N-chlorotaurine, a potent weapon against multiresistant bacteria.

AIMS: N-chlorotaurine (NCT) is a body-own mild oxidizing antiseptic that can be applied topically as a well-tolerated anti-infective at many body sites. The objective of this study was to demonstrate its activity against representative nosocomial multidrug-resistant bacteria. METHODS AND RESULTS: The bactericidal activity of NCT was tested in quantitative killing assays against a panel of multiresistant Gram-positive and Gram-negative clinical isolates. N-chlorotaurine (1%, 55 mmol l-1 ) reduced the number of CFU of strains of methicillin-resistant Staphylococcus aureus, linezolid-resistant Staphylococcus epidermidis, vancomycin-resistant, and linezolid- and vancomycin-resistant Enterococcus faecium, 3MRGN and 4MRGN Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae by at least 2 log10 steps after 15 min and completely or nearly to the detection limit after 30 min at pH 7·1 and 37°C. CONCLUSION: The activity of NCT against these clinical isolates is similar to that against non-resistant ATCC strains and therefore not influenced by antibiotic resistance. This can be explained by the oxidizing and chlorinating mechanism of action of NCT, which leads to an attack of multiple targets in the microorganisms. SIGNIFICANCE AND IMPACT OF THE STUDY: The bactericidal spectrum of NCT is not restricted by resistance against antibiotics. Therefore, it can be used against resistant strains, too.

Childhood maltreatment in bariatric patients and its association with postoperative weight, depressive, and eating disorder symptoms.

PURPOSE: The present study aimed to compare prevalence rates of childhood maltreatment between patients with severe obesity undergoing bariatric surgery and patients without a surgical procedure. Second purpose was to calculate the association between childhood maltreatment and outcomes 6 and 12 months after a bariatric procedure. METHODS: Childhood maltreatment was assessed using the Childhood Trauma Questionnaire (CTQ) and compared between 120 bariatric surgery patients and 346 non-surgery patients with severe obesity. For the bariatric surgery subgroup, linear mixed models with repeated measures were used to analyze the predictive value of childhood maltreatment on weight outcomes and psychopathology. Additionally, between- and within-group comparisons were calculated to compare patients with and without childhood maltreatment regarding BMI and weight loss (%TWL, %EWL), depression severity (BDI-II), eating disorder psychopathology (EDE-Q), and suicidal ideation (BSS), at baseline, 6- and 12-month assessment. RESULTS: Prevalence rates for childhood maltreatment, depression and suicidal ideation were significantly higher in non-surgery compared to bariatric surgery patients. Within the surgery group, no significant interaction effect between childhood maltreatment and time was found. Hence, childhood maltreatment did not impact the course of body weight, depression and eating disorder psychopathology from pre- to post-surgery. CONCLUSIONS: Significantly higher rates of childhood maltreatment were found within non-surgery patients with obesity in comparison to bariatric surgery patients. Childhood maltreatment did not predict poorer outcomes after surgery. Since history of childhood maltreatment may increase the risk for psychological disturbances, regular screening and, if necessary, psychological support should be offered to both groups. LEVEL OF EVIDENCE: Evidence obtained from well-designed cohort or case-control analytic studies, Level III. CLINICAL TRIAL REGISTRATION: Deutsches Register Klinischer Studien-German Clinical Trials Register: DRKS00003976.

Comparative Analysis of Microbicidal and Anti-inflammatory Properties of Novel Taurine Bromamine Derivatives and Bromamine T.

