Placental transfer and fetal distribution of lead in mice after treatment with dithiocarbamates

The distribution of i.v. administered lead (²⁰³Pb-acetate; 50 nmol/kg b.w.) was studied by means of autoradiography and impulse counting in pregnant C57BL mice (day 18) treated orally with dithiocarbamates. Diethyldithiocarbamate (DEDTC), disulfiram or thiram (2×1 mmol/kg b.w.) or vehicle (gelatine) alone, was given by gavage 2 h before and immediately after the injection of lead. All three dithiocarbamates, especially thiram, changed the distribution pattern of lead. Thiram and DEDTC had the greatest effect at 4 h after lead administration, disulfiram at 24 h. In the mother, most notably the brain concentration increased (70-fold for thiram at 4 h) while that of erythrocytes and skeleton decreased (50- and 4-fold, respectively). The total fetal concentration unexpectedly showed only a moderate increase (2-fold for thiram), which may be due partly to the low maternal plasma lead concentration. The partition within the fetal tissues was, however, changed by the dithiocarbamates in much the same way as in the mothers, e.g., the fetal brain of thiram treated animals had increased by a factor 15, while skeletal and blood concentrations were lowered compared to controls. In melanin containing structures of the maternal and fetal eyes a dramatic increase in lead concentration resulted from dithiocarbamate treatment (lead ions are known to bind to melanin in vitro). The pattern of changes in lead distribution caused by dithiocarbamates is consistent with the formation in the body of lipid soluble lead-dithiocarbamate complexes that pass biological barriers more easily than lead inorganic (to brain, fetus, melanocytes etc.), probably followed by a dissociation of the complexes in the tissues.     

骨转移瘤的X线和CT诊断价值

目的：分析X线和CT的检查结果,探讨其在骨转移瘤诊断上的价值。方法：选取本院2005年1月～2009年1月住院的骨转移瘤患者62例,对其X线和CT表现进行分析。结果：62例骨转移瘤患者中,发生溶骨性破坏者占85.5%,成骨性破坏占9.7%,混合性破坏占4.8%。结论：骨转移瘤的X线和CT诊断,是临床上较为有效的诊断方法。     

引导骨组织再生技术在口腔颌面部创伤后牙缺失伴骨缺损种植修复中的临床应用效果分析

目的 分析引导骨组织再生技术在口腔颌面部创伤后牙缺失伴骨缺损种植修复中的应用效果.方法 80例口腔颌面部创伤后牙缺失伴骨缺损患者,按照随机数字表法分为甲组和乙组,各40例.甲组患者采用上颚前牙二期种植修补术治疗,乙组患者采用引导骨组织再生技术进行治疗.对比两组患者的成骨效果、美学效果及种植修复效果.结果 治疗后,乙组红...     

Different distribution of paraquat and diquat in human poisoning cases after ingestion of a combined herbicide

This report describes a slight difference in the rate of decrease of serum paraquat and diquat concentrations in eight human cases of poisoning by the herbicide PreegloxL (containing paraquatCl₂, 5% and diquatBr₂, 7%) and the distribution of each in three autopsied cases. There was no variation between the serum concentrations of paraquat and diquat within 24 h after ingestion, but paraquat remained at a slightly higher concentration than diquat after more than 24 h. The decrease of urinary paraquat and diquat concentrations was almost the same during the 24-h determination period. In three autopsied cases, diquat concentrations in the tissues were relatively lower than those of paraquat, except in bile. Paraquat and diquat were unevenly distributed in various tissues and fluids, but the distribution patterns of each in any particular tissues were quite similar. As no difference was observed in the decrease of urinary paraquat and diquat, the much higher concentration of diquat in bile indicates that bile may be one of the effective factors in lowering the concentration of diquat in serum and in tissues of the human body long after ingestion.     

