Vitamin D in Corona Virus Disease 2019 (COVID-19) Related Multisystem Inflammatory Syndrome in Children (MIS-C).

Multisystem Inflammatory Syndrome in children (MIS-C) is a rare but devastating complication of coronavirus disease 19 (COVID-19). The development of prognostic biomarkers and more importantly the implementation of new treatment modalities would have a significant impact in clinical practice regarding the outcome of MIS-C. Vitamin D could be a potential candidate. In this mini review we analyze the immunomodulatory role of vitamin D in viral infections and specifically in COVID-19. We also examine the current literature regarding the association of vitamin D with MIS-C and Kawasaki disease. The vitamin D was evaluated not only as a biomarker but also as a nutritional supplement. We concluded that vitamin D levels could be valuable in predicting severe forms of MIS-C and correction of abnormal levels in severe MIS-C may influences its evolution. 25-hydroxyvitamin D3 [25(OH)D3] supplementation raising serum [25(OH)D] concentrations potentially have a favorable effect in reducing the severity of MIS-C in certain circumstances. Further studies are needed to confirm these results.

Shenmai Injection Upregulates Heme Oxygenase-1 to Confer Protection Against Severe Acute Pancreatitis.

BACKGROUND: To explore the mechanism of Shenmai injection (SMI) on severe acute pancreatitis (SAP) through heme oxygenase-1 (HO-1) signaling. METHODS: A total of 40 male Sprague-Dawley (SD) rats (220-260 g) were grouped into the following four categories (n = 10): SAP + SMI + Zinc protoporphyrin (ZnPP), SAP + SMI, SAP, and sham surgery groups. ZnPP is a specific inhibitor of HO-1. Four percent of sodium taurocholate (1 mL/kg) was retrogradely injected via the pancreatic duct to induce the SAP model. The SAP group rats received 1.6 mL/kg saline by intravenous injection 30 min after the induction of SAP. The SAP + SMI group rats received 1.6 mL/kg SMI by intravenous injection 30 min after the induction of SAP. The SAP + SMI + ZnPP group rats received an intravenous injection of 1.6 mL/kg SMI and intraperitoneal administration of 30 mg/kg ZnPP 30 min after the SAP induction. Twenty-four hours after the SAP induction, blood samples were collected for the measurement of amylase, lipase, creatinine, myeloperoxidase, interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and HO-1 level, while tissue specimens were harvested for the determination of HO-1, TNF-α, and IL-10 mRNA level. Meanwhile, histopathological changes in organs (pancreas, lung, and kidney) were stored. RESULTS: The serum concentration of amylase, lipase, creatinine, and myeloperoxidase was higher in the SAP group than in the SAP + SMI group. Treatment with SMI increased HO-1 and IL-10 level and reduced TNF-α level in serum and tissues compared to the SAP group (P < 0.05). Treatment with SMI abolished the organ-damaging effects of SAP (P < 0.05). Furthermore, suppression of HO-1 expression by ZnPP canceled the aforementioned effects. CONCLUSIONS: SMI confers protection against the SAP-induced systemic inflammatory response and multiple organs damage via HO-1 upregulation.

Low plasma vitamin D is associated with adverse colorectal cancer survival after surgical resection, independent of systemic inflammatory response.

OBJECTIVE: We assessed the effect of surgical resection of colorectal cancer (CRC) on perioperative plasma vitamin D (25OHD) and C-reactive protein (CRP) level. We investigated the relationship between circulating vitamin D level and CRC survival. DESIGN: We sequentially sampled 92 patients undergoing CRC resection, and measured plasma 25OHD and CRP. For survival analyses, we assayed 25OHD and CRP in two temporally distinct CRC patient cohorts (n=2006, n=2100) and investigated the association between survival outcome, circulating vitamin D and systemic inflammatory response. RESULTS: Serial sampling revealed a postoperative fall (mean 17.3 nmol/L; p=3.6e-9) in plasma 25OHD (nadir days 1-2). CRP peaked 3-5 days postoperatively (143.1 mg/L; p=1.4e-12), yet the postoperative fall in 25OHD was independent of CRP. In cohort analyses, 25OHD was lower in the 12 months following operation (mean=48.8 nmol/L) than preoperatively (54.8 nmol/L; p=1.2e-5) recovering after 24 months (52.2 nmol/L; p=0.002). Survival analysis in American Joint Committee on Cancer stages I-III demonstrated associations between 25OHD tertile and CRC mortality (HR=0.69; 95% CI 0.46 to 0.91) and all-cause mortality (HR=0.68; 95% CI 0.50 to 0.85), and was independent of CRP. We observed interaction effects between plasma 25OHD and rs11568820 genotype (functional VDR polymorphism) with a strong protective effect of higher 25OHD only in patients with GG genotype (HR=0.51; 95% CI 0.21 to 0.81). We developed an online tool for predicted survival (https://apps.igmm.ed.ac.uk/mortalityCalculator/) that incorporates 25OHD with clinically useful predictive performance (area under the curve 0.77). CONCLUSIONS: CRC surgery induces a fall in circulating 25OHD. Plasma 25OHD level is a prognostic biomarker with low 25OHD associated with poorer survival, particularly in those with rs11568820 GG genotype. A randomised trial of vitamin D supplementation after CRC surgery has compelling rationale.

