Journal of Laboratory and Clinical Medicine最新文献

Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of tissue factor (TF)-induced blood coagulation. A positive association between very low density lipoproteins (VLDLs) and TFPI has been reported in vivo. In contrast, one in vitro study indicates that TFPI may enhance lipoprotein lipase (LPL) activity, thereby increasing triglyceride hydrolysis. The current study was conducted to investigate how native VLDL influenced the synthesis and release of TFPI in endothelial cells, and how TFPI affected the LPL-induced hydrolysis of VLDL in vitro and at the endothelial surface. A spontaneously transformed immortal endothelial cell line (ECV304) and primary coronary artery cells (CoEc) were used, and VLDL was isolated from healthy volunteers by density gradient ultracentrifugation. Sequential free fatty acid (FFA) measurements were used to evaluate the kinetics of the LPL-induced hydrolysis. The levels of TFPI mRNAs in the stimulated cells were determined by quantitative real-time reverse transcription-ploymerase chain reaction (qPCR) using the ABI PRISM 7700 Sequence Detection System. Stimulation of ECV304 cells for 24 hours with native VLDL (0–100 μg/mL) caused a dose-dependent increase of TFPI in the medium (6.7–23.8 ng/10⁶ cells, P < 0.001), without affecting the cellular content of TFPI. The expression of TFPI mRNA was significantly upregulated after 10 minutes of stimulation with n-VLDL. Both recombinant TFPI (r-TFPI) and LPL showed a dose-dependent binding to ECV 304 cells without saturation, and no competitive binding interactions between LPL and TFPI were observed at the endothelial surface. The addition of increasing concentrations of r-TFPI to ECV 304 cells, preincubated with LPL, did not affect the hydrolysis of VLDL triglycerides. The maximal reaction velocity (V_max) of LPL-induced hydrolysis of n-VLDL was not affected by the addition of increasing concentrations of r-TFPI to the reaction mixture in vitro. The current experimental study indicates an upregulation of TFPI synthesis and release by VLDL. LPL-induced hydrolysis of VLDL in vitro was not influenced by TFPI neither in suspension nor at the endothelial surface.

The pathway of interferon-γ (IFN-γ)-induced suppression in tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis of fibroblast-like synovial cells (FLS) was investigated. rTRAIL triggered FLS apoptosis in a type II cell death manner, whereas IFN-γ pretreatment significantly inhibited TRAIL-mediated apoptosis. As disruption of mitochondrial transmembrane potential (ΔΨm), Leu-Glu-His-Asp ase (IETD ase) activity, and the appearance of hypodiploid DNA + cells were markedly suppressed in IFN-γ-treated FLS in response to TRAIL, IFN-γ-induced suppression was supposed to achieve at upstream of caspase-8. IFN-γ rapidly phosphorylated signal transducers and activators of transcription 1 (STAT1), STAT3, and STAT6 as well as ERK, whereas enhanced neither phosphorylation of Akt nor nuclear translocation of nuclear factor κB (NF-κB) p65. Janus kinase (JAK)-induced phosphorylation of STAT1/3/6, which acts at translational regulation, seemed to be crucial because chemical inhibition of JAK as well as cycloheximide (CHX) abolished both the phosphorylation of STAT1/3/6 and the IFN-γ-induced inhibitory effect. Although ERK was phosphorylated through IFN-γ, chemical inhibition of ERK by PD98059 did not abolish the IFN-γ-induced inhibitory effect. The authors tried to determine the responsible molecules; however, expression of TRAIL receptors; pro-caspase-3/-8/-9; Fas-associated death domain protein (FADD); tumor necrosis factor receptor 1-associated death domain protein (TRADD); silencer of death domain (SODD); FLICE inhibitory protein (FLIP); and Bcl-2, Bcl-xL, and Bax in FLS was not modulated by IFN-γ. Although the authors have not yet clarified the precise mechanism, these data suggest that IFN-γ/JAK/STAT pathway, which is supposed to be activated in inflammatory rheumatoid arthritis (RA) synovial tissues, contributes to form apoptosis resistance phenotype of the cells in situ, leading to a marked increase in cellularity of synovial cells.

Chronic kidney disease (CKD) is an increasingly common condition with limited treatment options that is placing a major financial and emotional burden on the community. The use of complementary and alternative medicines (CAMS) has increased many-fold over the past decade. Although several compelling studies show renal toxicities and an adverse outcome from use of some CAMS, there is also emerging evidence in the literature that some may be renoprotective. Many nephrologists are unaware of these potential therapeutic benefits in treating CKD, or they are reluctant to consider them in research trials for fear of adverse effects (including nephrotoxicity) or deleterious interaction with co-prescribed, conventional medicines. The increased use of self-prescribed CAMS by their patients suggests that practitioners and researchers should keep abreast of the current information on these agents. A primary goal of this article was to review the available scientific evidence for the use of herbs or natural substances as a complementary treatment for patients with CKD. A further goal was to report the literature on herbs that have been reported to cause kidney failure.