Taurine, the most abundant free amino acid in leukocyte cytosol traps hypohalous acids (HOCl and HOBr) to produce N-chlorotaurine (taurine chloramine, NCT and N-bromotaurine (taurine bromamine, Tau-NHBr,) respectively. Both haloamines show anti-inflammatory and antimicrobial properties. However, the therapeutic applicability of Tau-NHBr is limited due to its relatively poor stability. To overcome this disadvantage, we have synthesized the stable N-bromotaurine compounds N-monobromo-2,2-dimethyltaurine (Br-612) and N-dibromo-2,2-dimethyltaurine (Br-422). The aim of this study was to compare anti-inflammatory and microbicidal properties of Br-612 and Br-422 with that of Tau-NHBr and bromamine T (BAT). We have shown that all the tested compounds show similar anti-inflammatory properties. Importantly, the stable N-bromotaurine compounds exerted even stronger microbicidal activity than Tau-NHBr. Finally, for the purpose of topical application of these compounds we have developed a carbomer-based bioadhesive solid dosage form of BAT and Br-612, featuring sustained release of the active substance.

[Questionnaire "Coping Procedures - Goals and Appraisals": Development and First Psychometric Evaluation in Patients with Chronic Back Pain]. / Entwicklung des Fragebogens "Krankheitsbewältigung - Ziele und Bewertung" und erste psychometrische Prüfung bei Patienten mit chronischen Rückenschmerzen.

AIM: Development of a disease specific Common Sense Model of Self-Regulation (CSM) based questionnaire assessing 'coping procedures', and their 'appraisal'. In this article, we describe the questionnaire and conduct a psychometric evaluation of the 'coping procedures'. METHODS: The item pool was generated in a multimodal way. Data were collected from 9 orthopedic rehabilitation centres, with longitudinal measurement at 3 points in time. The sample comprised N=214 rehabilitation patients. RESULTS: The questionnaire comprises CSM-based items with respect to coping procedures, their goals, and their appraisal. The coping procedures items loaded onto 2 scales, which reflected coping procedures with a focus on activity vs. biomedicine. A confirmatory analysis of a model with these 2 factors indicated an acceptable model fit. The distribution characteristics of the scales were in the range of normal distribution. Internal consistency was acceptable. The data show construct validity, sensitivity to change, comprehensibility and acceptance of the questionnaire. CONCLUSIONS: The psychometric results were satisfactory. The practical implications of our results are discussed.

Comparison of the Microbicidal activity of monochloramine and iodine.

UNLABELLED: Recently, we showed that monochloramine (NH2 Cl) has a significantly stronger bactericidal and fungicidal activity than chloramine T despite its lower oxidizing power. This phenomenon was explained by increased penetration because of the higher lipophilicity and smaller bulk of NH2 Cl. As iodine (I2 ) has an even fivefold higher bulk than NH2 Cl, a comparison of both compounds regarding their microbicidal activity became the aim of this study. Aqueous solutions of I2 at a concentration of 10·7 µmol l(-1) killed 10(6) colony forming units per millilitre (CFU ml(-1) ) of Escherichia coli, Staphylococcus aureus or Pseudomonas aeruginosa to the detection limit of 10(2) CFU ml(-1) within 1 min at 20°C and pH 7·1, while a concentration of 36-355 µmol l(-1) of NH2 Cl was needed to achieve the same effect. Aspergillus fumigatus was inactivated within 5 min by 36 µmol l(-1) I2 and by 355 µmol l(-1) NH2 Cl, Candida albicans within 1 min by 10·7 µmol l(-1) I2 and by 355 µmol l(-1) NH2 Cl. The lipophilicity of I2 , determined with the octanol/water method, was three powers of 10 higher than that of NH2 Cl. The at least 10-fold stronger microbicidal activity of iodine suggests that the hindrance of penetration of the bulky molecule is outweighed by enhanced lipophilicity. SIGNIFICANCE AND IMPACT OF THE STUDY: The microbicidal activity of active halogen compounds increases not only with their reactivity, but also with higher lipophilicity and lower bulk, as shown recently. In this study, iodine showed a higher microbicidal activity than monochloramine and a 1000-fold higher lipophilicity. Therefore, the lipophilicity of a disinfectant may be more important than the bulk for bactericidal activity. These facts should be considered upon the design of new antiseptics and their clinical application.

["Active in rehab": development and formative evaluation of a patient education program to increase health literacy of patients with chronic illness]. / "Aktiv in der Reha": Entwicklung und formative Evaluation einer Patientenschulung zur Förderung der Gesundheitskompetenz von chronisch Kranken.

