Screening of the inhibitory effect of xenobiotics on alcohol metabolism using S9 rat liver fractions.

The purpose of this work was to develop and optimize a simple and suitable method to detect the potential inhibitory effect of drugs and medicines on alcohol dehydrogenase (ADH) activity in order to evaluate the possible interactions between medicines and alcohol metabolism. Commonly used medicines that are often involved in court litigations related with driving under the influence of alcohol were selected. Alprazolam, flunitrazepam and tramadol were tested as drugs with no known effect on ADH activity. Cimetidine, reported previously as having inhibitory effect on ADH, and 4-methylpyrazole (4-MP), a well known ADH inhibitor, were tested as positive controls. Apart from 4-MP, tramadol was identified as having the higher inhibitory effect with an IC50 of 44.7×10(-3)mM, followed by cimetidine (IC50 of 122.9×10(-3)mM). Alprazolam and flunitrazepam also reduced liver ADH activity but to a smaller extent (inhibition of 11.8±5.0% for alprazolam 1.0mM and 34.5±7.1% for flunitrazepam 0.04mM). Apart from cimetidine, this is the first report describing the inhibitory effect of these drugs on ethanol metabolism. The results also show the suitability of the method to screen for inhibitory effect of drugs on ethanol metabolism helping to identify drugs for which further study is justified.

Weak Form Tests of Efficient Market Hypothesis: Evidence from CEE-Countries and Russian Stock Markets

Tämän tutkielman tavoitteena on selvittää Venäjän, Slovakian, Tsekin, Romanian, Bulgarian, Unkarin ja Puolan osakemarkkinoiden heikkojen ehtojen tehokkuutta. Tämä tutkielma on kvantitatiivinen tutkimus ja päiväkohtaiset indeksin sulkemisarvot kerättiin Datastreamin tietokannasta. Data kerättiin pörssien ensimmäisestä kaupankäyntipäivästä aina vuoden 2006 elokuun loppuun saakka. Analysoinnin tehostamiseksi dataa tutkittiin koko aineistolla, sekä kahdella aliperiodilla. Osakemarkkinoiden tehokkuutta on testattu neljällä tilastollisella metodilla, mukaan lukien autokorrelaatiotesti ja epäparametrinen runs-testi. Tavoitteena on myös selvittääesiintyykö kyseisillä markkinoilla viikonpäiväanomalia. Viikonpäiväanomalian esiintymistä tutkitaan käyttämällä pienimmän neliösumman menetelmää (OLS). Viikonpäiväanomalia on löydettävissä kaikilta edellä mainituilta osakemarkkinoilta paitsi Tsekin markkinoilta. Merkittävää, positiivista tai negatiivista autokorrelaatiota, on löydettävissä kaikilta osakemarkkinoilta, myös Ljung-Box testi osoittaa kaikkien markkinoiden tehottomuutta täydellä periodilla. Osakemarkkinoiden satunnaiskulku hylätään runs-testin perusteella kaikilta muilta paitsi Slovakian osakemarkkinoilla, ainakin tarkastellessa koko aineistoa tai ensimmäistä aliperiodia. Aineisto ei myöskään ole normaalijakautunut minkään indeksin tai aikajakson kohdalla. Nämä havainnot osoittavat, että kyseessä olevat markkinat eivät ole heikkojen ehtojen mukaan tehokkaita

Testing the Random Walk Hypothesis on the Baltic Stock Markets

The purpose of the thesis is to analyze whether the returns of general stock market indices of Estonia, Latvia and Lithuania follow the random walk hypothesis (RWH), and in addition, whether they are consistent with the weak-form efficiency criterion. Also the existence of the day-of-the-week anomaly is examined in the same regional markets. The data consists of daily closing quotes of the OMX Tallinn, Riga and Vilnius total return indices for the sample period from January 3, 2000 to August 28, 2009. Moreover, the full sample period is also divided into two sub-periods. The RWH is tested by applying three quantitative methods (i.e. the Augmented Dickey-Fuller unit root test, serial correlation test and non-parametric runs test). Ordinary Least Squares (OLS) regression with dummy variables is employed to detect the day-of-the-week anomalies. The random walk hypothesis (RWH) is rejected in the Estonian and Lithuanian stock markets. The Latvian stock market exhibits more efficient behaviour, although some evidence of inefficiency is also found, mostly during the first sub-period from 2000 to 2004. Day-of-the-week anomalies are detected on every stock market examined, though no longer during the later sub-period.

