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PubMed1994

Tolerance development to butorphanol: comparison with morphine.

In order to evaluate and to compare the time course, dose response, and the degree of tolerance development to butorphanol and morphine, rats were continuously intracerebroventricularly (ICV) infused with saline vehicle (1 microliter/h), butorphanol (6.5, 13, 26, and 52 nmol/microliters/h), or morphine (1.6, 6.5, and 26 nmol/microliters/h) through osmotic minipumps for 1 to 3 days. The tail-flick responses were determined pre-, during, and postinfusion. Tolerance to morphine developed faster than that to butorphanol. The antinociceptive response to the ICV challenge dose (6 h after the termination of drug infusion) of butorphanol or morphine was decreased significantly and there was a negative correlation between the dose of the drug infused and the observed antinociceptive response. In terms of butorphanol and morphine tolerance, a parallel rightward shift in the dose-response curve was produced with the degree of shift proportional to the log of the infusion dose. In tail-flick tests, the shifts of the dose-response curves for butorphanol and morphine in tolerant animals were 11.8- and 46.3-fold, respectively. However, in the acetic acid writhing test, the shifts of the dose-response curves for butorphanol and morphine in tolerant animals were 11.3- and 11.7-fold, respectively. These results suggest that there is a greater degree of tolerance to morphine than there is to butorphanol, but the degree of butorphanol tolerance is still substantial. In addition, two pain assays (tail flick vs. writhing) yielded different estimations of tolerance in a comparison of morphine and butorphanol.

Animals↗
PubMed2001

Intravenous safety and pharmacokinetics of a novel dimerizer drug, AP1903, in healthy volunteers.

AP1903 is a novel gene-targeted drug that is being developed for use in drug-regulated cell therapies. An intravenous, single-blind, placebo- and saline-controlled, ascending-dose study was performed to evaluate the safety, tolerability, and pharmacokinetics of AP1903. Twenty-eight normal healthy male volunteers were randomized into five dosage groups of AP1903 (0.01, 0.05, 0.1, 0.5, and 1 mg/kg). Within each group, 4 volunteers received a single dose of AP1903, 1 volunteer received an equal volume of placebo, and 1 received an equal volume of normal saline. The only exception was in the 0.5 mg/kg group, in which 4 volunteers were dosed: 3 received AP1903 and 1 received normal saline. All dosages were administered as intravenous infusions over 2 hours. Clinical safety parameters were monitored, and serial blood and urine samples were collected for analysis of AP1903. No drug-related adverse events were observed at any of the dose levels with the possible exception of facial flushing in 1 volunteer at the 1.0 mg/kg dose level. AP1903 plasma levels were directly proportional to the administered dose, with mean Cmax values ranging from approximately 10 to 1,275 ng/mL over the 0.01 to 1.0 mg/kg dose range. Following the infusion period, blood concentrations revealed a rapid distribution phase, with plasma levels being reduced to approximately 18%, 7%, and 1% of the maximal concentration at 0.5, 2, and 10 hours postdose, respectively. AP1903 was shown to be safe and well tolerated at all dose levels and demonstrated a favorable pharmacokinetic profile at doses well above the anticipated therapeutic dose.

Adult↗
PubMed1989

On the development of behavioral tolerance to organophosphates. I: Behavioral and biochemical aspects.

The development of tolerance to organophosphates (OPs) was investigated by SC injections of saline and sublethal doses of DFP or soman three times per week or every other day for at least 4 weeks. Shuttlebox performance was tested 1 hr and 24 hr after the injections. Notwithstanding a progressive inhibition of AChE to very low values in various organs, shuttlebox performance was virtually normal 24 hr after the OP injections. However, whereas the performance decrements measured 1 h after the injection of DFP practically disappeared in the course of weeks, the decrements 1 hr after soman remained approximately the same. These differences between the effects of DFP and soman cannot be explained: 1) by differences in inhibition or de novo synthesis of AChE in various regions of the CNS, the striated muscle or blood, 2) by differences in the reductions of the muscarinic receptors in various regions of the CNS, 3) by differences in the number of nicotinic receptors in the diaphragm muscle, or 4) by differences in phosphorylphosphatase (DFP-ase or somanase) activity in blood plasma or liver.

