Quantification of sirolimus by liquid chromatography-tandem mass spectrometry using on-line solid-phase extraction

Quantification of the new immunosuppressant sirolimus (syn. rapamycin; Rapamune((R))) in whole blood by chromatography is essential for its clinical use since no immunoassay is available although monitoring is mandatory. Here we report on a rapid and convenient liquid chromatography (LC)-tandem mass spectrometry method and describe our practical experience with its routine use. Whole blood samples were hemolyzed and deproteinized using an equal volume (150 mul) of a mixture of methanol/zinc sulfate solution containing the internal standard desmethoxy-rapamycin. After centrifugation, the clear supernatants were submitted to an on-line solid-phase extraction procedure using the polymeric Waters Oasis HLB(R) material, with elution of the extracts onto the analytical column in the back-flush mode by column switching. For analytical chromatography a RP-C18 column was used with 90/10 methanol/2 mM ammonium acetate as the mobile phase. A 1:10 split was used for the transfer to the mass spectrometer, a Micromass Quattro LC-tandem mass spectrometry system equipped with a Z-spray((R)) source and used in the positive electrospray ionization mode. The following transitions were recorded: sirolimus, 931>864 m/z, and desmethoxy-rapamycin (I.S.), 901>834 m/z. The analytical running time was 5 min, including on-line extraction. The method has a linear calibration curve (r>0.99; range 1.6-50 mug/l) and is rugged and precise with monthly CVs <7% at a sirolimus concentration of 13.1 mug/l in routine use; the instrumentation proved to be reliable and required minimal maintenance

Effect of the reaction mixture on the structure and permeability of macroporous SiO[2], obtained by sol gel by method

In this paper, a number of porous silicone monoliths were synthesized under various conditions and their composition, structure, permeability coefficients k, and porosity were studied. The effect of the introduction of ethyl alcohol in the reaction mixture on the properties of the obtained silica was revealed

Ten-Year Results of a Randomized Trial Comparing Tacrolimus Versus Cyclosporine A in Combination With Mycophenolate Mofetil After Heart Transplantation

Background. Long-term results of prospective randomized trials comparing triple immunosuppressive strategies combining tacrolimus (TAC) or cyclosporine A (CsA) with mycophenolate mofetil (MMF) and steroids after heart transplantation (HTX) are rarely published. Therefore, we collected long-term follow-up data of an intervention cohort 10 years after randomization. Methods. Ten-year follow-up data of 60 patients included in a prospective, randomized trial between 1998 and 2000 were analyzed as intention-to-treat (TAC-MMF n=30; CsA-MMF n=30). Baseline characteristics were well balanced. Cardiac allograft vasculopathy (CAV) was graduated in accordance with the new ISHLT classification. Results. Survival at 1, 5, and 10 years was 96.7%, 80.0%, and 66.7% for TAC-MMF and 90.0%, 83.3%, and 80.0% for CsA-MMF (P=ns). Freedom from acute rejection (AR) was significantly higher in TAC-MMF versus CsA-MMF (65.5% vs. 21.7%, log-rank 8.3, P=0.004). Freedom from ISHLT >= CAV(1) after 5 and 10 years was in TAC-MMF 64.0% and 45.8%, and in CsA-MMF 36.0% (log-rank 3.0, P=0.085) and 8.0% (log-rank 9.0, P=0.003). No difference in long-term results for freedom from coronary angioplasty or stenting, renal dysfunction, diabetes mellitus, CMV infection, or malignancy was detected. Conclusion. Cross-over effects because of treatment switch may result in impairment of significance between the groups. The long-term analysis resulted in a significant difference in manifestation of CAV between the groups after 10 years. Less rejection in the TAC-group might have contributed to the lower incidence of CAV. Superior freedom from AR and CAV in the TAC-MMF group did not result in better long-term survival

Анализ методов увеличения нефтеотдачи на терригенных коллекторах месторождений Западной Сибири

