Biomedical subjects

Bin Xu

Publications and source records attributed to Bin Xu.

At least 73 records · Page 4Linked to original sources

PubMed2004

Vascular endothelial growth factor induces abnormal microvasculature in the endoglin heterozygous mouse brain.

Hereditary hemorrhagic telangiectasia (HHT), associated with brain arteriovenous malformations, is caused by a loss of function mutation in either the endoglin (HHT1) or activin receptor-like kinase 1 gene (ALK-1, HHT2). Endoglin heterozygous (Eng+/-)mice have been proposed as a disease model. To better understand the role of endoglin in vascular malformation development, we examined the effect of vascular endothelial growth factor (VEGF) hyperstimulation on microvessels in adult endoglin heterozygous (Eng+/-) mice using an adenoviral vector to deliver recombinant human VEGF165 cDNA (AdhVEGF) into basal ganglia. VEGF expression was increased in AdhVEGF mice compared with the AdlacZ and saline group (P < 0.05) and localized to multiple cell types (neurons, astrocytes, endothelial cells, and smooth muscle cells) by double-labeled immunostaining. VEGF overexpression increased microvessel count for up to 4 weeks in both the Eng+/+ and Eng+/- groups (Eng+/+ 185 +/- 14 vs. Eng+/- 201 +/- 10 microvessels/mm2). Confocal microscopic examination revealed grossly abnormal microvessels in eight of nine Eng+/- mouse brains compared with zero of nine in Eng+/+ mice (P < 0.05). Abnormal microvessels featured enlargement, clustering, twist, or spirals. VEGF receptor Flk-1 and TGF-beta receptor 1 (T beta R1) expression were reduced in the Eng+/- mouse brain compared with control. Excessive VEGF stimulation may play a pivotal role in the initiation and development of brain vessel malformations in states of relative endoglin insufficiency in adulthood. These observations are relevant to our general understanding of the maintenance of vascular integrity.

Animals↗

PubMed2004

Retroviral delivery of homeobox D3 gene induces cerebral angiogenesis in mice.

Angiogenesis is regulated by concerted actions of angiogenic and angiostatic factors. Homeobox D3 gene (HOXD3) is a potent proangiogenic transcription factor that promotes angiogenesis by modulating the expression of matrix-degrading proteinases, integrins, and extracellular matrix components. Application of HOXD3 can promote angiogenesis in the skin, but its role in other vascular beds has not been examined. The authors examined HOXD3 expression in human brain vessels by in situ hybridization. Although little or no HOXD3 mRNA was detected in normal brain vessels, increased levels of HOXD3 and its target gene, alpha V beta 3, were found in angiogenic vessels in human brain arteriovenous malformations. The authors further investigated whether HOXD3 plays a role in cerebral angiogenesis in a murine model. Expression of HOXD3 in mouse brain was achieved through retroviral vector-mediated HOXD3 gene transfer. HOXD3 expression lead to a significant induction of cerebral angiogenesis as shown by quantitative microvessel counting (HOXD3: 241 +/- 19 vessels/mm2 vs. saline: 150 +/- 14 vessels/mm2, P < 0.05). The data also showed that focal cerebral blood flow was increased in the angiogenic region with less vascular leakage. Moreover, expression of HOXD3 led to an increase in the expression of a direct downstream target gene alpha V beta 3 integrin. The data suggest that HOXD3 may play an important role in regulating cerebral angiogenesis, and that gene transfer of HOXD3 may provide a novel and potent means to stimulate angiogenesis.

Animals↗

PubMed2004

The endothelial cell-specific antibody PAL-E identifies a secreted form of vimentin in the blood vasculature.

