Clinical impact of tamsulosin on generic and symptom-specific quality of life for benign prostatic hyperplasia patients: Using international prostate symptom score and Rand Medical Outcomes Study 36-item Health Survey

AIM: To examine the efficiency of alpha1-blocker treatment on disease-specific and generic quality of life (QOL) in men with clinically diagnosed benign prostatic hyperplasia (BPH), the improvement of QOL scores with International prostate symptom score (I-PSS) and Rand Medical Outcomes Study 36-item Health Survey (SF-36) was prospectively analyzed. METHODS: A total of 68 newly diagnosed patients with symptomatic BPH that satisfied all inclusion and none of the exclusion criteria were prospectively recruited. All patients received 0.2 mg/day of tamsulosin for 12 weeks. All patients underwent pretreatment documentation of lower urinary tract symptoms (LUTS) and assessment of symptom-specific QOL. Symptoms and general health-related QOL (HRQOL) were assessed using the I-PSS and SF-36, respectively. Also, other objective variables, such as prostate volume, maximal urinary flow and postvoid residual urine volume, were evaluated. RESULTS: After 12 weeks, decrease in I-PSS was 27% compared with baseline (from 16.4 +/- 7.18 to 11.9 +/- 7.56). All questionnaires in the I-PSS showed improvement after tamsulosin treatment and the I-PSS QOL score was improved from 4.51 +/- 1.14 to 3.17 +/- 1.38 (P < 0.0001) at 12 weeks after tamsulosin administration. In intragroup comparisons of HRQOL scores with age-gender adjusted SF-36 Japanese national norms, three SF-36 subscales (bodily pain, BP; social function, SF; and mental health, MH) were worse in the BPH group aged over 70 years, while younger BPH groups aged <70 had better mean SF-36 physical function (PF) scores compared with age-gender adjusted Japanese national norms. In the BPH group with a prostatic volume > or =20 mL, three mean SF-36 scales (BP, SF and MH) were significantly improved after tamsulosin treatment. It is noteworthy that these SF-36 subscales were identical to those observed to worsen in the older BPH group compared to Japanese national norms. CONCLUSIONS: Treatment with tamsulosin for symptomatic BPH patients is associated with significant improvement in the generic HRQOL, in addition to disease-specific QOL and symptoms, at 3 months after drug administration. In particularly, for generic HRQOL with SF-36, tamsulosin treatment can efficiently improve three mean SF-36 subscales (BP, SF and MH) that are decreased in older BPH patients.     

Decreased serum carnitine is independently correlated with increased tissue accumulation levels of advanced glycation end products in haemodialysis patients

Aim: There is accumulating evidence that advanced glycation end products (AGE) play a role in cardiovascular disease (CVD) in patients with haemodialysis (HD). Carnitine deficiency is frequently observed in HD patients, which may also contribute to CVD. In this study, we examined whether carnitine deficiency was independently associated with increased tissue accumulation levels of AGE in HD patients. Methods: One hundred and twenty‐nine HD patients underwent determinations of blood chemistries including serum level of carnitine. Tissue AGE levels were evaluated by measuring skin autofluorescence with an AGE‐reader. Results: Serum carnitine levels were significantly lower, while skin AGE levels were significantly higher in HD patients compared with healthy controls (P < 0.001). In univariate analysis, β₂‐microglobulin (β₂‐MG) and carnitine (inversely) were correlated with skin AGE levels. Multiple stepwise regression analysis revealed that carnitine levels were one of the independent determinants of skin AGE levels (P = 0.024). When β₂‐MG‐adjusted skin AGE levels were stratified by serum carnitine levels, a statistical significance and dose‐response relationship were observed (P = 0.043). Furthermore, skin AGE levels were one of the independent determinants of serum carnitine levels as well (P = 0.012). Conclusion: The present study demonstrated that decreased carnitine levels were independently associated with increased skin AGE levels in HD patients. Since carnitine is reported to inhibit the formation of AGE in vitro, our study suggests that supplementation of carnitine may be a therapeutic target for preventing the accumulation of tissue AGE and subsequently reducing the risk of CVD in HD patients.     

