Effects of amphetamine on human nasal mucosa

The present study was devised to determine the effects of amphetamine on the sympathetic function of human nasal mucosa. A tissue bath method was employed on the vitro preparations of nasal turbinate mucosa from adult patients with nasal allergies or hypertrophic rhinitis. The effects of amphetamine on the contractile response of isolated human nasal mucosal blood vessels were investigated following electrical field stimulation and methoxamine. The results showed that amphetamine inhibited field stimulation and antagonized the effects on mucosal contraction induced by methoxamine. Likewise, the drug increased mucosal basal tension but had local drug toxicity when a 10^–4 M solution was used. Amphetamine could potentiate mucosal contraction induced by norepinephrine or epinephrine. The study indicated that amphetamine may increase sympathetic function by potentiating the effect of norepinephrine and that high concentrations of amphetamine may actually antagonize a-adrenoceptors.     

Efficacy of vardenafil in human nasal mucosa

ObjectiveLevitra, a phosphodiesterase-5 (PDE5) inhibitor, is the trade name of vardenafil. It is applied to treatment of erectile dysfunction. PDE5 inhibitors dilate the penile blood vessels and cause prolonged erections. However, the effects of Levitra on human nasal mucosa are not yet fully explored.Materials and methodsWe examined the effectiveness of Levitra on human nasal mucosa directly in vitro by testing: 1) effect on human nasal mucosa resting tension; 2) effect on contraction caused by 10⁻⁶ M methoxamine as a sympathetic mimetic; 3) effect of the drugs on electrically induced human nasal mucosa contractions.ResultsThe results showed that addition of methoxamine to the incubation medium caused the nasal mucosa to contract in a dose-dependent manner. Addition of Levitra at doses of 10⁻⁴ M elicited a significant relaxation response to 10⁻⁶ M methoxamine-induced mucosa strip contraction. Levitra could not inhibit electrical field stimulation-induced spike contraction and had a minimal effect on the basal tension of nasal mucosa as the concentration increased.ConclusionThis study indicated that high concentrations of Levitra had a significant spasmolytic effect by antagonizing α-adrenoceptors. Moreover, nasal obstruction might not be relieved in patients suffering from erectile dysfunction and stuffy noses who were concomitant using α-adrenergic agonist and Levitra.     

Interaction of cocaine with nasal mucosa

Canine nasal mucosa was studied in vitro to examine (1) the production of vasoconstriction by cocaine and, (2) the epithelial permeability of cocaine. Cocaine, by itself, failed to induce any contraction of the nasal blood vessels but did enhance contractions resulting from electrical stimulation or addition of norepinephrine. Results indicate that cocaine produces vasoconstriction by blocking the reuptake of endogenous norepinephrine rather than any direct action on vascular smooth muscle. Cocaine was found to be three times more permeable than sucrose, which has a similar molecular weight. The transepithelial permeability of cocaine was independent of direction and did not display competition. Results indicate that cocaine permeates by simple diffusion and that the relatively high permeability is due to a greater lipid solubility. Cocaine was found to accumulate in the nasal mucosa. A significant portion of the accumulation is associated with specific sites that are characteristic of catecholamine uptake sites.     

Responses of resistance and capacitance vessels in human nasal mucosa to beta-receptor agonists

To investigate the responses of nasal vessels, divided into resistance and capacitance vessels, to a beta-receptor agonist in human, mucosal blood flow of the inferior turbinate and nasal airway resistance were measured when 1.5 mg terbutaline was applied topically. Mucosal blood flow was measured by the hydrogen clearance method just beneath the site where terbutaline in physiological saline (0.02 ml) was applied on an extremely localized area of the nasal mucosa. Nasal airway resistance of the ipsilateral and contralateral nasal cavities was measured separately by anterior rhinomanometry when terbutaline in normal saline (0.1 ml) was sprayed in the unilateral nasal cavity. Topical application of terbutaline elicited neither a significant increase of mucosal blood flow of the inferior turbinate nor an increase of nasal airway resistance. beta-Receptors seem not to be as densely distributed both in the resistance vessels and in the capacitance vessels as to cause vasodilatation by their activation in the nasal mucosa.     

