The photodynamic and non-photodynamic actions of porphyrins

Porphyrias are a family of inherited diseases, each associated with a partial defect in one of the enzymes of the heme biosynthetic pathway. In six of the eight porphyrias described, the main clinical manifestation is skin photosensitivity brought about by the action of light on porphyrins, which are deposited in the upper epidermal layer of the skin. Porphyrins absorb light energy intensively in the UV region, and to a lesser extent in the long visible bands, resulting in transitions to excited electronic states. The excited porphyrin may react directly with biological structures (type I reactions) or with molecular oxygen, generating excited singlet oxygen (type II reactions). Besides this well-known photodynamic action of porphyrins, a novel light-independent effect of porphyrins has been described. Irradiation of enzymes in the presence of porphyrins mainly induces type I reactions, although type II reactions could also occur, further increasing the direct non-photodynamic effect of porphyrins on proteins and macromolecules. Conformational changes of protein structure are induced by porphyrins in the dark or under UV light, resulting in reduced enzyme activity and increased proteolytic susceptibility. The effect of porphyrins depends not only on their physico-chemical properties but also on the specific site on the protein on which they act. Porphyrin action alters the functionality of the enzymes of the heme biosynthetic pathway exacerbating the metabolic deficiencies in porphyrias. Light energy absorption by porphyrins results in the generation of oxygen reactive species, overcoming the protective cellular mechanisms and leading to molecular, cell and tissue damage, thus amplifying the porphyric picture.

Bi-directional actions of estrogen on the renin-angiotensin system

Estrogen stimulates the renin-angiotensin system by augmenting both tissue and circulating levels of angiotensinogen and renin. We show, however, that angiotensin converting enzyme (ACE) activity in the circulation and in tissues is reduced in two animal models of postmenopausal chronic hormone replacement. We observed a reduction of ACE activity in association with a significant increase in plasma angiotensin I (Ang I) and hyperreninemia in ovariectomized monkeys treated with Premarin (conjugated equine estrogen) replacement for 30 months. Plasma angiotensin II (Ang II) levels were not increased in monkeys treated with estrogen, suggesting that the decrease in ACE curtailed the formation of the peptide. The Ang II/Ang I ratio, an in vivo index of ACE activity, was significantly reduced by estrogen treatment, further supporting the biochemical significance of estrogen's inhibition of ACE. In ovariectomized transgenic hypertensive (mRen2)27 rats submitted to estrogen replacement treatment for 3 weeks, ACE activity in plasma and tissue (aorta and kidney) and circulating Ang II levels were reduced, whereas circulating levels of angiotensin-(1-7) (Ang-(1-7) were increased. Ang-(1-7), the N-terminal fragment of Ang II, is a novel vasodilator and antihypertensive peptide. Thus, the net balance of these effects of estrogen on the renin-angiotensin vasoconstrictor/vasodilator system is to promote the antihypertensive effect.

Reference values for lung function tests: I. Static volumes

Static lung volume (LV) measurements have a number of clinical and research applications; however, no previous studies have provided reference values for such tests using a healthy sample of the adult Brazilian population. With this as our main purpose, we prospectively evaluated 100 non-smoking subjects (50 males and 50 females), 20 to 80 years old, randomly selected from more than 8,000 individuals. Gender-specific linear prediction equations were developed by multiple regression analysis with total lung capacity (TLC), functional residual capacity (FRC), residual volume (RV), RV/TLC ratio and inspiratory capacity (IC) as dependent variables, and with age, height, weight, lean body mass and indexes of physical fitness as independent ones. Simpler demographic and anthropometric variables were as useful as more complex measurements in predicting LV values, independent of gender and age (R2 values ranging from 0.49 to 0.78, P<0.001). Interestingly, prediction equations from North American and European studies overestimated the LV at low volumes and underestimated them at high volumes (P<0.05). Our results, therefore, provide a more appropriate frame of reference to evaluate the normalcy of static lung volume values in Brazilian males and females aged 20 to 80 years.

