Aluminum is a known contaminant of parenteral nutrition (PN) solutions and it has been suspected to play a role in the development of parenteral nutrition associated cholestasis (PNAC). The primary purpose of my research was to monitor the relationship between serum aluminum level and the development of PNAC in the infants with gastrointestinal failure who required PN therapy. The secondary purpose was to develop a neonatal piglet model to compare different doses of aluminum or PN therapy with known aluminum level was associated with the development of PNAC. Sixteen infants with gastrointestinal pathology were enrolled in the study. Serum aluminum and bilirubin (direct and indirect) concentrations were determined on day 0, 7, 14, and 21 of PN therapy. Five of sixteen (31.3%) infants developed PNAC by day 21. Serum aluminum levels in infants receiving PN peaked at day 7 of therapy and declined thereafter. There was no direct correlation between serum direct bilirubin and serum aluminum levels. Twenty-four piglets, 2 to 4 days old, were placed into four groups: Control group (n=5); Low Al (aluminum) group (n=7), intravenous (iv) injection with aluminum dose at 20 ìgkg-1day-1; High Al (aluminum) group (n=6), iv with aluminum dose at 1500 ìgkg-1day-1; PN (parenteral nutrition) group (n=6), PN solutions with a mean aluminum intake at 37.8±14.3 ìgkg-1day-1. The experiment period was 21 days. Serum bilirubin was significantly (p<0.05) elevated in the High Al and PN groups. Liver aluminum concentration was significantly (p<0.05) elevated in all the experimental groups and the relationship was dose dependant. Serum, and urine concentrations of aluminum were significantly (p<0.05) elevated in High Al but not the Low Al and PN groups. Serum aluminum concentration was not correlated with serum total bilirubin levels. Cholestasis developed by 21 days in five infants and in the piglets of two experimental groups (the High Al group and the PN group). High dose injection of aluminum may play a role in the development of PNAC in the neonatal piglets. The impact of aluminum may depend on the amount of pareternal aluminum intake and the presence of other potential factors such as lack of enternal feeding and individual physiological abilities.

En el Hospital Edgardo Rebagliati Martins, el aporte de lípidos en la Nutrición Parenteral Total (NPT), viene dándose por ácidos grasos de cadena larga. En el presente estudio se compararon los niveles plasmáticos de carnitina de pacientes que reciben NPT basada en TCL y los que reciben NPT basada en TCL/TCM por tiempo prolongado (≥7 días). Previamente se determinaron los niveles plasmáticos de carnitina en personas aparentemente sanas, pacientes con desnutrición severa y pacientes que reciben NPT por más de 20 días. Al final del estudio se hallaron los siguientes valores medios de carnitina plasmática, expresadas en µmol/L: personas aparentemente sanas 34,26; que se halla dentro de los valores normales, en pacientes con desnutrición severa 68,29; pacientes con NPT por más de 20 días 23,64; pacientes con NPT basada en TCL (≥7 días) 43,27; pacientes con NPT basada en TCL/ TCM (≥7 días) 26,68; hallándose sólo diferencia significativa al comparar los grupos que reciben NPT basada TCL y los que reciben NPT basada en TCL/TCM (≥7 días), p meno a 0.05. Palabras Clave: Carnitina, Ácidos grasos, Nutrición parenteral Total, Lípidos. / At the Edgardo Rebagliati Martins Hospital, the contribution of the lipids in Total Parenteral Nutrition (TPN) is given by long chain fatty acids (LCT). This study compared the plasma levels of carnitine in patients receiving TPN based on LCT and patients receiving TPN -based LCT/MCT (≥ 7 days). Previously, had been determinated the plasmatics levels of carnitine in apparently healthy people, severe malnutrition patients and patients receiving TPN for more than 20 days. At the end of this study, we found the next plasmatics carnitine medium values, showed in µmol/L: apparently healthy people 34,26; this is within the normal values, in severe malnutrition patients 68,29; and patients receiving TPN for more than 20 days 23,64; patients with TPN based on LCT (≥ 7 days) 43,27; patients with TPN based LCT/MCT (≥ 7 days) 26,68; We met only significant difference when comparing groups receiving TPN based LCT and patients receiving TPN-based TCM / TCL (≥ 7 days), p menor a 0.05. Key Words: Carnitine, Fatty acids, Total Parenteral Nutrition, Lipids.

Thesis--PlanA (M.S.)--University of Wisconsin--Stout, 2002. / Includes bibliographical references.

Thesis (doctoral)--University of Göteborg.

