5,702 research outputs found

    Hydrazine compounds inhibit glycation of low-density lipoproteins and prevent the in vitro formation of model foam cells from glycolaldehyde-modified low-density lipoproteins

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    Aims/hypothesis: Previous studies have shown that glycation of LDL by methylglyoxal and glycolaldehyde, in the absence of significant oxidation, results in lipid accumulation in macrophage cells. Such 'foam cells' are a hallmark of atherosclerosis. In this study we examined whether LDL glycation by methylglyoxal or glycolaldehyde, and subsequent lipid loading of cells, can be inhibited by agents that scavenge reactive carbonyls. Such compounds may have therapeutic potential in diabetes-associated atherosclerosis. Materials and methods: LDL was glycated with methylglyoxal or glycolaldehyde in the absence or presence of metformin, aminoguanidine, Girard's reagents P and T, or hydralazine. LDL modification was characterised by changes in mobility (agarose gel electrophoresis), cross-linking (SDS-PAGE) and loss of amino acid residues (HPLC). Accumulation of cholesterol and cholesteryl esters in murine macrophages was assessed by HPLC. Results: Inhibition of LDL glycation was detected with equimolar or greater concentrations of the scavengers over the reactive carbonyl. This inhibition was structure-dependent and accompanied by a modulation of cholesterol and cholesteryl ester accumulation. With aminoguanidine, Girard's reagent P and hydralazine, cellular sterol levels returned to control levels despite incomplete inhibition of LDL modification. Conclusions/ interpretation: Inhibition of LDL glycation by interception of the reactive aldehydes that induce LDL modification prevents lipid loading and model foam cell formation in murine macrophage cells. Carbonyl-scavenging reagents, such as hydrazines, may therefore help inhibit LDL glycation in vivo and prevent diabetes-induced atherosclerosis. © Springer-Verlag 2006

    Frequent utilization of the emergency department for acute exacerbation of chronic obstructive pulmonary disease

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    Background: Little is known about patients who frequently visit the emergency department (ED) for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We aimed to quantify the proportion and characteristics of patients with frequent ED visits for AECOPD and associated healthcare utilization. Methods: We conducted a retrospective cohort study of adults aged ≥40 years with at least one ED visit for AECOPD between 2010 and 2011, derived from population-based all-payer data of State ED and Inpatient Databases for two large and diverse states: California and Florida. Outcome measures were frequency of ED visits for AECOPD, 30-day ED revisits, subsequent hospitalizations, near-fatal events (AECOPD involving mechanical ventilation), and charges for both ED and inpatient services (available only for Florida) during the year after the first ED visit. Results: The analytic cohort comprised 98,280 unique patients with 154,736 ED visits for AECOPD. During the 1-year period, 29.4% (95% CI, 29.1%-29.7%) of the patients had two or more (frequent) visits, accounting for 55.2% (95% CI, 54.9%-55.4%) of all ED visits for AECOPD. In the multivariable model, significant predictors of frequent ED visits were age 55–74 years (vs. 40–54 years), male sex, non-Hispanic white or black race, Medicaid insurance (vs. private), and lower median household income (all P < 0.001). At the visit-level, 12.3% of ED visits for AECOPD were 30-day revisit events (95% CI, 12.1%-12.4%). Additionally, 62.8% of ED visits for AECOPD (95% CI, 62.6%-63.0%) resulted in a hospitalization; patients with frequent ED visits comprised 55.5% (95% CI, 55.2%-55.8%) of all hospitalizations. Furthermore, 7.3% (95% CI, 7.3%-7.5%) of ED visits for AECOPD led to a near-fatal event; patients with frequent ED visits accounted for 64.4% (95% CI, 63.5%-65.3%) of all near-fatal events. Total charges for AECOPD were 1.94billion(951.94 billion (95% CI, 1.90-1.97 billion) in Florida; patients with frequent ED visits accounted for 1.07billion(951.07 billion (95% CI, 1.04-1.09 billion). Conclusions: In this large cohort study, we found that 29% had frequent ED visits for AECOPD and that lower socioeconomic status was significantly associated with a higher frequency of ED visits. Individuals with frequent ED visits for AECOPD accounted for a substantial amount of healthcare utilization and financial burden

