Fabrication of highly elastic resilin/silk fibroin based hydrogel by rapid photo-crosslinking reaction.

A new type of hydrogel combining the highly elastic soft phase of Rec1-resilin and the mechanically strong hard phase Bombyx mori Silk fibroin has been reported using a rapid photo-crosslinking method. The improved elasticity and strength through the use of a resilin-based material and silk fibroin has been shown for the first time.

Potential role of the cardiovascular non-antibiotic (helper compound) amlodipine in the treatment of microbial infections: scope and hope for the future.

The appearance of multiresistant bacterial strains coupled with the globally ongoing problem of infectious diseases point to the imperative need for novel and affordable antimicrobial drugs. The antibacterial potential of cardiovascular non-antibiotics such as amlodipine (AML), dobutamine, lacidipine, nifedipine and oxyfedrine has been reported previously. Of these drugs, AML proved to have the most significant antibacterial activity against Gram-positive and Gram-negative bacteria. Time-kill curve studies indicate that this Ca(2+) channel blocker exhibits bactericidal activity against Listeria monocytogenes and Staphylococcus aureus. AML could protect against murine listeriosis and salmonellosis at doses ranging within its maximum recommended human or non-toxic ex vivo dose. AML acts as a 'helper compound' in synergistic combination with streptomycin against several Gram-positive and Gram-negative bacterial strains in vitro as well as in the murine salmonellosis model in vivo. The present review focuses on the possible use of cardiovascular non-antibiotics such as AML as auxiliary compound targets for synergistic combinations in infections and hypertension conditions, rationalised on the basis of the activities of the compounds.

Experimental analyses of synergistic combinations of antibiotics with a recently recognised antibacterial agent, lacidipine.

The cardiovascular drug lacidipine (Lc) is known to possess antibacterial activity. Further potentiation of action is possible by synergism between Lc and an antibiotic or a non-antibiotic. The minimum inhibitory concentration (MIC) of antibiotics, Lc and other non-antibiotics were detected by the agar dilution technique in different bacteria. Synergism was determined by disc diffusion assay, the fractional inhibitory concentration (FIC) index through checkerboard assessment and, also, the protective capacity of the combination by administering the drugs along with 50 x LD(50) challenge dose of virulent Salmonella typhimurium in animal experiments. Synergism between Lc and penicillin was found to be statistically significant (P

The anti-inflammatory non-antibiotic helper compound diclofenac: an antibacterial drug target.

Diclofenac sodium (Dc) was found to possess antibacterial activity against both drug-sensitive and drug-resistant clinical isolates of Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Mycobacterium spp., in addition to its potent anti-inflammatory activity. The time-kill curve study indicates that this non-steroidal drug exhibits bactericidal activity against Listeria, E. coli, and M. tuberculosis. The antibacterial activity of Dc comes, in part, from its ability to inhibit the DNA synthesis of E. coli and L. monocytogenes. Dc could protect murine listeriosis, salmonellosis, and tuberculosis at doses ranged within its maximum recommended human or non-toxic ex-vivo dose. Dc possesses anti-plasmid activity and acts as a 'helper compound' in synergistic combination with streptomycin against E. coli and Mycobacterium or gentamicin against Listeria. This review focuses on the possible use of Dc, a non-antibiotic helper compound, in infections and inflammatory conditions, rationalized on the basis of the activities of the compounds.

In vitro synergistic effect of gentamicin with the anti-inflammatory agent diclofenac against Listeria monocytogenes.

AIMS: A total of nine Listeria monocytogenes strains (seven serotypes) were studied to ascertain whether the non-steroidal anti-inflammatory drug diclofenac (Dc) used in combination with the conventional antilisterial antibiotic gentamicin (Gm) or ampicillin (Am) synergistically augments the efficacy of the antibiotic in vitro. METHODS AND RESULTS: The effect of combination was evaluated by the checkerboard method to obtain a fractional inhibitory concentration (FIC) index followed by kill curves. Dc was synergistic with Gm (FIC 0.37) and there was indifference with Am (FIC 1) against L. monocytogenes ATCC 51774. The magnitude of the differences between killing by a single agent and the combination observed at 24 h was significant (P < 0.05) for Dc plus Gm but not Dc plus Am. CONCLUSIONS: Thus, the ability of extended antibiotic therapy may be improved with the help of this synergistic drug pair in listeriosis. SIGNIFICANCE AND IMPACT OF THE STUDY: Such findings may indicate parallel administration of anti-inflammatory and anti listeriosis drugs.

