Lipid peroxidation, detoxification capacity, and genome damage in mice after transplacental exposure to pharmaceutical drugs

Data on genome damage, lipid peroxidation, and levels of glutathione peroxidase (GPX) in newborns after transplacental exposure to xenobiotics are rare and insufficient for risk assessment. The aim of the current study was to analyze, in an animal model, transplacental genotoxicity, lipid peroxidation, and detoxification disturbances caused by the following drugs commonly prescribed to pregnant women: paracetamol, fluconazole, 5-nitrofurantoin, and sodium valproate. Genome damage in dams and their newborn pups transplacentally exposed to these drugs was investigated using the in vivo micronucleus (MN) assay. The drugs were administered to dams intraperitoneally in three consecutive daily doses between days 12 and 14 of pregnancy. The results were correlated, with detoxification capacity of the newborn pups measured by the levels of GPX in blood and lipid peroxidation in liver measured by malondialdehyde (HPLC-MDA) levels. Sodium valproate and 5-nitrofurantoin significantly increased MN frequency in pregnant dams. A significant increase in the MN frequency of newborn pups was detected for all drugs tested. This paper also provides reference levels of MDA in newborn pups, according to which all drugs tested significantly lowered MDA levels of newborn pups, while blood GPX activity dropped significantly only after exposure to paracetamol. The GPX reduction reflected systemic oxidative stress, which is known to occur with paracetamol treatment. The reduction of MDA in the liver is suggested to be an unspecific metabolic reaction to the drugs that express cytotoxic, in particular hepatotoxic, effects associated with oxidative stress and lipid peroxidation.

Hepatic inducible nitric oxide synthase expression increases upon exposure to hypergravity

Stimulation by a number of conditions, including infection, cytokines, mechanical injury, and hypoxia, can upregulate inducible nitric oxide synthase (iNOS) in hepatocytes. We observed that exposure to hypergravity significantly upregulated the transcription of the hepatic iNOS gene. The aim of this study was to confirm our preliminary data, and to further investigate the distribution of the iNOS protein in the livers of mice exposed to hypergravity. ICR mice were exposed to +3 Gz for 1 h. We investigated the time course of change in the iNOS expression. Hepatic iNOS mRNA expression progressively increased in centrifuged mice from 0 to 12 h, and then decreased rapidly by 18 h. iNOS mRNA levels in the livers of centrifuged mice was significantly higher at 3, 6, and 12 h than in uncentrifuged control mice. The pattern of iNOS protein expression paralleled that of the mRNA expression. At 0 and 1 h, weak cytoplasmic iNOS immunoreactivity was found in some hepatocytes surrounding terminal hepatic venules. It was noted that at 6 h there was an increase in the number of perivenular hepatocytes with moderate to strong cytoplasmic immunoreactivity. The number of iNOS-positive hepatocytes was maximally increased at 12 h. The majority of positively stained cells showed a strong intensity of iNOS expression. The expression levels of iNOS mRNA and protein were significantly increased in the livers of mice exposed to hypergravity. These results suggest that exposure to hypergravity significantly upregulates iNOS at both transcriptional and translational levels.

Long-term correlation of the electrocorticogram as a bioindicator of brain exposure to ionizing radiation

Understanding the effects of radiation and its possible influence on the nervous system are of great clinical interest. However, there have been few electrophysiological studies on brain activity after exposure to ionizing radiation (IR). A new methodological approach regarding the assessment of the possible effects of IR on brain activity is the use of linear and nonlinear mathematical methods in the analysis of complex time series, such as brain oscillations measured using the electrocorticogram (ECoG). The objective of this study was to use linear and nonlinear mathematical methods as biomarkers of gamma radiation regarding cortical electrical activity. Adult Wistar rats were divided into 3 groups: 1 control and 2 irradiated groups, evaluated at 24 h (IR24) and 90 days (IR90) after exposure to 18 Gy of gamma radiation from a cobalt-60 radiotherapy source. The ECoG was analyzed using power spectrum methods for the calculation of the power of delta, theta, alpha and beta rhythms and by means of the α-exponent of the detrended fluctuation analysis (DFA). Using both mathematical methods it was possible to identify changes in the ECoG, and to identify significant changes in the pattern of the recording at 24 h after irradiation. Some of these changes were persistent at 90 days after exposure to IR. In particular, the theta wave using the two methods showed higher sensitivity than other waves, suggesting that it is a possible biomarker of exposure to IR.

