WNT3A Promotes Neuronal Regeneration upon Traumatic Brain Injury.

The treatment of traumatic brain injury (TBI) remains a challenge due to limited knowledge about the mechanisms underlying neuronal regeneration. This current study compared the expression of WNT genes during regeneration of injured cortical neurons. Recombinant WNT3A showed positive effect in promoting neuronal regeneration via in vitro, ex vivo, and in vivo TBI models. Intranasal administration of WNT3A protein to TBI mice increased the number of NeuN+ neurons without affecting GFAP+ glial cells, compared to control mice, as well as retained motor function based on functional behavior analysis. Our findings demonstrated that WNT3A, 8A, 9B, and 10A promote regeneration of injured cortical neurons. Among these WNTs, WNT3A showed the most promising regenerative potential in vivo, ex vivo, and in vitro.

Effect of CYP3A4 genetic polymorphisms on the genotoxicity of 4,4'-methylene-bis(2-chloroaniline)-exposed workers.

OBJECTIVES: We investigated the relationship between 4,4'-methylene-bis(2-chloroaniline) (MBOCA) exposure and micronucleus (MN) frequency, and how this association was affected by genetic polymorphism of the cytochrome P450 enzyme (CYP3A4). METHODS: We divided the study population into an exposed group (n=44 with total urine MBOCA ≥20 µg/g creatinine) and a control group (n=47 with total urine MBOCA <20 µg/g creatinine). Lymphocyte MN frequency (MNF) and micronucleated cell (MNC) frequency were measured by the cytokinesis-block MN assay method. MNF reported as the number of micronuclei in binucleated cells per 1000 cells, and MNC reported as the number of binucleated cells with the presence of MN per 1000 cells. CYP3A4 alleles were measured by PCR-based restriction fragment length polymorphism (PCR-RFLP). RESULTS: The mean MNF (6.11 vs 4.46 MN/1000 cells, p<0.001) and MNC (5.75 vs 4.15 MN/1000 cells, p<0.001) in the exposed workers was significantly higher than that in the controls. The CYP3A4 polymorphism A/A+A/G influenced the difference in the mean MNF (5.97 vs 4.38 MN/1000 cells, p<0.001) and MNC (5.60 vs 4.15 MN/1000 cells, p<0.001) between the MBOCA-exposed and control groups. After adjusting risk factors, the MNF level in the MBOCA-exposed workers was 0.520 MN cells/1000 cells (p<0.001) higher than the control group among the CYP3A4 A/A+A/G genotype. Similarly, the MNC level in the MBOCA-exposed workers was 0.593 MN/1000 cells (p<0.001) higher than the control group among the CYP3A4 A/A+A/G genotype. However, the difference in adjusted MNF and MNC between the exposed and control groups was not significant for the CYP3A4 polymorphism with the G/G genotype. CONCLUSIONS: We recommend that lymphocytes MNF and MNC are good indicators to evaluate MBOCA genotoxicity. Individuals with the CYP3A4 polymorphism A/A and A/G genotypes appear to be more susceptible to MBOCA genotoxicity.

Hematological abnormalities of acute exposure to hexachloroethane smoke inhalation.

There has been no human epidemiological data regarding potential hematological effects of hexachloroethane-zinc oxide (HC/ZnO) inhalation. This is the first epidemiological study to investigate whether HC/ZnO inhalation exposure can induce hematological abnormalities in exposed soldiers. Twenty soldiers, who were exposed to a high concentration of HC/ZnO smoke for 3-10 min in a narrow tunnel (0.6 m in width) during military training, were recruited as the exposed group (n = 20). Another 64 soldiers, who were not visiting the explosion areas, were recruited as controls. Venous blood was collected from all participants for analyses of hematological parameters. After adjustment for potential confounders, there were significant differences in weekly mean hemoglobin (HB), red blood cell count (RBC), and hematocrit (HCT) between exposed soldiers and controls (p < .01) at the first follow-up through the first 4 weeks following exposure. In addition, mean white blood cell count (WBC) of exposed soldiers was significantly higher than that of controls at the 4-week follow-up. Further analysis showed HB, RBC, and HCT changes during the 1st week after exposure and reach lowest levels during the 2nd week. HB, RBC, HCT, and WBC returned to normal within 11 weeks after the HC/ZnO smoke exposure. All other hematological parameters remained unchanged at 72 weeks after the event. The authors concluded that inhalation of HC/ZnO smoke can induce acute, temporally related hematological abnormalities.

