Effect of sildenafil citrate on the cardiovascular system

Sildenafil citrate is a drug commonly used to manage erectile dysfunction. It is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H -pyrazolo[4,3-d]pyrimidin-5-yl)-4 ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate (C22H30N6O4 S). It is a highly selective inhibitor of cyclic guanine monophosphate-specific phosphodiesterase type 5. In late March through mid-November 1998, the US Food and Drug Administration (FDA) published a report on 130 confirmed deaths among men (mean age, 64 years) who received prescriptions for sildenafil citrate, a period during which >6 million outpatient prescriptions (representing about 50 million tablets) were dispensed. The US FDA recently reported that significant cardiovascular events, including sudden cardiac death, have occurred in men with erectile dysfunction who were taking sildenafil citrate. These reports have raised concerns that sildenafil citrate may increase the risk of cardiovascular events, particularly fatal arrhythmias, in patients with cardiovascular disease. In the past few years, the cardiac electrophysiological effects of sildenafil citrate have been investigated extensively in both animal and clinical studies. According to extensive data available to date, sildenafil citrate has been shown to pose minimal cardiovascular risks to healthy people taking this drug. Some precautions are needed for patients with cardiovascular diseases. However, the only absolute contraindication for sildenafil citrate is the concurrent use of nitrates. This article is intended to review sildenafil citrate's cardiovascular effects, as well as current debates about its arrhythmogenic effects.

Engagement of multifocal neural circuits during recall of autobiographical happy events

Happy emotional states have not been extensively explored in functional magnetic resonance imaging studies using autobiographic recall paradigms. We investigated the brain circuitry engaged during induction of happiness by standardized script-driven autobiographical recall in 11 healthy subjects (6 males), aged 32.4 ± 7.2 years, without physical or psychiatric disorders, selected according to their ability to vividly recall personal experiences. Blood oxygen level-dependent (BOLD) changes were recorded during auditory presentation of personal scripts of happiness, neutral content and negative emotional content (irritability). The same uniform structure was used for the cueing narratives of both emotionally salient and neutral conditions, in order to decrease the variability of findings. In the happiness relative to the neutral condition, there was an increased BOLD signal in the left dorsal prefrontal cortex and anterior insula, thalamus bilaterally, left hypothalamus, left anterior cingulate gyrus, and midportions of the left middle temporal gyrus (P < 0.05, corrected for multiple comparisons). Relative to the irritability condition, the happiness condition showed increased activity in the left insula, thalamus and hypothalamus, and in anterior and midportions of the inferior and middle temporal gyri bilaterally (P < 0.05, corrected), varying in size between 13 and 64 voxels. Findings of happiness-related increased activity in prefrontal and subcortical regions extend the results of previous functional imaging studies of autobiographical recall. The BOLD signal changes identified reflect general aspects of emotional processing, emotional control, and the processing of sensory and bodily signals associated with internally generated feelings of happiness. These results reinforce the notion that happiness induction engages a wide network of brain regions.

Purinergic signalling: past, present and future

The discovery of non-adrenergic, non-cholinergic neurotransmission in the gut and bladder in the early 1960's is described as well as the identification of adenosine 5'-triphosphate (ATP) as a transmitter in these nerves in the early 1970's. The concept of purinergic cotransmission was formulated in 1976 and it is now recognized that ATP is a cotransmitter in all nerves in the peripheral and central nervous systems. Two families of receptors to purines were recognized in 1978, P1 (adenosine) receptors and P2 receptors sensitive to ATP and adenosine diphosphate (ADP). Cloning of these receptors in the early 1990's was a turning point in the acceptance of the purinergic signalling hypothesis and there are currently 4 subtypes of P1 receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of G protein-coupled receptors. Both short-term purinergic signalling in neurotransmission, neuromodulation and neurosecretion and long-term (trophic) purinergic signalling of cell proliferation, differentiation, motility, death in development and regeneration are recognized. There is now much known about the mechanisms underlying ATP release and extracellular breakdown by ecto-nucleotidases. The recent emphasis on purinergic neuropathology is discussed, including changes in purinergic cotransmission in development and ageing and in bladder diseases and hypertension. The involvement of neuron-glial cell interactions in various diseases of the central nervous system, including neuropathic pain, trauma and ischemia, neurodegenerative diseases, neuropsychiatric disorders and epilepsy are also considered.

Central actions of glucocorticoids in the control of body fluid homeostasis: Review

The involvement of the hypothalamic-pituitary-adrenal axis in the control of body fluid homeostasis has been extensively investigated in the past few years. In the present study, we reviewed the recent results obtained using different approaches to investigate the effects of glucocorticoids on the mechanisms of oxytocin and vasopressin synthesis and secretion in response to acute and chronic plasma volume and osmolality changes. The data presented here suggest that glucocorticoids are not only involved in the mechanisms underlying the fast release but also in the transcriptional events that lead to decreased synthesis and secretion of these neuropeptides, particularly oxytocin, under diverse experimental conditions of altered fluid volume and tonicity. The endocannabinoid system, through its effects on glutamatergic neurotransmission within the hypothalamus and the nuclear factor κB-mediated transcriptional activity, seems to be also involved in the specific mechanisms by which glucocorticoids exert their central effects on neurohypophyseal hormone synthesis and secretion.

