Mitochondrial neurogastrointestinal encephalomyopathy: Clinical and biochemical impact of allogeneic stem cell transplantation in a Greek patient with one novel TYMP mutation.

We describe the case of a Greek female patient with the Classic form of the ultra- rare and fatal autosomal recessive disorder Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and the impact of allogeneic hematopoietic stem cell transplantation on the biochemical and clinical aspects of the disease. The patient presented at the age of 15 years with severe gastrointestinal symptoms, cachexia, peripheral neuropathy and diffuse leukoencephalopathy. The diagnosis of MNGIE disease was established by the increased levels of thymidine and deoxyuridine in plasma and the complete deficiency of thymidine phosphorylase activity. The novel c.[978dup] (p.Ala327Argfs*?) variant and the previously described variant c.[417 + 1G > A] were identified in TYMP. The donor for the allogeneic hematopoietic stem cell transplantation was her fully compatible sister, a carrier of the disease. The patient had a completely uneventful post- transplant period and satisfactory PB chimerism levels. A marked and rapid decrease in thymidine and deoxyuridine plasma levels and an increase of the thymidine phosphorylase activity to the levels measured in her donor sister was observed and is still present sixteen months post-transplant. Disease symptoms stabilized and some improvement was also observed both in her neurological and gastrointestinal symptoms. Follow up studies will be essential for determining the long term impact of allogeneic hematopoietic stem cell transplantation in our patient.

Distal Transradial Access for Diagnostic Cerebral Angiography and Neurointervention: Systematic Review and Meta-analysis.

BACKGROUND: Radial artery access for cerebral angiography is traditionally performed in the wrist. Distal transradial access in the anatomic snuffbox is an alternative with several advantages. PURPOSE: Our aim was to review the safety and efficacy of distal transradial access for diagnostic cerebral angiography and neurointerventions. DATA SOURCES: We performed a comprehensive search of the literature using PubMed, Scopus, and EMBASE. STUDY SELECTION: The study included all case series of at least 10 patients describing outcomes associated with distal transradial access for diagnostic cerebral angiography or a neurointervention. DATA ANALYSIS: Random-effects models were used to obtain pooled rates of procedural success and complications. DATA SYNTHESIS: A total of 7 studies comprising 348 (75.8%) diagnostic cerebral angiograms and 111 (24.2%) interventions met the inclusion criteria. The pooled success rate was 95% (95% CI, 91%-98%; I2 = 74.33). The pooled minor complication rate was 2% (95% CI, 1%-4%; I2 = 0. No major complications were reported. For diagnostic procedures, the combined mean fluoroscopy time was 13.53 [SD, 8.82] minutes and the mean contrast dose was 74.9 [SD, 35.6] mL. LIMITATIONS: A small number of studies met the inclusion criteria, all of them were retrospective, and none compared outcomes with proximal transradial or femoral access. CONCLUSIONS: Early experience with distal transradial access suggests that it is a safe and effective alternative to proximal radial and femoral access for performing diagnostic cerebral angiography and interventions. Additional studies are needed to establish its efficacy and compare it with other access sites.

Fluid-structure interaction simulations outperform computational fluid dynamics in the description of thoracic aorta haemodynamics and in the differentiation of progressive dilation in Marfan syndrome patients.

Abnormal fluid dynamics at the ascending aorta may be at the origin of aortic aneurysms. This study was aimed at comparing the performance of computational fluid dynamics (CFD) and fluid-structure interaction (FSI) simulations against four-dimensional (4D) flow magnetic resonance imaging (MRI) data; and to assess the capacity of advanced fluid dynamics markers to stratify aneurysm progression risk. Eight Marfan syndrome (MFS) patients, four with stable and four with dilating aneurysms of the proximal aorta, and four healthy controls were studied. FSI and CFD simulations were performed with MRI-derived geometry, inlet velocity field and Young's modulus. Flow displacement, jet angle and maximum velocity evaluated from FSI and CFD simulations were compared to 4D flow MRI data. A dimensionless parameter, the shear stress ratio (SSR), was evaluated from FSI and CFD simulations and assessed as potential correlate of aneurysm progression. FSI simulations successfully matched MRI data regarding descending to ascending aorta flow rates (R 2 = 0.92) and pulse wave velocity (R 2 = 0.99). Compared to CFD, FSI simulations showed significantly lower percentage errors in ascending and descending aorta in flow displacement (-46% ascending, -41% descending), jet angle (-28% ascending, -50% descending) and maximum velocity (-37% ascending, -34% descending) with respect to 4D flow MRI. FSI- but not CFD-derived SSR differentiated between stable and dilating MFS patients. Fluid dynamic simulations of the thoracic aorta require fluid-solid interaction to properly reproduce complex haemodynamics. FSI- but not CFD-derived SSR could help stratifying MFS patients.

