trans-Sialidase de Trypanosoma cruzi (TcTS) pertence à família de glicoproteínas de superfície do parasita e constitui um dos poucos exemplos naturais de glicosiltransferases superficiais encontradas em eucariotes. T. cruzi é incapaz de sintetizar ácido siálico e utiliza esta enzima para retirar este monossacarídeo de glicoconjugados do hospedeiro para sialilar moléculas aceptoras, como mucina-GPI, presentes na sua membrana plasmática. Esta enzima é específica em catalisar, preferencialmente, a transferência de ácido siálico para moléculas de mucina, originando ligações -2,3 com moléculas de galactose aceptoras na superfície do parasita. As moléculas de mucina sialiladas estão envolvidas no processo de aderência e subseqüente penetração do parasita nas células do hospedeiro. Considerando a heterogeneidade das moléculas de mucina de T. cruzi, não existem compostos disponíveis que atuem como substratos glicopeptídicos sintéticos. Desta forma, este trabalho teve como objetivo o desenvolvimento de métodos químicos e químico-enzimáticos de síntese de glicopeptídeos de mucina de T.cruzi para investigação da natureza das interações moleculares críticas envolvidas no reconhecimento e processamento de glicosídeos contendo ácido siálico, na presença de trans-sialidase. O melhor entendimento destas interações conduziu ao planejamento racional de potenciais inibidores seletivos de trans-sialidase de T. cruzi. Alguns dos principais glicopeptídeos, obtidos por metodologias de síntese em fase sólida e síntese químico-enzimática com a enzima 1,4-galactosiltransferase (1,4-GalT) foram: NH2(Thr)2-(LacNAc)-(Thr)3-GlyOH 2, NH2(Thr)2-(LacNAc)-(Thr)3-GlyOH 4 e NH2(Thr)2-(LacNAc)-(Thr)3-(LacNAc)-(Thr)3-GlyOH 5. Como precursores destes glicopeptídeos os blocos de construção GlcNAc-FmocThrOH 24, GlcNAc-FmocThrOH 25, Gal-FmocThrOH 27 e LacNAc-FmocThrOH 75 foram sintetizados por meio de reações de glicosilação do aminoácido treonina 18, contendo os grupos protetores N-Fmoc e O-Bn, com os correspondentes açúcares GlcNAcCl 12, GalBr 13 e LacN3Cl 33, seguidas de reações de hidrogenólise (10% Pd-C/ H2) para desproteção do grupo O-Bn e posterior acoplamento em cadeia peptídica rica em seqüência de treonina. Os aminoácidos glicosilados GlcNAc-ThrOH 22 e GlcNAc-ThrOH 23, totalmente desprotegidos, foram empregados em reações enzimáticas com a enzima 1,4-GalT, sendo obtidos os dissacarídeos glicosídicos LacNAc-ThrOH 53 e LacNAc-ThrOH 41 (também sintetizado quimicamente). Os dissacarídeos glicosídicos 41 e 53, os glicopeptídeos 2 e 4 e o aminoácido glicosilado Gal- ThrOH 28 foram submetidos aos ensaios enzimáticos com a enzima TcTS, sendo verificada a sialilação de todos os aceptores testados em rendimentos elevados, o que confirmou que estes compostos podem atuar como potenciais substratos da enzima TcTS. / Trypanosoma cruzi trans-sialidase (TcTS) belongs to the family of glycoproteins expressed on the surface of the parasite and constitutes one of the few examples of natural surface glycosyltransferases found in eucariotes. T. cruzi can not synthesize sialic acid itself and uses a trans-sialidase enzyme to scavenge this monosaccharide from host glycoconjugates to sialylate acceptors molecules, such as GPI (glycosylphosphatidylinositol)-anchored mucins, that are present in parasite plasma membrane. This enzyme is specific to catalise, preferentially, the transference of sialic acid to mucin glycoproteins, originating -2,3- linkages with acceptor galactose molecules in the parasite surface. The sialylated mucin molecules are involved in the attachment and subsequent penetration of the parasite into host cells. Given the heterogeneity of T. cruzi mucin molecules, there are no suitable synthetic occurring sources of TcTS glycopeptide substrates. Thus, the objective of this work was the development of chemical and chemoenzymatic methods of synthesis of T. cruzi mucin glycopeptides in order to investigate the nature of the molecular interactions involved in recognition and processing of containing sialic acid glycosides, in the presence of trans-sialidase. A better understanding of these interactions led to drug design of selective potential inhibitors for T. cruzi trans-sialidase. Some of the main glycopeptides obtained by methods of solid phase and chemoenzymatic synthesis with 1,4-galactosyltransferase (1,4-GalT) enzyme were: NH2(Thr)2-(LacNAc)- (Thr)3-GlyOH 2, NH2(Thr)2-(LacNAc)-(Thr)3-GlyOH 4 and NH2(Thr)2-(LacNAc)-(Thr)3- (LacNAc)-(Thr)3-GlyOH 5. As precursors of these glycopeptides, the building blocks GlcNAc-FmocThrOH 24, GlcNAc-FmocThrOH 25, Gal-FmocThrOH 27 and LacNAc- FmocThrOH 75 were synthesized by glycosylation reactions of the threonine amino acid 18, containing the protecting groups N-Fmoc and O-Bn, with the correspondent sugars GlcNAcCl 12, GalBr 13 and LacN3Cl 33, followed by hydrogenolysis reactions (10% Pd- C/ H2) for deprotection of O-Bn group and later coupling into the peptide chain rich in threonine sequence. The glycosylated amino acids GlcNAc-ThrOH 22 and GlcNAc-ThrOH 23, totally deprotected, were employed in enzymatic reactions with 1,4-GalT, being obtained the disaccharide glycosides LacNAc-ThrOH 53 and LacNAc-ThrOH 41 (also chemically synthesized). The disaccharide glycosides 41 and 53, the glycopeptides 2 and 4 and the glycosylated amino acid Gal-ThrOH 28 were submitted to enzymatic assays with TcTS enzyme, being verified the sialylation of all tested acceptors in high yields, which confirmed that these compounds can act as potential acceptors substrates for TcTS enzyme.

