Kuo Liang Chen

Involvement of oxidative stress-mediated ERK1/2 and p38 activation regulated mitochondria-dependent apoptotic signals in methylmercury-induced neuronal cell injury

Methylmercury (MeHg) is well-known for causing irreversible damage in the central nervous system as well as a risk factor for inducing neuronal degeneration. However, the molecular mechanisms of MeHg-induced neurotoxicity remain unclear. Here, we investigated the effects and possible mechanisms of MeHg in the mouse cerebrum (in vivo) and in cultured Neuro-2a cells (in vitro). In vivo study showed that the levels of LPO in the plasma and cerebral cortex significantly increased after administration of MeHg (50μg/kg/day) for 7 consecutive weeks. MeHg could also decrease glutathione level and increase the expressions of caspase-3, -7, and -9, accompanied by Bcl-2 down-regulation and up-regulation of Bax, Bak, and p53. Moreover, treatment of Neuro-2a cells with MeHg significantly reduced cell viability, increased oxidative stress damage, and induced several features of mitochondria-dependent apoptotic signals, including increased sub-G1 hypodiploids, mitochondrial dysfunctions, and the activation of PARP, and caspase cascades. These MeHg-induced apoptotic-related signals could be remarkably reversed by antioxidant NAC. MeHg also increased the phosphorylation of ERK1/2 and p38, but not JNK. Pharmacological inhibitors NAC, PD98059, and SB203580 attenuated MeHg-induced cytotoxicity, ERK1/2 and p38 activation, MMP loss, and caspase-3 activation in Neuro-2a cells. Taken together, these results suggest that the signals of ROS-mediated ERK1/2 and p38 activation regulated mitochondria-dependent apoptotic pathways that are involved in MeHg-induced neurotoxicity.

Pyrrolidine dithiocarbamate (PDTC)/Cu complex induces lung epithelial cell apoptosis through mitochondria and ER-stress pathways

Pyrrolidine dithiocarbamate (PDTC) is widely used in pesticides, fungicides, insecticides, and herbicides. Copper (Cu) is a toxic heavy metal in the environment, and an essential trace metal element in the body, which is involved in many biological processes as a catalytic cofactor. The present study is designed to investigate the cellular toxicity of PDTC, CuCl(2), and PDTC/Cu complex exposure in lung alveolar epithelial cells that serve primary structural and functional roles in the lungs. The results showed that PDTC or CuCl(2) alone did not affect cell viability, but PDTC/Cu complex significantly decreased lung alveolar epithelial cell viability. PDTC/Cu complex also significantly increased intracellular copper concentration, but PDTC or CuCl(2) alone had low levels of copper. PDTC/Cu complex dramatically enhanced the JNK protein phosphorylation and ERK protein phosphorylation proteins. PDTC/Cu complex did not affect the p38 protein phosphorylation. PDTC/Cu complex was capable of activating the apoptosis-related caspases including caspase-9, caspase-7, and caspase-3, which could be reversed by the addition of JNK inhibitor SP600125 or transfection of MAPK8 short hairpin RNA. PDTC/Cu complex also increased cytosolic cytochrome c and decreased mitochondrial transmembrane potential. The Bcl-2 mRNA and protein expressions were decreased in lung epithelial cells treated with PDTC/Cu complex, which could be reversed by SP600125. Furthermore, PDTC/Cu complex could trigger the expressions of ER stress-associated signaling molecules including Grp78, Grp94, caspase-12, ATF4, and CHOP, which could be reversed by SP600125. Taken together, these results indicate that exposure to PDTC/Cu complex induces cytotoxicity and apoptosis in alveolar epithelial cells via the mitochondria- and ER-stress-related signaling pathways.

Women urinate in the standing position do not increase post-void residual urine volumes.

The effects of standing while voiding have seldom been investigated in women. We evaluate urodynamic parameters of voiding while standing in healthy women using uroflowmetry and post‐void residual urine volume assessment. Results are compared with crouching and sitting.

Spontaneous ureteral rupture and review of the literature.

INTRODUCTION Spontaneous ureteral rupture is defined as non-traumatic urinary leakage from the ureter. This is a diagnosis that, although uncommon, is important for emergency physicians to know about. The literature is relatively sparse. MATERIALS AND METHODS This was a retrospective review of patients who were diagnosed with spontaneous ureteral rupture. From 2006 to 2012, 18 patients were diagnosed by radiography (computed tomography or intravenous urogram) with spontaneous ureteral rupture. These cases all showed extravasation of the contrast outside the excretory system. We evaluated underlying causes, diagnostic and therapeutic procedures, and outcomes. RESULTS There were 9 men and 9 women with a median age of 59 years (range, 22-82 years). In 56% of patients, a ureteral stone was the cause; in 17% of, a ureteral stricture; in 1 patient, a ureteral tumor; and in the remaining 22%, no cause was identified. In 13 patients (72.2%), primary ureteroscopy to place D-J stents was performed. The average duration of ureteral catheter stenting was 21 days (range, 8-45 days). The other 5 patients (27.8%) were managed conservatively with antibiotic treatment and the outcome was good. CONCLUSIONS Ureteral stones most commonly cause spontaneous ureteral rupture. In our experience, most patients received ureteroscopy and Double-J stenting. Conservative management with antibiotics also had good outcomes. Most patients had sudden onset of abdominal or flank pain. Spontaneous ureteral rupture should be kept in the differential diagnosis of patients with acute abdominal or flank pain in the emergency department.

The impact of gender and size on the pathology of small renal mass.

