Synthesis and evaluation on triglyceride inhibitory activities of novel indole alkaloids / 药学学报

Three tricyclic [6,5,7] and six tetracyclic [6,5,5,5] novel indole alkaloids were synthesized and evaluated on triglyceride inhibitory activities for the first time. Among them, compound 4c showed the most potent activity with IC50 value of 6.35 μmol·L-1. Meanwhile, compound 4c also exhibited a good safety profile at the cellular level. Preliminary mechanism study indicated that 4c might increase intracellular lipid metabolism by activating AMPK. These results provide a novel family of lead compounds for the discovery of anti-NAFLD candidates.

Dynamic changes of vestibular autorotation test in patients with unilateral vestibular dysfunction during rehabilitation / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the dynamic changes of vestibular autorotation test (VAT) before and after vestibular rehabilitation treatment in patients with unilateral vestibular hypofunction (UVH). Methods: A retrospective study was carried out,48 patients who were diagnosed with UVH and under vestibular rehabilitation in department of otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2019 to January 2021 were enrolled. Among them, there were 21 males and 27 females, with an average age of 46.9 years old, including 25 cases of Meniere's disease, 13 cases of sudden deafness with vertigo and 10 cases of vestibular neuritis. The course of disease ranged from 5 days to 10 years. Demographic characteristics, detailed case data and routine examination were collected for the patients. The horizontal gain/phase, vertical gain/phase, and asymmetry of VAT at different frequencies before and after vestibular rehabilitation were collected. The absolute value of the difference between the measured value of 2.0-5.9 Hz before and after rehabilitation and the standard value were statistically analyzed. Results: Before vestibular rehabilitation, the incidence of abnormal gain was 62.5% (30/48), the incidence of abnormal phase was 56.3% (27/48), and the incidence of asymmetry was 16.7% (8/48). After 4-6 weeks of vestibular rehabilitation, the incidence of gain abnormality was 22.9% (11/48), the incidence of phase abnormality was 31.3% (15/48), and the incidence of asymmetry was 12.5% (6/48).The horizontal gain at frequency of 2.0-3.9 Hz showed statistically significant difference compared with before vestibular rehabilitation (P<0.05), and the horizontal gain at frequency of 4.3-5.9 Hz showed that there was no significant difference (P>0.05); the horizontal phase at 5.9 Hz showed that the difference was statistically significant (P=0.043), and there was no significant difference before and after rehabilitation treatment at 2.0-5.5 Hz (P>0.05); the vertical gain at 4.3 Hz showed the difference was statistically significant (P=0.020), and the remaining frequency showed no significant difference (P>0.05); No frequency of asymmetry and vertical phase showed the difference before and after rehabilitation was statistically significant (P>0.05). Conclusion: VAT can be used to monitor the change trend of multiple frequency bands before and after vestibular rehabilitation in UVH, in order to provide reference for the formulation of personalized rehabilitation strategies.

Experimental study of anti-diabetic effects of gastrodin in KK-Ay mice / 中国药理学通报

Aim To study the anti-diabetic effects of natural product gastrodin ( GSTD ) in KK-Ay mice. Methods C57BL/6J mice were used as normal con-trol, while KK-Ay diabetic mice were divided into five groups, namely the untreated group, GSTD 10 mg· kg-1, 20 mg·kg-1, 50 mg·kg-1 groups, and the metformin ( Met) 200 mg·kg-1 group, respectively, with 10 mice in each group. GSTD and Met were ad-ministered intragastrically for eight weeks. Before ex-periment and once a week during the experiment, the fasting blood glucose ( FBG) levels were determined. During the 7th week of drug treatment, oral glucose tolerance test ( OGTT ) and insulin tolerance test ( ITT) were conducted. Before the end of experiment, 24 h urine samples were collected for the assay of rela-tive parameters. At the end of experiment, blood sam-ples were collected for the assay of glycosylated hemo-globin ( GHb) ; serums were isolated for the determina-tion of insulin concentration and other biochemical in-dexes. After sacrifice, the livers, kidneys, and pan-creases of the mice were harvested for pathological ex-amination; the contents of advanced glycation end product ( AGE) and triglyceride ( TG) in renal tissues were assayed by kits. Results GSTD at all doses sig-nificantly reduced FBG, urine glucose, GHb, serum insulin level, and the insulin resistance index in KK-Ay diabetic mice. In addition, GSTD greatly inhibited body weight gain and improved glucose tolerance and insulin tolerance ( P <0.05 or P <0.01 vs untreated group ) . The pathological examination showed that GSTD significantly increased the glycogen content of liver tissues, reduced islet volume and improved its pathological changes. In addition, the glomerulosclero-sis induced by diabetes was greatly ameliorated by GSTD. Meanwhile, GSTD greatly reduced serum crea-tine ( Scr) , 24 h urine amount, 24 h urine total pro-tein and microalbumin ( mAlb) , as well as renal AGE and TG contents in KK-Ay mice ( P <0.05 or P <0.01 vs untreated group) . The anti-diabetic effect of GSTD at 50 mg·kg-1 was comparable to that of 200 mg·kg-1 of Met. Conclusions When used to treat KK-Ay diabetic mice, GSTD has potent activities in lowering blood glucose, improving insulin resistance and ameliorating diabetic nephropathy. However, the detailed mechanisms of GSTD in modulating glucose metabolism and increasing insulin sensitivity still need further investigation.

