The impact of synapsins on synaptic plasticity and cognitive behaviors

Synapsins are a family of phosphoproteins specifically associated with the cytoplasmic surface of the synaptic vesicle membrane, appearing to regulate neurotransmitter release, the formation and maintenance of synaptic contacts. They could induce the change of the synaptic plasticity to regulate various adaptation reactions, and change the cognitive behaviors. So we presume that if some cognitive behavior are damaged, synapsins would be changed as well. This gives us a new recognition of better diagnosis and therapy of cognitive disorder desease.     

中成药天智颗粒对血管性痴呆大鼠脑内神经细胞增殖的影响

目的观察中成药天智颗粒对血管性痴呆大鼠学习记忆能力和神经前体细胞与星形胶质细胞增殖水平的影响。方法老年雄性SD大鼠192只,随机分为治疗组、模型组、假手术组和正常对照组,每组48只。治疗组、模型组采用双侧颈总动脉结扎方法建立血管性痴呆大鼠模型,于造模60d后治疗组大鼠应用天智颗粒5g/(kg·d)治疗30d。采用三等分Y型电迷宫测试各组大鼠的学习记忆能力,应用免疫组织化学尿嘧啶脱氧核苷(BrdU)和胶质纤维酸性蛋白(GFAP)染色方法标记并观察神经细胞增殖变化,以比较各组大鼠学习记忆能力和神经细胞增殖的变化规律和差异。结果与正常对照组相比,假手术组大鼠的学习记忆能力和免疫组织化学检测结果无明显变化。经天智颗粒治疗30d后,治疗组大鼠学习记忆能力明显改善,与模型组相比差异有统计学意义(P<0.05),BrdU阳性细胞显著增加(P<0.05),而星形胶质细胞明显减少(P<0.05);但与正常对照组相比,其学习记忆能力、BrdU阳性细胞和星形胶质细胞数量仍未恢复至正常水平(P<0.05)。结论天智颗粒可通过促进神经前体细胞的增殖而抑制星形胶质细胞的增殖,从而改善血管性痴呆大鼠的学习记忆能力。     

Differential actions of NPY on seizure modulation via Y1 and Y2 receptors: evidence from receptor knockout mice

PURPOSE: Neuropeptide Y (NPY) has been shown to modulate seizure activities. To provide further understanding of the involvement of two of the most abundantly expressed NPY receptors, Y1 and Y2, we assessed the effect of Y1 and Y2 gene deletion on systemic kainic acid-induced seizures. We also examined the effect of rAAV-mediated hippocampal NPY overexpression on seizure susceptibility in these receptor knockout mice. METHODS: Recombinant adeno-associated viral vector overexpressing NPY (rAAV-NPY) or an empty vector control (rAAV-Empty) was injected into the hippocampus of adult C57BL/6-129/SvJ wild-type male mice and mice deficient of Y1 or Y2 receptors on the same background. Four weeks after vector injection, mice were subjected to systemic kainic acid-induced seizures, and the seizure behaviors were scored. RESULTS: The rAAV-mediated hippocampal overexpression of NPY led to a twofold reduction in seizures induced by systemic kainic acid in wild-type mice and Y1 receptor knockout mice but not in mice deficient of Y2 receptors. A differential action by the receptors was observed in the seizure-induced mortality rate, with increased fatality in Y2-/- mice. In addition, although NPY overexpression did not significantly affect the mortality rate in Y2-/- and wild-type mice, it abolished KA-induced mortality in Y1-/-mice. CONCLUSIONS: This study shows for the first time an altered susceptibility to chemically induced seizures in Y1 and Y2 knockout mice and demonstrates a differential seizure modulation mediated by these receptors via a genetic approach.     