Electro-acupuncture attenuates inflammatory responses and intraabdominal pressure in septic patients: A randomized controlled trial.

BACKGROUND: A pathological increase in intraabdominal pressure (IAP) and inflammatory responses have negative effects on splanchnic, respiratory, cardiovascular, renal, and neurological function in septic patients with intestinal dysfunction. Electro-acupuncture (EA) has been evidenced to have a bidirectional neuron-endocrine-immune system regulating effect in patients with intestinal dysfunction. The purpose of current study was to evaluate the effects of EA at "Zusanli" (ST36) and "Shangjuxu" (ST37) on inflammatory responses and IAP in septic patients with intestinal dysfunction manifested syndrome of obstruction of the bowels Qi. METHODS: Eighty-two septic patients with intestinal dysfunction manifested syndrome of obstruction of the bowels Qi were randomly assigned to control group (n = 41) and EA group (n = 41). Patients in control group were given conventional therapies including fluid resuscitation, antiinfection, vasoactive agents, mechanical ventilation (MV), supply of enteral nutrition, and glutamine as soon as possible. In addition to conventional therapies, patients in EA group underwent 20-minutes of EA at ST36-ST37 twice a day for 5 days. At baseline, posttreatment 1, 3, and 7 days, serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) and IAP levels, were measured, respectively. And days on MV, length of stay in intensive care unit (ICU) and 28 days mortality were recorded. RESULTS: The serum levels of TNF-α and IL-1ß and IAP levels at posttreatment 1, 3, and 7 days were lower significantly in the EA group compared with the control group (mean [SD]; 61.03 [20.39] vs 79.28 [20.69]; P < .005, mean [SD]; 35.34 [18.75] vs 66.53 [30.43]; P < .005 and mean [SD]; 20.32 [11.30] vs 32.99 [20.62]; P = .001, respectively, TNF-α. Mean [SD]; 14.11 [5.21] vs 16.72 [5.59]; P = .032, mean [SD]; 9.02 [3.62] vs 12.10 [4.13]; P = .001 and mean [SD]; 5.11 [1.79] vs 8.19 [2.99]; P < .005, respectively, IL-1ß. Mean [SD]; 14.83 [5.58] vs 17.55 [3.37]; P = .009, mean [SD]; 11.20 [2.57] vs 14.85 [3.01]; P < .005 and mean [SD]; 8.62 [2.55] vs 11.25 [2.72]; P < .005, respectively, IAP). There were no significant differences in the duration of MV, length of stay in ICU, and 28d mortality between the groups. CONCLUSION: EA at ST36-ST37 attenuated inflammatory responses through reduction in serum levels of TNF-α and IL-1ß and IAP in septic patients with intestinal dysfunction manifested syndrome of obstruction of the bowels Qi.

Early local delivery of vancomycin suppresses ectopic bone formation in a rat model of trauma-induced heterotopic ossification.

Heterotopic ossification (HO) is a debilitating sequela of high-energy injuries. It frequently requires surgical excision once symptomatic and there is no practical prophylaxis for combat-injured patients. In this study, we examined the effect of local vancomycin powder on HO formation in a small animal model of blast-related, post-traumatic HO. Male Sprague-Dawley rats were subjected to a polytraumatic extremity injury and amputation with or without methicillin-resistant Staphylococcus aureus infection. Animals were randomized to receive a single local application of vancomycin (20 mg/kg) at the time of injury (POD-0, n = 34) or on postoperative day-3 (POD-3, n = 11). Quantitative volumetric measurement of ectopic bone was calculated at 12-weeks post-injury by micro-CT. Bone marrow and muscle tissues were also collected to determine the bacterial burden. Blood for serum cytokine analysis was collected at baseline and post-injury. Vancomycin treatment on POD-0 suppressed HO formation by 86% and prevented bone marrow and soft tissue infections. We concurrently observed a marked reduction histologically in nonviable tissue, chronic inflammatory cell infiltrates, bone infection, fibrous tissue, and areas of bone necrosis within this same cohort. Delayed treatment was significantly less efficacious. Neither treatment had a marked effect on the production of pro-inflammatory cytokines. Our study demonstrates that local vancomycin treatment at the time of injury significantly reduces HO formation in both the presence and absence of infection, with decreased efficacy if not given early. These findings further support the concept that the therapeutic window for prophylaxis is narrow, highlighting the need to develop early treatment strategies for clinical management. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2397-2406, 2017.

