小蘖碱对高脂血症鼠脂联素的调控作用及其对血脂指标和斑块形成的影响

目的 研究小蘖碱对高脂血症鼠脂联素的调控作用及其对血脂指标和斑块形成的影响。 方法 在40只Wistar雄性鼠随机选取30只并喂养高脂饲料饮食进行高血脂(HLP)造模,对照组(n=10)则喂养正常食物并自由摄取水。10周后,将HLP模型随机分为3组: HLP组(n=10)、HLP+LBB组(n=10)和HLP+HBB组(n=10)。对HLP+LBB组鼠进行低剂量小檗碱(berberine, BB)灌胃(150 mg/(kg·d)), HLP+HBB组高剂量小檗碱灌胃(300 mg/(kg·d)),对照组和HLP组则以生理盐水代替。连续喂养10周后测定并比较4组鼠血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)、血清总脂联素和高分子量脂联素含量,以及心肌梗死斑块面积。 结果 造模后,与对照组相比,HLP组大鼠TG、TC和LDL-C显著升高,HDL-C水平显著下降(P<0.05)。提示HLP大鼠造模成功。与HLP组相比,HLP+LBB组、HLP+HBB组TG、TC和LDL-C显著降低(P<0.001),HLP+LBB组HDL-C水平显著升高(P<0.05)。四组大鼠血清总脂联素含量差异无统计学意义(P>0.05),但HLP组中高分子量脂联素与总脂联素的比值显著低于对照组, 而HLP+HBB组显著高于HLP组(P<0.05)。与对照组比较,AdipoR1在HLP组中表达下调(P<0.05), 而HLP+HBB组显著高于HLP组,差异有统计学意义(P<0.05)。AdipoR2在HLP组中的表达无明显变化,但HLP+HBB组显著高于对照组(P<0.05)。HLP+HBB组梗塞面积[(11.4±1.0)%)]显著低于HLP组[(52.2±0.9)%]和HLP+LBB组[(33.1±1.1)%](均P<0.05)。 结论 小蘖碱可对抗高脂血症鼠血中脂联素的下调,这一干预可能在血脂指标和斑块形成方面起到改善作用。     

次氯酸钙,二氧化氯,臭氧对藻代谢物三氯甲烷生成的影响

实验室纯培养富营养化湖泊常见的藻类，收集其代谢产物，以化学耗氧量（ＣＯＤ）指示其含量高低，采用次氯酸钙（Ｃａ （ＯＣｌ）２）、二氧化氯（ＣｌＯ２）及臭氧（Ｏ３）对代谢物进行消毒处理，应用气相色谱检测各处理样品三氯甲烷（ＣＨＣｌ３）的生成量。结果表明：在达到卫生学标准且藻代谢物含量一致的条件下，消毒样品ＣＨＣｌ３生成量次序为：Ｃａ（ＯＣｌ）２〉ＣｌＯ２〉Ｏ３；降低藻代谢物含量可减少ＣＨＣｌ３的产生；     

Synthesis, in vitro cytotoxic and antiviral activity of cis-[Pt(R(-) and S(+)-2-alpha-hydroxybenzylbenzimidazole)2Cl2] complexes

A pair of enantiomeric platinum(II) complexes of cis-[Pt(R(-) and S(+)-HBB)2Cl2] (HBB=2-alpha-hydroxybenzylbenzimidazole) was synthesized and evaluated for its preliminary in vitro cytotoxic activity on the human MCF-7 breast cancer and HeLa cervix cancer cell lines and antiherpes virus activity against bovine herpesvirus type 1 (BHV-1). In general, it was found that Pt(II) complexes were less cytotoxic on both cell lines than cisplatin and were comparable to carboplatin. There was no significant difference in cytotoxicity between two enantiomers, and the antiviral test results showed that the Pt(II) complexes and their carrier ligands R(-) and S(+) HBB had no effects inhibiting replication of BHV-1.     

