A leptospirose é uma zoonose de ampla distribuição mundial, causada pela infecção por sorovares patogênicos do gênero Leptospira. Assim como outras espécies de animais acometidos, os cães que sobreviverem à fase aguda da doença podem se tornar portadores, excretando a bactéria através da urina. Algumas alterações no hemograma, bioquímica sérica e urinálise, juntamente com o histórico do paciente e fatores de risco, auxiliam na suspeita da doença; porém, o diagnóstico definitivo é realizado através de testes mais específicos. Estes testes incluem sorologia, técnicas moleculares como a reação em cadeia da polimerase (PCR) e cultura para isolamento do sorovar. O presente trabalho caracterizou e comparou a leptospirose em três populações caninas de Porto Alegre. Foram avaliados 33 cães com suspeita da doença, atendidos no Hospital de Clínicas Veterinárias (HCV) da Universidade Federal do Rio Grande do Sul (UFRGS); 65 cães provenientes do Centro de Controle de Zoonoses (CCZ) de Porto Alegre; e 155 cães residentes no bairro Arquipélago na zona urbana de Porto Alegre, onde existe uma alta incidência de leptospirose humana. O diagnóstico da leptospirose canina foi baseado na sorologia e PCR no soro e urina. Um total de 14,6% (37/253) dos cães apresentaram resultado positivo na PCR no sangue (leptospiremia) e 14,2 % (36/253) na urina (leptospirúria). Em relação à sorologia, 48,2% (122/253) foram positivos para um ou mais sorovares. Os sorovares mais prevalentes foram canicola, icterohaemorrhagiae e copenhageni. A presença de ratos no ambiente foi associada a leptospirúria (P=0,02). Na população do HCV, o aumento da creatinina sérica (P=0,009), icterícia (P=0,004) e glicosúria (P=0,04) foram associados com leptospirúria. Apesar destas associações encontradas, observou-se que a ausência de sinais clínicos ou de alterações no hemograma, bioquímica sérica ou urinálise não excluíram a infecção (P>0.05). Em um segundo estudo, foi investigada a eficácia da doxiciclina na eliminação do estado de portador renal em quatro cães assintomáticos. Destes, três estavam infectados com o sorogrupo Canicola e um com o sorogrupo Icterohaemorrhagiae. Os cães foram acompanhados por 30 dias após o início do tratamento, e a ausência de leptospiras na urina foi confirmada através de três resultados seriados de PCR negativa em cada cão. Finalmente, valor preditivo da proteína C reativa (C-RP) na leptospirose foi investigado em 62 cães, comparando sua concentração sérica e urinária com os resultados de sorologia e PCR. Sorologia positiva foi associada com C-RP urinária (P= 0,038). Houve apenas associação fraca entre proteína C-reativa sérica e PCR no sangue (área sob a curva= 0,68), e não foi observada associação entre C-RP urinária e PCR na urina. Não foram observadas vantagens de se incluir a C-RP como um teste de triagem para leptospirose em cães. As informações obtidas com os estudos aqui citados mostra a importância do diagnóstico definitivo, preferencialmente realizado através de PCR; a necessidade de se testar cães expostos a fatores de risco, independente de seu estado aparente de saúde; a importância de medidas sanitárias para a prevenção da doença e o tratamento adequado para que se elimine o possível estado de portador renal dos cães. / Leptospirosis is a zoonosis of worldwide distribution, caused by infection with pathogenic serovars of the genus Leptospira. As other affected species of animals, the dogs that survive the acute phase of the disease can become carriers, excreting the bacteria in the urine. Some alterations in blood count, serum biochemistry and urinalysis, along with patient history and risk factors, may contribute to a presumptive diagnosis, but the definitive diagnosis is made using more specific tests. These tests include serology, molecular techniques like polymerase chain reaction (PCR) and culture for the serovar isolation. The present study characterized and compared leptospirosis in three canine populations of Porto Alegre, RS. Thirty three dogs with suspected disease were evaluated at the Veterinary Hospital of the Federal University of Rio Grande do Sul, 65 dogs from the Control Center of Zoonoses from Porto Alegre and 155 dogs from Archipelago neighborhood, where there is a high incidence of human leptospirosis. The diagnosis of canine leptospirosis was based on serology and PCR in serum and urine. A total of 14.6% (37/253) of dogs tested positive in PCR in blood (leptospiremia) and 14.2% (36/253) in the urine (leptospiruria). With regard to serology, 48.2% (122/253) were positive for one or more serovars. The most prevalent serovars were canicola, icterohaemorrhagiae and copenhageni. The presence of rats in the environment was associated with leptospiruria (P = 0.02). In the Veterinary Hospital population, increased serum creatinine (P = 0.009), jaundice (P = 0.004) and glucosuria (P = 0.04) were associated with leptospiruria. Despite these associations, it was observed that the absence of clinical signs or changes in blood count, serum biochemistry and urinalysis did not exclude infection (P> 0.05). In a second study, we investigated the effectiveness of doxycycline to eliminate the carrier state in four asymptomatic dogs. Three were infected with serogroup Canicola and one with serogroup Icterohaemorrhagiae. The dogs were followed for 30 days after starting treatment, and the absence of leptospires in urine was confirmed by three serial results of negative PCR in each dog. Finally, the predictive value of C-reactive protein (C-RP) in leptospirosis was investigated in 62 dogs, comparing its serum and urinary concentrations with serology and PCR. Seropositivity was associated with urinary C-RP (P = 0.038). There was only a weak association between C-RP and serum PCR in blood (AUC = 0.68), and no association was found between urinary C-RP and PCR in urine. There were no advantages to include the C-RP as a screening test for leptospirosis in dogs. The information gathered from the studies cited here shows the importance of the definitive diagnosis, preferably performed by PCR; the need to test dogs exposed to risk factors, regardless of their apparent health condition, the importance of sanitary surveillance for the prevention of the disease, and adequate treatment to eliminate the carrier state.

