N-acetyicysteine prevents lps-lnduced pro-inflammatory cytokines and mmp2 production in gingival fibroblasts

Periodontitis is an inflammatory process that ultimately results in tooth loss. Although the primary etiologic agent for periodontitis is bacteria, the majority of periodontal tissue destruction is thought to be caused by an inappropriate host response. Reactive oxygen species (ROS) have been known to be involved in periodontal tissue destruction. We treated human gingival fibroblasts with lipopolysaccharide (LPS) obtained from E. coli and the periodontopathogens Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, and examined their inflammatory responses in the presence and absence of the antioxidant N-acetylcysteine (NAC). LPS enhanced ROS production, as well as, expression of pro-inflammatory cytokines such as interleukin-1beta, interleukin-6, interleukin-8 and tumor necrosis factor-alpha, and the production and activation of MMP2. NAC suppressed all LPS-induced inflammatory responses examined, suggesting that LPS-induced ROS may play a major regulatory role in these responses in gingival fibroblasts. In addition, NAC prevented LPS-induced activation of p38 MAPK and JNK but not phosphorylation and subsequent degradation of IkB. These results indicate that NAC exerts anti-inflammatory effects in LPS-stimulated gingival fibroblasts, functioning at least in part via down-regulation of JNK and p38 MAPK activation. Furthermore, this work suggests that antioxidants may be useful in adjunctive therapies that complement conventional periodontal treatments.     

Postmortem computed tomography and magnetic resonance imaging in a case of terminal-stage small cell lung cancer: an experience of autopsy imaging in tumor-related death

We report a case of terminal-stage small-cell lung cancer with multiple metastases in which postmortem computed tomography and magnetic resonance imaging (collectively called “autopsy imaging”) were performed and correlated with conventional autopsy findings. In this case, autopsy imaging provided contemporaneous data that supported conventional autopsy findings. Autopsy imaging revealed the process of primary tumor growth, changes in metastatic lesions, and occurrences of new metastases in the terminal stage and made it easier to understand the clinical course of the patient. The usefulness of autopsy imaging after traumatic death, sudden death from natural causes, or congenital anomaly has been reported. Here, we attempted a preliminary study of its use in the detection of death due to tumor. Our results indicated that autopsy imaging provides useful information in cancer-related death and may be an alternative when conventional autopsy cannot be performed.     

Clinical overview of extrapulmonary small cell carcinoma

The objective of this study was to review the natural history of extrapulmonary small cell carcinoma (EPSCC) with specific emphasis on clinical features, response to treatment and survival. The records of all patients (n=34) with EPSCC treated at Yeungnam University Medical Center and Catholic University of Daegu Medical Center between 1998 and 2005 were retrieved and reviewed. The primary sites of tumor were the esophagus and thymus in 6 patients (17.6%) each, pancreas and stomach in 5 patients each (14.7%); other sites included were the cervix, abdominal lymph nodes, abdominal wall, bladder, colon, maxillary sinus, nasal cavity, ovary, parotid gland and liver. Twenty three patients out of 34 had limited disease. The median survival of all patients was 14 months. Independent prognostic factors included stage and primary tumor location. The prognosis for the patients with extensive disease and in the gastrointestinal group was unfavorable. EPSCC is a non homogeneous disease entity. As a result of its frequent recurrence, multimodal therapy has a better outcome even in cases of limited disease. Combination chemotherapy plays a central role for treatment of extensive disease in EPSCC. Further multicenter studies are now needed to determine more details regarding disease sub-class and optimal treatment modality.     

