Vanishing bronchus intermedius syndrome in a pediatric patient with cystic fibrosis after lung transplantation

Hayes D Jr, Mansour HM. Vanishing bronchus intermedius syndrome in a pediatric patient with cystic fibrosis after lung transplantation. Abstract: Airway complications occur frequently after lung transplantation. Bronchial stenosis is the most frequently encountered complication with the most severe form of that being the vanishing bronchus intermedius syndrome (VBIS). This rare disorder has never been reported in the pediatric population. This is the first report of VBIS in a pediatric patient, specifically a 16‐yr‐old male patient with cystic fibrosis whose course was complicated by a lower airway infection with Aspergillus fumigatus. The VBIS responded to bronchoscopic balloon dilation and placement of an airway stent.     

不同培养条件对真菌菌丝形成影响的比较研究

目的 探讨不同培养条件在体外诱导实验中对白色念珠菌、烟曲霉菌菌丝形成率的影响.方法 通过添加胎牛血清(FBS)改变培养基成分、调整孢子浓度及培养时间诱导两种真菌菌丝的形成,以了解不同培养条件对真菌菌丝形成率的影响.结果 白色念珠菌在含10％ FBS的RPMI1640液体培养基中,孢子密度在1×106个/mL,培养时间为3h时菌丝形成率最高,为(99.3±0.6)％(P＜0.05);而烟曲霉菌在相同的培养基及孢子密度相同的条件下,培养时间为5h时,菌丝形成率最高,为(99.6±0.4)％(P＜0.05).结论 优化培养条件可提高白色念珠菌、烟曲霉菌菌丝形成率并缩短培养时间.     

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.     

WHAT REALLY BOTHERS ONCOLOGY PATIENTS

A 5-month-old boy with X-linked severe combined immunodeficiency (SCID) and aspergillus pneumonia was successfully transplanted. Before and during transplantation, the patient received O 2 administration, systemic amphotericin B, and itraconazole. The transplant was performed with a conditioning regimen of busulfan/cyclophosphamide and 2.9 &;#50 10 6 /kg of CD34 + selected bone marrow cells from his HLA haploidentical mother. Acute grade II graft-versus-host disease (GvHD) was well controlled. Neutrophil counts reached > 0.5 &;#50 10 9 /L by day 15 and platelet counts reached > 50 &;#50 10 9 /L by day 48. The T-cell subset (counts) in peripheral blood increased to 42.2% (0.31 &;#50 10 9 /L) by day 46. The pneumonia improved by day 54. The patient has been doing well with limited chronic GvHD of the gut with a follow-up of longer than 40 months after BMT. Conquest of aspergillus pneumonia in SCID infants could be achieved by CD34 + bone marrow cell transplantation together with appropriate anti-fungal treatment.     

Itraconazole in chronic cavitary pulmonary aspergillosis: a randomised controlled trial and systematic review of literature

Patients with aspergilloma can be safely managed with supportive therapy in absence of massive haemoptysis. We hypothesised that chronic cavitary pulmonary aspergillosis (CCPA) could also be managed on similar grounds. The aim of this prospective, randomised controlled trial was to evaluate the efficacy and safety of itraconazole in CCPA. Consecutive patients of CCPA with presence of chronic pulmonary/systemic symptoms; and pulmonary cavities; and presence of Aspergillus (immunological or microbiological) were randomised to receive either supportive treatment alone or itraconazole 400 mg daily for 6 months plus supportive therapy. Response was assessed clinically, radiologically and overall after 6 months therapy. A total of 31 patients (mean age, 37 years) were randomised to itraconazole (n = 17) or the control (n = 14) group. The number of patients showing overall response was significantly higher in the itraconazole group (76.5%) vs. the control (35.7%) group (P = 0.02). The numbers of patients demonstrating clinical or radiological response were also significantly higher in the itraconazole group (P = 0.016 and 0.01 respectively). Adverse events were noted in eight patients in the itraconazole group, however, none was serious or led to discontinuation of the study drug. Itraconazole was found to be superior to standard supportive treatment alone in stabilising cases of CCPA. (clinicaltrials.gov; NCT01259336).     