Association between NOx exposure and deaths caused by respiratory diseases in a medium-sized Brazilian city

Exposure to nitrogen oxides (NOx) emitted by burning fossil fuels has been associated with respiratory diseases. We aimed to estimate the effects of NOx exposure on mortality owing to respiratory diseases in residents of Taubaté, São Paulo, Brazil, of all ages and both sexes. This time-series ecological study from August 1, 2011 to July 31, 2012 used information on deaths caused by respiratory diseases obtained from the Health Department of Taubaté. Estimated daily levels of pollutants (NOx, particulate matter, ozone, carbon monoxide) were obtained from the Centro de Previsão de Tempo e Estudos Climáticos Coupled Aerosol and Tracer Transport model to the Brazilian developments on the Regional Atmospheric Modeling System. These environmental variables were used to adjust the multipollutant model for apparent temperature. To estimate association between hospitalizations owing to asthma and air pollutants, generalized additive Poisson regression models were developed, with lags as much as 5 days. There were 385 deaths with a daily mean (±SD) of 1.05±1.03 (range: 0-5). Exposure to NOx was significantly associated with mortality owing to respiratory diseases: relative risk (RR)=1.035 (95% confidence interval [CI]: 1.008-1.063) for lag 2, RR=1.064 (95%CI: 1.017-1.112) lag 3, RR=1.055 (95%CI: 1.025-1.085) lag 4, and RR=1.042 (95%CI: 1.010-1.076) lag 5. A 3 µg/m3 reduction in NOx concentration resulted in a decrease of 10-18 percentage points in risk of death caused by respiratory diseases. Even at NOx concentrations below the acceptable standard, there is association with deaths caused by respiratory diseases.

Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol

Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol), but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30–35 g, 8-10 per group) were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a “three-bottle choice” paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.

Inflammatory cytokines and plasma redox status responses in hypertensive subjects after heat exposure

Hypertension is characterized by a pro-inflammatory status, including redox imbalance and increased levels of pro-inflammatory cytokines, which may be exacerbated after heat exposure. However, the effects of heat exposure, specifically in individuals with inflammatory chronic diseases such as hypertension, are complex and not well understood. This study compared the effects of heat exposure on plasma cytokine levels and redox status parameters in 8 hypertensive (H) and 8 normotensive (N) subjects (age: 46.5±1.3 and 45.6±1.4 years old, body mass index: 25.8±0.8 and 25.6±0.6 kg/m2, mean arterial pressure: 98.0±2.8 and 86.0±2.3 mmHg, respectively). They remained at rest in a sitting position for 10 min in a thermoneutral environment (22°C) followed by 30 min in a heated environmental chamber (38°C and 60% relative humidity). Blood samples were collected before and after heat exposure. Plasma cytokine levels were measured using sandwich ELISA kits. Plasma redox status was determined by thiobarbituric acid reactive substances (TBARS) levels and ferric reducing ability of plasma (FRAP). Hypertensive subjects showed higher plasma levels of IL-10 at baseline (P<0.05), although levels of this cytokine were similar between groups after heat exposure. Moreover, after heat exposure, hypertensive individuals showed higher plasma levels of soluble TNF receptor (sTNFR1) and lower TBARS (P<0.01) and FRAP (P<0.05) levels. Controlled hypertensive subjects, who use angiotensin-converting-enzyme inhibitor (ACE inhibitors), present an anti-inflammatory status and balanced redox status. Nevertheless, exposure to a heat stress condition seems to cause an imbalance in the redox status and an unregulated inflammatory response.

Development of an Ecology-Oriented Software-Defined Networking Framework

ICT contributed to about 0.83 GtCO2 emissions where the 37% comes from the telecoms infrastructures. At the same time, the increasing cost of energy has been hindering the industry in providing more affordable services for the users. One of the sources of these problems is said to be the rigidity of the current network infrastructures which limits innovations in the network. SDN (Software Defined Network) has emerged as one of the prominent solutions with its idea of abstraction, visibility, and programmability in the network. Nevertheless, there are still significant efforts needed to actually utilize it to create a more energy and environmentally friendly network. In this paper, we suggested and developed a platform for developing ecology-related SDN applications. The main approach we take in realizing this goal is by maximizing the abstractions provided by OpenFlow and to expose RESTful interfaces to modules which enable energy saving in the network. While OpenFlow is made to be the standard for SDN protocol, there are still some mechanisms not defined in its specification such as settings related to Quality of Service (QoS). To solve this, we created REST interfaces for setting of QoS in the switches which can maximize network utilization. We also created a module for minimizing the required network resources in delivering packets across the network. This is achieved by utilizing redundant links when it is needed, but disabling them when the load in the network decreases. The usage of multi paths in a network is also evaluated for its benefit in terms of transfer rate improvement and energy savings. Hopefully, the developed framework can be beneficial for developers in creating applications for supporting environmentally friendly network infrastructures.