Diurnal changes of blood pressure,heart rate and body temperature during sleep in the rat

We have studied diurnal changes in mean arterial pressure (MAP), heart rate (HR) and body temperature (Tb) during wake (W), non-rapid eye movement sleep (NREMS) and REM sleep (REMS) in the rat. Although HR and Tb show a similar sinusoidal diurnal variation during all vigilance states, the diurnal profile for the MAP is vigilance-state dependent. During W, MAP values are higher during the dark phase, during NREMS, no significant diurnal change is seen, and during REMS, the MAP exhibits a reversed diurnal change, being higher during the light phase. The low frequency component (0.25–0.725 Hz) in the power spectral density of the blood pressure, an index of sympathetic activity, is also higher during the light phase than the dark phase in REMS. The present findings suggest that diurnal changes in MAP in the rat result from the wake rhythm, and that the mechanism for the diurnal control of MAP may be different from that for HR or Tb.     

Effect of ambient temperature on arterial pressure variability during sleep in the rat

Changes in mean arterial pressure (MAP) and heart rate (HR) during sleep were recorded at three ambient temperatures ( T _a: 16, 22 and 28°C). MAP and HR during sleep increased with lowering of T _a. The increase in MAP during the transition from NREM to REM sleep was decreased by lowering the T _a. At 28°C, the average HR increased in going from NREM to REM sleep, while, at 16°C, it decreased. The coefficient of variation (CV%) of the MAP during REM sleep decreased as the T _a was lowered, while that seen during NREM sleep was unchanged. This study suggests that T _a has a greater effect than sleep stage on the MAP and HR, and that MAP variability during REM sleep is greater at higher T _a.     

Immunotoxicological Insignificance of Fenitrothion in Mice and Rats

Fenitrothion was administered orally to mice or rats in dailydoses of up to of the LD50 for 14 days, and numbers of splenic plaque-forming cells against sheep redblood cells (SRBC-PFC), one of the most common immune parameters,were measured. Splenic SRBC-PFC number was suppressed by fenitrothiononly in rats which received 30 mg/kg body weight (bw) of thecompound. Other immune parameters, including the arthus reaction,delayed-type hypersensitivity, and activities of macrophagesand natural killer cells in rats, were not influenced by fenitrothion.Adrenal hyperfunction manifesting as increased organ weightand elevated plasma corticosterone level was noted along withstrong cholinergic signs in rats which received 30 mg/kg bwof fenitrothion. At lower doses such as 3 or 0.3 mg/kg bw offenitrothion, rats had no strong cholinergic signs, adrenalhyperfunction, or evidence of immunosuppression despite significantsuppression of systemic cholinesterase (ChE) activities. Inmice, no suppression of SRBC-PFC number or mixed lymphocytereaction was noted even at the highest dose (40 mg/kg bw) offenitrothion, at which significant suppression of systemic ChEactivities but no cholinergic signs were noted. These findingsstrongly suggest that the im-munosuppressive effect of fenitrothionnoted in rats was due to systemic, potent cholinergic stressand that fenitrothion has no immunotoxicity in mice and rats.     