No description available.

Motivation Hypertension and type 2 diabetes mellitus are common in the black population of South Africa. The literature also shows that elevated blood glucose concentrations can lead to an increase in blood pressure and a blunted decline in nocturnal blood pressure. Therefore, the motivation for this study was to determine if blood glucose may play a role regarding the blunted nocturnal decline in blood pressure in African and Caucasian men. Aim The aim of this study was to investigate the relationship between a blunted nocturnal decline in blood pressure and blood glucose in African and Caucasian men. Methodology A comparative population study was preformed that consisted of 202 school teachers (101 African and 101 Caucasian) between the ages of 25–60 years from the North West Province, South Africa. Subjects were excluded if their body temperature was elevated, had a dependence or abuse of psychotropic substances, were regular blood donors and/or vaccinated in the previous three months. Ambulatory systolic (SBP) and diastolic blood pressure (DBP) were measured. Blood samples from the antebrachial vein were collected in sodium fluoride tubes to determine the serum glucose level and glycosylated hemoglobin A1c (HbA1c) percentage. Estimated average glucose (eAG) was determined from the percentage HbA1c by means of a regression formula. Means and proportions were compared by standard t–test and the chi–square test, respectively. Pearson correlations were used to determine unadjusted associations and multiple regression analysis to determine adjusted associations between variables. Results and Conclusion African men had an elevated HbA1c (p<0.001), eAG (p<0.001), nighttime SBP (p<0.001) and DBP (p<0.001). These results remained similar when non–dipping African and Caucasian men were compared. The Africans also smoked more (p=0.012), consumed more alcohol (p=0.049), had a higher percentage of non–dippers (p=0.054), HIV infected subjects (p<0.001) and a larger number of subjects that used anti–hypertensive medication (p=0.049). The unadjusted analysis showed positive correlations between all the blood pressure measurements and serum glucose, HbA1c and eAG in the African non–dipper men. While in the non–dipper Caucasian men, only daytime SBP and nighttime SBP (22:00–06:00) correlated positively with serum glucose, HbA1c and eAG. Furthermore, when viewing the relationship between carotid intima–media thickness (CIMT) and the blood pressure measurements in the African population, only nighttime (00:00– 04:00) SBP (r=0.581, p<0.001) and DBP (r=0.566, p<0.001) showed positive associations. After adjustments were made for age and body mass index the associations between the various blood pressure measurements and blood glucose disappeared in the non–dipper Caucasian men. However, in the non–dipper African men both nighttime (22:00–06:00) SBP and (00:00– 04:00) SBP showed positive correlations with serum glucose, HbA1c and eAG. After full adjustments (age, BMI, smoking, alcohol intake, physical activity, C–reactive protein and baroreceptor sensitivity) were made, nighttime (00:00–04:00) SBP was the only measure of blood pressure that correlated positively with HbA1c (p=0.069) and eAG (p<0.001) in the nondipper African men. No significant relationships were found for Caucasian men. Furthermore, to determine if the association between nighttime (00:00–04:00) SBP and eAG were independent of CIMT, we adjusted for CIMT. By doing so the positive association between SBP and eAG remained significant in the non–dipper African men (R2=0.617; =0.438; p=0.008) and nonsignificant in the non–dipper Caucasian men (R2=0.423; =0.169; p=0.33). However, the relationship between CIMT and eAG disappeared when we adjusted for SBP, suggesting that the SBP and eAG relationship drives CIMT. In conclusion, the association between the early morning SBP (00:00–04:00) and the blood glucose in non–dipping African men suggests that the blunted decline in nocturnal blood pressure during the early morning hours is associated with chronically elevated blood glucose. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2011.