OBJECTIVE: The aim of the article is to describe the development, the process of manualisation and results from the formative evaluation of a patient-oriented patient education program to increase health literacy of patients with chronic illness ("Active in rehab"). METHODS: Themes of the patient education program were extracted from 17 focus groups. An expert meeting was conducted to validate the content of the patient education program. The formative evaluation was based on a questionnaire (N(max) = 295 patients and N(max) = 39 trainers). RESULTS: The patient education program includes 4 modules with 3 themes (bio-psycho-social model, rehabilitation goals, communication competencies). The evaluation of the modules was good to very good. An analysis of free texts and a follow-up survey among trainers helped us to infer important improvements to the patient education program. CONCLUSION: RESULTS from the formative evaluation show that the patient education program meets patients and trainers needs and is accepted.

Superior bactericidal activity of N-bromine compounds compared to their N-chlorine analogues can be reversed under protein load.

AIMS: To investigate and compare the bactericidal activity (BA) of active bromine and chlorine compounds in the absence and presence of protein load. METHODS AND RESULTS: Quantitative killing tests against Escherichia coli and Staphylococcus aureus were performed both in the absence and in the presence of peptone with pairs of isosteric active chlorine and bromine compounds: hypochlorous and hypobromous acid (HOCl and HOBr), dichloro- and dibromoisocyanuric acid, chlorantine and bromantine (1,3-dibromo- and 1,3 dichloro-5,5-dimethylhydantoine), chloramine T and bromamine T (N-chloro- and N-bromo-4-methylbenzenesulphonamide sodium), and N-chloro- and N-bromotaurine sodium. To classify the bactericidal activities on a quantitative basis, an empirical coefficient named specific bactericidal activity (SBA), founded on the parameters of killing curves, was defined: SBA= mean log reductions/(mean exposure times x concentration) [mmol 1(-1) min (-1)]. In the absence of peptone, tests with washed micro-organisms revealed a throughout higher BA of bromine compounds with only slight differences between single substances. This was in contrast to chlorine compounds, whose killing times differed by a factor of more than four decimal powers. As a consequence, also the isosteric pairs showed according differences. In the presence of peptone, however, bromine compounds showed an increased loss of BA, which partly caused a reversal of efficacy within isosteric pairs. CONCLUSIONS: In medical practice, weakly oxidizing active chlorine compounds like chloramines have the highest potential as topical anti-infectives in the presence of proteinaceous material (mucous membranes, open wounds). Active bromine compounds, on the other hand, have their chance at insensitive body regions with low organic matter, for example skin surfaces. SIGNIFICANCE AND IMPACT OF THE STUDY: The expected protein load is one of the most important parameters for selection of a suited active halogen compound.

[Comprehensibility of patient education in orthopaedic rehabilitation: a qualitative study on patients and providers]. / Verständlichkeit von Patientenschulungen in der orthopädischen Rehabilitation: Qualitative Erhebung bei Rehabilitanden und Schulungsleitern.