Acetylcholinesterase↗
PubMed1982

Intrastriatal injection of kainic acid prevents the development of postsynaptic dopamine receptor hypersensitivity after chronic haloperidol treatment.

Rats injected intrastriatally with kainic acid (KA), in contrast to sham-treated (control) animals, showed no tolerance toward catalepsy induced by chronic haloperidol treatment (28 days). After termination of chronic haloperidol treatment in control animals, apomorphine-induced stereotypy was significantly enhanced as compared to chronic saline-injected controls. Rats injected with kainic acid and treated with chronic haloperidol or saline showed no differences in apomorphine stereotypy. These results show that the development of tolerance and behavioural hypersensitivity after chronic neuroleptic treatment is mediated via striatal postsynaptic receptors sensitive to kainic acid lesions.

Animals↗
PubMed1999

Acute and chronic effects of nornicotine on locomotor activity in rats: altered response to nicotine.

RATIONALE: Nicotine, a tobacco alkaloid, is known to be important in the acquisition and maintenance of tobacco smoking. Nornicotine, an active nicotine metabolite, stimulates nicotinic receptors and may produce psychomotor effects similar to nicotine. OBJECTIVE: The present study determined the effects of acute and repeated administration of nornicotine on locomotor activity and compared its effects with those of nicotine. METHODS: R(+)-Nornicotine (0.3-10 mg/kg), S(-)-nornicotine (0.3-10 mg/kg), S(-)-nicotine (0.1-1 mg/kg) or saline was administered s.c. to rats acutely or repeatedly (eight injections at 48-h intervals). Activity was recorded for 50 min immediately after each injection. RESULTS: S(-)-Nicotine produced transient hypoactivity, followed by dose-related hyperactivity. Repeated S(-)-nicotine administration resulted in tolerance to the hypoactivity and sensitization to the hyperactivity. Subsequent testing following a saline injection revealed evidence of conditioned hyperactivity. Acute administration of 0.3 mg/kg or 1 mg/kg R(+)- or S(-)-nornicotine produced no effect. Transient hypoactivity was observed at 3 mg/kg and 10 mg/kg R(+)-nornicotine and at 10 mg/kg S(-)-nornicotine. However, rebound hyperactivity was not observed following acute administration of either nornicotine enantiomer, suggesting that nornicotine-induced psychomotor effects differ qualitatively from those of S(-)-nicotine. Repeated R(+)-nornicotine resulted in tolerance to the transient hypoactivity, however hyperactivity was not observed. Repeated S(-)-nornicotine resulted in tolerance to the hypoactivity and the appearance of hyperactivity. Repeated administration of either nornicotine enantiomer resulted in a dose-dependent alteration in response to a 1 mg/kg S(-)-nicotine challenge, suggesting some commonalities in the mechanism of action. CONCLUSION: Nornicotine likely contributes to the neuropharmacological effects of nicotine and tobacco use.

Animals↗
PubMedDate not supplied

Long-term retention of tolerance to amphetamine hypophagia following cessation of drug injections and feeding tests.

According to the instrumental learning model, tolerance to amphetamine hypophagia involves learning to suppress stereotyped movements that interfere with feeding. If both drug injections and feeding tests are then suspended, learning should be retained and no loss of tolerance should occur. However, previous studies have only assessed the retention of tolerance for 3-4 weeks. In the present study, retention intervals of 4-31 weeks were used. Rats were given daily injections of amphetamine (2 mg/kg) and access to milk for 30 min until tolerance developed to drug-induced hypophagia. Yoked controls were injected with saline. Both before and after this phase, dose-response (DR) tests were conducted. Drug injections and feeding tests were then suspended. At 4, 10, 18, and 31 weeks, both groups were injected with 2 mg/kg amphetamine and given access to milk for 30 min to assess the retention of tolerance. A final DR determination was then conducted. Most (88%) rats retained tolerance to 2 mg/kg amphetamine for 31 weeks. However, DR tests revealed that tolerance was not retained at 4 mg/kg. The results demonstrate that learned tolerance to amphetamine can be retained over long intervals when both drug injections and feeding tests are suspended.

Amphetamine↗
PubMed1997

Nalbuphine coadministered with morphine prevents tolerance and dependence.

