HOMO-raising strategies in aminocatalysis, from Enamine to Tetraenamine

Dissertação para obtenção do Grau de Mestre em Bioorgânica

Avaliação de parâmetros para o diagnóstico laboratorial de infecção genital feminina pela Chlamydia trachomatis

Foram examinadas prospectivamente189 amostras cervicais de mulheres sintomáticas e assintomáticas. Foram colhidas 2 amostras do canal endocervical, das quais uma foi examinada pela reação de imunofluorescência direta (IFD) com anticorpo monoclonal (MicroTrak), para verificação da adequação das amostras. A segunda amostra foi inoculada em cultura de células McCoy. Uma terceira amostra foi coletada para pesquisa de anticorpos das classes IgG e IgA. A Chlamydia trachomatis foi isolada de 14/166 (8,4%) das mulheres com sintomas e de 3/23 (13%) daquelas sem sintomas. Observamos que as 152 mulheres do grupo sintomático, com cultura negativa, possuiam sintomas equivalentes. Em relação ao número de células epiteliais, verificou-se que 13 das 17 (76,5%) amostras endocervicais positivas pela cultura e pela IFD, todas apresentavam mais de 5 células. Tomando-se como critério de positividade títulos ³ 1:8, foram detectados anticorpos das classes IgG e/ou IgA específicos para C. trachomatis em 11/189 (64,7%) das 17 mulheres com cultura positiva. Conclusões: a) não existe sintoma que seja específico de infecção por clamídia (p > 0,05); b) a quantidade de células epiteliais representariam fator de interferência na positividade da cultura, sendo, portanto, variáveis dependentes (p < 0,001); c) a pesquisa de anticorpos na cérvice não poderia ser utilizada como diagnóstico alternativo, pois a sua detecção depende da fase evolutiva da infecção e da resposta imunitária individual.

Efeitos adversos da poliquimioterapia em pacientes com hanseníase: um levantamento de cinco anos em um Centro de Saúde da Universidade Federal de Uberlândia

A implementação da poliquimioterapia (PQT/OMS) - composta pelas drogas dapsona, clofazimina e rifampicina - possibilitou a cura da hanseníase, porém não foram priorizados o manejo dos efeitos adversos pelas equipes de saúde. Objetivando determinar a magnitude dos efeitos adversos da poliquimioterapia para hanseníase e relacioná-los como possível causa de não adesividade do paciente ao tratamento, revisou-se prontuários de 187 pacientes tratados com PQT, de 1995 a 2000, no Centro de Saúde Escola (CSE) Symbol>-UFU, com registro de efeitos colaterais em 71 pacientes (37,9%). Dentre os 113 efeitos adversos, 80 (70,7%) relacionaram-se à dapsona, 7 (6,2%) à rifampicina, 26 (20,5%) à clofazimina. Esses efeitos levaram à mudança de esquema terapêutico em 28 (14,9%) dos 187 pacientes ou 39,4% dos 71 com efeitos adversos. Discute-se a importância de considerar os efeitos adversos da PQT na capacitação das equipes de saúde para maior adesão do paciente ao tratamento, colaborando para eliminar a hanseníase como problema de saúde pública.

Some Notes on the Reception of Josquin and of Northern Idioms in Portuguese Music and Culture

Although Josquin is by far the best-represented foreign composer in Gonçalo de Baena's Arte novamente inventada pera aprender a tanger (Lisbon, 1540), his music is undeniably under-represented both in the extant sixteenth-century Portuguese manuscripts containing Franco-Flemish polyphony and in volumes imported from the Netherlands such as Coimbra MM 2 and VienNB 1783. Josquin’s reputation made him, along with Ockeghem, a symbol in Portuguese humanistic culture, but up to at least the late 1530s his name seems to have been much better known than his music. Nevertheless, possible allusions to specific works by Josquin can be found in early- and mid-sixteenth-century Portuguese polyphony. By the 1520s, the general technical and stylistic characteristics of his and the following generation of northerners had begun to permeate locally produced polyphony. This eventually replaced the late-fifteenth- and early-sixteenth-century pan-consonant and homorythmic style associated with the Aragonese and the so-called Spanish court repertory.

