The concerted effects of thyroid function and dietary protein on growth and protein metabolism in mice at different growth stages

The effects of thyroxine (T4) and thiouracil (TU) on growth and protein metabolism were examined in male mice given diets containing different levels of protein (casein) at two different growth stages (25 and 60 days old). Changes in protein metabolism were assessed from the expiratory 14CO2 from [U-14C]leucine injected, the liver nucleic acid contents and the rates of synthesis and degradation of liver protein estimated by single injection method using [6-14C]arginine. Each mouse, excluding the control group, received daily intraperitoneal injection of 10 micrograms of L-thyroxine sodium salt per 100 g b.w. (T4 group) or were given a diet containing 0.05% 2-thiouracil (TU group). In the 25-day-old mice, growth of the T4 group was accelerated at protein levels above 15% and that of the TU group was severely retarded at protein levels below 10%. On the other hand, in the 60-day-old mice, growth of the TU group tended to be accelerated at protein levels from 10% to 25%, while it was significantly retarded at the 5%-protein level. The expiratory 14CO2 increased when the growth was retarded, and decreased when growth was accelerated by T4 or TU in both age groups, but was not significant in either case. The nucleic acid content of the liver was increased by both T4 and TU when the dietary protein level was above 15%. The rate of protein synthesis was increased, but not significantly, by T4, while it was not affected by TU. The rate of protein degradation was increased, but not significantly, by TU, while it was not affected by T4 in the 25-day-old mice. In the 60-day-old mice, the rates of both liver-protein synthesis and degradation were significantly increased by TU, while they were not affected by T4. These results definitely indicate that the growth stage and the dietary protein level change the effects of thyroid function on growth protein metabolism of mice.     

载硒酵母对小鼠化学性肝损伤的影响

观察不同剂量（３０，６０，９０ｍｇ／ｋｇ）载硒酵母（ｓｅｌｍｉｎｍ－ｅｎｒｉｃｈｅｄｙｅａｓｔ，ＳＥＹ）ｉｇ７天对ＣＣｌ４和Ｄ－Ｇａｌ－Ｎ引起的化学性肝损伤的保护作用。结果发现：ＳＥＹ６０ｍｇ／ｋｇ可降低ＣＣｌ４所致血清ＡＬＴ的升高，各剂量组均可降低Ｄ－Ｇａｌ－Ｎ所致血清ＡＬＴ和ＡＳＴ的升高，ＳＥＹ３０ｍｇ／ｋｇ可减轻Ｄ－Ｇａｌ－Ｎ所致肝病理损伤，各剂量组ＳＥＹ均可降低Ｄ－Ｇａｌ－Ｎ所致肝匀浆ＭＤＡ含量升高。提示ＳＥＹ在一定程度上可减轻ＣＣｌ４和Ｄ－Ｇａｌ－Ｎ的化学性损伤，其作用机制可能与抗氧化作用有关。     

The effects of petroleum of different stages of incubation in bird eggs

Summary Artificially incubated mallard eggs were treated externally with 5 l of No. 2 fuel oil or 5 l of Southern Louisiana crude oil at various times during the incubation period. Embryos were most sensitive to petroleum during the first 10 days of incubation. Southern Louisiana crude oil was more toxic to mallard embryos than No. 2 fuel oil. Hatching weights of ducklings from treated eggs were usually not different from hatching weights of control ducklings. Petroleum may cause bill abnormalities among embryos exposed to a lethal amount of oil early in incubation, but few external malformations of any kind were observed among survivors of the oil exposure. The breeding effort of colonial aquatic birds would be in the greatest danger from oil contamination when a large portion of the birds are in the early stages of incubation.     

