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1.
BMC Ophthalmol ; 23(1): 317, 2023 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-37442998

RESUMEN

BACKGROUND: Cataracts are the world's leading cause of avoidable blindness. In low-income countries, there are high rates of poor follow-up, which makes it very difficult to monitor surgical outcomes. To address this issue, the Better Operative Outcome Software Tool (BOOST Cataract app) predicts outcome on the first postoperative day and provides specific advice to improve outcomes. The aim of the study is to evaluate the ability of the BOOST Cataract app to categorise surgical outcomes and to analyse the possible factors that contribute to its performance. This was a prospective observational study performed at the General Hospital of Hospitalet of Llobregat. RESULTS: A total of 126 cataracts were included. Patients had a mean [SD] age of 75.8 [12.19] years, and 52% were females. Manual small-incision cataract surgery was involved in 57% and phacoemulsification in 43%. Thirty-eight percent of eyes presented significant corneal oedema on day 1. The BOOST Cataract app succeeded in categorising the final outcome in 65.6% of the eyes and in 93,4% of the eyes with good outcome.The agreement between the BOOST and UDVA outcomes was 0.353 (p< .000). The level of agreement improved to 0.619 (p< .000) in eyes with clear corneas. Success obtained by BOOST for both types of surgery was not statistically different. Eyes that obtained a good outcome on day one after surgery and eyes with clear cornea had 37 times higher odds (95% CI 6.66, 212.83) and 12 times higher odds (95% CI 3.13, 47.66) of being correctly categorised by the BOOST Cataract app than eyes that obtained a suboptimal (moderate and poor) outcome and eyes with corneal oedema on day 1. CONCLUSIONS: The BOOST Cataract app is an e-Health tool designed to address issues of measuring quality in low- and middle-income settings. Although its reliability is limited to eyes that obtain a good outcome and with clear corneas on day 1, the use of the tool on a regular basis facilitates monitoring and reporting outcomes when clinical data collection is challenging due to low postoperative follow-up rates.


Asunto(s)
Extracción de Catarata , Catarata , Edema Corneal , Facoemulsificación , Femenino , Humanos , Niño , Masculino , Estudios de Seguimiento , Reproducibilidad de los Resultados , Catarata/complicaciones , Resultado del Tratamiento
2.
J Chem Phys ; 150(14): 144507, 2019 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-30981249

RESUMEN

In this article, we present a molecular thermodynamic study of a system of N particles contained within a volume V and interacting via a hard-core pair potential with an attractive interaction according to the Wolf model for charged systems. This variable-range potential is characterized by three parameters: the repulsive hard-core diameter σ, the energy-well depth ϵ, and the inverse range α; a fourth parameter of the model is a cut-off distance xc that depends on α according to the relation xc = 2/α. Two equations of state (EOSs) are presented and derived from thermodynamic perturbation theory and Monte Carlo (MC) simulation data. The first EOS is given by the standard Zwanzig's high-temperature expansion of the Helmholtz free energy, where the first three perturbation terms a1, a2, and a3 were obtained from MC simulations in the canonical ensemble (NVT) and parameterized as functions of α and the reduced density of particles ρ* = Nσ3/V. The second EOS was obtained from the discrete perturbation theory applied to a discrete representation of the Wolf potential. Results for pressures, internal energies, and isochoric heat capacities are compared to the MC computer simulation data of the Wolf system, including vapor-liquid coexistence curves, for different values of α. Overall, both EOSs give a very good representation of the thermodynamic properties of the Wolf fluid when 0.3 ≤ α ≤ 1.0 and 0.05 ≤ ρ* ≤ 0.8. Since the Yukawa fluid can reproduce information of screened ionic interactions, we discuss the equivalence between the Wolf and Yukawa fluids in the context of equivalent systems in liquid theory.

