The coalburg seam coal is an example of difficult to float bituminous coal. Laboratory tests conducted on coalburg flotation feed sample revealed recovery values around 28% with 15% product ash when using fuel oil as collector under natural pH conditions. A detailed study showed that increasing pH from natural value of 5.6 to 7.5 provided a significant improvement in recovery of approximately 32 absolute percentage points. The improvement is believed to be result of the release of humic acids from the surface and the dispersion of clay particles thereby leaving a more hydrophobic surface. Based on the tests conducted with various commercially available collectors, oleic acid was selected as a model collector for oxidized coals. Conventional flotation tests found an increase in combustible recovery of 10 absolute percentage points above the pH improvement using 4:1 blend of fuel oil and oleic acid. The problem of higher ash in conventional cell product due to entrainment was minimized by the use of wash water in a flotation column. A flotation concentrate containing less than 7.5% ash was produced while recovering around 75% of the combustible material. Further testing using fatty acids-fuel oil blend also showed evidence of a near 200% increase in flotation rate.

Introdução: O Diabetes mellitus (DM) está associado a complicações crônicas micro e macrovasculares. A medida da hemoglobina glicada (HbA1c) avalia o grau do controle glicêmico em pacientes diabéticos e seus níveis são capazes de prognosticar o risco de desenvolvimento dessas complicações. Entre as origens das complicações causadas pela hiperglicemia, há a hipótese dos produtos finais de glicação avançada (AGEs) e do estresse oxidativo. A reação de glicação não enzimática das proteínas também está relacionada com as complicações diabéticas e é responsável pela formação da HbA1c. Entretanto, tem sido demonstrado um aumento dessa glicação em pacientes não diabéticos. Um dos prováveis mecanismos para esse aumento é a peroxidação lipídica, com conseqüente aumento nos níveis de malondialdeído (MDA) que modifica a apolipoproteína B (APO B) do colesterol de baixa densidade (LDL). A modificação oxidativa do LDL confere propriedades específicas pró-aterogênicas. A presença do LDL oxidado e o aumento da tendência do LDL à peroxidação lipídica, podem contribuir para o aumento dos níveis de HbA1c. Objetivo: Verificar a associação entre os níveis de HbA1c com o Colesterol LDL e LDL oxidado em Indivíduos não-diabéticos. Métodos: Foi realizado um estudo transversal observacional, no qual um total de 196 indivíduos, classificados como não-diabéticos, foram analisados e divididos em três grupos, conforme os valores de HbA1c e glicemia de jejum (GJ): Grupo 1 (n =64) - HbA1c <5,7% e GJ <100 mg/dL; Grupo 2 (n =69) - HbA1c ≥5,7 e ≤6,4% e GJ <100 mg/dL; Grupo 3 (n =63) - HbA1c ≥5,7 e ≤6,4% e GJ ≥100 e <126mg/dL. Amostras de sangue total e soro foram coletadas. O LDL oxidado foi medido por método imunoensaio enzimático (Mercodia ®), ApoB dosada por imunoturbidimentria, a relação Colesterol LDL(oxi)/Colesterol-HDL foi estimada, além das outras dosagens bioquímicas do perfil lipídico. Esses testes foram comparados e analisados entre os três diferentes grupos. Resultados: Houve diferença significativa nos níveis de LDL(oxi) (p< 0,001), Apo B (p= 0,026) e razão LDL(oxi)/HDL (p< 0,001) entre os três grupos. Os valores de HbA1c apresentaram correlação positiva com os valores de LDL (oxi) (r =0,431; p <0,001), LDL (r =0,148; p =0,039), Col Não-HDL (r =0,192; p =0,007) e Apo B (r =0,171; p <0,001). Estas associações positivas permaneceram significativas, mesmo após ajuste, por análise de regressão linear múltipla para as variáveis álcool, medicamentos, índice de massa corporal (IMC) e idade. Também apresentaram correlações positivas com os valores de HbA1c: razão LDL (oxi)/HDL (r =0,422; p <0,001), CT (r =0,142; p =0,048), triglicerídios (r =0,155; p =0,030) e IMC (r =0,263; p <0,001). Conclusão: Nosso estudo demonstrou associação dos níveis de HbA1c com as partículas lipídicas aterogênicas LDL, Apo B, colesterol não HDL e LDL (oxi). Os níveis de LDL, principalmente LDL (oxi), estão significativamente associados com os níveis de HbA1c e glicose, mesmo em indivíduos não-diabéticos. Os indivíduos classificados com alto risco de desenvolver DM ou DCV apresentam valores mais elevados de partículas de LDL oxidadas. Nossos dados sugerem que a presença de LDL (oxi) está relacionada com a glicação e ao aumento dos níveis sanguíneos de HbA1c em indivíduos não diabéticos. / Background: Diabetes mellitus (DM) is associated with chronic microvascular and macrovascular complications. The measurement of glycated hemoglobin (HbA1c) assesses the degree of glycemic control in diabetics patients and their levels are able to predict the risk of developing these complications. The formation of advanced glycation and products (AGEs) and oxidative stress are some of the hypothesis described to explain the diabetic complications. The reaction of nonenzymatic glycation of proteins is also related to these complications and is responsible for the formation of HbA1c. However, it has been shown an increase in glycation in nondiabetic patients, which is maybe due to lipid peroxidation, consequently, the levels of malondialdehyde (MDA) increase and there is modifications in the apolipoprotein B (apoB) of low-density cholesterol (LDL). The oxidative modification of LDL confers specific proatherogenic properties. The presence of oxidized LDL and an increased tendency to LDL peroxidation contribute to increased levels of HbA1c in diabetic patients. Objective: To investigate the association between HbA1c levels and the levels of LDL cholesterol and oxidized LDL in subjects without diabetes. Methods: We conducted an observational cross-sectional study in which a total of 196 individuals, classified as non-diabetics, were analyzed and divided into three groups according to the values of HbA1c and fasting plasma glucose (FPG): Group 1 (n = 64) - HbA1c <5.7% and FPG <100 mg / dL, Group 2 (n = 69) - HbA1c ≥ 5.7 and ≤ 6.4% and FPG <100 mg / dL, Group 3 (n = 63) - HbA1c ≥ 5.7 and ≤ 6.4% and FPG ≥ 100 and <126mg/dL. Samples of whole blood and serum were collected. Oxidized LDL was measured by enzyme immunoassay method (Mercodia ®), ApoB was measured by imunoturbidimentria and the ratio LDL cholesterol (oxi) / HDL-cholesterol was estimated. Other biochemical measurements of lipid profile were also carried out. Results: There were significant differences in LDL (oxi) (p <0.001), Apo B (p = 0.026), and ratio LDL (oxi) / HDL (p <0.001) between the three groups. HbA1c values showed positive association with LDL (oxi) (r = 0.431, p <0.001), LDL (r = 0.148, p = 0.039), non-HDL Col (r = 0.192, p = 0.007) and Apo B (r = 0.171, p <0.001). These positive associations remained significant even after adjustment for multiple linear regression analysis for variables such as alcohol, drugs, BMI and age. The ratio LDL (oxi) / HDL (r = 0.422, p <0.001), CT (r = 0.142, p = 0.048), triglycerides (r = 0.155, p = 0.030) and BMI (r = 0.263, p <0.001) also showed positive correlations with HbA1c values. Conclusions: Our study demonstrated that there is association between HbA1c levels and the atherogenic lipid particles LDL, Apo B, non-HDL cholesterol and LDL (oxi). LDL levels, especially LDL (oxi), are significantly associated with HbA1c and glucose levels, even in non-diabetics. Individuals classified with high risk of developing diabetes or CVD have higher levels of oxidized LDL particles. Our data suggest that the presence of LDL (oxi) is related to glycation and increased blood levels of HbA1c in nondiabetic individuals.

Introdução: O Diabetes mellitus (DM) está associado a complicações crônicas micro e macrovasculares. A medida da hemoglobina glicada (HbA1c) avalia o grau do controle glicêmico em pacientes diabéticos e seus níveis são capazes de prognosticar o risco de desenvolvimento dessas complicações. Entre as origens das complicações causadas pela hiperglicemia, há a hipótese dos produtos finais de glicação avançada (AGEs) e do estresse oxidativo. A reação de glicação não enzimática das proteínas também está relacionada com as complicações diabéticas e é responsável pela formação da HbA1c. Entretanto, tem sido demonstrado um aumento dessa glicação em pacientes não diabéticos. Um dos prováveis mecanismos para esse aumento é a peroxidação lipídica, com conseqüente aumento nos níveis de malondialdeído (MDA) que modifica a apolipoproteína B (APO B) do colesterol de baixa densidade (LDL). A modificação oxidativa do LDL confere propriedades específicas pró-aterogênicas. A presença do LDL oxidado e o aumento da tendência do LDL à peroxidação lipídica, podem contribuir para o aumento dos níveis de HbA1c. Objetivo: Verificar a associação entre os níveis de HbA1c com o Colesterol LDL e LDL oxidado em Indivíduos não-diabéticos. Métodos: Foi realizado um estudo transversal observacional, no qual um total de 196 indivíduos, classificados como não-diabéticos, foram analisados e divididos em três grupos, conforme os valores de HbA1c e glicemia de jejum (GJ): Grupo 1 (n =64) - HbA1c <5,7% e GJ <100 mg/dL; Grupo 2 (n =69) - HbA1c ≥5,7 e ≤6,4% e GJ <100 mg/dL; Grupo 3 (n =63) - HbA1c ≥5,7 e ≤6,4% e GJ ≥100 e <126mg/dL. Amostras de sangue total e soro foram coletadas. O LDL oxidado foi medido por método imunoensaio enzimático (Mercodia ®), ApoB dosada por imunoturbidimentria, a relação Colesterol LDL(oxi)/Colesterol-HDL foi estimada, além das outras dosagens bioquímicas do perfil lipídico. Esses testes foram comparados e analisados entre os três diferentes grupos. Resultados: Houve diferença significativa nos níveis de LDL(oxi) (p< 0,001), Apo B (p= 0,026) e razão LDL(oxi)/HDL (p< 0,001) entre os três grupos. Os valores de HbA1c apresentaram correlação positiva com os valores de LDL (oxi) (r =0,431; p <0,001), LDL (r =0,148; p =0,039), Col Não-HDL (r =0,192; p =0,007) e Apo B (r =0,171; p <0,001). Estas associações positivas permaneceram significativas, mesmo após ajuste, por análise de regressão linear múltipla para as variáveis álcool, medicamentos, índice de massa corporal (IMC) e idade. Também apresentaram correlações positivas com os valores de HbA1c: razão LDL (oxi)/HDL (r =0,422; p <0,001), CT (r =0,142; p =0,048), triglicerídios (r =0,155; p =0,030) e IMC (r =0,263; p <0,001). Conclusão: Nosso estudo demonstrou associação dos níveis de HbA1c com as partículas lipídicas aterogênicas LDL, Apo B, colesterol não HDL e LDL (oxi). Os níveis de LDL, principalmente LDL (oxi), estão significativamente associados com os níveis de HbA1c e glicose, mesmo em indivíduos não-diabéticos. Os indivíduos classificados com alto risco de desenvolver DM ou DCV apresentam valores mais elevados de partículas de LDL oxidadas. Nossos dados sugerem que a presença de LDL (oxi) está relacionada com a glicação e ao aumento dos níveis sanguíneos de HbA1c em indivíduos não diabéticos. / Background: Diabetes mellitus (DM) is associated with chronic microvascular and macrovascular complications. The measurement of glycated hemoglobin (HbA1c) assesses the degree of glycemic control in diabetics patients and their levels are able to predict the risk of developing these complications. The formation of advanced glycation and products (AGEs) and oxidative stress are some of the hypothesis described to explain the diabetic complications. The reaction of nonenzymatic glycation of proteins is also related to these complications and is responsible for the formation of HbA1c. However, it has been shown an increase in glycation in nondiabetic patients, which is maybe due to lipid peroxidation, consequently, the levels of malondialdehyde (MDA) increase and there is modifications in the apolipoprotein B (apoB) of low-density cholesterol (LDL). The oxidative modification of LDL confers specific proatherogenic properties. The presence of oxidized LDL and an increased tendency to LDL peroxidation contribute to increased levels of HbA1c in diabetic patients. Objective: To investigate the association between HbA1c levels and the levels of LDL cholesterol and oxidized LDL in subjects without diabetes. Methods: We conducted an observational cross-sectional study in which a total of 196 individuals, classified as non-diabetics, were analyzed and divided into three groups according to the values of HbA1c and fasting plasma glucose (FPG): Group 1 (n = 64) - HbA1c <5.7% and FPG <100 mg / dL, Group 2 (n = 69) - HbA1c ≥ 5.7 and ≤ 6.4% and FPG <100 mg / dL, Group 3 (n = 63) - HbA1c ≥ 5.7 and ≤ 6.4% and FPG ≥ 100 and <126mg/dL. Samples of whole blood and serum were collected. Oxidized LDL was measured by enzyme immunoassay method (Mercodia ®), ApoB was measured by imunoturbidimentria and the ratio LDL cholesterol (oxi) / HDL-cholesterol was estimated. Other biochemical measurements of lipid profile were also carried out. Results: There were significant differences in LDL (oxi) (p <0.001), Apo B (p = 0.026), and ratio LDL (oxi) / HDL (p <0.001) between the three groups. HbA1c values showed positive association with LDL (oxi) (r = 0.431, p <0.001), LDL (r = 0.148, p = 0.039), non-HDL Col (r = 0.192, p = 0.007) and Apo B (r = 0.171, p <0.001). These positive associations remained significant even after adjustment for multiple linear regression analysis for variables such as alcohol, drugs, BMI and age. The ratio LDL (oxi) / HDL (r = 0.422, p <0.001), CT (r = 0.142, p = 0.048), triglycerides (r = 0.155, p = 0.030) and BMI (r = 0.263, p <0.001) also showed positive correlations with HbA1c values. Conclusions: Our study demonstrated that there is association between HbA1c levels and the atherogenic lipid particles LDL, Apo B, non-HDL cholesterol and LDL (oxi). LDL levels, especially LDL (oxi), are significantly associated with HbA1c and glucose levels, even in non-diabetics. Individuals classified with high risk of developing diabetes or CVD have higher levels of oxidized LDL particles. Our data suggest that the presence of LDL (oxi) is related to glycation and increased blood levels of HbA1c in nondiabetic individuals.

