Dyslipidemia: a prospective controlled randomized trial of intensive glycemic control in sepsis

Cappi, Sylas B.; Noritomi, Danilo Teixeira; Velasco, Irineu Tadeu; Curi, Rui; Loureiro, Tatiana Carolina Alba; Soriano, Francisco Garcia

doi:10.1007/s00134-011-2458-z

Cited by 35 publications

(29 citation statements)

References 41 publications

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“…While glycemic control lowered the lipoproteins and total cholesterol, FFAs, triglycerides and oxidized low density lipoprotein remained high which suggested that FFA response continued even under glycemic control [32]. This study suggests that FFA might represent a better therapeutic target in patients with sepsis [32]. …”

Section: Discussionmentioning

confidence: 99%

Inhibition of lipogenesis reduces inflammation and organ injury in sepsis

Idrovo

Yang

Jacob

et al. 2016

Journal of Surgical Research

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Background Sepsis is a life threatening acute inflammatory condition associated with metabolic complications. Accumulation of free fatty acids (FAA) induces inflammation and causes lipotoxic effects in the liver. Since fatty acid metabolism plays a role in the inflammatory response, we hypothesized that the administration of C75, a fatty acid synthase inhibitor, could alleviate the injury caused by sepsis. Methods Male mice were subjected to sepsis by cecal ligation and puncture (CLP). At 4 h after CLP, different doses of C75 (1 or 5 mg/kg BW) or vehicle (20% DMSO in saline) were injected intraperitoneally. Blood and liver tissues were collected at 24 h after CLP. Results C75 treatment with 1 mg- and 5 mg/kg BW significantly lowered FFA levels in the liver after CLP by 28% and 53%, respectively. Administration of C75 dose dependently reduced serum indexes of organ injury (AST, ALT, LDH) and serum levels of TNF-α and IL-6. In the liver, C75 treatment reduced inflammation (TNF-α, IL-6) and oxidative stress (iNOS, COX-2) in a dose-dependent manner. The 5 mg dose improved the 10-day survival rate to 85% from that of 55% in the vehicle. In the presence of C75, TNF-α release in RAW 246.7 cells with 4 h LPS stimulation were also significantly reduced. Conclusions C75 effectively lowered FFA accumulation in the liver, which was associated with inhibition of inflammation and organ injury as well as improvement in survival rate after CLP. Thus, inhibition of FFA by C75 could ameliorate the hepatic dysfunction seen in sepsis.

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Section: Discussionmentioning

confidence: 99%

Inhibition of lipogenesis reduces inflammation and organ injury in sepsis

Idrovo

Yang

Jacob

et al. 2016

Journal of Surgical Research

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“…Our analysis included 14,495 patients from 27 studies 128, 330, 331, 332, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359. None of the studies were especially prone to bias.…”

Section: Cq14: Blood Glucose Managementmentioning

confidence: 99%

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG2016)

Nishida

Ogura

Egi

et al. 2018

Acute Medicine & Surgery

157

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Background and PurposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG 2016), a Japanese‐specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 in Japanese. An English‐language version of these guidelines was created based on the contents of the original Japanese‐language version.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ), and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two‐thirds (>66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J‐SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation and its supporting evidence were also added to each recommendation statement. We conducted meta‐analyses for 29 CQs. Thirty seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for 5 CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese‐specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non‐specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

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“…[1][2][3] Critically ill patients present with various lipid disorders: high levels of triglycerides and free fatty acids (FFA); low levels of low-density lipoproteins; and low levels of high-density lipoproteins. 4 Increased lipolysis after burn injuries causes increased circulating triglycerides and FFA levels, These M2 macrophages inhibit conversion from resident macrophage to M1; 9,10 however, the mechanisms underlying M2 dominance in these tissues in critical illness are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Palmitate differentially regulates the polarization of differentiating and differentiated macrophages

Xiu

et al. 2015

Immunology

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SummaryThe tissue accumulation of M1 macrophages in patients with metabolic diseases such as obesity and type 2 diabetes mellitus has been well-documented. Interestingly, it is an accumulation of M2 macrophages that is observed in the adipose, liver and lung tissues, as well as in the circulation, of patients who have had major traumas such as a burn injury or sepsis; however, the trigger for the M2 polarization observed in these patients has not yet been identified. In the current study, we explored the effects of chronic palmitate and high glucose treatment on macrophage differentiation and function in murine bone-marrow-derived macrophages. We found that chronic treatment with palmitate decreased phagocytosis and HLA-DR expression in addition to inhibiting the production of pro-inflammatory cytokines. Chronic palmitate treatment of bone marrows also led to M2 polarization, which correlated with the activation of the peroxisome proliferator-activated receptor-c signalling pathway. Furthermore, we found that chronic palmitate treatment increased the expression of multiple endoplasmic reticulum (ER) stress markers, including binding immunoglobulin protein. Preconditioning with the universal ER stress inhibitor 4-phenylbutyrate attenuated ER stress signalling and neutralized the effect of palmitate, inducing a pro-inflammatory phenotype. We confirmed these results in differentiating human macrophages, showing an anti-inflammatory response to chronic palmitate exposure. Though alone it did not promote M2 polarization, hyperglycaemia exacerbated the effects of palmitate. These findings suggest that the dominant accumulation of M2 in adipose tissue and liver in patients with critical illness may be a result of hyperlipidaemia and hyperglycaemia, both components of the hypermetabolism observed in critically ill patients.

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Dyslipidemia: a prospective controlled randomized trial of intensive glycemic control in sepsis

Abstract: Free fatty acids respond to intensive glycemic control and, because of their high toxicity, can be a therapeutic target in patients with sepsis.

Cited by 35 publications

References 41 publications

Inhibition of lipogenesis reduces inflammation and organ injury in sepsis

Inhibition of lipogenesis reduces inflammation and organ injury in sepsis

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG2016)

Palmitate differentially regulates the polarization of differentiating and differentiated macrophages

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