Honokiol, an active compound of Magnolia officinalis, is involved in restoring normal baroreflex sensitivity in hypercholesterolemic rabbits.

This study investigated the effects of methanol extract Magnolia officinalis (MEMO) on baroreceptor reflex sensitivity (BRS) in the hypercholesterolemic rabbits and the involved molecular mechanisms. Male New Zealand white rabbits were randomly divided into Control (normal diet), Cholesterol (0.5% w/w cholesterol diet), and Magnolia groups (0.5% w/w cholesterol diet plus 1% w/w MEMO). The animals were treated with the designated diet for 4 or 8 weeks. BRS in the control of heart rate was assessed by linear regression method. After 8 weeks of treatments, plasma total cholesterol (TC) was significantly elevated in the Cholesterol/Magnolia groups. The arterial blood pressure (aBP) was increased in the Cholesterol and Magnolia groups. The depression of BRS observed in the Cholesterol group was significantly ameliorated in the Magnolia group. After L-NAME (Nω-nitro-Larginine methyl ester, 20 mg/kg, iv), the BRS of the Cholesterol group was significantly improved. Results from our in vitro study further indicated that honokiol, the principle component of MEMO, would protect human umbilical vein endothelial cells (HUVECs) from H2O2-induced damages and inhibit H2O2-induced vascular smooth muscles cells (VSMCs) proliferation, which was evident by the decreased expression of pFAK, and p-Erk1/2. The results of the present study suggested that the improvement of BRS by MEMO in the hypercholesterolemic rabbits might be mediated by the antioxidant property of MEMO as indicated by the results from the L-NAME and in vitro honokiol studies.

Ursolic acid suppresses leptin-induced cell proliferation in rat vascular smooth muscle cells.

Accumulating lines of evidence indicate that high leptin levels are associated with adverse cardiovascular health in obese individuals. Proatherogenic effects of leptin include endothelial cell activation and vascular smooth muscle cell proliferation and migration. Ursolic acid (UA) has been reported to exhibit multiple biological effects including antioxidant and anti-inflammatory properties. In this study, we investigated the effect of UA on leptin-induced biological responses in rat vascular smooth muscle cells (VSMCs). A-10 VSMCs were treated with leptin in the presence or absence of UA. Intracellular reactive oxygen species (ROS) was probed by 2',7'-dichlorofluorescein diacetate. The expression of extracellular signal-regulated kinase (ERK)1/2, phospho-(ERK)1/2, nuclear factor-kappa B (NF-κB) p65 and p50, and matrix metalloproteinase-2 (MMP2) was determined by Western blotting. Immunocytochemistry and confocal laser scanning microscopy were also used for the detection of NF-κB. The secretion of MMP2 was detected by gelatin zymography. UA exhibited antioxidant activities in vitro. In rat VSMCs, UA effectively inhibited cell growth and the activity of MMP2 induced by leptin. These suppressive effects appeared by decreasing the activation of (ERK)1/2, the nuclear expression and translocation of NF-κB, and the production of ROS. UA appeared to inhibit leptin-induced atherosclerosis, which may prevent the development of obesity-induced cardiovascular diseases.

Ursolic acid plays a protective role in obesity-induced cardiovascular diseases.

The metabolic disturbance of obesity is one of the most common risk factors of atherosclerosis. Resistin, an obesity-induced adipokine, can induce the expression of cell adhesion molecules and the attachment of monocytes to endothelial cells, which play an important role in the development of atherosclerosis. Ursolic acid, a pentacyclic triterpenoid found in fruits and many herbs, exhibits an array of biological effects such as anti-inflammatory and antioxidative properties. The aim of this study was to investigate the potential underlying mechanisms of the effect of ursolic acid on resistin-induced adhesion of U937 cells to human umbilical vein endothelial cells (HUVECs). Our data indicated that ursolic acid suppressed the adhesion of U937 to HUVECs and downregulated the expression of adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule-1 (ICAM-1), and E-selectin, in resistin-induced HUVECs by decreasing the production of intracellular reaction oxygen species (ROS) and attenuating the nuclear translocation of NFκB. Ursolic acid appeared to inhibit resistin-induced atherosclerosis, suggesting that ursolic acid may play a protective role in obesity-induced cardiovascular diseases.