Design, synthesis and evaluation of cytisinic derivatives for hypoglycemic activity / 药学学报

Taking cytosine, an unique natural product alkaloid as the lead, we designed thirty cytisinic derivatives with different types of 12N-substituents, which were synthesized and evaluated for their activity in the regulation of glucose metabolism in vitro. The compounds 3d, 3g and 6h exhibited the potential hypoglycemic activity and compound 3d had a good pharmacokinetics profile. In terms of mechanism of glucose consumption, the compounds 3d and 6h increased cellular glucose consumption. which might be associated with up-regulation of glucose transporter Glut4 expression and activation of AMPK. The results revealed important roles of these new skeleton compounds as potential new drug candidates for control of blood glucose.

Analysis of the efficacy and compliance of conventional immunotherapy and rush immunotherapy in patients with allergic rhinitis / 临床耳鼻咽喉头颈外科杂志

To analyze the efficacy and compliance of conventional immunotherapy(CIT)and rush immunotherapy(RIT)in patients with allergic rhinitis.This trial was a prospective study involved 404 patients with persistent AR who were allergic to house dust mite.328 patients were assigned to the conventional immunotherapy reaching the maintenance dose within 14 weeks,and 76 patients were assigned to the rush immunotherapy reaching the maintenance dose within 1 week.The visual analog scale(VAS)score and the patients' compliance were recorded during treatment and follow-up.After CIT and RIT,the VAS score were significantly reduced in each group,but the decrement of VAS score of RIT group was more evident than that of CIT in half ayear(<0.05).After 5 years follow-up,the VAS score of two groups was also significantly reduced.The rate of treatment continuation of CIT group in 1 year,2 years and 3 years were 18.5%,39.0% and 57.3%,higher than RIT group(11.8%,26.3%,42.1%),respectively.Both CIT and RIT were beneficial for allergic rhinitis patients,and the clinical efficacy lasts for at least 5 years.But RIT has the superiority of faster onset and better compliance.

Serum sex hormone levels in different severity of male adult obstructive sleep apnea-hypopnea syndrome in East Asians / 华中科技大学学报（医学）（英德文版）

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a serious health issue, which can impact the hormone secretion. The aim of this study is to analyze the relationship between serum sex hormone concentrations and different severity degree of OSAHS, and to evaluate the influence of OSAHS on sex hormone levels. We enrolled 116 subjects who were subjected to polysomnography (PSG). They were divided into three groups: control group (n=10) [apnea hypopnea index (AHI) <5/h], mild-moderate OSAHS group (n=15) (5≤AHI<30/h), and severe OSAHS group (n=91) (AHI≥30/h). The patients in OSAHS group were subdivided into obesity and non-obesity subgroups. The parameters such as AHI, body mass index (BMI), lowest oxygen saturation (LSaO2), and mean oxygen saturation (MSaO2) were recorded. Serum levels of testosterone, polactin, estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined in the morning immediately after waking up. Mean levels of hormones were compared among groups. The correlation between hormone levels and sleep-breathing parameters was analyzed. No significant differences in serum sex hormone levels were found among control, mild-moderate OSAHS, and severe OSAHS groups (P>0.05). There was no correlation between AHI and sex hormone levels (P>0.05). Testosterone was significantly negatively correlated with BMI (P<0.05). These results suggested that BMI might have a direct effect on testosterone level, and it might be an important factor affecting testosterone level in male OSAHS patients, and there may be no correlation between severity of OSAHS and sex hormones levels.

