Choriogenin transcription in medaka embryos and larvae as an alternative model for screening estrogenic endocrine-disrupting chemicals.

This study assessed the transcription levels of estrogen-responsive genes, such as vitellogenins (Vtg1 and Vtg2), choriogenins (ChgL, ChgH, and ChgHm), cytochrome P450 aromatase (CYP19a1b), and ER subtypes (ERα, ERß1, and ERß2), in 7 days-post-fertilization (dpf) embryos and 9 and 12 dpf larvae of medaka (Oryzias latipes) exposed to estrogenic endocrine-disrupting chemicals (EDCs). The <5 h-post-fertilization embryos were exposed to EDCs such as 17ß-estradiol (E2), p-n-nonylphenol (NP), and bisphenol A (BPA). In E2 (0.10-222 nM)-treated 7 dpf embryos and 9 or 12 dpf larvae, ChgL, ChgH, and ChgHm expression was up-regulated in a concentration-dependent manner. By contrast, interestingly, Vtg1 and Vtg2 expression was not induced in E2-treated 7 dpf embryos but was significantly induced in 9 and 12 dpf larvae, suggesting a developmental-stage-specific regulatory mechanism underlying Vtg expression. The maximum concentrations of NP (0.09-1.5 µM) and BPA (1.8-30 µM) up-regulated Chg expression in 9 or 12 dpf larvae, and the relative estrogenic potencies (REPs) of E2, NP, and BPA were 1, 2.1 × 10-4, and 1.0 × 10-5, respectively. Chg messenger RNA (mRNA) in medaka embryos and larvae can be used as a sensitive biomarker for screening potential estrogenic EDCs. Our assay system using embryos and larvae can be used as an in vivo alternative model because independent feeding stages (e.g., embryonic and early larval stages) are suitable alternatives.

Nanosecond pulsed electric field incorporation technique to predict molecular mechanisms of teratogenicity and developmental toxicity of estradiol-17ß on medaka embryos.

Herein, we propose using a nanosecond pulsed electric field (nsPEF) technique to assess teratogenicity and embryonic developmental toxicity of estradiol-17ß (E2 ) and predict the molecular mechanisms of teratogenicity and embryonic developmental defects caused by E2 on medaka (Oryzias latipes). The 5 hour post-fertilization embryos were exposed to co-treatment with 10 µm E2 and nsPEF for 2 hours and then continuously cultured under non-E2 and nsPEF conditions until hatching. Results documented that the time to hatching of embryos was significantly delayed in comparison to the control group and that typical abnormal embryo development, such as the delay of blood vessel formation, was observed. For DNA microarray analysis, 6 day post-fertilization embryos that had been continuously cultured under the non-E2 and nsPEF condition after 2 hour co-treatments were used. DNA microarray analysis identified 542 upregulated genes and one downregulated gene in the 6 day post-fertilization embryos. Furthermore, bioinformatic analyses using differentially expressed genes revealed that E2 exposure affected various gene ontology terms, such as response to hormone stimulus. The network analysis also documented that the estrogen receptor α in the mitogen-activated protein kinase signaling pathway may be involved in regulating several transcription factors, such as FOX, AKT1 and epidermal growth factor receptor. These results suggest that our nsPEF technique is a powerful tool for assessing teratogenicity and embryonic developmental toxicity of E2 and predict their molecular mechanisms in medaka embryos.

Generation of electron beams carrying orbital angular momentum.

All forms of waves can contain phase singularities. In the case of optical waves, a light beam with a phase singularity carries orbital angular momentum, and such beams have found a range of applications in optical manipulation, quantum information and astronomy. Here we report the generation of an electron beam with a phase singularity propagating in free space, which we achieve by passing a plane electron wave through a spiral phase plate constructed naturally from a stack of graphite thin films. The interference pattern between the final beam and a plane electron wave in a transmission electron microscope shows the 'Y'-like defect pattern characteristic of a beam carrying a phase singularity with a topological charge equal to one. This fundamentally new electron degree of freedom could find application in a number of research areas, as is the case for polarized electron beams.

Gene expression analyses of vitellogenin, choriogenin and estrogen receptor subtypes in the livers of male medaka (Oryzias latipes) exposed to equine estrogens.