STUDY OBJECTIVE: An important requirement for achieving postulated goals in the context of patient education is that patient education be conducted in a way that the patients can understand it. It is the objective of this explorative study to examine how patients and providers evaluate the comprehensibility and patients' comprehension of patient education under routine conditions during orthopaedic rehabilitation. Furthermore, we aim to explore the influencing factors that patients and providers describe as conducive and counterproductive to the comprehensibility of patient education, and the ideas or desires they have as to how patient education can be made more comprehensible. METHODS: We conducted guided focus groups with 50 patients with chronic back pain or osteoarthritis aged between 22 and 71 years (M=50.4, SD=9.4) and 35 patient education providers aged between 26 and 61 years (M=44.9, SD=9.8) in a total of 9 orthopaedic rehabilitation centres. Qualitative analyses of the interview transcripts were conducted according to Mayring's content analytic approach using Atlas.ti software. RESULTS: Patients and providers evaluate patient education as generally comprehensible. The involvement of patients in patient education is reported by both patients and providers as the main conducive factor. Patients describe poor (e. g. superficial or contradictory) information as counterproductive regarding comprehensibility, while providers tend to mention patients' lack of motivation and of taking personal responsibility as hindering patients' comprehension. Patients' and providers' proposals and ideas can be organized in the topics patient education (e. g. stronger reference to patients' everyday life), providers (e. g. improving providers' tutoring skills), information (e. g. more information), patient involvement (e. g. stronger consideration of patients' interests), organization (e. g. smaller groups), and goal clarification (e. g. consideration of patients' expectations). CONCLUSION: Our results reveal that good comprehensibility can be achieved in patient education during routine orthopaedic rehabilitation. They also show the factors that account for good comprehensibility. The counterproductive factors described by patients and providers provide evidence of the factors that may hold potential for improving patient education with regard to comprehensibility.

Antimicrobial and anticoagulant activities of N-chlorotaurine, N,N-dichloro-2,2-dimethyltaurine, and N-monochloro-2,2-dimethyltaurine in human blood.

The aim of this study was to determine the potential application of N-chlorotaurine (NCT), N,N-dichloro-2,2-dimethyltaurine (NVC-422), and N-monochloro-2,2-dimethyltaurine (NVC-612) as catheter lock solutions for the prevention of catheter blockage and catheter-related bloodstream infections by testing their anticoagulant and broad-spectrum antimicrobial activities in human blood. NCT, NVC-422, NVC-612, and control compounds were serially diluted in fresh human blood to evaluate the effects on prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, and direct thrombin inhibition. Quantitative killing assays against pathogens, including methicillin-resistant Staphylococcus aureus, Escherichia coli, and Candida albicans, were performed in the presence of heparin and human blood. NCT and NVC-612 (1.38 mM each) and 1.02 mM NVC-422 prolonged prothrombin time (Quick value, 17 to 30%), activated partial thromboplastin time 3- to 4-fold to 76 to 125 s, and thrombin time 2- to 4-fold to 34 to 68 s. Fibrinogen decreased from 258 to 283 mg/dl (range of controls) to <40 mg/dl. No direct thrombin inhibition was observed by NVC-422 or NVC-612. Heparin did not influence the bactericidal activity of NCT. The microbicidal activities of NCT, NVC-422, and NVC-612 were maintained in diluted human blood. NCT, NVC-612, and NVC-422 have broad-spectrum antimicrobial activity in blood and anticoagulant activity targeting both intrinsic and extrinsic pathways of the coagulation system. These properties support their application as catheter lock solutions.

[The development of an instrument assessing the relevance of rehabilitation outcomes for patient participation: retest reliability and descriptive results]. / Die Entwicklung eines Instruments zur Erfassung der Teilhabe-Relevanz von Rehabilitationseffekten: Retest-Reliabilität und deskriptive Ergebnisse.

OBJECTIVE: In the context of an increasing patient orientation in health care, surveying patients on the success of treatment has become highly relevant. The objective of the study was to develop and test an instrument for surveying the patients' perceptions of the participation relevance of changes in health status after inpatient medical rehabilitation with respect to various areas of life for 3 diagnoses: breast cancer, chronic ischemic heart disease, and chronic back pain. METHODS: The instrument refers to certain disease-specific areas of health (e. g., mobility) with regard to which the patients are asked whether they perceived an improvement and if so, what improvement in participation had ensued as a result. A questionnaire study (measuring time points: end of rehab and 6 months after the end of rehab) was conducted in 3 samples (breast cancer: n=297, chronic ischemic heart disease: n=295, chronic back pain: n=186) to test the methodology. The share of missing values and undesirable ceiling/floor effects were assessed to analyze the distribution characteristics. In a partial sub-sample, a third measuring time point was introduced approx. 10 days after the second measuring time point, and the retest reliability of the assessment of participation relevance is determined using the ICC. We also present descriptive results relative to the participation relevance from the patient perspective. RESULTS: The instrument shows good distribution characteristics for the items. Regarding retest reliability, there were satisfactory values for all diagnoses in all areas of health. The descriptive analyses showed that patients who perceived a noticeable improvement in their health status at the end of rehabilitation or 6 months after inpatient rehab generally assessed the participation relevance of this improvement in health to be "moderate" to "strong". DISCUSSION: The concept of assessing the participation relevance from the patient perspective is a satisfactorily reliable construct. By including the subjective significance of treatment success it takes into account the concept of clinical significance from the patient's perspective, a concept which has thus far been considered only insufficiently. Results show that patients ascribe the health improvements achieved by rehabilitation a noticeable relevance for their participation.

