Os antipsicóticos são drogas utilizadas no tratamento de muitos transtornos psiquiátricos, sendo classificados em dois grupos: típicos e atípicos. Os típicos formam o grupo de drogas que bloqueiam especialmente os receptores de dopamina e, por isto, causam efeitos colaterais característicos, que se manifestam através de sintomas extrapiramidais e podem terminar em discinesia tardia. Os atípicos apresentam eficácia antipsicótica similar à dos antipsicóticos típicos, mas produzem menos efeitos colaterais extrapiramidais e não causam discinesia tardia. Os antipsicóticos se ligam às proteínas plasmáticas, principalmente a albumina, a qual representa cerca de 60% do total das proteínas no soro humano. Neste trabalho estudamos os processos de interação de duas drogas antipsicóticas atípicas, risperidona e sulpirida, com as albuminas séricas humana (HSA) e bovina (BSA), através da técnica de supressão da fluorescência intrínseca do triptofano. A partir dos espectros de fluorescência, a análise dos dados foi feita obtendo-se os gráficos e as constantes de Stern-Volmer. A análise da supressão da fluorescência foi feita a partir da média aritmética dos dados oriundos dos experimentos realizados em cada condição adotada. Como a molécula da sulpirida é fluorescente desenvolvemos uma modelagem matemática do processo de interação, que nos permitiu então obter os dados referentes à supressão da fluorescência da proteína. Os resultados mostraram que a risperidona e a sulpirida suprimem a fluorescência de ambas albuminas por um processo de quenching estático, formando complexos droga-albumina. A risperidona tem uma afinidade com a HSA cerca de 6,5 vezes maior do que a sulpirida, a 37 oC. As constantes de associação calculadas para a interação risperidona-HSA, através da Teoria de Stern-Volmer, foram 1,43 ( 0,05) x 105 M-1, a 37 C, e 2,56 ( 0,09) x 105 M-1, a 25 C1; e para a sulpirida, 2,20 ( 0,08) x 104 M-1, a 37 C, e 5,46 ( 0,20) x 104 M-1, a 25 C. Como a taxa de quenching da BSA foi maior do que a da HSA, sugerimos que o sítio primário para a risperidona nas albuminas esteja localizado mais próximo ao domínio do triptofano 134 da BSA do que do domínio do triptofano 212 da HSA. O mesmo sugerimos com relação ao sítio para a sulpirida a 37 C. / Antipsychotics are drugs used to treat many psychiatric disorders. They are classified into two groups: typical and atypical. The typical group act blocking dopamine receptors in particular and it causes characteristic side effects with extrapyramidal symptoms, and can lead to tardive dyskinesia. The atypical group presents similar efficacy to typical group, but they produce less extrapyramidal side effects and does not cause tardive dyskinesia. Antipsychotics bind to plasmatic proteins, mainly to albumin, which represents about 60% of total human serum proteins. In this study we studied the interactions of two atypical antipsychotic drugs, risperidone and sulpiride, with human serum albumin (HSA) and bovine (BSA) through the technique of intrinsic tryptophan fluorescence quenching. From the fluorescence spectra, a data analysis was made to obtain Stern-Volmer plots and constants. Quenching analysis was performed used from using arithmetic means of data from experiments for each adopted condition. As sulpiride molecule is fluorescent, a mathematical modeling for interaction process was made. It allows us then to obtain the data referents to fluorescence quenching of protein. Results showed that risperidone and sulpiride quench the fluorescence for both albumins by static quenching process, forming complexes drug-albumin. The risperidone affinity to HSA is about 6.5 higher than supiride, at 37 oC. Stern-Volmer constants for interaction risperidone-HSA were 1.43 ( 0.05) x 105 M-1, at 37oC, and 2.56 ( 0.09) x 105 M-1, at 25 oC; and for sulpiride were 2.20 ( 0.08) x 104 M-1, at 37 oC, and 5.46 ( 0.20) x 104 M-1, at 25 oC. As the quenching ratio for BSA was higher than HAS, we suggested that the primary site for risperidone on albumin is closer of the domain of trypthophan 134 of BSA than the domain of trypthophan 212 of HAS. The same is suggested for the primary site of supiride at 37oC.