3.
J Inherit Metab Dis ; 41(6): 1037-1042, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29594644

RESUMEN

INTRODUCTION: McArdle disease is an inborn disorder of muscle glycogen metabolism that produces exercise intolerance, and has been recently associated with low values ​​of lean mass (LM) and bone mineral content (BMC) and density (BMD) in affected adults. Here we aimed to study whether this bone health problem begins in childhood. METHODS: Forty children and adolescents were evaluated: 10 McArdle disease and 30 control children (mean age of both groups, 13 ± 2y). Body composition was evaluated by dual-energy X-ray absorptiometry and creatine kinase (CK) levels were determined in the patients as an estimate of muscle damage. RESULTS: Legs bone mass was significantly lower in patients than in controls (-36% for BMC and -22% for BMD). Moreover, patients had significantly higher LM values in the legs than controls, whereas no difference was found for fat mass. CK levels were positively associated with LM in McArdle patients. A correlation was found between LM and BMD variables in the control group but not in McArdle patients. CONCLUSION: We have identified a 'non-osteogenic muscle hypertrophy' in children with McArdle disease. This phenomenon warrants special attention since low osteogenesis at an early age predicts a high risk for osteoporosis later in life.


Asunto(s)
Composición Corporal , Densidad Ósea , Creatina Quinasa/metabolismo , Enfermedad del Almacenamiento de Glucógeno Tipo V/metabolismo , Músculo Esquelético/patología , Absorciometría de Fotón , Adolescente , Índice de Masa Corporal , Estudios de Casos y Controles , Niño , Estudios Transversales , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo V/complicaciones , Humanos , Hipertrofia/patología , Pierna/fisiología , Masculino , Osteoporosis/etiología , Osteoporosis/patología
4.
Phys Chem Chem Phys ; 20(44): 28308-28318, 2018 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-30398498

RESUMEN

We analyze the water vapour-liquid and solid-liquid phase transitions from the perspective of hydrogen bond networks. Using molecular dynamics simulation data for the TIP4P/2005 and TIP4P/ice water models, we built hydrogen bond networks in the neighbourhood of the transitions. We studied the behaviour of some topological network properties: the average degree, clustering coefficient, and average path length. We found that these properties exhibit a discontinuity while approaching a phase transition region, similar to those that appear for some thermodynamic properties in the same region. This approach can be extended to characterize other water phase transitions. Besides, it can also be applied to study the phase transitions of other hydrogen-bonded substances or to other scenarios whose relevant "interaction" could be identified together with a "proper criterion" defined in an analogous way as in the case of hydrogen bonded systems.

5.
J Viral Hepat ; 24(3): 226-237, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27976491

RESUMEN

Over the last 5 years, therapies for hepatitis C virus (HCV) infection have improved significantly, achieving sustained virologic response (SVR) rates of up to 100% in clinical trials in patients with HCV genotype 1. We investigated the effectiveness and safety of ombitasvir/paritaprevir/ritonavir±dasabuvir in an early access programme. This was a retrospective, multicentre, national study that included 291 treatment-naïve and treatment-experienced patients with genotype 1 or 4 HCV infection. Most patients (65.3%) were male, and the mean age was 57.5 years. The mean baseline viral load was 6.1 log, 69.8% had HCV 1b genotype, 72.9% had cirrhosis and 34.7% were treatment-naïve. SVR at 12 weeks posttreatment was 96.2%. Four patients had virological failure (1.4%), one leading to discontinuation. There were no statistical differences in virological response according to genotype or liver fibrosis. Thirty patients experienced serious adverse events (SAEs) (10.3%), leading to discontinuation in six cases. Hepatic decompensation was observed in five patients. Four patients died during treatment or follow-up, three of them directly related to liver failure. Multivariate analyses showed a decreased probability of achieving SVR associated with baseline albumin, bilirubin and Child-Pugh score B, and a greater probability of developing SAEs related to age and albumin. This combined therapy was highly effective in clinical practice with an acceptable safety profile and low rates of treatment discontinuation.


