Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2016-09-09T12:48:51Z No. of bitstreams: 4 Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 1.pdf: 3581171 bytes, checksum: 0e5521af5f633f8415423063cda690f3 (MD5) Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 2.pdf: 902776 bytes, checksum: 16eddca9ca127b94fc6c55ed6a691300 (MD5) Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 3.pdf: 128655 bytes, checksum: 236893a1942f321bbe3d36424a293450 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-09T15:24:50Z (GMT) No. of bitstreams: 4 Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 1.pdf: 3581171 bytes, checksum: 0e5521af5f633f8415423063cda690f3 (MD5) Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 2.pdf: 902776 bytes, checksum: 16eddca9ca127b94fc6c55ed6a691300 (MD5) Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 3.pdf: 128655 bytes, checksum: 236893a1942f321bbe3d36424a293450 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-09-09T15:24:50Z (GMT). No. of bitstreams: 4 Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 1.pdf: 3581171 bytes, checksum: 0e5521af5f633f8415423063cda690f3 (MD5) Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 2.pdf: 902776 bytes, checksum: 16eddca9ca127b94fc6c55ed6a691300 (MD5) Dissertação - Luma Tatiana Silva Castro - 2016 - Parte 3.pdf: 128655 bytes, checksum: 236893a1942f321bbe3d36424a293450 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-03-02 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Surgeries and anesthesia performed on dogs could cause kidney injury or worsen their renal functions if they are already sick. There is a literature gap in studies discussing post-surgery monitoring and its effects. This study aimed to evaluate dogs who undergone surgeries, in animals considered healthy and in those who had any renal alterations before surgery to evaluate if they developed any renal impairment due to surgery and anesthesia. Dogs were monitored and evaluated before and after surgeries in order to detect if they had any renal injury due to surgery or post-operative procedures. Evaluation took place right after the surgery and after certain time range from the surgery (Two, Seven, 28 and 90 days). Blood and Urine samples were drawn from the dogs to better classify them as healthy or having kidney injury. Consequently, hematological, urinary and blood gases profiles were proceeded. Few dogs with normal renal function that were submitted to surgery had transitory renal injury (23%). Nephropatic dogs that received specific therapy for renal protection did not presented tubular lesion due to surgery. Hypotension occurred in nephropatic dogs despite the use of non-hypotensive drug therapy but in a low frequency and had brief renal impairment. Anesthesia induced hypotension in non nephropatic dogs (54%) for the usage of hypotensive drug therapy. / Procedimentos anestésicos podem contribuir para a disfunção renal no paciente hígido ou mesmo agravar a injúria do nefropata. Na medicina veterinária, há um déficit de literatura sobre a temática relacionando lesão renal decorrente da anestesia e monitorização destes animais, uma vez que o acompanhamento no pós-operatório, na maioria das vezes, não é realizado. O estudo objetivou avaliar a morfofuncionalidade do rim em 23 cães submetidos a cirurgia atendidos no Hospital Veterinário da Escola de Veterinária e Zootecnia da Universidade Federal de Goiás. Exames clínicos e laboratoriais foram feitos para determinação do perfil renal dos pacientes e, posteriormente, determinar se os mesmos seriam incluídos no grupo nefropata ou no grupo não nefropata. Exames de bioquímica sérica e urinária, exame de urina, razão PU/CU, hemogasometria, hemograma e excreção fracionada de sódio e potássio foram procedidos. Os pacientes foram monitorizados com mensurações dos parâmetros clínicos e laboratoriais anterior ao procedimento, ao final da cirurgia, com dois dias, sete, 28 e 90 dias. Constatou-se que cães sem evidência clínica e laboratorial de nefropatia e submetidos a condições adequadas de pré, trans e pós-operatório houve lesão tubular secundária a anestesia foi transitória e em poucos pacientes (23%). Cães nefropatas estabilizados e submetidos protocolos diferenciados no pré, trans e pósoperatório, não apresentaram indicativo de lesão tubular secundária a anestesia. Na cirurgia, os cães nefropatas (30%) submetidos a protocolos anestésicos sem acepromazina, apresentam menor ocorrência de hipotensão que os não nefropatas (54%), submetidos a protocolos anestésicos com acepromazina. Hipotensão anestésica afeta a integridade renal de forma transitória.

