艾塞那肽对糖尿病大鼠肾脏损伤的保护作用

目的：探讨GLP-1类似物艾塞那肽（exenatide）对链脲佐菌素诱导的糖尿病大鼠肾脏的保护作用。方法：SD大鼠随机分为正常组（NC组,n=8）和模型组;模型组给予高脂高糖饲料,喂养4周后腹腔注射STZ（30 mg·kg^-1）建模,72 h后以血糖≥ 16.7 mmol·L^-1为糖尿病成模标准,将成模大鼠随机分为糖尿病对照组（DM组,n=10）、3 μg·kg^-1艾塞那肽干预（Ex-1）组和6μg·kg^-1艾塞那肽干预（Ex-2）组;艾塞那肽组连续皮下注射艾塞那肽（bid）12周,NC组和DM组注射等容积溶剂;测定各组大鼠糖脂代谢变化和肾功能指标如血肌酐（Scr）、尿肌酐（Ucr）、尿素氮（BUN）、24 h尿微量白蛋白排出率（24 h UMA）并计算肌酐清除率（Ccr）;测定肾组织氧化应激指标超氧化物歧化酶（SOD）、丙二醛（MDA）和谷胱甘肽过氧化物酶（GSH-Px）;HE染色观察肾组织病理形态及ELISA法测定肾组织糖基化终末产物AGEs水平。结果：与糖尿病组相比,艾塞那肽可明显改善糖尿病大鼠糖脂代谢,血糖、糖基化血红蛋白（HbAlc）、甘油三脂及胆固醇值均下降（P < 0.05）,肾功能指标明显好转（P < 0.05）且肌酐清除率下降（P < 0.05）,提示肾小球高滤过状态;同时改善糖尿病引起的肾组织病理结构改变,AGEs浓度下降（P < 0.05）,氧化应激指标SOD和GSH-Px活力升高,MDA含量降低（P < 0.05）。结论：艾塞那肽具有肾脏保护作用,其机制可能与抑制糖尿病大鼠肾组织的AGEs生成和改善氧化应激有关。     

全柱成像毛细管等电聚焦电泳测定艾塞那肽等电点

目的:采用新一代全柱成像毛细管等电聚焦电泳技术(CIEF-WCID)测定艾塞那肽等电点。方法:采用互补性金属氧化物半导体成像技术对样品等电聚焦过程进行实时记录,根据适宜的marker计算得到艾塞那肽的等电点,并对方法的准确度与重复性进行考察。结果:测得艾塞那肽等电点为5.46,与凝胶电泳结果基本一致,相对标准偏差为0.11%。CIEF-WCID方法快速准确,相对误差小于2.5%,重复性良好。结论:CIEF-WCID作为一种新的技术手段可用于艾塞那肽等电点的分析,方法快速、准确、重复性好,可为多肽的质量控制提供一种可靠的分析方法。     

Daily,weekly and annual patterns in children’s accidental sport injuries*

Details of serious injuries to children ≤16 yrs. of age that necessitated urgent surgical intervention by the Department of Pediatric Surgery of the University Hospital of Lausanne, Switzerland were recorded into a database registry. Some 15 110 entries listed the precise time of injury, and 3114 (20.6%) of these resulted from participating in sport-associated activities. Time-of-day, day-of-week and month-of-year differences in the total number of children’s accidental sport injuries (CASI) were validated. Time-of-day patterns were substantiated for “All Sports”, for both boys and girls 5–16 yrs. of age, with more boys than girls experiencing incidents at almost every clock hour. Moreover, they were substantiated for this age group for each of the six different considered individual and team CASI categories – Physical Exercises at School; Bicycle Riding; Roller Skating and Skateboarding; Snow Skiing, Sledding, and Tobogganing; Soccer; and Basketball – for which sample sizes were sufficiently large (n > 230) to perform statistical assessment by ANOVA, t-test and/or cosinor analyses. CASI happened primarily between 06:00 and 17:00 h and rarely evening or overnight. Features – specific clock-time and number of peaks and troughs – of the CASI daily curve pattern of the individual six sport categories differed somewhat; nonetheless, excess or greatest number of CASI typically happened between 12:00 and 14:00 h, even when summertime and other scheduled school and family vacation periods were taken into account. Time-of-day and day-of-week patterns in the boy/girl sex ratio were also validated, with midday and Friday/Saturday peaks, respectively. We hypothesize the prominent 24 h patterns of CASI of 5–16 yr. olds, in particular, are representative of a combination of several determinants. These include exogenous periodic and cyclic environmental and sociocultural phenomena, genetic sex-related traits, plus endogenous circadian cognitive and physiologic rhythms, with the common midday injury excess of many sport categories, at least in part, the consequence of the well-documented midday dip in attention and vigilance of children.     