Modified titration intratympanic gentamicin injection for unilateral intractable Ménière's disease / 华中科技大学学报（医学）（英德文版）

This study looked into the efficacy of a modified titration protocol of intratympanic gentamicin injection (ITG) in the patients with unilateral intractable Ménière's disease (MD). Modified titration protocol of ITG at a low dose (20 mg/mL) was administered to 10 patients with definite unilateral intractable MD. After initial first two fixed ITGs on weekly basis, the patients might or might not be given any more injections, depending on the appearance of unilateral vestibular loss (UVL). ITG was terminated if the patients satisfied the criteria of UVL. All patients were followed-up for at least two years. The effects of ITG on the vertigo attack, functional level scores and postural balance were evaluated. Of the 10 cases, 8 showed the sign of UVL after receiving initial two ITGs and were not given any more intratympanic injections, and the other 2 patients were administered three ITGs. A two-year follow-up revealed that complete and substantial vertigo control was achieved in 9 cases, and limited vertigo control in 1 patient. Hearing level was lowered in 2 patients. The posture stability and functional level scores were improved. Our study showed that the modified titration protocol of ITG at a low dose could effectively control vertigo in patients with unilateral intractable MD.

Effects of IL-17 on expression of GRO-α and IL-8 in fibroblasts from nasal polyps / 华中科技大学学报（医学）（英德文版）

Recent studies indicated that interleukin (IL)-17, growth-related oncogene (GRO)-α and IL-8 play an important role in the pathogenesis of nasal polyps. However, the effects of the increased amount of IL-17 and the production of GRO-α and IL-8 in human nasal polyp fibroblasts are not completely understood. This study aimed to determine the effects of the increased IL-17 on the changes of GRO-α and IL-8 expression in human nasal polyp fibroblasts and further investigate the mechanism of neutrophil infiltration in nasal polyps. Nasal polyp fibroblasts were isolated from six cases of human nasal polyps, and the cells were stimulated with five different concentrations of IL-17. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of GRO-α and IL-8. The mRNA of GRO-α and IL-8 was expressed in unstimulated controls and remarkably increased by stimulation with IL-17. Moreover, the levels of GRO-α and IL-8 produced by fibroblasts were increased gradually with the increases in IL-17 concentrations. The present study showed that nasal fibroblasts can produce GRO-α and IL-8, and their production is remarkably enhanced by IL-17 stimulation, thereby clarifying the mechanism of the IL-17 mediated neutrophil infiltration in nasal polyps. These findings might provide a rationale for using IL-17 inhibitors as a treatment for nasal inflammatory diseases such as nasal polyps.

Effects of IL-17 on expression of GRO-α and IL-8 in fibroblasts from nasal polyps / 华中科技大学学报（医学）（英德文版）

Recent studies indicated that interleukin (IL)-17, growth-related oncogene (GRO)-α and IL-8 play an important role in the pathogenesis of nasal polyps. However, the effects of the increased amount of IL-17 and the production of GRO-α and IL-8 in human nasal polyp fibroblasts are not completely understood. This study aimed to determine the effects of the increased IL-17 on the changes of GRO-α and IL-8 expression in human nasal polyp fibroblasts and further investigate the mechanism of neutrophil infiltration in nasal polyps. Nasal polyp fibroblasts were isolated from six cases of human nasal polyps, and the cells were stimulated with five different concentrations of IL-17. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of GRO-α and IL-8. The mRNA of GRO-α and IL-8 was expressed in unstimulated controls and remarkably increased by stimulation with IL-17. Moreover, the levels of GRO-α and IL-8 produced by fibroblasts were increased gradually with the increases in IL-17 concentrations. The present study showed that nasal fibroblasts can produce GRO-α and IL-8, and their production is remarkably enhanced by IL-17 stimulation, thereby clarifying the mechanism of the IL-17 mediated neutrophil infiltration in nasal polyps. These findings might provide a rationale for using IL-17 inhibitors as a treatment for nasal inflammatory diseases such as nasal polyps.