A cistatina C sérica tem sido apontada como um marcador de filtração glomerular. Neste trabalho realizamos a validação de um método específico e automatizado, a imunonefelometria, mensurando os níveis séricos de cistatina C através do nefelômetro da empresa Behring (BN II). O ensaio perfaz o intervalo de referência de 0.23-7.25 mg/L, até sete vezes acima dos limites considerados normais. A imprecisão intra e interensaio foram de 8,73% and 5,38% , respectively. A recuperação analítica de cistatina C após adição de controle foi entre 86,7 % e 98% (média 92,3%). A estabilidade da cistatina C a temperatura ambiente, sob refrigeração e sob congelamento foi testada. A perda mais significativa foi encontrada nas amostras armazenadas sob temperatura ambiente, onde foi perdido até 10% da concentração inicial. Nós encontramos CV de 14,79 % para sensibilidade analítica. Durante todo o processo nós comparamos os resultados com o controle de qualidade e obtivemos bons resultados. Depois destes testes, nós comparamos as correlações em 3 grupos de pacientes transplantados renais sob diferentes esquemas de imunossupressão (n=197) [azatioprina (n=36), micofenolato mofetil (n=131) ou sirolimus (n=30)], entre as equações de estimativa de filtração glomerular( Cockroft Gault, Nankivell e MDRD) e cistatina C sérica ou creatinina sérica. Nós concluimos que o ensaio nefelométrico cistatina C pode perfeitamente ser adequado à nossa rotina laboratorial e as correlações entre creatinina sérica e as diferentes equações de estimativa de filtração glomerular são melhores do que quando comparamos as mesmas à cistatina C nos 3 grupos independentemente da terapia imunossupressora utilizada. / Serum cystatin C has been suggested as a marker of glomerular filtration rate (GFR). We describe a validation of an automated and rapid particle-enhanced nephelometric immunoassay (PENIA) for measuring serum cystatin C on the Behring nephelometer (BN II). The assay covers the range 0.23-7.25 mg/L, up to seven times the upper limit of normal. The intra- and interassay imprecision are 8,73% and 5,38% , respectively. The analytical recovery by cystatin C addition between 86,7% and 98% (mean 92,3%). The estability of cistatyn C room temperature, refrigerator temperature and frozen temperature was tested. The higher lost was when we stored sample in a room temperature, when we can lost until 10% of initial concentration. We found CV of 14,79 % for analytical sensibility. During all the process we compare the results with a quality control and we obtained good results. After this validation, we have compared the correlation, in 3 different patients groups after renal transplant (n=197) were using different imunossupressors [azatioprine (n=36), micophenolic acid (n=131) or sirolimus (n=30), between glomerular filtration equations (Cockroft Gault, Nankivell and MDRD) and cystatin C or creatinine serum levels. We concluded cystatin C assay may be perfectly used in our laboratory and the correlation between serum creatinine and glomerular filtration equations are better then cystatin C at the same groups independent of imunosupressor therapy.

Orientador: José Antonio Rocha Gontijo / Tese (doutorado) - Universidade Estaual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-20T13:09:43Z (GMT). No. of bitstreams: 1 Lima_MarceloCardosode_D.pdf: 7673135 bytes, checksum: e538dba1f2c8583b18739df7c2e1a919 (MD5) Previous issue date: 2012 / Resumo: O presente estudo avaliou a repercussão da restrição protéica gestacional sobre os receptores da Angiotensina II (AT1R e AT2R) no sistema nervoso central e seu impacto na programação da hipertensão arterial na vida adulta. Os resultados deste estudo demonstraram que o ambiente intrauterino inadequado, desencadeou nos animais do grupo hipoprotéico (LP), um baixo peso ao nascimento, uma expressão significativamente menor de receptores AT1R no extrato de tecido hipotalâmico aos 12 dias de idade e não significativa na 16a semana de vida quando comparados com os animais do grupo normoprotéico (NP). Inversamente, foi observado uma maior e significativa expressão de receptores AT2R no estrato total de hipotálamo de animais do grupo LP com 12 dias de vida, permanecendo nos animais com 16 semanas de vida, quando comparados ao grupo NP. Adicionalmente, observou-se a redução na resposta dipsogênica frente à administração Intracerebroventricular (i.c.v.) de Angiotensina II (AngII) nos animais LP em comparação com os animais do grupo NP. Estes resultados podem estar relacionados à expressão diminuída de vasopressina (AVP) hipotalâmico, demostrada aqui pela imunohistoquímica, na prole submetida à restrição protéica gestacional. A presente investigação também demonstrou uma menor expressão de receptores mineralocorticóide (MR) e glicocorticóide (GR) associada a uma elevação de propiomelanocortina (POMC) e hormônio adrenocorticotrófico (ACTH), assim sugerindo uma participação de mineralocorticoides e glicocorticóides como resposta compensatória ao longo da vida para atenuar as alterações na fisiologia renal comprovadas pela queda acentuada na excreção fracional de sódio urinário (FENa+) nos animais