Asunto(s)
Antivirales/uso terapéutico , Genotipo , Hepacivirus/clasificación , Hepatitis C Crónica/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Combinada/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , España , Respuesta Virológica Sostenida , Resultado del Tratamiento
6.
Mol Ecol ; 26(3): 887-903, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28026895

RESUMEN

Population genetic studies are efficient for inferring the invasion history based on a comparison of native and invasive populations, especially when conducted at species scale. An expected outcome in invasive populations is variability loss, and this is especially true in self-fertilizing species. We here focus on the self-fertilizing Pseudosuccinea columella, an invasive hermaphroditic freshwater snail that has greatly expanded its geographic distribution and that acts as intermediate host of Fasciola hepatica, the causative agent of human and veterinary fasciolosis. We evaluated the distribution of genetic diversity at the largest geographic scale analysed to date in this species by surveying 80 populations collected during 16 years from 14 countries, using eight nuclear microsatellites and two mitochondrial genes. As expected, populations from North America, the putative origin area, were strongly structured by selfing and history and harboured much more genetic variability than invasive populations. We found high selfing rates (when it was possible to infer it), none-to-low genetic variability and strong population structure in most invasive populations. Strikingly, we found a unique genotype/haplotype in populations from eight invaded regions sampled all over the world. Moreover, snail populations resistant to infection by the parasite are genetically distinct from susceptible populations. Our results are compatible with repeated introductions in South America and flash worldwide invasion by this unique genotype/haplotype. Our study illustrates the population genetic consequences of biological invasion in a highly selfing species at very large geographic scale. We discuss how such a large-scale flash invasion may affect the spread of fasciolosis.


Asunto(s)
Genética de Población , Autofecundación , Caracoles/genética , Animales , Genes Mitocondriales , Genotipo , Haplotipos , Especies Introducidas , Repeticiones de Microsatélite , América del Norte , América del Sur
7.
Clin Genet ; 91(1): 46-53, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27256614

RESUMEN

We report clinical and biochemical finding from three unrelated patients presenting ONCE (Optic Neuropathy, Cardiomyopathy and Encephalopathy with lactic acidosis and combined oxidative phosphorylation deficiency) syndrome. Whole-exome sequencing (WES) of the three patients and the healthy sister of one of them was used to identify the carry gene. Clinical and biochemical findings were used to filter variants, and molecular, in silico and genetic studies were performed to characterize the candidate variants. Mitochondrial DNA (mtDNA) defects involving mutations, deletions or depletion were discarded, whereas WES uncovered a double homozygous mutation in the MTO1 gene (NM_001123226:c.1510C>T, p.R504C, and c.1669G>A, p.V557M) in two of the patients and the homozygous mutation p.R504C in the other. Therefore, our data confirm p.R504C as pathogenic mutation responsible of ONCE syndrome, and p.V557M as a rare polymorphic variant.


Asunto(s)
Anomalías Múltiples/genética , Proteínas Portadoras/genética , Predisposición Genética a la Enfermedad/genética , Mutación Missense , Polimorfismo de Nucleótido Simple , Anomalías Múltiples/patología , Acidosis Láctica , Adolescente , Secuencia de Aminoácidos , Encefalopatías , Cardiomiopatías , Exoma/genética , Salud de la Familia , Femenino , Homocigoto , Humanos , Masculino , Enfermedades Mitocondriales , Enfermedades del Nervio Óptico , Linaje , Proteínas de Unión al ARN , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Síndrome , Adulto Joven
8.
Rev Gastroenterol Mex ; 82(2): 129-133, 2017.
Artículo en Inglés, Español | MEDLINE | ID: mdl-28318702