Comparison of the porphyrinogenic activity of hexabromobenzene and hexachlorobenzene in primiparous wistar rats

Summary and conclusion It can be concluded that HBB used in this study was more porphyrinogenic than HCB. The results suggest that HBB was an effective porphyrinogen even at a concentration in the liver of only 1/8 that of HCB. Further studies should be encouraged to determine the biochemical and pharmacological significance of HBB in the development of hepatic phorphyria. The effects of lactation on the body burden of HBB or HCB should also be investigated.This study showed that HCB-treated primiparous rats did not show elevated esterase activity after over three months of continous feeding on a diet containing 8 0 ppm HCB. Some of these dams showed elevated levels of porphyrin although the HCB residue levels in the liver were similar to those of the non-porphyric, HCB-fed dams. This discrepancy in the response suggests genetic hetero-geneity of predisposition to, or ability to recover from, acquired porphyria in the rat. The low porphyrin levels in some cases may also be due to reduction of HCB concentrations during lactation. This, perhaps, suggests that lactation may have exerted some therapeutic effects on certain porphyric animals but it could consequently be deleterious to the nursing pups (MENDOZA et al. 1975).     

藻类代谢产物对饮用水致突变性影响的研究

纯培养富营养化湖泊常见的４种藻类，在不同加氯量、不同代谢产物含量的条件下模拟饮用水氯化消毒工艺。应用Ａｍｅｓ致突变试验检测氯化样品的致突变性，应用气相色谱分析法测定氯化样品的三氯甲烷（ＨＣｌ３）生成量。结果表明：氯化样品的致突变活性与藻类代谢物含量及加氧量均呈正相关（Ｐ＜０．０５）；ＣＨＣｌ３生成量随代谢物含量、加氯量增加而增加，与致突变活性之间无明显相关关系。     

深圳市南山区2 898例地中海贫血基因检测结果分析

目的 研究深圳市南山区地中海贫血基因型和分布特征,探讨检测该病的优化方案。方法 以2017年3月 - 2018年3月在某院进行地中海贫血检测的2 898例就诊者为研究对象,采用跨越断裂点PCR法、反向斑点杂交法和Sanger测序进行基因分析。结果 2 898例受检者中检出地中海贫血基因变异804例,检出率达27.74%。常规地贫基因检测方法检出α-地中海贫血545例,--SEA/αα检出率（11.84%）最高,其次是-α3.7/αα（3.00%）和-α4.2/αα（1.83%）;β-地中海贫血225例,CD41-42（-TTCT）杂合突变和IVS－Ⅱ－654（C＞T）杂合突变为2种检出率最高的突变类型,检出率为3.00%和2.52%;αβ复合地中海贫血30例;Sanger测序分析检出4例少见杂合变异,分别为:HBA1基因上CD5 (GCC＞ACC );HBB基因CD37G＞A、IVS-Ⅱ-806(G＞C)、IVS-Ⅱ-81C＞T。结论 深圳市南山区地中海贫血发病率较高,基因型与广东省其他地区基本一致。当血液学表型和常规基因检测不相符时,应进行基因测序排除罕见型地中海贫血或异常血红蛋白变异。     

苯并（a）芘腹腔一次注射对小鼠体液免疫功能的影响

Mice were exposed to benzo(a)pyrene at a dosage of 50, 100 and 200 micrograms/g by single intraperitoneal injection route. The control mice were given vehicle alone (olive oil). The mice were killed 5 days later. At above dosage, it was found the body weight, thymus and spleen weights, and the leukocyte count in peripheral blood were significantly reduced as compared to control. In the plaque forming cell (PFC) assay, it was also found the IgM antibody forming response to the thymus independent antigen (TNP-Ficoll) and the thymus dependent antigen (TNP-KLH) were inhibited about 57-94% and 58-80%, respectively, (P less than 0.05). The serum anti-TNP-Ficoll antibody titer was suppressed 46-98% and parallelled to the corresponding spleen PFC response. The results suggested the benzo(a)pyrene or its metabolites may directly affect the more matured B lymphocyte's function.     

