Remedia Sternutatoria over the Centuries: TRP Mediation.

Sneezing (sternutatio) is a poorly understood polysynaptic physiologic reflex phenomenon. Sneezing has exerted a strange fascination on humans throughout history, and induced sneezing was widely used by physicians for therapeutic purposes, on the assumption that sneezing eliminates noxious factors from the body, mainly from the head. The present contribution examines the various mixtures used for inducing sneezes (remedia sternutatoria) over the centuries. The majority of the constituents of the sneeze-inducing remedies are modulators of transient receptor potential (TRP) channels. The TRP channel superfamily consists of large heterogeneous groups of channels that play numerous physiological roles such as thermosensation, chemosensation, osmosensation and mechanosensation. Sneezing is associated with the activation of the wasabi receptor, (TRPA1), typical ligand is allyl isothiocyanate and the hot chili pepper receptor, (TRPV1), typical agonist is capsaicin, in the vagal sensory nerve terminals, activated by noxious stimulants.

The effect of tramadol on sneeze-induced urethral continence reflex through µ-opioid receptors in the spinal cord in rats.

AIMS: We examined the efficacy of tramadol on the urethral reflex during sneezing, as well as the role of µ-opioid receptors in the spinal cord, in rats. METHODS: Forty-one female Sprague-Dawley rats were used. The rats were divided into normal female rats and rats with vaginal distension (VD), which mimics stress urinary incontinence (SUI) in humans. Under urethane anesthesia, the sneeze-induced amplitude of urethral responses (AUR) and baseline pressure (BP) were examined after intravenous injection of tramadol using a microtransducer-tipped catheter in both rat groups. The effect of intrathecal cyprodime, a selective µ-opioid receptor antagonist, following intravenous tramadol injection was examined in normal rats. The tilt leak point pressure (tilt LPP) after intravenous tramadol injection was also evaluated in both groups. RESULTS: In normal rats, tramadol enhanced the AUR and BP by 33.2% and 19.5%, respectively. Tramadol also increased BP by 13.9% in rats with VD, but it did not change AUR. Intrathecal cyprodime alone did not change AUR, but it decreased BP. However, tramadol-provoked increments in AUR were blocked by intrathecal cyprodime, while BP was recovered to the level that it was before administration of cyprodime. Tramadol was associated with a significant elevation in tilt LPP: 24.8% and 19.5% in normal and VD rats, respectively. CONCLUSIONS: These findings suggest that tramadol effectively enhances the AUR at the spinal level and BP peripherally. Therefore, stimulation of the spinal µ-opioid receptors may be useful for the treatment of SUI.

Comparison of the Benefit Feeling Rate Based on the Sho of OTC Kakkonto, Cold Remedy and Cold Remedy with Kakkonto Combination Product.

Kakkonto (KK), a traditional Japanese Kampo formulation for cold and flu, is generally sold as an OTC pharmaceuticals used for self-medication. Kampo formulations should be used according to the Sho-symptoms of Kampo medicine. These symptoms refer to the subjective symptoms themselves. Although with OTC pharmaceuticals, this is often not the case. We surveyed the relationship of agreement of Sho with the benefit feeling rate (BFR) of patients who took KK (n=555), cold remedies with KK (CK, n=315), and general cold remedies (GC, n=539) using internet research. BFR of a faster recovery was greater in participants who took the medication early and who had confidence in their physical strength in all treatment groups. BFR was significantly higher in the GC group than in the KK group for patients with headache, runny nose, blocked nose, sneezing, and cough. BFR was also significantly higher in the GC group than in the CK group for headache (males) and cough (females). BFR was the highest in the KK group for stiff shoulders. All cold remedies were more effective when taken early, and the larger the number of Sho that a patient had, the greater the BFR increased. Therefore, a cold remedy is expected to be most effective when there are many cold symptoms and when it is taken at an early stage of the common cold.

Strontium chloride hexahydrate as a candidate molecule for long-term treatment of allergic rhinitis.

