Biomedical subjects

J W Ding

Publications and source records attributed to J W Ding.

At least 19 recordsLinked to original sources

PubMed2006

Lattice dynamics of carbon chain inside a carbon nanotube.

Based on the density functional theory, we obtain the optimum geometry of carbon chain inside a carbon nanotube. The phonon spectrum and specific heat of such a chain and nanotube hybrid system are calculated in terms of lattice dynamics theory. Some new phonon branches that have been obtained come from the coupling vibrations of the nanotube and the chain. The bending and stretching modes of the chain appear at about 520 cm(-1)and 1935 cm(-1) at Gamma point, respectively. It is found that the softening of G modes results mainly from the chain induced variations in the bond length on nanotube, independent of van der Waals interaction, while the stiffening of radial breathing mode is developed by the competition between the two factors. In the low-frequency region, the vibrational density of states are very different from that of the bare nanotube. Its specific heat implies the underlying quantized phonon structures and much large thermal conductivity in the hybrid system. In addition, the chain-length dependent vibration modes are calculated, from which it is expected that a finite chain of about 14 carbon atoms in the nanotube may produce the experimental Raman peak at about 1850 cm(-1).

Journal Article↗

PubMed2006

Liver ischemia contributes to early islet failure following intraportal transplantation: benefits of liver ischemic-preconditioning.

Early graft failure following intraportal islet transplantation (IPIT) represents a major obstacle for successful islet transplantation. Here, we examined the role of islet emboli in the induction of early graft failure and utilized a strategy of ischemic-preconditioning (IP) to prevent early islet destruction in a model of syngeneic IPIT in STZ-induced diabetic mice. Numerous focal areas of liver necrosis associated with the islet emboli were observed within 24 h post-IPIT. Pro-inflammatory cytokines, IL-1beta and IL-6, were significantly increased 3 h after IPIT, while TNF-alpha was elevated for up to 5 days post-IPIT. Caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling positive cells were observed in the transplanted islets trapped in areas of necrotic liver at 3 h and 1 day post-IPIT. Hyperglycemia was corrected immediately following IPIT of 200 islets, but recurrence of hyperglycemia was observed within 14 days associated with a poor response to glucose challenge. IP, a procedure of pre-exposure of the liver to transient ischemia and reperfusion, protected the liver from embolism-induced ischemic injury and prevented early islet graft failure. These data suggest that islet embolism in the portal vein is a major cause of functional loss following IPIT that can be prevented by liver IP.

Animals↗

PubMed2001

Activation of the novel prothrombinase, fg12, as a basis for the pregnancy complications spontaneous abortion and pre-eclampsia.

PROBLEM: Impaired trophoblast invasion during the first trimester of pregnancy is linked to spontaneous abortion, and defective invasion in the second trimester to hypertension + proteinuria (pre-eclampsia). Hypertension developing during the third trimester of human pregnancy represents, in part, a corrective response in the mother to provide adequate placental perfusion for fetal growth when trophoblast has not to invaded and converted the myometrial porprtion of maternal spiral arteries into to low resistance-high capacitance conduits. Deportation of vesicles from hypoxemic trophoblast is thought to cause hypertension plus proteinuria, vascular damage and a systemic coagulopathy. Trophoblast invasion may be inhibited by local cytokines, such as TGF-betas but Thl-type cytokines associated with pre-eclapmsia and spontaneous abortions (e.g., IL-1, TNF-alpha, IFN-gamma) are not known to inhibit migration at in situ concentrations. Trophoblast invasion is also inhibited by the binding of surface integrins to fibronectin and fibrin, and fibrin production is stimulated by these Th1 cytokines via up-regulation of prothrombinases(s) such as fg12 which directly and via TNF-alpha-facilitated inflamation compromise trophoblast cell integrity. We, therefore, asked if fg12 expression and TNF-alpha are increased in first trimester human miscarriage and in third trimester pre-eclampsia. METHODS: fg12 mRNA was detected using in situ hybridization and fg12 protein by immunohistochemistry. TNF-alpha mRNA and protein were similarly tested. The techniques were validated using uterine sections from day 8.5 of CBA x DBA/2 pregnancies, and then were applied to sections of placentae from normal and pre-eclamptic pregnancies with and without intrauterine fetal growth restriction (IUGR). Fibrin was detectectd by immunohistochemistry. RESULTS: Expression of fg12 protein correlated with fg12 mRNA expression in mouse uteri and in placentae from normal human pregnancies. Increased expression of fg12 and TNF-alpha mRNA and protein, and increased fibrin deposition was detected in placental trophoblast. CONCLUSIONS: Activation of fg12 prothrombinase by Th1-type cytokines in pregnancy may lead to spontaneous abortion, or in ongoing pregnancy, to pre-eclampsia and/or IUGR.

