Protective effects of tanshinone â ¡A on sepsis-induced multiple organ dysfunction: a literature review.

TanshinoneⅡA (TanⅡA) is a noteworthy lipophilic diterpene compound derived from the dried roots of the Traditional Chinese Medicine Danshen () that has various pharmacological properties, including anti-inflammatory, antibacterial, and antioxidative effects. Sepsis is a life-threatening organ dysfunction induced by a dysregulated host response to infection. Recently, increasing attention has been paid to sepsis-induced dysfunction of the intestine, car-diovascular system, lungs, kidneys, liver, and other organs. Experimental studies have shown that TanⅡA has therapeutic potential for sepsis-induced organ dysfunction owing to its anti-inflammatory, anti-apoptotic and regulatory effects on multiple signalling pathways. The purpose of this article is to evaluate the potential multiorgan protective effects of TanⅡA in sepsis.

Vitamin C as a treatment for organ failure in sepsis.

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with a high morbidity and mortality rate. Exogenous vitamin C supplementation is a potential therapeutic option for the treatment of multi-organ dysfunction in sepsis due to the significantly lower levels of vitamin C in the circulating blood of sepsis patients compared to healthy subjects and the importance of vitamin C in many of the physiological processes of sepsis. Vitamin C may influence the function of numerous organs and systems, including the heart, lungs, kidneys, brain, and immune defences, by reducing oxidative stress, inhibiting inflammatory factor surges, regulating the synthesis of various mediators and hormones, and enhancing immune cell function. With the development of multiple clinical randomized controlled trials, the outcomes of vitamin C treatment for critically ill patients have been discussed anew. This review's objectives are to provide an overview of how vitamin C affects various organ functions in sepsis and to illustrate how it affects each organ. Understanding the pharmacological mechanism of vitamin C and the organ damage caused by sepsis may help to clarify the conditions and clinical applications of vitamin C.

Plantamajoside alleviates acute sepsis-induced organ dysfunction through inhibiting the TRAF6/NF-κB axis.

CONTEXT: Plantamajoside (PMS) possesses rich pharmacological characteristics that have been applied to remedy dozens of diseases. However, the understanding of PMS in sepsis remains insufficient. OBJECTIVE: Role of PMS in sepsis-regulated organ dysfunction and potential mechanisms were investigated. MATERIALS AND METHODS: Thirty C57BL/6 male mice were adaptive fed for three days and used to establish acute sepsis model by caecal ligation and perforation (CLP). These experimental mice were divided into Sham, CLP, CLP + 25 mg PMS/kg body weight (PMS/kg), CLP + 50 mg PMS/kg and CLP + 100 mg PMS/kg (n = 6). The pathological and apoptotic changes of lung, liver and heart tissues were observed via HE and TUNEL staining. The injury-related factors of lung, liver and heart were detected by corresponding kits. ELISA and qRT-PCR were applied to assess IL-6/TNF-α/IL-1ß levels. Apoptosis-related and TRAF6/NF-κB-related proteins were determined using Western blotting. RESULTS: All doses of PMS enhanced the survival rates in the sepsis-induced mouse model. PMS remitted sepsis-mediated lung, liver and heart injury through prohibiting MPO/BALF (70.4%/85.6%), AST/ALT (74.7%/62.7%) and CK-MB/CK (62.3%/68.9%) levels. Moreover, the apoptosis index (lung 61.9%, liver 50.2%, heart 55.7% reduction) and IL-6/TNF-α/IL-1ß levels were suppressed by PMS. Furthermore, PMS lowered TRAF6 and p-NF-κB p65 levels, whereas TRAF6 overexpression reversed the protective influences of PMS in organ injury, apoptosis and inflammation triggered by sepsis. DISCUSSION AND CONCLUSIONS: PMS suppressed sepsis-induced organ dysfunction by regulating the TRAF6/NF-κB axis, and PMS treatment may be considered as a novel strategy for sepsis-caused damage in future.

Randomized Clinical Trial of Antioxidant Therapy Patients with Septic Shock and Organ Dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System.

