Experimental acute sinusitis in rabbits. Energy metabolism in sinus mucosa and secretion

In previous studies, sinus secretions have been analysed concerning pO2, pCO2 and pH. In this study the energy metabolism in the maxillary sinus mucosa and secretion was studied in 33 New Zealand White rabbits. In freeze-dried samples, glucose and lactate were analysed by enzymatic assays and ATP by HPLC. In the purulent sinusitis, lactate concentration in the mucosa was 5.67 mmol X kg-1 w.w. and significantly higher than in the control sinus. Also in the non-purulent sinusitis, lactate was increased in the mucosa. The lactate concentrations in the secretion were 9.8 and 8.4 mmol X kg-1 w.w. in purulent and non-purulent secretions respectively and are probably the result of a diffusion from the mucosal cells and of leukocyte metabolism. A reduced ATP content, with increases in ADP and AMP, in the sinus mucosa of the purulent sinusitis suggests a relative energy depletion which could result in impaired epithelial function.     

Experimentally induced sinusitis: the importance of vasomotor regulation

An acute pneumococcal maxillary sinusitis was induced in New Zealand white rabbits by unilateral obstruction of the sinus ostium and then injecting 10(8) Streptococcus pneumoniae into the sinus. After subjecting this bacterial strain to one animal passage, the bacteria were reisolated in nine of ten infected maxillary sinuses. All rabbits developed a unilateral purulent sinusitis, while a non-purulent sinusitis could be induced by occlusion only of the maxillary ostium. By using a non-diffusable tracer, microspheres labelled with Sn113, blood flow measurements were performed on these sinuses. These studies showed that the blood flow of the infected sinuses was significantly higher than on the control side. However, in chronic sinusitis (with a blocked ostium), the blood flow did not differ significantly from that on the control side. Biochemical studies in the animals with purulent sinusitis demonstrated that lactate concentration in the mucosa was significantly higher as compared to the control side. The glucose concentration was significantly lower in the mucosa of the infected side, as was the ATP content of the sinus mucosa in purulent sinusitis. These results indicate an increased glycolysis as well as a relative energy depletion in the sinus mucosa in purulent sinusitis, which could result in an impaired epithelial function.     

Experimentally induced sinusitis: the importance of vasomotor regulation

Summary An acute pneumococcal maxillary sinusitis was induced in New Zealand white rabbits by unilateral obstruction of the sinus ostium and then injecting 10⁸ Streptococcus pneumoniae into the sinus. After subjecting this bacterial strain to one animal passage, the bacteria were reisolated in nine of ten infected maxillary sinuses. All rabbits developed a unilateral purulent sinusitis, while a non-purulent sinusitis could be induced by occlusion only of the maxillary ostium. By using a non-diffusable tracer, microspheres labelled with Sn¹¹³, blood flow measurements were performed on these sinuses. These studies showed that the blood flow of the infected sinuses was significantly higher than on the control side. However, in chronic sinusitis (with a blocked ostium), the blood flow did not differ significantly from that on the control side. Biochemical studies in the animals with purulent sinusitis demonstrated that lactate concentration in the mucosa was significantly higher as compared to the control side. The glucose concentration was significantly lower in the mucosa of the infected side, as was the ATP content of the sinus mucosa in purulent sinusitis. These results indicate an increased glycolysis as well as a relative energy depletion in the sinus mucosa in purulent sinusitis, which could result in an impaired epithelial function.Presented at the First European Congress of Oto-Rhino-Laryngology and Cervico-Facial Surgery, Paris, 26–29 September 1988     

Antileukoprotease in patients with maxillary sinusitis

Antileukoprotease, an inhibitor of leukocyte elastase, was studied in paired sera from 12 patients with maxillary sinusitis. The serum concentration of antileukoprotease was increased at the day of admission to hospital, compared with the serum concentration in convalescence sera. In purulent maxillary sinus secretions antileukoprotease was found in complex with leukocyte elastase, as shown by gel filtration. The findings suggest a local protective function of antileukoprotease in maxillary sinus.     