Abortion, Spontaneous↗

PubMed2001

Fgl2 prothrombinase expression in mouse trophoblast and decidua triggers abortion but may be countered by OX-2.

Spontaneous abortion of normal karyotype embryos in mice and in humans is associated with an increase in uterine T helper (Th) 1 type proinflammatory cytokines, tumour necrosis factor (TNF)-alpha, interferon-gamma and interleukin (IL)-1, and a deficiency of Th2/3 type cytokines, IL-4, IL-10, and transforming growth factor (TGF)-beta2. In mice, Th1 cytokines up-regulate a novel prothrombinase, fgl2, which via thrombin, leads to activation of polymorphonuclear leukocytes that terminate the pregnancy. Here we show that Th1 cytokines up-regulate fgl2 mRNA in fetal trophoblast and secondary decidua of CBA/JxDBA/2 and CBA/JxBALB/c matings, and promote fibrin deposition. This pattern is accompanied by a high rate of abortion. However, the spontaneous abortion rates in abortion-prone CBAxDBA/2 matings and in low abortion rate CBAxBALB/c matings were significantly lower than that expected from the frequency of implantations with high levels of fibrin and fgl2 mRNA(hi). As the glycoprotein OX-2 occurs in the pregnant rat uterus and can deviate cytokine responses to Th2/3, we investigated OX-2 in pregnant CBA/J mice. We found OX-2 mRNA was present at the same sites as fgl2 mRNA, but was reduced in response to Th1 cytokines. Furthermore, anti-OX-2 raised the abortion rate to predicted levels, while recombinant OX-2 dramatically reduced the abortion rate. Fgl2 prothrombinase may provide a mechanism explaining pregnancy loss, and conversely, successful pregnancy may be due in part to OX-2-dependent activation of maternal tolerance mechanisms at the feto-maternal interface.

Abortion, Spontaneous↗

PubMed1999

The emerging role of immunoregulation of fibrinogen-related procoagulant Fgl2 in the success or spontaneous abortion of early pregnancy in mice and humans.

PROBLEM: Abortion of chromosomally normal embryos in the CBA X DBA/2 mating combination is triggered by release of Th1 cytokines (tumor necrosis factor [TNF]-alpha, interferon [IFN]-gamma, and interleukin [IL]-1), which cause abortion via a novel prothrombinase, Fgl2, and polymorphonuclear leukocytes. The site of activation may be maternal vascular endothelium on arteries and veins nourishing the placenta. Activation of coagulation is also prominent in spontaneous abortion of chromosomally normal human embryos. We asked where is Fgl2 up-regulated in the uterus in murine abortions, and if similar Fgl2 expression occurs in human pregnancy failure. METHODS: Control CBA X DBA/2 pregnant mice, or from mice injected with TNF-alpha + IFN-gamma on day 7.5 of gestation, were removed on day 8.5, fixed, sectioned, and subject to in situ hybridization for Fgl2. Sections were also stained for fibrin. Elective first trimester termination samples or biopsies taken early in the course of a recurrent miscarriage were similarly fixed, sectioned, and analyzed by in situ hybridization. Control and cytokine-treated mice were anticoagulated with heparin, an activator of antithrombin III, and/or the direct anti-thrombin inhibitor hirudin. RESULTS: Low level Fgl2 expression localized to basal decidua remote from the embryo was noted in control mice; cytokine treatment, which causes greater than 80% of abortions, produced a striking up-regulation in this area as well as in a band at the junction of decidua and myometrium. Trophoblast also became strikingly positive. Fgl2 expression was associated with increased fibrin staining. Anticoagulation significantly protected against abortions, but doses were limited by the complication of retroplacental hemorrhage. In tissue from normal first trimester pregnancy, minimal Fgl2 positivity was seen in some villous syncytiotrophoblast, in villous stroma, cytotrophoblast, and in some cells in decidua. In spontaneous abortion of normal embryo, striking Fgl2 positivity was seen in syncytiotrophoblast and extravillous cytotrophoblast, in association with areas of thrombus formation. CONCLUSIONS: Fgl2 appears to be physiologically expressed and may protect against the internal danger of maternal and/or fetal bleeding during pregnancy and at parturition; a role in inhibiting transplacental traffic is also possible. External dangers in the form of stress, endotoxin, and antigens eliciting Th1 cytokine responses upregulate Fgl2 prothrombinase in trophoblast as well as in decidua, which results in spontaneous abortion of immunogenetically "weaker" embryos.

