RESUMO
Psychological factors have been shown to influence the process of wound healing. This study examined the effect of Mindfulness-Based Stress Reduction (MBSR) on the speed of wound healing. The local production of pro-inflammatory cytokines and growth factors was studied as potential underlying mechanism. Forty-nine adults were randomly allocated to a waiting-list control group (n = 26) or an 8-week MBSR group (n = 23). Pre- and post-intervention/waiting period assessment for both groups consisted of questionnaires. Standardized skin wounds were induced on the forearm using a suction blister method. Primary outcomes were skin permeability and reduction in wound size monitored once a day at day 3, 4, 5, 6, 7, and 10 after injury. Secondary outcomes were cytokines and growth factors and were measured in wound exudates obtained at 3, 6, and 22 h after wounding. Although there was no overall condition effect on skin permeability or wound size, post hoc analyses indicated that larger increases in mindfulness were related to greater reductions in skin permeability 3 and 4 days after wound induction. In addition, MBSR was associated with lower levels of interleukin (IL)-8 and placental growth factor in the wound fluid 22 h after wound induction. These outcomes suggest that increasing mindfulness by MBSR might have beneficial effects on early stages of wound healing. Trial Registration NTR3652, http://www.trialregister.nl.
Assuntos
Atenção Plena , Estresse Psicológico/prevenção & controle , Estresse Psicológico/terapia , Cicatrização , Adulto , Biomarcadores/sangue , Citocinas/sangue , Feminino , Humanos , Interleucina-8/sangue , Masculino , Permeabilidade , Fator de Crescimento Placentário/sangue , Estresse Psicológico/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto JovemRESUMO
BACKGROUND: Short-chain fatty acids (SCFAs), fermentation products of undigested fibers, are considered beneficial for colonic health. High plasma concentrations are potentially harmful; therefore, information about systemic SCFA clearance is needed before therapeutic use of prebiotics or colonic SCFA administration. OBJECTIVE: The aim of this study was to investigate the effect of rectal butyrate administration on SCFA interorgan exchange. METHODS: Twelve patients (7 men; age: 66.4 ± 2.0 y; BMI 24.5 ± 1.4 kg/m(2)) undergoing upper abdominal surgery participated in this randomized placebo-controlled trial. During surgery, 1 group received a butyrate enema (100 mmol sodium butyrate/L; 60 mL; n = 7), and the other group a placebo (140 mmol 0.9% NaCl/L; 60 mL; n = 5). Before and 5, 15, and 30 min after administration, blood samples were taken from the radial artery, hepatic vein, and portal vein. Plasma SCFA concentrations were analyzed, and fluxes from portal-drained viscera, liver, and splanchnic area were calculated and used for the calculation of the incremental area under the curve (iAUC) over a 30-min period. RESULTS: Rectal butyrate administration led to higher portal butyrate concentrations at 5 min compared with placebo (92.2 ± 27.0 µmol/L vs. 14.3 ± 3.4 µmol/L, respectively; P < 0.01). In the butyrate-treated group, iAUCs of gut release (282.8 ± 133.8 µmol/kg BW · 0.5 h) and liver uptake (-293.7 ± 136.0 µmol/kg BW · 0.5 h) of butyrate were greater than in the placebo group [-16.6 ± 13.4 µmol/kg BW · 0.5 h (gut release) and 16.0 ± 13.8 µmol/kg BW · 0.5 h (liver uptake); P = 0.01 and P < 0.05, respectively]. As a result, splanchnic butyrate release did not differ between groups. CONCLUSION: After colonic butyrate administration, splanchnic butyrate release was prevented in patients undergoing upper abdominal surgery. These observations imply that therapeutic colonic SCFA administration at this dose is safe. The trial was registered at clinicaltrials.gov as NCT02271802.
