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BACKGROUND: Risk stratification has been one of the main steps in preventing contrast-induced nephropathy (CIN), which is a common complication after percutaneous coronary intervention (PCI). Elevated arterial lactate is a biomarker indicating severe disease condition and post-intervention complications. The relationship between lactate and CIN has not been established. This study is performed to investigate the relationship between elevated arterial lactate level and contrast-induced nephropathy (CIN). METHODS: Patients diagnosed with ST-segment elevated myocardial infarction (STEMI) were prospectively enrolled, with lactate measured within 0.5–1 hours before primary percutaneous coronary intervention (PCI). Patients with cardiopulmonary resuscitation, any forms of severe anaerobic condition, or end-stage renal disease undergoing dialysis were excluded. CIN was defined as an increase in serum creatinine ≥0.5 mg/dL or 25% within 72 hours after PCI. The Mehran Risk Score (MRS) is widely regarded as a classic risk model for CIN and the risk factors of MRS were applied in our multivariate regression analysis. RESULTS: Of the 227 enrolled patients, 47 (20.7%) developed CIN according to the definition. The mean lactate level was higher in the CIN group than in the non-CIN group (2.68±2.27 vs. 1.74±1.94, P

Rosiglitazone (RSG) is a potent drug used in the treatment of insulin resistance; however, it is associated with marked skeletal toxicity. RSG-induced osteoporosis may contribute to the promotion of adipogenic differentiation at the expense of osteogenic differentiation in bone marrow stromal cells. The aim of this study was to investigate whether RSG-induced bone toxicity can be reversed by combined treatment with all-trans retinoic acid (ATRA). We examined different osteogenic markers in mouse embryonic fibroblasts (MEFs) following treatment with RSG, ATRA, or RSG and ATRA in combination. We examined the effects of RSG and/or ATRA on ectopic bone formation, and dissected the possible molecular mechanisms underlying this process. We found that ATRA or RSG both induced alkaline phosphatase (ALP) activity in the MEFs, and that the ATRA-induced ALP activity was enhanced by RSG and vice versa. However, only the combination of RSG and ATRA increased the expression of osteopontin and osteocalcin, promoted matrix mineralization, and induced ectopic ossification in MEFs. Mechanistically, we found that the osteogenic differentiation induced by the combination of RSG and ATRA may be mediated partly by suppressing RSG-induced adipogenic differentiation and activating bone morphogenetic protein (BMP)/Smad signaling. On the whole, our findings demonstrate that RSG in combination with ATRA promotes the commitment of MEFs to the osteoblast lineage. Thus, the combination of these two agents may prove to be a promising and novel therapeutic regimen for insulin resistance without skeletal toxicity. It may also be a better strategy with which to prevent RSG-induced osteoporosis.

The decline of hippocampus-dependent learning and memory during normal aging is not associated with neuron death and synapse loss. Until now, age-related changes in the myelinated fibers of the hippocampus have not been investigated. Therefore, in this study, the myelinated fibers in the hippocampi of young (6 months), middle-aged (18 months), and old-aged (28 months) male Sprague-Dawley rats were studied with transmission electron microscope and stereological methods, following spatial learning tests in a Morris water maze. The results showed that hippocampus-dependent spatial learning was impaired in old-aged rats but that the total volume, length, and mean diameter of the myelinated fibers in the hippocampus, as well as the hippocampal volume, remained constant during the normal aging process. Our results suggest that the age-related decline in hippocampus-dependent spatial learning is not attributable to myelinated fiber changes in the hippocampus and that other, undetermined factors are responsible. Anat Rec, 297:1490–1497, 2014. © 2014 Wiley Periodicals, Inc.

We investigated whether high-sensitivity C-reactive protein (hsCRP) levels were associated with contrast-induced nephropathy (CIN) and long-term mortality after coronary angiography (CAG). Patients (N = 2133) undergoing CAG with preprocedural hsCRP were consecutively enrolled. High-sensitivity C-reactive protein was measured before angiography. Median follow-up was 2.3 years. The overall incidence of CIN was 2.77% (59 of 2133). There was a positive trend of hsCRP quartiles (Q) with rates of CIN: 0.9% for Q1 (11.3 mg/L; P < .05). The receiver operating characteristic (ROC) analysis showed that the cutoff point of hsCRP was 7.3 mg/L for predicting CIN with a 72.7% sensitivity and a 67.0% specificity (area under the curve [AUC] = 0.742, 95% confidence interval [CI] 0.672-0.810; P < .05). The predictive value of hsCRP was similar to the Mehran score for CIN (AUChsCRP = 0.742 vs AUCMehran = 0.801; P = .228). After adjustment for other potential risk factors, hsCRP >7.3 mg/L still was an independent predictor of CIN (odds ratio [OR] = 2.83, 95% CI: 1.44-5.58; P = .003). Furthermore, hsCRP >7.3 mg/L was associated with higher mortality (OR = 2.04, 95% CI: 1.30-3.19; P = .002).