BACKGROUND AND AIM: Here, we assess the effect of adjuvant antioxidant therapies in septic shock patients with organ dysfunction and their effect on the enzymatic and non-enzymatic antioxidant systems. METHODS: Randomized clinical trial run between 2018 and 2022. One hundred and thirty-one patients with septic shock were included in five groups with 25, 27, 24, 26 and 29 patients each. Group 1 received vitamin C (Vit C), Group 2 vitamin E (Vit E), Group 3 n-acetylcysteine (NAC), Group 4 melatonin (MT) and group 5 no treatment. All antioxidants were administered orally or through a nasogastric tube for 5 days as an adjuvant to standard therapy. RESULTS: All patients had multiple organ failure (MOF) and low Vit C levels. Vit C therapy decreased CRP, PCT and NO3-/NO2- but increased Vit C levels. The SOFA score decreased with MT in 75%, Vit C 63% and NAC 50% vs. controls 33% (p = 0.0001, p = 0.03 and p = 0.001 respectively). MT diminished lipid peroxidation (LPO) (p = 0.01) and improved total antioxidant capacity (TAC) (p = 0.04). Vit E increased thiol levels (p = 0.02) and tended to decrease LPO (p = 0.06). Selenium levels were decreased in the control group (p = 0.04). CONCLUSIONS: Antioxidants used as an adjuvant therapy in the standard treatment of septic shock decrease MOF and oxidative stress markers. They increase the TAC and thiols, and maintain selenium levels.

Multi-organ dysfunction as a presentation of calcium channel blocker intoxication.

SummaryWe report the case of a 73-year-old woman who intentionally ingested 400 mg of amlodipine in a suicidal attempt who initially presented with hypotension which persisted despite aggressive therapy with fluid resuscitation, multiple pressor support, high-dose insulin therapy and calcium infusion. Her haemodynamic instability evolved to include bradycardia requiring atropine and transcutaneous pacing. Eventually she required salvage therapy with intravenous lipid emulsion (ILE) therapy . Despite all aggressive therapy, she developed multi-organ failure resulting in death. The literature on high-dose insulin euglycaemic therapy (HIET) and ILE therapy shows mixed results with some showing significant improvement in haemodynamic status. In our case, it had no significant positive impact on the outcome.

Methionine supplementation for multi-organ dysfunction in MetRS-related pulmonary alveolar proteinosis.

INTRODUCTION: Pulmonary alveolar proteinosis related to mutations in the methionine tRNA synthetase (MARS1) gene is a severe, early-onset disease that results in death before the age of 2 years in one-third of patients. It is associated with a liver disease, growth failure and systemic inflammation. As methionine supplementation in yeast models restored normal enzymatic activity of the synthetase, we studied the tolerance, safety and efficacy of daily oral methionine supplementation in patients with severe and early disease. METHODS: Four patients received methionine supplementation and were followed for respiratory, hepatic, growth and inflammation-related outcomes. Their course was compared to those of historical controls. Reactive oxygen species production by patient monocytes before and after methionine supplementation was also studied. RESULTS: Methionine supplementation was associated with respiratory improvement, clearance of the extracellular lipoproteinaceous material and discontinuation of whole-lung lavage in all patients. The three patients who required oxygen or noninvasive ventilation could be weaned off within 60 days. In addition, liver dysfunction, inflammation and growth delay improved or resolved. At a cellular level, methionine supplementation normalised the production of reactive oxygen species by peripheral monocytes. CONCLUSION: Methionine supplementation was associated with important improvements in children with pulmonary alveolar proteinosis related to mutations in the MARS1 gene. This study paves the way for similar strategies for other tRNA synthetase deficiencies.

Therapeutic potential of megadose vitamin C to reverse organ dysfunction in sepsis and COVID-19.

Sepsis induced by bacteria or viruses can result in multiorgan dysfunction, which is a major cause of death in intensive care units. Current treatments are only supportive, and there are no treatments that reverse the pathophysiological effects of sepsis. Vitamin C has antioxidant, anti-inflammatory, anticoagulant and immune modulatory actions, so it is a rational treatment for sepsis. Here, we summarise data that support the use of megadose vitamin C as a treatment for sepsis and COVID-19. Megadose intravenous sodium ascorbate (150 g per 40 kg over 7 h) dramatically improved the clinical state and cardiovascular, pulmonary, hepatic and renal function and decreased body temperature, in a clinically relevant ovine model of Gram-negative bacteria-induced sepsis. In a critically ill COVID-19 patient, intravenous sodium ascorbate (60 g) restored arterial pressure, improved renal function and increased arterial blood oxygen levels. These findings suggest that megadose vitamin C should be trialled as a treatment for sepsis and COVID-19.