Effect of neonatal immunization with different dosage allergen on the immunity of mice when grown up / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the effect of neonatal immunization with different dosage allergen on the immunity of mice when grown.</p><p><b>METHODS</b>Fifty neonatal BALB/c mice were divided into 4 groups randomly and subcutaneous injected with different dosage of ovalbumin (OVA) on day 1, 8 and 15 after born [NS group(10): injected with saline alone; NS + AL group (10): injected with saline and AL(OH)3; small dosage (SD) group (15): injected with 10 microg OVA and AL(OH)3; large dosage (LD) group (15): injected with 1000 microg OVA and AL(OH)3]. The mice were then challenged using caudal vein injection on 5 weeks old (NS group and NS + AL group were challenged with saline, SD group and LD group were challenged with 100 microg OVA). The blood was collected 1 week later to examine OVA specific IgE, IgG1 and IgG2a. Mononuclear cells were drawn from the spleen and cultured. Concentration of IL-4, IFN-r, IL-10 was examined in the cultural supernatant. Flow cytometry was used to test the expression of CD4+ IL-4+, CD4+ IFN-gamma+, CD4 IL-10 cells.</p><p><b>RESULTS</b>It was found that concentration of OVA specific IgE (OVA-sIgE) in SD group (0.33 +/- 0.18) was significantly higher than that of NS (0.07 +/- 0.01) and NS + AL (0.09 +/- 0.04) group (t value was -3.46 and -3.21, all P < 0.01), and LD group (0.17 +/- 0.10) as well (t = 2.58, P < 0.05). The concentration of OVA-sIgE was higher in LD group than that of NS group (t = -2.53, P < 0.05), but similar with that of NS + AL group (t = -2.04, P > 0.05). Both the concentration of OVA-sIgG1 and sIgG2a was higher in SD and LD group than that of NS and NS + AL group (all P < 0.05). The concentration of IL-4, IFN-gamma and IL-10 in the cultural supernatant of spleen mononuclear was all higher in SD group than that of NS and NS + AL group (all P < 0.01). The ratio of IFN-gamma/IL-4 was significantly lower in SD group than that of NS and NS + AL group (t value was 2.14, 3.44, all P < 0.05), while the same ratio was higher in LD group than that of NS and NS + AL group (t value was -2.14, -1.61, all P < 0.05). Ratio of CD4+ IL-4+ cells was significant lower in LD group than that of SD group (P < 0.05), while it was not different with that of NS and NS + AL group (P > 0. 05).</p><p><b>CONCLUSION</b>Neonatal immunization with low dosage OVA could generate a specific immunity with Th2 direction, while with large dosage OVA could generate a specific immunity with Th1 direction.</p>

Comparation between modified coblation assisted uvulopalatopharyngoplasty and conventional uvulopalatopharyngoplasty in operative complication / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To compare the operative effectivity and incidence of postoperative complication between conventional uvulopalatopharyngoplasty (UPPP) and modified coblation assisted UPPP (M-CAUP) in treating patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). And to explore the more effective, safer and minimally invasive operative method in surgical therapy of OSAHS.</p><p><b>METHODS</b>It was a controlled trial. A retrospective analysis was made on surgical complications of conventional UPPP and of M-CAUP performed on OSAHS patients from 1995 to 2010. There were 451 patients in UPPP group and 323 patients in M-CAUP group. χ(2) test and Fisher's Exact test were used in statistical analysis.</p><p><b>RESULTS</b>The incidence of serious surgical complications was higher in conventional UPPP group (3.77%, 17/451) than that in M-CAUP group (0.62%, 2/323), χ(2) = 7.800, P < 0.01, while the incidence of short-term complications was higher in M-CAUP group (90.40%, 292/323) than that in conventional UPPP group (60.98%, 275/451), χ(2) = 83.186, P < 0.01. The difference of long-term complications was not statistically significant between M-CAUP group and conventional UPPP group (P = 0.1331, Fisher Exact test). There was no significant difference in incidence of asphyxia between M-CAUP group and conventional UPPP group (P < 0.01, Fisher Exact test). However, the incidence of post-operative primary hemorrhage was obviously lower in M-CAUP group than that in conventional UPPP group (3.99%, 18/451), χ(2) = 12.133, P < 0.01. While the incidence of delayed hemorrhage, temporal velopharyngeal insufficiency, and foreign body sensation at pharynx were higher in M-CAUP group (8.05%, 12.69%, 68.42%, respectively) than that in conventional UPPP group (3.77%, 3.33%, 51.00%, respectively) P < 0.01, respectively. There was no significant difference in incidence of permanent velopharyngeal insufficiency, stenosis of nasopharynx and nasopharyngeal atresia, alteration of taste, throat itch and coughing.</p><p><b>CONCLUSION</b>Compared to the conventional UPPP, M-CAUP was more effective and safer in treating OSAHS with less severe complications during and after the operation.</p>

