Fuel feeds function: Energy balance and bovine peripheral blood mononuclear cell activation

A general phenomenon in peripartum mammals is the breakdown of (acquired) immunity. The incidence of parasite load, disease and inflammation often rise during the specific energetically demanding time of pregnancy and lactation. In this period, blood leukocytes display decreased DNA synthesis in response to mitogens in vitro. Leukocyte activation, the phase of the cell cycle preceding the DNA synthetic phase has hardly been investigated, but the few studies suggest that leukocyte activation may also be impaired by the limited energy/nutrient availability. Leukocyte activation is characterized by manifold processes, thus, we used the cellular oxygen consumption rate (OCR) as a measure of ATP turnover to support all these processes. We hypothesized that the activation of peripheral blood mononuclear cells (PBMC) – in terms of oxygen consumed over basal levels after in vitro stimulation – is altered by energy balance around parturition. We studied peripartum high-yielding dairy cows because they undergo substantial fluctuations in energy intake, energy output and body fat mass. We established a fluorescence-based test strategy allowing for long-term (≥ 24 h) quantification of O₂-consumption and studied the peripartum period from 5 weeks ante partum to 5 weeks postpartum. In addition, we determined cellular lactate production, DNA/RNA synthesis and cell size and zoo-technical parameters such as animal energy intake and milk yield were assessed, as well as selected plasma parameters, e.g. glucose concentration. The basal OCR of PBMC from pregnant, non-lactating cows (n = 6, ? 5 weeks ante partum) was 1.19 ± 0.15 nmol min^? 1 (10⁷ cells)^? 1 and increased to maximum levels of 2.54 ± 0.49 nmol min^? 1 (10⁷ cells)^? 1 in phytohemagglutinin (PHA)-stimulated PBMC. The basal OCR did not change over the peripartum period. Whereas the activation indices, herein defined as the PHA-induced 24 h-increase of OCR above baseline, amounted to 1.1 ± 0.3, 4.2 ± 0.3, 4.1 ± 1.1, 2.1 ± 0.3, and 2.7 ± 0.5 at weeks ? 5, ? 1, + 1, + 2, and + 5 relative to parturition, respectively. Because the activation index was positively correlated to plasma glucose levels and to energy balance during late pregnancy (week ? 5/week ? 1) and transition to lactation (week ? 1/week + 2), we conclude that PBMC activation is modulated by energy/nutrient availability. In future studies, the activation index should aid the identification of causal mechanisms of disparity in PBMC activation, such as attenuated ion transport or macromolecule synthesis.     

Breast MRI in nonpalpable breast lesions: a randomized trial with diagnostic and therapeutic outcome – MONET – study

Background

In orthodontic treatment, anchorage control is a fundamental aspect. Usually conventional mechanism for orthodontic anchorage control can be either extraoral or intraoral that is headgear or intermaxillary elastics. Their use are combined with various side effects such as tipping of occlusal plane or undesirable movements of teeth. Especially in cases, where key-teeth are missing, conventional anchorage defined as tooth-borne anchorage will meet limitations. Therefore, the use of endosseous implants for anchorage purposes are increasingly used to achieve positional stability and maximum anchorage.

Methods/Design

The intended study is designed as a prospective, multicenter randomized controlled trial (RCT), comparing and contrasting the effect of early loading of palatal implant therapy versus implant loading after 12 weeks post implantation using the new ortho-implant type II anchor system device (Orthosystem Straumann, Basel, Switzerland). 124 participants, mainly adult males or females, whose diagnoses require temporary stationary implant-based anchorage treatment will be randomized 1:1 to one of two treatment groups: group 1 will receive a loading of implant standard therapy after a healing period of 12 week (gold standard), whereas group 2 will receive an early loading of orthodontic implants within 1 week after implant insertion. Participants will be at least followed for 12 months after implant placement. The primary endpoint is to investigate the behavior of early loaded palatal implants in order to find out if shorter healing periods might be justified to accelerate active orthodontic treatment. Secondary outcomes will focus e.g. on achievement of orthodontic treatment goals and quantity of direct implant-bone interface of removed bone specimens. As tertiary objective, a histologic and microtomography evaluation of all retrieved implants will be performed to obtain data on the performance of the SLA surface in human bone evaluation of all retrieved implants. Additionally, resonance frequency analysis (RFA, Osstell? mentor) will be used at different times for clinically monitoring the implant stability and for histological comparison in order to measure the reliability of the resonance frequency measuring device.

Trial registration

Current Controlled Trials ISRCTN97142521.     

Successful immunotherapy with matrix metalloproteinase-derived peptides in adjuvant arthritis depends on the timing of peptide administration

We have recently found that matrix metalloproteinases (MMPs) are targets for T-cell and B-cell reactivity in experimental arthritis. In the present article, we investigate whether modulation of MMP-specific T-cell responses could influence the course of adjuvant arthritis (AA). Lewis rats were treated nasally with MMP peptides prior to or after AA induction. Administration of the MMP-10 or the MMP-16 peptide prior to AA induction reduced the arthritic symptoms. In contrast, administration of the MMP-10 peptide after AA induction aggravated the arthritic symptoms. The present study shows the possible usefulness of MMP peptides for immunotherapy. However, a clear understanding of proper timing of peptide administration is crucial for the development of such therapies.     