Motivation Hypertension and type 2 diabetes mellitus are common in the black population of South Africa. The literature also shows that elevated blood glucose concentrations can lead to an increase in blood pressure and a blunted decline in nocturnal blood pressure. Therefore, the motivation for this study was to determine if blood glucose may play a role regarding the blunted nocturnal decline in blood pressure in African and Caucasian men. Aim The aim of this study was to investigate the relationship between a blunted nocturnal decline in blood pressure and blood glucose in African and Caucasian men. Methodology A comparative population study was preformed that consisted of 202 school teachers (101 African and 101 Caucasian) between the ages of 25–60 years from the North West Province, South Africa. Subjects were excluded if their body temperature was elevated, had a dependence or abuse of psychotropic substances, were regular blood donors and/or vaccinated in the previous three months. Ambulatory systolic (SBP) and diastolic blood pressure (DBP) were measured. Blood samples from the antebrachial vein were collected in sodium fluoride tubes to determine the serum glucose level and glycosylated hemoglobin A1c (HbA1c) percentage. Estimated average glucose (eAG) was determined from the percentage HbA1c by means of a regression formula. Means and proportions were compared by standard t–test and the chi–square test, respectively. Pearson correlations were used to determine unadjusted associations and multiple regression analysis to determine adjusted associations between variables. Results and Conclusion African men had an elevated HbA1c (p<0.001), eAG (p<0.001), nighttime SBP (p<0.001) and DBP (p<0.001). These results remained similar when non–dipping African and Caucasian men were compared. The Africans also smoked more (p=0.012), consumed more alcohol (p=0.049), had a higher percentage of non–dippers (p=0.054), HIV infected subjects (p<0.001) and a larger number of subjects that used anti–hypertensive medication (p=0.049). The unadjusted analysis showed positive correlations between all the blood pressure measurements and serum glucose, HbA1c and eAG in the African non–dipper men. While in the non–dipper Caucasian men, only daytime SBP and nighttime SBP (22:00–06:00) correlated positively with serum glucose, HbA1c and eAG. Furthermore, when viewing the relationship between carotid intima–media thickness (CIMT) and the blood pressure measurements in the African population, only nighttime (00:00– 04:00) SBP (r=0.581, p<0.001) and DBP (r=0.566, p<0.001) showed positive associations. After adjustments were made for age and body mass index the associations between the various blood pressure measurements and blood glucose disappeared in the non–dipper Caucasian men. However, in the non–dipper African men both nighttime (22:00–06:00) SBP and (00:00– 04:00) SBP showed positive correlations with serum glucose, HbA1c and eAG. After full adjustments (age, BMI, smoking, alcohol intake, physical activity, C–reactive protein and baroreceptor sensitivity) were made, nighttime (00:00–04:00) SBP was the only measure of blood pressure that correlated positively with HbA1c (p=0.069) and eAG (p<0.001) in the nondipper African men. No significant relationships were found for Caucasian men. Furthermore, to determine if the association between nighttime (00:00–04:00) SBP and eAG were independent of CIMT, we adjusted for CIMT. By doing so the positive association between SBP and eAG remained significant in the non–dipper African men (R2=0.617; =0.438; p=0.008) and nonsignificant in the non–dipper Caucasian men (R2=0.423; =0.169; p=0.33). However, the relationship between CIMT and eAG disappeared when we adjusted for SBP, suggesting that the SBP and eAG relationship drives CIMT. In conclusion, the association between the early morning SBP (00:00–04:00) and the blood glucose in non–dipping African men suggests that the blunted decline in nocturnal blood pressure during the early morning hours is associated with chronically elevated blood glucose. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2011.