During mammalian vascular development, endothelial cells form a complex array of vessels that differ markedly in structure and function, but the molecular basis for this vascular complexity is poorly understood. Recent insights into endothelial diversity have come from the identification of molecular markers expressed on distinct endothelial cell populations. One such marker, the PAL-E antibody, has been used for almost 20 years to distinguish blood and lymphatic vessels, but the identity of the protein recognized by PAL-E has been unknown. In the present study we have used protein purification and tandem mass spectrometry analysis of tryptic peptides to identify the PAL-E antigen as a secreted form of vimentin. Vimentin has been well characterized as an intracellular intermediate filament protein expressed broadly in mesenchymal cells. In contrast, PAL-E-reactive vimentin is secreted extracellularly, its synthesis is restricted to a distinct population of blood endothelial cells and activated macrophages, and PAL-E-reactive vimentin is found in circulating human blood. PAL-E-reactive vimentin does not arise from an endothelial cell-specific mRNA transcript but is the product of cell-specific posttranslational modification. The PAL-E antibody therefore defines secretion of vimentin as a molecular distinction among endothelial cells and exposes a novel, extracellular role for vimentin in the blood vasculature.

Amino Acid Sequence↗

PubMed2004

Molecular recognition at purine and pyrimidine nucleotide (P2) receptors.

In comparison to other classes of cell surface receptors, the medicinal chemistry at P2X (ligand-gated ion channels) and P2Y (G protein-coupled) nucleotide receptors has been relatively slow to develop. Recent effort to design selective agonists and antagonists based on a combination of library screening, empirical modification of known ligands, and rational design have led to the introduction of potent antagonists of the P2X(1) (derivatives of pyridoxal phosphates and suramin), P2X(3)(A-317491), P2X(7) (derivatives of the isoquinoline KN-62), P2Y(1)(nucleotide analogues MRS 2179 and MRS 2279), P2Y(2)(thiouracil derivatives such as AR-C126313), and P2Y(12)(nucleotide/nucleoside analogues AR-C69931X and AZD6140) receptors. A variety of native agonist ligands (ATP, ADP, UTP, UDP, and UDP-glucose) are currently the subject of structural modification efforts to improve selectivity. MRS2365 is a selective agonist for P2Y(1)receptors. The dinucleotide INS 37217 potently activates the P2Y(2)receptor. UTP-gamma-S and UDP-beta-S are selective agonists for P2Y(2)/P2Y(4)and P2Y(6)receptors, respectively. The current knowledge of the structures of P2X and P2Y receptors, is derived mainly from mutagenesis studies. Site-directed mutagenesis has shown that ligand recognition in the human P2Y(1)receptor involves individual residues of both the TMs (3, 5, 6, and 7), as well as EL 2 and 3. The binding of the negatively-charged phosphate moiety is dependent on positively charged lysine and arginine residues near the exofacial side of TMs 3 and 7.

Adenine Nucleotides↗

PubMed2004

Diabetes-associated mutations in insulin identify invariant receptor contacts.

Mutations in human insulin cause an autosomal-dominant syndrome of diabetes and fasting hyperinsulinemia. We demonstrate by residue-specific photo cross-linking that diabetes-associated mutations occur at receptor-binding sites. The studies use para-azido-phenylalanine, introduced at five sites by total protein synthesis. Because two such sites (Val(A3) and Phe(B24)) are largely buried in crystal structures of the free hormone, their participation in receptor binding is likely to require a conformational change to expose a hidden functional surface. Our results demonstrate that this surface spans both chains of the insulin molecule and includes sites of rare human mutations that cause diabetes.

Azides↗

PubMed2004

[Preliminary experimental study on treatment of portal hypertension with auxiliary partial orthotopic liver transplantation].