The relationship between varicoceles and obesity in a young adult population.

To determine whether a relationship between obesity and varicocele occurrence exists, the prevalence and severity of varicoceles related to obesity were investigated in a general population of young males. A total of 1050 young males attending the Navy Recruit Training Center were evaluated from their physical screening examinations. All subjects underwent history taking and physical examinations to evaluate for the presence and severity of varicocele. The anthropometric indexes including body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) were recorded. All subjects were categorized by quartiles according to each anthropometric index. Means were compared with the Student's t-test. Severity was compared by analysis of variance testing and frequency was analysed using the chi-square method. Statistical significance was considered at p <0.05. A total of 490 (46.67%) subjects had varicoceles. The means of BMI, WC and WHR of those without varicoceles was 23.99 +/- 3.82 kg/m(2), 83.20 +/- 9.97 cm and 0.85 +/- 0.05, respectively. These judged values were greater than those with varicoceles (22.02 +/- 3.18 kg/m(2), 79.19 +/- 9.01 cm and 0.83 +/- 0.05) (p < 0.001). In the univariate regression analysis, BMI, WC and WHR all had a significantly negative correlation with severity of varicocele (all p < 0.001). Analysis comparing varicocele frequency based on each grade per anthropometric index group was performed. The logistic regression revealed that the prevalence of grade II and III varicoceles showed a statistically inverse association with all three anthropometric indexes. The prevalence and severity of varicoceles inversely correlated with obesity. The present data support the explanation that obesity may result in a decreased nutcracker effect, which accounts for prevention of the renal vein compression by the adipose tissue.

Hepatic injuries of hexachloroethane smoke inhalation: the first analytical epidemiological study.

UNLABELLED: There has been no human epidemiological data regarding the hepatic injuries of hexachloroethane-zinc oxide (HC/ZnO) inhalation. This is the first epidemiological study to investigate whether HC/ZnO inhalation exposure can induce hepatic dysfunction in exposed soldiers. Twenty soldiers, exposed to high concentration of HC/ZnO smoke for 3-10 min in a narrow tunnel (0.6 m in width) during military training, were recruited as exposed group and they were divided into high-exposed group (n=10) and low-exposed group (n=10) by the distance from the explosion locale as a surrogate of exposure condition. Another 64 soldiers, not visiting the explosion areas, were recruited as referents. Venous blood was collected for liver function analyses. After log transformation of alanine aminotransferase (ALT) and adjustment for potential confounders, serum ALT in high-exposed soldiers was statistically significantly higher than those of referents for the 3 weeks following exposure. The serum ALT in low exposed soldiers was statistically significantly higher than those of referents at the 3rd week following exposure. The mean ALT levels also showed decreasing gradients by the distance from exposure locale. In addition, the proportions of abnormality on ALT (>40U/L) were also significantly different among three exposure conditions. Follow-up study showed that the hepatic dysfunction started from 1 to 2 weeks and peaked from 3rd to 5th week after exposure. ALT level was then returned to normal within 6-8 weeks after removing from HC/ZnO smoke exposure. No sequelas in hepatic dysfunction were found until 72 weeks follow-up. CONCLUSION: We concluded that inhalation of HC/Zn smoke can induce acute, dose-dependent and definite temporal relationship hepatic dysfunction.

Laparoscopic radical prostatectomy: initial experience of robotic surgery in Taiwan.

BACKGROUND: The incidence of prostate cancer is lower in Taiwan compared to Europe and North America. Only a few urologists have been trained to perform laparoscopic radical prostatectomies (LRP). The initial experience of robotic LRP in Taiwan is reported. PATIENTS AND METHODS: Twenty-four patients with localized prostate carcinomas underwent robotic LRP between November 2004 and December 2006. Data collection included basic demographics, prostate specific antigen (PSA), stages, Gleason scores, operative time, estimated blood loss (EBL), catheterization time, pathology, complications and return of continence. RESULTS: The mean operative time was 310 minutes, the mean EBL was 234 mL and the average urethral catheterization time was 7.1 days. Three patients had a total of three complications. Continence was 20.8% at one week, 59.1% at six weeks and 75% at three months postoperatively. CONCLUSION: Our initial experience with robotic LRP indicated that the procedure was safe and effective. Six case experiences were required to establish a standard operating procedure. Eighteen operations were needed to complete the learning curve and achieve stable results.