晚期糖基化终末产物及受体在实验性2型糖尿病大鼠种植体周围的变化及表达

目的 建立2型糖尿病大鼠动物模型,探讨晚期糖基化终末产物及其受体在实验性2型糖尿病大鼠种植体骨整合过程中的变化及表达.方法 45只3个月龄SD健康雄性大鼠,将大鼠随机分为糖尿病模型组25只和正常对照组20只.首先建立2型糖尿病大鼠模型,建模成功后将模型大鼠随机分为DM组和DM种植组,每组10只.将20只正常组大鼠随机分为正常对照组和正常种植组,每组10只.分别于正常种植组和DM种植组的胫骨近骺端植入纯钛种植体,植入10周后于下腔静脉采血,保存所采集标本,用RF-5301PC型荧光分光光度计测定血清中AGEs含量的变化.硬组织标本采用不带种植体脱钙切片,以正常组为对照,HE染色后用免疫组织化学方法检测种植体周围RAGE的表达.结果 10周后,DM种植组和DM组与正常对照组和正常种植组相比,血清中AGEs的变化差异有统计学意义（P ＜0.05）,正常种植组和DM种植组与正常对照组的种植体周围骨组织RAGE表达比较,差异均有统计学意义（P ＜0.05）;DM种植组与DM组比较,差异亦有统计学意义（P ＜0.05）.结论 种植体骨组织愈合过程中AGEs和RAGE相互作用是影响2型糖尿病种植体骨结合的机制之一.     

APPswe/Aβ regulation of osteoclast activation and RAGE expression in an age‐dependent manner

Alzheimer's disease (AD), one of the most dreaded neurodegenerative disorders, is characterized by cortical and cerebrovascular amyloid β peptide (Aβ) deposits, neurofibrillary tangles, chronic inflammation, and neuronal loss. Increased bone fracture rates and reduced bone density are commonly observed in patients with AD, suggesting one or more common denominators between both disorders. However, very few studies are available that have addressed this issue. Here, we present evidence for a function of amyloid precursor protein (APP) and Aβ in regulating osteoclast (OC) differentiation in vitro and in vivo. Tg2576 mice, which express the Swedish mutation of APP (APPswe) under the control of a prion promoter, 1 exhibit biphasic effects on OC activation, with an increase of OCs in younger mice (< 4 months old), but a decrease in older Tg2576 mice (> 4 months old). The increase of OCs in young Tg2576 mice appears to be mediated by Aβ oligomers and receptor for advanced glycation end products (RAGE) expression in bone marrow macrophages (BMMs). However, the decrease of OC formation and activity in older Tg2576 mice may be due to the increase of soluble rage (sRAGE) in aged Tg2576 mice, an inhibitor of RANKL‐induced osteoclastogenesis. These results suggest an unexpected function of APPswe/Aβ, reveal a mechanism underlying altered bone remodeling in AD patients, and implicate APP/Aβ and RAGE as common denominators for both AD and osteoporosis. © 2011 American Society for Bone and Mineral Research.     

Effect of hyaluronic acid on urine nerve growth factor in cyclophosphamide‐induced cystitis

Objectives: To investigate how hyaluronic acid (HA) affects nerve growth factor (NGF) production and bladder overactivity in a cyclophosphamide (CYP)‐induced cystitis rat model. Methods: Female Sprague–Dawley rats received three intermittent intraperitoneal injections of CYP (75 mg/kg) or saline. Before or after CYP injection, HA was given intravesically and urine NGF was checked with creatinine correction. Bladder function was evaluated by cystometrograms under Zoletil anesthesia. Furthermore, the effect of HA was counteracted with hyaluronidase (HYAL). Bladder structural change was compared among groups with trichrome stain. Results: The intercontraction interval (ICI) significantly decreased in CYP‐injected rats in comparison to the saline‐injected controls. In the CYP‐injected groups, bladder HA instillation significantly increased the ICI, but did not change the maximum voiding pressure in comparison to the saline instillation. NGF production significantly increased in CYP‐injected rats, but decreased significantly with HA treatment. Treatment with HA had a more significant effect on urine NGF and the use of HYAL would eliminate this effect. Specific staining showed mucosa swelling after CYP treatment. Little HA coating on bladder mucosa could be found in HA‐treated rats. Conclusions: Present findings raise the possibility that HA could be an effective treatment for CYP‐related bladder overactivity through the involvement of NGF signaling.     

Improving on National Quality Indicators of Breast Cancer Care in a Large Public Hospital as a Means to Decrease Disparities for African American Women

Background

In April 2007, the National Quality Forum (NQF) endorsed the first nationally recognized hospital-based performance measures for stage I, II, and III breast cancer. The purpose of this study was to document compliance with the 3 NQF breast quality indicators during 2 time intervals in a metropolitan public hospital.