Bacteria and inflammatory cells in maxillary sinusitis

Summary A series of maxillary sinus mucosal specimens and a series of smears of retained maxillary sinus secretions were studied with regard to the relationship between bacteria and inflammatory cells in order to illustrate aspects of the inflammatory process and to investigate the cause of mucosal damage in maxillary sinusitis. The results show that the granulocytes in the retained secretions are actively phagocytizing organisms if conditions are favourable for the granulocytes. Such situations are present in mucopurulent secretions but mostly not in strictly purulent secretions. A correlation was found between the presence of large numbers of inflammatory cells and tissue destruction, whereas bacterial invasion of the mucosa was a rare phenomenon and seen only in areas where the epithelial lining was destroyed. This indicates strongly that the mucosal damage in sinusitis is caused by inflammatory cells and not primarily by bacteria.     

Na/K-ATPase in rabbit paranasal sinus mucosa during induced sinusitis

Summary Sinusitis was produced in rabbits, after which animals were separated into three groups: allergic sinusitis, induced purulent sinusitis, and spontaneous purulent sinusitis. Mucosal specimens were taken from these animals and normal controls. Na/K-ATPase was localized cytochemically and its activity studied in order to define the energy metabolism of secretion. The Na/K-ATPase reaction was unable to be clearly distinguished in either the allergic sinusitis specimens or the normal mucosa. In both purulent sinusitis groups, an intensive reaction was observed in the subepithelial glands and a weak reaction was found in the goblet cells. The Na/K-ATPase activity in the purulent sinusitis groups was significantly higher than that in the normal control group. The increased Na/K-ATPase activity may be an affect of hyperactivity of the secretory cells. Offprint requests to: M. Miyaguchi, Department of Otolaryngology, Kagawa Medical School, 1750-1 Miki-cho Kita-gun, Kagawa 761-07, Japan     

Bacteria in chronic maxillary sinusitis.

Sixty-one chronically inflamed maxillary sinuses produced 131 bacterial strains from mucosal pieces that were taken during a Caldwell-Luc operation and cultured aerobically and anaerobically. Sinus secretions showed only 62 and nasal secretions 106 bacterial strains. Fourteen mucosal strains, including 11 Haemophilus influenzae, grew heavily. None of 24 mucosal anaerobes showed heavy growth. Of 52 antral mucosae with culturable bacteria, 37 disclosed mixed and 15 pure growth. The bacteriological characteristics of the diseased sinus and the nose did not correlate. The duration or extent of the disease, the macroscopic appearance of the diseased sinus, or the presence or absence of allergy were unrelated to bacteriological findings, except that H influenzae was concentrated in purulent sinuses. Intraoperative culture of antral mucosa seems to give the most reliable picture of the bacteriological condition in chronic maxillary sinusitis.     

Chemotactic properties of retained maxillary sinus secretions

The chemotactic activity of 82 aspirated maxillary sinus secretions obtained from 32 sinuses in 29 patients was assayed with a modified Boyden chamber technique. The secretions were also analysed with respect to the proteolytic activity according to a modification of a technique described by Moroz. In only 3 of 24 sinus secretions obtained from untreated patients with purulent or mucopurulent sinusitis, but in 5 of 8 serous secretions from untreated patients with serous sinusitis a chemotactic activity exceeding random migration was found. A high proteolytic activity was found to be incompatible with a high chemotactic activity. Regarding mucopurulent and purulent sinusitis, treatment by repeated antral aspiration resulted in an increase of the proportion of chemotactically active secretions and a decrease of the proteolytic activity. Repeated antral aspirations in patients with serous sinusitis resulted in less uniform changes of the chemotactic activity.     

A protease inhibitor from human allergic nasal secretions

Protease and antiprotease activities were estimated in nasal secretions from patients with chronic sinusitis and nasal allergy, using [3H]-casein as substrate. In the purulent nasal secretions, strong protease activity was measured, but there was less activity in the allergic nasal secretions. In contrast, trypsin inhibitory activity in allergic nasal secretions was much higher than in nasal secretions from the patients with chronic sinusitis. A protease inhibitor was partially isolated from nasal secretions of the nasal allergic patients by Sephadex G-150 gel chromatography and characterized. This protease inhibitor has an apparent molecular weight of 10,000 D, determined by SDS-polyacrylamidegel electrophoresis. It depresses the activities of bovine pancreatic trypsin, bovine pancreatic chymotrypsin and proteases in nasal purulent secretions, whereas it does not inhibit porcine pancreatic elastase, papain, or human plasmin.     