Assuntos
Butiratos/administração & dosagem , Butiratos/sangue , Ácidos Graxos Voláteis/metabolismo , Fígado/efeitos dos fármacos , Acetatos/metabolismo , Administração Oral , Idoso , Índice de Massa Corporal , Relação Dose-Resposta a Droga , Ácidos Graxos Voláteis/sangue , Feminino , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Veia Porta/efeitos dos fármacos , Veia Porta/metabolismo , Prebióticos , Propionatos/metabolismoRESUMO
PURPOSE: Splanchnic hypoperfusion is a physiological phenomenon during strenuous exercise. It has been associated with gastrointestinal symptoms and intestinal injury and may hamper athletic performance. We hypothesized that L-citrulline supplementation improves splanchnic perfusion and decreases intestinal injury by enhancing arginine availability. The aim of this study was to determine the effect of L-citrulline intake on splanchnic perfusion, intestinal injury, and barrier function during exercise. METHODS: In this randomized, double-blind crossover study, 10 men cycled for 60 min at 70% of their maximum workload after L-citrulline (10 g) or placebo (L-alanine) intake. Splanchnic perfusion was assessed using gastric air tonometry. Sublingual microcirculation was evaluated by sidestream dark field imaging. Plasma amino acid levels and intestinal fatty acid binding protein concentrations, reflecting enterocyte damage, were assessed every 10 min. Urinary excretion of sugar probes was measured to evaluate intestinal permeability changes. RESULTS: Oral L-citrulline supplementation enhanced plasma citrulline (1840.3 ± 142.3 µM) and arginine levels (238.5 ± 9.1 µM) compared with that in placebo (45.7 ± 4.8 µM and 101.5 ± 6.1 µM, respectively, P < 0.0001), resulting in increased arginine availability. Splanchnic hypoperfusion was prevented during exercise after L-citrulline ingestion (reflected by unaltered gapg-apCO2 levels), whereas gapg-apCO2 increased with placebo treatment (P < 0.01). Accordingly, L-citrulline intake resulted in an increased number of perfused small sublingual vessels compared with that in placebo (7.8 ± 6.0 vs -2.0 ± 2.4, P = 0.06). Furthermore, plasma intestinal fatty acid binding protein levels were attenuated during exercise after L-citrulline supplementation compared with that in placebo (AUC0-60 min, -185% ± 506% vs 1318% ± 553%, P < 0.01). No significant differences were observed for intestinal permeability. CONCLUSIONS: Pre-exercise L-citrulline intake preserves splanchnic perfusion and attenuates intestinal injury during exercise in athletes compared with placebo, probably by enhancing arginine availability. These results suggest that oral L-citrulline supplementation is a promising intervention to combat splanchnic hypoperfusion-induced intestinal compromise.
Assuntos
Citrulina/administração & dosagem , Suplementos Nutricionais , Exercício Físico/fisiologia , Intestino Delgado/irrigação sanguínea , Intestino Delgado/patologia , Circulação Esplâncnica/fisiologia , Administração Oral , Adulto , Arginina/sangue , Ciclismo/fisiologia , Citrulina/sangue , Estudos Cross-Over , Método Duplo-Cego , Enterócitos/patologia , Proteínas de Ligação a Ácido Graxo/sangue , Humanos , Masculino , Microcirculação , Adulto JovemRESUMO
BACKGROUND: Impaired microcirculation during endotoxemia correlates with a disturbed arginine-nitric oxide (NO) metabolism and is associated with deteriorating organ function. Improving the organ perfusion in endotoxemia, as often seen in patients with severe infection or systemic inflammatory response syndrome (SIRS) is, therefore, an important therapeutic target. We hypothesized that supplementation of the arginine precursor citrulline rather than arginine would specifically increase eNOS-induced intracellular NO production and thereby improve the microcirculation during endotoxemia. METHODOLOGY/PRINCIPAL FINDINGS: To study the effects