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The disease is characterized by the triggering of some inflammatory pathways that are ultimately proven deleterious to the host organism. Although antibiotics, fluid administration, vasopressor therapy and infectious source control remain the recommended management strategies, emerging scientific data proposes statins as a new line of treatment. These drugs were first introduced in clinical practice for their cholesterol-lowering effect but the inhibition of HMG-CoA reductase and cholesterol biosynthetic pathway exhibits some less studied effects generally referred to as pleiotropic: anti-inflammatory, antithrombotic, immunomodulatory and antioxidant properties.

Objective: To asses and compare the anti-inflammatory hpv wart removal over the counter of two statins - Simvastatin and Rosuvastatin - measuring blood levels of IL-1β, IL-6 and TNFα using a previously described murinic model of sepsis. Statins were administered in two doses 18 and 3 hours before surgical intervention. Sepsis was induced using the caecal ligation and puncture technique. Blood samples were obtained by venepuncture from each subject in day 1, 4, 7 and 14 the last samples were obtained by cardiac puncture.

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Results: White blood cell counts differed across the groups showing a higher count for the septic but untreated group. Procalcitonin reacted in all septic groups but both statin treated groups had lower levels when compared to untreated group.

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IL-1β levels were higher in the Rosuvastatin treated group. IL-6 levels hpv wart removal over the counter more heterogeneously dispersed but higher levels were noticed in the untreated septic group. The Simvastatin treated group had higher levels compared to the Rosuvastatin treated one. TNFα levels were higher in the septic untreated group and in the Rosuvastatin treated one. For the Simvastatin treated subjects, the level of TNFα was similar with the control group.

Conclusion: We concluded that both drugs showed anti-inflammatory effects on the murinic CLP-induced sepsis model. Between the two, Simvastatin had greater impact by lowering blood levels of established pro-inflammatory markers.

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Rezumat Introducere: Sepsisul este o boala caracterizată printr-un răspuns sistemic inflamator cauzat o infecție care poate evolua către sepsis sever și șoc septic. Sepsisul se caracterizează prin declasnșarea unor căi imune pro-inflamatorii cu rol de apărare a organismului dar care ulterior se dovedesc a fi extrem de dezajantajoase.

Deși antibioterapia, resuscitarea volemică, terapia vasopresoare și controlul sursei de hpv wart removal over the counter rămân strategiile recomandate în tratamentul sepsisului, date publicate recent propun statinele ca o noua linie de tratament. Aceste medicamente au fost introduse în practica clinică datorită efectului hipocolesterolemiant însă inhibarea reductazei HMG-CoA și a biosintezei colesterolului induce o serie de efecte mai puțin studiate denumite generic pleiotrope: anti-inflamatoare, antitrombotice, imunomodulatoare și antioxidante.

Obiective: În cadrul acestui experiment ne-am propus să evaluăm și să comparăm efectul antiinflamator al Simvastatinei și Rosuvastatinei măsurând nevelele serice ale IL-1β, IL-6 și TNF-α folosind un model consacrat de sepsis la șobolan. Hpv wart removal over the counter au fost administrate în două doze cu 18 și 3 ore înaintea intervenției chirurgicale. Sepsisul a fost obținut prin tehnica ligaturării și puncției cecale. De la fiecare subiect au fost recoltate eșantioane de sânge prin puncție venoasă în zilele 1, 4, 7 și 14 ultimele eșantioane au fost obținute prin puncție cardiacă.

Rezultate: Numărul total al leucocitelor a fost mai mare pentru grupul septic dar netratat. Procalcitonina a fost reacționată în toate grupurile septice însă valori mai mici au fost observate în grupurile tratate cu Simvastatină și Rosuvastatină în comparație cu grupul netratat. Nivelul de IL-1β a fost mai mare în grupul tratat cu Rosuvastatină.

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Nivelele de IL-6 au avut o dispersie heterogenă în cadrul experimentului însă au fost înregistrate niveluri hpv wart removal hpv wart removal over the counter the counter înalte în cadrul grupului septic netratat. Grupul tratat cu Simvastatină a avut nivele serice mai mari comparativ cu hpv wart removal over the counter tratat cu Rosuvastatină. Nivelele de TNF-α au fost mai mari pentru grupul septic netratat și cel tratat cu Rosuvastatină. Pentru grupul tratat cu Simvastatină nivelele TNF-α a fost similare cu cele din grupul control.

Concluzii: Ambele statine au efecte anti-inflamatorii în cadrul acestui model de sepsis la șobolan indus prin tehnica ligaturării și puncției cecale. Dintre cele două, Simvastatina a avut un impact mai mare prin scăderea nivelelor circulante a unor markeri proinflamatori consacrați.

Cuvinte cheie : sepsis ; model experimental ; șobolan ; murinic ; statine ; reductază HMG-CoA ; Simvastatină ; Rosuvastatină ; interleukine ; citokine References 1. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: Crit Care Med. DOI: Epidemiology of severe sepsis in the United Dysbiosis ibd analysis of incidence, outcome, and associated costs of care.

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Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol.

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The effect of rosuvastatin in a murine model of influenza A infection. PLoS One. Effect of the simvastatin in abdominal sepsis of diabetic rats. Rev Col Bras Cir.

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Statin pretreatment in experimental acute pancreatitis. J Pancreas.

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Google Scholar 9. Effects of HMG-CoA reductase inhibition by simvastatin on vascular dysfunction induced by lipopolysaccharide in rats. Hemodynamic effects of peri-operative statin therapy in on-pump cardiac surgery patients.

J Cardiothorac Surg. Association between statin therapy and outcomes in critically ill patients: a nested cohort study. BMC Clin Pharmacol. Google Scholar Preadmission statin use and one-year mortality among patients in intensive care - a cohort study.

Crit Care. Effects of statins on postoperative sepsis, systemic inflammatory response syndrome and mortality after colorectal surgery.

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Statin use and mortality within days after bacteremia: a population-based cohort study. E4 Crossref Google Scholar Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction HARP-2 trial: study protocol for a randomized controlled trial. The effects of statin therapy on inflammatory cytokines in patients with bacterial infections: a randomized double-blind placebo controlled clinical trial.

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Continuation of statin therapy in patients with presumed infection: a randomized controlled trial. A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis. A randomized clinical trial of hydroxymethylglutaryl- coenzyme a reductase inhibition for acute lung injury The HARP Study. Statins and sepsis: good bullet, disappearing target.

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Studies in recent years have shown that this interaction is more complex, involving multiple cellular and molecular mechanisms.

Can statins improve outcome in colorectal surgery? Part I. J Coloproctology Rio Janeiro. Statins and sepsis. Br J Anaesth. Cecal ligation puncture procedure.

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J Vis Exp. Cecal ligation and puncture. Sepsis and septic shock--a review of laboratory models and a proposal.

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J Surg Res. Procalcitonin as a diagnostic marker and IL-6 as a prognostic marker for sepsis. Diagn Microbiol Infect Dis. Lee H.

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Procalcitonin as a biomarker of infectious diseases. Korean J Intern Med. Faix JD. Biomarkers of Sepsis. Crit Rev Clin Lab Sci.