海藻酸盐的理化特性及其在组织工程研究和临床中的应用

目的:对藻酸钠和藻酸钙的理化特性及在骨、软骨组织工程研究和临床中的应用作一系统回顾。资料来源:检索2000/2006 Medline与藻酸钠或藻酸钙相关的文献,检索词"sodium alginate,Calcium alginate",并限定文章语言种类为"English";同时检索中国医院数字图书馆1994/2006中国医学核心期刊关于藻酸钠或藻酸钙的相关文献,检索词"藻酸钠,藻酸钙",限定文章语言种类为中文。同时手工检索相关书籍。资料选择:对检索到的与藻酸钠或藻酸钙相关文献212篇进行筛选,并排除综述类文献,符合纳入标准的有71篇。资料提炼:对71篇文献进行分类整理,排除重复性文献,纳入33篇文献,其中22篇关于海藻酸理化特性,11篇为临床应用。资料综合:①藻酸钠水溶液在钙离子的作用下发生侧向交联由液态变为凝胶态,该水凝胶具有很好的亲水性,营养物质易于渗透扩散,其酶解产物对人体无毒害作用。这类凝胶以其良好的生物相容性在骨或软骨组织工程中、在药物缓释系统、创伤修复、治疗返流性食管炎等临床过程和改善水质、净化环境等方面发挥重要作用。②藻酸钙凝胶是藻酸钠的置换物,是一种中性偏碱的基质材料,除机械强度较差外,它在生物相容性、可降解性、细胞-材料界面、三维立体多孔结构和可塑性等方面都有利于种子细胞的接种和生长,是理想的组织工程基质材料,尤其在骨和软骨组织工程中。结论:海藻酸盐主要从海藻中提取,其凝胶具有良好的生物相容性,在组织工程及临床应用方面有巨大的潜力。     

Science review: Searching for gene candidates in acute lung injury

Acute lung injury (ALI) is a complex and devastating illness, often occurring within the setting of sepsis, and carries an annual mortality rate of 30–50%. Although the genetic basis of ALI has not been fully established, an increasing body of evidence suggests that genetic predisposition contributes to disease susceptibility and severity. Significant difficulty exists, however, in defining the exact nature of these genetic factors, including large phenotypic variance, incomplete penetrance, complex gene–environment interactions, and strong potential for locus heterogeneity. We utilized the candidate gene approach and an ortholog gene database to provide relevant gene ontologies and insights into the genetic basis of ALI. We employed a Medline search of selected basic and clinical studies in the English literature and studies sponsored by the HopGene National Institutes of Health sponsored Program in Genomic Applications. Extensive gene expression profiling studies in animal models of ALI (rat, murine, canine), as well as in humans, were performed to identify potential candidate genes . We identified a number of candidate genes for ALI, with blood coagulation and inflammation gene ontologies being the most highly represented. The candidate gene approach coupled with extensive gene profiling and novel bioinformatics approaches is a valuable way to identify genes that are involved in ALI.     

Prevalence and Severity of Iodine Deficiency Disorder Among Children 6–12 Years of Age in Shebe Senbo District,Jimma Zone,Southwest Ethiopia

Background

Iodine deficiency disorder is a major problem worldwide, especially during pregnancy and childhood. The magnitude of the problem is quite big in Ethiopia. The main aim of the present study was to determine the prevalence and severity of iodine deficiency disorders.

Methods

A cross-sectional survey was conducted in Shebe Senbo District on January 2011. Three elementary schools were selected by lottery method from 20 schools. From each school, students were selected by simple random sampling. Spot urine sample (5 ml) was taken to measure urine iodine level; physical exam was made to palpate goiter and salt samples were collected to estimate iodine content.

Results

Out of 389 participants, 179 (46%) were males. The total goiter rate was 59.1% (Grade 1: 35.2%; Grade 2:23.9%). The median urinary iodine level was 56 4g/L that indicates iodine deficiency. Out of 389 households in the study area, 277 (71.2%) were using non-iodinated salt, 102 (26.2%) of the households were using iodinated salt. Cabbage usage was significantly associated with goiter.

Conclusion

Endemic goiter is quite prevalent in the study area. Median urinary iodine value of the study samples was found to be far lower than standards. Quality of the salt used by the study population was found to be poor in its iodine content. The use of cabbage (goitrogen) has shown remarkable influence on the development of goiter. Therefore, awareness creation and distribution of iodized salt are highly recommended.     

