Melatonin inhibits LPS-induced NO production in rat endothelial cells

Endothelial cells produce NO by activation of constitutive nitric oxide synthase (NOS) and transcription of inducible NOS (iNOS). We have previously shown that melatonin, in the nanomolar range, inhibits activation of constitutive NOS, and in the present paper, we evaluated whether it could interfere with the expression of iNOS, which is activated by lipopolysaccharide (LPS), a major component of gram-negative bacteria cell walls. Primary cultures of rat endothelial cells were loaded with fluorescent probe for NO detection. Nuclear factor kappa B (NF-kappa B) translocation in endothelial cells elicited by LPS was measured by electromobility shift assay, and the vasodilation of aortic rings was accessed by recording isometric contraction. Melatonin in a micromolar but not in a nanomolar range inhibits the NO production induced by LPS. This effect is not dependent on the activation of G protein-coupled melatonin receptors. The nuclear NF-kappa B translocation is a process necessary for iNOS transcription, and melatonin also inhibits its translocation. LPS induced vasodilation only in endothelium-intact aortic rings, and melatonin (10 mu m) inhibits the vasodilation. Here, we show that concentrations compatible with nocturnal melatonin surge (nm) did not interfere with the activity of iNOS. Considering that micromolar melatonin concentrations could be locally achieved through production by activated immune competent cells, extra-pineal melatonin could have a protective effect against tissue injury. We propose that melatonin blocked the LPS-induced vasodilation by inhibiting the NF-kappa B pathway. Finally, we propose that the effect of melatonin on vascular reactivity is one of the mechanisms that underlies the protective effect of this indolamine against LPS.

TLR4 and CD14 receptors expressed in rat pineal gland trigger NFKB pathway

Nuclear factor-kappa B (NFKB), a pivotal player in inflammatory responses, is constitutively expressed in the pineal gland. Corticosterone inhibits pineal NFKB leading to an enhancement of melatonin production, while tumor necrosis factor (TNF) leads to inhibition of Aa-nat transcription and the production of N-acetylserotonin in cultured glands. The reduction in nocturnal melatonin surge favors the mounting of the inflammatory response. Despite these data, there is no clear evidence of the ability of the pineal gland to recognize molecules that signal infection. This study investigated whether the rat pineal gland expresses receptors for lipopolysaccharide (LPS), the endotoxin from the membranes of Gram-negative bacteria, and to establish the mechanism of action of LPS. Here, we show that pineal glands possess both CD14 and toll-like receptor 4 (TLR4), membrane proteins that bind LPS and trigger the NFKB pathway. LPS induced the nuclear translocation of p50/p50 and p50/RELA dimers and the synthesis of TNF. The maximal expression of TNF in cultured glands coincides with an increase in the expression of TNF receptor 1 (TNFR1) in isolated pinealocytes. In addition, LPS inhibited the synthesis of N-acetylserotonin and melatonin. Therefore, the pineal gland transduces Gram-negative endotoxin stimulation by producing TNF and inhibiting melatonin synthesis. Here, we provide evidence to reinforce the idea of an immune-pineal axis, showing that the pineal gland is a constitutive player in the innate immune response.

Effect of antidepressants on melatonin metabolite in depressed patients

Antidepressants increase melatonin levels, but it is still unclear whether this effect is related to the improvement of depressive symptoms or to unrelated pharmacological action of antidepressants. To answer this question, the effect of antidepressants on 6-sulphatoxymelatonin (aMT6s), the main melatonin urinary metabolite, was examined in drug-free depressed patients - most of them antidepressant-naive. aMT6s was evaluated in 34 depressed patients, before and after 8 weeks of placebo (n = 12) or antidepressant (n = 22; fluoxetine, duloxetine or Hypericum perforatum). Both groups showed an improvement of depressive symptoms after treatment compared to baseline (Hamilton Depression scores): 17.0 +/- 1.4 vs. 9.0 +/- 2.8, P = 0.007 for placebo, and 18.6 +/- 1.1 vs. 11.8 +/- 1.6, P < 0.001 for antidepressants). After treatment, aMT6s levels increased after antidepressants (P < 0.01), but not after placebo (P > 0.05). As depressive symptoms improved both in patients taking antidepressant and in those taking placebo, but an effect of antidepressants could only be seen in those taking antidepressants, we suggest that melatonin changes after antidepressants are more likely due to a pharmacological action of these drugs on melatonin secretion.