Introdução: O Diabetes mellitus (DM) está associado a complicações crônicas micro e macrovasculares. A medida da hemoglobina glicada (HbA1c) avalia o grau do controle glicêmico em pacientes diabéticos e seus níveis são capazes de prognosticar o risco de desenvolvimento dessas complicações. Entre as origens das complicações causadas pela hiperglicemia, há a hipótese dos produtos finais de glicação avançada (AGEs) e do estresse oxidativo. A reação de glicação não enzimática das proteínas também está relacionada com as complicações diabéticas e é responsável pela formação da HbA1c. Entretanto, tem sido demonstrado um aumento dessa glicação em pacientes não diabéticos. Um dos prováveis mecanismos para esse aumento é a peroxidação lipídica, com conseqüente aumento nos níveis de malondialdeído (MDA) que modifica a apolipoproteína B (APO B) do colesterol de baixa densidade (LDL). A modificação oxidativa do LDL confere propriedades específicas pró-aterogênicas. A presença do LDL oxidado e o aumento da tendência do LDL à peroxidação lipídica, podem contribuir para o aumento dos níveis de HbA1c. Objetivo: Verificar a associação entre os níveis de HbA1c com o Colesterol LDL e LDL oxidado em Indivíduos não-diabéticos. Métodos: Foi realizado um estudo transversal observacional, no qual um total de 196 indivíduos, classificados como não-diabéticos, foram analisados e divididos em três grupos, conforme os valores de HbA1c e glicemia de jejum (GJ): Grupo 1 (n =64) - HbA1c <5,7% e GJ <100 mg/dL; Grupo 2 (n =69) - HbA1c ≥5,7 e ≤6,4% e GJ <100 mg/dL; Grupo 3 (n =63) - HbA1c ≥5,7 e ≤6,4% e GJ ≥100 e <126mg/dL. Amostras de sangue total e soro foram coletadas. O LDL oxidado foi medido por método imunoensaio enzimático (Mercodia ®), ApoB dosada por imunoturbidimentria, a relação Colesterol LDL(oxi)/Colesterol-HDL foi estimada, além das outras dosagens bioquímicas do perfil lipídico. Esses testes foram comparados e analisados entre os três diferentes grupos. Resultados: Houve diferença significativa nos níveis de LDL(oxi) (p< 0,001), Apo B (p= 0,026) e razão LDL(oxi)/HDL (p< 0,001) entre os três grupos. Os valores de HbA1c apresentaram correlação positiva com os valores de LDL (oxi) (r =0,431; p <0,001), LDL (r =0,148; p =0,039), Col Não-HDL (r =0,192; p =0,007) e Apo B (r =0,171; p <0,001). Estas associações positivas permaneceram significativas, mesmo após ajuste, por análise de regressão linear múltipla para as variáveis álcool, medicamentos, índice de massa corporal (IMC) e idade. Também apresentaram correlações positivas com os valores de HbA1c: razão LDL (oxi)/HDL (r =0,422; p <0,001), CT (r =0,142; p =0,048), triglicerídios (r =0,155; p =0,030) e IMC (r =0,263; p <0,001). Conclusão: Nosso estudo demonstrou associação dos níveis de HbA1c com as partículas lipídicas aterogênicas LDL, Apo B, colesterol não HDL e LDL (oxi). Os níveis de LDL, principalmente LDL (oxi), estão significativamente associados com os níveis de HbA1c e glicose, mesmo em indivíduos não-diabéticos. Os indivíduos classificados com alto risco de desenvolver DM ou DCV apresentam valores mais elevados de partículas de LDL oxidadas. Nossos dados sugerem que a presença de LDL (oxi) está relacionada com a glicação e ao aumento dos níveis sanguíneos de HbA1c em indivíduos não diabéticos. / Background: Diabetes mellitus (DM) is associated with chronic microvascular and macrovascular complications. The measurement of glycated hemoglobin (HbA1c) assesses the degree of glycemic control in diabetics patients and their levels are able to predict the risk of developing these complications. The formation of advanced glycation and products (AGEs) and oxidative stress are some of the hypothesis described to explain the diabetic complications. The reaction of nonenzymatic glycation of proteins is also related to these complications and is responsible for the formation of HbA1c. However, it has been shown an increase in glycation in nondiabetic patients, which is maybe due to lipid peroxidation, consequently, the levels of malondialdehyde (MDA) increase and there is modifications in the apolipoprotein B (apoB) of low-density cholesterol (LDL). The oxidative modification of LDL confers specific proatherogenic properties. The presence of oxidized LDL and an increased tendency to LDL peroxidation contribute to increased levels of HbA1c in diabetic patients. Objective: To investigate the association between HbA1c levels and the levels of LDL cholesterol and oxidized LDL in subjects without diabetes. Methods: We conducted an observational cross-sectional study in which a total of 196 individuals, classified as non-diabetics, were analyzed and divided into three groups according to the values of HbA1c and fasting plasma glucose (FPG): Group 1 (n = 64) - HbA1c <5.7% and FPG <100 mg / dL, Group 2 (n = 69) - HbA1c ≥ 5.7 and ≤ 6.4% and FPG <100 mg / dL, Group 3 (n = 63) - HbA1c ≥ 5.7 and ≤ 6.4% and FPG ≥ 100 and <126mg/dL. Samples of whole blood and serum were collected. Oxidized LDL was measured by enzyme immunoassay method (Mercodia ®), ApoB was measured by