Inhibitory effects of lycopene on HMGB1-mediated pro-inflammatory responses in both cellular and animal models

High mobility group box 1 (HMGB1) mediates proinflammatory responses in inflammatory diseases. Lycopene found in tomatoes and tomato products has anti-oxidant, anti-cancer and antiinflammatory effects. The potential anti-inflammatory roles of lycopene in HMGB1-mediated proinflammatory responses in both primary human umbilical vein endothelial cells (HUVECs) and animal were investigated. The anti-inflammatory effects of lycopene were determined including permeability, monocyte adhesion and migration, and activation of proinflammatory proteins and HMGB1 receptors on HMGB1 activated HUVECs. In the in vivo model, the anti-inflammatory effect of lycopene was assessed by monitoring vascular permeability and migration of leukocytes to the peritoneal cavity of mice injected with lycopene. Lycopene inhibited lipopolysaccharide (LPS)-mediated release of HMGB1, expression of HMGB1-mediated tumor necrosis factor (TNF)-secretory phospholipase A2 (sPLA2)-IIA, and HMGB1-mediated pro-inflammatory signaling responses in endothelial cells. It did this through down-regulation of cell surface expression of cell adhesion molecules (CAMs), HMGB1 receptors, toll-like receptor (TLR)-2, and -4, and receptors for advanced glycation end products (RAGE). These findings suggest that lycopene promotes barrier integrity, inhibits monocyte adhesion and migration to HMGB1 activating HUVECs by blocking activation of proinflammatory cytokines and expression of CAMs and HMGB1 receptors, thereby showing its usefulness as a therapy for vascular inflammatory diseases.     

The bark of Betula platyphylla var. japonica inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice

The bark of Betula platyphylla Sukat. var. japonica Hara (Asian White Birch, AWB) is one of the herbs used in Eastern countries for the treatment of various inflammatory diseases including atopic dermatitis (AD). The present study was performed to examine if and how the bark of AWB inhibits the development of AD-like skin lesions in NC/Nga mice induced by repeated application of picryl chloride (PC). With this aim, we examined the skin symptom severity, itching behavior, serum immunoglobulin (Ig) E level and mRNA expression of cytokines at iliac and cervical lymph nodes in the mice. Oral administration of AWB extracts (25, 100 and 250 mg/kg) to the PC-treated mice inhibited the development of AD-like skin lesions as exemplified by a significant decrease in the total skin severity scores, itching behavior and a decrease in hypertrophy and infiltration of inflammatory cells into dermis. The serum IgE level was also significantly reduced by AWB extract. In the RT-PCR results, the expression of interleukin-4 mRNA was reduced by AWB extract, whereas the expression of interferon-gamma mRNA was not changed. These results suggest that AWB inhibits the development of AD-like skin lesions in NC/Nga mice through the suppression of the T-helper 2 cell response.     

Clinical analysis of synchronous primary neoplasms of the female reproductive tract

OBJECTIVES: In this study, a histopathologic review of synchronous primary neoplasms including gynecologic malignancies is presented, and the possible correlation among discrete tumor subsets, natural history, and survival is evaluated. METHODS: Between the years 2000 and 2005, 20 patients suffering from synchronous primary cancers of gynecologic malignancy were identified. Clinical and pathologic information was obtained from medical records. Kaplan-Meier survival analyses were conducted. RESULTS: Patients with synchronous primary malignancies constituted 0.63% of all genital malignancies. The most frequently observed synchronous neoplasm was ovarian cancer coexistent with endometrial cancer (40%). The mean age of patients suffering from synchronous ovarian and endometrial cancer was 45.2 years. All patients with synchronous primary genital malignancies underwent hysterectomy with bilateral salpingo-oophorectomy and/or adjuvant therapy. The mean duration of survival was 57 months (S.E.: 10.0; 95% confidence interval: 37-77). CONCLUSION: Patients suffering from primary genital malignancies are sometimes co-afflicted with other primary cancers. Synchronous ovarian and endometrial cancer constitutes the most common of these cases, and is detected at a relatively early age, with generally favorable prognoses.     

