ULTRASTRUCTURAL CHANGE OF THE GLOMERULAR BASEMENT MEMBRANE IN RATS WITHHEYMANN NEPHRITIS REVEALED BY ULTRAHIGH RESOLUTION SCANNING ELECTRON MICROSCOPY

To assess the relationship between the glomerular injury induced by immune complex deposition and proteinuria, ultrastructural changes of the glomerular basement membrane (GBM) were investigated in Heymann nephritis. Active Heymann nephritis was induced in rats by injecting them with tubular brush border antigen, known as Fx1A, emulsified in complete Freund's adjuvant (CFA). Measurement of urinary protein excretion and histological examinations were carried out for up to 15 weeks after immunization. Proteinuria developed in rats within 10 weeks of immunization and coincided with the development of subepithelial deposits with minimal spike-like basement membrane protrusion. Acellular glomeruli were prepared by detergent treatment and were subjected to tannic acid–osmium conductive staining prior to examination with an ultrahigh resolution scanning electron microscope (HSEM). HSEM of the acellular GBM prepared from control rats injected with CFA alone revealed a meshwork structure, with pores of about 9 nm in diameter. Proteinuric rats immunized with Fx1A showed a loosened meshwork structure, with pores of about 15 nm in the acellular GBM adjacent to the deposits. The newly formed GBM overlying the deposit consisted of a meshwork structure associated with unorganized thin fibrils. Ultrastructural changes were never seen in GBM devoid of deposits. These findings indicate that subepithelial deposits are closely involved in the development of proteinuria by injuring the size selectivity of the GBM.     

Protective Effects of Dilazep and its Derivative K-7259 on the Haemolysis Induced by Amphiphiles in Rat Erythrocytes

The effects of dilazep and K-7259, a dilazep derivative, on the haemolysis (as evidenced by release of haemoglobin) induced by palmitoyl-l -carnitine (PAL-CAR) or palmitoyl 1-α-lysophosphatidylcholine (PAL-LPC) have been determined in rat erythrocytes. At concentrations above the critical micelle concentration both PAL-CAR and PAL-LPC induced haemolysis; the concentrations of PAL-CAR and PAL-LPC producing 50% haemolysis were approximately 13 and 14 μm , respectively. The 50% haemolysis induced by PAL-CAR or PAL-LPC was attenuated by dilazep (1, 10 or 100 μm ) but not at the highest concentration used (1 mm ). K-7259 attenuated the 50% haemolysis induced by PAL-CAR or PAL-LPC at concentrations ranging from 1 μm to 1 mm . Similarly, dilazep (1 to 100 μm ) and K-7259 (1 μm to 1 mm ) significantly or insignificantly attenuated the 25% and 75% haemolysis induced by PAL-CAR or PAL-LPC. Neither dilazep nor K-7259 affected micelle formation by PAL-CAR or PAL-LPC, nor, at concentrations of 1 and 10 μm , did they attenuate the haemolysis induced by osmotic imbalance (hypotonic haemolysis). These results suggest that both dilazep and K-7259 protect the erythrocyte membrane from the damage induced by PAL-CAR or PAL-LPC. The protective effects of dilazep and K-7259 are mediated by some mechanism other than prevention of micelle formation or protection of the erythrocyte membrane against osmotic imbalance.     

Effects of Flavonoids Isolated from Scutellariae Radix on the Production of Tissue-type Plasminogen Activator and Plasminogen Activator Inhibitor-1 Induced by Thrombin and Thrombin Receptor Agonist Peptide in Cultured Human Umbilical Vein Endothelial Cells

