敌敌畏、乐果和马拉硫磷混合染毒对雄性小鼠生殖功能的影响

目的 研究敌敌畏、乐果和马拉硫磷混合染毒后对雄性小鼠生殖功能影响的特点和可能机制。方法 将105只雄性ICR小鼠按体重分层随机分成7组,每组15只,即对照组(0 mg/kg),敌敌畏、乐果和马拉硫磷混合低( 10.8 mg/kg)、中(21.5mg/kg)、高剂量组(43.0 mg/kg),以及敌敌畏组(5.1 mg/kg)、乐果组(12.6 mg/kg)和马拉硫磷组(25.3 mg/kg),经口连续灌胃染毒35 d,每天1次。染毒第36天后处死动物。测量小鼠体重、精子活力,观察精子数量及精子畸形率,检测血清中性激素[包括睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)等]的水平,并观察睾丸及附睾的病理及电镜下改变。结果 染毒后第14天,混合高剂量组小鼠体重[(22.40±3.07)g]低于对照组[(26.73±2.82)g](P＜0.05);染毒后第28天,混合中剂量组小鼠体重[(30.00±4.93)g]亦低于对照组[(33.13±3.29)g](P ＜0.05)。混合中、高剂量组精子数[分别为(321.17±18.19)×106/g附睾重、(225.00±19.67)×106/g附睾重]和精子活力[分别为(64.67±9.91)％、(57.83±9.66)％]均低于对照组[分别为( 373.33±14.65)× 106/g附睾重、(75.17±7.68)％](P值均＜0.05);精子畸形率[分别为(43.33 ±8.66)‰、(55.00±13.80)‰]高于对照组[(32.67±8.17)‰]（P值均＜0.05）;与对照组相比[FSH、E2、LH、T分别为(1.41±0.20)、(17.32±2.72)、(8.75±1.32)、（3.45±0.80）nmol/L],混合中、高剂量组小鼠血清中FSH[分别为(3.14±0.62)、(3.85±0.37) nmol/L]、E2[分别为(36.81±6.68)、（43.76±9.82）nmol/L]水平升高（P值均＜0.01）,LH[分别为(5.21 ±1.23)、(4.27±1.09) nmol/L]、T[分别为(1.37±0.38)、(0.73±0.18)nmol/L]水平降低（P值均＜0.01）。混合高剂量组小鼠睾丸成熟精子数减少,并可见结构异常的精子头、精子尾。结论 敌敌畏、乐果和马拉硫磷混合联合染毒可直接损害小鼠睾丸及附睾的结构和功能,而导致生殖细胞生成过程异常;并导致下丘脑-垂体-性腺轴性激素的分泌紊乱。     

Selenium dietary supplementation as a mechanism to restore hepatic selenoprotein regulation in rat pups exposed to alcohol

Ethanol exposure during gestation and lactation decreases selenium (Se) intake, disrupting body Se balance and inducing oxidative stress in rat offspring. Selenium-supplemented diet (0.5 ppm) was administered to ethanol-exposed (20% v/v) dams during gestation and lactation. When the dams' pups were 21 days old, the pups' levels of the main hepatic selenoproteins glutathione peroxidase (GPx1 and GPx4) and selenoprotein P (SelP) were measured. The pups were divided into control (C), alcohol (A), control-selenium (CS), and alcohol-selenium (AS) groups. The purpose was to evaluate the effect of the selenium-supplemented diet on the levels of Se deposits present in the livers of their pups. Alcohol decreases hepatic Se deposits, GPx activity, and GPx1 expression; alcohol increases GPx4 and SelP expression. Se was measured by furnace graphite atomic absorption spectrometry, the antioxidant activity of GPx and concentration of hepatic phospholipids (PL) were determined by spectrophotometry, and the selenoprotein expressions were detected by Western blotting. Selenite treatment prevented alcohol's effects of diminishing the Se deposits, GPx activity, and GPx1 expression, while maintaining the high levels of the expression of GPx4 and SelP. These results suggest that depletion of hepatic Se levels in rat pups, caused by ethanol exposure to their dams, affects the synthesis of the 3 main hepatic selenoproteins in different ways, which is related to a decrease in GPx activity and PL concentration, and an increase in serum Se levels. Selenium supplementation to the dams increased the expression of GPx1, GPx4, and SelP in their pups.     