Alteration in bone geometric and mechanical properties,histomorphometrical parameters of trabecular bone,articular cartilage,and growth plate in adolescent rats after chronic co-exposure to cadmium and lead in the case of supplementation with green,black, red and white tea

Adolescent male Wistar rats were used to check whether regular consumption of black, red, white, or green tea would have a protective effect on femur development during 12-week exposure to Cd and Pb (7 mg Cd and 50 mg Pb in 1 kg of the diet). The animals were randomly divided (n = 12) into a positive control (without Cd, Pb and teas), a negative control group (Cd and Pb), and groups supplemented additionally with green (GT), black (BT), red (RT), and white tea (WT). Heavy metals reduced the geometric and densitometric parameters and the total thickness of articular cartilage irrespective of tea administration and influenced mechanical endurance, growth plate thickness, and trabecular histomorphometry depending on the tea type. It is difficult to indicate which tea has the best protective effects on bone and hyaline cartilage against heavy metal action.     

内分泌治疗后前列腺癌上皮间质转化标志物的变化

目的探讨内分泌治疗后前列腺癌患者肿瘤组织中上皮间质转化(EMT)标志物表达的变化。方法收集山西医科大学第一医院2006年1月至2012年12月收治的17例经过内分泌治疗前后的前列腺癌患者肿瘤组织标本,采用免疫组织化学链霉亲和素-生物素复合物(SABC)法检测上皮钙黏素(E Cadherin),波形蛋白(Vimentin)、神经钙黏素(N Cadherin)等分子标志物的表达。结果经过内分泌治疗后,前列腺癌患者肿瘤组织中上皮细胞标志E Cadherin表达阳性率由(87.8±5.4)%下降到(6.3±1.7)%,间充质细胞标志N Cadherin表达阳性率由(1.2±0.6)%增加到(46.1±5.6)%,Vimentin表达阳性率由(0.61±0.24)%增加到(28.53±3.52)%,经配对样本t检验,按a=0.05水准,差异均具有统计学意义(P均<0.001)。结论前列腺癌内分泌治疗控制肿瘤生长一段时间后,可以导致EMT特点的细胞数量增加,肿瘤侵袭转移能力增强,这可能是现有内分泌治疗最终失败的原因之一。     

The involvement of oxidative stress in the mechanisms of damaging cadmium action in bone tissue: a study in a rat model of moderate and relatively high human exposure

It was investigated whether cadmium (Cd) may induce oxidative stress in the bone tissue in vivo and in this way contribute to skeleton damage. Total antioxidative status (TAS), antioxidative enzymes (glutathione peroxidase, superoxide dismutase, catalase), total oxidative status (TOS), hydrogen peroxide (H₂O₂), lipid peroxides (LPO), total thiol groups (TSH) and protein carbonyl groups (PC) as well as Cd in the bone tissue at the distal femoral epiphysis and femoral diaphysis of the male rats that received drinking water containing 0, 5, or 50 mg Cd/l for 6 months were measured. Cd, depending on the level of exposure and bone location, decreased the bone antioxidative capacity and enhanced its oxidative status resulting in oxidative stress and oxidative protein and/or lipid modification. The treatment with 5 and 50 mg Cd/l decreased TAS and activities of antioxidative enzymes as well as increased TOS and concentrations of H₂O₂ and PC at the distal femur. Moreover, at the higher exposure, the concentration of LPO increased and that of TSH decreased. The Cd-induced changes in the oxidative/antioxidative balance of the femoral diaphysis, abundant in cortical bone, were less advanced than at the distal femur, where trabecular bone predominates. The results provide evidence that, even moderate, exposure to Cd induces oxidative stress and oxidative modifications in the bone tissue. Numerous correlations noted between the indices of oxidative/antioxidative bone status, and Cd accumulation in the bone tissue as well as indices of bone turnover and bone mineral status, recently reported by us (Toxicology 2007, 237, 89-103) in these rats, allow for the hypothesis that oxidative stress is involved in the mechanisms of damaging Cd action in the skeleton. The paper is the first report from an in vivo study indicating that Cd may affect bone tissue through disorders in its oxidative/antioxidative balance resulting in oxidative stress.     

