T-helper cell polarisation following severe polytrauma

Introduction Severe polytrauma induces an immunosuppressive response and is associated with a very high incidence of nosocomial infections. Previous studies have inferred that this detrimental immune response results from polarisation of the T helper (Th) response towards an anti-inflammatory, TH2 dominated, response at the expense of a bactericidal, Th1 response [1]. Objectives 1) To define alterations in TH cell subsets following severe blunt polytrauma. Methods Patients presenting to the emergency department within 2 hours of severe polytrauma were eligible if intubated either at the scene or in ED. Isolated head injuries and those not expected to survive 24 hours were excluded. EDTA anti-coagulated blood was drawn at 0hr (within 2 hours of injury), at 24 and 72hrs. Samples were immediately lysed, washed, stained and analysed using a standardised human 8-colour TH 1, 2 & 17 panel [2] on an LSR II flow cytometer. A paired white cell count differential was obtained at each sampling point. Patients were followed until discharge or death. Data were analysed using non-parametric statistics, with results presented as median and IQR. Results 15 consecutive severe polytrauma patients requiring Intensive Care Unit (ICU) admission were recruited. Demographic and clinical data are outlined in Figure 1. Twelve (80%) lymphocytosis (3.3x109/L, 2.5 - 4.4x109/L) (Figyre 2A). At 72 hours leukocytes had fallen (P < 0.01, figure 2A) such that 6 (54%) of those surviving were lymphopenic (0.9x109/L, 0.6 - 1.2x109/L). Circulating CD4+ (P = 0.01; Figure 2B) and CD4+CD25+ (P < 0.05) lymphocytes increased over 72 hours. When expressed as a percentage of total circulating lymphocytes no significant change in the proportions of the TH 1, 2 & 17 subpopulations was detected (Figure 2C-E). Conclusions Severe polytrauma patients swiftly become lymphopenic. Although a failure to normalise this during the ICU stay correlates with higher mortality [3] our study of TH cell subtypes demonstrates no evidence of a switch to a detrimental anti-inflammatory TH2 subtype at the expense of the potentially protective bactericidal TH1 subtype

Giant dispersion of critical currents in superconductor with fractal clusters of a normal phase

The influence of fractal clusters of a normal phase on the dynamics of a magnetic flux trapped in a percolative superconductor is considered. The critical current distribution and the current-voltage characteristics of fractal superconducting structures in the resistive state are obtained for an arbitrary fractal dimension of the cluster boundaries. The range of fractal dimensions, where the dispersion of critical currents becomes infinite, is found. It is revealed that the fractality of clusters depresses of the electric field caused by the magnetic flux motion thus increasing the critical current value. It is expected that the maximum current-carrying capability of a superconductor can be achieved in the region of giant dispersion of critical currents.Comment: 7 pages with 3 figure

Preimplantation development of in vitro-matured and in vitro-fertilized ovine zygotes: comparison between coculture on oviduct epithelial cell monolayers and culture under low oxygen atmosphere.

The roles of medium composition, serum source, embryo coculture, and culture under low O2 conditions on the development of in vitro-matured and in vitro-fertilized (IVMF) ovine zygotes were investigated in three separate experiments. In the first experiment, the proportion of cocultured IVMF zygotes developing to the blastocyst stage was significantly higher (38.0% vs. 3.5%; p \u3c 0.05) than that of non-cocultured zygotes treated within three embryo culture media (TCM-199 + 10% fetal bovine serum [FBS]; bicarbonate-buffered, glucose-free synthetic oviduct fluid medium [mod-SOFM] + 10% FBS; and bicarbonate-buffered BSA-free Tyrode\u27s salt solution [mod-TALP] + 10% FBS) under a 5% CO2 atmosphere in air. In a second experiment, a significantly higher (p \u3c 0.05) proportion of cocultured zygotes placed in TCM-199 medium survived to the blastocyst stage (37.4% blastocysts vs. 23.4% in mod-SOFM). No significant effect of serum (FBS vs. human serum [HS]) was observed on embryonic development, but coculture was confirmed to exert a significant influence on development to the blastocyst stage. In the final experiment, survival of the embryo under a reduced oxygen (5% CO2:5% O2:90% N2) atmosphere was investigated. In contrast to results in the initial experiments, embryonic survival was significantly higher (p \u3c 0.05) in the non-cocultured treatment groups (21.9% blastocysts vs. 0.4% for cocultured zygotes). Serum source also had a significant (p \u3c 0.05) influence upon the development of non-cocultured zygotes: 32.3% of zygotes cultured with HS progressed to the blastocyst stage vs. 11.5% of zygotes cultured in FBS-supplemented medium. These results have characterized two distinct culture environments, each capable of supporting the development of high frequencies of unselected IVMF zygotes to the blastocyst stage in vitro