do grupo LP sem ocorrer alteração na filtração glomerular estimada pelo clearance de creatinina (CCr). O Clearance de lítio demonstrou que esta excreção urinária aumentada foi devida à perda da capacidade reabsortiva do néfron proximal a despeito do aumento na reabsorção pós-proximal. Estes efeitos foram associados com um significativo aumento na pressão arterial no grupo LP, mas, o mecanismo exato destes fenómenos permanecem desconhecidos / Abstract: Recent studies have shown that the central nervous system, during development, can be influenced by alterations in the intrauterine environment. This organizational phenomenon is termed 'early-life programming'. Here, in maternal protein-deprived offspring model, we focus on adult hypertension development, hypothalamic changes and renal function disorders as an outcome and confirm the hypothalamus as a structure in which there are early and permanent changes that underlie the developing hypertension. The present study shows that LP male pup body weight was significantly reduced when compared to that of NP pups. However, the body masses at 12-days-old and 16-wk-old were similar to observed in NP age-matched group. Furthermore, the immunoblotting analysis in the current study demonstrated a significantly decreased expression of type 1 AngII receptors in the entire hypothalamic tissue extract of LP rats at 12 days of age and unaltered expression in16-wk-old rats, compared to that observed in NP offspring. The unchanged AT1R expression by blotting in the whole hypothalamic extract of 16- wk LP rats may results of uneven expression of protein, revealed by immunohistochemistry, of different analyzed hypothalamic structures. Conversely, the expression of the type 2 AngII receptors in 12-days and 16-wk-old LP hypothalamus was significantly increased, when compared with the NP agematched group. The current data shows the influence of central AngII administration on spontaneous water consumption in a concentration-dependent fashion, but also demonstrated that the water intake response to graded AngII concentrations was strikingly attenuated in 16-wk-old LP, compared with agematched NP controls. These results may be related with decreased brain AVP expression showed in maternal protein-restricted offspring. The present investigation also shows an early and pronounced decrease in fractional urinary sodium excretion in maternal protein-restricted offspring. It also shows a decreased central expression of MR and GR associated, reciprocally, with enhanced immunoreactivity to POMC e ACTH. The decreased FENa was accompanied by a fall in FEPNa and occurred despite unchanged CCr and an enhanced FEPPNa. All these effects was associated with a significant enhance in arterial blood pressure in the LP group but, the precise mechanism of these phenomena remains unknown / Doutorado / Biologia Estrutural, Celular, Molecular e do Desenvolvimento / Doutor em Ciências

Thesis (M.Sc. (Physiology)) -- University of Limpopo, 2021 / The purpose of this study was to investigate the effect of cART on renal function and assess the association between renal function and cardiovascular risk factors in a black rural HIV-positive population in Limpopo Province, Mankweng district. We have conducted a cross-sectional study which included both male and female cART-treated patients (n=84), cART-naïve patients (n=27) and HIV-negative controls (n=44). We have measured biomarkers of renal function (plasma cystatin C, clusterin, retinol binding protein 4 [RBP4]) and determined the estimated glomerular filtration rate (eGFR) using the chronic kidney disease-epidemiology collaboration formula (CKD-EPI). We have also measured blood pressure (BP), body mass index (BMI) and fasting blood glucose (FBG). The prevalence of renal dysfunction was similar among the study groups. A significant difference in RBP4 was found among the groups after controlling for covariates (age, gender, alcohol consumption, BMI, systolic blood pressure and FBG) (F (2, 146) = [4.479], p=0.010). The significant difference in RBP4 was specifically observed between the cART-treated and cART-naïve groups (p=0.008). Cystatin C, clusterin and eGFR were not significantly different among the study groups after controlling for the covariates. The cardiovascular risk factors age (β=0.207; p=0.039), CD4+ T-cell count (β=-0.236; p=0.040), and duration of cART (β=0.232; p=0.043) were independently associated with cystatin C. The use of cART independently associated with RBP4 (β=0.282; p=0.004). Age (β=-0.363; p=0.001), CD4+ T-cell count (β=0.222; p=0.034) and duration of cART (β=-0.230; p=0.034) independently associated eGFR. Renal dysfunction is common in this HIV-positive population, with similar rates as the HIV-negative population. Plasma cystatin C as a promising alternative renal biomarker need to be re-evaluated in this HIV-positive population. RBP4 may be a more promising renal function biomarker in the HIV-positive population. Cardiovascular risk factors are associated with renal dysfunction in this rural HIV-positive population and CD4+ T-cell count may be an independent predictor for renal function.

