Antimicrobial Activity of Platelet‐Rich Plasma and Other Plasma Preparations Against Periodontal Pathogens

Background: In addition to releasing a pool of growth factors during activation, platelets have many features that indicate their role in the anti‐infective host defense. The antimicrobial activities of platelet‐rich plasma (PRP) and related plasma preparations against periodontal disease–associated bacteria were evaluated. Methods: Four distinct plasma fractions were extracted in the formulation used commonly in dentistry and were tested for their antibacterial properties against three periodontal bacteria: Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Fusobacterium nucleatum. The minimum inhibitory concentration of each plasma preparation was determined, and in vitro time‐kill assays were used to detect their abilities to inhibit bacterial growth. Bacterial adhesion interference and the susceptibility of bacterial adherence by these plasma preparations were also conducted. Results: All plasma preparations can inhibit bacterial growth, with PRP showing the superior activity. Bacterial growth inhibition by PRP occurred in the first 24 hours after application in the time‐kill assay. PRP interfered with P. gingivalis and A. actinomycetemcomitans attachment and enhanced exfoliation of attached P. gingivalis but had no influences on F. nucleatum bacterial adherence. Conclusions: PRP expressed antibacterial properties, which may be attributed to platelets possessing additional antimicrobial molecules. The application of PRP on periodontal surgical sites is advisable because of its regenerative potential and its antibacterial effects.     

The Cyclic Peptide Ecumicin Targeting ClpC1 Is Active against Mycobacterium tuberculosis In Vivo

Drug-resistant tuberculosis (TB) has lent urgency to finding new drug leads with novel modes of action. A high-throughput screening campaign of >65,000 actinomycete extracts for inhibition of Mycobacterium tuberculosis viability identified ecumicin, a macrocyclic tridecapeptide that exerts potent, selective bactericidal activity against M. tuberculosis in vitro, including nonreplicating cells. Ecumicin retains activity against isolated multiple-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of M. tuberculosis. The subcutaneous administration to mice of ecumicin in a micellar formulation at 20 mg/kg body weight resulted in plasma and lung exposures exceeding the MIC. Complete inhibition of M. tuberculosis growth in the lungs of mice was achieved following 12 doses at 20 or 32 mg/kg. Genome mining of lab-generated, spontaneous ecumicin-resistant M. tuberculosis strains identified the ClpC1 ATPase complex as the putative target, and this was confirmed by a drug affinity response test. ClpC1 functions in protein breakdown with the ClpP1P2 protease complex. Ecumicin markedly enhanced the ATPase activity of wild-type (WT) ClpC1 but prevented activation of proteolysis by ClpC1. Less stimulation was observed with ClpC1 from ecumicin-resistant mutants. Thus, ClpC1 is a valid drug target against M. tuberculosis, and ecumicin may serve as a lead compound for anti-TB drug development.     

Esthesioneuroblastoma: An Update on the UCLA Experience, 2002–2013

Objectives To profile the clinical presentation and treatment results of esthesioneuroblastomas at the University of California, Los Angeles (UCLA), from 2002 to 2013. Design Retrospective review. Setting Tertiary academic institution. Participants Forty-one patients with esthesioneuroblastomas treated at UCLA. Main Outcome Measures Overall survival (OS) and recurrence-free survival (RFS). Results Thirty-six patients were included with a mean age of 50.1 years and a median duration of follow-up of 33 months. The 5-year RFS and OS were 54% and 82%, respectively. Modified Kadish stage was the only factor identified to affect OS. Multivariate analysis demonstrated that tumor grade was the only factor that had an independent impact on RFS. There was no statistical difference in survival among the surgical approaches chosen. Conclusions The updated data on the UCLA experience reveals that all three surgical approaches chosen provide comparable survival, although longer follow-up will be needed to ascertain if these findings hold true. The endoscopic approach had a statistically significant decrease in length of hospital stay and a trend toward reduced blood loss, intensive care unit admission, and complications. The modified Kadish staging was the only factor identified to predict OS. Multivariate analysis revealed that tumor grade was an independent predictor of recurrence; therefore, its importance should be emphasized in future staging systems.     

Recent increase in antibiotic-resistant microorganisms in patients with spontaneous bacterial peritonitis adversely affects the clinical outcome in Korea

BACKGROUND AND AIM: Recently, antibiotic-resistant microorganisms have been increasingly noted in Korean patients with spontaneous bacterial peritonitis (SBP). The present study investigated the changing pattern of antibiotic resistance and its effects on the clinical outcome in treating SBP. METHODS: The present study retrospectively analyzed 87 episodes of SBP in 1995, 222 in 1998, and 271 in 1999. The isolated microorganisms and their antibiotic susceptibility were compared, and prognostic factors for survival were analyzed. RESULTS: Microorganisms were isolated in 41% of total episodes. The three most frequently isolated organisms were Escherichia coli (48%), Klebsiella pneumoniae (15%), and Aeromonas (8%). Strains that were resistant to cefotaxime in Gram-negative bacilli significantly increased from 7% in 1995 to 28% in 1999, and those to ciprofloxacin increased from 10% to 32%. Treatment failure also increased from 6% to 23%. Combined hepatocellular carcinoma and SBP caused by extended-spectrum beta-lactamase-producing strains were two independent prognostic factors for survival. CONCLUSION: Considering the increase in antibiotic-resistant microorganisms related to SBP, measures to prevent the in-hospital spread of resistant strains and the indiscriminate use of antibiotics should be instituted more stringently.     

Histone Acetylation Level and Histone Acetyltransferase/Deacetylase Activity in Ejaculated Sperm from Normozoospermic Men

Purpose

The aim of this work was to evaluate nuclear histone acetylation level and total histone acetyltransferase (HAT) and deacetylase (HDAC) activity in ejaculated sperm and their relevance to conventional sperm parameters.

Materials and Methods

Thirty-three normozoospermic men were included in this study. Semen samples were processed by swim-up and then immunostained by six acetylation antibodies (H3K9ac, H3K14ac, H4K5ac, H4K8ac, H4K12ac, and H4K16ac). Our preliminary study verified the expression of HAT/HDAC1 in mature human sperm. From vitrified-warmed sperm samples, total HAT/HDAC activity was measured by commercially available kits. Nuclear DNA integrity was also measured by TUNEL assay.

Results

The levels of six acetylation marks were not related with conventional sperm parameters including sperm DNA fragmentation index (DFI) as well as HAT/HDAC activity. However, sperm DFI was positively correlated with HAT activity (r=0.038 after adjustment, p<0.02). HAT activity showed a negative relationship with HDAC activity (r=-0.51, p<0.01). Strict morphology was negatively correlated with acetylation enzyme index (=HAT activity/HDAC activity) (r=-0.53, p<0.01).

Conclusion

Our works demonstrated a significant relationship of acetylation-associated enzyme activity and strict morphology or sperm DFI.