Reduction of β-Endorphin-Containing Immune Cells in Inflamed Paw Tissue Corresponds with a Reduction in Immune-Derived Antinociception: Reversible by Donor Activated Lymphocytes

The functional integrity of the immune system is essential for peripheral antinociception. Previous studies have demonstrated that immune cells elicit potent antinociception in inflamed tissues and that corticotropin-releasing factor-induced antinociception is significantly inhibited in animals that have undergone cyclosporin A (CsA)-induced immunosuppression. In this study, we examined the effect of a single bolus of CsA on inflammatory nociception. CsA-treated rats had substantially increased nociception compared with nonimmunosuppressed rats, consistent with a reduction in circulating and infiltrating lymphocytes. Furthermore, CsA-treated rats had inhibition of corticotropin-releasing factor-induced immune-derived antinociception, which was dose-dependently reversed by IV injection of concanavalin A-activated donor lymphocytes (1.0-7.0 X 10(6) cells/0.1 mL). In conclusion, our findings provided further evidence that opioid-containing immune cells are essential for peripheral analgesia. It is evident from these findings that control of inflammatory pain relies heavily on a functioning immune system.

Community-based interventions for the prevention of burns and scalds in children

Background Burns and scalds are a significant cause of morbidity and mortality in children. Successful counter-measures to prevent burn and scald-related injury have been identified. However, evidence indicating the successful roll-out of these counter-measures into the wider community is lacking. Community-based interventions in the form of multi-strategy, multi-focused programmes are hypothesised to result in a reduction in population-wide injury rates. This review tests this hypothesis with regards to burn and scald injury in children. Objectives To assess the effects of community-based interventions, defined as coordinated, multi-strategy initiatives, for reducing burns and scalds in children aged 14 years and under. Search strategy We searched the Cochrane Injuries Group's specialised register, CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, National Research Register and the Web of Knowledge. We also handsearched selected journals and checked the reference lists of selected publications. The searches were last updated in May 2007. Selection criteria Included studies were those that reported changes in medically attended burn and scald-related injury rates in a paediatric population (aged 14 years and under), following the implementation of a controlled community-based intervention. Data collection and analysis Two authors independently assess studies for eligibility and extracted data. Due to heterogeneity between the included studies, a pooled analysis was not appropriate. Main results Of 39 identified studies, four met the criteria for inclusion. Two of the included studies reported a significant decrease in paediatric burn and scald injury in the intervention compared with the control communities. The failure of the other two studies to show a positive result may have been due to limited time-frame for the intervention and/or failure to adequately implement the counter-measures in the communities. Authors' conclusions There are a very limited number of research studies allowing conclusions to be drawn about the effectiveness of community-based injury prevention programmes to prevent burns and scalds in children. There is a pressing need to evaluate high-quality community-based intervention programmes based on efficacious counter-measures to reduce burns and scalds in children. It is important that a framework for considering the problem of burns and scalds in children from a prevention perspective be articulated, and that an evidence-based suite of interventions be combined to create programme guidelines suitable for implementation in communities throughout the world.

Protein utilisation and turnover in lines of chickens selected for different aspects of body composition