孕期不同阶段铅暴露对大鼠胎盘和仔鼠的影响

目的探讨孕期不同阶段铅暴露对大鼠胎盘和子代的影响。方法108只大鼠随机分为4组,于孕期不同阶段饮服0.025%醋酸铅。对照组孕期全程饮服蒸馏水;实验1组孕早期染毒,孕后期饮服蒸馏水;实验2组孕早期饮服蒸馏水,孕后期染毒;实验3组孕期全程染毒。孕末期腹腔静脉取血,原子吸收光谱法测定血铅,检测仔鼠数目、体重、身长和尾长。从大体、光镜和电镜等不同水平观察铅对大鼠胎盘结构的影响。结果实验组大鼠孕末期血铅水平均高于0.483μmol/L;孕期全程染毒组的胎盘重量[(0.31±0.13)g]和仔鼠的体重[(2.08±0.88)g]、身长[(2.37±0.32)cm]、尾长[(0.98±0.09)cm]均最低,与对照组比较,差异均有统计学意义。血铅水平与胎盘重量呈负相关,与仔重无相关性。实验组胎盘海绵带滋养叶巨细胞和空泡化细胞增多,迷路带及海绵带滋养细胞呈退行性改变,绒毛周围纤维蛋白沉积增多。胎盘超微结构显示胎盘滋养细胞周围微绒毛短小、稀疏,线粒体肿胀、数目减少,粗面内质网扩张,膜上核糖体数量减少。结论孕期不同阶段铅暴露可能对胎盘滋养细胞有损伤作用,从而妨碍胎盘的血液供应及母子间营养物质及氧气的交换,导致胎盘重量减低和仔鼠生长发育不良。     

7种有机磷农药对不同来源乙酰胆碱酯酶活性的抑制作用比较

目的研究7种不同有机磷农药对不同来源的乙酰胆碱酯酶的敏感性,筛选出适于指示这些农药的敏感酶。方法测定倍硫磷、草甘磷、对硫磷、马拉硫磷、毒死蜱、久效磷、甲拌磷7种有机磷农药对家蝇(Musca domestica)AChE、电鳗(Electrophorus electricus)电器官AChE活性。结果倍硫磷、草甘磷、对硫磷、毒死蜱、久效磷对家蝇AchE敏感,活性抑制率高于电鳗电器官AchE,在农药质量浓度为1000μg/L时,抑制率最高,分别为85.14%、75.28%、40.94%、85.43%、55.68%;马拉硫磷、甲拌磷对电鳗电器官AchE敏感,抑制率高于家蝇AchE,在农药质量浓度为1000μg/L时,抑制率最高,分别为45.29%、80.58%。结论倍硫磷、草甘磷、对硫磷、毒死蜱、久效磷对家蝇AChE敏感,马拉硫磷、甲拌磷对电鳗电器官AChE敏感。     

Worker exposure and a risk assessment of malathion and fenthion used in the control of Mediterranean fruit fly in South Australia