BACKGROUND & OBJECTIVES: Neurogenic inflammation plays a role in the pathophysiology of allergic rhinitis (AR). Strontium salts are highly effective in reducing the sensory irritation. This study was aimed to investigate the efficacy of strontium chloride (SC) on AR symptoms based on the duration of SC use before the symptoms begin. METHODS: Wistar albino rats (n=18) were randomly divided into three groups: Group 1, received 1µg mometasone furoate (MF); Group 2, three per cent SC; and Group 3 received five per cent SC (2 µl/site). Drugs were administered to the each nasal cavity for three weeks every morning. On the days 7, 14 and 21, histamine dihydrochloride (HD) 5 µmol (2 µl/site) was administered and the frequencies of nasal rubbing and sneezing were counted for 15 min. RESULTS: After 7, 14 and 21 day medication period, the groups were compared in terms of the frequency of sneezing and nasal rubbing following HD. There was a significant difference among the groups in terms of the frequency of sneezing on the day 7 (PPInterpretation & conclusions: Our results showed that three and five per cent SC were less effective than MF for sneezing during the first week, but the efficiency was equal to that of MF after the first 14 days. Long-term use of SC was as effective as MF on nasal rubbing. SC can be as effective as MF on both sneezing and nasal rubbing on regular use over three weeks.

Prostaglandin D2 Modulates Neuronal Excitation of the Trigeminal Ganglion to Augment Allergic Rhinitis in Guinea Pigs.

Prostaglandin D2(PGD2) is involved in the pathogenesis of allergic rhinitis. However, the sensory nervous system-mediated contributions of PGD2to the symptoms of allergic rhinitis remain unclear. We investigated the involvement of PGD2in these symptoms and in neuronal excitation by in vivo and ex vivo experiments. In an ovalbumin-induced model of allergic rhinitis in guinea pigs, the number of sneezing, nasal rubbing, and nasal secretion events were assessed after the nasal cavity instillation of PGD2, histamine, or a combination of PGD2and histamine. In situ hybridization for PGD2receptor 1 (DP1) mRNA transcripts and immunohistochemical analysis of histamine H1receptor protein expression in guinea pig trigeminal ganglion (TRG) were performed. The effects of DP1receptor activation on the excitability of TRG neurons to electrical and histamine stimuli were assessed using whole-cell patch-clamp recordings. Histamine induced more sneezing, nasal rubbing, and nasal secretion events than PGD2 PGD2augmented histamine-induced responses, whereas pretreatment with a DP1receptor-selective antagonist completely suppressed PGD2-induced augmentation. DP1receptor mRNA transcripts and H1receptor protein expression could be detected in TRG neurons. Moreover, a DP1receptor agonist caused significant increases in the number of histamine-induced action potentials and depolarization, and reduced the current threshold in small-diameter neurons. Our findings show that PGD2-DP1receptor signaling augments the symptoms of allergic rhinitis via the sensory nervous system by modulating nasal neuronal activation to various stimuli, such as histamine. These findings suggest that DP1receptor antagonist has therapeutic potential for the treatment of allergic rhinitis.

Establishment and characterization of an experimental mouse model of allergic rhinitis.

Allergic rhinitis (AR) is a common worldwide disease. Animal studies on AR were adopted in various investigations. However, animal studies simply aimed at establishing an animal model for AR have been seldom seen. The purpose of this study was to introduce an easy-to-establish experimental mouse model of AR. To develop a mouse model of AR, 38 Balb/c mice were randomly assigned to two groups. Mice in the study group were sensitized by intraperitoneal (IP) injection of ovalbumin (OVA) on day 1 and 6, followed by continuous inhalation (IH) of OVA solution for 1 week (day 8-14) using a newly designed inhalation box. The control group mice received sensitization of IP normal saline and IH sterilized distilled water instead of OVA. Before and after sensitization, the frequencies of nasal symptoms (sneezing, nasal rubbing) were recorded and the serum levels of total immunoglobulin E (IgE) were evaluated using ELISA. Finally, the murine nasal mucosal tissues were stained by Giemsa solution to estimate the degree of mast cell infiltration. After sensitization by IP and IH OVA, the study group showed significant phenotypic changes including increased sneezing and rubbing. Pathological and cytological findings also confirmed significant elevated serum total IgE titer and local mast cell infiltration in the study group statistically. We successfully developed a workable experimental animal model for AR that was more easily sensitized using our new-designed inhalation box, with less stress and more precisely to be observed.

Inhibitory role of the spinal cholinergic system in the control of urethral continence reflex during sneezing in rats.