To observe the effect of total coptis alkaloids (TCA) on beta -amyloid peptide (A beta 25-35) induced learning and memory dysfunction in rats, and to explore its mechanism.Forty male Wistar rats were randomly divided into four groups: the control group, the model group, the TCA low dose (60 mg/kg) group and the TCA high dose (120 mg/kg) group, 10 in each. A beta 25-35 (5microl, 2 microg/microl) was injected into bilateral hippocampi of each rat to induce learning and memory dysfunction. TCA were administered through intragavage for consecutive 15 days. Morris Water Maze test was used to assess the impairment of learning and memory; concentration of malondialdehyde (MDA) in cerebral cortex was determined by thiobarbituric acid reactive substance to indicate the level of lipid peroxidation in brain tissues; activity of manganese-superoxide dismutase (Mn-SOD) in cerebral cortex was determined by xanthine-oxidase to indicate the activity of the enzyme; and NF- kappa B protein expression in cerebral cortex was measured by SP immunohistochemistry.(1) Morris Water Maze test showed that, during the 4 consecutive days of acquisition trials, the rats in the model group took longer latency and searching distance than those in the control group (P0.01), which could be shortened by high dose TCA (P0.05); during the spatial probe trial on the fifth day, the rats in the model group took shorter searching time and distance on the previous flat area than those in the control group (P0.01), which could be prolonged after TCA treatment (for low dose group, P0.05; for high dose group, P0.01). (2) Analysis of cerebral cortical tissues showed that, compared with the control group, MDA level got significantly increased and Mn-SOD activity decreased in the model group (both P0.01). After having been treated with TCA, the MDA level got significantly decreased (P0.05 and P0.01 respectively for low and high dose group), while relative increase of Mn-SOD activity only appeared in high dose group (P0.05). (3) Immunohistochemistry analysis showed the protein expression of NF- kappa B got significantly increased after modeling, while high dose TCA can significantly inhibit it.TCA could improve A beta 25-35 induced dysfunction of learning and memory in rats, and its protective mechanism is associated with its actions in decreasing MDA level, increasing Mn-SOD activity and inhibiting the expression of NF-kappa B in cerebral cortex.

Background— Few studies have investigated the safe limits of contrast to prevent contrast-induced nephropathy (CIN) based on hydration data. We aimed to investigate the relative safe maximum contrast volume adjusted for hydration volume in a population with a relatively low risk of CIN. Methods and Results— The ratios of contrast volume-to-creatinine clearance (V/CrCl) and hydration volume to body weight (HV/W) were determined in patients undergoing cardiac catheterization. Receiver–operator characteristic curve analysis based on the maximum Youden index was used to identify the optimal cutoff for V/CrCl in all patients and in HV/W subgroups. Eighty-six of 3273 (2.6%) patients with mean CrCl 71.89±27.02 mL/min developed CIN. Receiver–operator characteristic curve analysis indicated that a V/CrCl ratio of 2.44 was a fair discriminator for CIN in all patients (sensitivity, 73.3%; specificity, 70.4%). After adjustment for other confounders, V/CrCl >2.44 continued to be significantly associated with CIN (adjusted odds ratio, 4.12; P P 12 mL/kg). The best cutoff value for V/CrCl was 1.87 (sensitivity, 67.9%; specificity, 64.4%; adjusted odds ratio, 3.24; P =0.011) in the insufficient hydration subgroup (HV/W, ≤12 mL/kg; CIN, 1.32%) and 2.93 (sensitivity, 69.0%; specificity, 65.0%; adjusted odds ratio, 3.04; P =0.004) in the sufficient hydration subgroup (HV/W, >12 mL/kg; CIN, 5.00%). Conclusions— The V/CrCl ratio adjusted for HV/W may be a more reliable predictor of CIN and even long-term outcomes after cardiac catheterization. We also found a higher best cutoff value for V/CrCl to predict CIN in patients with a relatively sufficient hydration status, which may be beneficial during decision-making about contrast dose limits in relatively low-risk patients with different hydration statuses.

