Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-03-10T20:24:54Z No. of bitstreams: 1 MayaraSantaRosaLima_DISSERT.pdf: 1762065 bytes, checksum: 81b2ba7e141b5e4144aae1950f65a16e (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-03-17T00:16:56Z (GMT) No. of bitstreams: 1 MayaraSantaRosaLima_DISSERT.pdf: 1762065 bytes, checksum: 81b2ba7e141b5e4144aae1950f65a16e (MD5) / Made available in DSpace on 2016-03-17T00:16:56Z (GMT). No. of bitstreams: 1 MayaraSantaRosaLima_DISSERT.pdf: 1762065 bytes, checksum: 81b2ba7e141b5e4144aae1950f65a16e (MD5) Previous issue date: 2015-05-26 / A vitamina A ? um nutriente essencial em diversos processos fisiol?gicos, como crescimento e desenvolvimento, de modo que um adequado estado nutricional nesse nutriente ? fundamental na gesta??o e lacta??o. Mulheres lactantes e crian?as em aleitamento materno s?o consideradas grupos de risco para a defici?ncia de vitamina A e alguns fatores podem aumentar o risco de hipovitaminose, como a prematuridade. O objetivo deste trabalho foi avaliar a concentra??o de vitamina A em lactantes e rec?m-nascidos pr?-termo e a termo, por meio da determina??o do retinol no soro materno, no soro do cord?o umbilical e no leite materno coletado at? 72 horas p?s-parto. Foram recrutadas 182 parturientes, divididas em grupo pr?-termo (GPT; n=118) e grupo termo (GT; n=64). No grupo pr?- termo tamb?m foram analisadas amostras de leite de transi??o (7?-15? dia; n=68) e leite maduro (30?-55? dia; n=46). O retinol foi analisado por cromatografia l?quida de alta efici?ncia (CLAE). A concentra??o materna de retinol s?rico foi 48,6 ? 12,3 ?g/dL no GPT e 42,8 ? 16,3 ?g/dL no GT (p<0,01). O retinol no soro do cord?o umbilical foi 20,4 ? 7,4 ?g/dL no GPT e 23,2 ? 7,6 ?g/dL no GT (p>0,05). Entre os rec?m-nascidos, 43% dos prematuros e 36% dos a termo apresentaram baixos n?veis de retinol s?rico no cord?o umbilical (<20 ?g/dL). No colostro, lactantes pr?- termo e termo apresentaram m?dia de retinol de 100,8 ? 49,0 ?g/dL e 127,5 ? 65,1 ?g/dL, respectivamente (p<0,05). A m?dia de retinol no leite pr?-termo aumentou para 112,5 ? 49,7 ?g/dL na fase de transi??o e reduziu para 57,2 ? 23,4 ?g/dL no leite maduro, diferindo significativamente entre todas as fases (p<0,05). Ao comparar com a recomenda??o de ingest?o de vitamina A (400 ?g/dia) o leite colostro do GT atingiu a recomenda??o para lactentes, por?m no GPT a recomenda??o n?o foi atingida em nenhuma das fases. As m?es de rec?m-nascidos prematuros possu?am concentra??o s?rica de retinol superior ? de m?es a termo, entretanto, isso n?o foi refletido no retinol do soro do cord?o umbilical, uma vez que os prematuros apresentaram menor concentra??o da vitamina. Tal condi??o pode ser explicada devido ? menor hemodilui??o fisiol?gica materna e transfer?ncia placent?ria de retinol para o feto durante a gesta??o pr?-termo. A compara??o do retinol no colostro evidenciou menor concentra??o no GPT, no entanto na fase de transi??o houve um aumento importante do conte?do de retinol liberado pela gl?ndula mam?ria de lactantes pr?-termo. Essa situa??o evidencia uma adapta??o fisiol?gica pr?pria da prematuridade, provavelmente no sentido de contribuir mais para a forma??o das reservas hep?ticas de retinol dos lactentes prematuros. / Vitamin A is an essential nutrient for many physiological processes such as growth and development, so that their adequate nutritional state is essential during pregnancy and lactation. Lactating women and children in breastfeeding are considered risk groups for vitamin A deficiency and some factors may increase the risk of vitamin A deficiency, such as prematurity. The aim of this work was to evaluate the vitamin A concentration in preterm and term lactating women and newborns by determination of retinol in maternal serum, umbilical cord serum and breast milk collected until 72 hours postpartum. 182 mothers were recruited and divided into preterm group (GPT; n = 118) and term group (GT, n = 64). In preterm group were also analyzed transition milk (7th-15th day; n = 68) and mature milk (30th-55th day; n = 46) samples. Retinol was analyzed by high-performance liquid chromatography (HPLC). Maternal retinol concentration in serum was 48.6 ? 12.3 ?g/dL in GPT and 42.8 ? 