Reference values for lung function tests: II. Maximal respiratory pressures and voluntary ventilation

The strength of the respiratory muscles can be evaluated from static measurements (maximal inspiratory and expiratory pressures, MIP and MEP) or inferred from dynamic maneuvers (maximal voluntary ventilation, MVV). Although these data could be suitable for a number of clinical and research applications, no previous studies have provided reference values for such tests using a healthy, randomly selected sample of the adult Brazilian population. With this main purpose, we prospectively evaluated 100 non-smoking subjects (50 males and 50 females), 20 to 80 years old, selected from more than 8,000 individuals. Gender-specific linear prediction equations for MIP, MEP and MVV were developed by multiple regression analysis: age and, secondarily, anthropometric measurements explained up to 56% of the variability of the dependent variables. The most cited previous studies using either Caucasian or non-Caucasian samples systematically underestimated the observed values of MIP (P<0.05). Interestingly, the self-reported level of regular physical activity and maximum aerobic power correlates strongly with both respiratory and peripheral muscular strength (knee extensor peak torque) (P<0.01). Our results, therefore, provide a new frame of reference to evaluate the normalcy of some useful indexes of respiratory muscle strength in Brazilian males and females aged 20 to 80.

Reference values for lung function tests: III. Carbon monoxide diffusing capacity (transfer factor)

Carbon monoxide diffusing capacity (DLCO) or transfer factor (TLCO) is a particularly useful test of the appropriateness of gas exchange across the lung alveolocapillary membrane. With the purpose of establishing predictive equations for DLCO using a non-smoking sample of the adult Brazilian population, we prospectively evaluated 100 subjects (50 males and 50 females aged 20 to 80 years), randomly selected from more than 8,000 individuals. Gender-specific linear prediction equations were developed by multiple regression analysis with single breath (SB) absolute and volume-corrected (VA) DLCO values as dependent variables. In the prediction equations, age (years) and height (cm) had opposite effects on DLCOSB (ml min-1 mmHg-1), independent of gender (-0.13 (age) + 0.32 (height) - 13.07 in males and -0.075 (age) + 0.18 (height) + 0.20 in females). On the other hand, height had a positive effect on DLCOSB but a negative one on DLCOSB/VA (P<0.01). We found that the predictive values from the most cited studies using predominantly Caucasian samples were significantly different from the actually measured values (P<0.05). Furthermore, oxygen uptake at maximal exercise (VO2max) correlated highly to DLCOSB (R = 0.71, P<0.001); this variable, however, did not maintain an independent role to explain the VO2max variability in the multiple regression analysis (P>0.05). Our results therefore provide an original frame of reference for either DLCOSB or DLCOSB/VA in Brazilian males and females aged 20 to 80 years, obtained from the standardized single-breath technique.

Relationship between the actions of atrial natriuretic peptide (ANP), guanylin and uroguanylin on the isolated kidney

Guanylin and uroguanylin are peptides that bind to and activate guanylate cyclase C and control salt and water transport in many epithelia in vertebrates, mimicking the action of several heat-stable bacteria enterotoxins. In the kidney, both of them have well-documented natriuretic and kaliuretic effects. Since atrial natriuretic peptide (ANP) also has a natriuretic effect mediated by cGMP, experiments were designed in the isolated perfused rat kidney to identify possible synergisms between ANP, guanylin and uroguanylin. Inulin was added to the perfusate and glomerular filtration rate (GFR) was determined at 10-min intervals. Sodium was also determined. Electrolyte dynamics were measured by the clearance formula. Guanylin (0.5 µg/ml, N = 12) or uroguanylin (0.5 µg/ml, N = 9) was added to the system after 30 min of perfusion with ANP (0.1 ng/ml). The data were compared at 30-min intervals to a control (N = 12) perfused with modified Krebs-Hanseleit solution and to experiments using guanylin and uroguanylin at the same dose (0.5 µg/ml). After previous introduction of ANP in the system, guanylin promoted a reduction in fractional sodium transport (%TNa+, P<0.05) (from 78.46 ± 0.86 to 64.62 ± 1.92, 120 min). In contrast, ANP blocked uroguanylin-induced increase in urine flow (from 0.21 ± 0.01 to 0.15 ± 0.007 ml g-1 min-1, 120 min, P<0.05) and the reduction in fractional sodium transport (from 72.04 ± 0.86 to 85.19 ± 1.48, %TNa+, at 120 min of perfusion, P<0.05). Thus, the synergism between ANP + guanylin and the antagonism between ANP + uroguanylin indicate the existence of different subtypes of receptors mediating the renal actions of guanylins.