In the present study, we investigated transcriptional profiles of estrogen-responsive genes, such as vitellogenins (Vtg1 and Vtg2), choriogenins (ChgL and ChgH) and estrogen receptor subtypes (ERα, ERß1, and ERß2), in the liver of male medaka fish (Oryzias latipes) that were exposed to six equine estrogens (1-300 ng l(-1) ) for 3 days. Our quantitative reverse transcription-polymerase chain reaction (RT-PCR) analyses revealed that the expression levels of hepatic Vtg, Chg and ERα genes in male medaka responded to various types and concentrations of equine estrogens. The estrogenic potentials of the tested chemicals were in the order of equilin > 17ß-estradiol > equilenin > 17ß-dihydroequilin > 17ß-dihydroequilenin > 17α-dihydroequilin > 17α-dihydroequilenin, showing the higher estrogenic potential of equilin than that of 17ß-estradiol. Our results also showed that the estrogenicities of 17ß-dihydroequilin and 17ß-dihydroequilenin were more potent than that of 17α-dihydroequilin and 17α-dihydroequilenin. Furthermore, in gene expression analyses of hepatic ER subtypes, observations were made to note that 17ß-estradiol and equilin induced ERα transcription in male medaka, and the ERα transcription level had significantly positive correlations with the expression of Vtg and Chg genes. In contrast, in the same 17ß-estradiol and equilin treatment groups, it was shown that the transcription levels of hepatic ERß1 and/or ERß2 had significantly negative correlations with the expression of Vtg and Chg genes. These results suggested some potential involvement of the ER subtypes in the regulation of Vtg and Chg gene expressions in the liver. This is the first report describing the comprehensive analyses of in vivo estrogenicity of the equine estrogens in male medaka. Copyright © 2016 John Wiley & Sons, Ltd.

Transcriptional response of mysid crustacean, Americamysis bahia, is affected by subchronic exposure to nonylphenol.

Nonylphenol (NP) has been classified as an endocrine-disrupting chemical. In this study, we conducted mysid DNA microarray analysis with which has 2240 oligo DNA probes to observe differential gene expressions in mysid crustacean (Americamysis bahia) exposed to 1, 3, 10 and 30 µg/l of NP for 14 days. As a result, we found 31, 27, 39 and 68 genes were differentially expressed in the respective concentrations. Among these genes, the expressions of five particular genes were regulated in a similar manner at all concentrations of the NP exposure. So, we focused on one gene encoding cuticle protein, and another encoding cuticular protein analogous to peritrophins 1-H precursor. These genes were down-regulated by NP exposure in a dose-dependent manner, and it suggested that they were related in a reduction of the number of molting in mysids. Thus, they might become useful molecular biomarker candidates to evaluate molting inhibition in mysids.

Endocrine-disrupting potentials of equine estrogens equilin, equilenin, and their metabolites, in the medaka Oryzias latipes: in silico and DNA microarray studies.

Although several previous studies have demonstrated the presence of equine estrogens in the aquatic environment, limited data are currently available on the endocrine-disrupting potentials in fish and the risks they pose to aquatic organisms. To investigate the interactions of major equine estrogens equilin (Eq) and equilenin (Eqn), as well as their metabolites 17α-dihydroequilin, 17ß-dihydroequilin, 17α-dihydroequilenin and 17ß-dihydroequilenin, with the estrogen receptor α (ERα) of medaka (Oryzias latipes), a three-dimensional model of the ligand-binding domain (LBD) of ERα was built in silico, and docking simulations were performed. The docking simulation analysis indicated that the interaction of 17ß-dihydroequilenin with the ERα LBD is the most potent, followed by those of 17α-dihydroequilin and 17ß-dihydroequilin, whereas those of Eq and Eqn were least potent. We further analyzed gene expression profiles in the livers of male medaka exposed to Eq and Eqn. A DNA microarray representing 6000 genes revealed that 24-h exposure to Eq and Eqn (100 ng/L) upregulated the expression of 6 and 34 genes in the livers of males, respectively. Genes upregulated by Eq included the estrogenic biomarker genes vitellogenins and choriogenins, suggesting the estrogenic potential of Eq. In contrast, Eqn exposure upregulated several cancer-related genes, such as mediator complex subunit 16 and RAS oncogene family members, suggesting a carcinogenic potential for Eqn. These results suggest that equine estrogens may have not only endocrine-disrupting potentials via the ERα signaling pathway but also carcinogenic potency in male medaka.

[Preoperative evaluation of surgery for intractable aspiration based on the prognostic nutritional index].