Estandarización cromática de la orina / No disponible

La enfermera en urología adjudica a menudo adjetivos subjetivos a la orina de los pacientes a su cargo. Pretendemos dotar a los profesionales de una herramienta ágil y visual para disminuir la variabilidad con la que se describe el color de la orina. Para ello se ha elaborado un póster fotográfico tras una búsqueda bibliográfica y una observación directa de las palabras utilizadas para describir la diuresis por parte de las enfermeras del Servicio de Urología del Hospital Miguel Servet de Zaragoza

The urology nurse often assigns subjective adjectives to the urine of the patients in her care. We aim to equip professionals with an agile and visual tool to reduce the variability with which the color of the urine is described. For this purpose, a photographic poster was created after a bibliographical search and a direct observation of the words used to describe the diuresis by the nurses of the Urology Service of the Miguel Servet Hospital of Zaragoza

New cationic vesicles prepared with double chain surfactants from arginine: Role of the hydrophobic group on the antimicrobial activity and cytotoxicity.

Cationic double chain surfactants have attracted much interest because they can give rise to cationic vesicles that can be used in biomedical applications. Using a simple and economical synthetic approach, we have synthesized four double-chain surfactants with different alkyl chain lengths (LANHCx). The critical aggregation concentration of the double chain surfactants is at least one order of magnitude lower than the CMC of their corresponding single-chain LAM and the solutions prepared with the LANHCx contain stable cationic vesicles. Encouragingly, these new arginine derivatives show very low haemolytic activity and weaker cytotoxic effects than conventional dialkyl dimethyl ammonium surfactants. In addition, the surfactant with the shortest alkyl chain exhibits good antimicrobial activity against Gram-positive bacteria. The results show that a rational design applied to cationic double chain surfactants might serve as a promising strategy for the development of safe cationic vesicular systems.

Effect of fatty acids on self-assembly of soybean lecithin systems.

With the increasing interest in natural formulations for drug administration and functional foods, it is desirable a good knowledge of the phase behavior of lecithin/fatty acid formulations. Phase structure and properties of ternary lecithin/fatty acids/water systems are studied at 37°C, making emphasis in regions with relatively low water and fatty acid content. The effect of fatty acid saturation degree on the phase microstructure is studied by comparing a fully saturated (palmitic acid, C16:0), monounsaturated (oleic acid, C18:1), and diunsaturated (linoleic acid, C18:2) fatty acids. Phase determinations are based on a combination of polarized light microscopy and small-angle X-ray scattering measurements. Interestingly, unsaturated (oleic acid and linoleic acid) fatty acid destabilizes the lamellar bilayer. Slight differences are observed between the phase diagrams produced by the unsaturated ones: small lamellar, medium cubic and large hexagonal regions. A narrow isotropic fluid region also appears on the lecithin-fatty acid axis, up to 8wt% water. In contrast, a marked difference in phase microsctructure was observed between unsaturated and saturated systems in which the cubic and isotropic fluid phases are not formed. These differences are, probably, a consequence of the high Krafft point of the C16 saturated chains that imply rather rigid chains. However, unsaturated fatty acids result in more flexible tails. The frequent presence of, at least, one unsaturated chain in phospholipids makes it very likely a better mixing situation than in the case of more rigid chains. This swelling potential favors the formation of reverse hexagonal, cubic, and micellar phases. Both unsaturated fatty acid systems evolve by aging, with a reduction of the extension of reverse hexagonal phase and migration of the cubic phase to lower fatty acid and water contents. The kinetic stability of the systems seems to be controlled by the unsaturation of fatty acids.

Rare Late-Onset Presentation of Glutaric Aciduria Type I in a 16-Year-Old Woman with a Novel GCDH Mutation.

