Differential risks of subsequent vascular events for transient ischaemic attack and minor ischaemic stroke.

Using a prospective hospital-based registry, 146 patients with transient ischaemic attack (TIA) were compared with 376 patients with minor first-ever ischaemic stroke with respect to the 3-month risk of subsequent vascular events, in order to clarify the distinctions between the disease entities. All patients were enrolled within 48 h of onset. The risk factor distribution for the two groups was comparable, except that the TIA patients had more previous TIAs. Large artery atherosclerosis (34%) and small vessel occlusion (32%) were the main aetiologies in the TIA group, whereas small vessel occlusion (49%) was the major cause in the stroke group. The 3-month risk of combined endpoints of stroke, myocardial infarction, and vascular death for TIA patients was higher than that for the minor stroke group (15.1% vs. 3.2%; hazard ratio 4.6, 95% confidence interval 2.3-9.3 in multivariate analysis). Large artery atherosclerosis and male sex were the other significant predictors. TIA may demand more urgent management than minor stroke. The fact that aetiology is a predictor, highlights the need for rapid diagnostic tests to establish pathogenesis.     

The effects of using erbium,chromium-doped:yttrium-scandium-gallium-garnet laser on the surface modification,bacterial decontamination,and cell adhesion on zirconia discs: an in vitro study

Lasers in Medical Science - The use of zirconia for implants and abutments has become more prevalent in implant dentistry as an alternative to the commonly used titanium implants, and peri-implant...     

The pharmacological mechanisms of omalizumab in patients with very high IgE levels—Clues from studies on atopic dermatitis

Seventeen case series investigating the effects of omalizumab on patients with atopic dermatitis included patients whose pretreatment serum IgE was above 700 IU/ml, the upper inclusion limit specified in the product label. In all, 107 patients received omalizumab at doses of ≤375 mg every 2 weeks, which is recommended for patients with IgE <700 IU/ml. Among them, 87 improved in clinical symptoms and some did so after the first dose. Among these 87 patients, 35 and 12 had pretreatment serum IgE in the range 700–7000 IU/ml and 7000–121,000 IU/ml, respectively. These results not only suggest the pathogenic roles of IgE and the potential utility of omalizumab in atopic dermatitis, but also raise questions concerning the pharmacological mechanisms of omalizumab in patients with very high IgE levels. If omalizumab at regular doses is proven to treat patients with ultra high IgE (e.g. above 7000 IU/ml) effectively, it probably achieves this without neutralizing most of the IgE produced in the patients and downregulating the high-affinity IgE-Fc receptors on basophils and mast cells. Herein, we propose that a potential main pharmacological mechanism of omalizumab in patients with ultra high IgE is the ability of the rapidly accumulated IgE:omalizumab complexes to trap allergens.     

Is peptic ulcer disease a risk factor of postherpetic neuralgia in patients with herpes zoster?

Postherpetic neuralgia is the most common complication of herpes zoster which is caused by a reactivation of latent varicella zoster virus. The pathogenesis of postherpetic neuralgia may involve peripheral and central mechanisms. Reported risk factors for postherpetic neuralgia include female gender, old age, diminished cell-mediated immunity and nutritional deficiencies. Based on our clinical observation which revealed that peptic ulcer disease (PUD) is one of the common comorbidities in patients with postherpetic neuralgia, we hypothesize that herpes zoster patients with PUD may be at a greater risk for the development of postherpetic neuralgia due to their impaired cellular immunity and depressed nutritional status. Major causes of PUD include Helicobacter pylori infection and usage of ulcerogenic medications. Patients with H. pylori infection may develop T cell dysfunctions and nutritional deficiencies including vitamin C, iron, cobalamin, carotenes and alpha-tocopherol. Ulcerogenic medications such as nonsteroidal anti-inflammatory drugs and steroids have been found not only to be ulcerogenic but also immunosuppressive to T cells. In addition, usage of steroids and nonsteroidal anti-inflammatory drugs may cause deficiencies of alpha-tocopherol, carotenes, cobalamin, iron, zinc and vitamin C. Vitamin C, carotenes and alpha-tocopherol are anti-inflammatory and the major oxidant scavengers in the aqua phase and biomembranes. Deficiencies of these nutrients may induce dysregulated inflammation and oxidative damage leading to neuropathic pain in patients with herpes zoster. Furthermore, nutrient deficiencies including zinc, iron, cobalamin and vitamin C are associated with dysregulation of Ca(v)3.2 T-channels and N-methyl-d-aspartate receptors, upregulation of nitric oxide synthase, the increase of nitric oxide formation and dysfunction of central norepinephrine inhibitory pain pathway. Prospective cohort studies are suggested to test the hypothesis. We further propose that a follow-up study that contains two groups of herpes zoster patients, i.e., with or without gastroendoscopy-proven PUD, be conducted to determine their incidence of postherpetic neuralgia. In addition, despite of the high proportion of zoster patients having been treated with antiviral therapies, prevention and treatment of postherpetic neuralgia remain challenging in clinical practice. The potential risk of postherpetic neuralgia in zoster patients with PUD could mean that physicians need to pay more attention to the comorbidity - PUD in patients with herpes zoster and treat PUD earlier in order to prevent the development of postherpetic neuralgia.     

