of the left anterior descending coronary artery supplying myocardium with normal left ventricular function in the setting of stable angina pectoris. Patients were randomly allocated to be administered adenosine intracoronarily (20 mg/10 min) or an equal amount of saline, providing a control population. Results of standardized chest pain questionnaires, tolerated inflation times, ST-segment shifts, left ventricular and aortic pressures, isovolumetric phase indexes, and indexes of volume and ejection fraction during the course of PTCA between the two groups were compared. RESULTS: Patients administered adenosine tolerated significantly longer balloon-inflation times (188 +/- 41 versus 153 +/- 36 s; P = 0.03), which were associated with less pronounced signs of ischemia, and exhibited less deterioration of isovolumetric phase indexes during PTCA. Deterioration of left ventricular ejection fraction was slightly less severe with adenosine (72 +/- 5% before PTCA versus 64 +/- 6% during angioplasty) than it was for the control group (71 +/- 7% before PTCA versus 60 +/- 7% during angioplasty; P = 0.11). CONCLUSIONS: Intracoronary application of adenosine prior to coronary angioplasty increases tolerance of ischemia and prevents deterioration of left ventricular hemodynamics during ischemia. One potential explanation of these results is that induction of ischemic preconditioning took place.

Adenosine↗
PubMed1997

A possible role of trehalose in osmotolerance and ethanol tolerance in Saccharomyces cerevisiae.

The effect of salt stress on ethanol endurance of yeast cells was studied. Cells grown under increased NaCl concentrations were more ethanol tolerant than controls. The increase in trehalose content under hyper-saline conditions has been suggested to allow cells to withstand higher ethanolic conditions. There seems to be an overlap between osmotolerance and ethanol endurance in Saccharomyces cerevisiae.

Ethanol↗
PubMed2000

The modification of the membrane of Oceanomonas baumannii when subjected to both osmotic and organic solvent stress.

Oceanomonas baumanniioff a novel halotolerant bacterium which was isolated from the estuary of the river Wear (Sunderland, UK). When grown in tryptone soya broth it can tolerate high levels of phenol, which is not utilised as a carbon source in this medium. However, the level of tolerance was reduced from 35 mM to 3 mM phenol as salinity increased from 1% to 12% NaCl (w/v). Increasing salinity up to 12% NaCl also decreased the growth rate 8-fold and caused modifications to the cytoplasmic membrane particularly anionic phosphatidylglycerol levels, which doubled at the expense of zwitterionic phosphatidylethanolamine. In addition, changes in the phospholipid fatty acid composition were noted, cis-vaccenic acid decreased significantly at higher salinities. Intracellular solute levels also increased with increasing salinity and there was an accumulation of the compatible solutes ectoine, glycine betaine and glutamate. The addition of phenol to osmotically compromised cultures led to a further modification of the cytoplasmic membrane phospholipid composition, in particular, that the decrease in zwitterionic phosphatidylethanolamine and the increase of anionic phospholipid species was much less pronounced. A further decrease in unsaturation, particularly in the proportion of cis-vaccenic acid, and the mean chain length of the fatty acids suggested that this response was important in maintaining membrane integrity in the presence of phenol.

Cell Membrane↗