FIZZ1在炎症相关性肺动脉高压中的作用

低氧诱导促有丝分裂因子(hypoxia-induced mitogenic factor,HIMF)是一类富含半胱氨酸的分泌蛋白.HIMF首先在炎症区域被发现,并且扮演着炎症细胞标志物的角色,HIMF同时又称作发现于炎症区域1(found in inflammatory zone 1,FIZZ1).由于该蛋白家族成员在低氧与炎症相关生理病理过程中起不可忽视的作用,国内外对该蛋白家族的研究越来越多.目前该因子在血管生长、平滑肌增殖、气道炎症、肠道免疫等方面的作用已有相关研究.     

六分钟步行距离试验在鉴别肺高血压血流动力学类型中的价值

目的 探讨6 min步行距离试验在鉴别肺高血压血流动力学类型中的意义.方法 收集164例心功能Ⅱ～Ⅲ级初诊肺高血压患者的临床资料进行回顾性分析.根据肺高压血流动力学指标及右心功能状况分为A组(毛细血管前肺动脉高压、右心功能正常,62例)、B组(毛细血管后肺动脉高压、右心功能正常,58例)、C组(毛细血管前肺动脉高压合并右心功能不全,44例),主要分析指标为6 min步行距离及运动前后动脉血氧饱和度.结果 A组、B组和C组6 min步行距离分别为(397±112)、( 299±63)和(294±111)m,A组明显高于B组和C组,组间差异有统计学意义(P＜0.01)；B组与C组间比较差异无统计学意义(P＞0.05).结论 肺高血压合并心功能不全6 min步行距离明显减少；但单独6 min步行距离检查不能区分血流动力学类型.     

腹腔镜囊肿剔除术对卵巢良性肿瘤患者免疫功能及卵巢功能的影响

目的探讨腹腔镜囊肿剔除术对卵巢良性肿瘤患者免疫功能及卵巢功能的影响。方法选取97例卵巢良性肿瘤患者根据术式不同分为腹腔镜组63例(行腹腔镜下卵巢囊肿剔除术)和开腹组34例(行开腹卵巢囊肿剔除术),记录两组手术情况及不良反应发生情况,观察手术前后患者免疫功能及卵巢功能的变化。结果与开腹组比较,腹腔镜组手术时间、肠功能恢复时间和住院时间明显缩短(P0.01),术中出血量明显减少(P0.05)。术后1 d,两组Ig G水平较术前明显降低,腹腔镜组术后3 d恢复正常,开腹组略有升高,但仍低于腹腔镜组(P0.05);术前及术后1 d、3 d,腹腔镜组CD3+、CD4+、CD8+和CD4+/CD8+指标未见明显变化(P0.05),开腹组术后1 d明显降低,术后3 d除CD3+恢复正常外,其余各指标略有升高。术后3个月及1年,两组性激素水平逐渐恢复正常,但腹腔镜组恢复程度明显优于开腹组(P0.01);术后1个月、3个月及1年,腹腔镜组收缩期峰值流速(PSV)较术前明显增加,阻力指数(RI)明显降低(P0.01),而对照组未见明显变化(P0.05)。两组术后不良反应比较差异有统计学意义(P0.05)。结论腹腔镜囊肿剔除术对卵巢良性肿瘤患者免疫功能、近远期卵巢功能的损害均小于开腹囊肿剔除术,有利于患者的术后恢复。     

Factors correlated with prostate volume in middle-aged men with bothersome lower urinary tract symptoms

ObjectiveThe aim of this study was to investigate the predictive factors of prostate volume (PV) by analyzing potential predictors in a population of middle-aged men with bothersome lower urinary tract symptoms (LUTS) and use a prediction model for PV estimation to compare with digital rectal examination (DRE) alone.Materials and methodsPatients between the ages of 40 years and 64 years who underwent transrectal prostate ultrasound as part of a self-paid medical check-up were enrolled. Participant demographics, medical history, and voiding symptoms were assessed by the International Prostate Symptoms Score (IPSS) questionnaire. A multiple linear regression with stepwise selection was used to analyze the correlations between PV and all potential predictors.ResultsTwo hundred and twenty-eight men with bothersome LUTS (IPSS > 7) were enrolled as study participants at a mean age of 56.4 years. Patients with PV > 25 mL were significantly older and had higher serum prostate-specific antigen (PSA) levels and scores for total IPSS, storage, urgency items, and nocturia items. DRE, serum PSA, age, and urgency score were independent predictors for PV, especially for men with PV > 25 mL, for which the standardized regression equation was PV = 0.74 × (DRE estimation) + 0.10 × (age) + 0.12 × (serum PSA) + 0.079 × (urgency score) (adjusted R² = 0.80).ConclusionIn the current study, we confirmed that serum PSA, age, and urgency score are significant predictors of PV. The prediction model including DRE, PSA, age, and urgency score was a better method to estimate PV than DRE alone, especially for men with a larger prostate (PV > 25 mL).     