Introdução: Neutropenia febril é uma emergência médica que demanda um diagnóstico precoce e administração de antibióticos o mais breve possível. A procalcitonina (PCT) é um marcador inflamatório que vem sendo utilizado como um indicador de infecção bacteriana grave. A detecção precoce do quadro séptico é difícil, principalmente numa população heterogênea como no caso dos neutropênicos febris. A possibilidade de um único exame laboratorial poder identificar precocemente os quadros de sepse contribuiria de forma significativa para melhorar o prognóstico destes pacientes. Objetivo: Avaliar os níveis de PCT como marcador de infecção sistêmica comparados aos níveis de proteína C-reativa (PCR) em pacientes neutropênicos febris. Métodos: Foram estudadas amostras de 65 pacientes com a finalidade de determinar as concentrações séricas de PCT, PCR e outros parâmetros hematológicos em três momentos diferentes: antes da febre, no momento da febre e 72 após o término da febre. Os pacientes foram divididos inicialmente em quatro grupos: com infecção sistêmica comprovada laboratorial ou clinicamente (I), com febre de origem indeterminada - FOI- (II), com infecção localizada (III) e com infecção fúngica confirmada (IV). Posteriormente, os grupos I e IV foram denominados de 1 (com infecção sistêmica) e os grupos II e III de 2 (sem infecção sistêmica). Treze pacientes não apresentaram febre durante a internação sendo excluídos da comparação PCT/PCR. Resultados: A concentração de PCT mostrou estar associada com o diagnóstico de infecção grave e neutropenia febril. Não houve correlação entre os níveis de PCT e PCR. Conclusão: Fica evidente que a PCT demonstrou ser um marcador útil para o diagnóstico de infecção sistêmica em neutropenia febril, sendo provavelmente, superior à PCR. Pode-se caracterizar a PCT como um auxiliar de indicador de infecção sistêmica já no primeiro dia de apresentação da febre. A PCT, ao contrário da PCR, foi capaz de distinguir entre infecção sistêmica e infecção localizada ou febre de origem indeterminada, tendo boa capacidade diagnóstica. Entretanto, a PCT não se correlacionou com o prognóstico, possivelmente pelo pequeno tamanho da amostra, apesar da curva ROC da PCT do grupo com infecção sistêmica com evolução para óbito ter delimitado uma área estatisticamente diferente da esperada pelo acaso. / Introduction: Febrile neutropenia is a medical emergency that calls for a precocious diagnosis and the administration of antibiotics as soon as possible. The procalcitonin (PCT) is an inflammatory marker that has been used as an indicator of severe bacterial infection. Considering that neutropenic population is heterogeneous, an early and only reliable laboratory test that could identify septic patients would be of great value to improve its outcome. Objective: Assess the diagnostic value of PCT as a marker of systemic infection, comparing with C-reactive protein (CRP) levels in febrile neutropenia. Methods: Sixty-five adults patients were enrolled in the study. Blood sample was collected in order to determine the serum concentrations of PCT, CRP and other hematological parameters at three different moments: before the beginning of fever, at the onset of fever and 72 hours after cessation of it. Firstly, the patients were divided into four groups: with clinical or laboratorial proven systemic infection (I), with fever of undetermined origin (FUO) (II), with localized infection (III) and with proven fungal infection (IV). After that, the groups I and IV were named as 1:- with systemic infection. The groups II and III were named 2:- without systemic infection. Thirteen patients did not present fever during evolution and were excluded from the PCT/PCR comparison among febrile patients. Results: The PCT concentration showed it was associated with the diagnosis of severe infection in febrile neutropenia. No correlation could be found between the levels of PCT and CRP. Conclusion: PCT seems to be an useful marker for the diagnosis of systemic infection in febrile neutropenia, probably better than CRP. We could assume that PCT could indicate systemic infection at the very first day of the outcome of fever. Only PCT (and not CRP) could be able to distinguish between systemic infection and localized infection or FUO, with excellent diagnostic capacity. However none of the markers (PCT and CRP) could be correlated to prognosis, possibly due to the small size of the sample. Nevertheless, PCT ROC curve for evolution to death as a result of systemic infection limit an area under the curve statistically different that expected by chance.

