Protective effect of β-glucan on lung injury after cecal ligation and puncture in rats

Objective Understanding the biological mediators involved in the complex inflammatory response of sepsis and acute lung injury offers the possibility of future investigations targeting treatment based on these mediators. This study investigated whether macrophage activator -glucan has a protective effect on acute lung injury in an experimental model of sepsis.Design and setting Experimental study in an experimental research center.Materials 30 rats randomized into three groups (sham, sepsis, and -glucan).Interventions Cecal ligation and puncture were performed in the -glucan and sepsis groups. The -glucan group was given a single intraperitoneal dose of -glucan (4 mg/kg) following cecal ligation.Measurements and results Rats treated with -glucan had fewer circulating neutrophils, more blood monocytes, and higher serum interleukin 6 levels than septic animals. The percentages of neutrophils and lymphocytes from the bronchoalveolar lavage fluid and the myeloperoxidase activity measured in the lung tissue were lower in the -glucan group than in the sepsis group. Less alveolar hemorrhage and neutrophil infiltration were observed in lungs from animals in the -glucan group in the septic groups.Conclusions In this rat model of intra-abdominal sepsis -glucan treatment partially protected against secondary lung injury, decreased lung hemorrhages, and lung neutrophilia. These results suggest that -glucan protects against sepsis-associated lung damage.     

Does fear of movement mediate the relationship between pain intensity and disability in patients following whiplash injury? A prospective longitudinal study

The aim of this study was to test the capacity of the Fear Avoidance Model to explain the relationship between pain and disability in patients with whiplash-associated disorders. Using the method of Baron and Kenny [1], we assessed the mediating effect of fear of movement on the cross-sectional and longitudinal relationships between pain and disability. Two hundred and five subjects with neck pain due to a motor vehicle accident provided pain intensity (0 to 10 numerical rating scale), fear of movement (Tampa Scale of Kinesiophobia and Pictorial Fear of Activity Scale) and disability (Neck Disability Index) scores within 4 weeks of their accident, after 3 months, and after 6 months. The analyses were consistent with the Fear Avoidance Model mediating approximately 20% to 40% of the relationship between pain and disability. Contrary to our initial hypothesis, the proportion of the total effect of pain on disability that was mediated by fear of movement did not substantially change as increasing time elapsed after the accident. The proportion mediated was slightly higher when fear of movement was measured by Tampa Scale of Kinesiophobia as compared with Pictorial Fear of Activity Scale. The findings of this study suggest that the Fear Avoidance Model plays a role in explaining a moderate proportion of the relationship between pain and disability after whiplash injury.     

Suppression of bone marrow–derived microglia in the amygdala improves anxiety-like behavior induced by chronic partial sciatic nerve ligation in mice

Chronic neuropathic pain causes abnormal sensitivities such as hyperalgesia and allodynia, and emotional abnormalities such as anxiety and depression. Although spinal cord microglia are involved in abnormal sensitivity to neuropathic pain, no previous studies have examined the mechanism of neuropathic pain–induced anxiety. Here, we examined the involvement of bone marrow (BM)–derived microglia aggregated in the amygdalae of mice with chronic neuropathic pain in the development of anxiety-like behavior. We prepared partial sciatic nerve ligations (PSNL) in mice that received bone marrow transplantation from green fluorescent protein (GFP)–Tg mice after irradiation with head protection, and examined GFP-positive microglia in the central nuclei of the amygdalae (CeA). On day 28 after PSNL, BM-derived microglia aggregated in the CeA concurrent with anxiety-like behavior. BM-derived microglia in the CeA highly expressed interleukin (IL)–1β and C-C chemokine receptor type 2 (CCR2). In addition, neurons in the CeA highly expressed monocyte chemotactic protein–1 (MCP-1), a ligand for CCR2, in PSNL-treated mice compared to sham-operated mice, suggesting that the MCP-1/CCR2 axis is involved in the recruitment of BM-derived microglia. Oral administration of a CCR2 antagonist decreased the number of BM-derived microglia in the CeA, and successfully reversed the anxiety-like behavior and hypersensitivity to mechanical stimuli in PSNL-treated mice. Microinjections of an IL-1β receptor antagonist directly into the CeA successfully reversed the anxiety-like behavior in the PSNL-treated mice even though the neuropathic pain persisted. These results suggest that the recruitment of BM-derived microglia to the CeA via the MCP-1/CCR2 axis and neuron–microglia interactions might be important in the pathogenesis of neuropathic pain–induced anxiety.     

Does sex make a difference in the prescription of treatments and the adaptation to chronic pain by cancer and non-cancer patients?