    A randomized, controlled trial comparing ganciclovir to ganciclovir plus foscarnet (each at half dose) for preemptive therapy of cytomegalovirus infection in transplant recipients

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    Forty-eight patients who provided 2 consecutive blood samples that tested positive for cytomegalovirus DNA by polymerase chain reaction (PCR) were randomized to receive either full-dose ganciclovir ( 5 mg/kg intravenously [iv] twice daily) or half-dose ganciclovir (5 mg/kg iv once daily) plus half-dose foscarnet (90 mg/kg iv once daily) for 14 days. In the ganciclovir arm, 17 (71%) of 24 patients reached the primary end point of being CMV negative by PCR within 14 days of initiation of therapy, compared with 12 (50%) of 24 patients in the ganciclovir-plus-foscarnet arm (P = .12). Toxicity was greater in the combination-therapy arm. In patients who failed to reach the primary end point, baseline virus load was 0.77 log(10) higher, the replication rate before therapy was faster (1.5 vs. 2.7 days), and the viral decay rate was slower (2.9 vs. 1.1 days) after therapy. Bivariable logistic regression models identified baseline virus load, bone-marrow transplantation, and doubling time and half-life of decay as the major factors affecting response to therapy within 14 days. This study did not support a synergistic effect of ganciclovir plus foscarnet in vivo

    MSI PARENTERAL PARECOXIB FOLLOWED BY ORAL VALDECOXIB AFTER MAJOR GENERAL SURGERY REDUCES OPIOID CONSUMPTION AND OPIOID-RELATED SYMPTOMS

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    Eruption of kimberlite magmas: physical volcanology, geomorphology and age of the youngest kimberlitic volcanoes known on earth (the Upper Pleistocene/ Holocene Igwisi Hills volcanoes, Tanzania)

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    The Igwisi Hills volcanoes (IHV), Tanzania, are unique and important in preserving extra-crater lavas and pyroclastic edifices. They provide critical insights into the eruptive behaviour of kimberlite magmas that are not available at other known kimberlite volcanoes. Cosmogenic 3He dating of olivine crystals from IHV lavas and palaeomagnetic analyses indicates that they are Upper Pleistocene to Holocene in age. This makes them the youngest known kimberlite bodies on Earth by >30 Ma and may indicate a new phase of kimberlite volcanism on the Tanzania craton. Geological mapping, Global Positioning System surveying and field investigations reveal that each volcano comprises partially eroded pyroclastic edifices, craters and lavas. The volcanoes stand 102 to 106 Pa s) for kimberlite, attributed to degassing and in-vent cooling. Each volcano is inferred to be the result of a small-volume, short-lived (days to weeks) monogenetic eruption. The eruptive processes of each Igwisi volcano were broadly similar and developed through three phases: (1) fallout of lithic-bearing pyroclastic rocks during explosive excavation of craters and conduits; (2) fallout of juvenile lapilli from unsteady eruption columns and the construction of pyroclastic edifices around the vent; and (3) effusion of degassed viscous magma as lava flows. These processes are similar to those observed for other small-volume monogenetic eruptions (e.g. of basaltic magma)

    Recognition without identification, erroneous familiarity, and déjà vu

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    Déjà vu is characterized by the recognition of a situation concurrent with the awareness that this recognition is inappropriate. Although forms of déjà vu resolve in favor of the inappropriate recognition and therefore have behavioral consequences, typical déjà vu experiences resolve in favor of the awareness that the sensation of recognition is inappropriate. The resultant lack of behavioral modification associated with typical déjà vu means that clinicians and experimenters rely heavily on self-report when observing the experience. In this review, we focus on recent déjà vu research. We consider issues facing neuropsychological, neuroscientific, and cognitive experimental frameworks attempting to explore and experimentally generate the experience. In doing this, we suggest the need for more experimentation and amore cautious interpretation of research findings, particularly as many techniques being used to explore déjà vu are in the early stages of development.PostprintPeer reviewe

    Physio-chemical assessment of beauty leaf (Calophyllum inophyllum) as second-generation biodiesel feedstock

