Internal thiols and reactive oxygen species in candidacidal activity exerted by an N-terminal peptide of human lactoferrin

We previously showed that the energized mitochondrion and extracellular ATP are essential for the candidacidal activity of the N-terminal peptide of human lactoferrin, subsequently referred to as hLF(1-11). The present study focuses on the involvement of internal thiols and reactive oxygen species (ROS) in the candidacidal activity exerted by hLF(1-11). Our results reveal that hLF(1-11) reduced the internal thiol level of Candida albicans by 20%. In agreement, N-acetyl-L-cysteine (NAC), which is a precursor of glutathione and an ROS scavenger, inhibited the candidacidal activity of hLF(1-11). In addition, azodicarboxylic acid bis(N,N-dimethylamide) (diamide), which oxidizes internal thiols, was candidacidal. Furthermore, hLF(1-11) increased the level of ROS production by C. albicans in a dose-dependent manner, and a correlation between ROS production and candidacidal activity was found. 6-Hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox), which is an ROS scavenger, partially inhibited the hLF(1-11)-induced, but not the diamide-triggered, candidacidal activity. It is of interest that hLF(1-11) and diamide acted synergistically in killing C. albicans and in ROS production. In agreement, oxidized ATP, an irreversible inhibitor of extracellular ATP receptors, partially blocked the hLF(1-11)-induced, but not the diamide-triggered, candidacidal activity. Finally, the hLF(1-11)-induced activation of mitochondria was inhibited by NAC, indicating that internal thiols and ROS affect mitochondrial activity. Therefore, the candidacidal activity of hLF(1-11) involves both generation of ROS and reduction of internal thiols.     

Effectiveness of a risk-based visitor-prioritizing system at a sexually transmitted infection outpatient clinic

OBJECTIVE: The objective of this study was to study the efficacy/effectiveness of a risk-based visitor-prioritizing system at a sexually transmitted infection (STI) clinic aimed to improve screening capacity by providing tailored service. STUDY DESIGN: In April 2004, a prioritizing system was implemented that classifies visitors as high or low risk depending on reported sexual behavior and previous STI events. The high- and low-risk groups are assigned to standard and short screening protocols, respectively. Both protocols include diagnostic testing for syphilis, urogenital gonorrhea, chlamydia, and optional for HIV. To assess the effectiveness of the system, differences in prevalence of STI diagnoses in the standard and short protocol were analyzed by chi test. RESULTS: In total, 14,391 visitors (64%) received standard screening and 8,056 visitors (36%) received short screening. The STI prevalence in both groups was 18.1% and 7.6%, respectively (P <0.001); prevalence of HIV was 1.8% and 0.3%, respectively (P <0.001). The sensitivity of the prioritizing system was 74%. Specificity was substantially lower (42%). CONCLUSIONS: This prioritizing system is effective in differentiating between visitors at high and low risk for STI, contributing to provision of tailored STI service, increasing efficiency, and client access to STI service.     

Der Einfluss der Accommodation auf die Wahrnehmung von Tiefenunterschieden

Ohne Zusammenfassung     

Dietary patterns and colorectal adenomas in Lynch syndrome

BACKGROUND:

Patients with Lynch syndrome (LS) have a high risk of developing colorectal cancer due to mutations in mismatch repair genes. Because dietary factors, alone and in combination, influence sporadic colorectal carcinogenesis, the association of dietary patterns with colorectal adenomas in LS patients was assessed.

METHODS:

In the GEOLynch cohort of 486 persons with LS, dietary information was collected, using a food frequency questionnaire. Dietary pattern scores were obtained by principal components analysis. Hazard ratios (HR) between dietary patterns and colorectal adenomas were calculated using Cox regression models. Robust sandwich variance estimates were used to control for dependency within families. Final models were adjusted for age, sex, smoking habits, colorectal adenoma history, and extent of colon resection.

RESULTS:

During a median follow‐up of 20 months, colorectal adenomas were detected in 58 persons. Four dietary patterns were identified: a “Prudent,” “Meat,” “Snack,” and “Cosmopolitan” pattern. Individuals within the highest tertile of the “Prudent” pattern had a HR of 0.73 (95% confidence interval [CI], 0.32‐1.66) for colorectal adenomas, compared with the lowest tertile. Those with high “Meat” pattern scores had a HR of 1.70 (95% CI, 0.83‐3.52). A high “Snack” pattern was associated with an increased risk of colorectal adenomas (HR, 2.16; 95% CI, 1.03‐4.49). A HR of 1.25 (95% CI, 0.61‐2.55) was observed for persons in the highest tertile of the “Cosmopolitan” pattern.

CONCLUSIONS:

These findings suggest that dietary patterns may be associated with development of colorectal adenoma in patients with Lynch syndrome. The directions of these findings are corroborative with those observed in studies investigating sporadic colorectal cancer. Cancer 2013. © 2012 American Cancer Society.     

Molecular epidemiology of Neisseria gonorrhoeae in Amsterdam, The Netherlands, shows distinct heterosexual and homosexual networks

Molecular typing, added to epidemiological data, can better identify transmission patterns of gonorrhea in Western countries, where the incidence has recently been rising. From September 2002 to September 2003, patients with a laboratory-confirmed diagnosis of gonorrhea at the Clinic for Sexually Transmitted Infections in Amsterdam, The Netherlands, were subjected to a questionnaire pertaining to sexual risk behavior and sexual partners in the 6 months prior to the diagnosis. The Neisseria gonorrhoeae isolates were all genotyped using PCR-restriction fragment length polymorphism of the porin and opacity genes. All patients with a completed questionnaire and genotyped isolates were included in the study. We obtained 885 N. gonorrhoeae isolates from 696 patients that revealed 88 clusters and 46 unique genotypes. Patients infected at multiple anatomical sites with one or more strains and patients infected several times during the study period were shown to pursue high-risk sexual behavior and were considered core groups. There were 11 clusters of > or =20 patients; in seven clusters, 81% to 100% of patients were men who have sex with men (MSM), three clusters contained 87 to 100% heterosexual men and women, and one cluster was formed by equal proportions of MSM and heterosexual male and female patients. However, the various clusters differed in characteristics such as types of coinfections, numbers of sexual partners, Internet use to seek sexual partners, and locations of sexual encounters. Molecular epidemiology of gonococcal isolates in Amsterdam revealed core groups and clusters of MSM and heterosexual patients that probably indicate distinct transmission networks.