Glutaric acidemia type I (GA-I) is a treatable autosomal recessive disorder of lysine, hydroxylysine, and tryptophan metabolism caused by glutaryl-CoA dehydrogenase (GCDH) deficiency. Presentation and progression of disease are variable ranging from asymptomatic carrier state to catastrophic encephalopathy. GA-I usually presents before age 18 months, usually triggered by childhood infection, with mild or severe acute encephalopathy, striatal degeneration, and movement disorder, most often acute dystonia. At a presymptomatic stage diagnosis is suggested clinically by macrocephaly, radiologically by widened Sylvian fissures and biochemically by the presence of excess 3-hydroxyglutaric acid and glutaric acid in urine. Treatment consists of lysine-restricted diet and carnitine supplementation, specific diet restrictions, as well as symptomatic and anticatabolic treatment of intercurrent illness. Presymptomatic diagnosis and treatment are essential to prognosis. We report the case of 16-year-old macrocephalic female with late-onset GA-I and unusual paucisymptomatic presentation with fainting after exercise and widespread white matter signal changes at MRI. She was compound heterozygote for a novel mutation (IVS10-2A>G) affecting splicing at GCDH and a common missense mutation (c. 1240C>T; p.Arg402Trp, R402W). Interestingly, the site of the novel mutation is the nucleotide position of a common mutation found almost exclusively in patients of Chinese/Taiwanese origin (IVS10-2A>C).

Niosomes based on synthetic cationic lipids for gene delivery: the influence of polar head-groups on the transfection efficiency in HEK-293, ARPE-19 and MSC-D1 cells.

We designed niosomes based on three lipids that differed only in the polar-head group to analyze their influence on the transfection efficiency. These lipids were characterized by small-angle X-ray scattering before being incorporated into the niosomes which were characterized in terms of pKa, size, zeta potential, morphology and physical stability. Nioplexes were obtained upon the addition of a plasmid. Different ratios (w/w) were selected to analyze the influence of this parameter on size, charge and the ability to condense, release and protect the DNA. In vitro transfection experiments were performed in HEK-293, ARPE-19 and MSC-D1 cells. Our results show that the chemical composition of the cationic head-group clearly affects the physicochemical parameters of the niosomes and especially the transfection efficiency. Only niosomes based on cationic lipids with a dimethyl amino head group (lipid 3) showed a transfection capacity when compared with their counterparts amino (lipid 1) and tripeptide head-groups (lipid 2). Regarding cell viability, we clearly observed that nioplexes based on the cationic lipid 3 had a more deleterious effect than their counterparts, especially in ARPE-19 cells at 20/1 and 30/1 ratios. Similar studies could be extended to other series of cationic lipids in order to progress in the research on safe and efficient non-viral vectors for gene delivery purposes.

Cerebrospinal fluid synaptic proteins as useful biomarkers in tyrosine hydroxylase deficiency.

Tyrosine hydroxylase (TH) deficiency is an inborn error of dopamine biosynthesis and a cause of early parkinsonism. Two clinical phenotypes have been described. Type "B": early onset severe encephalopathy; type "A": later onset, less severe and better response to L-dopa. We aimed to study the expression of several key dopaminergic and gabaergic synaptic proteins in the cerebrospinal fluid (CSF) of a series of patients with TH deficiency and their possible relation with the clinical phenotype and response to L-DOPA. Dopamine transporter (DAT), D2-receptor and vesicular monoamine transporter (VMAT2) were measured in the CSF of 10 subjects with TH deficiency by Western blot analysis. In 3 patients, data of pre- and post-treatment with L-DOPA were available, and in one of them, GABA vesicular transporter was determined. Results were compared to an age-matched control population. The concentration of D2-receptors in CSF was significantly higher in patients with TH deficiency than in controls. Similarly, DAT and vesicular monoamine transporter type 2 were up-regulated. Studies performed before L-DOPA, and on L-DOPA therapy showed a paradoxical response with D2 receptor expression increase as L-Dopa doses and homovanillic concentration gradually raised in a B phenotype patient. The opposite results were found in two patients with A phenotype. However, this is a very small sample, and further studies are needed to conclude robust differences between phenotypes. Synaptic proteins are detectable in the CSF and their quantification can be useful for understanding the pathophysiology of neurotransmitter defects and potentially to adjust and personalize treatments in the future.

Complex rhamnolipid mixture characterization and its influence on DPPC bilayer organization.