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    Recently, biodiesels from non-edible vegetable oil, known as second generation biodiesel, are receiving more attention because it can overcome food versus fuel crisis related to edible oils. The Beauty Leaf tree (Calophyllum Inophyllum) is a potential source of non-edible vegetable oil for producing future generation biodiesel because of its sustainability in a wide range of climate conditions, easy cultivation, high fruit production rate, and the high oil content in the seed. In this study, bio-oil was extracted from beauty leaf tree seeds through three different oil extraction methods. The important physical and chemical properties of produced beauty leaf oils were experimentally analysed and compared with commercial edible vegetable oils. Biodiesel was produced using a two-stage esterification process consisting of acid catalysed pre-esterification and alkali catalysed Transesterification. Fatty acid methyl ester (FAME) profile and physicochemical properties including kinematic viscosity, density, higher heating value and acid value were measured using laboratory standard testing equipment following internationally recognized testing procedures. Other fuel properties including oxidation stability, iodine value, cetane number, flash point, cold filter plugging point, cloud point and pour point temperature were estimated using Fatty acid methyl ester (FAME) of biodiesel. Physicochemical properties of beauty leaf oil biodiesels are described briefly and compared with recognised biodiesel standards and commercially available biodiesels produced from edible oil feedstock. Quality of produced biodiesel was assessed based 13 important chemical and physical properties through Preference Ranking Organisation Method for Enrichment Evaluation (PROMETHEE) and Graphical Analysis for Interactive Assistance (GAIA) analysis. This study found that Mechanical extraction using the screw press can produce oil from correctly prepared product at a low cost, however overall this method is ineffective with relatively low oil yields. The study found that seed preparation has a significant impact on oil yields, especially in the mechanical oil extraction method. High temperature and pressure in extraction process increases the performance of oil extraction. On the contrary, this process increases the free fatty acid content in the oil. Clear difference was found in physical properties of beauty leaf oils that eventually affected the oil to biodiesel conversion process. However, beauty leaf oils methyl esters (biodiesel) were very consistent and able to meet almost all indicators of biodiesel standards. Furthermore, it showed as a better automobile fuel compared to most of the commercially available biodiesels produced from edible oil sources. Result of this study indicated that, Beauty Leaf oil seed is readily available feedstock to commence the commercial production of 2nd generation biodiesel. The findings of this study are expected to serve as the basis from which industrial scale biodiesel production from Beauty Leaf can be made

    Kainate Receptor-Mediated Modulation of Hippocampal Fast Spiking Interneurons in a Rat Model of Schizophrenia

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    Kainate receptor (KAR) subunits are believed to be involved in abnormal GABAergic neurotransmission in the hippocampus (HIPP) in schizophrenia (SZ) and bipolar disorder. Postmortem studies have shown changes in the expression of the GluR5/6 subunits of KARs in the stratum oriens (SO) of sectors CA2/3, where the basolateral amygdala (BLA) sends a robust projection. Previous work using a rat model of SZ demonstrated that BLA activation leads to electrophysiological changes in fast-spiking interneurons in SO of CA2/3. The present study explores KAR modulation of interneurons in CA2/3 in response to BLA activation. Intrinsic firing properties of these interneurons through KAR-mediated activity were measured with patch-clamp recordings from rats that received 15 days of picrotoxin infusion into the BLA. Chronic BLA activation induced changes in the firing properties of CA2/3 interneurons associated with modifications in the function of KARs. Specifically, the responsiveness of these interneurons to activation of KARs was diminished in picrotoxin-treated rats, while the after-hyperpolarization (AHP) amplitude was increased. In addition, we tested blockers of KAR subunits which have been shown to have altered gene expression in SO sector CA2/3 of SZ subjects. The GluR5 antagonist UBP296 further decreased AP frequency and increased AHP amplitude in picrotoxin-treated rats. Application of the GluR6/7 antagonist NS102 suggested that activation of GluR6/7 KARs may be required to maintain the high firing rates in SO interneurons in the presence of KA. Moreover, the GluR6/7 KAR-mediated signaling may be suppressed in PICRO-treated rats. Our findings indicate that glutamatergic activity from the BLA may modulate the firing properties of CA2/3 interneurons through GluR5 and GluR6/7 KARs. These receptors are expressed in GABAergic interneurons and play a key role in the synchronization of gamma oscillations. Modulation of interneuronal activity through KARs in response to amygdala activation may lead to abnormal oscillatory rhythms reported in SZ subjects
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