防止银器文物变色的唑系复合缓蚀剂Ⅰ. 缓蚀剂成膜处理工艺与防变色性能的评定

:通过按正交法设计的紫外光照曝露等加速大气腐蚀实验 ,研究了用于防止银变色的唑系复合缓蚀剂成膜处理的工艺 ,并评定其对模拟文物银试片的防变色性能。采用极化曲线和交流阻抗Nyquist图 ,讨论了防变色作用的电化学机理。实验结果表明 ,缓蚀剂 PMTA、MBI和 MBO具有较好的协同作用 ,银试片在 5 0°C、p H 3.0、组分 MBO∶ PMTA∶ MBI为 1∶ 1 .7∶ 3(摩尔比 )、复合缓蚀剂浓度为 0 .0 1 89mol/L的溶液中 4h成膜处理后 ,经 48h硫华气氛和 36h紫外光曝露腐蚀实验 ,无色斑出现 ,表明缓蚀膜明显地提高了银试片的抗变色能力     

Invasive pulmonary aspergillosis

In susceptible patients, invasive aspergillosis has a high incidence and a mortality of up to 80%. The diagnosis of this condition is difficult, especially in the early stages of the disease and, as a consequence, antifungal therapy, despite its expense and toxicity, is often initiated empirically. Until recently, there were very few effective antifungal agents for established invasive aspergillosis, but the introduction of two new drugs, voriconazole and caspofungin, has increased the treatment options. These newer antifungal therapies, combined with improved early diagnosis due to the introduction of newer microbiologic techniques, offer the hope that there will be a significant improvement in the substantial morbidity and mortality associated with invasive aspergillosis over the next 5 years.     

Systemic treatment of skin candidosis: a randomized comparison of terbinafine and ketoconazole

Terbinafine is an antimycotic drug which has a much higher in vitro activity against dermatophytes than against yeasts. To investigate the clinical relevance of these in vitro data, 118 patients with cutaneous candidosis were enrolled in a randomized, double-blind study and allocated to a 4-week treatment with a daily dose of either 250 mg b.i.d. terbinafine or 200 mg once-daily ketoconazole. At the final assessment, 3 weeks after cessation of therapy, mycological cure rates (negative culture and negative microscopy) were 82% in the terbinafine group and 73% in the ketoconazole group. Effective treatment with negative mycology and no or minimal signs or symptoms could be achieved in 65% of those who received terbinafine and in 57% of those randomized to ketoconazole. Five per cent and 7% of the patients taking terbinafine and ketoconazole, respectively, complained about adverse events, which were usually mild and did not lead to discontinuation of treatment. In one patient in the ketoconazole group, abnormal liver enzymes were noted at the final laboratory assessment. The results of this study indicate that terbinafine 500 mg daily can be an alternative to ketoconazole when systemic treatment of skin candidosis is required.     

Kontroversen bei der Standardisierung der Empfindlichkeits-prüfung von Hefen gegen Azol-Antimyotika

Zusammenfassung. Die unterschiedlichen physikalisch-chemischen Eigenschaften der therapeutisch ein-gesetzten Azol-Antimykotika erfordern ein Testverfahren, welches diesen gerecht wird. Fluconazol kann innerhalb der Gruppe der Azol-Antimykotika aufgrund seiner Hydrophilie als unproblematische Testsubstanz angesehen werden. Die extreme Hydrophobizität des Itraconazols läßt eine Übertragung der Testbedingungen für Fluconazol auf die Itraconazoltestung nicht zu. Die aktuellen Empfehlungen des NCCLS werden dieser Problematik nicht gerecht. Deshalb ist es notwendig, einen einheitlichen Standard für die In-vitro-Testung der Gruppe der Azol-Antimykotika festzulegen.
Summary. Due to the different physical-chemical conditions of the therapeutical azoles it is necessary to choose an adequate testing procedure. In the group of azoles caused by its hydrophilia fluconazole susceptibility testing can be handled easily. However it is not possible to take the same test conditions for itraconazole as for fluconazole due to the extreme high hydrophobicity of itraconazole. The current recommendations of NCCLS should be considering these problems. Therefore it is necessary to standardize susceptibility testing for all azoles possible.     