Differential Roles of GABAA Receptor Subtypes in Benzodiazepine-Induced Enhancement of Brain-Stimulation Reward

Benzodiazepines such as diazepam are widely prescribed as anxiolytics and sleep aids. Continued use of benzodiazepines, however, can lead to addiction in vulnerable individuals. Here, we investigate the neural mechanisms of the behavioral effects of benzodiazepines using the intracranial self-stimulation (ICSS) test, a procedure with which the reward-enhancing effects of these drugs can be measured. Benzodiazepines bind nonselectively to several different GABA_A receptor subtypes. To elucidate the α subunit(s) responsible for the reward-enhancing effects of benzodiazepines, we examined mice carrying a histidine-to-arginine point mutation in the α1, α2, or α3 subunit, which renders the targeted subunit nonresponsive to diazepam, other benzodiazepines and zolpidem. In wild-type and α1-point-mutated mice, diazepam caused a dose-dependent reduction in ICSS thresholds (reflecting a reward-enhancing effect) that is comparable to the reduction observed following cocaine administration. This effect was abolished in α2- and α3-point-mutant mice, suggesting that these subunits are necessary for the reward-enhancing action of diazepam. α2 Subunits appear to be particularly important, since diazepam increased ICSS thresholds (reflecting an aversive-like effect) in α2-point-mutant animals. Zolpidem, an α1-preferring benzodiazepine-site agonist, had no reward-enhancing effects in any genotype. Our findings implicate α2 and α3 subunit containing GABA_A receptors as key mediators of the reward-related effects of benzodiazepines. This finding has important implications for the development of new medications that retain the therapeutic effects of benzodiazepines but lack abuse liability.     

Current problems in hypertension and nephrology

The aim of this issue of Expert Opinion on Pharmacotherapy is to present the most important and controversial problems in hypertension and nephrology. To this end, the most important points of the current (2009) recommendations of the European Society of Hypertension (ESH) are discussed, including aspects related to the treatment of hypertension – the role of beta-blockers, combined therapy with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) the treatment of hypertension in elderly patients, and role of destiffening therapy. The authors also present current recommendations for the management of dyslipidemia in hypertensive and chronic kidney disease (CKD) patients, and new strategies to prevent cardiovascular risk in CKD patients, the optimal level of blood pressure in patients with hypertensive nephropathy and which hypotensive drugs are the most nephroprotective. The Editors are aware that many other important problems have not been addressed in this issue of the journal; however, they hope the readers find it interesting and useful.     

The Effect of Atropine or Atropene Methylnitrate on Salt-induced Hypertension in the Inbred S/JR and R/JR Dahl Rat

The cholinergic antagonists atropine (ATR) and atropine methylnitrate (ATRMN) were chronically administered to inbred Dahl hypertension-sensitive (S/JR) and -resistant (R/JR) rats maintained on an 8.0% NaCl-containing diet. The effects on blood pressure (BP), heart rate (HR), and mortality were then examined during and after a four week period of treatment. Administration of ATR (7.2 mg/day) or ATRMN (2.4 mg/day) attenuated the development of salt-induced hypertension (HT) in the S/JR strain but had relatively little effect on BP in the R/JR strain. HR during the treatment period was significantly greater in S/JR and R/JR rats that received ATR or ATRMN than vehicle-treated controls. Each drug also reduced HT-related mortality in S/JR rats. In general, the effects of ATR on BP and mortality were greater than those of ATRMN. However, the results suggest that the central and peripheral cholinergic systems participate in the development of salt-induced HT in the S/JR rat     

Alterations in the Cellular Immune Response of Patients with Cerebral Glioma,Benign Intracranial Tumour,and Spontaneous Subarachnoid Haemorrhage Measured In Vitro by the Leucocyte Migration Inhibition Test

Leucocyte migration inhibition in response to ubiquitous antigens was studied in 104 patients as an in vitro indicator of cell-mediated immunity. Patients with cerebral glioma, benign intracranial tumours, and subarachnoid haemorrhage demonstrated impaired inhibition of leucocyte migration compared with control subjects. The greatest impairment occurred in patients with subarachnoid haemorrhage, while the least impairment was seen in patients with glioma. Significant rises in inhibition of leucocyte migration in response to antigen preparations from glioma and normal brain were seen in the early post-operative period in patients with glioma and subarachnoid haemorrhage. Impaired cellular immunity, together with sensitivity of lymphocytes to brain-derived antigens, are features of cerebral disease in general and not specific for glioma.     

The Renin — Angiotensin — Aldosterone System in Pre-Eclampsia

Pre-eclampsia is characterised physiologically by plasma volume contraction, intravascular coagulation and intense vasoconstriction. It was originally thought that the renin-angiotensin-aldosterone (RAA) system would be overactive but studies have shown a more complex picture.

Plasma renin activity (PRA) and concentration (PRC) and plasma angiotensin II (AII) and aldosterone concentrations (PAC) are reduced compared to normal pregnancy. Total renin concentration is normal and plasma concentrations of high molecular weight angiotensinogen are increased in pre-eclampsia though total angiotensinogen is normal.

PRA and PRC respond appropriately to physiologic stimuli in pre-eclampsia except for impaired renin release following frusemide, possibly due to prostacyclin deficiency. Although plasma AII concentrations are reduced there is heightened pressor sensitivity to infused AII — the mechanism(s) for this are unknown. PAC is reduced but the ratio PAC:PRC is twofold greater in pre-eclampsia than normal pregnancy. This does not appear to be due to changes in potassium, atrial natriuretic peptide, dopamine or ACTH, and may be another manifestation of increased (adrenal) sensitivity to AII in pre-eclampsia.

There is an inverse relationship between the plasma active renin to prorenin ratio and the clinical severity of pre-eclampsia. Understanding the mechanisms producing these changes in the RAA system in pre-eclampsia will give strong clues to the overall pathogenesis of this disorder.