Prenatal diagnosis of Apert syndrome: report of two cases

Two de novo cases with Apert Syndrome detected prenatally are presented herein. In the first, fetal ultrasound findings of syndactyly of the hands, craniosynostosis and proptosis resulted in a prenatal diagnosis in the nineteenth week of gestation. This is the earliest prenatal diagnosis of this syndrome in a not-at-risk case. Following counseling, this pregnancy was terminated and subsequent pathological examination and DNA analysis confirmed the diagnosis of Apert Syndrome and coarctation of the aorta. In the second case, fetal ultrasound at 21 weeks' gestation revealed a hypoplastic left heart and clover-leaf skull. Following counseling, this pregnancy was also terminated. Further examination of the fetus and DNA analysis led to a diagnosis of Apert Syndrome. These cases emphasize the need to complete a thorough fetal ultrasound in cases with potentially lethal cardiac abnormality and the importance of incorporating a fetal pathologist, as well as a medical geneticist, in the investigations performed after delivery or pregnancy termination when a fetal abnormality is detected on ultrasound. Copyright © 2003 John Wiley & Sons, Ltd.     

Sanfilippo D syndrome: Correction of glucosamine-6-sulphatase deficiency following fibroblast culture in chang's media

The de-O-sulphation of α-linked glucosamine-6-sulphate residues in heparan sulphate requires a specific sulphatase, glucosamine-6-sulphatase, which has been shown to be deficient in tissues of Sanfilippo D, or mucopolysaccharidosis type IIID (MPS IIID), patients. MPS IIID fibroblasts cultured in Basal Eagle's medium supplemented with either fetal calf serum or heat-inactivated fetal calf serum, MDCB or Ultraserg media had residual glucosarnine-6-sulphatase activities towards a heparin-derived trisaccharide substrate, O-(α-N-acetylglucosamine-6-sulphate)-(1→4)-L -O-(α-iduronic acid-2-sulphate)-(1→4)-D -O-2,5-anhydro [1-³H]mannitol-6-sulphate, GlcNAc6S-IdoA2S-anM6S, which were less than 1 per cent of the normal range for fibroblasts cultured in Basal Eagle's medium supplemented with fetal calf serum. However, the glucosamine-6-sulphatase activities of MPS IIID fibroblasts grown in Chang's medium were similar to the activities in normal control fibroblasts which were cultured in Basal Eagle's medium. These results indicate that caution is required for prenatal diagnosis of MPS IIID patients using chorionic villi or amniotic cells cultured in Chang's medium.     

Endocrine Disruptors in Mediterranean top marine predators

- DOI: http://dx.doi.org/10.1065/espr2006.01.018 Background, Aims and Scope Man-made Endocrine Disruptors (EDs) range across all continents and oceans. Some geographic areas are potentially more threatened than others: one of these is the Mediterranean Sea. Levels of some xenobiotics are much higher here than in other seas and oceans. In this paper we review the final results of a project in which the hypothesis that Mediterranean top predator species (such as large pelagic fish and marine mammals) are potentially at risk due to EDs was investigated. Methods In a four-year survey on the Mediterranean population of swordfish (Xiphias gladius), the potential toxicological effects of organochlorine compounds (OCs) on specimens of swordfish and tuna fish (Thunnus thynnus thynnus), caught in the spawning seasons from 1999 to 2002 in the Straits of Messina, Sicily (Italy), were investigated using vitellogenin (Vtg), Zona radiata proteins (Zrp), and cytochrome P4501A (CYP1A) activities (EROD, BPMO). Tissues (skin and blubber) were obtained from Stenella coeruleoalba, Tursiops truncatus, Delphinus delphis and Balaenoptera physalus from the western Ligurian Sea, between Corsica and the French-Italian coast, and Ionic Sea using biopsy darts launched with a crossbow. Benzo(á)pyrene monoxigenase (BPMO) activity was mesured in biopsies and cholrinated hydrocarbon levels were detected. Results and Discussion We illustrate the need to develop and apply sensitive methodological tools, such as biomarkers (Vitellogenin, Zona Radiata proteins and CYP1A activities) for evaluation of toxicological risk in Xiphias gladius and Thunnus thynnus thynnus), and nondestructive biomarkers (CYP1A activities and fibroblast cell culture in skin biopsy), for the hazard assessment of threatened marine mammals species (Stenella coeruleoalba, Tursiops truncatus, Delphinus delphis and Balaenoptera physalus) exposed to EDs. Conclusion The present research shows that: a) Vtg and Zrp can be used as diagnostic tools for fish stocks hazard assessment in the Mediterranean Sea; b) that CYP1A1 (BPMO) induction in cetaceans skin biopsy may be an early sign of exposure to EDs such as OCs and a potential alert for transgenerational effects. Recommendation and Outlook This research represents a warning signal of the potential reproductive alterations in marine top predators and suggest the need for continuous monitoring to avoid reductions in population and biodiversity in the Mediterranean Sea.     