1. Protein utilisation and turnover were measured in male chickens sampled from a line selected for high breast yield and a randombred control line (lines QL and CL, experiment 1) and in male chickens sampled from lines selected for either high or low abdominal fatness (lines FL and LL, experiment 2). In each experiment, 18 birds per line were given iso-energetic (12.9 MJ ME/kg) diets containing either 120 or 220 g CP/kg from 21 to 29 d (experiment 1) and 33 to 43 d (experiment 2). 2. Measurements were made of growth rate, food intake, body composition, excreta production and N-tau-methylhistidine excretion as a measure of myofibrillar protein breakdown, and fractional rates (%/d) of protein deposition, breakdown and synthesis were calculated. 3. In experiment 1, there were no significant differences between the line means for the fractional measures of protein turnover, but there was marked differential response in the two lines in the fractional rates of protein deposition, breakdown and synthesis, to increase in protein intake. The positive slope of the regressions of fractional (%/d) protein deposition and synthesis rates on protein intake (g/d/kg BW) were approximately 1.4- and 2.0-fold higher respectively in the QL than the CL line birds, and the negative slope of the regression of fractional breakdown rate on protein intake was approximately threefold greater in the CL than the QL line birds. 4. In experiment 2, fractional deposition rate was 6.2% lower, but fractional breakdown rate 9.4% higher in the LL than the FL birds, whilst there was essentially no difference in response of the FL and LL birds in the components of protein turnover to increase in protein intake. Line differences in deposition and breakdown rates were thus a reflection of the considerably higher (20%) food and hence protein intake in the FL than the LL birds. 5. The differential line responses in protein turnover in the two experiments suggest that selection for increased breast muscle yield and for reduced body fatness manipulate different physiological pathways in relation to protein turnover, but neither selection strategy results in an improvement in net protein utilisation at typical levels of protein intake by birds on commercial broiler diets, through a reduction in protein breakdown rate.

Renal and hepatic accumulation of cadmium and lead in the expression of CYP4F2 and CYP2E1

The present study examined accumulation of the metal toxins cadmium (Cd) and lead (Pb) in relation to the abundance of cytochrome P450 4F2 (CYP4F2), CYP2E1 and concentrations of zinc and copper in liver and kidney samples using immunoblotting coupled with metal analysis. The post mortem liver and kidney cortex samples were from 23 males and 8 females aged 3-89 years. All were Caucasians who had not been exposed to metals in the workplace. Average kidney cortex Cd load of 17.4 mu g/g w.w. was 17 times greater than average liver Cd load (1.1 mu g/g w.w.). In contrast, average kidney cortex Ph load of 0.09 mu g/g w.w. was two times lower than liver Pb load of 0.19 mu g/g w.w. Average Zn and Cu concentrations in the kidney cortex samples were 67% and 33% lower than those in the liver. Liver and kidney Cd loads, but not liver or kidney Ph loads, correlated positively with donors' age. After controlling for liver Cd load, an inverse correlation was seen between Zn and age (partial r = -0.39, P = 0.02), suggesting reduction in liver Zn levels in old age. Liver CYP2E1 protein abundance correlated with age-adjusted Cd load (partial r = 0.37, P = 0.02) whereas kidney CYP4172 protein abundance showed a positive correlation with age-adjusted Cd loads (partial r = 0.40, P = 0.02). These findings suggest that Cd may be an inducer of renal CYP4172 and hepatic CYP2E1 and that increased renal CYP4172 expression may implicate in Cd-linked renal tubular dysfunction and high blood pressure, involving CYP4F2-dependent arachidonic acid metabolism. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

White blood cell count predicts reduction in coronary heart disease mortality with pravastatin

Background-Elevated serum inflammatory marker levels are associated with a greater long-term risk of cardiovascular events. Because 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) may have an antiinflammatory action, it has been suggested that patients with elevated inflammatory marker levels may have a greater reduction in cardiovascular risk with statin treatment. Methods and Results-We evaluated the association between the white blood cell count (WBC) and coronary heart disease mortality during a mean follow-up of 6.0 years in the Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Study, a clinical trial comparing pravastatin (40 mg/d) with a placebo in 9014 stable patients with previous myocardial infarction or unstable angina. An increase in baseline WBC was associated with greater coronary heart disease mortality in patients randomized to placebo (hazard ratio for 1 X 10(9)/L increase in WBC, 1.18; 95% CI, 1.12 to 1.25; P<0.001) but not pravastatin (hazard ratio, 1.02; 95% CI, 0.96 to 1.09; P=0.56; P for interaction=0.004). The numbers of coronary heart disease deaths prevented per 1000 patients treated with pravastatin were 0, 9, 30, and 38 for baseline WBC quartiles of <5.9, 6.0 to 6.9, 7.0 to 8.1, and >8.2X10(9)/L, respectively. WBC was a stronger predictor of this treatment benefit than the ratio of total to high-density lipoprotein cholesterol and a global measure of cardiac risk. There was also a greater reduction (P=0.052) in the combined incidence of cardiovascular mortality, nonfatal myocardial infarction, and stroke with pravastatin as baseline WBC increased ( by quartile: 3, 41, 61, and 60 events prevented per 1000 patients treated, respectively). Conclusions-These data support the hypothesis that individuals with evidence of inflammation may obtain a greater benefit from statin therapy.

