Upregulation of hyaluronan and its binding receptors in an experimental model of chronic cyclosporine nephropathy

Aim: Hyaluronan (HA) is an important extracellular matrix (ECM) proteoglycan. The localization of HA and its binding receptors, CD44 and LYVE‐1, was evaluated in an experimental model of chronic cyclosporine A (CsA)‐induced nephropathy. Methods: Sprague–Dawley rats maintained on a low‐salt diet (0.05% sodium) received an s.c. injection of vehicle (1 mL/kg per day olive oil; VH groups) or CsA (15 mg/kg per day; CsA groups) for 1 or 4 weeks. Induction of chronic CsA nephropathy was evaluated according to renal function and pathology and expression of HA, CD44, LYVE‐1, ED‐1 and α‐smooth muscle actin (α‐SMA). Results: CsA treatment for 4 weeks caused renal dysfunction, which was accompanied by typical striped interstitial fibrosis. In the VH group, HA immunoreactivity was observed only in the inner medulla. However, the area of HA immunoreactivity increased with the duration of CsA treatment: CsA treatment for 1 week extended HA immunoreactivity to the outer medulla, and CsA treatment for 4 weeks caused a further extension of HA immunoreactivity to the cortex, which was vulnerable to CsA‐induced renal injury. HA binding receptor, CD44 and LYVE‐1 expression were also upregulated in the CsA groups, and were localized to the area of fibrosis and the peritubular capillaries of the cortex. In the CsA groups, ED‐1 and α‐SMA were predominantly expressed in fibrotic areas in which HA had accumulated. Conclusion: These findings suggest that upregulation of HA and its binding receptors are involved in interstitial fibrosis in chronic CsA‐induced renal injury.     

Local dopaminergic modulation of the motor activity induced by N-methyl-D-aspartate receptor stimulation in the ventral hippocampus.

Dopaminergic neurotransmission has been implicated in the motor activating effects induced by the local infusion of NMDA in the ventral hippocampus (VH). The nucleus accumbens and the ventral tegmental area (VTA) have been proposed to be the main loci where dopamine is acting as a positive modulator of the VH NMDA receptor-mediated motor activating effects. However, the existence of a relatively high dopamine innervation and dopamine receptor density in the VH suggests the possibility of local dopamine/NMDA receptor interactions. This hypothesis was tested by studying the effects of the bilateral local VH infusion of NMDA (0.05, 0.1, 0.5 and 1.0 microg/side), the dopamine D1/D5 receptor antagonist SCH 23390 (1 microg/side) and the dopamine D2 receptor antagonist raclopride (1 and 5 microg/side). Neither SCH 23390 nor raclopride induced any significant change in motor activity compared with the vehicle control group, but both compounds significantly antagonized the motor activation induced by NMDA. SCH 23390 (1 microg/side) was more potent that raclopride (minimal effective dose: 5 microg/side). These results demonstrate the existence of a strong tonic facilitating effect of dopamine, acting preferentially at dopamine D1/D5 receptors, on NMDA receptor-mediated effects in the VH.     

RNAi抑制PI3Kp85α蛋白活性对人乳腺癌细胞系MCF-7生长抑制的体外研究

目的:探讨敲低PI3Kp85α表达对人乳腺癌细胞系MCF-7细胞生长的影响和机制.方法:用靶向PI3Kp85α的siRNA转染人乳腺癌细胞系MCF-7,使用Real-time PCR法鉴定转染PI3Kp85α表达水平;MTT法评价PI3Kp85α siRNA对乳腺癌细胞系MCF-7生长的影响;流式细胞术检测转染后细胞周期分布和凋亡;采用免疫荧光染色及Western blot方法观察IA型PI3K/AKT通路主要成员的表达.结果:Real-timePCR结果显示PI3Kp85α siR-NA转染导致PI3Kp85α表达下调;MTT结果显示PI3Kp85α siRNA转染抑制肿瘤细胞生长;流式细胞术检测可见PI3Kp85α siRNA转染组细胞周期存在G_0/G_1期阻滞而且凋亡率显著高于对照组与空载体组(F=19.255,P=0.002).结论:应用PI3Kp85α siRNA转染人乳腺癌细胞系MCF-7细胞,可抑制其增殖和诱导细胞凋亡,因此PI3Kp85α可以作为人乳腺癌基因治疗的候选靶点.     