Microbial flora of nose and paranasal sinuses in chronic maxillary sinusitis

Nasal secretions, maxillary sinus aspirates and specimens of the maxillary sinus mucosa were collected in 44 patients aged between 25 and 60 affected by mono- or bilateral chronic maxillary sinusitis, in order to establish the best sampling technique for microbiological purposes, the most frequently involved bacteria and the physiopathological mechanism underlying chronic maxillary disease. The sinusal mucosa resulted to be the most reliable sample as it reduces contamination and microbial variability. Anaerobic bacteria were isolated in nasal swab (15.6%), in maxillary sinus aspirates (30.4%) and in maxillary sinus mucosa (36.4%) of maxillary sinusitis patients. In controls anaerobic bacteria were isolated only in one nasal swab (2.3%), while they could not be isolated in maxillary sinus aspirates and in maxillary sinus mucosa. The presence of anaerobic bacteria in chronic maxillary sinusitis patients and their absence in controls seem to confirm that anaerobic microorganisms represent the main pathogenetic agents of chronic maxillary sinusitis. The possible physiopathological mechanisms underlying chronic maxillary sinus disease are finally discussed.     

Autoradiographic findings in experimental sinusitis in rabbits

In order to study the effect of a purulent infection in the sinus cavity on the uptake of radionuclide in the surrounding bone, two series of experiments were performed; one using 45Ca-chloride (T1/2 = 153 d), that was given intravenously in a dose of 50 MBq to the previously infected animal, and in the other 99Tcm-DP was used in a dose of 530-1600 MBq. The animals were killed 4-6 hours later and analyzed using an autoradiographic technique and histological examination. Chronic unilateral infection of the maxillary sinus was induced experimentally according to the technique described by Kumlien and Schiratzki (1985). An acute unilateral maxillary sinusitis was induced experimentally according to Johansson et al. (1988). An increased uptake of 99Tcm-DP in the bone surrounding the sinus cavity with an infected mucosa could be seen. This uptake could be seen four days after induction of an acute, purulent, pneumococcal sinusitis, and five months after the induction of an purulent, chronic sinusitis. No increase in uptake could be seen in the mucosa of the sinus with purulent infection. The beta-emitting nuclide gave better resolution in autoradiography than did the gamma-emitting nuclide, and would give better possibilities in identifying structures; however, the specificity to bone of 45Ca was not high enough to be suitable.     

Bacteriology of chronic sinusitis in relation to middle meatal secretion

BACKGROUND: The bacteriology of chronic sinusitis has been studied widely, but some factors may affect the results, such as sample sources and sampling techniques. However, whether the presence of secretion in the middle meatus affects the culture result has been studied rarely. METHODS: When patients with chronic sinusitis underwent functional endoscopic sinus surgery, swab specimens were taken from the ipsilateral middle meatuses and ethmoid sinuses under endoscopic guidance. While taking specimens from the middle meatuses, we observed the presence of secretions in the middle meatuses. The severity of chronic sinusitis was evaluated by preoperative computed tomography, which was scored by the Lund-Mackay system. The scores of the frontal, anterior ethmoid, maxillary sinus, and ostiomeatal complex were cumulated. RESULTS: Between March 2001 and February 2004, 210 pairs of specimens were collected. The secretion was present in 82 middle meatuses and was absent in the other 128 middle meatuses. The culture rates of middle meatus and ethmoid sinus specimens were 70.7 and 51.2%, respectively, for patients with secretions in the middle meatuses and 53.1 and 44.5%, respectively, for patients without secretions in the middle meatuses. The culture rate was significantly different for middle meatus specimens (p = 0.011) and the mean cumulated computed tomography score also was significantly higher in patients with secretions in the middle meatuses than in patients without secretions in the middle meatuses (p < 0.001). CONCLUSION: The results of this study suggest that the presence of secretion in the middle meatus indicates more severe disease in the anterior group of paranasal sinuses.     

Bacterial location in chronic sinusitis

BACKGROUND: In chronic nonallergic sinusitis, it is often assumed that bacteria invade the sinus mucosa where the inflammatory condition begins and is maintained. However, the bacterial presence in a normal or moderately damaged epithelial layer has never been proved in biopsy studies. METHODS: In this study, mucosal samples from six consecutive patients with chronic sinusitis were examined. Transmission electron microscopy was used and the presence of bacterial invasion and formation of phagosomes containing bacteria as a marker of host response were studied. RESULTS: Phagocytosis of bacteria was observed in the sinus mucosa in samples from only one patient. In the other five patients, no signs of phagocytosis were seen. CONCLUSION: Based on these results, we concluded that in chronic sinusitis, bacterial invasion in sinus mucosa is not an obligatory phenomenon.     