Pharmacological characterization of the relaxant effect induced by adrenomedullin in rat cavernosal smooth muscle

The aim of the present study was to determine the mechanisms underlying the relaxant effect of adrenomedullin (AM) in rat cavernosal smooth muscle (CSM) and the expression of AM system components in this tissue. Functional assays using standard muscle bath procedures were performed in CSM isolated from male Wistar rats. Protein and mRNA levels of pre-pro-AM, calcitonin receptor-like receptor (CRLR), and Subtypes 1, 2 and 3 of the receptor activity-modifying protein (RAMP) family were assessed by Western immunoblotting and quantitative real-time polymerase chain reaction, respectively. Nitrate and 6-keto-prostaglandin F1α (6-keto-PGF1α; a stable product of prostacyclin) levels were determined using commercially available kits. Protein and mRNA of AM, CRLR, and RAMP 1, -2, and -3 were detected in rat CSM. Immunohistochemical assays demonstrated that AM and CRLR were expressed in rat CSM. AM relaxed CSM strips in a concentration-dependent manner. AM22-52, a selective antagonist for AM receptors, reduced the relaxation induced by AM. Conversely, CGRP8-37, a selective antagonist for calcitonin gene-related peptide receptors, did not affect AM-induced relaxation. Preincubation of CSM strips with NG-nitro-L-arginine-methyl-ester (L-NAME, nitric oxide synthase inhibitor), 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, quanylyl cyclase inhibitor), Rp-8-Br-PET-cGMPS (cGMP-dependent protein kinase inhibitor), SC560 [5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl pyrazole, selective cyclooxygenase-1 inhibitor], and 4-aminopyridine (voltage-dependent K+ channel blocker) reduced AM-induced relaxation. On the other hand, 7-nitroindazole (selective neuronal nitric oxide synthase inhibitor), wortmannin (phosphatidylinositol 3-kinase inhibitor), H89 (protein kinase A inhibitor), SQ22536 [9-(tetrahydro-2-furanyl)-9H-purin-6-amine, adenylate cyclase inhibitor], glibenclamide (selective blocker of ATP-sensitive K+ channels), and apamin (Ca2+-activated channel blocker) did not affect AM-induced relaxation. AM increased nitrate levels and 6-keto-PGF1α in rat CSM. The major new contribution of this research is that it demonstrated expression of AM and its receptor in rat CSM. Moreover, we provided evidence that AM-induced relaxation in this tissue is mediated by AM receptors by a mechanism that involves the nitric oxide-cGMP pathway, a vasodilator prostanoid, and the opening of voltage-dependent K+ channels.

A sermon, preached in Hingham and Quincy, 20th August 1812, the day of the national fast, on account of the war with Great Britain /

Bibliogr.

A sermon, preached in Boston, July 23, 1812, the day of the publick fast, appointed by the Executive of the Commonwealth of Massachusetts, in consequence of the declaration of war against Great Britain

Published at the request of the hearers Printed by Greenough and Stebbins

A sermon, preached in Hingham and Quincy, 20th August 1812, the day of the national fast, on account of the war with Great Britain

Printed by Joshua Belcher

A systematic analysis of the detrimental effect of hormonotherapy on skeletal and non-skeletal morbidities in male with prostate cancer

Plusieurs patients atteints d’un cancer de la prostate (CaP) se verront prescrire l'hormonothérapie (HT) en raison du stade avancé ou en cas d’une récidive de la maladie, pour freiner la progression de la maladie et améliorer leur survie. Cependant, l’HT présente des effets pouvant nuire significativement à la santé du patient.

Nonparametric estimation of the leverage effect: a trade-off between robustness and efficiency

We consider two new approaches to nonparametric estimation of the leverage effect. The first approach uses stock prices alone. The second approach uses the data on stock prices as well as a certain volatility instrument, such as the CBOE volatility index (VIX) or the Black-Scholes implied volatility. The theoretical justification for the instrument-based estimator relies on a certain invariance property, which can be exploited when high frequency data is available. The price-only estimator is more robust since it is valid under weaker assumptions. However, in the presence of a valid volatility instrument, the price-only estimator is inefficient as the instrument-based estimator has a faster rate of convergence. We consider two empirical applications, in which we study the relationship between the leverage effect and the debt-to-equity ratio, credit risk, and illiquidity.

