An in vitro ischemic penumbral mimic perfusate increases NADPH oxidase-mediated superoxide production in cultured hippocampal neurons.

The currently accepted scheme for reactive oxygen species production during ischemia/reperfusion injury is characterized by a deleterious mitochondria-derived burst of radical generation during reperfusion; however, recent examination of the penumbra suggests a central role for NADPH-oxidase (Nox)-mediated radical generation during the ischemic period. Therefore, we utilized a novel in vitro model of the penumbra to examine the free radical profile of ischemic murine hippocampal neurons using electron paramagnetic resonance spectroscopy, and also the role of Nox in this generation and in cell fate. We report that free radical production increased ~75% at 2 h of ischemia, and this increase was abolished by: (1) scavenging of extracellular free radicals with superoxide dismutase (SOD), (2) a general anion channel antagonist, or (3) the Nox inhibitor apocynin.

HMGB1 is overexpressed in tumor cells and promotes activity of regulatory T cells in patients with head and neck cancer.

HMGB1 has gained a prominent role in cancer development and is implicated in tumor escape phenomena. To date, only few data are available on effects of HMGB1 on regulatory T cells (Treg) in cancer patients. This study evaluates the prevalence of HMGB1 and its effects on Treg in patients with head and neck squamous cell carcinoma (HNSCC).

Hypoxia induces Kv channel current inhibition by increased NADPH oxidase-derived reactive oxygen species.

There is current discussion whether reactive oxygen species are up- or downregulated in the pulmonary circulation during hypoxia, from which sources (i.e., mitochondria or NADPH oxidases) they are derived, and what the downstream targets of ROS are.

Tumor-derived macrophage migration inhibitory factor modulates the biology of head and neck cancer cells via neutrophil activation.

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that has been reported to enhance the aggressiveness and metastatic potential of tumor cells. However, the mechanisms through which MIF influences tumor development and progression are not understood. The objectives of our study were to assess the effects of tumor-derived MIF on neutrophils in head and neck cancer (HNC) and to identify possible feedback effects on tumor cells.

Repeated intracoronary infusion of peripheral blood stem cells with G-CSF in patients with refractory ischemic heart failure--a pilot study.

Background: Recent investigations have suggested the clinical efficacy of granulocyte colony-stimulating factor (G-CSF) infusion alone or in combination with a single dose delivery of peripheral blood stem cells (PBSC) infusion in patients with myocardial infarction (MI) and congestive heart failure (HF). The current study tested the feasibility and effect of repeated intracoronary infusions PBSC and the mobilization of G-CSF in patients with refractory HF after MI.

Methods And Results: Patients with recent large MI and a lower left ventricular ejection fraction (LVEF) were enrolled into one of the following 3 groups: Group R (n=15) received repeated intracoronary infusion of PBSC and one-dose of G-CSF; Group S (n=15) received a single infusion of PBSC and a G-CSF dose; and Group C (n=15) received neither PBSC nor a G-CSF dose.

Efficient expression and purification of methyltransferase in acetyl-coenzyme a synthesis pathway of the human pathogen Clostridium difficile.

The Wood-Ljungdahl pathway is responsible for acetyl-CoA biosynthesis and used as a major mean of generating energy for growth in some anaerobic microbes. Series of genes, from the anaerobic human pathogen Clostridium difficile, have been identified that show striking similarity to the genes involved in this pathway including methyltetrahydrofolate- and corrinoid-dependent methyltransferase. This methyltransferase plays a central role in this pathway that transfers the methyl group from methyltetrahydrofolate to a cob(I)amide center in the corrinoid iron-sulfur protein.

Polymorphonuclear granulocytes in human head and neck cancer: enhanced inflammatory activity, modulation by cancer cells and expansion in advanced disease.

The progression of epithelial cancer is associated with an intense immunological interaction between the tumor cells and immune cells of the host. However, little is known about the interaction between tumor cells and polymorphonuclear granulocytes (PMNs) in patients with head and neck squamous cell carcinoma (HNSCC). In our study, we investigated systemic PMN-related alterations in HNSCC, the role of tumor-infiltrating PMNs and their modulation by the tumor microenvironment.