The effects of petroleum of different stages of incubation in bird eggs

Artificially incubated mallard eggs were treated externally with 5 microliter of No. 2 fuel oil or 5 microliter of Southern Louisiana crude oil at various times during the incubation period. Embryos were most sensitive to petroleum during the first 10 days of incubation. Southern Louisiana crude oil was more toxic to mallard embryos than No. 2 fuel oil. Hatching weights of ducklings from treated eggs were usually not different from hatching weights of control ducklings. Petroleum may cause bill abnormalities among embryos exposed to a lethal amount of oil early in incubation, but few external malformations of any kind were observed among survivors of the oil exposure. The breeding effort of colonial aquatic birds would be in the greatest danger from oil contamination when a large portion of the birds are in the early stages of incubation.     

BCG刺激的肺泡巨噬细胞培养上清液对肺成纤维细胞影响

７．５～６０ｍｇ／Ｌ卡介苗（ＢＣＧ）刺激的肺泡巨噬细胞（ＰＡＭ）培养上清液能显著促进肺成纤维细胞（ＰＦＢ）增殖和胶原合成。发现该上清液中含较高水平的肿瘤坏死因子（ＴＮＰ），且其促ＰＦＢ增殖作用与ＴＮＦ水平成正相关，提示ＢＣＧ在体外能刺激ＰＡＭ产生ＴＮＦ，ＴＮＦ为该上清液促ＰＦＢ增殖的主要因素；５０ｍｇ／ＬＳｉＯ２刺激的ＰＡＭ上清液亦能促进ＰＦＢ增殖和胶原合成，但上清液中几乎检测不到ＴＮＦ，说明其促ＰＦＢ增殖和胶原合成的成分是不同于ＴＮＦ的其它物质；ＴＮＦ能协同该物质促ＰＦＢ增殖和胶原合成。上述结果提示，结核菌刺激ＰＡＭ产生ＴＮＰ可能是矽肺结核病较单纯矽肺发展迅速的一个重要原因。     

吡非尼酮抗百草枯中毒小鼠肺纤维化的研究

目的 探讨吡非尼酮(PF)对百草枯(PQ)中毒小鼠肺纤维化的治疗作用,为临床治疗提供理论依据.方法 雄性ICR小鼠90只,随机分为正常对照组、PQ组、地塞米松组、25、50和100 mg/kgPF组,每组15只.正常对照组小鼠一次性空腹灌胃给予生理盐水,2 h后给予质量分数为1%羧甲基纤维素(CMC)灌胃,再每天定时空腹灌胃同等量CMC;PQ组、地塞米松组及各PF剂量组小鼠给予PQ100mg/kg一次性灌胃染毒,灌胃后2 h,再每天定时PQ组给予0.02ml/10 gCMC灌肠,PF组给予PF(25、50、100 mg/kg)和地塞米松(0.02 ml/10 g)灌胃,每天1次,共49 d.计算肺系数,HE染色,光学显微镜下观察肺组织病理改变;测定肺组织羟脯氨酸(HYP)含量,转化生长因子(TGF-β1)的mRNA表达水平、蛋白表达水平,支气管肺泡灌洗液(BALF)中的TGF-β1蛋白含量.结果 PQ组3 d生存率为53.33%,25、50、100 mg/kg PF组3 d生存率分别为46.67%、73.33%、86.67%,地塞米松组3 d生存率为80%,地塞米松组、50、100 mg/kg PF组3 d生存率明显高于PQ组和25 mg/kg PF组,差异有统计学意义(P＜0.05).25、50及100mg/kg PF组小鼠肺系数均明显低于PQ组,差异有统计学意义(P＜0.05).地塞米松组肺组织中HYP含量为(50.95±11.65)mg/g,25、50、100mg/kg PF组HYP含量分别为(44.52±9.48)、(43.27±6.01)、(40.82±5.90)mg/g,较PQ组[(74.27±3.68)mg/g]明显下降,差异均有统计学意义(P＜0.01).地塞米松组BALF中TGF-β1蛋白含量为(22.03±7.27)mg/ml,25、50、100 mg/kg PF组TGF-β1蛋白含量分别为(55.33±17.50)、(27.75±5.84)、(21.31±6.82)mg/ml,与PQ组[(52.52±15.51)mg/ml]相比,明显降低,差异有统计学意义(P＜0.01);100 mg/kg PF组肺组织TGF-β1mRNA表达水平与PQ组相比,明显下降,差异有统计学意义(P＜0.01)与PQ组比较,地塞米松组,50、100mg/kgPF组肺组织中TGF-β1蛋白表达下降,差异有统计学意义(P＜0.01).结论 PF可以减少百草枯中毒小鼠肺组织胶原沉积,减轻肺部纤维化程度.