In vitro and in vivo efficacies of amlodipine against Listeria monocytogenes.

Listeria monocytogenes causes suppurative gastritis in BALB/c mice. We investigated the effect of the antihypertensive drug amlodipine (Aml) on the growth of L. monocytogenes in vitro and in vivo. Aml showed noteworthy inhibitory action (minimum inhibitory concentration, MIC(90) 32 microg/ml) against Listeria strains and demonstrated cidal (minimum bactericidal concentration, MBC 64 microg/ml) activity. Aml administered orally at 2.5 microg/g in female BALB/c mice for 7 days, commencing 4 days before oral challenge (1 x 10(8) CFU/ml with L. monocytogenes ATCC 51774), significantly reduced bacterial counts in the stomach (P < 0.01), liver (P < 0.01), and spleen (P < 0.05), and decreased (P < 0.05) gastric lesions, neutrophilic infiltration, edema, vascular degeneration, and necrosis of gastric tissues. It caused the down-regulation of expression of inflammatory cytokines (IFN-gamma, IL-1 beta, and TNF-alpha) compared to drug-free control. Aml may be used in the presence of an antibiotic as adjunct therapy that boosts the host immunity against Listeria. Further, QSAR studies might contribute in manipulating it as a lead compound for the synthesis of new, more effective non-antibiotics (helper compounds), perhaps devoid of side-effects, that could be recommended as compassionate therapy for listeriosis.

Multiwavelength fiber ring laser based on a semiconductor and fiber gain medium.

We report a novel multi-wavelength laser source based on hybrid gain medium, with a semiconductor optical amplifier and erbium doped fiber amplifier, and a double-ring structure. More than 60 lines with more than 50 dB signal-to-noise ratio (SNR) have been achieved in our setup. The wavelength interval between the wavelengths is approximately 0.32 nm. The 3 dB spectral width of each lasing line is approximately 0.019 nm. The laser can be tuned from approximately 1526 nm to approximately 1562 nm by adjusting the loss in the cavity.

High speed all-optical PRBS generation based on quantum-dot semiconductor optical amplifiers.

A scheme to generate return-to-zero on-off keying (RZ-OOK) high speed all-optical pseudo random bit sequence (PRBS) based on quantum-dot semiconductor optical amplifiers (QD SOA) has been studied. By analyzing the performance of the core functional unit of this system, which is composed of QD SOA-based logic XOR and AND gates, as well as considering the saturation effect of the QD device and noise level of the system, we demonstrated the system's capability of producing stable high speed optical PRBS signals. Results show that the performance of the system depends on a number of parameters, including relaxation lifetime from QD excited state to ground state, injected current density, bit repetition rate, signal pulse width and single pulse energy. For devices with relaxation time approximately 1.0 ps, injected current density >1.8 kA/cm(2), single pulse energy <1.0 pJ with pulse width around 1.0 ps, the system is capable of PRBS generation at speeds of approximately 250 Gb/s.

The anti-inflammatory drug Diclofenac retains anti-listerial activity in vivo.

AIMS: The interactions between nonsteroidal anti-inflammatory drugs (NSAID) and Listeria monocytogenes have not been sufficiently documented to date. The aim of this study was to investigate the possible effects of Diclofenac (Dc) in a murine listerial infection model. METHODS AND RESULTS: Dc was administered orally at 2.5 mug g(-1) to female albino strain of laboratory mouse (BALB/c) thrice postinfection (1 x 10(8) CFU ml(-1) oral challenge with L. monocytogenes ATCC 51774), which resulted in significantly (P < 0.01) reduced bacterial counts in liver and spleen, decreased (10-fold, P < 0.05) hepatic colonization and necrosis, and caused up-regulation of the expression of inflammatory cytokines (interferon-gamma, interleukin-1beta, tumour necrosis factor-alpha), compared with drug-free control. CONCLUSIONS: Dc may be useful as a promising adjuvant to the existing therapies in controlling systemic listerial infection. Further, quantitative structure-activity relationship studies might contribute in manipulating it as a lead compound for the synthesis of new, more effective nonantibiotics, perhaps, devoid of side-effects that could be recommended as a compassionate therapy for listeriosis. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first in vivo study designed to evaluate the antilisterial effect of the NSAID Dc with special emphasis on the immunological mechanism of action of the drug.

In vitro efficacy of diclofenac against Listeria monocytogenes.

