At-home laser treatment of oral neuronal disorders : case reports

The neuronal disorders occurring in the oral district are mainly anaesthesia, paraesthesia, hypoesthesia and hyperaesthesia and they may occur frequently after surgical procedures. Medical treatment depends on degree of severity of the nerve injury but, in every case, it must be immediately carried out to reduce immune inflammatory reaction. The aim of this report is to investigate the effectiveness in the recovery of the peripheral nerve lesions of a new laser device recently proposed by the commerce that, due to its reduced size and to be a class I laser according the ANSI classification, may be used at home by the patient himself. Three different cases were treated with this ?at-home approach?: complete resolution of symptomatology was obtained after laser treatment with a good compliance for the patient and without reporting any side effect

A Novel Pathway for Metabolism of the Cardiovascular Risk Factor Homoarginine by alanine:glyoxylate aminotransferase 2

Low plasma concentrations of L-homoarginine are associated with an increased risk of cardiovascular events, while homoarginine supplementation is protective in animal models of metabolic syndrome and stroke. Catabolism of homoarginine is still poorly understood. Based on the recent findings from a Genome Wide Association Study we hypothesized that homoarginine can be metabolized by alanine:glyoxylate aminotransferase 2 (AGXT2). We purified human AGXT2 from tissues of AGXT2 transgenic mice and demonstrated its ability to metabolize homoarginine to 6-guanidino-2-oxocaproic acid (GOCA). After incubation of HepG2 cells overexpressing AGXT2 with isotope-labeled homoarginine-d4 we were able to detect labeled GOCA in the medium. We injected wild type mice with labeled homoarginine and detected labeled GOCA in the plasma. We found that AGXT2 knockout (KO) mice have higher homoarginine and lower GOCA plasma levels as compared to wild type mice, while the reverse was true for AGXT2 transgenic (Tg) mice. In summary, we experimentally proved the presence of a new pathway of homoarginine catabolism - its transamination by AGXT2 with formation of GOCA and demonstrated that endogenous AGXT2 is required for maintenance of homoarginine levels in mice. Our findings may lead to development of novel therapeutic approaches for cardiovascular pathologies associated with homoarginine deficiency

Caenorhabditis elegans AGXT-1 is a mitochondrial and temperature-adapted ortholog of peroxisomal human AGT1: New insights into between-species divergence in glyoxylate metabolism

In humans, glyoxylate is an intermediary product of metabolism, whose concentration is finely balanced. Mutations in peroxisomal alanine:glyoxylate aminotransferase (hAGT1) cause primary hyperoxaluria type 1 (PH1), which results in glyoxylate accumulation that is converted to toxic oxalate. In contrast, glyoxylate is used by the nematode Caenorhabditis elegans through a glyoxylate cycle to by-pass the decarboxylation steps of the tricarboxylic acid cycle and thus contributing to energy production and gluconeogenesis from stored lipids. To investigate the differences in glyoxylate metabolism between humans and C. elegans and to determine whether the nematode might be a suitable model for PH1, we have characterized here the predicted nematode ortholog of hAGT1 (AGXT-1) and compared its molecular properties with those of the human enzyme. Both enzymes form active PLP-dependent dimers with high specificity towards alanine and glyoxylate, and display similar three-dimensional structures. Interestingly, AGXT-1 shows 5-fold higher activity towards the alanine/glyoxylate pair than hAGT1. Thermal and chemical stability of AGXT-1 is lower than that of hAGT1, suggesting temperature-adaptation of the nematode enzyme linked to the lower optimal growth temperature of C. elegans. Remarkably, in vivo experiments demonstrate the mitochondrial localization of AGXT-1 in contrast to the peroxisomal compartmentalization of hAGT1. Our results support the view that the different glyoxylate metabolism in the nematode is associated with the divergent molecular properties and subcellular localization of the alanine:glyoxylate aminotransferase activity.This work was supported by the Spanish Ministry of Science and Innovation (CSD2009-00088, BIO2012-34937 and SAF2011-23933), the Junta de Andalucia (P11-CTS-7187), and the Oxalosis and Hyperoxaluria Foundation (OHF2012 to B.C.). A.L.P. acknowledges a Ramon y Cajal research contract (RyC2009-04147) from the Spanish Ministry of Science and Innovation and the University of Granada. N. M-T acknowledges a FPI predoctoral fellowship from the Spanish Ministry of Science and Innovation. A.C.C. and N.T. were supported by the grant IOS-1353845 from the National Science Foundation (NSF). N.T. acknowledges the Tetelman Fellowship for International Research on the Sciences awarded by Yale University.Peer Reviewe

Félicité. Una serva esemplare

From the first lines of the novel, Félicité appears to be the epitome of the servant. The sources of the literary topos of the «servante au grand cœur» go back in fact to the moral novel of the xviii century and to a philanthropic literature that probably inspired Flaubert. The comparison with a few examples of edifying literature of the same period depicting this character demonstrates that the author drew his inspiration from these clichés, though treating them in a paradoxical way. The paradox was already visible in the episode of Catherine Leroux in Madame Bovary, where the chemist’s annoyed reply is opposed to the servant’s loyal submission, and yet it is not possible for the reader to take a stance for either attitude. In Un cœur simple the demystification is emphasized by the arrival of the parrot, whose sources in the literature of the Enlightenment are also well known. From this moment on the edifying reading becomes impossible and the reader is sent back to an unsolvable opposition Enlightenment/religion that gives the novel a philosophical dimension

Reseña Rodríguez, Perla y Gayubas, Augusto (eds.) (2019) Poder y cultura en el Antiguo Egipto. Contribuciones a la reflexión histórica sobre el valle del Nilo y sus periferias. Salta:Instituto de Investigación en Ciencias Sociales y Humanidades- CONICET.