16.3 ?g/dL in the GT (p <0.01). Cord serum retinol was 20.4 ? 7.4 ?g/dL in GPT and 23.2 ? 7.6 ?g/dL in GT (p> 0.05). Among newborns, 43% of premature and 36% of term had low levels of serum retinol in umbilical cord (<20 ?g/dL). In colostrum, the retinol in preterm and term groups had an average of 100.8 ? 49.0 ?g/dL and 127.5 ? 65.1 ?g/dL, respectively (p <0.05). The retinol average in preterm milk increased to 112.5 ? 49.7 ?g/dL in transition phase and decreased to 57.2 ? 23.4 ?g/dL in mature milk, differing significantly in all stages (p <0.05). When comparing with the recommendation of vitamin A intake (400 ?g/day) GT colostrum reached the recommendation for infants, but in GPT the recommendation was not achieved at any stage. Mothers of premature infants had higher serum retinol than mothers at term; however, this was not reflected in serum retinol of umbilical cord, since premature had lower concentration of retinol. Such condition can be explained due to lower maternal physiological hemodilution and placental transfer of retinol to the fetus during preterm gestation. Comparison of retinol in colostrum showed lower concentrations in GPT; however the transition phase there was a significant increase of retinol content released by the mammary gland of preterm mothers. This situation highlights a specific physiological adaptation of prematurity, likely to more contribute to formation of hepatic reserves of retinol in premature infants.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-02-10T16:42:15Z No. of bitstreams: 1 CristianeSantosSanzioGurgel_TESE.pdf: 4190612 bytes, checksum: 773e7fec68bad460acc07eb6d8f76c81 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-02-10T21:19:07Z (GMT) No. of bitstreams: 1 CristianeSantosSanzioGurgel_TESE.pdf: 4190612 bytes, checksum: 773e7fec68bad460acc07eb6d8f76c81 (MD5) / Made available in DSpace on 2017-02-10T21:19:07Z (GMT). No. of bitstreams: 1 CristianeSantosSanzioGurgel_TESE.pdf: 4190612 bytes, checksum: 773e7fec68bad460acc07eb6d8f76c81 (MD5) Previous issue date: 2016-06-28 / Este estudo objetivou avaliar o estado de vitamina A de pu?rperas atendidas durante o parto na cidade de Natal/RN. Foram recrutadas no estudo 793 mulheres, 60.1% (n=485) da rede p?blica e 39.0% (n=310) a rede privada. Amostras de soro (n=619) e leite colostro (n=656) foram coletadas em ambiente hospitalar, ap?s jejum noturno. O leite maduro (n=154) foi coletado trinta dias ap?s o parto, em visita domiciliar. Os indicadores bioqu?micos (retinol no soro e leite materno) foram avaliados por local de moradia (capital vs interior) e por rede de atendimento em sa?de (p?blico vs privado). O consumo de vitamina A foi avaliado referente ao ?ltimo trimestre gestacional. Para avaliar as diferentes formas de suplementa??o materna com vitamina A e suas associa??es com os indicadores bioqu?micos (soro e leite materno) formaram-se subgrupos baseados nas suplementa??es que ocorreram durante a gesta??o: GC, F1, F2, F3 e no p?s-parto: GM. O retinol das amostras foi quantificado por cromatografia l?quida de alta efici?ncia (CLAE). Para o total de mulheres, a concentra??o m?dia de retinol s?rico foi de 41.8 ? 12.9?g/dL e a preval?ncia da DVA foi de 5.3% (n= 33) com retinol (<20 ?g/dL), com diferen?a significativa entre o retinol s?rico das mulheres provenientes da capital e do interior (p<0,01). Em Natal, as preval?ncias de defici?ncia encontradas nas regi?es norte, sul, leste e oeste foram respectivamente: 4.3% (n=6), 5.6% (n=7), 2.9% (n=3) e 11.9% (n=8). A m?dia de retinol no colostro no grupo total foi de 95,3+ 53.7?g/dL, entretanto 27.3% (n=179) apresentaram valores inadequados (<60 ?g/dL). Os valores m?dios estimados de retinol fornecido aos rec?m-nascidos atrav?s do colostro, n?o atingiram a recomenda??o m?nima de 400?g/RAE/dia da AI (Adequate Intake) para rec?m-nascidos, considerando a ingest?o de 396mL/dia. Houve diferen?a significativa entre o retinol no colostro das mulheres da capital e aquelas provenientes do interior (p<0.01). Ambos os grupos n?o forneceram a AI de vitamina A para o rec?m-nascido e tamb?m o mesmo foi observado com as lactantes das regi?es norte e oeste da cidade de Natal. No leite maduro, nenhum dos grupos de mulheres das diferentes regi?es atingiu a recomenda??o, considerando