Structure analysis of biologically important prokaryotic glycopolymers

Of the many post-translational modifications organisms can undertake, glycosylation is the most prevalent and the most diverse. The research in this thesis focuses on the structural characterisation of glycosylation in two classes of glycopolymer (lipopolysaccharide (LPS) and glycoprotein) in two domains of life (bacteria and archaea). The common theme linking these subprojects is the development and application of high sensitivity analytical techniques, primarily mass spectrometry (MS), for studying prokaryotic glycosylation. Many prokaryotes produce glycan arrangements with extraordinary variety in composition and structure. A further challenge is posed by additional functionalities such as lipids whose characterisation is not always straightforward. Glycosylation in prokaryotes has a variety of different biological functions, including their important roles in the mediation of interactions between pathogens and hosts. Thus enhanced knowledge of bacterial glycosylation may be of therapeutic value, whilst a better understanding of archaeal protein glycosylation will provide further targets for industrial applications, as well as insight into this post- translational modification across evolution and protein processing under extreme conditions. The first sub-project focused on the S-layer glycoprotein of the halophilic archeaon Haloferax volcanii, which has been reported to be modified by both glycans and lipids. Glycoproteomic and associated MS technologies were employed to characterise the N- and O-linked glycosylation and to explore putative lipid modifications. Approximately 90% of the S-layer was mapped and N-glycans were identified at all the mapped consensus sites, decorated with a pentasaccharide consisting of two hexoses, two hexuronic acids and a methylated hexuronic acid. The O-glycans are homogeneously identified as a disaccharide consisting of galactose and glucose. Unexpectedly it was found that membrane-derived lipids were present in the S- layer samples despite extensive purification, calling into question the predicted presence of covalently linked lipid. The H. volcanii N-glycosylation is mediated by the products of the agl gene cluster and the functional characterisation of members of the agl gene cluster was investigated by MS analysis of agl-mutant strains of the S-layer. Burkholderia pseudomallei is the causative agent of melioidosis, a serious and often fatal disease in humans which is endemic in South-East Asia and other equatorial regions. Its LPS is vital for serum resistance and the O-antigen repeat structures are of interest as vaccine targets. B. pseudomallei is reported to produce several polysaccharides, amongst which the already characterised ‘typical’ O-antigen of K96243 represents 97% of the strains. The serologically distinct ‘atypical’ strain 576 produces a different LPS, whose characterisation is the subject of this research project. MS strategies coupled with various hydrolytic and chemical derivatisation methodologies were employed to define the composition and potential sequences of the O-antigen repeat unit. These MS strategies were complemented by a novel NMR technique involving embedding of the LPS into micelles. Taken together the MS and NMR data have revealed a highly unusual O-antigen structure for atypical LPS which is remarkably different from the typical O-antigen. The development of structural analysis tools in MS and NMR applicable to the illustrated types of glycosylation in these prokaryotes will give a more consistent approach to sugar characterisation and their modifications thus providing more informative results for pathogenicity and immunological studies as well as pathway comparisons.Open Acces

Growth factors and experimental arterial grafts

Background: The production of growth factors from several experimental arterial conduits was determined. Methods: We implanted 105 experimental arterial grafts that were 1 cm long in the abdominal aorta of Lewis rats (average weight, 250 g). Five different types of grafts were analyzed: arterial isografts, vein grafts, arterial allografts, and polytetrafluoroethylene (PTFE) grafts with normal or decreased compliance. Animals were killed humanely 4 weeks after surgery and the production of platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), transforming growth factor-b, tumor necrosis factor-a, and interleukin-1 was analyzed. Results: Myointimal hyperplasia (MH) was evident in vein grafts, arterial allografts, and PTFE grafts, but not in arterial isografts. Growth factor production was increased for grafts prone to develop MH like vein, PTFE grafts, and arterial allografts. PDGF and bFGF were increased significantly for PTFE and vein grafts, but not for arterial allografts. The importance of bFGF and PGDF was confirmed by the capability of antibody to PDGF and to bFGF to reduce the mitogenic activity of smooth muscle cells, in vivo and in vitro, for PTFE and vein grafts, but not for arterial allografts, in which a predominant role was played by interleukin-1 and tumor necrosis factor-a. Conclusions: Agents able to neutralize this increased production of growth factors, either directly or by competition with their receptors, can prevent MH formation. (J Vasc Surg 2016;64:1444-9.) Clinical Relevance: Arterial grafts release growth factors, which can lead to myointimal hyperplasia formation and atherosclerosis progression in the arterial tree. Both phenomena can cause graft occlusion. Inhibition of growth factor release by arterial grafts can improve their clinical effectiveness

Low-level laser effect in patients with neurosensory impairment of mandibular nerve after sagittal split ramus osteotomy.Randomized clinical trial, controlled by placebo

