Synthesis of oxocarbon-encapsulated gold nanoparticles with blue-shifted localized surface plasmon resonance by pulsed laser ablation in water with CO2 absorbers.

Colloidal suspensions of oxocarbon-encapsulated gold nanoparticles have been synthesized in a one-step procedure by pulsed-laser ablation (PLA) at 532 nm of a solid gold target placed in aqueous solution containing CO2 absorbers, but without any stabilizing agent. Multi-wavelength surface enhanced Raman spectroscopy allows the identification of adsorbed amorphous carbon and graphite, Au-carbonyl, Au coordinated CO2-derived bicarbonates/carbonates and hydroxyl groups around the AuNPs core. Scanning electron microscopy, energy dispersive x-ray analysis and high resolution transmission electron microscopy highlight the organic shell structure around the crystalline metal core. The stability of the colloidal solution of nanocomposites (NCs) seems to be driven by solvation forces and is achieved only in neutral or basic pH using monovalent hydroxide counter-ions (NaOH, KOH). The NCs are characterized by a blue shift of the localized surface plasmon resonance (LSPR) band typical of metal-ligand stabilization by terminal π-back bonding, attributed to a core charging effect caused by Au-carbonyls. Total organic carbon measurements detect the final content of organic carbon in the colloidal solution of NCs that is about six times higher than the value of the water solution used to perform PLA. The colloidal dispersions of NCs are stable for months and are applied as analytical probes in amino glycoside antibiotic LSPR based sensing.

Predictores clínicos del resultado de la angioplastia infrapoplítea en pacientes con isquemia crítica / Clinical predictors of the results of infra-popliteal angioplasty in patients with critical ischaemia

OBJETIVOS: Describir los resultados de la angioplastia infrapoplítea en pacientes con isquemia crítica y determinar los factores pronósticos del resultado del procedimiento. MATERIAL Y MÉTODOS: Estudio retrospectivo sobre una cohorte de pacientes con isquemia crítica tratados con angioplastia infrapoplítea. Se recogieron variables sobre características demográficas, comorbilidades, presentación clínica, características arteriográficas de los vasos afectados, angiosoma afectado, descripción del procedimiento y de los resultados de la postangioplastia. Los eventos analizados fueron la supervivencia global, la supervivencia libre de amputación y la cicatrización de las lesiones tróficas. RESULTADOS: Se intervinieron 124 extremidades en 120 pacientes entre enero del 2011 y diciembre del 2013. El éxito técnico fue del 92%. La mediana de seguimiento fue de 12,6 meses. La supervivencia global a los 6, 12, 18 y 24 meses fue del 91,4, 89,4, 82,8 y 76,3% respectivamente. La supervivencia libre de amputación a los 12 y 24 meses fue del 88,1 y 76,3%. Un 64,3% experimentó una mejoría o cicatrización completa de las lesiones. La insuficiencia renal crónica terminal se asoció con un mayor riesgo de mortalidad (HR = 11,7 95% IC 2,8-48,4). El tratamiento con estatinas se asoció con una menor mortalidad (HR = 0,3, 95% IC 0,1-0,9). Los pacientes que presentaron un riesgo incrementado de amputación fueron aquellos con afectación arterial ultradistal (HR = 5,4 95% IC 1,5-18,4). La revascularización directa del angiosoma se asoció con la mejoría o cicatrización completa de las heridas (HR = 2,4 95% IC 1,2-4,9). CONCLUSIONES: La angioplastia del sector distal es una adecuada opción terapéutica para la supervivencia, el salvamento de extremidad y la cicatrización de lesiones tróficas. El tratamiento con estatinas se asocia a una menor mortalidad. La estrategia de revascularización en función del angiosoma puede ser efectiva para la curación de las heridas