No description available.

Hintergrund: Das akute Nierenversagen ist eine häufige Komplikation nach einer Herzoperation bei Neugeborenen, Säuglingen und Kleinkindern. Die Bedeutung der postoperativen Hämodynamik für eine Nierenschädigung ist gut bekannt, jedoch ist der Einfluß des kardiopulmonalen Bypasses und des tiefen hypothermen Kreislaufstillstandes weniger klar. Überdies gibt es Veränderungen der Blutviskosität während und nach der Herzoperation am kardiopulmonalen Bypass, welche die Nierenfunktion beeinflussen können. Aus diesem Grunde wurde der Einfluß der Blutviskosität am kardiopulmonalen Bypass und des tiefen hypothermen Kreislaufstillstandes auf die Nierenfunktion in dieser Patientengruppe untersucht. Methode: Untersucht wurden 44 Patienten mit einem Körpergewicht unter 10 kg, die am kardiopulmonalen Bypass operiert wurden. Von diesen erfolgte die Herzoperation bei 7 Patienten unter zusätzlicher Anwendung des tiefen hypothermen Kreislaufstillstandes. Bei allen Patienten wurden zu verschiedenen Zeitperioden Messungen zur Beschreibung der Nierenfunktion (Diurese, Kreatinin-Clearance und Gesamtprotein, Albumin, alpha-1-Mikroglobulin, Transferrin, IgG, N-Acetyl-beta-D-Glucosaminidase im Urin) und Bestimmungen der Blut- und Plasmaviskosität, der Erythrozytenaggregation und des kolloidosmotischen Druckes durchgeführt. Beide Gruppen wurden hinsichtlich des Einflusses des Kreislaufstillstandes auf die Nierenfunktion miteinander verglichen. Ergebnisse: Die während des kardiopulmonalen Bypasses im Zusammenhang mit einem erhöhten transglomerulären Filtrationsgradienten entstandene Polyurie und Proteinurie normalisierte sich innerhalb von 24 Stunden postoperativ. Die renale Ausscheidung von N-Acetyl-beta-D-Glucosaminidase und die erhöhte Natriumausscheidung zeigten zusätzlich eine tubuläre Schädigung an. Bei Hypothermie hatte die Plasmaviskosität einen deutlichen Einfluß auf die Blutviskosität, die während hypothermer Perfusion mit den im Urin gemessenen Werten von Albumin und N-Acetyl-beta-D-Glucosaminidase korrelierte. Die Patienten in der Kreislaufstillstandsgruppe hatten eine längere Bypasszeit und eine niedrigere minimale Körpertemperatur im Vergleich zu den Patienten ohne Kreislaufstillstand (p < 0,05). Diurese und Kreatinin-Clearance zeigten keine Differenzen zwischen beiden Gruppen. Während der Reperfusion wurde in der Kreislaufstillstandsgruppe signifikant mehr Albumin renal ausgeschieden als in der Vergleichsgruppe, ebenso Albumin und N-Acetyl-beta-D-Glucosaminidase nach dem kardiopulmonalen Bypass (p < 0,01). Schlußfolgerung: Die kardiopulmonale Bypassperfusion könnte eine Proteinurie und einen milden tubulären Schaden verursachen. Die Blutviskosität scheint dafür ein mitbestimmender Faktor zu sein und ist möglicherweise während hypothermer Perfusion wesentlich von der Plasmaviskosität abhängig. Es ist notwendig und wünschenswert anhand einer prospektiven Interventionsstudie den Einfluß der Blut- und Plasmaviskosität auf die postoperative Nierenfunktion zu untersuchen. Der tiefe hypotherme Kreislaufstillstand kann die Empfindlichkeit der Niere für einen Ischämie-Reperfusions-Schaden steigern. Obgleich die Befunde mild sind und keinen schweren ischämischen Nierenschaden anzeigen, sollte der durch den Kreislaufstillstand verursachte potentielle Nierenschaden für die Planung des chirurgischen Eingriffs bei Patienten mit angeborenen Herzfehlern als zusätzliches Risiko für ein akutes Nierenversagen mit in Betracht gezogen werden. / Background: Acute renal failure is a common complication after cardiopulmonary bypass in infants. Whereas it is well known that postoperative hemodynamics inflict acute renal failure, the influence of extracoporeal circulation on the kidney is less clear. Moreover, changes in blood viscosity occur during and after surgery, which may influence renal dysfunction. For this reason, the impact of blood viscosity during cardiopulmonary bypass and circulatory arrest on renal function was investigated. Methods: 44 patients weighting less than 10 kg operated on cardiopulmonary bypass were investigated, inclusive of 7 patients who additionally underwent circulatory arrest. In all patients analyses of renal function (diuresis, creatinine clearance, urinary total protein, albumin, alpha-1-microglobulin, transferrin, IgG, and N-acetyl-beta-D-glucosaminidase), blood, and plasma viscosity measurements, erythrocyte aggregation and colloid osmotic pressure were performed. Both groups were compared with regard to the impact of circulatory arrest on renal function. Results: Polyuria and proteinuria that appeared during cardiopulmonary bypass indicated an elevated