RESUMEN

INTRODUCTION AND AIMS: Evidence in Colombia and Latin America has been insufficient for establishing the clinical characteristics of patients with antibiotic-associated diarrhea (AAD). The present study attempts to describe the clinical characteristics of patients with AAD and to determine the presence of Clostridium difficile, utilizing the polymerase chain reaction (PCR) technique. MATERIALS AND METHODS: Forty-three patients with AAD, managed at the Hospital Universitario San Ignacio in Bogotá, Colombia, were evaluated. Prospective patient information was collected, with respect to demographic characteristics, profile of the antibiotic management received, clinical manifestations, risk factors, and paraclinical reports. In addition, the real time PCR test for Clostridium difficile (Cepheid Xpert®, Sunnyvale, CA, United States) was performed. RESULTS: Patient mean age was 58 years (19.31 SD). The majority of the patients received 2 or more antibiotics (62.9%) and the beta-lactams were the most frequently used. Hospital stay ranged from 2 to 104 days with a median of 10 days. The most frequent clinical manifestations were abdominal pain and bloating, followed by fever and tachycardia. At the time of diagnosis, 23 patients had noninflammatory results in the stool sample analyses and 18 had kidney failure. The mean level of albumin was 2.4mg/dl (0.7 SD). The presence of Clostridium difficile was documented through PCR in 6 patients (13.95% of the cases). CONCLUSIONS: AAD patients were characterized by a high frequency of severe comorbidities and prolonged hospital stay. The presence of Clostridium difficile in only 13.9% of the cases suggests that other causes of diarrhea in the hospitalized patient should be considered.


Asunto(s)
Antibacterianos/efectos adversos , Clostridioides difficile , Diarrea/etiología , Diarrea/microbiología , Adulto , Anciano , Enterocolitis Seudomembranosa/etiología , Enterocolitis Seudomembranosa/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estudios Prospectivos
9.
J Viral Hepat ; 22(5): 469-80, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25311757

RESUMEN

In many countries, first-generation protease inhibitors (PIs)/peginterferon/ribavirin (P/R) still represent the only treatment option for HCV-infected patients. Subjects with advanced disease and previous failure to P/R urgently need therapy, but they are under-represented in clinical trials. All treatment-experienced F3/4 Metavir patients who received boceprevir (BOC)+P/R in the Italian-Spanish Name Patient Program have been included in this study. Multivariate logistic regression analysis (MLR) was used to identify baseline and on-treatment predictors of SVR and adverse events (AEs). Four hundred and sixteen patients, mean age 57.7 (range 25-78 years), 70% males, 69.5% (289/416) F4, 14% (41/289) Child-Pugh class A6, 24% (70/289) with varices and 42% (173/416) prior null responders to P/R, were analysed. Overall, SVR rate (all 381 patients who received one dose of BOC) was 49%, (58% in F3, 45% in F4, 61% in relapsers, 51% in partial, 38% in null responders, and 72% in subjects with undetectable HCV-RNA at treatment-week (TW)8. Among patients with TW8 HCV-RNA ≥ 1000 IU/L, SVR was 8% (negative predictive value = 92%). Death occurred in 3 (0.8%) patients, while decompensation and infections were observed in 2.9% and 11%, respectively. At MLR, SVR predictors were TW4 HCV-RNA ≥ 1log10 -decline from baseline, undetectable TW8 HCV-RNA, prior relapse, albumin levels ≥3.5 g/dL and platelet counts ≥100 000/µL. Metavir F4, Child-Pugh A6, albumin, platelets, age and female gender were associated with serious and haematological AEs. Among treatment-experienced patients with advanced liver disease eligible for IFN-based therapy, TW8 HCV-RNA characterised the subset with either high or poor likelihood of achieving SVR. Using TW8 HCV-RNA as a futility rule, BOC/P/R appears to have a favourable benefit-risk profile.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Prolina/análogos & derivados , ARN Viral/sangre , Ribavirina/uso terapéutico , Carga Viral , Adulto , Anciano , Quimioterapia Combinada/métodos , Femenino , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/virología , Humanos , Italia , Masculino , Persona de Mediana Edad , Prolina/uso terapéutico , España , Resultado del Tratamiento
10.
Phys Chem Chem Phys ; 17(4): 2326-9, 2015 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-25407303

RESUMEN

DFT calculations predict that plasmon-like excitations in small metal clusters are able to selectively modify the relative intensities of specific SERS bands of adsorbed molecules. These electronic resonances provide new kinds of SERS selection rules which can explain the huge enhancement of mode 9a of pyridine in the spectra recorded at negative electrode potentials.