[Therapy-resistant otitis externa with additional tympanic membrane perforation: local therapy using N-chlorotaurine and dexamethasone]. / Therapieresistente Otitis externa mit zusätzlicher Trommelfellperforation: Lokaltherapie mit N-Chlortaurin und Dexamethason.

Ear canal infections may not always be clinically distinguished between a bacterial otitis externa, an otomycosis or a mixed infection. In addition, tympanic membrane perforations are often not immediately apparent. The use of a broad-spectrum antiseptic agent without an inner ear toxic effect would therefore be beneficial. We report the case of a female patient suffering from intractable otitis externa with tympanic membrane perforation, who was successfully treated locally with a mixture of 1% NCT and 0.1% dexamethasone.

Effect of N-chlorotaurine mouth rinses on plaque regrowth and plaque vitality.

The purpose of this 4-day plaque regrowth study was to assess the effect of N-chlorotaurine (NCT) mouth rinses on plaque inhibition and plaque vitality. Eighty volunteers participated in this investigator-blind, randomized, clinical controlled study in parallel groups. No oral hygiene was permitted except rinsing with a 2% or 3% NCT mouth rinse, a positive or a negative control. Primary parameters were the plaque index (Silness and Löe, Acta Odontol Scand, 22:121-135, 1964) and plaque vitality (Netuschil et al., J Clin Periodontol, 16:484-488, 1989) after the final rinse. In addition, another plaque index (Turesky et al., J Periodontol, 41:41-43, 1970), plaque area, and bleeding on probing were recorded. All parameters were taken at baseline and day 5. U test was applied on a 5% error level. No differences in plaque inhibition were found between the two NCT formulations and the negative control. However, a statistically significant reduction of plaque vitality compared to the negative and positive control was observed. Discoloration of the tongue and unpleasant taste were recorded in participants in the NCT groups. NCT mouth rinses did not inhibit plaque regrowth, but they did reduce the vitality of plaque bacteria. Methods of prolonging the substantivity of the NCT mouth rinses should be investigated to enhance the antibacterial properties of these formulations.

[Otitis externa: etiology, diagnostic and therapy]. / Otitis externa: Atiologie, Diagnostik und Therapie.

Otitis externa (OE) occurs during the lifetime in approximately 10% of the population, especially in warm and damp climates or from swimming (swimmer's ear). Females are most often affected around the age of 50 years and males around 70 years of age. Both auditory canals are affected in approximately 10% of cases. Causes of infection are mostly bacteria, and more rarely fungi or viruses. OE can be accompanied not only by relatively slight pain and light swelling of the skin of the auditory canal, but also by severe pain, complete obstruction of the external meatus and retroauricular swelling. An uncomplicated infection can normally be treated by cleaning of the meatus by an ENT specialist and local application of a broad-spectrum antibiotic or an antiseptic supplemented with corticoids as well as antimycotics. Complicated infections, such as necrotizing OE, are rare and normally only occur in elderly patients with diabetes mellitus or in an immunosuppressed condition.

Dissimilar attenuation of Candida albicans virulence properties by human immunodeficiency virus type 1 protease inhibitors.