AIMS: The urethral continence reflex during stress conditions such as sneezing or coughing is an important mechanism preventing stress urinary incontinence (SUI). Although the spinal noradrenergic and serotonergic pathways are known to modulate this reflex activity, the role of spinal cholinergic pathways in the control of urethral continence reflex has not been elucidated. We therefore investigated the effect of intrathecal administration of an acetylcholine esterase (AChE) inhibitor, which increases ACh in synaptic terminals, and anti-cholinergic agents on the sneeze-induced urethral reflex in rats. METHODS: Female SD rats were anesthetized with urethane. Urethral function was evaluated during sneezing induced by insertion of the rat whisker into the nostril. Effects of an AChE inhibitor, neostigmine, and muscarinic or nicotinic receptor antagonists administered at the level of L6-S1 spinal cord were examined. RESULTS: Neostigmine dose-dependently and significantly decreased the amplitude of urethral responses during sneezing (A-URS) with an approximately 70% reduction at 3 nmol, without changing urethral baseline pressure. The neostigmine-induced decrease in A-URS was significantly reversed by pretreatment with atropine (nonselective muscarinic receptor antagonist), methoctramine (M2 receptor antagonist) or 4-DAMP (M3 receptor antagonist), but not with pirenzepine (M1 receptor antagonist), tropicamide (M4 receptor antagonist), or mecamylamine (nicotinic receptor antagonist). CONCLUSIONS: These results indicate that an increase in endogenous ACh in the lumbosacral spinal cord inhibits the sneeze-induced urethral continence reflex via activation of M2 and/or M3-muscarinic receptors, implying the inhibitory role of spinal cholinergic pathways in the control of urethral continence reflex under stress conditions such as sneezing.

Naloxone blocks suppression of cough by codeine in anesthetized rabbits.

Opioid receptors which are involved in cough generation are abundantly expressed in the brainstem. Codeine is a potent µ-opioid receptor agonist. In the present study we examined the effects of naloxone, a µ-opioid receptor antagonist, on mechanically-induced tracheobronchial cough and on the cough suppressing effect of codeine in six pentobarbitone anesthetized spontaneously breathing rabbits. A single dose of naloxone (0.4 mg/kg) followed by a single dose of codeine (7 mg/kg) were administered intravenously. The number and amplitude of cough and sneeze reflexes were examined sequentially; before and after naloxone, and then after codeine. We found that neither did naloxone alone nor codeine given after prior naloxone pretreatment appreciably affect coughing or sneezing. Likewise, there were no significant differences in the diaphragm and abdominal muscles electromyographic moving averages, or the inspiratory and expiratory esophageal pressure amplitudes. However, we detected a tendency for the rise in expiratory motor drive during coughing and sneezing after injection of naloxone. The respiratory rate was significantly higher after naloxone in comparison with control (P < 0.001). No significant differences in arterial blood pressure were observed. We conclude that the failure of codeine to suppress the cough reflex on the background of naloxone pretreatment confirms the involvement of µ-opioid mechanism in the central antitussive effect of codeine.

Attenuation of histamine-induced airway effects by intranasal application of levocetirizine in mice.

The present study was performed to investigate the histamine-induced airway effect of levocetirizine, an active enantiomer of cetirizine, by intranasal application using ddY mice. Nasal rubbing and sneezing after histamine application into the nasal cavity were used as an index of histamine-induced airway effect in mice. Intranasal application of levocetirizine inhibited both nasal rubbing and sneezing concentration-dependently, and the ED50 values were 0.62 (0.51-0.77) and 0.70 (0.51-1.02) %/site for nasal rubbing and sneezing, respectively. ED50 values of cetirizine were 1.24 (1.02-1.59) and 1.35 (1.02-2.08) %/site for nasal rubbing and sneezing, respectively. Levocetirizine also inhibited nasal rubbing and sneezing when administered orally. These results clearly indicate that levocetirizine was about two times more potent than cetirizine by intranasal application, similar to the findings of the former's affinity for human histamine H1 receptors. In addition, the present findings raise the expectation of the development of levocetirizine nasal drops.

A comparison of decontamination effects of commercially available detergents in rats pre-exposed to topical sulphur mustard.