Flexibility of internal and external glenohumeral rotation of junior female tennis players and its correlation with performance ranking.

[Purpose] The purpose of this study was to compare the internal and external rotation of the dominant and nondominant shoulders of adolescent female tennis players. The correlation between the shoulder rotation range of motion and the player's ranking was also analyzed. [Subjects and Methods] Twenty-one female junior tennis players who were 13 to 18 years old participated in this study. A standard goniometer was used to measure the internal and external rotation of both glenohumeral joints. The difference in internal and external rotation was calculated as the glenohumeral rotation deficit. The year-end ranking of each player was obtained from the Chinese Taipei Tennis Association. [Results] The internal rotation of the dominant shoulder was significantly smaller than that of the nondominant shoulder. Moreover, player ranking was significantly and negatively correlated with the internal rotation range of motion of both shoulders. On the other hand, the correlations of the internal and external rotation ranges of motion with the age, height, and weight were not significant. [Conclusion] The flexibility of the glenohumeral internal rotation is smaller in the dominant shoulder than of the nondominant shoulder in these junior female tennis players. Flexibility of the glenohumeral internal rotation may be a factor affecting performance in junior female tennis players.

Thymol reduces oxidative stress, aortic intimal thickening, and inflammation-related gene expression in hyperlipidemic rabbits.

Atherosclerosis plays a key role in the development of cardiovascular diseases, and is often associated with oxidative stress and local inflammation. Thymol, a major polyphenolic compound in thyme, exhibits antioxidant and anti-inflammatory properties. In this study, we measured the in vitro antioxidant activity of thymol, and investigated the effect of thymol on high-fat-diet-induced hyperlipidemia and atherosclerosis. New Zealand white rabbits were fed with regular chow, high-fat and high-cholesterol diet (HC), T3, or T6 (HC with thymol supplementation at 3 mg/kg/d or 6 mg/kg/d, respectively) for 8 weeks. Aortic intimal thickening, serum lipid parameters, multiple inflammatory markers, proinflammatory cytokines, and atherosclerosis-associated indicators were significantly increased in the HC group but decreased upon thymol supplementation. In summary, thymol exhibits antioxidant activity, and may suppress the progression of high-fat-diet-induced hyperlipidemia and atherosclerosis by reducing aortic intimal lipid lesion, lowering serum lipids and oxidative stress, and alleviating inflammation-related responses.

The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer's Disease.

Amyloid precursor protein (APP) has been modified by ß and γ-secretase that cause amyloid deposits (plaques) in neuronal cells. Glyceraldhyde-derived AGEs has been identified as a major source of neurotoxicity in Alzheimer's disease (AD). In a previous study, we demonstrated that glyceraldehyde-derived AGEs increase APP and Aß via ROS. Furthermore, the combination of AGEs and Aß has been shown to enhance neurotoxicity. In mice, APP expression is increased by tail vein injection of AGEs. This evidence suggests a correlation between AGEs and the development of AD. However, the role played by AGEs in the pathogenesis of AD remains unclear. In this report, we demonstrate that AGEs up-regulate APP processing protein (BACE and PS1) and Sirt1 expression via ROS, but do not affect the expression of downstream antioxidant genes HO-1 and NQO-1. Moreover, we found that AGEs increase GRP78 expression and enhance the cell death-related pathway p53, bcl-2/bax ratio, caspase 3. These results indicate that AGEs impair the neuroprotective effects of Sirt1 and lead to neuronal cell death via ER stress. Our findings suggest that AGEs increase ROS production, which stimulates downstream pathways related to APP processing, Aß production, Sirt1, and GRP78, resulting in the up-regulation of cell death related pathway. This in-turn enhances neuronal cell death, which leads to the development of AD.

