vi, 211 leaves : ill., photos., tables, graphs ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.1976) from the Dept. of Human Physiology and Pharmacology, University of Adelaide

Thesis (Ph.D. 1976) from the Department of Human Physiology and Pharmacology, University of Adelaide.

by Joseph W.C. Leung. / Bibliography: leaves 181-203 / Thesis (M.D.)--Chinese University of Hong Kong, 1986

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

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.

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.

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 (M.S. in veterinary science)--Washington State University, August 2008. / Includes bibliographical references (p. 13-17).

by Francis Ka-leung Chan. / Thesis (M.D.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (p. 187-210). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.