The impact of everolimus in reducing cytomegalovirus events in kidney transplant recipients on steroid-avoidance strategy: 3-year follow-up of a randomized clinical trial.

There is no evidence of whether everolimus (EVR) reduces cytomegalovirus (CMV) events in patients receiving steroid-free regimens. Besides, studies evaluating a tacrolimus (TAC) and EVR regimen are limited to 1-year follow-up. In this single-center prospective randomized trial, the incidence of CMV and 3-year efficacy and safety outcomes of EVR were compared to those of mycophenolate sodium (MPS) in a steroid-free regimen based on low-exposure TAC. Both groups received rabbit anti-thymocyte globulin (r-ATG) induction (6 mg/kg) and the steroids were withdrawn at day 7. Maintenance immunosuppression consisted of TAC (4-7 ng/ml until month 3 and 2-4 ng/ml thereafter) plus EVR (3-8 ng/ml) in the EVR group (n = 59); and TAC (4-7 ng/ml during all follow-up) plus MPS (1440 mg) in the MPS group (n = 56). The EVR group presented with a lower incidence of CMV events (18.6% vs. 50%, P = 0.001). No differences were observed in biopsy-proven acute rejection (6.8% vs. 3.6%, P = 0.680),graft loss (0.0% vs. 1.8%, P = 0.487),death (6.8% vs. 1.8%, P = 0.365), or estimated glomerular filtration rate at 36 months (61.1 ± 25.4 vs. 66.3 ± 24 ml/min/1.73 m2 , P = 0.369). A higher proportion of patients discontinued MPS treatment (8.5% vs. 26.8%, P = 0.013) for safety issues. In conclusion, EVR was associated with lower rates of CMV events in patients induced with standard dose r-ATG and a maintenance steroid-free regimen based on TAC. This regimen effectively prevented acute rejection and demonstrated a more favorable safety profile. (ClinicalTrials.gov:NCT02084446).

Preconditioning with oil mixes of high ratio Omega-9: Omega-6 and a low ratio Omega-6:Omega-3 in rats subjected to brain ischemia/reperfusion.

PURPOSE: This study aimed to assess the effects of preconditioning with mixtures of oils containing high/low ratio of ω-6/ω-3 and ω-9/ω-6, respectively, in an experimental model of cerebral ischemia-reperfusion (I/R). METHODS: Forty-two Wistar rats were randomly distributed into two groups: control (n=24) and test (n=18). Control group was subdivided in 4 subgroups (n=6): G1: Sham-Water; G2: I/R-Water; G3: Sham-Isolipidic and G4: I/R-Isolipid. The animals received water or a isolipid mixture containing ω-3 oils (8:1 ratio) and ω-9/ω-6 (0.4:1 ratio) by gavage for seven days. Test group included 3 subgroups (n=6) G5: I/R-Mix1, G: 6 I/R-Mix2 and G7: I/R-Mix3. Test group animals received oily mixtures of ω-3 (1.4:1 ratio) and ω-6 (3.4:1 ratio), differing only in source of ω-3: G5 (alpha-linolenic acid); G6 (alpha-linolenic, docosahexaenoic and eicosapentaenoic acids), and G7 (alpha-linolenic and docosahexaenoic acids). On day 7 I/R rats underwent cerebral ischemia with bilateral occlusion of common carotid arteries for 1 hour followed by reperfusion for 3 hours. G1 and G3 animals underwent sham operation. Concluded the experiment, animals were decapitated and their brains sliced for red neurons (RN) count in CA3 area of the hippocampus. Variables were compared using ANOVA-Tukey test. RESULTS: The use of different mix preparations promoted a decrease in red cell count in all three groups (G5/G6/G7), compared with G2/G4, confirming the protective effect of different oil blends, regardless of ω-3 source. CONCLUSION: Pre-conditioning with mixtures of oils containing high ratio ω-6/ω-3 and low ω-9/ω-6 relationship protects brain neurons against I/R injury in an experimental model.

Preconditioning with oil mixes of high ratio Omega-9: Omega-6 and a low ratio Omega-6:Omega-3 in rats subjected to brain ischemia/reperfusion / Pré-condicionamento com misturas de óleos com Ômega-9: Ômega-6 (alta relação) e Ômega-6:Ômega-3 (baixa relação) em ratos submetidos à isquemia/reperfusão cerebral

