Evaluation of pure-tone audiometric protocols in vestibular schwannoma screening

The objective was to evaluate the pure-tone audiogram-based screening protocols in VS diagnostics. We retrospectively analyzed presenting symptoms, pure tone audiometry and MRI finding from 246 VS patients and 442 controls were collected to test screening protocols (AAO-HNS, AMCLASS-A/B, Charing Cross, Cueva, DOH, Nashville, Oxford, Rule3000, Schlauch, Seattle, Sunderland) for sensitivity and specificity. Results were pooled with data from five other studies, and analysis of sensitivity, specificity and positive likelihood ratio (LR+) for each protocol was performed. Our results show that protocols with significantly higher sensitivity (AMCLASS-A/B, Nashville) show also significantly lowest specificity, and tend to have low association (positive likelihood ratio, LR+) to the VS. The highest LR+ was found for protocols AAO-HNS, Rule3000 and Seattle. In conclusions, knowing their properties, screening protocols are simple decision-making tools in VS diagnostic. To use the advantage of the highest sensitivity, protocols AMCLASS-A + B or Nashville can be of choice. For more reasonable approach, applying the protocols with high LR+ (AAO-HNS, Rule3000, Seattle) may reduce the overall number of MRI scans at expense of only few primarily undiagnosed VS.     

姜黄素与丙酸酐不对称反应产物的合成

目的:合成姜黄素与丙酸酐的不对称反应产物——1-(4-丙酰氧基-3-甲氧基苯基)-7-(4-羟基-3-甲氧基苯基)-1,6-庚二烯-3,5-二酮(化合物1)。方法:以姜黄素和丙酸酐为原料,吡啶为催化剂,二氯甲烷/N,N-二甲基甲酰胺(DMF)为溶剂,进行不对称反应,经柱层析分离纯化,得目标化合物1,并进行核磁共振结构表征,以收率为指标,确定最佳反应条件(投料比、温度、时间、吡啶用量)。结果:制备得到了化合物1(收率:81.2%,纯度:99.0%),并经结构表征证实。化合物1的最佳反应条件是姜黄素与丙酸酐比为1∶1.5(m/m),反应温度为30Ⅸ,时间为30 min,吡啶用量为0.5%。结论:以确定的反应条件可得到目标化合物1。该工艺操作简便,收率和纯度高,可为姜黄素结构修饰的进一步研究提供参考。     

Metformin and oral contraceptive treatments reduced circulating asymmetric dimethylarginine (ADMA) levels in patients with polycystic ovary syndrome (PCOS)

There is a little information in literature about circulating asymmetric dimethylarginine (ADMA) concentrations in polycystic ovary syndrome (PCOS) and the results reported are discrepant. In this study, therefore, we aimed (1) to determine the circulating ADMA concentrations in 44 women with PCOS and 22 age- and BMI-matched healthy controls, (2) to evaluate its correlations with insulin resistance, gonadotrophins, and androgen secretion, and (3) to compare effects of metformin and ethinyl estradiol-cyproterone acetate (EE/CPA) treatments on circulating ADMA concentrations. In conclusion, our data indicate that circulating ADMA concentrations in non-obese, non-hypertensive and young women with PCOS are significantly higher than healthy controls and they improved by a 3-month course of metformin and oral contraceptive treatments.     

血清不对称二甲基精氨酸与服用质子泵抑制剂后初次发生急性冠状动脉综合征的相关性

目的本研究旨在探讨血清不对称二甲基精氨酸（ADMA）与服用质子泵抑制剂（PPI）后初次发生急性冠状动脉综合征（ACS）的关系。 方法研究纳入2017年1月至2018年10月因初次发生ACS入住徐州医科大学附属淮安医院的患者及体检中心同期健康体检者共210例,分为3组,PPI组（服用PPI＋初次发生ACS）患者70例,其中男性51例,女性19例,平均年龄为（62.80±11.87）岁;ACS组（未服用PPI＋初次发生ACS）患者70例,其中男性55例,女性15例,平均年龄为（62.66±12.13）岁;对照组为同期健康体检患者（未服用PPI＋未发生ACS）70人,其中男性54人,女性16人,平均年龄为（62.96±9.09）岁。采用酶联免疫吸附法检测血清ADMA浓度,同时测量总胆固醇、三酰甘油等指标。采用单因素方差分析、非参数检验和χ²检验比较3组研究对象一般人口学信息、各项生化指标及ADMA水平;组间两两比较采用Mann-Whitney U检验;采用Spearman相关分析分析血清ADMA水平与ACS传统危险因素的关系;采用多因素Logistic回归分析探讨ACS的独立危险因素。 结果PPI组和ACS组的血清ADMA水平均高于对照组,差异均有统计学意义（Z=-9.585、-4.793,P均<0.001）;PPI组的血清ADMA水平高于ACS组,差异具有统计学意义（Z=-8.750,P<0.001）;PPI组和ACS组（即ACS患者）的血清ADMA水平与年龄、性别、BMI、吸烟、糖尿病、高血压、总胆固醇、三酰甘油无相关性（P均>0.05）;Logistic回归分析显示血清ADMA水平是初发ACS患者的独立危险因素（β=0.017,OR=1.017,P<0.001）。 结论服用PPI后初次发生ACS患者的血清ADMA水平明显高于未服用PPI的初次发生ACS患者;初次发生ACS患者的血清ADMA水平明显高于健康对照者;血清ADMA升高是初次发生ACS的独立危险因素。     

