[Multicentric reticulohistiocytosis: A case report].

A 65-year-old woman developed erythema, papules and nodules over the body. Some nodules of her auricles and hands like string beads. Besides, she suffered from symmetrical swelling and pain of multiple joints, morning stiffness with deformity of joints; She had elevated erythrocyte sedimentation rate and C reactive protein levels; Her rheumatoid factor and antinuclear antibody were positive; Joints destruction was found with X-ray imaging; Skin pathology showed Dermal infiltrate of abundant histiocytes, part of them with a ground-glass appearance; A CD68 immunohistochemical stain was positive and the cells were negative for S100, CD1a. These findings were diagnostic evidences of multicentric reticulohistiocytosis (MRH). The patient received high-dose of glucocorticoids combinated with immunosuppressive agents, and achieved a satisfactory effect. MRH was a rare multisystem disease characterized by papulonodular mucocutaneous and destructive arthritis, and its pathogeny was not yet completely understood. The typical lesions of MRH were hard papules or nodules that usually occured on the hands, face and arms. Classic coral bead appearance from periungual cutaneous nodules that were characteristic of MRH. MRH was an inflammatory joint disease, affecting almost all the appendicular joints and characterized by joint multiple, symmetrical, destructive, progressive disability. Joints destruction of the distal interphalangeal joints was a unique feature of MRH. In addition to skin and joints, it could also involve other systems. There were no diagnostic laboratory markers for MRH. Laboratory examinations had often been found to be non-specific. Imageological examination mainly showed bone and joint destruction. Skin biopsy was the best test to diagnose MRH, the typical histopathological findings included an infiltrate with histiocytes and multinucleated giant cells with a ground-glass appearing in eosinophilic cytoplasm, and the immunohistochemical stain was positive for CD68. The diagnosis was typically made based on the clinical presentation, supportive radiographic findings and skin biopsy. MRH was easily possible to mistake for other more common autoimmune conditions, such as rheumatoid arthritis, psoriatic arthritis, osteoarthritis, and dermatomyositis, but the distinctive clinical, radiographic, and histologic features could aid in differentiating these diseases. MRH could mimic other rheumatic diseases, besides, it could also coexist with cancer or other autoimmune disorders. There was no standardized treatment for MRH. However, Nonsteroidal anti-inflammatory drugs, glucocorticoid, Immunosuppressant, biologic medications, and bisphosphonates had been used with varying degrees of curative effect. Treatment with glucocorticoid combined with immunosuppressants were effective for rash and arthritis, early use of them should be strongly considered, and refractory cases could be treated with biological agents. By reporting a MRH case and reviewing literature, this paper aims to help the clinicians improve the understanding of this rare disease, and suggests that when one diagnosis cannot explain the whole picture of the disease, and further evidence should be sought to confirm the diagnosis.

[Prevalence of deep venous thrombosis in chronic refractory wounds and its influencing factors].

Objective: To investigate the incidence and risk factors of lower extremities deep venous thrombosis (DVT) in patients with chronic refractory wounds (chronic wounds). Methods: A retrospective analysis of 722 cases of chronic wounds admitted to the First People's Hospital of Zhengzhou from January 1, 2015 to December 31, 2018 was carried out, and clinical data such as gender, age, wound involves the lower extremities, wound type, duration of wound, D-dimer level and complicated diabetes, hypertension, coronary heart disease, cerebral infarction, pneumonia and sepsis/septic shock were collected. The patients were divided into DVT group and non-DVT group according to the color ultrasound test. Multivariate binary logistic regression analysis was used to screen the independent risk factors of DVT in patients with chronic wounds. Results: There were 55 (7.6%) patients in DVT group, of which 44(80.0%) were diagnosed as chronic DVT by conventional lower extremities venous color ultrasound screening at admission, and the remaining 11(20.0%) were newly diagnosed during hospitalization. There were no significant differences in gender, wound involves the lower extremities, duration of wound, complicated diabetes and hypertension between DVT group and non-DVT group (all P>0.05); and the differences were statistically significant in age, wound type, D-dimer level, complicated coronary heart disease, cerebral infarction, pneumonia and sepsis/septic shock (all P<0.05). Multivariate binary logistic regression analysis showed age [OR=2.260 (95%CI: 1.584-3.224)], D-dimer level [OR=14.201 (95%CI: 6.101-33.055)], complicated coronary heart disease [OR=2.731 (95%CI: 1.210-6.162)] and sepsis/septic shock [OR=3.170 (95%CI: 1.115-9.016)] were independent risk factors for DVT (all P<0.05). Conclusion: Chronic wounds patients have a higher incidence of DVT, most of which are chronic DVT, and age, D-dimer level, complicated coronary heart disease and sepsis/septic shock are independent risk factors for DVT in chronic wounds.