of L-Citrulline and L-Arginine supplementation on jejunal microcirculation, intracellular arginine availability and NO production in a non-lethal prolonged endotoxemia model in mice. C57/Bl6 mice received an 18 hrs intravenous infusion of endotoxin (LPS, 0.4 µg ⢠g bodyweight(-1) ⢠h(-1)), combined with either L-Citrulline (6.25 mg ⢠h-1), L-Arginine (6.25 mg ⢠h(-1)), or L-Alanine (isonitrogenous control; 12.5 mg ⢠h(-1)) during the last 6 hrs. The control group received an 18 hrs sterile saline infusion combined with L-Alanine or L-Citrulline during the last 6 hrs. The microcirculation was evaluated at the end of the infusion period using sidestream dark-field imaging of jejunal villi. Plasma and jejunal tissue amino-acid concentrations were measured by HPLC, NO tissue concentrations by electron-spin resonance spectroscopy and NOS protein concentrations using Western blot. CONCLUSION/SIGNIFICANCE: L-Citrulline supplementation during endotoxemia positively influenced the intestinal microvascular perfusion compared to L-Arginine-supplemented and control endotoxemic mice. L-Citrulline supplementation increased plasma and tissue concentrations of arginine and citrulline, and restored intracellular NO production in the intestine. L-Arginine supplementation did not increase the intracellular arginine availability. Jejunal tissues in the L-Citrulline-supplemented group showed, compared to the endotoxemic and L-Arginine-supplemented endotoxemic group, an increase in degree of phosphorylation of eNOS (Ser 1177) and a decrease in iNOS protein level. In conclusion, L-Citrulline supplementation during endotoxemia and not L-Arginine reduced intestinal microcirculatory dysfunction and increased intracellular NO production, likely via increased intracellular citrulline and arginine availability.
Assuntos
Arginina/farmacologia , Citrulina/farmacologia , Endotoxemia/metabolismo , Endotoxemia/fisiopatologia , Microcirculação/efeitos dos fármacos , Óxido Nítrico/biossíntese , Animais , Arginina/metabolismo , Disponibilidade Biológica , Citrulina/metabolismo , Citrulina/farmacocinética , Suplementos Nutricionais , Endotoxemia/patologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismoRESUMO
INTRODUCTION: Anastomotic leakage is a common clinical complication with incidences up to 10% to 17% in colorectal surgery, leading to high morbidity and mortality. Butyrate is the product of colonic fermentation of indigestible carbohydrates and is considered beneficial to gastrointestinal healing. The aim of this study was to investigate the effect of intraluminal supplementation of butyrate on colonic anastomotic strength in a rat model. METHODS: Wistar rats were randomly assigned to one of 3 groups (18 animals each). All rats underwent a 1-cm left colonic resection and end-to-end anastomosis with 4 interrupted sutures. Group I underwent no other treatment and served as the control, group II received daily 5 mL of 60 mM sodium butyrate enemas postoperatively, and group III received placebo enemas. On the third or seventh postoperative day, rats (n = 9 per time point) were anesthetized and anastomotic bursting strength was assessed. RESULTS: As a consequence of anastomotic leakage, 3 rats (16.6%) in group I, 1 rat (5.6%) in group II, and 2 rats (11.2%) in group III died. Mean anastomotic bursting pressures at day 3 were not significantly different between groups (53, 64, and 68 mm Hg for group I, II, and III, respectively, P = .777). At day 7, bursting pressures were 118, 225, and 129 mm Hg for groups I, II, and III, respectively (P = .0006). Group II showed an increased mature-to-immature collagen ratio (P = .035). CONCLUSION: Postoperative intestinal butyrate supplementation enhances anastomotic bursting strength in a left-sided partial colonic resection rat model, which can be explained by increased collagen synthesis and maturation.