In 2001, an outbreak of Mediterranean fruit fly in Adelaide was controlled by South Australian Government workers applying organophosphorus insecticides (OPs) to domestic gardens. Residents made claims of adverse effects associated with allegations that worker application practices were poor and led to contamination of homes, residents and pets. The concerns led to a Parliamentary enquiry, the suspension of OP applications for fruit fly control, and the investigation of alternative methods of combating fruit fly in metropolitan Adelaide. The extent of exposure of workers and residents was not estimated. This paper describes a simulated application of the OPs concerned (fenthion and malathion) with measurements of potential exposure through inhalation, dermal contact and deposition of pesticides on surfaces. The data were used as part of a toxicological risk assessment to determine the likely impact of the use of these insecticides. Malathion, used as a 1% suspension in a protein bait mixture, was found to have little potential for airborne exposure, although some workers were found to have up to 0.315 microg/cm(2) malathion deposited on overalls (principally on forearms) and over 500 microg deposited on liner gloves and hats, respectively. Risks to workers and residents were low, with exposures likely to be a small fraction of the acceptable daily intake. Fenthion, used as a 0.05% foliar cover spray, was found between 0.02 and 0.23 mg/m(3) in air 10 m downwind from spray activity and was unlikely to pose a significant risk to residents, since exposures were of short durations of up to 20 min. Personal air samples of spray workers averaged 0.55 mg/m(3) (Workplace Exposure Standard 0.20mg/m(3)). Since workers were usually engaged in spraying for a large proportion of the day, this demonstrates the need for respiratory protective equipment. Maximum deposition of fenthion on workers overalls ranged from 0.06 to over 0.20 microg/cm(2), although little was found on gloves and hats, suggesting workers were skilled in avoiding the plume of overspray. Dialkyl phosphates (metabolites of OP insecticides) were not detected in urine of workers, and there were no changes observed in serum cholinesterase (SChE) enzyme activities 24h following the simulation. These data suggest absorption of OP insecticides by workers was negligible. Deposition on surfaces 5 and 10 m downwind ranged from none detected to 145 microg/cm(2), suggesting that exposure of residents and children in contact with contaminated surfaces (such as garden furniture or play equipment) is possible. Estimates of the potential dermal intake of fenthion by children from contaminated surfaces suggested that risks of acute and chronic effects are slight, since exposures may occur for short periods at intervals of approximately 10 days during fruit fly outbreaks.     

反复心理应激对大鼠儿茶酚胺和酪氨酸代谢的影响

采用ＣｏｍｍｕｎｉｃａｔｉｏｎＢｏｘ大鼠模型研究了反复心理应激对大鼠儿茶酚胺（ＣＡ）和酪氨酸（Ｔｙｒ）代谢的影响,及补充Ｔｙｒ的作用。实验发现：反复心理应激使心理应激组（Ｓ组）和心理应激补充Ｔｙｒ组（ＳＴ组）第１、３、７ｄ２４ｈ尿ＣＡ排出量高于对照组（Ｃ组）（Ｐ＜００５）;而第１４ｄＳＴ组血浆和脑匀浆Ｔｙｒ含量分别高于Ｓ组和Ｃ组（Ｐ＜００１）。反复心理应激７ｄ时,Ｓ组大鼠旷场试验得分低于Ｃ组（Ｐ＜００５）,产生行为缺陷,而补充Ｔｙｒ使ＳＴ组大鼠旷场试验得分降低有所减轻。     

石杉碱甲对急性水胺硫磷和辛硫磷中毒时AChE活力的影响

目的观察石杉碱甲(哈伯因,HupA)对水胺硫磷和辛硫磷急性染毒小鼠的AChE活力的影响。方法实验小鼠随机分为HupA干预组和未干预组,所有小鼠均经口给予一定剂量水胺硫磷或辛硫磷,干预组小鼠于染毒前2 h经口给予HupA,而后定时测定染毒后全血、红细胞和脑组织的AChE活力值。结果无论是水胺硫磷还是辛硫磷染毒,HupA干预组的全血、红细胞及脑组织AChE活力均高于同时点的未干预组。结论 HupA可以对抗水胺硫磷和辛硫磷对AChE活性的抑制作用,提示HupA可能具有预防和治疗水胺硫磷和辛硫磷中毒的作用。     

Acute alcohol exposure during gestational day 8 in the rat: Effects upon physical and behavioral parameters