Made available in DSpace on 2014-06-11T19:33:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-03-25Bitstream added on 2014-06-13T20:05:25Z : No. of bitstreams: 1 correa_fob_dr_arafo.pdf: 719555 bytes, checksum: 7ed0212e1fd2855b73aa40fa8cdc4f4f (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Objetivos: dois estudos prospectivos comparativos de intervenção foram realizados para avaliar o efeito do tratamento periodontal não-cirúrgico sobre parâmetros clínicos periodontais e imunológicos do fluido sulcular gengival e do plasma sanguíneo de pacientes com periodontite crônica portadores ou não de Diabetes mellitus Tipo 2. Material e Método: Vinte e três indivíduos com Diabetes mellitus Tipo 2 com controle metabólico inadequado e periodontite crônica (grupo diabetes) e 26 indivíduos sistemicamente saudáveis com periodontite crônica (grupo controle) foram avaliados quanto a parâmetros periodontais, marcadores inflamatórios do fluido sulcular gengival (interleucinas, metaloproteinases de matriz e atividade de elastase), marcadores inflamatórios no plasma sanguíneo (interleucinas, fator de necrose tumoral alfa, proteína C-reativa e fibrinogênio) e perfil lipídico, antes e após 3 meses do tratamento periodontal. Adicionalmente foi avaliada a influência do tratamento periodontal no controle glicêmico do grupo com diabetes. Resultados: houve redução significativa de todos os marcadores inflamatórios avaliados no fluido gengival, exceto a interleucina 18, após tratamento periodontal, associado a uma melhora da condição clínica periodontal em ambos os grupos. Sistemicamente, o grupo diabetes apresentou maiores níveis de proteina C reativa e triglicérides em ambos os períodos ao se comparar com o grupo controle. O tratamento periodontal foi efetivo em reduzir os níveis de TNF-_ e fibrinogênio no grupo diabetes. Houve melhora no controle glicêmico embora não significativa. Conclusão: os resultados do presente estudo sugerem que os pacientes portadores de Diabetes mellitus Tipo 2 com controle metabólico inadequado apresentam boa resposta ao tratamento periodontal nãocirúrgico, com redução de marcadores inflamatórios no fluido gengival. / Objetive: Two prospective comparative interventional studies were performed in order to evaluate the effect of non-surgical periodontal therapy on periodontal clinical and immunological parameters in gingival crevicular fluid (CGF) and plasma of patients with chronic periodontitis with or without type 2 Diabetes mellitus (T2DM). Material and Method: Twenty three individuals with inadequately controlled T2DM and chronic periodontitis (diabetes group) and 26 systemically healthy individuals with periodontitis (control group) were assessed for clinical parameters, inflammatory biomarkers in GCF (interleukins, matrix metalloproteinases and elastase activity), circulating markers of inflammation (interleukins, tumor necrosis factor alpha, C-reactive protein and fibrinogen and lipid profile before and 3 months after periodontal therapy. Additionally, the influence of periodontal treatment on glycemic control was evaluated in the diabetes group. Results: There was a significant reduction of all inflammatory biomarkers in GCF after therapy, except for interleukin 18 levels, and it was associated with improvement on periodontal status in both groups. Systemically, the diabetes group showed high levels of C-reactive protein and triglycerides compared with the control group in both periods. The periodontal therapy was effective in reducing TNF-_ circulating and fibrinogen in the diabetes group. The treatment did not change the glycemic control significantly. Conclusion: The results of the present study suggest that patients with inadequately controlled T2DM present a good response to nonsurgical periodontal treatment, with reduction of inflammatory biomarkers in GCF. However, 3 months after therapy, its influence on systemic inflammatory condition is limited.

