Protein-based nanodevices for therapeutic applications

Tese de Doutoramento em Biologia Molecular e Ambiental (área de especialização em Biologia Celular e Saúde).

Lewis Score - Prognostic value in patients with isolated small bowel Crohn's disease

Background and aims: Small bowel capsule endoscopy (SBCE) allows mapping of small bowel inflammation in Crohn’s disease (CD). We aimed to assess the prognostic value of the severity of inflammatory lesions, quantified by the Lewis score (LS), in patients with isolated small bowel CD. Methods: A retrospective study was performed in which 53 patients with isolated small bowel CD were submitted to SBCE at the time of diagnosis. The Lewis score was calculated and patients had at least 12 months of follow-up after diagnosis. As adverse events we defined disease flare requiring systemic corticosteroid therapy, hospitalization and/or surgery during follow-up. We compared the incidence of adverse events in 2 patient subgroups, i.e. those with moderate or severe inflammatory activity (LS =790) and those with mild inflammatory activity (135 = LS < 790). Results: The LS was =790 in 22 patients (41.5%), while 58.5% presented with LS between 135 and 790. Patients with a higher LS were more frequently smokers (p = 0.01), males (p = 0017) and under immunosuppressive therapy (p = 0.004). In multivariate analysis, moderate to severe disease at SBCE was independently associated with corticosteroid therapy during follow-up, with a relative risk (RR) of 5 (p = 0.011; 95% confidence interval [CI] 1.5–17.8), and for hospitalization, with an RR of 13.7 (p = 0 .028; 95% CI 1.3–141.9). Conclusion: In patients with moderate to severe inflammatory activity there were higher prevalences of corticosteroid therapy demand and hospitalization during follow-up. Thus, stratifying the degree of small bowel inflammatory activity with SBCE and LS calculation at the time of diagnosis provided relevant prognostic value in patients with isolated small bowel CD.

Activity of carvacrol against Coagulase-negative Staphylococci biofilm related infections

Dissertação de mestrado em Bioengenharia

Single molecule simulation of diffusion and enzyme kinetics

This work presents a molecular-scale agent-based model for the simulation of enzymatic reactions at experimentally measured concentrations. The model incorporates stochasticity and spatial dependence, using diffusing and reacting particles with physical dimensions. We developed strategies to adjust and validate the enzymatic rates and diffusion coefficients to the information required by the computational agents, i.e., collision efficiency, interaction logic between agents, the time scale associated with interactions (e.g., kinetics), and agent velocity. Also, we tested the impact of molecular location (a source of biological noise) in the speed at which the reactions take place. Simulations were conducted for experimental data on the 2-hydroxymuconate tautomerase (EC 5.3.2.6, UniProt ID Q01468) and the Steroid Delta-isomerase (EC 5.3.3.1, UniProt ID P07445). Obtained results demonstrate that our approach is in accordance to existing experimental data and long-term biophysical and biochemical assumptions.

Basel III liquidity rules : measuring the impact on portuguese small banks activity

Mestrado em Finanças

Terapéutica farmacológica y de pequeñas moléculas en patologías de atesoramiento lisosomal: focalización en las Lipofuscinosis Ceroideas Neuronales. Farmaceutical and small molecules therapy in lysosomal storage diseases: focus on the Neuronal Ceroid Lipofuscinoses.

Introducción: Las Lipofuscinosis Ceroideas Neuronales (LCNs) son un grupo de patologías neurodegenerativas hereditarias de atesoramiento lisosomal (PALs) caracterizadas por el almacenamiento en los lisosomas de materiales complejos pobremente reconocidos. Su curso es muy severo con desenlace fatal, habiendo sido definidos diversos tipos sobre la base del estudio de los fenotipos clínicos, enzimáticos, morfológicos y las mutaciones. Su incidencia es de 1:12.500 nacimientos vivos a nivel mundial. Las intervenciones farmacológicas con moléculas pequeñas han sido exitosas para algunas PALs; sin embargo, debido a que para cada una de las moléculas ha sido asumido un mecanismo de acción, la efectividad puede estar limitada a uno o a pocos desórdenes y no beneficiar a otros. Se han comprobado efectos diversos de una serie de moléculas tales como Miglustat, Chaperonas moleculares diseñadas, Clenbuterol, N-acetilcisteina (Mucomyst), Cisteamina, Gentamicina y PTC124. Los tratamientos farmacológicos/ con moléculas pequeñas podrían resultar exitosos para las LCNs, mereciendo consideración desarrollar terapias para estos desórdenesObjetivo generalo Investigar en un tipo de patologías del sistema nervioso central, las Lipofuscinosis Ceroideas Neuronales, el enfoque terapéutico-farmacológico con pequeñas moléculas aplicado a otras patologías hereditarias.Objetivos específicoso Desarrollar un prototipo de cultivo de fibroblastos de pacientes a nivel hospitalario en Córdoba y mantener cultivos de fibroblastos de pacientes afectados de una LCN de genotipo CLN2, con mutaciones conocidas. o Enriquecer los cultivos con fármacos/ moléculas pequeñas probadas en otras PALs.o Averiguar si se produce incremento de actividad enzimática de la Tripeptidil Peptidasa-I (TPP-I) lisosomal.Materiales y Métodos: cultivo de fibroblastos de pacientes con el agregado de fármacos/pequeñas moléculas. Los donantes serán diagnosticados en CEMECO a través de una estrategia sistematizada para el reconocimiento de las LCNs y se identificarán las mutaciones en el gen CLN2 causales de enfermedad. Se averiguará la actividad enzimática de TPP-I y se marcará la enzima con anticuerpos específicos en corridas electroforéticas por western blot. Resultados esperados: incrementos en la actividad enzimática de TPP-I en los cultivos celulares con agregado de fármacos/ pequeñas moléculas con respecto a los controles. Importancia del proyecto: se trata de una investigación traduccional (traslational research) en la cual la clínica y los servicios a pacientes se vinculan con la investigación científica, desde una perspectiva de integración. Se desarrolla en un Hospital Público, el Hospital de Niños de la Provincia de Córdoba, asiento del Centro de Estudio de las Metabolopatías Congénitas-CEMECO. Se beneficiarán los pacientes, dado que impactará sobre la calidad de los servicios hospitalarios al suministrar diagnósticos bajo los estándares internacionales, en estrecha vinculación con centros referenciales del exterior. Se obtendrán para los genes de las LCNs los datos del espectro de mutaciones y polimorfismos presentes en la región y se aportarán datos sobre posibilidades de las terapias farmacológicas en relación a cada una de las mutaciones.

