Pseudomembranous Aspergillus tracheobronchitis in a heart transplant recipient

A. Ramos, J. Segovia, M. Gómez-Bueno, C. Salas, M.T. Lázaro, I. Sanchez, L. Pulpón. Pseudomembranous Aspergillus tracheobronchitis in a heart transplant recipient.
Transpl Infect Dis 2010: 12: 60–63. All rights reserved
Abstract: Aspergillus tracheobronchitis (AT) is an uncommon clinical presentation of pulmonary aspergillosis that frequently progresses to invasive pulmonary aspergillosis. Diagnosis of AT may be delayed because of its insidious onset, non-specific signs and symptoms, and scarcity of radiographic abnormalities. We report the case of a patient who received a heart transplant (HT) because of cardiac amyloidosis and who developed pseudomembranous AT. Possible risk factors concurrent in this case were splenectomy, lymphocytopenia, and previous cytomegalovirus infection. Chest computed tomography scan showed thickening of the left bronchi and a 'tree-in-bud' pattern with multiple small nodules. Bronchoscopic examination revealed raised yellowish pseudomembranous plaques on the tracheobronchial tree. Bronchoalveolar lavage and aspirate cultures yielded Aspergillus fumigatus . The patient recovered with voriconazole. Clinicians should be aware of AT as a potential cause of respiratory symptoms with few radiographic abnormalities in HT recipients, as delay in performing bronchoscopy could result in an unfavorable prognosis.     

黄芩经侧耳菌和黑曲霉发酵后黄酮类成分的变化

目的:考察中药黄芩经侧耳菌和黑曲霉发酵后黄酮类成分变化。方法:以侧耳菌和黑曲霉发酵黄芩,应用高效液相色谱法对其黄酮类成分进行对比研究。结果:高效液相结果显示,黄芩经侧耳菌发酵后大部分黄酮类成分消失;而经黑曲霉发酵后,黄芩苷含量减少,黄芩素和汉黄芩素的含量分别是黄芩药材的2.73,5.77倍。结论:黄芩经侧耳菌和黑曲霉发酵后,苷类成分被转化为苷元或其他物质,有利于提高黄芩的生物利用度及药理活性。     

Toxicological studies on a novel phytase expressed from synthetic genes in Aspergillus oryzae

Phytases are widely used as feed additives for monogastric animals, which cannot easily utilise the phosphorus bound in phytate (myo-inositol hexakisphosphate). The current study presents a safety evaluation of a 6-phytase produced by an Aspergillus oryzae strain expressing two synthetic genes, both mimicking a phytase gene from a Citrobacter braakii strain. Oral administration of the phytase preparation to rats at a dose level of 0.86 g total organic solids/kg body weight/day for 13 weeks did not cause any adverse effect. The phytase preparation did not exhibit irritative potential when applied locally to the eyes of rabbits or when applied to the skin using the in vitro three-dimensional epidermis model of adult human-derived epidermal keratinocytes. Furthermore, the phytase preparation was found not to represent mutagenic or clastogenic potential in the bacterial reverse mutation assay and in the in vitro micronucleus assays. Based on the toxicological data, the large safety factors calculated under common recommended dose assumptions for broiler chickens and weaned piglets, and the fact that Aspergillus oryzae is considered a safe strain lineage, it is concluded that there are no reasons for safety concerns when using this phytase as a feed additive.     

烟曲霉感染对人脐静脉内皮细胞表达血管假性血友病因子的影响

目的通过建立烟曲霉菌丝感染人脐静脉内皮细胞（HUVEC）的体外模型,观察烟曲霉菌丝感染后HUVEC表达血管假性血友病因子（vWF）的变化,以及用不同干预因素处理对HUVEC表达vWF的影响,以探讨侵袭性曲霉病血管侵袭的机制。方法实验分六组,即空白对照组、TNF-α组、烟曲霉菌丝组、细胞松弛素D组、N-钙黏蛋白抗体组和地塞米松组,分别于2、6、12及18 h提取细胞培养上清液,采用ELISA法检测vWF浓度。结果与2 h比较,空白对照组和TNF-α组的vWF表达量在18 h增加（P〈0.05）,其余各组vWF表达量在6、12及18 h均增加（P〈0.05）;各实验组与空白对照组比较,除N-钙黏蛋白抗体组HUVEC的vWF表达量在2 h无明显变化外,其余各时间点vWF表达量均升高（P〈0.05）。TNF-α组HUVEC的vWF表达量在2 h高于烟曲霉菌丝组,而在18 h低于烟曲霉菌丝组。N-钙黏蛋白抗体组HUVEC的vWF表达量在2 h和6 h分别低于烟曲霉菌丝组相应时间点。细胞松弛素D组和地塞米松组vWF在各时间点与烟曲霉菌丝组的差异均无统计学意义。结论烟曲霉菌丝感染后,HUVEC过度表达vWF,N-钙黏蛋白单克隆抗体可减少vWF的表达,而细胞松弛素D和地塞米松对vWF的表达无明显影响。     

