Treatment with normobaric or hyperbaric oxygen and its effect on neuropsychometric dysfunction after carbon monoxide poisoning: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Carbon monoxide (CO) poisoning may result in acute neurological sequelae, cognitive sequelae, and delay neurological sequelae. The administration of hyperbaric oxygen (HBO) to prevent the development of delayed neurological sequelae in CO poisoning have extensively investigated but conflicting results have been reported. We performed a systematic literature review and meta-analysis of randomized controlled trials (RCTs) evaluating HBO treatment and its effect on neuropsychometric dysfunction after CO poisoning. METHODS: We searched Medline, Embase, Pubmed, and the Cochrane Register of Controlled Trials from inception to December 2017. Eligible studies compared HBO therapy with normobaric oxygen (NBO) in patients with CO poisoning. RESULTS: Six studies compared HBO with NBO in CO poisoning patients. Compared with patients treated with NBO, a lower percentage of patients treated with HBO reported headache (16.2% vs 16.5%, relative risk [RR] = 0.83, 95% CI = 0.38-1.80), memory impairment (18.2% vs 23.8%, RR = 0.80, 95% CI = 0.43-1.49), difficulty concentrating (15.0% vs 18.4%, RR = 0.86, 95% CI = 0.55-1.34), and disturbed sleep (14.7% vs 16.2%, RR = 0.91, 95% CI = 0.59-1.39). Two sessions of HBO treatment exhibited no advantage over one session. CONCLUSIONS: The meta-analysis indicated that compared with CO poisoning patients treated with NBO, HBO treated patients have a lower incidence of neuropsychological sequelae, including headache, memory impairment, difficulty concentrating, disturbed sleep, and delayed neurological sequelae. Taking into consideration the cost-effectiveness of one session of HBO, one session of HBO treatment could be an economical option for patients with CO poisoning with high severity.

Safety and efficacy of ferric citrate in phosphate reduction and iron supplementation in patients with chronic kidney disease.

Ferric citrate has been reported to have the potential to reduce phosphate and increase iron availability in patients with chronic kidney disease. In the present study, we evaluated its safety and efficacy in phosphate reduction and iron supplementation in chronic kidney disease stage 3-5 requiring dialysis patients. We systematically searched for clinical trials published in PubMed, Medline, and Cochrane databases. Only randomized controlled trials on the effects of ferric citrate in chronic kidney disease stage 3-5 requiring dialysis patients were selected. The primary outcomes were changes in serum phosphate, calcium, and anemia-related parameters. The secondary outcomes were the adverse effects of ferric citrate. Nine studies providing data on 1755 patients were included in the meta-analysis. Ferric citrate significantly reduced serum phosphate compared with placebo (mean difference, -1.39; 95% confidence interval, -2.12 to -0.66) and had a non-inferior effect compared with active treatment. Furthermore, ferric citrate significantly improved hemoglobin, transferrin saturation and ferritin. Adverse effects of constipation did not differ significantly between ferric citrate and placebo or active treatment. This review provides evidence that ferric citrate effectively alleviates hyperphosphatemia and iron deficiency in patients with chronic kidney disease stage 3-5 requiring dialysis patients. However, the included studies did not have cardiovascular complications or mortality information and could not assess whether ferric citrate affected the risk of all-cause death or cardiovascular complications in patients with chronic kidney disease. Further studies are required to assess whether the long-term use of ferric citrate can reduce the risk of cardiovascular events and all-cause mortality.

Efficient Mapping of Sulfated Glycotopes by Negative Ion Mode nanoLC-MS/MS-Based Sulfoglycomic Analysis of Permethylated Glycans.

We have previously developed the enabling techniques for sulfoglycomics based on mass spectrometry (MS) analysis of permethylated glycans, which preserves the attractive features of more reliable MS/MS sequencing compared with that performed on native glycans, while providing an easy way to separate and hence enrich the sulfated glycans. Unlike LC-MS/MS analysis of native glycans in negative ion mode that has been more widely in use, the characteristics and potential benefits of similar applications based on permethylated sulfated glycans have not been fully investigated. We report here the important features of reverse phase-based nanoLC-MS/MS analysis of permethylated sulfated glycans in negative ion mode and demonstrate that complementary sets of diagnostic fragment ions afforded can allow rapid identification of various fucosylated, sialylated, sulfated glycotopes and definitive determination of the location of sulfate in a way difficult to achieve by other means. A parallel acquisition of both higher collision energy and trap-based MS(2) coupled with a product dependent MS(3) is conceivably the most productive sulfoglycomic workflow currently possible and the manually curated fragmentation characteristics presented here will allow future developments in automating data analysis.

Isolation and characterization of φkm18p, a novel lytic phage with therapeutic potential against extensively drug resistant Acinetobacter baumannii.

