Catecholamines' enhancement of inducible nitric oxide synthase-induced nitric oxide biosynthesis involves CAT-1 and CAT-2A

Catecholamines enhance inducible nitric oxide synthase (iNOS) expression that results in nitric oxide (NO) overproduction in lipopolysaccharide (LPS)-stimulated macrophages. L-arginine transport mediated by cationic amino acid transporters (including CAT-1, CAT-2, CAT-2A, and CAT-2B) is crucial in regulating iNOS activity. We sought to assess the effects of catecholamines on L-arginine transport and CAT isozyme expression in stimulated macrophages. Confluent RAW264.7 cells were cultured with LPS with or without catecholamines (epinephrine or norepinephrine, 5 x 10(-6) M) for 18 h. NO production, L-arginine transport, and enzyme expression were determined. Our data revealed that LPS co-induced iNOS, CAT-2, and CAT-2B expression, whereas CAT-1 and CAT-2A expression remained unaffected. Significant increases in NO production and L-arginine transport (approximately eight-fold and three-fold increases, respectively) were found in activated macrophages. Catecholamines significantly enhanced NO production and L-arginine transport (approximately 30% and 20% increases, respectively) in activated macrophages. Catecholamines also enhanced the expression of iNOS, CAT-1, and CAT-2A but not CAT-2 or CAT-2B in LPS-stimulated macrophages. Furthermore, the enhancement effects of catecholamines were inhibited by either dexamethasone or propranolol. We provide the first evidence to indicate that L-arginine transport in activated macrophages could be enhanced by catecholamines. Furthermore, this catecholamine-enhanced L-arginine transport might involve CAT-1 and CAT-2A but not CAT-2 or CAT-2B.     

Oral and dental manifestations in diabetic and nondiabetic uremic patients receiving hemodialysis.

OBJECTIVE: The aim of this study was to examine the dental condition and oral manifestations in diabetic and nondiabetic uremic patients undergoing hemodialysis. STUDY DESIGN: A total of 128 patients undergoing hemodialysis therapy were classified into the diabetic and nondiabetic groups and examined for uremic oral manifestations, dental caries, and the periodontal status. All the patients received predialytic salivary pH examination. In the diabetic group, the correlation between oral findings and glycemic controlled levels, which was collected based on Hb A1C values, were further studied. RESULTS: The diabetic group exhibited significantly higher prevalence of caries and more severe dry mouth, taste change, and mucosa pain than the nondiabetic group. The diabetic group tended to have lower predialytic salivary pH, and patients with poor glycemic control (ie, Hb A1C > 9%) showed higher incidence of dry mouth, mucosal pain, and tongue coating. However, the DMFT and CPI index were not associated with glycemic control in the diabetic group. CONCLUSIONS: This study reveals that diabetic uremic patients undergoing maintained hemodialysis exhibited a potentially higher risk for dental decay and xerostomia. Lower salivary pH and poor glycemic control may affect oral manifestations. Further research is needed to clarify the combined influence of diabetic nephropathy on oral health.     

Healing of a critical-sized defect in the rat femur with use of a vascularized periosteal flap, a biodegradable matrix, and bone morphogenetic protein

BACKGROUND: The purpose of this study was to evaluate the osseous healing of a critical-sized femoral defect in a rat model with use of recombinant human bone morphogenetic protein-2 (rhBMP-2), a matrix fabricated of D,D-L,L-polylactic and hyaluronan acid (OPLA-HY), and a vascularized periosteal flap. METHODS: The carrier matrix OPLA-HY with or without rhBMP-2 was implanted in a 1-cm-long femoral defect and secured with a plate and screws. In some groups, a vascularized periosteal flap was harvested from the medial surface of the tibia. In group 1, the femoral defects in the animals were filled with the OPLA-HY matrix alone; in group 2, the OPLA-HY matrix was covered by the vascularized periosteal flap; in group 3, 20 mug of rhBMP-2 was added to the OPLA-HY matrix; and in group 4, the femoral defect containing the OPLA-HY matrix and 20 mug of rhBMP-2 was wrapped circumferentially by the vascularized periosteal flap. The presence and density of new bone formation in the femoral defect were evaluated radiographically, histologically, and with histomorphometry at four and eight weeks postoperatively. RESULTS: Groups 1 and 2, which were not treated with rhBMP-2, showed no radiographic or histologic evidence of mature bone formation at four or eight weeks. Both groups 3 and 4, which were treated with rhBMP-2, demonstrated excellent bone formation. However, with the periosteal flap, group 4 demonstrated more bone formation on histomorphometric analysis at eight weeks (43.1%) than did group 3 (28.3%) (p < 0.01). Additionally, heterotopic bone formed outside the boundaries of the defect in eight of the fifteen animals in group 3, which had no periosteal flap. CONCLUSIONS: Bone-tissue engineering with use of the OPLA-HY matrix and rhBMP-2 produced good bone formation in the rat femoral defect model. However, the addition of a vascularized periosteal flap significantly increased bone formation within the boundaries of the defect and prevented heterotopic ossification.     

<Emphasis Type="Italic">Ureaplasma urealyticum</Emphasis> and <Emphasis Type="Italic">Mycoplasma hominis</Emphasis> infections and semen quality in 19,098 infertile men in China

Objective

This study aimed to determine the incidence of Ureaplasma urealyticum and Mycoplasma hominis infections in infertile and fertile men and to investigate their effects on the semen quality. The study also aimed to analyze the drug susceptibility of UU and MH to provide guidance for reasonable antibiotic use.

Methods

A total of 19,098 semen specimens were obtained from infertile men at our hospital from January to December 2014. In addition to these specimens, 3368 semen specimens of sperm were obtained from donors at the sperm bank of our hospital from January 2011 to December 2014. Semen analysis was performed using the methods outlined by the World Health Organization.