Rhamnolipids (RL) are one of the most important classes of biosurfactants produced by microorganisms using a wide range of carbon sources, from a simple carbon source like glucose to complex wastes such as the used cooking oils used in this work. The objective of this work was to learn about the rhamnolipid-phospholipid dipalmitoyl phosphatidyl choline (DPPC) molecular interactions through the behaviour observed in the neat products and four RL/DPPC mixtures. Size and z-potential were used to characterize the size and the charge of the vesicles, and small angle X-ray scattering (SAXS) was used to measure the vesicle bilayer characteristics, and the release of carboxyfluorescein to study the bilayer disrupting effect promoted by rhamnolipids. The results show that rhamnolipids are disposed in ordered bilayers with long repeating distances, which are stabilized by the charging of the bilayer and also by a strong fluidity of the bilayers. The ability of rhamnolipids to increase the fluidity of DPPC bilayers may be related with the strong haemolytic power of these molecules.

Structure and phase equilibria of the soybean lecithin/PEG 40 monostearate/water system.

PEG stearates are extensively used as emulsifiers in many lipid-based formulations. However, the scheme of the principles of the lipid-surfactant polymer interactions are still poorly understood and need more studies. A new phase diagram of a lecithin/PEG 40 monostearate/water system at 30 °C is reported. First, we have characterized the binary PEG 40 monostearate/water system by the determination of the critical micelle concentration value and the viscous properties. Then, the ternary phase behavior and the influence of phase structure on their macroscopic properties are studied by a combination of different techniques, namely, optical microscopy, small-angle X-ray scattering, differential scanning calorimetry, and rheology. The phase behavior is complex, and some samples evolve even at long times. The single monophasic regions correspond to micellar, swollen lamellar, and lamellar gel phases. The existence of extended areas of phase coexistence (hexagonal, cubic, and lamellar liquid crystalline phases) may be a consequence of the low miscibility of S40P in the lecithin bilayer as well as of the segregation of the phospholipid polydisperse hydrophobic chains. The presence of the PEG 40 monostearate has less effect in the transformation to the cubic phase for lecithin than that found in other systems with simple glycerol-based lipids.

Nephrotic syndrome and AA amyloidosis revealing adult-onset cryopyrin-associated periodic syndrome.

Cryopyrin-associated periodic syndrome (CAPS) is due to gain-of-function mutations in the cryopyrin gene, which determines an overactive inflammatory response. AA amyloidosis is a complication of this syndrome. A 53-year-old man was referred to us because of lower limb edema. Past history: at the age of 20, he complained of arthralgia/arthritis and bilateral hypoacusis. At the age of 35, he presented posterior uveitis, several episodes of conjunctivitis, and progressive loss of visual acuity. Laboratory tests disclosed nephrotic syndrome, and renal biopsy showed AA amyloidosis. He was given anakinra with improvement of arthritis. A genetic study revealed the p.D303N mutation in the cryopyrin gene, and he was diagnosed as having AA amyloidosis due to CAPS. Twenty-one months after starting anakinra, the arthritis has disappeared, although nephrotic-range proteinuria persisted. It is important to be aware of cryopyrin-associated periodic syndrome because it can cause irreversible complications, and there is effective therapy.

Tocilizumab treatment for nephrotic syndrome due to amyloidosis in Behcet's disease.

Renal involvement is an unusual but significant Behcet´s disease (BD) complication and AA amyloidosis appears to be the most common etiology. IL-6 is a pro-inflammatory cytokine with an important role in AA amyloidosis development. Tocilizumab (TCZ) is a humanized anti-IL-6 receptor antibody that has emerged as an effective and specific treatment in AA amyloidosis secondary to chronic inflammatory disorders. We report on a patient diagnosed with BD who developed nephrotic syndrome caused by renal AA amyloidosis with an excellent response to TCZ therapy.

The production and physicochemical properties of a biosurfactant mixture obtained from Sphingobacterium detergens.