OBJECTIVE: To evaluate the therapeutic efficacy of auxiliary partial orthotopic liver transplantation (APOLT) on portal hypertension in liver cirrhosis with amelioration of portal vein congestion, changes in portal vein pressure and status of the graft. METHODS: The recipients were porcine model of biliary cirrhosis reproduced by ligation of the common bile duct. During transplantation, arterial blood pressure, central venous pressure were recorded. Buffer base, standard bicarbonate and pH of arterial blood samples were determined and analyzed in order to assess the impact of operation on the animals. The hemodynamics were also monitored. Color Doppler ultrasonographic examination was performed on recipients before operation, intra-operation and 7 days after operation, respectively. Portal vein pressure, blood bilirubin and variables of liver function were measured by using an autoanalyzer. Wedge biopsy specimens of each pig were obtained, stained with hematoxylin-eosin, and examined. Analysis of variance was performed. Otherwise non-parametric tests were used. RESULTS: Eight weeks after ligation of the common bile duct, biliary cirrhosis was reproduced in all the pigs, and histopathological examination of the liver specimen showed a large number of pseudo-lobules. In 6 pigs with hepatic cirrhosis liver transplantation was done. Five of the 6 (83.3%) animals survived for 7 days. One recipient died because of unsuccessful operation, the others showed stable hemodynamics during the operation. Seven days after transplantation, the blood flow of the two liver portal veins was observed by the use of color Doppler ultrasonography. It was found that the blood flow in the donor portal vein was much richer than that of native portal vein. The venous outflow of the graft was ample and smooth, and no thrombosis of the hepatic vein or portal vein was found. The variables, including alanine aminotransferase, aspartate aminotransferase, bilirubin and total bilirubin, were significantly improved 7 days after operation compared with pre-operative data. Portal pressure was found to be (20.76+/-2.42)cm H(2)O(1 cm H(2)O=0.098 kPa), (17.62+/-2.33)cm H(2)O and (14.72+/-2.25)cm H(2)O before the operation, during the operation, and 7 days after operation, respectively, and the difference was statistically significant(P<0.01). On the 7 days after transplantation, histopathological examination revealed evidence of damage with mild steatosis and sporadic necrotic hepatocytes and focal hepatic lobular degeneration in the graft, especially in the area around the central vein. CONCLUSION: APOLT is a hopeful option for the treatment of portal hypertension. This procedure can provide not only some improvement of the liver function but also decrease the pressure of portal vein.

Animals↗

PubMed2003

Surgical intervention for obstructive jaundice due to biliary tumor thrombus in hepatocellular carcinoma.

This retrospective study in eight surgically treated patients with obstructive jaundice due to biliary tumor thrombus in a patient with hepatocellular carcinoma (HCC) was performed to evaluate the role of surgical intervention. All biliary tumor thrombi were confirmed preoperatively or intraoperatively. Only two manifested intraluminal biliary obstructions due to a primary tumor that had not been found preoperatively. The operative procedures included hepatectomy with removal of the biliary tumor thrombus (n=3), hepatectomy combined with extrahepatic bile duct resection (n=1), thrombectomy through a choledochotomy (n=3), and piggyback orthotopic liver transplantation (n=1). The 1- and 3-year survival rates were 62.5% and 37.5%, respectively. Two patients survived more than 5 years. Surgical intervention was effective in patients with obstructive jaundice due to a biliary tumor thrombus in an HCC. Thus surgery for a recurrence can prolong survival, and liver transplantation is a treatment worthy of further investigation.

Adult↗

PubMed2003

Crystal structure of allo-Ile(A2)-insulin, an inactive chiral analogue: implications for the mechanism of receptor binding.

The crystal structure of an inactive chiral analogue of insulin containing nonstandard substitution allo-Ile(A2) is described at 2.0 A resolution. In native insulin, the invariant Ile(A2) side chain anchors the N-terminal alpha-helix of the A-chain to the hydrophobic core. The structure of the variant protein was determined by molecular replacement as a T(3)R(3) zinc hexamer. Whereas respective T- and R-state main-chain structures are similar to those of native insulin (main-chain root-mean-square deviations (RMSD) of 0.45 and 0.54 A, respectively), differences in core packing are observed near the variant side chain. The R-state core resembles that of the native R-state with a local inversion of A2 orientation (core side chain RMSD 0.75 A excluding A2); in the T-state, allo-Ile(A2) exhibits an altered conformation in association with the reorganization of the surrounding side chains (RMSD 0.98 A). Surprisingly, the core of the R-state is similar to that observed in solution nuclear magnetic resonance (NMR) studies of an engineered T-like monomer containing the same chiral substitution (allo-Ile(A2)-DKP-insulin; Xu, B., Hua, Q. X., Nakagawa, S. H., Jia, W., Chu, Y. C., Katsoyannis, P. G., and Weiss, M. A. (2002) J. Mol. Biol. 316, 435-441). Simulation of NOESY spectra based on crystallographic protomers enables the analysis of similarities and differences in solution. The different responses of the T- and R-state cores to chiral perturbation illustrates both their intrinsic plasticity and constraints imposed by hexamer assembly. Although variant T- and R-protomers retain nativelike protein surfaces, the receptor-binding activity of allo-Ile(A2)-insulin is low (2% relative to native insulin). This seeming paradox suggests that insulin undergoes a change in conformation to expose Ile(A2) at the hormone-receptor interface.