OBJECTIVE: The genotoxic vesicant sulphur mustard [bis-2-(chloroethyl)sulphide] is a chemical warfare agent which is easily available due to its relatively simple synthesis. Thus, sulphur mustard is a potential agent for mass contamination. In this study, we focused on sulphur mustard toxicity and decontamination in a rat model using commercially available detergent mixtures for dermal decontamination. METHODS: Male Wistar rats were percutaneously treated with sulphur mustard and subjected to wet decontamination 2 min postexposure. Commercially produced detergents Neodekont™, Argos™, Dermogel™ and FloraFree™ were tested for their decontamination efficacy against an exposed group and their protective ratios determined. RESULTS AND CONCLUSION: The results showed that all tested detergent solutions produced an increase in the median lethal dose [LD(50) = 9.83 (5.87-13.63) mg·kg(-1)] in comparison to controls, which led to increased survival of experimental animals. In general, all tested detergents provided modest decontamination efficacy (PR = 2.0-5.7). The highest protective ratio (5.7) was consistently achieved with Argos™. Accordingly, Argos™ should be considered in further investigation of mass casualty decontamination.

Efficacy of prophylactic treatment with montelukast and montelukast plus add-on loratadine for seasonal allergic rhinitis.

Cysteinyl leukotriene and leukotriene receptor occupancy have been linked to several processes in seasonal allergic rhinitis (SAR), including nasal congestion, rhinorrhea, and recruitment of inflammatory cells. We investigated whether add-on loratadine, an antihistamine, might be effective for SAR patients showing unsatisfactory control of symptoms with the leukotriene receptor antagonist (LTRA) montelukast alone. Patients with SAR caused by Japanese cedar pollen (SAR-JCP; mean age, 29.4 years) were given prophylactic montelukast for 1 month before peak JCP dispersal. Patients recorded the severity of the symptoms (sneezing, rhinorrhea, nasal congestion, and ocular symptoms) daily on visual analog scale (VAS). We selected patients with VAS scores of >50 for any of the symptoms just before the peak pollen season (March 2 to March 8) and designated them as "poorly controlled" patients. Then, in the peak JCP season (from March 9), we conducted a randomized, double-blind, placebo-controlled study to determine whether add-on loratadine might be effective for these "poorly controlled" patients. Montelukast alone was effective, as evaluated by improvement of the VAS scores, in 95 of the 137 patients (69.3%). Add-on loratadine significantly decreased the total scores for nasal symptoms (p < 0.05), sneezing (p < 0.05), and rhinorrhea (p < 0.05) when compared with placebo. The symptoms of SAR in two of three SAR-JP patients could be controlled (VAS score[s] under 50) by prophylactic treatment with montelukast alone under the condition of mild JCP dispersal. Furthermore, the effect of add-on antihistamine on sneezing and rhinorrhea was found in selected SAR-JCP patients.

The respiratory health effects of nitrogen dioxide in children with asthma.

There is growing evidence that asthma symptoms can be aggravated or events triggered by exposure to indoor nitrogen dioxide (NO(2)) emitted from unflued gas heating. The impact of NO(2) on the respiratory health of children with asthma was explored as a secondary analysis of a randomised community trial, involving 409 households during the winter period in 2006 (June to September). Geometric mean indoor NO(2) levels were 11.4 µg · m(-3), while outdoor NO(2) levels were 7.4 µg · m(-3). Higher indoor NO(2) levels (per logged unit increase) were associated with greater daily reports of lower (mean ratio 14, 95% CI 1.12-1.16) and upper respiratory tract symptoms (mean ratio 1.03, 95% CI 1.00-1.05), more frequent cough and wheeze, and more frequent reliever use during the day, but had no effect on preventer use. Higher indoor NO(2) levels (per logged unit increase) were associated with a decrease in morning (-17.25 mL, 95% CI -27.63- -6.68) and evening (-13.21, 95% CI -26.03- -0.38) forced expiratory volume in 1 s readings. Outdoor NO(2) was not associated with respiratory tract symptoms, asthma symptoms, medication use or lung function measurements. These findings indicate that reducing NO(2) exposure indoors is important in improving the respiratory health of children with asthma.

Inhibition of hematopoietic prostaglandin D synthase improves allergic nasal blockage in guinea pigs.