Materials and Methods

Tumor registry and medical records were used to identify patient demographics and treatments before (2005–2006) and after (2008) implementations in 2007 as a result of the NQF audit. Program changes included: hiring a dedicated medical oncology nurse practitioner, requiring the radiation oncology case manager to attend weekly multidisciplinary conferences, educating Patient Navigators of the importance of multimodal care, and providing support groups for patients addressing importance of completion of all treatment options.

Results

A total of 213 female patients were diagnosed with and treated for stage I, II, or III breast cancer in 2005–2006 and 2008. Of these, 189 (89%) were African American (AA) women. Also, 70 patients of 86 (81.3%) received radiation therapy, 60 of 77 (77.9%) received or were considered for adjuvant chemotherapy, and 124 of 144 (86.1%) for hormonal therapy according to NQF indicators. After 2007, patients receiving radiation therapy increased from 75.8 to 95.8%. Patients receiving or considered for adjuvant chemotherapy or hormonal therapy increased from 73.7 to 93.7% and from 84.1 to 90.0%, respectively.

Conclusions

NQF breast cancer indicators provided a mechanism to improve compliance of multimodal treatment in our center. Raising awareness of these indicators in the multidisciplinary conference, hiring dedicated personnel, and educating patients has led to major improvements in breast cancer care.     

Association between coronary artery calcification using low-dose MDCT coronary angiography and bone mineral density in middle-aged men and women

Summary

Six hundred sixty-one participants who had at least one cardiac risk factor but were without known coronary heart disease underwent low-dose multidetector computed tomography coronary angiography (MDCT-CA) and dual-energy X-ray absorptiometry. The association between presence of subclinical coronary calcified plaque and low bone mineral density for the middle-aged individual was not significant after multivariate adjustment.

Introduction

Results of previous clinical studies assessing the relationship between osteoporosis and coronary calcification are inconsistent. This study aimed to evaluate the association between subclinical coronary calcification and osteoporosis in middle-aged men, premenopausal women, and postmenopausal women by using low-dose MDCT-CA and bone mineral density (BMD).

Methods

This study enrolled 661 participants with at least one cardiac risk factor but without known coronary artery disease (CAD). All subjects underwent low-dose MDCT-CA and dual-energy X-ray absorptiometry on the same day.

Results

The mean age was 52.2 years for men, 44.8 years for premenopausal women, and 59.1 years for postmenopausal women. The prevalence of calcified plaques between men with normal BMD and low BMD at lumbar spine were significantly different (P?=?0.042). The prevalence of mixed plaque and calcified plaque between pre- and postmenopausal women with normal BMD and low BMD at lumbar spine and femoral neck were not significantly different (P?>?0.05). Possible association between lumbar spine, femoral neck, and total proximal femur BMD and the presence of CAP was evaluated for men, premenopausal women, and postmenopausal women using multivariate logistic regression analysis: results were not significant (P?>?0.05).

Conclusion

Our study demonstrates that the association between the presence of subclinical coronary calcification and low BMD among middle-aged men and women was not significant after controlling for age and other risk factors for CAD and osteoporosis.     

Slipped capital femoral epiphysis in an adult with panhypopituitarism

Slipped capital femoral epiphysis usually occurs in children going through a pubertal growth spurt, possibly because the immature proximal femoral physis is unable to bear the shear stress. It commonly occurs in adolescents between 10 and 16 years. Slipped capital femoral epiphysis in adults is uncommon, with only 10 cases reported in the literature. This article presents a case of a 29-year-old man with craniopharyngioma diagnosed when he was 19. He underwent surgery with subtotal tumor excision and postoperative radiotherapy, but received no further treatment for the panhypopituitarism concomitant with the tumor. He reported sudden onset of left hip pain after riding a bicycle and underwent surgical fixation 5 days later. He also underwent hormone replacement therapy, including prednisolone, thyroxin, desmopressin, and testosterone, and regular clinical follow-up. His hip function recovered with a painless gait. At 18-month follow-up, neither osteonecrosis nor contralateral slipped capital femoral epiphysis was noted. Furthermore, bilateral proximal femoral physes were also closed. For stable slippage as in this case, in situ pinning fixation is a commendable method. A high index of suspicion of endocrinal disorder and proper management are essential for successful treatment of adult slipped capital femoral epiphysis.