PACAP-38 in Acute ST-Segment Elevation Myocardial Infarction in Humans and Pigs: A Translational Study

Acute myocardial infarction (MI) is one of the most common causes of death worldwide. Pituitary adenylate cyclase activating polypeptide (PACAP) is a cardioprotective neuropeptide expressing its receptors in the cardiovascular system. The aim of our study was to examine tissue PACAP-38 in a translational porcine MI model and plasma PACAP-38 levels in patients with ST-segment elevation myocardial infarction (STEMI). Significantly lower PACAP-38 levels were detected in the non-ischemic region of the left ventricle (LV) in MI heart compared to the ischemic region of MI-LV and also to the Sham-operated LV in porcine MI model. In STEMI patients, plasma PACAP-38 level was significantly higher before percutaneous coronary intervention (PCI) compared to controls, and decreased after PCI. Significant negative correlation was found between plasma PACAP-38 and troponin levels. Furthermore, a significant effect was revealed between plasma PACAP-38, hypertension and HbA1c levels. This was the first study showing significant changes in cardiac tissue PACAP levels in a porcine MI model and plasma PACAP levels in STEMI patients. These results suggest that PACAP, due to its cardioprotective effects, may play a regulatory role in MI and could be a potential biomarker or drug target in MI.     

Clustering Empirical Failure Rate Curves for Reliability Prediction Purposes in the Case of Consumer Electronic Products

In this paper, a methodology based on the combination of time series modeling and soft computational methods is presented to model and forecast bathtub‐shaped failure rate data of newly marketed consumer electronics. The time‐dependent functions of historical failure rates are typified by parameters of an analytic model that grabs the most important characteristics of these curves. The proposed approach is also verified by the presentation of an industrial application brought along at an electrical repair service provider company. The prediction capability of the introduced methodology is compared with moving average‐based and exponential smoothing‐based forecasting methods. According to the results of comparison, the presented method can be considered as a viable alternative reliability prediction technique. Copyright © 2015 John Wiley & Sons, Ltd.     

Genetic Variation of the Endangered Gentiana lutea L. var. aurantiaca (Gentianaceae) in Populations from the Northwest Iberian Peninsula

Gentiana lutea L. (G. lutea L.) is an endangered plant, patchily distributed along the mountains of Central and Southern Europe. In this study, inter-simple sequence repeat (ISSR) markers were used to investigate the genetic variation in this species within and among populations of G. lutea L. var. aurantiaca of the Cantabrian Mountains (Northwest Iberian Peninsula). Samples of G. lutea L. collected at different locations of the Pyrenees and samples of G. lutea L. subsp. vardjanii of the Dolomites Alps were also analyzed for comparison. Using nine ISSR primers, 106 bands were generated, and 89.6% of those were polymorphic. The populations from the Northwest Iberian Peninsula were clustered in three different groups, with a significant correlation between genetic and geographic distances. Gentiana lutea L. var. aurantiaca showed 19.8% private loci and demonstrated a remarkable level of genetic variation, both among populations and within populations; those populations with the highest level of isolation show the lowest genetic variation within populations. The low number of individuals, as well as the observed genetic structure of the analyzed populations makes it necessary to protect them to ensure their survival before they are too small to persist naturally.     

Investigation of the Antiproliferative Properties of Natural Sesquiterpenes from Artemisia asiatica and Onopordum acanthium on HL-60 Cells in Vitro

Plants and plant extracts play a crucial role in the research into novel antineoplastic agents. Four sesquiterpene lactones, artecanin (1), 3β-chloro-4α,10α-dihydroxy-1α,2α-epoxy-5α,7αH-guaia-11(13)-en-12,6α-olide (2), iso-seco-tanapartholide 3-O-methyl ether (3) and 4β,15-dihydro-3-dehydrozaluzanin C (4), were isolated from two traditionally used Asteraceae species (Onopordum acanthium and Artemisia asiatica). When tested for antiproliferative action on HL-60 leukemia cells, these compounds exhibited reasonable IC₅₀ values in the range 3.6–13.5 μM. Treatment with the tested compounds resulted in a cell cycle disturbance characterized by increases in the G1 and G2/M populations, while there was a decrease in the S phase. Additionally, 1–3 elicited increases in the hypodiploid (subG1) population. The compounds elicited concentration-dependent chromatin condensation and disruption of the membrane integrity, as revealed by Hoechst 33258–propidium staining. Treatment for 24 h resulted in significant increases in activity of caspases-3 and -9, indicating that the tested sesquiterpenes induced the mitochondrial pathway of apoptosis. The proapoptotic properties of the sesquiterpene lactones were additionally demonstrated withannexin V staining. Compounds 1 and 2 increased the Bax/Bcl-2 expression and decreased the expressions of CDK1 and cyclin B2, as determined at the mRNA level by means of RT-PCR. These experimental results indicate that sesquiterpene lactones may be regarded as potential starting structures for the development of novel anticancer agents.     