Binding Sites↗

PubMed2003

2-Substitution of adenine nucleotide analogues containing a bicyclo[3.1.0]hexane ring system locked in a northern conformation: enhanced potency as P2Y1 receptor antagonists.

Preference for the northern (N) ring conformation of the ribose moiety of adenine nucleotide 3',5'-bisphosphate antagonists of P2Y(1) receptors was established by using a ring-constrained methanocarba (a bicyclo[3.1.0]hexane) ring as a ribose substitute (Nandanan et al. J. Med. Chem. 2000, 43, 829-842). We have now combined the ring-constrained (N)-methanocarba modification with other functionalities at the 2-position of the adenine moiety. A new synthetic route to this series of bisphosphate derivatives was introduced, consisting of phosphorylation of the pseudoribose moiety prior to coupling with the adenine base. The activity of the newly synthesized analogues was determined by measuring antagonism of 2-methylthio-ADP-stimulated phospholipase C (PLC) activity in 1321N1 human astrocytoma cells expressing the recombinant human P2Y(1) receptor and by using the radiolabeled antagonist [(3)H]2-chloro-N(6)-methyl-(N)-methanocarba-2'-deoxyadenosine 3',5'-bisphosphate 5 in a newly developed binding assay in Sf9 cell membranes. Within the series of 2-halo analogues, the most potent molecule at the hP2Y(1) receptor was an (N)-methanocarba N(6)-methyl-2-iodo analogue 12, which displayed a K(i) value in competition for binding of [(3)H]5 of 0.79 nM and a K(B) value of 1.74 nM for inhibition of PLC. Thus, 12 is the most potent antagonist selective for the P2Y(1) receptor yet reported. The 2-iodo group was substituted with trimethyltin, thus providing a parallel synthetic route for the introduction of an iodo group in this high-affinity antagonist. The (N)-methanocarba-2-methylthio, 2-methylseleno, 2-hexyl, 2-(1-hexenyl), and 2-(1-hexynyl) analogues bound less well, exhibiting micromolar affinity at P2Y(1) receptors. An enzymatic method of synthesis of the 3',5'-bisphosphate from the corresponding 3'-monophosphate, suitable for the preparation of a radiophosphorylated analogue, was explored.

Adenine Nucleotides↗

PubMed2003

[The role and significance of retrohepatic tunnel and the liver hanging tape passed through the tunnel in difficult hepatectomies].

OBJECTIVE: To explore the role and significance of liver hanging tape passed through the retrohepatic tunnel developed by dissecting the tissue plane between anterior surface of the inferior vena cava (IVC) and caudate lobe, in order to be substitute for control of in- and out-flow blood vessels in difficult hepatectomies. METHODS: Retrohepatic tunnel was developed by dissecting the anterior surface of the retrohepatic portion of the IVC, 7 difficult hepatectomies were performed with the use of liver hanging tape and hemostatic plate. RESULTS: Liver hanging tape was placed successfully in 7 cases. VIII segmentectomy, right hemihepatectomy, left hemihepatectomy and right trilobectomy plus complete caudate lobectomy were performed, there was no complication related to this maneuver. CONCLUSION: It is feasible for placing liver hanging tape through the retrohepatic tunnel. In addition, it has extensive indications and minimal influence on hemodynamic response. It is a better way for the difficult hepatectomy and for harvesting the liver graft in living related liver transplantation.

