Search PubMed⌕ Search

Biomedical subjects

L M Fu

Publications and source records attributed to L M Fu.

8 recordsLinked to original sources

The potential of human neutrophil peptides in tuberculosis therapy.

The problems of drug resistance and bacterial persistence in tuberculosis have prompted scientists to search for clues from the latest advances in microbiology and immunology. Recent research on human neutrophil peptides (HNPs) has highlighted their bactericidal action against Mycobacterium tuberculosis and suggested that neutrophils may play a more important defensive role in tuberculosis than previously thought. Human neutrophil peptides belong to a family of antimicrobial and cytotoxic peptides known as 'defensins'. Neutrophils use both oxidative and non-oxidative microbicidal mechanisms to provide the host with innate immunity against microbial infections. Defensins are most abundant among an array of oxygen-independent antimicrobial proteins and peptides in neutrophil granules. Defensins are effective against a wide spectrum of microbes including bacteria, viruses, fungi, spirochetes and mycobacteria. In addition to direct antimicrobial activity, HNPs can potentially influence the inflammatory or immune responses by modulating cytokine production or acting like opsonins or chemotactic factors. HNPs are active against M. tuberculosis grown in vitro or within macrophages. HNPs released by neutrophils recruited in the early lesion could attract monocytes to the site and macrophages may in vivo uptake the extracellular HNPs and kill the intracellular pathogens. As such, HNPs are potential therapeutic agents against tuberculosis. HNPs are also cytotoxic against a wide range of normal mammalian cells; however, there is evidence that defensins may not cause significant cytotoxicity at the therapeutic level. Finally, the clinical application of HNPs must be evaluated in the context of possible drug resistance, as some resistance-associated genes have been identified.

Anti-Infective Agents↗

Electrokinetic injection techniques in microfluidic chips.

The separation efficiency of a microfluidic chip is influenced to a significant degree by the flow field conditions within the injection microchannel. Therefore, an understanding of the physics of the flow within this channel is beneficial in the design and operation of such a system. The configuration of an injection system is determined by the volume of the sample plug that is to be delivered to the separation process. Accordingly, this paper addresses the design and testing of injection systems with a variety of configurations, including a simple cross, a double-T, and a triple-T configuration. This paper also presents the design of a unique multi-T injection configuration. Each injection system cycles through a predetermined series of steps, in which the electric field magnitude and distribution within the various channels is strictly manipulated, to effectuate a virtual valve. The uniquemulti-T configuration injection system presented within this paper has the ability to simulate the functions of the cross, double-T, and triple-T systems through appropriate manipulations of the electric field within its various channels. In other words, the proposed design successfully combines several conventional injection systems within a single microfluidic chip.

Journal Article↗

Is Mycobacterium tuberculosis a closer relative to Gram-positive or Gram-negative bacterial pathogens?

The phylogenetic position of Mycobacterium tuberculosis relative to other bacteria is controversial. Its cell wall has characteristics of both Gram-positive and Gram-negative bacteria. In the standard reference of bacterial phylogeny based on 16S ribosomal RNA sequence comparison, M. tuberculosis belongs to the high G+C Gram-positive bacteria that form a monophyletic group with the low G+C Gram-positive bacteria such as Bacillus subtilis. Some analyses indicate no particular relationship between these two groups. The availability of the complete genome sequence of M. tuberculosis allows us to reexamine this issue from genomic perspectives, as genome-based phylogenies may be more representative of the evolutionary history of whole organisms than molecular trees. In the genome tree constructed based on conserved gene content, M. tuberculosis is more related to Gram-negative than to Gram-positive bacteria as reflected by the evolutionary distance between nearest ancestral units. This conclusion may be supported by another analysis showing that M. tuberculosis shares relatively more orthologous genes for energy production and conversion with Gram-negative bacteria, in particular, Escherichia coli and Pseudomonas aeruginosa, than with Gram-positive bacteria.

Genome, Bacterial↗

Thalidomide and tuberculosis.

The anti-inflammatory and immunomodulatory effects of thalidomide have led scientists to explore its clinical therapeutic values. Thalidomide is now being considered as an adjuvant treatment for tuberculosis. This literature review examines the drug's mechanism of action and clinical applications. Thalidomide affects cytokine production and T lymphocyte proliferation. It appears that thalidomide suppresses TNF-alpha production by macrophages and thereby reduces inflammatory response. Thalidomide elevates the IFN-gamma level and modulates several other cytokines as well, noteworthily IL-2 and IL-12. Thalidomide costimulates T lymphocytes, with greater effect on CD8+ than on CD4+ T cells. This finding is important, since CD8+ T cells have been shown to be contributory to the protective immune response to Mycobacterium tuberculosis infection. The clinical application of thalidomide as part of standard tuberculosis therapy is inconclusive amid variability among reports. However, thalidomide has been shown to be an effective adjuvant for tuberculosis patients complicated with severe inflammatory reaction or wasting conditions.

Animals↗

Inhibitors of adenosine catabolism improve recovery of dog myocardium after ischemia.

The effects of inhibitors of adenosine catabolism on contractile function and metabolites were assessed during 15 minutes of ischemia followed by 30 minutes of reperfusion in the open-chest dog heart. As compared to sham treatment, pretreatment with erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and dipyridamole (DP) protected contractile function during ischemia, and improved recovery of high energy phosphate content and contractile function during reperfusion following ischemia. Testing EHNA and DP in a free-radical generating system indicated both compounds have some scavenging ability, suggesting the effect of EHNA + DP may not be on adenosine nucleotide metabolism alone. Comparison of end diastolic segment lengths to contractile function indicated the results were not affected by changes in preload resulting from peripheral vasodilation.

Adenine↗

Contractility, ATP, and creatine phosphate during myocardial ischaemia and reperfusion: the effects of adenosine and inhibition of adenosine catabolism in the dog heart.

Provision of AMP or adenosine to heart cells during recovery from episodes of myocardial ischaemia accelerates physiological, biochemical, and structural recovery. Inhibition of adenosine loss from the tissue during ischaemia should have a similar effect. This hypothesis was tested in dog heart by infusion of adenosine and inhibitors of adenosine catabolism prior to, during, and following ischaemia. Post-ischaemic recovery of ATP and contractile function was accelerated significantly by adenosine and by inhibitors of adenosine catabolism both singly and in combination. Contractility and ATP levels during ischaemia were also increased by these inhibitors.

Adenosine↗