Pregnant rats on the eighth day of gestation (GD 8) received 2 intraperitoneal injections (0.015 ml/g body weight) spaced by an interval of 4 hours, of either 0, 6, 12, 18, or 24% (v/v) alcohol solution. Brains of pups sacrificed 24 hours after delivery revealed a dose-related impairment in hemispheric and cerebellar length, width and weight. Statistically significant differences were also observed in body weights of culled pups during Post-partum Day 1. An open field test performed when offspring were 40–45 days old demonstrated a dose-dependent increase in ambulation and rearing scores for both males and females and in defecation scores for females only. Although behavioral studies revealed no effects on acquisition or retention of an active avoidance response, there was a dose-dependent impairment in transfer to passive avoidance conditioning. The present results demonstrate that in the rat, an alcohol insult during GD 8 is sufficient to induce morphological and behavioral alterations in the offspring.     

Phagocytosis and lysozyme activity in granulocytes from iron-deficient rat dams and pups

The effect of dietary iron deficiency during gestation and lactation on phagocyte function in rat dams and pups was investigated. Pregnant rats were fed ad libitum diets containing 7, 10 or 250 ppm iron throughout gestation and until day 17 of lactation when dams and their litters (7 pups) were sacrificed. Phagocytosis was measured by the nitroblue tetrazolium (NBT) dye reduction test. Lysozyme activity was measured in granulocytes separated from peripheral blood. A significant increase in percent phagocytes in whole blood in the 7 ppm iron pups was observed. Total white blood cell (WBC) counts were similar among groups. The 7 ppm iron pups had markedly decreased NBT reduction (per 10⁸ phagocytes). On a per ml of blood basis, there were no differences in NBT reduction among groups. Plasma activities of the two granulocyte enzymes measured, lysozyme and peroxidase, were significantly increased in 7 ppm iron pups. It was shown that this increase in plasma lysozyme activity was not due to an increased concentration of lysozyme in granulocytes.     

乐果对U87细胞HSP70表达及AChE活性的影响

[目的]研究乐果对神经胶质瘤细胞U87热应激蛋白70 (HSP70 )表达的影响规律,比较HSP70与乙酰胆碱酯酶(AChE)对乐果的敏感性。[方法]以不同浓度乐果(10 0、10、1、0 .1、0 .0 1、0 μmol/L)对体外培养的U87细胞分别进行2、4、8、16和2 4h染毒,再分别用Western blot法和DTNB法检测各组细胞HSP70表达和AChE活性的变化,比较这两个指标变化的幅度以及引起此变化所需乐果浓度和染毒时间的差异。[结果]乐果染毒2h即可引起HSP70表达的显著增高(P <0 .0 1) ,这一变化在染毒4h时出现于各剂量组,并可持续至染毒16h。在染毒2h和4h ,HSP70表达的变化与乐果剂量之间存在相关关系(Pearson相关系数分别为0 .916和0 .989,P <0 .0 1)。AChE活性的显著降低出现在染毒4h ,且仅出现在剂量较高的3个组,变化幅度也较小。[结论]乐果可以在相对较短时间内以较低剂量引起U87细胞HSP70表达的显著变化,并存在一定的剂量 反应关系。HSP70比AChE对乐果更为敏感。     

The influence of personal protection, environmental hygiene and exposure to pesticides on the health of immigrant farm workers in a desert country