Cell migration is regulated by AGE-RAGE interaction in human oral cancer cells in vitro.

Advanced glycation end products (AGEs) are produced in an irreversible non-enzymatic reaction of carbohydrates and proteins. Patients with diabetes mellitus (DM) are known to have elevated AGE levels, which is viewed as a risk factor of diabetes-related complications. In a clinical setting, it has been shown that patients with oral cancer in conjunction with DM have a higher likelihood of cancer metastasis and lower cancer survival rates. AGE-RAGE (a receptor of AGEs) is also correlated with metastasis and angiogenesis. Recent studies have suggested that the malignancy of cancer may be enhanced by glyceraldehyde-derived AGEs; however, the underlying mechanism remains unclear. This study examined the apparently close correlation between AGE-RAGE and the malignancy of SAS oral cancer cell line. In this study, AGEs increased ERK phosphorylation, enhanced cell migration, and promoted the expression of RAGE, MMP2, and MMP9. Using PD98059, RAGE antibody, and RAGE RNAi to block RAGE pathway resulted in the inhibition of ERK phosphorylation. Cell migration, MMP2 and MMP9 expression were also reduced by this treatment. Our findings demonstrate the importance of AGE-RAGE with regard to the malignancy of oral cancer, and help to explain the poor prognosis of DM subjects with oral cancer.

Induction of necrosis in human liver tumor cells by α-phellandrene.

α-Phellandrene (α-PA) is a component of dietary spices and herbs. The effect of α-PA on anticancer is unclear. This study aims to investigate the effects of α-PA on liver tumor cell death fate. Human liver tumor (J5) cells were incubated with α-PA and analyzed for cell cycle distribution, expression of Bax, Bcl-2, poly (ADP-ribose) polymerase (PARP) protein, and caspase-3 activity of J5 cells, and levels of nitric oxide (NO) production, lactate dehydrogenase (LDH) leakage, and ATP depletion were also analyzed in this study. Results found that α-PA significantly (P < 0.05) decreased the cell viability of J5 cells after 24-h treatment. The cell cycle distribution, Bax, Bcl-2, PARP protein levels, and caspase-3 activity of J5 cells did not change for 24 h after treatment with 30 µM α-PA. Reactive oxygen species levels significantly increased, mitochondrial membrane potential levels significantly decreased when J5 cells were treated with 30 µM α-PA for 24 h (P < 0.05). Thirty µM α-PA significantly (P < 0.05) increased the necrotic cell number, NO production, LDH leakage, and ATP depletion after 24 h of incubation. These results suggest that α-PA induced J5 cell necrosis but not apoptosis, and α-PA-induced necrosis possibly involved ATP depletion.

Effect of sulforaphane on growth inhibition in human brain malignant glioma GBM 8401 cells by means of mitochondrial- and MEK/ERK-mediated apoptosis pathway.

In recent studies, sulforaphane (SFN) has been seen to demonstrate antioxidant and anti-tumor activities as well as potent chemopreventive action against cancer. The present study investigates the anti-proliferation (using MTT assay, SFN demonstrated cytotoxic activity against GBM 8401 cell with IC(50) values at 35.52 µM) and induced apoptosis of SFN 24-h treatment in the cells of human brain malignant glioma GBM 8401 cells. We studied the MMP, caspase, MEK/ERK activation, and NF-κB transcription factor activity. Our results indicate that SFN inhibits cell proliferation as well as the activation of apoptosis in GBM 8401 cells. Both effects increased in proportion to the dosage of SFN, and apoptosis was induced via mitochondria- and caspase-dependent pathways. Daily s.c. injections of SFN for 3 weeks in severe combined immunodeficient mice (SCID) with GBM8401 s.c. tumors resulted in a decrease in mean tumor weight of 69-75 % compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, SFN may provide antitumor activity in established malignant glioma.

Demethoxycurcumin Retards Cell Growth and Induces Apoptosis in Human Brain Malignant Glioma GBM 8401 Cells.