姜黄素对动脉粥样硬化家兔血管内皮功能的影响

目的: 观察姜黄素对实验性动脉粥样硬化(atherosclerosis,AS)家兔血浆一氧化氮(NO)水平,结构型一氧化氮合酶(constitutive NOS, cNOS)活性和非对称性二甲基精氨酸(asymmetric dimethylarginine,ADMA)的影响,探讨姜黄素抗AS作用及与ADMA的相关性. 方法: 38只雄性日本大耳白兔随机分为4组,即对照组(8只,喂食普通饲料)、模型组(10只,喂食高脂饲料)、低剂量姜黄素组(10只,喂食高脂饲料+100 mg·kg^-1·d^-1姜黄素)和高剂量姜黄素组(10只,喂食高脂饲料+200 mg·kg^-1·d^-1姜黄素).于实验的第12周末测定血浆TC,LDL-C,NO,内皮素(endothelin,ET),ADMA水平,主动脉组织cNOS活力,同时留取主动脉组织行病理检查. 结果: 喂食高脂饲料的3组较对照组家兔血浆ADMA和ET水平浓度均有升高(P<0.01),血浆NO浓度、动脉组织cNOS活性降低(P<0.01).姜黄素组家兔血浆ADMA和ET水平较模型组低(P<0.05),血浆NO浓度、动脉组织cNOS活性则要高出于模型组(P<0.01),2个姜黄素组之间未见显著性差异. 结论: 姜黄素有可能通过降低血浆ADMA水平,在AS进程中发挥重要的内皮保护作用.     

葛根素对氧自由基培养的人脐静脉内皮细胞非对称型二甲精氨酸代谢的影响

目的:观察氧自由基(OFR)对体外培养的人脐静脉内皮细胞(HUVECs)产生内源性一氧化氮合酶抑制剂——非对称型二甲基精氨酸(ADMA)的影响及葛根素的干预作用。方法:以黄嘌呤氧化酶作用于次黄嘌呤产生的 OFR 作用于培养的 HUVECs;并加用葛根素进行干预,以高效液相色谱法(HPLC)和经流式细胞仪检测细胞培养液中 ADMA、L-arg 和细胞内游离钙水平,并测定一氧化氮(NO)及内皮素(ET)的含量。结果:OFR 使培养液中 ADMA、ET 含量显著增加,而 NO 水平则降低,并使胞质内[Ca~(2+)]i 浓度升高;加用葛根素后,ADMA 明显减少,NO 合成增加,细胞内[Ca~(2+)]i 显著降低。结论:OFR 能通过增加 ADMA 使NO 合成减少,葛根素能通过减少 ADMA 而抑制 OFR 导致的内皮细胞功能障碍。     

Testosterone Deficiency Causes Endothelial Dysfunction via Elevation of Asymmetric Dimethylarginine and Oxidative Stress in Castrated Rats

