Traditional Chinese medicine use may reduce medical utility in patients with asthma: a nationwide population-based retrospective cohort study.

BACKGROUND: Many patients with atopic diseases, including asthma, have sought complementary and alternative medicine and traditional Chinese medicine (TCM) treatments. But, limited clinical studies have yet examined TCM effects on medical utility in asthma patients. AIM: To assess the medical utility of TCM in patients with asthma. DESIGN: Population-based retrospective cohort study. METHODS: We performed a 13-year population-based retrospective cohort study. A total of 5235 asthma patients who were TCM users and 5235 propensity-score matched asthma patients who never used TCM were sampled from the Taiwan National Health Insurance Research Database from 2000 to 2012. We compared these two groups of patients to calculate their medical utility, including numbers of emergency visits and hospitalizations until 2013. Univariate analyses were performed using Chi-square tests for dichotomous variables and t-tests for continuous variables. Cox proportional hazard models were conducted to investigate the medical utility of asthma after TCM use. RESULTS: Compared with non-TCM patients, TCM patients had a significantly decreased medical utility of asthma admission [adjusted odds ratio (OR) = 0.63; 95% confidence interval (CI): 0.46-0.85; P < 0.05], especially in patients who used TCM for >60 days. Asthma medical utility in asthma emergencies was significantly higher for male than for female patients (adjusted OR = 1.45; 95% CI: 1.08-1.96). The most frequently used TCMs for asthma control or cough treatment were antitussive agents. CONCLUSION: This population-based retrospective cohort study showed a significantly decreased medical utility of emergency visits and admissions in TCM patients, especially using TCM for >60 days.

Short-term supplementation of isocaloric meals with L-tryptophan affects pig growth.

L-Tryptophan (Trp) and some of its metabolites regulate the circadian rhythm in mammals. We aimed to investigate the effects of short-term supplementation of Trp in isocaloric meals on growth performance using the parameters of multiple blood biomarkers and free amino acids in growing pigs. A total of 32 Landrace × Yorkshire barrows with a mean body weight of 8.64 (±1.13) kg were randomly assigned to four groups and then fed with various concentrations of Trp diets daily. Our results showed that sequential supplementation of different concentrations of Trp in isocaloric meals decreased the feed:gain (F:G) ratio (P = 0.079) and plasma urea and albumin (P = 0.019), whereas the level of total protein did not. Among the essential and conditionally essential amino acids, the concentrations of histidine, isoleucine, proline, threonine, arginine, and valine in the plasma decreased (P < 0.05), whereas the concentrations of Trp, glycine, serine, and methionine increased (P < 0.01). In addition, concentrations of branched chain amino acids also significantly decreased (P = 0.004), while the rate of conversion of Trp to branched chain amino acids increased (P < 0.001). Taken together, we show that administration of a high concentration of Trp in breakfast with decreasing concentrations of Trp in lunch and dinner positively affected feed utilization and improved feed efficiency, at least in part, through the optimization of amino acid interconversions and nitrogen utilization.

Only high levels of dabigatran attenuate catheter thrombosis in vitro and in rabbits.

In patients with mechanical heart valves, thromboembolic events were more frequent with dabigatran, an oral thrombin inhibitor, than with warfarin. This observation raises the possibility that dabigatran may be less effective than conventional anticoagulants in patients with other blood-contacting devices, such as catheters. To address this, we compared the capacity of dabigatran and/or heparin to inhibit catheter-induced thrombin generation in vitro and to attenuate catheter occlusion in rabbits. Using a catheter-induced thrombin generation assay, concentrations of dabigatran over 100 ng/ml prolonged the lag time and time to peak thrombin, and reduced the peak thrombin concentration and endogenous thrombin potential in a concentration-dependent fashion. Compared with saline in a rabbit model of catheter thrombosis, dabigatran prolonged the mean time to catheter occlusion by 2.9- and 1.9-fold when plasma levels were 173 and 140 ng/ml, respectively; values comparable to median peak levels in humans given dabigatran 150 mg twice daily. In contrast, low-dose dabigatran, which produced a level of 60 ng/ml; a value comparable to the trough level of dabigatran in humans, did not prolong the time to occlusion. Whereas a 70 U/kg bolus of heparin prolonged the mean time to occlusion by 3.4-fold, a 15 U/kg bolus had no effect. When low-dose dabigatran was given in combination with 15 U/kg heparin, the mean time to occlusion was prolonged by 2.7-fold. These findings suggest that only peak levels of dabigatran are sufficient to prevent catheter-induced clotting unless supplemented heparin is given.