Factors associated with cigarette smoking among young military conscripts in taiwan.

BACKGROUND: The purpose of this study was to identify the most important risk factors that influence cigarette smoking among young adult military conscripts in Taiwan. METHODS: A cross-sectional survey was conducted among young conscripts (19-25 years old) in Taiwan from August to December 2001. A total of 3,569 conscripts who had served more than 1 month in the military were chosen. Information regarding cigarette smoking and other factors was collected using a standard structured questionnaire. RESULTS: Subjects whose lifestyles included betel-nut chewing (OR, 16.81; 95% CI, 11.35-25.91) and alcohol drinking (OR, 2.11; 95% CI, 1.54-2.90) were more likely to smoke compared to subjects without these adverse behaviors. Subjects whose education stopped at junior high school or before were more likely to smoke compared to those with a university degree (OR, 5.36; 95% CI, 3.77-7.69). Subjects who had a higher proportion of peers who smoked were more likely to smoke compared to those with no peers who smoked (OR, 3.16; 95% CI, 2.42-4.15). Subjects whose parents and peers approved of smoking were also at a higher risk for smoking compared with those whose parents and peers disapproved (father's approval---OR, 3.28 and 95% CI, 2.02-5.43; mother's approval---OR, 3.11 and 95% CI, 1.47-7.12; peer approval---OR, 2.27 and 95% CI, 1.60-3.22). CONCLUSION: From this study, we found that education level, betel-nut chewing, alcohol intake, smoking behavior of peers, and the attitudes of parents and peers toward smoking are all associated with the risk of a young adult conscripts becoming a habitual cigarette smoker. These results provide insight for targeting critical risk factors in helping these individuals control or cease their cigarette smoking habit in the future.

Hematological follow-up of an intervention program adding rubber glove-wearing to local ventilation for 2-ethoxyethanol acetate-exposed workers.

The objective of this study was to evaluate an intervention program, implemented in year 1999, of wearing rubber gloves in addition to engineering control, and to follow-up the hematological effects of 2-ethoxyethanol acetate (2-EEA) exposure among workers in a silk-screening factory. All workers from the printing department with direct exposure to 2-EEA were recruited as the exposed group. Workers from the other departments were recruited as the comparison group. Hematological parameters were measured during health surveys conducted 3 times every two years. Information on personal characteristics and working habits was obtained through a structured questionnaire. More female workers were involved in manual printing resulting in higher exposure to 2-EEA. Hemoglobin and haematocrit levels in female exposed workers were significantly lower than those of female comparison workers in the 1st (1998) health survey, but not in the 2nd (2000) and 3rd (2002) health surveys. No difference was found between male exposed and comparison workers for all three surveys. Longitudinal analysis after adjusting for confounders using the general estimating equation model showed the hemoglobin, haematocrit, and RBC count were significantly higher for 2-EEA exposed workers than comparison workers across the 3 surveys (n=42). The results show that wearing rubber gloves in addition to local ventilation was effective at preventing direct dermal exposure to 2-EEA and ameliorated the hematological effects of 2-EEA exposure.

Oxidative DNA damage estimated by plasma 8-hydroxydeoxyguanosine (8-OHdG): influence of 4, 4'-methylenebis (2-chloroaniline) exposure and smoking.

Oxidative DNA damage may play an important role in the human carcinogenic process. Recently, we reported a case of bladder cancer among 4, 4'-methylenebis (2-chloroaniline) (MBOCA)-exposed workers. By measuring the plasma level of 8-hydroxydeoxyguanosine (8-OHdG), we investigated the association between oxidative DNA damage and MBOCA exposure. In addition, we examined the effects of different confounders on the plasma level of 8-OHdG. We undertook a cross-sectional survey at four MBOCA-producing factories in Taiwan (158 subjects). Plasma 8-OHdG levels and urinary MBOCA concentrations were measured by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). Personal characteristics were collected by questionnaire. The workers were classified according to their job titles as exposed (n=57) or unexposed (n=101) groups as well as classified according to urinary MBOCA levels as high urinary MBOCA (>20 microg/g creatinine) (n=45) or low urinary MBOCA (n=108) groups. Neither the MBOCA-exposed workers nor the high urinary MBOCA workers had a significant increase in the mean plasma 8-OHdG level, even after adjustment for potential confounders. Age and gender were significantly positively correlated with plasma 8-OHdG levels. Smokers among high urinary MBOCA workers also had significantly higher 8-OHdG levels than non-smokers among high urinary MBOCA workers. Our study provides evidence that smoking rather than MBOCA exposure induces elevation of plasma 8-OHdG levels among workers exposed to MBOCA, indicating that oxidative DNA damage does not play an important role in the carcinogenic processes of MBOCA.