Farm workers in developing countries tend not to use protective measures while handling pesticides. This study investigates the use of personal protection equipment and the practice of safety and hygiene procedures in the handling of pesticides in agriculture. Methods: Through a multi-stage sampling technique, one-fifth of the farms in a region were selected and all the farm workers at these farms were included in the study. A comparison population matching in age, socio-economic status and stay in the region was selected. A specifically designed questionnaire was used to collect information on the use of protective measures and the practice of safety and hygiene during work and on the disposal of empty pesticide containers. Blood pressure and erythrocyte acetylcholinesterase (AChE) activity were measured in the exposed and the unexposed populations. Results: Protective equipment was worn by a minority of farm workers – gloves, by 35%; work coveralls, by 36%; a scarf to cover the nose and mouth, by 39%; and shoes at work, by 79%. With regard to personal hygiene measures, 83% of the workers changed clothes after work and the same proportion took a shower after work; 63% and 46% drank and ate while at work respectively; and 11% used articles of domestic use in the preparation of pesticides on the farm. Most of the farm workers (96%) were asked to prepare pesticides for spraying by the foreman and 61% were asked to spray the pesticides on the crops. AChE activity was highly significantly depleted in the exposed population as compared with the unexposed population. Conclusions: AChE depletion was found to be negatively associated with the use of gloves, of work coveralls, and of a scarf to cover the nose and mouth and with the implementation of safety and hygiene procedures on the farm. AChE depletion was positively associated with the frequency of pesticide spraying. Received: 30 January 1998 / Accepted: 19 August 1998     

GC/MS／MS法测定水中林丹冯拉硫磷、西维因、溴氰菊酯杀虫剂

目的：建立应用GC／MS／MS测定林丹、马拉硫磷、西维因、溴氰菊酯4种杀虫剂的分析方法。方法：首先做GC／MS全扫描分析，确定这4种化合物的母离子，然后比较不同CID电压时二级质谱中特征子离子的峰面积大小及信噪比，对CID电压进行优化，从而确定各化合物的GC／MS／MS测定条件。结果：在0～100μg／L浓度范围内，4种化合物的线性相关系数大于0．995，方法检测限低于0．5μg／L，加标回收率在90％～110％之间，RSD〈10％。结论：该方法灵敏度高、准确性好，适合于水样中林丹、马拉硫磷、西维因、溴氰菊酯4种杀虫剂的分析测定。     

敌敌畏对大鼠脑组织N-甲基-D-天门冬氨酸受体活性的影响

目的 研究敌敌畏(DDVP)染毒后大鼠脑组织中N-甲基-D-天门冬氨酸(NMDA)受体的变化规律,探讨其在有机磷农药中毒中的作用。方法 55只雄性SD大鼠分为11组,每组5只,一组为生理盐水(NS)组,高剂量组(25mg/kg)和低剂量组(15mg/kg)各5组,染毒组分别以敌敌畏腹腔注射,染毒后4h、8h、16h、24h、48h处死,测定大鼠全血和脑组织的乙酰胆碱酯酶(AChE)活性以及脑组织中NMDA受体的活性。结果 DDVP染毒后大鼠全血和脑组织的AChE活性显著下降,且脑组织AChE活性下降更多,抑制率大于80％,恢复更迟缓。脑组织中NMDA受体的最大结合容量(Bmax)在4h便明显下降,于24h达到最低,然后逐渐升高,受体的平衡解离常数(Kd)在4h时明显上升,于24h达到最高,然后逐渐下降。结论 DDVP染毒对大鼠脑组织AChE活性抑制严重,说明中枢神经系统对DDVP的毒作用敏感。同时DDVP染毒对大鼠脑组织中NMDA受体产生下降调节,表现为受体数量减少、亲和力降低。推测这是机体的一种自身调节机制,可减少过度刺激并保护中枢神经系统。     

Comparative effectiveness of a standard behavioral and physical activity enhanced behavioral weight loss intervention in Black women

ABSTRACT

Black women typically lose small amounts of weight in behavioral weight loss interventions, partially due to low engagement in physical activity. Culturally relevant enhancement of the physical activity component may improve weight loss. This study compared the effectiveness of a culturally-relevant, physical activity-enhanced behavioral weight loss intervention to a standard behavioral weight loss intervention in Black women (n = 85) over 6 months. The study was conducted in two cohorts from March 2016 to February 2017 at the University of North Carolina at Chapel Hill. Participants had an average age of 48.30 ± 11.02 years with an average body mass index of 36.46 ± 4.50 kg/m². Standard and enhanced groups’ weight change (?2.83 kg and ?2.08 kg, respectively) and change in physical activity (43.93 min/ week and 15.29 min/week, respectively) did not differ between groups. Significantly more standard group participants lost 5% of baseline weight compared to enhanced group participants. This study produced typical weight loss results in Black women. Behavioral weight loss treatment remains moderately effective for Black women. Strategies to increase attendance and self-monitoring, and the inclusion of cultural contexts to weight-related behaviors are needed to improve outcomes.     