imunoturbidimentria and the ratio LDL cholesterol (oxi) / HDL-cholesterol was estimated. Other biochemical measurements of lipid profile were also carried out. Results: There were significant differences in LDL (oxi) (p <0.001), Apo B (p = 0.026), and ratio LDL (oxi) / HDL (p <0.001) between the three groups. HbA1c values showed positive association with LDL (oxi) (r = 0.431, p <0.001), LDL (r = 0.148, p = 0.039), non-HDL Col (r = 0.192, p = 0.007) and Apo B (r = 0.171, p <0.001). These positive associations remained significant even after adjustment for multiple linear regression analysis for variables such as alcohol, drugs, BMI and age. The ratio LDL (oxi) / HDL (r = 0.422, p <0.001), CT (r = 0.142, p = 0.048), triglycerides (r = 0.155, p = 0.030) and BMI (r = 0.263, p <0.001) also showed positive correlations with HbA1c values. Conclusions: Our study demonstrated that there is association between HbA1c levels and the atherogenic lipid particles LDL, Apo B, non-HDL cholesterol and LDL (oxi). LDL levels, especially LDL (oxi), are significantly associated with HbA1c and glucose levels, even in non-diabetics. Individuals classified with high risk of developing diabetes or CVD have higher levels of oxidized LDL particles. Our data suggest that the presence of LDL (oxi) is related to glycation and increased blood levels of HbA1c in nondiabetic individuals.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Os objetivos deste trabalho foram: modificar quimicamente o amido de inhame (Dioscorea esculenta L.) por oxidaÃÃo e fosforizaÃÃo, elaborar blendas com quitosana (CH) e poli (alcool vinilico) (PVA) e avaliar suas caracterÃsticas fÃsico-quÃmicas e funcionais. O amido oxidado (AOX) obtido com um alto grau de substituiÃÃo (GS= 1,86) promoveu grandes modificaÃÃes na estrutura do granulo do amido, que apresentou caracterÃsticas de um material amorfo, enquanto a fosforizaÃÃo foi bem sutil, (GS=0,002) conservando a estrutura e padrÃo cristalino tipo B do amido de inhame nÃo modificado. O amido fosforilado (AF) apresentou aumento na estabilidade de pasta e baixa tendÃncia a retrogradarÃo, ao contrario do amido oxidado que nÃo apresentou perfil de pasta devido a despolimerizaÃÃo decorrente da reaÃÃo. As blendas de AF/CH/PVA apresentaram boas caracterÃsticas de permeabilidade ao vapor dâÃgua, baixas solubilidades em tampÃo fosfato e Ãgua destilada em comparaÃÃo com o amido nÃo modificado. As blendas AF mostraram significativo intumescimento em tampÃo devido a reticularÃo entre os grupos fosfatos da soluÃÃo e do filme, o que e desejÃvel para uma provÃvel aplicaÃÃo desses filmes como curativos. As modificaÃÃes nas intensidades e formas das bandas nos espectros de infravermelho, assim como variaÃÃes nas temperaturas de gelatinizarÃo confirmaram a interaÃÃo do PVA e quitosana com as cadeias de amido nos filmes. A adiÃÃo de PVA melhorou as propriedades mecÃnicas dos filmes proporcionando maior flexibilidade. As blendas AF nÃo apresentaram atividade na inibiÃÃo de S. aureus e P. aeruginosa, porem as blendas AOX, apesar de nÃo serem efetivas na inibiÃÃo de P. aeruginosa, apresentaram atividade contra cepas de S. aureus, principalmente as blendas AOX 50 e AOX70, o que poderà favorecer sua utilizaÃÃo como inibidores da proliferaÃÃo desse microorganismo em infecÃÃes. / The aim of this study were to modify chemically the yam starch (Dioscorea esculenta L.) by oxidation and phosphorylation reactions, produce blends with chitosan (CH) and poly (vinyl alcohol) (PVA) and evaluate their physico-chemical and functional properties. The oxidized starch (AOX) had a high degree of substitution (DS=1.86) which promoted major changes in the granular structure showing characteristics of an amorphous material, whereas the phosphorylation was very subtle (GS=0.002), remaining its granular structure and crystalline pattern B-type of native yam starch. The phosphorylated starch (AF) showed improvement in paste stability and low tendency to retrogradation, unlike the AOX which showed no viscosity profile due to depolymerization caused by the reaction. The AF/CH/PVA blends showed good characteristics of water vapor permeability, low solubility in phosphate buffer and distilled water as compared to native starch. The blends AF showed significant swelling in buffer due to crosslinking between the phosphate groups of the solution and the film, which is desirable for a possible application of such films as dressings. The changes in intensities and shapes of the FTIR bands as well as variations in temperatures of gelatinization confirmed the interaction of PVA and chitosan with the starch chains in the films. The addition of PVA improved the characteristics of the films offering high flexibility. The AF blends showed no activity in the inhibition of S. aureus and P. aeruginosa, but the AOX blends, although not showing effectiveness in inhibition of P. aeruginosa, showed activity against strains of S. aureus, especially AOX50 and AOX70 blends, which may favor their use as inhibitors against proliferation of these microorganisms in infections.