Survival outcomes for patients with nasopharyngeal carcinoma in non–endemic region in the UK treated with intensity modulated based radiotherapy 65 Gy in 30 fractions ± weekly cisplatin chemotherapy

BackgroundNasopharyngeal carcinoma (NPC) is rare in the UK. The aim of the current study was to investigate survival outcomes for patients with NPC treated with (chemo)radiotherapy using 65 Gy in 30 fractions in a non-endemic region.Materials and methodsAll consecutive 62 patients with histology proven non-metastatic nasopharyngeal carcinoma diagnosed between January 2009 to June 2019 were included in this retrospective analysis.ResultsMedian age was 59 years (range:19–81). The majority of patients had stage III disease (66.1%). Induction chemotherapy was given in 21% of patients and 82.3% of patients received concomitant systemic therapy. All patients were treated with 65 Gy in 30 fractions. There was disease recurrence in 17.4% patients. The 5-year disease-free, disease-specific and overall survival were 81.9%, 79.2% and 76.4%, respectively. On univariate analysis, disease recurrence was associated with N-stage (p = 0.047) and overall stage group (p = 0.023).ConclusionTo the best of authors’ knowledge, this is the first report of the use of 65 Gy in 30 fractions of radiotherapy ± weekly cisplatin chemotherapy in NPC in a real-world setting. Our results are comparable to that from other non-endemic regions of the world using different dose fractionation of (chemo)radiotherapy. Future randomised control trials are warranted to compare various dose fractionations in these settings.     

Monitoring of brown stink bug (Hemiptera: Pentatomidae) population dynamics in corn to predict its abundance using weather data

The brown stink bug (BSB), Euschistus servus (Say)(Hemiptera: Pentatomidae), is a serious economic pest of corn production in the southeastern United States. The BSB population dynamics was mon itored for 17 weeks from tasseling to preharvest of corn plants (i.e., late May to mid-September) using pheromone traps in three corn fields from 2005 to 2009. The trap data showed two peaks in early June and mid-August, respectively. The relationship between trap catch and pregrowing season weather data was examined using correlation and stepwise multiple factor regression analyses. Weather indices used for the analyses were accumulated growing degree day (AGDD), number of days with minimum temperature below 0℃(Subz), accumulated daily maximum (AMaxT) and minimum temperatures (AMinT) and rainfall (ARain). The weather indices were calculated with lower (10℃) and upper (35℃) as biological thresholds. The parameters used in regression analysis were seasonal abundance (or overall mean of BSB adult catch)(BSBm), number of BSB adults caught at a peak (PeakBSB), and peak week (Peakwk). The BSBm was negatively related to high temperature (AmaxT or AGDD) consistently, whereas IstPeakBSB was positively correlated to both ARain and Subz, irrespective of weather data durations (the first 4, 4.5, and 5 months). In contrast, the 7-month weather data (AGDD7) were negatively correlated to the BSBm only, but not correlated to the second PeakBSB. The 5-year monitoring study demonstrated that weather data can be used to predict the BSB abundance at its first peak in tasseling corn fields in the southeastern U.S. states.     

Comparison of the efficacy and tolerability of a new once-a-week matricial estradiol transdermal system (Estrapatch 40 and Estrapatch 60) with a twice week system

OBJECTIVE: To compare the efficacy and tolerability of three transdermal systems (Estrapatch 40, Estrapatch 60 and Oesclim 50). METHODS: Multicentre, randomized, open, 3 parallel group study on 421 postmenopausal women presenting with at least 35 hot flushes in the week preceding inclusion and treated for six 28-day cycles with either Estrapatch 40 (n = 141) or Estrapatch 60 (n = 140) once a week or Oesclim 50 (n = 140) twice a week, associated to oral NETA (Millligynon 2x 0.6 mg tablets daily) from day 15 to day 28. Hot flushes, mastodynia, bleeding, local skin tolerability and adhesiveness were reported on daily cards. Endometrial thickness and estrogens were measured before and after treatment. RESULTS: Efficacy was clearly established for the three devices as early as after one cycle of treatment, with success rates (% of women with a decrease > or = 50% of the number of hot flushes) over 97% from cycle 2. The three treatments were equivalent on this criteria, except at cycle 1 for Estrapatch 40 which was not equivalent to both other treatments. Incidence and severity of mastodynia, bleeding pattern, endometrial thickness and specific estrogen-related adverse events reflected a significant higher estrogenic stimulation with Oesclim 50. Adhesiveness was very satisfactory for the three systems. CONCLUSIONS: Estrapatch 40 and 60 presents a better benefit/risk ratio compared to Oesclim 50. Thus Estrapach 40 appears to be a good choice for a first-line estrogen replacement therapy with the possibility to increase the dose to Estrapatch 60.     