Cedrus atlantica Extract Suppress Glioblastoma Growth through Promotion of Genotoxicity and Apoptosis: In Vitro and In Vivo Studies

Glioblastoma (GBM) is the most common malignant primary brain tumor in humans, exhibiting highly infiltrative growth and drug resistance to conventional chemotherapy. Cedrus atlantica (CAt) extract has been shown to decrease postoperative pain and inhibit the growth of K562 leukemia cells. The aim of this study was to assess the anti-GBM activity and molecular mechanism of CAt extract in vitro and in vivo. The results showed that CAt extract greatly suppressed GBM cells both in vitro and in vivo and enhanced the survival rate in subcutaneous and orthotopic animal models. Moreover, CAt extract increased the level of ROS and induced DNA damage, resulting in cell cycle arrest at the G₀/G₁ phase and cell apoptosis. Western blotting results indicated that CAt extract regulates p53/p21 and CDK4/cyclin D1 protein expression and activates extrinsic and intrinsic apoptosis. Furthermore, CAt extract enhanced the cytotoxicity of Temozolomide and decreased AKT/mTOR signaling by combination treatment. In toxicity assays, CAt extract exhibited low cytotoxicity toward normal cells or organs in vitro and in vivo. CAt extract suppresses the growth of GBM by induction of genotoxicity and activation of apoptosis. The results of this study suggest that CAt extract can be developed as a therapeutic agent or adjuvant for GBM treatment in the future.     

Anti-inflammatory effects of peptides from a marine algicolous fungus Acremonium sp. NTU492 in BV-2 microglial cells

Located in tropical and subtropical region, Taiwan is an island with high algal species diversity. In this study, a number of fungal strains were isolated from marine macroalgae collected from northeastern intertidal zone of Taiwan. Preliminary anti-inflammatory screening has shown that the methanolic extracts of solid fermented products of the red alga Mastophora rosea-derived fungal strain Acremonium sp. NTU492 exhibited significant bioactivity. In an attempt to disclose the active principles from this fungal strain, a series of separation and purification was thus undertaken, which has led to the isolation and characterization of seven compounds including four new peptides, namely acrepeptins A–D (1–4), along with previously reported destruxin B (5), guangomide A (6), and guangomide B (7). Their structures were elucidated by spectroscopic analysis and compared with literatures. Of these, acrepeptins A (1) and C (3) showed markedly inhibitory activities on nitric oxide production in lipopolysaccharide-activated microglial BV-2 cells with IC₅₀ values of 12.0 ± 2.3 and 10.6 ± 4.0 μM, respectively. Furthermore, acrepeptins A (1) and C (3) significantly attenuated the expression of inducible nitric oxide synthase in a concentration-dependent manner (5–40 μM).     

PM<Subscript>10</Subscript> concentration in relation to clinic visits for anxiety disorders: a population-based study of a high river-dust episode region in Taiwan

PM₁₀ exposure has been found to have significant effects on a variety of physical conditions. However, whether it acts on psychopathology remains unclear. This study used 8-year data to examine the relationship between PM₁₀ concentration and daily clinic visits of anxiety disorders. All residents of Yunlin County, Taiwan, which is a high river-dust exposure area, were selected as subjects. Data from the Taiwan National Health Insurance Research Database (NHIRD), 2002–2009, were analyzed. Individuals with any ICD code of 300.0 and 300.2 were categorized as with anxiety disorders. PM₁₀ data were based on the Lunbei station (located at Yunlin County) of EPA, Taiwan. Time-series analysis showed that, during the observed 8 years, the number of daily clinic visits for anxiety disorders increased with PM₁₀ levels, and the relationship remained significant after unemployment rate, and the Weighted Price Index of Taiwan Stock Exchange in the same period were controlled for. In particular, we found that there is a linear dose-response effect between daily clinic visits and PM₁₀ levels when PM₁₀ <?300 μg/m³; whereas a dramatically elevated daily clinic visits of anxiety disorders was found when PM₁₀ >?300 μg/m³. Findings from this study highlight that high level of PM₁₀ exposure derived from severe weather or environment condition may affect the occurrence of anxiety disorders. In addition, there seems to have a threshold of PM₁₀ in elevating the risk of anxiety disorders.     

PEDV Infection Generates Conformation-Specific Antibodies That Can Be Effectively Detected by a Cell-Based ELISA

Porcine epidemic diarrhea virus (PEDV) is a coronavirus that causes serious and highly contagious enteric disease in swine worldwide. In this study, we constructed a recombinant baculovirus (S-Bac) expressing full-length spike protein of the virulent epidemic genotype 2b (G2b) PEDV strain for serological studies of infected pigs. We found that most spike-specific antibodies produced upon PEDV infection in pigs are conformation-specific and they could be detected on S-Bac-infected insect cells by immunofluorescent assay, but they were insensitive to Western blot analysis, the typical method for antiserum analysis. These results indicated that spike conformation is crucial for serum recognition. Since it is difficult to purify trimeric spike membrane protein for conventional enzyme-linked immunosorbent assay (ELISA), we used S-Bac to generate a novel cell-based ELISA for convenient PEDV detection. We analyzed 100 pig serum samples, and our cell-based ELISA exhibited a sensitivity of 100%, a specificity of 97%, and almost perfect agreement [Cohen’s kappa coefficient value (κ) = 0.98] with immunocytochemical staining results. Our cell-based ELISA rapidly presented antigen for proper detection of conformation-specific antibodies, making PEDV detection more convenient, and it will be useful for detecting many viral diseases in the future.