Vaccination prepartum enhances the beneficial effects of melatonin on the immune response and reduces platelet responsiveness in sheep

Background

Eradication of bovine tuberculosis (bTB) through the application of test-and-cull programs is a declared goal of developed countries in which the disease is still endemic. Here, longitudinal data from more than 1,700 cattle herds tested during a 12?year-period in the eradication program in the region of Madrid, Spain, were analyzed to quantify the within-herd transmission coefficient (??) depending on the herd-type (beef/dairy/bullfighting). In addition, the probability to recover the officially bTB free (OTF) status in infected herds depending on the type of herd and the diagnostic strategy implemented was assessed using Cox proportional hazard models.

Results

Overall, dairy herds showed higher ?? (median 4.7) than beef or bullfighting herds (2.3 and 2.2 respectively). Introduction of interferon-gamma (IFN-??) as an ancillary test produced an apparent increase in the ?? coefficient regardless of production type, likely due to an increase in diagnostic sensitivity. Time to recover OTF status was also significantly lower in dairy herds, and length of bTB episodes was significantly reduced when the IFN-?? was implemented to manage the outbreak.

Conclusions

Our results suggest that bTB spreads more rapidly in dairy herds compared to other herd types, a likely cause being management and demographic-related factors. However, outbreaks in dairy herds can be controlled more rapidly than in typically extensive herd types. Finally, IFN-?? proved its usefulness to rapidly eradicate bTB at a herd-level.     

High protein binding and cidal activity against penicillin-resistant S. pneumoniae: a cefditoren in vitro pharmacodynamic simulation

Background

Although protein binding is a reversible phenomenon, it is assumed that antibacterial activity is exclusively exerted by the free (unbound) fraction of antibiotics.

Methodology/Principal Findings

Activity of cefditoren, a highly protein bound 3^rd generation cephalosporin, over 24h after an oral 400 mg cefditoren-pivoxil bid regimen was studied against six S. pneumoniae strains (penicillin/cefditoren MICs; µg/ml): S1 (0.12/0.25), S2 (0.25/0.25), S3 and S4 (0.5/0.5), S5 (1/0.5) and S6 (4/0.5). A computerized pharmacodynamic simulation with media consisting in 75% human serum and 25% broth (mean albumin concentrations = 4.85±0.12 g/dL) was performed. Protein binding was measured. The cumulative percentage of a 24h-period that drug concentrations exceeded the MIC for total (T>MIC) and unbound concentrations (fT>MIC), expressed as percentage of the dosing interval, were determined. Protein binding was 87.1%. Bactericidal activity (≥99.9% initial inocula reduction) was obtained against strains S1 and S2 at 24h (T>MIC = 77.6%, fT>MIC = 23.7%). With T>MIC of 61.6% (fT>MIC = 1.7%), reductions against S3 and S4 ranged from 90% to 97% at 12h and 24h; against S5, reduction was 45.1% at 12h and up to 85.0% at 24h; and against S6, reduction was 91.8% at 12h, but due to regrowth of 52.9% at 24h. Cefditoren physiological concentrations exerted antibacterial activity against strains exhibiting MICs of 0.25 and 0.5 µg/ml under protein binding conditions similar to those in humans.

Conclusions/Significance

The results of this study suggest that, from the pharmacodynamic perspective, the presence of physiological albumin concentrations may not preclude antipneumococcal activity of highly bound cephalosporins as cefditoren.     

Light responses in the green sulfur bacterium Prosthecochloris aestuarii: changes in prosthecae length, ultrastructure, and antenna pigment composition

The morphology (mainly prosthecae length), ultrastructure, and antenna pigment composition of the green sulfur bacterium Prosthecochloris aestuarii changed when grown under different light intensities. At light intensities of 0.5 and 5 micromol quanta m(-2) s(-1), the cells had a star-like morphology. Prosthecae, the characteristic appendages of the genus Prosthecochloris, were 232 nm and 194 nm long, respectively. In contrast, when grown at 100 micromol quanta m(-2) s(-1), these appendages were shorter (98 nm) and the cells appeared more rod-shaped. Transmission electron microscopy revealed a significant decrease in the cell perimeter to area ratio and in the number of chlorosomes per linear microm of membrane as light intensity increased. In addition to these morphological and ultrastructural responses, Prosthecochloris aestuarii exhibited changes in its pigment composition as a function of light regime. Lower specific pigment content and synthesis rates were found in cultures grown at light intensities above 5 micromol quanta m(-2) s(-1). A blue shift in the bacteriochlorophyll (BChl) c Q(y) absorption maximum of up to 17.5 nm was observed under saturating light conditions (100 micromol quanta m(-2) s(-1)). This displacement was accompanied by changes in the composition of BChl c homologs and by a very low carotenoid content. The morphological, ultrastructural and functional changes exhibited by Prosthecochloris aestuarii revealed the strong light-response capacity of this bacterium to both high and low photon-flux densities.     