Results

The prevalence of UU and MH significantly differed between infertile and fertile men. The mean progressive motility, total motility, and normal forms in the semen samples of infertile males positive for UU significantly differed from the corresponding values of uninfected men. However, the semen parameters did not differ between MH-infected and uninfected men. In the antibiotic sensitivity test, UU, MH, and UU mixed with MH were all found susceptible to doxycycline and josamycin with drug resistance rates below 6 %, but both species were highly resistant to ciprofloxacin.

Conclusions

Clinical assessment revealed a significant relationship between UU and MH infections and male infertility. UU was found to significantly affect sperm quality, but this was not the case with MH. Doxycycline and josamycin should be preferred for clinically treating UU and MH infections.

     

Estimated GFR for Living Kidney Donor Evaluation

All living kidney donor candidates undergo evaluation of GFR. Guidelines recommend measured GFR (mGFR), using either an endogenous filtration marker or creatinine clearance, rather than estimated GFR (eGFR), but measurement methods are difficult, time consuming and costly. We investigated whether GFR estimated from serum creatinine (eGFRcr) with or without sequential cystatin C is sufficiently accurate to identify donor candidates with high probability that mGFR is above or below thresholds for clinical decision making. We combined the pretest probability for mGFR thresholds <60, <70, ≥80, and ≥90 mL/min per 1.73 m² based on demographic characteristics (from the National Health and Nutrition Examination Survey) with test performance of eGFR (categorical likelihood ratios from the Chronic Kidney Disease Epidemiology Collaboration) to compute posttest probabilities. Using data from the Scientific Registry of Transplant Recipients, 53% of recent living donors had predonation eGFRcr high enough to ensure ≥95% probability that predonation mGFR was ≥90 mL/min per 1.73 m², suggesting that mGFR may not be necessary in a large proportion of donor candidates. We developed a Web‐based application to compute the probability, based on eGFR, that mGFR for a donor candidate is above or below a range of thresholds useful in living donor evaluation and selection.     

Distinguishing characteristics of stem cells derived from different anatomical regions of human degenerated intervertebral discs

Introduction

Several types of stem cells have been successfully demonstrated to exist in the human degenerated intervertebral disc (IVD), which is composed of annulus fibrosus (AF), nucleus pulposus (NP) and cartilage endplate (CEP). However, the differences in the biological characteristics among these and bone marrow derived mesenchymal stem cells (BM-MSCs) remain unclear.

Materials and methods

To investigate this issue, cells were harvested from human AF, NP, CEP, and bone marrow, respectively; passage 2 cells were selected using the agarose suspension culture system to obtain stem cell clones. Following expansion in vitro, stem cells from different anatomical regions were compared regarding the morphology, proliferation ability, immunophenotypic expression, and multi-lineage differentiation capacity. In addition, stem cell-alginate bead compositions were constructed for the comparison of DNA and sGAG content.

Results

There were subtle differences regarding cell morphology, but no significant differences in proliferation ability among the four types of stem cells. For the immunophenotypic analysis, all stem cells basically fulfilled the criteria for mesenchymal stem cells (MSCs), which have been published by the International Society for Cellular Therapy (ISCT), with a significant difference in CD105 expression. A comparison of the osteogenic capacities indicated: cartilage endplate-derived stem cells (CESCs) > annulus fibrosus-derived stem cells (AFSCs) > BM-MSCs > nucleus pulposus-derived stem cells (NPSCs). The chondrogenesis difference was similar to osteogenesis. For adipogenesis: BM-MSCs >NPSCs >CESCs >AFSCs. In the stem cell/alginate composition, the CESCs consistently showed the superior chondrogenic potential among all those cell types.

Conclusions

Our data indicated that all the four types of stem cells shared some similar biological properties (regarding shape, proliferation ability and immunophenotypic expression). CESCs, which had the strongest osteogenic and chondrogenic potentials, may serve as excellent seed cells for NP/cartilage or bone tissue engineering.

     

基于Cog Tool的数字界面交互行为认知模型仿真研究

目的确定人在视觉信息搜索中的通用认知模式,归纳符合用户认知模式的基本设计准则。方法在用户需求一致性的前提下,通过Cog Tool可视化仿真模型将用户交互过程中的每一步骤进行拆解分析,找出用户在面对不同界面引导作用下的内在认知规律,并探讨界面布局的不同对用户搜索用时的影响,同时结合眼动实验,对比用户在实际操作过程中与模拟操作情况下的认知差异。结果通过Cog Tool的仿真分析与眼动实验相结合的实验数值对比,将用户在交互过程中的内在认知规律提取出来。结论本研究提出的面向界面布局的设计准则,可帮助设计师提高信息认知效率。     

注射钆剂后弥散加权成像对乳腺肿瘤诊断的影响

目的：评估1.5 T MRI中乳腺肿瘤患者使用钆对比剂是否对弥散加权成像（DWI）有显著性影响。方法行乳腺MRI检查的女性患者40例（共计44个病灶）,分别测量增强前后DWI图像信噪比（SNR）和对比噪声比（CNR）、病灶增强前后的表观扩散系数（ADC）及指数表观扩散系数（eADC）。结果给药前后DWI图像的SNR及CNR差异无统计学意义。乳腺癌给药前后的ADC值（t=-4.023, P=0.001）及eADC值（t=4.082, P=0.001）差异有统计学意义,良性肿瘤给药前后的ADC值（t=-1.700, P=0.103）及eADC值（t=1.341, P=0.194）差异无统计学意义。结论增强后行DWI是可行的,并且有助于提高其鉴别乳腺良恶性肿瘤的能力。