Metal ion-oxytetracycline pharmacokinetic interactions after oral co-administration in broiler chickens.

The influence of the composition of calcium (Ca(2+)), magnesium (Mg(2+)), and iron (Fe(3+)) ions in two concentration levels (low-500 mg/L of CaCl2, 125 mg/L of MgCl2, and 10 mg/L of FeCl3 and high-2,500 mg/L of CaCl2, 625 mg/L of MgCl2, and 50 mg/L of FeCl3) contained in water on the pharmacokinetics (PK) of oxytetracycline (OTC) was determined. OTC hydrochloride was administered at a dose of 25 mg/kg of body weight to broiler chickens divided into four groups of nine birds each, including 3 oral groups (in deionized water -control, in water with low ion concentration, and in water with high ion concentration) and 1 intravenous group. OTC concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry, after which non-compartmental pharmacokinetic analysis was conducted.The absolute bioavailability of OTC in the group of birds exposed to higher ions concentration was reduced (8.68% ± 2.56) as compared to the control (13.71% ± 2.60). Additionally, in this group, decrease in PK parameters such as: area under the concentration-time curve from 0 to infinity (15.36 µg × h/mL ± 4.36), from 0 to t (14.78 µg × h/mL ± 4.37), area under the first moment of curve from 0 to t (107.54 µg × h/mL ± 36.48), and maximum plasma concentration (2.13 µg/mL ± 0.32) were also observed. It is noteworthy, all mentioned parameters demonstrated a downward trend with high correlation coefficient (P = 0.004, P = 0.002, P = 0.005, P = 0.004, P = 0.011, respectively), reflecting the influence of increasing concentrations of Ca(2+), Mg(2+), and Fe(3+) ions on the decreasing absorption rate of OTC.Based on the current research results, it can be assumed that high concentrations of several ions applied concomitantly are able to decrease the absorption of OTC from gastrointestinal tract in broiler chickens. This occurrence might impair the drug's clinical efficacy toward some pathogenic microorganisms. It implies that using OTC on a farm may require administration of higher doses than the routine one when infections are caused by less sensitive pathogens.

Distribution of CD4+CD8+ double positive T cells in a mouse model of allergic asthma.

The present study describes the distribution of CD4+CD8+ double-positive (DP) T cells in various immune compartments of mice with ovalbumin (OVA)-induced allergic asthma. It was found that the absolute number of DP T cells was considerably increased in the mediastinal lymph nodes and lungs of asthmatic mice as compared with that determined in the healthy subjects. On the contrary, the absolute counts of DP T cells was significantly decreased in the head and neck lymph nodes, and in peripheral blood of OVA-immunized mice. These results suggest that DP T cells may be involved in the pathogenesis of allergic asthma.

The behavior of cancellous bone from quasi-static to dynamic strain rates with emphasis on the intermediate regime.

Previous studies, conducted using quasi-static and dynamic compression tests, have shown that the mechanical strength of cancellous bone is strain rate dependent. However, these studies have not included the intermediate strain rate (ISR) regime (1/s to 100/s), which is important since it is representative of the loading rates at which non-fatal injuries typically occur. In this study, 127 bovine bone specimens were compressed in 3 regimes spanning 8 distinct strain rates, from 0.001/s to 600/s, using three different devices: a conventional quasi-static testing machine, a wedge-bar (WB) apparatus and a conventional split Hopkinson pressure bar (SHPB) implemented with a cone-in-tube (CiT) striker and a tandem momentum trap. Due to the large sample size, a new robust automated algorithm was developed with which the material properties, such as the apparent Young׳s modulus and the yield and ultimate values of stress and strain, were identified for each individual specimen. A statistical summary of the data is presented. Finally, this study demonstrates that results obtained at intermediate strain rates are essential for a fuller understanding of cancellous bone behavior by providing new data describing the transition between the quasi-static and dynamic regimes.

Control of Immune Response to Allogeneic Embryonic Stem Cells by CD3 Antibody-Mediated Operational Tolerance Induction.