Objectives: Evaluate the effect on the application of low level laser therapy, in patients that have been previously intervened with a sagittal ramus split osteotomy and present neurosensory impairment due to this surgery, com - pared with placebo. Study D esign: This preliminary study is a randomized clinical trial, with an experimental group (n=17) which received laser light and a control group (n=14), placebo. All participants received laser applications, divided after surgery in days 1, 2, 3, 5, 10, 14, 21 and 28. Neurosensory impairment was evaluated clinically with 5 tests; visual analog scale (VAS) for pain and sensitivity, directional and 2 point discrimination, thermal discrimination, each one of them performed before and after surgery on day 1, and 1, 2 and 6 months. Participants and results evalu - ator were blinded to intervention. Variables were described with absolute frequencies, percentages and medians. Ordinal and dichotomous variables were compared with Mann Whitney's and Fisher's test respectively. Results: Results demonstrate clinical improvement in time, as well as in magnitude of neurosensory return for laser group; VAS for sensitivity reached 5 (normal), 10 participants recovered initial values for 2 point discrimina - tion (62,5%) and 87,5% recovered directional discrimination at 6 months after surgery. General VAS for sensitiv - ity showed 68,75% for laser group, compared with placebo 21,43% ( p -value = (0.0095). Left side sensitivity (VAS) showed 3.25 and 4 medians for placebo and laser at 2 months, respectively ( p -value = (0.004). Conclusions: Low-level laser therapy was beneficial for this group of patients on recovery of neurosensory impair - ment of mandibula r nerve, compared to a placebo

Tratamiento con férula dental en bruxismo inducido por anticonvulsivo: reporte de caso

Signs of tooth wear and grinding are associated with bruxism, which is commonly observed in dental offices. Here, the authors describe a case of bruxism probably induced by the anti-seizure drug Valpromed®, that was successfully treated with a dental splint. A man was attended in the dental clinic for improvement of dental aesthetics. On clinical examination moderate overwear of the occlusal surfaces of molars was observed associated with a history of nightly grinding, characteristic of sleep bruxism. Approximately 5 months previously, the patient had started therapy with Valpromed® due to episodes of migraine. The drug had been prescribed by a neurologist to prevent convulsions since the patient had had neurocysticercosis during childhood. Based on the advice of an oral rehabilitation specialist and the literature reviewed, it was concluded that the presence of bruxism in this patient may be attributed to the therapy with the anti-seizure medication. Although the patient is still under controls, the dental splint seems to be a promising approach for the treatment of this condition. The patient was treated with a minimally invasive dental splint and is monitored periodically, showing good results.Los signos de desgaste y rechinamiento de los dientes están asociados con el bruxismo y se observan comúnmente en los consultorios dentales. En este reporte, las autoras describen un caso de bruxismo probablemente inducido por el medicamento anticonvulsivo Valpromed®, que fue tratado con éxito mediante una férula dental. El paciente llegó a la clínica declarando que deseaba mejorar su estética. En el examen clínico, se observó un desgaste moderado de las superficies oclusales de los molares asociado con antecedentes de rechinamiento nocturno, característico del bruxismo del sueño. Hace aproximadamente 5 meses, el paciente comenzó la terapia con Valpromed® por orden del neurólogo, debido a episodios de migraña. El medicamento se prescribió para evitar el riesgo de convulsiones ya que el paciente había sufrido de neurocisticercosis durante la infancia. Según los consejos del especialista en rehabilitación oral y la literatura revisada, las autoras concluyeron que el bruxismo podía atribuirse a la terapia con el medicamento anticonvulsivo. Para el tratamiento, se escogió una técnica mínimamente invasiva. Aunque el paciente todavía está en controles, la férula dental parece ser un enfoque prometedor para el tratamiento de esta afección

Adquisición de bienes y servicios y su relación en la gestión administrativa en la Municipalidad provincial Mariscal Nieto, Moquegua 2023

El presente trabajo titulado “Adquisición de bienes y servicios y su relación en la gestión administrativa en la Municipalidad provincial Mariscal Nieto, Moquegua, 2023”, presentó como objetivo el determinar cuál es la relación entre la Adquisición de bienes y servicios y la gestión administrativa de la Municipalidad provincial Mariscal Nieto, Moquegua, 2023. Se trabajó mediante una metodología de tipo aplicada, asimismo de enfoque cuantitativo y un diseño no experimental. Mostrando como población a 50 trabajadores de la municipalidad Mariscal Nieto, a través del muestreo no probabilístico teniendo 35 trabajadores de la municipalidad. El instrumento utilizado fue un cuestionario respecto al desarrollo de la gestión administrativa y la adquisición de bienes y servicios mediante 18 ítems medidos con la escala Likert. Como resultado mostró que la gestión administrativa tiene relación con los procesos de adquisición de bienes y servicios demostrándose con una significancia menor a 0,05 además de un Rho de Spearman de 0,937 afirmando que su correlación es positiva muy alta. Para concluir se aseguró que la gestión administrativa es determinante para el correcto manejo de la adquisición de bienes y servicios en la municipalidad provincial Mariscal Nieto, de Moquegua, 2023, debido a su alto grado de correlación