Chemotherapy is often futile in systemic listeriosis, translating to being a peril to public health. There is, thus, an imperative need for novel antilisterial compounds, possibly acting through mechanisms dissimilar to those of existing drugs. The present study describes one such agent-the non-steroidal anti-inflammatory drug (NSAID) diclofenac sodium (Dc). The National Committee for Clinical Laboratory Standards (NCCLS) minimum inhibitory concentration (MIC), mode of action, and two mechanisms of action, i.e., on bacterial DNA and membrane, have been characterized with respect to Dc. The drug showed noteworthy inhibitory action (MIC90 = 50 microg/ml) against Listeria strains, demonstrated cidal (minimum bactericidal concentration [MBC]=100 microg/ml) activity, inhibited listerial DNA synthesis (45.48%; incorporation of [methyl-3H] thymidine), and possessed bacterial membrane-damaging activity (37.33%; BacLight assay). Dc could be used as a lead compound for the synthesis of new, more active agents perhaps devoid of side effects. Further, quantitative structure-activity relationship (QSAR) studies will contribute to a new generation of promising adjuvants to existing antilisterial drugs.

Dispersion effects on the detuning properties of actively harmonic mode-locked fiber lasers.

Detuning properties for actively harmonic mode-locked fiber lasers has been studied both theoretically and experimentally while taking into account of finite cavity dispersions. The theoretical work is based on the self- consistent time domain circulating pulse method. By keeping terms which are usually neglected in previous studies, we have derived an analytic formula which can predict the saturation behavior associated with large modulation frequency detuning. It is found that for the case of medium cavity dispersion, both the pulse-modulator RF phase lag and the optical carrier frequency of the circulating pulse will change significantly as a function of the modulation frequency detuning. The analytical results are supported by both the numerical simulations as well as the experimental measurements. Our theory can potentially serve as a design guidance for cavity length feedback control of harmonic mode-locked fiber lasers.

Regeneratively stabilized 4th order rational harmonic mode-locked erbium doped fiber laser operating at 40Gb/s.

We report a long term stabilized 4th order rational harmonic mode-locked (RHML) erbium doped fiber laser operating at 40Gb/s. The cavity length drift induced laser instability is overcomed by constructing a modified regenerative type feedback loop to actively adjust the modulation frequency of the 10GHz driving signal. The 4th RHML fiber laser is tested to be highly stable against environmental perturbations.

In vitro and in vivo antimycobacterial activity of antiinflammatory drug, diclofenac sodium.

The non-steroidal antiinflammatory drug diclofenac sodium exhibited remarkable inhibitory action against both drug sensitive and drug resistant clinical isolates of Mycobacterium tuberculosis, as well as other mycobacteria. This agent was tested in vitro against 45 different strains of mycobacteria, most of which were inhibited by the drug at 10-25 microg/ml concentration. When tested in vivo, diclofenac, injected at 10 mg/kg body weight of a Swiss strain of white mice, could significantly protect them when challenged with a 50 median lethal dose of M. tuberculosis H37 Rv102. According to Chi-square test, the in vivo data were highly significant (P<0.01).

Studies on the antibacterial potentiality of isoflavones.

The isoflavonoid compounds 'YS11-YS21' were screened for possible antimicrobial property against 12 known Gram-positive and Gram-negative sensitive bacteria. YS11 and YS16 failed to show antimicrobial activity and YS12, 13, 14, 15, 17, 18 and 20 had moderate antimicrobial action. Compounds YS19 and YS21 showed pronounced antimicrobial property. YS19 and YS21 were then tested in vitro against 214 strains of bacteria from one Gram-positive and six Gram-negative genera. The minimum inhibitory concentration (MIC) of YS19 and YS21 was determined by agar dilution method and ranged from 25 to 200 mg/l in most strains. At concentrations of 30 and 60 microg/mouse these compounds offered significant protection to mice challenged with 50 median lethal dose (MLD) of a virulent strain of Salmonella Typhimurium.

Antimicrobial potentiality of a new non-antibiotic: the cardiovascular drug oxyfedrine hydrochloride.