Selenium, copper, zinc, iron levels and mortality in patients with sepsis and systemic inflammatory response syndrome in Western Black Sea Region, Turkey.

OBJECTIVE: To evaluate the changing levels of selenium, copper, zinc and iron in patients with sepsis and systemic inflammatory response syndrome and their influence on mortality. METHODS: The prospective study was conducted at a tertiary care university hospital in Zonguldak city in the western Black Sea region of Turkey from January 2012 to December 2013, and comprised patients with sepsis and systemic inflammatory response syndrome. Blood samples were taken on 1st, 3rd, 5th and 7th days to measure serum selenium, copper, zinc and iron levels. Patients' demographic data, presence of additional diseases and mortality were recorded. RESULTS: Of the 57 patients, 28(49.1%) were female and 29(50.9%) were male, with an overall mean age of 60.3±19.4 years, mean height of 166.1±11.4cm, mean weight of 76.5±17.5kg. Copper and zinc levels were in the normal range, while selenium and iron levels were lower than the limit values at all measuring periods. There was no significant difference between first and other days in accordance with element levels (p>0.05). Baseline copper levels in patients with malignancy were lower than patients without malignancy (p< 0.05). In hypertensive patients, baseline copper levels were higher and 7th day levels were lower than non-hypertensive (p< 0.05). Baseline selenium levels of those who died were lower than the other patients (p< 0.05). Selenium and iron levels were decreased in patients with sepsis-systemic inflammatory response syndrome and copper levels were lower in patients with malignancy, hypertension and chronic obstructive pulmonary disease (p< 0.05). There was no change in zinc levels of the patients. CONCLUSIONS: Reduced basal selenium levels of patients with sepsis and systemic inflammatory response syndrome were associated with mortality.

The effect of the systemic inflammatory response on plasma zinc and selenium adjusted for albumin.

BACKGROUND & AIM: The magnitude of systemic inflammatory response, as evidenced by C-reactive protein (CRP), is a major factor associated with lower zinc and selenium. They may also be influenced by their binding proteins, such as albumin. The aim of the present study was to examine the relationships between plasma zinc, selenium and the systemic inflammatory response in a large cohort of patients referred for nutritional screen and also to examine these relationships in patients with critical illness. METHODS: Patients referred for nutritional assessment of zinc (n = 743) and selenium (n = 833) and 114 patients with critical illness were examined. Intra-assay imprecision was <10% for these analytes. RESULTS: In the nutritional screen cohort, plasma zinc was significantly associated with CRP (rs = -0.404, p < 0.001) and albumin (rs = 0.588, p < 0.001). For each CRP category (≤10, 11-80, >80 mg/l) the zinc/albumin ratio x100 was similar (31, 33 and 32 respectively, p = 0.029). Plasma selenium was significantly associated with CRP (rs = -0.489, p < 0.001) and albumin (rs = 0.600, p < 0.001). With increasing CRP category (≤10, 11-80, >80 mg/l) the selenium/albumin ratio ×100 was lower (2.3, 2.1 and 1.8 respectively, p < 0.001). Similar relationships were also observed in the cohort of patients with critical illness. CONCLUSION: Plasma zinc was associated with both CRP and albumin. The impact of the systemic inflammatory response could be largely adjusted by albumin concentrations. Plasma selenium was associated with both CRP and albumin. The impact of the systemic inflammatory response on plasma selenium concentrations could not be reasonably adjusted by albumin concentrations.

[Impacts of electroacupucnture at Zusanli (ST 36) and Feishu (BL 13) on the postoperative inflammatory reaction and pulmonary complications in senile patients after radical resection of pulmonary carcinoma].

OBJECTIVE: To observe the impacts of electroacupuncture (EA) at Zusanli (ST 36) and Feishu (BL 13) applied 30 min before the operation till the end of the operation on the postoperative inflammatory reaction and pulmonary complications in the senile patients after radical resection of pulmonary carcinoma. METHODS: Eighty senile patients of pulmonary carcinoma were selected and randomized into an observation group and a control group, 40 cases in each one. In the observation group, EA stimulation at Zusanli (ST 36) and Feishu (BL 13) was used 30 min before the operation till the end of the operation. In the control group, electric stimulation was not used. Separately, before operation (T1, basic state), 12 h after operation (T2) and 24 h after operation (T3), blood sample was collected from the central vein. The concentrations of plasma tumor necrosis factor-ɑ (TNF-ɑ) and interleukin-10 (IL-10) were detected. Additionally, the radial arterial blood sample was collected at the above time points; oxygen partial pressure (PaO2) was determined; pulmonary alveoli-arterial partial pressure of oxygen (PA-aDO2) and oxygenation index (OI) were calculated. The pulmonary complication in the two days after operation was recorded. RESULTS: Compared with the control group, in the observation group, at T2 and T3, TNF-ɑ concentration and PA-aDO2 were lower (all P<0.05); plasma IL-10 concentration and OI were higher (all P<0.05). In the observation group, the incidences of postoperative pneumonia and acute pulmonary injury were lower than those in the control group (both P<0.05). CONCLUSIONS: EA reduces the postoperative inflammatory reaction in the senile patients with radical resection of pulmonary carcinoma and decreases the postoperative pulmonary complicattizen.

