Formulation and optimization of polymeric nanoparticles loaded with riolozatrione: a promising nanoformulation with potential anti-herpetic activity

Riolozatrione (RZ) is a diterpenoid compound isolated from a dichloromethane extract of the Jatropha dioica root. This compound has been shown to possess moderate anti-herpetic activity in vitro. However, because of the poor solubility of this compound in aqueous vehicles, generating a stable formulation for potential use in the treatment of infection is challenging. The aim of this work was to optimize and physiochemically characterize Eudragit® L100-55-based polymeric nanoparticles (NPs) loaded with RZ (NPR) for in vitro anti-herpetic application. The NPs formulation was initially optimized using the dichloromethane extract of J. dioica, the major component of which was RZ. The optimized NPR formulation was stable, with a size of 263 nm, polydispersity index < 0.2, the zeta potential of –37 mV, and RZ encapsulation efficiency of 89 %. The NPR showed sustained release of RZ for 48 h with release percentages of 95 and 97 % at neutral and slightly acidic pH, respectively. Regarding in vitro anti-herpetic activity, the optimized NPR showed a selectivity index for HSV-1 of ≈16 and for HSV-2 of 13

Information and Communication Technologies (ICT) applied in palliative care: topic review

Aim: To check the tools used on the e - health researches on the palliative care item on the five last years. Method: A bibliographic review was carried out in PubMed, Scopus and Bireme databases on the subject of palliative care, e-health and costs. Results: The use of the Information technologies, the majority of the surveys find favorably the use of technology in the users who receive palliative care, since it facilitates the evaluation and handling symptoms. It improves too the communication between patients and health professionals, reducing in some cases de geographic displacements and decreasing the associated cost to the attention of these patients. Conclusion: E-health implementation through different intervention models has proven to be valuable for individuals with advance disease in palliative care, offering potential educational and the optimization of time and means for patients and caregivers, which improve the contact with the health professionals

Intentional replantation: case report

Intentional reimplantation is a procedure in which an intentional tooth extraction is performed followed by reinsertion of the extracted tooth. We present the case of a 50-year-old male patient who came to the consultation due to incrustation detachment in tooth #37, when performing the radiographic study an extensive apical lesion was observed in tooth #36 with a sinuous path and the presence of purulent exudate. The tooth #36 was extracted, apicoectomy, retro preparation and retrograde filling were carried out for later reimplantation, showing bone regeneration after one year of evolution

Melting and transverse depinning of driven vortex lattices in the periodic pinning of Josephson junction arrays

We study the non-equilibrium dynamical regimes of a moving vortex lattice in the periodic pinning of a Josephson junction array (JJA) for {\it finite temperatures} in the case of a fractional or submatching field. We obtain a phase diagram for the current driven JJA as a function of the driving current I and temperature T. We find that when the vortex lattice is driven by a current, the depinning transition at $T_p(I)$ and the melting transition at $T_M(I)$ become separated even for a field for which they coincide in equilibrium. We also distinguish between the depinning of the vortex lattice in the direction of the current drive, and the {\it transverse depinning} in the direction perpendicular to the drive. The transverse depinning corresponds to the onset of transverse resistance in a moving vortex lattice at a given temperature $T_{tr}$. For driving currents above the critical current we find that the moving vortex lattice has first a transverse depinning transition at low T, and later a melting transition at a higher temperature, $T_{M}>T_{tr}$.Comment: 17 pages, 19 figure

Reconstructing the Indian Origin and Dispersal of the European Roma: A Maternal Genetic Perspective

Previous genetic, anthropological and linguistic studies have shown that Roma (Gypsies) constitute a founder population dispersed throughout Europe whose origins might be traced to the Indian subcontinent. Linguistic and anthropological evidence point to Indo-Aryan ethnic groups from North-western India as the ancestral parental population of Roma. Recently, a strong genetic hint supporting this theory came from a study of a private mutation causing primary congenital glaucoma. In the present study, complete mitochondrial control sequences of Iberian Roma and previously published maternal lineages of other European Roma were analyzed in order to establish the genetic affinities among Roma groups, determine the degree of admixture with neighbouring populations, infer the migration routes followed since the first arrival to Europe, and survey the origin of Roma within the Indian subcontinent. Our results show that the maternal lineage composition in the Roma groups follows a pattern of different migration routes, with several founder effects, and low effective population sizes along their dispersal. Our data allowed the confirmation of a North/West migration route shared by Polish, Lithuanian and Iberian Roma. Additionally, eleven Roma founder lineages were identified and degrees of admixture with host populations were estimated. Finally, the comparison with an extensive database of Indian sequences allowed us to identify the Punjab state, in North-western India, as the putative ancestral homeland of the European Roma, in agreement with previous linguistic and anthropological studies

Effects of Erythrocytes Treated with Alpha Hemolysin of E.Coli on Endothelial Cells