Optimizing counterparty credit risk portfolio by reducing exposure at default variance

Rahoitusyhtiöt pitävät omaa pääomaa taseessa harvinaisen suuria markkinamuutoksia varten ja tämän pääoman määrä on ohjattu valvontaviranomaisten toimesta. Euroopassa Basel akordi antaa suuntaviivat näille säädöksille. 2007 vuoden finanssikriisin jälkeen rahoitusyhtiöt sekä valvojat ovat olleet entistä kiinnostuneempia pääoman riittävyydestä. Tutkimuksia riskistä, säädöksistä ja pääomavaateen madaltamisesta on tehty aikaisemmin, mutta tässä tutkimuksessa keskitytään vaateen jatkuvan muutoksen suuruuteen. Tutkimus sisältää hypoteettisen vastapuoliriski portfolion, jossa on mukana valuuttajohdannaisia. Tätä portfoliota simuloidaan eri tavoin, jotta nähtäisiin kuinka suuri vaikutus portfolion koostumuksella voi olla pääomavaateen varianssiin. Jos tämä muuttuja on merkittävä, pitäisikö rahoitusyhtiöiden yrittää pienentää muutosta, jotta yhtiöiden varapääoman määrää voitaisiin alentaa? Tutkimuksessa on myös haastateltu Suomen johtavia vastapuoliriski asiantuntijoita, jotta nähtäisiin rahoitusalan oma näkemys asian merkittävyydestä. Tutkimusmenetelminä toimivat haastattelut sekä numeerinen analyysi hypoteettisella portfoliolla. Kaupat tähän vastapuoliriski portfolioon on luotu 14 vuoden ajalle ja se sisältää ainoastaan valuuttajohdannaisia viidessä eri valuutassa. Riski lasketaan markkina-arvo menetelmällä, joista lasketaan VaR-mallilla tulevaisuuden riski nettoutuksen kera. Portfolion rakennetta muutetaan simuloinneissa, jotta nähtäisiin vaikutus tulevaisuuden riskeille, joita käytetään edustamaan pääomavaateen määrää ja sen vaihtelua yli ajan. Portfolioiden riskejä lasketaan myös rasituskokeiden avulla, jotta tuloksista saataisiin mahdollisimman todenmukaisia. Analyyttinen osuus tutkimuksesta näyttää sen, että tämän kaltainen optimointi on suuresti riippuvainen alkuperäisestä portfoliosta, jonka määrittää yleisesti rahoitusyhtiön myyntistrategia. Yleisesti ottaen pääomavaateen varianssin muutos voi simuloinneissa olla melko suurta, varsinkin jos mukaan huomioidaan rasitus testit, puuttuvat tuotteet sekä muut pääomavaateen laskentaan huomioitavat seikat. Haastatteluissa saatiin selville millainen optimointi voisi olla mahdollista todellisuudessa. Huomattiin myös että tämän kaltainen ajattelumalli on jo huomattu alalla ennestään. Jon Gregory jopa mainitsi, että jotkin rahoitusyhtiöt ovat enemmän kiinnostuneita muutosten pienentämisestä kuin itse pääomavaateen suuruudesta. Näyttääkin siltä, että tämän aihepiiri vaatisi entistä enemmän tutkimusta, sillä sitä ei ennestään vielä ole, ja rahoitusyhtiöt ovat jo alkaneet etsimään uusia keinoja selvitäkseen rahoitusalalla, joka on yhä entisestään kilpailullisempi.

Influence of different sanitizers on food contaminant bacteria: effect of exposure temperature, contact time, and product concentration

The efficiency of four Sanitizers - peracetic acid, chlorhexidine, quaternary ammonium, and organic acids - was tested in this work using different bacteria recognized as a problem to meat industry, Salmonella sp., S. aureus, E. coli and L. monocytogenes. The effects of sanitizer concentration (0.2, 0.5, 0.6, 1.0, 1.1 and 1.4%), at different temperatures (10 and 45 °C) and contact time (2, 10, 15, 18 and 25 minutes) were evaluated. Tests in an industrial plant were also carried out considering previously obtained results. In a general way, peracetic acid presented higher efficiencies using low concentration (0.2%) and contact time (2 minutes) at 10 °C. The tests performed in industrial scale showed that peracetic acid presented a good performance in concentration and contact time lower than that suggested by the suppliers. The use of chlorhexidine and quaternary ammonium led to reasonable results at the indicated conditions, and organic acids were ineffective under concentration and contact time higher than those indicated by the suppliers in relation to Staphylococcus aureus. The results, in general, show that the choice for the most adequate sanitizer depends on the microorganism contaminant, the time available for sanitizer application, and also on the process cost.

