Dextran 70 administration after trauma-hemorrhagic shock does not impair cellular immune functions

: Although the effects of the colloid dextran 70 on induction of anaphylactoid reactions or reticulo-endothelial phagocytosis have been examined previously, its effects on specific cell-mediated immunity after trauma-hemorrhage shock remain unknown.

: Nonheparinized C3H/HeN mice underwent a laparotomy, were bled, and then maintained at a blood pressure of 35 mm Hg for 60 minutes. Then they were resuscitated with either 4 × the shed blood volume as lactated Ringer's solution (LRS) or 2 × LRS + 1 × dextran 70. Control mice underwent all operative protocols but were neither hemorrhaged, nor resuscitated. At 2 or 24 hours posthemorrhage, serum, splenocytes (SPL), and peritoneal macrophages (pMø, splenic Mo (sMø) were obtained. Bioassays were used to determine interleukin-2 (IL-2), IL-3, IL-6, and SPL proliferation.

: Trauma-hemorrhage markedly depressed lymphokine release, splenocyte proliferation, and IL-6 release at 2 hours after the insult. The combination of LRS + dextran did not restore lymphocyte functions, but also did not further suppress them. The release of IL-6 by pMø and sMø at 2 and 24 hours after dextran infusion and serum IL-6 remained at the same level as in LRS-treated animals.

: The combination of LRS and colloid dextran 70 does not adversely affect ex vivo cell-mediated immune functions during the first 24 hours after its administration after trauma-hemorrhage. Thus, from the immunological standpoint, dextran is a safe resuscitation adjunct.     

Kupffer cells are responsible for producing inflammatory cytokines and hepatocellular dysfunction during early sepsis.

BACKGROUND: Although hepatocellular dysfunction occurs early after the onset of sepsis, the mechanism responsible for this remains unknown. We tested the hypothesis that the reduction in Kupffer cell (KC) numbers prior to the onset of sepsis prevents the occurrence of hepatocellular dysfunction and reduces levels of the proinflammatory cytokines IL-1beta and IL-6 during the early stage of polymicrobial sepsis. MATERIALS AND METHODS: The number of KC in male adult rats was reduced in vivo by intravenous injection of gadolinium chloride 48 h before the induction of sepsis. KC-reduced and KC-normal rats were then subjected to cecal ligation and puncture (CLP, i.e., a model of polymicrobial sepsis) or sham operation followed by administration of normal saline solution. At 5 h after CLP (the early stage of sepsis), hepatocellular function [i.e., the maximal velocity of clearance (Vmax) and efficiency of active transport (Km) of indocyanine green] was measured using a fiber-optic catheter and in vivo hemoreflectometer. Whole blood was drawn to measure plasma levels of IL-1beta and IL-6 using enzyme-linked immunosorbent assays. RESULTS: Hepatocellular function was depressed and the circulating levels of IL-1beta and IL-6 were increased significantly at 5 h after CLP. KC reduction by prior administration of gadolinium chloride, however, prevented the occurrence of hepatocellular dysfunction and the upregulation of IL-1beta and IL-6. CONCLUSIONS: The KC-derived proinflammatory cytokines IL-1beta and IL-6 appear to be directly or indirectly responsible for producing hepatocellular dysfunction during early sepsis. Thus, pharmacologic agents that downregulate the production of one or both of these proinflammatory cytokines in the liver may be useful for maintaining hepatocellular function during the early stage of sepsis.     

Toxicity of Toxaphene in the Rat and Beagle Dog

Toxicity of Toxaphene in the Rat and Beagle Dog. CHU, I., VILLENEUVE,D.C, SUN, C., SECOURS, V., PROCTER, B., ARNOLD, E., CLEGG, D.,REYNOLDS, L., AND VALLI, V.E. (1986). Fundam Appl. Toxicol.7, 406-418. Residues of the insecticidal mixture, toxaphene,have been found in Great Lakes fish. The purpose of the presentstudy was to assess the subchronic toxicity of toxaphene inthe rat and beagle dog. In the rat study, groups of 10 maleand 10 female animals were fed diets containing 0, 4, 20, 100,or 500 ppm of the test compound for 13 weeks. No clinical signsof toxicity or spontaneous deaths were observed. Toxaphene treatmentup to 500 ppm had no effects on weight gain or food consumption.The liver/body weight ratio and hepatic microsomal enzyme activities(phenobarbital type) were increased in both sexes fed 500 ppmof the test compound. Toxaphene at the highest dose also causedkidney enlargement in male but not in female rats. Dose-dependenthistological changes were seen in the kidney, thyroid, and liver.Changes in the liver and thyroid were considered to be adaptativebut the injury in the proximal tubules of the kidney was focallysevere. Groups of six male and six female beagle dogs were fedtoxaphene in gelatin capsules at 0, 0.2, 2.0, and 5.0 mg/kgbody wt/day for 13 weeks. Food consumption and growth rate werenot affected. All animals survived the entire treatment period.No clinical signs of toxicity were observed. The liver/bodyweight ratio and serum alkaline phosphatase were increased indogs of both sexes fed 5.0 mg/kg. Mild to moderate dose-dependenthistological changes were observed in the liver and thyroid.Toxaphene was accumulated in a dose-dependent manner in thefat and liver of dogs and rats. Based on the biochemical, histological,and residue data, it was concluded that the no-adverse-effectlevels of the pesticide were 4.0 ppm (0.35 mg/kg) for the ratand 0.2 mg/kg for the dog.     