Abortion, Spontaneous↗

PubMed1998

Ribavirin inhibits viral-induced macrophage production of TNF, IL-1, the procoagulant fgl2 prothrombinase and preserves Th1 cytokine production but inhibits Th2 cytokine response.

Ribavirin, a synthetic guanosine analogue, possesses a broad spectrum of activity against DNA and RNA viruses. It has been previously shown to attenuate the course of fulminant hepatitis in mice produced by murine hepatitis virus strain 3. We therefore studied the effects of ribavirin on murine hepatitis virus strain 3 replication, macrophage production of proinflammatory mediators including TNF, IL-1, and the procoagulant activity (PCA), fgl2 prothrombinase; and Th1/Th2 cytokine production. Although ribavirin had inhibitory effects on viral replication (<1 log), even at high concentrations complete eradication of the virus was not seen. In contrast, at physiologic concentrations (up to 500 microg/ml), ribavirin markedly reduced viral-induced parameters of macrophage activation. With ribavirin treatment, the concentrations of PCA, TNF-alpha and IL-1beta all decreased to basal concentrations: PCA from 941 +/- 80 to 34 +/- 11 mU/10(6) cells; TNF-alpha from 10.73 +/- 2.15 to 2.74 +/- 0.93 ng/ml; and IL-1beta from 155.91 +/- 22.62 to 5.74 +/- 0.70 pg/ml. The inhibitory effects of ribavirin were at the level of gene transcription as evidenced by Northern analysis. Both in vitro and in vivo, ribavirin inhibited the production of IL-4 by Th2 cells, whereas it did not diminish the production of IFN-gamma in Th1 cells. In contrast, ribavirin had no inhibitory effect on TNF-alpha and IL-1beta production in LPS-stimulated macrophages. These results suggest that the beneficial effects of ribavirin are mediated by inhibition of induction of macrophage proinflammatory cytokines and Th2 cytokines while preserving Th1 cytokines.

Animals↗

PubMed1998

Resistance of naive mice to murine hepatitis virus strain 3 requires development of a Th1, but not a Th2, response, whereas pre-existing antibody partially protects against primary infection.