23Na Magnetic Resonance Imaging of the Lower Leg of Acute Heart Failure Patients during Diuretic Treatment

Objective

Na⁺ can be stored in muscle and skin without commensurate water accumulation. The aim of this study was to assess Na⁺ and H₂O in muscle and skin with MRI in acute heart failure patients before and after diuretic treatment and in a healthy cohort.

Methods

Nine patients (mean age 78 years; range 58–87) and nine age and gender-matched controls were studied. They underwent ²³Na/¹H-MRI at the calf with a custom-made knee coil. Patients were studied before and after diuretic therapy. ²³Na-MRI gray-scale measurements of Na⁺-phantoms served to quantify Na⁺-concentrations. A fat-suppressed inversion recovery sequence was used to quantify H₂O content.

Results

Plasma Na⁺-levels did not change during therapy. Mean Na⁺-concentrations in muscle and skin decreased after furosemide therapy (before therapy: 30.7±6.4 and 43.5±14.5 mmol/L; after therapy: 24.2±6.1 and 32.2±12.0 mmol/L; p˂0.05 and p˂0.01). Water content measurements did not differ significantly before and after furosemide therapy in muscle (p = 0.17) and only tended to be reduced in skin (p = 0.06). Na⁺-concentrations in calf muscle and skin of patients before and after diuretic therapy were significantly higher than in healthy subjects (18.3±2.5 and 21.1±2.3 mmol/L).

Conclusions

²³Na-MRI shows accumulation of Na⁺ in muscle and skin in patients with acute heart failure. Diuretic treatment can mobilize this Na⁺-deposition; however, contrary to expectations, water and Na⁺-mobilization are poorly correlated.     

Reliability of an injury scoring system for horses

Background

The risk of injuries is of major concern when keeping horses in groups and there is a need for a system to record external injuries in a standardised and simple way. The objective of this study, therefore, was to develop and validate a system for injury recording in horses and to test its reliability and feasibility under field conditions.

Methods

Injuries were classified into five categories according to severity. The scoring system was tested for intra- and inter-observer agreement as well as agreement with a 'golden standard' (diagnosis established by a veterinarian). The scoring was done by 43 agricultural students who classified 40 photographs presented to them twice in a random order, 10 days apart. Attribute agreement analysis was performed using Kendall's coefficient of concordance (Kendall's W), Kendall's correlation coefficient (Kendall's τ) and Fleiss' kappa. The system was also tested on a sample of 100 horses kept in groups where injury location was recorded as well.

Results

Intra-observer agreement showed Kendall's W ranging from 0.94 to 0.99 and 86% of observers had kappa values above 0.66 (substantial agreement). Inter-observer agreement had an overall Kendall's W of 0.91 and the mean kappa value was 0.59 (moderate). Agreement for all observers versus the 'golden standard' had Kendall's τ of 0.88 and the mean kappa value was 0.66 (substantial). The system was easy to use for trained persons under field conditions. Injuries of the more serious categories were not found in the field trial.

Conclusion

The proposed injury scoring system is easy to learn and use also for people without a veterinary education, it shows high reliability, and it is clinically useful. The injury scoring system could be a valuable tool in future clinical and epidemiological studies.

     

Diffusion is capable of translating anisotropic apoptosis initiation into a homogeneous execution of cell death

Background  

Apoptosis is an essential cell death process throughout the entire life span of all metazoans and its deregulation in humans has been implicated in many proliferative and degenerative diseases. Mitochondrial outer membrane permeabilisation (MOMP) and activation of effector caspases are key processes during apoptosis signalling. MOMP can be subject to spatial coordination in human cancer cells, resulting in intracellular waves of cytochrome-c release. To investigate the consequences of these spatial anisotropies in mitochondrial permeabilisation on subsequent effector caspase activation, we devised a mathematical reaction-diffusion model building on a set of partial differential equations.     

<Emphasis Type="Italic">TRAF1/C5</Emphasis>polymorphism is not associated with increased mortality in rheumatoid arthritis: two large longitudinal studies

Introduction  

Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients.     

Recent non‐native invertebrate plant pest establishments in Great Britain: origins,pathways, and trends

1 An appraisal of non‐native invertebrate plant pest establishments in Great Britain, between 1970 and 2004, was carried out to improve our understanding of current invasion processes by non‐native plant pests, and to assist national strategies in managing the risks they pose. 2 A total of 164 establishments, comprising 50 natural colonists and 114 human‐assisted introductions, were recorded across 13 major taxonomic groups. 3 The mean rate of establishment was 22.1 species per 5‐year period: 19.1 and 3.0 species outside and inside protected cultivation, respectively. Despite the continuing rapid growth in international trade and a general perception that rates of pest invasions are accelerating, no significant temporal trends in the rate of establishments in Great Britain were detected, either for natural colonists or human‐assisted introductions, or for pests of plants grown indoors or outside. 4 The plant trade, particularly in ornamental plants, accounted for nearly 90% of human‐assisted introductions; apiculture, biological control, timber imports, transport stowaways and intentional releases each contributed less than 5%. Only eight (4.9%) of the establishments could be considered as having no direct potential economic impact because all other species have been recorded as feeding on cultivated plants. A greater proportion of establishments by both natural colonists and human‐assisted introductions occurred on non‐native, woody plants. 5 The present study confirms previous work in other European countries that highlight the predominant role of the ornamental plant trade in introducing new plant pests to the European continent, mainly from Asia and North America.