Abstract：

Objective To study the curative effects of pirfenidone (PF)on pulmonary fibrosis induced by paraquat (PQ) in mice and to provide the theoretical basis for clinical treatment. Methods Ninety adult healthy male ICR mice were randomly divided into six groups: control group, PQ group , 2 mg/kg Dexamethasone group, 25 mg/kg PF group, 50 mg/kg PF group and 100 mg/kg PF group, there were 15 mice in each group. The corresponding volume of normal saline was given to the each mouse in control group according to the weight, after 2 h 0.1% CMC was given to the each mouse of control group one time by intragastric administration, then the CMC was administrated at regular time until sacrifice. All mice for other 5 groups were exposed to 100 mg/kg PQ by intragastric administration. At 2 h after exposure to PQ, 0.02 ml/10 g dexamethasone and 25、50、100 mg/kg PF were given to mice for dexamethasone group and for 3 PF groups by intragastric administration each day for 49 days, respectively. The lung coefficient was calculated and pathological changes of lung tissue were observed by HE staining for each mouse. The hydroxyproline (HYP)level in lung tissue was measured for each mouse. The mRNA level of and the protein level of TGF-β1 in lungtissue for each mouse were determined, and the protein level of TGF-β1 in the bronchus-alveolus lavage fluid (BALF) of each mouse was detected. Results The survival rates on the 3rd day in PQ group, 3 PF groups and dexamethasone group were 53.33%, 46.67%, 73.33%, 86.67% and 80%, respectively. The survival rates on the 3rd day in dexamethasone group, 50 mg/kg and 100 mg/kg PF groups were significantly higher than those of PQ group and 25 mg/kg PF group (P＜0.05). The lung coefficients of 3 PF groups were significantly lower than that of the PQ group (P＜0.05). The lung tissue HYP levels of dexamethasone group and 3 PF groups were 50.95±11.65, 44.52±9.48, 43.27±6.01 and 40.82±5.90 mg/g respectively, which were significantly lower than that (74.27±3.68) of PQ group(P＜0.01 ). The TGF-β1 protein levels of BALF in dexamethasone group, 50 and 100 mg/kg PF groups were 22.03±7.27, 27.75±5.84 and 21.31 ±6.82 ng/ml respectively, which were significantly lower than that(52.52±15.51 ) ng/mlof PQ group(P＜0.01 ). The expression level of TGF-β1 mRNA in 100 mg/kg PF group decreased significantly, as compared with PQ group (P＜0.01). Conclusion PF could reduce the collagen deposition and pulmonary fibrosis induced by PQ in mice lungs.     

In vitro effects of incinerator fly ash on pulmonary macrophages and epithelial cells

Fly ash from a municipal waste incinerator was used as a model for atmospheric particles in order to identify parameters relevant for the induction of adverse health effects. The aim of this study was to compare the biological effects of the total incinerator fly ash (IFA), the soluble and the insoluble fraction with the effects of quartz by in vitro toxicity studies. The previously sized fly ash (< 20 microns) was characterized by elemental composition and particle size distribution. The particles were administered to rat alveolar macrophages (NR8383) and human bronchial epithelial cells (BEAS-2B) at different amounts via the medium. The total IFA and its insoluble fraction were shown to induce cytotoxicity and cytokine release in a dose-dependent manner. The soluble fraction was nearly unable to induce cytotoxicity and TNF-alpha release but showed potent induction of IL-8 release in BEAS-2B cells at increasing concentrations. Quartz caused similar effects compared to IFA in NR8383 but was less effective in BEAS-2B.     

