University of Macau / Institute of Chinese Medical Sciences

Thesis (M.S.)--California Polytechnic State University, 2009. / Title from PDF title page; viewed on January 6, 2010. Major professor: Brooke D. Humphrey, Ph.D. "Presented to the faculty of California Polytechnic State University, San Luis Obispo." "In partial fulfillment of the requirements for the degree [of] Master of Science in Agriculture, with Specialization in Animal Science." "October 2009." Includes bibliographical references (p. 102).

Thesis (Ph.D.)--Victoria University of Wellington, 2008. / Includes bibliographical references.

Thesis (M.S.)--West Virginia University, 2008. / Title from document title page. Document formatted into pages; contains vii, 68 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 46-68).

Orientador: Aureo Evangelista Santana / Resumo: A hemorragia pulmonar induzida por exercício (HPIE) caracteriza-se pela ruptura de capilares pulmonares e extravasamento de sangue nas vias aéreas. Uma das formas mais utilizadas para diagnóstico é visibilização de sangue na traqueia por meio de exame endoscópico das vias aéreas. A HPIE ocasiona inflamação no sistema respiratório e a resposta de fase aguda leva à síntese de proteínas de fase aguda, como a amiloide A sérica (AAS). Diante disso, objetivou-se com a realização deste estudo avaliar se a HPIE causa aumento da AAS em equinos após corrida. Exame endoscópico das vias aéreas e amostras de sangue foram colhidas de equinos da raça Puro-sangue inglês (PSI), após corrida no Jockey Club Brasileiro, na Gávea, Rio de Janeiro. As amostras de soro foram utilizadas para efetuar análises de AAS, por meio de ensaio imunoenzimático pela técnica de ELISA indireto (Enzyme Linked Immuno Sorbent Assay), utilizando kit comercial. Os dados obtidos foram avaliados por meio de análise de variância e verificou-se diferenças (p ≤ 0,05) em relação à variável presença ou ausência de HPIE e a concentração de AAS. Setenta e um equinos, sendo 43 machos e 28 fêmeas, da raça PSI, foram distribuídos em dois grupos: o primeiro grupo, grupo controle (GC) com 28 animais (39%); o segundo, grupo hemorragia pulmonar induzida por exercício (GH), com 43 animais (61%). Houve diferença entre os grupos (p<0,0001) em relação à presença e à ausência de HPIE. A concentração de AAS no sangue dos animais dos grupos... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Exercise-induced pulmonar hemorrhage (EIPH) is characterized as the rupture of pulmonary capillaries and blood loss within the respiratory tract. One of the most important diagnostic means is the presence of fresh blood at the trachea during endoscopic examination of the respiratory tract. EIPH causes inflammation of the respiratory system and may cause an acute phase response leading to synthesis of acute phase proteins such as serum amiloyd A (SAA). Therefore the aim of this study was to evaluate if EIPH causes increase in SAA of horses after race. Endoscopic exam and blood samples were collected from Thoroughbred racehorses after a race at the Jockey Club Brasileiro, at Gávea, Rio de Janeiro. Serum samples were used to perform SAA analyses by immunosorbent assay with indirect ELISA technique (Enzyme Linked Immuno Sorbent Assay), using a commercial kit. The collected data was evaluated by ANOVA (p ≤ 0.05) for presence or absence of EIPH and to evaluate SAA data. Seventy one Thoroughbred race horses, 43 males and 28 females, were used in this study and were divided into two groups. The control group (GC) was enlisted with 28 horses (39%) and the EIPH positive (GH) with 43 horses (61%). There was a significant difference in between both groups (p<0.0001) related to EIPH positive and negative horses. There was no difference on the SAA values between groups GC e GH (p= 0.292), and the mean values and mean standard error (X±MSE) were 4.9 ±3.1 µg/mL e 7.5 ±3.0 µg/mL, respectively... (Complete abstract click electronic access below) / Doutor

Thesis (Ph. D.)--Case Western Reserve University, 2008. / [School of Medicine] Department of Biochemistry. Includes bibliographical references.