Because there is no absolute indicator of the nutritional status and prognosis in patients with severe aspiration problems, it is quite difficult to arrive at a true long-time prognosis. By performing surgery for intractable aspiration on such patients, both the prognosis and QOL of the patients could be expected to improve. In our department, we have experienced patients dying within 6 months after surgery. In these cases, the patient's preoperative nutritional status was not good. Therefore, we consider that, when we adopt this procedure, there should be some indicators we should use which could have an effect on the prognosis of such nutritionally-challenged patients. In patients who underwent surgery for intractable aspiration; we examined the relationship between their survival and the prognostic nutritional index (PNI) which is an indicator of the risk of complications such as post-operative events in the surgical field. We investigated the relationship between the prognosis and the postoperative indicators of each of the following: WBC, CRP, serum albumin level, and PNI. Out of a total of 31 cases, the average O-PNI of eight cases in which death occurred was 29.45, and the average of six cases in which death occurred within 6 months after surgery was 28.26. The average O-PNI of the survivors was 36.01. A significant association was noted between the early postoperative deaths and some of the four indicators namely that serum albumin level and O-PNI. Based on the ROC curve, the O-PNI offered higher precision than the albumin level. The cut-off value of the O-PNI value for early postoperative mortality rate was 32. The early postoperative mortality rate was 44.4% in patients with less than 32 O-PNI in the preoperative examination, but if it were O-PNI 32 or more, the early postoperative mortality rate was 9.1%, significantly lower. Therefore, O-PNI could be useful as one of the prognostic evaluation factors in the case of preoperative surgery for intractable aspiration. Based on the O-PNI score, it was possible to evaluate the survival benefit associated with this operative procedure. We showed a treatment algorithm based on the preoperative O-PNI value. We believe there is a necessity to develop preoperative effective nutritional therapy as a future issue.

Experiences of Percutaneous Endoscopic Approach for the Mastoid Lesions: A Novel Minimally Invasive Ear Surgery.

OBJECTIVES: We developed a novel keyhole surgery, named "percutaneous endoscopic ear surgery" (PEES), with the aim of further reducing the invasiveness of otologic surgery. We reported the cases we encountered and retrospectively analyzed the invasiveness of PEES. METHODS: We analyzed the ears of eight patients who underwent PEES for mastoid lesions that could not be manipulated with transcanal endoscopic ear surgery (TEES) at our hospital between July 2021 and November 2022. We performed PEES alone in three patients, including one case of type A (preauricular incision) and two cases of type B (retroauricular incision). The last five patients underwent combined endoscopic ear surgery, which is simultaneous PEES and TEES. In these cases, one patient underwent type A PEES, and four patients underwent type B PEES. RESULTS: PEES was performed in all patients without converting to conventional microscopic mastoidectomy. The mean length of skin incisions was 19.1 ± 4.5 mm, which was smaller than that in conventional mastoidectomy. In all cases, the average length of the major axis of the keyhole was <10 mm, indicating that sufficient minimally invasive surgery was achieved. The average depth from the keyhole to the deepest site was 21.6 ± 8.9 mm. There was no change in the mean hearing level before and after the surgery. CONCLUSION: PEES is a minimally invasive procedure for manipulating lesions in the mastoid. In addition, the combination of PEES and TEES is an ideal, minimally invasive procedure that can be used to treat all regions of the temporal bone.

Measuring the orbital angular momentum of electron vortex beams using a forked grating.

The present study experimentally examines how an electron vortex beam with orbital angular momentum (OAM) undergoes diffraction through a forked grating. The nth-order diffracted electron vortex beam after passing through a forked grating with a Burgers vector of 1 shows an OAM transfer of nℏ. Hence, the diffraction patterns become mirror asymmetric owing to the size difference between the electron beams. Such a forked grating, when used in combination with a pinhole located at the diffraction plane, could act as an analyzer to measure the OAM of input electrons.

Adverse effects of contamination by fipronil and its derivatives on growth, molting, and gene expression in the mysid crustacean, Americamysis bahia, in Japanese estuaries.