Advanced glycation end products influence oral cancer cell survival via Bcl-xl and Nrf-2 regulation in vitro.

An irreversible non-enzymatic reaction between carbohydrates and proteins results in the formation of advanced glycation end products (AGEs). AGEs have been demonstrated to be a risk factor of complications in patients with diabetes mellitus (DM). Previous studies have suggested that patients with DM exhibit a higher rate of metastasis of oral cancer and a lower cancer-associated survival rate. The receptor for AGEs (RAGE) has been associated with angiogenesis and an increase in cancer malignancy. Previous studies have suggested that AGE-RAGE regulates cell migration via extracellular signal-regulated kinase (ERK) phosphorylation. Nuclear factor-erythroid 2-related factor 2 (Nrf-2) is associated with the regulation of tumor protein p53 (p53) and the apoptotic response of oral cancer cells. AGEs are associated with oral cancer; however, the mechanism underlying this association remains to be elucidated. The present study hypothesized that AGEs regulate Nrf-2 and downstream pathways through ERK phosphorylation. The results of the current study demonstrated that AGEs inhibit the expression of Nrf-2, p53 and Bcl-2 associated × apoptosis regulator, and increase the expression of apoptosis regulator Bcl-x protein. The effect of AGEs was inhibited through the use of the PD98059. The present study demonstrated that AGEs regulate the downstream pathways Nrf-2 and Bcl-xl via ERK phosphorylation. It is suggested that AGEs regulate the survival of oral cancer cells via Nrf-2 and Bcl-xl through p53 regulation, which explains the poor prognosis of patients with DM who have oral cancer.

Serum lipid profiles are associated with semen quality.

We aimed to explore the associations between different lipid profiles and semen quality in a large-scale general male population. Sperm concentration, total sperm motility, progressive motility, and normal sperm morphology of total 7601 participants were recorded. The association of these semen parameters with the triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, and very low-density lipoprotein of serum lipid profiles was analyzed. Sperm concentration was statistically positively correlated with triglyceride and very low-density lipoprotein (adjusted P = 0.001 and P = 0.005, respectively). Total sperm motility and progressive motility were statistically increased with increasing low-density lipoprotein and cholesterol levels (both adjusted P = 0.008 and P < 0.001, respectively). The similar J-shaped associations (high-low-low-high) were noted between individual lipid profile and normal sperm morphology, especially low-density lipoprotein and cholesterol with statistical significance (adjusted P = 0.017 and P = 0.021, respectively). The prevalence of abnormal total sperm motility and progressive motility was decreased in participants with high levels of cholesterol (P = 0.008 and P = 0.019, respectively), and the reverse J-shaped associations (low-high-high-low) were noted between high-density lipoprotein, triglyceride, very low-density lipoprotein, and the prevalence of abnormal normal sperm morphology (P = 0.010, P = 0.037, and P = 0.025, respectively). A high cholesterol level was associated with better sperm motility. Similar J-shaped associations were noted between all lipid profiles and normal sperm morphology; meanwhile, the reverse J-shaped trends were identified between them and abnormal normal sperm morphology prevalence.

Risk of serous retinal detachment in patients with end-stage renal disease on dialysis.