В данной выпускной работе были рассмотрены и проанализированы особенности строения терригенных коллекторов, а также методы увеличения нефтеотдачи, применяемые на месторождениях Западной Сибири, имеющих терригенный тип коллекторов.In the final work, the structural features of terrigenous reservoirs, as well as oil recovery enhancement methods used in fields of Western Siberia having a terrigenous reservoir type, were considered and analyzed

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Ex Vivo Fluorescence Confocal Microscopy for Intraoperative Examinations of Lung Tumors as Alternative to Frozen Sections-A Proof-of-Concept Study

Kamm M, Hildebrandt F, Titze B, et al. Ex Vivo Fluorescence Confocal Microscopy for Intraoperative Examinations of Lung Tumors as Alternative to Frozen Sections-A Proof-of-Concept Study. Cancers. 2024;16(12): 2221.BACKGROUND: Intraoperative frozen sections (FS) are frequently used to establish the diagnosis of lung cancer when preoperative examinations are not conclusive. The downside of FS is its resource-intensive nature and the risk of tissue depletion when small lesions are assessed. Ex vivo fluorescence confocal microscopy (FCM) is a novel microimaging method for loss-free examinations of native materials. We tested its suitability for the intraoperative diagnosis of lung tumors.; METHODS: Samples from 59 lung resection specimens containing 45 carcinomas were examined in the FCM. The diagnostic performance in the evaluation of malignancy and histological typing of lung tumors was evaluated in comparison with FS and the final diagnosis.; RESULTS: A total of 44/45 (98%) carcinomas were correctly identified as malignant in the FCM. A total of 33/44 (75%) carcinomas were correctly subtyped, which was comparable with the results of FS and conventional histology. Our tests documented the excellent visualization of cytological features of normal tissues and tumors. Compared to FS, FCM was technically less demanding and less personnel intensive.; CONCLUSIONS: The ex vivo FCM is a fast, effective, and safe method for diagnosing and subtyping lung cancer and is, therefore, a promising alternative to FS. The method preserves the tissue without loss for subsequent examinations, which is an advantage in the diagnosis of small tumors and for biobanking

Endobronchial donor pre-treatment with ventavis: is a second administration during reperfusion beneficial to optimize post-ischemic function of non-heart beating donor lungs?

BACKGROUND: Lung retrieval from non-heart-beating donors (NHBD) has been introduced into clinical practice successfully. However, because of potentially deleterious effects of warm ischemia on microvascular integrity, use of NHBD lungs is limited by short tolerable time periods before preservation. Recently, improvement of NHBD graft function was demonstrated by donor pre-treatment using aerosolized Ventavis (Schering Inc., Berlin, Germany). Currently, there is no information whether additional application of this approach in reperfusion can further optimize immediate graft function. MATERIAL AND METHODS: Asystolic pigs (n = 5/group) were ventilated for 180-min of warm ischemia (groups 1-3). In groups 2 and 3, 100 microg Ventavis were aerosolized over 30-min using an ultrasonic nebulizer (Optineb). Lungs were then retrogradely preserved with Perfadex and stored for 3-h. After left lung transplantation and contralateral lung exclusion, grafts were reperfused for 6-h. Only in group 3, another dose of 100 microg Ventavis was aerosolized during the first 30-min of reperfusion. Hemodynamics, pO2/FiO2 and dynamic compliance were monitored continuously and compared to controls. Intraalveolar edema was quantified stereologically, and extravascular-lung-water-index (EVLWI) was measured. Statistics comprised ANOVA analysis with repeated measurements. RESULTS: Dynamic compliance was significantly lower in both Ventavis groups, but additional administration did not result in further improvement. Oxygenation, pulmonary hemodynamics, EVLWI and intraalveolar edema formation were comparable between groups. CONCLUSIONS: Alveolar deposition of Ventavis in NHBD lungs before preservation significantly improves dynamic lung compliance and represents an important strategy for improvement of preservation quality and expansion of warm ischemic intervals. However, additional application of this method in early reperfusion is of no benefit