Severe cutaneous aspergillosis in a premature neonate linked to nonsterile disposable glove contamination?

After having eliminated a dysfunction of the hospital's ventilation system and any other possible environmental reservoir, the investigation of a fatal case of primary cutaneous aspergillosis in a neonate with extremely low birth weight led to the conclusion that nonsterile disposable gloves kept stored in their native packages were the likely source of contamination.     

Fungal transformation of androsta-1,4-diene-3,17-dione by Aspergillus brasiliensis

Background

The biotransformation of steroids by fungal biocatalysts has been recognized for many years. There are numerous fungi of the genus Aspergillus which have been shown to transform different steroid substances. The possibility of using filamentous fungi Aspergillus brasiliensis cells in the biotransformation of androsta-1,4-diene-3,17-dione, was evaluated.

Methods

The fungal strain was inoculated into the transformation medium which supplemented with androstadienedione as a substrate and fermentation continued for 5 days. The metabolites were extracted and isolated by thin layer chromatography. The structures of these metabolites were elucidated using ¹H-NMR, broadband decoupled ¹³C-NMR, EI Mass and IR spectroscopies.

Results

The fermentation yielded one reduced product: 17β-hydroxyandrost-1,4-dien-3-one and two hydroxylated metabolites: 11α-hydroxyandrost-1,4-diene-3,17-dione and 12β-hydroxyandrost-1,4-diene-3,17-dione.

Conclusions

The results obtained in this study show that A. brasiliendsis could be considered as a biocatalyst for producing important derivatives from androstadienedione.     

卡泊芬净治疗心脏术后侵袭性真菌病20例临床分析

目的:探讨卡泊芬净治疗心脏术后并发侵袭性真菌感染(IFI)的疗效与安全性。方法:回顾分析我院呼吸科、心外科和急诊重症监护室(ICU),接受过卡泊芬净治疗的心脏术后合并IFI患者临床资料。结果:2005年5月至2010年12月,共有20例接受了卡泊芬净治疗。男性12例,女性8例,中位年龄65岁(23～82)岁。确诊10例,皆为念珠菌血症(白念珠菌4例,近平滑念珠菌3例,光滑念珠菌、热带念珠菌和克柔念珠菌各1例);临床诊断肺IFI 5例(念珠菌3例,曲霉2例);拟诊肺IFI 5例,病原真菌不明。冠状动脉搭桥(CABG)术8例,瓣膜手术8例,胸主动脉瘤手术2例,先天性心脏病(先心病)和马方综合征手术各1例。卡泊芬净的使用时间中位数为18(1～55)d。1例于用药当天死于心脏骤停疗效无法判断,19例可评估患者中,痊愈10例(10/19,52.6%),显效4例(4/19,21.1%),总有效率为73.7%,进步3例,无效2例。死亡6例(6/20,病死率30.0%)。治疗过程中未发现与卡泊芬净有关的不良反应。结论:卡泊芬净是治疗心脏术后并发IFI的有效安全药物,值得进一步临床验证。     

慢性烟曲霉暴露对支气管哮喘大鼠气道黏蛋白MUC5AC表达的影响

[目的]探讨慢性烟曲霉暴露对支气管哮喘(简称哮喘)大鼠气道黏蛋白MUC5AC表达的影响.[方法]将56只雄性Wistar大鼠按随机数字表法分为7组(每组8只):慢性哮喘(A)组、慢性哮喘+烟曲霉孢子吸入1周(B)、3周(C)和5周(D)组、慢性哮喘+生理盐水吸入(E)组、卵清白蛋白(OVA)致敏生理盐水激发(F)组和OVA致敏生理盐水激发+烟曲霉孢子吸入(G)组.测定各组大鼠基础气道阻力和应用乙酰胆碱后气道阻力变化率,RT-PCR测定肺组织MUC5AC mRNA的表达,免疫组织化学染色测定各组大鼠气道上皮细胞MUC5AC的表达,酶联免疫吸附(ELISA)法测定BALF中IL-13水平,肺组织切片过碘酸雪夫染色(PAS)观察气道上皮杯状细胞增生程度.[结果]B、C和D组大鼠肺组织MUC5AC mRNA(MUC5AC mRNA/β-actin mRNA)(分别为1.9±0.4、2.3±0.6、2.9±0.8)、气道上皮细胞MUC5AC表达(A值)(分别为278±58、566±64、891±80)、BALF上清液IL-13[分别为(96±16)、(136±22)、(197±34)μg/L]及杯状细胞/上皮细胞面积(分别为16％±5％、23％±7％、36％±9％)均高于A、E、F及G组(均P＜0.05);C和D组大鼠气道阻力变化率(分别为61.91％±5.26％、84.69％±6.38％)均高于A、E、F及G组(均P＜0.05).B、C和D组哮喘大鼠MUC5AC的A值及MUC5AC Mma/β-actin mRNA与气道上皮杯状细胞增生程度(PAS染色区面积/上皮细胞面积)呈正相关(r值分别为0.578和0.614,均P＜0.05),与气道反应性(Raw变化率)呈正相关(r值分别为0.638和0.564,均P＜0.05).[结论]慢性烟曲霉暴露可上调哮喘大鼠气道上皮黏蛋白MUC5AC的表达,促进杯状细胞增生,加重气道高反应.     

