Is the May-Thurner Syndrome a Major Risk Factor for Deep Vein Thrombosis in Total Hip Arthroplasty?

Background: May-Thurner syndrome (MTS) is iliac vein compression syndrome associated with postoperative deep vein thrombosis (DVT) resulting from chronic compression of the left iliac vein against lumbar vertebrae by the overlying right or left common iliac artery. MTS is not well known as a risk factor for DVT after total hip arthroplasty (THA). We evaluated the incidence of DVT after THA and analyzed if the MTS is a risk factor for DVT after THA. We hypothesized that MTS would be associated with an increased risk of developing DVT after THA. Methods: All patients > 65 years of age who underwent THA between January 1, 2009, and January 12, 2017, were identified. Among them, the patients who presented for postoperative DVT of the lower extremity were reviewed with medical record data. MTS was diagnosed with computed tomography (CT) angiography of the lower extremity. We analyzed the demographic data, symptoms, diagnoses, and treatment of MTS patients. Results: A total of 492 consecutive patients aged > 65 years who underwent operation for THA were enrolled. Among them, 5 patients (1.0%) presented for postoperative DVT of the lower extremity. After reviewing the CT angiography of the lower extremity, 4 out of 5 DVT patients (80%) were identified as having MTS. All MTS patients were female and presented with pain and swelling of the left leg. All MTS patients were treated with systemic anticoagulation, aspiration thrombectomy, and percutaneous transluminal angioplasty. Complete resolution of thrombus was observed in all patients. Conclusions: If the diagnosis of MTS is delayed, the morbidity and mortality rates are significantly increased. Orthopedic surgeons should be aware of MTS as a risk factor for DVT after THA. Moreover, preoperative evaluation with duplex sonography or CT angiography to confirm MTS should be considered. In this regard, this study is considered to have sufficient clinical value for early diagnosis and appropriate treatment of MTS after THA.

Inhibitory Action of 1,3,5-Trihydroxybenzene on UVB-Induced NADPH Oxidase 4 through AMPK and JNK Signaling Pathways.

Specific sensitivity of the skin to ultraviolet B (UVB) rays is one of the mechanisms responsible for widespread skin damage. This study tested whether 1,3,5-trihydroxybenzene (THB), a compound abundant in marine products, might inhibit UVB radiation-induced NADPH oxidase 4 (NOX4) in both human HaCaT keratinocytes and mouse dorsal skin and explore its cytoprotective mechanism. The mechanism of action was determined using western blotting, immunocytochemistry, NADP+/NADPH assay, reactive oxygen species (ROS) detection, and cell viability assay. THB attenuated UVB-induced NOX4 expression both in vitro and in vivo, and suppressed UVB-induced ROS generation via NADP+ production, resulting in increased cell viability with decreased apoptosis. THB also reduced the expression of UVB-induced phosphorylated AMP-activated protein kinase (AMPK) and phosphorylated c-Jun N-terminal kinase (JNK). THB suppressed UVB-induced NOX4 expression and ROS generation by inhibiting AMPK and JNK signaling pathways, thereby inhibiting cellular damage. These results showed that THB could be developed as a UV protectant.

Protective effect of rebamipide against Helicobacter pylori-CagA-induced effects on gastric epithelial cells.

BACKGROUND: Helicobacter pylori CagA dysregulates cell signaling pathways and leads to targeted transcriptional up-regulation of genes implicated in gastric cell injury. The aim of this study was to determine the effects of rebamipide on CagA-induced effects on gastric epithelial cells. We investigated the effects of rebamipide treatment (pre- or post-treatment before or after CagA transfection) on CagA-induced gastric cell injury. METHOD: We evaluated the morphologic changes (hummingbird phenotype) associated with ZO-1 mislocalization by confocal microscopy, IL-8 production by ELISA, and NF-κB activation by luciferase assay in AGS gastric epithelial cells and MDCK cells. RESULTS: Transfection of CagA into gastric epithelial cells induced morphologic changes (hummingbird phenotype), ZO-1 mislocalization, and IL-8 production in gastric epithelial cells. Pre-treatment with rebamipide inhibits CagA-induced effects on gastric epithelial cells, including morphologic changes (hummingbird phenotype) associated with ZO-1 mislocalization, IL-8 production, and NF-κB activity. CONCLUSIONS: These results suggest that rebamipide might have a potential role in the protection of H. pylori CagA-induced effects on gastric epithelial cells.

Atrophy of brown adipocytes in the adult mouse causes transformation into white adipocyte-like cells.