trans-Sialidase de Trypanosoma cruzi (TcTS) pertence à família de glicoproteínas de superfície do parasita e constitui um dos poucos exemplos naturais de glicosiltransferases superficiais encontradas em eucariotes. T. cruzi é incapaz de sintetizar ácido siálico e utiliza esta enzima para retirar este monossacarídeo de glicoconjugados do hospedeiro para sialilar moléculas aceptoras, como mucina-GPI, presentes na sua membrana plasmática. Esta enzima é específica em catalisar, preferencialmente, a transferência de ácido siálico para moléculas de mucina, originando ligações -2,3 com moléculas de galactose aceptoras na superfície do parasita. As moléculas de mucina sialiladas estão envolvidas no processo de aderência e subseqüente penetração do parasita nas células do hospedeiro. Considerando a heterogeneidade das moléculas de mucina de T. cruzi, não existem compostos disponíveis que atuem como substratos glicopeptídicos sintéticos. Desta forma, este trabalho teve como objetivo o desenvolvimento de métodos químicos e químico-enzimáticos de síntese de glicopeptídeos de mucina de T.cruzi para investigação da natureza das interações moleculares críticas envolvidas no reconhecimento e processamento de glicosídeos contendo ácido siálico, na presença de trans-sialidase. O melhor entendimento destas interações conduziu ao planejamento racional de potenciais inibidores seletivos de trans-sialidase de T. cruzi. Alguns dos principais glicopeptídeos, obtidos por metodologias de síntese em fase sólida e síntese químico-enzimática com a enzima 1,4-galactosiltransferase (1,4-GalT) foram: NH2(Thr)2-(LacNAc)-(Thr)3-GlyOH 2, NH2(Thr)2-(LacNAc)-(Thr)3-GlyOH 4 e NH2(Thr)2-(LacNAc)-(Thr)3-(LacNAc)-(Thr)3-GlyOH 5. Como precursores destes glicopeptídeos os blocos de construção GlcNAc-FmocThrOH 24, GlcNAc-FmocThrOH 25, Gal-FmocThrOH 27 e LacNAc-FmocThrOH 75 foram sintetizados por meio de reações de glicosilação do aminoácido treonina 18, contendo os grupos protetores N-Fmoc e O-Bn, com os correspondentes açúcares GlcNAcCl 12, GalBr 13 e LacN3Cl 33, seguidas de reações de hidrogenólise (10% Pd-C/ H2) para desproteção do grupo O-Bn e posterior acoplamento em cadeia peptídica rica em seqüência de treonina. Os aminoácidos glicosilados GlcNAc-ThrOH 22 e GlcNAc-ThrOH 23, totalmente desprotegidos, foram empregados em reações enzimáticas com a enzima 1,4-GalT, sendo obtidos os dissacarídeos glicosídicos LacNAc-ThrOH 53 e LacNAc-ThrOH 41 (também sintetizado quimicamente). Os dissacarídeos glicosídicos 41 e 53, os glicopeptídeos 2 e 4 e o aminoácido glicosilado Gal- ThrOH 28 foram submetidos aos ensaios enzimáticos com a enzima TcTS, sendo verificada a sialilação de todos os aceptores testados em rendimentos elevados, o que confirmou que estes compostos podem atuar como potenciais substratos da enzima TcTS. / Trypanosoma cruzi trans-sialidase (TcTS) belongs to the family of glycoproteins expressed on the surface of the parasite and constitutes one of the few examples of natural surface glycosyltransferases found in eucariotes. T. cruzi can not synthesize sialic acid itself and uses a trans-sialidase enzyme to scavenge this monosaccharide from host glycoconjugates to sialylate acceptors molecules, such as GPI (glycosylphosphatidylinositol)-anchored mucins, that are present in parasite plasma membrane. This enzyme is specific to catalise, preferentially, the transference of sialic acid to mucin glycoproteins, originating -2,3- linkages with acceptor galactose molecules in the parasite surface. The sialylated mucin molecules are involved in the attachment and subsequent penetration of the parasite into host cells. Given the heterogeneity of T. cruzi mucin molecules, there are no suitable synthetic occurring sources of TcTS glycopeptide substrates. Thus, the objective of this work was the development of chemical and chemoenzymatic methods of synthesis of T. cruzi mucin glycopeptides in order to investigate the nature of the molecular interactions involved in recognition and processing of containing sialic acid glycosides, in the presence of trans-sialidase. A better understanding of these interactions led to drug design of selective potential inhibitors for T. cruzi trans-sialidase. Some of the main glycopeptides obtained by methods of solid phase and chemoenzymatic synthesis with 1,4-galactosyltransferase (1,4-GalT) enzyme were: NH2(Thr)2-(LacNAc)- (Thr)3-GlyOH 2, NH2(Thr)2-(LacNAc)-(Thr)3-GlyOH 4 and NH2(Thr)2-(LacNAc)-(Thr)3- (LacNAc)-(Thr)3-GlyOH 5. As precursors of these glycopeptides, the building blocks GlcNAc-FmocThrOH 24, GlcNAc-FmocThrOH 25, Gal-FmocThrOH 27 and LacNAc- FmocThrOH 75 were synthesized by glycosylation reactions of the threonine amino acid 18, containing the protecting groups N-Fmoc and O-Bn, with the correspondent sugars GlcNAcCl 12, GalBr 13 and LacN3Cl 33, followed by hydrogenolysis reactions (10% Pd- C/ H2) for deprotection of O-Bn group and later coupling into the peptide chain rich in threonine sequence. The glycosylated amino acids GlcNAc-ThrOH 22 and GlcNAc-ThrOH 23, totally deprotected, were employed in enzymatic reactions with 1,4-GalT, being obtained the disaccharide glycosides LacNAc-ThrOH 53 and LacNAc-ThrOH 41 (also chemically synthesized). The disaccharide glycosides 41 and 53, the glycopeptides 2 and 4 and the glycosylated amino acid Gal-ThrOH 28 were submitted to enzymatic assays with TcTS enzyme, being verified the sialylation of all tested acceptors in high yields, which confirmed that these compounds can act as potential acceptors substrates for TcTS enzyme.