The aim of this retrospective, nationwide, matched cohort study was to investigate the association of serous retinal detachment with having end-stage renal disease (ESRD) while on dialysis. The cohort study included 94,024 patients with ESRD on dialysis registered between January 2000 to December 2009 in the Taiwan National Health Insurance Research Database. An age- and sex-matched control group comprised 94,024 patients selected from the Taiwan Longitudinal Health Insurance Database 2000. Information for each patient was collected from the index date until December 2011. Twenty-seven ESRD patients and 11 controls developed serous retinal detachment (P < 0.001) during follow-up, demonstrating a significantly increased risk of serous retinal detachment in patients with ESRD on dialysis compared with controls (incidence rate ratio = 3.39, 95% confidence interval [CI] = 1.68-6.83). After adjustment for potential confounders, patients were 3.86 times more likely to develop serous retinal detachment than the full cohort (adjusted HR = 3.86, 95% CI = 1.15-12.96). In conclusion, patients with ESRD on dialysis demonstrate an increased risk of serous retinal detachment. Interdisciplinary collaboration between nephrologists and ophthalmologists is important to deal with serous retinal detachment in patients with ESRD on dialysis and prevent impairments of visual acuity.

Case report: hexachloroethane smoke inhalation: a rare cause of severe hepatic injuries.

CONTEXT: We report on two patients, a 23-year-old man and a 24-year-old man, who had chemical pneumonitis and respiratory distress after inhaling hexachloroethane/zinc oxide (HC/ZnO) smoke during military training. CASE PRESENTATION: The patients had been healthy previously and denied any history of alcohol or drug abuse. Hematologic tests revealed leukocytosis with neutrophils predominant. The respiratory conditions of both patients improved after steroid therapy and oxygen support, but deterioration of liver function was found. The laboratory results showed that alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase levels were elevated about 1.5-fold the normal limits and that aspartate aminotransferase (AST) levels were marginally elevated. The elevation of liver aminotransferase started from day 1 and day 2 and peaked from day 18 to day 22. ALT/AST levels then returned to normal in 6 weeks. Common viral hepatitis was ruled out after serologic tests. Abdominal sonography and physical examination failed to show any specific findings. DISCUSSION: The hepatotoxic effect was attributed to inhalation of high-concentration HC/ZnO smoke in an enclosed area, where several hepatotoxicants, including ZnCl2, HC, and chlorinated vapors, could have been generated and mixed in the smoke. RELEVANCE TO CLINICAL PRACTICE: These case reports elaborate the hepatic effects that may occur in addition to pulmonary effects of HC/ZnO smoke.

The relationship between plasma and urinary 8-hydroxy-2-deoxyguanosine biomarkers measured by liquid chromatography tandem mass spectrometry.

Although 8-hydroxy-2-deoxyguanosine (8-OHdG) is a widely used promising biomarker of DNA damage, there are concerns about which tissues or body fluids should be sampled. The objective of this study is to evaluate the correlation of DNA oxidative damage biomarkers, 8-OHdG, between blood and urine and risk factors associated with 8OHdG. The study population was recruited from a baseline survey of a worksite lifestyle study including 92 office workers aged 23 to 60 years. A self-administered questionnaire was used to collect information on personal characteristics. The plasma and urinary 8-OHdG was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). In linear regression, a positive relation was found (p < 0.01) between the log-transformed plasma and urinary 8-OHdG levels adjusted for gender, age, BMI, and smoking status. Our findings showed that age, gender and smoking were significantly associated with plasma 8-OHdG, but not with urinary 8-OHdG. Our results suggest that there is a positive relation between the biomarkers of plasma (steady state DNA damage) and urinary 8-OHdG (total DNA damage). However, the plasma 8-OHdG is more sensitive than urinary 8-OHdG to detect increased oxidative damages induced by risk factors.

Emphysematous epididymo-orchitis as a camouflage of prostate invasion secondary to rectum cancer: A case report.

INTRODUCTION: Emphysematous epididymo-orchitis is a rare cause of acute scrotum pain characterized by gas formation within the tissue. Diabetes mellitus and recto-seminal fistula secondary to sigmoid diverticulitis are generally accepted as being responsible for this disease. However, prostate invasion secondary to rectal cancer may be considered to be a newly identified pathogenetic mechanism. Herein, we report this rare case and illustrate the pathogenesis. CASE PRESENTATION: A 69-year-old man arrived at our emergency department presenting with sepsis and acute scrotal pain. Emphysematous epididymo-orchitis was diagnosed by scrotal sonography initially; however, advanced rectal cancer with prostate invasion was diagnosed by CT after a recurrent episode. An exploratory laparotomy with abdominoperineal resection and radical prostectomy were performed after neoadjuvant chemoradiotherapy. Histopathologic analysis confirmed the previous diagnosis. Emphysematous epididymo-orchitis caused by advanced rectal cancer is very rare, and our case is the first to be reported according to a literature search. Neoadjuvant chemoradiotherapy plus extended surgery can achieve a good oncological outcome. CONCLUSION: This case indicated that the very rare presentation as emphysematous epididymo-orchitis caused by locally advanced colorectal cancer.

