Byoung Kwan Son

Synergistic Effects and Antibiofilm Properties of Chimeric Peptides against Multidrug-Resistant Acinetobacter baumannii Strains

ABSTRACT The increasing prevalence of drug-resistant pathogens highlights the need to identify novel antibiotics. Here we investigated the efficacies of four new antimicrobial peptides (AMPs) for potential drug development. The antibacterial activities, synergistic effects, and antibiofilm properties of the four chimeric AMPs were tested against Acinetobacter baumannii, an emerging Gram-negative, nosocomial, drug-resistant pathogen. Nineteen A. baumannii strains resistant to ampicillin, cefotaxime, ciprofloxacin, tobramycin, and erythromycin were isolated at a hospital from patients with cholelithiasis. All four peptides exhibited significant antibacterial effects (MIC = 3.12 to 12.5 μM) against all 19 strains, whereas five commercial antibiotics showed little or no activity against the same pathogens. An exception was polymyxin, which was effective against all of the strains tested. Each of the peptides showed synergy against one or more strains when administered in combination with cefotaxime, ciprofloxacin, or erythromycin. The peptides also exhibited an ability to prevent biofilm formation, which was not seen with cefotaxime, ciprofloxacin, or erythromycin, though polymyxin also inhibited biofilm formation. Indeed, when administered in combination with ciprofloxacin, the AMP HPMA exerted a potent synergistic effect against A. baumannii biofilm formation. Collectively, our findings indicate that the AMPs tested have no cytotoxicity but possess potent antibacterial and antibiofilm activities and may act synergistically with commercial antibiotics.

Antibiotic and synergistic effect of Leu–Lys rich peptide against antibiotic resistant microorganisms isolated from patients with cholelithiasis

Pseudomonas aeruginosa has eventually developed resistance against flomoxef sodium, isepamicin and cefpiramide. Therefore, in this study, the antibacterial activity and synergistic effects of the amphipathic-derived P5-18mer antimicrobial peptide were tested against pathogens associated with cholelithiasis that have developed resistance against commonly used antibiotics. The results were then compared with the activities of the amphipathic-derived peptide, P5-18mer, melittin and common antibiotics. Growth inhibition of planktonic bacteria was tested using the National Committee for Clinical Laboratory Standards (NCCLS). The bactericidal activity of the antimicrobial peptides was measured using time-kill curves. Synergistic effects were evaluated by testing the effects of P5-18mer alone and in combination with flomoxef sodium, isepamicin or cefpiramide at 0.5xMIC. P5-18mer peptide displayed strong activity against pathogens and flomoxef sodium, isepamicin and cefpiramide-resistant bacteria cell lines obtained from a patient with gallstones; however, it did not exert cytotoxicity against the human keratinocyte HaCat cell line. In addition, the results of time-kill curves indicated that P5-18mer peptide exerted bactericidal activity against four strains of P. aeruginosa. Finally, the use of P5-18mer and antibiotics exerted synergistic effects against cell lines that were resistant to commonly used antibiotics. These results indicate that this class of peptides has a rapid microbicidal effect on flomoxef sodium, isepamicin and cefpiramide-resistant strains of P. aeruginosa. Therefore, these peptides may be used as a lead drug for the treatment of acquired pathogens from patients with cholelithiasis who are affected with antibiotic-resistant bacteria.

Intramural gallbladder hematoma mimicking gallbladder neoplasm in a 55-year-old male patient.

Hemorrhage in the gallbladder (GB) is usually associated with cholecystitis, GB neoplasm, trauma, hemobilia, and cystic artery aneurysm. Our patient had not experienced any previous abdominal trauma, and GB hemorrhage was unlikely to result from cholecystitis or bleeding diathesis. A 55-year-old male was admitted because of right upper quadrant pain. Both prothrombin time and partial thromboplastin time were normal. Abdominal computed tomography, endoscopic ultrasound and magnetic resonance cholangiopancreatography were performed. Image studies revealed GB wall thickening and an intraluminal mass. Laparoscopic cholecystectomy was performed. Upon opening the GB postoperatively, a large amount of fresh blood and old blood clot was noted. The incidence of GB hematoma is very rare. GB hematoma should always be considered in the differential diagnosis of GB tumor. In such a situation, surgical intervention is needed for further patient evaluation and management. We present a rare case of intramural GB hematoma, of which we were unable to make a definitive diagnosis preoperatively.

A case of eosinophilic esophagitis with food hypersensitivity.

Eosinophilic esophagitis (EoE) is a disorder characterized by isolated eosinophilic infiltration of the esophagus with esophageal symptoms. Although some patients with EoE are related to food hypersensitivity, it is hard to identify causative foods. This report describes a case of EoE with dysphagia. A 28-year-old man presented with dysphagia and substernal discomfort for 15 days. He had taken a protein complex for 2 months. Endoscopy showed several linear furrows and multiple mucosal nodularities on the lower and mid esophagus, and the biopsies of esophagus revealed marked eosinophil infiltration in the mucosa. The skin testing for the protein complex was positive. The patient was successfully treated with withholding treatment.

Diaphragm disease compared with cryptogenic multifocal ulcerous stenosing enteritis.