a ingest?o de 780mL/dia pelos rec?m-nascidos. Ao avaliar as pu?rperas separadamente por rede de atendimento em sa?de (p?blico vs privado) foi encontrada diferen?a significativa entre o retinol s?rico e retinol no colostro (p<0.0001), mas n?o houve diferen?a para o leite maduro (p>0.05). Na estimativa do fornecimento de retinol atrav?s do colostro e leite maduro, as mulheres da rede p?blica n?o forneceram vitamina A dentro da recomenda??o m?nima para o rec?m-nascido (AI=400?g/RAE/dia), ao contr?rio das mulheres da rede privada, que forneceram. O consumo diet?tico m?dio total de vitamina A das parturientes foi de 987.1 + 674.4 ?gRAE/dia, sendo 872.2 + 639.2 ?gRAE/dia na da rede p?blica e 1169.2 + 695.2 ?gRAE/dia na rede privada, com diferen?a altamente significativa (p<0,00001). Na avalia??o individual, 38.4% (n=100) e 17.3% (n=28) das mulheres das redes p?blica e privada tinham ingest?o abaixo da ideal. Ao se estudar as diferentes formas de suplementa??o com vitamina A, n?o foram encontrados casos de DVA nos grupos suplementados com F1, F2 e F3. Ao se analisar o efeito da suplementa??o sobre o retinol do colostro, o grupo F2 (betacaroteno) apresentou mais casos de inadequa??o (40%). Os grupos F2 e GM n?o forneceram a quantidade de retinol m?nima recomendada pela AI aos rec?m-nascidos. No retinol do leite maduro n?o houve diferen?a entre os grupos GC, F1, F2, F3 e GM e com percentuais de inadequa??o mais baixos no GM (14.3%) e os grupos GC e F2 n?o forneceram a quantidade de retinol m?nima recomendada pela AI para os rec?m-nascidos. Concluiu-se que a preval?ncia de DVA entre as pu?rperas atendidas em Natal foi considerada um problema "leve" de sa?de p?blica na popula??o em geral. Os grupos de alto risco neste estudo viviam em cidades do interior, eram atendidos na rede p?blica de sa?de e n?o tomavam vitamina A, como o suplemento regular durante a gesta??o. / This study aimed to evaluate the vitamin A status of women who delivered in Natal/RN. A total of 795 women were enrolled in the study. Serum (n=619) and colostrum (n=656) samples were collected in the hospital after an overnight fast. Mature milk samples (n=15) were collected at the women?s house thirty days after delivery. Biochemical indicators were evaluated according to home location (capital city vs. country towns) and type of health care system (public vs. private). Vitamin A intake was assessed using a food-frequency questionnaire (FFQ) corresponding to the last trimester of pregnancy. In order to evaluate the different forms of maternal supplementation with vitamin A and their associations with biochemical markers (maternal serum and breast milk), subgroups were formed based on the type of supplementation that occurred during pregnancy: GC, F1, F2, F3 and postpartum: GM. Retinol concentrations in the biological samples were quantified by high performance liquid chromatography (HPLC). For the total sample, the mean serum retinol concentration was 41.8 ?12.9?g/dL and the prevalence of VAD was 5.3% (n=33) of women presenting retinol concentrations (<20 ?g/dL), evidencing a significant difference in serum retinol concentrations between women from the capital city and from the countryside (p <0.01). In Natal, the prevalence of disability found in the north, south, east and west were, respectively, 4.3% (n= 6), 5.6% (n= 7), 2.9% (n= 3) and 11.9% (n= 8). The overall mean retinol concentration in colostrum was 95.3 ? 53.7?g/dL; however, 27.3% (n=179) of women presented inadequate values (<60 ?g/dL). The average estimated amounts of retinol provided to newborns through colostrum did not meet the minimum recommendation of 400 ?g/RAE/day of AI (Adequate Intake) for newborns in both groups, considering the intake of 396mL/day. It was found a significant difference in colostrum retinol concentrations between women from the capital city and from the countryside (p<0.01). In Natal, colostrum milk of women from the northern and western regions did not meet the AI. For mature milk, none of the groups from the different regions met the recommendation, considering the intake of 780mL/day. Evaluating the sample separately by childbirth care system (public vs. private), it was found a significant difference in serum and colostrum retinol concentrations between the groups (p <0.0001); there was no difference for the mature milk (p>0.05). Estimating the retinol supply through colostrum and mature milk, women attending the public health system did not provide the minimum vitamin A amount recommended for newborns (AI= 400?g/RAE/day), unlike women's private network, which provided. The average total dietary vitamin A intake of pregnant women was 987.1 ? 