Although it has been suggested that prostaglandin (PG) D(2) is involved in the pathogenesis of allergic rhinitis, whether the inhibition of hematopoietic PGD(2) synthase (H-PGDS) shows beneficial effects on allergic rhinitis has been unclear. We evaluated the effects of a selective H-PGDS inhibitor, TFC-007, on nasal symptoms on Japanese cedar pollen-induced allergic rhinitis of guinea pigs. Sensitized animals were challenged with the pollen once a week. TFC-007 (30mg/kg, p.o.) given once before a challenge almost completely suppressed PGD(2) production in the nasal tissue early and late after the challenge. Although pre-treatment did not affect the incidences of sneezing and early phase nasal blockage, late phase nasal blockage was partially but significantly attenuated; however, nasal eosinophilia was not suppressed. In contrast, when TFC-007 was given once 1.5h after the challenge, the late phase response was not affected. Collectively, PGD(2) produced by H-PGDS early after an antigen challenge can participate in the induction of late phase nasal blockage, although the mechanism may be independent of eosinophil infilatration. The strategy for H-PGDS inhibition may be beneficial for allergic rhinitis therapy.

Intranasal administration of semaphorin-3A alleviates sneezing and nasal rubbing in a murine model of allergic rhinitis.

Sneezing and persistent itching of the nasal mucosa are distressing symptoms of allergic rhinitis (AR). Recent studies have revealed that hyperinnervation of sensory neurons in the nasal turbinate is one of the underlying causes of sneezing and itching. Since Semaphorin-3A (Sema3A) has been previously shown to restrict innervation of sensory neurons, it is presumed that reduced Sema3A expression in the nasal mucosa might contribute to the hypersensitivity. Analysis of the mouse model of ovalbumin-sensitized AR demonstrated a decreased expression of Sema3A in the nasal epithelium, which was accompanied by an increased nerve fiber density in the lamina propria of the turbinate. In rescue experiments, intranasal administration of recombinant Sema3A in the AR model mice alleviated sneezing and nasal rubbing symptoms. In addition, histological examinations also revealed that nerve fiber density was decreased in the lamina propria of the Sema3A-treated nasal turbinate. These results suggest that the nasal hypersensitivity of AR may be attributed to reduction of Sema3A expression and intranasal administration of Sema3A may provide a novel approach to alleviate the allergic symptoms for AR treatment.

Prophylactic effects of the histamine H1 receptor antagonist epinastine and the dual thromboxane A2 receptor and chemoattractant receptor-homologous molecule expressed on Th2 cells antagonist ramatroban on allergic rhinitis model in mice.

The prophylactic use of anti-allergic drugs has been proposed to be effective in the treatment of seasonal allergic rhinitis in humans. However, there is little information regarding the prophylactic effect of thromboxane A(2) (TXA(2)) receptor antagonist on allergic rhinitis. Recent studies revealed that a TXA(2) receptor antagonist ramatroban could block the prostaglandin D(2) (PGD(2)) receptor and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). In the present study, we investigated the prophylactic effects of the histamine H(1) receptor antagonist epinastine and the TXA(2) receptor antagonist ramatroban and seratrodast on mouse models of allergic rhinitis. Female BALB/c mice were sensitized by an intraperitoneal injection of ovalbumin and alum on days 0, 5, 14 and 21. Seven days later, mice were sensitized by intranasal application of ovalbumin thrice a week. Drugs were administered once a day from day 22. The severity of allergic rhinitis was assessed by determining the extent of 2 nasal allergic symptoms (sneezing and nasal rubbing). Histamine sensitivity and eosinophil infiltration into the nasal mucosa were also determined. Epinastine and ramatroban significantly reduced nasal symptoms and the number of eosinophils in the nasal mucosa. Seratrodast showed no effect on nasal symptoms and eosinophil infiltration into the nasal mucosa. In addition, histamine sensitivity was reduced by epinastine and ramatroban. These results indicate that epinastine and ramatroban induce the prophylactic effect on allergic rhinitis.

The safety and efficacy of using a concentrated intranasal midazolam formulation for paediatric dental sedation.