Soluble CD14 subtype (sCD14-ST) presepsin in premature and full term critically ill newborns with sepsis and SIRS.

Neonatal sepsis still remains a major cause of morbidity and mortality in neonatal intensive care unit (NICU). Recently, soluble CD14 subtype (sDC14-ST) also named presepsin, was proposed as an effective biomarker for diagnosing, monitoring, and assessing the risk of neonatal sepsis and septic shock. The aim of this study was to investigate the diagnostic accuracy of sCD14-ST presepsin in diagnosing neonatal bacterial sepsis and in discriminating non-bacterial systemic inflammatory response syndrome (SIRS) from bacterial sepsis. This study involved 65 critically ill full-term and preterm newborns admitted to the neonatal intensive care unit (NICU), divided into three groups: 25 newborns with bacterial neonatal sepsis (group A); 15 newborns with a diagnosis of non-bacterial SIRS and with no localizing source of bacterial infection (group B); and 25 babies with no clinical or bacteriological signs of systemic or local infection receiving routine NICU care, most of them treated with phototherapy for neonatal jaundice (group C). A total of 102 whole blood samples were collected, 40 in group A, 30 in group B and 32 in group C. In 10 babies included in group A, sCD14-ST presepsin was also measured in an additional second blood sample collected 3 days after the start of antibiotic treatment. sCD14-ST presepsin was measured by a commercially available chemiluminescent enzyme immunoassay (CLEIA) optimized on an automated immunoassay analyzer. Statistical analysis was performed by means of MedCalc® statistical package; receiver operating characteristic (ROC) analysis was computed, and the area under the ROC curve (AUC) was used to evaluate the ability of sCD14-ST to discriminate neonatal bacterial sepsis from non-bacterial SIRS. Blood sCD14-ST presepsin levels were found significantly higher in bacterial sepsis when compared with controls (p<0.0001); similarly, they were higher in non-bacterial SIRS when compared with controls (p<0.0001). However, no statistically significant difference was found between bacterial sepsis and non-bacterial SIRS (p=0.730). In our population, CRP and sCD14-ST did not correlate with each other. ROC analysis revealed that sCD14-ST presepsin has an area under the curve (AUC) of 0.995 (95% C.I.: 0.941-1.00) greater than that of CRP (0.827; 95% C.I.: 0.72-0.906). Similarly, in the group of babies with non-infectious SIRS, sCD14-ST AUC was greater than CRP AUC (0.979; 95% C.I.: 0.906-0.999 versus 0.771; 95% C.I.: 0.647-0.868). In controls, preliminary reference intervals for sCD14-ST ranged 223.4-599.7 ng/L, being significantly different from those previously published elsewhere. In conclusion, sCD14-ST presepsin could be introduced in clinical practice as a diagnostic tool for improving the management of neonatal sepsis and non-bacterial SIRS.

Biomarkers in critically ill patients with systemic inflammatory response syndrome or sepsis supplemented with high-dose selenium.

OBJECTIVE: Low levels of selenium (Se) and glutathione peroxidase (GSHPx), a key selenoenzyme, were documented in systemic inflammatory response syndrome (SIRS) and sepsis, both associated with high mortality. Se supplementation had mixed effects on outcome. We hypothesized that Se supplementation could have a different impact on biomarkers and 28-day mortality in patients with SIRS vs. sepsis. METHODS: Adult patients with SIRS or sepsis were randomized to either high-dose (Se+, n = 75) or standard-dose (Se-, n = 75) Se supplementation. Plasma Se, whole blood GSHPx activity, C-reactive protein (CRP), procalcitonin (PCT), prealbumin, albumin and cholesterol levels were measured serially up to day 14. RESULTS: There was no difference in mortality between Se- (24/75) vs. Se+ group (19/75; p = 0.367) or between SIRS and septic patients (8/26 vs. 35/124; p = 0.794). There was a trend to reduced mortality in SIRS patients in the Se+ vs. Se- group (p = 0.084). Plasma Se levels increased in the Se+ group only in patients with sepsis but not in patients with SIRS. Plasma Se levels correlated with GSHPx. In SIRS/Se+ group, Se correlated only with GSHPx. In SIRS/Se- group, Se correlated with cholesterol but not with other biomarkers. In sepsis patients, Se levels correlated with cholesterol, GSHPx and prealbumin. Cholesterol levels were higher in survivors in the Se- group. CONCLUSIONS: Se levels correlated with GSHPx activity and other nutritional biomarkers with significant differences between SIRS and sepsis groups. High-dose Se supplementation did not affect mortality but a strong trend to decreased mortality in SIRS patients warrants further studies in this population.