Towards a contextual understanding of B2B salespeople's selling competencies – An exploratory study among purchasing decision-makers of internationally-oriented technology firms

ABSTRACT Towards a contextual understanding of B2B salespeople’s selling competencies − an exploratory study among purchasing decision-makers of internationally-oriented technology firms The characteristics of modern selling can be classified as follows: customer retention and loyalty targets, database and knowledge management, customer relationship management, marketing activities, problem solving and system selling, and satisfying needs and creating value. For salespeople to be successful in this environment, they need a wide range of competencies. Salespeople’s selling skills are well documented in seller side literature through quantitative methods, but the knowledge, skills and competencies from the buyer’s perspective are under-researched. The existing research on selling competencies should be broadened and updated through a qualitative research perspective due to the dynamic nature and the contextual dependence of selling competencies. The purpose of the study is to increase understanding of the professional salesperson’s selling competencies from the industrial purchasing decision- makers’ viewpoint within the relationship selling context. In this study, competencies are defined as sales-related knowledge and skills. The scope of the study includes goods, materials and services managed by a company’s purchasing function and used by an organization on a daily basis. The abductive approach and ‘systematic combining’ have been applied as a research strategy. In this research, data were generated through semi- structured, person-to-person interviews and open-ended questions. The study was conducted among purchasing decision-makers in the technology industry in Finland. The branches consisted of the electronics and electro-technical industries and the mechanical engineering and metals industries. A total of 30 companies and one purchasing decision-maker from each company were purposively chosen for the sampling. The sample covers different company sizes based on their revenues, their differing structures – varying from public to family companies –that represent domestic and international ownerships. Before analyzing the data, they were organized by the purchasing orientations of the buyers: the buying, procurement or supply management orientation. Thematic analysis was chosen as the analysis method. After analyzing the data, the results were contrasted with the theory. There was a continuous interaction between the empirical data and the theory. Based on the findings, a total of 19 major knowledge and skills were identified from the buyers’ perspective. The specific knowledge and skills from the viewpoint of customers’ prevalent purchasing orientations were divided into two categories, generic and contextual. The generic knowledge and skills apply to all purchasing orientations, and the contextual knowledge and skills depend on customers’ prevalent purchasing orientations. Generic knowledge and skills relate to price setting, negotiation, communication and interaction skills, while contextual ones relate to knowledge brokering, ability to present solutions and relationship skills. Buying-oriented buyers value salespeople who are ‘action oriented experts, however at a bit of an arm’s length’, procurement buyers value salespeople who are ‘experts deeply dedicated to the customer and fostering the relationship’ and supply management buyers value salespeople who are ‘corporate-oriented experts’. In addition, the buyer’s perceptions on knowledge and selling skills differ from the seller’s ones. The buyer side emphasizes managing the subject matter, consisting of the expertise, understanding the customers’ business and needs, creating a customized solution and creating value, reliability and an ability to build long-term relationships, while the seller side emphasizes communica- tion, interaction and salesmanship skills. The study integrates the selling skills of the current three-component model− technical knowledge, salesmanship skills, interpersonal skills− and relationship skills and purchasing orientations, into a selling competency model. The findings deepen and update the content of these knowledges and skills in the B2B setting and create new insights into them from the buyer’s perspective, and thus the study increases contextual understanding of selling competencies. It generates new knowledge of the salesperson’s competencies for the relationship selling and personal selling and sales management literature. It also adds knowledge of the buying orientations to the buying behavior literature. The findings challenge sales management to perceive salespeople’s selling skills both from a contingency and competence perspective. The study has several managerial implications: it increases understanding of what the critical selling knowledge and skills from the buyer’s point of view are, understanding of how salespeople effectively implement the relationship marketing concept, sales management’s knowledge of how to manage the sales process more effectively and efficiently, and the knowledge of how sales management should develop a salesperson’s selling competencies when managing and developing the sales force. Keywords: selling competencies, knowledge, selling skills, relationship skills, purchasing orientations, B2B selling, abductive approach, technology firms

Foreign exchange exposure management in a fuel procurement company operating in the commodity markets

Fluctuating commodity prices, foreign exchange rates and interest rates are causing changes in cash flows, market value and the companies’ profit. Most of the commodities are quoted in US dollar. Companies with non-dollar accounting face a double risk in the form of the commodity price risk and foreign exchange risk. The objective of this Master’s thesis is to find out how companies under commodity should manage foreign exchange exposure. The theoretical literature is based on foreign exchange risk, commodity risk and foreign exchange exposure management. The empirical research is done by using constructive modelling of a case company in the oil industry. The exposure is model with foreign exchange net cash flow and net working capital. First, the factors affecting foreign exchange exposure in case company are analyzed, then a model of foreign exchange exposure is created. Finally, the models are compared and the most suitable method is defined. According to the literature, foreign exchange exposure is the foreign exchange net cash flow. However, the results of the study show that foreign exchange risk can be managed also with net working capital. When the purchases, sales and storage are under foreign exchange risk, the best way to manage foreign exchange exposure is with combined net cash flow and net working capital method. The foreign exchange risk policy of the company defines the appropriate way to manage foreign exchange risk.