Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk

BackgroundElevated levels of total plasma homocysteine are a risk factor for atherosclerotic disease.AimsThe rationale behind this study is to explore the correlation between degree and site of coronary lesion and hyperhomocysteinemia in Lebanese CAD patients and assess environmental and genetic factors for elevated levels of total plasma homocysteine.MethodsA total of 2644 patients were analyzed for traditional CAD risk factors. Logistic regression was performed to determine the association of hyperhomocysteinemia with degree and site of coronary lesions controlling for risk factors. Environmental and genetic factors for hyperhomocysteinemia were analyzed by logistic regression using a candidate gene approach.ResultsTraditional risk factors were correlated with stenosis. Hyperhomocysteinemia associated with increased risk of overall stenosis, and risk of mild and severe occlusion in major arteries. Hyperhomocysteinemia and hypertension were highly correlated suggesting that hyperhomocysteinemia acts as a hypertensive agent leading to CAD. Diuretics and genetic polymorphisms in MTHFR and SLCO1B1 were associated with hyperhomocysteinemia.ConclusionsHyperhomocysteinemia is a medical indicator of specific vessel stenosis in the Lebanese population. Hypertension is a major link between hyperhomocysteinemia and CAD occurrence. Genetic polymorphisms and diuretics’ intake explain partly elevated homocysteine levels. This study has important implications in CAD risk prediction.     

Serum albumin (SA) levels and 10-year mortality in a community-dwelling 70-year-old population

Although an association between SA concentrations and mortality in the patients is well known, this association is not conclusive in elderly community-dwelling populations. We therefore attempted to determine whether this association could be extended to a Japanese 70-year-old community-dwelling population. Seventy-year-old subjects residing in Niigata City, Japan participated. Baseline examinations including a determination of SA concentrations were performed in June 1998 in 600 participants, and they were followed for 10 years. During the 10-year follow up, 80 subjects died. Albumin levels were divided into four groups (highest > 45 g/l, higher 43-44 g/l, lower 41-42 g/l, lowest <40 g/l). The survival rate using Kaplan-Meier methods was longer in the highest and higher albumin groups than in the lowest and lower groups. No differences were found between the four groups in the mortalities from cancer, cardiovascular disease (CVD) or pneumonia. Individuals with the lowest albumin levels had 2.7 or 2.9 times higher total mortality, whether adjusted with confounding factors or not, using Cox regression analysis. The mortality hazard ratio (HR) found in the lowest group was compared to the highest group. In an elderly 70-year-old Japanese community-dwelling population, lower SA concentrations were an independent predictor of total mortality, but not mortality due to cancer, CVD, or pneumonia.     

Establishment of mesenchymal cell line derived from human developing odontoma

Oral Diseases (2012) 18, 756-762 Objectives: An odontoma, which shows proliferating odontogenic epithelium and mesenchymal tissue, is one of the most common odontogenic tumors encountered. These are commonly found in tooth-bearing regions, although the etiology remains unknown. There are no previous reports of an established line of immortalized human odontoma cells. Methods: Using odontoma fragments obtained from a girl treated at our department, we established an immortalized human odontoma cell line and investigated cell morphology, dynamic proliferation, the presence of contamination, and karyotype. Moreover, cell characterization was examined using osteogenic and odontogenic markers. Results: We successfully established a mesenchymal odontoma cell (mOd cells). The cells were found to be fibroblastic and had a high level of telomerase activity. Cell growth was confirmed after more than 200 population doublings without significant growth retardation. mOd cells expressed mRNA for differentiation markers, including collagen type I (COLI), alkaline phosphatase, bone sialoprotein, osteopontin, osteocalcin, cementum-derived protein (CP-23), dentin sialophosphoprotein (DSPP), and distal-less homeobox 3 (DLX3), as well as bone morphogenetic proteins (BMPs). In addition, they showed a high level of calcified nodule formation activity in vitro. Conclusions: We successfully established a cell line that may be useful for investigating the mechanisms of normal odontogenesis as well as characteristics of odontoma tumors.     

Immunolocalization of water channel aquaporins in human knee articular cartilage with intact and early degenerative regions

Aquaporins (AQPs), a family of water channel proteins expressed in various cells and tissues, serve as physiological pathways of water and small solute transport. Articular cartilage is avascular tissue with unique biomechanical structure, a major component of which is “water”. Our objective is to investigate the immunolocalization and expression pattern changes of AQPs in articular cartilage with normal and early degenerative regions in the human knee joint, which is the joint most commonly involved in osteoarthritis (OA). Two isoforms (AQPs 1 and 3) of AQPs were examined by immunohistochemical analyses using isoform-specific antibodies with cartilage samples from OA patients undergoing total knee arthroplasty. AQP 1 and AQP 3 were expressed in human knee articular cartilage and were localized in chondrocytes, both in the intact and early degenerative cartilage regions. Compared to the intact cartilage, both AQP 1 and AQP 3 immunopositive cells were observed at the damaged surface area in the degenerative region. These findings suggest that these AQPs play roles in metabolic water regulation in articular cartilage of load bearing joints and that they are responsible for OA onset.     