Increased plasma selenium is associated with better outcomes in children with systemic inflammation.

OBJECTIVE: The aim of this study was to assess the effects of changes in plasma selenium on the outcome of critically ill children. METHODS: Plasma selenium was prospectively measured in 99 children with acute systemic inflammation. The exposure variables were selenium level on admission and on day 5 of stay in the intensive care unit (ICU) and the difference in selenium concentrations between day 5 post-admission and the ICU admission (delta selenium). Selenium was given only as part of enteral diets. Age, malnutrition, red cell glutathione peroxidase-1 activity, serum C-reactive protein, Pediatric Index of Mortality 2, and Pediatric Logistic Organ Dysfunction scores were analyzed as covariates. The outcome variables were ventilator-free days, ICU-free days, and 28-d mortality. RESULTS: Plasma selenium concentrations increased from admission (median 23.4 µg/L, interquartile range 12.0-30.8) to day 5 (median 25.1 µg/L, interquartile range 16.0-39.0; P = 0.018). After adjustment for confounding factors, a delta selenium increase of 10 µg/L was associated with reductions in ventilator days (1.3 d; 95% confidence interval [CI], 0.2-2.3; P = 0.017) and ICU days (1.4 d; 95% CI, 0.5-2.3; P < 0.01). Delta selenium >0 was associated with decreased 28-d mortality on a univariate model (odds ratio, 0.67; 95% CI, 0.46-0.97; P = 0.036). The mean daily selenium intake (6.82 µg; range 0-48.66 µg) was correlated with the increase in selenium concentrations on day 5. CONCLUSIONS: An increase in plasma selenium is independently associated with shorter times of ventilation and ICU stay in children with systemic inflammation. These findings raise the hypothesis that selenium supplementation could be beneficial in children with critical illnesses.

[Pharmaconutrition with parenteral selenium in sepsis]. / Farmaconutrición parenteral con selenio en la sepsis.

Critical illness is characterized by oxidative stress which leads to multiple organ failure, and sepsis-related organ dysfunction remains the most common cause of death in the intensive care unit. Over the last 2 decades, different antioxidant therapies have been developed to improve outcomes in septic patients. According to recent evidence, selenium therapy should be considered the cornerstone of the antioxidant strategies. Selenium given as selenious acid or sodium selenite should be considered as a drug or pharmaconutrient with prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is administered, particularly in the early stage of severe sepsis/septic shock. To date, several phase ii trials have demonstrated that selenium therapy may be able to decrease mortality, improve organ dysfunction and reduce infections in critically ill septic patients. The effect of selenium therapy in sepsis syndrome must be confirmed by large, well designed phase iii clinical trials. The purpose of this review is to discuss current evidence on selenium pharmaconutrition in sepsis syndrome.

Erythrocyte selenium concentration as a marker of selenium status.

BACKGROUND & AIMS: Plasma selenium concentration and glutathione peroxidase (GPx) activity are commonly used as markers of selenium nutritional status. However, plasma selenium concentrations fall independently of selenium status during the acute phase response and GPx is analytically problematic. The assay for erythrocyte selenium is robust and concentrations are unaffected by the systemic inflammatory response. This study was performed to investigate the validity of erythrocyte selenium measurement in assessing selenium status. METHODS: C-reactive protein (CRP), plasma and erythrocyte selenium concentrations and GPx activity were measured in 96 women from two regions of Malawi with low and high selenium dietary intakes. CRP and plasma and erythrocyte selenium was measured in 91 critically ill patients with a systemic inflammatory response. RESULTS & CONCLUSIONS: The median CRP value of all subjects from Malawi was 4.2 mg/L indicating no inflammation. The median CRP value for the critically ill patients was 126 mg/L indicating this group was inflamed. In the non-inflamed population there was a strong positive correlation (r = 0.95) between erythrocyte and plasma selenium and a strong positive correlation (r = 0.77) between erythrocyte selenium and erythrocyte GPx up to 6.10 nmol/g Hb after which maximal activity was reached. In the inflamed population, plasma selenium was low, erythrocyte selenium was normal and there was a weak correlation (r = 0.30) between selenium concentrations in plasma and erythrocytes. This demonstrates that plasma selenium is affected by the inflammatory response while erythrocyte selenium concentration is unaffected and can be used to reliably assess selenium status across a wide range of selenium intakes.

Extracts of Ficus exasperata leaf inhibit topical and systemic inflammation in rodents and suppress LPS-induced expression of mediators of inflammation in macrophages.