Detection of genetically modified maize events in Brazilian maize-derived food products

The Brazilian government has approved many transgenic maize lines for commercialization and has established a threshold of 1% for food labeling, which underscores need for monitoring programs. Thirty four samples including flours and different types of nacho chips were analyzed by conventional and real-time PCR in 2011 and 2012. The events MON810, Bt11, and TC1507 were detected in most of the samples, and NK603 was present only in the samples analyzed in 2012. The authorized lines GA21, T25, and the unauthorized Bt176 were not detected. All positive samples in the qualitative tests collected in 2011 showed a transgenic content higher than 1%, and none of them was correctly labeled. Regarding the samples collected in 2012, all positive samples were quantified higher than the threshold, and 47.0% were not correctly labeled. The overall results indicated that the major genetically modified organisms detected were MON810, TC1507, Bt11, and NK603 events. Some industries that had failed to label their products in 2011 started labeling them in 2012, demonstrating compliance with the current legislation observing the consumer rights. Although these results are encouraging, it has been clearly demonstrated the need for continuous monitoring programs to ensure consumers that food products are labeled properly.

Nijden terwellisten sanain muoto, 2 Tim. 1:13. Sijnä järjestyxesä kuin d. Lutheruxen Catechismus sen päkappaleisa sisällänspitä, nijden enimmäin catechismuxen selittäitten johdatuxen jälkeen, edeswetänyt ja kokoonpannut yxinkertaisisa kysymyxisä ja wastauxisa. Wuonna 1782. Eric Frosterus v. past. ja cappalainen Haukiputan kappelilla, Iin pitäjäsä

Arkit: A-M8 N6

Enfaldige spörsmåhl, nödige til catechismi förklaring, af the förnämste catecheticis utdragne, och i möjeligaste korthet them ungom och enfaldigom til tienst och nytta författade af L. H. Backmann. Past. Cajanab

Arkit: A-B12 C11.

Nijden terwellisten sanain muoto, 2 Tim. 1:13. Sijnä järjestyxesä kuin d. Lutheruxen Catechismus sen päkappaleisa sisällänspitä, nijden enimmäin catechismuxen selittäitten johdatuxen jälkeen, edeswetänyt ja kokoonpannut yxinkertaisisa kysymyxisä ja wastauxisa. Wuonna 1782. Eric Frosterus v. past. ja cappalainen Haukiputan kappelilla, Iin pitäjäsä

Arkit: A-M8 N6

Enfaldige spörsmåhl, nödige til catechismi förklaring, af the förnämste catecheticis utdragne, och i möjeligaste korthet them ungom och enfaldigom til tienst och nytta författade af L. H. Backmann. Past. Cajanab

Arkit: A-B12 C11.

Increased profitability and efficiency by improving the Meetings & Events Category S2P-process – Case Company

The purpose of this research was to examine the most optimal way to arrange meetings and events management and source to pay –process in a global company. The research is a qualitative multi-method case study and is a commission from a global company. The theoretical framework of this research structures around two approaches. First approach focus on a purchasing strategy and management that shows the current role of procure-ment and introduce different ways to organize purchasing functions. Second approach focus on purchasing process management and improvement methods. Annual spend analyze, external and internal interviews and internal survey were done to gain compre-hensive knowledge about the current state of operations and possible solutions. Gathered data were then combined to theoretical framework in order to create optimal solution for the case company. Based on the research a source to pay –process and global policy for meeting and event category was created. The solution includes all relevant matters that are needed in order to secure efficient and profitable operations. The results show that optimal way to arrange meetings and events structures around standardized source to pay –processes, central-ized procurement, preferred supplier and clearly defined roles and responsibilities be-tween different stakeholders.

The tree we heard fall : analyzing the societal processes following focusing events