T-helper cell polarisation following severe polytrauma

Introduction Severe polytrauma induces an immunosuppressive response and is associated with a very high incidence of nosocomial infections. Previous studies have inferred that this detrimental immune response results from polarisation of the T helper (Th) response towards an anti-inflammatory, TH2 dominated, response at the expense of a bactericidal, Th1 response [1]. Objectives 1) To define alterations in TH cell subsets following severe blunt polytrauma. Methods Patients presenting to the emergency department within 2 hours of severe polytrauma were eligible if intubated either at the scene or in ED. Isolated head injuries and those not expected to survive 24 hours were excluded. EDTA anti-coagulated blood was drawn at 0hr (within 2 hours of injury), at 24 and 72hrs. Samples were immediately lysed, washed, stained and analysed using a standardised human 8-colour TH 1, 2 & 17 panel [2] on an LSR II flow cytometer. A paired white cell count differential was obtained at each sampling point. Patients were followed until discharge or death. Data were analysed using non-parametric statistics, with results presented as median and IQR. Results 15 consecutive severe polytrauma patients requiring Intensive Care Unit (ICU) admission were recruited. Demographic and clinical data are outlined in Figure 1. Twelve (80%) lymphocytosis (3.3x109/L, 2.5 - 4.4x109/L) (Figyre 2A). At 72 hours leukocytes had fallen (P < 0.01, figure 2A) such that 6 (54%) of those surviving were lymphopenic (0.9x109/L, 0.6 - 1.2x109/L). Circulating CD4+ (P = 0.01; Figure 2B) and CD4+CD25+ (P < 0.05) lymphocytes increased over 72 hours. When expressed as a percentage of total circulating lymphocytes no significant change in the proportions of the TH 1, 2 & 17 subpopulations was detected (Figure 2C-E). Conclusions Severe polytrauma patients swiftly become lymphopenic. Although a failure to normalise this during the ICU stay correlates with higher mortality [3] our study of TH cell subtypes demonstrates no evidence of a switch to a detrimental anti-inflammatory TH2 subtype at the expense of the potentially protective bactericidal TH1 subtype

A growth factor phenotype map for ovine preimplantation development.

The reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the patterns of expression for several growth factor ligand and receptor genes during ovine preimplantation development. Transcripts for insulin-like growth factor (IGF)-I, IGF-II, and the receptors for insulin and IGF-I were detected throughout ovine preimplantation development from the 1-cell to the blastocyst stage. Transforming growth factor alpha (TGF alpha) transcripts were also detected throughout ovine preimplantation development. The mRNAs encoding basic fibroblast growth factor (bFGF) were detected in all stages of the ovine preimplantation embryo, although the relative abundance of this transcript consistently decreased from the 1-cell to the blastocyst stage, suggesting that it may represent a maternal transcript in early sheep embryos. Transcripts encoding ovine trophoblast protein (oTP) were detected only within blastocyst-stage embryos. Primary ovine oviduct cell cultures express the transcripts for IGF-II, IGF-I, TGF alpha, bFGF, TGF beta 1, and the receptors for insulin and IGF-I, suggesting that paracrine growth factor circuits may exist between the oviduct epithelium and the early ovine embryo. Transcripts for insulin, epidermal growth factor (EGF), and nerve growth factor (NGF) were not detected in any stage of the ovine preimplantation embryo or within the oviduct cell preparations. The expression of growth factor transcripts very early in mammalian development would predict that these molecules fulfil a necessary role(s) in supporting the progression of early embryos through the preimplantation interval. Our future efforts will be directed to understanding the nature of these putative regulatory pathways

Resistive state of superconducting structures with fractal clusters of a normal phase

The effect of morphologic factors on magnetic flux dynamics and critical currents in percolative superconducting structures is considered. The superconductor contains the fractal clusters of a normal phase, which act as pinning centers. The properties of these clusters are analyzed in the general case of gamma-distribution of their areas. The statistical characteristics of the normal phase clusters are studied, the critical current distribution is derived, and the dependencies of the main statistical parameters on the fractal dimension are found. The effect of fractal clusters of a normal phase on the electric field induced by the motion of the magnetic flux after the vortices have been broken away from pinning centers is considered. The voltage-current characteristics of fractal superconducting structures in a resistive state for an arbitrary fractal dimension are obtained. It is found that the fractality of the boundaries of normal phase clusters intensifies magnetic flux trapping and thereby increases the current-carrying capability of the superconductor.Comment: 15 pages with 8 figures, revtex3, alternative e-mail of author is [email protected]

Body mass index, estimated glucose disposal rate and vascular complications in type 1 diabetes: Beyond glycated haemoglobin

Aims To understand the relationship between insulin resistance (IR), assessed as estimated glucose disposal rate (eGDR), and microvascular/macrovascular complications in people with type 1 diabetes. Materials and methods Individuals with a confirmed diagnosis of type 1 diabetes were included in this cross-sectional study. BMI was categorised into normal weight (18.0–24.9 kg m−2), overweight (25.0–29.9 kg m−2) and obese groups (≥30.0 kg m−2). We categorised eGDR into four groups: eGDR >8, 6–7.9, 4–5.9 and <4 mg kg−1 min−1. Multiple logistic regression was used to identify associations with vascular complications, after adjusting for relevant confounders. Results A total of 2151 individuals with type 1 diabetes were studied. Median [interquartile range (IQR)] age was 41.0 [29.0, 55.0] with diabetes duration of 20.0 [11, 31] years. Odds ratio (OR) for retinopathy and nephropathy in obese compared with normal weight individuals was 1.64 (95% CI: 1.24–2.19; p = 0.001) and 1.62 (95% CI: 1.10–2.39; p = 0.015), while the association with cardiovascular disease just failed to reach statistical significance (OR 1.66 [95% CI: 0.97–2.86; p = 0.066]). Comparing individuals with eGDR ≥8 mg kg−1 min−1 and <4 mg kg−1 min−1 showed OR for retinopathy, nephropathy and macrovascular disease of 4.84 (95% CI: 3.36–6.97; p < 0.001), 8.35 (95% CI: 4.86–14.34; p < 0.001) and 13.22 (95% CI: 3.10–56.38; p < 0.001), respectively. Individuals with the highest eGDR category (≥8 mg kg−1 min−1) had the lowest complication rates irrespective of HbA1c levels. Conclusions Obesity is prevalent in type 1 diabetes and diabetes complications are not only related to glucose control. IR, assessed as eGDR, is strongly associated with both microvascular and macrovascular complications, regardless of HbA1c levels