As the use of drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) increases, so too do gastrointestinal ulcers, bleeding, perforation and obstruction. Diaphragm disease of the small intestine is formed by submucosal fibrosis and destruction of lamina muscularis due to chronic ulceration, which corresponds to the most severe stage of NSAID enteropathy. It may lead to stricture of the small intestine. If such ulcerations and strictures in the small intestine are multiple, differential diagnosis is between diaphragm disease and cryptogenic multifocal ulcerous stenosing enteritis (CMUSE), because the gross findings of diaphragm disease are similar to those of CMUSE. We report a rare case of diaphragm disease caused by NSAID. It has been finally confirmed by capsule endoscopy and the origin of chronic obscure gastrointestinal bleeding was found to be multiple ulcers and strictures in the small intestine. After operation, we diagnosed the patient with diaphragm disease rather than CMUSE.

Gastric Outlet Obstruction Due to Gastric Amyloidosis Mimicking Malignancy in a Patient with Ankylosing Spondylitis

Amyloidosis is a group of disorders characterized by the extracellular accumulation of insoluble, fibrillar proteins in various organs and tissues. It is classified, on the basis of the identity of the precursor protein, as primary, secondary, or familial amyloidosis. Gastrointestinal amyloidosis usually presents as bleeding, ulceration, malabsorption, protein loss, and diarrhea. However, gastric amyloidosis with gastric outlet obstruction mimicking linitis plastica is rare. We report a case of gastrointestinal amyloidosis with gastric outlet obstruction in a patient with ankylosing spondylitis. The patient was indicated for subtotal gastrectomy because of the aggravation of obstructive symptoms, but refused the operation and was transferred to another hospital. Three months later, the patient died of aspiration pneumonia during medical treatment.

A Case of Oral-contraceptive Related Ischemic Colitis in Young Woman

Ischemic colitis is generally considered a disease of the elderly. The causes of ischemic colitis include low-flow states due to cardiac dysfunction or hypovolemia and certain medications including estrogen. Here we report a case of ischemic colitis in a 26-year-old woman. She had no specific medical history except taking oral-contraceptives for a long time. The mechanism of estrogen-induced ischemic colitis is not clearly understood. But we recommend that oral-contraceptives should be considered as a cause of ischemic colitis in young women.

A High Ki67/BCL2 Index Could Predict Lower Disease-Free and Overall Survival in Intestinal-Type Gastric Cancer

Background: The heterogeneity of gastric cancer makes the identification of potential prognostic indicators particularly important. The Ki67 and BCL2 proteins are known prognostic markers for different types of cancer. Ki67 is associated with cell proliferation, whereas BCL2 has antiproliferative roles. A combined marker based on these opposite functions might provide improved prognostic information in gastric cancer. Method: Ki67 and BCL2 expression was assessed in 276 gastric adenocarcinoma tissue microarrays. A Ki67/BCL2 index based on the relative expression of each protein was divided into low- and high-risk groups using receiver operating characteristic curves. Results: A high Ki67/BCL2 index significantly correlated with advanced stage, recurrence, intestinal type, high histologic grade, and lymphatic and perineural invasion (all p < 0.05). Univariate and multivariate analyses revealed a significant relationship between disease-free or overall survival and the Ki67/BCL2 index in intestinal-type gastric cancer (all p < 0.05). Conclusions: A combined marker using Ki67 and BCL2 could be a useful indicator for predicting survival in patients with intestinal-type gastric cancer.

Current Issues in Duodenoscope-Associated Infections: Now Is the Time to Take Action

A duodenoscope has a very complex structure that contains many small parts which make reprocessing more challenging. The difficulty in cleaning duodenoscopes contributes to a higher risk of infection than that of conventional gastrointestinal endoscopes. However, a duodenoscope shares similar disinfection process with other gastrointestinal endoscopes. Recent outbreaks of carbapenem-resistant Enterobacteriaceae (CRE) infections associated with duodenoscopes used for endoscopic retrograde cholangiopancreatography procedures have raised many concerns worldwide. Duodenoscope-associated infections involving CRE or other multidrug-resistant bacteria pose a great threat to patients undergoing procedures using duodenoscopes and should be dealt with a great concern. Updated guidelines regarding cleaning and disinfection of duodenoscope needs to be developed urgently to prevent transmission of infection and ensure patient safety. Meanwhile, healthcare staff should pay special attention to thorough cleaning and disinfection of duodenoscopes.

Unicentric Castleman Disease Is Not Clearly Distinguished from Multicentric Type: A Case Report

Castleman disease (CD) was recently classified as a unicentric hyaline vascular variant, unicentric plasma cell variant, and multicentric plasma cell variant. It is rare that unicentric CD is presented as multiple retroperitoneal lymphadenopathy. The clinical manifestations and prognosis depends on histologic type. We report an unusual case of CD with multiple retroperitoneal lymphadenopathy, which had unicentric hyaline vascular variant histologically but was clinically multicentric. The patient experienced anemia, weight loss, elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome), and plasmacytosis in bone marrow without human herpesvirus-8 or HIV. After exploratory laparotomy and lymphadenectomy under presumptive diagnosis of CD, the patients symptoms recovered, and CRP and ESR decreased. Therefore, we suggest that unicentric CD is not clearly distinguished from multicentric, the type in this report, focusing on the useful role of CRP, ESR, and positron emission tomography/computed tomography in the disease activity of CD.