Binding sites and actions of Tx1, a neurotoxin from the venom of the spider Phoneutria nigriventer, in guinea pig ileum

Tx1, a neurotoxin isolated from the venom of the South American spider Phoneutria nigriventer, produces tail elevation, behavioral excitation and spastic paralysis of the hind limbs after intracerebroventricular injection in mice. Since Tx1 contracts isolated guinea pig ileum, we have investigated the effect of this toxin on acetylcholine release, as well as its binding to myenteric plexus-longitudinal muscle membranes from the guinea pig ileum. [125I]-Tx1 binds specifically and with high affinity (Kd = 0.36 ± 0.02 nM) to a single, non-interacting (nH = 1.1), low capacity (Bmax 1.1 pmol/mg protein) binding site. In competition experiments using several compounds (including ion channel ligands), only PhTx2 and PhTx3 competed with [125I]-Tx1 for specific binding sites (K0.5 apparent = 7.50 x 10-4 g/l and 1.85 x 10-5 g/l, respectively). PhTx2 and PhTx3, fractions from P. nigriventer venom, contain toxins acting on sodium and calcium channels, respectively. However, the neurotoxin PhTx2-6, one of the isoforms found in the PhTx2 pool, did not affect [125I]-Tx1 binding. Tx1 reduced the [3H]-ACh release evoked by the PhTx2 pool by 33%, but did not affect basal or KCl-induced [3H]-ACh release. Based on these results, as well as on the homology of Tx1 with toxins acting on calcium channels (w-Aga IA and IB) and its competition with [125I]-w-Cono GVIA in the central nervous system, we suggest that the target site for Tx1 may be calcium channels.

Vahinkoeläinsodasta psykologiseen omistajuuteen. Petokonfliktien historiallinen tausta ja nykypäivän hallinta

Suurpetojen kannanhoitoon, ja etenkin suden kannanhoitoon liittyvä monitahoinen konfl ikti esiintyy jännitteinä paikallisyhteisöjen ja keskushallinnon, maaseudun ja kaupunkien sekä maallikoiden ja tutkijoiden välillä. Suurpetopolitiikan legitimiteettikriisi näkyy kansallisen kannanhoidon tavoitteiden ja toimenpiteiden kiistämisenä passiivisin ja aktiivisin toimin. Tällä ajankohtaisella ongelmalla on mittavat historialliset juuret. Luonnon ja ihmisen välinen suhde on ollut jatkuvaa tasapainottelua konfl iktien ja niiden hallinnan kanssa, ja suurpedot ovat väistämättä olleet konfl iktin keskiössä lajityypillisten piirteidensä vuoksi. Tämän tutkimuksen tavoitteena on osoittaa ympäristöhistoriallisen tutkimusotteen kautta suomalaisen vahinkoeläinhistorian keskeiset toimet ja toimijat, sekä ymmärtää vahinkoeläinten kannanhoidon tavoite- ja toimenpideasettelun vaikutukset eläinpopulaatioihin historiallisessa ja ekologisessa kontekstissa. Tutkimuksen toinen tavoite on tuottaa synteesi nykypäivän suurpetojen kannanhoidon tavoite- ja toimenpiteiden tarkoituksenmukaisuudesta ja vaikuttavuudesta historiallisessa kontekstissa ja esittää uudenlainen lähestymismalli sosiaalisesti kestävämmälle suurpetopolitiikalle. Vahinkoeläinhistoriaa käsitellään deduktiivisella ja rekonstruktiivisella tutkimusotteella käyttäen aineistona lakitekstejä, maksettuja tapporahoja, sanomalehtikirjoituksia, sidosryhmien kirjoituksia sekä eläintieteellisiä julkaisuja. Etenkin laeissa ja asetuksissa eri eläimistä asetetut tapporahat ja toisaalta saalistilastojen perusteella maksetut palkkiot on nostettu tässä tutkimuksessa merkittävään rooliin asenteiden tulkinnan välineenä. Tarkastelu ulotetaan nisäkkäiden lisäksi myös lintuihin, jotka ovat edellä mainitun aineiston valossa olleet merkittävä vainottu eläinryhmä. Nykypäivän petokonfl iktin tarkastelussa keskiöön nostetaan suurpetoasenteet, niiden muodostuminen ja vaikutus suurpetopolitiikan tavoitteiden ja toimenpiteiden kiistämisessä. Suurpetopolitiikan legitimiteettikriisiä tarkastellaan paikallisten uhmakkuutena hallintoa kohtaan ja tulkinta keinoista puuttua sosiopoliittiseen rikokseen rakennetaan tätä ajatusta vasten. Suurpetojen salakaatajat toimivat yhteisönsä puolesta ja saavat tukensa toimilleen yhteisöltään. Sosiopoliittinen rikos ei siten ole ainoastaan salakaatajien vaan sen sijaan yhteisön yhteinen. Salakaatajat ja paikallisyhteisö pyrkivät häivyttämään yhteiskunnassa viranomaisten ja sidosryhmien taholta toimintaan liittämää stigmaa ja siten oikeuttamaan tekonsa vallitsevissa olosuhteissa. Arvoristiriitoihin perustuvat konfl iktit ovat haasteellisia hallita ja lähtökohtana on oltava ymmärrys siitä, että etenkin suteen liittyvät jännitteet ja ristiriidat ihmisten välisissä suhteissa ovat väistämättömiä. Tunnistamalla historiallisen aineiston merkittävyys nykypäivän ongelmakeskeisen kannanhoidon ratkaisun tietopohjana on mahdollista rakentaa sosiaalisesti kestävämpää suurpetojen kannanhoitoa. Tässä väitöskirjatyössä painotetaan suurpetoihin liittyen ajatusta, jonka mukaan paikallisilta suurpetoalueilla eläviltä ihmisiltä tai sidosryhmien edustajilta ei edellytetä arvomaailman muuttumista, vaan hyväksytään heidän käsityksensä suurpetojen roolista vahingontekijöinä. Sen sijaan vahvistetaan suurpetojen välineellistä roolia paikallisyhteisöjen resurssina ja oleellisten sidosryhmien roolia yhteisön toimijoina psykologisen omistajuuden rakentamisen kautta. Suurpetojen kestävä kannanhoito vaatii siten riistahallinnon toimintakulttuurin muutosta ja uudenlaista suhdetta yhteiskunnan eri toimijoihin.