Adipose tissue is an important endocrine regulator of glucose metabolism and energy homeostasis. Researches have focused on this tissue not only as a target for pharmacotherapy of obesity and insulin resistance but also as an endocrine tissue with leptin secretion and high insulin sensitivity. Brown adipose tissue (BAT) additionally plays a unique role in thermoregulation through the mitochondrial uncoupling protein 1 (UCP1), which uncouples oxidative phosphorylation. As a genetic tissue ablation model of BAT, we made transgenic mice expressing herpes simplex virus thymidine kinase (HSV-TK) driven by the brown adipocyte- specific UCP1 minimal regulatory element. The HSV-TK transgene was expressed specifically in BAT and more than 35% increase of apoptosis was induced by ganciclovir (GCV) treatment. Nevertheless, the expression level was not high enough to induce BAT ablation in GCV-treated adult mice. Importantly, however, we found that brown adipocytes in the periphery of interscapular BAT were transformed into white adipocyte-like unilocular cells. These cells express white adipocyte-specific leptin protein but are different in the ultrastructure of mitochondria from classical white adipocytes. Our data indicates that atrophy of BAT causes transformation into white adipocyte-like cells in the adult mouse and also suggests that further molecular understanding of adipocyte plasticity using our transgenic mouse model might be beneficial for the development of anti-obesity/anti-diabetic therapies.

Gastric pit dysplasia in adjacent gastric mucosa in 414 gastric cancers: prevalence and characteristics.

Despite wide acceptance of the chronic gastritis-intestinal metaplasia-dysplasia-carcinoma sequence, especially for intestinal-type gastric adenocarcinoma, the precise nature of the subtle precursor lesions of gastric cancer remains to be delineated. For example, pit dysplasia with surface foveolar maturation is not well defined, nor is its prevalence and biological characteristics well characterized. We have evaluated the surrounding gastric mucosa of 414 gastric cancers for the presence of gastric pit dysplasia. We investigated its relationship with various clinicopathological and immunophenotypic features of gastric adenocarcinoma, as well as the severity and extent of any surrounding gastritis and intestinal metaplasia. p53 expression and Ki-67 proliferation index were also evaluated. We have found that 21.0% (n=87) of gastric cancer cases showed pit dysplasia in adjacent gastric mucosa. Gastric cancers with pit dysplasia were significantly associated with older age, male sex, body/fundic location, and intestinal histologic type (P<0.05). Interestingly, gastric mucin-containing intestinal metaplasia (incomplete intestinal metaplasia) was highly associated with adenocarcinoma with pit dysplasia (P=0.000). In addition, MUC6 expression in gastric adenocarcinoma was associated with pit dysplasia (P=0.036). p53 overexpression and increased Ki-67 proliferation index were more evident in gastric pit dysplasia compared with adjacent gastric mucosa. We suggest that gastric pit dysplasia is an important candidate precursor of gastric adenocarcinoma and may represent another morphologic step in the pathogenesis of gastric adenocarcinoma, especially of intestinal type. More detailed prospective studies are needed to determine the precise significance of these findings.

Early treadmill training promotes motor function after hemorrhagic stroke in rats.

Rehabilitation after a stroke is very important because it has beneficial effects on brain function, including the promotion of plasticity. However, an optimal time window for rehabilitation interventions after hemorrhagic stroke has not been clearly defined. The aim of this study was to determine whether early exercise training initiated 24h after an intracerebral hemorrhage (ICH) might enhance neurologic recovery more than exercise initiated 1 week after ICH without hematoma expansion and edema volume increase. We subjected adult male Sprague-Dawley rats to experimental ICH by the intrastriatal administration of bacterial collagenase. The rats were randomly divided into the following 2 groups: early training group (treadmill exercise started 24h post-ICH; n=18) and late training group (treadmill exercise started 1-week post-ICH; n=18). Two weeks after surgery we performed neurologic tests (rota-rod, modified limb-placing, and adhesive-dot removal tests), and measured hematoma volumes and brain water content. In the late training group, compared with the pre-ICH performance on the rota-rod test (98.3+/-69.4s), the animals had significantly worse performance after the post-ICH rehabilitation (40.5+/-52.6s; p<0.01, paired t-test). In the early training group however, the motor performance after the post-ICH rehabilitation (56.4+/-73.5s) was not significantly different from the baseline pre-ICH performance (79.8+/-33.9s; p=0.24). There were no significant differences between the two groups with respect to the other neurologic tests. Early exercise did not increase hematoma size or brain water content. Early treadmill training could be performed safely, and enhanced motor recovery in a rat model of ICH. Further studies are required to translate the results into clinical significance.