RISE Bioeconomy is working with the biorefinery concept. That is, for the company, to utilize all wood derivatives in effective processes, resulting in unique products. RISE Bioeconomy is investigating the possibilities of producing holocellulose through an oxidative delignification process of wood, using peracetic acid (PAA). The product, high-purity holocellulose, can be used for the production of for example cellulose nanofibers, a product that in recent years have increased in interest. The PAA-delignification process relies on oxidative treatment with peracetic acid, where the lignin is solubilized in water through the formation of carboxylic groups in the lignin, yielding cellulose of very low lignin content and minimal degradation of the cellulose. In addition to the holocellulose, a solution containing water, acetic acid, salts and highly oxidized lignin is obtained. The PAA-delignification has yet only been performed in lab-scale, however, the aim is to scale up the process. There has not yet been any further utilization of the oxidized lignin and it has been proposed that esterification of the carboxylic groups with an alcohol is a possible valorization route. Due to the up-scaling of the PAA-delignification, it is of large interest to find a valorization route for the lignin by-product to fulfill the biorefinery concept. This master thesis focuses on evaluating esterification of an oxidized lignin, with the aim to propose a process suitable for up-scaling. The lab trials for the PAA-delignification of wood yielded limited amounts of lignin and due to difficulties while isolating this lignin, it was not partially characterized until months into the project. Therefore, model compounds were initially used to evaluate the process setup. Compounds with muconic acid type structures are some of the expected products from PAA-delignification of wood and muconic acid was therefore used as a model compound. In addition to this, vanillic acid was used to represent the phenolic lignin compounds. Gas Chromatography/Mass Spectrometry (GC/MS) analysis of the vanillic acid esterification was shown to be a suitable method for analyzing the conversion of this reaction. Due to the difficulties with the analysis of the model compounds, no results regarding the reaction procedures were obtained. As a “proof-of-concept”, a kraft lignin was oxidized, isolated and then esterified. Two different methods of esterification were performed, with and without a molecular sieve. It was assumed that the amount of carboxylic groups would increase after oxidation and decrease after a successful esterification. The amount of carboxylic groups after each process was analyzed with Phosphorus Nuclear Magnetic Resonance (31P-NMR). For the process without molecular sieve, the 31P-NMR analysis indicated that esterification of the lignin had occurred, to a limited extent. This was confirmed by Fourier Transform Infrared Spectrometry (FTIR). The process with molecular sieve showed no indication of esterification of the lignin. The project did prove the concept of esterifying an oxidized lignin and led to several different proposals for further work in the area. Due to the very wide scope of this project and several unexpected obstacles, this project did not fully answer the research questions given.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Obesity is a systemic low grade inflammation, that is associated to the increased production of proinflammatory molecules by adipose tissue. Besides, the adiposity elevated induces cellular apoptosis and release of a large amounts of free fatty acids from disrupted adipocyte. These molecules tend to accumulate in the liver and other body tissues like skeletal muscles causing a phenomenon known as lipotoxicity. Evidence suggests that in addition to fatty acids there are other molecules that could have a severe effect lipotoxicity. This is the case of the inflammatory cytokine interleukin 1 beta (IL-1β). The IL-1β is a major inflammatory cytokines in immunity system. Studies suggest that its continued production may act by reducing the glucose influx, and induces the free radicals production contributing to the maintenance of a state of oxidative stress. For this reason, some authors have suggested that IL-1β would be a molecule glicolipotóxic. In humans the expression of IL-1B is under strong genetic control. The single nucleotide polymorphism (SNP) of C to T at nucleotide position +3953 of the IL-1B gene appears to be functional because it has been