Extended follow-up of total inferior turbinate resection for relief of chronic nasal obstruction

Total inferior turbinectomy has been proposed as a treatment for chronic nasal airway obstruction refractory to other, more conservative, methods of treatment. Traditionally, it has been criticized because of its adverse effects on nasophysiology. In this study, patients who had previously undergone total inferior turbinectomy were evaluated with the use of an extensive questionnaire. It confirms that total inferior turbinectomy carries significant morbidity and should be condemned.     

Radio-frequency ablation of renal cell carcinoma in patients who were at significant risk

OBJECTIVE: Although radio-frequency ablation (RFA) has been recently applied as a minimally invasive treatment option for renal cell carcinoma (RCC), indication of this modality remains a critical issue due to the lack of complete tumor destruction as well as the uncertainty of its long-term efficacy. We report the efficacy of RFA for nine carefully selected patients with RCC who had significant reason to avoid invasive surgical treatment under general anesthesia. METHODS: Radio-frequency ablation was performed under epidural or local anesthesia by ultrasound or computed tomography (CT) guidance in nine patients with biopsy proven RCC (mean diameter, 38 mm; range, 20-53 mm), who were at significant operative or anesthetic risk for invasive surgery. Follow-up enhanced CT scans or magnetic resonance images were evaluated every 3-6 months and an evaluation of metastasis was performed every 6 months. RESULTS: At a mean follow-up of 17 months, seven (78%) of the nine patients with renal tumor showed no tumor enhancement. The renal function of all patients was well preserved. All patients were able to continue undergoing their respective treatments for active diseases in other organs in parallel to the RFA treatment. No distant metastasis, urine leakage were reported and one case of temporary hematuria and one case of peri-renal hemorrhage not requiring blood transfusion were encountered. Intra-operative ultrasonography was useful in the real-time monitoring of the minimally excessive extension of ablation into the normal parenchyma. CONCLUSION: Radio-frequency ablation appears to be an effective and safe minimally invasive therapeutic option for selected patients with RCC who have reason to avoid invasive surgery under general anesthesia.     

Significant relationship of time-dependent uroflowmetric parameters to lower urinary tract symptoms as measured by the International Prostate Symptom Score

AIMS: The aim of the present paper is to elucidate the possible involvement of time-dependent parameters as obtained by uroflowmetry in the manifestation of lower urinary tract symptoms (LUTS) in elderly patients. METHODS: Using simple and multiple regression analyses, the correlation of the International Prostate Symptom Score (IPSS) with objective parameters including age, postvoid residual, uroflowmetry and transrectal ultrasonic measurements of the prostate was analyzed in 206 male patients (average age of 68.0 +/- 7.4 years) who visited our outpatient clinic complaining of LUTS. RESULTS: In the 206 patients, the mean maximum flow rate was 12.2 mL/s (13.7 mL/s in mild, 11.9 mL/s in moderate, and 11.2 mL/s in severe IPSS total score) and average flow rate was 4.4 mL/s (5.4 mL/s in mild, 4.3 mL/s in moderate, and 3.5 mL/s in severe IPSS total score). Simple regression analyses demonstrated that age, voiding time, and average and maximum flow rates correlate significantly with symptom scores. In particular, relatively strong relationships were found between average flow rate and scores of intermittency, weak stream and total and voiding symptoms scores. Serum prostate specific antigen level, postvoid residual and prostatic ultrasonic measurements did not show a significant correlation with symptom scores. Multiple regression analyses revealed age and average flow rate to be independent determinants for symptom scores. These results suggest that the time-dependent function in micturition interferes in the manifestation of LUTS in elderly men who have borderline or pathologic maximum flow rate. When evaluating uro flowmetry in elderly male patients with LUTS, attention should be paid to time-dependent parameters such as voiding time and average flow rate.     

Differential effects of the dopamine antagonist remoxipride on apomorphine induced behaviour in the rat

The effects of the novel substituted benzamide remoxipride on apomorphine induced behaviour in rats was investigated by means of an automatic holeboard apparatus. The ability of remoxipride to antagonise locomotion and gnawing induced by a high dose of apomorphine (5 mg/kg) and inhibition of exploration induced by a low dose of apomorphine (0.05 mg/kg) was tested. It was found that remoxipride in moderate doses potentiate locomotion and inhibit gnawing induced by the high dose of apomorphine while higher doses of remoxipride inhibits both apomorphine induced gnawing and locomotion. The inhibition of exploration following the low dose of apomorphine was not antagonised by remoxipride pretreatment. The results demonstrated that remoxipride has an interesting and unique profile of dopamine antagonistic effects in rat behavioural models.