Vários complexos de ródio Rh2(L)4 (L = acetato, propionato, butirato, trifluoroaceta-to e trifluoroacetamidato) ligam-se à albumina de soro humana (HSA) em relações mola-res de aproximadamente 8:1. Medidas de dicroísmo circular mostraram que os carboxila-tos mais lipossolúveis (butirato e trifluoroacetato) provocaram as maiores alterações na estrutura secundária da HSA. As constantes de Stern-Volmer para a supressão de fluo-rescência da HSA por esses complexos também foram maiores para os compostos mais lipofílicos. O amidato lipossolúvel, Rh2(tfc)4, apresentou supressão intermediária e não provocou alterações estruturais. Isto mostra que é possível projetar metalofármacos anti-tumorais que se ligam a proteínas de transporte em grande quantidade, sem provocar al-terações estruturais importantes. Esses complexos tiveram também suas afinidades em relação à HSA determinadas por espectrofotometria, observando-se no caso dos alquil-carboxilatos uma correlação inversa com suas lipossolubilidades, o que sugere uma com-petição entre coordenação axial ao metal e interação hidrofóbica do ligante. A difusão dos complexos livres ou ligados à proteína para células de Ehrlich in vitro parece primordial-mente governada pelo caráter hidrofóbico do complexo. O complexo Rh2(tfc)4 apresentou afinidade pela proteína (K = 214,1), além de partição celular tanto em ausência (32,1%) como na presença (48,6%) de HSA. Desta forma, o composto HSA:Rh2(tfc)4 teve sua a-ção antitumoral investigada em camundongos Balb-c portadores de ascite de Ehrlich, mostrando que a HSA pode ser um reservatório para o complexo de ródio. / Various divalent rhodium complexes Rh2(L)4 (L = acetate, propionate, butyrate, tri-fluoroacetate and trifluoroacetamidate) have been found to bind to non-defatted human serum albumin (HSA) at molar ratios about 8:1. The circular dichroism measurements showed that the more liposoluble carboxylates butyrate and trifluoroacetate caused the major alterations of the secondary structure of HSA. Stern-Volmer constants for the fluo-rescence quenching by these complexes were also higher for the lipophilic metal com-pounds. In the case of the rhodium carboxylates it was observed that their denaturating and quenching properties could be explained in terms of their liposolubilities: the higher their lipophilic characters, the higher their abilities to penetrate inside the protein frame-work leading to structural alterations, and the closer they could get to the Trp214 residue causing fluorescence quenching. The liposoluble amidate complex Rh2(tfc)4, presented an intermediate quenching and did not cause structural alterations in the protein, presumably not penetrating inside the peptidic backbone. This shows that it is possible to design new antitumor metal complexes which bind to a large extent to a transporter protein causing little structural damage. The affinities for human albumin of these five rhodium(II) comple-xes were determined by spectrophotometry. In the case of the alkylcarboxylates, an inver-se correlation of affinity with their liposolubilities was observed. Diffusion of the free or pro-tein-bound complexes into Ehrlich cells in vitro seems to be primarily governed by the hy-drophobic character of the complex. The complex Rh2(tfc)4 exhibited considerable affinity towards the protein (K = 214.1) as well as cell partition both in the absence (32.1%) and presence (48.6%) of HSA. The compound HSA:Rh2(tfc)4 has had its antitumoral action in tumor-bearing Balb-c mice investigated, showing that HSA can be a drug reservoir for the rhodium complex.

Thesis (Ph.D. (Nutrition))--North-West University, Potchefstroom Campus, 2007.

No description available.

Bakgrund : Patient i hemodialys (HD) behandling är utsatt olika stressfaktorer, som till exempel den strikta diet, begränsat vattenintag, bundenhet till dialysenhet eller känsla av trötthet även på dialysfria dagar. Cirka 20 procent patienter i HD behandling utvecklar depression som i sin tur leder till låg plasma albumin. Syftet: Att belysa samband mellan stressfaktorer, depression, låg plasma albumin och mortalitet/morbiditet samt omvårdnadens betydelse för patienter i hemodialysbehandling. Metod: Studie genomfördes som en litteraturöversikt och granskning av vetenskapliga artiklar. Resultat: Resultat baserar på 15 artiklar, varav 1 kvalitativ, 14 kvantitativ . Resultatet delades i fem kategorier: stressfaktorer och deras koppling till depression, depression, låg plasma albumin, omvårdnadsåtgärder vid låg plasma albumin, omvårdnadsåtgärder vid depression. Diskussion: I diskussion lyfts upp samband mellan högre morbiditet/mortalitet och depression samt låg plasma albumin hos patienter i HD behandling. Det tas upp även vikten av omvårdnadsinsatser vid depression och låg plasma albumin hos patient i HD behandling. Slutsats: Mer forsknings behövs för att sjuksköterska kan erbjuda patienten effektiva strategier som hjälper denne att hantera de stressfaktorerna och livsstilförändringar som HD innebär.