New Antifungal Compounds from Aspergillus terreus Isolated from Desert Soil

Two new butyrolactone I derivatives: 3‐[3‐hydroxy‐4‐(3‐methyl‐but‐2‐enyl)‐phenyl]‐5‐(?4‐hydroxybenzyl)‐4‐methyl‐dihydrofuran‐2(3H)‐one (1) and (Z)‐3‐[3‐hydroxy‐4‐(3‐methyl‐but‐2‐enyl)‐phenyl]‐5‐(?4‐hydroxybenzylidene)‐4‐methyl‐dihydrofuran‐2(3H)‐one (2), in addition to the previously described (S)‐methyl‐4‐hydroxy‐2‐[4‐hydroxy‐3‐(3‐methyl‐but‐2‐enyl)‐benzyl]‐3‐(4‐hydroxy‐phenyl)‐5‐oxo‐2,5‐dihydro‐furan‐2‐carboxylic acid methyl ester (3), were identified from a strain of Aspergillus terreus Thom (Trichocomaceae) isolated from desert soil. The antifungal activities of both intra‐ and extracellular metabolites of A. terreus grown on yeast extract sucrose and malt extract media were determined. Only the secondary metabolites of A. terreus grown on yeast extract sucrose medium were active against Aspergillus fumigatus RCMB 002008. The antifungal activity of A. terreus was attributed to the presence of the compounds (1) and (2), whose minimum inhibitory concentrations (MIC) against A. fumigatus were found to be 32.00 and 16.00 µg/mL respectively. Structure elucidation was carried out using UV spectrometry, electrospray ionization mass spectrometry (ESIMS), high resolution electron impact (HREIMS) spectrometry, ¹H‐ and ¹³ C‐NMR, proton–proton correlation spectroscopy (¹H–¹H Cosy), distortionless enhancement by polarization transfer (DEPT), heteronuclear single quantum coherence (HSQC) and heteronuclear multiple bond correlations (HMBC) spectroscopy. Copyright © 2012 John Wiley & Sons, Ltd.     

A strategy for managing fungal infections in haematopoietic stem cell transplantation

As more indications continue to be found for allogeneic haematopoietic transplantation, more patients are at risk for invasive fungal infectious diseases (IFID), particularly candidiasis and aspergillosis. Risk factors for disease are becoming better defined and diagnostic methods have improved considerably. In addition, there is now international agreement that three elements form the basis for defining IFID (host factors, clinical evidence, and mycological results), that imaging is acceptable for diagnosing disease, and that indirect tests such as antigen detection are also adequate mycological proof of cause. There are also more drugs available and still more to come, offering the potential for selective prophylaxis as well as preemptive and specific therapy, as well as for flexible administration. Hence, all the elements are in place for designing and testing an effective and economically sound strategy for dealing with IFID.     

Production and characterization of monoclonal antibodies to serine proteinase allergens in Penicillium and Aspergillus species.

BACKGROUND: Alkaline and/or vacuolar serine proteinases are major allergens in prevalent airborne Penicillium and Aspergillus species. OBJECTIVE: The object of this study is to generate and characterize monoclonal antibodies against these serine proteinase allergens. METHODS: BALB/c mice were immunized individually with the Penicillium citrinum culture medium or the crude extract and culture medium preparations of Aspergillus fumigatus. Hybridoma cells that secrete monoclonal antibodies against serine proteinase allergens were selected by immunoblotting. Antigens in three different Penicillium (P. citrinum, P. notatum and P. oxalicum) and two different Aspergillus species (A. fumigatus, and A. flavus) recognized by these monoclonal antibodies were analysed by sodium dodecyl sulphate and two-dimensional polyacrylamide gel electrophoresis immunoblotting and N-terminal amino acid sequence analysis. RESULTS: Four (PCM8, PCM10, PCM16 and PCM39) and one (FUM20) monoclonal antibodies against serine proteinase allergens were generated after fusion of NS-1 cells with spleen cells obtained from BALB/c mice immunized with antigens from P. citrinum and A. fumigatus, respectively. Immunoblotting results showed that PCM8 reacted with an alkaline serine proteinase allergen in P. citrinum and P. notatum. PCM10 and PCM39 reacted with the alkaline serine proteinase in two Penicillium (P. citrinum, P. notatum) and two Aspergillus species (A. fumigatus, and A. flavus) tested. PCM16 reacted with the alkaline serine proteinase allergen in P. citrinum, A. fumigatus and A. flavus but not with that in P. notatum. MoAb FUM20 reacted with the alkaline serine proteinase allergen in two Aspergillus species (A. fumigatus and A. flavus) but not with that in two different Penicillium species (P. citrinum, P. notatum) tested. Among these five monoclonal antibodies generated, only PCM39 and FUM20 can react with the vacuolar serine proteinase allergen in P. notatum, P. oxalicum and in A. fumigatus. The 35 kDa P. citrinum component that reacted with FUM20 has an N-terminal amino acid sequence of DSPSVEKNAP. CONCLUSION: Five monoclonal antibodies against different epitopes of the serine proteinase major allergens in prevalent Penicillium and Aspergillus species were generated in the present study. Antibodies obtained may be useful in the characterization and standardization of serine proteinase allergens in crude fungal extracts.     

EFFICACY OF MICONAZOLE IN EXPERIMENTAL KERATOMYCOSIS

For the first time comparative efficacy of 1 % miconazole in ointment base and drops has been evaluated against Candida, Aspergillus and Fusarium organisms In experimental heratomycosis. The findings of the present study reveal that miconazole in ointment drug delivery system has the advantage of being more effective in healing the fungal ulcers and associated lesions. It requires much less frequent application than drops, a parameter of great importance in improving patient compliance. Miconazole ointment was well tolerated by the rabbit eye and produced no ocular or systemic toxicity. The present study confirms that miconazole is a broad-spectrum antifungal agent and it could be a better alternative to presently available drugs to treat human heratomycosis .