The literature suggests that the sex of patients is an important factor in understanding how they are treated by health care professionals and how they adapt to their symptoms. In two groups of patients with chronic pain (n = 428 non-cancer (Study 1) and n = 143 cancer-related (Study 2)), men and women were compared on medications prescribed, treatment history, and coping and adaptation. In Study 1 with the non-cancer pain patients, there were no significant differences between the sexes in past treatments, current analgesic use, pain, or disability. Women were significantly more depressed and were more likely to receive antidepressants than men. Subgrouping patients on the basis of pain-adaptation responses yielded groups with distinct psychosocial and behavioral characteristics. In Study 2 with the cancer pain patients, men and women did not show significant differences on any variables. Consistent with the results of Study 1, however, psychological subgroups differed significantly in pain severity, mood and disability regardless of sex. The results of both studies suggest that the role of patients' sex in chronic pain may be less important than their psychosocial and behavioral responses. Thus, it appears that knowing the psychological characteristics of patients may be more important than their sex.     

Modification of the rates of chain cleavage of poly(ϵ-caprolactone) and related polyesters in the solid state

The rates of chain cleavage of poly(ϵ-caprolactone) (PCL), poly (l-lactic acid) (PLLA), and a 3:7 copolymer of glycolic acid and l-lactic acid (PGLA) as films in water, alcohols, and acidic and basic reagents were determined by measurements of intrinsic viscosities and molecular weights. Partial ethoxylation of the carboxylic acid end groups of PCL reduced the rate of chain cleavage in water, consistent with an autocatalytic mechanism. The firstorder rate constants for hydrolysis of PCL, PLLA, and PGLA were 7.5 × 10⁻⁵, 7.4 × 10⁻⁵, and 1.2 × 10⁻³ h⁻¹, respectively. Ethanol, pentanol, 5% oleic acid, decylamine, and tributylamine increased the rate of chain cleavage of PCL but not that of PLLA. The rate of erosion but not the rate of chain cleavage of PGLA was enhanced by these reagents, with the exception of pentanol. Changes in the morphology of the polymers during degradation were characterized by differential scanning calorimetry. The origin of the more rapid rate of hydrolysis of PGLA, relative to PCL and PLLA, appears to be the intrinsic reactivity of the glycolate linkage.     

Blockade of nuclear factor-κB activation prevents hypodynamic shock and gastric hypoperfusion induced by endotoxin in anesthetized dogs

Objective To investigate whether pyrrolidinone derivative (N2733), an inhibitor of nuclear factor (NF)-B activation, improves altered metabolic and hemodynamic changes and organ dysfunctions caused by endotoxic shock.Design and setting Prospective, randomized, animal study in a laboratory at a university hospital.Subjects Twenty-three anesthetized male beagle dogs (10–14 kg).Interventions Dogs were mechanically ventilated and monitored with a pulmonary arterial catheter and a gastric tonometer. A central venous catheter was inserted into the femoral vein, and lactated Ringers solution (10 ml/kg per hour) was administered throughout the study period. Three groups of animals were studied: (a) the lipopolysaccharide (LPS) group (n=8), which received LPS (250 ng/kg per minute for 2 h); (b) the LPS plus N2733 group (n=8), which received N2733 (30 mg/kg intravenously and 10 mg/kg hour for 6 h) after the start of LPS; and (c) the N2733 group (n=7), which received N2733 (30 mg/kg intravenously and 10 mg/kg per hour for 6 h).Measurements and results Changes in hemodynamics, blood gas, gastric intramural pH, and renal and hepatic function were measured for 6 h. Coadministration of N2733 increased oxygen delivery index and prevented the LPS-induced hypotension, metabolic acidosis, and gastric mucosal acidosis but did not affect renal or hepatic function.Conclusions Administration of N2733 increased oxygen delivery index and prevented the LPS-induced hypotension and metabolic and gastric mucosal acidosis in an anesthetized canine endotoxic shock model, suggesting its beneficial effect on local blood flow against tissue hypoxia. These findings suggest that blockade of NF-B activation prevents hypodynamic shock and gastric hypoperfusin in endotoxic shock.     

Does enalapril prevent peritoneal fibrosis induced by hypertonic (3.86%) peritoneal dialysis solution?