The functional polymorphism in monocyte chemoattractant protein-1 gene increases susceptibility to gastric cancer.

Monocyte chemoattractant protein-1 (MCP-1, CCL2) has been suggested to be associated with gastric cancer. We investigated whether the functional single nucleotide polymorphism A-2518G in CCL2 gene influenced susceptibility to gastric cancer. The CCL2 genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism in 1,216 individuals (608 gastric cancer patients and 608 age- and sex-matched controls).

Physiological loading of joints prevents cartilage degradation through CITED2.

Both overuse and disuse of joints up-regulate matrix metalloproteinases (MMPs) in articular cartilage and cause tissue degradation; however, moderate (physiological) loading maintains cartilage integrity. Here, we test whether CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2), a mechanosensitive transcriptional coregulator, mediates this chondroprotective effect of moderate mechanical loading. In vivo, hind-limb immobilization of Sprague-Dawley rats up-regulates MMP-1 and causes rapid, histologically detectable articular cartilage degradation.

Microvascular imaging using synchrotron radiation.

In vascular diseases, the involvement of small vessels can be very crucial physiologically. Morphological changes of vasculature and alterations may be promising characteristic criteria for investigating disease progression and for evaluating therapeutic effects. Visualization of microvasculatures is an important step in understanding the mechanism of early vessel disorders and developing effective therapeutic strategies.

[Evaluation of neointimal coverage and thrombosis at 3 months and 2 years post sirolimus-eluting stent implantation by optical coherence tomography].

Objective: To evaluate the short- and long-term prevalence of persistent uncovered struts and in-stent thrombus after sirolimus-eluting stent (SES) implantation by optical coherence tomography (OCT).

Methods: OCT was performed for 31 SES in 21 patients at 3 months and for 30 SES in 21 patients at 2 years post SES implantation. Thickness of new intima inside each strut was measured and thickness equal to 0 microm was defined as an uncovered strut.

Lung cancer and angiogenesis imaging using synchrotron radiation.

Early detection of lung cancer is the key to a cure, but a difficult task using conventional x-ray imaging. In the present study, synchrotron radiation in-line phase-contrast imaging was used to study lung cancer. Lewis lung cancer and 4T1 breast tumor metastasis in the lung were imaged, and the differences were clearly shown in comparison to normal lung tissue.

Matrix metalloproteinase-3 in articular cartilage is upregulated by joint immobilization and suppressed by passive joint motion.

Both underloading and overloading of joints can lead to articular cartilage degradation, a process mediated in part by matrix metalloproteinases (MMPs). Here we examine the effects of reduced loading of rat hindlimbs on articular cartilage expression of MMP-3, which not only digests matrix components but also activates other proteolytic enzymes. We show that hindlimb immobilization resulted in elevated MMP-3 mRNA expression at 6h that was sustained throughout the 21day immobilization period.

Development and validation of a motion and loading system for a rat knee joint in vivo.

The influence of biomechanical stimuli on modulating cartilage homeostasis is well recognized. However, many aspects of cellular mechanotransduction in cartilage remain unknown. We developed a computer-controlled joint motion and loading system (JMLS) to study the biological response of cartilage under well-characterized mechanical loading environments.

Food waste decomposition in leachbed reactor: role of neutralizing solutions on the leachate quality.

The neutralization effects of 0.1M NaHCO(3), KPO(4)-buffer (pH 7.0) and sodium acetate (NaOAc) solutions (500 ml/kg food waste/day) on controlling the pH and leachate quality in an acidogenic reactor of food waste anaerobic digestion was investigated.

Insulin/PI3K signaling protects dentate neurons from oxygen-glucose deprivation in organotypic slice cultures.

It is known that ischemia/reperfusion induces neurodegeneration in the hippocampus in a subregion-dependent manner. This study investigated the mechanism of selective resistance/vulnerability to oxygen-glucose deprivation (OGD) using mouse organotypic hippocampal cultures. Analysis of propidium iodide uptake showed that OGD-induced duration- and subregion-dependent neuronal injury.

