Modelagem molecular na caracterização eletrônica de oligopeptídeos e na descrição quântica da interação fármaco-receptor

In this dissertation, the theoretical principles governing the molecular modeling were applied for electronic characterization of oligopeptide α3 and its variants (5Q, 7Q)-α3, as well as in the quantum description of the interaction of the aminoglycoside hygromycin B and the 30S subunit of bacterial ribosome. In the first study, the linear and neutral dipeptides which make up the mentioned oligopeptides were modeled and then optimized for a structure of lower potential energy and appropriate dihedral angles. In this case, three subsequent geometric optimization processes, based on classical Newtonian theory, the semi-empirical and density functional theory (DFT), explore the energy landscape of each dipeptide during the search of ideal minimum energy structures. Finally, great conformers were described about its electrostatic potential, ionization energy (amino acids), and frontier molecular orbitals and hopping term. From the hopping terms described in this study, it was possible in subsequent studies to characterize the charge transport propertie of these peptides models. It envisioned a new biosensor technology capable of diagnosing amyloid diseases, related to an accumulation of misshapen proteins, based on the conductivity displayed by proteins of the patient. In a second step of this dissertation, a study carried out by quantum molecular modeling of the interaction energy of an antibiotic ribosomal aminoglicosídico on your receiver. It is known that the hygromycin B (hygB) is an aminoglycoside antibiotic that affects ribosomal translocation by direct interaction with the small subunit of the bacterial ribosome (30S), specifically with nucleotides in helix 44 of the 16S ribosomal RNA (16S rRNA). Due to strong electrostatic character of this connection, it was proposed an energetic investigation of the binding mechanism of this complex using different values of dielectric constants (ε = 0, 4, 10, 20 and 40), which have been widely used to study the electrostatic properties of biomolecules. For this, increasing radii centered on the hygB centroid were measured from the 30S-hygB crystal structure (1HNZ.pdb), and only the individual interaction energy of each enclosed nucleotide was determined for quantum calculations using molecular fractionation with conjugate caps (MFCC) strategy. It was noticed that the dielectric constants underestimated the energies of individual interactions, allowing the convergence state is achieved quickly. But only for ε = 40, the total binding energy of drug-receptor interaction is stabilized at r = 18A, which provided an appropriate binding pocket because it encompassed the main residues that interact more strongly with the hygB - C1403, C1404, G1405, A1493, G1494, U1495, U1498 and C1496. Thus, the dielectric constant ≈ 40 is ideal for the treatment of systems with many electrical charges. By comparing the individual binding energies of 16S rRNA nucleotides with the experimental tests that determine the minimum inhibitory concentration (MIC) of hygB, it is believed that those residues with high binding values generated bacterial resistance to the drug when mutated. With the same reasoning, since those with low interaction energy do not influence effectively the affinity of the hygB in its binding site, there is no loss of effectiveness if they were replaced.

Níveis de homocisteína e desempenho cognitivo em uma amostra populacional de idosos da cidade do Natal-RN

The imprecision of the frontier that separates those cognitive deficits inherent to the human physiological aging process from those which represent the early signs of nervous system degenerative pathologies ,very prevalent among the elderly, has brought attention to the need of studies aiming to establish clinical and/or laboratorial criteria to allow this differentiation. Elderly people living in poor and developing countries are frequently exposed to precarious socioeconomic conditions which facilitate the development of an array of pathologies which have metabolic and nutritional dysfunctions as the established or proposed etiological agents. The levels of certain micronutrients, such as the vitamins B12 and B9 (folic acid), and of some intermediary metabolites, such as homocysteine are being thought of as etiological factors and/or as biological markers of a group of alterations which affect the normal functioning of the nervous system with important reflexes upon cognitive performance. This study aims to investigate the influence of homocysteine, B12 vitamin and folic acid levels on the cognitive performance of the low income elderly population. This transversal study took place in Natal, Rio Grande do Norte State, Brazil, and involved 205 dwelling elderly people, users of the Programa de Saúde da Família, a public healthcare program, maintained by the city s health authorities. A multidimensional questionnaire was used to assess the socio-demographic aspects and the overall health and nutrition conditions. The cognitive performance was measured by the use of the Portuguese version of the Mini Mental State Exam (MMSE). The serum levels of homocysteine, B12 vitamin and folic acid were determined by chemiluminescence. The association between the socio-demographic and serum levels of Hcy, B12 vitamin and folic acid was determined by multiple linear regression. Serum levels higher than 13.5 μmol/l, indicative of hyperhomocysteinemia (HHcy), were found on 25.4% of the sample, being more prevalent in men (p<0.05). Deficitary levels of folic acid (<5ng/mol) and of B12 vitamin (<193 pg/ml) were found on 3.9% and 10.2% of the sample respectively. A negative correlation was found between cognitive performance with both age and HHcy and a positive correlation was found between cognitive performance and schooling. The isolated HHcy R2 values were an explanation to only 4% of the variance of the MMSE scores. However, when associated with schooling and age, this model explains about 25% of this association