OBJECTIVE: Peritoneal fibrosis (PF) is one of the most serious causes of failure in continuous ambulatory peritoneal dialysis (PD). Although the underlying mechanism responsible for the genesis of PF is still unknown, transforming growth factor beta (TGFbeta1) has been shown to be associated with PF. Angiotensin converting enzyme inhibitors have been shown to prevent the stimulating effect of growth factors. The aim of the present study was to investigate the effect of enalapril on peritoneal function and morphology in a rat model of experimental PF. METHODS: Twenty-one albino Wistar rats were divided into three groups: (1) the control group (C) received 10 mL isotonic saline intraperitoneally (i.p.), (2) the dextrose (Dx) group 10 mL 3.86% dextrose PD solution i.p., and (3) the enalapril-treated group (ENA) 10 cc 3.86% dextrose PD solution i.p. plus 100 mg/L enalapril in drinking water. After 4 weeks, a 1-hour peritoneal equilibration test was performed with 20 mL 2.27% dextrose PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration (UF) volume, and levels of dialysate protein, TGFbeta1, and cancer antigen 125 (CA125) were determined. The parietal peritoneum was evaluated histologically by light microscopy. RESULTS: Administration of enalapril resulted in preserved UF (-0.2 +/- 0.7 mL vs 1.7 +/- 0.3 mL, p < 0.05), protein loss (2.3 +/- 0.5 g/L vs 1.6 +/- 0.2 g/L, p > 0.05), and peritoneal thickness (77 +/- 7 microns vs 38 +/- 5 microns, p < 0.001). D/P urea increased significantly in the Dx group (p< 0.05). Both higher levels of TGFbeta1 (undetectable vs 298 +/- 43 pg/mL, p < 0.001) and lower levels of CA125 in dialysate effluent (0.94 +/- 0.5 U/L vs 0.11 +/- 0.1 U/L, p > 0.05) were determined in the Dx group. CONCLUSION: These findings show that peritoneal morphology and function tests were dramatically deranged in the Dx group. The same properties were partially preserved in the ENA group. The production of TGFbeta1 was significantly reduced but peritoneal thickness was not completely inhibited. In conclusion, by inhibiting the production of TGFbeta1, enalapril can preserve peritoneal histology, peritoneal function, and remodeling of mesothelial cells.     

Does obesity affect the non-invasive measurement of cardiac output performed by electrical cardiometry in children and adolescents?

Electrical cardiometry (EC) is a non-invasive and inexpensive method for hemodynamic assessment and monitoring. However, its feasibility for widespread clinical use, especially for the obese population, has yet to be determined. In this study, we evaluated the agreement and reliability of EC compared to transthoracic Doppler echocardiography (TTE) in normal, overweight, and obese children and adolescents. We measured stroke volume (SV) and cardiac output (CO) of 131 participants using EC and TTE simultaneously. We further divided these participants according to BMI percentiles for subanalyses: <85% normal weight (n?=?41), between 85 and 95% overweight (n?=?7), and >95% obese (n?=?83). Due to small sample size of the overweight group, we combined overweight and obese groups (OW+OB) with no significant change in results (SV and CO) before and after combining groups. There were strong correlations between EC and TTE measurements of SV (r?=?0.869 and r?=?0.846; p?<?0.0001) and CO (r?=?0.831 and r?=?0.815; p?<?0.0001) in normal and OW+OB groups, respectively. Bias and percentage error for CO measurements were 0.240 and 29.7%, and 0.042 and 29.5% in the normal and OW+OB groups, respectively. Indexed values for SV were lower in the OW+OB group than in the normal weight group when measured by EC (p?<?0.0001) but no differences were seen when measured by TTE (p?=?0.096). In all weight groups, there were strong correlations and good agreement between EC and TTE. However, EC may underestimate hemodynamic measurements in obese participants due to fat tissue.     

Paraoxonase (PON)-1 activity in septic neonates: One more arrow in the quiver of biomarkers of neonatal sepsis?

Paraoxonase-1 (PON-1), a calcium ion-dependent high-density lipoprotein (HDL)-associated enzyme, has been proposed as a negative acute phase reactant biomarker in animal and human adult studies. The aim of this study was to evaluate the value of PON-1 activity in the diagnosis and monitoring of neonatal sepsis. Serum PON-1 activity, as paraoxonase and arylesterase, was prospectively studied in 48 septic neonates and matched controls. PON-1 activity was decreased at the acute phase of sepsis in comparison with values at recovery and values in controls. Paraoxonase or arylesterase at enrollment correlated significantly with serum Amyloid-A, CRP and IL-6 and could also discriminate septic than non-septic neonates. In conclusion, our results are promising regarding the role of PON-1 as a biomarker of neonatal sepsis. Larger studies are needed to validate the clinical utility of PON-1 in neonatal medicine.     

Does potentized HgCl2 (Mercurius corrosivus) affect the activity of diastase and alpha-amylase?