Without surgery, it is hard to predict the histology of small (≦ 4 cm) renal masses (SRMs) based on images. This study attempted to investigate whether clinical parameters were correlated with the pathological presence of SRM carcinomas. We conducted a retrospective chart review of 60 patients with 61 suspicious SRMs on radiological examination who received radical nephrectomy (RN) or partial nephrectomy (PN) between January 2003 and February 2011 in the China Medical University Hospital (CMUH). The correlations between patient age, gender, tumor size, and pathological features were calculated and analyzed. Of the 61 SRMs, there were 51 (83.6%) renal cell carcinoma (RCC), seven (11.5%) angiomyolipoma, two (3.3%) oncocytoma, and one (1.6%) metanephric adenoma. Regarding the histological variants of these cases of RCC, 44 were categorized as the clear cell type, two as the papillary type, and five as the chromophobe type. The incidence of benign tumor was greater in females (p = 0.014) and tumor size 2 cm or less (p = 0.02), compared with males and tumor size more than 2 cm, respectively. Surgical intervention is generally recommended for medically fit patients.

Prostate Health Index (PHI) improves prostate cancer detection at initial biopsy in Taiwanese men with PSA 4–10 ng/mL

In this study, we aimed to validate the Prostate Health Index (PHI) for the detection of prostate cancer (PCa). We prospectively enrolled patients aged 50–75 years with a serum prostate specific antigen (PSA) level of 4–10 ng/mL undergoing transrectal biopsy of the prostate between April 2016 and May 2017. The primary outcome was the diagnostic performance of various PSA derivatives (total PSA, free PSA, %fPSA, p2PSA, %p2PSA, and PHI) to predict PCa. The secondary outcome was comparisons of PSA derivatives between patients with a Gleason score (GS) ≤ 6 and GS ≥ 7. PCa was diagnosed in 36 of 154 (23.4%) patients, and 26 (16.9%) had a GS ≥ 7. The areas under the receiver operating characteristic curves were significantly greater in %p 2PSA and PHI than in PSA (0.76 vs. 0.57, p = 0.015 and 0.77 vs. 0.57, p = 0.004, respectively). Patients with a GS ≥ 7PCa had marginally higher %p2PSA and PHI than those with a GS of 6 (17.8 vs. 12.73, p = 0.06; 46.58 vs. 31.55, p = 0.05). At a PHI cutoff value of 29.6, the sensitivity and specificity were 77.8% and 67.8% in detecting PCa, respectively. In addition, 57.1% of the patients avoided an unnecessary biopsy, while three patients (1.9%) with GS 7 PCa were missed. In conclusion, the ability of %p2PSA and PHI to predict prostate biopsy outcome was better than that of PSA and %fPSA in the initial biopsy in Taiwanese men with serum PSA between 4 and 10 ng/mL.

Continuous positive airway pressure therapy improves stage 1 and stage 2 sleep nocturia in individuals with obstructive sleep apnea.

An exercise intervention without nutritional intervention may worsen nutritional status in frail older women. Nutritional requirements may increase in response to an exercise intervention, so it is recommended that frail older people avoid energy and protein deficiency, or increase protein intake, when they do strength training. The exercise group had lower iron intake and worse iron status after the intervention but still took in more iron than the control group. The enzyme supplement digests protein, carbohydrate, fat, and dietary fiber, improving absorption of amino acids, cholesterol, and sugars. Previous nutritional intervention studies used supplements, but some studies have suggested that the use of a supplement decreases nutritional intake from food. The major limitation of this study was that subjects were not allocated randomly to the groups. It was carefully checked that diet and physical activity were constant in the groups during the study. The exercise and exercise with supplementation groups had the same exercise program, although Barthel Index and grip strength were higher in the exercise group than in the exercise with supplementation group. Differences in these conditions or other factors may have affected the present results, although it appears that an exercise intervention without paying attention to nutrition may worsen nutritional status. Nutritional condition should be assessed when older people undertake an exercise intervention.

The role of retrograde pyelography for evaluation of hematuria in patients with normal and impaired renal function

Purpose. Hematuria can be a sign of urinary tract disorders; therefore, it is necessary to arrange complete imaging studies to evaluate the entire urinary system. Our purpose is to elucidate the efficacy of retrograde pyelography (RP) for evaluating patients who present with hematuria. Methods. From 2000 to 2002, a total of 634 patients underwent RP procedures because of hematuria. After excluding the 378 patients with urothelial carcinoma, stone disease, and urinary tract infection, 256 patients were included in this study. Patients were divided into two groups based on renal function: Group I: normal renal function (n=156); Group Ⅱ: poor renal function (Cr＞2.0) (n=100). Patients in Group Ⅰ were further classified into either group Ⅰa: gross hematuria (n=104) or Ⅰb: microscopic hematuria (n=52). Patients in Group II were further subdivided into either Group Ⅱa uremia (n=39) or Ⅱb: chronic renal function impairment (n=61). Results. Patients in Group Ⅱ(50.0%) were more likely to have malignancy (OR=4.2, 95% CI=2.5 to 7.0, p＜0.001) than those in Group Ⅰ(19.2%). In Group Ⅱ, uremia (74.3%) was most closely associated with urothelial carcinoma (OR=5.5, 95% CI=2.3 to 13.1, p＜0.05). The rate of stone disease was significantly higher for Group Ⅱ(OR=2.0, 95% CI=1.1 to 3.8, p＜0.005). Conclusions. Patients with impaired renal function are more likely to have urinary stone disease and urothelial cancer than those with normal renal function. Thus, RP is more valuable for evaluating hematuria in patients with impaired renal function than in those with normal renal function. Among the patients with impaired renal function, uremic patients are at highest risk of having urothelial cancer in Taiwan. Therefore, it is crucial to perform RP and cystoscopy for patients with impaired renal function, especially for those with uremia.