The secreted aspartyl proteinase (Sap) of Candida albicans, which is believed to represent an important virulence factor of this opportunistic yeast, and the human immunodeficiency virus type 1 (HIV-1) protease, which is obligatory for the production of infectious virions, both belong to the same family of aspartyl proteinases. We have previously shown that the HIV-1 protease inhibitor Indinavir directly inhibits secretion and proteinase activity of Sap in a dose-dependent manner. Furthermore, at very high concentrations, viability of C. albicans is markedly reduced by Indinavir, indicating that HIV-1 protease inhibitors may possess antifungal activity. We thus proposed that these drugs may add to the resolution of mucosal candidiasis in HIV-1 infected subjects. We have now compared three different HIV-1 protease inhibitors. The rank order of Sap inhibition, already significant at 0.1 mg/ml for all protease inhibitors, was Ritonavir > Indinavir > Saquinavir. However, the cross-reactivity of Ritonavir to pepsin was also more pronounced compared with the other two. Indinavir did not affect Candida viability at concentrations up to 1 mg/ml, in line with our previous study. In contrast, at this concentration Saquinavir was even fungicidal as assessed by three different viability assays (colony formation assay, MTT assay, propidium iodide staining) whereas Ritonavir significantly affected the mitochondrial activity only (MTT assay). No influence on Candida viability was observed for any of the three at concentrations of 0.1 mg/ml or lower. It remains to be examined whether HIV-1 protease inhibitors or derivatives thereof may be suitable for in vivo therapy of subjects suffering from mucosal candidiasis resistant to current antimycotics.

Activity of N-chlorotaurine against herpes simplex- and adenoviruses.

N-chlorotaurine, an essential weak oxidant produced by stimulated human leukocytes, is known to have bactericidal, fungicidal and vermicidal properties. This study for the first time demonstrates its virucidal activity. By viral suspension tests at incubation times between 5 and 60 min, virus titers of both Herpes simplex virus type 1 and 2 were reduced about 1.3-2.9 log10 and 2.8-4.2 log10 by 0.1 and 1%, (5.5 and 55 mM) N-chlorotaurine, respectively. Virus titer reduction of adenovirus type 5 between 15 and 60 min was 0.5-2.0 and 0.6-4.0 log10, respectively, by the same concentrations of N-chlorotaurine. These findings support a contribution of N-chlorotaurine in destruction of pathogens during inflammatory reactions and also the possibility of its application as an antiviral agent in human medicine.

N-chlorotaurine, a novel endogenous antimicrobial agent: tolerability testing in a mouse model.

OBJECTIVE: To investigate the tolerability of N-chlorotaurine, a new antimicrobial agent, by application to the middle ear in a mouse model. METHODS: Five BALB/c mice were each injected through the tympanic membrane with 5 microL of 0.1%, 1.0%, and 10% N-chlorotaurine and compared with animals in which 0.9% isotonic sodium chloride solution, 0.2% gentamicin sulfate, and 0.25% trimethyltin chloride were instilled. Auditory brainstem responses to clicks were evaluated repeatedly between 4 and 75 days after injection, and histologic investigations of the inner ear were performed subsequently. Three additional groups of mice were injected with isotonic sodium chloride solution, 1.0% N-chlorotaurine, and 0.25% trimethyltin, and brainstem responses to tone bursts of 8, 16, and 32 kHz were tested. In addition, the middle ear was examined histologically. RESULTS: Mice treated with isotonic sodium chloride solution, 0.1% N-chlorotaurine, and 0.2% gentamicin sulfate did not show changes in response threshold. Treatment with 1.0% and 10% N-chlorotaurine caused a reversible increase in auditory brainstem response threshold by 20 dB 4 days after application because of local irritation around the perforation of the tympanic membrane. In contrast, 0.25% trimethyltin showed a permanent elevation of auditory brainstem response threshold of 10 to 15 dB and a scattered loss of outer hair cells predominantly in the apical turn. No alterations of the inner ear were observed in the other treatment groups. The mucous membrane of the middle ear remained unaffected in all test groups. CONCLUSION: Application of N-chlorotaurine to the middle ear is well tolerated without adverse effects and may be a useful new endogenous antimicrobial agent for local treatment of otologic infections.