Nos últimos vinte anos houve um aumento substancial no número de revisões sistemáticas e ensaios clínicos que avaliaram intervenções farmacêuticas para pacientes com doenças crônicas, em especial o diabetes. No entanto, existem poucos estudos que avaliam criticamente tais publicações, bem como modelos de prática desenvolvidos no contexto do sistema público de saúde brasileiro. O presente trabalho teve como objetivos avaliar revisões sistemáticas e ensaios clínicos controlados randomizados sobre serviços clínicos farmacêuticos para pacientes com diabetes e avaliar o efeito de modelo de colaboração médico- farmacêutico conduzido em ambulatório de cuidado secundário para pacientes com diabetes tipo 2 não controlada. Para tanto, busca abrangente da literatura foi conduzida nas bases de dados PubMed, SCOPUS, LILACS, Scielo e DOAJ por revisões sistemáticas e ensaios clínicos controlados randomizados. As revisões sistemáticas foram avaliadas em relação à qualidade da apresentação textual e metodológica, sendo identificados campos para melhorias futuras. A seguir, foi realizada uma descrição dos componentes-chave das intervenções e fontes de heterogeneidade clínica e metodológica entre os ensaios clínicos controlados randomizados. Ainda, foi conduzido um ensaio clinico controlado randomizado no ambulatório de doenças metabólicas do Hospital Universitário da Universidade de São Paulo, com duração de 12 meses, para 80 pacientes com diabetes tipo 2 não controlada. O grupo intervenção recebeu consultas farmacêuticas face a face, com suporte remoto por telefone. O farmacêutico realizou intervenções sistemáticas objetivando resolver ou prevenir problemas relacionados aos medicamentos. Os desfechos primários incluíram a redução e controle dos níveis de hemoglobina glicada. A busca bibliográfica identificou 101 registros, dos quais sete revisões completaram os critérios de inclusão. Em média, apenas dois terços dos itens sobre qualidade da apresentação textual e metodológica foram cumpridos nas publicações. Os problemas mais frequentes incluíram o não registo de protocolo do estudo, a ausência de lista dos estudos excluídos, e a falta de reconhecimento claro do conflito de interesses. A busca por ensaios clínicos randomizados de intervenções farmacêuticas identificou 2271 registros, sendo incluídos 24 na síntese qualitativa. A maioria dos estudos para pacientes com diabetes tipo 2 foi desenvolvida nos Estados Unidos, em ambulatório, com contato individual face a face. Todos realizaram intervenções educativas e o processo de uso dos medicamentos foi avaliado pela maioria deles. A amostra exibiu risco de viés incerto ou alto na maior parte dos itens avaliados, o que resultou em baixa qualidade metodológica. De um total de 80 pacientes, 73 completaram o ensaio clínico, sendo 36 do grupo intervenção e 37 do controle. Comparado ao cuidado usual, o grupo intervenção apresentou maior redução nos níveis de hemoglobina glicada, bem como aumento na taxa de controle da pressão arterial sistólica, na proporção de pacientes aderentes e na pontuação da adesão. Os resultados desta tese apontam que a qualidade da apresentação textual e a metodológica estavam abaixo do ideal entre as revisões e que melhoria no desenho e na descrição das revisões e dos estudos primários é necessária para garantir resultados mais robustos. Ainda, o modelo de cuidado proposto é viável e mais efetivo que o cuidado usual na redução da hemoglobina glicada em pacientes diabéticos tipo 2. / Over the last twenty years, there was an important increase in the number of systematic reviews and clinical trials about pharmacist interventions in patients with chronic diseases, including diabetes. Nevertheless, few studies exist which assess critically such publications, as well as models of practice developed in the context of the Brazilian Public Health System. The study aimed to assess the systematic reviews and randomized controlled trials on clinical pharmacy services for patients with diabetes and to assess the effect of a pharmacist- physician collaborative care model for patients with poorly controlled type 2 diabetes. For this, comprehensive literature search was performed in databases PubMed, SCOPUS, LILACS, Scielo and DOAJ for systematic reviews and randomized controlled trials. The systematic reviews were assessed for the reporting characteristics and methodological quality, been identified rooms for future improvements. The following, it was performed a description of the key components of pharmacist interventions and of the sources of clinical and methodological heterogeneity between randomized controlled trials. In addition, a 12-month randomized controlled trial of pharmacist-physician collaborative interventions for eighty diabetic patients was conducted at University Hospital of University of São Paulo. The pharmaceutical interviews were conducted face-to-face, with remote support by telephone. Pharmacist performed systematic interventions aiming to solve and prevent drug-related