INTRODUCTION Tuberculosis remains a major public health threat globally and the Human Immunodeficiency Virus (HIV) pandemic afflicting developing and developed countries has resulted in enormous increases in tuberculosis infections worldwide. Researchers have previously documented very low plasma vitamin C levels in patients with active pulmonary tuberculosis. This was attributed to a number of factors including: accelerated turnover of vitamin C, shifts in plasma concentrations, increased collagen formation and tissue repair and decreased vitamin C intake. Vitamin C appears to have a role in steroid-genesis and catecholamine synthesis. Decreased plasma vitamin C levels may therefore impact on the stress hormone response and acute phase reaction of patients with active tuberculosis. AIM The primary aims of the study were to measure plasma vitamin C levels, as well as stress hormone levels and acute phase reaction in patients with newly diagnosed active pulmonary tuberculosis and control patients (without tuberculosis), to determine if there was any relationship between vitamin C levels and the levels of these other variables. METHODS AND MATERIALS This was a prospective study of seventy one (71) consecutive patients admitted to Helen Joseph Hospital (between March and October 2002) with newly diagnosed active pulmonary tuberculosis and eighty nine (89) control patients with medical conditions other than tuberculosis. Demographic, clinical and laboratory data were captured and analyzed using SPSS 7.5 soft-ware. Continuous variables were analyzed using students t-test. Categorical data were analyzed by non parametric analysis and Pearsons linear regression model was used to determine the correlation between vitamin C and the other variables in the two groups. RESULTS There were no differences in race, gender, age, suburb of residence and occupational distributions in the study group with tuberculosis compared to the control group. There were more smokers and consumers of alcohol in the control group (54 and 62 patients respectively) than in the study group (28 and 31 patients respectively). The study patients had lower blood pressure (average 90/40 mmHg versus 100/60 mmHg of controls), higher mean pulse rate (101.87 ± 15.14 beats/minute versus 82.92 ± 8.88 beats/minute, p< 0.01), higher mean temperature (38.66 ± 0.67oC versus 37.14 ± 0.44oC, p< 0.01), and lower body mass index (18.29 ± 3.80 Kg/ M2 versus 23.20 ± 5.35 Kg/ M2, p< 0.01). Laboratory data comparing study group and controls also showed marked differences as follows: White cell count (WCC) 8.68×106 / L ± 5.44 versus 11.00×106 / L ± 4.94, p = 0.01; Haemoglobin 9.56gm / dl ± 1.93 versus 12.92gm / dl ± 2.34, p < 0.01 and platelet count 369.21× 106/L ± 190.71 versus 295.94×106 / L ± 94.64, p = 0.01. White cell vitamin C levels (normal range – 20-40 μg/108 leucocytes) were low in half of the patients in both groups (study patients mean 29.85 ± 28.70μg/108 leucocytes versus controls 31.39 ± 30.24μg/108 leucocytes, p = NS). Plasma vitamin C levels were reduced (normal range 10-20 mg/ml) in both groups but more so in the controls (mean 3.87 ± 2.82 mg/ml versus 4.81 ± 3.21 mg / ml in study patients, p= 0.053). Mean cortisol levels were slightly higher in the study patients (448.11 ± 197.41ηmol/L) than controls (392.70 ± 191.25ηmol/L, p = NS). Norepinephrine levels were slightly higher in the study patients than controls (study patients mean 2531.61 ± 2043.60 ρmol/L versus 2178.98 ± 1719.98 ρmol/L of controls, p = NS). Dopamine levels were higher in the study patients than in the controls (468.42 ± 377.57 ρmol/L in study patients versus 293.37 ± 355.84 ρmol/L in controls, p = 0.01). Epinephrine levels were higher in the controls (control patients mean 680.64 ± 743.78 ρmol/L versus 449.41 ± 380.04 ρmol/L of the study patients, p = 0.03). Ferritin levels were much higher in the study patients compared with controls (study patients mean 3005.87 ± 5023.26 μg/L versus 466.51 ± 1774.76 μg/L of the controls, p<0.01) as were CRP levels (125.91 ± 54.77 mg/L in the study patients versus 77.22 ± 81.17 mg/L in the controls, p=0.01). Mean urine cotinine levels were 16.42 ± 24.26μM/L for controls and 9.28 ± 11.59 μM / L for the study patients (p=0.027). Correlation studies did not show any significant differences between the different variables. There was an inverse correlation between CRP levels and urine cotinine levels in the control group (R squared=0.058 and p= 0.024). DISCUSSION There were no differences in the demographic profile of the two groups. Smoking and alcohol consumption were more common in the control group than in the study patients. Over 90 % of patients in both groups had low plasma vitamin C levels, while half of the patients in each group had low white cell vitamin C levels. The low levels of vitamin C could be due to some of the reasons given above or possibly due to the fact that generally there are low levels in Africans for reasons that are not apparent. The control group had increased mean urine cotinine levels suggesting a possible influence of cigarette smoking on vitamin C homeostasis in these patients. In both groups, the majority of patients had normal cortisol levels as well as normal to high catecholamine levels. Also, Ferritin and CRP levels were much higher in the study group than in the controls. The low levels of vitamin C did not, however, have any relationship with stress hormone levels and acute phase reactants. CONCLUSION This study has reaffirmed low plasma and white cell vitamin C levels in patients with new onset pulmonary tuberculosis but has also found low levels in control patients with diseases other than pulmonary tuberculosis. The study demonstrates adequate stress hormone responses in tuberculosis patients, which was not different from non- tuberculosis patients. Acute phase responses were found to be of higher magnitude in tuberculosis patients than in the controls. There were, however, no correlations between plasma vitamin C and stress hormones or acute phase reactants.