11.
J Chem Phys ; 142(11): 114501, 2015 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-25796255

RESUMEN

In this work, we present an equation of state for an interesting soft-core continuous potential [G. Franzese, J. Mol. Liq. 136, 267 (2007)] which has been successfully used to model the behavior of single component fluids that show some water-type anomalies. This equation has been obtained using discrete perturbation theory. It is an analytical expression given in terms of density, temperature, and the set of parameters that characterize the intermolecular interaction. Theoretical results for the vapor-liquid phase diagram and for supercritical pressures are compared with previous and new simulation data and a good agreement is found. This work also clarifies discrepancies between previous Monte Carlo and molecular dynamics simulation results for this potential.

12.
Eur J Orthop Surg Traumatol ; 25(2): 273-80, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24871876

RESUMEN

OBJECTIVES: The purpose of this study was to analyze functional and radiologic results of a consecutive series of elderly patients who underwent uncemented hemiarthroplasty as primary treatment of complex proximal humeral fractures. METHODS: Twenty-one patients with severe proximal humerus fracture (three or four fragments and three- or four-fragment fracture dislocations) were treated with uncemented proximal humerus hemiarthroplasty. Patients were evaluated using the Constant-Murley Score, the Quick scale Disabilities of Arm, Shoulder and Hand (Quick-DASH) Score, range of motion, residual pain, radiographic parameters, and complications including clinical and radiologic data of mobilization. RESULTS: After a mean postoperative period of 20.57 months (range 12-42 months), the mean Constant-Murley Score was 44 points (20-57), the mean Quick-DASH score was 24 points (16-39), postoperative pain according to a mean visual analogue scale was 1 (0-8), active abduction was 50° (30-135), and active flexion 70° (20-120). There were no cases of infection, deep vein thrombosis, dislocation, blood transfusions, or reoperation because of prosthetic loosening. Bivariate analysis of demographic data, radiologic findings, and other variables showed associations between duration of surgery and a higher Quick-DASH score (0.606; p = 0.037), and the number of sessions of rehabilitation with a higher Quick-DASH score (0.708; p = 0.015). CONCLUSIONS: The results of treatment of severe proximal humerus fractures in the elderly with an uncemented hemiarthroplasty are safe and promising; however, a comparative cohort study (cemented vs. uncemented) and long-term follow-up are still needed.


Asunto(s)
Hemiartroplastia/métodos , Fracturas del Hombro/cirugía , Anciano , Anciano de 80 o más Años , Cementos para Huesos , Femenino , Estudios de Seguimiento , Hemiartroplastia/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Dimensión del Dolor , Dolor Postoperatorio/etiología , Radiografía , Rango del Movimiento Articular , Fracturas del Hombro/diagnóstico por imagen , Fracturas del Hombro/rehabilitación , Índices de Gravedad del Trauma
13.
Phys Chem Chem Phys ; 16(42): 22958-61, 2014 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-25255295

RESUMEN

DFT calculations predict two different electronic structures of metal-molecule hybrids which are selected depending on the surface charge. While the metal-to-molecule CT states are very sensitive to the charge, the energies of the reverse molecule-to-metal CT processes are surprisingly not modified at all by the charge of the metal.