Murine hepatitis virus strain 3 (MHV-3) produces a host-strain-dependent spectrum of disease. The development of liver necrosis has been shown to be related to production of a unique macrophage procoagulant activity (PCA), encoded by the gene fgl-2, in susceptible mice. These studies were designed to examine the influence of Th1/Th2 cells on resistance/susceptibility and production of macrophage procoagulant activity (PCA) in resistant (A/J) and susceptible (Balb/cJ) strains of mice following infection with MHV-3. Immunization of A/J mice with MHV-3 induced a Th1 cellular immune response and one Th1 cell line (3F9.1) protected susceptible mice and inhibited production of PCA by macrophages both in vitro and in vivo. In contrast, immunization of Balb/cJ mice with an attenuated variant of MHV-3 derived from passaging MHV-3 in YAC-1 cells resulted in a Th2 response. Transfer of spleen cells and T cell lines from immunized Balb/cJ mice failed to protect naive susceptible syngeneic mice from infection with MHV-3 and augmented production of IL-1 beta, TNF-alpha and PCA by macrophages to MHV-3 in vitro. Serum from immunized Balb/cJ mice contained high titered neutralizing antibody which protected naive Balb/cJ animals from lethal primary MHV-3 infection. These results demonstrate that susceptible Balb/cJ mice generate a Th2 response following MHV-3 infection and that these Th2 cells neither inhibit MHV-3-induced macrophage PCA production nor protect naive mice from MHV-3 infection. The results suggest that antibody protects against primary infection, but could not eradicate ongoing infection. Ribavirin, a synthetic guanosine analogue prolonged survival to MHV-3 infection, inhibited production and transcription of the macrophage pro-inflammatory cytokines IL-1 beta and TNF-alpha and Th2 cytokines while preserving Th1 cytokine production. Thus, this data defines the differential role of Th1/Th2 lymphocytes in primary and secondary MHV-3 infection and further defines the importance of macrophage inflammatory mediators in the pathogenesis of MHV-3 infection.

Animals↗

PubMed1998

Expression of the fgl2 and its protein product (prothrombinase) in tissues during murine hepatitis virus strain-3 (MHV-3) infection.

Murine Hepatitis Virus Strain 3 (MHV-3) produces fulminant hepatitis with 80-90% mortality in Balb/cJ mice. Previous studies in our laboratory have shown that peritoneal macrophages from MHV-3 infected mice produce a procoagulant (PCA) which has the ability to cleave prothrombin to thrombin (prothrombinase) encoded by the gene fgl2 located on chromosome 5. PCA accounts for sinusoidal thrombosis and hepatic necrosis and the necrosis and mortality can be prevented by treatment of animals with a monoclonal antibody to PCA. These present studies were designed to examine the expression of this gene (mRNA by Northern analysis and in situ hybridization) and the gene product PCA (immunochemistry) in tissues recovered from MHV-3 infected Balb/cJ mice in an attempt to explain the liver specific nature of MHV-3 disease. Fgl2 gene expression was detected as early as 8 hours after MHV-3 infection which persisted to 48 hours in the liver, spleen and lungs whereas no gene expression was seen in the brain or kidneys despite the fact that equivalent viral titers were detected in all tissues at all times. In the liver, fgl2 gene expression was confined to endothelial and Kupffer cells with no expression in hepatocytes. Immunochemistry localized the PCA protein to Kupffer cells and endothelial cells and necrotic foci within the liver. No PCA protein was detected by immunochemistry in any other tissues at any time during the course of MHV-3 infection. These results explain the liver specific nature (fulminant hepatitis) of MHV-3 infection and provides further evidence for the role of PCA in the pathogenesis of fulminant hepatitis. MHV-3 induces selective transcription of the gene fgl2 and only hepatic reticuloendothelial cells produce functional protein (PCA) which is known to account for fulminant hepatic failure produced by MHV-3.

Animals↗

PubMed1998

Resistance to murine hepatitis virus strain 3 is dependent on production of nitric oxide.

The strain-specific spectrum of liver disease following murine hepatitis virus type 3 (MHV-3) infection is dependent on inflammatory mediators released by macrophages. Production of nitric oxide (NO) by macrophages has been implicated in resistance to a number of viruses, including ectromelia virus, vaccinia virus, and herpes simplex virus type 1. This study was undertaken to define the role of NO in MHV-3 infection. Gamma interferon-induced production of NO inhibited growth of MHV-3 in a murine macrophage cell line (RAW 264.7). Viral inhibitory activity was reproduced by the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP), whereas N-acetyl-DL-pencillamine (NAP), an inactive analog of SNAP, had no effect. Electron microscopy studies confirmed the inhibitory effects of NO on viral replication. Peritoneal macrophages isolated from A/J mice known to be resistant to MHV-3 produced a fivefold-higher level of NO and higher levels of mRNA transcripts of inducible NO synthase in response to gamma interferon than macrophages from susceptible BALB/cJ mice. SNAP inhibited growth of MHV-3 in macrophages from both strains of mice to similar degrees. In vivo inhibition of NO by N-monomethyl-L-arginine resulted in loss of resistance to MHV-3 in A/J mice. These results collectively demonstrate a defect in the production of NO in macrophages from susceptible BALB/cJ mice and define the importance of endogenous NO in resistance to MHV-3 infection in resistant A/J mice.