Intravenous rifampicin use in the management of amanita phalloides toxicity.

Context: Amanita phalloides related toxicity from amatoxins can result in acute liver and multi-organ failure and is responsible for 90% of all mushroom poisoning death. However, more evidence is needed in regards to different management strategies.Case details: We present two cases of amanita mushroom ingestion who were treated with intravenous rifampicin.Discussion: Further study is needed to establish the efficacy and role of rifampicin in amatoxin related mushroom poisoning.

Refractory gram-negative septic shock complicated by extended purpura fulminans and multiple organ failure in a 23-year-old puerpera -a case report.

BACKGROUND: Pregnancy-related infections are the third most common cause of maternal death worldwide. The aim of this report is to present a case of pregnancy-related infection, which progressed into refractory septic shock accompanied by purpura fulminans and multiple organ failure. CASE: A 23-year-old woman in the postpartum period developed fulminant, refractory septic shock complicated by purpura fulminans and multiple organ failure syndrome (acute respiratory distress syndrome, acute kidney injury, and encephalopathy). Management included antibacterial therapy, fluid and transfusion therapy, nutritional support, protective mechanical ventilation, hydrocortisone, a large dose of ascorbic acid, and thiamine. There were no neurological consequences and all organ functions returned to normal, although the predicted hospital mortality based on the Sequential Organ Failure Assessment (SOFA) score was more than 90%. CONCLUSIONS: Septic shock is a significant, yet not completely understood life-threatening condition, which can be associated with purpura fulminans, multiple organ dysfunction, disseminated intravascular coagulation, and massive tissue necrosis.

[Effectiveness of Xuebijing in treatment of multiple organ dysfunction syndrome: a Meta analysis].

OBJECTIVE: To systematical evaluate the effect of Xuebijing injection in the treatment of multiple organ dysfunction syndrome (MODS). METHODS: With the keywords including Xuebijing, multiple organ dysfunction syndrome, multiple organ dysfunction and multiple organ failure, PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP and Wanfang Data from the database start until March 4th, 2018 were searched for relevant randomized controlled trials (RCTs) related to Xuebijing injection combined conventional treatment versus conventional treatment alone for MODS. The control group received conventional western medicine treatment, including etiological treatment, antibiotics, mechanical ventilation, nutritional support, and comprehensive treatment to maintain fluid, electrolyte, acid and alkali balance. The experimental group was given traditional western medicine combined with Xuebijing injection. The observation parameters included 7-day and 28-day mortality, acute physiology and chronic health evaluation II (APACHE II) and Marshall score, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), the number of platelets, activated partial thromboplastin time (APTT) and prothrombin time (PT). According to the inclusion and exclusion criteria, two evaluators independently screened the literature, extracted data and evaluated the methodological quality of the included studies. RevMan 5.3 software was used for Meta analysis. Funnel plot was used to analyze publication bias. RESULTS: A total of 35 RCTs and 2 131 patients were enrolled, including 1 076 in the experimental group and 1 055 in the control group. The results of Meta analysis showed that compared with control group, Xuebijing combined conventional treatment was in favor to decrease the mortality of patients with MODS [7-day mortality: odds ratio (OR) = 0.42, 99% confidence interval (99%CI) = 0.26-0.69, P < 0.000 01; 28-day mortality: OR = 0.31, 99%CI = 0.21-0.45, P < 0.000 01], also could obviously reduce critical condition degree of APACHE II score and the organ function of Marshall score [APACHE II: mean difference (MD) = 3.24, 99%CI = 2.00-4.49, P < 0.000 01; Marshall score: MD = 1.95, 99%CI = 0.50-3.40, P = 0.000 5]. Meanwhile, the results of conventional western medicine combined with Xuebijing in the removal of IL-6 and TNF-α, platelets increase and improvement of PT were better than those of conventional western medicine (IL-6: MD = 5.56, 99%CI = 1.44-9.68, P = 0.000 5; TNF-α: MD = 4.97, 99%CI = 3.44-6.50, P < 0.000 01; platelets: MD = -50.79, 99%CI = -74.84 to -26.74, P < 0.000 1; PT: MD = 4.55, 99%CI = 3.96-5.14, P < 0.000 01), however, there was no obvious advantage in improving APTT (MD = 0.96, 99%CI = -5.08-7.00, P = 0.68). The analysis of funnel map showed that the effect points of various studies were mainly centered on the amount of combined effect, and the "inverted funnel" type was generally symmetrical distribution. However, because the number of the included studies was less, the literature bias could not be completely eliminated. CONCLUSIONS: Xuebijing injection may through its strong cytokines clearance, platelet increase and blood coagulation improvement to protect the organ function in patients with MODS, so as to reduce the mortality and improve the prognosis.