The effects of different flavonoids isolated from the roots of Scutellaria baicalensis Georgi on the production of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) induced by thrombin and thrombin receptor agonist peptide, Ser-Phe-Leu-Leu-Arg-Asn-Pro-Asn-Asp-Lys-Tyr-Glu-Pro-Phe, have been examined in cultured human umbilical vein endothelial cells (HUVECs). Thrombin and thrombin receptor agonist peptide induced production of both t-PA and PAI-1 and the elevation of intracellular free calcium concentration ([Ca²⁺]_i). Baicalein isolated from Scutellariae Radix dose-dependently inhibited PAI-1 production induced by thrombin and thrombin receptor agonist peptide; its concentrations for 50% inhibition (IC50) were 6.8 and 3.5 μm , respectively. Other flavonoids had no effect. In contrast, flavonoids isolated from Scutellariae Radix had no effect on production of t-PA induced by thrombin and thrombin receptor agonist peptide. Baicalein inhibited the elevation of [Ca²⁺]; induced by thrombin and thrombin receptor agonist peptide and, at a concentration of 1000 μm , slightly increased t-PA production. These findings suggest that the mechanism by which baicalein inhibits PAI-1 production induced by thrombin and thrombin receptor agonist peptide might be by reduction of [Ca²⁺]_i elevation. The results suggest that baicalein in Scutellariae Radix might be active as a drug in the treatment of arteriosclerosis and thrombosis.     

Significance of electrostimulation in detecting neurovascular bundle during radical prostatectomy

OBJECTIVE: The reported rate of erectile dysfunction after nerve-sparing prostatectomy varies according to physicians. Because exact preservation of the neurovascular bundle (NVB) solely depends on the judgment of the physician, he or she should try to correctly identify the NVB and also avoid neurophysiologic injury of the NVB during the procedure. The purpose of the present study is to assess the status of the NVB preservation by physician's judgment at the operation, the changes in intracavernous pressure related to intraoperative electrical stimulation and postoperative histopathological examination. PATIENTS AND METHODS: Thirty-eight patients who underwent nerve-sparing radical prostatectomy judged by intraoperative electrical stimulation of the NVB were included in this study. Bilateral, unilateral and non-nerve-sparing procedures were performed in 18, 17, and 3 cases, respectively. The NVB preservation evaluated by intraoperative physician's judgment was compared to that evaluated by postoperative histopathological examination. Furthermore, the NVB preservation evaluated by intraoperative electrical stimulation was compared to that by physician's judgment and postoperative histopathological examination. RESULTS: For 68 of 76 NVB (89.5%), intraoperative subjective judgment and histopathological assessment were identical. For 66 of 76 NVB (86.8%), electrical stimulation findings and the physician's judgments were identical, and for 70 of 76 NVB (92.1%), electrical stimulation findings and histopathological findings were identical. CONCLUSION: Even if physicians are convinced of a successful nerve-sparing procedure, there are some cases in which the NVB is not preserved accurately or neurophysiological damage is suffered. Therefore, intraoperative electrical stimulation of the NVB as well as the cavernosal nerve is very useful in evaluation of NVB preservation.     

Radiofrequency Catheter Ablation of Left Ventricular Outflow Tract Tachycardia from the Coronary Cusp: A New Approach to the Tachycardia Focus

INTRODUCTION: Idiopathic ventricular tachycardia (VT) originating from the left ventricular outflow tract (LVOT) is rare. Previously reported were two cases of LVOT tachycardia which were treated with radiofrequency (RF) catheter ablation through endocardial aortomitral continuity. We report here a case of a repetitive LVOT tachycardia in which the QRS morphology during VT exhibited an atypical left bundle branch block and inferior axis. Pace mapping revealed that the origin of this VT was very close to the left sinus of Valsalva. Transcoronary cusp RF catheter ablation abolished the VT in this patient and is a new approach for the treatment of this kind of VT. The application of this approach to the other types of VT has yet to be determined.     