苯乙烯对大鼠不同脑区多巴胺递质含量及单胺氧化酶活性的影响

目的观察苯乙烯在不同染毒期限和染毒剂量下对大鼠神经系统多巴胺递质含量及单胺氧化酶活性的影响。方法大鼠随机分为5组,每组12只动物,雌雄各半。苯乙烯急性染毒剂量为600mg/kg,亚急性染毒剂量为150~600mg/kg,恢复组在苯乙烯染毒后正常饲养3周,L-dopa组在苯乙烯染毒同时腹腔注射600mg/kgbw的L-dopa。方法监测动物尿中苯乙烯代谢物苯乙醇酸(MA)和苯乙醛酸(PGA)的含量作为苯乙烯染毒的内剂量,测定苯乙烯染毒大鼠不同脑区多巴胺(DA)含量及参与多巴胺代谢的单胺氧化酶(MAO)活性的变化。结果尿中的PGA和MA含量与染毒剂量均呈正相关,由于存在一定的环境本底,MA比PGA在作为苯乙烯染毒内剂量的指标上更有代表性。视网膜、垂体和纹状体中的DA含量在苯乙烯染毒下显著降低,垂体中的MAO活性增加,而纹状体和视网膜中的MAO活性减小。结论苯乙烯可以通过多巴胺通路产生对机体的神经损伤。     

在体微透析观察大鼠急性一氧化碳中毒后纹状体多巴胺及其代谢产物的变化

[目的]研究急性一氧化碳(carbon monoxide,CO)中毒对大鼠脑纹状体多巴胺(DA)及其代谢产物二羟苯乙酸(DOPAC)、高香草酸(HVA)水平的影响。[方法]将大鼠随机分成对照组和CO中毒组,采用腹腔注射CO法染毒,首次染毒剂量为120ml/kg,然后每隔4h注射一次,共3次维持剂量60ml/kg,对照组以同样方法和剂量注射空气。观察首次染毒后24h内各组动物血碳氧血红蛋白(HbCO)浓度变化,同时利用在体微透析技术观察脑纹状体DA及其代谢产物在末次染毒后11h内及第10d的变化特点。[结果]腹腔注射CO染毒后,大鼠血HbCO浓度迅速增高,在首次染毒后1～2h达高峰,维持剂量连续染毒时,血HbCO浓度可维持在55%以上达15h,末次染毒6h后降至正常水平;朱次染毒后,大鼠脑纹状体DA水平增加,其代谢产物明显减少,至第4～6h开始逐渐恢复,第11h恢复到正常水平;末次染毒后第10天中毒组动物纹状体DA水平与对照组比较再次明显降低,其代谢产物水平明显升高。[结论]CO中毒血HbCO浓度恢复正常水平后,提示DA及其代谢产物再次出现异常变化可能与急性CO中毒迟发性锥体外系神经精神症状有关。     

Fenitrothion: toxicokinetics and toxicologic evaluation in human volunteers

An unblinded crossover study of fenitrothion 0.18 mg/kg/day [36 times the acceptable daily intake (ADI)] and 0.36 mg/kg/day (72 X ADI) administered as two daily divided doses for 4 days in 12 human volunteers was designed and undertaken after results from a pilot study. On days 1 and 4, blood and urine samples were collected for analysis of fenitrothion and its major metabolites, as well as plasma and red blood cell cholinesterase activities, and biochemistry and hematology examination. Pharmacokinetic parameters could only be determined at the higher dosage, as there were insufficient measurable fenitrothion blood levels at the lower dosage and the fenitrooxone metabolite could not be measured. There was a wide range of interindividual variability in blood levels, with peak levels achieved between 1 and 4 hr and a half-life for fenitrothion of 0.8-4.5 hr. Although based on the half-life, steady-state levels should have been achieved; the area under the curve (AUC)(0-12 hr) to AUC(0-(infinity) )ratio of 1:3 suggested accumulation of fenitrothion. There was no significant change in plasma or red blood cell cholinesterase activity with repeated dosing at either dosage level of fenitrothion, and there were no significant abnormalities detected on biochemical or hematologic monitoring.     

Bioavailability and biotransformation of benzo(a)pyrene in an isolated perfused In situ catfish intestinal preparation.