Occupational bladder cancer in a 4,4 -methylenebis(2-chloroaniline) (MBOCA)-exposed worker.

A 52-year-old male chemical worker was admitted to the hospital with a history of paroxysmal microscopic hematuria for about 2 years and nocturia with gross hematuria about five times per night for 2 months. He was a nonsmoker and denied a history of any other bladder carcinogen exposure except for occasional pesticide application during agricultural work. Intravenous urogram imaging showed a mass occupying half of the bladder capacity. Cystoscopy revealed a mass over the left dome of the bladder. Cystoscopic biopsy revealed a grade 3 invasive transitional cell carcinoma with marked necrosis. From 1987 until hospital admission in 2001, the patient had worked in a company that produced the 4,4 -methylenebis(2-chloroaniline) (MBOCA) curing agent. He did not wear any personal protective equipment during work. Ambient air MBOCA levels in the purification process area (0.23-0.41 mg/m3) exceeded the U.S. Occupational Safety and Health Administration's permissible exposure level. Urinary MBOCA levels (267.9-15701.1 microg/g creatinine) far exceeded the California Occupational Safety and Health Administration's reference value of 100 microg/L. This patient worked in the purification process with occupational exposure to MBOCA for 14 years. According to the environmental and biologic monitoring data and latency period, and excluding other potential bladder carcinogen exposure, this worker was diagnosed as having occupational bladder cancer due to high exposure to MBOCA through inhalation or dermal absorption in the purification area. This case finding supports that MBOCA is a potential human carcinogen. Safe use of skin-protective equipment and respirators is required to prevent workers from MBOCA exposure.

Suppression of antioxidant Nrf-2 and downstream pathway in H9c2 cells by advanced glycation end products (AGEs) via ERK phosphorylation.

Diabetic cardiomyopathy is related to oxidative stress and correlated with the presence of advanced glycation end products (AGEs). In a clinical setting, AGEs can be detected in patients presenting diabetic cardiomyopathy; however, the underlying mechanism has yet to be elucidated. In our previous study, AGEs increase cell hypertrophy via ERK phosphorylation in a process closely related to ROS production. Thus, we propose that AGEs regulate the antioxidant gene nuclear factor-erythroid 2-related factor (Nrf-2). In H9c2 cells treated with AGEs, the expression of Nrf-2 was reduced; however, ERK phosphorylation was shown to increase. Treatment with H2O2 was also shown to increase Nrf-2 and ERK phosphorylation. In cells pretreatment with ROS scavenger NAC, the effects of H2O2 were reduced; however, the effects of the AGEs remained largely unchanged. Conversely, when cells were pretreated with PD98059 (ERK inhibitor), the expression of Nrf-2 was recovered following treatment with AGEs. Our results suggest that AGEs inhibit Nrf-2 via the ERK pathway; however, this influence is partly associated with ROS. Our finding further indicated that AGEs possess both ROS-dependent and ROS-independent pathways, resulting in a reduction in Nrf-2. This report reveals an important mechanism underlying the regulation of diabetic cardiomyopathy progression by AGEs.

The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer's Disease.

Amyloid precursor protein (APP) has been modified by ß and γ-secretase that cause amyloid deposits (plaques) in neuronal cells. Glyceraldhyde-derived AGEs has been identified as a major source of neurotoxicity in Alzheimer's disease (AD). In a previous study, we demonstrated that glyceraldehyde-derived AGEs increase APP and Aß via ROS. Furthermore, the combination of AGEs and Aß has been shown to enhance neurotoxicity. In mice, APP expression is increased by tail vein injection of AGEs. This evidence suggests a correlation between AGEs and the development of AD. However, the role played by AGEs in the pathogenesis of AD remains unclear. In this report, we demonstrate that AGEs up-regulate APP processing protein (BACE and PS1) and Sirt1 expression via ROS, but do not affect the expression of downstream antioxidant genes HO-1 and NQO-1. Moreover, we found that AGEs increase GRP78 expression and enhance the cell death-related pathway p53, bcl-2/bax ratio, caspase 3. These results indicate that AGEs impair the neuroprotective effects of Sirt1 and lead to neuronal cell death via ER stress. Our findings suggest that AGEs increase ROS production, which stimulates downstream pathways related to APP processing, Aß production, Sirt1, and GRP78, resulting in the up-regulation of cell death related pathway. This in-turn enhances neuronal cell death, which leads to the development of AD.