PURPOSE: This study aimed to assess the effects of preconditioning with mixtures of oils containing high/low ratio of ω-6/ω-3 and ω-9/ω-6, respectively, in an experimental model of cerebral ischemia-reperfusion (I/R). METHODS: Forty-two Wistar rats were randomly distributed into two groups: control (n=24) and test (n=18). Control group was subdivided in 4 subgroups (n=6): G1: Sham-Water; G2: I/R-Water; G3: Sham-Isolipidic and G4: I/R-Isolipid. The animals received water or a isolipid mixture containing ω-3 oils (8:1 ratio) and ω-9/ω-6 (0.4:1 ratio) by gavage for seven days. Test group included 3 subgroups (n=6) G5: I/R-Mix1, G: 6 I/R-Mix2 and G7: I/R-Mix3. Test group animals received oily mixtures of ω-3 (1.4:1 ratio) and ω-6 (3.4:1 ratio), differing only in source of ω-3: G5 (alpha-linolenic acid); G6 (alpha-linolenic, docosahexaenoic and eicosapentaenoic acids), and G7 (alpha-linolenic and docosahexaenoic acids). On day 7 I/R rats underwent cerebral ischemia with bilateral occlusion of common carotid arteries for 1 hour followed by reperfusion for 3 hours. G1 and G3 animals underwent sham operation. Concluded the experiment, animals were decapitated and their brains sliced for red neurons (RN) count in CA3 area of the hippocampus. Variables were compared using ANOVA-Tukey test. RESULTS: The use of different mix preparations promoted a decrease in red cell count in all three groups (G5/G6/G7), compared with G2/G4, confirming the protective effect of different oil blends, regardless of ω-3 source. CONCLUSION: Pre-conditioning with mixtures of oils containing high ratio ω-6/ω-3 and low ω-9/ω-6 relationship protects brain neurons against I/R injury in an experimental model.

OBJETIVO: Avaliar os efeitos do pré-condicionamento com misturas de óleos contendo relação alta/baixa de ω-6/ω-3 e ω-9/ω-6, respectivamente, em um modelo experimental de isquemia/reperfusão (I/R) cerebral. MÉTODOS: Quarenta e dois ratos foram distribuídos aleatoriamente em dois grupos: controle (n=24) e teste (n=18). Grupo controle foi subdividido em quatro subgrupos (n=6): G1: Sham-Água; G2: I/R-Água; G3: Sham-Isolipídico e G4: I/R-Isolipídico. Os animais receberam água ou uma mistura isolipidica contendo ω-6/ω-3 óleos (8:1) e ω-9/ω-6 (0,4:1) por gavagem, durante sete dias. O grupo teste incluiu três subgrupos (n=6) G5: I/R-Mix1, G: 6 I/R-Mix2 e G7: I/R-Mix3. Animais do grupo teste receberam de misturas de óleos ω-6/ω-3 (1,4:1) e ω-9/ω-6 (3,4:1), diferindo apenas na fonte de -3: G5:alpha-linolênico; G6: ácidos alpha-linolênico, eicosapentaenóico e docosahexaenóico e G7:ácidos alpha-linolênico e docosahexaenóico. No 7º dia os grupos I/R foram submetidos à isquemia cerebral (1h) por oclusão bilateral das artérias carótidas comuns seguida de reperfusão (3h). Ratos G1 e G3 foram submetidos à operação simulada. Concluído o experimento, os animais foram decapitados e seus cérebros fatiados para contagem dos neurônios vermelhos na área CA3 do hipocampo. As variáveis foram comparadas pelo teste de ANOVA-Tukey. RESULTADOS: A utilização de diferentes misturas de óleos promoveu uma diminuição na contagem de células vermelhas nos grupos G5/G6/G7, em comparação com G2/G4, confirmando o efeito protetor das misturas de óleos, independentemente da origem de ω-3. CONCLUSÃO: O pré-condicionamento com misturas de óleos contendo alta proporção de ω-6/ω-3 e baixa proporção de ω-9/ω-6 protege os neurônios cerebrais da lesão de I/R em um modelo experimental.

L-alanyl-glutamine preoperative infusion in patients with critical limb ischemia subjected to distal revascularization reduces tissue damage and protects from oxidative stress.

BACKGROUND: Critical limb ischemia (CLI) is the most severe form of peripheral vascular disease where there is inadequate blood flow to a limb. Our aim was to examine the effects of preoperative infusion of l-alanyl-glutamine (l-Ala-Gln) during the ischemic period and during the first 30 minutes following blood reflow in patients with CLI who are undergoing distal femoral artery bypass surgery. METHODS: Thirty-two patients with CLI were alternately allocated to group 1 (saline) or group 2 (l-Ala-Gln). Saline (1000 mL) or L-Ala-Gln 250 mL plus 750 mL of saline were infused intravenously over a 3-hour period prior to surgery. Samples (muscle and blood) were collected at the beginning of the surgical procedure, at the end of ischemia, and at 15 and 30 minutes after reperfusion. RESULTS: l-Ala-Gln induced elevation in glutathione (GSH) muscle concentrations while promoting reduction in thiobarbituric acid reactive substance concentrations, demonstrating enhancement of antioxidant capacity and protection from lipid peroxidation. Decreases in LDH, lactate, and glucose blood concentrations in l-Ala-Gln-treated patients suggest increased glucose utilization by muscle and peripheral tissues. Reduction in creatine phosphokinase blood concentrations may reflect smaller muscle cell damage in l-Ala-Gln-treated patients. CONCLUSION: l-Ala-Gln pretreatment reduces muscle cell damage and enhances antioxidant capacity in patients with CLI.