associated with increased production of IL-1β in vivo. Therefore, the aim of this study was to analyze the association between the polymorphism +3953 IL-1B gene with obesity, the influence on glycemic control, lipid and oxidized LDL molecule (oxLDL). For this, two studies were performed. The first was a case-control study with 880 Caucasian individuals, classified to obesity (non-obese = 283, overweight = 334, obese = 263), age between 18-92 years, and genotyped to IL-1B +3953 polymorphism. It was measured the bioanthropometric variables (DBP, SBP, IBM, height, weight, waist circumference) and serum parameters of blood glucose, lipid profile. In the second study, we included 225 subjects genotyped previously and measured the oxLDL serum levels, besides bioanthropometric and lipid profile measures. In both studies the volunteers did not smoke and had no cardiovascular disease or chronic degenerative diseases that could affect results. The IL-1B polymorphism genotypes were determined by PCR-RFLP and biochemical parameters by spectrophotometry. The first study results showed that the C allele (CC and CT) had a higher frequency in the group of obese and overweight when compared to the non obese group. The odds ratio showed 1.340 (95% CI: 1.119-1.605) times more chance of the obese group being CC carriers compared to non-obese group independent of gender and age. The second study showed that TT genotype carriers presented lower levels of oxLDL than patients with other genotypes. However no significant influence was observed of this polymorphism in blood glucose levels. Multivariate analysis showed that this result is independent of sex, age, obesity and hypertension. Thus, these results support the hypothesis that IL-1β is a molecule indeed obesogenic and lipotoxicity as previously suggested from animal models studies. Key-word: obesity. Interleukin-1beta. Oxidized-LDL / A obesidade é um inflamação sistêmica de baixo grau associado a elevada liberação de moléculas pró-inflamatórias pelo tecido adiposo. O aumento da adiposidade resulta em necrose tecidual e liberação de ácidos graxos, a partir dos adipócitos, que tendem a se acumular em outros tecidos corporais causando um fenômeno conhecido como lipotoxicidade. A IL-1β é uma das principais citocinas pró-inflamatórias do sistema imune, e a sua produção continuada pode agir diminuindo o influxo da glicose para dentro da célula, e induzir a produção de radicais livres contribuindo para a manutenção de um estado de estresse oxidativo. Por este motivo, alguns autores sugeriram que a IL- 1β seria uma molécula glicolipotóxica. Nos seres humanos a IL-1β possui um polimorfismo +3953 do gene da IL-1B parece ser funcional pois tem sido associado a variações na produção da IL-1β in vivo. Portanto, o objetivo deste estudo foi o de analisar a associação entre o polimorfismo +3953 do gene da IL-1B com a obesidade, a influencia nos níveis glicêmicos, lipídicos e da molécula de LDL- oxidado (LDL-ox). Para isso, foram realizados dois estudos. O primeiro foi um estudo caso-controle com 880 indivíduos Caucasianos classificados para obesidade (não obesos= 283, sobrepeso=334, obesos= 263), com idade entre 18 e 92 anos, genotipados para IL-1B +3953 determinados por PCR-RFLP. As variáveis PAD, PAS, circunferência abdominal, IMC, altura, peso, bem como o perfil glicêmico e lipídico foram medidos. No segundo estudo foram selecionados 225 indivíduos, previamente genotipados para IL-1B +3953, e medido os níveis séricos de LDL-ox, além das medidas bioantropométricas e perfil glicêmico e lipídico. Em ambos os estudos os voluntários não fumavam e não apresentavam doenças cardiovasculares ou crônico-degenerativas que pudessem interferir nos resultados. Os resultados, do primeiro estudo, mostraram que o alelo C (CT CC) apresentou uma frequência maior no grupo dos obesos e sobrepeso quando comparado ao grupo dos não obesos. A chance dos indivíduos obesos de serem portadores do genótipo CC foi de 1,34 (IC 95%, 1,119- 1,605). Estes resultados foram independente do gênero e idade. O segundo estudo mostrou que indivíduos com o genótipo CC e CT apresentaram níveis mais elevados de LDL-ox do que os portadores do genótipo TT. A análise multivariada mostrou que este resultado é independente do gênero, idade e obesidade. Entretanto, em ambos os estudos, não foi observada influência deste polimorfismo nos níveis glicêmicos. Assim, podemos concluir que a IL-1β é uma molécula, com efeito obesogênico e lipotóxico, corroborando estudos prévios em modelos animais.