Effect of Left Subclavian Artery Revascularisation in Thoracic Endovascular Aortic Repair: A Systematic Review and Meta-analysis.

OBJECTIVE/BACKGROUND: Thoracic endovascular aortic repair (TEVAR) is an emerging therapy for thoracic aortic pathologies. However, the role of left subclavian artery (LSA) revascularisation in patients with LSA coverage in TEVAR has not been established. A systematic review and meta-analysis was done to investigate the effect of LSA revascularisation in TEVAR when the LSA was covered. METHODS: PubMed, Embase, and the Cochrane Library were searched to find relevant randomised controlled trials (RCTs) and cohort studies. The Cochrane Risk of Bias Tool and Newcastle-Ottawa Scale was used to evaluate the methodological quality of RCTs and cohort studies respectively. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated to express differences for dichotomous outcomes. Random effects models were used to combine outcomes for studies with I2 > 50%; otherwise, fixed effects models were used. Subgroup analyses and sensitivity analyses were performed to further validate the results. RESULTS: Sixteen cohort studies with a total of 2591 patients were included in this systematic review and meta-analysis. The average score of the included studies was 7.56. Of the included patients, the peri-operative stroke rate was 6.8% (n = 176/2591). The peri-operative stroke rates of the with and without LSA revascularisation groups were 5.4% and 7.8%, respectively. Compared with no LSA revascularisation, patients with LSA revascularisation had a significantly lower peri-operative stroke rate (RR 0.61; 95% CI 0.45-0.82; I2 = 20%) and peri-operative spinal cord ischaemia (SCI) rate (RR 0.59; 95% CI 0.39-0.90; I2 = 0). No significant difference was found between the with and without LSA revascularisation groups with respect to peri-operative mortality (RR 0.86; 95% CI 0.60-1.21; I2 = 35%) and peri-operative paraplegia (RR 0.81; 95% CI 0.45-1.44; I2 = 17%). CONCLUSION: The results of this review reveal that LSA revascularisation was associated with significantly lower peri-operative stroke and SCI rates. LSA revascularisation should be recommended for patients with LSA coverage in TEVAR. High quality RCTs are needed to further validate the conclusion.

[The contamination and dietary exposure analysis for seven mycotoxins in the Fifth Chinese Total Diet Study].

Objective: To investigate the contamination levels and dietary intakes of seven mycotoxins in Chinese diets. Methods: In Chinese Total Diet Study, food aggregation was based on the food consumption of local residents, thus generating the sampling scheme. According to the sampling scheme, the food items were sampled at three survey points in each province and then mixed in the same proportion. The mixed dietary samples were prepared after being cooked and processed. The samples comprised of 13 categories of food: cereals, beans, potatoes, meat, eggs, aquatic products, milk, vegetables, fruits, saccharides, beverages and drinking water, alcohol, and condiments. Condiments were used in cooking, so there were in total 12 varieties of samples for determination. Altogether, the study included 240 mixed dietary samples from 20 provinces with 12 varieties. The contamination levels of the seven mycotoxins, including sterigmatocystin (SMC), citrinin (CIT), cyclopiazonic acid (CPA), moniliformin (MON), gliotoxin (GLIO), mycophenolateacid (MPA) and verruculogen (Verru), were analyzed by UPLC-MS/MS method, and dietary intakes of residents were estimated as well. Results: Among the detected seven mycotoxins, MPA,GLIO and Verru were not detected. The content range of CPA in beans was 0.47-1.57 µg/kg and in alcohol was 0.19-2.26 µg/kg, and the detection rate of CPA was 7.1% (17/240). The content of SMC in aquatic products of Guangxi, in saccharides of Beijing, and in beverages of Liaoning was 2.88 µg/kg, 0.01 µg/kg, and 0.53 µg/kg, respectively. The content range of SMC in aquatic products was 0.70-1.76 µg/kg, and the detection rate was 2.9% (7/240). In addition, the content of CIT in fruit of Sichuan was 5.31 µg/kg, and the content of MON in milk of Jilin was 3.60 µg/kg. According to the dietary exposure analysis, the exposure levels of the seven mycotoxins in China's general population were low. MPA, GLIO and Verru were not detected, and the exposure range of the other four mycotoxins were 0.000-8.132 (CIT), 0.000-27.448 (SMC), 0.000-3.026 (CPA), and 0.000-62.847 ng·kg(-1)·d(-1) (MON), respectively. Conclusion: In the detected seven mycotoxins, CPA, SMC, CIT and MON were detected only in the individual diet in some areas with a low dietary exposure level. However, the contamination level of CPA in alcohol merits attention.

