Antibody-Functionalized Copper Oxide Nanoparticles with Targeted Antibacterial Activity.

Copper oxide nanoparticles (CuO-NPs) were functionalized with specific antibodies to target their antibacterial activity against Gram-positive or Gram-negative bacteria. The CuO-NPs were covalently functionalized to cover their surface with specific antibodies. The differently prepared CuO-NPs were characterized by X-ray diffraction, transmission electron microscopy and dynamic light scattering. The antibacterial activities of the unmodified CuO-NPs and the antibody-functionalized nanoparticles (CuO-NP-AbGram- and CuO-NP-AbGram+ ) were determined for both Gram-negative Escherichia coli and Gram-positive Bacillus subtilis bacteria. The antibody-functionalized NPs showed a differential increase of their antibacterial activity according to the specific antibody. The CuO-NP-AbGram- in E. coli showed reduced half maximal inhibitory concentration (IC50 ) and minimum inhibitory concentration (MIC) values when compared with unfunctionalized CuO-NPs. On the other hand, the CuO-NP-AbGram+ also showed reduced IC50 and MIC values in B. subtilis, when compared with non-functionalized CuO-NPs. Thus, the functionalized CuO nanoparticles with specific antibodies showed enhanced specificity of their antibacterial activity. The advantages of "smart" antibiotic nanoparticles are discussed.

Detection of large rearrangements in the cystic fibrosis transmembrane conductance regulator gene by multiplex ligation-dependent probe amplification assay when sequencing fails to detect two disease-causing mutations.

AIMS: Most of the over 1600 mutations and sequence variants identified to date in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are point mutations or small deletions/insertions detectable by conventional sequencing. However, large rearrangements (deletions, duplications, or insertion/deletion mutations) have recently been reported to constitute 1-2% of CFTR mutations. The CFTR sequencing protocol at ARUP Laboratories interrogates the coding regions of all 27 exons and all intron/exon boundaries of the gene. This study was undertaken to determine whether testing for large gene rearrangements could improve the mutation detection rate. RESULTS: Nine cases with abnormal quantitative pilocarpine iontophoresis sweat chloride (SC) values (>60 mEq/L) and 20 cases with borderline SC levels (40-60 mEq/L) with only one or no mutations detected by the ARUP 32 mutation panel, including the 23 mutations recommended by American College of Medical Genetics (ACMG) for carrier screening, followed by sequencing, were tested using a multiplex ligation-dependent probe amplification (MLPA) assay. MLPA analysis identified one deletion among nine patients with SC >60 who had previously been tested with sequencing. None of the cases with borderline SC levels showed rearrangements. CONCLUSION: The MLPA assay for detection of large rearrangements may be valuable in individuals with positive SC levels where one or no mutations have been identified by sequencing.

Improved renal function, with similar proteinuria, after two years of early tacrolimus withdrawal from a regimen of sirolimus plus tacrolimus.

Results at 1 year of a pilot randomized trial with 87 kidney graft recipients, comparing the maintenance treatment with sirolimus, tacrolimus and steroids (group I) versus tacrolimus withdrawal since the third month onward, followed by maintenance with SRL and steroids (group II) have shown that early elimination of tacrolimus may result in improved renal function and blood pressure control. At 2 years, 26 and 25 patients in groups I and II, respectively, were analyzed in an on-therapy and an ITT analysis. In the on-therapy analysis, group II showed lower serum creatinine (1.3+/-0.2 vs. 1.6+/-0.6 mg/dL) and lower diastolic blood pressure (74+/-9 vs. 80+/-11 mm Hg). No acute rejections occurred during the second year of follow-up. In more than 90% of patients, proteinuria was less than 1 g/d, and in 50% it was negative. In the ITT analysis, differences were found only in diastolic blood pressure (80+/-10 vs. 74+/-8 mm Hg in groups I and II respectively, P=0.009). Tacrolimus withdrawal from a combination of sirolimus and tacrolimus, in selected patients, may be observed at 2 years by an improvement in renal function and blood pressure without a higher incidence of proteinuria.

Peripheral blood lymphocyte populations in end-stage liver diseases.

GOALS/BACKGROUND: The aim of this study was to decipher whether end-stage liver failure modifies peripheral blood lymphocytes (PBL) in a homogeneous manner, independently of the base pathology, or, if on the contrary, PBL subsets show a different profile in each hepatic disease. METHODS: We studied PBL subsets in 71 patients with end-stage liver disease, before liver transplant, and 74 healthy controls by flow cytometry. The results were statistically compared between patients and controls, and cohorts of patients classified according to their base pathology. RESULTS: We observed lower absolute numbers in all lymphocyte populations in patients compared with controls. We found an increment of CD3+ activated cells (P<10) and CD45RO+CD4+ (P<10) in chronic hepatitis C virus versus controls; hepatitis B virus showed high TCRgammadelta+ and CD8+ T cells with respect to controls (P=0.008 and P=0.029, respectively); alcoholic cirrhotic patients showed low CD8+, mainly CD45RA+CD8+ (P=0.007) and high CD45RO+CD4+ (P<10) compared with the normal population; autoimmune diseases showed lower CD3+ and TCRalphabeta+ (P=0.002 and P=0.0001) than controls. CONCLUSIONS: Regardless of the base pathology, patients with end-stage liver disease show a low absolute number of lymphocyte populations compared with controls. However, PBL profiles are different, characteristic, and specific of every disease causing chronic liver failure.

Disolución medicamentosa de Cálculos Biliares ¿una alternativa? / Disolving biliary stones, an alternative of treatment

En la última decada en varios centros médicos se ha venido tratando los casos de litiasis vesicular con diferentes métodos como una alternativa a la colecistectomía. Se han empleado difrentes ácido biliares por vial oral, así como también otros diluyentes que se aplican directamente a la vesicula como por ejemplo el metil etil butil éter, habiendose conseguido resultados halagadores. Ultimamente se ha venido usando el método de destrucción de cálculos biliares a través de la aplicación extracorporal de ondas de choques. Refiriendose en particular a la disolución medicamentosa, debemos decir que de éste métodos se benifician exclusivamente los pacientes portadores de calculos de colesterol .