Evaluation of the vestibular ocular reflex in patients with unilateral peripheral vestibular disorder by the head impulse test / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To evaluate the function of vestibular ocular reflex (VOR) in patients with unilateral peripheral vestibular disorder (uPVD) by the head impulse test (HIT).</p><p><b>METHODS</b>The HIT and caloric test were carried out in 135 cases of patients with uPVD. The results of HIT were considered as normal (negative reaction) and abnormal (positive reaction). The results of vestibular function evaluated by caloric test were divided into three kinds, including normal, decreased and deficit according to the degree of canal paresis as less than 30 percent, from 30 to 99 percent, and equal to 100 percent, respectively. The sensitivity, specificity, positive and negative predictive value of HIT in assessing the vestibular function was analyzed.</p><p><b>RESULTS</b>For the 135 patients with uPVD, the HIT was normal in 90 (66.7%) cases and abnormal in 45 (33.3%) cases. When the caloric test was normal, the HIT was normal or abnormal in 58 cases and 6 cases, respectively. And when the canal paresis was from 30 to 99 percent, the HIT was normal or abnormal in 28 and 24 cases, respectively. When the vestibular function was deficit (CP was 100%), the HIT was normal or abnormal in 4 cases and 15 cases, respectively. When the results of caloric test were considered as the standard method to evaluate the VOR, the sensitivity, specificity, positive and negative predictive value of HIT were 54.9%, 90.6%, 86.7%, and 64.4%, respectively.</p><p><b>CONCLUSIONS</b>When assessing the function of VOR in patients with uPVD, the HIT could not replace the caloric test, but it can be a supplementary method. The information from both the HIT and caloric test can be combined to evaluate the patients with vestibular hypofunction comprehensively.</p>

Effect of early allergen immunization on the development of allergic rhinitis in mouse / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of early allergen exposure on later development of allergic rhinitis in mouse.</p><p><b>METHODS</b>Twenty-four BALB/c neonates were randomly divided into 4 groups (low-dose group, high-dose group, negative control group and positive control group), each group had 6 mice. The mice were administered ovalbumin (OVA) by subcutaneous injection on day 1, 5, 12 after birth (10 μg OVA in 0.05 ml saline for low-dose group, 1000 μg OVA in 0.05 ml saline for high-dose group, only saline for negative and positive control group). Then the mice were sensitized and intranasally challenged with OVA (saline without OVA was used in negative control group) after 6 weeks. Symptoms, histopathological changes of nasal mucosa were observed, OVA-IgE in serum was examined, cytokines IL-4, IL-5 and IFN-gamma were detected in the supernatant of cultured splenic mononuclear cells.</p><p><b>RESULTS</b>Compared to the positive control group, symptoms and nasal mucosa histological changes of high-dose group was indistinctive. The level of OVA-IgE and cytokines IL-4, IL-5 (x(-) +/- s) in high-dose group [(265.11 +/- 26.29), (446.39 +/- 72.83) and (171.24 +/- 15.66) pg/ml, respectively] were significantly lower than those in positive control group [(665.85 +/- 43.15), (1113.45 +/- 30.47), (255.36 +/- 30.96) pg/ml, respectively, t value were 0.000, 0.000 and 0.009, respectively, all P < 0.05]. The level of IFN-γ in high-dose group [(319.74 +/- 56.30) pg/ml] was significantly higher than those in positive control group [(170.02 +/- 14.50) pg/ml, t = 0.000, P < 0.05]. There was no significant difference of the results between the low-dose group and positive control group.</p><p><b>CONCLUSIONS</b>Neonatal immunization with high-dose OVA inhibited the future allergic rhinitis symptoms, nasal histological changes, serum OVA-IgE levels and Th1/Th2 cytokine imbalance, resulting in the protective effect.</p>