Insulin Resistance and Cancer Risk: An Overview of the Pathogenetic Mechanisms

Insulin resistance is common in individuals with obesity or type 2 diabetes (T2D), in which circulating insulin levels are frequently increased. Recent epidemiological and clinical evidence points to a link between insulin resistance and cancer. The mechanisms for this association are unknown, but hyperinsulinaemia (a hallmark of insulin resistance) and the increase in bioavailable insulin-like growth factor I (IGF-I) appear to have a role in tumor initiation and progression in insulin-resistant patients. Insulin and IGF-I inhibit the hepatic synthesis of sex-hormone binding globulin (SHBG), whereas both hormones stimulate the ovarian synthesis of sex steroids, whose effects, in breast epithelium and endometrium, can promote cellular proliferation and inhibit apoptosis. Furthermore, an increased risk of cancer among insulin-resistant patients can be due to overproduction of reactive oxygen species (ROS) that can damage DNA contributing to mutagenesis and carcinogenesis. On the other hand, it is possible that the abundance of inflammatory cells in adipose tissue of obese and diabetic patients may promote systemic inflammation which can result in a protumorigenic environment. Here, we summarize recent progress on insulin resistance and cancer, focusing on various implicated mechanisms that have been described recently, and discuss how these mechanisms may contribute to cancer initiation and progression

In Vitro Characterization of an Anodized Surface of a Dental Implant Collar and Dental Abutment on Peri-Implant Cellular Response

The purpose of this paper was to determine the effect of anodization on the in vitro proliferation and adhesion of immortalized human keratinocytes (HaCats) and mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) in Titanium Grade 23 (Ti6Al4V ELI) discs and to describe the surface topography, roughness, and composition of dental implants (body and collar) and abutments submitted to an area-specific anodization process. HaCat cells and BM-MSCs were seeded onto discs with three different surface treatments: machined, area-specific anodization for abutments, and area-specific anodization for implant collars. Cell proliferation was assessed using a resazurin-based fluorescent dye on days 1, 3, and 7, while cell adhesion was examined using scanning electron microscopy (SEM). Surface topography, roughness, and composition were evaluated for six implant bodies with an anodized rough surface, six anodized implant smooth collars, and six anodized prosthetic abutments. Both HaCats and BM-MSCs showed increased viability over time (p < 0.001 ) with no statistically significant differences among the different surfaces (p = 0.447 HaCats and p = 0.631 BM-MSCs). SEM analysis revealed an enhanced presence and adhesion of HaCat cells on the anodized surface for the implant collars and an increased adhesion of BM-MSCs on both the anodized and machined surface abutments. The topography characteristics of the treated implants and abutments varied depending on the specific implant region. Chemical analysis confirmed the presence of oxygen, calcium, phosphorus, and sodium on the anodized surfaces. The area-specific anodization process can be utilized to create variable topography, increase the specific surface area, and introduce oxygen, calcium, phosphorus, and sodium to dental implants and abutments. While BM-MSCs and HaCat cells showed similar adhesion and proliferation on anodized and machined surfaces, a positive interaction between anodized Ti6Al4V ELI surfaces and these two cell lines present in the peri-implant mucosa was observed. Due to the limitations of the present study, further research is necessary to confirm these findings

Antioxidant, phase II and III responses induced by lipoic acid in the fish Jenynsia multidentata (Anablapidae) and its influence on endolsulfan accumulation and toxicity

Antioxidants like lipoic acid (LA) are known to trigger augmented antioxidant and phase II and III responses. This study aimed to evaluate the effect of LA in P-glycoprotein (Pgp) expression, glutathione-S-transferase (GST) activity, total antioxidant competence, levels of lipid peroxides (TBARS) and accumulation of the organochlorine insecticide endosulfan (Endo: α-, β-isomers and sulfate metabolite) in different organs of the fish Jenynsia multidentata. One hundred and twenty females (1.55 ± 0.07 g) were fed during 8 days with (n = 60) or without (n = 60) a LA enriched ration (6000 mg/kg). Four experimental groups were defined: −LA/−Endo; +LA/−Endo; −LA/+Endo; and +LA/+Endo. Endo groups were exposed during 24 h to 1.4 μg of insecticide/L. Results showed that only LA induced a significant increment in liver Pgp expression. GST activity was augmented in liver after exposure to LA or Endo. TBARS levels were lowered in liver and gills after LA pre-treatment. Total antioxidant capacity was lowered in liver of Endo exposed fish, a result that was reversed by LA pre-treatment. It is concluded that LA induced the expected effects in terms of Pgp expression, GST activity and reduced TBARS levels although favored α-Endo accumulation in brain. However, the Endo metabolism to the more persistent endosulfan sulfate was not facilitated by LA pre-treatment.Fil: Monserrat, José María. Universidade Federal do Rio Grande do Norte; Brasil. Instituto de Ciências Biológicas; BrasilFil: Garcia, M. L.. Universidade Federal do Rio Grande do Norte; Brasil. Instituto de Ciências Biológicas; BrasilFil: Ventura Lima, J.. Universidade Federal do Rio Grande do Norte; Brasil. Instituto de Ciências Biológicas; BrasilFil: Gonzalez, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Ballesteros, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Miglioranza, Karina Silvia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Amé, María Valeria. Universidad Nacional de Córdoba; ArgentinaFil: Wunderlin, Daniel Alberto. Universidad Nacional de Córdoba; Argentin

