Research - Sepsis
The Effect of Rhubarb Pre-Treatment on Intestinal Microcirculation in Septic Rats
Yun-Liang Cui,*,a Lv Wang,†,a Zhao-Tao Tian,* Zhao-Fen Lin† and De-Chang Chen†
*Department of Critical Care Medicine Jinan Military General Hospital, Jinan, China
† Department of Emergency Medicine, Changzheng Hospital Second Military Medical University, Shanghai,China
The intestine plays a vital role in the pathophysiology of sepsis development. The objective of the present study was to explore the effects of rhubarb on intestinal microcirculation in septic rats. We used moorFLPI laser speckle imaging to detect the blood flow of the intestinal mucosa and wall. Using an ELISA, we assayed the concentration of lactate (L) and pyruvic acid (P) in the intestinal tissue to calculate the ratio of lactate to pyruvic acid (L/P ratio). To observe the intestinal mucosal capillaries, gelatin and ink were perfused into the intestine and subsequently stained with hematoxylin and eosin (HE) to measure the ratio of the vessel area.We then used immunohistochemistry to measure CD31 expression. Using an MTT assay, the effect of the rhubarb extract on the proliferation of human umbilical vein endothelial cells (HUVECs) was analyzed. The blood flow in the intestinal wall and mucosa of the control, sham and rhubarb-treated groups was significantly higher, while the sepsis group had relatively low blood flow. The L/P ratio in the intestinal tissue was larger in the sepsis group than in the other three groups. The microvascular area (MVA) in the sepsis group was smaller than in the control group, sham group or rhubarb group. Positive expression for CD31 was observed in the cytoplasm of vascular endothelial cells. The intestinal mucosal capillaries were reduced in septic rats as compared to the other three groups. HUVEC proliferation was enhanced by the rhubarb extract monomers at 1 mol/L, but suppressed at higher concentrations of 10 to 100 mol/L. These results suggest that pre-treatment with rhubarb prior to sepsis induction promotes the expansion of the intestinal mucosal capillaries, protects intestinal mucosal capillary endothelial cells and increases the number of functional intestinal capillaries
Source : Am J. Chinese Medicine
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Low Vitamin D Tied to Poor Sepsis Outcomes
Patients who are deficient in vitamin D had a greater risk of developing sepsis and an increased mortality risk if they do develop it, two studies showed.Those who had low serum levels of 25-hydroxyvitamin D (25(OH)D) before being admitted to the hospital were significantly more likely to develop sepsis after hospitalization than patients with normal pre-hospital vitamin D levels (OR 1.51, 95% CI 1.35 to 2.08), according to Kenneth Christopher, MD, of Brigham and Women's Hospital in Boston and colleagues.
And among the patients who developed sepsis, the odds of dying within 30 days was greater for those with deficient or insufficient vitamin D levels (OR 1.55, 95% CI 1.02 to 2.34), Christopher reported at the Society of Critical Care Medicine meeting here.
Another study, presented by H. Bryant Nguyen, MD, of Loma Linda University in California, revealed a similar association between deficient levels of 1,25-dihydroxyvitamin D (1,25(OH)2D) -- the active metabolite of 25(OH)D -- and a greater mortality risk in patients with sepsis.
Christopher noted that interventional trials are ongoing in the U.S., Europe, and Australia to determine whether improving vitamin D status can change outcomes in critically ill patients, although he was skeptical.
"I think the engine is so hot when patients become septic that I can't see a vitamin actually changing the course of that disease," he said, although he added that vitamin D supplementation might shorten recovery time.
"It's hard to say that this is a magic bullet that's going to stop sepsis in its tracks," he said. "I just can't imagine that that's possible."
Christopher and his colleagues examined data from 3,386 adult patients (mean age 66) who received care in the medical and surgical ICUs at one of two Boston hospitals -- Massachusetts General Hospital or Brigham and Women's Hospital -- from 1998 to 2011 and who had a serum 25(OH)D measurement in the year leading up to the hospitalization.
Vitamin D deficiency was defined as a 25(OH)D level of 15 ng/mL or less. Levels greater than 15 ng/mL but less than 30 ng/mL were deemed insufficient and levels of 30 ng/mL or greater were considered sufficient. The average level was 29.4 ng/mL.
While in the hospital, 17% of the patients developed sepsis.