OBJECTIVES: To describe the results of infra-popliteal angioplasty in patients with critical ischaemia, as well as to determine the prognostic factors of the results of the procedure. MATERIAL AND METHODS: A retrospective study on a patient cohort with critical ischemia treated with infra-popliteal angioplasty. Variables were collected on the demographic characteristics, comorbidities, clinical presentation, arteriography features of the affected vessels, and the affected angiosome. A description of the procedure and the post-angioplasty results were also recorded. The events analysed were, the overall survival, amputation-free survival, and the healing of trophic lesions. RESULTS: A total of 124 limbs were operated on in 120 patients between January 2011 and December 2013. The technical success was 92%. The median follow-up was 12.6 months. The overall survival at 6, 12, 18, and 24 months was 91.4%, 89.4%, 82.8% and 76.3%, respectively. The amputation-free survival at 12 and 24 months was 88.1% and 76.3%, with 64.3% experiencing an improvement or complete healing of the lesions. Chronic kidney failure was associated with a higher mortality risk (HR: 11.7 95% CI 2.8-48.4). Treatment with statins was associated with a lower mortality (HR: 0.3, 95% CI 0.1-0.9). Patients with ultra-distal arterial involvement had a higher amputation risk (HR: 5.4 95% CI 1.5-18.4). Direct revascularisation of the angiosome was associated with an improvement or complete healing of the wounds (HR: 2.4 95% CI 1.2-4.9). CONCLUSIONS: Angioplasty of the distal sector is a suitable therapeutic option for survival, limb salvage, and healing of the trophic lesions. The revascularisation strategy as regards the angiosome may be effective for the healing of the wounds

A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome.

OBJECTIVE: Individual sensitivity to recombinant human GH (r-hGH) is variable. Identification of genetic factors contributing to this variability has potential use for individualization of treatment. The objective of this study was to identify genetic markers and gene expression profiles associated with growth response on r-hGH therapy in treatment-naïve, prepubertal children with GH deficiency (GHD) or Turner syndrome (TS). DESIGN: A prospective, multicenter, international, open-label pharmacogenomic study. METHODS: The associations of genotypes in 103 growth- and metabolism-related genes and baseline gene expression profiles with growth response to r-hGH (cm/year) over the first year were evaluated. Genotype associations were assessed with growth response as a continuous variable and as a categorical variable divided into quartiles. RESULTS: Eleven genes in GHD and ten in TS, with two overlapping between conditions, were significantly associated with growth response either as a continuous variable (seven in GHD, two in TS) or as a categorical variable (four more in GHD, eight more in TS). For example, in GHD, GRB10 was associated with high response (≥ Q3; P=0.0012), while SOS2 was associated with low response (≤ Q1; P=0.006), while in TS, LHX4 was associated with high response (P=0.0003) and PTPN1 with low response (P=0.0037). Differences in expression were identified for one of the growth response-associated genes in GHD (AKT1) and for two in TS (KRAS and MYOD1). CONCLUSIONS: Carriage of specific growth-related genetic markers is associated with growth response in GHD and TS. These findings indicate that pharmacogenomics could have a role in individualized management of childhood growth disorders.

Monogenic and polygenic models detected in steroid 21-hydroxylase deficiency-related paediatric hyperandrogenism.

AIMS: Hyperandrogenism, although mostly due to polygenic interactions, is monogenic for some enzymatic adrenal deficiencies. This study evaluates mono- and biallelic 21-hydroxylase deficiency (21OHD)-related hyperandrogenism in pediatric patients. Sensitizing and protective polymorphisms were investigated in carriers and cryptic forms of 21OHD. METHODS: The study involved a monogenic analysis of CYP21A2 in patients (375 nonclassical 21OHD [NC21OHD] children; 306 hyperandrogenic 21OHD carriers, n = 306) and a polygenic association study (CAPN10-UCSNP44, PON1-108, TNFR2-M196R, IGF2-ApaI and IRS1-G972R polymorphisms) of 170 hyperandrogenic carriers plus 277 family members (control groups). The metabolic marker 17OH progesterone defined the degree of deficiency; clinical expressivity was determined by pediatric endocrinologists. RESULTS: The group of 21OHD carriers manifesting hyperandrogenism was enriched in the CAPN-UCSNP44 rare variant in homozygosity (4.9 vs. 0.4%, NCBI data for the general population; p = 0.004). In our patients and controls, contrasting distributions were observed for this and another polymorphism, TNFR2-196R. In a recessive model, their rare variants were more frequently detected among the forms with high (p = 0.048) and low (p = 0.034) expressivity respectively. CONCLUSIONS: 21OHD-related pediatric hyperandrogenism follows monogenic and polygenic models. The opposite behaviors in terms of clinical expressivity detected for CAPN-UCSNP44 and TNFR2-M196R rare variants suggest these variants to be sensitizing and protective factors respectively in adrenal hyperandrogenism.