Relationship between nasal discharge eosinophils and responses to treatment of inhaled glucocorticosteroid in patients with allergic rhinitis / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To evaluate the treatment responses of persistent allergic rhinitis with and without nasal discharge eosinophilia (EOS) to inhaled glucocorticosteroid (CS), and therefore to verify whether low nasal discharge eosinophils predict poor response to treatment with CS.</p><p><b>METHODS</b>Forty-two symptomatic allergic rhinitis patients, who had not received CS therapy in three months preceding the study, were examined before and 2 month,4 months and 6 months after treatment with CS. At each visit, all patients underwent symptom scoring and physical sign scoring. The level of eosinophil cationic protein (ECP) in the nasal discharge supernatants was measured by radioimmunoassay. The patients were divided into 2 groups according to nasal discharge EOS percentages, an EOS group (group A, EOS > or = 0.03) and a non-EOS group (group B, EOS < 0.03). The response to CS therapy (as measured by symptom and physical sign scores) and the changes of nasal discharge measurements were compared between the 2 groups.</p><p><b>RESULTS</b>In the group A, the baseline EOS [0.086 (0.065; 0.176)] and ECP level [(326 +/- 145) microg/L] were significantly higher than those of the group B [0.016 (0.005; 0.022)] and ECP level (154 +/- 58) microg/L], respectively, t = 4.40, 3.33, both, all P < 0.01. After 2 month and 6 months CS therapy, the nasal discharge EOS, ECP pred were 0.038 (0.006; 0.070), 0.019 (0.010; 0.060), (175 +/- 122) microg/L, (175 +/- 153) microg/L, respectively in the EOS group, which were significantly different as compared to baseline values (F = 6.73, 7.38, respectively, all P < 0.05). But in the non-EOS group, the nasal discharge EOS ECP pred were 0.014 (0.004; 0.032), 0.015 (0.000; 0.026), (118 +/- 60) microg/L, (112 +/- 60) microg/L, respectively at 2 and 6 months, which showed that the the nasal discharge EOS pred and the symptom and physical sign scores improved did not change (F = 0.82, P > 0.05), but the ECP level improved (F = 3.78, P < 0.05). and the average daily dose of CS wear not different between the two groups at any visits.</p><p><b>CONCLUSIONS</b>In persistent allergic rhinitis with low nasal discharge EOS, CS therapy for 6 months failed to improve symptom and physical sign.</p>

Protection of cochlear function from aminoglycosides ototoxicity by manganese superoxide dismutase gene in aging rat / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>determine the feasibility of manganese superoxide dismutase (MnSOD) gene therapy for protecting the cochlear function against aminoglycoside-induced oxidative stress in aging rats.</p><p><b>METHODS</b>The aging model of SD rats were obtained with 8 weeks daily of D-gal (150 mg/kg per day) hypodermic injection. In the 9th week, amikacin (500 mg/kg per day) were injected intramuscularly into some aging SD rats. The viral particles of recombinant adeno-associated viral vector II/MnSOD (6 microl, 5 x 10(11) vector genomes/ml) were injected into the perilymph through the round window membrane (RWM). The feasibility of MnSOD gene therapy against aminoglycoside-induced oxidative stress in aging rats was evaluated with the methods of caspase-3 protein analysis, apoptosis detection with immunohistochemical, the detection of MnSOD concentration, stretched preparation of basilar membrane and evaluation of hearing threshold with ABR-click.</p><p><b>RESULTS</b>Compared with the control group, the concentration of MnSOD of cochlear tissue was increased (P < 0.05), and the active fragment expression of caspase-3, the numbers of apoptosis bodies and the hearing threshold were decreased (P < 0.05).</p><p><b>CONCLUSIONS</b>MnSOD could play a partly role to treat cochlear aminoglycoside-induced oxidative damage in aging rats.</p>