Modern climate change in Georgia. Radiatively active small atmospheric admixtures

წიგნში წარმოდგენილია საქართველოში ზოგიერთი ოპტიკურად აქტიური მცირე ატმოსფერული მინარევის მრავალწლიური კვლევის შედეგები. წარმოდგენილია მონაცემები C02, CHx, S02 და აეროზოლების ანთროპოგენური ემისიების შესახებ. დაწვრილებითაა შესწავლილი აეროზოლების თვლადი კონცენტრაციის ვერტიკალური განაწილება ტროპოსფეროში საქართველოს სხვადასხვა რეგიონისთვის. ჩატარებულია ოზონის საერთო რაოდენობის, ატმოსფერული აეროზოლების ოპტიკური სიმკვრის და სხვა ნაერთების გრძელვადიანი ვარიაცების დეტალური ანალიზი. წარმოდგენილია ზოგიერთი ნაერთის გავლენის თეორიული შეფასება საქართველოში მზის პირდაპირი და გაბნეული რადიაციის რეჟიმზე.

Rolle des Neural Cell Adhesion Molecule (NCAM) in amygdalo-hippokampaler Interaktion und der Salienzkodierung des kontextuellen Furchtgedächtnisses

Magdeburg, Univ., Medizin. Fakultät, Diss., 2010

Entwicklung kardiovaskulärer Risikofaktoren bei Small for gestational age-Geborenen im jungen Erwachsenenalter und der Vergleich der metabolischen Situation dieser Patienten mit der von normotroph Geborenen

Magdeburg, Univ., Medizin. Fakultät, Diss., 2008

Technique and clinical applications of double balloon enteroscopy for the evaluation of small bowel diseases

Magdeburg, Univ., Med. Fak., Diss., 2012

The small species of Belostoma (Heteroptera, Belostomatidae): I. Key to species groups and a revision of the denticolle group

A key to species groups of the genus Belostoma Latreille, 1807, using new taxonomic characters are presented as well as the revision of the four species included in the denticolle group: B. denticolle Montandon, 1903, and three new species: B. orbiculatum from eastern Argentina and southern Brazil, B. retusum from eastern Argentina and B. amazonum from northern Brazil which are described and illustrated.

On some small collections of inland shells from South America / Fritz Haas.

v.34:no.35(1955)

New and imperfectly known small mammals from Africa, by Wilfred H. Osgood.

v.20:no.21(1936)

Feeding ecology in the small neotropical amphisbaenid Amphisbaena munoai (Amphisbaenidae) in southern Brazil

We analyzed the alimentary tract of 66 specimens of Amphisbaena munoai Klappenbach, 1969 from the Serra do Sudeste, state of Rio Grande do Sul, southern Brazil. Forty specimens (60.6%) had prey items in their gut. The diet consisted mainly of small invertebrate prey, such as termites, insect larvae and ants. The most abundant prey item was termites, found in 62.5% of the non empty stomachs. The high number of individual prey items in the majority of stomachs, the small size of the regular prey items, and the absence of gut content in specimens of A. munoai kept alive for about two days, indicate that this species forages very frequently. The predominance of fossorial prey items and the occasional records of nomadic ants lead us to suggest that A. munoai usually feeds underground, and occasionally forages on the surface.

Intraspecific and interspecific variation in the Cryptotis nigrescens species complex of small-eared shrews (Insectivora, Soricidae) : with the description of a new species from Colombia / Neal Woodman, Robert M. Timm.

n.s. no.74(1993)