Actions of Crotalus durissus terrificus venom and crotoxin on the isolated rat kidney

Many studies have reported the occurrence of lethal acute renal failure after snakebites. The aim of the present investigation was to determine alterations in renal function produced by Crotalus durissus terrificus venom and crotoxin as well as the histological alterations induced by these venoms. Isolated kidneys from Wistar rats weighing 240 to 280 g were perfused with Krebs-Henseleit solution containing 6 g% of previously dialyzed bovine serum albumin. The effects of Crotalus durissus terrificus venom and crotoxin were studied on glomerular filtration rate (GFR), urinary flow (UF), perfusion pressure (PP) and percentage sodium tubular transport (%TNa+). The infusion of Crotalus durissus terrificus venom (10 µg/ml) and crotoxin (10 µg/ml) increased GFR (control80 = 0.78 ± 0.07, venom80 = 1.1 ± 0.07, crotoxin80 = 2.0 ± 0.05 ml g-1 min-1, P<0.05) and UF (control80 = 0.20 ± 0.02, venom80 = 0.32 ± 0.03, crotoxin80 = 0.70 ± 0.05 ml g-1 min-1, P<0.05), and decreased %TNa+ (control100 = 75.0 ± 2.3, venom100 = 62.9 ± 1.0, crotoxin80 = 69.0 ± 1.0 ml g-1 min-1, P<0.05). The infusion of crude venom tended to reduce PP, although the effect was not significant, whereas with crotoxin PP remained stable during the 100 min of perfusion. The kidneys perfused with crude venom and crotoxin showed abundant protein material in the urinary space and tubules. We conclude that Crotalus durissus terrificus venom and crotoxin, its major component, cause acute nephrotoxicity in the isolated rat kidney. The current experiments demonstrate a direct effect of venom and crotoxin on the perfused isolated kidney.