Demethoxycurcumin (DMC; a curcumin-related demethoxy compound) has been recently shown to display antioxidant and antitumor activities. It has also produced a potent chemopreventive action against cancer. In the present study, the antiproliferation (using the MTT assay, DMC was found to have cytotoxic activities against GBM 8401 cell with IC(50) values at 22.71 µM) and induced apoptosis effects of DMC have been investigated in human brain malignant glioma GBM 8401 cells. We have studied the mitochondrial membrane potential (MMP), DNA fragmentation, caspase activation, and NF-κB transcriptional factor activity. By these approaches, our results indicated that DMC has produced an inhibition of cell proliferation as well as the activation of apoptosis in GBM 8401 cells. Both effects were observed to increase in proportion with the dosage of DMC treatment, and the apoptosis was induced by DMC in human brain malignant glioma GBM 8401 cells via mitochondria- and caspase-dependent pathways.

Altered nitroxidergic and NMDA receptor-mediated modulation of baroreflex-mediated heart rate in obese Zucker rats.

Arterial baroreflex, an important physiological regulatory system for buffering systemic blood pressure, is impaired in obesity. This study investigated whether the blunted baroreflex function in obesity is attributed to the altered nitroxidergic or N-methyl--aspartate (NMDA) mechanism. Baroreflex bradycardia responses, blood pressure and heart rate in 30 lean and 30 obese anesthetized Zucker rats (8-12 weeks of age) were assessed after injecting phenylephrine with intravenous preadministration of saline (control), dextromethorphan (DXM, NMDA receptor antagonist, 10 mg kg(-1)) or N(G)-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor, 100 mg kg(-1)). Compared with lean rats (-2.00+/-0.29 b.p.m. mm Hg(-1)), the baroreflex sensitivity (BRS) in obese rats (-0.43+/-0.05 b.p.m. mm Hg(-1)) was significantly blunted. The BRS was significantly suppressed by DXM in lean rats but not in obese rats. After administration of L-NAME, BRS was significantly suppressed in lean Zucker rats but not in obese Zucker rats. The normal BRS was significantly suppressed in lean rats after administration of both DXM and L-NAME, and the blunted BRS in obesity was significantly blocked to nearly no BRS after administration of both DXM and L-NAME. This study suggests that BRS is blunted in obese rats and that blunted baroreflex is, at least in part, attributed to altered nitroxidergic or NMDA receptor-mediated modulation.

Chlorogenic acid attenuates adhesion molecules upregulation in IL-1beta-treated endothelial cells.

BACKGROUND: Expression of cell adhesion molecules (CAM) on the endothelium and the attachment of monocytes to endothelium may play a major role in the early atherogenic process. Chlorogenic acid is a phenolic compound present in coffee, apples, pears, berries, almonds, artichokes, and aubergines. Previous studies have indicated that CA possesses antioxidant activity in vitro. AIM: We investigated the effects of chlorogenic acid and probucol on monocyte-like adhesion, adhesion molecule expression, NF-kappaB translocation and ROS production in IL-1beta-induced human umbilical vein endothelial cells (HUVECs). RESULTS: According to the results of the MTT assay, we chose 25 and 50 mumol/L to perform the experiments. Chlorogenic acid dose-dependently suppressed IL-1beta-induced mRNA expression of vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1 and endothelial cell selectin. Chlorogenic acid also suppressed the IL-1beta-induced production of ROS. We also observed that chlorogenic acid attenuated or blocked IL-1beta-induced nuclear translocation of nuclear factor-kappaB subunits p50 and p65, which in turn attenuated CAM expression at the transcription level. Furthermore, chlorogenic acid significantly reduced the adhesion of human monocyte cells (U937) to IL-1beta-treated HUVECs in a dose-response manner. These results are similar to that of probucol. CONCLUSIONS: We conclude that chlorogenic acid exhibit anti-inflammatory effects in HUVECs by inhibition of U937 monocyte-like adhesion, adhesion molecule expression, NF-kappaB translocation, and ROS production. The anti-inflammatory activity of chlorogenic acid in HUVECs suggests that chlorogenic acid could be useful in the prevention of atherosclerosis.

