Bakgrund: Idag finns det en stor marknad som enbart fokuserar sig på kostillskott, vars uppgift är att få styrketränande människor att prestera maximalt. Många sätter idag sin tro på de preparat som säljs i kostillskottsbutiker, detta medför att försäljningen av kosttillskott under de senaste åren har ökat explosionsartat runt om i världen, inte minst i Sverige. Syfte: Syftet med denna studie är att undersöka friska, fysiskt aktiva mäns styrka, muskulära uthållighet och deras mentala tillstånd vid konsumtion av prestationshöjande preparat (PWO) med ingredienserna koffein, beta-alanin, kreatin, och L-arginin. Metod: Denna studie använde en randomiserad, dubbelblind, placebokontrollerad studiedesign där 18 fullt friska, fysiskt aktiva män deltog. Testpersonerna utförde styrketester, uthållighetstester samt tester gällande deras mentala tillstånd vid intag av PWO och placebo (PL). Testresultaten analyserades sedan i SPSS.  Resultat: Bänkpressen samt uthållighetstestet påvisade ingen signifikant skillnad (p=0,362), (p=0,195). Styrketestet i knäböj visade däremot en signifikant skillnad mellan PWO och PL (Placebo) där deltagarana presterade bättre efter PWO (p=0,007). Den mentala energinivån visade ingen signifikant skillnad mellan PWO och PL (P=0,340). PWO visade dock på en signifikant förbättring av trötthetsnivå, (P=0,002), vakenhetsnivå (P=0,003) och fokuseringsnivå (P=0,002). Diskussion: Om nu PWO till förstone är anpassat och framför allt används av personer med en tydlig träningsinriktning i egenskap av att öka styrka. Prestationsökningen är något som är viktigt för inte bara personer som tränar utan även för dem som antigen rehab-tränar eller för dem som, av olika anledningar, ordineras träning av läkare. Frågan är om PWO kan användas på annat sätt än enbart för gymintresserade personer? Slutsats: PWO har en effekt att den möjliggör en förbättring av träningsresultaten på friska styrketränande individer 24 år ± 4 år

Chronic damage to pulmonary vessels leads to pulmonary hypertension (PH). Different forms of PH are quite frequent and are associated with significant morbidity and mortality. The treatment of PH is most successful, if its cause can be identified and removed before irreversible damage to the pulmonary vascular bed occurs. For patients, in whom the elimination of the underlying cause is not possible or where the cause is unknown, the treatment is aimed at reduction of pulmonary vascular resistance and improvement of cardiac and circulatory response to pressure overload of the right ventricle. One option for the PH treatment is modification of metabolism of cyclic guanosine monophosphate (GMP), which is the second messenger of nitric oxide and induces vascular vasodilation. Cyclic GMP is degraded by phosphodiesterases (PDE 5). In the clinical part, we tested the hypothesis that acute inhibition of PDE5 by sildenafil provides more selective pulmonary vasodilation than high doses of prostaglandin E1 (PGE1). The study showed that the vasodilator effects of sildenafil on pulmonary circulation is more pronounced than in the systemic circulation and that sildenafil had a greater ability to detect reversible component precapillary PH due to advanced chronic heart failure than PGE1. The aim of our...

Chronic damage to pulmonary vessels leads to pulmonary hypertension (PH). Different forms of PH are quite frequent and are associated with significant morbidity and mortality. The treatment of PH is most successful, if its cause can be identified and removed before irreversible damage to the pulmonary vascular bed occurs. For patients, in whom the elimination of the underlying cause is not possible or where the cause is unknown, the treatment is aimed at reduction of pulmonary vascular resistance and improvement of cardiac and circulatory response to pressure overload of the right ventricle. One option for the PH treatment is modification of metabolism of cyclic guanosine monophosphate (GMP), which is the second messenger of nitric oxide and induces vascular vasodilation. Cyclic GMP is degraded by phosphodiesterases (PDE 5). In the clinical part, we tested the hypothesis that acute inhibition of PDE5 by sildenafil provides more selective pulmonary vasodilation than high doses of prostaglandin E1 (PGE1). The study showed that the vasodilator effects of sildenafil on pulmonary circulation is more pronounced than in the systemic circulation and that sildenafil had a greater ability to detect reversible component precapillary PH due to advanced chronic heart failure than PGE1. The aim of our...