transglomerular filtration gradient, which recovered within 24 hours. The appearance of N-acetyl-beta-D-glucosaminidase in the urine and elevated sodium excretion were additionally indicative of mild tubular damage. With hypothermia, plasma viscosity could had a major impact on the blood viscosity, which, during hypothermic perfusion, seemed to be related to proteinuria and N-acetyl-beta-D-glucosaminidase values. The patients of the circulatory arrest group had a longer bypass time and a lower body temperature in compare to the patients without circulatory arrest (p < 0.05). Diuresis and creatinine clearance revealed no differences between both groups. During reperfusion in the circulatory arrest group significantly more albumin were excreted as in the comparison group, likewise albumin and N-acetyl-beta-D-glucosaminidase after cardiopulmonary bypass (p < 0.01). Conclusions: Cardiopulmonary bypass perfusion could cause proteinuria and mild tubular damage. Blood viscosity may be one possible contributing factor, which in hypothermia may depend mainly on plasma viscosity. It is necessary and desirable to investigate the impact of blood, and plasma viscosity on postoperative renal function based on a prospective intervention study. The deep hypothermic circulatory arrest can increase the sensitivity of the kidney to an ischemia-reperfusion injury. Although the findings are mild and do not indicate severe ischemic renal damage, potential renal damage by deep hypothermic circulatory arrest should be taken into account for planning surgical procedures for congenital heart disease patients with additional risks of acute renal failure.

Introdução: A Poluição do ar e a inatividade física são dois importantes fatores de risco para saúde. Ainda não são bem conhecidos o balanço sobre os efeitos na saúde da realização de exercícios em ambientes poluídos. Objetivos: Avaliar o impacto da realização de exercício físico em ambientes com diferentes concentrações de poluentes sobre a toxicidade pulmonar, em marcadores sanguíneos e na função renal. Métodos: 40 soldados do exército brasileiro, não fumantes, saudáveis, do sexo masculino e praticantes de corrida de rua regulares foram avaliados. Participaram de corridas de 7,5 km todas as manhãs, a uma velocidade de 10 km/h, por uma semana em um circuito dentro de um Parque Florestal (PQ) e uma semana em um circuito em Vias Públicas (VP). Foram coletadas amostras de sangue e urina antes e depois da corrida em dois dias de cada semana, sendo determinados marcadores sanguíneos, de toxicidade pulmonar e da função renal. Os níveis de MP2,5 foram registrados durante todos os dias das semanas no período em que foram feitas as avaliações. Resultados: A concentração de MP2,5 no circuito PQ foi de 24 ug/m3 (IQR: 8-39) e no circuito VP de 62 ug/m3 (IQR: 37-103), P < 0,001. Trinta e nove participantes concluíram. Idade: 19 ± 1 anos, Índice de Massa Corpórea: 23,5 ± 2,38 kg/m2, Frequência cardíaca repouso: 69,1 ± 10,4 bpm. A concentração de proteína CC16 urinária aumentou após as corridas em ambos circuitos, mas de forma mais acentuada no circuito PQ. Marcadores sanguíneos e de função renal se alteraram após a corrida, sem diferenças significativas entre os circuitos. Conclusão: A realização de atividade física esteve relacionada à inflamação sistêmica e alteração da função renal, sem diferença entre os circuitos em diferentes ambientes. A proteína CC16, marcador de toxicidade e alteração de permeabilidade pulmonar foi o único que se elevou, com maior magnitude, no circuito localizado no interior de um parque. / Introduction: The Air pollution and physical inactivity are two important risk factors for health. The assessment of the health effects of exercising in polluted environments are still not well known. To assess the impact of performing physical exercise in environments with different concentrations of pollutants on lung toxicity in blood markers and renal function. Methods: 40 soldiers from the Brazilian army, non-smoking, healthy male and regular street runners were evaluated. Participated in races of 7.5 km every morning at a speed of 10 km/h, for a week in a circuit within a Forest Park (PK) and a week in a circuit in Public Ways (PS). Blood and urine samples were collected before and after running over two days each week, with certain blood markers, pulmonary toxicity and renal function. The levels of PM2.5 were recorded during every day of the week in the period they were made evaluations. Results: The concentration of the PM2.5 circuit PK was 24 ug/m3 (IQR: 8-39) and PS circuit 62 ug/m3 (IQR: 37-103), P < 0.001. Thirty-nine participants completed. Age: 19 ± 1 years, body mass index: 23.5 ± 2.38 kg/m2, resting heart rate: 69.1 ± 10.4 bpm. The concentration of urinary protein CC16 increased after the races on both circuits, but more sharply in the PK circuit. Blood markers and markers of renal function are altered after the run, with no significant differences between the circuits. Conclusion: Physical activity was related to the variation of the markers indicating inflammation and changes in renal function, with no difference between the environments except for the marker of pulmonary toxicity that increased with greater magnitude in the PK circuit