Brain pharmacokinetics and tissue distribution of tetrahydropalmatine enantiomers in rats after oral administration of the racemate

Tetrahydropalmatine (THP), a racemic mixture, is a biologically active ingredient isolated from a traditional Chinese herb Rhizoma Corydalis (yanhusuo). The main objective of this study was to determine the brain pharmacokinetics and tissue distribution of THP enantiomers in rats after oral administration of racemic THP (rac-THP). Rats (5 animals/group/per time) were given a single oral dose of rac-THP and killed after different post-treatment times. The concentrations of THP enantiomers in plasma, cortex, cerebellum, diencephalon, brain stem, striatum and hippocampus were measured using a validated chiral high performance liquid chromatographic (HPLC) method coupled with an achiral column. The pharmacokinetic profiles of the two enantiomers in six brain regions were significantly different. The peak concentrations (Cmax) and AUC(0-infinity) values of the (-)-enantiomer were significantly greater than the corresponding values for the (+)-enantiomer while the striatum contained the highest peak concentrations compared with the plasma and other brain regions. The tissue distribution studies also revealed significant differences between the two enantiomers in all tissues except the lung. The highest concentrations of both enantiomers were found in the liver. The (-)/(+)-THP ratios in six brain regions and other tissues were consistent with that observed in plasma indicating that the stereoselective disposition of THP in rat brain and other tissues reflects the situation in plasma.     

Distribution of gold in human platelets after in-vitro interaction and during chrysotherapy with gold sodium thiomalate

We have studied the distribution of gold in platelets from patients with rheumatoid arthritis (RA) undergoing chrysotherapy and, in vitro, in platelets reacted with gold sodium thiomalate. In vitro, electron dense fibrillar particles within membrane bound structures were detected in preparations containing 50 μg/ml or more of Au. Energy dispersive spectroscopy confirmed the presence of gold and sulphur in these particles. Gold was detected in platelets from RA patients by neutron activation analysis, but not by electron microscopy.     

Paralytic shellfish poisoning: post-mortem analysis of tissue and body fluid samples from human victims in the Patagonia fjords.

In July 5, 2002 fishermen working in harvesting sea urchin (Loxechinus albus) in the Patagonia Chilean fjords were intoxicated by consumption of filter-feeder bivalve Aulacomya ater. After the ingestion of 7-9 ribbed mussel, two fishermen died 3-4 h after shellfish consumption. The forensic examination in both victims did not show pathological abnormalities with the exception of the lungs conditions, crackling to the touch, pulmonary congestion and edema. The toxic mussel sample showed a toxicity measured by mouse bioassay of 8575 microg of STX (saxitoxin) equivalent by 100 g of shellfish meat. Using post-column derivatization HPLC method with fluorescent on line detection was possible to measure mass amount of each paralytic shellfish poisoning (PSP) toxin yielding individual toxin concentrations. These PSP toxins were identified in the gastric content, body fluids (urine, bile and cerebrospinal fluid) and tissue samples (liver, kidney, lung, stomach, spleen, heart, brain, adrenal glands, pancreas and thyroids glands). The toxin profiles of each body fluid and tissue samples and the amount of each PSP toxin detected are reported. The PSP toxins found in the gastric content, were STX and the gonyautoxins (GTX4, GTX1, GTX5, GTX3 and GTX2) which showed to be the major amount of PSP toxins found in the victims biological samples. The PSP toxin composition in urine and bile showed as major PSP toxins neoSaxitoxin (neoSTX) and GTX4/GTX1 epimers, both STX analogues with an hydroxyl group (-OH) in the N(1) of the tetrahydropurine nucleus. The neoSTX was not present in the gastric content sample, indicating that the oxidation of N(1) in the STX tetrahydropurine nucleus resulted neoSTX, in a similar way that GTX3/GTX2 epimers were transformed in GTX4/GTX1 epimers. Beside this metabolic transformation, also the hydrolysis of carbamoyl group from STX to form its decarbomoyl analogue decarbamoylsaxitoxin was detected in liver, kidney and lung. These two findings show that PSP toxins went under metabolic transformation during the 3-4 h of human intoxication period, in which PSP toxins showed enzymatic oxidation of N(1) in the tetrahydropurine nucleus, producing neoSTX and GTX4/GTX1 epimers starting from STX and GTX3/GTX2 epimers, respectively. This study conclude, that PSP toxins are metabolically transformed by humans and that they are removed from the body by excretion in the urine and feces like any other xenobiotic compound.     