Silibinin inhibits VEGF secretion and age-related macular degeneration in a hypoxia-dependent manner through the PI-3 kinase/Akt/mTOR pathway.

BACKGROUND AND PURPOSE: Hypoxia-mediated neovascularization plays an important role in age-related macular degeneration (AMD). There are few animal models or effective treatments for AMD. Here, we investigated the effects of the flavonoid silibinin on hypoxia-induced angiogenesis in a rat AMD model. EXPERIMENTAL APPROACH: Retinal pigmented epithelial (RPE) cells were subjected to hypoxia in vitro and the effects of silibinin on activation of key hypoxia-induced pathways were examined by elucidating the hypoxia-inducible factor-1 alpha (HIF-1α) protein level by Western blot. A rat model of AMD was developed by intravitreal injection of VEGF in Brown Norway rats, with or without concomitant exposure of animals to hypoxia. Animals were treated with oral silibinin starting at day 7 post-VEGF injection and AMD changes were followed by fluorescein angiography on days 14 and 28 post-injection. KEY RESULTS: Silibinin pretreatment of RPE cells increased proline hydroxylase-2 expression, inhibited HIF-1α subunit accumulation, and inhibited VEGF secretion. Silibinin-induced HIF-1α and VEGF down-regulation required suppression of hypoxia-induced phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway. In the rat model of AMD, silibinin administration prevented VEGF- and VEGF plus hypoxia-induced retinal oedema and neovascularization. CONCLUSION AND IMPLICATIONS: The effects of silibinin, both in vitro and in vivo, support its potential as a therapeutic for the prevention of neovascular AMD.

A novel approach to arterial thrombolysis.

Achieving early, complete, and sustained reperfusion after acute myocardial infarction does not occur in approximately 50% of patients, even with the most potent established thrombolytic therapy. Bleeding is observed with increased concentrations of thrombolytics as well as with adjunctive antithrombotic and antiplatelet agents. A novel approach to enhance thrombolytic therapy is to inhibit the activated form of thrombin-activatable fibrinolysis inhibitor (TAFI), which attenuates fibrinolysis in clots formed from human plasma. Identification of TAFI in rabbit plasma facilitated the development of a rabbit arterial thrombolysis model to compare the thrombolytic efficacy of tissue-plasminogen activator (tPA) alone or with an inhibitor, isolated from the potato tuber (PTI), of activated TAFI (TAFIa). Efficacy was assessed by determining the time to patency, the time the vessel remained patent, the maximal blood flow achieved during therapy, the percentage of the original thrombus, which lysed, the percentage change in clot weight, the net clot accreted, and the release of radioactive fibrin degradation products into the circulation. The results indicate that coadministration of PTI and tPA significantly improved tPA-induced thrombolysis without adversely affecting blood pressure, activated partial thromboplastin time, thrombin clotting time, fibrinogen, or alpha-2-antiplasmin concentrations. The data indicate that inhibitors of TAFIa may comprise novel and very effective adjuncts to tPA and improve thrombolytic therapy to achieve both clot lysis and vessel patency.

Choline monooxygenase, an unusual iron-sulfur enzyme catalyzing the first step of glycine betaine synthesis in plants: prosthetic group characterization and cDNA cloning.

Plants synthesize the osmoprotectant glycine betaine via the route choline --> betaine aldehyde --> glycine betaine. In spinach, the first step is catalyzed by choline monooxygenase (CMO), a ferredoxin-dependent stromal enzyme that has been hypothesized to be an oligomer of identical subunits and to be an Fe-S protein. Analysis by HPLC and matrix-assisted laser desorption ionization MS confirmed that native CMO contains only one type of subunit (Mr 42,864). Determination of acid-labile sulfur and nonheme iron demonstrated that there is one [2Fe-2S] cluster per subunit, and EPR spectral data indicated that this cluster is of the Rieske type--i.e., coordinated by two Cys and two His ligands. A full-length CMO cDNA (1,622 bp) was cloned from spinach using a probe generated by PCR amplification for which the primers were based on internal peptide sequences. The ORF encoded a 440-amino acid polypeptide that included a 60-residue transit peptide. The deduced amino acid sequence included two Cys-His pairs spaced 16 residues apart, a motif characteristic of Rieske-type Fe-S proteins. Larger regions that included this motif also showed some sequence similarity (approximately 40%) to Rieske-type proteins, particularly bacterial oxygenases. Otherwise there was very little similarity between CMO and proteins from plants or other organisms. RNA and immunoblot analyses showed that the expression of CMO in leaves increased several-fold during salinization. We conclude that CMO is a stress-inducible representative of a new class of plant oxygenases.