Nasal mucosal blood flow at rest and during exercise

Nasal airway resistance increases at rest in the supine position and decreases during exercise due to changes of the thickness of the nasal mucosa regulated by the capacitance vessels. The resistance vessels regulating blood flow have not not been evaluated in these conditions before. In 15 healthy subjects the nasal mucosal blood flow was measured in rest and exercise with the 133Xe washout method. No change in blood flow was registered during exercise, which demonstrates that the blood flow and the blood content of the human nasal mucosa are not affected in the same way by exercise.     

Low temperature decreased tension in isolated hypertrophic human nasal mucosa

BACKGROUND: The purpose of this study was to evaluate the effect of low temperature on basal tension in isolated hypertrophic human nasal mucosa with or without alpha1-agonist stimulation. METHODS: A tissue bath for isolated nasal mucosa was used. Tension in strips of human turbinate mucosa that were untreated and treated with an alpha1-adrenoreceptor agonist, methoxamine (10 microM), was recorded continuously in a stepwise manner in temperatures that varied from 37 to 10 degrees C. RESULTS: The changes of tension in the human nasal mucosa were found to be temperature-dependent in both untreated and treated tissues, with tension decreasing to 48.6% at 10 degrees C in comparison with 100% at 37 degrees C in the untreated group, the presence of methoxamine (10 microM) had minimal effect. CONCLUSION: Low temperature induced a rapid and reproducible relaxation in isolated hypertrophic human nasal mucosa that was not affected by the presence of the alpha1-agonist methoxamine (10 microM).     

A comparison of the effects of two commonly used vasoconstrictors on nasal mucosal blood flow and nasal airflow.

This study compared two commonly used vasoconstrictors, cocaine and xylometazoline. Non-invasive techniques of measurement were utilised, with active anterior rhinomanometry indirectly assessing changes in nasal mucosal blood volume, and laser Doppler flowmetry assessing changes in nasal mucosal blood flow. Twelve healthy volunteers received 0.1 ml of the topical vasoconstrictor at the anterior end of both inferior turbinates. Following the application of xylometazoline, a significant rise in nasal airflow (p less than 0.005), and a significant fall in blood flux occurred in the probe nostril (p less than 0.05). Following the application of cocaine, no significant change in nasal airflow occurred (p less than 0.05), but a significant fall in blood flux occurred in the probe nostril (p less than 0.02). A comparison of the paired data for the same subject demonstrated no significant difference in the change in blood flux produced by xylometazoline and cocaine, but a significant difference in the change in airflow produced by the two vasoconstrictors (p less than 0.005).     

On ciprofloxacin concentration in chronic rhinosinusitis

Objective

Considering that all the evidence indicates that chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are distinct entities, the aim of this study was to compare the concentrations obtained in plasma and in sinonasal mucosa with oral and nasal topical ciprofloxacin, in patients with and without nasal polyps, without evaluating the effectiveness of the use of an antibiotic.

Absorption of Topical Cocaine in Rhinologic Procedures

Although topical intranasal cocaine remains a common anesthetic in nasal surgery, controversy surrounds its dosage and mucosal absorption. A prospective study of 12 patients undergoing nasal surgery was performed to evaluate the absorption of cocaine solution from standard cotton pledgets. Of a 160-mg cocaine solution applied, a mean amount of 102 mg or 63.8% was recovered by gas chromatography/mass spectrometry analysis. Similar analysis of nasopharyngeal packs revealed less than 1.5% cocaine loss in the nasopharynx. Serum levels of cocaine were rarely detectable and did not correlate with either the amount of nasal absorption or time of mucosal contact. These results indicate that less than 37% of cocaine is absorbed from cotton pledgets during nasal surgery. The cocaine dose of 160 mg, used by many otolaryngologists, did not result in significant plasma levels. Laryngoscope, 106:1223-1225, 1996     

Suppression and recovery of voltage-gated currents after cocaine treatments of olfactory receptor cells

Objective

Cocaine (1–5% concentrations) is commonly used as a local anesthetic for the otorhinolaryngeal surgery of the nasal cavity. Recent reports indicate that some patients complain of olfactory deficits after surgery, and decreased olfaction is found in cocaine abusers. In spite of these reports, the effects of cocaine on the olfactory receptor cells are unknown.

