Kaempferol inhibits IL‑1β‑induced proliferation of rheumatoid arthritis synovial fibroblasts and the production of COX‑2, PGE2 and MMPs

Inflammatory cytokines, matrix metalloproteinases (MMPs) and cyclooxygenase (COX)‑2 released from rheumatoid arthritis synovial fibroblasts (RASFs) are involved in the destruction of both articular bone and cartilage. Kaempferol has been reported to act as an antioxidant and anti‑inflammatory agent by inhibiting nitric oxide synthase and COX enzymes. The aim of the present study was to determine the effects of kaempferol on the interleukin‑1β (IL‑1β)‑induced proliferation of RASFs and the production of MMPs, COX and prostaglandin E2 (PGE2) by RASFs. The proliferation of the RASFs stimulated with IL‑1β and treated with/without kaempferol was evaluated by CCK‑8 assay. The expression of MMPs, TIMP metallopeptidase inhibitor‑1 (TIMP‑1), COXs, PGE2 and that of intracellular MAPK signaling molecules, including p‑ERK, p‑p38, p‑JNK and nuclear factor‑κB (NF‑κB) was examined by immunoblotting or semi‑quantitative reverse transcription‑polymerase chain reaction (RT‑PCR) and ELISA under the conditions described above. Kaempferol inhibited the proliferation of both unstimulated and IL‑1β‑stimulated RASFs, as well as the mRNA and protein expression of MMP‑1, MMP-3, COX‑2 and PGE2 induced by IL‑1β. Kaempferol also inhibited the phosphorylation of ERK‑1/2, p38 and JNK, as well as the activation of NF‑κB induced by IL‑1β. These results indicate that kaempferol inhibits synovial fibroblast proliferation, as well as the production of and MMPs, COX‑2 and PGE2, which is involved in articular inflammation and destruction in rheumatoid arthritis (RA). Our data suggest that kaempferol may be a novel therapeutic agent for the treatment of RA

Identification of novel urinary biomarkers for assessing disease activity and prognosis of rheumatoid arthritis

To optimize treatment for rheumatoid arthritis (RA), it is ideal to monitor the disease activity on a daily basis because RA activity fluctuates over time. Urine can be collected routinely at home by patients. Recently, we identified four urinary biomarker candidates-gelsolin (GSN), orosomucoid (ORM)1, ORM2 and soluble CD14 (sCD14)-in RA patients through transcriptomic and proteomic studies. Here, we investigated the clinical significance of the aforementioned urinary biomarker candidates in a prospective manner. For the first time, we found that urinary ORM1, ORM2 and sCD14 levels, but not GSN, were elevated in RA patients and had a positive correlation with the status of the disease activity. In particular, urine tests for ORM 1, ORM 2 and sCD14 efficiently represented the presence of high RA activity without the need for measuring blood markers. In a parallel study, a more rapid radiographic progression over 3 years was observed in patients with higher ORM2 levels. Combined measurements of urinary ORM2 and serum C-reactive protein synergistically increased the predictability of the radiographic progression of RA (odds ratio: 46.5). Collectively, our data provide evidence that blood-free, urinary biomarkers are promising surrogates for assessing disease activity and prognosis of RA. We anticipate that our urinary biomarkers will provide novel candidates for patient-driven measurements of RA activity at home and can shift the paradigm from blood to urine testing in the assessment of RA activity and prognosis in hospitals.1

Current Antimicrobial Usage for the Management of Neutropenic Fever in Korea: A Nationwide Survey