Overexpression of cathepsin S induces chronic atopic dermatitis in mice

Atopic dermatitis (AD) is a chronically relapsing, noncontagious pruritic skin disease with two phases: acute and chronic. Previous studies have shown that the cysteine protease cathepsin S (CTSS) is linked to inflammatory processes, including atherosclerosis and asthma. The possibility that this or other cysteine proteases might cause itching or be part of a classical ligand-receptor signaling cascade has not been previously considered. Recently, CTSS was shown to be a ligand for proteinase-activated receptor-2 (PAR-2), which is associated with itching. In this study, we show that CTSS-overexpressing transgenic (TG) mice spontaneously develop a skin disorder similar to chronic AD. The results of this study suggest that CTSS overexpression triggers PAR-2 expression in dendritic cells (DCs), resulting in the promotion of CD4(+) differentiation, which is involved in major histocompatibility complex (MHC) class II expression. In addition, we investigated mast cells and macrophages and found significantly higher mean levels of T helper type 1 (Th1) cell-associated cytokines than T helper type 2 (Th2) cell-associated cytokines in CTSS-overexpressing TG mice. These results suggest that increased PAR-2 expression in DCs as a result of CTSS overexpression induces scratching behavior and Th1 cell-associated cytokine expression, and can trigger chronic AD symptoms.     

Apolipoprotein B is highly associated with the risk of coronary heart disease as estimated by the Framingham risk score in healthy Korean men

The aim of this study was to examine the association between serum apolipoprotein B (apoB) and the risk of coronary heart disease (CHD) using Framingham risk score (FRS) in healthy Korean men. A total of 13,523 men without medication history of diabetes and hypertension were enrolled in this study. The FRS is based on six coronary risk factors. FRS ≥ 10% was defined as more-than-a-moderate risk group and FRS ≥ 20% as high risk group, respectively. The logistic regression analyses were conducted. When quartile 1 (Q1) set as a reference, in unadjusted analyses, the Q2, Q3, Q4 of apoB level had increased odds ratio (OR) for the risk of CHD in both more-than-a-moderate risk and high risk group, respectively. After adjusting for confounding variables, multivariable-adjusted logistic regression analyses showed a strong relationship between the quartiles of apoB level and more-than-a-moderate risk and high risk group, respectively. These associations were attenuated, but still remained statistically significant. ApoB is found to be independently related to the risk of CHD using FRS in healthy Korean men, and the link between apoB and the risk of CHD is dose-dependent.     

DMBA/TPA-induced tumor formation is aggravated in human papillomavirus type 16 E6/E7 transgenic mouse skin

Human papillomavirus type 16 (HPV16) is a major causative factor in the development of uterine cervical carcinomas. We investigated the role of E6/E7 in tumor formation. Skin-specific E6/E7 transgenic mice showed approximately twice as many tumors compared with nontransgenic mice in dimethylbenz[a]anthracene (DMBA)-initiated and a 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted two-stage skin carcinogenesis. This model showed a significant increase of epidermal cell proliferation in the transgenic mice. The 8-hydroxy-2'deoxyguanosine (8OH-dG) detection assay showed that oxidative DNA damage was significantly higher in the transgenic mice after TPA treatments. The overexpression of E6/E7 in the skin in the DMBA/TPA two-stage-induced carcinogenesis model aggravated the incidence of tumor formation. HPV16 E6/E7 appears to act as an enhancer of carcinogenesis that requires initiation by DMBA and promotion by TPA.     

The Association between Uric Acid and Chronic Kidney Disease in Korean Men: A 4-Year Follow-up Study

There have been many studies between serum uric acid (UA) and chronic kidney disease (CKD). However, as far as we know, little research has been done to examine the prospective association between serum UA and development of CKD in Korean men. This prospective cohort study was performed using 18,778 men who participated in a health checkup program both on January, 2005 and on December, 2009. CKD was defined as an estimated glomerular filtration rate < 60 mL/min per 1.73 m². The odds ratio (OR) from binary logistic regressions for the development of CKD was determined with respect to the quintiles grouping based on serum UA. During 74,821.4 person-years of follow-up, 110 men were found to develop CKD. The OR for the development of CKD increased as the quintiles for baseline serum UA levels increased from the first to fifth quintiles (1.00 vs 1.22, 1.19, 2.59, and 3.03, respectively, p for linear trend < 0.001) after adjusting for covariates. The adjusted OR comparing those participants with hyperuricemia ( ≥ 7.0 mg/dL) to those with normouricemia ( < 7.0 mg/dL) was 1.96 (1.28-2.99). Elevated serum UA levels were independently associated with increased likelihood for the development of CKD in Korean men (IRB number: {"type":"entrez-protein","attrs":{"text":"KBC10034","term_id":"622629790","term_text":"KBC10034"}}KBC10034).