Nalbuphine, an opioid mixed agonist-antagonist, prevents many morphine-related side effects. In this study, we compared the effects of nalbuphine versus naloxone on the prevention of morphine tolerance and dependence in Sprague-Dawley rats. Group 1 received a morphine 5 mg/kg intraperitoneal (I.P.) injection. Groups 2 and 3 received single doses of nalbuphine (0.01 to 5 mg/kg I.P.) or naloxone (1 to 500 microg/kg I.P.) coadministered with morphine (5 mg/kg I.P.), respectively. Group 4 received a saline I.P. injection. Treatments were continued for 4 days. The occurrence of tolerance was estimated by comparing the antinociceptive effect of morphine on Day 1 (Group 1) and Day 5 (each group). The severity of dependence was determined by precipitated withdrawal signs (incidence of diarrhea and teeth chattering) induced by naloxone (10 mg/kg I.P.). We found that coadministration of nalbuphine or naloxone with morphine dose-dependently blocked the development of morphine tolerance and dependence. However, unlike naloxone, nalbuphine did not attenuate the antinociceptive effect of morphine.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1990

Centrally acting vasopressin contributes to endotoxin tolerance.

Repeated daily intravenous injections of bacterial endotoxin induce a refractory state to their usual pyrogenic effects. The neuropeptide arginine vasopressin (AVP) has been implicated in natural fever suppression and may be involved in the process of pyrogenic tolerance to intravenous endotoxin. This study was conducted to test this hypothesis. Tolerance was induced by two successive daily intravenous injections of Escherichia coli endotoxin (50 micrograms/kg) into conscious unrestrained rats. This tolerance was maintained, unaltered, after a third or fourth subsequent injection. However, bilateral administration of an AVP V1-receptor antagonist (0.43-4.3 nmol) into the ventral septal area (VSA) of the rat brain markedly enhanced the thermoregulatory response to a third or fourth endotoxin challenge compared with saline controls. The effect of the V1 antagonist was dose related. In contrast, an AVP V2 antagonist (0.43 nmol) bilaterally injected into the VSA did not affect the tolerant reaction to endotoxin. Furthermore, neither saline nor the V1 antagonist significantly affected core temperature when administered within the VSA without subsequent endotoxin. These results are consistent with the hypothesis that AVP acts as an endogenous antipyretic within the VSA during fever. Moreover, the data suggest a possible role for centrally acting vasopressin during pyrogenic tolerance to E. coli endotoxin.

Animals↗
PubMedDate not supplied

Acute and subacute toxicity of 7.5% hypertonic saline-6% dextran-70 (HSD) in dogs. 2. Biochemical and behavioral responses.

7.5% Hypertonic saline-6% Dextran-70 (HSD) is currently being evaluated in our laboratory as a resuscitation solution for the treatment of hypovolemia at a dose of 4 ml kg-1 body weight. A few reports of dextran toxicity, particularly of the kidney, have been cited in the literature, so the present study evaluated the acute and subacute toxicity of HSD administered i.v. to beagle dogs. In the acute toxicity studies animals were infused with a single dose of HSD, or its components of hypertonic saline (HS) or Dextran-70 (D-70), at the maximum tolerated dose (MTD: 20 ml kg-1). Controls received Ringers lactate (RL). In the HSD-infused dogs, transient but significant increases in serum alanine (ala) aminotransferase (AT), aspartate (asp) AT and alkaline phosphatase (AP) were observed for the first 72 h. In most cases this increase was also observed in the HS group. In the subacute studies, dogs were infused daily with the MTD of the above test solutions. Serum ala AT activity was 2-3-fold higher in the HSD than the RL group for the first 3 days. Again, a similar effect was observed in the HS group. Slight, transient increases in asp AT and AP activity were also observed in the HSD group. Higher lactate dehydrogenase (LDH) activity was only observed at Day 14 in dogs infused with the MTD of HSD or HS. In both studies, no adverse effects on blood urea nitrogen (BUN) or serum creatinine were observed and other transient changes in serum parameters were attributable to hemodilution induced by HSD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Conditioned facilitation of brain reward function after repeated cocaine administration.