14.
J Chem Phys ; 140(3): 034502, 2014 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-25669395

RESUMEN

Ionic solutions exhibiting multiple association are described within the binding mean spherical approximation (BiMSA). This model is based on the Wertheim formalism, in the framework of the primitive model at the McMillan-Mayer level. The cation and the anion form the various complexes according to stepwise complexation-equilibria. Analytic expressions for the Helmholtz energy, the internal energy, the speciation, and for the osmotic and activity coefficients are given considering a binary solution with an arbitrary number of association sites on one type of ion (polyion) and one site on the ions of opposite sign (counterions). As an alternative, mean field expressions, as developed in SAFT-type theories, are also presented. The result obtained from the latter approximate method exhibits a reasonable agreement with those from BiMSA for the speciation, and a remarkable one for the osmotic coefficient.

15.
Arch Soc Esp Oftalmol (Engl Ed) ; 97(3): 165-167, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35248398

RESUMEN

A cyclodialysis cleft is a rare disease that is produced as a result of a separation of the longitudinal fibers of the ciliary body muscle from the scleral spur. A stepwise approach is the best course of action to treat cyclodialysis, starting with medical therapy and continuing with more invasive surgical options. We report a case of ocular hypotony due a traumatic cyclodialysis successfully resolved with transscleral cryotherapy.


Asunto(s)
Hendiduras de Ciclodiálisis , Lesiones Oculares , Hipotensión Ocular , Cuerpo Ciliar/cirugía , Crioterapia , Lesiones Oculares/complicaciones , Lesiones Oculares/cirugía , Humanos , Hipotensión Ocular/etiología , Hipotensión Ocular/cirugía
16.
Arch Soc Esp Oftalmol (Engl Ed) ; 97(6): 310-316, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35292224

RESUMEN

PURPOSE: To evaluate the spectrum of glaucoma surgery undertaken among members of the Spanish Glaucoma Society (SEG). METHODS: A 10 question web-based anonimous survey was mailed through the Annals of the Spanish Glaucoma Society to all its members on January, February and July 2019 to determine their preferred surgical approach. MAIN OUTCOME MEASURES: Age, type of Glaucoma, surgery undertaken, type of anti-scarring strategy and prothesis introduced for the last 10 surgeries since the survey was received. The surgeon experience was registered in years of practice. RESULTS: A total of 97 SEG members across the country answered the survey. Sixty-two (63.4%) responders had more than 10 years of experience. Primary open angle glaucoma was the most frequent type of glaucoma (60.6%). The most popular surgery was deep-sclerectomy (37.3%) followed by trabeculectomy (17,6%) and the collagen microshunt (XEN® Allergan Inc., Irvine, CA) (14.1%). Glaucoma drainage device (GDD) was used in 10.5% of the cases. Up to 21.7% of surgeries were reinterventions, where GDD was used in 27.3% and trabeculectomy in 20.3% of the cases. Glaucoma surgery was combined with phacoemulsification in 47.3% of the eyes. Mitomycin C (MMC) was used in 54,8% of the cases, collagen matrix (Ologen®, Aeon Astron Corporation, Taipei, Taiwan) was used alone in 8.2% of the cases and in 13,7% combined with MMC. MMC was used in a soaked sponge in 79% of cases (concentrations of 0.02% in 99% and 0.04% in 1%) and in 21% of cases MMC was injected subconjunctivally (concentrations of 0,01% in 81% and 0.02% in 19%). CONCLUSIONS: Although the glaucoma surgeon performs a wide range of surgical techniques, deep sclerectomy remains the most widely used surgical technique in Spain. Combined cataract and glaucoma surgery is performed almost in half of the patients and MMC is the most frequently selected antifibrotic agent, alone or combined with collagen matrix. The new minimal invasive surgical techniques represent the 20% of the total.