一氧化碳中毒迟发型神经损伤临床特点及预后分析

目的探讨一氧化碳中毒迟发型神经损害临床特点及预后。方法对本院收治的23例一氧化碳中毒迟发型神经损害患者的临床特点及资料进行系统分析,并对预后进行评定。结果在药物对症治疗基础上行高压氧治疗,有效率为95.7%。一氧化碳中毒迟发型神经损害患者预后情况与年龄、昏迷时间、高压氧开始时间、治疗次数,以及并发症等密切相关。结论临床需加强对一氧化碳中毒迟发性神经损伤的认识,高压氧开始时间早及治疗持续时间长,预后越好。     

腹足纲Helix pomatia βC-血清蛋白的功能单位d,e和f中一个半胱氨酸-组氨酸之间硫醚桥键的鉴定

对腹足纲软体动物罗曼蜗牛Helix pomatia的氧运输蛋白（βc-血清蛋白）的功能单位d，e和，中的一个半胱氨酸-组氨酸之间的硫醚桥键进行了研究。以该βc-血清蛋白为载体，通过限制性胰蛋白酶水解，产生片段a—c，ef，以及功能单位d，g，和h。以片段ef降解后的产物为研究对象，通过亲合色谱的分离纯化，得到功能单位P和f。通过对羧甲基化功能单位d的胰蛋白酶和链霉蛋白酶水解，得到一个含有硫醚桥键的4肽。同样在吡啶乙基化功能单位e和f的胰蛋白酶水解产物中也分离得到一个含有相同硫醚桥键的小肽。因此一个半胱氨酸-组氨酸之间硫醚桥键的存在似乎是腹足纲软体动物罗曼蜗牛Helix pomatia氧运输蛋白（βc-血清蛋白）功能单位的一个共有的特征。     

TJ0711盐酸盐的血浆蛋白结合率及其在大鼠体内的组织分布

目的:建立生物样品中TJ0711盐酸盐的浓度的测定方法,测定TJ0711盐酸盐在人标准血浆和大鼠血浆中的蛋白结合率,考察其在大鼠组织中的分布特性。方法:用平衡透析法测定血浆蛋白结合率,用高效液相-荧光检测法测定血浆中药物总浓度及游离药物浓度。大鼠灌胃给予TJ0711盐酸盐30 mg.kg-1,测定10,25,60,180 min TJ0711盐酸盐在各组织中的含量。结果:当TJ0711盐酸盐的血药浓度为0.5,2.0,4.0,8.0μg.mL-1时,其在大鼠血浆中的蛋白结合率分别为(88.7±2.3)%,(87.8±1.0)%,(85.8±2.0)%和(86.8±0.9)%,在人血浆中的蛋白结合率分别为(92.1±0.8)%,(89.8±1.4)%,(90.4±1.0)%和(90.4±1.7)%。药物在大鼠体内以肾、肝、肺中分布较多,脑和脂肪组织也能检测到药物,绝大多数组织的药物含量在给药后10 min或25 min最高1,80 min后药物含量显著下降。结论:TJ0711盐酸盐在人和大鼠血浆中的蛋白结合率均属于高度结合(>80%),且不随药物浓度的增加发生变化,但在人和大鼠血浆中的蛋白结合率差异具有显著性(...     

胫骨前肌瓣联合邮票植皮和负压引流术在修复胫骨外露伴软组织缺损创面中的应用

目的探讨胫骨前肌瓣联合邮票植皮和负压引流术在修复胫骨外露伴软组织缺损创面中的应用疗效。方法19例胫骨骨折伴有软组织缺损合并骨外露患者,予行胫骨前肌瓣转移修复,封闭式负压引流,创面二期行自体刃厚邮票植皮、负压引流术。结果术后18例肌瓣及创面肉芽生长良好,经刃厚邮票植皮后愈合。1例肌瓣远端出现坏死,经清创换药后,创面二期愈合。所有患者愈合时间10～28d,平均19．5d,随访1～24个月（平均12．5个月）,皮片色泽、质地、弹性良好,骨折均愈合。结论胫骨前肌瓣联合自体刃厚邮票植皮和负压引流术,适用于胫骨骨折伴胫骨外露伴软组织缺损创面的修复。     

The effect of gabapentin and pregabalin on bone turnover and bone strength: A prospective study in Wistar rats