Cocaine lowers brain reward thresholds, reflecting increased brain reward function. The authors investigated whether, similar to acute cocaine administration, cocaine-predictive conditioned stimuli would lower intracranial self-stimulation (ICSS) thresholds. Rats received a saline injection for 5 days, a cocaine injection (10 mg/kg) for 20 consecutive days, then saline for 5 additional days. Thresholds were measured immediately before and 10 min after each injection. The initial 5 saline injections had no effect on thresholds, whereas cocaine significantly lowered thresholds for 20 days. There was no tolerance or sensitization to this effect of cocaine over days. During the last 5 days when cocaine administration was substituted with saline, rats demonstrated a conditioned lowering of thresholds during the 2nd daily ICSS session. These data demonstrate that cocaine-predictive conditioned stimuli induce a conditioned facilitation of brain reward function.

Animals↗
PubMed1998

Effect of chronic m-CPP on locomotion, hypophagia, plasma corticosterone and 5-HT2C receptor levels in the rat.

1. The present study examined 5-HT2C receptor agonist-induced behavioural tolerance and 5-HT2C receptor down-regulation in adult rat brain. The effect of chronic subcutaneous infusion of the 5-HT2C receptor agonist, m-chlorophenylpiperazine (m-CPP, 10 mg kg(-1), day(-1)), for 14 days was examined on daily food intake, the ability of acute m-CPP (2.5 mg kg(-1), i.p.) to induce hypolocomotion in a novel arena and elevate plasma corticosterone levels and on ex vivo cortical [3H]-mesulergine binding and hippocampal 5-HT2C receptor protein levels. 2. Before chronic infusion, m-CPP (2.5 mg kg(-1), i.p.) attenuated the number of turns and rears made in a novel open field arena. In contrast, while m-CPP still elicited this hypolocomotion following 14 days, saline infusion, no such hypolocomotion occurred in rats given chronic m-CPP (10 mg kg(-1) day(-1)), indicating that almost complete tachyphylaxis of this behaviour occurred with chronic 5-HT2C receptor agonist injection. 3. During chronic infusion of m-CPP, rats consumed less food per day than saline-treated controls. Acute challenge with m-CPP following two weeks, treatment still attenuated food intake over the next four hours (by 43% and 30%, respectively from that on the previous day) in saline and m-CPP infusion groups, showing that only partial tolerance to 5-HT2C receptor agonist-induced hypophagia occurred. 4. In naive home cage rats, plasma corticosterone was elevated in a dose-dependent manner 35 min after m-CPP injection (0.5, 1 and 3 mg kg(-1), i.p.) but levels were comparable to control values 16 h after m-CPP (2, 5 and 10 mg kg(-1), i.p.). Sixteen hours after a single m-CPP injection (2.5 mg kg(-1), i.p.), plasma corticosterone levels were comparable in a group of rats which had received 14 days infusion of m-CPP or saline. However, following a similar acute m-CPP injection (2.5 mg kg(-1), i.p., - 16 h) in rats previously infused for 14 days with m-CPP, plasma corticosterone levels were lower than those in a separate group which received no chronic infusions (but only acute m-CPP injection), even though the plasma m-CPP levels were comparable in both groups. The data are consistent with the proposal that chronic m-CPP induced some down-regulation of hypothalamic 5-HT2C receptors which contribute, in a tonic manner, to plasma corticosterone secretion under the conditions investigated. 5. Chronic m-CPP infusion reduced the amount of [3H]-mesulergine binding (by 27%, without altering the KD) in membranes prepared from parietal/occipital/temporal cortex (under conditions to exclude binding to 5-HT2A receptors) and 5-HT2C receptor protein-like immunoreactive levels measured by radioimmunoassay in the hippocampus by 38%, confirming that 5-HT2C receptor down-regulation had occurred. 6. Even after 14 days m-CPP infusion only partial behavioural tolerance and 5-HT2C receptor down-regulation were observed, which may vary in different brain regions of the rat. Thus the hypophagia produced by m-CPP may involve activation of 5-HT2C receptors in the hypothalamus, where there is a greater receptor reserve or which are more resistant to agonist-induced down-regulation than 5-HT2C receptors in limbic areas (striatum and nucleus accumbens) mediating m-CPP-induced hypolocomotion.

Animals↗
PubMed1991

Freeze-thaw injury in erythrocytes of the freeze-tolerant wood frog, Rana sylvatica.

