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211.
The widespread use of various cyclodextrin (CyD)-appended polymers and polyrotaxanes as gene carriers has been reported. Among the various polyamidoamine dendrimer (dendrimer) conjugates with CyDs (CDE), the dendrimer (G3) conjugate with α-CyD having an average degree of substitution (DS) of 2.4 (α-CDE (G3, DS 2)) displayed remarkable properties as DNA carriers. In an attempt to develop cell-specific gene transfer carriers, we prepared some sugar-appended α-CDEs, e.g. mannosylated, galactosylated, and lactosylated α-CDEs. In addition, PEGylated Lac-α-CDEs (G3) were prepared and evaluated as a hepatocyte-selective and serum-resistant gene transfer carrier. Moreover, PEGylated-α-CDE/CyD polypseudorotaxane systems for novel sustained DNA release system have been developed. Interestingly, glucronylglucosyl-β-cyclodextrin (GUG-β-CyD) conjugates with dendrimer (G2) (GUG-β-CDE (G2)) had superior gene transfer activity to α-CDE (G2), expecting a development of new series of sugar-appended CDEs over α-CDEs (G2). Collectively, sugar-appended α-CDEs have the potential as novel cell-specific and safe carriers for DNA. 相似文献
212.
Miguel Munar-Qués Jaime Masjuan Teresa Coelho Paul Moreira Carlos Viader-Farré María J. M. Saraiva 《Amyloid》2013,20(2):147-152
We present two families, from Spain and Portugal, with familial amyloid polyneuropathy (FAP) associated with the mutation TTRSer50Arg. This mutation was first described in two Japanese patients from independent families and later in a French-Italian patient and a Vietnamese family. The two families presented here, are the first to be diagnosed with this mutation in the Iberian Peninsula. In the patients of both families, FAP was very aggressive as they rapidly developed multiple symptoms with progressive deterioration; we emphasize the presence of severe orthostatic hypotension in the Spanish proband which confined him to a wheelchair. This proband was the first patient with this mutation to have undergone liver transplantation and results were encouraging. The mutation was detected in four patients and one disease-free relative by DNA sequencing of exon 3 and induced mutation restriction analysis. The most outstanding feature was the single base transversion A to C in codon 50 (CGT instead of AGT), whereas in both Japanese patients and the French-Italian patient it was T to G (AGG instead of AGT). To our knowledge only six FAP mutations with more than one single nucleotide mutation for the same codon have been reported to date. 相似文献
213.
Introduction
Management of oral anticoagulant therapy (OAT) in children is complex and frequent testing of the International Normalised Ratio (INR) is a significant burden. This study evaluates the impact of a home INR self-testing (home ST) program on the quality of life (QoL) of children and their families. The aim of the study was to determine if participation in a home ST program improves QoL for children requiring long-term OAT and their families.Materials and Methods
Children aged eight to 18 years requiring long-term OAT and parents of children participated. Quantitative methods comprised three validated QoL questionnaires; the anticoagulation specific PAC QL©, the PedsQL™ and the PedsQL FIM™. Questionnaires were completed before commencing home ST and 6–12 months later. Qualitative methods consisted of open-ended questions which participants answered when completing the questionnaires for the second time. Results of INRs tested at home were collected.Results
Fifty-five parents and 35 children participated. The percentage of time the children’s INRs were in their target therapeutic range was 71.3. Parents reported statistically significant improvements in QoL for themselves (mean increase 6.9), their family (mean increase 8.6) and their child (mean increase 11.1) following the commencement of home ST (difference p ≤ 0.003 on all questionnaires). The children did not report a statically significant improvement in QoL.Conclusion
Parents reported significant improvement for their child’s QoL, their QoL and the families’ function following commencement of home ST. Children did not report a significant improvement in their QoL, but clearly identified satisfaction with home ST. 相似文献214.