The leaves of Ficus exasperata are mashed and prepared as poultices that are placed on swellings, wounds, and arthritic joints to relieve swelling and pains by the Igede tribal community of Nigeria. The leaf and stalk are also squeezed and used to mitigate itching or inflammation. These claimed benefits inspired this study in which topical and systemic (acute, chronic) anti-inflammatory activities of a methanol/methylene chloride leaf extract of F. exasperata (MFE) were assessed in rodents. Effects of an aqueous leaf extract (AFE) on lipopolysaccharide-induced expression of interleukin-1ß (IL-1ß), tumor necrosis factor (TNF)-α, and inducible nitric oxide (iNO) were also investigated in murine bone marrow-derived macrophage (BMDM) cultures. Treatment of rats with MFE (200 and 400 mg/kg) led to significant inhibition of acute and chronic inflammation induced by, respectively, agar and formaldehyde in the paws. Topically, pre-application of mice with MFE (5 µg/ear) also significantly inhibited (by up to 21%) ear edema induced by xylene. In vitro, pre-treatment of BMDM with 5-100 µg AFE/ml significantly inhibited IL-1ß, TNFα, and iNO production in a dose-related manner. BMDM viability was not significantly affected AFE at concentrations up to 200 µg/ml. Initial studies showed that flavonoids, alkaloids, and terpenoids were the predominant phytoconstituents in each extract. In conclusion, the results of the various investigations indicated that F. exasperata leaf extracts possess anti-inflammatory properties that could underlie the benefits associated with the folklore use of the plant. The results also show that the extracts may be acting through a suppression of mediators of inflammation, such as IL-1ß, TNFα, and iNO.

[Protection of huanglian jiedu decoction on systemic and vascular immune responses of high fat induced apoE(-/-) mice].

OBJECTIVE: To observe the effect of Huanglian Jiedu IJecoction (HJU) on systemic and vascular immune responses of high fat diet fed apoE deficient (apoE(-/-)) mice. METHODS: Eight wild type C57BL6 mice were recruited as the wild type common food group. Totally 24 apoE(-/-) mice were randomly divided into the ApoE'common food group, the ApoE(-/-) hyperlipidemia group, and the ApoE(-/-) hyperlipidemia plus HJD group, 8 in each group. In the present study, the common food mice and high fat fed mice were fed with a chow diet or a high cholesterol diet for 4 weeks. HJD was given to mice in the ApoE(-/-) hyperlipidemia plus HJD group at the daily dose of 5 g/kg by gastrogavage, while equal volume of pure water was given to mice in the rest groups by gastrogavage. Four weeks later, the plasma levels of blood lipids, the ratio of peripheral blood mononuclear cells, and expressions of Toll-like receptor 4 (TLR-4) and CD36 on the monocytes were detected. The pathological changes and expressions of cytokines in local aorta were detected. The plasma cytokine levels in response to lipopolysaccharide (LPS) were analyzed. Results (1) Compared with the wild type common food group, TO, TG, and LDL-O significantly increased in the ApoE(-/-) common food group (P < 0. 05, P < 0.01). Compared with the ApoE(-/-) common food group, TC and LDL-C significantly increased in the hyperlipidemia group (P < 0. 05). There was no statistical difference in each index between the ApoE(-/-) hyperlipidemia group and the ApoE(-/-) hyperlipidemia plus HJD group (P > 0.05). (2) Compared with the wild type common food group, no obvious change of the ratio of peripheral blood mononuclear cells happened, the TLR4 expression level significantly increased in the ApoE'common food group (P < 0. 05). Compared with the ApoE common food group, the ratio of peripheral blood mononuclear cells and the TLR4 expression level significantly increased in the ApoE' hyperlipidemia group (P < 0.05). Compared with the ApoE(-/-) hyperlipidemia group, the ratio of peripheral blood mononuclear cells and the TLR4 expression level significantly decreased. Besides, the CD36 expression level also significantly decreased (P<0.05). (3) After stimulated by LPS for 3 h, compared with the wild type common food group, plasma TNF-ct and IL-b expressions significantly increased in the ApoE(-/-) common food group (P < 0.05). Compared with the ApoE(-/-) common food group, plasma expressions of IL-12, TNF-alpha, MCP-1, and IL-10 increased, but with no statistical difference in the ApoE(-/-) hyperlipidemia group (P > 0.05). After 4-week intervention of HJD, compared with the ApoE(-/-) hyperlipidemia group, the MCP-1 expression was significantly down-regulated, while the IL-10 expression significantly increased, showing statistical difference (P < 0.05). Compared with the wild type common food group, mRNA expression levels of IFN-gamma, MCP-1 , TNF-alpha, IL-10, and IL-1beta significantly increased (P < 0. 05, P < 0.01). Compared with the ApoE(-/-) common food group, not only mRNA expression levels of IFN-gamma, MCP-1, TNF-alpha, and IL-1beta, further significantly increased, but also IL-12, IL-10, and TGF-beta significantly increased (P < 0. 05, P < 0. 01). After 4-week intervention of HJD, compared with the ApoE(-/-) hyperlipidemia group, mRNA expression levels of MCP-1, TNF-alpha, IL-1beta, and IL-12 significantly decreased in the ApoE(-/-) hyperlipidemia plus HJD group (P < 0.05, P < 0.01). CONCLUSIONS: High fat diet induced systemic reaction and inflammatory reactions of local vessels. The local inflammatory response of vessels exceeded systemic inflammatory response. Intervention of HJD could attenuate inflammatory response, especially in local arteries. Meanwhile, it enhanced systemic anti-inflammatory reactions.