Identification and comparative proteomic study of quail and duck egg white protein using 2-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry analysis.

A proteomic study of egg white proteins from 2 major poultry species, namely quail (Coturnix coturnix) and duck (Anas platyrhynchos), was performed with comparison to those of chicken (Gallus gallus) through 2-dimensional polyacrylamide gel electrophoresis (2-DE) analysis. By using matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF MS/MS), 29 protein spots representing 10 different kinds of proteins as well as 17 protein spots designating 9 proteins were successfully identified in quail and duck egg white, respectively. This report suggested a closer relationship between quail and chicken egg white proteome patterns, whereas the duck egg white protein distribution on the 2-DE map was more distinct. In duck egg white, some well-known major proteins, such as ovomucoid, clusterin, extracellular fatty acid-binding protein precursor (ex-FABP), and prostaglandin D2 synthase (PG D2 synthase), were not detected, while two major protein spots identified as "deleted in malignant brain tumors 1" protein (DMBT1) and vitellogenin-2 were found specific to duck in the corresponding range on the 2-DE gel map. These interspecies diversities may be associated with the egg white protein functions in cell defense or regulating/supporting the embryonic development to adapt to the inhabiting environment or reproduction demand during long-term evolution. The findings of this work will give insight into the advantages involved in the application on egg white proteins from various egg sources, which may present novel beneficial properties in the food industry or related to human health.

Estimation of egg freshness using S-ovalbumin as an indicator.

The aim of this research was to study S-ovalbumin as a reference index for the freshness of commercial shell eggs in terms of equivalent egg age. The S-ovalbumin content, yolk index, albumen pH, and Haugh units were determined at the storage temperature of 25 and 37°C, respectively, using 85 fresh-laid eggs. A correlation analysis showed a high correlation coefficient of S-ovalbumin content to storage time as well as to the 3 frequently used freshness indices (Haugh unit, yolk index, and albumen pH). Furthermore, a prediction model of equivalent egg age at 25°C was established using S-ovalbumin content as an index on the basis of the correlation analysis. This study confirmed the possibility of using S-ovalbumin as a reference index to express commercial shell egg freshness as equivalent egg age.

Ruptured hepatocellular carcinoma disguising as heterotopic pregnancy.

The incidence of hepatocellular carcinoma (HCC) in pregnancy is rare but is typically aggressive, with a 1-year survival rate of 23%. One of the complications of HCC is spontaneous rupture, resulting in haemoperitoneum. A 36-year-old pregnant Chinese immigrant who was positive for hepatitis B virus and in her first trimester presented to the emergency department of Wyong Hospital, Hamlyn Terrace, New South Wales, Australia, with severe epigastric and right upper quadrant pain and haemodynamic instability. Spontaneous rupture of a heterotopic pregnancy was initially suspected. However, histopathological staining of the lesions excised during surgery revealed HCC. To our knowledge, this is the first case of spontaneous rupture of HCC with haemoperitoneum during pregnancy in Australia. As developed countries receive global migrants, similar cases may be seen in the future. Epidemiological studies suggest that immigrants from China and Vietnam have the highest incidence of chronic hepatitis B virus carrier status.

[Structural change of the corpus callosum fibers in toddlers with autism spectrum disorder: two-year follow-up].