Human urinary metabolite pattern of a new synthetic cannabimimetic,methyl 2-(1-(cyclohexylmethyl)-1<Emphasis Type="Italic">H</Emphasis>-indole-3-carboxamido)-3,3-dimethylbutanoate

A number of metabolites of a new synthetic cannabimimetic, which is a derivative of 2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoic acid, were identified in human urine. The parent compound, a methyl ester of this acid, was identified in seizures in persons from the same city where analysis of drug-intoxication urine samples revealed the presence of the compound’s metabolites. This compound named ‘MDMB-CHMICA’ was reported to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) via the Early Warning System (EWS) in 2014. Hydrolysis of the ester was found to be the main metabolic pathway followed by mono-, di- and tri-hydroxylation, ketone formation, ketone formation with monohydroxylation, dealkylation, and dealkylation combined with hydroxylation. Additionally, the products by internal dehydration of hydroxylated forms with lactone formation were detected. Mono-hydroxylated metabolites were detected from their glucuronidated forms. Identification of metabolites was made on the basis of gas chromatography–mass spectrometry and liquid chromatography with time-of-flight mass spectrometry and ion trap mass spectrometry. To our knowledge, this is the first report on the metabolites of MBDB-CHMICA in human urine.     

Hierarchical looping of zigzag nucleosome chains in metaphase chromosomes

The architecture of higher-order chromatin in eukaryotic cell nuclei is largely unknown. Here, we use electron microscopy-assisted nucleosome interaction capture (EMANIC) cross-linking experiments in combination with mesoscale chromatin modeling of 96-nucleosome arrays to investigate the internal organization of condensed chromatin in interphase cell nuclei and metaphase chromosomes at nucleosomal resolution. The combined data suggest a novel hierarchical looping model for chromatin higher-order folding, similar to rope flaking used in mountain climbing and rappelling. Not only does such packing help to avoid tangling and self-crossing, it also facilitates rope unraveling. Hierarchical looping is characterized by an increased frequency of higher-order internucleosome contacts for metaphase chromosomes compared with chromatin fibers in vitro and interphase chromatin, with preservation of a dominant two-start zigzag organization associated with the 30-nm fiber. Moreover, the strong dependence of looping on linker histone concentration suggests a hierarchical self-association mechanism of relaxed nucleosome zigzag chains rather than longitudinal compaction as seen in 30-nm fibers. Specifically, concentrations lower than one linker histone per nucleosome promote self-associations and formation of these looped networks of zigzag fibers. The combined experimental and modeling evidence for condensed metaphase chromatin as hierarchical loops and bundles of relaxed zigzag nucleosomal chains rather than randomly coiled threads or straight and stiff helical fibers reconciles aspects of other models for higher-order chromatin structure; it constitutes not only an efficient storage form for the genomic material, consistent with other genome-wide chromosome conformation studies that emphasize looping, but also a convenient organization for local DNA unraveling and genome access.The physical packaging of megabase pairs of genomic DNA stored as the chromatin fiber in eukaryotic cell nuclei has been one of the great challenges in biology (1). The limited resolution and disparate levels that can be studied by both experimental and modeling studies of chromatin, which exhibits multiple spatial and temporal scales par excellence, make it challenging to present an integrated structural view, from nucleosomes to chromosomes (2). Because all fundamental template-directed processes of DNA depend on chromatin architecture, advances in our understanding of chromatin higher-order organization are needed to help interpret numerous regulatory events from DNA damage repair to epigenetic control.At the primary structural level, the DNA makes ∼1.7 left-superhelical turns around eight core histones to form a nucleosome core. The nucleosome cores are connected by linker DNA to form nucleosome arrays. An X-ray crystal structure of the nucleosome core has been solved at atomic resolution (3), and a short, four-nucleosome array has also been solved (4). Next, at the secondary structural level, the nucleosome arrays, aided by linker histones (H1 or H5), form a compact chromatin fiber with a diameter of ∼30 nm and longitudinal compaction of 5–7 nucleosomes per 11 nm (5–8). However, evidence for 30-nm fibers in interphase nuclei of living cells has been controversial (reviewed in refs. 9 and 10). For example, whereas a distinct 30-nm fiber architecture is observed in terminally differentiated cells (11, 12), neither continuous nor periodic 30-nm fibers are observed in the nuclei of proliferating cells (13–15). However, zigzag features of the chromatin fibers are well supported by nucleosome interaction mapping in vitro (16) and in vivo (15).For chromatin architecture within metaphase chromosomes, fluorescence studies of mitotic chromosome condensation in vivo (17), cryo-EM observations of unfixed and unstained chromosomes in situ (18), and small-angle X-ray scattering (19) show no structures resembling folded 30-nm fibers and instead suggest random folding of soft polymers. Evidence is also accumulating that during chromosome condensation in mitosis, chromatin higher-order structure is dramatically altered at the global level (20) by significant increase in looping (21). A random type of looping, however, cannot explain sharp chromosomal boundaries separating the translocated genomic regions in metaphase chromosomes (22) as well as formation of highly localized fibers of transgenic DNA, up to 250 nm in diameter, detected by fluorescence imaging in vivo (17). In contrast, a hierarchical or layered looping could explain the above aspects of chromosome organization; in addition, it could help reconcile the experiments in living cells with in vitro data and determine which aspects of the secondary structure are retained in the metaphase chromosome and how these features correlate with the polymer melt model (18, 23).Here we apply the EM-assisted nucleosome interaction capture (EMANIC) technique, which captures nearest-neighbor interactions in combination with mesoscale modeling of chromatin fibers (16) to deduce chromatin architecture in interphase nuclei and metaphase chromosomes. Our results reveal persistence of the zigzag geometry as a dominant architectural motif in these types of chromatin. For metaphase chromosomes, we report a dramatic increase in longer-range interactions, consistent with intrafiber looping, quite different from that seen in compact chromatin fibers in vitro and interphase chromatin in vivo. Modeling also shows hierarchical looping for long fibers, with the loop occurrence strongly modulated by the density of linker histones. Such looping of loosely folded zigzag arrays appears to be an efficient mechanism for both condensing and unraveling the genomic material. Our hierarchical looping mechanism can also explain how distant regulatory DNA sites can be brought together naturally for genic interactions and how linker histone levels and epigenetic histone modifications can further modulate global and local chromatin architecture.     