Lower whole blood selenium level is associated with higher operative risk and mortality following cardiac surgery.

PURPOSE: The authors intended to test their hypothesis that a low blood selenium level is associated with higher mortality, morbidity, and increased inflammatory response following cardiac surgery. METHODS: A single-center clinical survey was conducted on 197 consecutive patients undergoing on-pump operation in Debrecen, Hungary. Blood samples for whole blood selenium analysis were taken immediately before the surgery. Their risk profiles were evaluated according to the EuroSCORE. The outcome parameters were as follows: 30-day mortality, incidence of systemic inflammatory response syndrome, and cardiac and renal dysfunction. The main laboratory outcome variables were the postoperative concentrations of C-reactive protein and cardiac troponin I. RESULTS: The mean blood selenium level was significantly lower in non-survivors 102.2 ± 19.5 µg/L compared with survivors 111.1 ± 16.9 µg/L (p = 0.047), and the mean age, EuroSCORE values, and troponin concentrations were significantly higher in the non-survivors. To exclude these potential confounders a logistic regression model was fitted to our data, with mortality as the outcome and the EuroSCORE, the degree of troponin elevation, and selenium concentration as explanatory variables. This model revealed that a lower selenium level was a minor but apparently existing risk factor for postoperative mortality. CONCLUSION: Further examinations are required to clarify the question that remained unanswered in this study: the role of low selenium in the causality chain leading to higher postoperative mortality.

Superiority of a fish oil-enriched emulsion to medium-chain triacylglycerols/long-chain triacylglycerols in gastrointestinal surgery patients: a randomized clinical trial.

OBJECTIVE: Compared with soybean oil, a fish oil-enriched emulsion can improve the clinical outcomes of patients requiring parenteral nutrition. However, the superiority of fish oil emulsion to medium-chain triacylglycerols/long-chain triacylglycerols for short-term administration has seldom been discussed. METHODS: Sixty-four adult patients with gastrointestinal diseases were randomly assigned to receive isocaloric and isonitrogenous total parenteral nutrition with an ω-3 fatty acid-enriched emulsion (Lipoplus; study group, n = 32) or medium-chain triacylglycerols/long-chain triacylglycerols (Lipofundin; control group, n = 32) for 5 d after surgery. Safety and efficacy parameters were assessed on postoperative days 1, 3, and 6. RESULTS: Clinical outcomes including infectious complications and systemic inflammatory response syndrome were comparable between the two groups. Total bilirubin decreased over time in the study group versus an increase in the control group (P = 0.017). Activated partial thromboplastin time in the study group was prolonged significantly compared with the control group from days 1 to 3 (P = 0.002), although the prolongation stopped at the study termination. There were no differences in changes of C-reactive protein, interleukin (IL)-1, IL-8, IL-10, vascular endothelial growth factor (VEGF), and the distribution of the T-cell subpopulation between the two groups. However, fish oil consumption led to an increase in leukotriene B5/ leukotriene B4 and significant decreases in IL-6, tumor necrosis factor-α, and nuclear factor-κB. Furthermore, the overall changes in tumor necrosis factor-α and nuclear factor-κB were positively associated (R(2) = 0.295, P < 0.001). CONCLUSIONS: Gastrointestinal surgery patients benefited from a fish oil-enriched emulsion rather than medium-chain triacylglycerols/long-chain triacylglycerols in the amelioration of liver function and immune status. The positive association of tumor necrosis factor-α and nuclear factor-κB might be involved in the potential anti-inflammation mechanism of fish oil.

Propolis derivatives inhibit the systemic inflammatory response and protect hepatic and neuronal cells in acute septic shock.