Changing clinical presentations and survival pattern in trisomy 18.

BACKGROUND: The clinical presentations and survival patterns of infants with trisomy 18 have changed with increasing utilization of prenatal ultrasound and amniocentesis, and improvements in neonatal intensive care. METHODS: We obtained data on duration of survival, male to female ratio, and clinical details for patients with trisomy 18, and calculated the prevalence rate. RESULTS: We studied 31 consecutive trisomy 18 infants. The estimated prevalence was 1/4, 144. Eleven (35%) were premature infants, and 20 (65%) were full term. Mean birth weight was 1896 g. Median life expectancy was 12 days; 11 days for males and 14 days for females (p = 0.87). The short-term survival rates of 1 week, 4 weeks, and 6 months were 58%, 32%, and 10%, respectively. The long-term survival rates of 1 year, 2 years, and 3 years were 6%, 6%, and 3%, respectively. Families signed do-not-resuscitate consent forms for five male (50%) and 19 female infants (90%) (p = 0.043). CONCLUSION: All trisomy 18 infants in this study were preterm or full-term deliveries. Mean birth weight was lower than previously reported, and a high percentage of families signed do-not-resuscitate consent forms. Females did not survive longer than males, due to more females not being resuscitated. Most infants died in the first few weeks of life, but 3-6% of infants lived for 21 year. The possibility of long-term survival should be considered when counseling parents regarding trisomy 18.

Early or late surgical ligation of medical refractory patent ductus arteriosus in premature infants.

Optimal time to surgical ligation of patent ductus arteriosus (PDA) in very-low-birth-weight (< 1500 g) premature infants remains an area of controversy. We compared the outcomes of early or late ligation of medical refractory PDA in very-low-birth-weight premature infants. Fifty-six infants underwent surgical closure of PDA after failure of or having contraindications to medical treatment. Thirteen infants were in the early ligation (< or = 14 days) and 43 in the late ligation (> 14 days) groups. Basic clinical features, major morbidity of prematurity and mortality were compared. Clinical features and major outcomes were similar. The early ligation group had earlier onset of symptomatic PDA (5.7 +/- 1.6 days vs. 8.1 +/- 3.6 days, p = 0.024), and fewer days of total parenteral nutrition (TPN) (39.6 +/- 13.9 days vs. 60.4 +/- 31.4 days, p = 0.025) and ventilator use (11.1 +/- 6.7 days vs. 18.6 +/- 10.5 days, p = 0.019). Early ligation of medical refractory PDA in very-low-birth-weight premature infants improves enteral feeding tolerance and reduces TPN and ventilator use, but long-term benefits need further investigation.

Genomic-wide analysis of lymphatic metastasis-associated genes in human hepatocellular carcinoma.

AIM: To identify the genes related to lymph node metastasis in human hepatocellular carcinoma (HCC), 32 HCC patients with or without lymph node metastasis were investigated by high-throughput microarray comprising 886 genes. METHODS: The samples of cancerous and non-cancerous paired tissue were taken from 32 patients with HCC who underwent hepatectomy with lymph node dissection. Total RNA was extracted from the cells obtained by means of laser microdissection (LCM) and was amplified by the T7-based amplification system. Then, the amplified samples were applied in the cDNA microarray comprising of 886 genes. RESULTS: The results demonstrated that 25 up-regulated genes such as cell membrane receptor, intracellular signaling and cell adhesion related genes, and 48 down-regulated genes such as intracellular signaling and cell cycle regulator-related genes, were correlated with lymph node metastasis in HCC. Amongst them were included some interesting genes, such as MET, EPHA2, CCND1, MMP2, MMP13, CASP3, CDH1, and PTPN2. Expression of 16 genes (MET, CCND1, CCND2, VEGF, KRT18, RFC4, BIRC5, CDC6, MMP2, BCL2A1, CDH1, VIM, PDGFRA, PTPN2, SLC25A5 and DSP) were further confirmed by real-time quantitative reverse transcriptional polymerase chain reaction (RT-PCR). CONCLUSION: Tumor metastasis is an important biological characteristic, which involves multiple genetic changes and cumulation. This genome-wide information contributes to an improved understanding of molecular alterations during lymph node metastasis in HCC. It may help clinicians to predict metastasis of lymph nodes and assist researchers in identifying novel therapeutic targets for metastatic HCC patients.