problem in the diabetic patients. The primary outcomes included the reduction and control of the levels of glycosylated hemoglobin. The literature search yielded 101 records, of which 7 reviews for diabetic patients satisfied the inclusion criteria. On average, only two-thirds of reporting and methodological quality items were fulfilled in included reviews. The most frequent problems included the non-registration of study protocol, the absence of a list of excluded studies, and unclear acknowledgment of the conflict of interests. The literature search for randomized clinical trials of pharmacist interventions identified 2271 records, 24 of them were included in the qualitative synthesis. The majority of studies was developed in the United States, in ambulatory, with individual contact face to face. All of them performed educational interventions and the process of use of the medications was assessed in the majority of them. The sample showed risk of bias uncertain or high in the majority of the items assessed, which resulted in low methodological quality. Of a total of 80 patients, 73 completed the clinical trial (37 of control and 36 of intervention). In comparison with the usual care, the intervention group presented higher reduction in the levels of glycosylated hemoglobin, as well as increase in the rate of control of the systolic blood pressure, in the proportion of adherent patients and in the score of the medication adherence. The results of this thesis point out that the report and methodological quality was below the ideal in the reviews and that improvement in the design and in the description of the reviews and of the primary studies is necessary to warrant results that are more robust. Still, the model of care proposed is viable and more effective than the usual care in reducing the levels of glycosylated hemoglobin in patients with diabetes type 2.

Magister Public Health - MPH (Public Health) / The prevalence of diabetes in Africa has been on the increase. A prevalence of 1%- 10% has been reported by different authors in different regions in Nigeria. The International Diabetes Federation estimates that 1.9% of Nigerians are diabetic and most of them have complications at the time of diagnosis. Laboratory measurement of Glycosylated hemoglobin (HbA1c) is the method of choice for monitoring glycaemic control but due to its cost and limited availability, most developing countries use fasting plasma glucose (FPG) measurement (which is less reliable) to assess glycaemic control. Most diabetic patients in Nigeria have poor glycaemic control and several factors have been implicated especially socio-economic, behavioral and treatment-related factors. Understanding the reasons for poor glycaemic control is essential in order to reduce the rate of diabetes complications.

<div> <p>Proper understanding of materials science is critical in understanding the functionality of ingredients in food products, as well as their behavior in these products over time. Amorphous materials are metastable, eventually rearranging to the thermodynamically stable crystalline state. Amorphous materials have properties which are beneficial in some food products: they are softer in texture and dissolve more rapidly. The amorphous state of sucrose might provide an increase in quality in applications like powdered beverages where rapid dissolution is preferred. A number of classes of compounds have been shown to delay the crystallization of amorphous sucrose; however, polyphenols, particularly their glycosylated forms, have been little explored. Glycosylated polyphenols contain two distinct structural regions: a more hydrophilic sugar unit(s) and a more hydrophobic polyphenol backbone. While the sugar unit should be able to easily associate with sucrose molecules, the polyphenolic backbone may not and might provide hindrance to crystal nucleation and growth.</p> <p> </p> <p> Thiamine is an essential nutrient that is found naturally in foods such as whole grains and pork. The processing of grains removes nearly the entirety of the natural thiamine content; thus, foods are often enriched with synthetic thiamine. Two salts of thiamine are used commercially: thiamine mononitrate and thiamine chloride hydrochloride. The two forms have specific applications driven by their specific properties, specifically their aqueous solubility and hygroscopicity. While these two salts provide adequate functionality, it is possible new salts may have properties beneficial in certain food applications. A method making use of silver nitrate was developed to produce new salt forms. An intermediate in this reaction, TCl·H₂O, was characterized including measurements of stability in aqueous solutions and solid state properties.</p> </div> <br>