AIM: To add to the evidence base for safe and effective paediatric conscious sedation techniques in primary dental care. OBJECTIVE: To consider the safety and effectiveness of an alternative sedation technique for facilitating dental treatment in anxious children, thereby avoiding dental general anaesthetic. SETTING: Leagrave Dental Sedation Clinic. A primary care-based general and referral clinic for anxious patients, special care dentistry and oral surgery. SUBJECTS, MATERIALS AND METHODS: This is a prospective service evaluation of 114 selected anxious children requiring invasive dental treatment. Each child was administered 0.25 mg/kg intranasal midazolam using a concentrated 40 mg/ml midazolam (INM) in 2% lignocaine solution. MAIN OUTCOME MEASURES: Successful completion of intended dental treatment with a child who is co-operative and who meets the UK accepted definition of conscious sedation. RESULTS: 57% of the children found the administration of the new formulation acceptable. Of the 114 patients who received INM, 104 completed the treatment (91%). The 10 children who could not complete the treatment with INM were converted to intravenous sedation and treatment was completed successfully at the same appointment. During treatment there was no desaturation and only one patient desaturated briefly in the recovery area. Parents rated the technique acceptable in 76% of cases and would have the procedure repeated in 83% of cases. Parents rated this technique as having 8.3 out of 10 with only 5 parents awarding a score of less than 7 out of 10. Side effects included blurred vision, sneezing, headaches, restlessness with one patient having post-operative nausea and vomiting. CONCLUSION: In selected cases intranasal sedation provides a safe and effective alternative for dental GA in short invasive procedures limited to one or two quadrants in children. Other techniques, e.g., oral and intravenous sedation, appear to have a much higher acceptability of administration. This technique may be useful if inhalation sedation, oral sedation or intravenous sedation is considered and the child is still unco-operative, either as a technique on its own or to facilitate cannulation for intravenous sedation. It is recommended that this technique should only be used by dentists skilled in intravenous paediatric sedation with midazolam with the appropriate staff training and equipment at their disposal.

[Clinical trial on the effect of buphenine, aminophenazone and diphenylpyraline hydrochloride in treating the common cold in children of 6 to 24 months of age]. / Ensayo clínico sobre el efecto de la bufenina, aminofenazona y el clorhidrato de difenilpiralina en el tratamiento del resfriado común en niños de seis a 24 meses de edad.

INTRODUCTION: Acute respiratory infections are the second leading cause of morbidity in children under 18 years. Several drugs have been used with variable efficacy and safety, trying to reduce the associated symptoms and improve quality of life. OBJECTIVE: To evaluate the efficacy and safety of buphenine, aminophenazone and diphenylpyraline hydrochloride when compared with placebo for the control of symptoms associated with common cold in children 6-24 months of age. MATERIAL AND METHODS: Randomized clinical trial, double blind, placebo controlled, in 100 children < 24 months of any gender, with symptoms associated to common cold. They received the drug under study vs. placebo for seven days. Both groups received acetaminophen. The change on common cold related symptoms were evaluated. Statistic analysis was made with STATA 11.0 for Mac. RESULTS: Fifty-three children were randomized to study drug and forty-seven to placebo. Age of children in each group was similar (12.2 +/- 5.8 months vs. 12.7 +/- 5.8 months, p NS). There were significant differences between groups in relation to rhinorrea and sneezing resolution, with better results in Flumil group and no adverse events observed. CONCLUSIONS: The results in this study indicates that Flumil is a safe and effective drug for control of symptoms present in the common cold in children aged 6-24 months.

Factors prompting sneezing in intravenously sedated patients receiving local anesthetic injections to the eyelids.