In vivo analysis of growth hormone receptor signaling domains and their associated transcripts

The growth hormone receptor (GHR) is a critical regulator of postnatal growth and metabolism. However, the GHR signaling domains and pathways that regulate these processes in vivo are not defined. We report the first knock-in mouse models with deletions of specific domains of the receptor that are required for its in vivo actions. Mice expressing truncations at residue m569 (plus Y539/545-F) and at residue m391 displayed a progressive impairment of postnatal growth with receptor truncation. Moreover, after 4 months of age, marked male obesity was observed in both mutant 569 and mutant 391 and was associated with hyperglycemia. Both mutants activated hepatic JAK2 and ERK2, whereas STAT5 phosphorylation was substantially decreased for mutant 569 and absent from mutant 391, correlating with loss of IGF-1 expression and reduction in growth. Microarray analysis of these and GHR(-/-) mice demonstrated that particular signaling domains are responsible for the regulation of different target genes and revealed novel actions of growth hormone. These mice represent the first step in delineating the domains of the GHR regulating body growth and composition and the transcripts associated with these domains.

Linewidth reduction in a large-smile laser diode array

We present theory and simulations for a spectral narrowing scheme for laser diode arrays (LDAs) that employs optical feedback from a diffraction grating. We calculate the effect of the so-called smile of the LDA and show that it is possible to reduce the effect by using a cylindrical lens set at an angle to the beam. The scheme is implemented on a 19-element LDA with smile of 7.6 mu m and yields frequency narrowing from a free-running width of 2 to 0.15 nm. The experimental results are in good agreement with the theory. (c) 2005 Optical Society of America.

Acupressure for the in-patient treatment of nausea and vomiting in early pregnancy: A randomized control trial

Objective: The purpose of this study was to evaluate the efficacy of acupressure at the P6 point for the in-patient treatment of severe nausea and vomiting in early pregnancy. Study design: This was a prospective single-blind randomized control trial that involved 80 patients with nausea and vomiting plus ketonuria before 14 weeks of gestation. Results: There was no difference between length of stay, amount of medication, or fluid required between the acupressure and placebo groups, although acupressure reduced the number of patients who stayed >= 4 nights in the hospital. Acupressure was well tolerated and not associated with an increase in perinatal morbidity or death. Conclusion: The use of acupressure Lit the P6 point does not reduce the amount of antiemetric medication that is required, the requirement for intravenous fluid, and median duration of inpatient stay more than the use of placebo. A small reduction was seen in the number of women who required >= 4 days in the hospital. (c) 2006 Mosby, Inc. All rights reserved.

Genome reduction in Leptospira borgpetersenii reflects limited transmission potential

Leptospirosis is one of the most common zoonotic diseases in the world, resulting in high morbidity and mortality in humans and affecting global livestock production. Most infections are caused by either Leptospira borgpetersenii or Leptospira interrogans, bacteria that vary in their distribution in nature and rely on different modes of transmission. We report the complete genomic sequences of two strains of L. borgpetersenii serovar Hardjo that have distinct phenotypes and virulence. These two strains have nearly identical genetic content, with subtle frameshift and point mutations being a common form of genetic variation. Starkly limited regions of synteny are shared between the large chromosomes of L. borgpetersenii and L. interrogans, probably the result of frequent recombination events between insertion sequences. The L. borgpetersenii genome is ≈700 kb smaller and has a lower coding density than L. interrogans, indicating it is decaying through a process of insertion sequence-mediated genome reduction. Loss of gene function is not random but is centered on impairment of environmental sensing and metabolite transport and utilization. These features distinguish L. borgpetersenii from L. interrogans, a species with minimal genetic decay and that survives extended passage in aquatic environments encountering a mammalian host. We conclude that L. borgpetersenii is evolving toward dependence on a strict host-to-host transmission cycle.