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / O veneno do escorpiÃo Tityus serrulatus à uma mistura de peptÃdeos tÃxicos e nÃo tÃxicos com diversas aÃÃes locais e sistÃmicas. O objetivo deste trabalho foi estudar os efeitos cardiovasculares e renais induzidos pelo veneno total do escorpiÃo T. serrulatus e de suas fraÃÃes TsTx-V, Toxina &#947; e NatriurÃtica. Foram utilizados ratos Wistar machos (250-300g) para os experimentos de perfusÃo de rim isolado, leito mesentÃrico, pressÃo arterial e perfusÃo in vivo. Para os ensaios de canal deferente foram utilizados camundongos Swiss (30-40g). O veneno de T. serrulatus apresentou efeito sobre o sistema nervoso autÃnomo observado atravÃs da contraÃÃo do vaso deferente. O veneno total mostrou efeito adrenÃrgico demonstrado pela reversÃo dos seus efeitos renais apÃs prÃ-tratamento dos rins com antagonista &#945;-adrenÃrgico prazosin, especialmente sobre a resistÃncia vascular renal (RVRVTs = 7,51  0,96 vs RVRPz = 5,51  0,43 mmHg/mL.g-1.min-1*,*p<0,05) e pressÃo de perfusÃo (PPVTs = 150,1  18,40 vs PPPz = 118,1  4,00 mmHg*,*p<0,05). As fraÃÃes isoladas mostraram efeitos renais somatÃrios, haja visto que TsTx-V promoveu aumento da diurese e a Toxina &#947; causou efeitos pressÃricos. ApÃs avaliaÃÃo histopatolÃgica dos efeitos renais das fraÃÃes isolados do veneno de T. serrulatus, observamos a presenÃa de material protÃico nos espaÃos urinÃrios glomerulares e nos tÃbulos. Entretanto, no leito vascular mesentÃrico, somente a toxina &#947; mostrou-se ativa. Os efeitos renais induzidos pela fraÃÃo natriurÃtica (0,03 e 0,1Âg/mL) revelaram aumento da pressÃo e, de maneira concentraÃÃo-dependente, diminuiÃÃo da reabsorÃÃo de eletrÃlitos e aumento da excreÃÃo urinÃria de guanosina monofosfato cÃclico (GMPc). Nos experimentos in vivo, tanto o veneno total quanto a fraÃÃo natriurÃtica causaram aumento da pressÃo arterial mÃdia (PAM) e diminuiÃÃo do hematÃcrito. Em adiÃÃo, a fraÃÃo natriurÃtica causou ainda a elevaÃÃo do fluxo urinÃrio e da freqÃÃncia cardÃaca. O clearance de inulina foi utilizado para a avaliaÃÃo da funÃÃo renal in vivo. O veneno total diminui significativamente o clearance da inulina, enquanto a fraÃÃo natriurÃtica causou elevaÃÃo. O fluxo plasmÃtico renal cortical, avaliado atravÃs do clearance de p-aminohipurato, foi reduzido por aÃÃo do veneno total de T. serrulatus. Em conclusÃo, o veneno de Tityus serrulatus promoveu efeitos hemodinÃmicos renais que foram prontamente revertidos in vitro pelo prazosin. Os experimentos in vivo mostraram que o veneno de Tityus serrulatus induziu a elevaÃÃo da pressÃo arterial mÃdia, taquicardia e alteraÃÃo da funÃÃo renal. / The venom of Tityus serrulatus has a mixture of toxic and non toxic peptides presenting diverse systemic and local effects. The aim of this work was to investigate the cardiovascular and renal effects promoted by the crude venom of the scorpion Tityus serrulatus and its isolated components such as Tityus serrulatus toxin V (TsTx-V), Gamma Toxin and the newly isolated Natriuretic Peptide. The experiments of isolated perfused rat kidney, isolated mesenteric bed, arterial pressure and in vivo perfusion were performed using male Wistar rats weighing 250-300g. The assays with vas deferens were done using Swiss mice weighing 30-40g. The crude venom presented autonomic nervous system effects showed by the contraction of vas deferens. Adrenergic effects were demonstrated specially with the decrease of renal vascular resistance (RVRVTs = 7.51  0.96 vs RVRPz = 5.51  0.43 mmHg/mL.g-1.min-1*,*p<0.05) and renal perfusion pressure (PPVTs = 150.1  18.40 vs PPPz = 118.1  4.00 mmHg*,*p<0.05) induced by the crude venom after kidneys pre-treatment with prazosin. The venoms isolated components showed kidney addictional effects, where TsTx-V caused diuresis while Gamma Toxin increased perfusion pressure. We could also observe the presence of protein inside the tubules and in glomerular spaces after renal histopathologic evaluation in the groups treated with the isolated