Modificações introduzidas pelos treinamentos cardiopulmonar e neuromuscular nos níveis séricos basais de fatores de crescimento insulina símile i (igf-1), cortisol, autonomia funcional e qualidade de vida de mulheres idosas

Changes introduced by cardiopulmonar and neuromuscular training on basal serum insulin-like grow factor-1 (IGF-1) and cortisol levels, functional autonomy and quality of life in elderly women The aim of this study was to compare the effects of strength and aerobic training on basal serum IGF-1 and Cortisol levels, functional autonomy (FA) and quality of life (QoL) in elderly women after 12 weeks of training. The subjects were submitted the strength training (75-85% 1-RM) with weight exercises (SG; n=12; age=66.08 ± 3,37 years; BMI=26,77 ± 3,72 kg/m2), aerobic training with aquatic exercises (AG; n=13; age=68,69 ± 4,70 years; BMI=29,19 ± 2,96 kg/m2) and control group (CG; n=10; age=68,80 ± 5,41 years; BMI=29,70 ± 2,82 kg/m2). Fasting blood was analyzed to measure basal IGF-1 and cortisol levels by chemiluminescence method. The t-Student test showed increased IGF-1 in the SG (p<0.05) for intragroup comparison. The Repeated-measure ANOVA presented increased IGF-1 (p<0.05) in the SG compared to the other two groups. There were no differences in cortisol levels. All the FA tests (GDLAM autonomy protocol) presented decreased significant in the time marked in seconds to the SG. The same results were found in the AG, except in the rise from a sitting position test. The autonomy index presented significant improvements (p<0.05) in the SG related to the AG and CG and in the AG to the CG. The SG showed increased QoL (p<0.05) (by WHOQOL-Old questionnaire) in the facet 1 (sensorial functioning) and facet 5 (death and dying). Thus, the SG obtained positive changes on IGF-1 and FA levels when compared to the AG. This suggests that strength training can indicated to decrease the effects of ageing.

Disfunção sexual feminina e níveis dos hormônios esteroidais em mulheres obesas atendidas no ambulatório de cirurgia bariátrica do hospital universitário Onofre Lopes em Natal/RN

A disfunção sexual corresponde a alterações em uma ou mais fases da resposta sexual humana e apresenta maior prevalência na população feminina. Ademais, a participação de alguns fatores como obesidade e níveis dos hormônios esteroidais na disfunção sexual feminina (DSF) permanece incerta. O presente estudo deteve-se na análise da ocorrência de DSF numa população de mulheres portadoras de obesidade, cadastradas no Ambulatório de Cirurgia Bariátrica do Hospital Universitário Onofre Lopes, da Universidade Federal do Rio Grande do Norte, no município de Natal, RN. O estudo foi realizado em uma amostra composta por trinta e uma mulheres, com idade entre 20 e 50 anos, com índice de massa corpórea (IMC) > 30 Kg/m2. A todas as pacientes foi aplicado um questionário composto por uma seção com dados socio-econômicos, e outra abordando a saúde sexual feminina, sendo esta última correspondente ao Female Sexual Function Index (FSFI), para diagnóstico de DSF. A partir dessa caracterização, as pacientes foram reunidas nos grupos CD (pacientes com disfunção, n= 9) e SD (sem disfunção, n= 22). Para a análise do efeito da obesidade na DSF, as pacientes foram reunidas nos grupos 1 (6 pacientes com IMC grau I e II: entre 30 e 40 Kg/m2) e 2 (25 com IMC grau III: acima de 40). Para o estudo da participação dos hormônios esteroidais foram determinadas as concentrações séricas de cortisol, estradiol e dehidroepiandrosterona (DHEA) pelo método de quimiluminescência. A análise estatística dos dados foi realizada usando os testes ANOVA, MANOVA (Pillai), além de análise de Cluster. Para identificar as diferenças entre os domínios do FSFI, foi usado o teste T de Student. A significância considerada para todos os testes foi para p< 0,01. Das pacientes estudadas, 25,8% apresentaram DSF de acordo com o escore total do FSFI. A análise estatística posterior evidenciou que as diferenças ocorreram para os domínios desejo, excitação e orgasmo. Não foi encontrada relação da presença de DSF com os diferentes graus de obesidade ou com os níveis hormonais dos esteróides cortisol, estradiol ou DHEA. Contudo, foi encontrado aumento significativo nos níveis séricos de estradiol para o grupo 1, que corresponde ao de menor índice de IMC. Estes resultados mostram que a prevalência de DSF não diferiu entre os graus I,II e III de obesidade das pacientes deste estudo mas, quando presente, a disfunção ocorre nos domínios desejo, excitação e orgasmo. A maior concentração de estradiol encontrada nas pacientes de menor índice de IMC sugere uma possível relação entre as duas variáveis que precisa ser investigada em estudos futuros.