Hintergrund. L-Arginin spielt eine komplexe Rolle in der renalen Matrixexpansion, eingeschlossen der endogene Stoffwechsel der Aminosäure in Stickoxid (NO), Polyamine, L-Prolin und Agmatin. Bei Ratten mit einer induzierten Anti-Thy1-Glomerulonephritis (GN) ist gezeigt worden, dass die diätetische Gabe von L-Arginin die Überproduktion von transforming growth factor (TGF)-beta sowie die Matrixakkumulation limitieren konnte. Die vorliegende Studie testet die Hypothese, dass die günstigen Effekte auf die Überexpression von TGF-beta in vivo durch die Generierung von NO vermittelt wird. Methoden. Einen Tag nach Induktion einer Anti-Thy-1-Glomerulonephritis wurden männliche Wistar Ratten, die mit normal proteinhaltigen Futter ernährt worden sind, in die folgenden Gruppen zugeordnet worden: (1) normale Kontrollen; (2) GN; (3) GN-Arg [plus 500 mg L-Arginin/die]; (4) GN-Arg-NAME [plus 500 mg L-Arginin/die und 75 mg/die des NO-Synthase-Inhibitors Nitro-L-Arginin-Methyl-Ester (L-NAME) im Trinkwasser] und (5) GN-Molsi [plus 10 mg/die des NO-Donors Molsidomin]. In Versuchsprotokoll 1 wurde die Behandlung bis Tag 7, in Protokoll 2 bis Tag 12 nach Induktion der Glomerulonephritis durchgeführt. Analysiert wurden die Daten des systolischen Blutdrucks, die histologische glomeruläre Matrixexpansion, die Proteinurie sowie die glomeruläre mRNA- und Protein-Expression des Schlüsselfibrogens TGF-beta, des Matrixproteins Fibronektin und des Protease-Inhibitors Plasminogen-Aktivator-Inhibitor Typ 1(PAI-1). Ergebnisse. Die Blutdruckwerte zeigten sich normal in unbehandelten Anti-Thy-1-Tieren und nicht signifikant beeinflusst durch eine der Behandlungen. Verglichen mit unbehandelten, nephritischen Ratten, reduzierten die Gabe von L-Arginin sowie von Molsidomin signifikant die glomeruläre TGF-beta Überexpression und auch in ähnlichem Mass in beiden Studienprotokollen. Die günstigen Effekte von L-Arginin wurden durch gleichzeitige Blockade der NOS-Synthese mit L-NAME aufgehoben. Die glomeruläre Matrixakkumulation, Fibronektin und PAI-1 mRNA- und Protein-Expression folgten eng der TGF-beta-Expression. Die Proteinurie wurde durch keine der Behandlungen signifikant beeinflusst.Schlussfolgerung. Die vorliegende Studie zeigt, dass die antifibrotischen Effekte der Aminosäure L-Arginin in der normotensiven Anti-Thy-1-Glomerulonephritis der Ratte hauptsächlich über die endogene Produktion von NO vermittelt werden. Diese Daten lassen vermuten, dass NO in vivo die TGF-beta-Überexpression auf einem blutdruck-unabhängigen Weg limitiert und dass NO-Donoren sich günstig in der Behandlung von menschlichen fibrotischen Nierenerkrankungen auswirken könnten. / Background. L-arginine olays a complex role in renal matrix expansion, involving endogenous metabolism into nitric oxide (NO), polyamines, L-prolin and agmatine. Supplementing dietary L-arginine intake has been shown to limit transforming growth factor (TGF)-beta1 overproduction and matrix accumulation in rats with induced anti-thy1 glomerulonephritis (GN). The present study tests the hypothesis that this beneficial effect on in vivo TGF-beta overproduction is mediated via the generation of NO. Methods. One day after inducion of anti-thy1 GN, male wistar rats fed a normal protein diet were assigned to the following groups: (1) normal controls; (2) GN; (3) GN-Arg [plus 500 mg L-arginine/day]; (4) GN-Arg-NAME [plus 500 mg L-arginine/day and 75 mg/day of the NO synthase inhibitor nitro-L-arginine-methyl ester (L-NAME) in the drinking water] and (5) GN-Molsi [plus 10 mg/day of the NO donor molsidomine]. In protocol 1, treatment lasted until day 7 and in protocol 2 until day 12 after disease induction, respectively. Analysis included systolic blood pressure, proteinuria, a glomerular histologic matrix score and the glomerular mRNA and protein expression of the key fibrogen TGF-beta1, the matrix protein fibronectin and the protease inhibitor plasminogen activator inhibitor type 1 (PAI-1). Results. Blood pressure was normal in untreated anti-thy1 animals and not significantly affected by any of the treatments. Compared to nephritic rats, administration of both L-arginine and molsidomine reduced glomerular TGF-beta1 overexpression significantly and to a similar degree in both protocols, while the beneficial effect of L-arginine was abolished by concomitant NO synthesis inhibition. Glomerular matrix accumulation, fibronectin and PAI-1 mRNA and protein expression cloxely followed the expression of TGF-beta1. Proteinuria was not significantly affected by any treatment. Conclusion. The present study shows that L-arginine´s antifibrotic action in normothensive anti-thy1 GN is mainly mediated by endogenous production of NO. The data suggest that NO limits in vivo TGF-beta overexpression in a pressur-independent manner and that NO donors may be of benefit in the treatment of human fibrotic renal disease.