Concentrations of fipronil (Fip) and several of its derivatives were detected in samples from four rivers and four estuaries in Japan. LC-MS/MS analysis detected Fip and its derivatives, except for fipronil detrifluoromethylsulfinyl, in almost all samples. The total concentrations of the five compounds were approximately two-fold greater in river water (mean: 21.2, 14.1, and 9.95 ng/L in June, July, and September, respectively) compared to those in estuarine water (mean: 10.3, 8.67, and 6.71 ng/L, respectively). Fipronil, fipronil sulfone (Fip-S), and fipronil sulfide (Fip-Sf) represented more than 70 % of all compounds. This is the first report to demonstrate the contamination of estuarine waters of Japan by these compounds. We further investigated the potentially toxic effects of Fip, Fip-S, and Fip-Sf on the exotic mysid, Americamysis bahia (Crustacea: Mysidae). The lowest effective concentrations of Fip-S (10.9 ng/L) and Fip-Sf (19.2 ng/L) on mysid growth and molting was approximately 12.9- and 7.3-fold lower than Fip (140.3 ng/L), suggesting they had higher toxicity. Quantitative reverse transcription polymerase chain reaction analysis revealed that ecdysone receptor and ultraspiracle gene expression were not affected after 96-h of exposure to Fip, Fip-S, and Fip-Sf, suggesting that these genes may not be involved in the molting disruption induced by Fip, Fip-S, and Fip-Sf. Our findings suggest that environmentally relevant concentrations of Fip and its derivatives can disrupt the growth of A. bahia by promoting molting. However, further studies are required to elucidate its molecular mechanism.

Developmental toxicity and transcriptome analysis of equine estrogens in developing medaka (Oryzias latipes) using nanosecond pulsed electric field incorporation.

Equine estrogens (EQs) are steroidal hormones isolated from the urine of pregnant mares and are used in the formulation of human medications. This study initially investigated the embryonic developmental toxicity of equilin (Eq) and equilenin (Eqn) in medaka (Oryzias latipes). Malformations were observed in embryos exposed to nominal concentrations of 1 and 10 mg/L of Eq and Eqn. Delayed hatching was observed at 1 mg/L of Eq. To further investigate the molecular mechanism of developmental toxicity caused by Eq and Eqn, transcriptome and bioinformatics analyses were performed. Among 2016 and 3855 total differentially expressed genes (DEGs), 1117 DEGs overlapped between Eq. (55.4 % of total DEGs) and Eq. (29.0 % of total DEGs). Gene ontology indicated effects in terms related to blood circulation and cell junctions. Pathway analyses using DEGs revealed that both Eq and Eqn treatments at 10 mg/L affected various KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, such as neuroactive ligand-receptor interaction, mitogen-activated protein kinase signaling, retinol metabolism, and cytokine-cytokine receptor interaction. These results suggest that the disruption of these KEGG pathways is involved in the developmental toxicity of EQs in medaka embryos.

Production of electron vortex beams carrying large orbital angular momentum using spiral zone plates.

We report the production of electron vortex beams carrying large orbital angular momentum (OAM) using micro-fabricated spiral zone plates. A series of the spherical waves, focussing onto different positions along the propagating direction of the electron beam, were observed. The nth order vortex beam has an OAM n times larger than that of the first-order vortex beam. We observed an electron vortex with an OAM up to in a high-order diffracted wave. A linear dependence of the diameter of the vortex beam on the OAM was observed, being consistent to numerical simulations.

Orbital angular momentum-resolved convergent-beam electron diffraction by the post-selected injection of electron beam.

Recent advances in the production of electron vortex beams carrying orbital angular momentum (OAM) offer unique opportunities to explore materials at the nanoscale level. We present a novel method for observing convergent-beam electron diffraction (CBED) patterns by using an electron vortex beam. In a transmission electron microscope, a series of electron vortex beams generated by a forked grating mask located above the specimen illuminate the specimen, and CBED patterns are imaged onto the observation plane of the microscope, selecting one of the electron vortex beams using an aperture located beneath the specimen. We demonstrate that the post-selection method yields the same OAM-resolved CBED patterns as when a single convergent electron beam is injected. The formation mechanism of the post-selected CBED is also discussed. This post-selection method is general and can be applied to electron energy-loss spectroscopy to probe multipole excitations using electron vortex beams.

[A case of Schneiderian middle-ear and sinonasal papilloma with intracranial complications].

Unlike Schneiderian papilloma, a widespread benign epithelial neoplasm arising in the sinonasal tract mucosa of the nasal cavity, paranasal sinus, trachea, and larynx, middle-ear Schneiderian papilloma is extremely rare. We report a case of recurrent Schneiderian papilloma spreading to the bilateral middle ear and right paranasal sinus, and eventually causing cerebellar complications. A-52-year old woman seen for episodes of inarticulateness was first, found to have middle right ear and right ethmoid papilloma, that occurred thereafter is the middle left ear. This bilateral middle-ear papilloma is, to our knowledge, the only case reported thus far, and fell into a low-risk malignant formation group based on HPV-DNA testing. Given previous cases, we concluded that ours warranted meticulous follow-up because recurrence and malignancy are more common in multiple-site middle-ear papilloma as in our case rather than papilloma of the middle ear alone.

