Jesús Esteban

SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V

Sánchez‐Ferrero E, Coto E, Beetz C, Gámez J, Corao A, Díaz M, Esteban J, del Castillo E, Moris G, Infante J, Menéndez M, Pascual‐Pascual SI, López de Munaín A, Garcia‐Barcina MJ, Alvarez V on behalf of the Genetics of Spastic Paraplegia study group. SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V.

Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia.

BackgroundHereditary Spastic Paraplegias (HSP) are characterized by progressive spasticity and weakness of the lower limbs. At least 45 loci have been identified in families with autosomal dominant (AD), autosomal recessive (AR), or X-linked hereditary patterns. Mutations in the SPAST (SPG4) and ATL1 (SPG3A) genes would account for about 50% of the ADHSP cases.MethodsWe defined the SPAST and ATL1 mutational spectrum in a total of 370 unrelated HSP index cases from Spain (83% with a pure phenotype).ResultsWe found 50 SPAST mutations (including two large deletions) in 54 patients and 7 ATL1 mutations in 11 patients. A total of 33 of the SPAST and 3 of the ATL1 were new mutations. A total of 141 (31%) were familial cases, and we found a higher frequency of mutation carriers among these compared to apparently sporadic cases (38% vs. 5%). Five of the SPAST mutations were predicted to affect the pre-mRNA splicing, and in 4 of them we demonstrated this effect at the cDNA level. In addition to large deletions, splicing, frameshifting, and missense mutations, we also found a nucleotide change in the stop codon that would result in a larger ORF.ConclusionsIn a large cohort of Spanish patients with spastic paraplegia, SPAST and ATL1 mutations were found in 15% of the cases. These mutations were more frequent in familial cases (compared to sporadic), and were associated with heterogeneous clinical manifestations.

Lateral Medullary Infarction Secondary to Vertebral Artery Dissection Presenting as a Trigeminal Autonomic Cephalalgia

A 51‐year‐old woman had an attack of severe hemifacial pain with autonomic features as the presenting symptom of a lateral medullary infarction. A bilateral vertebral artery dissection was demonstrated. The existence of secondary cases may lead to a better understanding of the pathophysiology of trigeminal autonomic cephalalgias.

A severe case of Hirayama disease successfully treated by anterior cervical fusion

Hirayama disease, or juvenile amyotrophy of distal upper extremity, is a benign, self-limiting cervical myelopathy consisting of selective unilateral weakness of the hand and forearm. The weakness slowly progresses until spontaneous arrest occurs within 5 years of onset. The condition predominantly affects Asian males and is thought to be secondary to spinal cord compression during neck flexion, because of a forward displacement of the posterior dural sac. The authors present what is to their knowledge the first reported case of a Caucasian male with a severe form of Hirayama disease, suffering from weakness of the leg as well as the forearm. An abnormal range of cervical flexion was observed at the C5-6 level. The patient was successfully treated by anterior cervical discectomy and fusion.

Mitochondrial DNA polymorphisms/haplogroups in hereditary spastic paraplegia

Mitochondrial dysfunction could contribute to the development of spastic paraplegia. Among others, two of the genes implicated in hereditary spastic paraplegia encoded mitochondrial proteins and some of the clinical features frequently found in these patients resemble those observed in patients with mitochondrial DNA (mtDNA) mutations. We investigated the association between common mtDNA polymorphisms and spastic paraplegia. The ten mtDNA polymorphisms that defined the common European haplogroups were determined in 424 patients, 19% with a complicated phenotype. A rare haplogroup was associated with the disease in patients without a SPG3A, SPG4, or SPG7 mutation. Allele 10398G was more frequent among patients with a pure versus complicated phenotype. This mtDNA polymorphism was previously associated with the risk of developing other neurodegenerative diseases. In conclusion, some mtDNA polymorphisms could contribute to the development of spastic paraplegia or act as modifiers of the phenotype.

Sustainable joint solventless coproduction of glycerol carbonate and ethylene glycol via thermal transesterification of glycerol

This study focuses on the thermal reaction between glycerol and ethylene carbonate to obtain glycerol carbonate and ethylene glycol under solventless homogeneous operation, the process being a transcarbonation of glycerol or a glycerolysis of ethylene carbonate. As the two reagents constitute an immiscible system at 40 °C evolving into a single phase at 80 °C, the evolution of phases with temperature was studied by focused beam reflectance measurement. As the biphasic system was inert, runs were completed under a monophasic regime from 100 to 140 °C with molar ratios of ethylene carbonate to glycerol of 2 and 3, achieving quantitative conversion of glycerol, as corroborated by a thermodynamic study. Second order potential kinetic models were proposed and fitted to the data. Finally, a comparison with analogous catalytic approaches was made, showing that this process performs better material-wise.