Development of novel ionic liquids based on biological molecules

Ionic Liquids (ILs) belong to a class of compounds with unusual properties: very low vapour pressure; high chemical and thermal stability and the ability to dissolve a wide range of substances. A new field in research is evaluating the possibility to use natural chiral biomolecules for the preparation of chiral ionic liquids (CILs). This important challenge in synthetic chemistry can open new avenues of research in order to avoid some problems related with the intrinsic biodegradability and toxicity associated to conventional ILs. The research work developed aimed for the synthesis of CILs, their characterization and possible applications, based on biological moieties used either as chiral cations or anions, depending on the synthetic manipulation of the derivatives. Overall, a total of 28 organic salts, including CILs were synthesized: 9 based on L-cysteine derivatives, 12 based on L-proline, 3 based on nucleosides and 4 based on nucleotides. All these new CILs were completely characterized and their chemical and physical properties were evaluated. Some CILs based on L-cysteine have been applied for discrimination processes, including resolution of racemates and as a chiral catalyst for asymmetric Aldol condensation. L-proline derived CILs were also studied as chiral catalysts for Michael reaction. In parallel, the interactions of macrocyclic oligosugars called cyclodextrins (CDs) with several ILs were studied. It was possible to improve the solubility of CDs in water and serum. Additionally, fatty acids and steroids showed an increase in water solubility when ILs-CDs systems were used. The development of efficient and selective ILs-CDs systems is indispensable to expand the range of their applications in host-guest interactions, drug delivery systems or catalytic reactions. Novel salts derived from nucleobases were used in order to enhance the fluorescence in aqueous solution. Additionally, preliminary studies regarding ethyl lactate as an alternative solvent for asymmetric organocatalysis were performed.

Prevalence of neurocognitive disorders and depression in a Brazilian HIV population

AbstractINTRODUCTION:Combined antiretroviral therapy has enabled human immunodeficiency virus (HIV) carriers to live longer. This increased life expectancy is associated with the occurrence of degenerative diseases, including HIV-associated neurocognitive disorders (HAND), which are diagnosed via a complex neuropsychological assessment. The International HIV Dementia Scale (IHDS) is a screening instrument validated in Brazil for use in the absence of neuropsychological evaluation. HIV patients are frequently diagnosed with depression. We aimed to determine the prevalence of neurocognitive impairment using the IHDS and depressive disorders using the Hamilton Rating Scale for Depression (HAM-D17), compare the IHDS performance with the performances on the Timed Gait Test (TGT), the Digit Symbol Coding Test (DS) and the Brazilian version of the Scale of Instrumental Activities of Daily Living (IADL), and evaluate the association between the IHDS performance and clinical-demographic variables.METHODS:One hundred fourteen patients were evaluated in a cross-sectional study conducted in a public outpatient clinic for infectious diseases in Marília City, State of São Paulo, Brazil. Data were collected following consultation. Statistical analysis was performed in accordance with the nature and distribution of the data and hypotheses.RESULTS:According to the IHDS, 53.2% of the sampled patients were neuropsychologically impaired. According to the HAM-D17, 26.3% had depressive disorders. There were significant associations between the IHDS and the TGT and DS. Multiple regression analysis indicated that female gender, educational level, and cluster of differentiation 4 (CD4) levels were significantly and independently associated with neurocognitive impairment.CONCLUSIONS:The prevalence of neurocognitive impairment according to the IHDS is high and associated with female gender, education level, and low CD4 levels.

Pressure sores among malnourished necropsied adults - preliminary data

Pressure sores are common among bedridden, elderly, or malnourished patients, and may occur in terminal ill patients because of impaired mobility, fecal or urinary incontinence, and decreased healing capacity. The aim of this study was to compare frequency of pressure sores between malnourished and non-malnourished necropsied adults. METHOD: All (n = 201) adults (age ³ 18 years) autopsied between 1986 and 1996 at the Teaching Hospital of Triangulo Mineiro Medical School (Uberaba) were eligible for the study. Gender, race, weight, height and main diagnoses were recorded. Ninety-six cases were excluded because of probable body water retention (congestive heart failure, hepatic insufficiency, nephrotic syndrome) or pressure sores secondary to peripheral vascular ischemia. Body mass index (BMI) was used to define malnourished (BMI < 18.5 kg/m²) and non-malnourished (BMI > 18.5kg/m²) groups. RESULTS: Except for weight (42.5kg; range: 28-57 vs. 60; 36-134.5kg) and BMI (16.9; range: 12.4-18.5 vs. 22.7; range: 18.5-54.6kg/m²), respectively, there were no statistical differences among 43 malnourished and 62 non-malnourished cases in relation to age (54.9 ± 20.4 vs. 52.9 ± 17.9 years), percentage of white persons (74.4 vs. 64.5%), male gender (76.7 vs. 69.3%) and main diagnoses. Five malnourished (11.6%) and 7 (11.5%) non-malnourished cases had pressure sores (p=0.89). CONCLUSION: Pressure sores were equally common findings in necropsied persons with protein-energy malnutrition, as assessed by body mass index.