Introdução: A readmissão de pacientes nas unidades de terapia intensiva (UTIs) está associada a piores desfechos durante a internação hospitalar. Através da análise de preditores existe a possibilidade de identificar os pacientes sob risco de readmissão e planejar possíveis intervenções visando melhorar a segurança destes pacientes. Objetivos: Avaliar o desempenho da saturação venosa central (SvcO2), do lactato, do déficit de bases (DB), dos níveis de proteína C reativa (PCR), do Sequential Organ Failure Assessment (SOFA), do Stability and Workload Index for Transfer (SWIFT) escore do dia da alta da UTI como preditores e fatores de risco para readmissão de pacientes na unidade de terapia intensiva (UTI), além de verificar a frequência de readmissões na UTI. Métodos: O estudo avaliou pacientes criticamente enfermos internados consecutivamente na unidade de terapia intensiva do Hospital Nossa Senhora da Conceição que receberem alta da UTI, no período entre Agosto/2011 e Agosto/2012. Resultados principais: Utilizando análise multivariada o SOFA e o SWIFT da alta foram identificados como fatores de risco independentemente associados à readmissão na UTI. Entretanto, com uma área sob a curva receiver operating characteristic (ROC) de 0,63 e 0,66 respectivamente, estes escores podem não ter grande aplicabilidade clínica em nossa população. A PCR, a SvcO2, o DB e o lactato não estão associados a readmissão de pacientes críticos. Conclusões: Apesar do grande impacto clínico e econômico associado à readmissão de pacientes na UTI, nossa capacidade para discriminar os pacientes sob risco de readmissão e objetivar os critérios de alta dos pacientes críticos segue inadequada. / Background: Readmission of patients in intensive care units (ICUs) is associated with worse outcomes during hospitalization. Possibly, identifying patients at risk for readmission through the analysis of predictors, some intervention may be planned for the security of these patients. Objectives: To evaluate the performance of central venous oxygen saturation (ScvO2), lactate, base deficit (BD), C-reactive protein (CRP), the Sequential Organ Failure Assessment (SOFA) score and the Stability and Workload Index for Transfer (SWIFT) score at the day of discharge from the intensive care unit (ICU) as predictors and risk factors for readmission or unexpected death among critically ill patients and to identify the frequency of readmissions in the ICU. Design: Prospective observational study. Location: academic tertiary hospital in Brazil. Patients: A total of 1,360 patients admitted to a 59 beds medical-surgical ICU from August 2011 to August 2012. Methods: We compared the characteristics and laboratory data of readmitted patients and not readmitted patients discharged from the ICU. Through multivariate analysis we identified potential risk factors independently associated with readmission. Main results: SOFA and SWIFT were identified as significant risk factors for ICU readmission. However, with an area under the ROC curve of 0.63 and 0.66, these scores would appear to have limited clinical applicability in our population. CRP, ScvO2, BD and lactate were not associated with readmission of critically ill patients. Conclusions: Perfusion and inflammatory markers are not good predictors of ICU readmission. Despite the clinical and economic impact associated with readmission in ICU, our ability to predict which patients will be readmitted is still inadequate.