Oxidative stress experimental model of rat with stria vascularis marginal cells injury induced by hydrogen peroxide in vitro / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To set up the oxidative stress experimental model of rat cochlea with stria vascularis marginal cells injury induced by hydrogen peroxide in vitro.</p><p><b>METHODS</b>Cultured marginal cells of rat were treated by 200, 300, 400, 600 and 800 micromol/L hydrogen peroxide (H(2)O(2)) for 0.5, 1, 2, 4, 16 and 24 hours, respectively. Cell viability was assessed by the CCK-8 assay. The content of the lipid peroxidation production malondialdehyde (MDA) were detected in H(2)O(2) induced marginal cells injury with different concentration H(2)O(2). Apoptosis was assessed by flow cytometry by propidium sodium staining. The expression of the cleaved-caspase-3 was assessed by Western blot.</p><p><b>RESULTS</b>Being exposed to H(2)O(2), marginal cells displayed nuclear pyknosis and margination, cytoplasmic condensation, cell shrinkage and formation of membrane and bounded apoptotic bodies. A time-dependent and dose-dependent decrease of cellular viability was detected with the treatment of H(2)O(2). Cellular maleic dialdehyde was generated in proportion to the concentration of H(2)O(2) at 2 hours and the number of apoptotic cells increased significantly (P < 0. 05). Western blot showed the expression of the cleaved-caspase-3 increased when 200 micromol/L, 300 micromol/L and 400 micromol/L H(2)O(2) treated cultured marginal cells. Thereafter the expression of the cleaved-caspase-3 decreased with 600 micromol/L H(2)O(2) and with 800 micromol/L H(2)O(2) the expression of cleaved-caspase-3 was weak.</p><p><b>CONCLUSIONS</b>The findings indicated that the experimental model can be established successfully using cultured cells exposed to H(2)O(2) and activation of caspase-3 is associated with hydrogen peroxide induced rat marginal cells the oxidative stress injury.</p>

Co-location of ACh-sensitive BK channels and L-type calcium channels in type II vestibular hair cells of guinea pig / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To explore the mechanisms of the influx of calcium ions during the activation of ACh-sensitive BK channel (big conductance, calcium-dependent potassium channel) in type II vestibular hair cells of guinea pigs.</p><p><b>METHODS</b>Type II vestibular hair cells were isolated by collagenase type IA. Under the whole-cell patch mode, the sensitivity of ACh-sensitive BK current to the calcium channels blockers was investigated, the pharmacological property of L-type calcium channel activator-sensitive current and ACh-sensitive BK current was compared.</p><p><b>RESULTS</b>Following application of ACh, type II vestibular hair cells displayed a sustained outward potassium current, with a reversal potential of (-70.5 +/- 10.6) mV (x +/- s, n = 10). At the holding potential of -50 mV, the current amplitude of ACh-sensitive potassium current activated by 100 micromol/L ACh was (267 +/- 106) pA (n = 11). ACh-sensitive potassium current was potently sensitive to the BK current blocker, IBTX (iberiotoxin, 200 nmol/L). Apamin, the well-known small conductance, calcium-dependent potassium current blocker, failed to inhibit the amplitude of ACh-sensitive potassium current at a dose of 1 micromol/L. ACh-sensitive BK current was sensitive to NiCl2 and potently inhibited by CdCl2. NiCl2 and CdCl2 showed a dose-dependent blocking effect with a half inhibition-maximal response of (135.5 +/- 18.5) micromol/L (n = 7) and (23.4 +/- 2.6) micromol/L (n = 7). The L-type calcium channel activator, (-) -Bay-K 8644 (10 micromol /L), mimicked the role of ACh and activated the IBTX-sensitive outward current.</p><p><b>CONCLUSION</b>ACh-sensitive BK and L-type calcium channels are co-located in type II vestibular hair cells of guinea pigs.</p>

Electrophysiological findings for 106 cases with auditory neuropathy / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To analyses the clinical characteristics and electrophysiological finding of 106 patients with auditory neuropathy (AN). Investigate the differential curve type of pure tone audiogram and the abnormal ABR.</p><p><b>METHODS</b>Review the history of patients, pure tone audiometry, middle ear acoustic reflexes, auditory brainstem response, distortion product otoacoustic emission and radiologic imaging studies of the brain of 106 patients with AN during December 2001 to May 2007 in retrospect.</p><p><b>RESULTS</b>The 106 patients with AN were of both genders. The age were between 11-37 years old, and the average age was 17.5 years old. The most patients were adolescence (70.8%). Twelve cases of the 106 patients had evidence of other peripheral neuropathy in addition to hearing loss. Another 94 patients were idiopathic origins. The pure tone audiogram showed a minimal to moderate sensorineural hearing loss at low frequencies 0.5 kHz and 0.25 kHz in 209 ears (98.6%). The average hearing threshold (WHO 1997) in 23.2% of disordered ears at less than 25 dB in the "normal" range. Auditory brainstem response could not be recorded in 124 ears (58.5%) at maximum stimulus. The other 88 ears showed 1 or 2 wave, but the wave were small. There were 23 patients which one side ear ABR was 1 or 2 small waves presented, but the contralateral side were all waves absent. In 3 cases of AN with other peripheral neuropathy which ABR were both ears 1 or 2 small wave ear recorded. However, 1 patient in our sample could not be detected distortion product otoacoustic emission at 3-6 kHz (left ear) and 5-6 kHz (right ear).</p><p><b>CONCLUSIONS</b>AN was not rare in adolescence. The average hearing threshold for AN should be discussed.</p>

