The first major extended-spectrum beta-lactamase outbreak in Scandinavia was caused by clonal spread of a multiresistant Klebsiella pneumoniae producing CTX-M-15

Between May and December 2005, 64 multidrug-resistant isolates of Klebsiella pneumoniae were detected from patients admitted to Uppsala University Hospital. This represented a dramatic increase in ESBL-producing K. pneumoniae compared to previous years. To investigate the epidemiology and to characterize the resistance mechanisms of the isolates, a study was initiated. Antibiotic susceptibility was determined by means of the Etest and the disc diffusion method. Extended-spectrum beta-lactamase (ESBL) production was identified by clavulanic acid synergy test and confirmed with PCR amplification followed by DNA sequencing. DNA profiles of the isolates were examined with pulsed-field gel electrophoresis (PFGE). All isolates were resistant or exhibited reduced susceptibility to cefadroxil, cefuroxime, cefotaxime, ceftazidime, aztreonam, piperacillin/tazobactam, ciprofloxacin, tobramycin, and trimethoprim-sulfamethoxazole. They produced ESBL of the CTX-M-15 type, and the involvement of a single K. pneumoniae clone was shown. This is the first major clonal outbreak of multiresistant ESBL-producing K. pneumoniae in Scandinavia. The outbreak demonstrates the epidemic potential of enterobacteria containing ESBLs of the CTX-M type, even in a country with a relatively low selective pressure and a low prevalence of multiresistant bacteria.     

The prevalence of ESBL-producing E. coli and Klebsiella strains in the Copenhagen area of Denmark

The main purpose of the study was to investigate the frequency of ESBL-producing E. coli and Klebsiella strains in the Greater Copenhagen area. Four collections of strains were investigated: A) 380 consecutive E. coli and Klebsiella isolates primarily from urine, B) 200 gentamicin-resistant E. coli and Klebsiella isolates primarily from urine, C) 210 consecutive E. coli isolates from blood cultures, and D) 68 cefuroxime-resistant E. coli and Klebsiella isolates primarily from urine. Only one strain per patient was included. Strains with a zone diameter for cefpodoxime CTX-M (n=41), SHV (n=14), AmpC (n=9), CTX-M and AmpC (n=2), SHV and AmpC (n=1). In conclusion, the frequency of ESBL-producing E. coli and Klebsiella isolates was low in the Copenhagen area of Denmark (0.8 %). The most common ESBL genes found in our study were ctx-m and shv genes.     

Alternative G protein coupling and biased agonism: New insights into melanocortin-4 receptor signalling

The melanocortin-4 receptor (MC4R) is a prototypical G protein-coupled receptor (GPCR) that plays a considerable role in controlling appetite and energy homeostasis. Signalling initiated by MC4R is orchestrated by multiple agonists, inverse agonism and by interactions with accessory proteins. The exact molecular events translating MC4R signalling into its physiological role, however, are not fully understood. This review is an attempt to summarize new aspects of MC4R signalling in the context of its recently discovered alternative G protein coupling, and to give a perspective on how future research could improve our knowledge about the intertwining molecular mechanisms that are responsible for the regulation of energy homeostasis by the melanocortin system.     

Characteristics of Vibrio cholerae O1 isolated from water of the River Ganga,Varanasi, India

Background: Vibrio cholerae is an autochthonous inhabitant of fresh and brackish water and estuarine system. Investigation of V. cholerae from the River Ganga seems important to find variation in CTX arrangement and genomic diversity. Objectives: To investigate V. cholerae O1 strains for the presence of virulence and regulatory genes, variation in number and organisation of the pre-CTXΦ and/or CTXΦ, and for the genomic diversity. Materials and Methods: Polymerase chain reaction (PCR) was used to detect virulence and regulatory genes, type of rstR and location of CTXΦ on the chromosome. Southern hybridisation was conducted to see the number and arrangement of pre-CTXΦ and CTXΦ. Ribotyping and pulsed-field gel electrophoresis were used to find genetic relatedness. Results: Seven strains gave positive results by PCR for the gene encoding for ctxA, zot, ace, tcpA (El Tor), ompU, and toxR, except one strain that was negative for the ctxA. Three strains were positive for the tcpA (El Tor), ompU and toxR genes. Determination of CTX organisation showed that among the ctx-positive strains, four harboured two copies of CTX^ETΦ arranged in tandem and two harboured one copy of CTX^ETΦ, and one ctx-negative strain harboured only one copy of pre-CTX^ETΦ. Pulsotype and ribotype analysis showed existence of at least three pulsotype and ribotypes indicating diversity in genomic content among them. Conclusion: This study thus indicates that multiple clones (ribotypes/pulsotypes) of V. cholerae O1 carrying pre-CTXΦ and/or CTXΦ and ctx-negative strains were present in the water of the River Ganga, Varanasi, India.     