BACKGROUND: Homeopathic drugs even with dilutions beyond 10(23) (high potencies) are frequently used, although their working mechanism is still unknown. Curative information preserved in solvent structure is postulated to exert biologic effects. OBJECTIVE: The objective was to test for a stimulating or inhibiting effect of high potencies of the homeopathic remedy HgCl2 (Mercurius corrosivus) on two sugar hydrolases. METHODS: High potencies were produced using stepwise dilution plus shaking. Controls included potentized solvent (aqua bidestillata), equimolar dilutions without shaking, and enzyme-free references. Tested were potencies with dilution factors 1:200 (CC) on diastase extract from winter barley, and 1:100 (C) on alpha-amylase from hog pancreas. Enzyme activity was colorimetrically determined by Lugol's iodine-starch reaction. RESULTS: An inhibiting effect of HgCl2 on enzyme activities was observed only in low potencies and dilutions. Statistically significant differences between potencies and controls were not found in randomized and blinded experiments. CONCLUSIONS: This experimental design provided independent reproducible results of cell-free in vitro assays. However, it did not indicate an effect of potentized HgCl2 on hydrolases. Demonstrating potency effects may require additional experimental features.     

Does the orientation of the distal radioulnar joint influence the force in the joint and the tension in the interosseous membrane?

OBJECTIVE: To investigate the effect of change in the orientation of the distal radioulnar joint on the force in the joint and the strain in the interosseous membrane. DESIGN: Biomechanical study in fresh frozen cadavers. BACKGROUND: The articular surfaces of the distal radioulnar joint may be orientated in parallel with the long axis of the forearm (a Type I joint) or at an oblique angle opening distally to the ulnar side (a Type II joint). METHODS: Three cadaveric upper limbs were held on a custom built frame allowing measured rotation and axial loading across the wrist. Measurements of force in the distal radioulnar joint and strain in the interosseous membrane were taken and repeated after replacement of the distal radioulnar joint with prosthetic Type I and Type II joints. FINDINGS: The force in the joint and the strain in the interosseous membrane increased with increasing load across the wrist (P < 0.0001). The force in the Type I joint was reduced compared to the normal or Type II joint. This difference was greater with increasing load and was significant at 8 kg (P < 0.001). The strain in the interosseous membrane was maximal at neutral forearm rotation and decreased with increasing pronation and supination. INTERPRETATION: The force in the joint is greater with the Type II distal radioulnar joint. We believe this compressive force increases joint stability and this orientation of the articular surfaces should be considered in the design of a total distal radioulnar joint arthroplasty.     

Vascular tissue construction on poly(ε-caprolactone) scaffolds by dynamic endothelial cell seeding: effect of pore size

In vitro tissue engineering for fabrication of small diameter vascular grafts probably undergoes a sequence of events similar to the in vivo angiogenesis process. In both cases endothelial cells (ECs) play the crucial role in generating a non-thrombogenic vessel lumen and stabilization of ECs in the lumen of new vessels requires the deposition of collagen IV and elastin. Shear stress is an important in vivo signal for inducing synthesis of extracellular matrix (ECM) components, collagen IV and elastin, which form the basement membrane in the case of new blood vessels. Stimulation of ECs may therefore produce collagen and elastin in the lumen of a polymeric scaffold during the vascular tissue-engineering process if appropriate biochemical and mechanical signals are presented. However, the morphology and physicochemical characteristics of polymer scaffolds may also be crucial for EC monolayer formation and ECM deposition. In this study, tubular scaffolds made of biodegradable poly(ε-caprolactone) (PCL) with biomimetic fibrin-based coating were evaluated to compare the effects of pore sizes on surface coverage of ECs and synthesis of ECM under dynamic culture conditions. Actin was stained for identification of cells, while specific antibodies were used for locating collagen IV and elastin deposition on the scaffolds. It was found that dynamic seeding of ECs in the lumen stabilized the cells and aligned them along the direction of flow, with better deposition of insoluble elastin and collagen IV when ～75% of pores were < 24 μm in diameter. In addition, monolayer on the ε-PCL scaffolds with lower pore sizes was found to produce nitric oxide (NO), indicating a non-thrombogenic EC layer in the lumen.     

RETRACTED: Children’s non-accidental injuries at an Accident and Emergency department: Does the age of the child and the type of injury matter?

Physical child abuse is a significant social and medical problem within the United Kingdom, and elsewhere. This study considers the role of emergency medical services in the detection of non-accidental childhood injury by examining paediatric attendances at a central London Accident and Emergency department over a two year period. There were 183 recorded episodes of non-accidental injury out of 17,582 paediatric attendances to the A&E department over two years. At bivariate level, non-accidental injury was associated with the age of the patient, and the primary clinical diagnosis groups of wounds, poisoning and burns (p < .01). Attendances by children over the age of 10 years, along with attendances for the treatment of wounds or burns, were statistically significant multivariate predictors of non-accidental injury being recorded in A&E (p < .001). This study shows that about 1 in 100 paediatric attendances at A&E are recorded as non-accidental injury. Young children are less likely to be recorded as non-accidentally injured, compared to adolescents. Health professionals need to be vigilant to the possibility of non-accidental injury for all children using emergency health services.