In the aquatic environment, diet is an important route of exposure for the common contaminant and procarcinogen benzo(a)pyrene (BaP). Dietary organisms vary in their BaP content and in contaminated areas often contain other xenobiotics including cytochrome P4501A inducers. This study examined the effect of dose and previous dietary exposure to the inducer ss-naphthoflavone (BNF) upon the intestinal metabolism of BaP and the systemic bioavailability of BaP-derived products in catfish. BaP was administered at 2 and 20 microM into in situ-isolated perfused intestines of control and BNF-pretreated catfish. The intestine formed an array of metabolites in all treatments including potentially hazardous metabolites such as BaP-7,8 and 9,10 dihydrodiols and 6-methyl-BaP. BNF treatment disproportionally increased the contribution of BaP-7,8 and 9,10 dihydrodiols relative to the contributions of other metabolites. A greater percentage of metabolites was evident as conjugates in 2 microM controls, whereas a greater percentage of unconjugated metabolites was evident for 20 microM controls and BNF treatments of both dosages. BNF pretreatment and the higher 20 microM BaP dosage resulted in greater bioavailability, with 2.6-5.5-fold and 3.0-6. 3-fold increases in systemically available BaP products, respectively. Metabolites represented 10.2-23.1% of the increased bioavailability with BNF treatment, suggesting that mechanisms, in addition to induced metabolism, may be operative. These results indicate that intestinal bioavailability, level of biotransformation, and the metabolic profile of BaP-derived products entering the blood from the intestine may be altered by dose and dietary BNF pretreatment.     

Retinoic acid metabolites in plasma are higher after intake of liver paste compared with a vitamin A supplement in women.

The objectives of the present study were to compare the bioavailability of vitamin A from liver paste and from a vitamin A supplement at three nutritionally relevant levels of intake, and to estimate levels of "safe" intake based on concentrations of retinoic acid and its metabolites in plasma after a single dose of vitamin A from liver paste. Women (n = 35; 19-47 y of age) consumed 3.0, 7.5 or 15 mg vitamin A as liver paste or as a vitamin A supplement with a test meal in a randomized design, with a combined crossover (two sources) and parallel approach (three dosages). Retinyl esters and retinoic acid (RA) metabolites were quantified in blood samples at 2-24 h after dosing. The areas under the time-response curves (AUC) were calculated to evaluate responses in plasma vitamin A after intake of liver paste and the vitamin A supplements. For retinyl esters, the AUC was significantly affected by the dosage, but not by the source. The formation of 13-cis-RA, 13-cis-4-oxo-RA, and to a lesser extent all-trans-RA was significantly higher after consumption of liver paste compared with the supplement, especially at higher dosages. Long-term baseline concentrations of retinol were not affected by a single intake of vitamin A. In conclusion, the bioavailability of vitamin A from single doses of liver paste and a vitamin A supplement does not differ, but the plasma concentrations of RA metabolites are higher after intake of liver paste. Thus, pregnant women should indeed limit the intake of vitamin A from liver products.     

Toxicological evaluations of some brominated biphenyls.

Extensive toxicological studies were carried out to define the probable hazard of octabromobiphenyl (OBB) to workers, users, and the environment. OBB had low acute toxicity in mammals and birds by various routes of administration. It was essentially non-irritating to rabbit eyes, non-irritating to human skin and caused only mild skin irritation and no sensitization in the guinea pig. OBB caused equivocal effects in the rat fetus. OBB was stored in the body fat of rats and caused liver enlargement at high single doses or low repeated doses. The studies indicate probable low safety factors in application and use and probable bioaccumulation. Hexabromobiphenyl (HBB) was more acutely toxic than OBB by skin absorption in the rabbit and caused liver enlargement at lower single doses.     

重庆市土家族和苗族育龄人群地中海贫血基因检测结果分析

目的:了解重庆市土家族和苗族育龄人群地中海贫血（简称地贫）基因的携带率和基因突变类型。方法:2019年3-7月,采用前瞻性设计和多阶段分层整群随机抽样方法,在重庆市的11个调查点,采集土家族和苗族育龄人群的空腹静脉血,利用跨越断裂点（Gap）-PCR和高通量测序方法进行地贫基因检测。结果:共调查土家族人群516例,年龄...     