Human Exposure to Mercury Through Fish Consumption: Risk Assessment of Riverside Inhabitants of the Urrá Reservoir,Colombia

This study evaluated the risk to human health from mercury exposure through fish consumption in three riverside populations: Children (CH, 2–15 years old), women of childbearing age (WCHA, 16–49 years old), and the rest of the population (RP) from the Urrá reservoir area, Colombia. Questionnaire-based surveys were used to collect data and information about the weekly amount of fish consumed (WAFC) and the relative importance of each fish species in the diet of the study participants. There were no significant differences in WAFC between population groups. CH recorded the highest weekly intake of total Hg (WIT-Hg) (0.6–55.4 μg/kg bodyweight/week), with significant differences (p < .05) from WCHA (0.2–26.7 μg/kg bw/w) and RP (0.1–23.6 μg/kg bw/w). A high percentage (90%) of estimated WIT-Hg values exceeded the provisional tolerable weekly intake (PTWI) established in order to protect the embryo and fetus. Results suggested that sensitive subgroups, such as pregnant women or those who may become pregnant and young children should limit or avoid consumption of certain fish of higher trophic levels due to their high total Hg (T-Hg) concentrations (up to 2.73 μg/g). In sum, the high values of WIT-Hg in children and women of childbearing age revealed a worrying situation, which should be reviewed carefully in order to prevent a potential public health crisis.     

Purity,cell viability,expression of GFAP and bystin in astrocytes cultured by different procedures

Primary astrocyte cultures are the most commonly used in vitro model for neurobiological studies. We speculated that different protocols might induce differences not only in the percentage of astrocytes but also in their biological characteristics. In this study, we investigated the effects of four major protocols on the purity of astrocytes, cell viability, expression of glial fibrillary acidic protein (GFAP) and bystin of cultured astrocytes using MTT assay, immunocytochemical staining, and Western blot analysis. We demonstrated that the purity of astrocytes (98.9%) generated by the subculture (SC) procedure is significantly higher than those generated by primary culture (PC), shaken once culture (SK‐1) or shaken twice culture (SK‐2). We also showed that expressions of GFAP and bystin in astrocytes that are purified by the SK‐2 or SK‐1 procedures are significantly higher than those in astrocytes prepared by PC or SC. In addition, astrocytes cultured by SK‐2 or SK‐1 have a higher level of cell viabilities at most time points after ischemia compared with astrocytes cultured by PC or SC. These suggested that physical stimulation induced by “shaken” or culture operation might be able to activate astrocytes and implied that different procedures induce differences not only in the purity but also in the biological characteristics of astrocytes, such as the percentage of activated astrocytes, GFAP, and bystin expressions and responses to ischemia. A more detailed analysis about the effect of “culture protocol factor” on the biological characteristics of astrocytes is absolutely needed. J. Cell. Biochem. 109: 30–37, 2010. © 2009 Wiley‐Liss, Inc.     

Exenatide promotes cognitive enhancement and positive brain metabolic changes in PS1-KI mice but has no effects in 3xTg-AD animals

Recent studies have shown that type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction or dementia. Insulin resistance is often associated with T2DM and can induce defective insulin signaling in the central nervous system as well as increase the risk of cognitive impairment in the elderly. Glucagone like peptide-1 (GLP-1) is an incretin hormone and, like GLP-1 analogs, stimulates insulin secretion and has been employed in the treatment of T2DM. GLP-1 and GLP-1 analogs also enhance synaptic plasticity and counteract cognitive deficits in mouse models of neuronal dysfunction and/or degeneration. In this study, we investigated the potential neuroprotective effects of long-term treatment with exenatide, a GLP-1 analog, in two animal models of neuronal dysfunction: the PS1-KI and 3xTg-AD mice. We found that exenatide promoted beneficial effects on short- and long-term memory performances in PS1-KI but not in 3xTg-AD animals. In PS1-KI mice, the drug increased brain lactate dehydrogenase activity leading to a net increase in lactate levels, while no effects were observed on mitochondrial respiration. On the contrary, exenatide had no effects on brain metabolism of 3xTg-AD mice. In summary, our data indicate that exenatide improves cognition in PS1-KI mice, an effect likely driven by increasing the brain anaerobic glycolysis rate.