Can folate replacement induce lymphoma progression?

A 43-year-old Japanese man with a low haemoglobin level of 1.3 g/dL and multiorgan dysfunction syndrome (MODS) was admitted to our hospital. He was diagnosed with folate deficiency, which was initially attributed to his malnutrition. He was transfused with several units of packed red blood cells and treated with folate, thiamine and vitamin B12 supplements; he showed a prompt haematological response and recovery from MODS. However, 3 weeks after the initial recovery, he had a relapse of pancytopenia and developed high-grade fever along with rapidly enlarging, generalised lymphadenopathy. Bone marrow biopsy revealed hemophagocytosis, and lymph node biopsy revealed peripheral T-cell lymphoma, not otherwise specified. Folate supplementation may have promoted lymphoma progression.

Vitamin C Pharmacokinetics in Critically Ill Patients: A Randomized Trial of Four IV Regimens.

BACKGROUND: Early high-dose IV vitamin C is being investigated as adjuvant therapy in patients who are critically ill, but the optimal dose and infusion method are unclear. The primary aim of this study was to describe the dose-plasma concentration relationship and safety of four different dosing regimens. METHODS: This was a four-group randomized pharmacokinetic trial. Patients who were critically ill with multiple organ dysfunction were randomized to receive 2 or 10 g/d vitamin C as a twice daily bolus infusion or continuous infusion for 48 h. End points were plasma vitamin C concentrations during 96 h, 12-h urine excretion of vitamin C, and oxalate excretion and base excess. A population pharmacokinetic model was developed using NONMEM. RESULTS: Twenty patients were included. A two-compartment pharmacokinetic model with creatinine clearance and weight as independent covariates described all four regimens best. With 2 g/d bolus, plasma vitamin C concentrations at 1 h were 29 to 50 mg/L and trough concentrations were 5.6 to 16 mg/L. With 2 g/d continuous, steady-state concentrations were 7 to 37 mg/L at 48 h. With 10 g/d bolus, 1-h concentrations were 186 to 244 mg/L and trough concentrations were 14 to 55 mg/L. With 10 g/d continuous, steady-state concentrations were 40 to 295 mg/L at 48 h. Oxalate excretion and base excess were increased in the 10 g/d dose. Forty-eight hours after discontinuation, plasma concentrations declined to hypovitaminosis levels in 15% of patients. CONCLUSIONS: The 2 g/d dose was associated with normal plasma concentrations, and the 10 g/d dose was associated with supranormal plasma concentrations, increased oxalate excretion, and metabolic alkalosis. Sustained therapy is needed to prevent hypovitaminosis. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02455180; URL: www.clinicaltrials.gov.

Effects and mechanisms of compound Chinese medicine and major ingredients on microcirculatory dysfunction and organ injury induced by ischemia/reperfusion.

Microcirculation dysfunction and organ injury after ischemia and reperfusion (I/R) result from a complex pathologic process consisting of multiple links, with metabolism impairment in the ischemia phase and oxidative stress in the reperfusion phase as initiators, and any treatment targeting a single link is insufficient to cope with this. Compound Chinese medicine (CCM) has been applied in clinics in China and some Asian nations for >2000years. Studies over the past decades revealed the protective and therapeutic effect of CCMs and major ingredients on I/R-induced microcirculatory dysfunction and tissue injury in the heart, brain, liver, intestine, and so on. CCM contains diverse bioactive components with potential for energy metabolism regulation; antioxidant effect; inhibiting inflammatory cytokines release; adhesion molecule expression in leukocyte, platelet, and vascular endothelial cells; and the protection of thrombosis, albumin leakage, and mast cell degranulation. This review covers the major works with respect to the effects and underlying mechanisms of CCM and its ingredients on microcirculatory dysfunction and organ injury after I/R, providing novel ideas for dealing with this threat.