Methods

Effect of cocaine was examined in olfactory receptor cells isolated from the newt. Under the voltage clamp with the whole-cell recording configuration, the voltage-gated currents were recorded when the membrane potential was depolarized from a holding potential of −100 mV in a step wise between −90 mV and +40 mV.

Results

When cocaine was applied by a puff pressure (5%) and the extracellular solution, the voltage-gated currents, including inward and outward components, were significantly reduced. The dose–suppression curves of cocaine for sodium and potassium currents could be fitted by the Hill equation. Half-blocking concentration of sodium and potassium currents were 43 μM and 557 μM; Hill coefficient was 1.1 and 0.9, respectively.

Conclusion

This rapid and complete recovery from the suppression was confirmed even after the treatments with the high concentration cocaine. This fact implies that cocaine does not affect olfactory ability after locally high dose treatments of nasal cavity in surgical operation.     

Scanning electron microscopy of nasal arterioles effected by vasoactive agents

Summary Morphological changes in nasal blood vessels induced by - and -adrenergic and cholinergic agonists were studied under a scanning electron microscope after removal of extracellular connective tissue and the basal lamina. Arterioles were constricted and dilatated following topical application of -adrenergic and cholinergic agonists. Distinctive morphological changes were observed on their smooth muscle cells. Smooth muscle cells of constricted arterioles had a rugged surface with numerous fine invaginations. However, in dilatated arterioles the cells had a smooth surface and intercellular spaces were clearly revealed. No remarkable changes were produced in smooth muscle cells by the -adrenergic agonist. It is concluded that nasal arterioles are sensitive to -adrenergic and cholinergic stimulation but not to -adrenergic stimulation.     

Insulin-like growth factor I is a possible pathogenic mechanism in nasal polyps

High concentrations of the trophic peptide insulin-like growth factor I (IGF-I; somatomedin C; SmC) were demonstrated immunocytochemically in all nasal polyps examined, except in areas with necrosis or tissue defects. Most epithelial cells, activated macrophages, and proliferating blood vessels, proved positive, contrasting with the low degree of cellular staining in adjacent normal nasal mucosa. It is proposed that nasal mucosal inflammatory reactions induce local formation and accumulation of IGF-I, which may eventually result in very high IGF-I concentrations in the paranasal sinuses due to the tendency these have to be enclosed, i.e. producing reduced drainage. Assuming that IGF-I constitutes the pathogenic factor, appropriate treatment should be given to reduce the inflammatory reactions and improve drainage.     

Changes in the nasal mucosal microvascular with allergic rhinitis]

The nasal mucosal microvascular of 37 patients with allergic rhinitis had been studied by nasal mucosal microcirculation microscope. It was found that the nasal mucosal microvascular diameter was wider after the nasal challenge test than before, but both after and before the nasal challenge test, the nasal mucosal microvascular diameter in patients with allergic rhinitis was narrower than in normal persons. The number of the microvascular in patients was also less than that in normal persons. The results indicate that the nasal mucosal microvascular with allergic rhinitis are characterized by dilated capacitance vessels and exchange vessels and constricted resistance vessels after nasal allergen challenge.     

A new in vitro method of decongestant assay of nasal mucosa: a preliminary report

