Aerosolized amphotericin B as prophylaxis for invasive pulmonary aspergillosis: a meta-analysis

SummaryObjectivesInvasive pulmonary aspergillosis (IPA) is associated with high mortality in high-risk (immunosuppressed) patients. Many studies have investigated whether prophylactic inhalation of amphotericin B (AMB) reduces the incidence of IPA, but no definitive conclusions have been reached. The present meta-analysis was performed to evaluate the efficacy of prophylactic inhalation of AMB for the prevention of IPA.MethodsMEDLINE and other databases were searched for relevant articles published until December 2013. Randomized controlled trials that compared aerosolized AMB with placebo were included. Two reviewers independently assessed and extracted the data of all trials.ResultsSix animal studies and two clinical trials involving 768 high-risk patients were eligible. The animal studies showed lower overall mortality rate among animals that underwent aerosolized AMB prophylaxis (odds ratio (OR) 0.13, 95% confidence interval (CI) 0.08–0.21). Similarly, the clinical trials showed a lower incidence of IPA among patients who underwent aerosolized AMB prophylaxis (OR 0.42, 95% CI 0.22–0.79).ConclusionsThis analysis provides evidence supporting the notion that the prophylactic use of aerosolized AMB effectively reduces the incidence of IPA among high-risk patients

Efficacy of the Combination of Voriconazole and Caspofungin in Experimental Pulmonary Aspergillosis by Different Aspergillus Species

OBJECTIVES: Invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus, Aspergillus flavus, or Aspergillus niger is associated with high mortality. We evaluated the efficacy and compared the therapeutic effect differences of voriconazole (VRC) in combination with caspofungin (CAS) in transiently neutropenic rats infected by A. fumigatus, A. flavus, or A. niger. METHODS: Treatment groups consisted of VRC (10 mg/kg q12 h) monotherapy, CAS (1 mg/kg/day) monotherapy, combination of VRC (10 mg/kg q12 h) + CAS (1 mg/kg/day), and no drug for 10 consecutive days. The efficacy and the difference in the treatments were evaluated through prolongation of survival, reduction in serum galactomannan levels and residual fungal burden, and histological studies. RESULTS: For all the strains, the combination of VRC and CAS led to significant prolongation in survival (P < 0.05) and reduction in residual fungal burden (P < 0.05) compared with CAS alone, and decrease in serum galactomannan levels (P < 0.05) compared with either agent alone. The survival in the combined therapy groups was significantly improved compared to VRC monotherapy for the strains of A. flavus and A. niger (P < 0.05), but no significant difference for the strains of A. fumigatus (P > 0.05). CONCLUSIONS: Combination of VRC and CAS was synergistic in IPA by A. flavus and A. niger, but small efficacy benefits in IPA by A. fumigatus

1,4-Bis(4,5-dihydro-1H-imidazol-2-yl)benzene–terephthalic acid–water (1/1/4)

The asymmetric unit of the title compound, C12H14N4·C8H6O4·4H2O, consists of one half of the 1,4-bis­(4,5-dihydro-1H-imidazol-2-yl)benzene (bib) mol­ecule, one half of the terephthalic acid (TA) mol­ecule and two water mol­ecules. Both the bib and the TA mol­ecules reside on crystallographic inversion centers, which coincide with the centroids of the respective benzene rings. The bib and the TA, together with the water mol­ecules, are linked through inter­molecular O—H⋯O, O—H⋯N and N—H⋯O hydrogen bonds, forming a three-dimensional network of stacked layers. Weak inter­molecular C—H⋯O contacts support the stability of the crystal structure

The pyrrolidinoindoline alkaloid Psm2 inhibits platelet aggregation and thrombus formation by affecting PI3K/Akt signaling

Psm2, one of the pyrrolidinoindoline alkaloids isolated from whole Selaginella moellendorffii plants, has shown a potent antiplatelet activity. In this study, we further evaluated the antiplatelet effects of Psm2, and elucidated the underlying mechanisms

Quenched Charmed Meson Spectra using Tadpole Improved Quark Action on Anisotropic Lattices

Charmed meson charmonium spectra are studied with improved quark actions on anisotropic lattices. We measured the pseudo-scalar and vector meson dispersion relations for 4 lowest lattice momentum modes with quark mass values ranging from the strange quark to charm quark with 3 different values of gauge coupling $\beta$ and 4 different values of bare speed of light $\nu$. With the bare speed of light parameter $\nu$ tuned in a mass-dependent way, we study the mass spectra of $D$, $D_s$, $\eta_c$, $D^{\ast}$, $D_s^{\ast}$ and $J/\psi$ mesons. The results extrapolated to the continuum limit are compared with the experiment and qualitative agreement is found.Comment: 8 pages, 2 figures, latex fil