Vaccine-associated paralytic Poliomyelitis: a case report of domiciliary transmission

Poliomyelitis associated with live strain vaccine is defined as the paralytic form of the acute anterior poliomyelitis related to the vaccine strain. Since these strains behave similarly to the wild-type virus, we can differentiate, epidemiologically, two types of vaccine-associated poliomyelitis: cases in which the patient was vaccinated and cases in which the patient had had contact with vaccinated individuals. We herein present the case of an unvaccinated child, with a clinical picture of an acute anterior poliomyelitis associated with the live strain vaccine, whose brother received the Sabin vaccine 20 days before the onset of the symptoms. Vaccine strain of the type 3 poliovirus was isolated in fecal culture and a presented mutation in nucleotide 472 (C®U) in the 5' non-coding region, which is strongly related to the higher strain virulence.

Causes of low vision and use of optical aids in the elderly

PURPOSE: To determine the causes of low vision in an elderly population attended by a university visual rehabilitation service and to check for the use of prescribed optical aids. METHOD: A cross-sectional study was carried out on patients aged 60 years or over attending for the first time a university low vision service in 2001. Ophthalmic reevaluation and interview were performed by means of a structured questionnaire in 2002. RESULTS: The sample comprised 50 subjects aged between 60 and 90 years. Severe low vision (Symbol><20/200) was present in 68.0% of patients. The main cause of low vision was age-related macular degeneration (44.0%). Regarding literacy, 16.0% were illiterate and 72.0% had completed fundamental schooling. Thirty-one patients (62.0%) had been prescribed optical aids; 54.8% of these patients stated that they use them. A majority (70.6%) held a favorable opinion of these aids. CONCLUSIONS: The main cause of low vision was age-related macular degeneration. Approximately half of those receiving prescriptions reported actually using the aids in their daily activities. Making best use of residual vision in the elderly population with visual impairment is a priority, given the social context, if the independence necessary for enhanced quality of life is to be achieved.

Assessment of a novel Cu (II) complex as a potential anticancer agent

Widely used in cancer treatment, chemotherapy still faces hindering challenges, ranging from severe induced toxicity to drug resistance acquisition. As means to overcome these setbacks, newly synthetized compounds have recently come into play with the basis of improved pharmacokinetic/pharmacodynamic properties. With this mind-set, this project aimed towards the antiproliferative potential characterization of a group of metallic compounds. Additionally the incorporation of the compounds within a nanoformulation and within new combination strategies with commercial chemotherapeutic drugs was also envisaged. Cell viability assays presented copper (II) compound (K4) as the most promising, presenting an IC50 of 6.10 μM and 19.09 μM for HCT116 and A549 cell line respectively. Exposure in fibroblasts revealed a 9.18 μM IC50. Hoechst staining assays further revealed the compound’s predisposition to induce chromatin condensation and nuclear fragmentation in HCT116 upon exposure to K4 which was later demonstrated by flow cytometry and annexin V-FITC/propidium iodide double staining analysis (under 50 % cell death induction). The compound further revealed the ability to interact with major macromolecules such as DNA (Kb = 2.17x105 M-1), inducing structural brakes and retardation, and further affecting cell cycle progression revealing delay in S-phase. Moreover BSA interactions were also visible however not conclusive. Proteome profiling revealed overexpression of proteins involved in metabolic activity and underexpression of proteins involved in apoptosis thus corroborating Hoechst and apoptosis flow cytometry data. K4 nanoformulation suffered from several hindrances and was ill succeeded in part due to K4’s poor solubility in aqueous buffers. Other approaches were considered in this regard. Combined chemotherapy assays revealed high cytotoxicity for afatinib and lapatinib strategies. Lapatinib and K4 proteome profiling further revealed high apoptosis rates, high metabolic activity and activation of redundant proteins as part of compensatory mechanisms.