A prolactina humana (hPRL) é um hormônio polipeptídico secretado pela hipófise anterior sob regulação do hipotálamo, envolvido em uma variedade de processos biológicos como o desenvolvimento da glândula mamária e lactação. O produto recombinante é importante no diagnóstico médico e no tratamento de insuficiência da lactação. Este hormônio pode ocorrer sob a forma de proteína não glicosilada (NG-hPRL) e glicosilada (G-hPRL), com pesos moleculares de aproximadamente 23 e 25 kilodalton (kDa), respectivamente; possui um único sítio de N-glicosilação localizado na asparagina (Asn) posição 31, que é parcialmente ocupado, representando assim um modelo particularmente interessante de glicosilação. A atividade biológica da G-hPRL é muito menor comparada à NG-hPRL (~4 vezes) e sua função fisiológica ainda não é bem definida: a porção de carboidrato parece ter um importante papel na biossíntese, secreção, atividade biológica, e sobrevivência plasmática do hormônio. O objetivo principal desse trabalho foi comparar as estruturas dos N-glicanos presentes na prolactina glicosilada hipofisária (G-hPRL-NHPP) com a recombinante. Para obter a G-hPRL recombinante foi realizada uma produção em escala laboratorial a partir de células de ovário de hamster chinês (CHO) geneticamente modificadas e adaptadas ao crescimento em suspensão. Foi adicionada, ao meio de cultura cicloheximida (CHX), cujo efeito principal foi aumentar a relação G-hPRL/NGhPRL que passou de 5% para 38%, facilitando assim a purificação da G-hPRL. A G-hPRL foi purificada em duas etapas, uma troca catiônica seguida de purificação por cromatografia liquida de alta eficiência de fase reversa (RP-HPLC) que se demonstrou eficiente na separação das duas isoformas de hPRL. A G-hPRL recombinante IPEN foi assim analisada por diversas técnicas confirmando a sua pureza e atividade biológica, incluindo comparações com outras amostras de referências de origem hipofisária adquirida junto ao National Hormone & Peptide Program (NHPP-E.U.A.) . Foi realizada também a determinação inédita de Nglicanos presentes na G-hPRL produzida por células CHO e na G-hPRL nativa, produzida pela hipófise humana, possibilitando comparar as duas estruturas de carboidratos e alcançando assim uma das principais metas desse projeto. Entre as principais diferenças encontradas nas estruturas dos dois N-glicanos, destacam-se a baixa quantidade de ácido siálico (NeuAc), a alta porcentagem de glicanos sulfatos (74,0%) e com fucose (Fuc) (93,3%) presentes na amostra hipofisária e a tendência da preparação recombinante de apresentar glicanos com maior peso molecular e com uma menor variação nas isoformas. / Human prolactin (hPRL) is a polypeptide hormone secreted by the anterior pituitary under the regulation of the hypothalamus, involved in a variety of biological processes such as mammary gland development and lactation. The recombinant product is important in medical diagnosis and treatment of failure of lactation. This hormone may occur in the form of non-glycosylated protein (NGhPRL) and glycosylated (G-hPRL) with molecular weights of approximately 23 and 25 kilodalton (kDa), respectively; has a single N-glycosylation site located at asparagine (Asn) position 31, which is partially occupied, thus being a particularly interesting model of glycosylation. The biological activity of G-hPRL is lower compared to NG-hPRL (~4 times) and its physiological function is not well defined: the portion of carbohydrate appears to have an important role in the hormone biosynthesis, secretion, biological activity, and plasma survival of the hormone. The main objective of this study was to compare the structures of N-glycans present in glycosylated pituitary prolactin (G-hPRL-NHPP) with those present in the recombinant. To obtain the recombinant G-hPRL the production was performed in laboratory scale from Chinese hamster ovary cells (CHO), genetically modified and adapted to growth in suspension. Cycloheximide (CHX), whose main effect was to increase the ratio G-hPRL/NG-hPRL from 5% to 38% was added to the culture medium, thereby facilitating the purification of G-hPRL. The G-hPRL was purified in two steps, a cation exchanger followed by a purification by reversed-phase high performance liquid chromatography (RP-HPLC) which demonstrated the efficient separation of the two isoforms of hPRL. Recombinant G-hPRL-IPEN was well characterized by several techniques confirming its purity and biological activity, including comparisons with other reference preparation of pituitary origin purchased from the \"National Hormone & Peptide Program (NHPPU. S.)\". The composition of N-glycans present in the G-hPRL, produced by CHO cells, and that of native G-hPRL, produced by the human pituitary gland, were also determined for the first time, allowing the two structures of carbohydrates to be compared and thus, achieving one of the main goals of this project. Among the main differences in N-glycan structures, we highlight the low presence of sialic acid (NeuAc) and the high percentage of sulfated glycans (74.0%) and of fucose (Fuc) (93.3%) in the pituitary sample and the tendency of the recombinant preparation to present glycans with higher molecular weight and less isoforms variation.