Proteomics profiling asthma induced-lysine acetylation

Asthma is a chronic inflammatory disease that has been extensively studied for many years. However, finding a complete cure remains a significant challenge. Protein acetylation, especially histone acetylation, plays a significant role in the anti-asthma process. Histone deacetylation inhibitors (HDACi) have been shown to have a curative effect on asthma in clinical practice. An asthmatic mouse model was created by ovalbumin induction. Proteome and acetylproteome analysis were performed on lung tissues. HDACi were tested in the asthmatic mice. A total of 5346 proteins and 581 acetylation sites were identified, among which 154 proteins and 68 acetylation peptides were significantly altered by asthma. Many activated and deactivated processes, pathways, and protein groups were identified through bioinformatics analysis. Sequence motif preference analysis gave rise to a novel Kac-related core histone region, -KAXXK-, which was postulated as a key regulatory unit of histone acetylation. Asthma involves a variety of proteome dynamics and is controlled by protein lysine acetylation through the core motif -KAXXK-. These findings provide novel avenues to target and treat asthma

A Novel Direct Factor Xa Inhibitory Peptide with Anti-Platelet Aggregation Activity from Agkistrodon acutus Venom Hydrolysates

Snake venom is a natural substance that contains numerous bioactive proteins and peptides, nearly all of which have been identified over the last several decades. In this study, we subjected snake venom to enzymatic hydrolysis to identify previously unreported bioactive peptides. The novel peptide ACH-11 with the sequence LTFPRIVFVLG was identified with both FXa inhibition and anti-platelet aggregation activities. ACH-11 inhibited the catalytic function of FXa towards its substrate S-2222 via a mixed model with a Ki value of 9.02 μM and inhibited platelet aggregation induced by ADP and U46619 in a dose-dependent manner. Furthermore, ACH-11 exhibited potent antithrombotic activity in vivo. It reduced paralysis and death in an acute pulmonary thrombosis model by 90% and attenuated thrombosis weight in an arterio-venous shunt thrombosis model by 57.91%, both at a dose of 3 mg/kg. Additionally, a tail cutting bleeding time assay revealed that ACH-11 did not prolong bleeding time in mice at a dose of 3 mg/kg. Together, our results reveal that ACH-11 is a novel antithrombotic peptide exhibiting both FXa inhibition and anti-platelet aggregation activities, with a low bleeding risk. We believe that it could be a candidate or lead compound for new antithrombotic drug development

Detection of genome-wide polymorphisms in the AT-rich Plasmodium falciparum genome using a high-density microarray

<p>Abstract</p> <p>Background</p> <p>Genetic mapping is a powerful method to identify mutations that cause drug resistance and other phenotypic changes in the human malaria parasite <it>Plasmodium falciparum</it>. For efficient mapping of a target gene, it is often necessary to genotype a large number of polymorphic markers. Currently, a community effort is underway to collect single nucleotide polymorphisms (SNP) from the parasite genome. Here we evaluate polymorphism detection accuracy of a high-density 'tiling' microarray with 2.56 million probes by comparing single feature polymorphisms (SFP) calls from the microarray with known SNP among parasite isolates.</p> <p>Results</p> <p>We found that probe GC content, SNP position in a probe, probe coverage, and signal ratio cutoff values were important factors for accurate detection of SFP in the parasite genome. We established a set of SFP calling parameters that could predict mSFP (SFP called by multiple overlapping probes) with high accuracy (≥ 94%) and identified 121,087 mSFP genome-wide from five parasite isolates including 40,354 unique mSFP (excluding those from multi-gene families) and ~18,000 new mSFP, producing a genetic map with an average of one unique mSFP per 570 bp. Genomic copy number variation (CNV) among the parasites was also cataloged and compared.</p> <p>Conclusion</p> <p>A large number of mSFP were discovered from the <it>P. falciparum </it>genome using a high-density microarray, most of which were in clusters of highly polymorphic genes at chromosome ends. Our method for accurate mSFP detection and the mSFP identified will greatly facilitate large-scale studies of genome variation in the <it>P. falciparum </it>parasite and provide useful resources for mapping important parasite traits.</p