Synthesis and characterization of novel 4H-pyran-4-ylidene indole-based heterocyclic systems for several optical applications

The development of organic materials displaying high two-photon absorption (TPA) has attracted much attention in recent years due to a variety of potential applications in photonics and optoelectronics, such as three-dimensional optical data storage, fluorescence imaging, two-photon microscopy, optical limiting, microfabrication, photodynamic therapy, upconverted lasing, etc. The most frequently employed structural motifs for TPA materials are donor–pi bridge–acceptor (D–pi–A) dipoles, donor–pi bridge–donor (D–pi–D) and acceptor–pi bridge-acceptor (A–pi–A) quadrupoles, octupoles, etc. In this work we present the synthesis and photophysical characterization of quadrupolar heterocyclic systems with potential applications in materials and biological sciences as TPA chromophores. Indole is a versatile building block for the synthesis of heterocyclic systems for several optoelectronic applications (chemosensors, nonlinear optical, OLEDs) due to its photophysical properties and donor electron ability and 4H-pyran-4-ylidene fragment is frequently used for the synthesis of red light-emitting materials. On the other hand, 2-(2,6-dimethyl-4H-pyran-4-ylidene)malononitrile (1) and 1,3-diethyl-dihydro-5-(2,6-dimethyl-4H-pyran-4-ylidene)-2-thiobarbituric (2) units are usually used as strong acceptor moieties for the preparation of π-conjugated systems of the push-pull type. These building blocks were prepared by Knoevenagel condensation of the corresponding ketone precursor with malononitrile or 1,3-diethyl-dihydro-2-thiobarbituric acid. The new quadrupolar 4H-pyran-4-ylidene fluorophores (3) derived from indole were prepared through condensation of 5-methyl-1H-indole-3-carbaldehyde with the acceptor precursors 1 and 2, in the presence of a catalytical amount of piperidine. The new compounds were characterized by the usual spectroscopic techniques (UV-vis., FT-IR and multinuclear NMR - 1H, 13C).

Risk assessment in a research laboratory during sol–gel synthesis of nano-TiO2

The occupational risks in the nanotechnology research laboratories are an important topic since a great number of researchers are involved in this area. The risk assessment performed by both qualitative and quantitative methods is a necessary step for the management of the occupational risks. Risk assessment could be performed by qualitative methods that gather consensus in the scientific community. It is also possible to use quantitative methods, based in different technics and metrics, as indicative exposure limits are been settled by several institutions. While performing the risk assessment, the information on the materials used is very important and, if it is not updated, it could create a bias in the assessment results. The exposure to TiO2 nanoparticles risk was assessed in a research laboratory using a quantitative exposure method and qualitative risk assessment methods. It was found the results from direct-reading Condensation Particle Counter (CPC) equipment and the CB Nanotool seem to be related and aligned, while the results obtained from the use of the Stoffenmanager Nano seem to indicate a higher risk level.

Determinação de idade e crescimento do mapará (Hypophthalmus marginatus) na Amazônia Central

O presente trabalho visa contribuir para a conservação e manejo do mapará (Hypophthalmus marginatus), um importante recurso pesqueiro de exportação do Amazonas para o qual é necessário conhecer informações essenciais de sua dinâmica de populações. Para contribuir à esta finalidade, o presente trabalho estabeleceu como objetivo identificar o par de otólito mais adequado para leitura de anéis etários, determinar os parâmetros de crescimento do mapará (H. marginatus), Amazônia Central, Amazonas - Brasil. O trabalho foi efetuado através da análise de otólitos coletados no período de dezembro de 1996 á agosto de 1997. Os otólitos escolhidos foram os asteriscus, sendo a leitura efetuada em lupa estereoscópica com monitor acoplado. As marcas de crescimento foram validadas por meio da análise do incremento marginal relativo, sendo encontrado dois anéis/ano. Os valores estimados para os parâmetros no período foram LSymbol>¥ = 52,63 cm; k = 0,555 ano; to = -0,029 e M = 0,552. O ciclo hidrológico e comportamento reprodutivo estão relacionados com a marcação de anéis etários.

Lima de Freitas: O simbólico da obra pública – contributos para uma estética educacional

Tese de Doutoramento em Ciências da Educação - Especialidade em Filosofia da Educação