Gene duplications in 21-hydroxylase deficiency: the importance of accurate molecular diagnosis in carrier detection and prenatal diagnosis.

BACKGROUND: The detection of 21-OH deficiency (21OHD) carriers in the general population requires that misinterpretations of apparently severe mutations in alleles carrying duplicated genes be avoided. Prenatal treatment prevents virilization in female fetuses and genetic counseling may be offered to couples in which one partner is either a patient or a carrier. This paper proposes a semiquantitative PCR method involving primer extension that distinguishes the severe point mutation Q318X in single gene copy alleles from the normal/nondeficient variant in gene-duplicated alleles. SAMPLES AND METHODS: DNA from 65 individuals carrying Q318X variants, that of 85 partners of 21OHD carriers or patients, and one fetal sample (as well as the DNA of his family) were analyzed. 21OHD alleles were studied by gene-specific PCR/allele-specific oligonucleotides hybridization for common mutations, Southern analysis, complementary direct sequencing and microsatellite typing. Primer extension analysis of the Q318X variants using fluorescent dideoxynucleotides was performed on CYP21A2 gene-specific PCR-amplified DNA samples from controls, patients, potential carriers and prenatal samples. RESULTS: Different fluorescence patterns were seen for the severe mutation (single gene copy) and the nondeficient (gene-duplicated) alleles carrying Q318X. The normal/mutant fluorescence peak (N/M) ratio was < 1 in all heterozygous carriers (mean 0.83; min. 0.70; max. 0.95). In all normal individuals carrying the gene-duplicated Q318X normal variant, the N/M ratio was > 1 (mean 1.69; min. 1.44; max. 2.02). CONCLUSION: The proposed method discriminated between the severe Q318X mutation and the normal Q318X variant in gene duplication, and could be a useful complementary tool in prenatal diagnosis and carrier detection.

Tratamiento de pseudoaneurismas arteriales yatrógenos con inyección de trombina humana / Treatment of iatrogenic arterial pseudoaneurysms with human thrombin injections

Introducción. La incidencia de pseudoaneurismas yatrógenos ha aumentado debido al mayor número de procedimientos intervencionistas y a la anticoagulación asociada. La búsqueda de tratamientos eficaces frente a la cirugía ha sido un reto en los últimos años. Objetivo. Analizar la eficacia y seguridad del tratamiento con trombina humana (TH) de una serie de 10 pseudoaneurismas y atrógenos. Pacientes y métodos. Ocho pacientes (cinco mujeres y tres varones), de edad media 67 años (46-85), sumaban un total de 10 pseudoaneurismas en la arteria femoral común, secundarios a cateterismo cardíaco (cinco), arteriografía diagnóstica (uno), embolización de aneurisma cerebral (uno) y fibrinólisis intrarterial (uno). La selección para su tratamiento fue: diámetro superior a 15 mm (15-35) y localización anterior respecto a la arteria. Se empleó solución salina de TH (100 U/cm 3, procedente de Tissucol ®) y aguja 22G. Se inyectaron en la cavidad 100-400 U mediante inyección percutánea guiada por ecografía. Dos pacientes estaban anticoagulados durante el procedimiento. Se exploraron índices tobillo/brazo y pulsos, antes y después de la inyección. Se hicieron controles a las 24 horas, 2 y 6 meses. Resultados. La trombosis total de la cavidad se produjo a los pocos segundos, sin cambios en el índice talón-rodilla o pulsos. Sólo hubo una recidiva en un pseudoaneurisma, a las 24 horas. Conclusiones. La inyección percutánea de TH es una técnica efectiva (90 per cent de trombosis primaria), segura (sin dolor ni complicaciones en nuestra serie) y de corta duración para el tratamiento de primera línea de los pseudoaneurismas femorales y atrógenos (AU)