Predominance of IncL/M and IncF plasmid types among CTX‐M‐ESBL‐producing Escherichia coli and Klebsiella pneumoniae in Bulgarian hospitals

Our objective was to investigate the plasmid replicon‐types involved in spread of ESBLs among Bulgarian Klebsiella pneumoniae and Escherichia coli. Sixty‐three isolates, with transferable beta‐lactam resistance determinants, collected between 2007 and 2009 in six medical institutions, were analysed with respect to their antimicrobial susceptibility, ESBL‐, RAPD‐, and plasmid replicon‐type. Phylogenetic typing and screening for the O25b‐ST131 lineage were carried out for E. coli. The predominant ESBLs were CTX‐M‐15 (81%) among E. coli and CTX‐M‐3 (58%) among K. pneumoniae. Other sporadically found ESBLs were SHV‐12 and TEM‐139, and for the first time in Bulgaria, CTX‐M‐1 and CTX‐M‐14. Replicon typing revealed that plasmids carrying bla_CTX‐M‐3 exclusively belonged to IncL/M‐type, while bla_CTX‐M‐15 was predominantly (94%) associated with IncF‐type plasmids. Among E. coli, 59% of the isolates were clonally related. Isolates of that cluster produced CTX‐M‐15, belonged to the O25b‐ST131 lineage, predominantly harboured plasmids with the FIA replicon, and were found in five centres. Among CTX‐M‐3‐producing K. pneumoniae, two prevailing RAPD‐types were found, one remained restricted to one centre and the second was found in three centres. The incompatibility groups IncN and IncA/C linked with bla_SHV‐12 respectively bla_TEM‐139 were found only once. To the best of our knowledge, this is the first detailed investigation of plasmids carrying ESBL genes among Bulgarian isolates demonstrating wide distribution of conjugative IncF plasmids among CTX‐M‐15‐producing E. coli and IncL/M plasmids among CTX‐M‐3 positive K. pneumoniae isolates.     

一种新的编码霍乱毒素的丝状噬菌体CTAKΦ

目的 探讨介导霍乱弧菌毒素基因水平转移的一种独特的遗传结构。方法 从O139群霍乱弧菌菌株FJ97129上清中分离出丝状噬菌体颗粒CTAKΦ，并进行电镜观察。从丝状噬菌体颗粒CTAKΦ中纯化出DNA，并进行链型分析。对pCTAK进行酶谱分析。用ctxAB、zot引物对pCTAK进行PCR扩增检测，用RS1探针对pCTAK进行Southern blot检测；用pCTAK转化DH5α和IEM101得到DX29和4329，将pCTAK克隆于pUC18载体并转入DH5α得到UD29，用GM1－ELISA检测DX29、4329、UD29的CT表达。对pCTAK的ctxAB、zot基因片段进行测序，并用DNASTAR软件和BLAST算法，在国际互联网上对测序结果进行序列分析。结果 发现和分离了一种编码霍乱毒素的质粒pCTAK，它以稳定的高拷贝数存在于1株天然的O139霍乱弧菌FJ97129中；酶谱分析发现其明显不同于CTX元件酶谱，在CTX元件中相当保守的酶切位点：BglⅡ、EcoRⅤ、PstⅠ、EcoRⅠ，在pCTAK中没有切点。ctxAB、zot引物对pCTAK的PCR扩增检测呈阳性，RS1探针杂交呈阳性；pCTAK的ctxAB、zot基因序列与已报道的序列有很高的同源性。pCTAK能直接或经载体转化DH5α和IEM101并表达CT。从FJ97129培养上清中分离出丝状噬菌体颗粒CTAKΦ，电镜观察并计算其直径大小为7nm左右。其全基因组大小为8.5kb，为单链DNA。结论 发现了一种新的编码霍乱毒素的丝状噬菌体CTAKΦ。     

Genetics of cerebrotendinous xanthomatosis (CTX): An autosomal recessive trait with high gene frequency in Sephardim of Moroccan origin

We describe 6 patients (from 3 families) affected with cerebrotendinous xanthomatosis (CTX). All are Sephardic Jews of Moroccan extraction. In view of the small number of CTX patients diagnosed in the world (a total of 50 including our 6 patients), we are probably dealing with an ethnic subgroup with a high CTX gene frequency, which we have estimated to be 1/108. Since there are differences in expression in this disease, we recommend cholestanol study in cases of undiagnosed cataract or tendinous xanthomas in childhood or early adolescence. The diagnosis in CTX is important not only for genetic counseling, but also in view of possible treatment.     