The purpose of this study was to investigate whether or not gender differences may be present in the expression of a number of urinary proteins which may serve as markers of inflammation and oxidative stress. Males and females have different patterns of illness and different life spans, suggesting basic biological traits exert significant control on the incidence of rhabdomyolysis, renal failure, atherosclerosis, myocardial ischemia, myocardial contraction band formation, autoimmune disorders and general inflammatory diseases. Men are at greater risk for cardiovascular disease; however women, particularly elderly women, have higher fatality rates due to heart failure. Renal diseases progress far more quickly in men, possibly due to testosterone. Men also have higher kidney bulk related to androgen expression. Gender disparity may be most obvious in autoimmune disorders; of the estimated 8.5 million people diagnosed with autoimmune disorders, approximately 80% are women. Hashimoto’s thyroiditis, the most common form of hypothyroidism, is up to 10 times more common in women. Systemic Lupus Erythematosus (SLE), an autoimmune disease characterized by acute and chronic inflammation, is 9 times more common in women. Rheumatoid arthritis (RA), an autoimmune disease affecting approximately 1.3 million people in the United States, is four times more common in women. Diabetes mellitus (DM), affecting more than 17 million people – the majority of which are women, is linked to microvascular and macrovascular diseases such as kidney failure, strokes and atherosclerosis. These conditions are linked to physiological changes that may alter the expression of certain biomarkers of inflammation and oxidative stress. Over the past several decades, it has become increasingly clear that the role of diet, smoking, and other lifestyle choices clearly influence the etiology and pathophysiology of these diseases. The use of drugs, both licit and illicit, has been clearly linked to many of these diseases. Illicit substances, particularly cocaine, have been demonstrated to produce pathophysiological changes to many systems in the body which can greatly influence the progression of existing and drug-induced disease states leading to systemic damage. A relationship between the expression of markers of inflammation, oxidative stress, cardiac damage, or other systemic injury, gender and cocaine use has not been clearly established. Urine is an important medium for assessment of general health status. It has classically been used to monitor disease states; glucosuria as an indicator of diabetes and renal dysfunction, microorganisms signifying urinary tract or bladder infection, and biomarkers such as human chorionic gonadotropin to confirm pregnancy. Recently urine has been used to assess biomarker expression and disease states. Urine is an ideal clinical tool for toxicological screens; it is readily accessible, non invasive and typically supplied in sufficient quantity to accommodate multiple tests. In this study, urine specimens were collected and analyzed for creatinine, cocaine, total protein, aldosterone, c-reactive protein (hsCRP), myeloperoxidase (MPO), microalbumin (MAB), neutrophil gelatinase-associated lipocalin (NGAL), heat shock protein 90α (hsp90α), vascular endothelial growth factor (VEGF), myoglobin, pro atrial natriuretic peptide (proANP) and interleukins 1α, 1 β , and 6 using ELISA and colorimetric assays. Urine specimens that tested negative for all illicit substances in the standard National Institute on Drug Abuse (NIDA) 10 panel showed differences in a number of these biomarkers which strongly suggested significant differences between males and females for aldosterone, IL1α and IL1β. In addition, significance is suggested for MPO and CRP. Although sex specific differences in serum expression have been noted for some of the markers in both animal and human models, this has not been previously demonstrated in human urine. This may have implications for what is typically referred to as ‘normal’ values. Gender specific differences were not apparent in urine specimens that tested positive for cocaine. Also, in males only, the levels of myoglobin and aldosterone significantly increased.