Hierro intravenoso,recuperación funcional y delirium en pacientes con fractura de cadera. Estudio FEDEREF. Ensayo clínico unicéntrico aleatorizado,controlado con placebo,doble ciego. Número EudraCT: 2014-001923-53

Introduction

There are no previous studies evaluating the effect of intravenous iron therapy on functional and cognitive status of patients with hip fracture (HF).

Contributions of in situ microscopy to the current understanding of stone biodeterioration.

In situ microscopy consists of simultaneously applying several microscopy techniques without separating the biological component from its habitat. Over the past few years, this strategy has allowed characterization of the biofilms involved in biodeterioration processes affecting stone monuments and has revealed the biogeophysical and biogeochemical impact of the microbiota present. In addition, through in situ microscopy diagnosis, appropriate treatments can be designed to resolve the problems related to microbial colonization of stone monuments.     

Synthesis and membrane action of polymyxin B analogues.

We have designed synthetic peptides that mimic the primary and secondary structure of the cationic lipopeptide antibiotic polymyxin B (PxB) in order to determine the structural requirements for membrane action and to assess possible therapeutic potential. Two analogues with related sequences to that of PxB, but including synthetic simplifications (disulphide bridge between two cysteines in positions 4 and 10, N-terminal nonanoic acid), have been synthesized. Peptide-lipid interactions have been studied by fluorescence resonance energy transfer between pyrene and 4,4-difluoro-5-methyl-4-bora-3alpha,4alpha-diaza-s-indacene-3-dodecanoyl (BODIPY)probes covalently linked to phospholipids, and the possibility of membrane disruption or permeabilization has been assessed by light scattering and fluorescence quenching assays. The synthetic peptide sP-B, which closely mimics the primary and secondary structures of PxB, binds to vesicles of anionic 1-palmitoyl-2-oleoylglycero-sn-3-phosphoglycerol (POPG) or of lipids extracted from Escherichia coli membranes, and induces apposition of the vesicles and selective lipid exchange without permeabilization of the membrane. We conclude that sP-B forms functional vesicle-vesicle contacts that are selective, as previously described for PxB. The second analogue, sP-C, has a permutation of two amino acids that breaks the hydrophobic patch formed by D-Phe and Leu residues on the cyclic part of the sequence. sP-C lipopeptide is more effective than sP-B in inducing lipid mixing, but shows no selectivity for the lipids that exchange through the vesicle-vesicle contacts, and at high concentrations has a membrane-permeabilizing effect. The deacylated and non-antibiotic derivative PxB-nonapeptide (PxB-NP) does not induce the formation of functional intervesicle contacts in the range of concentrations studied.     

Heritability of running economy: a study made on twin brothers

Running economy (RE), defined as the steady-state of oxygen uptake (V˙O₂) for a given running velocity, is a factor of sports performance the genetic component of which has seldom been reported to date. We studied this component using a heritability index (HI) in a group of 32 male twins, 8 monozygotic (MZ) and 8 dizygotic (DZ) pairs, all sportsmen with similar perinatal and environmental backgrounds. Zygocity was determined by the identity of erythrocytic antigenic, protein and enzymatic polymorphism, and human leucocyte antigen serologic types between co-twins. The subjects exercised twice on a treadmill, once until exhaustion and again at submaximal intensities. Pulmonary gas exchange was measured continuously using an automatic analyser system during both tests. Blood samples were obtained during the recovery period to determine lactate concentrations. No significant differences were observed between MZ and DZ, in respect of RE at any speed or in maximal V˙O₂ relative to body mass. Nevertheless, significant HI (P < 0.05) was found in maximal lactate concentrations (HI = 0.75) and in respiratory equivalent for oxygen at two speeds, 7 km · h⁻¹ (HI = 0.71) and 8 km · h⁻¹ (HI = 0.79), differences which probably suggest that there are differences in RE. In conclusion, we did not detect a genetic component in RE or in maximal oxygen uptake, but a genetic component for markers of anaerobic metabolism was present. Accepted: 5 November 1997