Multilocus binding increases the relaxivity of protein-bound MRI contrast agents.
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Binding Sites↗
Biomedical subjects
Zhaoda Zhang
Publications and source records attributed to Zhaoda Zhang.
Gadolinium meets medicinal chemistry: MRI contrast agent development.
Magnetic resonance imaging (MRI) contrast agents are utilized adjunctively to enhance the contrast between normal and abnormal structures on MRI scans. Along with the rapid evolution of the field has come a new appreciation for the medicinal chemistry of this unique class of metallopharmaceuticals. The efficacy of MRI agents is a complex function of chemical, biophysical, and pharmacological properties, which must be married in a package of exquisite safety. This report illustrates the wide range of medicinal chemistry relevant to existing agents that are either approved or in clinical development, as well as concepts, which may result in exciting new pharmaceuticals in the future.
Chelating Agents↗
[Establishment of whole pancreaticoduodenal allotransplantation model with jejunum drainage and portal venous drainage in pigs].
OBJECTIVE: To establish a pig model of pancreaticoduodenal transplantation with jejunum drainage and portal venous drainage. METHODS: Forty pigs were randomly divided into the donor group and recipient group. University of Wisconsin (UW) solution was used for both in situ flush and storage of all organs under cold storage conditions. Whole pancreaticoduodenal graft was harvested with segments of abdominal aorta and portal vein and shaped under cold UW solution. Then, the end-to-end anastomosis was performed with the donor iliac artery bifurcation Y graft to the recipient superior mesenteric arteries and celiac artery. Furthermore, type I diabetes model was made by removal of the recipient pancreas The venous anastomosis was reconstructed between the donor portal vein and the recipient superior mesenteric vein. Meanwhile, the end-to-side anastomosis was performed with the donor common iliac artery bifurcation Y graft to the recipient abdomial aorta, and the side-to-side intestinal anastomosis between the donor duodenum and the recipient jejunum was performed. RESULTS: Twenty piges were subjected to pancreaticoduodenal transplantation, in which 1 died from respiratory depression because of anesthesia, and 2 had thrombus and infarction in the pancreatic graft after transplantation. 17 cases showed normal blood sugar in peripheral circulation 24 hours after operation, the mean survival of the graft was 18.6 +/- 2.6 days. CONCLUSION: The technique of duodenal transplantation with jejunum drainage and portal venous drainage may pave the way for the further development of pancreas transplantation in clinical practice. It can be utilized in basic research of pancreas transplantation.
Anastomosis, Surgical↗
[The effects of traditional Chinese medicine on distribution of F-actin of leukocytes in acute edematous pancreatitis].
OBJECTIVE: To explore the distribution of F-actin of leukocytes in local circulation of pancreas and system circulation and assess the effects of traditional Chinese medicine WPY complex there on in the case of acute edematous pancreatitis(AEP). METHODS: AEP model of Wistar rats was induced with subcutaneous injection of cerulein. In the treatment group, rats were given 50% WPY (1.5 ml every time) at 0, 2, 4, 6 and 8 hours during the experiment. The leukocytes of blood from the splenic vein and inferior vena cava were incubated with TRITC-Phalloidin for F-actin, and the images were taken with confocal laser scanning microscope. The The distribution of F-actin at the border or central part of leukocyte was analyzed by using Mias system. Results ratio of F-actin border/center gray value of leukocytes increased at the 2nd, 4th and 6th hour, then declined at the 8th hour in AEP rats, but the ratio of F-actin border/center gray value of leukocytes in the blood from the inferior vena cava declined significantly at the 6th hour in the WPY-treated AEP rats(P < 0.01). At 6 hours following the onset of experimental acute edematous pancreatitis, F-actin polymerization and redistribution in the border region of leukocytes were prominent. CONCLUSION: These evidences indicate that leukocytes play an important role in the development of acute pancreatitis. Traditional Chinese medicine WPY can regulate actin redistribution of leukocytes; moreover, WPY may attenuate the stiffness of leukocytes and render them more flexible and transformable in microcirculation.
Actins↗
[The change of cryptdin-4 mRNA expression in the intestine of mouse with experimental pancreatitis].
OBJECTIVE: experimental pancreatitis and explore the mechanism of bacterial translocation at the molecular level in mice with severe acute pancreatitis. METHODS: Thirty-six ICR mice were randomly divided into 6 groups with 6 mice in each group. The animals in the experimental groups (from A to E) received seven intraperitoneal injections of caerulein (50 microg/kg body weight) at hourly intervals over 6 hours, and were killed at 9, 18, 24, 48 and 72 hours after the first injection. The control group (F) received intraperitoneal injection of the same volume of saline, and the animals were killed at the 18th hour after the first injection. Blood and pancreatic tissue samples were obtained after the animals were killed. Amylase and pancreatic pathological alterations were observed. The ileum sequential segments were removed from each mouse. The amplification products of RT-PCR were electrophoresed and the images were analyzed by UVI software. RESULTS: Acute necrotizing pancreatitis in ICR mice were induced by the intraperitoneal injection of caerulein at large doses. Markedly pathological lesions were observed at the 18th hour after the first injection of caerulein. And, intestinal cryptdin-4 mRNA expression was down regulated slightly at the 9th hour and most markedly at the 18th hour (P < 0.05). After 24 hours, the cryptdin-4 mRNA expression recovered to the normal level gradually. CONCLUSION: Acquired cryptdin-4 deficiency may play an important role in the pathogenesis of bacterial tanslocation in acute necrotizing pancreatits.
Acute Disease↗
Technology evaluation: EPI-2010, EpiGenesis.
EpiGenesis, in collaboration with Taisho and Chiesi, is developing EPI-2010, a 21-mer phosphorothioate respirable antisense oligonucleotide (RASON) that blocks the synthesis of the adenosine A1 receptor, for the potential treatment of asthma.
Administration, Inhalation↗
[An in vivo study of reseeding endothelial cell for attenuation of hyperacute rejection after xenotransplantation].
UNLABELLED: To investigate the possible significance and usefulness of reseeding the endothelial cell of recipient for the prevention of hyperacute rejection (HAR) resulting from the xenograft. METHODS: Discordant xenotransplantation model (guinea pig-to-rat) was adopted in this study. Firstly endothelial cells from rat abdominal aorta were separated and cultured. Secondly the guinea pig abdominal aorta of which the endothelium had been removed was cultured with the suspension containing rat endothelial cells (4 x 10(6)/ml). The viability of cultured vessel was assessed using light microscopy and transmission electron microscopy. Thirdly, the guinea pig vessels reseeded with rat endothelial cells were transplanted to rat in vivo. The thrombrosis time was observed. The condition of deposit of IgM and C3 in the recipient's transplanted vessel endothelium was examined by immuno-fluorescence staining assay. RESULTS: The thrombrosis time of the guinea pig vessel reseeded with rat endothelial cells (20.3 + 4.42 h) was significantly prolonged as compared with that of the normal guinea pig vessel (0.35 + 0.284 h) and the guinea pig vessel that had been deprived of endothelium (0.165 + 0.77 h). No deposit of IgM and C3 was seen in the new endothelium of guinea pig vessel in the treated group, whereas deposit of IgM and C3 was observed in the untreated normal guinea pig aorta. CONCLUSION: Donor vessels reseeded with endothelial cells from the recipient will undergo less severe rejection and this technique may be very useful in the attenuation of HAR.
Animals↗