Orientador: Helena Zerlotti Wolf Grotto / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-14T15:00:17Z (GMT). No. of bitstreams: 1 Anjos_BarbaraLimados_M.pdf: 1374406 bytes, checksum: ec94e23babc71511d9a13089be02f29c (MD5) Previous issue date: 2009 / Resumo: Introdução: A resposta de fase aguda é composta de uma complexa rede de eventos envolvendo diversas células e mediadores pró e anti-inflamatórios. O diagnóstico clínico dessa condição nem sempre é facilmente obtido. O desempenho de diversos marcadores da resposta aguda é constantemente avaliado em variados grupos de doença, com o objetivo de otimizar o diagnóstico, proporcionando ao médico e ao paciente uma definição terapêutica precisa e em curto espaço de tempo. Além de parâmetros como os relacionados aos leucócitos e velocidade de hemossedimentação, a determinação de proteínas como a proteína C reativa (PC-R) e a amilóde sérico A (SAA) são propostas como úteis na detecção da presença do processo inflamatório/infeccioso. O objetivo do presente estudo foi a avaliação de alguns marcadores da resposta inflamatória, comparando a eficiência entre eles na identificação de crianças atendidas num Serviço de Urgência com suspeita de apresentarem inflamação ou infecção, além disso, nas crianças com quadro suspeito de dengue avaliar tais parâmetros. Materiais e métodos: Foram estudadas 90 crianças com idade entre 1 mês e 10 anos atendidas na Unidade de Emergência Referenciada do Hospital das Clínicas da UNICAMP. De acordo com os dados clínicos, consulta dos prontuários e exames subsidiários, essas crianças foram divididas em grupo inflamatório (n= 17) e infeccioso (n= 66) e dentro do infeccioso em sugestivo de infecção bacteriana, viral e dengue. Foram avaliados os seguintes parâmetros: contagem de leucócitos e presença de granulócitos imaturos por equipamentos hematológicos automatizados e por observação microscópica do esfregaço de sangue; dosagem de PC-R por 2 sistemas, determinação dos níveis de SAA e IL-6 por kits comerciais. Resultados: O melhor marcador do processo inflamatório/infeccioso foi a PC-R (> 80% de positividade pelos 2 sistemas), seguido da SAA (73,3%) e da VHS (72,1%). A contagem de leucócitos e a detecção de granulócitos imaturos revelaram desempenho inferior ao recomendado, não sendo úteis para o diagnóstico. Não houve diferença nos valores de leucócitos, VHS, PC-R, SAA e IL-6 entre os grupos inflamatório e infeccioso, mas apresentaram níveis superiores no grupo bacteriano quando comparado ao viral a contagem de leucócitos, níveis de PC-R e SAA. Nos pacientes com suspeita clínica de dengue apresentaram níveis inferiores de leucócitos e plaquetas e quanto aos marcadores séricos a VHS apresentou valores significativamente diminuídos. Conclusões: A PC-R foi o biomarcador com melhor desempenho no grupo de crianças estudado, enquanto as informações fornecidas pelo hemograma identificaram o menor número de pacientes. Os resultados da SAA foram semelhantes aos da PC-R sendo, portanto, discutível a sua utilização na rotina diagnóstica. De acordo com os nossos dados, deve ser encorajada a associação da interpretação de mais de um parâmetro na detecção do processo inflamatório/infeccioso. / Abstract: Introduction: the acute-phase response consists of a complex network of events involving various cells and pro anti-inflammatory mediators. The clinical diagnosis of this condition is not always easily obtained. The performance of several markers of the acute response is constantly evaluated in different groups of diseases, aiming to optimize the diagnosis and in order to establish a precise therapeutic in a short time. In addition to parameters such as those related to leukocyte and erythrocyte sedimentation rate (ESR), the determination of levels of proteins such as C-reactive protein (CR-P) and serum amyloid A (SAA) are proposed as useful in detecting the presence of the inflammatory/infection process. The objective of this study was the assessment of some markers of inflammatory response, comparing the efficiency among them in identifying children from the emergency room with infection or inflammation suspicious. Materials and methods: a total of 90 children aged between 1 month and 10 years with a clinical suspicious to have inflammation or infection diseases attended in the Emergency Unit of Clinical Hospital of the UNICAMP were enrolled. According to clinical data, medical records and subsidiary exams, these children were divided into inflammatory (n = 17) and infectious groups (n = 66). Infectious group was subdivided into bacterial or viral infection. The following parameters were evaluated: white blood cell count and presence of immature granulocytes by automated hematology equipment and microscopic observation of blood smears, determination of PC-R by 2 systems, and measurement of SAA and IL-6 levels by commercial kits. Results: the best marker of the inflammatory/infection process was the CR-P (> 80% positivity from both systems), followed by SAA (73.3%) and ESR (72.1%). The leukocyte count and the detection of immature granulocytes showed performance below the recommended and, consequently not useful for diagnosis. There was no difference in the values of leukocytes, ESR, CR-P, SAA and IL-6 between inflammatory and infectious groups, but higher leukocyte counting, PC-R and SAA levels were observed in the bacterial group when compared to the viral one. Conclusions: The CR-P was the biomarker with better performance in the group of children studied, while information supplied by the blood cells analysis identified the smallest number of patients. The results of SAA was similar to PC-R; therefore is questionable the SAA measurement utility in routine diagnosis. According to our data, the association of more than one parameter in the detection of the inflammatory/ infection response should be encouraged. / Mestrado / Ciencias Biomedicas / Mestre em Ciências Médicas