674.4 ?gRAE/day, was 872.2 + 639.2 ?gRAE/day for women attending the public health system and 1169.2 + 695.2 ?gRAE/day for those attending the private system, evidencing a highly significant difference (p<0.001). Individually assessing the participants, 38.4% (n=100) e 17.3% (n=28) of women in the public and private systems had vitamin A intakes below the ideal. There was no difference in serum retinol concentrations between the CG, F1, F2, F3 and MG groups (p<0.05), although only the supplemented groups F1, F2 and F3 had no cases of VAD. Regarding colostrum retinol levels, the F2 group (beta-carotene) presented the highest number of inadequate cases (40%). The F2 and MG groups did not provide the minimum amount of retinol recommended by AI for newborns. Regarding retinol concentrations in mature milk, there was no difference between the CG, F1, F2, F3 and MG groups, and the MG group presented the lowest percentage of inadequacy (14.3%), while the CG and F2 groups did not provide the minimum amount of retinol recommended by the AI for infants. It was concluded that the prevalence of VAD among mothers who delivered in Natal was considered a ?mild? public health problem in the overall population. High-risk groups in this study lived in towns, were attended in the public health system and did not take vitamin A as regular supplement during pregnancy.

Made available in DSpace on 2014-06-12T22:57:03Z (GMT). No. of bitstreams: 2 arquivo3043_1.pdf: 9787970 bytes, checksum: 7341c405cb9a9af441cdd4732c316284 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2011 / A suplementação de puérperas com megadose de vitamina A no pós-parto imediato é uma estratégia no combate à hipovitaminose A e parece reduzir a morbi-mortalidade infantil. Entretanto, estudos têm mostrado que a suplementação materna com uma dose de 200.000 UI de vitamina A parece não assegurar níveis adequados de retinol no leite materno, soro e nas reservas hepáticas de recém-nascidos em aleitamento materno. Sendo assim, novos esquemas posológicos tem sido proposto a exemplo da megadose com 400.000 UI (protocolo IVACG). O objetivo desse estudo foi comparar o impacto da suplementação materna, no pós-parto imediato, com 400.000 UI vs 200.000UI de vitamina A na morbidade infantil. Foi realizado um ensaio clínico, randomizado, controlado e triplo cego, de base hospitalar em duas maternidades públicas da cidade do Recife, Nordeste do Brasil, no período de agosto de 2007 a junho de 2009. 276 pares de mãe-filho foram alocados em dois grupos de suplementação: 400.000 UI ou 200.000 UI de vitamina A. As concentrações de retinol dos RNs (cordão umbilical) e materna (venipuntura braquial) foram analisadas pela cromatografia líquida de alta resolução antes da randomização. A morbidade foi avaliada quinzenalmente através de questionários estruturado aplicados a cada consulta clínica e visita domiciliar durante os seis meses de vida da criança. Os resultados mostraram prevalência de 23,1% (IC95% 13,9 - 35,5) de baixas concentrações de retinol (< 0,70 &#956;mol/L) nos RNs e de 23,0% (IC95% 13,5 35,8) de concentrações inadequadas (< 1,05&#956;mol/L) nas mães. As taxas de incidência de febre (RT 0,92; IC95% 0,75-1,14), diarréia (RT 0,96; IC95% 0,72-1,28), otite (RT 0,94; IC95% 0,48-1,85), infecção respiratória (RT 1,03; IC95% 0,88-1,21), necessidade de rehidratação venosa (RT 2,08; IC95% 0,64-2,07) e uso de antibioticoterapia (RT 0,80; IC95% 0,43-1,47) não diferiram entre os 2 grupos de tratamento. Nossos resultados mostram alta prevalência de hipovitaminose A na criança ao nascer, entretanto, a ausência de redução significativa nos eventos de morbidade entre os grupos de tratamento não respaldam a proposta de incremento da megadose padrão existente no protocolo da OMS, para suplementação materna no pósparto imediato

No description available.