AIMS: To isolate phages against extensively drug resistant Acinetobacter baumannii (XDRAB) and characterize the highest lytic capability phage as a model to evaluate the potential on phage therapy. METHODS AND RESULTS: Eight phages were isolated from hospital sewage and showed narrow host spectrum. Phage φkm18p was able to effectively lyse the most XDRAB. It has a dsDNA genome of 45 kb in size and hexagonal head of about 59 nm in diameter and no tail. Bacterial population decreased quickly from 10(8) CFU ml(-1) to 10(3) CFU ml(-1) in 30 min by φkm18p. The 185 kDa lysis protein encoded by φkm18p genome was detected when the extracted protein did not boil before SDS-PAGE; it showed that the lysis protein is a complex rather than a monomer. Phage φkm18p improved human lung epithelial cells survival rates when they were incubated with A. baumannii. Combination of phages (φkm18p, φTZ1 and φ314) as a cocktail could lyse all genotype-varying XDRAB isolates. CONCLUSION: Infections with XDRAB are extremely difficult to treat and development of a phage cocktails therapy could be a therapeutic alternative in the future. Phage φkm18p is a good candidate for inclusion in phage cocktails.

Silibinin and Paclitaxel Cotreatment Significantly Suppress the Activity and Lung Metastasis of Triple Negative 4T1 Mammary Tumor Cell in Mice.

The in vitro and in vivo bioactivities of silibinin (SB), paclitaxel (PTX) and SB and PTX in combination (SB+PTX) against murine metastatic mammary 4T1 cancer cell line were investigated. Isobologram and combination index (CI) analyses showed that SB and PTX can function synergistically in the inhibition of 4T1 cell proliferation with a CI value < 1. Both SB and PTX alone or SB+PTX treatment inhibited 4T1 cell migration and motility possibly through downregulation of the serpin protease nexin-1 (PN-1) and N-cadherin expression, inhibition of matrix metalloprotease (MMP)-9 activity, and upregulation of E-cadherin. Flow cytometry and Western blot analyses demonstrated that both drugs deregulated cell-cycle mediators and induced apoptosis in 4T1 cells. A real-time in vivo bioluminescence imaging system to monitor the breast cancer cell metastasis in syngeneic BALB/c mice was established using a stable 4T1(pGL-COX-2/Luc) cell clone carrying a COX-2 promoter driven-luciferase reporter gene. In vivo study using the allograft 4T1(pGL-COX-2/Luc) metastatic mouse model indicated that SB co-treated with PTX can significantly suppress lung metastasis of 4T1 cells likely through inhibiting cell proliferation and angiogenesis. Together, this study demonstrates that SB could act synergistically with PTX in 4T1 cells, providing a therapeutic option for highly metastatic triple negative breast cancer.

Screening for HIV protease inhibitors by protection against activity-mediated cytotoxicity in Escherichia coli.

Expressed retroviral proteases are often cytotoxic to the hosts. The cytotoxicity of a tethered dimer HIV protease described previously is particularly severe that transformed Escherichia coli cells could not survive the bactericidal activity of the low-level protease produced under uninduced conditions. The presence of HIV protease inhibitors protected the transformed cells from cytotoxic effects and allowed the growth of these cells on plates and in broth. A high throughput screening method was developed to seek compounds that served as "growth factors" for the HIV protease restricted cells. Several compounds identified by this screening supported the growth of these cells, preserved their viability, and inhibited HIV protease. This assay could be used as a general method for screening for inhibitors of recombinant enzymes that produce a cytotoxic phenotype in host cells.

Antitumor mechanism of evodiamine, a constituent from Chinese herb Evodiae fructus, in human multiple-drug resistant breast cancer NCI/ADR-RES cells in vitro and in vivo.

Drug resistance is one of the main obstacles to the successful treatment of cancer. The availability of agents that are highly effective against drug-resistant cancer cells is therefore essential. The present study was performed to examine the anticancer effects of evodiamine, a major constituent of the Chinese herb Evodiae fructus, in adriamycin-resistant human breast cancer NCI/ADR-RES cells. Evodiamine inhibited the proliferation of NCI/ADR-RES cells in a concentration-dependent manner with a GI50 of 0.59 +/- 0.11 microM. This agent also caused a substantial apoptosis at 1 microM. FACScan flow cytometric analysis of cell cycle progression revealed that a G2/M arrest was initiated after a 12-h exposure to the drug. Evodiamine increased tubulin polymerization as determined by the immunocytochemical and in vivo tubulin polymerization analyses. In a time- and concentration-dependent manner, evodiamine also promoted the phosphorylations of Raf-1 kinase and Bcl-2. The phosphorylation site of Raf-1 kinase was identified to be serine338. The in vivo anticancer effects of evodiamine were evaluated in Balb-c/nude mice following a tumor xenograft implantation of NCI/ADR-RES cells. The antitumor activity of evodiamine against the human multiple-drug resistant tumor xenograft was found to be superior to that of paclitaxel. Evodiamine therefore represents a highly promising chemotherapeutic agent in the treatment of human multiple-drug resistant cancer cells.

Studies on the immuno-modulating and antitumor activities of Ganoderma lucidum (Reishi) polysaccharides: functional and proteomic analyses of a fucose-containing glycoprotein fraction responsible for the activities.

A fucose-containing glycoprotein fraction which stimulates spleen cell proliferation and cytokine expression has been identified from the water-soluble extract of Ganoderma lucidum. Proteomic analysis of mouse spleen cells treated with this glycoprotein fraction showed approximately 50% change of the proteome. Further studies on the activities of this glycoprotein fraction through selective proteolysis and glycosidic cleavage indicate that a fucose containing polysaccharide fraction is responsible for stimulating the expression of cytokines, especially IL-1, IL-2 and INF-gamma.