Adolescent↗

PubMed2003

Molecular profile of the unique species of traditional Chinese medicine, Chinese seahorse (Hippocampus kuda Bleeker).

A cDNA library of male Chinese seahorse (Hippocampus kuda Bleeker) was constructed to investigate the molecular profile of seahorse as one of the most famous traditional Chinese medicine materials, and to reveal immunological and physiological mechanisms of seahorse as one of the most primitive vertebrates at molecular level. A total of 3372 expressed sequence tags (ESTs) consisting of 1911 unique genes (345 clusters and 1566 singletons) were examined in the present study. Identification of the genes related to immune system, paternal brooding and physiological regulation provides not only valuable insights into the molecular mechanism of immune system in teleost fish but also plausible explanations for pharmacological activities of Chinese seahorse. Furthermore, the occurrence of high prevalent C-type lectins suggested that a lectin-complement pathway might exert a more dominant function in the innate immune system of teleost than mammal. Carbohydrate recognition domain (CRD) without a collagen-like region in the lectins of seahorse was likely an ancient characteristic of lectins similar to invertebrates.

Amino Acid Sequence↗

PubMed2003

Chronic lithium treatment inhibits pilocarpine-induced mossy fiber sprouting in rat hippocampus.

Lithium remains the gold standard in the treatment of bipolar disorder. Long-term treatment with lithium may lead to specific adaptational changes in gene expression that contribute to a neuroprotective effect. In this study, the pilocarpine model of spontaneous limbic epilepsy was used to induce mossy fiber sprouting (axonal growth of the dentate granule cells that synapse on the pyramidal cells of the CA3 region) to examine the prophylactic neuroprotective effects of lithium in vivo. There were four groups of animals: pilocarpine treated (Pil+/Li-); pilocarpine treated followed by lithium (Pil+/Li+); lithium alone (Pil-/Li+); control (Pil-/Li-). Timm staining was used to obtain density measurements in the stratum oriens and the inner molecular layer of the hippocampus. Mossy fiber density was higher in the pilocarpine-treated animals compared to controls. Chronic lithium following pilocarpine treatment attenuated the density of mossy fibers but lithium alone had no effect. No changes in hilar volume or neuronal number were detected using stereological procedures. The ability of lithium to attenuate activation-induced reorganization in the hippocampus provides evidence for its role as a neuroprotective agent in an in vivo model that may be relevant to its clinical effects in bipolar disorder.

Animals↗

PubMed2003

Experimental characterization of transition to chaos in the presence of noise.

Transition to chaos in the presence of noise is an important problem in nonlinear and statistical physics. Recently, a scaling law has been theoretically predicted which relates the Lyapunov exponent to the noise variation near the transition. Here we present experimental observation of noise-induced chaos in an electronic circuit and obtain the fundamental scaling law characterizing the transition. The experimentally obtained scaling exponent agrees very well with that predicted by theory.

Journal Article↗

PubMed2003

Identical alpha-chain T-cell receptor transcripts are present on T cells infiltrating coronary arteries of human cardiac allografts with chronic rejection.

Chronic cardiac allograft rejection is characterized by graft arteriopathy and is a major obstacle of graft survival. We investigated T-cell receptor (TCR) alpha-chain transcripts of T cells infiltrating human epicardial coronary arteries from cardiac allografts with chronic rejection. The non-palindromic adaptor-polymerase chain reaction (NPA-PCR) was used to specifically amplify TCR alpha-chain transcripts from five explanted cardiac allografts with chronic rejection. The amplified products were cloned and sequenced to obtain the entire ValphaJalpha region. Immuno-histochemistry was used to identify the mononuclear cell infiltrates in the coronary arteries. All the five coronary artery specimens exhibited large populations of infiltrating mononuclear cells, which were primarily comprised of T cells and macrophages. In three specimens, high proportions ( approximately 80%) of identical alpha-chain TCR transcripts were detected. In peripheral blood mononuclear cells from a healthy individual, alpha-chain TCR transcripts were unique when compared to each other. Endomyocardial biopsies collected from one patient six months before the allograft was explanted, contained identical alpha-chain TCR transcripts to those found to be clonally expanded in the coronary arteries from this patient. These results indicate that T cells infiltrating the epicardial arteries of cardiac allografts with chronic rejection undergo proliferation and clonal expansion in response to a specific antigen, which very likely is an (allo)antigen(s).