Evaluation of the cholinomimetic actions of trimethylsulfonium, a compound present in the midgut gland of the sea hare Aplysia brasiliana (Gastropoda, Opisthobranchia)

Trimethylsulfonium, a compound present in the midgut gland of the sea hare Aplysia brasiliana, negatively modulates vagal response, indicating a probable ability to inhibit cholinergic responses. In the present study, the pharmacological profile of trimethylsulfonium was characterized on muscarinic and nicotinic acetylcholine receptors. In rat jejunum the contractile response induced by trimethylsulfonium (pD2 = 2.46 ± 0.12 and maximal response = 2.14 ± 0.32 g) was not antagonized competitively by atropine. The maximal response (Emax) to trimethylsulfonium was diminished in the presence of increasing doses of atropine (P<0.05), suggesting that trimethylsulfonium-induced contraction was not related to muscarinic stimulation, but might be caused by acetylcholine release due to presynaptic stimulation. Trimethylsulfonium displaced [³H]-quinuclidinyl benzilate from rat cortex membranes with a low affinity (Ki = 0.5 mM). Furthermore, it caused contraction of frog rectus abdominis muscles (pD2 = 2.70 ± 0.06 and Emax = 4.16 ± 0.9 g), which was competitively antagonized by d-tubocurarine (1, 3 or 10 µM) with a pA2 of 5.79, suggesting a positive interaction with nicotinic receptors. In fact, trimethylsulfonium displaced [³H]-nicotine from rat diaphragm muscle membranes with a Ki of 27.1 µM. These results suggest that trimethylsulfonium acts as an agonist on nicotinic receptors, and thus contracts frog skeletal rectus abdominis muscle and rat jejunum smooth muscle via stimulation of postjunctional and neuronal prejunctional nicotinic cholinoreceptors, respectively.

Developmental norms for the Gardner Steadiness Test and the Purdue Pegboard: a study with children of a metropolitan school in Brazil

Norms for the Gardner Steadiness Test and the Purdue Pegboard were developed for the neuropsychological assessment of children in the metropolitan area of Rio de Janeiro. A computer-generated unbiased sample of 346 children with a mean age of 9.4 years (SD = 2.76), who were attending a large normal public school in this urban area, was the subject of this study. Two boys were removed from the study, one for refusing to participate and the other due to severe strabismus. Therefore, the final sample contained 344 children (173 boys and 171 girls). Sex and age of the child and hand preferred for writing, but not ethnic membership or social class, had significant effects on performance in the Gardner Steadiness Test and the Purdue Pegboard. Girls outperformed boys. Older children performed better than younger children. However, the predictive relationship between age of the child and neuropsychological performance included linear and curvilinear components. Comparison of the present results to data gathered in the United States revealed that the performance of this group of Brazilian children is equivalent to that of US children after Bonferroni's correction of the alpha level of significance. It is concluded that sex and age of the child and hand preferred for writing should be taken into account when using the normative data for the two instruments evaluated in the present study. Furthermore, the relevance of neurobehavioral antidotes for the obliteration of some of the probable neuropsychological effects of cultural deprivation in Brazilian public school children is hypothesized.