Emtricitabine (FTC) is used for the treatment of HIV infection and pre-exposure chemoprophylaxis. It is often used in combination with tenofovir disoproxil fumarate (TDF). This study was designed to evaluate FTC pharmacokinetics in healthy male Chinese volunteers. Sixty subjects were recruited into this single-centre, randomised, open-label study and randomly received single (groups A, B and C) or multiple oral doses (once daily for 6 days; groups D, E and F) of 200-mg FTC capsules alone (A and D), or combined with 300-mg TDF tablets (B and E), or 200 mg of FTC plus 300 mg of TDF with a high-fat diet (C and F), respectively. FTC was well-tolerated in all groups. After a single dose, there were no differences in the mean AUC0-∞ values; however, there were significant differences in the mean Tmax values (1.05, 1.40 and 2.10 h for groups A, B and C, respectively; p < 0.05). In the multiple-dose study, our results were significantly different from published t1/2 values following single-dose FTC.

An enriched environment has been shown to enhance learning and memory and to induce morphological changes in the hippocampus. In the present study, 14-month (middle-aged) female and male Sprague-Dawley rats were randomly divided into enriched environment (EE) rats and standard environment (SE) rats. EE rats were reared in an enriched environment and SE rats were reared in a standard environment for 4 months. The spatial learning capacity was assessed with Morris water maze. The hippocampus and the myelinated fibers in the rat hippocampus were quantitatively investigated with a transmission electronic microscope technique and stereological methods. The female rats housed in an enriched environment showed improved performance in the Morris water maze. There was no significant difference in the total volume of hippocampus between SE rats and EE rats. The total length and total volume of the myelinated fibers in the hippocampus of the female and male EE rats were significantly increased, respectively, when compared to the female and male SE rats. The increase of the total length of the myelinated nerve fibers in the hippocampus was mainly due to the increase of the myelinated fibers with diameters from 0.5 to 0.9 μm. Our results showed that a 4 month enriched environment had significant effects on the spatial learning capacity and the myelinated fibers in the hippocampus of middle-aged rats. The present study might provide an important theoretical basis for searching for an ethological strategy to delay the progress of brain aging in the future.

Fulminant hepatic failure (FHF) remains an extremely poor prognosis and high mortality; better treatments are urgently needed. Tetrandrine (TET), a traditional anti-inflammatory drug, has been reported to exhibit hepatoprotective activities in several liver injury models. We now investigated the effects and underlying mechanisms of TET on lipopolysaccharide (LPS) and d -galactosamine ( d -GalN)-induced FHF in mice. TET (50, 100, and 200 mg/kg) was given intraperitoneally 1 h before LPS/ d -GalN injection in mice. The mortality and liver injury was evaluated subsequently. The results showed that administering TET to mice reduced mortality and improved liver injury induced by LPS/ d -GalN in a dose-dependent manner. In addition, TET dose-dependently inhibited LPS/ d -GalN-induced NF-κB activation, serum and hepatic tissues tumor necrosis factor-α (TNF-α) production, caspase-3 activation and hepatocellular apoptosis, myeloperoxidase (MPO) activity, intercellular adhesion molecule-1 (ICAM-1) and endothelial cell adhesion molecule-1 (ECAM-1) expression. Our experimental data indicated that TET might alleviate the FHF induced by LPS/ d -GalN through inhibiting NF-κB activation to reduce TNF-α production.

Background Elevated lipoprotein(a) [Lp(a)] levels predict cardiovascular events incidence in patients with coronary artery disease (CAD). Genetic variants in the rs3798220, rs10455872 and rs6415084 single-nucleotide polymorphisms (SNPs) in the Lp(a) gene (LPA) correlate with elevated Lp(a) levels, but whether these SNPs have prognostic value for CAD patients is unknown. The present study evaluated the association of LPA SNPs with incidence of subsequent cardiovascular events in CAD patients after percutaneous coronary intervention (PCI). Methods TaqMan SNP genotyping assays were performed to detect the rs6415084, rs3798220 and rs10455872 genotypes in 517 Chinese Han patients with CAD after PCI. We later assessed whether there was an association of these SNPs with incidence of major adverse cardiovascular events (MACE: cardiac death, nonfatal myocardial infarction, ischemic stroke and coronary revascularization). Serum lipid profiles were also determined using biochemical methods. Results Only the rs6415084 variant allele was associated with higher Lp(a) levels [41.3 (20.8, 74.6) vs. 18.6 (10.3, 40.9) mg/dl, p LPA genetic variants (rs6415084 and rs3798220) and MACE incidence (p > 0.05). Conclusions Our data did not support a relationship between genetic LPA variants (rs6415084 and rs3798220) and subsequent cardiovascular events after PCI in Chinese Han CAD patients.