Objective: To conduct a follow-up investigation of structural changes of the corpus callosum fibers of toddlers (2 to 5 years of age) with autism spectrum disorder(ASD) and to explore the associations with clinical symptoms. Method: In this prospective randomized controlled study, ASD children who were diagnosed in the Child Mental Health Research Center, Nanjing Brain Hospital Affiliated to Nanjing Medical University from May 2011 to November 2012 were included in the ASD group, and developmentally delayed children were included in the control group (DD group). Diffusion tensor imaging (DTI) data from the two groups were obtained at two age levels: 2-3 years of age, and 4-5 years of age. Region of interest analysis was applied to assess characteristic values of total area and sub-regions of corpus callosum: the fraction anisotropy (FA), the mean diffusivity (MD), the radial diffusivity (RD) and the axial diffusivity (AD). All children were assessed using the Autism Diagnostic Interview-Revised (ADI-R) and Autism Treatment Evaluation Checklist (ATEC). The characteristic values of total area and sub-regions of corpus callosum of ASD group at two age levels were analyzed by paired sample t test; the characteristic values of total area and sub-regions of corpus callosum of ASD group and DD group were analyzed by independent-sample t test; the correlations between FA values of the total area and sub-regions of corpus callosum and ADI-R or ATEC scores were analyzed by Pearson correlation analysis. Result: Forty cases meeting inclusion criteria were enrolled in ASD group, and 31 eligible cases were enrolled in the control group. Four children in the ASD group were lost to follow-up, and 5 children in the control group were lost to follow-up. Longitudinal comparison between the two age subgroups of ASD patients showed that the FA values of the total corpus callosum increased (0.499 55±0.027 59 vs. 0.505 83±0.086 64, t=4.88, P<0.05), but MD values, RD values and AD values of the total corpus callosum area decreased (0.000 89±0.000 03 vs. 0.000 81±0.000 14, 0.000 61±0.000 04 vs. 0.000 55±0.000 09, 0.001 43±0.000 03 vs. 0.001 38±0.000 03, t=9.31, 7.90, 8.66, P<0.05 for all comparisons). In the area of corpus callosum genu, FA and AD values increased (t=5.59, 8.48, P<0.05 for both comparisons), but MD and RD values decreased (t=12.67, 11.28, P<0.05 for both comparisns). In the area of corpus callosum body, FA and RD values increased(t=5.46, 8.48, P<0.05 for both comparisons), but MD and AD values decreased (t=8.08, 6.22, P<0.05 for both comparisons). In the area of corpus callosum splenium, MD, RD and AD values decreased (t=6.81, 4.44, 5.51, P < 0.05 for all comparisons). Among the participants 2 to 3 years of age, there were no significantly differences in FA values of total area and sub-regions of corpus callosum between ASD group and the DD group (P > 0.05 for all comparisons); as compared with the DD group, ASD group had higher AD values of total area and splenium of corpus callosum (0.001 43±0.000 03 vs. 0.001 40±0.000 04, 0.001 34±0.000 03 vs. 0.001 32±0.000 04, t=1.56, 1.14, P < 0.05 for both comparisons); ASD group had lower AD values but higher RD and MD values of corpus callosum genu (t=0.07, 0.55, 0.07, P < 0.05 for all comparisons); ASD group had lower RD values of corpus callosum body (t=0.07, P < 0.05). Among the participants 4 to 5 years of age, as compared with the DD group, ASD group had higher FA value of total corpus callosum area(0.505 83±0.086 64 vs. 0.483 77±0.099 30, t=8.56, P < 0.05), lower RD value of total corpus callosum(0.000 55±0.000 09 vs. 0.000 56±0.000 12, t=14.44, P < 0.05), lower RD values of corpus callosum body (t=2.20, P < 0.05), higher FA values (t=3.35, P < 0.05) but lower AD values of corpus callosum splenium (t=2.20, P < 0.05). A correlation analysis between FA values of total area and sub-regions of corpus callosum and clinical variables showed that the FA values of total area and splenium of corpus callosum in ASD group at 2 to 3 years of age were negatively correlated with the scores of language skills in ATEC (r=-0.35,-0.36, P < 0.05 for both comparisons). And after two years, FA values of total corpus callosum were positively correlated with the scores of social communication in ATEC (r=0.34, P < 0.05). There was no significant correlation between FA values of sub-regions of corpus callosum and the scores of ATEC (P > 0.05 for all comparisons). There was no significant correlation between FA values of total area and sub-regions of corpus callosum and the scores of ADI-R (P > 0.05 for all comparisons). Conclusion: The fiber structure of corpus callosum was still in the process of maturing during the age of 2 to 5 years; however, compared with DD group, ASD group had more extensive structural abnormalities of the corpus callosum fibers as age increased, and the structural abnormalities had correlation with the core symptoms of ASD. Trial registration Chinese Clinical Trial Registry, ChiCTR-OPC-17011995.