Outcomes of Ablation of Paroxysmal Atrial Fibrillation in Patients on Chronic Hemodialysis

AF Ablation in HD Patients . Introduction: It is not common for patients on chronic hemodialysis (HD) to undergo catheter ablation of atrial fibrillation (AF). We aimed to show the outcomes of AF ablation in the HD patients. Methods and Results: Thirty HD patients who underwent pulmonary vein (PV) isolation for drug refractory paroxysmal AF were retrospectively studied, and their AF recurrence free rate and frequency of periprocedural complications were compared to 60 age‐ and gender‐matched control patients not requiring HD. A nonirrigated ablation catheter was used in both patient groups. During a mean follow‐up period of 821 ± 218 days, 16 (54%) of the HD patients remained free from AF recurrence without any antiarrhythmic agents versus 47 (78%) of the control patients with an initial ablation (P = 0.013). A second ablation procedure was performed in 12 patients with an AF recurrence, and consequently 20 (67%) of the HD patients were in sinus rhythm compared to 53 (88%) of the controls during a follow‐up duration of 747 ± 221 after the last ablation (P = 0.012). Bleeding from the venipuncture site requiring a prolonged hospital stay was identified in 2 HD patients and 1 control subject, while no life‐threatening complications were observed in either patient group. Conclusion: Although the success rate of the PV isolation in HD patients was far from satisfactory, it may be considered as one of the therapeutic options for them. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1289‐1294, December 2012)     

去氢表雄酮通过调节丝/苏氨酸蛋白激酶信号传导通路抑制大鼠Morris肝细胞瘤生长

目的 探讨去氢表雄酮(DHEA)的体内抗癌作用及其机制.方法 Buffalo大鼠21只随机分为空白对照组、肿瘤对照组(把Morris肝细胞瘤移植到大鼠的两肋皮下,建立Morris肝细胞瘤移植的Buffalo大鼠的体内模型,基础饲料喂养)、DHEA肿瘤组(建立Morris肝细胞瘤移植模型后,在喂养的基础饲料中添加DHEA)和去氢表雄酮硫酸酯(DHEAs)肿瘤组(建立Morris肝细胞瘤移植模型后,在喂养的基础饲料中添加DHEAs).分别喂养4周后,Western blot和免疫组织化学方法检测磷酸化丝/苏氨酸蛋白激酶(Akt)、PTEN等蛋白的表达,流式细胞术检测大鼠CD3,CD4、CD8和CD4/CD8.单因素方差分析对数据进行处理.结果 DHEA肿瘤组的肝细胞瘤的质量为(8.31±0.61)g,较肿瘤对照组的(14.57±0.56)g显著减轻(P＜0.05).Westem blot及免疫组织化学染色结果显示,DHEA肿瘤组的磷酸化Akt蛋白表达量降低,而PTEN蛋白表达增强;CD3阳性细胞百分率(74.97%±8.29%)较肿瘤对照组(56.45%±6.12%)明显提高(t=4.92,P＜0.05),CD4/CD8比值升高(1.75±0.22).而DHEAs肿瘤组CD3阳性细胞百分率(60.04%±6.69%)较空白对照组(75.38%±9.76%)明显降低(t=3.87,P＜0.05),同时CD4/CD8比值也降低(1.48±0.56).结论 DHEA对体内的肿瘤具有明显的抑制作用,此作用可能是其通过调节体内的Akt信号传导通路和免疫功能来完成的.     

Successful bone marrow transplantation for idiopathic hypereosinophilic syndrome

A 21-year-old man who had an increased number of eosinophils with morphological abnormalities, bone marrow fibrosis and multiple organ dysfunction failed to respond to methylprednisolone and hydroxyurea. He was diagnosed with hypereosinophilic syndrome (HES) probably due to myeloproliferative disorder, and underwent allogeneic bone marrow transplantation (allo-BMT) from an HLA-identical sibling. The engraftment was confirmed on day 21 after BMT, but the patient developed acute graft-versus-host disease (GVHD) with grade I veno-occlusive disease, and transient increase of eosinophils of the donor type followed by chronic GVHD of the extensive type. These complications were eventually controlled with cyclosporin A. The patient survived free of disease for more than a year after BMT. Allo-BMT seems to be a possible treatment of HES/MPD.