Die fortschreitende Vermehrung extrazellulärer Matrixproteine ist zentrales Kennzeichen von chronisch-progressiver Niereninsuffizienz. L-Arginin ist eine semi-essentielle Aminosäure und über seinen endogenen Metaboliten Stickoxid (NO) in komplexer Weise mit renaler Matrixvermehrung verbunden. In dieser Arbeit wurde untersucht, wie sich die Gabe von L-Arginin auf die Matrixexpansion bei experimenteller, immun-vermittelter Nierenerkrankung auswirkt. Im Modell der akuten Anti-Thy1-Glomerulonephritis der Ratte und der chronischen Lupusnephritis der MRL/lpr-Maus wurde gezeigt, daß die Aktivierung des L-Arginin-NO-Stoffwechsels sowohl mit günstigen als auch mit ungünstigen Wirkungen auf die renale Matrixakkumulation verbunden ist. Diese "duale" Wirkung von L-Arginin ist im wesentlichen als Ausdruck der "ambivalenten" Wirkung von NO zu deuten. Antifibrotische Wirkungen von L-Arginin stehen in enger Verbindung mit einer gesteigerten endothelialen NO-Synthese. Neben renaler Blutdrucksenkung vermittelt die endotheliale NO-Synthase auch parakrin wichtige antifibrotische Effekte. Profibrotische Wirkungen von L-Arginin stehen in engem Zusammenhang mit einer gesteigerten NO-Synthese durch induzierbare, destruktive NO-Synthasen. Folgen sind verstärkte Organschädigung und beschleunigte Progression von renaler Funktionseinschränkung. / Ongoing expansion of extracellular matrix proteins is a hallmark of progressive chronic renal insufficiency. L-Arginine is a semi-essential amino acid and alters renal matrix accumulation via its endogenous metabolite nitric oxide (NO) in a complex manner. The present study analyzed how administration of L-arginine affects renal matrix accumulation in experimental immune-mediated disease. In acute anti-Thy1 glomerulonephritis of the rat and chronic lupus nephritis of MRL/lpr-mice, activation of the L-arginine-NO-pathway was related to both beneficial and detrimental actions on renal matrix accumulation. This "dual" effect of L-arginine administration essentially reflects the "ambivalent" nature of NO. Antifibrotic actions of L-arginine are associated with increased endothelial NO synthesis. In addition to lowering glomerular blood pressure, endothelial NO production mediates important paracrine antifibrotic actions. Profibrotic effects of L-arginine are related to increased NO production by inducible, destructive NO synthases, resulting in increased organ damage and accelerated progression of chronic kidney insufficiency.

O objetivo deste estudo foi avaliar o efeito da sinvastatina, isolada e associada ao α-tocoferol e à L-arginina, sobre os inibidores endógenos da óxido nítrico sintase, os metabólitos do óxido nítrico e tióis, em pacientes hipercolesterolêmicos. Analisou-se um grupo de 16 pacientes hipercolesterolêmicos que seguiram o seguinte protocolo: período de washout (sem medicação), 1 mês; sinvastatina (20mg/dia), 2 meses; sinvastatina (20mg/dia) + α-tocoferol (400U/dia), 2 meses; sinvastatina (20mg/dia, washout), 1 mês; sinvastatina (20mg/dia) + L-arginina (7g/dia), 2 meses. A sinvastatina reduziu significativamente as concentrações do colesterol total e LDL-colesterol e a razão LDL-colesterol/HDL-colesterol. O tratamento com sinvastatina, isolada e associada ao α-tocoferol, promoveu diminuição nas concentrações de S-nitrosotióis. A L-arginina associada à sinvastatina, aumentou os níveis de colesterol total quando comparada com a sinvastatina isoladamente. As concentrações plasmáticas de α-tocoferol e L-arginina não aumentaram em decorrência da suplementação, devido à grande dispersão dos dados obtidos, embora as medianas das concentrações plasmáticas de Larginina e α-tocoferol tenham sido mais elevadas após as suplementações. O tratamento com sinvastatina, isolada ou associada à L-arginina e ao α-tocoferol, não alterou as concentrações dos inibidores endógenos da óxido nítrico sintase (ADMA e SDMA), dos metabólitos do óxido nítrico, da nitrotirosina total e dos tióis analisados. / The aim of this study was to evaluate the effect of sinvastatin, isolated and associated to α-tocopherol and to L-arginine, on the endogenous inhibitors of nitric oxide synthase, on nitric oxide metabolytes and thiols, in hypercholesterolemic patients. A group of 16 