Ten cardiovascular drugs, having diverse pharmacological action, were screened for possible antimicrobial property against known eight sensitive bacteria, belonging to Gram positive and Gram negative types. Although five drugs failed to show antimicrobial activity and three had moderate antimicrobial action, oxyfedrine HCl and dobutamine were seen to possess pronounced antimicrobial property. Oxyfedrine was further tested in vitro against 471 strains of bacteria from two Gram positive and fourteen Gram negative genera. The minimum inhibitory concentration (MIC) of oxyfedrine was determined by agar dilution method, which ranged from 50-200 microg/ml in most of the strains, while some strains were inhibited at even lower concentrations. In animal experiments, this compound was capable of offering significant protection to Swiss strain of white mice, challenged with 50 median lethal dose (MLD) of a virulent strain of Salmonella typhimurium at concentrations of 15, 30 and 60 microg/mouse. The in vivo results were highly significant according to chi-square test.

Evaluation of in vitro and in vivo antibacterial activity of dobutamine hydrochloride.

PURPOSE: To determine the in vitro and in vivo antibacterial activity of a cardiovascular drug dobutamine hydrochloride. METHODS: The minimum inhibitory concentration (MIC) of dobutamine was determined both by agar and broth dilution methods against 331 strains of bacteria from three gram positive and 13 gram negative genera. The antibacterial action of dobutamine was further tested in animal models. RESULTS: Dobutamine was seen to possess powerful inhibitory action (5-200mg/mL) against most test bacteria in in vitro studies. It was bacteriostatic in nature. In vivo studies showed that the drug offered significant protection (p< 0.001) to mice challenged with a virulent bacterium. CONCLUSION: Dobutamine showed remarkable antibacterial property against several pathogenic bacteria. Its potential as an antibacterial agent may be confirmed after further pharmacological studies.

Amlodipine: a cardiovascular drug with powerful antimicrobial property.

Ten cardiovascular drugs were procured in pure form from their manufacturers in India and screened for antimicrobial property against fifteen known bacteria belonging to both gram-positive and gram-negative types. These bacteria were inhibited by the common antibiotics at 1-5 mg ml(-1) level through our earlier studies. Since most of the bacteria were moderate to highly responsive to amlodipine, this compound was further tested in vitro against 504 bacteria comprising 4 genera of gram-positive and 15 genera of gram-negative bacteria. Most of these were inhibited by the drug at 50-200 microg ml(-1) level and few strains were sensitive even at lower concentrations (10 microg ml(-1)). The bacteria could be arranged in the decreasing order of sensitivity towards amlodipine in the following manner: Staphylococcus aureus, Vibrio cholerae, Vibrio parahemolyticus, Shigella spp., Salmonella spp., Bacillus spp., whereas Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa were found to be resistant to the lower concentrations of the drug. Amlodipine was found to be bactericidal in nature when its mode of action was studied against S. aureus 6571, V. cholerae 14035 and Sh boydii 8 NCTC 254/66. The antibacterial activity of amlodipine could also be confirmed in vivo. When it was given to Swiss strain of white mice at different dosages (30 and 60 microg/mouse), it could significantly protect the animals challenged with 50 MLD of Salmonella typhimurium NCTC 74. According to Chi square test the in vivo data were highly significant (p<0.001).

Potentiality of a new compound for in vitro differentiation between halophilic and non-halophilic vibrios.

Sensitivity of 21 halophilic vibrios and 16 clinical isolates of non-halophilic vibrios was determined against a new possible antivibrio agent, a pyrimidine analogue, 4, 6-dimethylpyrimidine -2-thiol (4,6-DMPT). It appeared to be a vibriocidal agent, having a mean MIC and MBC of 32 microg/ml for halophilic strains and 64 microg/ml for non-halophilic strains and an LD50 of 300 mg/Kg body weight of mice. Thus, 4,6-DMPT may help an in vitro distinction between halophilic and non-halophilic vibrios. Sensitivity of these strains was also studied with respect to pteridine, crystal violet and Tween 80 hydrolysis as further markers distinguishing between these 2 groups which could also be differentiated by their growth on TCBS or/and CLED media.

Cancellation of coherent artifacts in optical coherence tomography imaging.

Coherent artifacts in optical coherence tomography (OCT) images can severely degrade image quality by introducing false targets if no targets are present at the artifact locations. Coherent artifacts can also add constructively or destructively to the targets that are present at the artifact locations. This constructive or destructive interference will result in cancellation of the true targets or in display of incorrect echo amplitudes of the targets. We introduce the use of a nonlinear deconvolution algorithm, CLEAN, to cancel coherent artifacts in OCT images of extracted human teeth. The results show that CLEAN can reduce the coherent artifacts to the noise background, sharpen the air-enamel and enamel-dentin interfaces, and improve the image contrast.