Soy Reduces Bone Turnover Markers in Women During Early Menopause: A Randomized Controlled Trial

Menopausal estrogen loss leads to an increased bone loss. Soy isoflavones can act as selective estrogen receptor modulators, their role in bone turnover is unclear. The primary outcome was assessing changes in plasma bone turnover markers. The secondary outcomes were assessing changes in cardiovascular risk markers including insulin resistance, blood pressure, and lipid profile. We performed a double‐blind randomized parallel study in which 200 women within 2 years after the onset of their menopause were randomized to 15 g soy protein with 66 mg isoflavone (SPI) or 15 g soy protein alone (SP), daily for 6 months. There was a significant reduction in type I collagen crosslinked beta C‐telopeptide (βCTX) (bone‐resorption marker) with SPI supplementation (0.40 ± 0.17 versus 0.15 ± 0.09 μg/L; p < 0.01) compared to SP supplementation (0.35 ± 0.12 versus 0.35 ± 0.13 μg/L; p = 0.92) after 6 months. There was also a significant reduction in type I procollagen‐N‐propeptide (P1NP) (bone formation marker) with SPI supplementation (50.5 ± 25.0 versus 34.3 ± 17.6 μg/L; p < 0.01), more marked between 3 and 6 months. Following SPI there was a significant reduction in fasting glucose, fasting insulin, insulin resistance, and systolic blood pressure whereas no significant changes in these parameters was observed with SP. There were no significant changes in fasting lipid profile and diastolic blood pressure with either preparation. There was a significant increase in TSH and reduction in free thyroxine (p < 0.01) with SPI supplementation though free tri‐iodothyronine was unchanged. In conclusion, soy protein with isoflavones may confer a beneficial effect on bone health, analogous to the mode of action of antiresorptive agents, albeit to a less magnitude. There was a significant improvement of cardiovascular risk markers, but a significant increase in TSH and reduction in free thyroxine after SPI supplementation indicating a detrimental effect on thyroid function. © 2016 American Society for Bone and Mineral Research.     

氯沙坦钾联合环磷酰胺治疗2型糖尿病肾病大鼠肾组织中TGF-β1、CD68和MCP-1表达的影响

目的 探讨氯沙坦钾联合环磷酰胺在治疗2型糖尿病肾病大鼠时对转化生长因子β1 (TGF-β1)、CD68和单核细胞趋化因子蛋白-1(MCP-1)表达的影响.方法 选择45只雄性健康SD大鼠,按随机数字表法分为正常对照组、2型糖尿病肾病模型组和氯沙坦钾联合环磷酰胺治疗组大鼠各15只.造模成功后,观察三组大鼠的血生化指标和肾脏病理学改变等,并采用免疫组化染色比较其TGF-β1、CD68和MCP-1的表达情况.结果 与正常对照组相比,模型组和治疗组的体质量较低,在尿蛋白、血糖、甘油三酯、胆固醇和肌酐等血生化指标以及TGF-β1、CD68和MCP-1表达方面均显著高于对照组,且差异均有统计学意义(P＜0.05);治疗组与模型组相比,甘油三酯、肌酐以及TGF-β1、CD68和MCP-1表达均较低(P＜0.05).结论 氯沙坦钾联合环磷酰胺在治疗2型糖尿病肾病大鼠时,可以通过降低肾组织中TGF-β1、CD68和MCP-1的表达水平来降低炎细胞浸润和免疫反应程度,从而延缓糖尿病肾病病情的进展,但是否能用于临床有待于进一步研究.     

环磷酰胺冲击治疗难治性肾病综合征疗效分析

目的　探讨环磷酰胺冲击疗法对难治性肾病综合征的疗效。方法　选择２０ 例难治性肾病综合征患儿,分别给予环磷酰胺（ＣＴＸ）每次１２ｍｇ／ｋｇ,加入１０ ％ 葡萄糖溶液２５０ｍｌ 中静滴,每隔３ ～４ 周１ 次,连用８～１０ 次,后改为每３ 个月１ 次,维持缓解半年至１ 年后停药。累积量１２０～１５０ｍｇ／ｋｇ,ＣＴＸ 冲击同时联合应用强的松方案常规治疗。结果　冲击治疗后,血浆总蛋白及白蛋白有不同程度的升高,２４ 小时尿蛋白定量有明显降低,冲击治疗前后有显著性差异（ Ｐ＜ ０－０１） 。血肌酐（ＳＣｒ）及内生肌酐清除率（ＣＣｒ） 冲击治疗前后无显著性差异（ Ｐ＞ ０－０５） 。随着冲击次数增加,完全及部分缓解例数增多。结论　环磷酰胺冲击疗法对难治性肾病可获较好疗效,尤其对频繁复发和激素依赖的患儿治疗效果好。