黏蛋白基因MUC2在慢性鼻-鼻窦炎筛窦黏膜中的表达

目的：定量检测慢性鼻-鼻窦炎（CRS）筛窦黏膜中黏蛋白基因MUC2的表达,探讨其在CRS黏液过量分泌中的意义。方法：采用荧光定量RT-PCR检测32例CRS患者（CRS组）和8例正常筛窦黏膜患者（正常对照组）中MUC2 mRNA的表达。结果：MUC2 mRNA在CRS组中的表达[（10．55±3．31）×10^10拷贝／g]较正常对照组[（1．40±0．44）×10^10拷贝／g]增高,两组间差异有统计学意义（P〈0．01）。结论：MUC2 mRNA在CRS筛窦黏膜中表达上调,可能是CRS黏液过度分泌的重要因素之一。     

A study on collagenase production of nasal polyp-derived fibroblasts stimulated by nasal secretions of chronic sinusitis

The collagenase produced by mesenchymal cells has been thought to have a great importance in the pathophysiology of connective tissue metabolism and prolongation of chronic inflammation. The factors, such as IL-1 and PMN factor, released by inflammatory cells have been known to induce mesenchymal cells to produce collagenase. In the present study, the collagenase activity of the nasal secretions were estimated using FITC-labelled collagens as substrates. The factor, enhancing the fibroblasts to produce collagenase, was also isolated from nasal secretions and partially characterized. The fibroblasts used in the present study were cultured with explant of the sections of nasal polyp obtained from a patient with chronic sinusitis. The collagenase activity in nasal secretions from patients with chronic sinusitis was high, whereas that of allergic nasal secretions was extremely low. Furthermore, the collagenase productions of nasal polyp-derived fibroblasts were enhanced by the extracts of nasal secretions from patients with chronic sinusitis. Crude extracts of nasal secretions were fractionated by ammonium sulfate precipitation. The active materials precipitated by 50% to 80% ammonium sulfate were further purified by Sephadex G-75 gel chromatography. The molecular weight determination of the active fraction checked by HPLC utilizing for TSK 2,000 SW gel column indicates 20,000 daltons for the active materials. However, the collagenase production of human microvascular endothelial cells derived from nasal mucosa was not enhanced by this factor. Although either the origin or the nature was not confirmed, the factor was considered to relate to the prolongation of chronic inflammation in the nasal and paranasal sinus pathology. Analysis of these factors will expected to establish methods for new therapeutics in chronic inflammation.     

Quantitative analysis of mucin and lectin in maxillary sinus fluids in patients with acute and chronic sinusitis

OBJECTIVES: Sinusitis is characterized by quantitative and qualitative changes in mucus biosynthesis that contribute to sinus disease. In general, patients with acute sinusitis complain of purulent rhinorrhea, whereas those with chronic sinusitis complain of mucoid or mucopurulent rhinorrhea Locally produced mucin largely contributes to the high viscoelasticity of mucus in sinusitis. In this study, the authors attempt to quantify the concentrations of mucin and lectin in the maxillary sinus fluids from these patients. STUDY DESIGN: To assess the concentrations of mucin and lectin in aspirates of 11 acutely and 11 chronically inflamed maxillary sinuses, the concentration of mucin was measured by enzyme-linked immunosorbent assay (ELISA) and that of lectin by sandwiched enzyme-linked lectin assay (ELLA). RESULTS: The concentrations of mucin and lectin that were measured using monoclonal antibodies (HCS 4, HCS 14, and HCS 18) and Ulex europaeus agglutinin-1 (UEA-1) in chronic sinusitis were higher than those in acute sinusitis. The concentration of total protein in chronic sinusitis was lower than that in acute sinusitis. Each mucin and lectin versus total protein ratio in chronic sinusitis was higher than that in acute sinusitis. CONCLUSIONS: These data suggest that hypersecretion in chronic sinusitis may result from locally increased mucin production. Comprehension of this mechanism may be a strategy to prevent the viscous cycle of paranasal sinus fluids in chronic sinusitis.     

