Co-Delivery of D-LAK Antimicrobial Peptide and Capreomycin as Inhaled Powder Formulation to Combat Drug-Resistant Tuberculosis

INTRODUCTION: The emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) posed a severe challenge to tuberculosis (TB) management. The treatment of MDR-TB involves second-line anti-TB agents, most of which are injectable and highly toxic. Previous metabolomics study of the Mtb membrane revealed that two antimicrobial peptides, D-LAK120-A and D-LAK120-HP13, can potentiate the efficacy of capreomycin against mycobacteria. AIMS: As both capreomycin and peptides are not orally available, this study aimed to formulate combined formulations of capreomycin and D-LAK peptides as inhalable dry powder by spray drying. METHODS AND RESULTS: A total of 16 formulations were prepared with different levels of drug content and capreomycin to peptide ratios. A good production yield of over 60% (w/w) was achieved in most formulations. The co-spray dried particles exhibited spherical shape with a smooth surface and contained low residual moisture of below 2%. Both capreomycin and D-LAK peptides were enriched at the surface of the particles. The aerosol performance of the formulations was evaluated with Next Generation Impactor (NGI) coupled with Breezhaler®. While no significant difference was observed in terms of emitted fraction (EF) and fine particle fraction (FPF) among the different formulations, lowering the flow rate from 90 L/min to 60 L/min could reduce the impaction at the throat and improve the FPF to over 50%. CONCLUSIONS: Overall, this study showed the feasibility of producing co-spray dried formulation of capreomycin and antimicrobial peptides for pulmonary delivery. Future study on their antibacterial effect is warranted

Diffusion tensor imaging of renal ischemia/reperfusion injury

Session 67: Functional MRI of the Abdomen - Oral presentationRenal ischemia/reperfusion injury (IRI) is a major cause of acute renal failure in native and in transplanted kidneys. IRI in kidney associated with transplantation may also influence early graft function and late changes. Recently, anisotropy measurement with diffusion tensor imaging (DTI) has been found to provide additional information about functional and structural status of kidney. In this study, we aim at characterizing diffusion properties of kidney with mean diffusivity (MD) and fractional anisotropy (FA) in an experimental rat model of renal IRI. The experimental results demonstrated that DTI is useful in identifying renal IRI by characterizing the changes in MD and FA.published_or_final_versionThe 17th Scientific Meeting & Exhibition of the International Society of Magnetic Resonance in Medicine (ISMRM), Honolulu, HI., 18-24 April 2009. In Proceedings of ISMRM 17th Scientific Meeting & Exhibition, 2009, p. 66

Optional elements and variant structures in the productions of bei2 to give dative constructions in Cantonese-speaking adults and three-year-old children

To express object transfer, Cantonese-speakers use a ditransitive ([V-R-T] or [V-T-R] where V=Verb, T=Theme, R=Recipient), or a more complex prepositional/serial-verb (P/SV) construction. Clausal elements in Cantonese datives can be optional (resulting in full versus non-full forms) or appear in variant orders (full non-canonical and full canonical). We report on usage of dative constructions with the word bei2 to give in 86 parents and 53 three-year-old children during conversations. The parents used more P/SV than ditransitive bei2-datives, and vice versa for the children. Both groups showed a similar usage pattern of optional elements and variant structures in their ditransitive and P/SV bei2-datives. The roles of multiple construction types, optional elements and variant structures in children's learning of bei2-dative constructions are described. Copyright © 2009 Cambridge University Press.published_or_final_versio

Changing student mindset by community involvement: the impact of service leadership internship

The Service Leadership Internship (SLI) in the University of Hong Kong is funded by the Li and Fung Service Leadership Initiative. It provides students in Social Sciences and Business a chance to hone their leadership skills through authentic experiential learning. The SLI takes place in the summer as a credit bearing course spanning 6 – 8 weeks and has been offered since 2012. To help community partners in real-life problems, the students from different disciplines work as a team to generate innovative solutions. For examples, Business students provided consultation service to a small information technology company on operational problems, whereas social sciences students helped an NGO to launch a public education program …postprin

Involving parents in paired reading with preschoolers: Results from a randomized controlled trial

postprin

Storage stability of lysostaphin solution and its pulmonary delivery

Methicillin-resistant Staphylococcus aureus (MRSA) has become a leading causative pathogen of nosocomial pneumonia with an alarming in-hospital mortality rate of 30%. Last resort antibiotic, vancomycin, has been increasingly used to treat MRSA infections, but the rapid emergence of vancomycin-resistant strains urges the development of alternative treatment strategies against MRSA-associated pneumonia. The bacteriolytic enzyme, lysostaphin, targeting the cell wall peptidoglycan of S. aureus, has been considered as a promising alternative for MRSA infections. Its proteinaceous nature is likely benefit from direct delivery to the lungs, but the challenges for successful pulmonary delivery of lysostaphin lying on a suitable inhalation device and a formulation with sufficient storage stability. In this study, the applicability of a vibrating mesh nebulizer (Aerogen Solo®) and a soft mist inhaler (Respimat®) was investigated. Both devices were capable of aerosolizing lysostaphin solution into inhalable droplets and caused minimum antibacterial activity loss. In addition, lysostaphin stabilized with phosphate-buffered saline and 0.1% Tween 80 was proved to have acceptable stability for at least 12 months when stored at 4 °C. These promising data encourage further clinical development of lysostaphin for management of MRSA-associated lung infections. Graphical abstract: [Figure not available: see fulltext.] Lysostaphin had insignificant activity loss after aerosol generation by a vibrating mesh nebulizer and a soft mist inhaler.Most of the lysostaphin aerosols generated by the vibrating mesh nebulizer and soft mist inhaler are inhalable.The vibrating mesh nebulizer and soft mist inhaler are suitable device for pulmonary delivery of lysostaphin

Pathway of psychiatric care in Hong Kong

published_or_final_versio

Detection of Head-to-Tail DNA Sequences of Human Bocavirus in Clinical Samples

Parvoviruses are single stranded DNA viruses that replicate in a so called “rolling-hairpin” mechanism, a variant of the rolling circle replication known for bacteriophages like ϕX174. The replication intermediates of parvoviruses thus are concatemers of head-to-head or tail-to-tail structure. Surprisingly, in case of the novel human bocavirus, neither head-to-head nor tail-to-tail DNA sequences were detected in clinical isolates; in contrast head-to-tail DNA sequences were identified by PCR and sequencing. Thereby, the head-to-tail sequences were linked by a novel sequence of 54 bp of which 20 bp also occur as conserved structures of the palindromic ends of parvovirus MVC which in turn is a close relative to human bocavirus

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for rapid identification of mold and yeast cultures of Penicillium marneffei

published_or_final_versio