PACAP-38 and PAC1 Receptor Alterations in Plasma and Cardiac Tissue Samples of Heart Failure Patients

Pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) is a multifunctional neuropeptide, which may play a role in cardioprotection. However, little is known about the presence of PACAP-38 in heart failure (HF) patients. The aim of our study was to measure the alterations of PACAP-38 like immunoreactivity (LI) in acute (n = 13) and chronic HF (n = 33) and to examine potential correlations between PACAP-38 and HF predictors (cytokines, NT-proBNP). Tissue PACAP-38 LI and PAC1 receptor levels were also investigated in heart tissue samples of patients with HF. Significantly higher plasma PACAP-38 LI was detected in patients with acute HF, while in chronic HF patients, a lower level of immunoreactivity was observed compared to healthy controls (n = 13). Strong negative correlation was identified between plasma PACAP-38 and NT-proBNP levels in chronic HF, as opposed to the positive connection seen in the acute HF group. Plasma IL-1 β, IL-2 and IL-4 levels were significantly lower in chronic HF, and IL-10 was significantly higher in patients with acute HF. PACAP-38 levels of myocardial tissues were lower in all end-stage HF patients and lower PAC1 receptor levels were detected in the primary dilated cardiomyopathy group compared to the controls. We conclude that PACAP-38 and PAC1 expression correlates with some biomarkers of acute and chronic HF; therefore, further studies are necessary to explore whether PACAP could be a suitable prognostic biomarker in HF patients.     

The Irritant Effects of Pharmaceutically Applied Surfactants

Dermal or transdermal medication may lead to irritant contact dermatitis. However, little information is available on the irritant effect of surfactants which are applied in topical formulations. Our aim was to examine the irritant effect of the most frequent compounds in topical products. A murine model was applied. The following compounds were examined: sodium lauryl sulphate (SLS), polyethoxylated (40EO) hydrogenated castor oil and sucrose laurate. SLS led to severe erythema, increase in transepidermal water loss (TEWL) and induced necrosis and accumulation of neutrophylic granulocytes and lymphocytes. Exposure to sucrose laurate resulted in an elevation of TEWL, but histology did not reveal impairment of the skin structure. Application of polyethoxylated (40EO) hydrogenated castor oil was not accompanied by tissue damage. Special attention should be paid to the irritant effect of SLS. Polyethoxylated (40EO) hydrogenated castor oil seems to be a non-irritant agent and sucrose laurate is also a promising candidate for application in topical preparations.     

Quantitative detection of trichloroacetic acid in human urine using isotope dilution high-performance liquid chromatography-electrospray ionization tandem mass spectrometry

The chemical disinfection of drinking water to control microbial contaminants results in the formation of disinfection byproducts (DBPs). The volatile trihalomethanes and the nonvolatile haloacetic acids (HAAs) are the most prevalent DBPs. It is important to monitor human exposure to HAAs because of their potential adversehealth effects, such as cancer. Among the HAAs, urinary trichloroacetic acid (TCAA) is a potential valid biomarker for assessing chronic ingestion exposure to HAAs from drinking water. We have developed a rugged, high-throughput, sensitive, accurate, and precise assay for the measurement of trace levels of TCAA in human urine using a simple solid-phase extraction (SPE) cleanup followed by isotope dilution high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). TCAA is extracted from the urine using SPE, separated from other extract components by reversed-phase HPLC, and analyzed by negative ion electrospray ionization-isotope dilution-MS/MS using a multiple reaction monitoring experiment. The method is simple and fast and is not labor intensive (sample preparation and analysis can be performed in approximately 15 min) with a limit of detection of 0.5 ng/mL in 1 mL of urine.     

Investigation of the photodecomposition of phenol in near-UV-irradiated aqueous TiO2 suspensions. I: Effect of charge-trapping species on the degradation kinetics

The effects of charge-trapping species on the kinetics of phenol decomposition were studied in near-UV-irradiated aqueous TiO₂ (anatase) suspensions in a batch photoreactor. The influence of catalyst loading, initial phenol concentration, dissolved O₂ concentration, Ag⁺ content and H₂O₂ concentration on the rate of phenol degradation is reported. The observed heterogeneous degradation of phenol followed apparently zero-order kinetics up to ca. 70% conversion. The Langmuir–Hinshelwood kinetic model successfully described the influence of the initial phenol concentration and dissolved O₂ concentration on the rate of heterogeneous photooxidation of phenol. The data obtained by applying the Langmuir–Hinshelwood treatment are consistent with the available kinetic parameters. The results of the experiments in the presence of Ag⁺ indicated that the phototransformation of phenol can proceed via direct electron transfer, neither dissolved O₂ nor its reduction forms playing a significant role in the degradation mechanism.     

Beurteilung von hals-verbindungen

QUALIFICATION OF HALS COMPOUNDS A complex method of examination has been developed suitable for the qualification of light stabilizers; by this method, according to experience, the efficacy of HALS compounds can be extensively and expediently characterized. Several light stabilizers of the HALS-type were examined and qualified, used alone or together with a UV-absorber. It has been found that, when selecting the appropriate structure for a given polymer, the weatherability of polyolefine foils is effectively increase to six-eightfold; the increase is even tenfold when the stabilizer is combined with a benzophenone-type compound. As a utilization of these experiences, a contract with the industry, led to the production of an LDPE based agricultural foil with a life-time of several years.