Enzymatic synthesis of ibuprofen monoglycerides catalyzed by free Candida antarctica lipase B in a toluene–glycerol biphasic medium

The enzymatic esterification of glycerol and ibuprofen in different organic media to obtain a monoester of ibuprofen was studied in an open and close system, selecting an adequate kinetic model in both cases. The solubility of ibuprofen was tested in various solvents, leading to the selection of toluene as the most appropriate organic medium. Preliminary runs led to fixing the concentration of lipase CALB-L at 2 g L−1, stirring speed at 720 rpm, a water content of 6% v/v and a glycerol to toluene volume ratio of 20/5. Kinetic runs were performed at several ibuprofen initial concentrations (20 to 100 g L−1) and temperatures (50 to 80 °C). Two systems were defined, one of which contemplated continuous removal of water with toluene. Considering kinetic and thermodynamic data, several kinetic models were proposed and fitted to all available data making use of physical and statistical criteria to select the best ones. In the first system, the chosen model was an irreversible hyperbolic model, whereas in the other system, the selected model was a Michaelis–Menten-based reversible model of pseudo-first order with respect to the concentration of ibuprofen and the monoester.

Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain

Mutations in the GDAP1 gene can cause Charcot-Marie-Tooth disease. These mutations are quite rare in most Western countries but not so in certain regions of Spain or other Mediterranean countries. This cross-sectional retrospective multicenter study analyzed the clinical and genetic characteristics of patients with GDAP1 mutations across Spain. 99 patients were identified, which were distributed across most of Spain, but especially in the Northwest and Mediterranean regions. The most common genotypes were p.R120W (in 81% of patients with autosomal dominant inheritance) and p.Q163X (in 73% of autosomal recessive patients). Patients with recessively inherited mutations had a more severe phenotype, and certain clinical features, like dysphonia or respiratory dysfunction, were exclusively detected in this group. Dominantly inherited mutations had prominent clinical variability regarding severity, including 29% of patients who were asymptomatic. There were minor clinical differences between patients harboring specific mutations but not when grouped according to localization or type of mutation. This is the largest clinical series to date of patients with GDAP1 mutations, and it contributes to define the genetic distribution and genotype-phenotype correlation in this rare form of CMT.

Understanding and Modeling the Liquid Uptake in Porous Compacted Powder Preparations

Porous solid materials commonly undergo coating processes during their manufacture, where liquids are put in contact with solids for different purposes. The study of liquid penetration in porous substrates is a process of high relevance in activities in several industries. In particular, powder detergents are subject to coating with surfactants that will boost their performance, although this may affect the flowability and even cause caking of the particulate material, which can be detrimental to consumer acceptance. Here we present a methodology to make compacted preparations of powders relevant to detergent making and evaluate the internal structure of such porous substrates by means of X-ray microcomputed tomography. Liquid penetration in the preparation and the total mass uptake of fluid were monitored by a gravimetric technique based on a modified Wilhelmy plate method consisting of consecutive cycles. Taking into account the geometry of the system, two models were proposed to describe the liquid uptake based on the process being driven by mass (model 1) or pressure (model 2) gradients. A comparison between both from statistical and physical points of view led to the conclusion that the latter was more appropriate for describing the process and retrieving values of the permeability of the solid between 0.03 × 10-12 and 0.95 × 10-12 m2. Finally, with the parameters retrieved from model 2, the force balance observed throughout the experiment was simulated satisfactorily.

Solventless synthesis of solketal with commercially available sulfonic acid based ion exchange resins and their catalytic performance

Abstract As a means to valorize glycerol, the synthesis of solketal through a ketalization reaction with acetone was performed. Mild solventless conditions were applied to test the activity of different commercially available sulfonic ion exchange resins that had already been used for other applications, namely: Amberlyst 35dry, Amberlyst 36dry, Purolite CT275DR, Purolite CT276 and Lewatit GF101. Thorough characterization of the resins is herein provided and discussed, including acidity, elemental analysis, thermogravimetric, 13C-NMR, surface area and pore size distribution measurements. Lewatit GF101 showed the best performance reaching a yield to solketal of 47% after 6 h of operation at 313 K using a molar excess of acetone to glycerol of 4.5 to 1, owing to a greater availability of active centers as well as the ease of access to them than in the rest of the resins. Additionally, reutilization with and without regeneration was performed in up to five cycles, showing that Purolite CT276 had the lowest relative drop of its maximum activity, despite being the least active in each of the cycles.