Sodium Glucose Cotransporter-2 Inhibitors as an Add-on Therapy to Metformin Plus Dipeptidyl Peptidase-4 Inhibitor in Patients with Type 2 Diabetes

PurposeTo date, no study has compared the effects of adding sodium glucose cotransporter-2 (SGLT-2) inhibitors to the combination of metformin plus dipeptidyl peptidase-4 (DPP-4) inhibitors to the effects of adding other conventional anti-diabetic drugs (ADDs) to the dual therapy. We aimed to compare the effect of adding SGLT-2 inhibitors with that of adding sulfonylurea (SU) in type 2 diabetes (T2D) patients inadequately controlled with metformin plus DPP-4 inhibitors.Materials and MethodsThis study was designed to evaluate the non-inferiority of SGLT-2 inhibitor to SU as an add-on therapy to the dual combination of metformin plus DPP-4 inhibitors. A total of 292 T2D patients who started SU or SGLT-2 inhibitors as an add-on therapy to metformin plus DPP-4 inhibitors due to uncontrolled hyperglycemia, defined as glycated hemoglobin (HbA1c) ≥7%, were recruited. After propensity score matching, 90 pairs of patients remained, and 12-week changes in HbA1c levels were reviewed to assess glycemic effectiveness. Data from these patients were analyzed retrospectively.ResultsAfter 12 weeks of triple therapy, both groups showed significant changes in HbA1c levels, with a mean of -0.9% in each group. The inter-group difference was 0.01% [95% confidence interval (CI): -0.26–0.27], and the upper limit of the 95% CI was within the limit for non-inferiority (0.40%). There were no inter-group differences in the changes of liver enzyme levels and kidney function.ConclusionAdding SGLT-2 inhibitors is not inferior to adding SU as a third-line ADD to metformin plus DPP-4 inhibitor combination therapy.     

A Retrospective National Study on Colonization Rate and Antimicrobial Susceptibility of Streptococcus agalactiae in Pregnant Korean Women, 2018–2020

PurposeThe prevalence of Group B Streptococcus (GBS) colonization in pregnant Korean women is increasing; however, nationwide studies are lacking. Therefore, we aimed to analyze regional colonization rates and antimicrobial susceptibility for GBS in pregnant Korean women through a nationwide survey.Materials and MethodsFrom January 2018 to December 2020, data from the Seoul Clinical Laboratories on vaginal swab cultures were retrospectively analyzed to detect maternal GBS carriers. Each swab specimen was inoculated onto a 5% blood agar plate and incubated at 35℃–37℃ in a 5% CO₂ incubator for 24 h. GBS isolates were identified using a Microflex MALDI Biotyper. Antimicrobial susceptibility tests were performed using the Vitek 2 automated system.ResultsThe overall nationwide GBS colonization rate in pregnant Korean women was found to be 10.6% (3578/33721). The maternal GBS colonization rates ranged from 10.5%–10.8% over the 3-year study period. The GBS colonization rates by province, in descending order, were as follows: Jeolla-do, 13.2%; Gangwon-do, 12.0%; Chungcheong-do, 11.8%; Gyeonggi-do, 11.3%; Seoul, 10.2%; and Gyeongsang-do, 9.6%. During the study period, the resistance rates against chloramphenicol, levofloxacin, clindamycin, erythromycin, and tetracycline were 2.6%–2.7%, 18.2%–19.6%, 33.4%–35.7%, 35.6%–36.8%, and 50.5%–53.3%, respectively.ConclusionIn pregnant Korean women, GBS colonization rates were in the range of 9.6%–13.2%, with Gyeongsang-do being the lowest and Jeolla-do the highest. The resistance rate against clindamycin was high (33.4%–35.7%). GBS colonization rates during pregnancy should be studied nationwide according to the Centers for Disease Control and Prevention-recommended guidelines with periodic antimicrobial resistance monitoring.     

