Effects of Ethanol Exposure during the Third Trimester Equivalent on Neuron Number in Rat Hippocampus and Dentate Gyrus

An artificial rearing procedure was used to expose neonatal rats to a formula containing 3.74% ethanol during postnatal days 4 through 10. This treatment produced a mean blood ethanol concentration of 379.8 +/- 17.3 mg/dl. When the pups were killed on the afternoon of postnatal day 10, brain weight to body weight ratio in the ethanol-exposed rats was reduced 22.4% and 21.5% compared to suckle and pair-fed controls, respectively. Ethanol exposure also resulted in a 16% reduction of neurons in hippocampal field CA4, compared to controls, but did not produce deficits in fields CA1 or CA3. There was also a 10% increase in the number of neurons (a population of cells in the midst of a proliferative phase at the time of the exposure) in the granule cell layer of the dentate gyrus. The ethanol exposure did not affect cell size in any of the four neuron populations measured. These results suggest, that within the dose and timing parameters examined, ethanol exposure during the third trimester equivalent appears to be preferentially harmful to specific populations of developing neurons.     

Differential gene expression in cultured osteoblasts and bone marrow stromal cells from patients with Paget's disease of bone.

Paget's disease is a focal condition of bone. To study changes in cells within pagetic lesions, we cultured osteoblasts and stromal cells from 22 patients and compared gene expression in these cells to cells from healthy bone. We identified several differentially regulated genes, and we suggest that these changes could lead to the formation of the lesions. INTRODUCTION: Paget's disease is a focal condition of bone of unknown cause. Although it is regarded as primarily an osteoclast disorder, the tight coupling of the activity of osteoclasts and osteoblasts suggests that the osteoblast could play a key role in its pathogenesis. The aim of the study was to identify possible changes in pagetic osteoblasts and stromal cells that might contribute to the development of pagetic lesions. MATERIALS AND METHODS: Candidate genes were identified based on known bone cell regulators, supplemented with microarray analysis. Gene expression was determined by real-time PCR in primary cultures of osteoblasts and bone marrow stromal cells from pagetic patients and control subjects. Concentrations of secreted proteins were determined by ELISA. RESULTS: Dickkopf1 mRNA and protein levels were increased in both pagetic osteoblast and stromal cell cultures, and interleukin (IL)-1 and IL-6 were overexpressed in pagetic osteoblasts. These changes parallel recent findings in myeloma bone disease, which shares some clinical similarities with Paget's disease. Alkaline phosphatase was overexpressed, and bone sialoprotein and osteocalcin were underexpressed in pagetic osteoblasts, consistent with their circulating levels in pagetic patients. It is hypothesized that overexpression of Dickkopf1, IL-1, and IL-6 would result in stimulation of osteoclast proliferation and inhibition of osteoblast growth, leading to the development of the characteristic lytic bone lesions. By stimulating osteoblast differentiation, Dickkopf1 and IL-6 may also promote mineralization, leading to the conversion of lytic lesions to sclerotic. CONCLUSIONS: These findings suggest that dysregulated gene expression in pagetic osteoblasts could cause the changes in bone cell number and function characteristic of Paget's disease.     

Cognitive and neuroimaging predictors of instrumental activities of daily living.

Impaired ability to conduct daily activities is a diagnostic criterion for dementia and a determinant of healthcare services utilization and caregiver burden. What predicts decline in instrumental activities of daily living (IADLs) is not well understood. This study examined measures of episodic memory, executive function, and MRI brain volumes in relation to baseline IADLs and as predictors of rate of IADL change. Participants were 124 elderly persons with cognitive function between normal and moderate dementia both with and without significant small vessel cerebrovascular disease. Random effects modeling showed that baseline memory and executive function (EXEC) were associated with baseline IADL scores, but only EXEC was independently associated with rate of change in IADLs. Whereas hippocampal and cortical gray matter volumes were significantly associated with baseline IADL scores, only hippocampal volume was associated with IADL change. In a model including cognitive and neuroimaging predictors, only EXEC independently predicted rate of decline in IADL scores. These findings indicate that greater executive dysfunction at initial assessment is associated with more rapid decline in IADLs. Perhaps executive function is particularly important with respect to maintaining IADLs. Alternatively, executive dysfunction may be a sentinel event indicating widespread cortical involvement and poor prognosis.     

142Effects of Low‐Frequency Ultrasound Applied In Vitro to Highly Antibiotic‐Resistant Acinetobacter Isolates Recovered From Soldiers Returning From Iraq

Abstract  Brooke Army Medical Center isolated 25 highly antibiotic‐resistant Acinetobacter ssp . (primarily A. baumannii ) from wounded soldiers returning from Iraq. Concern about effective treatment of these organisms led our institution to begin investigating low‐frequency ultrasound (LFU) as a method of increasing the effectiveness of antibiotics on A.baumannii in wound management. Studies have suggested that LFU applied in conjunction with antibiotics may increase their overall effectiveness. We hypothesize that combining antibiotics with LFU may be an effective method of wound management and that this combination may be synergistic in its overall effect. In this initial work, we wanted to determine if sonocation would have an effect on our organism of interest, A. baumannii . We selected several organisms, both gram positive and gram negative, that have been shown to be killed by sonocation ( E. coli, S. aureus , and S. pyogenes ) and added three highly resistant A. baumannii isolates. Bacterial death was measured by both colony counts after 24 hours of growth and acridine orange staining using a standard protocol.
Colony counts were significantly reduced by sonocation. Furthermore, A.'baumannii colony counts were also greatly reduced by sonocation. Actual cell destruction was also visualized using acridine orange staining. Our data support the assertion that sonocation has an antibacterial effect on some bacteria, including A. baumannii . Our next step is to add antimicrobial agents and determine if their effectiveness can be increased by sonocation.     