ReviewReseña Rodríguez, Perla y Gayubas, Augusto (eds.) (2019) Poder y cultura en el Antiguo Egipto. Contribuciones a la reflexión histórica sobre el valle del Nilo y sus periferias. Salta:Instituto de Investigación en Ciencias Sociales y Humanidades- CONICET, 169 pág. ISBN 978-987-46978-2-

Molecular and cellular insights into defects of human alanine:glyoxylate aminotransferase variants associated with Primary Hyperoxaluria Type I

L\u2019 Iperossaluria primaria di tipo I (PH1) \ue8 una malattia genetica rara a trasmissione autosomica recessiva caratterizzata dalla deposizione di sali insolubili di ossalato di calcio dapprima nei reni, nel tratto urinario e successivamente, in assenza di trattamenti appropriati, in tutto il corpo. La PH1 \ue8 causata dall\u2019assenza di alanina:gliossilato aminotransferasi (AGT), un\u2019 enzima epatico perossisomale dipendente dal piridossal 5\u2019-fosfato (PLP), che converte il gliossilato in glicina prevenendo la sua ossidazione ad ossalato e la formazione dei cristalli di ossalato di calcio. Ad oggi sono disponibili solo due approcci curativi per il trattamento della PH1: la somministrazione di piridossina, il precursore del PLP, che \ue8 efficace solo ne 10-30% dei pazienti, e il trapianto di fegato, una procedura molto invasiva. L\u2019AGT \ue8 codificata dal gene AGXT di cui esistono due varianti polimorfiche: l\u2019allele maggiore (AGT-Ma) e l\u2019allele minore (AGT-Mi). Fino ad oggi sono state identificate pi\uf9 di 150 mutazioni patogeniche e sono stati eseguiti diversi studi al fine di cercare di chiarificare le correlazioni genotipo/fenotipo. Ciononostante i meccanismi attraverso i quali ogni mutazione porta alla carenza di AGT a livello proteico sono poco conosciuti. Per questo motivo \ue8 stata eseguita una comparazione in termini di attivit\ue0 catalitica, legame del coenzima, caratteristiche spettroscopiche, stato di oligomerizzazione e stabilit\ue0 termica sia della forma apo che di quella oloenzimatica, tra l\u2019AGT normale e nove varianti patogeniche nella loro forma ricombinante purificata. Inoltre \ue8 stato intrapreso uno studio approfondito sulle propriet\ue0 strutturarli della variante S187F-Ma e sulle propriet\ue0 molecolari e cellulari delle varianti della Gly161. I dati ottenuti hanno permesso di (i) capire l\u2019impatto funzionale e/o strutturale di ogni mutazione sulla proteina, (ii) di rivalutare dati precedenti ottenuti su lisati cellulari, e (iii) di suggerire quale possa essere la terapia migliore, tra quelle disponibili, e di proporre nuove strategie terapeutiche per pazienti recanti le mutazioni analizzate.Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder characterized by the deposition of insoluble calcium oxalate crystals at first in the kidneys and urinary tract and then, in the absence of appropriate treatments, in the whole body. PH1 is caused by the deficiency of human liver specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). AGT is a pyridoxal 5'-phosphate (PLP)-dependent enzyme, which converts glyoxylate to glycine, thus preventing glyoxylate oxidation to oxalate and calcium oxalate formation. Only two curative therapeutic approaches are currently available for PH1: the administration of pyridoxine, a precursor of PLP, which is only effective in a minority of patients (10-30%), and liver transplantation, a very invasive procedure. AGT is encoded by the gene AGXT for which two main polymorphisms can be found: the major allele (AGT-Ma) and the minor allele (AGT-Mi). Up to now, more than 150 mutations have been identified that lead to PH1 and several studies have tried to clarify the genotype/phenotype correlations. However, the mechanisms by which each mutation causes AGT deficiency at the protein level are still poorly understood. Therefore, we performed a side-by-side comparison between normal AGT and nine purified pathogenic variants in terms of catalytic activity, coenzyme binding mode and affinity, spectroscopic features, oligomerization and thermal stability of both the holo- and apo-form. Moreover a detailed analysis of the structural properties of the S187F-Ma variant and of the molecular and cellular properties of Gly161 variants has been undertaken. Altogether, the data obtained has allowed us (i) to provide evidence for the structural and/or functional effects caused by each mutation on the protein, (ii) to reassess previous data obtained with crude cellular extracts, and (iii) to indicate a suitable therapy among those already available, and to suggest new treatments strategies for patients bearing the mutations analysed