Biliary tract infection due to bile-soluble bacteria: An intriguing paradox

published_or_final_versio

Liposomes prolong the therapeutic effect of anti-asthmatic medication via pulmonary delivery

Xiaoyu Chen, Wenhua Huang, Blenda Chi Kwan Wong, Linlin Yin, Yuen Fan Wong, Min Xu, Zhijun YangSchool of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong KongPurpose: The main objective of this study was to develop a novel aerosolized liposome formulation for pulmonary delivery of anti-asthmatic medication and to explore the relationship between the bioavailability and anti-asthmatic efficacy of such a formulation. Asthma treatment usually requires frequent administration of medication for sustained bronchodilating response. Liposomes are known for their capability for sustained drug release and thus would be a suitable delivery system for anti-asthmatic medication for prolonged therapeutic effect. Salbutamol sulfate (SBS) was chosen as the model drug in this study because of its high water solubility and fast absorption after administration.Methods: SBS was efficiently encapsulated into liposomes by the vesicular phospholipid gel technique. SBS permeability across the pulmonary membrane of an Asian toad was determined by in vitro study. Intratracheal administration of liposomes labeled with the fluorescent dye 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide (DiR) in a rat model was assessed by a small animal imaging system and pharmacokinetic analysis. Pharmacodynamic analysis was performed in guinea pigs using the Konzett–Rössler method.Results: SBS was efficiently encapsulated into liposomes with encapsulation efficiency as high as 70%. The particle size of the SBS liposome suspension was approximately 57 ± 21 nm. In the in vitro study of permeability across the pulmonary membrane of Asian toads, SBS from liposomes demonstrated a slower transport rate compared to free SBS solution. Pulmonary delivery of liposomes in a rat model showed that the liposomes were effectively distributed in the respiratory tract and lungs, and that the release of SBS from liposomes was sustained for at least 48 hours. Pharmacodynamic analysis in a guinea pig model showed that the anti-asthmatic effect of SBS liposomes persisted for up to 18 hours, whereas that of free SBS solution was less than 8 hours.Conclusion: The overall results demonstrated that liposomes could increase the concentration and retention time of SBS in the lungs and therefore prolong its therapeutic effect.Keywords: salbutamol sulfate, asthma, intratracheal administration, sustained releas

Effectiveness of Chinese herbal medicine in treating liver fibrosis: a systematic review and meta-analysis of randomized controlled trials

<p>Abstract</p> <p>Background</p> <p>The studies on the effectiveness of Chinese herbal medicines (CHM) in treating liver fibrosis (LF) were not consistent. This study aims to systematically review the effectiveness of CHM on treating LF patients.</p> <p>Methods</p> <p>Databases including MEDLINE, AMED, EMBASE, The Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, TCMOnline, Chinese Biomedical Literature Database, and Chinese Medical Current Contents were searched up to March 2011. Randomized controlled trials (RCTs) involving LF patients receiving CHM, Western medicine, combined CHM and Western medicine compared with placebo, Western medicine or no intervention were included. LF markers including serum hyaluronic acid (HA), laminin (LN), procollagen type III (PC-III), type IV collagen (IV-C), matrix metalloproteinase (MMP), and tissue inhibitors of metalloproteinase (TIMP) were measured as primary outcomes. Liver biochemistry, including alanine aminotransferase (ALT) and aspartarte aminotransferase (AST), and improvement of related clinical symptoms were measured as secondary outcomes. Risk of bias of allocation sequence, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases were assessed.</p> <p>Results</p> <p>Twenty-three RCTs with 2123 participants were analyzed in subgroups of types of comparison and study quality. Fifteen studies were graded as good quality. CHM alone and combined with Western medicine showed significant improvements in HA, LN, PC-III and IV-C compared with Western medicine alone. However, there were no significant differences observed between CHM and placebo treatments.</p> <p>Conclusion</p> <p>The current inconclusive results in determining the effectiveness of CHM treatment on LF, due to the poor methodological quality and high heterogeneity of the studies, suggests that large RCTs using standardized Chinese medicine syndrome diagnosis and CHM formulae with longer follow-up are required for further evaluation.</p

An optimized high-performance liquid chromatography (HPLC) method for benzoylmesaconine determination in Radix Aconiti Lateralis Preparata (Fuzi, aconite roots) and its products

