Elution kinetics,antimicrobial activity,and mechanical properties of 11 different antibiotic loaded acrylic bone cement

Antibiotic-loaded acrylic bone cements (ALABC) spacers are routinely used in the treatment of prosthetic joint infections. The objectives of our study were to evaluate different ALABC for elution kinetics, thermal stability, and mechanical properties. A 10 or 20% mixture (w/w) beads of medium viscosity bone cement (DePuy, Inc) and vancomycin (VAN), gentamycin (GM), daptomycin (DAP), moxifloxacin (MOX), rifampicin (RIF), cefotaxime (CTX), cefepime (FEP), amoxicillin clavulanate (AmC), ampicillin (AMP), meropenem (MER), and ertapenem (ERT) were formed and placed into wells filled with phosphate-buffered saline. Antibiotic concentrations were determined using high-performance liquid chromatography. Antimicrobial activity was tested against Micrococcus luteus ATCC 9341 or Escherichia coli ATCC 25922. AmC, AMP, and FEP concentration rapidly decreased after day 2, being almost undetectable at day 4. Sustained and high elution rates were observed with VAN, GM, MOX, and RIF for the 30-day duration of the experiment. DAP, MER, ERT, and CTX elution rates constantly decreased from day 4. All antibiotics tested retained antimicrobial activity proving thermal stability. Mechanical properties of ALABC were maintained except when RIF was used.     

The Complete Nucleotide Sequence of the Carbapenem Resistance-Conferring Conjugative Plasmid pLD209 from a Pseudomonas putida Clinical Strain Reveals a Chimeric Design Formed by Modules Derived from Both Environmental and Clinical Bacteria

The complete sequence of the carbapenem-resistance-conferring conjugative plasmid pLD209 from a Pseudomonas putida clinical strain is presented. pLD209 is formed by 3 well-defined regions: an adaptability module encompassing a Tn402-like class 1 integron of clinical origin containing bla_VIM-2 and aacA4 gene cassettes, partitioning and transfer modules, and a replication module derived from plasmids of environmental bacteria. pLD209 is thus a mosaic of modules originating in both the clinical and environmental (nonclinical) microbiota.     

Mitochondrial-derived peptide humanin as therapeutic target in cancer and degenerative diseases

Introduction: Mitochondrial-derived peptides (MDPs) are encoded within the mitochondrial genome. They signal within the cell or are released to act as autocrine/paracrine/endocrine cytoprotective factors playing a key role in the cellular stress response. The first reported and better characterized MDP is humanin (HN), which exerts robust protective effects against a myriad of cytotoxic stimuli in many cell types. These effects have led to the evaluation of HN and its analogs as therapeutic targets for several chronic diseases.

Areas covered: We describe the latest findings on the mechanism of action of HN and discuss the role of HN as therapeutic target for neurodegenerative and cardiovascular diseases, diabetes, male infertility, and cancer. Since HN can be detected in circulation, we also depict its value as a biomarker for these diseases.

Expert opinion: HN analogs and peptide mimetics have been developed over the last decade and show promising results in preclinical models of degenerative diseases. Local administration of gene therapy vectors that overexpress or silence endogenous HN could also hold therapeutic potential. Controversy on the role of HN in cancer progression and chemoresistance should be addressed before the translation of these therapeutic approaches.     

Metabolic Syndrome Does Not Improve the Prediction of 5-Year Cardiovascular Disease and Total Mortality Over Standard Risk Markers. Prospective Population Based Study

Metabolic syndrome (MS) is widely believed to be an important risk factor for cardiovascular disease (CVD). We assessed whether a model based on MS improved prediction of CVD and total mortality over the Framingham''s general CVD system (FRS) and whether MS was better than its individual components.Prospective cohort study of 855 participants randomly selected from the general population. Cox proportional hazards models were used to estimate the hazard ratios selecting a composite endpoint of CVD and total mortality. The performance of the FRS was compared with that of 4 MS-based models that differed in their use of individual components of MS as well as in the use of optimized cut-points of MS. The assessment included metrics of discrimination, calibration, and risk reclassification.Of all the models, only the model containing the 5 optimized components of MS improved model fit (deviance 10.7, P = 0.005), discrimination (difference of areas under the receiving operating curves 0.018), and risk reclassification in participants without events (net reclassification index 5.97, P = 0.01). The addition of optimized waist circumference to the FRS model improved the performance more than any other MS-based model. Every model containing the dichotomous definition of MS failed to improve model fit, discrimination, and risk reclassification.MS did not contribute predictive information over the FRS for the 5-year risk of CVD and total mortality. Some individual components of MS, in particular waist circumference, might play a role as part of the FRS provided their cut-off points are optimized.