Oxidative stress in sepsis: Pathophysiological implications justifying antioxidant co-therapy.

Sepsis is one of the main causes of death among critically ill patients. Sepsis pathogenesis includes infection by gram-negative and gram-positive bacteria, fungi, or both; exacerbated inflammatory response; hypotension, with potential to cause vasodilatory shock; and lesser delivery of oxygen to tissues due to impairment of oxygen utilization by cells. The participation of reactive species and/or free radicals such as nitric oxide (NO), peroxynitrite (ONOO-), superoxide (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (OH) has been reported to underlie these effects. Mitochondrial dysfunction is related to loss of inner membrane potential and inhibition of the mitochondrial electron transfer chain and FoF1-adenosine triphosphate-synthase, resulting in cellular energetic failure. In addition, overproduction of NO due to inducible nitric oxide synthase (iNOS) activity has been associated with harmful effects such as general vasodilatation and hypo-responsiveness to therapeutic vasoconstrictor agents. Considering that iNOS expression is regulated by nuclear factor-κB, which may be activated by ROS, antioxidants could inhibit the overexpression of iNOS in sepsis. In line with this, several antioxidants such as vitamins C and E, polyphenols, melatonin, ß-glucan, N-acetylcysteine, mitochondrion-targeted antioxidants (MitoQ, MitoE, and peptides associated with dimethyltyrosine), selenium salts, and organoselenium compounds were effective in ameliorating oxidative stress in animal models of sepsis and in a number of clinical trials with septic patients.

Berberine in combination with yohimbine attenuates sepsis-induced neutrophil tissue infiltration and multiorgan dysfunction partly via IL-10-mediated inhibition of CCR2 expression in neutrophils.

Infiltration of activated neutrophils into the vital organs contributes to the multiple organ dysfunctions in sepsis. In the present study, we investigated the effects of berberine in combination with yohimbine (BY) on neutrophil tissue infiltration and multiple organ damage during sepsis, and further elucidated the involved mechanisms. Sepsis was induced in mice by cecal ligation and puncture (CLP). BY or CCR2 antagonist was administered 2h after CLP, and anti-IL-10 antibody (IL-10 Ab) or control IgG was injected intraperitoneally just before BY treatment. We found that IL-10 production was enhanced by BY therapy in septic mice. BY significantly attenuated neutrophil tissue infiltration and multiple organ injury in CLP-challenged mice, all of which were completely reversed by IL-10 Ab pretreatment. The levels of KC, MCP-1, MIP-1α and MIP-2 in the lung, liver and kidney were markedly increased 6h after CLP. BY reduced the tissue concentrations of these chemokines in septic mice, but IL-10 Ab pretreatment did not completely eliminate these inhibitory effects of BY. Particularly, dramatically increased CCR2 expression in circulating neutrophils of septic mice was reduced by BY and this effect was completely abolished by IL-10 Ab pretreatment. Furthermore, CCR2 antagonist also inhibited lung and renal injury and neutrophil infiltration in septic mice. Taken together, our data strongly suggest that BY therapy attenuates neutrophil tissue infiltration and multiple organ injury in septic mice, at least in part, via IL-10-mediated inhibition of CCR2 expression in circulating neutrophils.

THE PROTECTIVE ROLE OF CURCUMIN IN ZYMOSAN-INDUCED MULTIPLE ORGAN DYSFUNCTION SYNDROME IN MICE.