Kallet til livets embete : mødre i helse og lidelse

Mothers represent the natural caring. Natural caring is the object of caring science and of research interest because it establishes the central core of professional caring. In this study, we encounter patients who are mothers in need of care in a psychiatric context. Motherhood involves taking responsibility that extends beyond one's own life, because the child represents possibilities in a yet unknown future. Understanding and knowledge about the mothers' struggle in health and suffering are of crucial importance to enable clinical practice to make provisions for and adapt to the individual patient. The overall purpose of this dissertation is to illuminate how the innermost essence of caring emerges in health and suffering in patients who are mothers in psychiatric care. The purpose of the study in a clinical sense is to seek to understand and illuminate the patient's inner world in health and suffering in terms of contextual, existential, ontological and ethical dimensions. The dissertation is exploratory and descriptive in nature and encompasses induction, deduction and abduction as logics tools of reasoning. A theoretical model of natural caring and a universal theoretical model of the innermost essence of caring is developed as seen from the patient's world in a psychiatric context. The dissertation is anchored in human science's view of the human being and the world and in caring science's perspective. Caring science's view of the human being as a unity comprising body, soul and spirit is central in the study's concept of the patient. This multi-dimensional conception of the human being encompasses the dissertation's basic values and is decisive for choice of methodology. Hermeneutic epistemology guided the interpretation of the empirical data, the paradigmatic theses and assumptions. The dialectical movement in interpretation moves back and forth between empirical data, caring science theory and philosophical theory and reveals deeper insight into meaningful content in the clinical context. The interpretation process comprises four levels of abstraction: rational, contextual, existential and ontological. Hermeneutic philosophy guides the inductive and deductive approach to interpretation, as well as the movement between the clinical context and the caring science paradigm. In this encounter between the visible and invisible reality, the image of natural caring – motherliness emerged. The dissertation consists of four studies. The first study is a systematic review of nineteen research articles. The three other studies are hermeneutical interpretations based on text materials from open interviews. Fifteen participants were interviewed, all of whom are mothers of children between 0 and 18 years of age. All were outpatients in the psychiatric specialist health service. In the interpretation process, the mothers' struggle in health and suffering emerges as a struggle between the inner and outer world. Being a mother and patient in health and suffering in a psychiatric context means to struggle to be oneself, to create oneself, to live and realize one's good deeds as a mother and human being. To be oneself, to possess oneself as a mother is not only a question of tending, playing and learning in order to master a practical situation or to survive. It involves constituting a deep, inner desire to courageously create oneself so that the child is able to realize his or her potential in health and suffering. Motherliness manifests itself in caring as a call to ministering humanity and life. The voice of motherliness is understood as the voice of life—the eternal, inner call of love and freedom. The inner call craves fulfilment. Motherliness in natural caring does not retreat. Motherliness defines the Other as freedom and proceeds without regard for all other exterior requirements to realizing wellbeing. The inner essence of caring is attentive, aware and heeds the call of the heart. The innermost essence of caring is to be and to make oneself responsible for the Other. Responsibility cannot be relinquished; free choice consists in whether or not to follow the call. To renounce the inner call to responsibility is to deny oneself and one's dignity as a human being. The theoretical models provide clinical and systematic caring science with knowledge and understanding based on the natural caring spirit inherent in the human being. The study elucidates and strengthens the ontological basic assumptions about the human being as a unity of body, soul and spirit, the sanctity of the human being and the core of caring, ethos. The results of the dissertation will provide clinical practice with knowledge about the inner movements of the mothers' souls in relation to their responsibility as mothers and human beings. Being able to understand the basic conditions for responsibility is crucial for developing care that encompasses mother and child and the mutual relationship between them. This is basic knowledge for developing attitudes and actions that meet and provide for the needs of the patient as mother and as a whole, suffering human being.

High concentrations of KCl release noradrenaline from noradrenergic neurons in the rat anococcygeus muscle

The aim of the present study was to investigate the effects of high concentrations of KCl in releasing noradrenaline from sympathetic nerves and its actions on postsynaptic alpha-adrenoceptors. We measured the isotonic contractions induced by KCl in the isolated rat anococcygeus muscle under different experimental conditions. The contractile responses induced by KCl were inhibited by alpha-adrenoceptor antagonists in 2.5 mM Ca2+ solution. Prazosin reduced the maximum effect from 100 to 53.9 ± 10.2% (P<0.05) while the pD2 values were not changed. The contractile responses induced by KCl were abolished by prazosin in Ca2+-free solution (P<0.05). Treatment of the rats with reserpine reduced the maximum effect induced by KCl as compared to the contractile responses induced by acetylcholine from 339.5 ± 157.8 to 167.3 ± 65.5% (P<0.05), and increased the pD2 from 1.57 ± 0.01 to 1.65 ± 0.006 (P<0.05), but abolished the inhibitory effect of prazosin (P<0.05). In contrast, L-NAME increased the contractile responses induced by 120 mM KCl by 6.2 ± 2.3% (P<0.05), indicating that KCl could stimulate the neurons that release nitric oxide, an inhibitory component of the contractile response induced by KCl. Our results indicate that high concentrations of KCl induce the release of noradrenaline from noradrenergic neurons, which interacts with alpha1-adrenoceptors in smooth muscle cells, producing a contractile response in 2.5 mM Ca2+ (100%) and in Ca2+-free solution, part of which is due to a direct effect of KCl on the rat anococcygeus muscle.

Consumer online communication of corporate social responsibility in the sin industry context: Cases in the global online gambling industry.

