Comparison of dipstick and quantitative tests for proteinuria and hematuria in middle-aged, male Japanese employees: A single-center study.

BACKGROUND AND AIMS: The early and reliable detection of chronic kidney disease is important. In the present study, we aimed to compare the diagnostic results for proteinuria and hematuria between the dipstick test used in primary occupational health examinations and the quantitative tests used in more thorough examinations in clinics. METHODS: We conducted a single-center observational study of male staff (N = 573) at Kagoshima University who underwent a health examination in 2017. Both dipsticks and biochemical methods were used to assess proteinuria and hematuria. RESULTS: For the dipstick test, the sensitivity, specificity, and positive predictive value were 55.6%, 92.4% and 10.4% for proteinuria, and 64.3%, 98.3% and 66.7% for hematuria, respectively. Four participants for whom false-negative results were obtained using dipsticks for proteinuria, and two of these had 3+ urinary glucose. CONCLUSION: Qualitative tests for proteinuria and hematuria had low sensitivities and positive predictive values. Therefore, for the early and reliable detection of chronic kidney disease, the use of quantitative urine tests should be considered during occupational health examinations.

uPA Attenuated LPS-induced Inflammatory Osteoclastogenesis through the Plasmin/PAR-1/Ca(2+)/CaMKK/AMPK Axis.

Chronic inflammatory diseases, such as rheumatoid arthritis and periodontitis-caused bone destruction, results from an increase of bone-resorbing osteoclasts (OCs) induced by inflammation. However, the detailed mechanisms underlying this disorder remain unclear. We herein investigated that the effect of urokinase-type plasminogen activator (uPA) on inflammatory osteoclastogenesis induced by lipopolysaccharide (LPS), which is a potent stimulator of bone resorption in inflammatory diseases. We found that the uPA deficiency promoted inflammatory osteoclastogenesis and bone loss induced by LPS. We also showed that LPS induced the expression of uPA, and the uPA treatment attenuated the LPS-induced inflammatory osteoclastogenesis of RAW264.7 mouse monocyte/macrophage lineage cells. Additionally, we showed that the uPA-attenuated inflammatory osteoclastgenesis is associated with the activation of plasmin/protease-activated receptor (PAR)-1 axis by uPA. Moreover, we examined the mechanism underlying the effect of uPA on inflammatory osteoclastogenesis, and found that uPA/plasmin/PAR-1 activated the adenosine monophosphate-activated protein kinase (AMPK) pathway through Ca2+/calmodulin dependent protein kinase kinase (CaMKK) activation, and attenuated inflammatory osteoclastogenesis by inactivation of NF-κB in RAW264.7 cells. These data suggest that uPA attenuated inflammatory osteoclastogenesis through the plasmin/PAR-1/Ca2+/CaMKK/AMPK axis. Our findings may provide a novel therapeutic approach to bone loss caused by inflammatory diseases.

α2AP mediated myofibroblast formation and the development of renal fibrosis in unilateral ureteral obstruction.

Renal fibrosis is the final common pathway of a wide variety of chronic kidney diseases. Myofibroblast formation via the differentiation of from tissue-resident fibroblasts and bone marrow-derived mesenchymal stem cells (MSCs), and epithelial-to-mesenchymal transition (EMT) is known to play a pivotal role in the development of renal fibrosis. However, the detailed mechanisms underlying this disorder remain unclear. We herein investigated the role of alpha 2-antiplasmin (α2AP) in myofibroblast formation and the development of renal fibrosis. We observed the development of renal fibrosis using unilateral ureteral obstruction (UUO). α2AP had accumulated in the UUO-induced obstructed kidneys and α2AP deficiency attenuated UUO-induced renal fibrosis in mice. The degree of myofibroblast formation in the obstructed kidneys of α2AP(-/-) mice was less than that in α2AP(+/+) mice. In vitro, α2AP induced myofibroblast formation in renal tubular epithelial cells (RTECs), renal fibrosblasts, and bone marrow-derived mesenchymal stem cells (MSCs). α2AP also induced the production of TGF-ß, which is known to be a key regulator of myofibroblast formation and fibrosis. α2AP-induced the TGF-ß production was significantly reduced by SP600125, c-Jun N-terminal kinase (JNK) specific inhibitor. Our findings suggest that α2AP induces myofibroblast formation in the obstructed kidneys, and mediates the development of renal fibrosis.

Altered behavior in mice with deletion of the alpha2-antiplasmin gene.

BACKGROUND: The α2-antiplasmin (α2AP) protein is known to be a principal physiological inhibitor of plasmin, and is expressed in various part of the brain, including the hippocampus, cortex, hypothalamus and cerebellum, thus suggesting a potential role for α2AP in brain functions. However, the involvement of α2AP in brain functions is currently unclear. OBJECTIVES: The goal of this study was to investigate the effects of the deletion of the α2AP gene on the behavior of mice. METHODS: The motor function was examined by the wire hang test and rotarod test. To evaluate the cognitive function, a repeated rotarod test, Y-maze test, Morris water maze test, passive or shuttle avoidance test and fear conditioning test were performed. An open field test, dark/light transition test or tail suspension test was performed to determine the involvement of α2AP in anxiety or depression-like behavior. RESULTS AND CONCLUSIONS: The α2AP knockout (α2AP-/-) mice exhibited impaired motor function compared with α2AP+/+ mice. The α2AP-/- mice also exhibited impairments in motor learning, working memory, spatial memory and fear conditioning memory. Furthermore, the deletion of α2AP induced anxiety-like behavior, and caused an anti-depression-like effect in tail suspension. Therefore, our findings suggest that α2AP is a crucial mediator of motor function, cognitive function, anxiety-like behavior and depression-like behavior, providing new insights into the role of α2AP in the brain functions.

Baseline data of Shizuoka area in the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study).

The Japan Multi-Institutional Collaborative Cohort (J-MICC) Study launched in 2005 by ten research groups throughout Japan aimed to examine gene-environment interactions in lifestyle-related diseases, especially cancers. This paper describes one component of the J-MICC Study, named Shizuoka Study, in which visitors aged 35 to 69 years to the Seirei Preventive Health Care Center in Hamamatsu were enrolled. Among 13,740 visitors matching eligibility criteria, 5,040 persons (36.7%) were enrolled from January 2006 to December 2007. Their lifestyle, disease history, and family history were surveyed using a self-administrated questionnaire. Blood and urine were collected from the participants. By the end of December 2008, 8 withdrawers and 1 ineligible participant had been removed, leaving 5,031 participants (3,419 males and 1,612 females) as the baseline dataset. Current smokers were 23.3% among males, and 4.4% among females, and those who drank once or more per month were 76.9% and 38.6%, respectively. Those with a cancer history were 3.0% for males and 3.8% for females. Measurements out of a normal range in males and females were 11.3% and 4.0% for diastolic blood pressure > or = 90 mmHg, 11.0% and 7.6% for systolic blood pressure > or = 140 mmHg, 5.9% and 1.7% for fasting blood glucose > or = 126 mg/dl, respectively. Collected information and specimens will be cooperatively used to examine the associations of biomarkers with lifestyle, genotypes, and their combinations, as well as for a part of the J-MICC Study.