BACKGROUND: Severe pathogenic infection triggers excessive release of cytokines as part of the massive inflammatory response associated with septic shock. OBJECTIVES: To investigate the protective effect of caffeic acid phenethyl ester (CAPE) against lipopolysaccharide (LPS) induced endotoxemia, hepatic and neuronal damage and the associated systemic inflammatory response (SIR). METHODS: Fifty male Wister rats were divided into: control, LPS, and CAPE+LPS groups. Plasma concentrations of various cytokines, including TNF-α, IL-1α, IL-1ß, IL-6, IL-4, IL-10, and sICAM-1 were evaluated. In addition, the histopathological changes in the hepatic and neural cells were assessed. RESULTS: The LPS group showed high inflammatory cytokines and sICAM-1 levels reflecting the presence of SIR. Hepatocyte necrosis, apoptosis, extensive hemorrhage and inflammatory cellular infiltration together with brain astrocytes swelling, early neuron injury and presence of inflammatory foci confirmed the toxic tissue damage. Use of CAPE decreased the inflammatory cytokines and increased the anti-inflammatory cytokines levels. This biochemical evidence of decreased SIR was confirmed histologically by decreased cellular infiltration in the liver and brain tissue which coincides with preserved structure and protection of the liver and brain cells from the toxic effects of LPS. CONCLUSION: The ability of CAPE to alleviate the SIR, hepatic and neuronal cell damage induced by LPS and galactosamine could be attributed to its ability to reverse the imbalance of the pro- and anti-inflammatory cytokines which may lead to the inhibition of adhesion molecules' expression. CAPE is a promising agent that could help in the prophylaxis and treatment of septic shock.

Propolis derivatives inhibit the systemic inflammatory response and protect hepatic and neuronal cells in acute septic shock

BACKGROUND: Severe pathogenic infection triggers excessive release of cytokines as part of the massive inflammatory response associated with septic shock. OBJECTIVES: To investigate the protective effect of caffeic acid phenethye ester (CAPE) against lipopolysaccharide (LPS) induced endotoxemia, hepatic and neuronal damage and the associated systemic inflammatory response (SIR). METHODS: Fifty male Wister rats were divided into: control, LPS, and CAPE+LPS groups. Plasma concentrations of various cytokines, including TNF-α, IL-1α, IL-1β, IL-6, IL-4, IL-10, and sICAM-1 were evaluated. In addition, the histopathological changes in the hepatic and neural cells were assessed. RESULTS: The LPS group showed high inflammatory cytokines and sICAM-1 levels reflecting the presence of SIR. Hepatocyte necrosis, apoptosis, extensive hemorrhage and inflammatory cellular infiltration together with brain astrocytes swelling, early neuron injury and presence of inflammatory foci confirmed the toxic tissue damage. Use of CAPE decreased the inflammatory cytokines and increased the anti-inflammatory cytokines levels. This biochemical evidence of decreased SIR was confirmed histologically by decreased cellular infiltration in the liver and brain tissue which coincides with preserved structure and protection of the liver and brain cells from the toxic effects of LPS. CONCLUSION: The ability of CAPE to alleviate the SIR, hepatic and neuronal cell damage induced by LPS and galactosamine could be attributed to its ability to reverse the imbalance of the pro- and anti-inflammatory cytokines which may lead to the inhibition of adhesion molecules' expression. CAPE is a promising agent that could help in the prophylaxis and treatment of septic shock.

Autotransfusion system or integrated automatic suction device in minimized extracorporeal circulation: influence on coagulation and inflammatory response.

OBJECTIVE: To measure surrogate markers of coagulation activation as well as of the systemic inflammatory response in patients undergoing primary elective coronary artery bypass grafting (CABG) using either the so-called Smart suction device or a continuous autotransfusion system (C.A.T.S.®). METHODS: Fifty-eight patients being operated with a miniaturized circuit (minimal extracorporeal circuit, MECC) were prospectively randomized to using a so-called Smart suction device or a routine continuous autotransfusion system (C.A.T.S.®) for collection of mediastinal shed blood. The coagulation response was measured by thrombin-antithrombin complex (TAT) and D-dimer. The inflammatory response was measured by Interleukin 6 (IL-6) and complement factor 3a (C3a) at three different time points, before surgery, 2h after surgery, as well as 18 h after surgery. RESULTS: No serious adverse cardiovascular event was observed. Serum levels of TAT significantly differed between both groups 2h after surgery (Smart suction 16.12 ± 13.51 µg l⁻¹ vs C.A.T.S® 9.83 ± 7.81 µg l⁻¹, p = 0.040) and returned to baseline values after 18 h in both groups. Serum levels of D-dimer showed a corresponding pattern with a peak 2h after surgery (Smart suction 1115 ± 1231 ng ml⁻¹ vs C.A.T.S.® 507 ± 604 ng ml⁻¹, p = 0.025). IL-6 levels also significantly differed between both groups 2h after surgery (Smart suction 186 ± 306 pg ml⁻¹ vs C.A.T.S.® 82 ± 71 pg ml⁻¹, p = 0.072). No significant changes in serum levels of C3a over time could be observed. CONCLUSIONS: Despite no differences in the clinical course of patients with either Smart suction or C.A.T.S.® being observed, surrogate markers of coagulation and inflammation seem to be less pronounced in patients where cardiotomy blood is not being directly reinfused. As such, C.A.T.S.® should be preferred in routine CABG, as long as no extensive volume substitution is anticipated.