Role of QuantiFERON-TB-Gold In Tube assay for active and latent tuberculosis infection in investigation of tuberculosis outbreak in a university.

BACKGROUND: Identification and monitoring of active tuberculosis (TB) and latent tuberculosis infection (LTBI) are the key steps to prevent transmission during a TB outbreak. The aim of this study was to evaluate the role of QuantiFERON-TB-Gold In Tube assay (QFT-GIT) in the investigation of active TB and LTBI cases during a TB outbreak in a university. METHODS: In this study, enrolled students and teachers were evaluated with chest radiograph, questionnaire, and QFT-GIT test. The diagnosis of active pulmonary TB was based on sputum studies and chest radiographs. The questionnaire, which covered demographic information, underlying diseases, and environmental exposures, was applied to assess the association of risk factors by multiple logistic regressions. RESULTS: A total of 159 participants completed the study protocol. Positive QFT-GIT results were demonstrated in class A (75.7%; 25/33), class B (57.1%; 20/35), and class C (37.5%; 3/8) in institute 1; class D (17.3%; 8/46) in institute 2; and class E (3.1%; 1/32) in institute 3; but none among the (0/5) administrative officers, who comprised the control group. "Number of contact with active TB cases" was strongly associated and correlated with the prediction of a positive QFT-GIT result in multivariate analysis (odds ratio = 1.99; 95% confidence interval, 1.52-2.61; p < 0.0001). Seven cases progressed to active TB infection, all showing positive QFT-GIT results (100%; 7/7). CONCLUSION: Inclusion of QFT-GIT may be helpful in controlling and monitoring of active TB and LTBI cases during an investigation of a TB outbreak. The finding demonstrated that the QFT-GIT test was useful in accurately identifying infected and uninfected students, permitting rapid intervention.

Correlation of CD44v5 expression with invasiveness and prognosis in renal cell carcinoma.

BACKGROUND AND PURPOSE: The expression of specific CD44 isoforms is associated with metastasis and poor prognosis in human malignant tumors. We retrospectively investigated the expression of the CD44 variant isoform v5 (CD44v5) in human renal cell carcinoma (RCC) specimens by immunohistochemistry. METHODS: We studied the expression of CD44v5 immunohistochemistry in archival tissue specimens from 72 RCC patients (47 men and 25 women) with a mean age of 60.1 years (range, 30 to 83 years) who underwent resection in our hospital from 1986 to 1996. The patients were divided into non-invasive (pT1, pT2, and pT3a; n = 49) and invasive groups (pT3b, pT3c, and any T with N+; n = 23). Among the 72 patients, 67 were followed for at least 60 months (up to 190 months) after radical nephrectomy. Twenty nine renal specimens, including 15 of normal renal parenchyma and 14 of inflammatory or immune renal diseases, were used as controls. RESULTS: All control group tissues expressed CD44v5. CD44v5 expression was detected in 66 of 72 RCC specimens (91.7%). In general, the expression of CD44v5 was higher in the non-invasive group [47/49 (95.9%) vs 19/23 (82.6%), p < 0.05]. Five cases were lost to follow-up. Thirty three of 67 patients (49.3%) died of RCC-related causes during the follow-up period. The CD44v5 non-expression group had a higher mortality rate than the expression group [4/5 (80%) vs 29/62 (46.8%), p < 0.001]. The 5-year and 10-year survival rates were significantly higher in patients with CD44v5 expression than in those without (p < 0.001). CONCLUSIONS: This study found that CD44v5 expression was greater in early stage than in advanced stage RCC and was associated with tumor progression and long-term survival. Although the survival analysis showed both tumor stage and CD44v5 expression were significant prognostic factors in RCC, only tumor stage remained an independent factor.