In vitro effects of fibrous and nonfibrous silicon nitride on bovine pulmonary macrophages

Bovine pulmonary macrophages were exposed in vitro to 0.3, 0.1, 0.03, or 0.01 mg/ml of a fibrous silicon nitride, nonfibrous (milled) silicon nitride comminuted from the fibrous powder, alpha-quartz (an active control), or glass beads (an inert control). Functional evaluation of the exposed cells indicated that the fibrous silicon nitride was as cytotoxic as quartz, while the nonfibrous silicon nitride was relatively inert. To further evaluate the mechanisms of cytotoxicity, the cells were exposed to 1 mg/ml of the control and test materials and biochemical studies were performed. Quartz increased release of both the cytoplasmic enzyme, lactate dehydrogenase (LDH), and the lysosomal enzyme, acid phosphatase (AP), consistent with both cell membrane and lysosome lysis. In addition, total protein levels were significantly depressed, suggesting significant impairment of cellular synthetic processes. LDH, but not AP, values were increased with fibrous silicon nitride treatment, but not with the nonfibrous silicon nitride. In contrast to quartz, which increased LDH levels by 65%, the fibrous silicon nitride only increased LDH levels by 11%. Scanning electron micrographs further indicated that the fibrous silicon is cytotoxic and poorly tolerated by macrophages. These studies provide further evidence of morphology as a primary determinant of cytotoxicity since the milled powder test article was comminuted from the fibrous material.     

Kupffer cells ameliorate hepatic insulin resistance induced by high-fat diet rich in monounsaturated fatty acids: the evidence for the involvement of alternatively activated macrophages

Background

Resident macrophages (Kupffer cells, KCs) in the liver can undergo both pro- or anti-inflammatory activation pathway and exert either beneficiary or detrimental effects on liver metabolism. Until now, their role in the metabolically dysfunctional state of steatosis remains enigmatic. Aim of our study was to characterize the role of KCs in relation to the onset of hepatic insulin resistance induced by a high-fat (HF) diet rich in monounsaturated fatty acids.

Methods

Male Wistar rats were fed either standard (SD) or high-fat (HF) diet for 4 weeks. Half of the animals were subjected to the acute GdCl₃ treatment 24 and 72 hrs prior to the end of the experiment in order to induce the reduction of KCs population. We determined the effect of HF diet on activation status of liver macrophages and on the changes in hepatic insulin sensitivity and triacylglycerol metabolism imposed by acute KCs depletion by GdCl₃.

Results

We found that a HF diet rich in MUFA itself triggers an alternative but not the classical activation program in KCs. In a steatotic, but not in normal liver, a reduction of the KCs population was associated with a decrease of alternative activation and with a shift towards the expression of pro-inflammatory activation markers, with the increased autophagy, elevated lysosomal lipolysis, increased formation of DAG, PKCε activation and marked exacerbation of HF diet-induced hepatic insulin resistance.

Conclusions

We propose that in the presence of a high MUFA content the population of alternatively activated resident liver macrophages may mediate beneficial effects on liver insulin sensitivity and alleviate the metabolic disturbances imposed by HF diet feeding and steatosis. Our data indicate that macrophage polarization towards an alternative state might be a useful strategy for treating type 2 diabetes.

