Posaconazole concentrations after allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Posaconazole is recommended for prophylaxis of fungal infections and for salvage therapy of invasive aspergillosis after stem cell transplantation. An impact of drug concentration on efficacy has been suggested. METHODS: In this study, we investigated serum levels of posaconazole in 262 samples from 64 allogeneic stem cell recipients. RESULTS: A high degree of interindividual variation was observed. Concentrations were significantly higher for male patients compared with female patients (median 570 and 426 ng/mL, respectively), but no differences for age or dosing groups (400 mg twice daily [BID] or 200 mg three times a day) could be detected. The predictive value of the first determined posaconazole concentration in steady state and of a concentration >500 and 700 ng/mL at any time was evaluated, compared with patients with a first level <300 ng/mL (mean 10.3%, median 0%). CONCLUSION: In patients receiving 400 mg BID, the mean rate of serum levels >500 ng/mL in subsequent determinations was higher, if the first serum concentration during steady state was >300 ng/mL (mean 61.1%, median 60%, P = 0.002) or >500 ng/mL (67.7%, median 75%, P = 0.002). Based on this retrospective analysis, a posaconazole serum concentration >500 ng/mL at any time point might also help to predict sufficient drug concentrations.

[Tuberculosis as a rare cause for an abdominal mass: report on three cases and review of the literature]. / Tuberkulose als seltene Ursache abdomineller Raumforderungen - drei Kasuistiken und Literaturübersicht.

Here we present 3 patients with abdominal pain, weight loss and fever in combination with abdominal tumours which were all attributable to an ongoing mycobacterial infection. Worldwide, but especially in developing countries, tuberculosis is still an important cause of morbidity and death. In industrialised countries, however, tuberculosis is rarely considered as a differential diagnosis, especially when the primary lesion is not localised in the lung. Primary abdominal manifestations, in particular, are a frequent cause of delayed diagnosis due to the often elaborated necessary diagnostics. Once the diagnosis has been established, a combination therapy starting with isoniazid, rifampicin, pyrazinamide and ethambutol, i. e., the standard therapeutic regimen for pulmonary tuberculosis, is recommended. Concomitant diseases and atypical courses, however, often constitute serious challenges to the treating physician. Therefore, we here give a review of the literature and discuss three cases of abdominal tuberculosis with regard to clinical characteristics, diagnostic pitfalls and courses of disease.

Analyzing Thiol-Dependent Redox Networks in the Presence of Methylene Blue and Other Antimalarial Agents with RT-PCR-Supported in silico Modeling.

BACKGROUND: In the face of growing resistance in malaria parasites to drugs, pharmacological combination therapies are important. There is accumulating evidence that methylene blue (MB) is an effective drug against malaria. Here we explore the biological effects of both MB alone and in combination therapy using modeling and experimental data. RESULTS: We built a model of the central metabolic pathways in P. falciparum. Metabolic flux modes and their changes under MB were calculated by integrating experimental data (RT-PCR data on mRNAs for redox enzymes) as constraints and results from the YANA software package for metabolic pathway calculations. Several different lines of MB attack on Plasmodium redox defense were identified by analysis of the network effects. Next, chloroquine resistance based on pfmdr/and pfcrt transporters, as well as pyrimethamine/sulfadoxine resistance (by mutations in DHF/DHPS), were modeled in silico. Further modeling shows that MB has a favorable synergism on antimalarial network effects with these commonly used antimalarial drugs. CONCLUSIONS: Theoretical and experimental results support that methylene blue should, because of its resistance-breaking potential, be further tested as a key component in drug combination therapy efforts in holoendemic areas.

Labeling of the mitochondrial membrane D-3-hydroxybutyrate dehydrogenase (BDH) with new bifunctional phospholipid analogues.

D-3-Hydroxybutyrate dehydrogenase (BDH), an inner mitochondrial protein, is a well-known phospholipid dependent enzyme. It is a primary dehydrogenase of the oxidative phosphorylation system and is involved in the redox balance of the NAD+/NADH pool. The preparation of fluorescent phospholipids and newly synthesized bifunctional phospholipid analogues (fluorescent and photoactivatable) allowed us to study the structural requirement for lipid activation of the purified enzyme. This paper reports the chemical synthesis protocols to prepare these new phospholipids and their characterization. Illumination experiments of complexes between bifunctional phospholipids and BDH which lead to a cross-linked polypeptide indicate that both the polar head and the hydrophobic moiety of phospholipids interact with BDH. The bifunctional phospholipids were also tested on other lipid-binding proteins, i.e., horse cytochrome c and bovine serum albumin, and demonstrated the promising potential of this new type of photoactivatable molecules which can be followed merely by fluorescence without radioactive labeling.