BackgroundThere are limited data on the effects of GBP on bone and no data for PGB. Some data suggest that there is a significant influence of sex hormone balance on the susceptibility of bone to antiepileptic drug-induced bone loss.MethodsForty-eight male Wistar rats were divided into six groups that were subjected to two surgeries, sham (noORX) or real orchidectomy (ORX), and were fed three diets, a SLD, a SLD enriched with GBP or a SLD enriched with PGB. Dual energy X-ray absorptiometry was used to measure the bone mineral density. The concentrations of bone turnover markers were assayed. The femurs were biomechanically tested.ResultsSignificant reductions in bone mineral density, weight and biomechanical strength were observed in ORX animals. GBP or PGB exposure did not cause significant alterations in bone mineral density or biomechanical strength. No changes in bone turnover markers were observed, except for RANKL. A significant increase was found in the ORX GBP and ORX PGB groups. Within the orchidectomized animal group, RANKL levels were significantly higher in the ORX PGB group than in the ORX GBP group.ConclusionsBecause neither GBP nor PGB affected bone mineral density or mechanical bone strength, both of these antiepileptic drugs could be considered drugs with lower risks to bone health. A shift in RANKL levels indicates that the effects of GBP and PGB on osteoclast activity may be dependent on the hormonal status of animals.     

Induction of CYP1A1 and CYP1B1 in liver and lung by benzo(a)pyrene and 7,12-d imethylbenz(a)anthracene do not affect distribution of polycyclic hydrocarbons to target tissue: role of AhR and CYP1B1 in bone marrow cytotoxicity

Polycyclic aromatic hydrocarbons (PAHs) (50 mg/kg, i.p.) selectively deplete mouse bone marrow (BM) hematopoietic cells through a process that is dependent on CYP1B1. 7,12-dimethylbenz(a)anthracene (DMBA), which forms greater amounts of dihydrodiol-epoxide-DNA adducts in BM, is much more effective in depleting BM cells than benzo(a)pyrene (BP). BM toxicity by BP is restored in congenic mice expressing a weakly responsive aryl hydrocarbon receptor (AhR(d) replaces AhR(b)). BP strongly induces CYP1A1 around the hepatic vein whereas DMBA produces a weaker diffuse response, paralleling differences in CYP1A1 protein. These responses are absent in AhR(d) mice. BP and DMBA broadly and equally induce CYP1A1 in the lung, while CYP1B1 is induced in bronchial blood vessels. In sternum, CYP1B1 is induced in BM and white fat, whereas CYP1A1 is induced only in brown fat. BP and DMBA levels were similar within blood, lung, and BM and did not rise in AhR(d) mice. In liver, selective decrease of BP was consistent with induced metabolism via CYP1A1, which nevertheless does not determine the blood levels and distribution to BM. Effective delivery of BP to BM is indicated by formation of BP-quinone DNA adducts and the effective induction of CYP1B1. The low formation of BP-dihydrodiol-epoxide-DNA adducts suggests effective AhR induction of BM detoxifying reactions that prevents their formation from dihydrodiols. These findings contrast with the substantial hepatic CYP1A1 contribution for PAHs previously seen for intragastric administration where first pass elimination limits the amount of PAHs reaching the BM.     

Case studies putting the decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping) into practice

Case studies covering carbonaceous nanomaterials, metal oxide and metal sulphate nanomaterials, amorphous silica and organic pigments were performed to assess the Decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping). The usefulness of the DF4nanoGrouping for nanomaterial hazard assessment was confirmed. In two tiers that rely exclusively on non-animal test methods followed by a third tier, if necessary, in which data from rat short-term inhalation studies are evaluated, nanomaterials are assigned to one of four main groups (MGs). The DF4nanoGrouping proved efficient in sorting out nanomaterials that could undergo hazard assessment without further testing. These are soluble nanomaterials (MG1) whose further hazard assessment should rely on read-across to the dissolved materials, high aspect-ratio nanomaterials (MG2) which could be assessed according to their potential fibre toxicity and passive nanomaterials (MG3) that only elicit effects under pulmonary overload conditions. Thereby, the DF4nanoGrouping allows identifying active nanomaterials (MG4) that merit in-depth investigations, and it provides a solid rationale for their sub-grouping to specify the further information needs. Finally, the evaluated case study materials may be used as source nanomaterials in future read-across applications. Overall, the DF4nanoGrouping is a hazard assessment strategy that strictly uses animals as a last resort.