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Investigations detailed in this thesis constitue a part of continuing programme of research work undertaken in this laboratory on vitamin binding proteins. Avidin from the chicken egg white, streptavidin &om the bacterium Streptromyces avidin and biotin binding proteins (BBP-I and BBP-11) from chicken egg yolk constitute a family of proteins that bind the vitamin biotin with extremely high affinities. The yolk BBPs are involved in the deposition of the vitamin in the developing oocyte in chicks whereas an antimicrobial function has been attributkl to avidin.. The fact that all these proteins bind the vitamin in the same manner, unlike biotin-dependent enzymes, indicates that the structural features involved in ligand binding could be similar, if not identical in these proteins. To delineate the basis of putative structural similarity among these proteins, studies were carried out using antibodies as the immunological probes. Avidin, a homotetremer glycoprotein, with a subunit Mr of 17,000 has been purified to homogeneity from chicken egg white using a novel procedure involving ammonium sulphate fractionation, ethanol precipitation and S-Sepharose column chromatography. Despite their lesser abundance in chicken egg yolk associated with a large amount of interfering lipids during the purification, both BBP-I (monomer and shown to be precursor for BBP-11) and BBP-I1 (tetramer) have been purified to homogeneity by employing a common method using butanol extraction to remove the lipids, DEAE-Sephacel column chromatography, biotin-AH-Sepharose affinity chromatography and fast performance liquid chrometography (FPLC) system. The purity of all these proteins was confirmed by SDS-PAGE analysis.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

The reactions of the early and intermediate stages of protein glycation were studied using bovine serum albumin and hen egg white lysozyme as model proteins, and D-glucose and D-fructose as model reducing sugars. The reactions were studied under low moisture and limiting sugar conditions in the presence and absence of oxygen in a closed system. Several analytical methods, including the fluorescamine assay, total Maillard fluorescence and solubility measurement, size exclusion chromatography, and electrospray ionization mass spectrometry were used to follow the glycation reaction. The effect of glycation on the structure of proteins was also studied by electrospray ionization mass spectrometric peptide mapping. The results showed that under low moisture conditions, the initial rate of glucation was 5 to 6 times higher than the initial rate of fructation, both in the presence and in the absence of oxygen. The presence of oxygen in the reaction system induced selectivity of the glycation of the protein amino groups during the initial stages of the reaction, due to competition between glycation and glycoxidation. The reaction, however, occurred at a higher rate in the presence of oxygen than in its absence, especially during the latter stages of the reaction. The more reactive glycoxidation products, formed during the initial stages of the reaction also participated in the glycation reaction and increased the involvement of arginine residues in the glycation reaction. The glycation reaction also resulted in a heterogeneous mixture of protein glycoforms with varying degrees and extent of glycation. The heterogeneity of the glycated species was further complicated by the involvement of glycoxidation products in the glycation reaction, resulting in a distribution of different classes of glycoconjugates. Limited glycation improved protein solubility and increased solvent accessibility into the interior of the protein, thereby, increasing protein digestibility. Electrospr