Modelos factoriales de la Escala de Autoestima de Rosenberg en adolescentes peruanos

Factorial models of Rosenberg’s Self-esteem Scale in Peruvian adolescentsAbstract: The Rosenberg Self-Esteem Scale (RSE) is an instrument widely used and designed to measure self-esteem in a single dimension. The aim of this research was to analyze the internal structure and the reliability of the RSE in Peruvian adolescents. The scale was administered to a total of 715 adolescents (51.3% female) with an average age of 12.20 years. Six models were identified by confirmatory factor analysis, which correspond to factorial structures reported in previous studies. The results showed a better goodness of fit for the one-dimensional model with control of method effects on inverse items, eliminating item 8 due to its ambiguity. Reliability was adequate and was calculated using the omega coefficient. The unifactorial structure of the RSE is discussed and it is concluded that the instrument reports evidence of validity and adequate internal consistency to be used in the Peruvian context.Keywords: Self-esteem; teenagers; validity; reliability.Resumen: La Escala de Autoestima de Rosenberg (RSE) es un instrumento ampliamente utilizado que fue diseñado para medir la autoestima en una sola dimensión. La presente investigación tuvo como objetivo principal analizar la estructura interna y la fiabilidad de la RSE en adolescentes peruanos. La escala fue administrada a un total de 715 adolescentes (51.3% de sexo femenino; M edad = 12.20 años). Se identificaron seis modelos mediante análisis factorial confirmatorio, los cuales corresponden a estructuras factoriales reportadas en estudios previos. Los resultados mostraron mejores bondades de ajuste para el modelo unidimensional con control del efecto del método en ítems inversos eliminando el ítem 8 por su ambigüedad. La fiabilidad fue adecuada y se calculó a través del coeficiente omega. Se discute la estructura unifactorial de la RSE y se concluye que el instrumento proporciona evidencia de validez y consistencia interna adecuadas para ser utilizada en el contexto peruano.Palabras clave: Autoestima; adolescentes; validez; fiabilidad

Perfil epidemiológico de los donadores de dientes humanos extraídos en establecimientos de Salud Pública, ubicados en Santa Ana, San Salvador y San Vicente durante el año 2019.

RESUMEN Objetivo: Determinar el perfil epidemiológico de los donadores de dientes humanos extraídos en establecimientos de salud pública, durante el año 2019. Metodología: Se realizó un estudio de tipo observacional, descriptivo y transversal de 224 donadores de dientes humanos entre 7 a 71 o más años que acudieron a las UCSF de Chalchuapa, Planes de Renderos, Cuscatancingo, Vía Mariona y San Lorenzo. Fueron caracterizados según indicadores sociales, clínicos bucales e historia médica del donador, causas de extracción y características físicas de los dientes extraídos. La recolección de datos se realizó con cédulas de entrevista y guías de observación. Se realizaron 250 extracciones. Resultados: El sexo prevalente es el femenino con 68.75%, siendo la zona urbana más afectada con el 66.97% y el grupo etario de 21 a 30 años con 23.21%, el 14.73% presentó hipertensión arterial. Según los indicadores clínicos bucales, el 10.27% mostró bruxismo, siendo la caries dental la enfermedad más prevalente con un 91.96%, observando un nivel ISHO óptimo de 58.48%. La principal causa de extracción fue la caries dental con 67.20%, el diente extraído con mayor frecuencia fue el 4-6(FDI). Entre las características de la corona, el 64.4% presentaron caries cavitadas > 2 mm. Respecto a la raíz el 94.40% poseen raíz completa y el 44.40% 1 raíz. Conclusión: La caries dental es la principal causa de extracción afectando más a las mujeres de 21 a 30 años que residen en el área urbana, siendo el diente 4- 6 el más afectado. Palabras claves: Perfil epidemiológico, donador, órgano dental