Neisseria gonorrhoeae strains with reduced susceptibility to cefixime (MICs, 0.25 to 0.5 g/ml) were isolated from male urethritis patients in Tokyo, Japan, in 2000 and 2001. The resistance to cephems including cefixime and penicillin was transferred to a susceptible recipient, N. gonorrhoeae ATCC 19424, by transformation of the penicillin-binding protein 2 gene (penA) that had been amplified by PCR from a strain with reduced susceptibility to cefixime (MIC, 0.5 g/ml). The sequences of penA in the strains with reduced susceptibilities to cefixime were different from those of other susceptible isolates and did not correspond to the reported N. gonorrhoeae penA gene sequences. Some regions in the transpeptidase-encoding domain in this penA gene were similar to those in the penA genes of Neisseria perflava (N. sicca), Neisseria cinerea, Neisseria flavescens, and Neisseria meningitidis. These results showed that a mosaic-like structure in the penA gene conferred reductions in the levels of susceptibility of N. gonorrhoeae to cephems and penicillin in a manner similar to that found for N. meningitidis and Streptococcus pneumoniae.
Biological surfaces are very complex in nature. They have wide distribution in molecular species; including positive and negative charges, polar and non-polar groups. [1] A material to show adhesion to such biological surfaces should have the capability of creating enough adhesive interacting sites with these species in wet environment. [2] Conventional hydrogels usually have poor adhesion to biological surfaces. [3] This is because the adhesion in wet environment is usually based on the Columbic interaction that strongly depends on the charge combinations. [3,4] Many of the biological surfaces and hydrogels have net negative surface charge [5] and they are repulsive in water. Developing adhesives that possess the ability of quick, strong, and reversible adhesion to hydrogels and biological tissues regardless their net charge identity will substantially promote the application of hydrogels in biomedical applications. Several research groups have tried to develop different adhesive hydrogels based on surface modification, [6] mechanical interlocking, [7] making composites, [8] supramolecular recognition, [9] and nano-particles. [10,11] But these approaches have limitations in practical applications, such as lengthy and complicated way of processing, lack of water resistivity and universality, inability in non-residual removal, etc. [12] The clue to develop adhesives working for hydrogels and biological tissues hides in nature.Bacteria cells, ubiquitous in environment, can attach with almost any surfaces including human tissues, regardless the diversity in the surface chemistry. The self-adjustable capability of the extracellular polymeric matrix (EPM) of bacteria cells has made this possible. [13,14] EPM can provide sufficient interacting sites for adsorption of species at interface in response to substrates mechanical and chemical properties through re-distribution of their charged groups. [15] Inspired from nature, we intend to find out a self-adjustable hydrogel adhesive for adhesion to hydrogels and tissues. A self-adjustable surface is such a surface which can offer its species for the formation of attractive interaction depending on substrate charges through dynamic reorganization process. A possible design for achieving such a self-adjustable 3 adhesive is a hydrogel composed of both positively and negatively charged monomers.Presence of both charges in the hydrogel is expected to create attractive interacting sites with any charged surfaces regardless of their charge identity to facilitate adsorption. But this seems to be tricky, because incorporation of both type charges in the same hydrogel sometime encounters strong self-ionic association, which will made it impossible for the formation of bonds with other species residing in different surfaces or in some cases imbalance in component inside hydrogel offers a strong net charge over the surface, [16] which will prevent their non-specific adhesion property. We can overcome this problem by choosing a neutral (charge balanced) polyampholyte (PA) hydrogel th...
Our results suggest that decreased bactericidal activity, or the in vitro PAE of carbapenems and fluoroquinolones, is related to the reduced in vivo protective effect against infection caused by high inoculum with S. aureus or P. aeruginosa.