Contrairement aux HDL de sujets sains, les HDL de patients diabétiques ont perdu leur capacité à contrecarrer les effets inhibiteurs des LDL oxydées sur la vasorelaxation endothélium dépendante. Les mécanismes en cause ne sont pas connus. Or la glycation et l’oxydation sont deux phénomènes majeurs au cours du diabète. Nous avons donc étudié in vitro, le rôle de la glycation (associée ou non à une oxydation spontanée), et de l’oxydation d’HDL issues de sujets sains, sur leurs capacités à contrecarrer les effets inhibiteurs des LDL oxydées sur la vasorelaxation endothélium dépendante. Chaque condition a conduit au même constat: les HDL modifiées perdent leur pouvoir vasorelaxant en présence de LDL oxydées. En revanche, en l’absence de LDL oxydées, elles n’altèrent pas la vasorelaxation induite par l’acétylcholine. Ainsi les modifications structurelles des HDL (glycation, oxydation, ou les deux) induisent une perte de leur capacité à protéger l’endothélium du stress oxydatif, plutôt qu’un effet délétère direct sur l’endothélium. Un des mécanismes majeur impliqué dans ce phénomène est probablement l’absence de fixation de ces HDL modifiées à leur récepteur SR-BI. Elles ne pourraient plus alors s’opposer au niveau des cavéoles aux effets délétères des LDL oxydées, et ne favoriseraient plus la production de NO. Mais si aussi bien la glycation que l’oxydation des HDL entraînent ces effets néfastes, il semblerait qu’en condition physiopathologique (oxydation spontanée des HDL glyquées), l’oxydation ne majore pas cette perte de capacité des HDL à contrecarrer les effets inhibiteurs des LDL oxydées sur la vasorelaxation. / Contrary to HDL from normolipidaemic and normoglycaemic subjects, HDL from diabetic patients have lost their capacity to reverse the inhibition of vasorelaxation induced by oxidized LDL. Mechanisms involved are unknown. The glycation and oxidation of HDL are two major phenomena in diabetes mellitus. The aim of this work was to study in vitro the role of glycation (with or without spontaneous oxidation) and oxidation of HDL, on their capacity to counteract the inhibitory effect of oxidized LDL on endothelium-dependent vasorelaxation. Each state showed the same result, modified HDL lost their vasorelaxing power in stress conditions (with oxidized LDL). Nevertheless, modified HDL alone (without oxidized LDL) did not alter vasorelaxation induced by acetylcholine, after noradrenaline-induced vasoconstriction. Thus, modifications of HDL induce a loss of the ability to protect vessels from oxidative stress rather than have a direct deleterious effect on the vessel. One of the major mechanisms involved in this phenomenon is probably the loss of SR-BI binding of these modified HDL, that could lead to the inability of HDL to protect caveolae from deleterious effects induced by oxidized LDL and could not preserve NO production. However, though glycation, like oxidation of HDL, leads to these deleterious effects, it would seem that during physiopathological conditions, with the spontaneous oxidation of glycated HDL, oxidation does not aggravate the loss of the capacity of diabetic HDL to counteract the inhibitory effect of oxidized LDL on endothelium-dependent vasorelaxation.

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Correct diagnosis of disease is essential in the effort to save and improve lives. Point of care (POC) diagnostics are in-vitro tests that assist in patient diagnosis and can be used at the location of patient care. POC diagnostics are easy to use and provide near-instant readouts allowing medical providers and patients to make rapid decisions about treatment. Increased access to POC testing is especially beneficial to low-income and low resource areas that cannot afford expensive lab testing. The World Health Organization (WHO) has outlined at least 113 diseases for which POC diagnostics are needed. Because of this, developing effective, efficient, and economical methods for creating new POC tests is essential. Work in section one of this thesis describes strategies by which new POC bio-diagnostics can be created. The use of oxidized cellulose as a vector for antibody immobilization was explored in several cellulose-based materials to provide quick, economical tests while still obtaining effective limits of detection when used to detect the pregnancy hormone Human Chorionic Gonadotropin (HCG) in a proof of concept study. The majority of these tests could detect as low as 100 ng/mL of HCG well below the clinical level necessary for detection at 2400 ng/mL. The use of a hand-powered syringe-based POC named the fast flow immunoassay (FFI) was tested for its ability to increase observable signal in a sandwich immunoassay by passing the sample through the test filter multiple times. 10 passes through the filter resulted in a signal approximately 17x more intense than a 1-hour dot-blot sandwich immunoassay. Both oxidized cotton and FFI systems can be used to develop new POC assays quickly and economically. Future use of these POC systems could help expand the availability of diagnostic testing to disadvantaged areas. Gold-based drugs have been used and investigated as medications multiple times throughout history to treat various diseases such as Rheumatoid arthritis, parasitic infections, and cancer. In the last few decades, gold nanoparticles have been used as drug delivery agents and catalysts for various reactions. Recently catalytic gold nanocrystals have been characterized for their ability to treat neurodegenerative diseases. Although these results were promising, much is still unknown about their mechanism of action. Section two of this thesis investigates potential molecular pathways that gold nanocrystals could be affecting, specifically the IL-6/Jak/STAT3 inflammation pathway and the Nrf2 antioxidant pathway. The gold nanocrystals we tested did not affect these pathways at physiologically obtainable concentrations. Additional work was done to characterize protein interactome or protein corona of gold nanocrystals. Preliminary proteomic characterization of this protein corona in fetal bovine serum (FBS) identified 118 potential interactors and classified those based on function and structure. Future work will need to be done to follow up on these identifications and to determine what mechanistic implications they may have.