Animals↗

PubMed1998

Inhibition of amiloride-sensitive sodium-channel activity in distal lung epithelial cells by nitric oxide.

Distal lung epithelial cells (DLECs) play an active role in fluid clearance from the alveolus by virtue of their ability to actively transport Na+ from the alveolus to the interstitial space. The present study evaluated the ability of activated macrophages to modulate the bioelectric properties of DLECs. Low numbers of lipopolysaccharide (LPS)-treated macrophages were able to significantly reduce amiloride-sensitive short-circuit current (Isc) without affecting total Isc or monolayer resistance. This was associated with a rise in the flufenamic acid-sensitive component of the Isc. The effect was reversed by the addition of N-monomethyl-L-arginine to the medium, implying a role for nitric oxide. We hypothesized that macrophages exerted their effect by expressing inducible nitric oxide synthase (iNOS) in DLECs. The products of LPS-treated macrophages increased the levels of iNOS protein and mRNA transcripts in DLECs as well as causing a rise in iNOS activity. Immunofluorescence microscopy of LPS-stimulated macrophage-DLEC cocultures with anti-nitrotyrosine antibodies provided evidence for the generation of peroxynitrite in macrophages but not in DLECs. These data indicate that activated macrophages in the lung may contribute to impaired resolution of acute respiratory distress syndrome and suggest a novel mechanism whereby nitric oxide might alter cell function by altering its ion-transporting phenotype.

Amiloride↗

PubMed1997

Function of reduced-size liver transplant in the rat.

We have studied the function of partial orthotopic liver transplantation in the rat by evaluating prothrombin time (PT), liver blood flow, basal and glucose-stimulated insulin secretion and glucose tolerance, and the reticuloendothelial function (RES) in hepatectomized rats subjected to partial liver transplantation. A graft corresponding to 68% of a normal liver was transplanted to totally hepatectomized rats. Comparison was made between control rats and rats subjected to 32% liver resection. PT was not significantly different in the transplanted group compared with liver-resected and control rats. Laser Doppler flowmetry showed that at 28 days after surgery, blood flow had increased in the transplanted livers. Furthermore, on the third day after transplantation, basal plasma insulin was increased and the plasma insulin response to glucose was exaggerated, suggesting reduced insulin action and impaired insulin degradation. Finally, uptake of radioactive-labeled E. coli bacteria, as a measure of RES function, was not compromised in transplanted animals. Based on these results, we conclude that reduced-size liver transplant in out-bred rats results in fast normalization of liver function after surgery although, immediately after surgery, glucose intolerance is seen.

Animals↗

PubMed1997

Fulminant hepatic failure in murine hepatitis virus strain 3 infection: tissue-specific expression of a novel fgl2 prothrombinase.

Activation of the immune coagulation system has been implicated in the pathogenesis of fulminant liver failure caused by murine hepatitis virus strain 3 (MHV-3). The recent discovery of the fgl2 gene, which encodes for MHV-3-induced prothrombinase (fgl2 prothrombinase), allows for fundamental studies to determine the molecular basis for fulminant liver failure. Transcription of the fgl2 gene and translation of the protein it encodes were examined in the liver and other organs of susceptible mice following MHV-3 infection. No constitutive expression of the fgl2 gene or the fgl2 prothrombinase was detected. Within 12 to 24 h of MHV-3 infection, however, fgl2 gene transcripts were detected in large amounts in the liver, spleen, and lungs, all of which are rich in reticuloendothelial cells, but were only focally present in small amounts in the kidney and brain. There was sequential detection of fgl2 prothrombinase in the liver, where it was localized specifically to the endothelium of intrahepatic veins and hepatic sinusoids; this was allowed by fibrin deposition, which resulted in confluent hepatocellular necrosis. These results provide further evidence for the role of the selective expression of this novel fgl2 prothrombinase in the pathogenesis of MHV-3-induced fulminant liver failure.