AIM: Multiple Organ Dysfunction Syndrome (MODS) is characterized as progressive and uncontrolled inflammatory response which involves activation of inflammatory cascades, cytokines release, and endothelial dysfunction, leading to deterioration of several organ functions. Curcumin is a natural polyphenol related to the yellow color of turmeric and has been reported to exert an anti-inflammatory, anti-oxidative, and anti-tumor effect. We conducted the study to investigate the effects of curcumin in non-septic MODS caused by zymosan in mice model. METHOD: The mice were randomly allocated into five groups (six mice per group): control group (treated with physiological saline, 0.1 mL daily for 3 days before and 1 h after physiological saline treatment), DMSO group (treated with DMSO, 0.1 mL daily for 3 days before and 1 h after physiological saline treatment), Curcumin group (200 mg/kg, suspended in DMSO, in a final volume of 0.1 mL, used for 3 days daily before and 1 h after physiological saline treatment), Zymosan+DMSO group (treated with DMSO, 0.1 mL daily for 3 days before and 1 h after zymosan treatment) and Zymosan+ Curcumin group (treated with curcumin, suspended in DMSO at a dose of 0.1 mL daily for 3 days before and 1 h after zymosan treatment).Mice in groups were sacrificed, and then the blood and tissues were collected to evaluate the severity of acute peritonitis, tissue histopathological changes, NO formation, oxidative stress, PMN infiltration, cytokines production, organ function, and NF-κB activation 18 h after when zymosan or physiological saline was injected. In another set of experiments, the mice were also grouped (20 mice per group) for monitoring the loss of body weight and mortality for 7 days after zymosan or physiological saline administration. RESULTS: Curcumin induces a significant reduction of the volume exudate and the neutrophil infiltration. It also could exhibit an outstanding protective effect against histopathological injury by decreasing the NO formation, oxidative stress, cytokines production, and infiltration of inflammatory cells. The organ function is also improved by administration of curcumin. Moreover, the activation of NF-κB is attenuated by curcumin in the MODS mice model, suggesting that curcumin attenuated the zymosan-induced MODS via inhibiting the expression of NF-κB possibly. In addition, curcumin-treated mice were shown to alleviate the severity of MODS characterized by a minor systemic toxicity, less body weight loss, and lower mortality caused by zymosan administration. CONCLUSION: Curcumin attenuates zymosan-induced MODS.

Polydatin: a new therapeutic agent against multiorgan dysfunction.

BACKGROUND: Polydatin (PD), a monocrystalline and polyphenolic drug isolated from a traditional Chinese herb (Polygonum cuspidatum), is protective against mitochondrial dysfunction and has been approved for clinical trials in the treatment of shock. However, whether the administration of PD has a therapeutic effect on multiple-organ dysfunction syndrome (MODS) requires investigation. MATERIAL AND METHODS: MODS was induced in Sprague-Dawley rats via hemorrhage and ligation and puncture of cecum-induced sepsis. The rats were divided into three groups as follows: MODS + PD, MODS + normal saline, and a control group (no treatment). Survival time, blood biochemical indexes, and histopathologic changes in various organs were evaluated; serum oxidative stress (advanced oxidative protein products [AOPPs]) and proinflammatory cytokines (tumor necrosis factor-α, interleukin 1ß, and interleukin 6) were assayed using enzyme-linked immunosorbent assay. Apoptosis-related protein expression (B-cell lymphoma-2 [Bcl-2] and Bax) was assayed by immunohistochemical and Western blotting methods, whereas caspase-3 activity was assayed by spectrophotometry. RESULTS: PD improved organ function, prolonged survival time, and reduced MODS incidence and serum levels of AOPPs and proinflammatory cytokines. It also decreased Bax levels and caspase-3 activity and increased Bcl-2 levels in the kidney and liver. CONCLUSIONS: PD may serve as a potential therapeutic for MODS, as it suppresses oxidative stress, inhibits inflammatory response, attenuates apoptosis, and protects against mitochondrial dysfunction.

[Mitigation of the damage of intestinal smooth muscle of rats with multiple organ dysfunction syndrome by Dachengqi decoction through mitochondrial pathway].