Sensitivity to the ototoxicity of kanamycin of the rat model for mimetic aging in the inner ear / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To research the animal model with mimetic aging effect in the inner ear predispose to the ototoxicity of kanamycin.</p><p><b>METHODS</b>Fifty wistar rats were randomly divided into four groups: group A (D-galactose group, n = 14) were treated with hypodermic 5% D-galactose (150 mg x kg(-1) x d(-1)) for 8 weeks and then with intraperitoneal saline for 10 days; group B (D-galactose and kanamycin group, n = 14) were given the same dose of D-galactose but kanamycin (500 mg x kg(-1) x d(-1)) instead of saline; group C (kanamycin group, n = 12) were treated with saline for 8 weeks and then with intraperitoneal kanamycin for 10 days;group D (control group, n = 10) were given saline only. Auditory brainstem response (ABR) was used to detect the hearing threshold of rats and colorimetry was used to analyze the activity of the GSH-PX. The inner ear tissue was harvested and the mitochondrial DNA was amplified to identify the 4834 bp deletion mutation by nested primer polymerase chain reaction (nested PCR) technique.</p><p><b>RESULTS</b>The incidence of mitochondrial DNA 4834 bp deletion mutation was 100% (28/28) in group A, 92.86% (26/28) in group B and 0% in group C or group D. The activity of GSHPX in group A was (59.07 +/- 8.70)U, (63.29 +/- 12. 40)U in group B, (136.67 +/- 9.53)U in group C and (142.10 +/- 7.02)U in group D. The difference between group A and D was significant (P = 0.000) while the difference between group A and B was not significant (P = 0.307), which was similarly as between group C and group D (P = 0.151). ABR threshold was (5.36 +/- 3.08) dB peSPL in group A, (61.79 +/- 11.20) dB peSPL in group B, (34.17 +/- 4.69) dB peSPL in group C and (6.50 +/- 3.37) dB peSPL in group D. No difference was found between group A and D (P = 0.398) while the difference in shift of ABR threshold between group B and group C (or group D) was significant (P = 0.000).</p><p><b>CONCLUSIONS</b>The mimetic aging effect in the inner ear of the rat can be induced by D-galactose, and these rats present high incidence of mtDNA4834 deletion which can greatly enhance the sensitivity of the inner ear to the kanamycin.</p>

Intrinsic membrane properties of rat medial vestibular nucleus neurons and their responses to simulated vestibular input signals / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the membrane properties of rat medial vestibular nucleus (MVN) neurons and their firing responses to simulated input signals of peripheral vestibular system, and to discuss how the intrinsic membrane properties contribute to physiologic functions in central vestibular system.</p><p><b>METHODS</b>By using infrared differential interference contrast technique, whole-cell recordings were made from rat MVN neurons under direct observation. On the basis of their averaged action potential shapes, the MVN neurons were classified. Linear and non-linear currents were put into the neurons to simulate the input signals of peripheral vestibular system. The differences of intrinsic membrane properties and firing response dynamics were observed between two types.</p><p><b>RESULTS</b>The discharge activities were recorded in MVN neurons, which remained in low Ca2+-high Mg2+ artificial cerebrospinal fluid (ACSF). Neurons are classified as type A (33%) characterized by a single deep after-hyperpolarization (AHP) and A-like rectification, or type B (63%) characterized by double AHP, and another two neurons with all or none of the characters. The passive membrane properties were not significantly different between type A and type B neurons, while part of active membrane properties was significantly different. Both type A and B neurons well responded to simulated current inputs, but disparities existed in response range and firing dynamics.</p><p><b>CONCLUSIONS</b>The discharge activities of MVN neurons were initiated by their intrinsic membrane properties. Most MVN neurons were classified as type A and B, while several showed unrepresentative firing properties. Linear and nonlinear inputs evoked a heterogeneous range of firing responses. The differences of response range and firing dynamics between neurons may determine their different physiological functions.</p>