Age-related changes in cerebellar phosphatase-1 reduce Na,K-ATPase activity

We evaluated whether changes in protein content and activity of PP-1 and PP-2A were the mechanism underneath the basal age-related reduction in alpha(2/3)-Na,K-ATPase activity in rats cerebella and whether this occurred through the cyclic GMP-PKG pathway. PP1 activity, but not its expression, increased with age, whereas PP-2 was not changed. The activity Of ot2/3-Na,K-ATPase varied with age. and there was a negative association between the PP-1 and alpha(2/3)-Na,K-ATPase activities. In young rats, the inhibition of PP-1 and PP-2A by okadaic acid (OA) increased in a dose-dependent manner alpha(1)- and alpha(2/3)-Na,K-ATPase, but had no effect on Mg-ATPase activity. A direct stimulation of PKG with 8-Br-cyclic GMP did not surmount the effect of OA. This analogue of cyclic GMP inhibited PP-1 activity only, indicating that at least part of the increase in alpha(1)- and alpha(2/3)-Na,K-ATPase activity induced by OA was mediated by the cyclic GMP-PKG-PP-1 cascade. Taking into account that PP1 inhibition increased alpha(2/3)-Na,K-ATPase activity, we propose that an age-related increase in PP-1 activity due to a decrease in cyclic GMP-PKG modulation plays a role for the age-related reduction of alpha(2/3)-Na,K-ATPase activity in rat cerebellum. (C) 2007 Elsevier Inc. All rights reserved.

Intracellular peptides as natural regulators of cell signaling

Protein degradation by the ubiquitin proteasome system releases large amounts of oligopeptides within cells. To investigate possible functions for these intracellularly generated oligopeptides, we fused them to a cationic transactivator peptide sequence using reversible disulfide bonds, introduced them into cells, and analyzed their effect on G protein-coupled receptor (GPCR) signal transduction. A mixture containing four of these peptides (20-80 mu M) significantly inhibited the increase in the extracellular acidification response triggered by angiotensin II (ang II) in CHO-S cells transfected with the ang II type 1 receptor (AT1R-CHO-S). Subsequently, either alone or in a mixture, these peptides increased luciferase gene transcription in AT1R-CHO-S cells stimulated with ang II and in HEK293 cells treated with isoproterenol. These peptides without transactivator failed to affect GPCR cellular responses. All four functional peptides were shown in vitro to competitively inhibit the degradation of a synthetic substrate by thimet oligopeptidase. Overexpression of thimet oligopeptidase in both CHO-S and HEK293 cells was sufficient to reduce luciferase activation triggered by a specific GPCR agonist. Moreover, using individual peptides as baits in affinity columns, several proteins involved in GPCR signaling were identified, including alpha-adaptin A and dynamin 1. These results suggest that before their complete degradation, intracellular peptides similar to those generated by proteasomes can actively affect cell signaling, probably representing additional bioactive molecules within cells.

Relative roles of biogenic emissions and Saharan dust as ice nuclei in the Amazon basin