Orientador: Luiz Cláudio Nogueira Mendes / Coorientador: Juliana Regina Peiró / Banca: Valéria Marçal Félix de Lima / Banca: José Paes de Oliveira Filho / Resumo: Objetivando-se avaliar as concentrações séricas de Interleucina 6 (IL-6) e proteinograma de ovinos submetidos à endotoxemia experimental. Dez ovinos (4 anos) foram divididos em dois grupos, Grupo Controle (GC, n=4) inoculados com NaCl 0,9 %, IV e Grupo Tratado (GT, n= 6) inoculados com 400 ng/Kg de LPS de Escheria coli. O exame físico foi realizado, imediatamente antes da inoculação (M0), bem como a coleta de sangue para perfil hematológico e bioquímico, dosagem de IL-6 e proteinograma. As amostras foram coletadas em M0 e após 2, 4, 6, 12, 24, 36, 48 e 60 horas, de realizada a inoculação. A dosagem de IL-6 foi feita pelo método de ELISA e o proteinograma pelo método de eletroforese em poliacrilamida com dodecil sulfato de sódio (SDS-PAGE), para o perfil hematológico utilizou-se contador de células automático (BCVet- 2800), o perfil bioquímico foi realizado utilizando-se kits comerciais (Labtest®) e por fim, a concentração de glicose foi mensurada por meio de um monitor de glicemia (Breeze 2, Bayer®). Constatou-se um aumento na concentração de IL-6 60 horas pós-inoculação de LPS. O pico febril ocorreu quatro horas pós-indução endotoxêmica. Constatou- se leucopenia com neutropenia e redução na concentração da proteína total, albumina e glicoproteína ácida duas horas após a administração de LPS, acompanhados por uma elevação inicial na concentração de glicose, seguida de redução, seis horas pós-inoculação. Concluiu-se que a dosagem de Interleucina 6 e o proteinograma sérico são métodos de diagnósticos eficientes para detectar e monitorar a progressão e gravidade de processos inflamatórios provenientes de uma endotoxemia induzida experimentalmente em ovinos / Abstract: Aiming to evaluate serum concentrations of interleukin 6 (IL-6) and proteinogram of sheep undergoing experimental endotoxemia. Ten animals (4 years old) were divided into two groups, Control Group (CG, n= 4) inoculated with NaCl 0,9%, IV and Treated Group (TG, n= 6) inoculated with 400 ng/Kg of LPS from Escheria coli. The physical examination was performed immediately before inoculation (M0), as well as blood collection for hematological and biochemical profiles, dosage of IL-6 and proteinogram. Samples were collected at M0 and after 2, 4, 6, 12, 24, 36, 48 and 60 hours after of inoculation. The dosage of IL-6 was done by ELISA and the proteinogram by method of eletrophoresis in polyacrylamide sodium dodecyl sulphate (SDS-PAGE), for hematological profile was used automatic cell counter (BC-2800Vet), the biochemical profile was performed using commercial kits (Labtest®) and the glucose concentrations was measured using glucose monitor (Breeze2, Bayer®). It was found an increase in the dosage of IL-6 60 hours after LPS injection. The fever peak occurred four hours after induction of endotoxemia. There was leukopenia, with neutropenia and reduction in concentration of total protein, albumin and acid glycoprotein two hours after LPS administration, accompanied by an initial increase in glucose concentrations followed by a reduction six hours post-inoculation. It was conclude that the dosage of IL-6 and the proteinogram are effective diagnostic methods to detect and monitor the progression and severity of inflammatory processes from an experimentallay induced endotoxemia in sheep / Mestre