Cell Movement↗

PubMed2003

Induction of focal angiogenesis through adenoviral vector mediated vascular endothelial cell growth factor gene transfer in the mature mouse brain.

Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen and morphogen, which stimulates angiogenesis in a wide variety of tissues and lesions in vivo. In this study, we applied adenoviral vector delivered human VEGF165 cDNA to develop focal non-tumor angiogenesis in the mature mouse brain. Seventy-two adult CD-1 mice underwent Ad h VEGF, Ad lacZ, and saline injection for up to fourweeks. An adenoviral suspension containing 1 x 10(9) particles was injected stereotactically into the right hemisphere of the brain. The results showed that VEGF expression was increased in the Ad h VEGF transduced mice compared to Ad lacZ or saline injected mice ( P < 0.05). VEGF-positive cells were mainly located in the injection hemisphere of Ad h VEGF transduced mice. Quantitative vessel counting showed that microvessels in the Ad h VEGF transduced mice increased following 2 weeks of Ad h VEGF gene transfer compared to the other two groups (Ad h VEGF:241 +/- 19 vs. Ad lacZ :148 +/- 17 and Saline:150 +/- 14 vessels/mm2, P < 0.05). Morphology showed typical angiogenic changes. PCNA-positive staining confirmed these microvessels were actively proliferating. Our study demonstrates that Ad h VEGF-induced VEGF hyper-stimulation causes focal angiogenesis in the mature mouse brain. This novel method of inducing in vivo brain focal angiogenesis provides an opportunity to study the molecular mechanisms independent of the confounding effects of upstream inciting stimuli such as ischemia or tumor.

Adenoviridae↗

PubMed2003

Effect of ischemic preconditioning on P-selectin expression in hepatocytes of rats with cirrhotic ischemia-reperfusion injury.

AIM: To investigate the effects and mechanisms of ischemic preconditioning (IPC) on the ischemia/reperfusion (I/R) injury of liver cirrhosis in rats and the effect of IPC on P-selectin expression in hepatocytes. METHODS: Forty male SD rats with liver cirrhosis were randomly divided into sham operation group (SO group), ischemia/reperfusion group (I/R group), ischemic preconditioning group (IPC group), L-Arginine preconditioning group (APC group), L-NAME preconditioning group (NPC group), eight rats in each group. Hepatocellular viability was assessed by hepatic adenine nucleotide level and energy charge (EC) determined by HPLC, ALT, AST and LDH in serum measured by auto- biochemical analyzer and bile output. The expression of P-selectin in the liver tissue was analyzed by immunohistochemical technique. Leukocyte count in ischemic hepatic lobe was calculated. RESULTS: At 120 min after reperfusion, the level of ATP and EC in IPC and APC groups was higher than that in I/R group significantly. The increases in AST, ALT and LDH were prevented in IPC and APC groups. The livers produced more bile in IPC group than in I/R group during 120 min after reperfusion (0.101+/-0.027 versus 0.066+/-0.027 ml/g liver, P=0.002). There was a significant difference between APC and I/R groups, (P=0.001). The leukocyte count in liver tissues significantly increased in I/R group as compared with SO group (P<0.05). The increase in the leukocyte count was prevented in IPC group. Administration of L-arginine resulted in the same effects as in IPC group. However, inhibition of NO synthesis (NPC group) held back the beneficial effects of preconditioning. Significant promotion of P-selectin expression in hepatocytes in the I/R group was observed compared with the SO group (P<0.01). IPC or L-arginine attenuated P-selectin expression remarkably (P<0.01). However, inhibition of NO synthesis enhanced P-selectin expression (P<0.01). The degree of P-selectin expression was positively correlated with the leukocyte counts infiltrating in liver (r=0.602, P=0.000). CONCLUSION: IPC can attenuate the damage induced by I/R in cirrhotic liver and increase the ischemic tolerance of the rats with liver cirrhosis. IPC can abolish I/R induced leukocyte adhesion and infiltration by preventing post-ischemic P-selectin expression in the rats with liver cirrhosis via a NO-initiated pathway.