Asunto(s)
Glaucoma de Ángulo Abierto , Glaucoma , Colágeno , Glaucoma/cirugía , Glaucoma de Ángulo Abierto/cirugía , Humanos , Presión Intraocular , Mitomicina , España
17.
Mol Metab ; 66: 101648, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36455789

RESUMEN

BACKGROUND: McArdle disease is caused by myophosphorylase deficiency and results in complete inability for muscle glycogen breakdown. A hallmark of this condition is muscle oxidation impairment (e.g., low peak oxygen uptake (VO2peak)), a phenomenon traditionally attributed to reduced glycolytic flux and Krebs cycle anaplerosis. Here we hypothesized an additional role for muscle mitochondrial network alterations associated with massive intracellular glycogen accumulation. METHODS: We analyzed in depth mitochondrial characteristics-content, biogenesis, ultrastructure-and network integrity in skeletal-muscle from McArdle/control mice and two patients. We also determined VO2peak in patients (both sexes, N = 145) and healthy controls (N = 133). RESULTS: Besides corroborating very poor VO2peak values in patients and impairment in muscle glycolytic flux, we found that, in McArdle muscle: (a) damaged fibers are likely those with a higher mitochondrial and glycogen content, which show major disruption of the three main cytoskeleton components-actin microfilaments, microtubules and intermediate filaments-thereby contributing to mitochondrial network disruption in skeletal muscle fibers; (b) there was an altered subcellular localization of mitochondrial fission/fusion proteins and of the sarcoplasmic reticulum protein calsequestrin-with subsequent alteration in mitochondrial dynamics/function; impairment in mitochondrial content/biogenesis; and (c) several OXPHOS-related complex proteins/activities were also affected. CONCLUSIONS: In McArdle disease, severe muscle oxidative capacity impairment could also be explained by a disruption of the mitochondrial network, at least in those fibers with a higher capacity for glycogen accumulation. Our findings might pave the way for future research addressing the potential involvement of mitochondrial network alterations in the pathophysiology of other glycogenoses.


Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo V , Masculino , Femenino , Ratones , Animales , Enfermedad del Almacenamiento de Glucógeno Tipo V/metabolismo , Glucógeno/metabolismo , Músculo Esquelético/metabolismo , Tolerancia al Ejercicio , Mitocondrias/metabolismo
18.
Biochim Biophys Acta ; 1802(5): 443-53, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20153825

RESUMEN

BACKGROUND: Complex I (CI) deficiency is the most frequent cause of OXPHOS disorders. Recent studies have shown increases in reactive oxygen species (ROS) production and mitochondrial network disturbances in patients' fibroblasts harbouring mutations in CI subunits. OBJECTIVES: The present work evaluates the impact of mutations in the NDUFA1 and NDUFV1 genes of CI on mitochondrial bioenergetics and dynamics, in fibroblasts from patients suffering isolated CI deficiency. RESULTS: Decreased oxygen consumption rate and slow growth rate were found in patients with severe CI deficiency. Mitochondrial diameter was slightly increased in patients' cells cultured in galactose or treated with 2'-deoxyglucose without evidence of mitochondrial fragmentation. Expression levels of the main proteins involved in mitochondrial dynamics, OPA1, MFN2, and DRP1, were slightly augmented in all patients' cells lines. The study of mitochondrial dynamics showed delayed recovery of the mitochondrial network after treatment with the uncoupler carbonyl cyanide m-chlorophenyl hydrazone (cccp) in patients with severe CI deficiency. Intracellular ROS levels were not increased neither in glucose nor galactose medium in patients' fibroblasts. CONCLUSION: Our main finding was that severe CI deficiency in patients harbouring mutations in the NDUFA1 and NDUFV1 genes is linked to a delayed mitochondrial network recovery after cccp treatment. However, the CI deficiency is neither associated with massive mitochondrial fragmentation nor with increased ROS levels. The different genetic backgrounds of patients with OXPHOS disorders would explain, at least partially, differences in the pathophysiological manifestations of CI deficiency.