Introdução: Estudos relatam uma maior prevalência de fatores de risco cardiovascular desfavoráveis em indivíduos com migrânea, mas os resultados são conflitantes. Objetivos: Investigar a presença de fatores de risco cardiovascular em mulheres adultas portadoras de migrânea e comparar com controles sadios. Métodos: Cinquenta e nove mulheres participaram deste estudo caso-controle. Sujeitos do estudo foram divididos em grupos de pacientes eutróficas e obesas e comparadas a grupos controle pareados por idade e índice de massa corporal. Níveis séricos de lipídios, glicemia de jejum, insulinemia, resistência à insulina, pressão arterial, tabagismo, atividade física, escore de Framingham, proteína creativa, história familiar de doenças cardiovasculares (DCV), distúrbios do sono, depressão e ângulo de fase por bioimpedância elétrica foram investigados. Resultados: As pacientes obesas com migrânea apresentaram menores valores de HDL-c do que pacientes e controles eutróficas; a resistência à insulina e a insulinemia foram relacionadas à obesidade; todas as pacientes com migrânea eram sedentárias, independentemente de seu estado nutricional; o escore de Framingham foi mais elevado em pacientes obesas com migrânea; pacientes com migrânea tiveram maiores escores de depressão; assim como curta duração do sono, especialmente as obesas. Conclusão: Resultados preliminares apontam nitidamente para sedentarismo e depressão e possíveis distúrbios do sono em pacientes com migrânea, além de plausível sobreposição de efeito da obesidade e da migrânea sobre os níveis séricos de HDL-c e escore de risco de Framingham. / Background: Studies have reported a higher prevalence of unfavorable cardiovascular risk factors amongst migraineurs, but results have been conflicting. Objective: To investigate cardiovascular risk factors in adult women with migraine and compare with health controls. Design and Methods: Fifty nine adult female probands participated in this case-control study. The study group was divided into normal weight and obese migraineurs and control groups matched by age and body mass index. Serum levels of lipids, fasting glucose, insulinemia, insulin resistance, blood pressure, smoking, physical inactivity, Framingham risk, C-reactive protein, family history of cardiovascular disease, sleep disturbances, depression and bioelectrical impedance phase angle were investigated. Results: Obese migraineurs had lower HDL-c than eutrophic controls and migraineurs, insulin resistance and insulinemia were obese-related, all migraineurs were sedentary irrespective of nutritional status, Framingham risk score was higher in obese migraineurs, migraineurs had higher depression scores and shorter sleep duration, obese migraineurs and also migraineurs taken together had worst sleep quality scores. Conclusion: Preliminary results points to marked inactivity, depression and some sleep disturbance in migraine patients, and also probably overlapped effects of obesity and migraine in HDL-c levels and 10-year Framingham general cardiovascular disease risk.

The anti-pneumococcal function of native C-reactive protein (CRP) involves its binding to phosphocholine molecules present on Streptococcus pneumoniae and subsequent activation of the complement system. However, when pneumococci recruit complement inhibitory protein factor H on their surface, they escape complement attack. Non-native forms of CRP have been shown to bind immobilized factor H. Accordingly, we hypothesized that modified CRP would bind to factor H on pneumococci, masking its complement inhibitory activity, allowing native CRP to exert its anti-pneumococcal function. As reported previously, native CRP protected mice from lethal pneumococcal infection when injected 30 minutes before infection but not when injected 24 hours after infection. However, a combination of native and mutant CRP was found to protect mice even when administered 24 hours after infection. Therefore, it is concluded that while native CRP is protective only against early-stage infection, a combination of native and mutant CRP offers protection against late-stage infection.

Bisphenol A (BPA), a widely used chemical in plastic, has drawn wide attention due to its presence in many consumer products and the environment. The purpose of this study was to examine the association between urinary BPA and the reporting of cardiovascular diseases (CVD), and then to examine the effect of C-reactive protein (CRP) as a moderating variable. The data used in this research were extracted from the National Health and Nutrition Examination Survey collected in 2009-2010. Guided by the advanced epidemiological triangle, analysis involved 2 stepwise binary logistic regressions. The first step suggested that the controls were significant in predicting CVD (Ï?2 (5) = 83.72, p < .001, R2 = .15). The Nagelkerke R2 coefficient of determination indicated that the controls explained approximately 15% of the variance in instances of CVD. The second step of the binary logistic regression included the controls and BPA level in the model together. The regression analysis suggested that the Nagelkerke coefficient of determination (Ï?2 (6) = 83.76, p < .001, R2 = .15) did not increase from the 15% explained by the controls, and BPA level was found to be a nonsignificant predictor of CVD (p = .853). Due to lack of association between BPA and CVD, the analysis was shifted to examine the association between urinary BPA and serum CRP. The association between urinary BPA and serum CRP was also statistically nonsignificant (Spearman correlation coefficient, rs= .06, p = .015). The results may have positive social change by contributing to the body of knowledge on BPA and by increasing scientific scrutiny for substances used in people's daily lives.

