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.     

中医治疗脑卒中后抑郁症的最新临床进展

脑卒中后抑郁症为脑卒中后常见的并发症之一,给患者、家属及社会带来沉重负担。查阅近年来临床相关文献,并进行总结综述。表明中医治疗脑卒中后抑郁症具有多样疗法,且便于操作,疗效确切,无不良反应。依据临床相关研究,在今后研究发展上,提出了问题并指明了方向。     

Morphogenesis and Regulation of Bergmann Glial Processes During Purkinje Cell Dendritic Spine Ensheathment and Synaptogenesis

星形胶质细胞在突触形成中发挥重要作用,但星形胶质细胞突起如何在发育过程中与突触结构相联系还不是很清楚。本文分析在小脑突触发生过程中Bergmann胶质细胞(BG)突起生长的类型。本文发现在这个过程中,BG突起向外生长与树突棘增多的包被作用相关。此外,双光子时间分辩显像显示BG突起是高度动态的,在棘包被过程中突起趋于稳定。虽然突触活力依赖于肌动蛋白的聚合作用,但细胞骨架调节器Rac1和RhoG的活动在胶质细胞突起的动力或密度上并未发挥作用,而是对于保持突起长度起关键性作用。本文扩展这个发现,探查突起形态和包被之间的关系,发现缩短的突起导致棘覆盖的减少。本文进一步发现在BG表达dn-Rac1和低水平突触包被的区域,显示突触数量的增加。这些分析提示BG突起如何生长并包围突触结构,阐明BG突起结构对突触包被适当发育的重要性,并提示包被在突触形成中的作用。     

Expression of NEDD‐1, a PTEN regulator,in gastric and colorectal carcinomas

Recent studies have disclosed that NEDD4‐1 regulates PTEN activity by ubiquitination. NEDD4‐1 negatively regulates PTEN in cytosol and acts as an oncogenic protein. By contrast, NEDD4‐1 promotes PTEN nuclear import and acts as a tumor suppressor. Despite the importance of NEDD4‐1 in PTEN regulation in cancer cells, expression of NEDD4‐1 protein in cancer tissues is unknown. The aim of this study was to analyze NEDD4‐1 expression in colorectal and gastric cancer tissues. We investigated NEDD4‐1 protein expression in 103 colorectal and 60 gastric carcinoma tissues by immunohistochemistry using a tissue microarray approach. In the cancers, expression of NEDD4‐1 was detected in 82 (80%) of the colorectal carcinomas and 45 (75%) of the gastric carcinomas in cytoplasm. By contrast, the normal mucosal cells of both stomach and colon showed no or very weak expression of NEDD4‐1. There was no significant association of NEDD4‐1 expression with clinicopathologic characteristics, including invasion, metastasis and stage. Our data indicate that NEDD4‐1 overexpression is a feature of both colorectal and gastric carcinomas. The increased expression of NEDD4‐1 in malignant gastric and colorectal cells compared to their normal epithelial cells suggests that NEDD4‐1 expression may play a role in colorectal and gastric cancer development.     

Dose—response relationships for topically applied antigens

Patch-test responses to serially diluted nickel sulphate and potassium dichromate solutions in patients with nickel and chrome sensitivity were assessed by pulsed A-scan ultrasound to determine skin thickness and laser-Doppler flowmeter techniques to evaluate blood flow, as well as clinical scoring. There was a relationship between the dose of antigen and the test responses as measured by ultrasound and laser-Doppler flowmeter techniques in both nickel and chrome sensitive patients. Our data suggest that both techniques may be useful in the detection of allergic contact dermatitis in which there is a doubtful patch-test reaction as well as in experimental sensitization studies.     

Prostate-specific antigen adjusted for the transition zone volume as a second screening test: A prospective study of 248 cases

AIM: This study was conducted to verify the effectiveness of prostate-specific antigen adjusted for the transition zone volume (PSATZ), and its availability as a second screening test for prostate cancer detection. MATERIALS AND METHODS: Total prostate-specific antigen (PSA) and free PSA was measured in male patients who visited our outpatient department for voiding difficulty or screening for prostate cancer. Patients who had an intermediate PSA level between 4.0 and 10.0 ng/mL, with an apparently normal prostate on a digital rectal examination, were enrolled. PSATZ, free-to-total PSA ratio (F/T ratio) and PSA density (PSAD) were calculated and statistical comparisons between biopsy-positive (cancer) and biopsy-negative patients (benign) were conducted. RESULTS: Of 248 patients, 51 (20.6%) had prostate cancer and 197 (79.4%) had benign prostatic hyperplasia (BPH) on pathologic examination. Mean PSA, PSAD, F/T ratio and PSATZ were 7.48 +/- 1.77 ng/mL, 0.23 +/- 0.09 ng/mL per mL, 0.14 +/- 0.08 and 0.71 +/- 0.44 ng/mL per mL in patients with prostate cancer and 6.59 +/- 1.60 ng/mL, 0.16 +/- 0.07 ng/mL per mL, 0.21 +/- 0.11 and 0.36 +/- 0.30 ng/mL per mL in patients with benign, respectively. Receiver operating characteristics (ROC) curve analysis demonstrated that PSATZ predicted the biopsy outcome better than F/T ratio. With a cut-off value of 0.37 ng/mL per mL, PSATZ had a sensitivity of 74.5% and a specificity of 72.6% for predicting prostate cancer. The maximal cut-off value that preserves 100% of sensitivity was 0.2, and at this cut-off value, 16.1% of unnecessary biopsies could be reduced. CONCLUSIONS: Prostate-specific antigen adjusted for the transition zone volume may be more useful than other strategies in detecting prostate cancer in patients with intermediate PSA levels of 4.0-10.0 ng/mL. It can be used as a second screening test to reduce unnecessary biopsy.