Local geometric changes in left ventricular remodeling post-infarction can lead to apparent reduction in scar thickness

Serial reduction in scar thickness has been shown in animal models. We sought whether this reduction in scar thickness may be a result of dilatation of the left ventricle (LV) with stretching and thinning of the wall. Contrast enhanced magnetic resonance imaging (CMRI) was performed to delineate radial scar thickness in 25 patients (age 63±10, 21 men) after myocardial infarction. The LV was divided into 16 segts and the absolute radial scar thickness (ST) and percentage scar to total wall thickness (%ST) were measured. Regional end diastolic (EDV) and end systolic volumes (ESV) of corresponding segments were measured on CMRI. All patients underwent revascularization and serial changes in ST, %ST, and regional volumes were assessed with a mean follow up of 15±5 months. CMRI identified a total of 93 scar segments. An increase in EDV or ESV was associated with a serial reduction inST(versusEDV, r =−0.3, p = 0.01; versusESV, r =−0.3, p = 0.005) and%ST(versusEDV, r =−0.2, p = 0.04; versus ESV, r =−0.3, p = 0.001). For segts associated with a positive increase in EDV (group I) or ESV (group II) there was a significant decrease in ST and %ST, but in those segts with stable EDV (group III) or ESV (group IV) there were no significant changes in ST and %ST (Table).

Reduction in scar thickness post myocardial infarction is secondary to increase in regional left ventricular volumes

We sought to determine the relative impact of myocardial scar and viability on post-infarct left ventricular (LV) remodeling in medically-treated patients with LV dysfunction. Forty patients with chronic ischemic heart disease (age 64±9, EF 40±11%) underwent rest-redistribution Tl201 SPECT (scar = 50% transmural extent), A global index of scarring for each patient (CMR scar score) was calculated as the sum of transmural extent scores in all segts. LV end diastolic volumes (LVEDV) and LV end systolic volumes (LVESV) were measured by real-time threedimensional echo at baseline and median of 12 months follow-up. There was a significant positive correlation between change in LVEDV with number of scar segts by all three imaging techniques (LVEDV: SPECT scar, r = 0.62, p < 0.001; DbE scar, r = 0.57, p < 0.001; CMR scar, r = 0.52, p < 0.001) but change in LV volumes did not the correlate with number of viable segments. ROC curve analysis showed that remodeling (LVEDV> 15%) was predicted bySPECTscars(AUC= 0.79),DbEscars(AUC= 0.76),CMR scars (AUC= 0.70), and CMR scar score (AUC 0.72). There were no significant differences between any of the ROC curves (Z score

Costs and decisions in population management: Koalas on Kangaroo Island

Many populations have a negative impact on their habitat, or upon other species in the environment, if their numbers become too large. For this reason they are often managed using some form of control. The objective is to keep numbers at a sustainable level, while ensuring survival of the population.+Here we present models that allow population management programs to be assessed. Two common control regimes will be considered: reduction and suppression. Under the suppression regime the previous population is maintained close to a particular threshold through near continuous control, while under the reduction regime, control begins once the previous population reaches a certain threshold and continues until it falls below a lower pre-defined level. We discuss how to best choose the control parameters, and we provide tools that allow population managers to select reduction levels and control rates. Additional tools will be provided to assess the effect of different control regimes, in terms of population persistence and cost.In particular we consider the effects of each regime on the probability of extinction and the expected time to extinction, and compare the control methods in terms of the expected total cost of each regime over the life of the population. The usefulness of our results will be illustrated with reference to the control of a koala population inhabiting Kangaroo Island, Australia.