Erythrocytes from the freeze-tolerant wood frog (Rana sylvatica) were subjected to in vitro tests of freeze tolerance, cryoprotection, and osmotic fragility. The responses of cells from frogs acclimated to 4 or 15 degrees C were similar. Erythrocytes that were frozen in saline hemolyzed at -4 degrees C or lower. The addition of high concentrations (150 and 1,500 mM) of glucose or glycerol, cryoprotectants produced naturally by freeze-tolerant frogs, significantly reduced cell injury at -8 degrees C, but concentrations of 1.5 or 15 mM were ineffective. Hemolysis was reduced by 94% with 1,500 mM glycerol and by 84% with 1,500 mM glucose; thus glycerol was the more effective cryoprotectant. Mean fragility values for frog erythrocytes incubated in hypertonic and hypotonic saline were 1,938 and 49 mosM, respectively. Survival in freeze tolerance and cryoprotection experiments was comparable for erythrocytes from frogs and humans, suggesting that these cells may respond similarly to freezing-related stresses. However, the breadth of osmotic tolerance, standardized for differences in isotonicity, was greater for frog erythrocytes than for human erythrocytes. Our data suggest that erythrocytes from R. sylvatica are adequately protected by glucose under natural conditions of freezing and thawing.

Animals↗
PubMed1996

[Polyethylene glycol versus sodium phosphate: comparison of 2 preparations for colonoscopy].

The intention of this study is to compare the efficacy and tolerability of an electrolytic solution containing polyethylene glycol (PEG) with a saline solution containing sodium phosphate in the preparation of colon for an endoscopic examination. 80 patients were subdivided at random into two groups: Group 1; PEG 4 liters - Group 2; sodium phosphate 3 packets plus one microenema. The efficacy of the two preparations was decided on the basis of: presence or absence of liquid/solid faecal residues observed by the endoscopist during the exploration of the large intestine, and classified as follows: perfect, good, mediocre and bad. Acceptability was established on the basis of patient tolerability in completing or not the preparation as well as presence of any side effect. The PEG solution was observed to be more efficient than sodium phosphate solution while both preparations had comparable tolerability. The cost of the PEG preparation was higher compared to the sodium phosphate preparation.

Adult↗
PubMed2005

Intermittent dosing prolongs tolerance to the antinociceptive effect of morphine microinjection into the periaqueductal gray.

Tolerance to the antinociceptive effect of microinjecting morphine into the ventrolateral periaqueductal gray (vPAG) develops with repeated administration. The objective of the present experiment was to determine whether the magnitude and duration of tolerance differ depending on the interval between injections. Rats were injected with morphine or saline into the vPAG either once daily for 4 days or twice daily for 2 days. All rats were injected with morphine into the vPAG for the fifth injection to determine whether tolerance had developed. Morphine microinjection produced tolerance in both morphine-pretreated groups regardless of inter-dose interval. One and two weeks later, microinjection of morphine produced an increase in hot plate latency in all groups except rats pretreated with daily morphine microinjections. That is, tolerance was evident 2 weeks following the induction of tolerance produced by daily, but not twice daily injections of morphine. Although a long inter-dose interval has been shown to prolong the duration of tolerance after systemic morphine administration, this is the first report showing a similar effect with direct administration of morphine into the brain. Given that associative learning underlies prolonged tolerance with systemic morphine administration, the present data suggest that associative mechanisms of tolerance are also engaged when morphine administration is restricted to the PAG.

Analgesics, Opioid↗
PubMed2003

Prenatal morphine exposure decreases analgesia but not K+ channel activation.

The present study has investigated the possible supraspinal adaptive changes induced by prenatal administration of morphine, including morphine-induced supraspinal antinociception in vivo, the density and binding affinity of mu-opioid receptors in the brain and the cellular action of morphine in brain slices in vitro. The cellular action of morphine was assessed by its activation of K+ channels in the ventrolateral periaqueductal gray (PAG), a crucial area for the supraspinal analgesic effect of morphine. Female rats were treated with morphine 7 days before mating at 2 mg/kg. The treatment was continued during pregnancy and after delivery at doses which increased by 1 mg/kg every 2 weeks. Experiments were conducted in the offspring at p14 days. Prenatal morphine exposure induced tolerance to supraspinal morphine-induced tail-flick response. The binding affinity and maximal binding of [(3)H]DAMGO in whole brain were not significant different between the morphine- or saline-treated dams. Autoradiographic analysis shows that the mu-opioid receptor density was decreased in the striatum, thalamus and amygdala but not in the midbrain, nucleus accumbens, hippocampus or cortex in morphine offspring. In ventrolateral PAG neurons, morphine activated inwardly rectifying K+ channels in 59% of recorded neurons of morphine offspring. Neither the magnitude of K channel activation nor the percentage of sensitive neurons was different between the saline- and morphine-treated offspring. It is concluded that prenatal morphine exposure induces tolerance to supraspinal analgesia and this tolerance is not attributed to a change in the mu-opioid receptor density or the receptor-function coupling efficiency in the midbrain periaqueductal gray.

