p66~(Shc)基因敲除对小鼠缺血缺氧性脑损伤的保护作用

目的探讨p66Shc基因敲除对小鼠缺血缺氧性脑损伤(hypoxic-ischemic brain injury,HIBI)的保护作用及可能的机理。方法将C57小鼠分为假手术组(野生型,sham operation,SO)、HIBI野生型组(hypoxic-ischemic wild type,HIWT)和HIBI-p66Shc基因敲除组(hypoxic-ischemic knock-out,HIKO),每组20只。采用右侧颈总动脉结扎-浸入低氧环境的方法制备小鼠HIBI模型。随后对各组小鼠神经功能障碍情况、HIBI损伤灶体积、血清神经元特异性烯醇化酶(neuronspecific enolase,NSE)水平和脑组织匀浆中白细胞介素-1β(interleukin-1β,IL-1β)的水平进行测量和比对。结果 HIBI造模24 h后,HIKO组小鼠的神经功能缺损程度评分(1.87±0.30)低于HIWT组小鼠(2.49±0.26),HIKO组小鼠脑梗死灶体积[(22.66±4.20)mm3]小于HIWT组小鼠[(27.31±3.23)mm3],HIKO组小鼠血清NSE含量[(8.97±0.74)ng/ml]显著低于HIWT组小鼠[(11.26±0.68)ng/ml],HIKO组小鼠脑组织IL-1β含量[(1.72±0.30)ng/ml]显著低于HIWT组小鼠[(2.07±0.28)ng/ml],P均<0.05。结论 p66Shc基因敲除可通过降低小鼠HIBI发生后脑组织IL-1β的表达,起到脑保护作用。     

Lung cancer: What are the links with oxidative stress,physical activity and nutrition

Oxidative stress appears to play an essential role as a secondary messenger in the normal regulation of a variety of physiological processes, such as apoptosis, survival, and proliferative signaling pathways. Oxidative stress also plays important roles in the pathogenesis of many diseases, including aging, degenerative disease, and cancer. Among cancers, lung cancer is the leading cause of cancer in the Western world. Lung cancer is the commonest fatal cancer whose risk is dependent on the number of cigarettes smoked per day as well as the number of years smoking, some components of cigarette smoke inducing oxidative stress by transmitting or generating oxidative stress. It can be subdivided into two broad categories, small cell lung cancer and non-small-cell lung cancer, the latter is the most common type. Distinct measures of primary and secondary prevention have been investigated to reduce the risk of morbidity and mortality caused by lung cancer. Among them, it seems that physical activity and nutrition have some beneficial effects. However, physical activity can have different influences on carcinogenesis, depending on energy supply, strength and frequency of exercise loads as well as the degree of exercise-mediated oxidative stress. Micronutrient supplementation seems to have a positive impact in lung surgery, particularly as an antioxidant, even if the role of micronutrients in lung cancer remains controversial. The purpose of this review is to examine lung cancer in relation to oxidative stress, physical activity, and nutrition.     

Relationship between plasma osteopontin and oxidative stress in patients with coronary artery disease

Background: It is known that oxidative stress plays an important role in the pathogenesis of atherosclerosis and that an association exists between osteopontin (OPN) and atherosclerosis. Objectives: It was proposed that malondialdehyde (MDA), a biomarker of lipid peroxidation and oxidative stress, would be related to plasma OPN levels in patients with coronary artery disease (CAD). Methods/results: Plasma OPN and MDA levels were measured in 71 patients (60 males and 11 females; mean age 61.7 ± 10 years). Fifty-eight patients had significant CAD (group I) and 13 patients were free of CAD as defined angiographically (group II). Plasma OPN was measured by enzyme-linked immunosorbent assay (ELISA), while MDA was determined spectrophotometrically. Multivariate regression analysis revealed that ln-transformed OPN levels were independently associated with MDA after adjustment for age, hypertension and diabetes mellitus (R² = 0.278, p = 0.0004 and β regression coefficient = 0.252 [standard error = 0.0958], p = 0.011). OPN and MDA levels were higher in patients with diabetes (73.6 ± 36.2 ng/ml versus 56.1 ± 30.9 ng/ml, p = 0.02 and 2.5 ± 0.5 μM versus 2.0 ± 0.5 μM, p = 0.002, respectively). Conclusions: The association between OPN and MDA levels in patients with CAD suggests an interaction between OPN and oxidative stress. This interaction may play a role in the pathogenesis of atherosclerosis.     

Combined Effects of Multiple Endoplasmic Reticulum Stresses on Cytokine Secretion in Macrophage

Cells show various stress signs when they are challenged with severe physiological problems. Majority of such cellular stresses are conveyed to endoplasmic reticulum (ER) and unfolded protein response (UPR) serves as typical defense mechanism against ER stress. This study investigated an interaction between ER stress agents using macropage cell line Raw 264.7. When activated by lipopolysaccharide (LPS), the cell lines showed typical indicators of ER stress. Along with molecular chaperones, the activation process leads to the production of additional infl ammatory mediators. Following activation, the macrophage cell line was further treated with TUN and characterized in terms of chaperone expression and cytokine secretion. When treated with TUN, the activated macrophage cell leads to increased secretion of IL-6 although expression of ER stress markers, GRP94 and GRP78 increased. The secretion of cytokines continued until the addition of BFA which inhibits protein targeting from ER to Golgi. However, secretion of cytokines was ceased upon dual treatments with BFA and TG. This result strongly implies that cells may differently deal with various polypeptides depending on the urgency in cellular function under ER stress. Considering IL-6 is one of the most important signal molecules in macrophage, the molecule might be able to circumvent ER stress and UPR to reach its targeting site.     