<p>Abstract</p> <p>Background</p> <p>Benzoylmesaconine (BMA) is the main <it>Aconitum </it>alkaloid in <it>Radix Aconiti Lateralis Preparata </it>(<it>Fuzi</it>, aconite roots) with potent pharmacological activities, such as analgesia and anti-inflammation. The present study developed a simple and reliable method using BMA as a marker compound for the quality control of processed aconite roots and their products.</p> <p>Methods</p> <p>After extraction, a high-performance liquid chromatography (HPLC) determination of BMA was conducted on a RP-C₁₈column by gradient elution with acetonitrile and aqueous phase, containing 0.1% phosphoric acid adjusted with triethylamine to pH 3.0.</p> <p>Results</p> <p>A distinct peak profile was obtained and separation of BMA was achieved. Method validation showed that the relative standard deviations (RSDs) of the precision of BMA in all intra-day and inter-day assays were less than 1.36%, and that the average recovery rate was 96.95%. Quantitative analysis of BMA showed that the content of BMA varied significantly in processed aconite roots and their products.</p> <p>Conclusion</p> <p>This HPLC method using BMA as a marker compound is applicable to the quality control of processed aconite roots and their products.</p

Prognostic factors in severe exacerbation of chronic hepatitis B

Forty-seven patients with severe hepatitis B exacerbation were compared with patients who had mild exacerbation (n = 96) or no exacerbation (n = 96). Seventeen patients (36.2%) died or underwent liver transplantation. Preexisting cirrhosis and a prothrombin time (PT) of >30 s were associated with adverse outcome in 60.9% and 87.5% of patients, respectively. The rate of adverse outcome increased to 92.3% when albumin levels of ≤35 g/L and bilirubin levels of >200 μM were present. Other factors associated with adverse outcomes included peak bilirubin level, peak PT, time to reach peak PT, and the presence of encephalopathy and/or ascites. There was no difference in the frequency of precore mutations in patients with severe or mild exacerbation or without exacerbation. A significantly lower prevalence of core promoter mutants was found in patients with severe exacerbation (50%), compared with those who had mild exacerbation (81.3%; P = .004). Patients with severe exacerbation of hepatitis B with poor prognostic factors should be considered for early liver transplantation.published_or_final_versio

Correlation of liver stiffness and histological features in healthy persons and in patients with occult hepatitis B, chronic active hepatitis B, or hepatitis B cirrhosis

OBJECTIVES: Liver stiffness measurement using transient elastography has become a popular tool to assess liver fibrosis. The aim of this study was to determine liver stiffness values and histological features in healthy subjects and in patients with chronic hepatitis B (CHB).METHODS: A total of 157 people were included (28 healthy subjects and 18 patients with occult hepatitis B infection, 102 with active CHB, and 9 with end-stage hepatitis B cirrhosis). Histology and liver stiffness measurements were obtained from all patients.RESULTS: The median liver stiffness in healthy subjects and in occult hepatitis B, active hepatitis B, and end-stage cirrhosis patients was 4.6, 4.2, 8.7, and 33.8 kPa, respectively. In healthy subjects and in patients with occult hepatitis B infection, none had significant fibrosis on histology, and all had liver stiffness 7.2 kPa. In patients with active CHB, 32 (31%) had liver stiffness 11.0 kPa, but only four (12%) had cirrhosis on histology. Using liver stiffness to predict cirrhosis in this group had a sensitivity of 100%, a specificity of 69%, a positive predictive value of 10%, and a negative predictive value of 100%. All nine patients with end-stage liver cirrhosis had liver stiffness 11.0 kPa. The overall area under the ROC curve (AUROC) for diagnosing cirrhosis using a cutoff of 11.3 kPa was 0.89.CONCLUSIONS: Liver stiffness measurement has an overall good diagnostic accuracy with excellent negative predictive value. However, in active CHB with elevated alanine aminotransferase (ALT) levels, the positive predictive value for diagnosing cirrhosis is poor, and further studies are needed to optimize the use of transient elastography in this important group. © 2010 by the American College of Gastroenterology.postprin

Virulence determinants, drug resistance and mobile genetic elements of Laribacter hongkongensis: a genome-wide analysis

