Trehalose preserves DDA/TDB liposomes and their adjuvant effect during freeze-drying

Disaccharides are well-known reagents to protect biostructures like proteins and phospholipid-based liposomes during freezing and drying. We have investigated the ability of the two disaccharides trehalose and sucrose to stabilize a novel, non-phospholipid-based liposomal adjuvant composed of the cationic dimethyldioctadecylammonium (DDA) and trehalose 6,6′-dibehenate (TDB) upon freeze-drying. The liposomes were freeze-dried using a human dose concentration containing 2.5 mg/ml DDA and 0.5 mg/ml TDB with varying concentrations of the two sugars. The influence on particle size upon rehydration was investigated using photon correlation spectroscopy (PCS) and the gel to fluid phase transition was examined by differential scanning calorimetry (DSC). Data revealed that concentrations above 211 mM trehalose protected and preserved DDA/TDB during freeze-drying, and the liposomes were readily rehydrated. Sucrose was less efficient as a stabilizer and had to be used in concentrations above 396 mM in order to obtain the same effect. Immunization of mice with the tuberculosis vaccine candidate Ag85B-ESAT-6 in combination with the trehalose stabilized adjuvant showed that freeze-dried DDA/TDB liposomes retained their ability to stimulate both a strong cell-mediated immune response and an antibody response. These findings show that trehalose at isotonic concentrations protects cationic DDA/TDB-liposomes during freeze-drying. Since this is not the case for liposomes based on DDA solely, we suggest that the protection is facilitated via direct interaction with the headgroup of TDB and a kosmotropic effect, whereas direct interaction with DDA plays a minor role.     

Maximal oxygen deficit of sprint and middle distance runners

Anaerobic energy capacity was evaluated by maximal oxygen deficit (MOD) as well as by blood gas and muscle biopsy variables during short exhausting running in six recreational (RR) and eight competitive sprint and middle distance runners (SMDR). On 3 days runs to exhaustion were executed. Two runs were performed at a treadmill gradient of 15% at speeds which resulted in exhaustion after approximately 1 (R_{15%, 1min}) and 2–3 min (R_{15%, 2–3min}), respectively. On the 3rd day, the subjects ran with the treadmill at a gradient of 1% at a speed which caused exhaustion after 2–3 min (R_{1%, 2–3min}). The runner performance was assessed from 400 m [RR, median 64.8 (range 62.2–69.6) s; SMDR, median 49.4 (range 48.5–52.0) s] and 800 m [RR, median 158.8 (range 153.3–170.2) s; SMDR, median 115.2 (range 113.3–123.3) s] track times. Muscle biopsies from gastrocnemius muscle were obtained before and immediately after R_{15%, 2–3min}, from which muscle lactate and creatine phosphate (CP) concentrations, fibre type distribution, capillaries per fibre, total lactate dehydrogenase (LDH) activity and the LDH isoenzyme pattern were determined. The MOD increased with the treadmill gradient and duration. During both treadmill and track runs, SMDR performance was superior to that of RR, but no significant differences were observed with respect to MOD, muscle fibre type distribution, total LDH activity, its iso-enzyme pattern, changes in muscle lactate or CP concentrations. However, after treadmill runs, peak venous lactate concentration and partial pressures of carbon dioxide were higher, and pH lower in SMDR. Also the number of capillaries per muscle fibre and the maximal oxygen uptake were larger in SMDR. These findings would suggest that the superior performance of SMDR depended more on their aerobic than on their anaerobic capacity.     

Reduced use of antimicrobials after vaccination of pigs against porcine proliferative enteropathy in a Danish SPF herd

The present study explored whether the use of group medication with antibiotics in a Danish pig herd was reduced after vaccination of the pigs against proliferative enteropathy (PE) caused by Lawsonia intracellularis. 7900 pigs originating from a single commercial sow herd were vaccinated against L. intracellularis, whereas 7756 pigs were kept as non-vaccinated controls. The pigs were included batch-wise in the study with every second batch being vaccinated. In the vaccinated batches, the consumption of oxytetracykline to treat PE was reduced by 79%, with a significantly lower number of pigs being treated (P < 0.0001). Vaccination also resulted in a highly significant improvement of average daily weight gain (+ 46 g/day; P = 9.55 × 10^-31) and carcase weight (+ 1.25 kg; P = 4.54 × 10^-05) as well as a shortened fattening period (-8 days; P = 2.01 × 10^-45).     

The infant gut resistome associates with E. coli,environmental exposures,gut microbiome maturity,and asthma-associated bacterial composition

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