OBJECTIVE: To discuss the mechanism of promotion of gastrointestinal motility during multiple organ dysfunction syndrome (MODS) by Dachengqi decoction, by examining the expression of Bcl-2, Bax of mitochondrial pathway, and nuclear factor-ΚB (NF-ΚB) in smooth muscle of the small intestinal in rats. METHODS: According to the random number table, 100 healthy adult Wistar rats were divided into three groups: control group with 20 rats, model group with 40 rats, and Dachengqi decoction group with 40 rats. Rat model of MODS was reproduced by bacterial peritonitis induced by an injection of 1 mL Escherichia coli suspension (8×10(8) cfu/mL) into peritoneal cavity. The rats in control group were given 1 mL normal saline intraperitoneally. The rats in Dachengqi decoction group were given 10 mL/kg Dachengqi decoction by gavage, twice a day, before inoculation of the bacterial suspension. Twenty-four hours after modelling, rats in all groups were sacrificed by cervical vertebra luxation, and the upper small intestine was harvested to detect the protein expressions of Bcl-2, Bax, and NF-ΚB in smooth muscle tissue using immunohistochemical staining. RESULTS: In the control group, a large amount of Bcl-2 protein was expressed and it was distributed uniformly in small intestinal smooth muscle. On the other hand, a small amount of Bax and NF-ΚB protein was expressed, and they were also distributed uniformly. Compared with the control group, Bcl-2 protein was distributed only sparsely, and it was scattered in intestinal smooth muscle in blocks in the model group. The expression of Bcl-2 protein was obviously down-regulated [integral optical density (A) value: 7 115.3±1 797.2 vs. 22 085.5±4 892.2, P < 0.05], and this phenomenon was more prominent in circular muscle layer. Bax and NF-ΚB were densely distributed, and their expressions were upgraded obviously [Bax (A value): 33 802.6±5 778.0 vs. 7 984.4±1 804.5, NF-ΚB (A value): 2 465.9±664.8 vs. 1 572.6±256.0, both P < 0.05]. This phenomenon was more outstanding in circular muscle layer. Compared with that of the model group, the expression of Bcl-2 protein was stronger obviously in intestinal smooth muscle in Dachengqi decoction group (A value: 12 458.6±2 491.1 vs. 7 115.3±1 797.2, P < 0.05). The expressions of Bax and NF-ΚB were down-regulated obviously [Bax (A value): 12 529.2±2 018.5 vs. 33 802.6±5 778.0, NF-ΚB (A value): 1 843.1±373.6 vs. 2 465.9±664.8, both P < 0.05], and the change was more obvious in circular muscle layer. CONCLUSIONS: Dachengqi decoction may promote recovery of gastrointestinal motility through an increase of Bcl-2 expression in nuclear membrane, thus preventing translocation of Bax to mitochondrion, thereby reduces mitochondrial damage in MODS.

Pharmaconutrition with selenium in critically ill patients: what do we know?

Selenium is a component of selenoproteins with antioxidant, anti-inflammatory, and immunomodulatory properties. Systemic inflammatory response syndrome (SIRS), multiorgan dysfunction (MOD), and multiorgan failure (MOF) are associated with an early reduction in plasma selenium and glutathione peroxidase activity (GPx), and both parameters correlate inversely with the severity of illness and outcomes. Several randomized clinical trials (RCTs) evaluated selenium therapy as monotherapy or in antioxidant cocktails in intensive care unit (ICU) patient populations, and more recently several meta-analyses suggested benefits with selenium therapy in the most seriously ill patients. However, the largest RCT on pharmaconutrition with glutamine and antioxidants, the REducing Deaths due to Oxidative Stress (REDOXS) Study, was unable to find any improvement in clinical outcomes with antioxidants provided by the enteral and parenteral route and suggested harm in patients with renal dysfunction. Subsequently, the MetaPlus study demonstrated increased mortality in medical patients when provided extra glutamine and selenium enterally. The treatment effect of selenium may be dependent on the dose, the route of administration, and whether administered with other nutrients and the patient population studied. Currently, there are few small studies evaluating the pharmacokinetic profile of intravenous (IV) selenium in SIRS, and therefore more data are necessary, particularly in patients with MOD, including those with renal dysfunction. According to current knowledge, high-dose pentahydrate sodium selenite could be given as an IV bolus injection (1000-2000 µg), which causes transient pro-oxidant, cytotoxic, and anti-inflammatory effects, and then followed by a continuous infusion of 1000-1600 µg/d for up to 10-14 days. Nonetheless, the optimum dose and efficacy still remain controversial and need to be definitively established.