米曲菌胰酶片治疗功能性消化不良的上市后药物经济学评价

目的:对米曲菌胰酶片治疗功能性消化不良的成本-效果进行分析。方法:收集多中心非随机同期病例数据,采用成本-效果分析对其进行药物经济学评价。结果:米曲菌胰酶片组相对于对照组(非米曲菌胰酶片治疗),每增加1个效果单位,成本可节约768.52元。使用米曲菌胰酶片治疗可通过提高治疗效果而降低病人的总费用。结论:米曲菌胰酶片治疗功能性消化不良有效、经济。     

Extracellular proteinase formation in carbon starving Aspergillus nidulans cultures--physiological function and regulation

Extracellular proteinase formation in carbon depleted cultures of the model filamentous fungus Aspergillus nidulans was studied to elucidate its regulation and possible physiological function. As demonstrated by gene deletion, culture optimization, microbial physiological and enzymological experiments, the PrtA and PepJ proteinases of A. nidulans did not appear to play a decisive role in the autolytic decomposition of fungal cells under the conditions we tested. However, carbon starvation induced formation of the proteinases observable in autolytic cultures. Similar to other degradative enzymes, production of proteinase was regulated by FluG-BrlA asexual developmental signaling and modulated by PacC-dependent pH-responsive signaling. Under the same carbon starved culture conditions, alterations of CreA, MeaB or heterotrimeric G protein mediated signaling pathways caused less significant changes in the formation of extracellular proteinases. Taken together, these results indicate that while the accumulation of PrtA and PepJ is tightly coupled to the initiation of autolysis, they are not essential for autolytic cell wall degradation in A. nidulans. Thus, as Aspergillus genomes contain a large group of genes encoding proteinases with versatile physiological functions, selective control of proteinase production in fungal cells is needed for the improved industrial use of fungi.     

Analysis of Aspergillus nidulans germination, initial growth and carbon source response by flow cytometry

In this work, flow cytometry was utilized to analyze the initial vegetative growth of the model fungus Aspergillus nidulans as measured by the number of events increasing size and internal complexity. It was established the ideal parameters for the analysis of conidial populations, whose growth was followed after germination in glucose or sucrose. While glucose in culture increased growth several magnitudes in comparison to control cultures in saline, growth was less intense in cultures amended with sucrose. Results indicated that flow cytometry could be a useful tool to study fungal germination and initial growth since it allowed rapid identification of different populations by means of their increasing in size and granularity with good reproducibility and without the need for direct observation and count of individual cells.     

An isoquinoline alkaloid, berberine, can inhibit fungal alpha amylase: enzyme kinetic and molecular modeling studies

Aspergillus flavus is a commonly found fungal pathogen, which produces aflatoxins, highly toxic and hepatocarcinogenic natural compounds. Inhibition of fungal alpha amylase activity has been found to limit the ability of the fungus to produce aflatoxins. Berberine, an isoquinoline alkaloid commonly found in many medicinal plants, was identified to inhibit the growth of A. flavus. The amount of berberine required to inhibit the fungal mycelial growth was determined. The compound was also found to inhibit the alpha amylase from the A. flavus. The binding affinity of the compound toward alpha amylase and the enzyme inhibitory activity have been determined by enzyme kinetic studies and Isothermal Titration Calorimetric analysis. Molecular modeling and docking studies were carried out to understand the enzyme–ligand interactions.     

Cerebral aspergillosis caused by Aspergillus ustus following orthotopic heart transplantation: case report and review of the literature

Abstract:  This report describes the first case of cerebral aspergillosis in a heart transplantation patient caused by Aspergillus ustus and reviews 15 previously reported cases of invasive aspergillosis in immunocompromised hosts caused by this mold. The utility of molecular analysis for the identification of unusual fungal pathogens is also described. The refractory nature of A. ustus to treatment is similar to other Aspergillus species and treatment options are reviewed.     

Use of a microbial toxicity test (Microtox) to determine the toxigenicity of Aspergillus fumigatus strains isolated from different sources

The toxic activity of Aspergillus fumigatus is attributable to substances secreted by its cells. Specific toxic compounds synthesized by the fungi such as gliotoxin, can be detected by sensitive chemical procedures like TLC or HPLC. Measuring the total toxigenicity of a strain extract, however, requires a bioassay. In the present study, we evaluated the possibility of using the Microtox^® bioassay to determine the toxigenicity of A. fumigatus, using 32 strains from different sources. The Microtox^® method is based on the ability of Vibrio fischeri to produce luminescence, and their sensitivity to toxins. A. fumigatus strains, grouped according to their original sources, showed differences in toxigenicity. Strains isolated from invasive aspergillosis patients proved to be more toxigenic than environmental strains, or strains from colonized patients. Since the strains that were more toxigenic were isolated from sick patients, it is not surprising they showed more virulence than the other strains, and as expected, virulence could be correlated with high toxigenicity. The Microtox bioassay could be a useful tool in the study of toxigenicity of the mycelial fungi and their possible pathogenic roles, and for rapid assessment of secreted toxic compounds.