Some aerosol particles, known as ice nuclei, can initiate ice formation in clouds, thereby influencing precipitation, cloud dynamics and the amount of incoming and outgoing solar radiation. In the absence of biomass burning, aerosol mass concentrations in the Amazon basin are low(1). Tropical forests emit primary biological particles directly into the atmosphere; secondary organic aerosols form from the emission and oxidation of biogenic gases(2). In addition, particles derived from biomass burning in central Africa, marine aerosols, and windblown dust from North Africa(3-5) often reach the central part of the Amazon basin during the wet season. The contribution of these aerosol sources to ice nucleation in the region is uncertain. Here we present observations of the concentration and elemental composition of ice nuclei in the Amazon basin during the wet season. Using transmission electron microscopy combined with energy-dispersive X-ray spectroscopy, we show that ice nuclei are primarily composed of carbonaceous material and dust. We show that biological particles dominate the carbonaceous fraction, whereas import of Saharan dust explains the intermittent appearance of dust-containing nuclei. We conclude that ice-nucleus concentration and abundance can be explained almost entirely by local emissions of biological particles supplemented by import of Saharan dust. Using a simple model, we tentatively suggest that the contribution of local biological particles to ice nucleation is increased at higher atmospheric temperatures, whereas the contribution of dust particles is increased at lower temperatures.

On the motion under focal attraction in a rotating medium

New results are established here on the phase portraits and bifurcations of the kinematic model in system (1), first presented by H.K. Wilson in [3], and by him attributed to L. Markus (unpublished). A new, self-sufficient, study which extends that of [3] and allows an essential conclusion for the applicability of the model is reported here.

Medhörning i studio

I denna uppsats undersöker jag hur musikerns prestation påverkas av medhörningen. Jag har inriktat mig på sångare och sånginspelning i studio. I undersökningen har jag använt mig av tre informanter som fick sjunga till fem olika mixar i medhörningen. Jag analyserade sedan deras intonering, rytmisering och sångstyrka. Resultaten av undersökningen blev att intoneringen till viss del påverkas av medhörningen, rytmiseringen och sångstyrkan påverkas i hög grad av medhörningen.

Processens inverkan på den dragna stångens rakhet samt dragskivans slitage

Examensarbetets syfte var att undersöka vilka parametrar som har störst inverkan på rakheten i processen dragen stång, med avseende på kortvågighet samt vilka faktorer som har störst inverkan på dragskivans slitage. Materialet som undersöktes var OVAKO 803 D som är en storvolymsprodukt, 6 stycken trådringar testades varav 3st var valsad tråd och resterande 3 st skalsvarvade. Parametrar som undersöktes var dragkonans vinkel, bärningens längd och övergångsradien mellan dessa. Statistisk försöksplanering med fullständigt faktorförsök har använts.

Lärares yrkesetiska principer : Fenomenografisk studie kring sex gymnasielärares uppfattningar om principernas syfte, applicerbarhet och diskursaktualitet

Undersökningens syfte är att med hjälp av intervjuer redovisa sex gymnasielärares uppfattningar om deras yrkesetiska principer. Fokus ligger på principernas syfte, diskursaktualitet och applicerbarhet. Resultatet visar att lärarna ser yrkesetiken som ett förhållningssätt samt en del i status- och professionsfrågan. Diskursaktualiteten uppfattas som frånvarande på den aktuella skolan, men intresse för större aktivitet önskas hos några av dem. Yrkesetikens applicerbarhet anses som relativt god, men att problem finns.

Omvårdnad vid Amyotrofisk lateral skleros : erfarenheter ur ett patient och anhörigperspektiv : En systematisk litteraturstudie

Amyotrofisk lateral skleros (ALS) är en fortskridande neurologiska sjukdom som ger den drabbade och de anhöriga mycket sorg och smärta. Syftet med föreliggande systematiska litteraturstudie var att utifrån aktuell vetenskaplig litteratur beskriva upplevelsen och behovet av omvårdnad som den sjuke i ALS och deras anhöriga behövde. Syftet var också att beskriva vilken typ av information och stöd som behövdes. De vetenskapliga artiklarna som ligger till grund för denna litteraturstudie har sökt på databaserna Elin@Dalarna och Blackwell Synergy. Artiklarna skulle vara publicerade mellan åren 2000-2007 och vara skrivna på engelska. Även manuella sökningar har gjorts. Resultatet visade att sjukvården hade ett stort ansvar att stötta, hjälpa och informera vid denna fortskridande neurologiska sjukdom. Det fanns behov av multiinriktad omvårdnad där många olika professioner ingick för att kunna ge patienterna den helhetsvård de behövde. Det framkom att anhöriga var de som hade den givna omvårdnadsrollen och att de hade ett behov av avlastning och information om sjukdomen, behandlingen och symtomen. Anhöriga upplevde sjukdomen som en stor börda och påverkade deras egna hälsa.