Association analysis of genes in the renin‐angiotensin system with subclinical cardiovascular disease in families with Type 2 diabetes mellitus: The Diabetes Heart Study

Aims Cardiovascular disease (CVD) is a major complication of Type 2 diabetes mellitus. The renin‐angiotensin system (RAS) and nitric oxide production are both important regulators of vascular function and blood pressure. Genes encoding proteins involved in these pathways are candidates for a contribution to CVD in diabetic patients. We have investigated variants of the angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AT1R) and endothelial nitric oxide synthase (NOS3) genes for association with subclinical measures of CVD in families with Type 2 diabetes mellitus (T2DM). Methods Atherosclerosis was measured by carotid intima‐media thickness and calcification of the carotid and coronary arteries in 620 European Americans and 117 African Americans in the Diabetes Heart Study. Because of the role of these systems in blood pressure regulation, blood pressure was also investigated. Results Compelling evidence of association was not detected with any of the SNPs with any outcome measures after adjustments for covariates despite sufficient power to detect relatively small differences in traits for specific genotype combinations. Conclusions Genetic variation of the RAS and NOS3 genes do not appear to strongly influence subclinical cardiovascular disease or blood pressure in this diabetic population.     

奥利司他对肥胖青少年体重和机体组分的影响——随机对照试验

背景：儿童和青少年超重和肥胖正迅速增加。在该人群，单纯行为疗法减肥及维持体重下降的效果有限，但是对药物治疗尚未进行广泛的研究。 目的：确定奥利州他（Orlistat）在青少年体重治疗方面的效果及其安个性。 设计、地点和病例：于美国和加拿大32个中心、539例肥胖青少年（12—16岁；体重指数[body mass index，BMI]在第95百分化之上≥2单位）进行的多ln0、54剧（2000年8月至2002年10月）随机双盲研究。 干预：给予奥利司他（n=357）或安慰剂（n=182）120mg，每口3次，持续1年；加适度低热卡饮食（脂肪占30％）、运动和行为治疗。 主要观察指标：BMI变化；二级指标包括腰围和髋用、体重下降、脂质测量以及机体对口服葡萄糖的血糖和胰岛素反心。 结果：至12周时，两组BMI均有下降；此后，奥利司他组体重维持稳定而安慰剂组则超过基线。研究结束时，奥利司他组BMI下降0．55。而安慰剂组则增加0．31（P=0．001）。与安慰剂组的15．7％相比，奥利司他组26．5％的病例BMI下降≥5％（P=0．005）；BMI下降≥10％者分别为4．5％和13．3％（P=0．002）。在研究结束时，奥利司他组体重增加0．53kg，安慰剂组增加3．14kg（P〈0．001）。双能X线吸收测量娃示，这种差异可用脂肪体再的变化解释。奥利司他组腰围下降，安慰剂组腰围上升（-1．33cm比＋0．12cm；P〈0．05）。奥利司他组发生轻至中度胃肠道不良事件者为9％-50％，安慰剂组为1％～13％。 结论：与安慰剂比较，奥利司他与饮食、运动和行为改善联合可显著改善肥胖青少年体重的治疗。在这个青少年人群，连续使用奥利司他1年并无重要安全问题，尽管奥利司他组胃肠道不良事件较为常见。     

Spermatozoal characteristics from fresh and frozen donor semen and their correlation with fertility outcome after intrauterine insemination.

OBJECTIVE: To determine if conventional sperm parameters, specific characteristics of sperm motion determined by computer-aided semen analysis (CASA), sperm penetration assay (SPA), and/or spontaneous acrosome reaction assay could best predict fertility outcome after intrauterine insemination (IUI) from frozen donor sperm. DESIGN: A retrospective analysis of 2,245 cycles of therapeutic donor IUIs were initially studied; 1,147 cycles that met selection criteria were used in this report. SETTING: A university-based assisted reproductive technology center. PATIENTS, PARTICIPANTS: All IUIs were performed on women with documented patency of at least one fallopian tube, ovulatory cycles, and who did not receive human menopausal gonadotropins. Sperm donors had to be used for at least four different recipients (mean of 15) and at least 14 different cycles of insemination (mean of 41). INTERVENTIONS: None. MAIN OUTCOME MEASURE: Pregnancy. RESULTS: Statistical comparisons were made between donors of different relative fertility by using the Mann-Whitney test, Spearman's rank correlation, and multiple regression analysis. These analyses demonstrated that the most significant predictors of the fertility of frozen-thawed donor sperm were curvilinear velocity, straight line velocity, and the total number of motile sperm inseminated. The number of sperm with spontaneous acrosome reactions negatively correlated with fertility outcome, and SPA provided no predictive value. CONCLUSIONS: Our study supports the hypothesis that the study of sperm motion characteristics using CASA after thawing and washing of cryopreserved sperm is a better predictor of fertile outcome after IUI than analysis of fresh semen.