components. However, only Gamma Toxin promoted an increase of the mesenteric bed perfusion pressure. The Natriuretic Peptide (0.03 and 0.1Âg/mL) increased renal perfusion pressure. In addition, the natriuretic peptide increased cyclic guanosine monophosphate (cGMP) urinary excretion, but reduced electrolytes reabsorption in a dependent-concentration manner. The crude venom and the natriuretic peptide increased the arterial blood pressure, but decreased the hematocrit values, evaluated after in vivo experiments. However, the natriuretic peptide increased urinary flow and heartbeat frequency. In vivo renal function was evaluated by the clearance of inulin. The scorpion crude venom decreased the clearance of inulin, but this parameter was increased after natriuretic peptide treatment. The renal cortex blood flux, estimated by the clearance of p-aminohippurate, was reduced after the crude venom treatment. In conclusion, we demonstrated that Tityus serrulatus venom induced renal hemodynamic effects that were blocked in vitro by prasozin. In vivo experiments showed how the crude venom and its isolated components act increasing arterial blood pressure, heartbeat frequency and altered renal function.

Introdução: A Poluição do ar e a inatividade física são dois importantes fatores de risco para saúde. Ainda não são bem conhecidos o balanço sobre os efeitos na saúde da realização de exercícios em ambientes poluídos. Objetivos: Avaliar o impacto da realização de exercício físico em ambientes com diferentes concentrações de poluentes sobre a toxicidade pulmonar, em marcadores sanguíneos e na função renal. Métodos: 40 soldados do exército brasileiro, não fumantes, saudáveis, do sexo masculino e praticantes de corrida de rua regulares foram avaliados. Participaram de corridas de 7,5 km todas as manhãs, a uma velocidade de 10 km/h, por uma semana em um circuito dentro de um Parque Florestal (PQ) e uma semana em um circuito em Vias Públicas (VP). Foram coletadas amostras de sangue e urina antes e depois da corrida em dois dias de cada semana, sendo determinados marcadores sanguíneos, de toxicidade pulmonar e da função renal. Os níveis de MP2,5 foram registrados durante todos os dias das semanas no período em que foram feitas as avaliações. Resultados: A concentração de MP2,5 no circuito PQ foi de 24 ug/m3 (IQR: 8-39) e no circuito VP de 62 ug/m3 (IQR: 37-103), P < 0,001. Trinta e nove participantes concluíram. Idade: 19 ± 1 anos, Índice de Massa Corpórea: 23,5 ± 2,38 kg/m2, Frequência cardíaca repouso: 69,1 ± 10,4 bpm. A concentração de proteína CC16 urinária aumentou após as corridas em ambos circuitos, mas de forma mais acentuada no circuito PQ. Marcadores sanguíneos e de função renal se alteraram após a corrida, sem diferenças significativas entre os circuitos. Conclusão: A realização de atividade física esteve relacionada à inflamação sistêmica e alteração da função renal, sem diferença entre os circuitos em diferentes ambientes. A proteína CC16, marcador de toxicidade e alteração de permeabilidade pulmonar foi o único que se elevou, com maior magnitude, no circuito localizado no interior de um parque. / Introduction: The Air pollution and physical inactivity are two important risk factors for health. The assessment of the health effects of exercising in polluted environments are still not well known. To assess the impact of performing physical exercise in environments with different concentrations of pollutants on lung toxicity in blood markers and renal function. Methods: 40 soldiers from the Brazilian army, non-smoking, healthy male and regular street runners were evaluated. Participated in races of 7.5 km every morning at a speed of 10 km/h, for a week in a circuit within a Forest Park (PK) and a week in a circuit in Public Ways (PS). Blood and urine samples were collected before and after running over two days each week, with certain blood markers, pulmonary toxicity and renal function. The levels of PM2.5 were recorded during every day of the week in the period they were made evaluations. Results: The concentration of the PM2.5 circuit PK was 24 ug/m3 (IQR: 8-39) and PS circuit 62 ug/m3 (IQR: 37-103), P < 0.001. Thirty-nine participants completed. Age: 19 ± 1 years, body mass index: 23.5 ± 2.38 kg/m2, resting heart rate: 69.1 ± 10.4 bpm. The concentration of urinary protein CC16 increased after the races on both circuits, but more sharply in the PK circuit. Blood markers and markers of renal function are altered after the run, with no significant differences between the circuits. Conclusion: Physical activity was related to the variation of the markers indicating inflammation and changes in renal function, with no difference between the environments except for the marker of pulmonary toxicity that increased with greater magnitude in the PK circuit