The commercial application of a new biosurfactant such as the one produced by Sphingobacteriumdetergens needs a cost-effective process and knowledge of its properties. In the present study, a specific medium and a downstream process have been developed to enhance biosurfactant production. Optimal concentrations of nutrients in MCA medium were (g/L) the following: KH(2)PO(4), 1; K(2)HPO(4), 2; CO(NH(2))(2) 0.88; CaCl(2) 0.01; FeSO(4)·7H(2)O, 0.01; MgSO(4)·7H(2)O 0.5; KCl, 1.0; trace elements 0.05 mL. Biosurfactant production in the MCA medium required a bacterial co-metabolism of glucose and an n-alkane. A fed-batch culture with supernatant lyophilization prior to organic extraction produced 466 mg/L of organic extract, which represents a 6.9-fold increase in production. The newly obtained biosurfactant was a complex mixture of molecules. The three characterized fractions consisted of the complete fraction and two second-level purification fractions with apolar and polar characteristics. The complete and apolar fractions have been shown to self-aggregate in the form of lamellar liquid crystals at a high concentration and bilayers at lower concentrations. Negatively charged particles were identified, which were neutralized at a low pH with a concomitant increase in size. The pH affected the surface tension of the solutions congruently with phosphate headgroups.

PLP1 gene analysis in 88 patients with leukodystrophy.

Pelizaeus-Merzbacher disease (PMD) is caused in most cases by either duplications or point mutations in the PLP1 gene. This disease, a dysmyelinating disorder affecting mainly the central nervous system, has a wide clinical spectrum and its causing mutations act through different molecular mechanisms. Eighty-eight male patients with leukodystrophy were studied. PLP1 gene analysis was performed by the Multiplex Ligation-dependent Probe Amplification technique and DNA sequencing, and, in duplicated cases of PLP1, gene dosage was completed by using array-CGH. We have identified 21 patients with mutations in the PLP1 gene, including duplications, short and large deletions and several point mutations in our cohort. A customized array-CGH at the Xq22.2 area identified several complex rearrangements within the PLP1 gene region. Mutations found in the PLP1 gene are the cause of PMD in around 20% of the patients in this series.

Isolation and partial characterization of a biosurfactant mixture produced by Sphingobacterium sp. isolated from soil.

Strain 6.2S, isolated from soil and identified as a Sphingobacterium sp., is the first strain in this genus to be reported as a biosurfactant producer, being able to reduce the surface tension of its culture supernatant to 32 mN/m. In this work, biosurfactants from the culture supernatant were purified and partially characterized. The crude extract (10 g/L) was very effective in reducing surface tension (22 mN/m). Thin layer chromatography (TLC) indicated that a mixture of various biosurfactants was present in the 6.2S crude extract. After purification, Fraction A, a phospholipid mixture, reduced surface tension to 33 mN/m. Fraction B was a mixture of lipopetides and at least one glycolipid. The surface tension-concentration curve showed two plateaux, the first of which can be attributed to a critical aggregation concentration of the biosurfactant with a protein (2.7 g/L) and the second to the true cmc in water (6.3g/L).

Acidosis láctica y pancitopenia por linezolid / No disponible

No disponible

[Determination of brain natriuretic peptide in patients undergoing different haemodiafiltration techniques]. / Determinación del péptido natriurético cerebral en pacientes sometidos a diferentes técnicas de hemodiafiltración.

UNLABELLED: IB-type natriuretic peptide is a cardíac neurohormone secreted by the cardíac ventricules in response to ventricular dilatation so plasma BNP level correlate with left ventricular mass and dysfunction. Dialysis patients have much greater levels of BNP due to the volume overload and because of reduced renal clearance. The aim of this study was to mesure and compare the BNP levels in three groups of patients who received different hemodiafiltration techniques: Daily online hemodiafiltration (HDFOLd), on-line hemodiafiltration (HDFOL) and low convective volume hemodiafiltration (HDF). Fifteen patients were included, five in each group. Pre and postdialysis BNP leves were measured during 8 weeks. The measure was done at the beginning of the week (long period), and at the end (short period), in order to study if there were significative differences between techniques and periods. We found significative differences between predialysis BNP levels in the short period (BNPpreC) and the long period (BNPpre-L). We also found significative differences with the posdialysis BNP in both periods; BNPpre- L vs. BNPpos-L (1069+/-1031 vs. 612 +/- 540). After comparing the three techniques the study showed significative differences between BNPpreC in HDF and HDFOL compared with HDFOld. And also after dialysis between BNPpos-C in HDFOLd compared with the other techniques. CONCLUSION: Although previous papers have shown that BNP levels have limited potential for assessment of hydration in hemodialysis patients, in this study our data demonstrate that after dialysis BNP levels decline in a significative way in the long and short period and we have found that patients on daily hemodialysis show lower BNP levels, and maybe this could be explained because daily on-line haemodiafiltration patients had lower weight rise between dialysis sessions and also better haemodynamic tolerance.