Animals↗

PubMed1995

Effect of bile obstruction on liver regeneration following major hepatectomy: an experimental study in the rat.

The regeneration of the liver following resection is regulated by a variety of factors and it might be expected that jaundice influences the process. We therefore evaluated the regenerative response to major hepatectomy in bile-obstructed rats. Two weeks after ligation of the common bile duct, a standardized 77% hepatectomy was undertaken. The jaundiced animals showed an augmented liver regeneration compared to nonjaundiced individuals (p < 0.01). However, blood clearance of radiolabelled Escherichia coli bacteria was impaired (p < 0.01) in animals with bile obstruction at 7 days after the hepatectomy, accompanied by reduced bacterial uptake in the liver as a sign of impaired reticuloendothelial system function.

Animals↗

PubMed1994

Enhanced Kupffer cell activity after repeated hepatic arterial ischaemia in an experimental model.

Kupffer cells are important for host defence against both foreign invaders and neoplasia. Several studies have demonstrated that ischaemia and reperfusion activates Kupffer cells. The effect of hepatic arterial ischaemia on Kupffer cell function was assessed using blood clearance and organ uptake of radiolabelled Escherichia coli. Transient ischaemia for 1 h did not alter Kupffer cell function in comparison with sham operation. However, prolonging arterial ischaemia for 2 h stimulated Kupffer cell function; both the phagocytic index and liver uptake of radiolabelled E. coli increased significantly (P < 0.01). Furthermore, this enhanced Kupffer cell activity was achieved each time the ischaemia was induced over a period of 5 days compared with repeated sham procedures (P < 0.05). Serum tumour necrosis factor (TNF) was significantly released after both single and repeated arterial occlusion for 2 h (P < 0.01). These observations show that transient arterial ischaemia enhances Kupffer cell function and induces TNF production.

Animals↗

PubMed1994

Obstructive jaundice impairs reticuloendothelial function and promotes bacterial translocation in the rat.

Septic complications and renal insufficiency following biliary tract surgery are frequently seen in patients with obstructive jaundice. The precise mechanisms for understanding the susceptibility of the jaundiced patients to sepsis are, however, not clear. The present study aimed at investigating the influence of biliary obstruction on the reticuloendothelial function and bacterial translocation at various time intervals in the rat. Reticuloendothelial system (RES) function, as evaluated by measuring blood clearance of intravenously injected 125I-labeled Escherichia coli, and bacterial translocation were studied 3 days and 1, 2, and 3 weeks following either sham operation or common bile duct ligation (CBDL) and transection in the rat. RES function was significantly impaired and renal uptake of radiolabeled E. coli was significantly higher in jaundiced animals from Day 3 and on after CBDL (P < 0.01) concomitant with elevation of plasma levels of bilirubin and liver enzymes (P < 0.001) compared with their corresponding controls. The incidence of bacterial translocation 3 days and 1 and 2 weeks after biliary obstruction significantly increased (P < 0.05). We conclude that RES phagocytic function is impaired and the incidence of bacterial translocation is increased in jaundiced rats. These findings might contribute to explain the high susceptibility of postoperative septic complications and renal dysfunction in patients with obstructive jaundice.

Acute Kidney Injury↗

PubMed1994

Inhibition of bacterial translocation in obstructive jaundice by muramyl tripeptide phosphatidylethanolamine in the rat.