Efficacy of perampanel for epileptic seizures and daily behavior in a patient with Leigh syndrome: A case report.

BACKGROUND: Leigh syndrome (LS) is a mitochondrial disorder that shows abnormal basal ganglia lesion and psychomotor regression. Although vitamins have been used for LS, we have not found any effective drug. CASE PRESENTATION: A 26-year-old man who showed psychomotor delay and short stature at the age of 1 year was diagnosed with LS according to the results of cerebrospinal fluid and high signal intensity in the bilateral striatum on T2-weighted magnetic resonance imaging. He demonstrated psychomotor delay and breathing disorders, but the progression was very slow. His symptoms suddenly worsened at the age of 24 years after acute epididymitis. He showed epileptic seizures simultaneously and his activities of daily living (ADL) significantly worsened. Several antiepileptic drugs were ineffective, but his seizures were suppressed by a low dose of perampanel and his ADL improved. CONCLUSION AND DISCUSSION: Our case showed that low-dose perampanel could be a drug for epileptic seizures and improvement of ADL in patients with LS.

Natural Molybdenite- and Tyrosinase-Based Amperometric Catechol Biosensor Using Acridine Orange as a Glue, Anchor, and Stabilizer for the Adsorbed Tyrosinase.

To develop a natural mineral-based electrochemical enzyme biosensor, natural molybdenite (MLN), tyrosinase (TYR), and acridine orange (AO) were coadsorbed onto a glassy carbon electrode (GCE). The developed TYR/AO/MLN-GCE-based amperometric TYR biosensor exhibited excellent performance for highly sensitive determination of catechol (linear range, 0.1-80 µM; sensitivity, 0.0315 µA/µM; LOD, 0.029 µM; response time, <4 s) with good reproducibility and good operational and storage stabilities. The electrochemical impedance spectroscopy (EIS) and quartz crystal microbalance with dissipation (QCM-D) revealed interesting roles of AO: (1) an efficient glue for enhancing the amount of the adsorbed TYR on the MLN-GCE, (2) an anchor for efficient orientation of the adsorbed TYR on the MLN-GCE, and (3) a stabilizer providing a suitable microenvironment for the adsorbed TYR on the MLN-GCE surface. This physical adsorption-based AO-coupled enzyme-modification strategy onto natural MLN would be a versatile strategy to develop cost-effective and environment-friendly natural mineral-based electrochemical biosensors and bioelectronic devices.

In vivo and in silico analyses of estrogenic potential of equine estrogens in medaka (Oryzias latipes).

Equine estrogens (EEs) are widely used in hormone replacement therapy pharmaceuticals for postmenopausal women. Previous studies have shown that EEs occur in the aquatic environment; however, the potential estrogenicity and risk of EEs in aquatic organisms, including fish, have yet to be studied in detail. Therefore, we evaluated the estrogenic potential of major EEs, namely equilin (Eq), 17α-dihydroequilin (17α-Eq), 17ß-dihydroequilin (17ß-Eq), equilenin (Eqn), 17α-dihydroequilenin (17α-Eqn), and 17ß-dihydroequilenin (17ß-Eqn), on medaka (Oryzias latipes) using in vivo and in silico assays. Quantitative real-time RT-PCR analyses revealed that expression levels of choriogenin L (ChgL) and choriogenin H (ChgH) in medaka embryos responded to various types and concentrations of EEs in a concentration-dependent manner, whereas transcription levels of vitellogenin 1 were not significantly affected by any of the EEs in the concentration range tested. The order of the in vivo estrogenic potencies of EEs was as follows: 17ß-Eq > Eq > 17ß-Eqn > Eqn > 17α-Eqn > 17α-Eq. Additionally, the 50% effective concentrations (EC50) of 17ß-Eq was lower than that of 17ß-estradiol. We also investigated the interaction potential of EEs with medaka estrogen receptor (ER) subtypes in silico using a three-dimensional model of the ligand-binding domain (LBD) for each ER and docking simulations. All six EEs were found to interact with the LBDs of ERα, ERß1, and ERß2. The order of the in silico interaction potentials of EEs with each ER LBD was as follows: 17ß-Eq > 17α-Eq > Eq > 17ß-Eqn > 17α-Eqn > Eqn. Furthermore, we identified the key amino acids that interact with EEs in each ER LBD; our findings suggest that amino acids and/or their hydrogen bonding may be responsible for the ligand-specific interactions with each ER. This study is the first to comprehensively analyze the estrogenic potential of EEs in medaka both in vivo and in silico.