Carnosic acid prevents the migration of human aortic smooth muscle cells by inhibiting the activation and expression of matrix metalloproteinase-9.

The migration and matrix metalloproteinase (MMP) activation of vascular smooth muscle cells may play key roles in the development of atherosclerosis. Carnosic acid (CA) is a phenolic compound found in herbs, including rosemary and sage. Previous studies indicated that CA possesses antioxidant activity in vitro. In this study, we investigated the effects of CA on TNF-alpha-induced cell migration, the formation of intracellular reactive oxygen species, the translocation of NF-kappaB and the activation and expression of MMP-9 in human aortic smooth muscle cells (HASMC). The Matrigel migration assay showed that CA (10 and 20 micromol/l) effectively inhibited TNF-alpha-induced migration of HASMC as compared with the control group. To explain this inhibitory effect, MMP-9 was assayed by gelatin zymography and Western blot. The results indicated that CA inhibited MMP-9 activity and expression. Furthermore, the production of reactive oxygen species and the nuclear translocation of NF-kappaB p50 and p65 induced by TNF-alpha were dose-dependently suppressed by CA pretreament. These results indicate that CA has anti-inflammatory properties and may prevent the migration of HASMC by suppressing MMP-9 expression through down-regulation of NF-kappaB.

Ellagic acid suppresses oxidised low-density lipoprotein-induced aortic smooth muscle cell proliferation: studies on the activation of extracellular signal-regulated kinase 1/2 and proliferating cell nuclear antigen expression.

Proliferation of intimal vascular smooth muscle cells is an important component in the development of atherosclerosis. Ellagic acid is a phenolic compound present in fruits (raspberries, blueberries, strawberries) and walnuts. The present study investigated the effect of ellagic acid on the oxidised LDL (ox-LDL)-induced proliferation of rat aortic smooth muscle cells (RASMC). The study found that ellagic acid significantly inhibited ox-LDL-induced proliferation of RASMC and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Furthermore, ellagic acid also blocked the ox-LDL-induced (inducible) cell-cycle progression and down regulation of the expression of proliferating cell nuclear antigen (PCNA) in RASMC. Therefore, ellagic acid reduced the amount of ox-LDL-induced proliferation of RASMC via inactivation of the ERK pathway and suppression of PCNA expression. These results may significantly advance the understanding of the role that antioxidants play in the prevention of atherosclerosis.

Inhibitory effect of Magnolia officinalis and lovastatin on aortic oxidative stress and apoptosis in hyperlipidemic rabbits.

Oxidative stress and apoptosis are 2 major characteristics of the progression of atherosclerosis. Both lovastatin and Magnolia officinalis are hypocholesterolemic agents. Therefore, we investigated the effect of M. officinalis extract on the prevention of atherosclerosis in comparison with lovastatin. Twenty hyperlipidemic rabbits were served one of the following diets: a high-fat and cholesterol diet (cholesterol group, 10% corn oil and 0.5% cholesterol), a high fat and cholesterol diet supplemented with M. officinalis extract (300 mg/kg) or lovastatin (6 mg/kg). The plasma lipids, oxidative stress (measured by free radical, malondialdehyde, and oxidative DNA damage), and arterial lesions significantly decreased in the M. officinalis and lovastatin groups when compared with the cholesterol group. Moreover, the expressions of Fas ligand, caspase 8, and caspase 9 in the aortic arches were also markedly lowered after M. officinalis and lovastatin supplements. Therefore, the results indicate that the antiatherogenic effect of M. officinalis is involved with a suppression of oxidative stress and with the down-regulation of apoptosis-related gene expression in hyperlipidemic rabbits.