Evaluation of the Toxic Effect from Eupatorium Microphyllum L.F. (Asteraceae) Extracts on Aedes Aegypti Larvae (Diptera: Culicidae) in Laboratory Conditions

In the present work the toxic activity of extracts of Eupatorium microphyllum L.F. was evaluated on 4th instar larvae of the mosquito Aedes aegypti (Linneaus), under laboratory conditions. Aqueous extracts were utilized in concentrations of 500 mg L-1, 1,500 mg L-1 and 2,500 mg L-1 and acetone in concentrations of 10 mg L-1, 20 mg L-1, 30 mg L-1, 40 mg L-1and 50 mg L-1. The bioassays were carried out for triplicate each one with 20 larvae, exposed for 24 hours to 150 mL of solution. In all the bioassays were employed control groups. In the evaluation of the acetone extracts, a negative control was employed to avoid that the mortality of the larvae to occur on account of the solvent. The Aqueous extracts showed low moderate action in the mortality of larvae, less than 20%. On the contrary, the action of the acetone extracts was observed to 10 and 20 mg L-1with 15% of mortality, while to 30 and 40 mg L-1 were registered 22 to 38% of mortality. However, to 50 mg L-1 the mortality was of 95.4% with highly significant statistical results. The concentrations of the acetone extracts showed to be the most efficient for the control of the mosquitoes selected. Both types of extracts showed toxic effect in larvae of A. aegypti, nevertheless, greater effect in the acetone extracts was observed relating to the aqueous extracts of E. microphyllum, which constitutes a viable alternative in the search of new larvicides from composed natural.

Development of a quantitative tool for the comparison of the prebiotic effect of dietary oligosaccharides

Aims: To develop a quantitative equation [prebiotic index ( PI)] to aid the analysis of prebiotic fermentation of commercially available and novel prebiotic carbohydrates in vitro, using previously published fermentation data. Methods: The PI equation is based on the changes in key bacterial groups during fermentation. The bacterial groups incorporated into this PI equation were bifidobacteria, lactobacilli, clostridia and bacteroides. The changes in these bacterial groups from previous studies were entered into the PI equation in order to determine a quantitative PI score. PI scores were than compared with the qualitative conclusions made in these publications. In general the PI scores agreed with the qualitative conclusions drawn and provided a quantitative measure. Conclusions: The PI allows the magnitude of prebiotic effects to be quantified rather than evaluations being solely qualitative. Significance and Impact of the Study: The PI equation may be of great use in quantifying prebiotic effects in vitro. It is expected that this will facilitate more rational food product development and the development of more potent prebiotics with activity at lower doses.

Functional petit-suisse cheese: measure of the prebiotic effect

Prebiotics and probiotics are increasingly being used to produce potentially synbiotic foods, particularly through dairy products as vehicles. It is well known that both ingredients may offer benefits to improve the host health. This research aimed to evaluate the prebiotic potential of novel petit-suisse cheeses using an in vitro fermentation model. Five petit-suisse cheese formulations combining candidate prebiotics (inulin. oligofructose. hone) and probiotics (Lactobacillus acidophilus, Bifidobacterium lactis) were tested in vitro using, sterile. stirred, batch culture fermentations with human faecal slurry. Measurement of prebiotic effect (MPE) values were generated comparing bacterial changes through determination of maximum growth rates of groups, rate of substrate assimilation and production of lactate and short chain fatty acids. Fastest fermentation and high lactic acid production, promoting increased growth rates of bifidobacteria and lactobacilli. were achieved with addition of prebiotics to a probiotic cheese (made using starter + probiotics). Addition of probiotic strains to control cheese (made using just a starter culture) also resulted in high lactic acid production. Highest MPE values were obtained with addition of prebiotics to a probiotic cheese, followed by addition of prebiotics and/or probiotics to a control cheese. Under the in vitro conditions used, cheese made with the combination of different prebiotics and probiotics resulted in the most promising functional petit-suisse cheese. The study allowed comparison of potentially functional petit-suisse cheeses and screening of preferred synbiotic potential for future market use. (c) 2007 Elsevier Ltd. All rights reserved.