<p>Abstract</p> <p>Background</p> <p><it>Laribacter hongkongensis </it>is associated with community-acquired gastroenteritis and traveler's diarrhea. In this study, we performed an in-depth annotation of the genes in its genome related to the various steps in the infective process, drug resistance and mobile genetic elements.</p> <p>Results</p> <p>For acid and bile resistance, <it>L. hongkongensis </it>possessed a urease gene cassette, two <it>arc </it>gene clusters and bile salt efflux systems. For intestinal colonization, it possessed a putative adhesin of the autotransporter family homologous to those of diffusely adherent <it>Escherichia coli </it>(<it>E. coli</it>) and enterotoxigenic <it>E. coli</it>. To evade from host defense, it possessed superoxide dismutase and catalases. For lipopolysaccharide biosynthesis, it possessed the same set of genes that encode enzymes for synthesizing lipid A, two Kdo units and heptose units as <it>E. coli</it>, but different genes for its symmetrical acylation pattern, and nine genes for polysaccharide side chains biosynthesis. It contained a number of CDSs that encode putative cell surface acting (RTX toxin and hemolysins) and intracellular cytotoxins (patatin-like proteins) and enzymes for invasion (outer membrane phospholipase A). It contained a broad variety of antibiotic resistance-related genes, including genes related to β-lactam (n = 10) and multidrug efflux (n = 54). It also contained eight prophages, 17 other phage-related CDSs and 26 CDSs for transposases.</p> <p>Conclusions</p> <p>The <it>L. hongkongensis </it>genome possessed genes for acid and bile resistance, intestinal mucosa colonization, evasion of host defense and cytotoxicity and invasion. A broad variety of antibiotic resistance or multidrug resistance genes, a high number of prophages, other phage-related CDSs and CDSs for transposases, were also identified.</p

Transport genes and chemotaxis in Laribacter hongkongensis: a genome-wide analysis

<p>Abstract</p> <p>Background</p> <p><it>Laribacter hongkongensis </it>is a Gram-negative, sea gull-shaped rod associated with community-acquired gastroenteritis. The bacterium has been found in diverse freshwater environments including fish, frogs and drinking water reservoirs. Using the complete genome sequence data of <it>L. hongkongensis</it>, we performed a comprehensive analysis of putative transport-related genes and genes related to chemotaxis, motility and quorum sensing, which may help the bacterium adapt to the changing environments and combat harmful substances.</p> <p>Results</p> <p>A genome-wide analysis using Transport Classification Database TCDB, similarity and keyword searches revealed the presence of a large diversity of transporters (n = 457) and genes related to chemotaxis (n = 52) and flagellar biosynthesis (n = 40) in the <it>L. hongkongensis </it>genome. The transporters included those from all seven major transporter categories, which may allow the uptake of essential nutrients or ions, and extrusion of metabolic end products and hazardous substances. <it>L. hongkongensis </it>is unique among closely related members of <it>Neisseriaceae </it>family in possessing higher number of proteins related to transport of ammonium, urea and dicarboxylate, which may reflect the importance of nitrogen and dicarboxylate metabolism in this assacharolytic bacterium. Structural modeling of two C^₄-dicarboxylate transporters showed that they possessed similar structures to the determined structures of other DctP-TRAP transporters, with one having an unusual disulfide bond. Diverse mechanisms for iron transport, including hemin transporters for iron acquisition from host proteins, were also identified. In addition to the chemotaxis and flagella-related genes, the <it>L. hongkongensis </it>genome also contained two copies of <it>qseB/qseC </it>homologues of the AI-3 quorum sensing system.</p> <p>Conclusions</p> <p>The large number of diverse transporters and genes involved in chemotaxis, motility and quorum sensing suggested that the bacterium may utilize a complex system to adapt to different environments. Structural modeling will provide useful insights on the transporters in <it>L. hongkongensis</it>.</p

Paediatric liver transplantation at Queen Mary Hospital

Conference Theme: Challenges to specialists in the 21st centurypublished_or_final_versio

Clinical outcome and virologic profiles of severe hepatitis B exacerbation due to YMDD mutations

Background/Aims: To study the outcome and the virologic profiles of severe hepatitis exacerbations due to YMDD mutants in lamivudine-treated patients. Methods: Eighteen lamivudine-treated patients with severe hepatitis exacerbations due to YMDD mutants were recruited. Laboratory and clinical parameters were monitored. Viral genotypes and YMDD mutations were determined. Results: None of the 18 patients had YMDD wild-type during exacerbations. Three (17%) and 15 (83%) patients had genotypes B and C, respectively. Elevated bilirubin levels and prolonged prothrombin time were found in 11 (61%) and six patients (33%) respectively. Three patients (17%) had adverse outcome with the development of ascites and/or encephalopathy. One of these patients required liver transplantation and one died. Both patients had evidence of cirrhosis before treatment and hepatitis B e antigen (HBeAg) seroreversion from anti-HBe positivity. The remaining 16 patients (89%) have no evidence of pre-existing cirrhosis. Thirty seven percent of patients had normal alanine aminotransferase levels at the last follow-up. The median HBV DNA level at the last follow-up was significantly lower than the pre-treatment level (P = 0.009). Conclusions: Though the majority of patients with severe hepatitis exacerbations due to YMDD mutants had uneventful course, early liver transplantation should be considered in patients with pre-existing cirrhosis and HBeAg seroreversion. © 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.postprin