TNF-alpha and endotoxin increase hypoxia-induced VEGF production by cultured human nasal fibroblasts in synergistic fashion

OBJECTIVE: Vascular endothelial growth factor (VEGF) promotes angiogenesis and is associated with the invasion and metastasis of malignant tumors. It enhances vascular permeability and is expressed in inflammatory nasal as well as middle-ear mucosa. As the mechanism of VEGF induction during chronic inflammation, such as chronic paranasal sinusitis (CPS) remains to be clarified, we studied the factors regulating the production of VEGF in cultured human nasal fibroblasts and discussed the role of VEGF in the pathogenesis of CPS. METHODS: We used ELISA to quantify VEGF levels in paranasal sinus effusions, nasal secretions, and serum from patients with CPS. In addition, we cultured human nasal fibroblasts isolated from nasal polyps of CPS patients and studied the effects of hypoxia, TNF-alpha, and endotoxin on their production of VEGF using ELISA and PCR. RESULTS: The VEGF concentration was significantly higher in paranasal sinus effusions than in nasal secretions and serum. Nasal fibroblasts produced high levels of VEGF, when cultured under hypoxic condition and this production was remarkably enhanced in the presence of TNF-alpha or endotoxin. CONCLUSION: VEGF is locally produced in paranasal sinuses as well as nasal mucosa and its production is increased in patients with CPS. Hypoxia is associated with the production of VEGF by nasal fibroblasts and TNF-alpha and endotoxin may act synergistically to enhance VEGF production in paranasal sinuses under hypoxic condition.     

Predictive value of nasal bacterial culture for etiological agents in acute maxillary sinusitis

Nasal secretion, aspiration yield and lavage content from the sinus were studied for bacteria in 175 patients (247 sinuses) with acute maxillary sinusitis. The same pathogen was cultured from the nose and aspiration fluid in 91% of cases of acute purulent sinusitis. This indicated a significant predictive value of the nasal bacteriological culture for presence of pathogenic bacteria in the sinus in purulent cases. In cases with no growth of pathogens in the aspirate, the nasal culture showed pathogenic bacteria in about 50%. Examination of the aspiration fluid may occasionally give false negative result in purulent maxillary sinusitis (at least 3% in the present series). In these cases, culture of the irrigation yield may prove helpful.     

鼻咽癌放疗后继发慢性鼻窦炎的临床特征

目的 分析鼻咽癌放疗后继发慢性鼻窦炎的临床特征。方法 对2011年1月至2013年5月来我科门诊及住院治疗的放疗致慢性鼻窦炎患者(放疗组)及单纯慢性鼻窦炎患者(对照组)各40例行视觉模拟评分法(VAS)评价鼻部主观症状、鼻内镜检查、鼻窦CT检查, 并给予相应评分。放疗组中15例及对照组中36例接受鼻内镜鼻窦手术, 术中行上颌窦穿刺, 抽取脓性分泌物行细菌培养。结果 VAS评分:放疗组为鼻塞4.0±0.8, 流脓涕6.5±1.2, 头痛4.3±0.6, 嗅觉减退5.1±1.4, 咳嗽2.7±1.2, 打喷嚏3.7±0.8, 面部疼痛和压迫感4.3±1.2, 耳痛5.3±1.1;对照组为鼻塞4.3±0.7, 流脓涕5.3±1.0, 头痛3.3±0.8, 嗅觉减退4.0±0.9, 咳嗽3.3±1.0, 打喷嚏3.7±0.9, 面部疼痛和压迫感2.2±0.5;其中流脓涕、耳痛症状放疗组较对照组明显;鼻窦CT Lund-Mackay评分: 放疗组为8.2±1.1, 对照组为 6.5±1.3;鼻内镜Lund-Kenndy评分:放疗组为6.2±1.1, 对照组为4.7±0.7;上颌窦分泌物细菌培养结果:放疗组以金黄色葡萄球菌(6/15)、流感嗜血杆菌(3/15)为主, 还有部分未查到细菌生长(4/15);对照组以金黄色葡萄球菌(24/36)、流感嗜血杆菌(6/36)、草绿色链球菌(5/36)为主。结论 放疗致鼻窦炎较单纯慢性鼻窦炎有其自身特点, 其发生机制可能与放射损伤鼻窦纤毛功能, 窦口肿胀、阻塞, 继发细菌感染有关。