Increased prevalence of interleukin-1 receptor antagonist gene polymorphism in patients with chronic rhinosinusitis.

OBJECTIVE: To assess the association of the interleukin (IL)-1beta and the IL-1 receptor antagonist (IL-1Ra) gene polymorphisms with chronic rhinosinusitis (CRS). DESIGN: Genotyping of the 2 IL-1beta gene (IL1B) polymorphisms (promoter and exon) and the IL-1Ra gene (IL1RN) polymorphism (intron 2) was performed using polymerase chain reaction and restriction length fragment polymorphism analyses. SETTING: Prospective study, tertiary medical center. PATIENTS: The study population comprised 88 consecutive adult Taiwan-Chinese patients who met stringent criteria for CRS and received endoscopic sinus surgery and 103 healthy volunteers of the same ethnicity and similar age range. Of the 88 patients, 61 had CRS with nasal polyps, while the other 27 had CRS without nasal polyps. RESULTS: There were significant differences in the distribution of the IL1RN polymorphism between the control subjects and patients with CRS (P<.05). The II allele of IL1RN occurred more frequently in the CRS patient group, and the odds ratio for subjects with I/II genotype was 3.39 (95% confidence interval, 1.25-9.18). In the case of CRS without nasal polyps, the odds ratio for subjects with I/II genotype was further increased to 4.75 (1.39-16.25). There was no association between the other 2 polymorphisms of IL1B and CRS. CONCLUSION: Increased prevalence of IL1RN polymorphism in patients with CRS suggests that this polymorphism, or a polymorphism in linkage disequilibrium with it, may be involved in the development of CRS.

Altered expression profile of superoxide dismutase isoforms in nasal polyps from nonallergic patients.

OBJECTIVE/HYPOTHESIS: Nasal polyposis (NP) is a chronic inflammatory disease of the upper respiratory tract. The pathophysiology is unknown but has been shown to be multifactorial. Free radical-mediated damage has been implicated in the pathogenesis of NP. Superoxide dismutases (SODs) are the first and the most important line of antioxidant enzyme defense against reactive oxygen species. Moreover, isozymes of the SOD family are critical for modulating the activity of nitric oxide, a gaseous free radical that is believed to play roles in the physiology and pathology of respiratory tracts. However, the expression profile of SOD isoforms in NP remains unclear. We aimed to investigate the expression profile of the SOD isoforms in nasal polyps from nonallergic patients. STUDY DESIGN: Prospective study. METHODS: Nasal polyp tissues were obtained from eight nonallergic patients who underwent elective polypectomy; mucosal specimens from the middle turbinates were acquired from eight subjects without NP as control tissues. The expression profile of SOD isoenzymes, SOD1, SOD2, and SOD3, in the nasal tissues was determined by reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blotting (WB). RESULTS: NP in all eight of the NP patients manifested as severe or recurrent sinonasal polyposis clinically. The expression pattern of SOD isoenzymes evaluated by RT-PCR analysis indicated that the mean levels of SOD1 mRNA and, to a greater extent, SOD3 mRNA were higher in polyp tissues than in control tissues. There was no significant difference in the expression levels of SOD2 mRNA between the two groups. The data from ELISA and WB analysis showed that there were increased expressions of SOD1 and SOD3 protein in polyp tissues compared with the control tissues, but there was no difference in the expression of SOD2 protein between the two groups. The results from RT-PCR, ELISA, and WB were paralleled and revealed that the expressions of SOD1 and, to a greater extent, SOD3 were higher in polyp tissues than in the control group. CONCLUSIONS: The expressions of SOD3 and SOD1 were higher in polyp tissues. These results are consistent with previously reported data and support the hypothesis that there is increased oxidative stress in NP. Our data also suggest that the SODs might be important in the pathogenesis of NP; however, the roles these SOD isoforms, especially SOD3, play in both normal nasal mucosa and NP require further clarification.