Tenomodulin蛋白对血管内皮细胞增生的抑制作用

目的研究tenomodulin（TeM）蛋白对血管内皮生长因子（VEGF）诱导的人视网膜血管内皮细胞（RECs）和人脐静脉内皮细胞（UVECs）增生及其对体外血管样结构形成的作用。方法将传代至3～6代的人RECs和人UVECs生长至融合时用含质量分数0.5%胎牛血清（FBS）的培养基孵箱中培养6h,加入不同质量浓度的VEGF或VEGF＋TeM混合物,继续培养12h,ELISA法检测TeM对VEGF诱导的血管内皮细胞增生的影响。将含10%FBS、1%FBSDMEM培养基的人RECs和人UVECs悬液分别接种于预先放置基质胶的24孔培养板表面,含1%FBS培养基的细胞培养板内分别加入VEGF（100μg/L）或VEGF＋TeM混合物37℃继续培养6h,共焦显微镜下观察,图像处理分析软件量化分析TeM蛋白对毛细血管样结构形成的作用。结果随着VEGF质量浓度的增加,血管内皮细胞DNA合成增加,其吸光度（A）值呈明显上升曲线,而添加TeM组的A值比VEGF组降低,差异有统计学意义（P〈0.01）。含10%FBS和1%FBS培养基的血管内皮细胞在基质胶表面形成毛细血管样结构,并连接成网状;在基质胶表面同时添加VEGF的血管内皮细胞,其毛细血管样结构明显增多,长度明显变长。添加TeM组的血管内皮细胞和其毛细血管样结构破坏,每个视野内血管内皮细胞毛细血管样结构显著破坏,管形细胞总长度明显变短。结论 TeM蛋白对血管内皮细胞的增生及体外血管样结构的形成有明显抑制作用。     

Successful Slow Pathway Ablation in a Patient with Atrioventricular Nodal Reentrant Tachycardia Having a Proximal Common Pathway

Radiofrequency catheter ablation was attempted in a patient with atrioventricular nodal reentrant tachycardia (AVNRT). AVNRT was easily inducible but an intermittent loss of the atrial activation was observed during AVNRT suggesting the presence of a proximal common pathway. During sinus rhythm, a relatively delayed activation that was compatible with a slow potential, was recorded anterior to the ostium of coronary sinus, and radiofrequency catheter ablation application (20 watts) to the site induced junction tachycardia. After an additional radiofrequency catheter ablation application to close the site, AVNRT became noninducible without deterioration of atrioventricular conduction through a fast pathway. This is the first case in which radiofrequency catheter ablation application to the slow potential recording site has been successful, even in AVNRT having a proximal common pathway.     

Fas-mediated apoptosis is involved in the elimination of gene-transduced hepatocytes with E1/E3-deleted adenoviral vectors

Gene-transduced hepatocytes with E1/E3-deleted adenoviral vectors are eliminated immediately and the expression of transduced genes disappears rapidly following the vector administration. In this report, we analysed the involvement of apoptotic cell death in the elimination of hepatocytes infected with adenoviral vectors. An E1/E3-deleted adenoviral vector expressing Escherichia coli β-galactosidase (LacZ) was injected via the portal vein into congenitally Fas-deficient mice (lpr), Fas ligand-deficient mice (gld) and their control mice, MRL and C3H. 5-Bromo-4-chloro-3-indolyl-β-D-galactoside (X-gal) staining of the liver specimens showed that 80–100% of hepatocytes were LacZ positive at 7 days after virus administration, suggesting that most of the hepatocytes received the injected adenoviral vectors. In normal mice, the number of LacZ-positive cells decreased dramatically at 14 and 21 days after transduction and few positive cells were observed at day 28. β-Galactosidase activity, quantified by the O-nitrophenyl-beta-D-galactopyranoside assay, gave comparable results to X-gal staining. At days 14 or 21, many apoptotic hepatocytes and apoptotic infiltrating cells were detected with the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) in situ apoptosis detection method. This observation suggested that the apoptotic process was associated with the elimination of adenovirus-infected hepatocytes. To test the involvement of the Fas—Fas ligand interaction in this apoptotic process, the period of transgene expression was measured in 1pr and gld mice, which had received the same amount of AxCALacZ. X-Gal histochemical analysis detected many LacZ-positive cells in 1pr or gld mice liver even at 21 or 28 days after AxCALacZ injection. There were significant differences in the reduction rates of β-galactosidase activity of liver homogenates between lpr and MRL, or gld and C3H mice. Based on these observations, we conclude that the Fas-mediated apoptotic process is involved in the elimination of hepatocytes infected with E1/E3-deleted adenoviral vectors.