     

不同神经发育阶段铅暴露对大鼠海马神经元数目的影响

目的:探讨不同神经发育阶段铅暴露对海马神经元数目的影响。方法:将Wistar大鼠随机分为孕期染铅组、断乳后染铅组和对照组,处理组经水给予PbCl2400μmol/L,对照组自来水。至观察终点采用免疫组化法检测海马CA3区神经元数目。结果:仔鼠出生第1天,孕期染铅组与对照组神经元数目均数分别是315.52±42.12、435.25±25.38,明显低于对照组(P<0.05);至2月龄,孕期染铅组仔鼠神经元均数仍显著低于对照组(P<0.05),而出生断乳后染铅组神经元均数与对照组相比,差别无统计学意义P﹥0.05,其均数分别是45.00±7.83、58.25±7.85和58.74±4.92。结论:孕期铅暴露可导致仔鼠海马神经元数目减少,而出生后铅暴露则对海马组织神经元数目没有明显影响。     

隐孢子虫对不同免疫状态小鼠肠黏膜超微结构的损伤

目的 探讨隐孢子虫对不同免疫状态小鼠肠黏膜超微结构的损伤情况.方法 将昆明小鼠80只随机分为4组,A组为空白对照,其余3组小鼠采用不同免疫方法制备隐孢子虫小鼠模型:B组饮用水中加入地塞米松;C组腹腔注射地塞米松;D组腹腔注射环磷酰胺.免疫抑制后每日观察小鼠的发病情况,并进行粪便检查,5周后处死动物,取虫体寄生较多的回盲部,用电镜观察肠黏膜超微结构的改变.结果 扫描电镜示C组和D组小鼠肠黏膜可见有少量虫体粘附,微绒毛水肿、变形,数量减少.B组实验鼠可见大量虫体粘附和侵入肠黏膜,局部黏膜上皮细胞破损严重,呈不规则网状.透射电镜示C组和D组小鼠肠黏膜上皮细胞细胞膜损伤变薄,细胞连接增宽.B组实验鼠肠黏膜病理损伤较C组和D组重,肠黏膜增厚,部分上皮细胞水肿、坏死,细胞连接融合、消失,细胞内可见空泡和异常沉积物.空白对照组小鼠未发现虫体寄生,肠黏膜结构正常.结论 隐孢子虫对小鼠肠黏膜的损伤程度与免疫抑制方法有关,饮用水中加入地塞米松制备的免疫抑制小鼠肠黏膜损伤较重.     

环境因素对不同青春期阶段儿童青少年屈光发育的影响因素分析

  目的  探讨青春期对儿童青少年屈光发育的影响及其与户外活动、近距离用眼和电子产品使用的交互作用,为近视干预策略的制定提供参考。  方法  采用整群抽样从上海市某所九年一贯制学校选取776名7~13岁的儿童青少年参与研究,随访周期为2年(2015—2017年)。所有参与者每年进行1次睫状肌麻痹下屈光检查和眼轴测量,通过问卷调查和问询获取青春发育表征、日均户外时长、近距离用眼时长、电子产品使用时长等信息。采用广义估计方程分析不同青春期阶段屈光参数的影响因素及其交互效应。  结果  基线时有634名儿童青少年参与散瞳验光,其中350名近视(55.2%)。不同青春发育阶段眼轴长度进展、日均户外时长、近距离用眼时长和电子产品使用时长差异均有统计学意义(F值分别为4.10,4.25,5.54,9.20,P值均 < 0.05)。青春期阶段与日均户外时长对眼轴长度的影响存在交互作用(β=0.133,P＜0.05),与近距离用眼时长、电子产品使用时长的交互作用无统计学意义(P值均>0.05)。  结论  青春期可能在中国儿童青少年户外时间与屈光发育之间的关系中起调节作用。     

The effects of polychlorinated biphenyls given prenatally on the neurobehavioral development of mice.

When tested at adulthood, albino mice exposed in utero to 3,4,3′,4′-tetrachlorobiphenyl (TCB) demonstrated signs of neurotoxicity. The most severely affected subjects (TCB-spinners) displayed a neurobehavioral syndrome consisting of intermittent stereotypic circling, head bobbing, and hyperactivity. TCB-spinners were found to be markedly hyperactive during the dark phase of the diurnal phase and showed impaired forelimb grip strength, ability to traverse a wire rod, visual placement responding, and acquisition of one-way avoidance. Some mice did not display the spinning syndrome (TCB-nonspinners), but were found to be deficient in traversing a wire rod and avoidance acquisition. None of the TCB-exposed mice were found to have depressed neuromuscular reflexes in response to a variety of stimuli. Tissue distribution studies demonstrated that TCB levels were not detectable in adult mice following prenatal exposures. The results of these experiments demonstrate that prenatal exposure to TCB can influence neurobehavioral functioning of mice during adulthood and, in some cases, such effects can be observed in the absence of clinical signs of toxicity.     