Precipitation Polymerization in Ethanol and Ethanol/Water to Prepare Uniform Microspheres of Poly(TMPTA-styrene).

The precipitation polymerization of styrene-trihydroxymethyl propane triacrylate has been carried out using ethanol and an ethanol/water mixture as the solvent. Uniform microspheres with high monomer conversion are achieved within 4 h, a much shorter polymerization time than that reported for the precipitation polymerization of divinyl benzene-styrene in acetonitrile. The results clearly demonstrate that use of water as a co-solvent is indeed very effective to promote the polymerization to high conversion and to obtain uniform microspheres.

[Magnetic resonance assessment the effect of manipulation on knee cartilaginous recovery of osteoarthritis].

Objective: To observe and assess the effect of manipulation on knee cartilaginous recovery with knee osteoarthritis (OA) by using magnetic resonance (MR).

Methods: Fifty cases which were suffering from knee OA involved this retrospective study. They were matched-pairs into 2 groups according to their gender, age and severity.

Hypoxia increases activity of the BK-channel in the inner mitochondrial membrane and reduces activity of the permeability transition pore.

Hypoxia can cause severe damage to cells by initiating signaling cascades that lead to cell death. A cellular oxygen sensor, other than the respiratory chain, might exist in sensitive components of these signaling cascades. Recently, we found evidence that mitochondrial ion channels are sensitive to low levels of oxygen.

Modulation of hSlo BK current inactivation by fatty acid esters of CoA.

Lipid metabolism influences membrane proteins, including ion channels, in health and disease. Fatty acid esters of CoA are important intermediates in fatty acid metabolism and lipid biosynthesis. In the present study, we examined the effect of acyl-CoAs on hSlo BK currents.

Cell death in an ischemic infarct rim model.

Using an in vitro model that simulates the microenvironment in the ischemic infarct rim, we have examined the temporal profile and possible mechanisms of cell death in the neuropil (an astrocyte-rich area or ARA) of organotypic hippocampal slice cultures. Two-photon confocal microscopy, propidium iodide, and GFAP-GFP transgenic mice were used to confirm cell death in astrocytes. An 'ischemic solution' (IS) induced major cell death throughout the hippocampus over 24 h, with the earliest injury starting in ARA.

Hypoxia increases BK channel activity in the inner mitochondrial membrane.

To explore the potential function of the BK channel in the inner mitochondrial membrane under physiological and hypoxic conditions, we used on-mitoplast and whole-mitoplast patches. Single BK channels had a conductance of 276+/-9 pS under symmetrical K(+) solutions, were Ca(2+)- and voltage-dependent and were inhibited by 0.1 microM charybdotoxin.

Chronic high-inspired CO2 decreases excitability of mouse hippocampal neurons.

To examine the effect of chronically elevated CO(2) on excitability and function of neurons, we exposed mice to 8 and 12% CO(2) for 4 wk (starting at 2 days of age), and examined the properties of freshly dissociated hippocampal neurons obtained from slices. Chronic CO(2)-treated neurons (CC) had a similar input resistance (R(m)) and resting membrane potential (V(m)) as control (CON). Although treatment with 8% CO(2) did not change the rheobase (64 +/- 11 pA, n = 9 vs.

Antiapoptotic mechanism of insulin in reoxygenation-induced injury in cultured cardiomyocytes of neonatal rats.

To examine the protective effect of insulin on reoxygenation-induced injury and explore the underlying mechanisms, the model of anoxia/reoxygenation (A/R) injury was established by inducing anoxia for 2 h and reoxygenation for 4 h in cultured cardiomyocytes of neonatal rats. The rats were randomized to four groups receiving vehicle, insulin, LY294002, insulin plus LY294002 at the onset of reoxygenation after 2 h of anoxia. At the end of reoxygenation of 4 h, activity of lactate dehydrogenase (LDH) and content of malondialdehyde (MDA) were spectrophotometrically determined, apoptosis of cardiomyocytes were detected by using TUNEL and DNA Ladder, and Western blotting was employed to examine the expression of phosphorylated Akt in all groups.