Fokuserande händelser är plötsliga, ovanliga och för med sig negativa konsekvenser för ett stort antal människor. Det handlar om det vi i vardagligt tal kallar kriser och katastrofer. En intensiv medierapportering i kombination med oroade medborgare gör att kriser och katastrofer är viktiga samhällspåfrestningar som beslutsfattare måste hantera. Syftet med avhandlingen är att öka förståelsen för hur fokuserande händelser påverkar samhälleliga processer. Avhandlingens två övergripande forskningsfrågor tar fasta på jämförelsen av olika typer av fokuserande händelser. För det första, skillnader i hur naturkatastrofer och katastrofer som tillkommit genom mänskligt handlade påverkar samhället, och för det andra, hur händelser med olika stark fokuseringskraft påverkar samhället. Medborgarreaktioner studeras i en experimentell laboratoriestudie, den mediala rapporteringen analyseras genom kvantitativ innehållsanalys av texter och bilder, och på den parlamentariska arenan analyseras riksdagsdebatten genom kvantitativ innehållsanalys. De temaområden som identifieras i den teoretiska referensramen ligger till grund för analysen och tar fasta på de känslor som händelsen ger upphov till, hur händelsen kontextualiseras (framing), skuldbeläggning samt möjliga lösningar som förs fram. Resultatet från studierna visar att skillnader mellan olika typer av händelser syns tydligast hos medborgare, uttryckt genom starkare emotionella reaktioner för händelser med stark fokusering, och på den mediala arenan, genom mer utrymme för dessa händelser. Då kriser och katastrofer med olika stark fokuseringskraft når riksdagen får de däremot ett relativt likadant mottagande. I jämförelsen mellan naturkatastrofer och människoskapade händelser visar resultaten att naturkatastrofer ofta diskuteras som specifika händelser, medan människoskapade händelser placeras i en bredare samhällelig kontext och diskuteras under längre tid. Avhandlingen bidrar till diskussionen om hur våra känslor och vår kognition samspelar i krissituationer. De omedvetna signaler som vår kropp ger oss gällande hur vi ska reagera på en farlig situation kan påverka om vi är rädda, oroliga eller till och med positivt inställda. I ljuset av de tre studierna är det tydligt att de emotionella reaktionerna minskar ju högre upp i den politiska processen vi kommer. Trots att medborgare och medier reagerar starkt är de emotionella reaktionerna på den politiska arenan relativt milda och skuldbeläggningen näst intill icke-existerande.

Perceived modifiability of self-blame attributions for negative life events : implications for well-being /

Research suggests that self-blame attributions are important in the process of adjustment to negative life events. Much of the research originates from JanofTBulman's (1979) theory regarding behavioural and characterological self-blame. She argued that attributing negative events to one's behaviour is adaptive because behavioural self-blame involves attributions to a modifiable source, which implies that a similar event can be avoided in the future. In contrast, attributing negative events to one's character is believed to be maladaptive because character is seen as relatively stable and unmodifiable. Unfortunately, the empirical literature does not show consistent relations between these two types of self-blame attributions and well-being as predicted by Janoff-Bulman. For this thesis, I proposed that one reason for this inconsistency is that Janoff-Bulman's assumption about the perceived modifiability of behavioural versus characterological causes is incorrect — people often dlo perceive character (as well as behaviour) to be modifiable. Sixty-two participants completed a questionnaire regarding a recent negative life event and its impact on their well-being. Consistent with my argument, I found that both behavioural and characterological self-blame attributions following a negative life event were seen as modifiable. As hypothesized, perceived modifiability of causes v^as related to well-being. For example, overall modifiability was related to greater coping efficacy, less social dysfunction, less severe depression, and greater positive affect; however. contrary to predictions, the relation between perceived modifiability of causes and wellbeing was not mediated by the perception that similar events could be avoided in the future. Individual differences in attributional style were also assessed in this study. An attributional style that tended to be more internal, stable, and specific was related to wellbeing as expected; however, neither the perceived modifiability of blame attributions nor the perceived avoidability of similar future events mediated this relation. Implications for professionals dealing with trauma victims and potential directions for future research are discussed.

The micromorphology of Paleoseismic soft sediment deformation structures in glacial deposits from three sample sites in Scotland /

The nature of this research is to investigate paleoseismic deformation of glacial soft sediments from three sampling sites throughout the Scottish Highlands; Arrat's Mills, Meikleour and Glen Roy. The paleoseismic evidence investigated in this research will provide a basis for applying criteria to soft sediment deformation structures, and the trigger mechanisms that create these structures. Micromorphology is the tool used in this to investigate paleoseismic deformation structures in thin section. Thin section analysis, (micromorphology) of glacial sediments from the three sampling sites is used to determine microscale evidence of past earthquakes that can be correlated to modem-day events and possibly lead to a better understanding of the impact of earthquakes throughout a range of sediment types. The significance of the three sampling locations is their proximity to two major active fault zones that cross Scotland. The fault zones are the Highland Boundary Fault and the Great Glen Fault, these two major faults that parallel each other and divide the country in half Sims (1975) used a set of seven criteria that identified soft sediment deformation structures created by a magnitude six earthquake in Cahfomia. Using criteria set forth by Sims (1975), the paleoseismic evidence can be correlated to the magnitude of the deformation structures found in the glacial sediments. This research determined that the microstructures at Arrat's Mill, Meikleour and Glen Roy are consistent with a seismically induced origin. It has also been demonstrated that, even without the presence of macrostructures, the use of micromorphology techniques in detecting such activity within sediments is of immense value.