The in vitro and in vivo activities of T-3811ME, a novel des-F(6)-quinolone, were evaluated in comparison with those of some fluoroquinolones, including a newly developed one, trovafloxacin. T-3811, a free base of T-3811ME, showed a wide range of antimicrobial spectra, including activities against Chlamydia trachomatis, Mycoplasma pneumoniae, andMycobacterium tuberculosis. In particular, T-3811 exhibited potent activity against various gram-positive cocci, with MICs at which 90% of the isolates are inhibited (MIC90s) of 0.025 to 6.25 μg/ml. T-3811 was the most active agent against methicillin-resistant Staphylococcus aureus and streptococci, including penicillin-resistant Streptococcus pneumoniae (PRSP). T-3811 also showed potent activity against quinolone-resistant gram-positive cocci with GyrA and ParC (GrlA) mutations. The activity of T-3811 against members of the familyEnterobacteriaceae and nonfermentative gram-negative rods was comparable to that of trovafloxacin. In common with other fluoroquinolones, T-3811 was highly active against Haemophilus influenzae, Moraxella catarrhalis, andLegionella sp., with MIC90s of 0.0125 to 0.1 μg/ml. T-3811 showed a potent activity against anaerobic bacteria, such as Bacteroides fragilis and Clostridium difficile. T-3811 was the most active agent against C. trachomatis (MIC, 0.008 μg/ml) and M. pneumoniae(MIC90, 0.0313 μg/ml). The activity of T-3811 againstM. tuberculosis (MIC90, 0.0625 μg/ml) was potent and superior to that of trovafloxacin. In experimental systemic infection with a GrlA mutant of S. aureus and experimental pneumonia with PRSP in mice, T-3811ME showed excellent therapeutic efficacy in oral and subcutaneous administrations.
We report, for the first time, the quantitative measurement of the local electric potential of brittle polyelectrolyte hydrogels using the microelectrode technique (MET). Given the solid-like nature of the hydrogels, the difficulty of applying MET is how to make a good contact of the microelectrode to the hydrogel. Poor local contact substantial underestimates the potential. We observed that, the potential measured decays exponentially with the increase of capillary diameter of the microelectrode. This behavior is related to the capillary wall thickness that determines the contact distance of the electrode probe to the hydrogel. The characteristic decay length in respective to the wall thickness is very close to the local Debye length around the capillary. The latter is much larger than that of the bath solution due to the reverse osmosis effect. By using microelectrodes with a tip wall thickness less than the local Debye length, the Donnan potential of polyelectrolyte gel could be accurately measured. Using a micromanipulator, the inserting process of the microelectrode is precisely controlled, and the depth profile of electric potential in the hydrogels can be measured with a spatial resolution down to ∼5 nm. From the spatial distribution of potential, the microstructure of hydrogels both in bulk and near the surface, the thickness of ultrathin hydrogels, and the heterogeneous layered structure of composite gels, can be determined accurately. The MET established in this work provides a powerful tool for direct characterization of the spatial distribution of electric potential of hydrogels
SUMMARYElectric fields are pervasively present in the environment and occur both as a result of man-made activities and through natural occurrence. We have analysed the behaviour of cockroaches to static electric fields and determined the physiological mechanisms that underlie their behavioural responses. The behaviour of animals in response to electric fields was tested using a Y-choice chamber with an electric field generated in one arm of the chamber. Locomotory behaviour and avoidance were affected by the magnitude of the electric fields with up to 85% of individuals avoiding the charged arm when the static electric field at the entrance to the arm was above 8-10 kV m -1 . Electric fields were found to cause a deflection of the antennae but when the antennae were surgically ablated, the ability of cockroaches to avoid electric fields was abolished. Fixation of various joints of the antennae indicated that hair plate sensory receptors at the base of the scape were primarily responsible for the detection of electric fields, and when antennal movements about the head-scape joint were prevented cockroaches failed to avoid electric fields. To overcome the technical problem of not being able to carry out electrophysiological analysis in the presence of electric fields, we developed a procedure using magnetic fields combined with the application of iron particles to the antennae to deflect the antennae and analyse the role of thoracic interneurones in signalling this deflection. The avoidance of electric fields in the context of high voltage power lines is discussed.
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