双酚A与壬基酚混合染毒对小鼠生精功能的影响

目的　研究双酚A (BPA)与壬基酚 (NP)混合染毒对小鼠生精功能的影响。方法　选择健康性成熟的雄性昆明种小鼠 6 0只 ,按随机区组分为阴性对照组、阳性对照组 (环磷酰胺 ,CP)和低剂量组(82mg/kgBPA+5 0mg/kgNP)、中剂量组 (1 6 3mg/kgBPA +1 0 0mg/kgNP)和高剂量组 (32 5mg/kgBPA+2 0 0mg/kgNP) ,连续灌胃染毒 5d ,分别于首次染毒后第 1 4天和第 35天 ,每组随机处死 5只小鼠 ,检测睾丸、附睾、精囊腺重量和脏器系数、精子数、精子活动度、活精率、精子畸形率和初级精母细胞染色体畸变率。结果　精子数、直线运动精子数和活精率随染毒剂量增加而减少 ,静止不动精子数、精子畸形率和初级精母细胞染色体畸变率均随染毒剂量增加而升高。中、高剂量组的上述结果与阴性对照组比较 ,差异均有显著性 (P <0 0 5 ,P <0 0 1 ) ,均存在明确的剂量 -反应关系 ,相关系数依次为 :- 0 987,- 0 895 ,- 0 981 ,0 981 ,0 95 8和 0 96 2 (均P <0 0 5 )。结论　BPA、NP及其代谢产物能损伤小鼠的生精功能 ,由于BPA、NP在环境中往往共存 ,所以在评价BPA、NP生殖功能的损伤作用时 ,必须考虑两化学物间的相互作用。     

脑纹状体多巴胺系统在急性CO中毒后的变化研究

目的观察急性一氧化碳(CO)中毒后纹状体多巴胺(DA)及其代谢产物含量的动态变化,探讨单胺氧化酶B(MAO-B)及DA系统变化在急性CO中毒迟发性脑病(delayed neruopsychologic sequelae,DNS)发病中的意义。方法采用腹腔注射CO法制备急性CO中毒大鼠模型,利用阿朴吗啡诱导旋转实验鉴定DNS模型,分析不同模型脑组织纹状体DA系统、MAO-B活性变化。结果急性CO中毒后纹状体MAO-B活性即明显降低,仅为对照组水平的43%;同时用清醒动物脑微透析实验观察纹状体DA及其代谢产物浓度变化发现,CO中毒后1 h DA浓度即增加,其代谢产物则明显降低,提示急性CO中毒早期DA代谢显著降低;中毒14 d后DNS模型大鼠纹状体MAO-B活性显著增加,为对照组活性的1.7倍,DA浓度则显著降低,仅为对照组的29%,代谢产物浓度明显增加,提示出现运动功能障碍的DNS模型脑纹状体MAO-B活性显著升高,DA代谢明显增加。结论急性CO中毒DNS大鼠脑纹状体MAO-B活性可异常升高,加速DA代谢,影响DA神经系统保持锥体及锥体外系运动协调功能,同时生成的大量DA代谢产物具有毒性作用,可进一步加重脑循环...     

六氯苯对大鼠机体氧化损伤和抗氧化酶活性的影响

目的 研究六氯苯（HCB）对大鼠的毒性作用,探讨HCB中毒的氧化应激机制.方法 2个染毒组分别以含HCB 2.5%（低剂量组）、20.0%（高剂量组）的饲料染毒大鼠14 d,测定血清中碱性磷酸酶等11项血清学指标;测定大脑（皮层、海马）、肝脏和血清中丙二醛（MDA）水平、总超氧化物歧化酶（T-SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）活力.结果 （1）高剂量HCB染毒组大鼠大脑皮层、海马、肝和血清中MDA含量均高于对照组,低剂量染毒组海马和血清中MDA也较对照组明显增加,差异有统计学意义（P＜0.01或P＜0.05）.（2）2个剂量组大鼠大脑皮层和海马中T-SOD活力明显增加,与对照组比较,差异有统计学意义（P＜0.01）;但高剂量组大鼠血清T-SOD活力却明显降低,与对照组比较,差异有统计学意义（P＜0.01）.（3）高剂量染毒组大鼠海马CAT活力高于对照组,差异有统计学意义（P＜0.01）.（4）高剂量染毒组大鼠大脑皮层、海马和低剂量染毒组海马中GSH-Px活力高于对照组,差异有统计学意义（P＜0.01）,但两组大鼠肝脏中GSH-Px活力却明显降低,与对照组比较,差异有统计学意义（P＜0.01）.（5）2个剂量染毒组大鼠血清白蛋白、总胆固醇都较对照明显增加,而血清碱性磷酸酶活力却明显降低,与对照组比较,差异有统计学意义（P＜0.01）.结论 HCB可导致大鼠机体氧化损伤、抗氧化酶活力改变,氧化应激是其重要的毒作用机制.     