No description available.

The purpose of this research was to study vitamin A status in grazing horses throughout the year and to evaluate the effectiveness of vitamin A and β-carotene as supplements. Vitamin A status was assessed by serum retinol concentrations (SR) and the relative dose response (RDR) which was adapted for use in the horse. The horses (45 Thoroughbred mares) were divided into three diet groups: pasture and hay only (PH); pasture, hay and vitamin A-free concentrate (PHC); and hay and vitamin A-free concentrate (HC). The mares, as well as their foals, were assessed for vitamin A status during the summer, fall and winter. After eight months, each diet group was subdivided and supplemented with either: retinyl palmitate at two times the recommended level (A), the equivalent in water dispersible β-carotene (B), or a placebo (C). Supplementation continued for 20 months during which the vitamin A status was assessed every 60 days in the mares, and at birth in the neonates. During both the depletion and the repletion phase the mares were kept on a regular breeding schedule and the reproductive rates were determined as well as the general health of the mares and their offspring. The RDR proved more sensitive at detecting changes in vitamin A status than SR, and a combination of both was used. A measurable decline in vitamin A stores was seen in the HC group within 2 months, and in PH and PHC groups during the winter. The HC group remained lower in vitamin A status throughout the study. A seasonal fluctuation of vitamin A status was observed regardless of supplementation. Supplementation with retinyl palmitate improved vitamin A status in all three diet groups, however, supplementation with β-carotene did not. Both neonates and young growing horses were lower in vitamin A status than the adult. A respiratory infection observed in the weanlings affected vitamin A status as well. Supplementation of the dam had no effect on neonatal vitamin A status. Deleterious effects on reproductive rates and health were also observed with vitamin A depletion. Supplementation of β-carotene had a negative effect on reproductive rates in this study. / Ph. D.

In der vorliegenden Arbeit wurde untersucht, inwieweit die Reproduktionsbiologie von aquatischen Lebewesen durch die Gewässerbelastung mit endokrin wirksamen Substanzen (endocrine disruptors, ED) beeinflusst wird. Mit dem Amphib Xenopus laevis steht ein etabliertes Studienmodell zur Untersuchung der Wirkungen von ED auf die Reproduktionsbiologie zur Verfügung, das für die vorliegenden Studien modifiziert und erweitert sowie mit gewässeranalytischen Methoden verknüpft wurde. Die Gefährdung wasserlebender Tiere durch Gewässerbelastung mit ED kann erfasst werden, indem die Wirkung einer ausgewählten Einzelsubstanz auf die Reproduktionsbiologie untersucht wird. Anschließend erfolgt ein Nachweis der Substanz in Umweltproben. Durch Expositionsversuche, histologische Untersuchungen und Expressionsnachweis eines molekularen östrogenen Biomarkers konnte festgestellt werden, dass Bisphenol A (BPA) in Kaulquappen von Xenopus laevis verweiblichend wirkt und seine Effekte über eine Bindung an den Östrogenrezeptor vermittelt. Chemische Analysen während der Expositionsversuche zeigten, dass BPA von den Kaulquappen aufgenommen wird und dass eine geringe Abbaubarkeit der Substanz während eines Zeitraums von 48 Stunden besteht. Die Analyse von BPA in Wasserproben, die aus dem Fluss Alb oder aus Kläranlagenausläufen stammten, zeigte, dass BPA im Gewässer in relevanten Konzentrationen vorhanden ist und hauptsächlich durch eine Kläranlage in den Fluss eingeleitet wird. In einem Gewässer liegt allerdings ein Gemisch aus unterschiedlichen ED mit verschiedenen Wirkmechanismen vor. Die Gewässerbelastung mit endokrin wirksamen Substanzen kann weiterhin untersucht werden, indem Gewässerextrakte fraktioniert und in in vitro-Screeningmethoden getestet werden. Als Screeningmethoden dienten Rezeptorbindungsstudien an Östrogen- und Androgenrezeptoren sowie die Behandlung von Leberzellkulturen mit den Gewässerextrakten aus der Alb, um eine Regulation der Expression bestimmter Biomarkergene durch potenzielle ED nachzuweisen. Dazu wurde als neuer (anti)androgener und (anti)östrogener Biomarker das Retinol-binding Protein eingeführt. Die Untersuchung der Gewässerextrakte mit diesen Methoden zeigte, dass die Alb eine Belastung mit endokrin wirksamen Substanzen aufweist und dass hauptsächlich östrogen wirksame Substanzen vorkommen. Die Proben aus den Kläranlagenausläufen weisen die höchste endokrine