Restriction site-free insertion of PCR products directionally into vectors.

A restriction site-free cloning method has been developed for inserting a PCR product into a vector flexibly and precisely at any desired location with high efficiency. The method uses a pair of DNA integration primers with two portions. The 3' portion isolates the inserts by PCR, and the 5' portion integrates the PCR products into the homologous region of the vector. For mutagenesis, a third portion of mutation-generating sequences can be placed in between the 3' and 5' portions. This method has been used to clone the E. coli gene that codes for peptidyl-tRNA hydrolase, expressing it as a native protein and as a glutathione S-transferase fusion protein. It was also applied to convert a construct of the E. coli fatty acid biosynthesis protein with an N-terminal hexa-histidine tag into a construct with a C-terminal hexa-histidine tag.

[Distributions and gene frequencies of PGM1 subtype, EsD, GLO1, AK, ADAand 6-PGD in 20 races of China].

The distributions and gene frequencies of PGM1, subtype EsD, GLO1, AK, ADA and 6-PGD of 4171 healthy donors in 20 races of China were detected using gel electrophoresis. Some isoenzymes such as PGM1, PGM1 subtype, EsD and GLO1 have better distribution and higher discriminating power than the others. Sixty-eight samples with PGM1(6) gene were observed in 12 races. The frequency in zhuang population is the highest among 20 races. The phenotype of PGM1 6-1 is up to 4.15%. The band of PGM1(6) of all 68 samples is in the same position in the gel. In general speaking, the gene frequencies of EsD in most races of southern part of China are higher than those of northern part. Phenotype EsD 2 in Hani, Lisu, Dai, Naxi, She, Zhuang, Dong, Miao are over 15%, Hani is up to 32.4%. The gene frequency of GLO1 in Tajik and Uygur are 0.297 and 0.2112 respectively. The others range from 0.0714 to 0.1527. In Qiang it is 0.0583. The gene frequencies of AK1. ADA1 and 6-PGDA are very high in 20 races, and with very low discriminating power.

[Analysis of musk rheumatic oil by GC/FTIR].

This paper studied musk rheumatic oil by GC/FTIR. Ten main components were identified qualitatively, and methyl salicylate, eugenol, cinnamaldehyde were determined by GC internal standard method quantitatively. Average recoveries are within 100 +/- 1.0%, variation coefficients are less than 2.0%.

[Studies on the analytical method of a new anti-arrhythmic guan-fu base A in rabbit plasma].

Guan-fu base A, a new antiarrhythmic alkaloid with a structure of C20-diterpenoid, was first isolated from the tuber of Aconitum coreanum (Levl.) Raipaics in China in 1966. An analytical method of GC-ECD has been established in this paper for the determination of its concentration in rabbit plasma in order to study its pharmacokinetics in preclinical pharmacology. Guan-fu base A and the internal standard alprenolol (ALP) was found to react rapidly and quantitatively with trifluoroacetic anhydride (TFAA) to produce derivatives GFA-TFAA and ALP-TFAA which were identified by GC-MSD. An optimal GC-ECD system for the separation and determination of the derivatives following the sample preparation was established. There was a wide linear range of the method from 10-2 x 10(4) ng/ml (r = 0.9984). The average recovery of Guan-fu base A from the spiked plasma was 97.52%. The coefficient of variation of between-day and within-day were less than 9% and 7%, respectively. The method was used to determine Guan-fu base A in the plasma of 15 rabbits following intravenous administration of 3 dosages of 0.4, 2 and 10 mg per kg of body weight.

Determination of Guan-Fu Base A, a new anti-arrhythmic, in human plasma by gas chromatography and electron-capture detection.