Rapid killing of Mycobacterium terrae by N-chlorotaurine in the presence of ammonium is caused by the reaction product monochloramine.

We have studied the activity of the weak endogenous oxidant N-chlorotaurine against Mycobacterium terrae. The study revealed slow killing of more than 2h duration by 1% (55 mM) N-chlorotaurine. In the presence of ammonium chloride, however, killing times decreased to a few minutes, even by 0.1% N-chlorotaurine. This phenomenon is explained by formation of the lipophilic and therefore more bactericidal monochloramine as a result of transhalogenation of ammonia by N-chlorotaurine.

The influence of plasma on the disinfecting activity of the new antimicrobial agent N-chlorotaurine-sodium in comparison with chloramine T.

The phenomenon of increasing bactericidal activity of N-chlorotaurine in the presence of chlorine-consuming material has been investigated both on a chemical-analytical and microbiological basis using plasma as substrate and chloramine T for comparison. Chlorine consumption assessed by iodometric titration showed a biphasic time-course with a very fast loss of oxidation capacity within one minute (N-chlorotaurine: -9.3%, chloramine T: -16.8%) followed by a slow loss which could still be detected after 24 h (total loss -61.7% and -74.1%, respectively). Killing curves revealed that an increase in bactericidal activity, in spite of improved consumption, did not occur with all strains, and could be detected only at a certain degree of consumption. Escherichia coli and Pseudomonas aeruginosa showed the most pronounced effect, Streptococcus pyogenes and Proteus mirabilis a medium-sized one, while it was absent in Staphylococcus aureus. With chloramine T, an increase in bactericidal activity could not be proved. The chemical basis of these consumption effects can be reduced to four reaction types: oxidation of thiols; chlorine substitution of activated C-H compounds; transhalogenation; and hydrolytic degradation of N-chloro-alpha-amino acids and -peptides emerging by transhalogenation. The initial fast loss of oxidation capacity can be attributed mainly to oxidation of thiols, while the subsequent slower decrease is caused by the other types of reaction. The increase in bactericidal activity, on the other hand, can be explained by transhalogenation, leading to the formation of more bactericidal N-chloro compounds by which the loss of N-chlorotaurine is over-compensated.

Influence of sequential cultivation on virulence of Legionella pneumophila and Staphylococcus aureus.

Virulence of Legionella pneumophila strain Monza 3 and Staphylococcus aureus strain Smith diffuse was investigated after sequential cultures on nutrient media. L. pneumophila lost its ability to multiply within Acanthamoeba polyphaga after 50 passages on Legionella selective agar, while S. aureus maintained its pathogenicity in the mouse peritonitis model after 100 sequential cultures on tryptic soy agar. These results demonstrate high preservation of virulence in staphylococci in contrast to legionellae. Differentiation of virulent and avirulent phenotypes of legionellae by the protozoal model may be helpful for detecting sources of infection in water hygiene.

Tolerance of N-chlorotaurine, an endogenous antimicrobial agent, in the rabbit and human eye--a phase I clinical study.

N-chlorotaurine (NCT), an essential weak oxidative N-chloro compound produced by stimulated human leukocytes, shows bactericidal, fungicidal, virucidal and vermicidal efficacy. A double-blind, randomized and placebo controlled study was done to evaluate the tolerance of the aqueous NCT solution by application to rabbit and human conjunctiva. In six rabbits treated with 1% and 3% NCT regimen for nine days no ocular and behaviour changes could be observed. In a pilot study with two volunteers, treatment with 2.8% NCT for five days caused a self-limited conjunctival injection of one subject, while 1% NCT was well tolerated. Subsequently, eight healthy volunteers participated in a phase I clinical study. One percent NCT was applied for five days and was well tolerated by all subjects except for minimal eye burning after the application. Because of these positive results, usage of the antimicrobial agent NCT in ophthalmology is suggested.