Physical activity and depression in MS: The mediating role of behavioral activation

BackgroundDepression is a common comorbid condition among individuals with multiple sclerosis (MS) and is associated with greater overall disease burden and lower quality of life. Numerous clinical trials have supported physical activity interventions versus education, usual care, and attention control conditions for improving depressive symptoms in individuals with MS. However, little is known about the psychological mechanisms that may underlie physical activity-related improvements in depression. Behavioral activation posits that depression may stem from a reduction or loss of personally meaningful and rewarding activity. The process of behavioral activation involves re-engaging with these experiences. Behavioral activation might represent one mechanism by which physical activity interventions improve depression.ObjectiveTo examine behavioral activation as a mechanism mediating the effects of physical activity intervention on depressive symptom improvement in individuals with MS.MethodsMediational path analysis using data from a randomized controlled trial (N = 64) comparing telephone-based physical activity counseling (TC) to education (EC).ResultsParticipation in TC resulted in greater improvements in behavioral activation from months 0–3. Improvements in behavioral activation were associated with fewer baseline-adjusted depressive symptoms at month 6. The corresponding indirect (mediational) pathway was significant.ConclusionBehavioral activation may represent one mechanism by which physical activity improves depression in MS. Future physical activity trials should capitalize on this relationship and place additional emphasis on identifying and engaging in personally meaningful life activity. Future trials of therapies focused on behavioral activation might benefit from encouraging physical activity goals.Trial registrationTrial Registration clinicaltrials.gov Identifier: NCT01198977.     

田间作业致有机磷农药中毒与口服中毒的临床比较

目的 探讨田间作业中毒和口服有机磷农药中毒在临床表现及治疗上的差异.方法 回顾性分析我院2007年7月至2010年7月收治的85例中、重度急性有机磷农药中毒患者的临床资料,按中毒途径分为口服组(51例)和非口服组(34例),比较不同途径中毒后的临床表现、治疗特点及预后.结果 口服组中度中毒患者的肌颤肌痉挛和共济失调的发生率(86.4%、90.9%)均明显高于非口服组(50.0%、55.0%),差异有统计学意义(P＜0.05,P<0.01);口服组重度中毒患者的肺水肿、肌颤肌痉挛及昏迷的发生率(100.0%、89.7%、93.1%)均明显高于非口服组(71.4%、64.3%、50.0%),差异有统计学意义(P<0.05 ).非口服组解毒时间[中度:(35.0±6.2)h、重度:(45.0±11.1)h]较口服组[中度:(49.0±7.7)h、重度:(77.0±10.3)h]明显缩短,差异有统计学意义(P＜0.05).治疗后24、48、72 h,中、重度非口服组胆碱酯酶活力明显高于口服组,差异有统计学意义(P<0.05或P<0.01);中、重度非口服组的氯磷定用量、阿托品化用量及阿托品总量明显低于口服组,差异有统计学意义(P＜0.05或P<0.01).结论 田间作业有机磷农药中毒在临床表现上与口服中毒不尽相同,且治疗的阿托品及氯磷定用量相对较少,胆碱酯酶活力恢复较快.