BACKGROUND: The calculation of cell planar surface area, successfully used for glomerular mesangial cell-altered contractility, also is a reasonable methodology to assess nasal mucosal contractility. A simple technique that works particularly well with vasoconstriction-inducing agents has been introduced to test the effects of several drugs on patient turbinate nasal mucosa in vitro. This report will introduce this technique and present some of the initial findings. METHODS: We tested epinephrine, norepinephrine, pseudoephedrine HCl, and methoxamine, respectively, for effectiveness as a vasoconstricting drug. We also tested the effectiveness of verapamil as a vasodilating drug. A piece of nasal mucosa approximately 3 x 4 mm in size was mounted with a 27-gauge needle and submersed in a 4-mL muscle bath in a Petri dish at room temperature. The bath consisted of 4 mL of Kreb's solution. We recorded the decrease of nasal mucosa planar surface area in response to the application of vasoconstricting agents, as measured using a digital microscope connected to a Pentium III with morphometric software, as the estimated degree of contraction. A photograph of the same mucosa was taken every 3 minutes for a total period of 18 minutes. RESULTS: Nasal mucosa that was mounted in a muscle bath in a Petri dish and treated with a small dose of a nasal decongestant was l observed to contract. Drug dosage determined the degree of nasal mucosa contraction. Nasal mucosa similarly prepared but treated with a vasodilating agent, such as verapamil, exhibited a relaxation response only when pretreated with a vasoconstricting agent, such as methoxamine. Both vasoconstricting and vasodilating drugs induce dose-related responses in planar surface calculation. CONCLUSION: In this study, drug dosage determined the degree of nasal mucosa contraction. We also found that the rate of contraction and percent of contraction were dose dependent. We believe this new method will prove useful in studying the effects of drugs on nasal blood vessels.     

Lignocaine with adrenaline: is it as effective as cocaine in rhinological practice?

This double-blind study compares the effectiveness of two local anaesthetics with vasoconstrictive activity (10% cocaine and 4% lignocaine with adrenaline 1:1000) used in the nose. Anterior rhinomanometry was used to assess changes in nasal mucosal blood volume from a reduction in congestion of the nasal mucosa with a resulting reduction in nasal resistance. Nasendoscopy was then performed and the degree of subjective discomfort evaluated. Twenty patients presenting with nasal obstruction but without evidence of structural disease and nine healthy volunteers were entered into the study. Each received 10% cocaine in one nostril, and 4% lignocaine with adrenaline (1: 1000)) in the other in a double-blind study. In all subjects, there was a significant reduction of nasal resistance after the administration of both drugs (P < 0.005). The anaesthetic effects of both agents were comparable with subjects reporting only a mild discomfort during nasendoscopy. We conclude from this study that 4% lignocaine with adrenaline (1: 1000) solution is as effective as 10% cocaine.     

Efficacy of ice packs in the management of epistaxis

There are no uniformly accepted criteria for the management of epistaxis. The usefulness of ice application in the treatment of epistaxis as a first aid method is not generally accepted, but is widespread. In order to evaluate the effect of cold application on the blood vessels of the nasal mucosa, their blood flow and blood content were investigated on 56 healthy volunteers before and after exposure to cold in the neck area. Nasal mucosal microcirculatory blood flow was measured directly by non-invasive laser Doppler flowmetry in Kiesselbach's area. Changes in the nasal mucosal blood content were estimated using a conventional computer-aided rhinomanometer by measuring alterations in nasal airflow. After ice application in the neck area, no statistically significant effects on the blood vessels of the nasal mucosa were seen. These results do not support the usefulness of this manoeuvre in the treatment of epistaxis.     

Beta-adrenergic mechanisms in the nasal mucosa vascular bed

In thiopentone-anesthetized mature pigs (n = 7), local intra-arterial infusion of the ₂-adrenoceptor agonists terbutaline and salbutamol and the ₃-agonist BRL 37344 induced dose-dependent increases in nasal arterial blood flow (BF) and volume of the nasal mucosa (reflecting capacitance vessel function). Increases were also found in the laser Doppler flowmeter signal, reflecting superficial mucosal BE. In contrast to terbutaline and salbutamol, BRL 37344 showed marked effects on volume. Pretreatment with the -adrenoceptor blocker propranolol significantly reduced the vasodilatory effects of terbutaline and salbutamol, whereas the BF increase evoked by BRL 37344 was not affected. Exogenous noradrenaline (NA) induced in vitro dose-dependent contractions of human nasal mucosa biopsies obtained from patients with non-allergic chronic rhinitis (n = 21) or non-allergic nasal polyposis (NANP, n = 16). On a molar basis, the contractile effect of NA was significantly greater in nasal mucosa samples without histological abnormalities when compared to biopsies with abundant inflammatory cells and edema within the submucosa. In the presence of propranolol, the vasoconstrictor effect of NA was significantly enhanced in biopsies with abundant inflammatory cells obtained from patients with NANP (P<0.01). This observation suggests the possible occurrence of a ₂ hyper-reactivity in the nasal mucosa of patients with NANP. After precontraction in a Krebs-Ringer solution with 50 nM K⁺, all nasal biopsies studied showed dose-dependent relaxation to terbutaline, salbutamol and BRL 37344. This relaxant effect was markedly reduced after pretreatment with propranolol. These observations suggest that ₂- and ₃-adrenergic vasodilatatory mechanisms may be similar in the nasal mucosa of the pig and man.     