Orally Administered Liposomal Lactoferrin Inhibits Inflammation‐Related Bone Breakdown Without Interrupting Orthodontic Tooth Movement

Background: Bovine lactoferrin (bLF) modulates the production of tumor necrosis factor‐alpha (TNF‐α) and inhibits alveolar bone breakdown associated with periodontitis. This study is designed to examine the effects of orally administered liposomal bLF (LbLF) on orthodontic force (OF)‐induced alveolar bone remodeling during experimental tooth movement. Methods: Two groups of male Wistar rats were treated with either LbLF or control solution in drinking water 7 days before OF application. Lipopolysaccharide (LPS) was injected into the gingival sulcus in half the rats in each group. Thus, four groups: OF, OF+LbLF, OF+LPS, and OF+LPS+LbLF were established. Results: Orally administered LbLF significantly reduced apical migration of junctional epithelium in the OF and OF+LPS groups. In OF+LPS, osteoclast number in the alveolar crestal area was increased by LPS treatment, whereas osteoclast number was significantly reduced in OF+LPS+LbLF through suppression of TNF‐α production. Osteoclastic induction in the middle part, mainly from OF application, was not affected by LbLF administration. Inhibition of tooth movement was not induced by LbLF. Conclusions: Orally administered LbLF significantly inhibits LPS‐induced alveolar bone resorption but not OF‐induced bone remodeling. LbLF could be a potent therapeutic and preventive agent to control periodontal inflammation in patients undergoing orthodontic treatment.     

Obstructive sleep apnea as a potential risk factor for aortic disease

Obstructive sleep apnea (OSA) is not only a cause of hypertension; it also possibly affects the pathogenesis and progression of aortic disease because an inspiratory effort-induced increase in negative intrathoracic pressure generates mechanical stress on the aortic wall. The objective of the present study was to examine the incidence by location of OSA as a complication in patients with aortic aneurysm and patients with aortic dissection (AD). An overnight sleep study was conducted in the following study groups: the aortic disease group (n?=?95) consisting of patients with thoracic aortic aneurysm (TAA, n?=?32), patients with abdominal aortic aneurysm (AAA, n?=?36), and patients with AD (n?=?27); and a control group (n?=?32), consisting of patients with coronary risk factors who were matched with the aortic disease group for age, gender, and body mass index (BMI). The 3% oxygen desaturation index (ODI) was significantly higher in all the TAA, AAA, and AD groups (P?=?0.045, P?=?0.003, and P?=?0.005, respectively) than in the control group. The incidence of moderate to severe OSA [apnea hypopnea index (AHI) ??15 events/h] was significantly higher in the first three groups (P?=?0.026, P?=?0.001, P?=?0.003, respectively) than in the control group, while no significant difference was found between the TAA group and the AAA group with respect to these variables. Furthermore, no significant differences were found between the thoracic AD subgroup and the abdominal AD subgroup with respect to AHI and 3% ODI, as well as with respect to the incidences of moderate to severe OSA. Patients with TAA, patients with AAA, and patients with AD showed high incidences of moderate to severe OSA. Although this result suggests that OSA may be one of risks for aortic disease, unelucidated mechanism(s) other than negative intrathoracic pressure may be involved in the pathogenesis of aortic disease.     

Clinical outcomes of endoscopic submucosal dissection and endoscopic mucosal resection for laterally spreading tumors larger than 20 mm

Background and Aims: Colorectal laterally spreading tumors (LST) > 20 mm are usually treated by endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR). Endoscopic piecemeal mucosal resection (EPMR) is sometimes required. The aim of our study was to compare the outcomes of ESD and EMR, including EPMR, for such LST. Methods: A total of 269 consecutive patients with a colorectal LST > 20 mm were treated endoscopically at our hospital from April 2006 to December 2009. We retrospectively evaluated the complications and local recurrence rates associated with ESD, hybrid ESD (ESD with EMR), EMR, and EPMR. Results: ESD and EMR were performed successfully for 89 and 178 LST, respectively: 61 by ESD; 28 by hybrid ESD; 70 by EMR; and 108 by EPMR. Between‐group differences in perforation rates were not significant. Local recurrence rates in cases with curative resection were as follows: 0% (0/56) in ESD; 0% (0/27) in hybrid ESD; 1.4% (1/69) in EMR; and 12.1% (13/107) in EPMR; that is, significantly higher in EPMR. No metastasis was seen at follow up. The recurrence rate for EPMR yielding ≥ three pieces was significantly high (P < 0.001). All 14 local recurrent lesions were adenomas that were cured endoscopically. Conclusions: As for safety, ESD/hybrid ESD is equivalent to EMR/EPMR. ESD/hybrid ESD is a feasible technique for en bloc resection and showed no local recurrence. Although local recurrences associated with EMR/EPMR were seen, which were conducted based on our indication criteria, all local recurrences could obtain complete cure by additional endoscopic treatment.