A nationwide questionnaire-based survey was performed to evaluate the current clinical practices for the management of neutropenic fever in hematology units and hematopoietic stem cell transplantation (HSCT) centers throughout Korea. A 86.9% response rate was obtained from a total of 46 doctors and practical policies of the 33 sites were analysed. Approximately 42.4% and 84.8% of the sites responded that they used oral fluoroquinolone as prophylaxis for neutropenic patients receiving chemotherapy and HSCT, respectively. Additionally, 42.4% of the sites responded that they used antifungal prophylaxis in the chemotherapy groups whereas 90.9% of the sites responded that they used antifungal prophylaxis in HSCT recipients. Approximately half of the responding sites prescribed combination regimen with 3rd or 4th cephalosporin plus aminoglycoside as a first-line therapy. Most of the sites considered persistent fever for 2-4 days or aggravated clinical symptoms for 1-2 days as failure of the first-line regimen, and they changed antibiotics to second-line regimens that varied widely among the sites. Twenty-seven sites (84.4%) responded that they considered adding an antifungal agent when fever persisted for 5-7 days despite antibacterial therapy. Amphotericin B deoxycholate was preferred as a first-line antifungal, which was probably due to the limitations of the national health insurance system. The role of oral antibiotics in the management of neutropenic fever still accounted for a small portion. To the best of our knowledge, this survey is the first report to examine the practical policies currently in place for the management of neutropenic fever in Korea and the results of this survey may help to establish a Korean guideline in the future

Current Trends of Infectious Complications following Hematopoietic Stem Cell Transplantation in a Single Center

This study was to analyze the infectious complications after hematopoietic stem cell transplantation (HSCT) according to the recent changes of HSCT. Medical records of 379 adult patients who underwent HSCT consecutively at Catholic HSCT Center from January 2001 to December 2002 were reviewed retrospectively. Allogeneic HSCT accounted for 75.7% (287/379) and autologous HSCT for 24.3% (92/379). During pre-engraftment period, bacterial infection was predominant, and E. coli was still the most common organism. After engraftment, viral infection was predominant. The incidence of invasive fungal infection showed bimodal distribution with peak correlated with neutropenia and graft-versus-host disease (GVHD). The overall mortality and infection-related mortality rates according to 3 periods were as follows; during pre-engraftment, 3.16% (12/379) and 1.8% (7/379); during midrecovery period, 7.9% (29/367) and 4.1% (15/367); during late-recovery period, 26.9% (91/338), and 15.9% (54/338). Risk factors for infection-related mortality were as follows; during pre-engraftment period, fungal infection and septic shock; during the mid-recovery period, hemorrhagic cystitis and delayed engraftment; during the late-recovery period, fungal infection, chronic GVHD, and relapse. In conclusion, infection was still one of the main complications after HSCT and highly contributes to mortality. The early diagnosis and the effective vaccination strategy are needed for control of infections

Congenital Epidermoid Cyst of the Oral Cavity: Prenatal Diagnosis by Sonography

Epidermoid cysts are benign developmental anomalies that are rarely observed in the oral cavity of neonate. If large in size, especially in the developing fetus or newborn infant, they can cause swallowing difficulty and occasionally respiratory difficulty. We report a case of epidermoid cyst in the oral cavity detected prenatal sonography. The sonographic finding was large cystic mass, measuring 30×25 mm. In this case, supplies and equipment for an emergency tracheostomy were made available prior to the delivery. However, the infant did not require intervention to secure the airway. The lesion was surgically excised, and histologic diagnosis was epidermoid cyst. After 6 months of follow up, the cyst had not recurred. This case illustrates the value of accurate prenatal diagnosis and planned perinatal management using a team approach

Prognostic Factors Influencing Infection-related Mortality in Patients with Acute Leukemia in Korea

We retrospectively reviewed the medical records of 284 patients with neutropenic fever following chemotherapy for acute leukemia at the Catholic Hematopoietic Stem Cell Transplantation Center from January 1998 to December 1999, to identify prognostic factors for infection related mortality. Twenty-eight patients died of infections. There was no difference in median age, gender ratio, or underlying disease between the dying and surviving groups. Bacteria were the main pathogens following chemotherapy, and Gram positive organisms predominated in the dying group. Pneumonia and sepsis were the main causes of death. There were 72 cases of invasive fungal infection and their mortality was 27.8%. Invasive fungal infection and previous history of fungal infection were independent prognostic factors for outcome. Recovery from neutropenia was the significant protective factor for mortality. In conclusion, the prognostic factors identified in this study could be useful for deciding on more intensive treatment for those patients at greater risk of death. To our knowledge, this is the first Korean study delineating prognostic factors in acute leukemic patients with infectious complications