Implantation of embryonic stem cells (ESCs) and their differentiated derivatives into allogeneic hosts triggers an immune response that represents a hurdle to clinical application. We established in autoimmunity and in transplantation that CD3 antibody therapy induces a state of immune tolerance. Promising results have been obtained with CD3 antibodies in the clinic. In this study, we tested whether this strategy can prolong the survival of undifferentiated ESCs and their differentiated derivatives in histoincompatible hosts. Recipients of either mouse ESC-derived embryoid bodies (EBs) or cardiac progenitors received a single short tolerogenic regimen of CD3 antibody. In immunocompetent mice, allogeneic EBs and cardiac progenitors were rejected within 20-25 days. Recipients treated with CD3 antibody showed long-term survival of implanted cardiac progenitors or EBs. In due course, EBs became teratomas, the growth of which was self-limited. Regulatory CD4(+)FoxP3(+) T cells and signaling through the PD1/PDL1 pathway played key roles in the CD3 antibody therapeutic effect. Gene profiling emphasized the importance of TGF-ß and the inhibitory T cell coreceptor Tim3 to the observed effect. These results demonstrate that CD3 antibody administered alone promotes prolonged survival of allogeneic ESC derivatives and thus could prove useful for enhancing cell engraftment in the absence of chronic immunosuppression.

Links between mechanical behavior of cancellous bone and its microstructural properties under dynamic loading.

Previous studies show that in vivo assessment of fracture risk can be achieved by identifying the relationships between microarchitecture description from clinical imaging and mechanical properties. This study demonstrates that results obtained at low strain rates can be extrapolated to loadings with an order of magnitude similar to trauma such as car crashes. Cancellous bovine bone specimens were compressed under dynamic loadings (with and without confinement) and the mechanical response properties were identified, such as Young׳s modulus, ultimate stress, ultimate strain, and ultimate strain energy. Specimens were previously scanned with pQCT, and architectural and structural microstructure properties were identified, such as parameters of geometry, topology, connectivity and anisotropy. The usefulness of micro-architecture description studied was in agreement with statistics laws. Finally, the differences between dynamic confined and non-confined tests were assessed by the bone marrow influence and the cancellous bone response to different boundary conditions. Results indicate that architectural parameters, such as the bone volume fraction (BV/TV), are as strong determinants of mechanical response parameters as ultimate stress at high strain rates (p-value<0.001). This study reveals that cancellous bone response at high strain rates, under different boundary conditions, can be predicted from the architectural parameters, and that these relations with mechanical properties can be used to make fracture risk prediction at a determined magnitude.

Prostaglandin E2 inhibits IL-10 production by bovine CD4+ T cells.

Although prostaglandin E2 (PGE2) is a pro-inflammatory mediator, it also produces some effect which is anti-inflammatory in character. It is suggested that one of the mechanisms responsible for the latter effect is the increased synthesis of IL-10. The aim of this study has been to determine the influence of PGE2 on IL-10 production by bovine CD4+ and CD8+ T cells and NK cells. With this aim, peripheral blood mononuclear cells collected from 12-month-old heifers (n = 10) were treated without or with PGE2 (10(-6) M). Flow cytometric analysis showed that PGE2 caused a reduction in the percentage of IL-10 producing CD4+ T cells (P < 0.001), while leaving the secretion of this cytokine by CD8+ T cells and NK cells unaffected. This seems to indicate that PGE2 in cattle does not produce an anti-inflammatory effect by increasing the synthesis of IL-10; contrary to this, it may aggravate an inflammatory response by inhibiting the secretion of this cytokine by CD4+ T cells.

The Lac repressor provides a reversible gene expression system in undifferentiated and differentiated embryonic stem cell.

Control of mammalian gene promoters by the bacterial LacI repressor provides reversible regulation and dose-response levels of derepressed expression by the lactose analog isopropyl thiogalactose (IPTG). Here, we show that insertion of LacI-binding sites in the ubiquitous beta-actin promoter confers a strong and dose-dependent IPTG-regulatable expression of transiently transfected reporter genes in mouse embryonic stem (ES) cells expressing LacI. We established ES cell lines stably expressing reporter genes under inducible control and found a five- to tenfold IPTG induction of transgene expression. The kinetics of induction is rapid and stable, and can be rapidly reversed after IPTG removal. Importantly, this regulatable expression was maintained throughout the differentiation process of ES cells, and observed in individual differentiated cardiomyocyte-like cells and neuronal-like cells. This reversible system is the first to function from undifferentiated to individual well-differentiated ES cells, providing a very useful tool to understand molecular mechanisms underlying ES cell self-renewal, commitment and differentiation.