PURPOSE: To investigate the frequency of sneezing among patients receiving intravenous sedation and periocular local anesthetic for oculoplastic procedures in a single center. To identify potential risk factors involved. DESIGN: Prospective, consecutive, interventional case series in a single tertiary-referral oculoplastic unit. PARTICIPANTS: A total of 294 patients undergoing 314 isolated oculoplastic procedures, performed under intravenous sedation with periocular local anesthetic from November 2007 to November 2008. METHODS: Prospective data collection on patient demographics, history of photic sneezing, intravenous sedative, depth of sedation, nasal oxygen, and periocular infiltration site. Standard local anesthetic was used in all cases, but the intravenous sedation was at the discretion of the attending anesthesiologist (7 in total). MAIN OUTCOME MEASURES: Sneezing or attempted sneezing within 5 minutes of injection of the local anesthetic, as determined by agreed observation between attending staff. RESULTS: Sneezing was observed in 16% of cases. No association was found between sneezing and patient age or presence of nasal oxygen. A weakly positive association was observed with male gender (55% sneezers vs. 37% non-sneezers, P = 0.03, relative risk [RR] = 1.5, confidence interval [CI], 1.1-2.0), bilateral infiltration (65% vs. 40%, P = 0.005, RR = 1.6, CI, 1.2-2.1), and upper eyelid infiltration (73% vs. 54%, P = 0.01, RR = 1.4, CI, 1.1-1.7). Photic sneezing was described in 47% of sneezers and 19% of non-sneezers (P = 0.0004, RR = 2.6, CI, 1.6-4.0). Because propofol was given to 95% of patients, no association with sneezing could be ascertained. However, opioid derivatives were found to be protective (12% vs. 43%, P<0.0001, RR = 0.3, CI, 0.1-0.6), whereas midazolam doubled the risk of sneezing (45% vs. 22%, P = 0.0008, RR = 2.1, CI, 1.4-3.0). Deep sedation (Ramsay score 5-6) also strongly increased the sneeze risk (65% vs. 23%, P<0.0001, RR = 2.8, CI, 2.1-3.8). CONCLUSIONS: Propofol-based intravenous sedation, in combination with periocular local anesthetic injections, induces sneezing in approximately one sixth of general oculoplastic cases. Male gender, a history of photic sneezing, bilateral or upper eyelid infiltration, deep sedation, and the concurrent administration of midazolam all increased the risk, whereas adjunctive opioid use reduced the risk.

Characterization of anti-inflammatory properties and evidence for no sedation liability for the novel antihistamine SUN-1334H.

BACKGROUND: The anti-inflammatory potential of antihistamines has significant clinical utility. Long-term pharmacotherapy of so-called 'safe' antihistamines may be hampered by side effects in the central nervous system. In the present study, the new potential antihistamine SUN-1334H was compared with different antihistamines for anti-inflammatory effects, sedation potential and interaction with alcohol. METHOD: Nasal and skin allergy were induced in guinea pig and mice by ovalbumin sensitization and challenge. Neurogenic nasal inflammation was induced by capsaicin. Sedation potential and interaction with alcohol were assessed by i.v. and intracerebroventricular pentobarbital-induced sedation and alcohol-induced ataxia models. RESULTS: Ovalbumin sensitization and challenge caused rhinitis pathology including inflammatory cell infiltration, IL-4, and protein leakage in the nasal lavage fluid (NLF) and presence of inflammatory cells in nasal epithelium. A 5-day treatment of antihistamines reduced these markers of inflammation. SUN-1334H, cetirizine and hydroxyzine caused comparable inhibition of NLF leukocytes, IL-4 and total protein concentrations. Fexofenadine and desloratadine showed moderate inhibition of NLF leukocytes and had no significant effect on IL-4 concentration. While fexofenadine had no effect on total protein concentration, the effect of desloratadine was comparable with the other antihistamines. In neurogenic nasal inflammation induced by capsaicin, SUN-1334H and fexofenadine caused better inhibition at lower and middle dose levels than the other antihistamines. In skin allergy models, SUN-1334H showed potent reduction of passive and active cutaneous anaphylactic reactions. In central nervous system side effects models, SUN-1334H, desloratadine and fexofenadine were devoid of any significant effects. CONCLUSIONS: The results are suggestive of a high anti-inflammatory to sedation index of SUN-1334H among leading antihistamines.

Participation of prostaglandin E2 receptor in nasal congestion of Brown Norway rats.

The aim of the present study was to clarify the involvement of prostaglandin E(2) (PGE(2)) in nasal congestion in Brown Norway (BN) rats. For this purpose, we studied the effects of PGE(2) receptor (EP(1), EP(2), EP(3) and EP(4)) agonists on nasal congestion and sneezing induced by toluene 2,4-diisocyanate (TDI). Enhanced pause (Penh) was increased 1 h (early phase) and 4 h (late phase) after TDI challenge. Sulprostone (an EP(3) receptor agonist) inhibited the increase of Penh, an index of nasal congestion, in both early and late phase responses. On the other hand, PGE(1) alcohol (an EP(4) agonist) increased Penh in the early phase response. Moreover, sulprostone inhibited sneezing, an immediate response by TDI challenge. These results indicate that EP(3) receptor is responsible for the relief of nasal congestion in both early and late phase responses, and EP(4) receptor is correlated with the development of nasal congestion in the early phase response. In addition, EP(3) receptor also participates in sneezing in allergic rhinitis induced by TDI challenge in BN rats.