BackgroundTestosterone is believed to mediate the penile erectile response by producing adequate nitric oxide; therefore, testosterone deficiency results in erectile dysfunction through decreased nitric oxide bioavailability. However, the mechanisms underlying endothelial dysfunction in testosterone deficiency remain unclear.AimTo investigate the mechanism of endothelial dysfunction in a rat model of testosterone deficiency.MethodsRats were distributed into 3 groups: castrated (Cast), castrated and supplemented with testosterone (Cast + T), and sham (Sham). In the Cast + T group, castrated rats were treated daily with subcutaneous testosterone (3 mg/kg daily) for 4 weeks; Sham and Cast rats received only the vehicle.OutcomesErectile function using intracavernosal pressure and mean arterial pressure measurements after electrical stimulation of the cavernous nerve, endothelial function using isometric tension, asymmetric dimethylarginine (ADMA) levels using ultra-performance liquid chromatography and tandem mass spectrometry, and inflammatory biomarker expression were performed 4 weeks after the operation.ResultsIn the Cast group, the ratio of intracavernosal pressure to mean arterial pressure significantly decreased, acetylcholine-induced relaxation was lower, and serum ADMA, oxidative stress, and inflammation biomarker levels were significantly increased (P < .01). Testosterone injection significantly improved each of these parameters (P < .01).Clinical TranslationThe present results provide scientific evidence of the effect of testosterone deficiency on erectile function and the effect of testosterone replacement therapy.Strengths and LimitationsThis study provides evidence of the influence of testosterone deficiency on endothelial function by investigating ADMA and oxidative stress. A major limitation of this study is the lack of a direct link of increased ADMA by oxidative stress to inflammation.ConclusionTestosterone deficiency increased not only ADMA levels but also oxidative stress and inflammation in castrated rats, which can cause damage to the corpus cavernosum, resulting in erectile dysfunction.Kataoka T, Hotta Y, Maeda Y, Kimura K. Testosterone Deficiency Causes Endothelial Dysfunction via Elevation of Asymmetric Dimethylarginine and Oxidative Stress in Castrated Rats. J Sex Med 2017;14:1540–1548.     

Identification at strain level ofRhizoctonia solani AG4 isolates by direct sequence of asymmetric PCR products of the ITS regions

The relatedness of nine isolates ofRhizoctonia solani, belonging to anastomosis group (AG) 4, and one isolate of AG1 was determined by comparative sequence analysis based on direct sequencing of PCR-amplified ribosomal DNA [the internal transcribed spacer (ITS) region and the 5.8 s ribosomal DNA]. The 5.8s rDNA is completely conserved, but both ITS regions show variation among strains. AG1 was an outgroup based on anastomosis ability and RFLP analyses. Phylogenetic analyses based on the ITS sequences suggest that the analyzed AG4 strains can be divided into three groups that correlate with habitat and virulence.     

Elevated asymmetric dimethylarginine in young adult survivors of childhood acute lymphoblastic leukemia: A preliminary report

Background: Adult survivors of childhood malignancy are predisposed to late cardiovascular (CV) complications. Our aim was to estimate plasma levels of the endogenous nitric oxide formation inhibitor asymmetric dimethylarginine (ADMA), in long-term survivors of childhood acute lymphoblastic leukemia (ALL) treated with only chemotherapy. Methods: ADMA and its isomer symmetric dimethylarginine (SDMA) were measured in 25 former ALL patients (aged 18–28 years) who had survived without recurrent disease ≥ 5 years from completing chemotherapy without cranial irradiation, and in 20 healthy controls (aged 20–31 years). Results: Characteristics of the both groups were similar, except for lower high-density lipoproteins-cholesterol (HDL-C) in ALL survivors. Compared to controls, the former ALL patients exhibited significant, albeit small, rises in levels of ADMA (0.63 ± 0.09 [SD] vs. 0.57 ± 0.07 μmol/L; p = 0.016), but not SDMA, with a consequently increased ADMA to SDMA ratio (1.08 ± 0.22 vs. 0.91 ± 0.16; p = 0.004). The effect of former ALL on ADMA was attenuated (intergroup p = 0.10 [ANCOVA]) upon adjustment for HDL-C (ADMA vs. HDL-C regression coefficient: −0.065 ± 0.030 [SEM]; p = 0.03). Conclusions: ADMA is elevated in adult childhood ALL survivors, which can reflect late detrimental chemotherapy effects, partially related to minor lipid profile changes. Whether these subtle ADMA elevations might herald future CV morbidity, remains to be elucidated.     

冠心病患者不对称二甲基精氨酸和同型半胱氨酸对一氧化氮合酶和一氧化氮的影响

目的探讨冠心病患者不对称二甲基精氨酸(ADMA)和同型半胱氨酸(Hcy)对一氧化氮合酶(NOS)和一氧化氮(NO)的影响。方法冠心病患者60例和健康体检者30例,测定其ADMA、Hcy、NOS和NO以及血糖、血脂等。结果冠心病组和对照组的ADMA分别为(1.30±0.58)μmol/L和(0.57±0.18)μmol/L、Hcy分别为(31.53±13.26)μmol/L和(20.98±6.39)μmol/L、NOS分别为(5.06±1.82)μ/mg蛋白和(7.03±1.37)μ/mg蛋白、NO分别为(2.56±0.95)nmol/L和(4.21±1.12)nmol/L,两组之间的差异显著(P<0.01)。经相关分析,NOS和NO分别与ADMA和Hcy呈负相关(P<0.05)。结论冠心病患者ADMA和Hcy显著增高,NOS活性降低和NO水平下降与ADMA和Hcy增高有关。