Y Kato S Tamaki K Haraguchi S Ikushiro M Sekimoto C Ohta T Endo N Koga S Yamada M Degawa 《Toxicology and applied pharmacology》2012,263(3):323-329
The relationships between the changes in the levels of serum total thyroxine (T4), serum T4-transthyretin (TTR) complex, and accumulation of T4 in tissues by 2,2′,4,5,5′-pentachlorobiphenyl (PentaCB) were examined using wild-type C57BL/6 (WT) and its TTR-deficient (TTR-null) mice. The constitutive level of serum total T4 was much higher in WT mice than in TTR-null mice. In WT mice 4 days after a single intraperitoneal injection with PentaCB (112 mg/kg), serum total T4 level was significantly decreased along with a decrease in serum T4-TTR complex, and the levels of serum total T4 in the PentaCB-treated WT mice were almost the same to those in PentaCB-untreated (control) TTR-null mice. In addition, a slight decrease in serum total T4 by PentaCB treatment was observed in TTR-null mice. Furthermore, clearance of [125I]T4 from the serum after [125I]T4-administration was promoted by the PentaCB-pretreatment in either strain of mice, especially WT mice. On the other hand, accumulation level of [125I]T4 in the liver, but not in extrahepatic tissues, was strikingly enhanced in the PentaCB-pretreated WT and TTR-null mice. Furthermore, in both strains of mice, PentaCB-pretreatment led to significant increases in the steady-state distribution volume of [125I]T4 and the concentration ratio of the liver to serum. The present findings demonstrate that PentaCB-mediated decrease in serum T4 level occurs mainly through increase in accumulation level of T4 in the liver and further indicate that the increased accumulation of T4 in the liver of WT mice is primarily dependent on the PentaCB-mediated inhibition of serum T4-TTR complex formation. 相似文献
215.
A. B. Massie N. M. Desai R. A. Montgomery A. L. Singer D. L. Segev 《American journal of transplantation》2010,10(7):1613-1620
We recently showed that DonorNet 2007 has reduced the efficiency of kidney distribution in the United States, particularly for those with prolonged cold ischemia time (CIT), by requiring systematic allocation of all kidneys regardless of quality. Reliable early identification of those most likely to be discarded or significantly delayed would enable assigning them to alternate, more efficient distribution strategies. Based on 39 035 adult kidneys recovered for possible transplantation between 2005 and 2008, we created a regression model that reliably (AUC 0.83) quantified the probability that a given kidney was either discarded or delayed beyond 36 h of CIT (Probability of Discard/Delay, PODD). We then analyzed two PODD cutoffs: a permissive cutoff that successfully flagged over half of those kidneys that were discarded/delayed, while only flagging 7% of kidneys that were not eventually discarded/delayed, and a more stringent cutoff that erroneously flagged only 3% but also correctly identified only 34%. Kidney transplants with high PODD were clustered in a minority of centers. Modifications of the kidney distribution system to more efficiently direct organs with high PODD to the centers that actually use them may result in reduced CIT and fewer discards. 相似文献
216.
使用说明书作为随机文件的重要组成部分,其真实性、准确性、完整性十分重要。一本好说明书可以帮助厂商解决很多麻烦。本文简要介绍了如何按照GB4793.1-2007的要求写好使用说明书。 相似文献
217.
Kristoffersen AH Thue G Ajzner E Claes N Horvath AR Leonetti R Kallion K Kitchen D Kitchen S Kutt M Meijer P Muller M Nilsson E Perich C Plum I Rogic D Tirimacco R van der Meer FJ Watine J Sandberg S 《Thrombosis research》2012,130(3):309-315
Introduction
Standardisation of treatment with vitamin K antagonists (VKAs) is still an issue after 60 years of use. The study aimed to explore aspects of VKA monitoring in primary and secondary care.Methods
Two case histories were distributed to physicians in 13 countries. Case history A focused on a patient with atrial fibrillation on stable anticoagulation (latest INR 2.3). Physicians were asked about frequency of INR measurement, when to change the VKA dose, and the patient's annual risk of ischemic stroke and bleeding. Case history B focused on a patient with an unexpected INR of 4.8, asking for the patient's 48-hour bleeding risk, the immediate dose reduction and time until a repeat INR.Results
Altogether, 3016 physicians responded (response rate 8 - 38%), of which 82% were from primary care and 18% from secondary care. Answers varied substantially within and between countries regardless of level of care and VKA used. Median number of weeks between INR measurements was 4 - 6 weeks. Median threshold INR for increasing or decreasing the VKA dose was 1.9 and 3.1, respectively. Risk of ischemic stroke and bleeding were overestimated 2 - 3 times. In case history B, the median dose reduction the two first days was 75% for GPs and 55% for specialists, irrespective of estimates of bleeding risk; with one week to a repeat INR.Conclusion
Variation in VKA monitoring is substantial implying clinical consequences. Guidelines seem either unknown or may be considered impracticable. Further efforts towards standardisation of VKA management are needed. 相似文献218.
We report an amyloidogenic transthyretin (ATTR) Val30Met homozygote showing extremely early-onset, severe familial amyloid polyneuropathy (FAP). Although homozygotes have been reported to show late-onset and mild clinical manifestations, detailed analyses of the present and previously reported families suggest that homozygotes have a slightly more severe clinical course than heterozygotes. This is the youngest reported patient with ATTR Val30Met FAP, a condition believed to be attributable to homozygosity of this mutation. The clinical severity is consistent with TTR protein instability. 相似文献