Cellular mechanisms of injury after major trauma

This is the Fourth article in the Journal's series on major trauma. Chaudry and Bland, leading experts in the field, consider the cellular implications of injury. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Differential alterations in systemic and regional oxygen delivery and consumption during the early and late stages of sepsis.

BACKGROUND: Studies have indicated that regional changes in oxygen utilization during sepsis cannot be predicted from the changes in the whole body oxygen delivery (DO2) and consumption (VO2). The aim of this study, therefore, was to determine whether differential alterations in systemic and regional DO2 and VO2 occur during the early and late stages of sepsis. METHODS: Adult male Sprague-Dawley rats were subjected to sepsis by cecal ligation and puncture (CLP). At 5 hours (i.e., the early, hyperdynamic phase of sepsis) or 20 hours (i.e., the late, hypodynamic phase) after CLP, cardiac output, and organ blood flow were measured by radioactive microspheres. Systemic and regional DO2 and VO2 were determined and plasma levels of lactate were measured. RESULTS: Cardiac output and blood flow to the liver, small intestine, and kidneys increased at 5 hours and decreased at 20 hours after CLP. Although both systemic DO2 and VO2 increased at 5 hours after CLP, systemic DO2 but not VO2 decreased at 20 hours. At 5 hours after CLP, intestinal and renal DO2 increased. However, DO2 in all the tested organs decreased at 20 hours after CLP. VO2 increased in the liver, small intestine, and kidneys at 5 hours after CLP but decreased only in the liver and small intestine at 20 hours after the onset of sepsis. Moreover, plasma lactate levels increased at the late stage of sepsis. CONCLUSION: Because hepatic and intestinal VO2 but not systemic and renal VO2 decreased at 20 hours after CLP, the liver and small intestine seem to be more vulnerable to the hypoxic insult during the hypodynamic stage of polymicrobial sepsis.     

The use of parallel imaging for MRI assessment of knees in children and adolescents

Background  

Parallel imaging provides faster scanning at the cost of reduced signal-to-noise ratio (SNR) and increased artifacts.     

Patterns of In-Hospital Mortality and Bleeding Complications Following PCI for Very Elderly Patients: Insights from the Dartmouth Dynamic Registry

Background Very elderly patients (age ≥ 85 years) are a rapidly increasing segment of the population. As a group, they experience high rates of in-hospital mortality and bleeding complications following percutaneous coronary intervention (PCI). However, the relationship between bleeding and mortality in the very elderly is unknown. Methods Retrospective review was performed on 17,378 consecutive PCI procedures from 2000 to 2015 at Dartmouth-Hitchcock Medical Center. Incidence of bleeding during the index PCI admission (bleeding requiring transfusion, access site hematoma > 5 cm, pseudoaneurysm, and retroperitoneal bleed) and in-hospital mortality were reported for four age groups (< 65 years, 65–74 years, 75–84 years, and ≥ 85 years). The mortality of patients who suffered bleeding complications and those who did not was calculated and multivariate analysis was performed for in-hospital mortality. Lastly, known predictors of bleeding were compared between patients age < 85 years and age ≥ 85 years. Results Of 17,378 patients studied, 1019 (5.9%) experienced bleeding and 369 (2.1%) died in-hospital following PCI. Incidence of bleeding and in-hospital mortality increased monotonically with increasing age (mortality: 0.94%, 2.27%, 4.24% and 4.58%; bleeding: 3.96%, 6.62%, 10.68% and 13.99% for ages < 65, 65–74, 75–84 and ≥ 85 years, respectively). On multivariate analysis, bleeding was associated with increased mortality for all age groups except patients age ≥ 85 years [odds ratio (95% CI): age < 65 years, 3.65 (1.99–6.74); age 65–74 years, 2.83 (1.62–4.94); age 75–84 years, 3.86 (2.56–5.82), age ≥ 85 years: 1.39 (0.49–3.95)]. Conclusions Bleeding and mortality following PCI increase with increasing age. For the very elderly, despite high rates of bleeding, bleeding is no longer predictive of in-hospital mortality following PCI.     

Dehydroepiandrosterone modulates toll-like receptor expression on splenic macrophages of mice after severe polymicrobial sepsis

Toll-like receptors (TLRs) play a pivotal role in the induction of innate immunity after the transactivation of proinflammatory cytokine genes. However, the responses of TLRs during severe polymicrobial sepsis have not been thoroughly examined. Although dehydroepiandrosterone (DHEA), a steroid hormone, is reported to have an immunomodulatory effect after sepsis, the mechanism responsible for its salutary is not known. To investigate this, male ICR/Jcl mice (5-8 weeks old) were subjected to sepsis by cecal ligation and puncture (CLP) or sham operation. The mice received vehicle or DHEA (40 mg/kg body weight) subcutaneously immediately after the surgery. Plasma IL-10 levels and splenic macrophage TNF-alpha production, as well as the expression levels of CD14, TLR2, and TLR4 mRNAs on splenic macrophages, were assessed 6 h after the surgery. The results indicate that mice with sepsis show a marked increase in the plasma IL-10 levels and a decrease in TNF-alpha production by splenic macrophages. TLR2 and TLR4 mRNA expression levels after CLP were significantly lower compared with those after the sham operation. TNF-alpha production and TLR2 and TLR4 mRNA expression on splenic macrophages are restored with DHEA administration. Furthermore, administration of DHEA after CLP delayed the mortality of animals. These results indicate that the anti-inflammatory phase of sepsis induces a marked down-regulation of TLR expression on splenic macrophages; however, administration of DHEA resulted in the restoration of TLR2 and TLR4 mRNA expression.