Parenteral nutrition (PN) is an essential life sustaining therapy for premature and critically ill infants. However, prolonged PN therapy can lead to life-threatening liver damage, and cause parenteral nutrition associated cholestasis (PNAC). There has been some recent evidence that aluminum accumulation in the livers of PN-fed subjects may lead to hepatic damage leading to liver injury. This dissertation aimed to investigate the role of aluminum as a toxic component of parenteral nutrition and as a risk factor in developing PNAC. The project composed of two main studies. The objectives of the first study were: 1) Evaluate the early morphological changes in piglet liver after intravenous administration of aluminum chloride hexahydrate at a dose of 1500 µg/kg/d.; 2) Determine whether the morphological changes deteriorate further with increasing duration of exposure and whether these changes correlate with changes in biochemical markers of cholestasis; 3) Identify the appropriate imaging technique for studying the ultrastructural changes in the liver; 4) Determine if intravenous injection of high dose aluminum into neonatal piglets disrupts iron homeostasis in the liver. The results showed that intravenous infusion of aluminum in neonatal piglets led to marked elevation in serum total bile acids, and transmission electron microscopy-energy dispersive microanalysis (TEM-EDX) was suitable in detecting the site of Al deposition in the liver and in demonstrating histopathological changes associated with Al infusion. The objectives of the second part were to: 1) Investigate the role of aluminum as a toxic component of parenteral nutrition and as a risk factor in causing liver injury; 2) Evaluate the effect of reducing aluminum content of parenteral nutrition on liver iron homeostasis; 3) Investigate the effect of low aluminum PN and high aluminum PN (regular PN) on the mRNA expression of Bsep and Mrp2. The results showed that administration of PN solution with lower Al content led to reduced levels of serum and hepatic Al in low Al PN group compared to regular PN group. This reduction was associated with less histopathological changes in the liver. On the other hand, administration of regular PN in piglets led to decreased expression of transporter Mrp2. This work suggests that reducing Al content in PN may reduce the development and severity of liver injury in the piglets.

Parenteral nutrition (PN) is an essential life sustaining therapy for premature and critically ill infants. However, prolonged PN therapy can lead to life-threatening liver damage, and cause parenteral nutrition associated cholestasis (PNAC). There has been some recent evidence that aluminum accumulation in the livers of PN-fed subjects may lead to hepatic damage leading to liver injury. This dissertation aimed to investigate the role of aluminum as a toxic component of parenteral nutrition and as a risk factor in developing PNAC. The project composed of two main studies. The objectives of the first study were: 1) Evaluate the early morphological changes in piglet liver after intravenous administration of aluminum chloride hexahydrate at a dose of 1500 µg/kg/d.; 2) Determine whether the morphological changes deteriorate further with increasing duration of exposure and whether these changes correlate with changes in biochemical markers of cholestasis; 3) Identify the appropriate imaging technique for studying the ultrastructural changes in the liver; 4) Determine if intravenous injection of high dose aluminum into neonatal piglets disrupts iron homeostasis in the liver. The results showed that intravenous infusion of aluminum in neonatal piglets led to marked elevation in serum total bile acids, and transmission electron microscopy-energy dispersive microanalysis (TEM-EDX) was suitable in detecting the site of Al deposition in the liver and in demonstrating histopathological changes associated with Al infusion. The objectives of the second part were to: 1) Investigate the role of aluminum as a toxic component of parenteral nutrition and as a risk factor in causing liver injury; 2) Evaluate the effect of reducing aluminum content of parenteral nutrition on liver iron homeostasis; 3) Investigate the effect of low aluminum PN and high aluminum PN (regular PN) on the mRNA expression of Bsep and Mrp2. The results showed that administration of PN solution with lower Al content led to reduced levels of serum and hepatic Al in low Al PN group compared to regular PN group. This reduction was associated with less histopathological changes in the liver. On the other hand, administration of regular PN in piglets led to decreased expression of transporter Mrp2. This work suggests that reducing Al content in PN may reduce the development and severity of liver injury in the piglets.

Thesis (doctoral)--University of Göteborg.

Thesis (M.S.)--University of Hong Kong, 1999. / Includes bibliographical references (leaves 92-125).

Thesis (M.S.)--University of Hong Kong, 1999. / Includes bibliographical references (leaves 92-125) Also available in print.