The interplay between inflammasome activation and antifungal host defense

Fungal infections cause significant morbidity and mortality in humans, and they are a growing problem due to the increased usage of broad-spectrum antibiotics and immunosuppressive therapies. The equilibrium between the commensal microbial flora and the immune system that protects the host against invasive fungal infection is disturbed during disease, and understanding this disturbed balance is important to develop new therapeutic interventions for the treatment of fungal infection. In the context of tolerating fungi during colonization and eliciting a vigorous immune response to eliminate invading fungal pathogens when needed, the inflammasome has been identified as an integral component of antifungal host defense. It contributes to mucosal host defense by regulating T-helper 17 (Th17) cell responses, and contributes to protective responses such as neutrophil influx during fungal sepsis. Several aspects are important for understanding the role of the inflammasome for antifungal host defense, such as the role of fungal cell wall morphology and its components in triggering the inflammasome, the pattern recognition pathways and downstream signaling cascades involved in the activation of the inflammasome, and the effects of inflammasome activation during fungal infection. The future perspectives of inflammasome research in fungal immunology, with emphasis on targeting the inflammasome for the design of future immunotherapies, is also discussed.     

Fungal rhinosinusitis: A clinicomycological perspective

Purpose: Chronic rhinosinusitis (CRS) is a widely prevalent condition globally as well as in India. The spectrum of fungal involvement in CRS runs from benign colonisation to potentially life-threatening invasive disease. Successful treatment of such mycotic infections largely depends on the accurate identification of the pathogen, early and appropriate intervention by surgical clearance, supported with antifungal medication as per standard regimen. Thus, this study was undertaken to determine the prevalence of fungal rhinosinusitis (FRS), and to analyse its clinicomycological profile. Materials and Methods: Fifty-two patients with clinical suspicion of CRS attending a tertiary care hospital during a one-year period were included in this retrospective analysis. The sinonasal specimens were subjected to microscopy by KOH mount and fungal culture as per standard mycological technique. Tissue specimens were also subjected to histopathological examination. Results: Male to female ratio was 1.25:1; age varied from 14 years to 62 years with majority of patients (37%) belonging to age group 21-40 years. The prevalence of FRS was 44%, and 74% of it was caused by Aspergillus sp. Aspergillus flavus (A. flavus) (52%) was the most prevalent fungus isolated. Allergic fungal rhinosinusitis (AFRS) was the most common presentation (79%). Conclusion: FRS is a continuous spectrum of disease varying in presentation, treatment and long-term sequelae. Correct identification of the fungus remains essential for appropriate treatment.     

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.     

Safety evaluation of an IPP tripeptide-containing milk protein hydrolysate

Tensguard™ is a milk protein hydrolysate containing the lactotripeptide IPP. It is derived from cow’s milk, which is present in the human diet and has a safe history of consumption. The final Tensguard™ product, a supplement or a functional food ingredient, is intended for use by people who want to follow a healthy diet and lifestyle in order to manage their blood pressure. The safety-in-use of commercial lactotripeptide-containing products has been confirmed in several in vitro and in vivo toxicity studies and in studies with humans. To support the safety, Tensguard™ was examined in three in vitro genotoxicity tests (bacterial reverse mutation test, mammalian cell gene mutation test and mammalian chromosomal aberration test) and in a 90-day repeated-dose oral toxicity study in rats. The genotoxicity tests confirm that Tensguard™ is not mutagenic or clastogenic. The NOAEL from the 90-day study was at the highest dose tested, i.e. 4% in the diet. The NOAEL is equivalent to an overall mean intake of 2 g Tensguard™/kg body weight/day and corresponds to 40 mg IPP/kg body weight/day. This is 141-fold higher than the maximal anticipated intake. In conclusion, Tensguard™ is safe under the conditions of intended use.