<p>Objective - To correlate blood pressure and inflammatory markers with urine albumin analysed with a point-of-care testing (POCT) instrument, nephelometric determination of albumin and creatinine related urine albumin in elderly males.</p><p>Methods and Results - The study population consisted of 103 diabetic and 603 nondiabetic males (age 77 years) in a cross-sectional study in central Sweden. We analyzed urine albumin with a HemoCue® Urine Albumin POCT instrument and a ProSpec® nephelometer and creatinine related urine albumin. There were strong correlation between both systolic and diastolic blood pressure and all three urine albumin methods (p<0.0001). There were also significant correlations between the different urine albumin measurements and SAA, hsCRP and IL-6.</p><p>Conclusions - Hypertension has a strong impact on hyperfiltration in diabetic and nondiabetic elderly males.</p>

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

This thesis examines the effect of surgical weight loss on gut and adipose tissue peptides involved in appetite regulation and energy homeostasis in morbidly obese humans. Roux-en-Y gastric bypass (RYGBP) is the gold standard operation used for effective long-term weight loss and improved health. The exact mechanisms for this outcome are under investigation. We measured ghrelin, a recently discovered hunger hormone, insulin, adiponectin and leptin along with anthropometry measures in 66 morbidly obese patients prior to and 6 and 12 months after RYGBP. Impressive weight loss occurred postoperatively as did alterations in the peptides. Consistent correlations were found between weight, leptin, ghrelin and insulin. The main findings were low ghrelin concentrations in obesity and an increase after RYGBP. We explored inflammatory proteins C-reactive protein (CRP), serum amyloid A and interleukin-6 before and during massive weight loss 6 and 12 months after RYGBP in morbidly obese subjects. The studied proteins declined after surgery and a correlation between CRP and homeostatic model of assessment for insulin resistance, independent of BMI, strongly linked insulin resistance and inflammation. CRP declined most in insulin-sensitive subjects. We examined the excluded stomach mucosa and vagus nerve by measuring gastrin, pepsinogen I (PGI), pancreatic polypeptide (PP) and ghrelin levels during week 1 and year after RYGBP. Ghrelin levels rose with weight loss but declined 24-hours after surgery, like PP, indicating transient vagal nerve damage. Low levels of gastrin and PGI suggest a resting mucosa. We evaluated gut peptides: peptide YY (PYY), glucaogon like peptide-1 (GLP-1), pro-neurotensin (pro-NT) and PP, in lean (young and middle-aged), obese and postoperative RYGBP subjects pre- and postprandially. RYGBP subjects had exaggerated levels of PYY and GLP-1 postprandially and higher basal proNT levels, implying a ‘satiety peptide tone’ that may contribute to the maintenance of weight loss. In summary, RYGBP results in marked weight loss and alterations in gut and adipose tissue peptides involved in appetite regulation and energy homeostasis. These postoperative peptide changes may contribute to impressive weight loss observed after RYGBP.

A novel concept for protein recognition has been developed. The recognition unit is a hybrid molecule obtained by conjugation of a small organic molecule to a synthetic polypeptide selected from a 16-membered set of 42 amino acid residue sequences. The sequences are unordered and have no prior relation to the target proteins. The concept is based on the hypothesis that a small set of sequences capable of hydrophobic interactions, hydrogen bonding and electrostatic interactions can yield a binder for any selected protein, provided that the small molecule shows medium affinity or better and is reasonably selective. The concept has been illustrated by the design, synthesis and evaluation of binders for three different proteins, the C-reactive protein, CRP, human Carbonic anhydrase II, HCAII, and Acetylcholine esterase, AChE. Highly efficient binders for CRP have been developed by conjugation of a derivative of the natural ligand, phosphocholine, to the side chain of one of the amino acids in each polypeptide. The binders in the set show a wide range of affinities for CRP and the tightest binder, 4-C10L17-PC6, binds almost irreversibly. Selected binders have been evaluated in human serum, where they capture CRP with high selectivity.High-affinity binders have been developed for HCAII, and the selectivity evaluated by extraction of the protein from blood. The binder 4-C37L34-B, a polypeptide conjugated to a spacered benzenesulphonamide residue, was able to extract Carbonic anhydrases specifically and to discriminate between the two isoforms of human Carbonic anhydrase. The conjugation of an acridine derivative to a polypeptide via a 14 atom spacer has been shown to yield a binder with high affinity and selectivity for AChE. The selectivity was demonstrated by extraction of AChE from Cerebrospinal fluid. This thesis focuses on the development of a fast and reliable procedure for the construction, selection and evaluation of protein binders, with the ambition to develop a technology that is applicable to the development of binders for all proteins.