硫酸镁对小鼠肾缺血再灌注损伤保护作用

目的 观察硫酸镁对小鼠肾缺血再灌注损伤的抗氧化保护作用.方法 雄性小鼠随机分为假手术组、模型组和硫酸镁高、低剂量(120、60 mg/kg)组,无创动脉夹夹闭左肾蒂45 min和再灌注3 h制备急性肾缺血再灌注损伤模型,检测肾脏指数、血清尿素氮(BUN)和肌酐含量、肾组织丙二醛(MDA)含量以及超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活力,HE染色观察肾组织学变化.结果 硫酸镁高、低剂量组小鼠肾指数分别为(0.72±0.05)和(0.74±0.07)、血清BUN含量为(12.36±2.24)和(15.58±1.92)mmol/L、血清肌酐水平为(98.23±4.37)和(114.63±6.24)μmol/L、肾组织MDA含量为(2.11±0.24)和(2.27±0.21)nmol/(mg.prot),肾组织SOD活力为(4.03±0.68)和(3.51±0.58)U/(mg.prot),硫酸镁高剂量组肾组织GSH-Px活力为(323.90±23.50)U/(mg.prot),与模型组比较,差异均有统计学意义(P<0.05),且肾组织病理变化较轻.结论 硫酸镁对小鼠急性肾缺血再灌注损伤具有保护作用,其机制可能与抑制脂质过氧化反应有关.     

Low-dose dietary resveratrol has differential effects on colorectal tumorigenesis in adiponectin knockout and wild-type mice

Obesity is associated with a decrease in the antiinflammatory hormone, adiponectin, and increases in the circulating concentrations of multiple proinflammatory cytokines. These changes contribute to colon tumorigenesis. Resveratrol increases adiponectin production in adipocytes and attenuates the development of colon cancer. Thus, we hypothesized that adiponectin is an integral component of the mechanism by which resveratrol antagonizes colorectal tumorigenesis. To investigate this, we induced tumorigenesis in adiponectin knockout (KO) and wild-type (Wt) C57BL/6 mice through combined azoxymethane and dextran sodium sulfate treatment during which mice were fed a high-fat, lard-based diet, or the same diet containing 20 mg/kg resveratrol. After 14?wk on diet, Wt mice gained more weight and, on a percentage basis, had higher fat mass and lower lean mass than KO mice. Resveratrol tended to attenuate this response in male Wt mice. Resveratrol also tended to reduce aberrant crypt foci development and decrease circulating interleukin 6 and insulin concentrations in male but not female Wt mice. Taken together, resveratrol improved overall health of obese Wt but not KO mice as hypothesized with a differential sex response.     

Chronic pulmonary insufficiency in children and its effects on growth and development

Conditions leading to chronic pulmonary insufficiency can affect infants and children. These can lead to growth failure and delayed development. Among the most common and severe of these are bronchopulmonary dysplasia (BPD) and cystic fibrosis. In addition to the respiratory consequences of these diseases, there is ample evidence that they lead to decreased growth as a result of decreased energy intake and increased energy expenditure. Furthermore, there is evidence that infants with BPD may also have delayed development, independent of the effects of their prematurity. Enhancing the long-term outlook for these conditions may therefore require consideration of both improved pulmonary management and aggressive nutritional management to limit growth failure and potentially enhance developmental outcome. Specific micronutrient supplementation, such as antioxidant therapy, may also enhance pulmonary and nutritional status.