For the overall cohort, the in-hospital mortality rate was 12.2%. Within 1 year, 26% of the patients died. At each time point, the mortality rate was higher for those with sepsis, reaching 44.6% at 1 year.
Pre-admission vitamin D deficiency was associated with a greater risk of sepsis whether it was defined according to diagnostic codes or (OR 1.51) to international sepsis conference guidelines (OR 2.45). The relationship remained significant after adjustment for potential confounders.
Christopher acknowledged that the observational data precluded any definitive assessment of the causal relationship between vitamin D levels and either sepsis or mortality, and also that the study was limited by potential selection and ascertainment biases and confounding by unmeasured factors.
But the study presented by Nguyen appeared to offer some support to the findings.
Nguyen and his colleagues looked at the relationship between serum 1,25(OH)2D levels measured in the first 72 hours of hospitalization and 30-day mortality in patients with sepsis.
The study included 91 adult patients who presented to the emergency department and were admitted to the ICU. The mean age of the patients was 59.1 and 53% were female.
Overall, 11% of the patients died within the first 30 days.
Compared with those who survived the first 30 days, those who died had significantly lower levels of 1,25(OH)2D at hospital admission (20.4 versus 31.5 pg/mL, P=0.04). There was no difference at any time during the study in levels of 25(OH)D, however.
Parathyroid hormone levels did not differ at admission between survivors and those who died, but they were significantly higher among the patients who died at 24, 48, and 72 hours.
In a multivariate analysis, 30-day mortality was significantly predicted by older age (OR 1.08, 95% CI 1.03 to 1.12). The odds of dying within 30 days were lower with higher levels of calcium (OR 0.55, 95% CI 0.38 to 0.80) and 1,25(OH)2D (OR 0.84, 95% CI 0.76 to 0.92).
The discriminatory power of all three of those predictors of 30-day mortality -- as measured using the area under the receiving operating characteristics curve -- was 0.98.
Nguyen acknowledged that the study was limited by the small sample size and the lack of statistical power.
But he said, the study "does suggest that 1,25(OH)2D may be a viable therapeutic target in the design of future sepsis clinical trials while we're trying to tease out the various mechanisms of vitamin D deficiency in these patients."
Source : Science Daily via
Society of Critical Care Medicine
Moromizato T, et al "Pre-hospital vitamin D deficiency and sepsis in the critically ill" SCCM 2013; Abstract 24.
Additional source: Society of Critical Care Medicine
Sai A, et al "Discovery of a novel outcome prognosticator for sepsis with therapeutic implications: decreased serum 1,25-dihydroxyvitamin D" SCCM 2013; Abstract 23.
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It Is Not Just Folklore: The Aqueous Extract of Mung Bean Coat Is Protective against Sepsis
Shu Zhu,1,2 Wei Li,1,2 Jianhua Li,1 Arvin Jundoria,1 Andrew E. Sama,1,2 and Haichao Wang1,2
1Laboratory of Emergency Medicine, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA
2Department of Emergency Medicine, North Shore University Hospital, The Hofstra North Shore-LIJ School of Medicine at the Hofstra University, Manhasset, NY 11030, USA
Mung bean (Vigna Radiata) has been traditionally used in China both as nutritional food and herbal medicine against a number of inflammatory conditions since the 1050s. A nucleosomal protein, HMGB1, has recently been established as a late mediator of lethal systemic inflammation with a relatively wider therapeutic window for pharmacological interventions. Here we explored the HMGB1-inhibiting capacity and therapeutic potential of mung bean coat (MBC) extract in vitro and in vivo. We found that MBC extract dose-dependently attenuated LPS-induced release of HMGB1 and several chemokines in macrophage cultures. Oral administration of MBC extract significantly increased animal survival rates from 29.4% (in saline group, N=17 mice) to 70% (in experimental MBC extract group, N=17 mice, P < 0.05) in vitro, MBC extract stimulated HMGB1 protein aggregation and facilitated both the formation of microtubule-associatedprotein-1-light-chain-3-(LC3-)containing cytoplasmic vesicles, and the production of LC3-II in macrophage cultures. Consequently, MBC extract treatment led to reduction of cellular HMGB1 levels in macrophage cultures, which was impaired by coaddition of two autophagy inhibitors (bafilomycin A1 and 3-methyladenine). Conclusion. MBC extract is protective against lethal sepsis possibly by stimulating autophagic HMGB1 degradation.
Source : Evidence-Based Complementary and Alternative Medicine Volume 2012 (2012)
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