Obstructive jaundice is frequently associated with septic complications and enteric bacteria have been isolated from both the infectious focus and bile in jaundiced patients. The present study aimed to evaluate bacterial translocation and the influence of a macrophage-stimulant (muramyl tripeptide phosphatidylethanolamine) on bacterial translocation in obstructive jaundice. Male Sprague-Dawley rats were subjected to sham operation (n = 10) or common bile-duct ligation and transection (n = 35). Two weeks later, jaundiced animals received either physiological saline (n = 15), muramyl tripeptide phosphatidylethanolamine liposomes (n = 10) or placebo (empty) liposomes (n = 10) orally, while sham-operated rats received physiological saline, 48 h prior to evaluation of enteric bacterial translocation. Blood, bile and caecal contents were collected and cultured aerobically and anaerobically, as were tissue samples from the liver, spleen and mesenteric lymph nodes. Positive mesenteric lymph node cultures in animals with jaundice + saline (7/15; 47%) and jaundice + placebo liposomes (4/10; 40%) significantly differed (p < 0.05) from sham-operated animals (1/10; 10%) and muramyl tripeptide phosphatidylethanolamine treated animals (0/10). Caecal counts (CFU/g) of Escherichia coli, Lactobacilli and aerobic and microaerobic bacteria did not differ statistically among the groups, although the number of E. coli tended to be higher in jaundiced animals. Thus, liposomal muramyl tripeptide phosphatidylethanolamine inhibits bacterial translocation, probably by activating mucosal macrophages and enhancing reticuloendothelial system function in rats with biliary obstruction.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1994

Abdominal rubber drain piece aggravates intra-abdominal sepsis in the rat.

Biomaterials in the peritoneal cavity disrupt the physiology of the host and may cause bacterial translocation. The current study was performed to determine whether biomaterials exacerbate intra-abdominal infections. Adult male rats were divided into four groups: group 1, celiotomy+intraperitoneal (i.p.) saline; group 2, celiotomy+i.p. Escherichia coli (3 x 10(8) cfu); group 3, i.p. rubber+i.p. saline; and group 4, i.p. rubber+i.p. E. coli (3 x 10(8) cfu). Twelve h after the challenge, enteric bacterial translocation, bacterial population levels in the cecum and serum levels of IL-6 and TNF were measured. Bacterial translocation to mesenteric lymph nodes and the liver was observed in animals from groups 2 and 3, but significantly increased in group 4 with a concomitant elevation of serum levels of TNF and IL-6, as compared with group 1. Histological examination revealed a more pronounced inflammatory reaction in the peritoneum and distal ileum in group 4 than in groups 2 and 3. These results suggest that the presence of rubbers in the peritoneal cavity aggravates intra-abdominal sepsis.

Abdomen↗

PubMed1994

Macrophage phagocytic dysfunction and reduced metabolic response in experimental obstructive jaundice.

OBJECTIVE: To investigate the metabolic response as measured by microcalorimetry and the phagocytic activity or peritoneal macrophages that had been harvested from jaundiced and normal rats and incubated with Escherichia coli in vitro. DESIGN: Open laboratory study. SETTING: University departments of surgery and immunology. MATERIAL: 12 Male Sprague-Dawley rats. INTERVENTIONS: Ligation and transsection of the common bile duct (n = 6) or sham operation (n = 6). MAIN OUTCOME MEASURES: Metabolic response (pW/cell) measured by microcalorimetry and phagocytic function assessed by light microscopy after Giemsa stain two weeks after operation. RESULTS: The mean (SEM) maximal metabolic response of macrophages and the metabolic rate one hour after inoculation with E coli were significantly reduced in jaundiced rats compared with controls (6.95 (1.95) compared with 27.39 (7.24), p = 0.005, and 5.50 (1.05) compared with 20.10 (3.35) p = 0.016, respectively) as were the number of E coli phagocytosed by macrophages harvested from jaundiced animals (p = 0.0002). CONCLUSION: The reduced metabolic response and phagocytosis of E coli by peritoneal macrophages in rats by biliary obstruction is a sign of depressed reticuloendothelial function. This mechanism may explain the high incidence of infective complications inpatients with obstructive jaundice.

Animals↗