A gas chromatographic-electron capture detection (GC-ECD) method has been developed for determining Guan-Fu Base A (GFA), an experimental anti-arrhythmic, in human plasma. The method was based on one-step liquid-liquid extraction with toluene and chemical derivatization with pentafluoropropionic anhydride followed by GC-ECD. The derivatives of GFA and metoprolol (Met, internal standard) were confirmed by gas chromatography-mass spectrometry (GC-MS) to be dipentafluoropropionyl-GFA and dipentafluoropropionyl-Met. The method was linear over the concentration ranges of 0.1-20.0 and 1.0-30.0 microg/ml with the detection limit of 0.05 microg/ml at S/N=5. The intra- and inter-assay precisions were less than 6 and 10%, and accuracy 99.70+/-3.30 and 97.60+/-5.99%, respectively. The absolute recoveries were 81.88, 77.35, 80.79 and 83.85% for GFA at concentrations of 0.5, 1.0, 5.0 and 14.0 microg/ml and 88.24% for Met at 3.0 microg/ml, respectively.

ATP hydrolysis is not required for the dissociation of a substance P.BiP complex.

BiP is a member of the hsp70 family of proteins that is present in the endoplasmic reticulum where it functions as a molecular chaperone. Rapid quantitative assays have been used to study the effect of mutating BiP residue 229, located in the ATP binding site, from threonine to glycine. Although binding of ATP to the mutant BiP was not affected, the mutant protein possessed 10-20% of the wild-type BiP ATPase activity. Binding to a model peptide substrate, substance P (Brot et al. (1994) Proc. Natl. Acad. Sci. USA 91, 12120-12124), was twofold higher with mutant BiP at 4 degrees C than with wild-type BiP, and was ATP dependent. Under these conditions the substance P that was bound to mutant BiP, but not the wild-type, could be released by higher levels of ATP (5-10 microM), and the ratio of substance P released to ATP hydrolyzed was greater than 10. These results suggest that stoichiometric ATP hydrolysis is not required for release of a chaperone from its substrate.

Interaction of BiP with substance P and nucleotides.

A rapid and simple spin column assay has been used to study interactions of BiP with substance P (SP) and ATP. At 4 degrees C, the binding of SP to BiP requires ATP and a stable SP-BiP.ATP complex is formed. Nonhydrolyzable ATP analogues or ADP cannot replace ATP. Although ATP converts BiP dimers to monomers, the requirement for ATP for SP binding is not solely due to BiP dissociation, because purified BiP monomers also require ATP for peptide binding. At 37 degrees C, there is rapid binding of SP to BiP even in the absence of ATP and, in fact, ATP at concentrations above 5 microM causes release of SP from BiP. At this higher temperature, there is also rapid hydrolysis of ATP bound to BiP. These results extend our previous results (Brot et al., 1994) that indicated the formation, at low ATP concentrations, of a labile SP.BiP.ATP complex that, after ATP hydrolysis, resulted in a stable SP.BiP.ADP complex.

Similarity of nucleotide interactions of BiP and GTP-binding proteins.

BiP is a member of the Hsp70 heat shock protein family found in the lumen of the endoplasmic reticulum, that binds to a variety of proteins destined to be secreted. Substance P (SP) has been used as a model peptide to study the interaction of BiP with protein substrates. SP stimulates BiP ATPase activity and forms a stable complex with BiP that is dissociated in the presence of levels of ATP > 50 microM. At lower concentrations of ATP, the SP remains bound to BiP, and the results are consistent with the view that a BiP-ATP complex is initially formed that reacts with SP to form a ternary complex, SP-BiP-ATP. Hydrolysis of ATP in this complex yields a SP-BiP-ADP complex. An exchange of ATP with ADP bound to BiP has also been demonstrated, and the results suggest that the interactions of BiP with ATP resemble those seen with GTP-binding proteins and GTP.

In vivo activity of posaconazole against Mucor spp. in an immunosuppressed-mouse model.

The in vivo activities of posaconazole, itraconazole, and amphotericin B in neutropenic mice with zygomycosis were compared. The in vitro MICs of posaconazole and itraconazole for the strains of Mucor spp. used in this study ranged from 0.125 to 8 microg/ml and 0.25 to 8 microg/ml, respectively. The in vitro MIC range for amphotericin B is 0.125 to 0.25 microg/ml. At twice-daily doses of >or=15 mg/kg of body weight, posaconazole prolonged the survival of the mice and reduced tissue burden.