OBJECTIVE: The main aim of this thesis was to investigate the role of nutrition during "early" HIV-infection in African women. METHODS: Data reported in this investigation formed part of two cross-sectional studies, the THUSA and Mangaung studies. The Mangaung study investigated women and, therefore, the sub-sample of the THUSA study was chosen accordingly. The data of the two studies were kept and analysed separately. The investigation consisted of 1040 women from the THUSA study, aged between 15 and 90 years of which 120 (11.5%) were HIV infected. The Mangaung study comprised of 488 women aged between 25 and 44 years of which 248 (51%) women were infected. Demographic data, anthropometric measurements, health outcome variables and habitual nutrient intakes by a quantified food frequency questionnaire were used. The SPSS statistical package (version 14.0; SPSS Inc., Chicago, Illinois, 2005) was used to analyse data. Descriptive statistics were done expressing variables as means, medians, standard deviations (SD), standard errors (SE) and confidence intervals (CI). An analysis of variance (ANOVA) was done to test for significance between the HIV-infected and non-infected groups in both studies. Partial correlations were done in the infected and non-infected groups to determine associations between dietary / nutrient intake, anthropometry and the biological health variables. In the THUSA study we controlled for age, education level, degree of urbanization and alcohol intake and in the Mangaung study for age, education level and alcohol intake. Nutrient intakes of both infected and non-infected women above and below median values as well as in the first and fourth quartile of total cholesterol (TC) and albumin distribution were compared to assess the role of nutrients in the observed decreases in TC and albumin of HIV-infected women. RESULTS AND DISCUSSION: The dietary intakes of the HIV-infected women in both the studies did not differ significantly from the non-infected women. Total serum cholesterol, albumin, fibrinogen and blood pressure were significantly lower in the HIV-infected women in both the THUSA and Mangaung studies. The non-infected THUSA women with lower serum cholesterol levels (than the median) had significantly lower intakes of percentage energy from fat (25.2 versus 26.4%, p ≤0.027), percentage energy from total protein (11.6 versus 12.1%, p≤0.000), animal protein (25.6 versus 27.7g, p≤0.005), and significantly higher intakes of plant protein (32.2 versus 29.4g, p≤0.002) and fibre (16.9 versus 15.89 p≤0.029). There were no significant differences observed in the nutrient intakes in the infected women with serum cholesterol levels above and below the median. In the Mangaung study no significant nutrient intake differences were observed in both of the HIV-infected and non-infected women with lower and higher than the median TC levels. In the THUSA study, higher intakes of fat (percentage energy) were close to significant (27.3 versus 24.5%, p≤0.053) in the infected women with higher (than the median) albumin levels. In the non-infected group with higher albumin levels, significant differences were observed in percentage energy from fat (26.6 versus 24.9%; p≤0.001) protein (12.2 versus 11.6%; p≤0.001) and carbohydrate (62.8 versus 65.2%; p≤0.000). Higher intakes of saturated fat (SATFAT) (17.7 versus 16.1g, p≤0.008), monounsaturated fats (MUFAT) (19.3 versus 17.4g, p≤0.004) as well as higher intakes of animal protein (28.5 versus 24.4g, p≤0.000) were observed in the group with higher than the median levels of serum albumin. In the Mangaung study the HIV-infected women (with higher than the median serum albumin levels), had significantly higher intakes of energy (13 275 versus 11 622 kJ, p≤0.022), polyunsaturated fatty acids (32.3 versus 17.3g, p≤0.036), dietary cholesterol (412.9 versus 344.5mg, p≤0.043) and plant protein (42.3 versus 35.3g, p≤0.008). No differences were observed in the non-infected women. The further analyses, comparing the dietary intakes in both studies of infected and non-infected women with TC and albumin levels in the first and fourth quartiles, showed that in the THUSA study, non-infected women with lower TC levels had significantly lower intakes of protein (% of total energy), total fat (% of total energy) and vitamin B12 and significantly higher intakes of total energy (TE), plant protein, total carbohydrate, % TE from carbohydrate, dietary fibre, added sugar and thiamine. In the infected women saturated fatty acids (SATFAT), calcium and the fat ratio (polyunsaturated/saturated ratio) differed significantly between women with TC levels in the first and the fourth quartile. A significant higher intake of riboflavin was seen in the non-infected women from Mangaung with TC levels in the fourth quartile, while significant higher intakes of energy, total protein, animal protein, total fat, SATFAT, MUFAT, total carbohydrate, phosphorus, chromium and iodine was seen in the infected women with TC levels in the fourth quartile. These results suggest that a more "westernized" diet with higher intakes of energy, and animal derived foods (SATFAT and calcium) could have protected against the detrimental decreases in TC observed in HIV infection. Significant differences were observed in the intakes in the non-infected THUSA women who had serum albumin in the first and fourth quartiles. lntakes in percentage energy from protein and fat, animal protein, total fat, SATFAT, MUFAT, calcium, zinc, vitamin C and fat ratio, were significantly lower in the women with albumin levels in the first quartile. Significantly higher carbohydrate intakes were observed in the women who had serum albumin levels in the first quartile. In the Mangaung study, significant differences were seen in the intakes between infected women who had serum albumin levels in the first and fourth quartiles. lntakes of total energy, protein, fat, MUFAT, SATFAT, carbohydrate, magnesium, zinc, chromium, biotin, pantothenic acid and iodine were significantly lower in the infected women with serum albumin levels in the first quartile. In the non-infected women significantly lower intakes of calcium were observed in the group who had serum albumin levels in the first quartile compared to those who had serum albumin levels in the fourth quartile. These results also suggest that a more "westernized” diet was associated with higher albumin levels in HIV-infected women. CONCLUSION: It is well known that nutrition has an integral part to play in the care of people living with HIV/AIDS (PLWHA). Maintaining proper nutrition, weight and immune function is thought to delay disease progression, prolong the asymptomatic phase and improve survival. These analyses suggest that the "prudent" diet generally regarded as an optimal diet for prevention of non-communicable diseases, may not be the optimal diet for PLWHA. The overall analyses therefore suggest that a more "westernized" diet, higher in fat and protein could be more beneficial to asymptomatic HIV-infected women compared to that of a more "prudent" diet. As these studies were not primarily designed to investigate HIV and nutrition, the role of a higher energy, fat and animal protein intake ("western" diet) in asymptomatic HIV warrants urgent investigation. / Thesis (Ph.D. (Nutrition))--North-West University, Potchefstroom Campus, 2007.