Potential mechanisms underlying embryonic developmental toxicity caused by benzo[a]pyrene in Japanese medaka (Oryzias latipes).

Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are widely distributed in air, water, and sediments; however, limited data are available regarding their potential adverse effects on the early life stages of fish. In this study, we evaluated the embryonic teratogenicity and developmental toxicity of BaP in Japanese medaka (Oryzias latipes) using a nanosecond pulsed electric field (nsPEF) technique and predicted their molecular mechanisms via transcriptome analysis. The gas chromatography/mass spectrometry analyses revealed that the BaP was efficiently incorporated into the embryos by nsPEF treatment. The embryos incorporating BaP presented typical teratogenic and developmental effects, such as cardiovascular abnormalities, developmental abnormalities, and curvature of backbone. DNA microarray analysis revealed several unique upregulated genes, such as those involved in cardiovascular diseases, various cellular processes, and neural development. Furthermore, the gene set enrichment and network analyses found several genes and hub proteins involved in the developmental effects of BaP on the embryos. These findings suggest a potential mechanism of teratogenicity and developmental toxicity caused by exposure to BaP. The nsPEF and transcriptome analyses in combination can be effective for evaluating the potential effects of chemical substances on medaka embryos.

Analysis of amino acid profiles of blood over time and biomarkers associated with non-alcoholic steatohepatitis in STAM mice.

The changes in free amino acid (AA) levels in blood during the progression from non-alcoholic steatohepatitis (NASH) to hepatocellular carcinoma (HCC) are unclear. We investigated serum AA levels, along with biochemical and histological events, in a mouse model of NASH. We induced NASH in male C57BL/6J mice with a streptozotocin injection and high-fat diet after 4 weeks of age (STAM group). We chronologically (6, 8, 10, 12, and 16 weeks, n=4-12 mice/group) evaluated the progression from steatohepatitis to HCC by biochemical and histological analyses. The serum AA levels were determined using an AA analyzer. Serum aspartate aminotransferase and alanine aminotransferase levels were higher in the STAM group than in the normal group (non-NASH-induced mice). Histological analysis revealed that STAM mice had fatty liver, NASH, and fibrosis at 6, 8, and 10 weeks, respectively. Moreover, the mice exhibited fibrosis and HCC at 16 weeks. The serum branched-chain AA levels were higher in the STAM group than in the normal group, especially at 8 and 10 weeks. The Fischer ratio decreased at 16 weeks in the STAM group, with increasing aromatic AA levels. These results suggested that this model sequentially depicts the development of fatty liver, NASH, cirrhosis, HCC, and AA metabolism disorders within a short experimental period. Additionally, serum amyloid A was suggested to be a useful inflammation biomarker associated with NASH. We believe that the STAM model will be useful for studying AA metabolism and/or pharmacological effects in NASH.

[Outcomes of endoscopic sinus surgery in chronic sinusitis cases complicated/ not complicated by bronchial asthma and eosinophilic infiltration of the sinus mucosa].

BACKGROUND: Intractable sinusitis is, in most cases, complicated by bronchial asthma and severe eosinophilic infiltration of the sinus mucosa. Our aim here was to study the postoperative outcomes of chronic sinusitis complicated/not complicated by bronchial asthma and of cases with eosinophilic sinusitis/non-eosinophilic sinusitis. METHODS: We conducted a prospective analysis of the outcome of 180 patients with or without bronchial asthma and eosinophilic infiltration who underwent endoscopic sinus surgery (ESS) for chronic sinusitis. The patients were divided into four groups by the presence/absence of asthma and presence/absence of eosinophilic infiltration of the sinus mucosa. One surgeon performed the ESS, and all the groups received the same postoperative treatment. RESULTS: The outcomes of ESS were significantly worse in the cases complicated by eosinophilic sinusitis and asthma, especially in relation to the incidence of smell disturbances and the endonasal findings. Patients suffering from chronic sinusitis without asthma showed good improvement following ESS. There was no significant differences in the outcome after ESS between cases of eosinophilic sinusitis and those with non-eosinophilic sinusitis among the patients without asthma. CONCLUSIONS: We contend that eosinophilic sinusitis without asthma may not represent intractable sinusitis. We wish to emphasize that complication by