Insights into antifolate activity of phytochemicals against Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic drug resistant pathogen. Drug interaction studies for phytochemicals (protocatechuic acid (PA), gallic acid (GA), quercetin (QUER), and myricetin (MYR)) in combination with antifolates (sulfamethoxazole (SMX) and trimethoprim (TMP)) are presented. Our results show that the combinations of SMX and phytochemicals are synergistic, whereas TMP in combination with phytochemicals results in additive mode of interaction. Molecular docking of phytochemicals in the active site of modeled P. aeruginosa dihydrofolate reductase (DHFR), an important enzyme in the folic acid biosynthesis pathway, shows that the phytochemicals QUER and MYR dock in the active site of P. aeruginosa DHFR with promoted binding at the NADP site, PA, and GA dock in the active site of P. aeruginosa DHFR with promoted binding at the folate binding site. Possible mode of action of these phytochemicals as anti-DHFR compounds in this bacterium is suggested. Taken together, the above findings provide novel insights to mode of interactions of these phytochemicals with antibiotics and may have significance as prospective leads in the development of antipseudomonal drug developments.

In vitro combinations of antibiotics and phytochemicals against Pseudomonas aeruginosa.

BACKGROUND AND PURPOSE: Antibiotic combinations are used to enhance antibacterial efficacy and to prevent the development of resistance. In this study, the in vitro activities of antibiotic and phytochemical combinations against Pseudomonas aeruginosa were tested by the fractional inhibitory concentration method, derived from the minimal inhibitory concentrations (MICs) of the agents in combination. METHODS: The antimicrobial activity of phytochemicals, alone and in combination with antibiotics, was evaluated using the checkerboard assay and time-kill curve methods. RESULTS: There was synergism between gentamicin and caffeic acid, and sulfadiazine and the 3 phytochemicals under investigation (protocatechuic acid, quercetin, caffeic acid). The MIC of sulfadiazine was 256 microg/mL, and of gentamicin was 2 microg/mL. When gentamicin was combined with one-quarter the MIC of caffeic acid, the MIC of gentamicin was reduced 4-fold. When sulfadiazine was tested with one-quarter the MIC of protocatechuic acid, quercetin, and caffeic acid, the MIC was reduced 4-fold in combination with each of the drugs. CONCLUSIONS: These results indicate the potential efficacy of phytochemicals in combination with antibiotics for enhancing total biological activity.

A computer-aided MFCC-based HMM system for automatic auscultation.

Auscultation, the act of listening to the sounds of internal organs, is a valuable medical diagnostic tool. Auscultation methods provide the information about a vast variety of internal body sounds originated by various organs such as heart, lungs, bowel, vascular disorders, etc. In this study, a cardiac sound registration system has been designed incorporating functions such as heart signals segmentation, classification and characterization for automated identification and ease of interpretation by the users. Considering a synergy with the domain of speech analysis, the authors introduced Mel-frequency cepstral coefficient (MFCC) to extract representative features and develop hidden Markov model (HMM) for signal classification. This system was applied to 1381 data sets of real and simulated, normal and abnormal domains. Classification rates for normal and abnormal heart sounds were found to be 95.7% for continuous murmurs, 96.25% for systolic murmurs and 90% for diastolic murmurs by a probabilistic comparison approach. This implies a high potential for the system as a diagnostic aid for primary health-care sectors.

Mammalian specific mouse genes are evolving faster than mouse genes conserved across other eukaryotic lineages.

Positive selection is usually considered in the context of a higher rate of substitutions in non-synonymous as compared to synonymous sites in complete coding sequences of genes or individual positions. We show that genes conserved in eukaryota, coelomata, and bilateria, that is, proteins that arose earlier in evolution as compared to mammalia specific genes evolve slowly and are subjected to negative selection. This finding supports the notion that evolutionary rates progressively diminish with the age of a gene. The data suggests that in both intron-containing and intronless genes synonymous sites may be subject to some degree of selection that is indicative of a relative acceleration of amino-acid substitution, which could be due to a relaxation of functional constraints and/or directional selection.

Overview on the analytical tools for quality control of natural product-based supplements: a case study of ginseng.

The quality of pharmaceutical products like ginseng is important for ensuring consumer safety and efficacy. Many ginseng products sold today are in various formulations such as powder, capsules, tablets, soft-gels, liquid extracts, and tea. This renders ginseng less identifiable by smell, taste, or physical appearance. Furthermore, as ginseng is expensive, adulteration with other cheaper products occurs. Hence quality assurance of ginseng is needed. This paper reviews the major techniques for ascertaining the level of ginsenosides, the primary active ingredients for ginseng, and covers high-performance liquid, gas, and thin-layer chromatographies, infrared and nuclear magnetic resonance spectroscopies, enzyme immunoassays, and other molecular methods. Supporting techniques such as ultraviolet, fluorescence, diode array and evaporative light scattering detections, and mass spectrometry will also be touched upon. This review also discusses the principles and applications of biosensors-in particular fiber optic-based sensors-and their feasibility in ginseng analysis based on preliminary studies. Despite their potential, there is currently no or limited commercial exploitation of fiber optic-based sensors to perform ginseng quality analysis. The opportunity for biosensors to be used for the rapid quality surveillance of ginseng is appealing, but several key issues still need to be addressed before they find widespread applications in the traditional Chinese medicine industry.

Determination of bacterial activity by use of an evanescent-wave fiber-optic sensor.

A novel technique based on fiber-optic evanescent-wave spectroscopy is proposed for the detection of bacterial activity in human saliva. The sensor determines th e specific concentration of Streptococcus mutans in saliva, which is a major causative factor in dental caries. In this design, one prepares the fiber-optic bacterial sensor by replacing a portion of the cladding region of a multimode fiber with a dye-encapsulated xerogel, using the solgel technique. The exponential decay of the evanescent wave at the core-cladding interface of a multimode fiber is utilized for the determination of bacterial activity in saliva. The acidogenic profile of Streptococcus mutans is estimated by use of evanescent-waveabsorption spectra at various levels of bacterial activity.