Susceptibility of clinical isolates of Fusarium to antifungal drugs

Summary. The inhibitory activities of amphotericin B, fluconazole, itraconazole, miconazole, ketoconazole and terbinafine against nine isolates from clinically apparent infections of Fusarium solani , four isolates of Fusarium moniliforme and 10 isolates of Fusarium oxysporum were determined with an agar diffusion method (Neo-sensitabs) and an agar dilution method. The inhibition zones obtained with antifungal Neo-sensitabs need very careful interpretation. We did not find a good correlation between the agar diffusion method using Neo-sensitabs preloaded with azoles and amphotericin B and the agar dilution method. Amphotericin B (12/23) and terbinafine (18/23) showed good activity. Miconazole (7/23) and ketoconazole (3/23) had poor inhibitory activity. Fluconazole and itraconazole (0/23) had no in vitro activity against any of the isolates tested.
Zusammenfassung. Die inhibitorische Aktivität von Amphotericin B, Fluconazol, Itraconazol, Miconazol, Ketoconazol und Terbinafin gegen 9 klinische Isolate von Fusarium solani , 4 von Fusarium moniliforme und 10 von Fusarium oxysporum wurde mit einer Agar-Diffusionstechnik (Neo-sensitabs) und einer Agar-Dilutionsmethode untersucht. Die Hemmhöfe mit Neo-sensitabs müssen mit Vorsicht interpretiert werden. Es wurde keine gute Korrelation zwischen der Agar-Diffusionstechnik mit Neo-sensitabs, beladen mit Azolen und Amphotericin B, und der Agar-Dilutionstechnik gefunden. Amphotericin B (12/23) und Terbinafin (18/23) zeigen eine gute Aktivität. Miconazol (7/23) und Ketoconazol (3/23) haben nur schwache inhibitorische Aktivität. Fluconazol und Itraconazol (0/23) zeigen in vitro keine Aktivität gegen die untersuchten Fusarium -Stämme.     

唑类抗真菌药的合成评述

对唑类抗真菌代表性药物酮康唑、特康唑、伊曲康唑、泊沙康唑、氟康唑和伏立康唑的主要合成方法进行了评述。     

Tacrolimus dosage requirements after initiation of azole antifungal therapy in pediatric thoracic organ transplantation

Azole antifungals inhibit the metabolism of tacrolimus mediated by CYP3A4. Upon initiation of azole therapy, the required dose reduction of tacrolimus is unknown. We reviewed our experience with azole antifungals in our pediatric thoracic transplant population receiving tacrolimus. Tacrolimus levels and dosage requirements were compared before and during azole therapy. Thirty-one patients received both tacrolimus and an azole antifungal (fluconazole = 9, itraconazole = 22). The tacrolimus dose was empirically reduced by approximately one-third when azole therapy was initiated. Mean tacrolimus dose requirements decreased by 68% within the first month of therapy (pre-azole: 0.27 +/- 0.14 mg/kg/day; 30 day post-azole: 0.087 +/- 0.069 mg/kg/day; p < 0.001). Despite a mean decrease in tacrolimus dose from baseline of 33, 42, and 55% on day 1, 2, and 4 of azole therapy, respectively, there was still an unintended 38% increase in tacrolimus levels during the first month of azole therapy. A calculated dose-reduction protocol of 50% on day of azole initiation, 70% on day 3, and 75% on day 14 should result in minimal mean changes in the tacrolimus levels. There was no difference in tacrolimus dose reduction between fluconazole and itraconazole groups. Azole antifungals markedly decrease tacrolimus requirements within the first few days of therapy. An initial reduction in tacrolimus dose by one-third is insufficient, and dose reduction of at least 50% upon azole initiation seems warranted. Once azole antifungal therapy is initiated, frequent therapeutic drug monitoring is required.     

Frequency and Evolution of Azole Resistance in Aspergillus fumigatus Associated with Treatment Failure

Azoles are the mainstay of oral therapy for aspergillosis. Azole resistance in Aspergillus has been reported infrequently. The first resistant isolate was detected in 1999 in Manchester, UK. In a clinical collection of 519 A. fumigatus isolates, the frequency of itraconazole resistance was 5%, a significant increase since 2004 (p<0.001). Of the 34 itraconazole-resistant isolates we studied, 65% (22) were cross-resistant to voriconazole and 74% (25) were cross-resistant to posaconazole. Thirteen of 14 evaluable patients in our study had prior azole exposure; 8 infections failed therapy (progressed), and 5 failed to improve (remained stable). Eighteen amino acid alterations were found in the target enzyme, Cyp51A, 4 of which were novel. A population genetic analysis of microsatellites showed the existence of resistant mutants that evolved from originally susceptible strains, different cyp51A mutations in the same strain, and microalterations in microsatellite repeat number. Azole resistance in A. fumigatus is an emerging problem and may develop during azole therapy.