Aktivität auf. / The present study examined the influence of endocrine active compounds (endocrine disruptors, ED), which are present in surface waters, on reproductive biology of aquatic organisms. The amphibian Xenopus laevis is a well-established model organism for the study of effects of ED on reproduction. It has been modified and broadened for the purpose of this study, and it was combined with chemical methods for water analyses. It is possible to assess water pollution with ED by detecting effects on repro-ductive biology of one particular substance, and then by looking for this substance in environmental water samples. We showed the feminizing potency of Bisphenol A (BPA) in conducting exposure experiments with tadpoles, in examining histological samples of gonads and in detecting the induction of the expression of a molecular estrogenic biomarker. BPA was recognized to mediate its effects via binding to the estrogen receptor. Moreover, analysis of BPA during exposure experiments revealed that BPA is taken up by tadpoles and is not readily degradable during a time period of 48 hours. Chemical analyses of environmental water samples from the river Alb or samples from sewage treatment works (STW) showed that BPA is released into the environment by STW effluents. In surface waters, there are different kinds of ED with different modes of action. Thus, it is another possibility to assess water pollution with ED by fractionating environmental water samples and by testing these fractions in rapid in vitro-screening methods. In the present work, receptor binding assays were carried out, both examining the binding to estrogen and androgen receptors. Furthermore, Xenopus laevis hepatocyte cultures were treated with fractions of environmental samples and biomarker expression was detected. A new biomarker to assess (anti)androgenic or (anti)estrogenic modes of action, respectively, was established. This new biomarker was the Retinol-binding Protein. The results obtained by these methods revealed that the river Alb is mainly polluted with estrogenic ED. Samples from STW effluents possessed the highest endocrine activity.

A RBP urinária tem seu papel bem definido como marcador de progressão de doença renal em tubulopatias, em glomerulopatias e em pacientes transplantados. No entanto, seu papel em DRC lato senso foi pouco estudado. Por sua vez, a dosagem de RBP sérica, caracterizada recentemente como biomarcador de resistência insulínica, também não teve seu papel esclarecido em população portadora de DRC. O objetivo do presente estudo foi avaliar a relação entre a RBP (urinária e sérica) e a função renal, assim como sua relação com fatores de risco cardiovascular em população de DRC. Para tanto, foram analisados os dados da linha de base da Coorte PROGREDIR, constituída por 454 participantes portadores de DRC, oriundos do Hospital das Clínicas, São Paulo. Inicialmente, além de estar inversamente relacionada às medidas de depuração de creatinina, a RBP urinária mostrou-se relacionada a diversos fatores de risco cardiovascular e variáveis associadas à função renal, como proteinúria, metabolismo ósseo, anemia, acidose, albumina, RPB sérica, Hb glicada, HOMA, lípides, velocidade de onda de pulso (VOP), átrio esquerdo (ECO AE), diâmetro diastólico do ventrículo esquerdo (ECO-Ddve), diâmetro sistólico do ventrículo esquerdo (ECO-Dsve) e fração de ejeção (ECO-Fe). Entretanto, após diversos modelos de regressão, permaneceram como variáveis independentemente associadas à RBP urinária a função renal, a pressão arterial sistólica, a albuminúria, a acidose e a medida do AE. Esse resultado se manteve quando o modelo foi repetido mediante estratificação por albuminúria, sugerindo que mesmo em população normoalbuminúrica a RBP urinária correlacione-se inversamente com função renal. Além disso, a relação inversa de RBP urinária com dilatação cardíaca sugere que, em população com DRC já estabelecida, a RBP urinária possa ter um papel em identificar mecanismos etiológicos, possivelmente por distinguir mecanismos hemodinâmicos daqueles onde há uma patologia renal intrínseca. Por sua vez, a RBP sérica relacionou-se inversamente à função renal e idade, e positivamente a triglicérides, albumina e potássio. Curiosamente, a RBP sérica não se mostrou associada às medidas de metabolismo de carboidrato, sugerindo que seu papel como biomarcador de resistência insulínica seja atenuado na DRC. Também não foram encontradas relações entre RBP urinária ou sérica e calcificação coronária ou espessura de carótidas. Nossos resultados sugerem