Adenosine Diphosphate↗

PubMed2003

Effects of glycine on plasma and liver tissue changes of TNF-alpha, ET-1 and nitric oxide contents in rats with obstructive jaundice.

AIM: To evaluate the effect of glycine on plasma and liver tissue changes of tumor necrosis factor-alpha (TNF-alpha), endothelin-1 (ET-1) and nitric oxide (NO) contents in rats with obstructive jaundice. METHODS: Ninety healthy Wistar rats of both sexes weighing 275+/-25 g were randomly divided into sham-operated, bile duct-ligated, and bile duct-ligated plus glycine-treated groups, the latter was performed with 5% glycine solution substituting for tap water drunk ad libium for 5 days before and 6 days after operation. Blood and liver tissue were sampled at the time of sacrifice on the 8th day post operation. Plasma total bilirubin, endotoxin, levels, as well as TNF-alpha, ET-1 and NO contents in liver tissue were determined. RESULTS: Plasma endotoxin and total bilirubin levels were significantly higher in both bile duct-ligated and bile duct-ligated plus glycine-treated rats than in sham-operated animals (P=0.000613, 0.00921 and 0.00737, 0.00841 respectively), whereas they did not display any statistically significant difference between the former groups (P=0.417 and 0.374 respectively). Likewise, TNF-alpha, ET-1 and NO contents in both plasma and liver tissue were significantly increased in both bile duct-ligated and bile duct-ligated plus glycine-treated rats compared with sham-operated animals(P=0.00813, 0.00793, 0.00671, 0.00804, 0.00872, and 0.00947 in plasma and 0.00531, 0.00785, 0.00912, 0.00981 and 0.00635 in liver tissue respectively). However, these inflammatory mediators in both plasma and liver tissue were significantly reduced in bile duct-ligated rats fed on 5% glycine solution compared with that without (P=0.00953, 0.00891, 0.0795, 0.00867, 0.0697 and 0.00907 in plasma and liver tissue respectively). CONCLUSION: Reduction of TNF-alpha, ET-1 and NO contents in plasma and liver tissue of rats fed on glycine may be helpful to alleviate pathological lesions in obstructive jaundice.

Animals↗

PubMed2003

Functional brain imaging in irritable bowel syndrome with rectal balloon-distention by using fMRI.

AIM: Irritable bowel syndrome (IBS) is characterized by abdominal pain and changes in stool habits. Visceral hypersensitivity is a key factor in the pathophysiology of IBS. The aim of this study was to examine the effect of rectal balloon-distention stimulus by blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) in visceral pain center and to compare the distribution, extent, and intensity of activated areas between IBS patients and normal controls. METHODS: Twenty-six patients with IBS and eleven normal controls were tested for rectal sensation, and the subjective pain intensity at 90 ml and 120 ml rectal balloon-distention was reported by using Visual Analogue Scale. Then, BOLD-fMRI was performed at 30 ml, 60 ml, 90 ml, and 120 ml rectal balloon-distention in all subjects. RESULTS: Rectal distention stimulation increased the activity of anterior cingulate cortex (35/37), insular cortex (37/37), prefrontal cortex (37/37), and thalamus (35/37) in most cases. At 120 ml of rectal balloon-distention, the activation area and percentage change in MR signal intensity of the regions of interest (ROI) at IC, PFC, and THAL were significantly greater in patients with IBS than that in controls. Score of pain sensation at 90 ml and 120 ml rectal balloon-distention was significantly higher in patients with IBS than that in controls. CONCLUSION: Using fMRI, some patients with IBS can be detected having visceral hypersensitivity in response to painful rectal balloon-distention. fMRI is an objective brain imaging technique to measure the change in regional cerebral activation more precisely. In this study, IC and PFC of the IBS patients were the major loci of the CNS processing of visceral perception.

Adult↗