Varför ska man dölja det? : -en kvalitativ studie av identitet i förhållande till läs-och skrivsvårigheter

In schools today, we expect student performances and achievements to be exceptional. Having good reading and writing skills are essential if students want to excel at their school assignments. Students with reading and writing difficulties have to work much harder than their other classmates. Their having to work harder coupled with being teenagers and facing all the uncertainties which are present at that age, these students face the difficult task of trying to find out who they are and who they want to be. In other words, they try to create their own individual identities. This study investigates the experiences of students with reading and writing difficulties in their interactions with other students and school personnel, in different situations. The collection of data has been done through group interviews. Thirteen, 15 year old students participated in these interviews. Some of the factors which characterise a hermeneutic approach have helped to form the basis on which the study lies. A hermeneutic approach suggests that the data collected is sorted and analysed to enable the identification of differences and patterns. These patterns are arranged to give results that are subjective and which also show an interpretation of the data collected. The results show that students are more comfortable with their identities, when they are diagnosed or made aware that their performances in school are directly affected by their reading and writing difficulties. The study also shows that having reading and writing difficulties tells the students who they are but, at the same time, plays an important role in their interactions with other classmates and adults. The outcomes of these interactions greatly affect the formation of their identities. The way in which school personnel treat students is also shown to be of great importance.

Deprimerade patienters upplevelse av ECT behandling : - en systematisk litteraturstudie

Syfte: Att undersöka patienters upplevelse av ECT-behandling. Metod: En systematisk litteraturstudie med deskriptiv ansats. Artikelsökning av både kvalitativa och kvantitativa artiklar har gjorts i fritextdatabaserna Cinahl, ELIN och Whiley interscience. Artiklar granskades enligt granskningsmallar för kvalitetsbedömning och var en modifierad version av Willman, Stoltz, Bahtsevani, (2006) och Forsberg, Wengström, (2008).Litteratur i introduktionsdelen har inhämtats enligt ett bekvämlighetsurval på respektive uppsatsförfattares hemort (Borlänge, Leksand). Resultat: Rädsla är ett återkommande tema när det gäller patienters upplevelse av ECT. De flesta kände rädsla före och under behandlingen, men upplevde en lägre grad av rädsla efteråt. Patienternas upplevelse av ECT-behandlingen var komplex vad gäller det egna ställningstagandet till positiv eller negativ behandlingsmetod, upplevelsen av ECT sågs dock som övervägande negativ. Minnesförlust och minskad kognitiv förmåga sågs som två huvudsakliga negativa faktorer med ECT behandlingen. Många patienter upplevde att informationen och undervisningen inför och under behandlingen var dålig. Attityd och kunskap om behandlingen stod i relation till varandra då mer kunskap om ECT ger bättre attityd till behandlingen. Attityden till behandlingen förändras heller inte efter behandlingen utan patienterna håller fast vid sin inställning. Boendemiljön har en inverkan vad gäller viljan att genomgå underhållsbehandling med ECT då patienter på institution är mer benägna att vägra behandlingen än patienter som genomgår behandlingen polikliniskt.

Interaction and Persuasion:An analysis of the use of rhetorical devices in Gordon Brown's speech to the Labour Party Conference, on September 25, 2006

This essay has identified and analysed rhetorical devices in Gordon Brown’s speech delivered at the Labour Party conference on September 25, 2006. The aim of the study was to identify specific rhetorical devices which are described as interactional resources, analyse their uses and discuss possible effects that they may have when included in a political speech. The results are based on my own interpretations but are supported by information provided in current literature by analysts and researchers of rhetoric use. The result findings could probably serve as evidence of the need for better understanding of the devices used by politicians in their relentless endeavours to influence audience decisions.