que a RBP urinária deva ser melhor explorada como marcador de função renal e, possivelmente, como marcador de risco de progressão da DRC / The role of urinary RBP as a biomarker of tubular injury and CKD progression in tubulopathies, glomerulopathies and in transplantation is well established. However, its role in CKD is less studied. In addition, serum RBP has been recently characterized as an insulin resistance marker, but controversial results have been shown. The aim of the study was to evaluate the association of both urinary RBP and serum RBP with kidney function and other variables related to the uremic syndrome and cardiovascular risk in a CKD population. We used the baseline data from the PROGREDIR Cohort, which comprehends 454 participants with CKD, recruited from Hospital das Clínicas, Sao Paulo. In univariate analysis, urinary RBP was inversely related to renal function. In addition, it was also related to albuminuria, SBP, anemia, mineral metabolism, acidosis, albumin, serum RPB, glycated hemoglobin, HOMA, lipids, pulse-wave velocity, left atrium diameter, left ventricle diastolic diameter, left ventricle systolic diameter and ejection fraction. However, in the multivariate analysis, only SBP, albuminuria, acidosis, left atrium diameter and renal function remained significantly associated to urinary RBP. After stratification for albuminuria levels, the same relationship was observed, suggesting that even in the normoalbuminuric population urinary RBP is significantly related to renal function. Interestingly, the inverse association between urinary RBP and cardiac dilation suggests that urinary RBP may play a role in identifying mechanisms related to CKD, by differentiating vascular/cardio-renal conditions versus more intrinsic kidney disease and possibly tubule-interstitial fibrosis. The serum RBP was positively related to renal function, triglycerides, albumin, age and potassium, but not to measurements of carbohydrate metabolism. No relationship between urinary or serum RBP and coronary calcification or carotid thickness was found. Our results suggest that urinary RBP should have its role as a marker of CKD and CKD progression further explored

A RBP urinária tem seu papel bem definido como marcador de progressão de doença renal em tubulopatias, em glomerulopatias e em pacientes transplantados. No entanto, seu papel em DRC lato senso foi pouco estudado. Por sua vez, a dosagem de RBP sérica, caracterizada recentemente como biomarcador de resistência insulínica, também não teve seu papel esclarecido em população portadora de DRC. O objetivo do presente estudo foi avaliar a relação entre a RBP (urinária e sérica) e a função renal, assim como sua relação com fatores de risco cardiovascular em população de DRC. Para tanto, foram analisados os dados da linha de base da Coorte PROGREDIR, constituída por 454 participantes portadores de DRC, oriundos do Hospital das Clínicas, São Paulo. Inicialmente, além de estar inversamente relacionada às medidas de depuração de creatinina, a RBP urinária mostrou-se relacionada a diversos fatores de risco cardiovascular e variáveis associadas à função renal, como proteinúria, metabolismo ósseo, anemia, acidose, albumina, RPB sérica, Hb glicada, HOMA, lípides, velocidade de onda de pulso (VOP), átrio esquerdo (ECO AE), diâmetro diastólico do ventrículo esquerdo (ECO-Ddve), diâmetro sistólico do ventrículo esquerdo (ECO-Dsve) e fração de ejeção (ECO-Fe). Entretanto, após diversos modelos de regressão, permaneceram como variáveis independentemente associadas à RBP urinária a função renal, a pressão arterial sistólica, a albuminúria, a acidose e a medida do AE. Esse resultado se manteve quando o modelo foi repetido mediante estratificação por albuminúria, sugerindo que mesmo em população normoalbuminúrica a RBP urinária correlacione-se inversamente com função renal. Além disso, a relação inversa de RBP urinária com dilatação cardíaca sugere que, em população com DRC já estabelecida, a RBP urinária possa ter um papel em identificar mecanismos etiológicos, possivelmente por distinguir mecanismos hemodinâmicos daqueles onde há uma patologia renal intrínseca. Por sua vez, a RBP sérica relacionou-se inversamente à função renal e idade, e positivamente a triglicérides, albumina e potássio. Curiosamente, a RBP sérica não se mostrou associada às medidas de metabolismo de carboidrato, sugerindo que seu papel como biomarcador de resistência insulínica seja atenuado na DRC. Também não foram encontradas relações entre RBP urinária ou sérica e calcificação coronária ou espessura