Comparison of cocaine alone or with adrenaline on nasal mucosal blood flow.

Cocaine is commonly used in ENT practice for its vasoconstrictor and anaesthetic properties. It is sometimes combined with adrenaline. The laser Doppler Flowmeter was used to compare the effect of 5 per cent cocaine alone or with adrenaline (1 in 1,000) on nasal mucosal blood flow. The results show an average fall in blood flow of 76.7 per cent for cocaine with adrenaline, compared to 61.2 per cent with cocaine alone. The difference is significant (P less than 0.05). The time taken for the blood flow to fall was an average of 131 s and 160 s respectively. These differences are not significant.     

Bilateral nasal vascular responses to unilateral sympathetic stimulation

Unilateral preganglionic cervical sympathetic stimulation in the anaesthetized cat evoked vasoconstriction in both nasal cavities, dependent on stimulation frequency. Vasoconstriction in the contralateral cavity was 15--20% of that of the stimulated side. Similar findings were obtained on unilateral Vidian nerve stimulation. Vasoconstriction evoked in the sympathectomized nasal cavity by stimulating the opposite cervical chain was reduced but not abolished by sectioning the posterior nasal and ethmoidal nerves of the stimulated side. It is suggested that vasoconstrictor fibres reach the opposite cavity either in these nerves or by way of blood vessels, but more likely that sympathetic fibres from these pathways innervate blood vessels which supply both nasal cavities.     

内毒素刺激前后鼻黏膜上皮细胞中Toll样受体4 mRNA及核因子κB p50亚型mRNA的表达及意义

目的探讨内毒素(即脂多糖,lipopolysaccharide,LPS)刺激前后 Toll 样受体4(Tolllike receptor 4,TLR4)mRNA 和核因子 kB(nuclear factor kB,NF-kB)p50亚型 mRNA 在正常鼻黏膜上皮细胞中的表达及意义。方法在15例成人鼻中隔偏曲患者(无鼻-鼻窦炎)矫正术中,取正常中鼻甲外侧黏膜组织各2份行组织外植块培养,其中15份加 LPS 刺激培养为 LPS 组,另外为培养组。应用 HE 染色光镜下观察鼻黏膜组织上皮细胞的病理形态学改变;应用核酸分子原位杂交技术检测离体培养正常鼻黏膜组织上皮细胞中 TLR4 mRNA 和 NF-kB p50 mRNA 的表达情况。结果①LPS刺激后,光镜下见正常鼻黏膜上皮细胞纤毛有粘连成束、胞体增大的病理形态学改变;②LPS 组 TLR4mRNA 表达明显高于培养组;LPS 组表达阳性区平均吸光度为1.283±0.027,培养组为0.538±0.038,二组间差异有统计学意义(t=1.761,P<0.05);③NF-kB p50 mRNA 在 LPS 组均出现阳性表达,而培养组阳性率仅为26.7%。LPS 组明显高表达于培养组,且以胞核表达为主,LPS 组表达阳性区平均吸光度为1.668±0.037;培养组为0.372±0.052,二组间差异有统计学意义(t=2.624,P<0.01)。结论 LPS 能通过 TLR4活化 NF-kB p50,进而激活正常鼻黏膜上皮细胞。这可能在 LPS 对鼻黏膜上皮细胞激活和损伤效应中具有一定的作用。