Fate of Fipronil and its Metabolites in/on Grape Leaves, Berries and Soil Under Semi Arid Tropical Climatic Conditions

Fate of fipronil and its major metabolites fipronil sulfide (MB 45950), fipronil-desulfinyl (MB 46513) and fipronil sulfone (MB 46136) were studied in/on grape leaves, berries and soil. As initial residue deposits on the leaves the major component was that of fipronil, while all the 3 metabolites were also present. Among metabolites residues of MB 46513 was highest followed by MB 46136 and MB 45950. In leaves fipronil degraded faster than its metabolites. The residues of fipronil in leaves degraded at the half-life of 9.6 and 18.3 days and that of total fipronil (sum of fipronil and its metabolites) at 13.6 and 20 days, from treatment at recommended and double the recommended dose, respectively. At the time of harvest in leaves, grape berries and soil residues of fipronil and all its metabolites were below the quantifiable limit of 0.01 mg kg^?1.     

液相色谱-串联质谱检测鸡蛋中氟虫腈及其代谢物的残留量

目的建立一种检测鸡蛋中氟虫腈及其代谢物残留的液相色谱-串联质谱(LC-MS/MS)定量分析方法。方法优化检测条件:用乙腈进行样品提取,选择C18固相萃取小柱和无水硫酸镁对提取样品净化后进行液质联用检测。结果经过优化后液相条件:流动相由2mmol/L的甲酸铵水溶液和甲醇组成,采用梯度洗脱方式在C18反相色谱柱中进行分离,进样量为4μL。质谱条件:离子源采用ESI负离子,通过SRM模式对样品中氟虫腈及其代谢物进行定量检测。优化后,氟虫腈及其代谢物在0~20ng/mL质量浓度范围内线性关系良好,R2均>0.9993,检出限(S/N=3)和定量限(S/N=10)分别0.2~0.4μg/kg和0.66~1.32μg/kg。实际样品中添加4.0、20.0、40.0μg/kg 3个质量浓度水平下,平均回收率在76.60%~98.24%,相对标准偏差(RSD)为1.03%~3.41%,符合定量检测要求。结论该方法操作简便、灵敏度高,可满足鸡蛋中氟虫腈及其代谢物的检测要求。     

In vivo comparison of the bioavailability of (+)-catechin, (-)-epicatechin and their mixture in orally administered rats.

We compared levels of (+)-catechin, (-)-epicatechin, and their metabolites in rat plasma and urine after oral administration. Rats were divided into four groups and given (+)-catechin (CA group), (-)-epicatechin (EC group), a mixture of the two (MIX group) or deionized water. Blood samples were collected before administration and at designated time intervals thereafter. Urine samples were collected 0-24 h postadministration. (+)-Catechin, (-)-epicatechin and their metabolites in plasma and urine were analyzed by HPLC-mass spectrometry after treatment with beta-glucuronidase and/or sulfatase. After administration, absorbed (+)-catechin and (-)-epicatechin were mainly present in plasma as metabolites, such as nonmethylated or 3'-O-methylated conjugates. In the CA and MIX groups, the primary metabolite of (+)-catechin in plasma was glucuronide in the nonmethylated form. In the EC and MIX groups, in contrast, the primary metabolites of (-)-epicatechin in plasma were glucuronide and sulfoglucuronide in nonmethylated forms, and sulfate in the 3'-O-methylated forms. Urinary excretion of the total amount of (-)-epicatechin metabolites in the EC group was significantly higher than the amount of (+)-catechin metabolites in the CA group. The sum of (+)-catechin metabolites in the urine was significantly lower in the MIX group than in the CA group, and the sum of (-)-epicatechin metabolites in the MIX group was also significantly lower than in the EC group. These results suggest that the bioavailability of (-)-epicatechin is higher than that of (+)-catechin in rats, and that, in combination, (+)-catechin and (-)-epicatechin might be absorbed competitively in the gastrointestinal tract of rats.