Proficiency in English sentence stress production by Cantonese speakers who speak English as a second language (ESL)

The present study examined English sentence stress produced by native Cantonese speakers who were speaking English as a second language (ESL). Cantonese ESL speakers' proficiency in English stress production as perceived by English-speaking listeners was also studied. Acoustical parameters associated with sentence stress including fundamental frequency (F0), vowel duration, and intensity were measured from the English sentences produced by 40 Cantonese ESL speakers. Data were compared with those obtained from 40 native speakers of American English. The speech samples were also judged by eight naïve listeners who were native speakers of American English for placement, degree, and naturalness of stress. Results showed that Cantonese ESL speakers were able to use F0, vowel duration, and intensity to differentiate sentence stress patterns. Yet, both female and male Cantonese ESL speakers exhibited consistently higher F0 in stressed words than English speakers. Overall, Cantonese ESL speakers were found to be proficient in using duration and intensity to signal sentence stress, in a way comparable with English speakers. In addition, F0 and intensity were found to correlate closely with perceptual judgement and the degree of stress with the naturalness of stress.     

Prognostiske prediktorer og langtidsforløpet for nevroser og andre psykiske lidelser: 20 års follow-up fra en psykiatrisk spesialistpraksis

Den psykiatriske solopraksis gir muligheter for utvikling av et nÆrt lege-pasientforhold. Vestfold er Norges minste fylke med en befolkning på ca. 174 000 i 1960 stigende til ca. 187 000 i 1980. Forfatteren har arbeidet som psykiatrisk spesialist i Vestfold i hele dette tidsrommet og har således hatt muligheter for å følge mange av pasientene gjennom et langt avsnitt av deres liv. Han har på den måten fått et inntrykk av langtidsforløpet ved psykiske lidelser og likeledes en formening om hvilke kategorier pasienter sorn klarer seg godt eller dårlig. Hensikten med denne undersøkelsen er å objektivisere forløpet og dokumentere bakgrunnsfaktorer med relasjon til prognosen. Ifølge Strømgren (1980) er dette to av flere mulige målsettinger for longitudinelle studier, som ellers stort sett har hatt sitt utgangspunkt i hospitaliserte pasienter og som oftest i endogene psykoser. Foreliggende arbeid omhandler imidlertid et diagnostisert uselektert poliklinisk klientell, og diagnostisk består materialet hovedsaklig av nevroser, men med innslag av psykoser, krisereaksjoner, karakteravvik og misbruksproblematikk.

Forfatteren er takknemlig for finansiell støtte fra Anders Jahres fond til vitenskapens fremme og for verdifull veiledning ved dosent dr. med. Ole Bratfos.     

Prenatal stress increased Snk Polo-like kinase 2, SCF β-TrCP ubiquitin ligase and ubiquitination of SPAR in the hippocampus of the offspring at adulthood

Exposure to excessive glucocorticoids during fetal development period contributes to later life psychopathology. Prenatal stress decreases dendritic spine density and impair LTP in the hippocampus of rat pups, however, the mechanisms regulating these changes are still unclear.     

综合护理干预对缓解住院新生儿家长焦虑的效果研究

目的探讨综合护理干预对减轻住院新生儿家长焦虑的效果。方法对120名住院新生儿家长进行心理反应和应激因素研究,并随机分组进行综合护理干预,在干预后1周和2周釆用焦虑自评量表(SAS)分别测量患儿家长的焦虑状况。结果住院新生儿家长明显存在焦虑情绪;与无综合护理干预组比较,综合护理干预组住院新生儿家长焦虑程度显著减轻(P0.01)。结论护理人员应高度重视住院新生儿家长焦虑情绪,综合护理措施能有效减轻其焦虑情绪。     

Effects of early and late adverse experiences on morpho-quantitative characteristics of Sprague-Dawley rat spleen subjected to stress during adulthood

Morpho-quantitative studies of the spleen indicate that the proportions of the compartments and sub-compartments are stable in normal conditions. However, disorders due to stress can influence the number and function of the immune cells in this organ. The aim of this study was to determine, through the model of altering the early mother-infant bond and altering the late social bond through isolation, the effect on the morpho-quantitative characteristics of the spleen in adult Sprague-Dawley rats subjected to intermittent chronic stress in adulthood. Twenty-five newborn female rats were used, kept under the standardized lactation and feeding conditions. The rats were assigned randomly to 2 control groups (C1 and C2) and 3 experimental groups, exposed to early (E1), late (E2) or early-late (E3) adverse experiences and then subjected to intermittent chronic stress in adulthood (C2, E1, E2 and E3). The spleen of each animal was isolated and its morphometric characteristics were determined: volume density (Vv) of the red pulp, white pulp, marginal zone, splenic lymph nodule, periarterial lymphatic sheath and germinal center; areal number density (Na), surface density (Sv), number density (Nv), diameter (D) and total number of splenic lymph nodules. The mass of each compartment was also determined. A one-way analysis of variance (ANOVA) and Scheffé’s post hoc test were used for the statistical analysis. The p values were considered significant when they were less than 0.05 (*) and very significant at less than 0.025 (**). There were significant differences in the Vv of the red pulp, white pulp and their sub-compartments between the control and experimental groups. The white pulp increased significantly (P = 0.000) in E1, E2 and E3 compared to C1 and C2. The average Na and D values of the splenic lymph nodules were also higher in the experimental groups. The ANOVA for the mass of the spleen and the red pulp revealed no differences between the groups. The mass of the white pulp and its subcompartments was greater in the experimental groups. A higher proportion of white pulp in the experimental groups could be associated with an increase in spleen immune activity, with alterations depending on certain cell subsets. The chronic stress produced morpho-quantitative changes in the rat spleen, and these depended on the animal’s history of stress, whether it had been previously stressed or not, with further exposure to stress in adulthood.