Abstract：

Objective To investigate the differences of clinical manifestation and therapy of organophosphorus pesticide poisoning (OPP) between oral exposure and occupational exposure in field work. Methods From July 2007 to July 2010, 85 patients with acute severe OPP were treated in a hospital, which were divided into oral poisoning group (51 cases) and non-oral poisoning group (34 cases). The differences of clinical manifestations, curative effects and prognosis between two groups were compared. Results The rates of myoclonus and ataxia in cases with moderate poisoning of oral poisoning group were 86.4% and 90.9%, which were significantly higher than those (50.0% and 55.0% ) of non-oral poisoning group (P<0.05 or P< 0.01). The rates of myoclonus, lung fluid and coma in cases with severe poisoning of oral poisoning group were 100.0%, 89.7% and 93.1%, respectively, which were significantly higher than those (71.4%, 64.3% and 50.0%) of non-oral poisoning group (P<0.05). The mean detoxification hours in cases with moderate poisoning and cases with severe poisoning of non-oral poisoning group were (35.0±6.2) and (45.0±11.1) hours which were significantly lower than those [(49.0±7.7) and (77.0±10.3) hours] in cases with moderate poisoning and cases with severe poisoning of oral poisoning group (P<0.05). In 24, 48 and 72 h after treatment, the cholinesterase (ChE) activities of non-oral poisoning group were higher than those of oral poisoning group (P< 0.05 or P<0.01). The used doses of pyraloxime methylchloride (PAM-Cl) or atropine and the used total dose of atropine in non-oral poisoning group were lower than those in oral poisoning group (P<0.05 or P<0.01). Conclusions The clinical manifestation of non-oral poisoning group is different from the clinical manifestation of oral poisoning group due to the high morbidity of OPP occurred at field site in summer. The used doses of atropine and PAM-Cl are less and the ChE activity recovers quickly for non-oral poisoning group.     

Leptin induces nitric oxide-mediated inhibition of lipolysis and glyceroneogenesis in rat white adipose tissue

Leptin is secreted by white adipose tissue (WAT) and induces lipolysis and nonesterified fatty acid (NEFA) oxidation. During lipolysis, NEFA efflux is the result of triglyceride breakdown, NEFA oxidation, and re-esterification via glyceroneogenesis. Leptin's effects on glyceroneogenesis remain unexplored. We investigated the effect of a long-term treatment with leptin at a physiological concentration (10 μg/L) on lipolysis and glyceroneogenesis in WAT explants and analyzed the underlying mechanisms. Exposure of rat WAT explants to leptin for 2 h resulted in increased NEFA and glycerol efflux. However, a longer treatment with leptin (18 h) did not affect NEFA release and reduced glycerol output. RT-qPCR showed that leptin significantly downregulated the hormone-sensitive lipase (HSL), cytosolic phosphoenolpyruvate carboxykinase (Pck1), and PPARγ genes. In agreement with its effect on mRNA, leptin also decreased the levels of PEPCK-C and HSL proteins. Glyceroneogenesis, monitored by [1-(14) C] pyruvate incorporation into lipids, was reduced. Because leptin increases nitric oxide (NO) production in adipocytes, we explored the role of NO in the leptin signaling pathway. Pretreatment of explants with the NO synthase inhibitor Nω-nitro-l-arginine methyl ester eliminated the effect of leptin on lipolysis, glyceroneogenesis, and expression of the HSL, Pck1, and PPARγ genes. The NO donor S-nitroso-N-acetyl-DL penicillamine mimicked leptin effects, thus demonstrating the role of NO in these pathways. The inverse time-dependent action of leptin on WAT is consistent with a process that limits NEFA re-esterification and energy storage while reducing glycerol release, thus preventing hypertriglyceridemia.     