MASCARENHAS, Mylenne Borges Jácome. Monitorização das etapas envolvidas na terapia de nutrição parenteral neonatal em uma maternidade pública de Fortaleza. 2009. 101 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal do Ceará. Faculdade de Farmácia, Odontologia e Enfermagem, Fortaleza, 2009. / Submitted by denise santos (denise.santos@ufc.br) on 2012-12-19T16:22:47Z No. of bitstreams: 1 2009_dis_mbjmascarenhas.pdf: 1518172 bytes, checksum: 92a5cd354361154da4f5518660e1d1a4 (MD5) / Approved for entry into archive by Erika Fernandes(erikaleitefernandes@gmail.com) on 2012-12-20T12:48:20Z (GMT) No. of bitstreams: 1 2009_dis_mbjmascarenhas.pdf: 1518172 bytes, checksum: 92a5cd354361154da4f5518660e1d1a4 (MD5) / Made available in DSpace on 2012-12-20T12:48:20Z (GMT). No. of bitstreams: 1 2009_dis_mbjmascarenhas.pdf: 1518172 bytes, checksum: 92a5cd354361154da4f5518660e1d1a4 (MD5) Previous issue date: 2009 / Many newborns (NB) require total parenteral nutrition (TPN) as main or adjuvant therapy, once they can not obtain an adequate nutrition through gastrointestinal system. The TPN offers to the debilitated patient the necessary electrolytes, the required protein source and the energy for metabolic processes. The nutritional therapy phases are: indication for nutritional support; medical prescription; pharmaceutical evaluation; manipulation of the solutions; delivery; conservation; administration; clinical and laboratorial controlling; and, final evaluation. Due to the complexity of the steps involved, it is important the integration of the multidisciplinary team, so that the therapy is used rationally, resulting in benefits to the NB in terms of safety, effectiveness and quality. The present work aimed to monitor the nutritional therapy in NB, observing the indication, prescription, manipulation and administration of the parenteral nutrition in a public maternity in Fortaleza – CE. It was performed an observational, descriptive and prospective study involving all phases. The data were collected from a structured formulary according to the inspection rule (Portaria 272/98, ANVISA). The statistical analysis was executed using the program Statistical Package for the Social Sciences, version 16.0, and it was considered a significance level of 5%. Among the 73 NB evaluated, 97,3% presented as main diagnostic pre-term newborn. Related to the medical prescriptions, 2,3% were not delivered to the pharmacy, 16,7 and 9% were delivered out of the established time and with problems in the prescriptions, respectively. During the manipulation, 0,6 and 6,15% of errors occurred, respectively in the aspiration or in the addition of the substances. At the moment of the administration, 99% of the NB did not have exclusive access for the TPN; neither 98,7% of the bags nor 99% of the labels were adequately checked. In 36% of catheter placement, no cleaning procedure was performed. In conclusion, the controlling of process involved in nutritional therapy and a more active multidisciplinary team will assess the correction of deviations and errors, once the prescription, manipulation and administration represent the critic steps for a successful therapy. / Recém-nascidos (RN) que não podem obter uma nutrição adequada através do trato gastrintestinal requerem nutrição parenteral total (NPT) como terapia exclusiva ou de apoio. A NPT fornece ao paciente debilitado os eletrólitos necessários, uma reserva protéica adequada, e energia para os processos metabólicos. As fases da terapia nutricional são: indicação de suporte nutricional; prescrição médica; avaliação farmacêutica; manipulação das soluções, transporte, conservação, administração, controle clinico, laboratorial e avaliação final. Em virtude da complexidade das etapas envolvidas, é importante a integração da equipe multidisciplinar, de modo que a terapia seja usada racionalmente, resultando em benefícios ao RN quanto à segurança, efetividade e qualidade. O presente trabalho objetivou monitorar a terapia nutricional em RN, observando a indicação, a prescrição, a manipulação e a administração da nutrição parenteral em uma maternidade pública do município de Fortaleza – CE. Foi realizado um estudo observacional, descritivo e prospectivo, envolvendo as etapas da terapia de nutrição parenteral. Os dados foram coletados a partir de um formulário estruturado de acordo com o roteiro de inspeção (Portaria 272/98, ANVISA). A análise estatística foi executada utilizando-se o programa Statistical Package for the Social Sciences versão 16.0 e foi considerada significância de 5%. Entre os 73 RN avaliados, 97,3% apresentaram a prematuridade como diagnóstico principal. Com relação às prescrições médicas, 2,3% não foram entregues ao serviço de farmácia, 16,7% e 9% foram enviadas fora do horário de entrega estabelecido e com problemas na prescrição, respectivamente. Durante a manipulação, 0,6 e 6,15% de erros ocorreram na aspiração e na adição das substâncias, respectivamente. No momento da administração, 99% dos RN não possuíam acesso exclusivo para a NPT; assim como, 98,7% das bolsas nem 99% dos rótulos foram adequadamente checados. Em 36% da inserção do cateter, nenhum procedimento de limpeza foi realizado. Dessa forma, conclui-se que um melhor controle do processo envolvido na terapia nutricional e uma equipe multidisciplinar mais atuante contribuirão para a correção dos desvios e erros, uma vez que a prescrição, a manipulação e a administração representam os passos críticos para uma terapia bem-sucedida.