By the year 2025, it is anticipated that over 300 million individuals world wide will have type 2 diabetes, with a projected increase from 84 to 288 million (170%) in developing countries and from 51 to 72 million (42%) in developed countries. Diabetes leads to a markedly increased risk of heart disease and renal failure and to expensive and debilitating retinopathy and neuropathy. Cognitive decline is also increased. As there is accumulating evidence of the beneficial effects of moderate carbohydrate, low fat dietary patterns compared to high carbohydrate diets, this thesis will focus on the effects of moderate carbohydrate high protein dietary patterns (total carbohydrate: protein: fat ratio of 40%:34%:26%) on glycemic control, risk factors for macrovascular disease and cognitive function. Information on two key areas in type 2 diabetes will be presented, 1. Acute effects of dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels assessed using continuous glucose monitoring systems (CGMS) with verification of these results through a small repeat study. 2. Chronic effects of energy restricted dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels, HbA1c, cognitive function, cardiovascular disease (CVD) risk markers and renal function. In the acute study, we recruited 23 subjects with type 2 diabetes. The participants were randomized to each of 4, 3-day interventions in a cross over design with a 4 day wash out period in which the carbohydrates were distributed differently at each meal; carbohydrates evenly distributed across the day, or carbohydrates loaded at breakfast, lunch or dinner. Glucose levels were continuously measured using CGMS. Outcomes were assessed by postprandial peak glucose (Gmax), time spent above 12 mmol/L (T>12) and total area under the glucose curve (AUC20). The intervention showed that an even distribution of carbohydrates did not optimise blood glucose control, whereas carbohydrates loaded at the lunch time meal provided the most favourable postprandial profile. To verify these results we conducted a repeat study. Six of the previous participants accepted the invitation to return and complete the even distribution arm of the study after a 20 week time lag. The intervention showed that although HbA1c, fasting blood glucose (FBG), AUC, exercise and ambient temperature remained constant there was a significant effect of change in sunlight hours on Gmax, suggesting an effect of sunlight. To assess the chronic effects of energy restricted dietary patterns on the determinants of HbA1c, cognitive function, CVD risk markers and renal function under conditions of weight loss, we recruited 82 participants with type 2 diabetes. These participants were randomised to one of two high protein energy restricted dietary patterns that differed in cholesterol content, for a 12 week period, in a parallel design. A sub group of these participants completed cognitive function testing with (n=34) or without (n=17) CGMS at baseline and at 8 weeks. After 8 weeks of the intervention the determinants of HbA1c under conditions of energy restriction were evaluated. The intervention showed the change in FBG accounted for most of the variance in change in HbA1c, but % energy reduction also contributed independently of FBG. Both energy restricted high protein diets equally improved glycemic control, particularly T>12, AUC, HbA1c and FBG. Fifty one participants completed cognitive testing to evaluate the effect of weight loss and blood glucose control on cognition. Cognitive function was not altered by time, diet, baseline lipid levels. Working memory was predicted by FBG. Short term memory was predicted by FBG, Gmax and AUC24. Sixty five participants completed 12 weeks of the intervention to assess CVD risk markers and renal function. Renal function was maintained and CV markers improved on both dietary patterns, with greatest improvement in HDL-C observed in the group consuming a high protein, energy restricted dietary pattern, high in dietary cholesterol. In conclusion, in the context of a high protein, carbohydrate restricted dietary pattern, cognitive function and renal function did not change, while glycemia and CV risk profiles improved with weight loss over the short term. Under conditions of energy balance diurnal glucose profiles were optimal when the carbohydrates were loaded in the lunch meal. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1342253 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008