hypercholesterolemic patients were analysed, acconting to the protocol: a washout period (without medication) of 1 month, sinvastatin (20 mg/day) for 2 months; sinvastatin (20 mg/day) + α-tocopherol (400U/day) for 2 months; sinvastatin (20 mg/day) for 1 months (washout period), sinvastatin (20 mg/day) + L-arginine (7g/day) for 2 months. Sinvastatin significantly reduced the concentrations of total cholesterol and LDL-cholesterol, as well as the LDL-cholesterol/HDLcholesterol ratio. The treatment with sinvastatina, alone and associate to α-tocoferol, resulted in a reduction of RSNO concentration. The L-arginine associated with sinvastatin, increase the level of total cholesterol as compared with simvastatin alone. The plasma concentrations of a-tocopherol and Larginine did not increase following supplementation due to the large dispersion of the data obtained, even though the median plasma concentrations of L-arginine and a-tocopherol were elevated after supplementation. Treatment with simvastatin, alone or associated to L-arginine and a-tocopherol did not alter the concentrations of the endogenous inhibitors of nitric oxide synthase (ADMA and SDMA), or that of nitric oxide metabolytes, total nitrotyrosine or the thiols analysed.

O objetivo deste estudo foi avaliar o efeito da sinvastatina, isolada e associada ao α-tocoferol e à L-arginina, sobre os inibidores endógenos da óxido nítrico sintase, os metabólitos do óxido nítrico e tióis, em pacientes hipercolesterolêmicos. Analisou-se um grupo de 16 pacientes hipercolesterolêmicos que seguiram o seguinte protocolo: período de washout (sem medicação), 1 mês; sinvastatina (20mg/dia), 2 meses; sinvastatina (20mg/dia) + α-tocoferol (400U/dia), 2 meses; sinvastatina (20mg/dia, washout), 1 mês; sinvastatina (20mg/dia) + L-arginina (7g/dia), 2 meses. A sinvastatina reduziu significativamente as concentrações do colesterol total e LDL-colesterol e a razão LDL-colesterol/HDL-colesterol. O tratamento com sinvastatina, isolada e associada ao α-tocoferol, promoveu diminuição nas concentrações de S-nitrosotióis. A L-arginina associada à sinvastatina, aumentou os níveis de colesterol total quando comparada com a sinvastatina isoladamente. As concentrações plasmáticas de α-tocoferol e L-arginina não aumentaram em decorrência da suplementação, devido à grande dispersão dos dados obtidos, embora as medianas das concentrações plasmáticas de Larginina e α-tocoferol tenham sido mais elevadas após as suplementações. O tratamento com sinvastatina, isolada ou associada à L-arginina e ao α-tocoferol, não alterou as concentrações dos inibidores endógenos da óxido nítrico sintase (ADMA e SDMA), dos metabólitos do óxido nítrico, da nitrotirosina total e dos tióis analisados. / The aim of this study was to evaluate the effect of sinvastatin, isolated and associated to α-tocopherol and to L-arginine, on the endogenous inhibitors of nitric oxide synthase, on nitric oxide metabolytes and thiols, in hypercholesterolemic patients. A group of 16 hypercholesterolemic patients were analysed, acconting to the protocol: a washout period (without medication) of 1 month, sinvastatin (20 mg/day) for 2 months; sinvastatin (20 mg/day) + α-tocopherol (400U/day) for 2 months; sinvastatin (20 mg/day) for 1 months (washout period), sinvastatin (20 mg/day) + L-arginine (7g/day) for 2 months. Sinvastatin significantly reduced the concentrations of total cholesterol and LDL-cholesterol, as well as the LDL-cholesterol/HDLcholesterol ratio. The treatment with sinvastatina, alone and associate to α-tocoferol, resulted in a reduction of RSNO concentration. The L-arginine associated with sinvastatin, increase the level of total cholesterol as compared with simvastatin alone. The plasma concentrations of a-tocopherol and Larginine did not increase following supplementation due to the large dispersion of the data obtained, even though the median plasma concentrations of L-arginine and a-tocopherol were elevated after supplementation. Treatment with simvastatin, alone or associated to L-arginine and a-tocopherol did not alter the concentrations of the endogenous inhibitors of nitric oxide synthase (ADMA and SDMA), or that of nitric oxide metabolytes, total nitrotyrosine or the thiols analysed.