So-called sin industries are often related to harmfulness, unethical business, and unproductiveness. Nowadays, the alcohol, gambling, and tobacco industries are most often considered to be part of sin industries, which is also the context of this study. However, the definition of a sin industry is always related to time and culture. Despite the controversies of sin industries, there are studies that have shown that corporate social responsibility (CSR) engagement is even more important for sin industries than for normal industries and that CSR has a positive effect on firm value in sin industries. With CSR this study refers to an ideology where company takes mostly voluntary actions towards various groups of stakeholders and the environment. In other words, the company goes beyond the legal norms and regulations. In particular, the purpose of this thesis is to find out how companies, operating in the online gambling industry, communicate about their CSR actions to consumers at their web pages. The online environment is essential for this study as online gambling environment is a source of many controversies in comparison to the traditional gambling halls and casinos. These include, for example, greater accessibility, anonymity, and availability of the service. This study uses qualitative textual analysis as its approach, more precisely the discourse analysis. In addition, as this study focuses on large international companies and their actions, also case study approach will be presented. The cases studied are Mybet, Unibet, and Bwin.Party. In order to study the subject, elements from discourse analysis are combined with insights of essential CSR theories, and the specific characteristics of the online gambling industry. As a background for the framework, this study uses the framework of Du & Vieira (2012). After analyzing the discourses of CSR communication and CSR practices, it seems that all of the case companies still do not use all the potential that the online environment provides in terms of CSR or stakeholder communication. There are large differences between different communication tools used at different web pages (gambling pages vs. corporation pages) and between the firms’ CSR profiles. Moreover, there are large differences in the CSR practices used in the web pages of the case companies. The findings of this study are partially alarming as the case companies represent the largest companies in the industry. There are major varieties between the companies’ CSR communication and clear shortcomings in some parts of the online communication. Moreover, the trust of the consumer was broken in some places. If this is the standard that the biggest players in the industry have set with regards to CSR communication, it is probable that the smaller players are performing even worse. Moreover, the regulators are most likely concentrating on the larger companies, so the smaller companies might have fewer incentives and pressure to perform according to the regulations or exceeding the legislation. The conclusions of this thesis provide insights to managers, regulators, and scholars. Suggestions for future studies are provided as well.

Effect of cyproterone acetate on alpha1-adrenoceptor subtypes in rat vas deferens

Gonadal hormones regulate the expression of alpha1-adrenoceptor subtypes in several tissues. The present study was carried out to determine whether or not cyproterone acetate, an anti-androgenic agent, regulates the alpha1-adrenoceptor subtypes that mediate contractions of the rat vas deferens in response to noradrenaline. The actions of subtype selective alpha1-antagonists were investigated in vas deferens from control and cyproterone acetate-treated rats (10 mg/day, sc, for 7 days). Prazosin (pA2 ~9.5), phentolamine (pA2 ~8.3) and yohimbine (pA2 ~6.7) presented competitive antagonism consistent with activation of alpha1-adrenoceptors in vas deferens from both control and treated rats. The pA2 values estimated for WB 4101 (~9.5), benoxathian (~9.7), 5-methylurapidil (~8.5), indoramin (~8.7) and BMY 7378 (~6.8) indicate that alpha1A-adrenoceptors are involved in the contractions of the vas deferens from control and cyproterone acetate-treated rats. Treatment of the vas deferens from control rats with the alpha1B/alpha1D-adrenoceptor alkylating agent chloroethylclonidine had no effect on noradrenaline contractions, supporting the involvement of the alpha1A-subtype. However, this agent partially inhibited the contractions of vas deferens from cyproterone acetate-treated rats, suggesting involvement of multiple receptor subtypes. To further investigate this, the actions of WB 4101 and chloroethylclonidine were reevaluated in the vas deferens from rats treated with cyproterone acetate for 14 days. In these organs WB 4101 presented complex antagonism characterized by a Schild plot with a slope different from unity (0.65 ± 0.05). After treatment with chloroethylclonidine, the complex antagonism presented by WB 4101 was converted into classical competitive antagonism, consistent with participation of alpha1A-adrenoceptors as well as alpha1B-adrenoceptors. These results suggest that cyproterone acetate induces plasticity in the alpha1-adrenoceptor subtypes involved in the contractions of the vas deferens.