A low-maintenance,primary cell culture model for the assessment of carbon nanotube toxicity

Carbon nanotubes (CNTs) have gained substantial interest as a material for biomedical devices with reliable properties suitable for electrically conducting biomedical devices. While CNTs combine ideal properties for a number of tissue-interfacing applications, their biocompatibility and safety have been the source of considerable conjecture. This study outlines a method for evaluating biocompatibility, using a low-cost, short-term assessment model of CNT with primary cells, which are more representative of an in vivo situation than cell lines. It was demonstrated that carboxylate-modified, multi-walled CNTs exhibit cytotoxic behavior in as little as 6 hr of exposure to primary fibroblasts. The resultant cell death was concentration dependent, demonstrating the efficacy of acute assessment of cytocompatibility. Although cell viability remained relatively high (being above 85% for all CNT concentrations up to 500 μg/ml), these results reflect similar relationships found for longer term exposures. This method has reliable potential for high-throughput assessment and quality control of CNTs in biomedical applications using a primary cell model.     

纳米二氧化钛暴露人胚肺细胞差异表达基因分析

为探讨纳米二氧化钛(Nano-TiO2)颗粒对人胚肺(HPF)细胞基因表达和基因功能的影响,使用粒径10nmTiO2暴露体外培养的人胚肺细胞24h,提取RNA,应用基因芯片方法,寻找差异表达基因,并对差异基因进行基因本体(GeneOntology,GO)分类.结果表明,纳米TiO2暴露人胚肺细胞,导致514条肺中表达的基因发生差异表达,基因分类显示400条基因涉及生物学过程;415条基因涉及分子学功能;391条基因涉及细胞构成.纳米TiO2作为外界刺激物质,与细胞膜上的受体结合,影响钙、钾离子通道,上调细胞免疫和炎症反应相关的细胞因子TNF、IL1B、IL1A等基因表达.     

Studies on mercuric sulfide,a component of cinnabar,a Chinese herbal medicine,on celluar functions in mouse lung and fibroblasts

Although the cytotoxic effects of mercuric chloride (HgCl₂) and methylmercury chloride (MeHg) have been extensively studied, the insoluble mercuric sulfide (HgS) has been the subject of fewer studies. Since the traditional Chinese mineral drug, cinnabar (containing >95% HgS) continues to be used as an ingredient for infant sedation, the pharmacological and toxicological effects of HgS need to be clarified. In previous experiments, HgS and cinnabar were shown to be absorbed from the gastrointestinal tract (GIT) and distributed in various tissues including the lungs. Thus, a preliminarily examination of whether HgS might exert any oxidative stress on a mouse lung was undertaken. HgS reduced GSH content and increased lipid peroxidation in the lung. Further studies on the cytotoxic effects and the possible mechanisms of action of HgS were compared with HgCl₂ and MeHg in cultured lung fibroblast V₇₉ cells. The results showed that HgS produced cytotoxicity at a concentration (400–1200 µM)in a dependent manner with IC₅₀ of 795.6 µM, as compared to HgCl₂ and MeHg, 8.1 µM and 5.9 µM, respectively. In addition, the HgS induced the phenomena of DNA fragmentation, increasing reactive oxygen species (ROS) and decreasing mitochondrial membrane potential, accompanied by decreased levels of intracellular ATP and GSH and higher lipid peroxidation levels, similar to HgCl₂ and MeHg, but with different toxicokinetic properties. These findings provide evidence for understanding the mechanisms underlying the toxic effects of HgS.