Uropathogenic strains of E. coli deliver the toxin alpha-hemolysin (HlyA) to optimize the host environment for the spread of infection. It was reported that at high concentrations, the toxin forms pores in eukaryotic membranes, leading to cell lysis, while lower concentrations might interfere with host-cell-signaling pathways, causing apoptosis. In the present investigation we demonstrate that a relatively low concentration of HlyA induces morphological changes and phosphatidylserine (PS) externalization of human erythrocytes. On the other hand, the unacylated nonhemolytic form of HlyA, ProHlyA induces similar morphological changes but no PS externalization. We performed osmoscan experiments to test the effect of both proteins on erythrocytes structure.Instituto de Investigaciones Bioquímicas de La PlataInstituto de Estudios Inmunológicos y Fisiopatológico

Full-Exon Pyrosequencing Screening of BRCA Germline Mutations in Mexican Women with Inherited Breast and Ovarian Cancer

Hereditary breast cancer comprises 10% of all breast cancers. The most prevalent genes causing this pathology are BRCA1 and BRCA2 (breast cancer early onset 1 and 2), which also predispose to other cancers. Despite the outstanding relevance of genetic screening of BRCA deleterious variants in patients with a history of familial cancer, this practice is not common in Latin American public institutions. In this work we assessed mutations in the entire exonic and splice-site regions of BRCA in 39 patients with breast and ovarian cancer and with familial history of breast cancer or with clinical features suggestive for BRCA mutations by massive parallel pyrosequencing. First we evaluated the method with controls and found 41–485 reads per sequence in BRCA pathogenic mutations. Negative controls did not show deleterious variants, confirming the suitability of the approach. In patients diagnosed with cancer we found 4 novel deleterious mutations (c.2805_2808delAGAT and c.3124_3133delAGCAATATTA in BRCA1; c.2639_2640delTG and c.5114_5117delTAAA in BRCA2). The prevalence of BRCA mutations in these patients was 10.2%. Moreover, we discovered 16 variants with unknown clinical significance (11 in exons and 5 in introns); 4 were predicted as possibly pathogenic by in silico analyses, and 3 have not been described previously. This study illustrates how massive pyrosequencing technology can be applied to screen for BRCA mutations in the whole exonic and splice regions in patients with suspected BRCA-related cancers. This is the first effort to analyse the mutational status of BRCA genes on a Mexican-mestizo population by means of pyrosequencing

NSUSY fits

We perform a global fit to Higgs signal-strength data in the context of light stops in Natural SUSY. In this case, the Wilson coefficients of the higher dimensional operators mediating g g -> h and h -> \gamma \gamma, given by c_g, c_\gamma, are related by c_g = 3 (1 + 3 \alpha_s/(2 \pi)) c_\gamma/8. We examine this predictive scenario in detail, combining Higgs signal-strength constraints with recent precision measurements of m_W, b-> s \gamma constraints and direct collider bounds on weak scale SUSY, finding regions of parameter space that are consistent with all of these constraints. However it is challenging for the allowed parameter space to reproduce the observed Higgs mass value with sub-TeV stops. We discuss some of the direct stop discovery prospects and show how global Higgs fits can be used to exclude light stop parameter space difficult to probe by direct collider searches. We determine the current status of such indirect exclusions and estimate their reach by the end of the 8 TeV LHC run.Comment: 41 pages, 13 figures. v3: final JHEP version, b to s gamma updated to latest data and typos correcte

Shiga Toxin 1 Induces on Lipopolysaccharide-Treated Astrocytes the Release of Tumor Necrosis Factor-alpha that Alter Brain-Like Endothelium Integrity

The hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia and renal dysfunction. The typical form of HUS is generally associated with infections by Gram-negative Shiga toxin (Stx)-producing Escherichia coli (STEC). Endothelial dysfunction induced by Stx is central, but bacterial lipopolysaccharide (LPS) and neutrophils (PMN) contribute to the pathophysiology. Although renal failure is characteristic of this syndrome, neurological complications occur in severe cases and is usually associated with death. Impaired blood-brain barrier (BBB) is associated with damage to cerebral endothelial cells (ECs) that comprise the BBB. Astrocytes (ASTs) are inflammatory cells in the brain and determine the BBB function. ASTs are in close proximity to ECs, hence the study of the effects of Stx1 and LPS on ASTs, and the influence of their response on ECs is essential. We have previously demonstrated that Stx1 and LPS induced activation of rat ASTs and the release of inflammatory factors such as TNF-α, nitric oxide and chemokines. Here, we demonstrate that rat ASTs-derived factors alter permeability of ECs with brain properties (HUVECd); suggesting that functional properties of BBB could also be affected. Additionally, these factors activate HUVECd and render them into a proagregant state promoting PMN and platelets adhesion. Moreover, these effects were dependent on ASTs secreted-TNF-α. Stx1 and LPS-induced ASTs response could influence brain ECs integrity and BBB function once Stx and factors associated to the STEC infection reach the brain parenchyma and therefore contribute to the development of the neuropathology observed in HUS