Animals↗
PubMed1999

Effect of gemcitabine on the tolerance of the lung to single-dose irradiation in C3H mice.

In an early phase II trial combining gemcitabine (dFdC) and radiotherapy for lung carcinomas, severe pulmonary toxicity was observed. In this framework, the objective of this study was to investigate the effect of dFdC on the tolerance of the lungs of C3H mice to single-dose irradiation. The thoraxes of C3H mice were irradiated with a graded single dose of 8 MV photons; dFdC (150 mg/kg) or saline (control animals) was administered i.p. 3 or 48 h prior to irradiation. Lung tolerance was assessed by the LD50 at 7-180 days after irradiation. For irradiation alone, the LD50 reached 14.45 Gy (95% CI 13.33-15.66 Gy). With a 3-h interval between administration of dFdC and irradiation, the LD50 reached 13.29 (95% CI 12.26-14.44 Gy); the corresponding value with a 48-h interval reached 13.01 Gy (95% CI 11.92-14.20 Gy). Our data also suggested a possible effect of dFdC on radiation-induced esophageal toxicity. dFdC has a minimal effect on lung tolerance after single-dose irradiation. However, a proper phase I-II trial should be designed before any routine use of combined dFdC and radiotherapy in the thoracic region.

Animals↗
PubMed1996

Learned tolerance to the corticosterone-increasing action of ethanol in rats.

Ethanol administration stimulates the hypothalamic-pituitary-adrenal (HPA) axis, resulting in increased plasma levels of corticosterone. As occurs with many other effects of ethanol, tolerance develops with repeated administration such that plasma corticosterone levels become less effected by subsequent ethanol administration. The present experiment explored the possibility that the environmental cues associated with the administration of ethanol can control the expression of tolerance to ethanol's corticosterone-elevating effects. Male Long-Evans rats received intragastric administrations of ethanol (3.2 g/ kg) in association with one set of environmental cues and intragastric saline in association with a different set of environmental cues. Plasma corticosterone levels were elevated after the first ethanol administration, but after the tenth ethanol administration, corticosterone levels failed to increase significantly above control values. After demonstrating tolerance, rats were administered ethanol in the saline-paired environment and plasma corticosterone levels were higher than in the ethanol-paired environment. This environmental specificity suggests that tolerance to the neuroendocrine effects of ethanol is not simply the result of long-term alterations in sensitivity of the HPA axis but is, at least in part, mediated by learned responses to cues that predict the effects of ethanol.

Animals↗
PubMed1997

[Effectiveness and tolerance of nasal irrigation following paranasal sinus surgery].

BACKGROUND: Cleaning of the nose with saline solution after endonasal sinus surgery is very often used for postoperative treatment. But the efficiency and acceptance of this method has not been examined thoroughly until now. METHODS: Performance, effectiveness and acceptance of the postoperative treatment was evaluated in a questionnaire. One hundred thirty-four of 180 patients answered. RESULTS: One hundred twenty-one patients (66.1%) cleaned their nose with Ems brine; 28.1% of the patients used saline solution. The nasal douche was the cleaning device used by 39.7% of the patients, whereas 53.7% sniffed the solution from their hand. Ninety-five percent found that this kind of treatment was easy to do; 84.7% found it equally pleasant. There was no difference between using Ems brine or NaCl solution nor between using the nasal douche or sniffing out of the hand. Fifty-one point four percent of the patients with an follow-up of 27 to 36 months rinsed their nose up to now; 55.9% resumed nasal irrigation after an interval. CONCLUSIONS: Rinsing of the nose after endonasal sinus surgery is judged positively by most of our patients and is integrated well in the daily routine. Although it is most common to sniff saline solution out of the hand, existing research recommends usage of warm Ems brine in combination with the nasal douche.

Ethmoid Sinus↗