Surgical Complications and the Risk Factors of Laparoscopy-Assisted Distal Gastrectomy in Early Gastric Cancer

Background Information on surgical complications of laparoscopy-assisted distal gastrectomy (LADG) and their risk factors is limited in the literature despite increasing popularity of this procedure. This study was performed to identify the surgical complications and their associated risk factors of LADG in early gastric cancer. Methods LADG was performed in 347 gastric cancer patients from January 2002 to December 2006 at the Korean National Cancer Center by four surgeons with ample experience of open gastric surgery before LADG. LADG indications for cases of gastric cancer at our institution are preoperatively diagnosed cT1N0 or cT1N1, except in cases with an absolute indication for endoscopic resection. Lymph node dissection of more than D1 + β was performed in all patients. Intraoperative and postoperative complications were reviewed and their risk factors were retrospectively analyzed by prospective database information. Results Forty complications occurred in 34 patients (9.8%), but there was no mortality. Intraoperative complications occurred in nine patients (2.6%), and open conversion was performed in eight (2.3%) of these patients. Early and late postoperative complications occurred in 21 (6.1%) and 10 (2.9%) patients, respectively. The most serious complication was vascular injury resulting in bleeding or organ ischemia, which occurred in seven patients. Degree of lymph node dissection and surgical inexperience were found to be risk factors of surgical complication (P = .023, odds ratio 2.832, 95% confidence interval 1.155–6.946 vs. P = .028, odds ratio 2.975, 95% confidence interval 1.127–7.854). Conclusions Lymph node dissection during LADG should be performed cautiously to prevent surgical complications like vascular injuries, especially during the surgeon’s early learning period.     

Effects of anesthetic agents on cellular <Superscript>123</Superscript>I-MIBG transport and in vivo <Superscript>123</Superscript>I-MIBG biodistribution

Objectives Small animal imaging with meta-iodobenzylguanidine (MIBG) allows characterization of animal models, optimization of tumor treatment strategies, and monitoring of gene expression. Anesthetic agents, however, can affect norepinephrine (NE) transport and systemic sympathetic activity. We thus elucidated the effects of anesthetic agents on MIBG transport and biodistribution. Methods SK-N-SH neuroblastoma and PC-12 pheochromocytoma cells were measured for ¹²³I-MIBG uptake after treatment with ketamine (Ke), xylazine (Xy), Ke/Xy, or pentobarbital (Pb). NE transporters were assessed by Western blots. Normal ICR mice and PC-12 tumor-bearing mice were injected with ¹²³I-MIBG 10 min after anesthesia with Ke/Xy, Ke, Xy, or Pb. Plasma NE levels and MIBG biodistribution were assessed. Results Cellular ¹²³I-MIBG uptake was dose-dependently inhibited by Ke and Xy but not by Pb. Treatment for 2 h with 300 μM Ke, Xy, and Ke/Xy decreased uptake to 46.0 ± 1.6, 24.8 ± 1.5, and 18.3 ± 1.6% of controls. This effect was completely reversed by fresh media, and there was no change in NE transporter levels. In contrast, mice anesthetized with Ke/Xy showed no decrease of MIBG uptake in target organs. Instead, uptakes and organ-to-blood ratios were increased in the heart, lung, liver, and adrenals. Plasma NE was notably reduced in the animals with corresponding decreases in blood MIBG, which partly contributed to the increase in target organ uptake. Conclusion In spite of their inhibitory effect at the transporter level, Ke/Xy anesthesia is a satisfactory method for MIBG imaging that allows favorable target tissue uptake and contrast by reducing circulating NE and MIBG. Bong-Ho Ko and Jin-Young Paik equally contributed to this work. This work was supported by the Korea Research Foundation Grant KRF-2005-202-E00116. Presented in part at the fifth Annual Meeting of the Society for Molecular Imaging, Hawaii, August 30–September 2, 2006.     

Comparative study of the extent of palatal lengthening by different methods

Palatal lengthening is often emphasized in performing palatoplasty. However, definitive data regarding the method of measuring palatal length and the extent of palatal lengthening expressed quantitatively have not been reported. The authors have devised an easy method of measuring palatal length that can be expressed quantitatively, and they examined the characteristics of various methods of palatoplasty that are presently used commonly. A paper ruler was used to measure both a straight-line and a curved distance while the patient was under general anesthesia before and immediately after the palatoplasty. According to this study, the straight-line distance was lengthened to a significantly greater degree than the curved distance was after pushback palatoplasty for incomplete types of cleft palate and two-flap palatoplasty for complete types. Furlow double-opposing Z-palatoplasty and two-flap palatoplasty appeared to allow for greater palatal lengthening than the pushback palatoplasty. Further investigations will be undertaken to determine the correlation between the extent of palatal lengthening and speech development.