de carótidas. Nossos resultados sugerem que a RBP urinária deva ser melhor explorada como marcador de função renal e, possivelmente, como marcador de risco de progressão da DRC / The role of urinary RBP as a biomarker of tubular injury and CKD progression in tubulopathies, glomerulopathies and in transplantation is well established. However, its role in CKD is less studied. In addition, serum RBP has been recently characterized as an insulin resistance marker, but controversial results have been shown. The aim of the study was to evaluate the association of both urinary RBP and serum RBP with kidney function and other variables related to the uremic syndrome and cardiovascular risk in a CKD population. We used the baseline data from the PROGREDIR Cohort, which comprehends 454 participants with CKD, recruited from Hospital das Clínicas, Sao Paulo. In univariate analysis, urinary RBP was inversely related to renal function. In addition, it was also related to albuminuria, SBP, anemia, mineral metabolism, acidosis, albumin, serum RPB, glycated hemoglobin, HOMA, lipids, pulse-wave velocity, left atrium diameter, left ventricle diastolic diameter, left ventricle systolic diameter and ejection fraction. However, in the multivariate analysis, only SBP, albuminuria, acidosis, left atrium diameter and renal function remained significantly associated to urinary RBP. After stratification for albuminuria levels, the same relationship was observed, suggesting that even in the normoalbuminuric population urinary RBP is significantly related to renal function. Interestingly, the inverse association between urinary RBP and cardiac dilation suggests that urinary RBP may play a role in identifying mechanisms related to CKD, by differentiating vascular/cardio-renal conditions versus more intrinsic kidney disease and possibly tubule-interstitial fibrosis. The serum RBP was positively related to renal function, triglycerides, albumin, age and potassium, but not to measurements of carbohydrate metabolism. No relationship between urinary or serum RBP and coronary calcification or carotid thickness was found. Our results suggest that urinary RBP should have its role as a marker of CKD and CKD progression further explored

<p>Megalin is an endocytotic receptor belonging to the low-density lipoprotein family. It has often been viewed only as merely a scavenger receptor of absorptive and secretory epithelia. Recent work has revealed that the megalin intracellular domain contains several motifs potentially binding proteins involved in signal transduction. </p><p>To find potential intracellular proteins binding to megalin, a yeast two-hybrid screening was initiated with the intracellular tail of megalin as the bait. A partial clone encoding the scaffolding protein postsynaptic protein 95 (PSD-95) was found to bind to megalin with its second PDZ-domain. Co-localization experiments in HEK-293 cells and kidney, placenta and parathyroid tissue confirmed this interaction. The PSD-95 related proteins PSD-93 and SAP102 were also confirmed to bind megalin with their PDZ2-domains, but the corresponding domain from SAP97 did not bind. Mutation analysis revealed that an amino acid residue change Ala to Thr was the cause of this.</p><p>Megalin has within the central nervous system (CNS) been shown to be expressed only in the ependymal cells and choroid plexus. Nothing has been known about megalin expression in the spinal cord. To study spatio-temporal expression of megalin in the spinal cord, extensive staining of prenatal and postnatal mouse spinal cord was undertaken. Megalin expression was found in the dorsal part of the embryonic spinal cord. Most of these cells also expressed vimentin, suggesting that megalin has a role in the normal development of astrocytes. In the postnatal mouse, megalin seems to be expressed in oligodendrocytes only in the spinal cord white matter, and co-incident with myelination. This suggests that megalin is involved in the formation and maintenance of myelin along long spinal pathways. Megalin staining was clearly seen in the nucleus of these cells, indicating that megalin works in a notch-like signalling pathway.</p><p>Uptake of retinol to the retina pigment epithelium (RPE) has long been thought to be a diffusion process. Staining for megalin in RPE revealed strong expression, and uptake experiments with 3H-retinol bound to retinol-binding protein and blocking with the LDL-receptor family specific antagonist receptor-associated protein (RAP) showed that megalin is a receptor for uptake of retinol to the RPE.</p>