Prostate specific antigen (PSA) is frequently used for prostate cancer (PCa) screening, but serum levels are also increased by prostate inflammation. Elevations in serum levels of α1-antitrypsin (ATT), a marker of inflammation, in cancer patients are well documented. However, an association between PSA and ATT has never been investigated. The authors, therefore, measured serum acute phase proteins (APPs) ATT, α1-acid glycoprotein, C-reactive protein, and α1-antichymotrypsin in 174 men without and 34 with newly diagnosed untreated PCa (38–80 years old). As expected, men with PCa had higher mean PSA levels than those without PCa (P < 0.00001). Men with PCa and those without PCa but with PSA >2 ng/mL (n = 68) had significantly higher ATT concentrations than those without these conditions (n = 106) (mean ± SEM g/L): 1.94±0.083, 1.92±0.066, 1.25±0.043, respectively; p <0.005). Interestingly, African-American men without PCa (n=111) had higher ATT levels than Caucasian men (n=63) (1.565±0.045 g/l versus 1.395±0.056 g/l; p <0.005); and differences persisted in men with PSA >2 ng/ml (2.094±0.07 g/l versus 1.593∀0.095 g/l; p<0.0002). There were no differences among groups in the levels of other APP. ATT showed the strongest correlation with PSA (r = 0.346 to 0.395; p <0.001) than any other APP (r ≤0.245). Our data suggest that men with PCa have higher ATT levels than those without PCa; and African-American men without PCa have higher ATT levels than Caucasian men. The possible implications of elevated ATT levels in African-American men on the risk of PCa are discussed.

The authors evaluated the correlation of post-cardiopulmonary bypass surgery bleeding, measured as 24-hour chest tube output/kilogram body weight, with platelet function tests using glass bead adhesion and Thrombelastograph Platelet Mapping (Haemoscope Corporation, Niles, Ill); coagulation tests; patient characteristics; surgery parameters; and visual assessment of surgical field bleeding before closure as not bleeding (code 1), oozing (code 2), and excessive bleeding (code 3). All platelet function and coagulation tests indicated significant dysfunction 15 minutes after protamine neutralization of heparin. With the exception of glass bead adherence, these assays indicated poor recovery of function 1 hour postoperatively. By multiple regression, the most significant predictors of postoperative bleeding were a low body mass index (BMI) (P < 0.0001), lowest core body temperature (P = 0.0006), and cross clamp time (P < 0.0001). Low core temperature was significantly (P < 0.0001) correlated with cross clamp time, which the authors believe is the most likely cause of coagulation and platelet dysfunction. None of the platelet function tests significantly correlated with bleeding. Looking at the highest quartile of chest tube output patients (n = 19) versus the upper and lower 50th percentile of coagulation and platelet function, bleeding could be explained for 11 patients by BMI plus surgery parameters along with coagulation and/or platelet dysfunction. In three cases without negative surgery parameters, coagulation dysfunction was observed. The remaining five cases did not give a clear indication of which parameters were primarily responsible for the bleeding.

Water, compared with plasma at a pH of 7.4, is a weak acid. The addition of free water to a patient should have an acidifying effect (dilutional acidosis) and the removal of it, an alkalinizing effect (concentrational alkalosis). The specific effects of free water loss or gain in a relatively complex fluid such as plasma has, to the authors’ knowledge, not been reported. This information would be useful in the interpretation of the effect of changes in free water in patients. Plasma samples from goats were either evaporated in a tonometer to 80% of baseline volume or hydrated by the addition of distilled water to 120% of baseline volume. The pH and partial pressure of carbon dioxide, sodium, potassium, ionized calcium, chloride, lactate, phosphorous, albumin, and total protein concentrations were measured. Actual base excess (ABE), standard bicarbonate, anion gap, strong ion difference, strong ion gap, unmeasured anions, and the effects of sodium, chloride, phosphate, and albumin changes on ABE were calculated. Most parameters changed 20% in proportion to the magnitude of dehydration or hydration. Bicarbonate concentration, however, increased only 11% in the evaporation trial and decreased only −2% in the dehydration trial. The evaporation trial was associated with a mild, but significant, metabolic alkalotic effect (ABE increased 3.2 mM/L), whereas the hydration trial was associated with a slight, insignificant metabolic acidotic effect (ABE decreased only 0.6 mM/L). The calculated free water ABE effect (change in sodium concentration) was offset by opposite changes in calculated chloride, lactate, phosphate, and albumin ABE effects.