Fecal transplant policy and legislation

Fecal microbiota transplantation(FMT) has garnered significant attention in recent years in the face of a reemerging Clostridium difficile(C.difficile) epidemic.Positive results from the first randomized control trial evaluating FMT have encouraged the medical community to explore the process further and expand its application beyond C.difficile infections and even the gastrointestinal domain.However promising and numerous the prospects of FMT appear,the method remains limited in scope today due to several important barriers,most notably a poorly defined federal regulatory policy.The Food and Drug Administrationhas found it difficult to standardize and regulate the administration of inherently variable,metabolically active,and ubiquitously available fecal material.The current cumbersome policy,which classifies human feces as a drug,has prevented physicians from providing FMT and deserving patients from accessing FMT in a timely fashion,and subsequent modifications seem only to be temporary.The argument for reclassifying fecal material as human tissue is well supported.Essentially,this would allow for a regulatory framework that is sufficiently flexible to expand access to care and facilitate research,but also appropriately restrictive and centralized to ensure patient safety.Such an approach can facilitate the advancement of FMT to a more refined,controlled,and aesthetic process,perhaps in the form of a customized and wellcharacterized stool substitute therapy.     

Nitrogen starvation of cyanobacteria results in the production of β-N-methylamino-L-alanine

β-N-methylamino-L-alanine, an unusual amino acid implicated in neurodegenerative disease, has been detected in cultures of nearly all genera of environmentally ubiquitous cyanobacteria tested. The compound is present within cyanobacterial cells in free and protein-associated forms, with large variations occurring in the concentration of these pools between species as well as within single strains. With a lack of knowledge and supporting data on the regulation of BMAA production and the role of this compound in cyanobacteria, the association between BMAA and cyanobacteria is still subject to debate. In this study we investigated the biosynthesis of BMAA in axenic non-diazotrophic cyanobacterial cultures using the stable isotope ¹⁵N. Nitrogen starvation of nutritionally replete cells resulted in an increase in free cellular ¹⁵N BMAA suggesting that BMAA may be the result of catabolism to provide nitrogen or that BMAA is synthesised to serve a functional role in the cell in response to nitrogen deprivation. The addition of NO₃⁻ and NH₄⁺ to the culture medium following starvation resulted in a decrease of free cellular BMAA without a corresponding increase in the protein-associated fraction. The use of ammonia as a nitrogen source resulted in a more rapid reduction of BMAA when compared to nitrate. This study provides the first data regarding the regulation of intracellular BMAA concentrations in cyanobacteria with results conclusively showing the production of ¹⁵N BMAA by an axenic cyanobacterial culture.     

On the ancestral recruitment of metalloproteinases into the venom of snakes

Tracing the evolutionary history of proteins can reveal insights into gene alterations responsible for changes in structure and function. Here, the origin of snake venom metalloproteinases was rigorously reassessed using phylogenetics and the reconstruction of ancestral sequences. Basal SVMPs are most closely related to ADAM 7, 28 and decysin-1 proteins. Reconstructing the evolutionary history of these proteins and their hypothetical ancestors reveals progressive alterations in the amino acid composition and structural characteristics of ADAMs/SVMPs through evolutionary time.     

Cutaneous loxoscelism caused by Loxosceles similis venom and neutralization capacity of its specific antivenom

Members of the spider genus Loxosceles pose a marked health risk to humans because of the seriousness of the necrotic and systemic effects of their bite, known as loxoscelism. The recent confirmation of Loxosceles similis in residences of Belo Horizonte in Minas Gerais Province, Brazil increases the local potential risk of loxoscelism at higher levels. The first characterization of the venom from this species showed that its main biological effects had a similar intensity as other species (e.g. Loxosceles intermedia, Loxosceles laeta, and Loxosceles gaucho). Therefore, we wished to further analyse the biological activity of the L. similis venom as well as the capacity of anti-L. similis-venom serum to reduce dermonecrotic effects to rabbit skin. Histological analysis of rabbit skin 2, 4 and 8 h after intradermal injection of L. similis venom demonstrated a dense inflammatory infiltrate, edema, degeneration and necrosis of the skin muscle, dissociation of collagen fibers, and disruption of reticular fibers. Importantly, pre-incubation of the venom with anti-L. similis-venom serum significantly decreased all of these effects. Anti-L. similis antivenom generated antibodies that were strongly reactive to L. similis venom and capable of neutralizing the dermonecrotic effects in rabbits caused by this venom. Moreover, the antivenom significantly reduced the sphingomyelinase activity of L. similis crude venom. Venoms produced by male and female spiders were equally reactive towards anti-L. similis and anti-L. intermedia antivenoms, but female venom induced larger lesions on rabbits. In contrast, female venom acted as an immunization enhancer and protected animals from L. similis envenomation to a greater degree than male venom. In conclusion, the results shown in this study for L. similis antivenom merits a more in depth study of its properties, which may become a valuable tool against loxoscelism.     