Dural ectasia in individuals with Marfan‐like features but exclusion of mutations in the genes FBN1, TGFBR1 and TGFBR2

Sheikhzadeh S, Rybczynski M, Habermann CR, Bernhardt AMJ, Arslan‐Kirchner M, Keyser B, Kaemmerer H, Mir TS, Staebler A, Oezdal N, Robinson PN, Berger J, Meinertz T, von Kodolitsch Y. Dural ectasia in individuals with Marfan‐like features but exclusion of mutations in the genes FBN1, TGFBR1 and TGFBR2. Mutations in the genes FBN1, TGFBR1, and TGFBR2 can result in heritable connective tissue disorders comprising the Marfan syndrome and the Loeys‐Dietz syndrome. Dural ectasia is a characteristic manifestation of both syndromes. However, dural ectasia has not yet been investigated in connective tissue disorders that are unrelated to mutations in the FBN1, TGFBR1 or TGFBR2 genes. Here, we assessed dural ectasia in 33 individuals both with typical manifestations of heritable connective tissue disease and in whom mutations in all three genes had been excluded. We identified 19 individuals with dural ectasia (58%), who exhibited major skeletal manifestations of the Marfan syndrome more frequently than the remaining 14 persons without dural ectasia (p = 0.06). Moreover, only persons with dural ectasia fulfilled clinical criteria of the Marfan syndrome (p = 0.01). Conversely, aortic aneurysm (12 patients; p = 0.8), aortic dissection (five patients; p = 0.1), spontaneous dissection of the carotid arteries (five patients; p = 1), and mitral valve prolapse (13 patients; p = 0.4) were similarly frequent irrespective of dural ectasia. We conclude that dural ectasia is a marker for connective tissue disease which coincides with skeletal rather than with cardiovascular manifestations, and which may involve currently uncharacterized pathogenetic mechanisms and syndromes.     

An impending crisis in the provision of histopathology expertise for mouse functional genomics

The generation of new mouse models of human disease is accelerating rapidly, due to the completion of whole‐genome sequencing efforts and technological advances in the manipulation of the mouse genome. We sought to investigate manpower issues in the provision of histopathology expertise for mouse functional genomics and compared this to the perceived demand from principal investigators (PIs). Through the European Commission (EC)‐funded PRIME pathology training initiative, two questionnaires were devised to collect information from pathologists and EC‐funded PIs on the current provision of mouse histopathology expertise in Europe and the demands for this service. We find that pathological analysis is being performed almost exclusively by professionally qualified pathologists, generally employed in clinical diagnostic posts, where the work is undertaken as collaboration outside of their contractual commitments but without previous training in veterinary or comparative pathology. The results indicate that there is a lack of both trainees and provision of specialist training in this field. Unsurprisingly, the availability of diagnostic expertise and advice falls far short of the number of genetically engineered mice (GEM) being generated for analysis. We analyse these results with reference to previous studies and discuss solutions for the future recruitment, training and funding for pathologists in mouse functional genomics in Europe. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.