During oxidative burst, neutrophils selectively generate HOCl to destroy invading microbial pathogens. Excess HOCl reacts with taurine, a semi-essential amino acid, resulting in the formation of the longer-lived biogenerated broad-spectrum antimicrobial agent, N-chlorotaurine (NCT). In the presence of an excess of HOCl or under moderately acidic conditions, NCT can be further chlorinated, or it can disproportionate to produce N,N-dichlorotaurine (NNDCT). In the present study, 2,2-dimethyltaurine was used to prepare a more stable N-chlorotaurine, namely, N,N-dichloro-2,2-dimethyltaurine (NVC-422). In addition, we report on the chemical characterization, in vitro antimicrobial properties, and cytotoxicity of this compound. NVC-422 was shown effectively to kill all 17 microbial strains tested, including antibiotic-resistant Staphylococcus aureus and Enterococcus faecium. The minimum bactericidal concentration of NVC-422 against Gram-negative and Grampositive bacteria ranged from 0.12 to 4 g/ml. The minimum fungicidal concentrations against Candida albicans and Candida glabrata were 32 and 16 g/ml, respectively. NVC-422 has an in vitro cytotoxicity (50% cytotoxicity ‫؍‬ 1,440 g/ml) similar to that of NNDCT. Moreover, our data showed that this agent possesses rapid, pH-dependent antimicrobial activity. At pH 4, NVC-422 completely killed both Escherichia coli and S. aureus within 5 min at a concentration of 32 g/ml. Finally, the effect of NVC-422 in the treatment of an E. coli-infected granulating wound rat model was evaluated. Treatment of the infected granulating wound with NVC-422 resulted in significant reduction of the bacterial tissue burden and faster wound healing compared to a saline-treated control. These findings suggest that NVC-422 could have potential application as a topical antimicrobial.As part of the innate immune system, leukocytes are capable of generating and releasing reactive oxygen species. During oxidative burst, neutrophils selectively generate hypochlorous acid to destroy invading microbial pathogens. In a secondary reaction, hypochlorous acid reacts with taurine, a semi-essential amino acid. The resulting N-chlorotaurine (NCT) is a wellknown antimicrobial and anti-inflammatory oxidant (12, 15). Furthermore, NCT has shown significant bactericidal and fungicidal properties with relatively low toxicity compared to other oxidants (13,14). In the presence of an excess of hypochlorous acid or under moderately acidic conditions, NCT can be further chlorinated or, alternatively, it can disproportionate to form N,N-dichlorotaurine (NNDCT), which also has broadspectrum antimicrobial activity (9). Unfortunately, both NCT and NNDCT have relatively short solution half-lives, decomposing by hydrolytic dehydrochlorination (5, 6, 16). Because of this instability, the potential usefulness of the endogenous Nchlorotaurines as marketable therapeutics is limited. Replacement of the hydrogens at the ␤-carbon of taurine by methyl groups prevents the dehydrochlorination process, thereby circumventing this instabi...

Noncytotoxic, 0.025% hypochlorous acid in normal saline, stabilized in amber glass, successfully eradicated Ralstonia pickettii in planktonic and mature biofilm on three types of silicone implants during initial five minute soak time and may be the preferred antimicrobial solution for pocket lavage. This preliminary study requires further investigation. Leaching and implant compatibility testing is currently in progress.

IntroductionAlthough the mechanistic target of rapamycin (mTOR) might be a promising molecular target to treat advanced bladder cancer, resistance develops under chronic exposure to an mTOR inhibitor (everolimus, temsirolimus). Based on earlier studies, we proposed that histone deacetylase (HDAC) blockade might circumvent resistance and investigated whether HDAC inhibition has an impact on growth of bladder cancer cells with acquired resistance towards temsirolimus.ResultsThe HDAC inhibitor valproic acid (VPA) significantly inhibited growth, proliferation and caused G0/G1 phase arrest in RT112res and UMUC-3res. cdk1, cyclin B, cdk2, cyclin A and Skp1 p19 were down-regulated, p27 was elevated. Akt-mTOR signaling was deactivated, whereas acetylation of histone H3 and H4 in RT112res and UMUC-3res increased in the presence of VPA. Knocking down cdk2 or cyclin A resulted in a significant growth blockade of RT112res and UMUC-3res.Materials And MethodsParental (par) and resistant (res) RT112 and UMUC-3 cells were exposed to the HDAC inhibitor VPA. Tumor cell growth, proliferation, cell cycling and expression of cell cycle regulating proteins were then evaluated. siRNA blockade was used to investigate the functional impact of the proteins.ConclusionsHDAC inhibition induced a strong response of temsirolimus-resistant bladder cancer cells. Therefore, the temsirolimus-VPA-combination might be an innovative strategy for bladder cancer treatment.

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Wound healing depends on controlling bacterial balance while maintaining the viability of the healing tissues. In vitro toxicity indexes provide helpful guidelines subsequent to in vivo evaluations and clinical applications. The study findings suggest that NeutroPhase, in contrast with many commercially available wound cleansers, has rapid bactericidal activity at concentrations that are safe for human cells.