《诸病源候论》中有关“毒”的病因研究

本研究运用文献计量学、分类学等研究方法,通过对我国现存的第一部病因病机证候学专著《诸病源候论》中有关病因"毒"的内容进行归纳整理和系统研究,结果发现书中提到"风毒"、"寒毒"、"热毒"等40种毒邪,涉及患斑毒病候、脚气痹弱候、夏日沸烂疮候等共186条,其中热毒、毒气、虫兽毒、风毒、食毒的出现频率较高,从而进一步完善、发展中医病因范畴"毒"之学说。     

Toxin synergism in snake venoms

Synergism between venom toxins exists for a range of snake species. Synergism can be derived from both intermolecular interactions and supramolecular interactions between venom components, and can be the result of toxins targeting the same protein, biochemical pathway or physiological process. Few simple systematic tools and methods for determining the presence of synergism exist, but include co-administration of venom components and assessment of Accumulated Toxicity Scores. A better understanding of how to investigate synergism in snake venoms may help unravel strategies for developing novel therapies against snakebite envenoming by elucidating mechanisms for toxicity and interactions between venom components.     

Reevaluation of the Premier Clostridium difficile toxin A and B immunoassay with comparison to glutamate dehydrogenase common antigen testing evaluating Bartels cytotoxin and Prodesse ProGastro Cd polymerase chain reaction as confirmatory procedures

Enzyme immunoassays are currently the most common tests used in the clinical laboratory for the detection of Clostridium difficile toxins; however, significant problems with their performance have recently been described. We prospectively reevaluated the Meridian Premier C. difficile toxin A/B assay with direct comparison to a 2-step algorithm that screened for C. difficile common antigen and compared cytotoxin and real-time polymerase chain reaction (PCR) as confirmatory procedures. The Premier assay lacked sufficient sensitivity, missing 25% of true-positive samples. PCR was the most sensitive method and the only procedure that allowed same day testing and reporting.     

Molecular characterization of toxin A-negative,toxin B-positive variant strains of Clostridium difficile isolated in Korea

A⁻B⁺Clostridium difficile strains are prevalent in Korea. We performed pulsed-field gel electrophoresis (PFGE), polymerase chain reaction ribotyping, and toxinotyping in 82 A⁻B⁺ clinical isolates in Korea. PFGE showed highest discriminatory capability among the 3 methods. By PFGE, persistence of a clone was found, suggesting this clone has adapted to the hospital environment.     

A型肉毒毒素对脑损伤后下肢痉挛的影响

目的 探讨A型肉毒毒素(botulinum toxin A,BTXa)能否有效、安全地治疗下肢肌痉挛,改善步行能力及步行速度.方法 27例中风、脑外伤患者,选择下肢肌肉局部注射国产BTXa.每个患者每次选择3～5块肌肉,每块肌肉总的注射剂量为50～100 IU,患者每次接受的注射总量≤400 IU.所有患者同时接受步态训练等康复治疗.注射前、注射后2周、4周按改良式Ashworth量表(modified ashworth scale, MAS)评定肌张力,足印分析法(footprint analysis) 测量并记录步行时的时间距离参数的变化,研究各肌群肌张力变化与步态参数的关系.结果 整体比较,注射后2周(股直肌除外)、4周各肌群肌张力降低,与注射前相比差异有显著性意义(P<0.05),步态时间距离参数值(T-D值)除步角外,各参数均有不同程度改善(P<0.001或<0.05).注射前与注射后4周比较,步长、步宽、步速差异均有显著性意义(P<0.05).注射后2周与4周比较,步长、步速有改善(P<0.05),而步宽、步角变化不大.Spearman相关分析表明各肌群肌张力降低与步长具有较好的相关性(r=0.650～-0.875).结论 下肢肌肉局部注射BTXa结合步态训练,可以明显改善中风、脑外伤的痉挛步态,表明局部的化学去神经方法结合康复训练,可以更好地改善特定的功能.     

用PCR方法检测粪便难辨梭状芽胞杆菌

目的：采用PCR方法检测粪便难辨梭状芽胞杆菌。方法：北京协和医院的36例应用抗生素后腹泻的病人粪便标本,采用PCR方法对难辨梭状芽胞杆菌（以下简称C．D）的毒素B基因和毒素A基因进行扩增,同时进行厌氧细菌培养。结果：PCR法毒素B基因的阳性率为46．7％（16／36）,毒素A基因为36．1％（13／36）;用厌氧菌培养的阳性率为19．2％（7／36）。PCR检测C．D毒素基因方法与厌氧培养法的一致性为100％。结论：用PCR方法检测C．D比厌氧培养法检出率明显增高（P＜0．05）,与厌氧菌培养法的一致性高。