Asunto(s)
Complejo I de Transporte de Electrón/metabolismo , Metabolismo Energético , Fibroblastos/enzimología , Mitocondrias/metabolismo , Enfermedades Mitocondriales/genética , Mutación/genética , NADH Deshidrogenasa/genética , Acidosis/genética , Acidosis/metabolismo , Acidosis/patología , Adenosina Trifosfato/metabolismo , Western Blotting , Células Cultivadas , Epilepsia/genética , Epilepsia/metabolismo , Epilepsia/patología , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Glucólisis , Humanos , Lactante , Leucoencefalopatías/genética , Leucoencefalopatías/metabolismo , Leucoencefalopatías/patología , Masculino , Mitocondrias/efectos de los fármacos , Enfermedades Mitocondriales/metabolismo , NADH Deshidrogenasa/metabolismo , Consumo de Oxígeno , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Piel/citología , Piel/metabolismo
19.
Anal Chem ; 83(7): 2518-25, 2011 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-21391577

RESUMEN

Silver nanoparticles (NPs) functionalized with the molecular assembler bis-acridinium dication lucigenin (LG) have been used as a chemical sensor system to detect a group of polycyclic aromatic hydrocarbon (PAH) pollutants in a multicomponent mixture by means of surface-enhanced raman scattering (SERS). The effectiveness of this system was checked for a group of PAHs with different numbers of fused benzene rings, namely anthracene, pyrene, triphenylene, benzo[c]phenanthrene, chrysene, and coronene. In order to determine the host capacity of this sensor system, the self-assembly of the LG viologen on a metallic surface has been checked by analyzing SERS intensities of PAH bands at different LG concentrations. The NP-LG-analyte affinity is derived from the analysis of PAH band intensities at different concentrations of pollutants, the adsorption isotherm of each PAH on NP-LG cavities has been studied, and the corresponding adsorption constants have been evaluated. The limit of detection at trace-level concentration is confirmed by the presence of their characteristic fingerprint vibrational bands. The SERS spectra of PAH mixtures confirm that LG viologen dication shows a higher analytical selectivity to PAHs constituted by four fused benzene rings, mainly pyrene and benzo[c]phenanthrene, in agreement with their higher affinity which is also related to their better fit into the intermolecular LG cavities. As a conclusion, SERS spectra recorded on modified NP-LG surfaces are a powerful chemical tool to detect organic pollutants.

20.
Gynecol Obstet Invest ; 72(2): 117-22, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21372552

RESUMEN

AIMS: To measure endometrial volume and endometrial-subendometrial vascularization by 3-D power Doppler ultrasound in patients undergoing cycles of artificial insemination with ovarian stimulation, to evaluate their relationship with patients' age and pregnancy development. METHODS: We included patients with primary and secondary infertility of one year of evolution. We measured vascular indexes and endometrial volume by 3-D power Doppler ultrasound. RESULTS: Seventy-nine consecutive cycles were studied. Endometrial volume average was 4.7 ± 2.66 ml. We did not find any difference between the endometrial volumes in women who did versus did not become pregnant (9 vs. 70 women, respectively). The endometrial vascular index was significantly higher in patients aged between 31 and 33 years old. In patients between the ages of 31 and 33, both the endometrial flow index (FI; p = 0.017) and the endometrial vascular FI (p = 0.013) were higher. At the subendometrial area, the vascular FI was lower in women older than 33 years old (p = 0.024), while the FI was higher in patients that achieved pregnancy (p = 0.047). CONCLUSIONS: Endometrial volumes were independent of pregnancy development. Endometrial and subendometrial vascularization FIs were significantly higher in younger women. The subendometrial FI was significantly higher in patients who achieved pregnancy.


Asunto(s)
Implantación del Embrión , Endometrio/irrigación sanguínea , Endometrio/diagnóstico por imagen , Imagenología Tridimensional , Infertilidad Femenina/diagnóstico por imagen , Ultrasonografía Doppler , Adulto , Endometrio/patología , Femenino , Humanos , Valor Predictivo de las Pruebas , Embarazo , Resultado del Embarazo , Adulto Joven
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