孕期PFOS暴露诱导胎鼠肺损伤中糖皮质激素影响

目的探讨孕期全氟辛烷磺酸(PFOS)暴露诱导的胎鼠肺损伤中糖皮质激素影响。方法通过低、中、高(5、10、20 mg/kg)剂量PFOS对孕期SD大鼠染毒7 d,于受孕第19 d取胎鼠全肺采用实时荧光聚合酶链式反应、western blot及酶联免疫吸附试验检测胎鼠肺脏中糖皮质激素含量及相关调控基因mRNA、蛋白表达。结果与对照组比较,PFOS组胎鼠肺脏中糖皮质激素含量有升高趋势;高剂量PFOS组11β-羟基类固醇脱氢酶1(11βHSD1)mRNA表达(99.07±15.06)高于对照组(P<0.05),11βHSD2 mRNA表达(1.140±0.303 2)明显低于对照组(P<0.01),11βHSD2蛋白水平低于对照组(P<0.05);与对照组比较,高剂量PFOS组己糖-6-磷酸脱氢酶(H6PDH)mRNA(21.37±3.013)升高(P<0.05);肺表面活性物质相关蛋白C(SP-C)表达无明显变化。结论孕期PFOS暴露诱导的胎鼠肺损伤中,糖皮质激素未发生明显变化,推测肺损伤不是肺表面张力破坏引起的。     

Comparative investigation of behavioral, neurotoxicological, and immunotoxicological indices in detection of subacute combined exposure with methyl parathion and propoxur in rats

The effects of 6 weeks of oral exposure to propoxur (PR; at doses of 0.851 and 8.51 mg/kg body wt.), methylparathion (MP; at doses of 0.218 and 0.872 mg/kg body wt.), and their combinations were investigated in male Wistar rats. Measurement endpoints of the investigation were certain general toxicological parameters (body weight gain, organ weights), plaque-forming cell (PFC) count from the spleen, open field (OF) behavior, auditory startle response (ASR), prepulse inhibition (PPI), rotarod performance, somatosensory and auditory cortical evoked potentials, and peripheral nerve conduction velocity. The treated rats did not show any sign of acute intoxication during the 6 weeks of exposure. The higher dose of PR, but not of MP, significantly decreased the relative liver weight. Both agents produced a significant dose-dependent increase of OF activity, with larger expression after 2 weeks than after 6 weeks. The number of ASR responses and the ASR amplitude increased. The amplitude after PPI was increased by MP but only minimally altered by PR and the combinations. There was a small, but with high-dose PR significant, increase in the latency of the somatosensory evoked potentials. Neither of the two substances alone had any effect on the PFC response. The effect of the combination of high-dose PR and low-dose MP was significantly different from that of high-dose PR alone on the liver weight, on the ASR amplitude, and on the PFC/10(6) cell and PFC/spleen counts. With high-dose MP and low-dose PR, no such interaction was observed. According to the results, the noneffective dose of MP can influence the toxicity of the effective dose of PR in a combined exposure situation.     

Learning behavior in rat offspring after in utero and lactational exposure to either TCDD or PCB126

Objectives We studied and compared the possible effects of in utero and lactational exposure to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) or 3, 3′, 4, 4′, 5-pentachlorobiphenyl (PCB126) on learning behavior in offspring. Methods Pregnant Long–Evans Hooded rats were administered either TCDD (50, 200, or 800 ng/kg) or PCB126 (500, 2,000 or 8,000 ng/kg) on gestational day 15. A procedure of schedule-controlled operant behavior was applied to examine learning behavior in the male and female offspring at 11 weeks of age for 30 days. Three indices, namely, response rates in a fixed ratio (FR) and in a differential reinforcement of low rates (DRL), and reward rate in the DRL component in multiple FR 20 DRL 20 s (mult-FR 20 DRL 20-s) test sessions, were used for the evaluation of learning behavior. Results Toxic effects on learning behavior in male and female pups following in utero and lactational exposure to TCDD or PCB126 were observed mainly in the FR learning component. However, no linear dose-dependent effects of either of the two compounds were observed for the above three indices. The response rates of animals in the low-dose TCDD and PCB126 groups decreased and those in medium-dose TCDD and PCB126 groups appeared to induce hyperactive behavior. The high dose of PCB126 appeared to have a distinct toxicity from that of TCDD in terms of the acquisition of learning behavior. Conclusions Toxicities of PCB126 and TCDD in learning behavior might be similar to each other and the current toxic equivalency factor (TEF) of 0.1 for PCB126 can be considered to be appropriate for this endpoint.