Assuntos
Butiratos/administração & dosagem , Colectomia/métodos , Colo/cirurgia , Enema/métodos , Técnicas de Sutura/normas , Anastomose Cirúrgica , Animais , Colo/fisiopatologia , Modelos Animais de Doenças , Masculino , Pressão , Ratos , Ratos WistarRESUMO
OBJECTIVE: Early gut wall integrity loss and local intestinal inflammation are associated with the development of inflammatory complications in surgical and trauma patients. Prevention of these intestinal events is a potential target for therapies aimed to control systemic inflammation. Previously, we demonstrated in a rodent shock model that lipid-rich enteral nutrition attenuated systemic inflammation and prevented organ damage through a cholecystokinin receptor-dependent vagal pathway. The influence of lipid-rich nutrition on very early intestinal compromise as seen after shock is investigated. Next, the involvement of cholecystokinin receptors on the nutritional modulation of immediate gut integrity loss and intestinal inflammation is studied. DESIGN: Randomized controlled in vivo study. SETTING: University research unit. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Liquid lipid-rich nutrition or control low-lipid feeding was administered per gavage before hemorrhagic shock. Cholecystokinin receptor antagonists were used to investigate involvement of the vagal antiinflammatory pathway. MEASUREMENTS AND MAIN RESULTS: Gut permeability to horseradish peroxidase increased as soon as 30 mins postshock and was prevented by lipid-rich nutrition compared with low-lipid (p<.01) and fasted controls (p<.001). Furthermore, lipid-rich nutrition reduced plasma levels of enterocyte damage marker ileal lipid binding protein at 60 mins (p<.05). Early gut barrier dysfunction correlated with rat mast cell protease plasma concentrations at 30 mins (rs=0.67; p<.001) and intestinal myeloperoxidase levels at 60 mins (rs=0.58; p<.05). Lipid-rich nutrition significantly reduced plasma rat mast cell protease (p<.01) and myeloperoxidase (p<.05) before systemic inflammation was detectable. Protective effects of lipid-rich nutrition were abrogated by cholecystokinin receptor antagonists (horseradish peroxidase; p<.05 and rat mast cell protease; p<.05). CONCLUSIONS: Lipid-rich enteral nutrition prevents early gut barrier loss, enterocyte damage, and local intestinal inflammation before systemic inflammation develops in a cholecystokinin receptor-dependent manner. This study identifies activation of the vagal antiinflammatory pathway with lipid-rich nutrition as a potential therapy in patients prone to develop a compromised gut.
Assuntos
Nutrição Enteral/métodos , Gastroenterite/prevenção & controle , Lipídeos/uso terapêutico , Receptores da Colecistocinina/metabolismo , Animais , Enterócitos/metabolismo , Gastroenterite/etiologia , Gastroenterite/imunologia , Absorção Intestinal/efeitos dos fármacos , Intestinos/imunologia , Intestinos/inervação , Intestinos/patologia , Lipídeos/administração & dosagem , Masculino , Mastócitos/metabolismo , Vias Neurais , Transportadores de Ânions Orgânicos Dependentes de Sódio/sangue , Peptídeo Hidrolases/sangue , Peroxidase/sangue , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores da Colecistocinina/antagonistas & inibidores , Choque Hemorrágico/complicações , Simportadores/sangue , Nervo Vago/fisiopatologiaRESUMO
Dietary fish-oil (FO) supplementation has been shown to inhibit inflammation in various clinical disease states and to be beneficial in experimental models of inflammation and bacterial and plasmodial infection. In mice, FO increases macrophage production of tumour necrosis factor alpha (TNF). Production of TNF has been reported to be important in the resistance of mice against various Leishmania spp. We investigated whether dietary supplementation with FO protects susceptible Balb/c mice against infection with Leishmania amazonensis. No influence of the FO diet on the course of infection was observed, as evaluated by the increase in thickness of infected footpads over forty days. Lipopolysaccharide (LPS)-induced TNF production of peritoneal cells was however significantly increased in FO fed mice (P<0.01). When L. amazonensis was used as a stimulus, the in-vitro production of TNF by isolated peritoneal cells was minimal and did not differ between the various treatment groups. Addition of interferon gamma did not restore the effect of FO on TNF production capacity. We conclude that dietary supplementation with FO is of no benefit in Leishmaniasis in susceptible Balb/c mice, and that L. amazonensis is an insufficient trigger for TNF production in this model.