摘要:

Nitric oxide (NO) decreases cytotoxicity and proliferation of cytotoxic lymphocytes (CTLs) in vitro. Both can be prevented by inhibitors of the NO synthase (NOS). To elucidate whether inhibition of the IL-2-induced NOS could boost efficacy of IL-2-stimulated CTLs in vivo, we assessed lung metastases in mice injected with IL-2, the NOS inhibitor aminoguanidine (AG), their combination and the diluent. No improvement was observed for IL-2 + AG compared to IL-2 while NO production was normalized. Since NO causes one of the two major side effects of IL-2 treatment, hypotension, we further studied whether capillary leak could be attributed to NO, too. While IL-2-inducible NO was reduced to control levels by AG, pulmonary edema was unaffected. Thus a decrease in NO does not improve antitumor effects of IL-2-stimulated CTLs nor does it attenuate IL-2-associated capillary leak.

ISSN:0014-312X    

DOI:10.1159/000129455

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

In two experimental studies we sought preliminary information about the behavior of concrements lost in the peritoneal cavity during laparoscopic cholecystectomy. Materials and Methods: In study 1, human gallstones were analyzed using X-ray diffraction, calssified in three groups and examined with an ultramicroscope; then they were implanted in the peritoneal cavity of rats. After 8 weeks or 6 months, the animals were sacrificed and the concrements analyzed again as before. The tissues surrouding the calculi were also examined histologically. In study 2, human gallstones were examined with regard to bacterial contamination on the surface or in the middle of the calculi. The cholesterol content was analyzed, and the stones were divided into three groups and implantated in the rats as in the first study. After 8 weeks, the animals were sacrificed and areas with identifiable tissue reactions were examined histologically and microbiologically. Results: The concrements lost their crystalline formation without any relation to their former cholesterol content, as shown by X-ray diffraction as well as ultramicroscopy. Mineralogically, these changes are a certain sign of structural dissolution. Cholesterol stones only caused abscess formations in association with gram-negative bowel germs. Sterile pigment concrements often led to a mesenchymal reaction such as granulomas. Contaminated pigment stones also resulted in extensive abscess formations.

ISSN:0014-312X    

DOI:10.1159/000129456

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The aim of this study was to characterize the changes in the quantitative expression of β2-integrins and L-selectin detected by means of fluorochrome-conjugated monoclonal antibodies and flow cytometry on leukocytes in the systemic circulation after a major musculoskeletal trauma, i.e. hip replacement surgery, and to relate these changes to parameters of the acute-phase response [plasma acute-phase reactants (C-reactive protein, CRP, and interleukin-6, IL-6) and parameters of coagulation activation (thrombin-antithrombin III complexes, TAT)]. Eight patients with either primary or secondary osteoarthritis of the hip received uncemented total hip prostheses. LFA-1 (CD 11 a/CD 18) was upregulated on granulocytes during the operation. MAC-1 (CD1 lb/CD 18) expression on monocytes increased to peak levels 20 h after surgery, whereas the L-selectin (CD62L) expression on monocytes and granulocytes reached peak values at the end of surgery. The changes in expression of LFA-1 on monocytes, MAC-1 on granulocytes and p150,95 (CD1 lc/CD18) on monocytes and granulocytes during and after the operation did not reach statistical significance. TAT and IL-6 increased during surgery and reached peak values at the end of the operation and 20 h after surgery, respectively. In contrast, CPR concentrations increased after surgery with peak levels 44 h postoperatively. Significant upregulation of LFA-1 on granulocytes and L-selectin on monocytes and granulocytes preceded the increase in IL-6 which again preceded the increase in CRP. However, the up- or downregulation of leukocyte β2-integrins and L-selectin during and after surgery was not significantly correlated with the increase in IL-6. The increases in TAT correlated well with the upregulation of L-selectin on monocytes, but not with the β2-integrins known to participate in the coagulation process in vitro. The rise in CRP was inversely correlated with the maximal increase in expression of MAC-1 on monocytes. In conclusion, the changes in leukocyte adhesion molecules during and after surgery indicate changes in critical leukocyte functions. The lack of correlation between quantitative up-and downregulation of leukocyte β2-integrins and parameters of the acute phase response suggests that these processes are regulated through independent pathways or that functional up- and downregulation of adhesion molecules, shedding, leukocyte-endothelial adhesion and mobilization of new unactivated cells may result in a net estimate of leukocyte activation not suspected to be positively correlated to acute-phase reacta

ISSN:0014-312X    

DOI:10.1159/000129457

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Obstructive jaundice impairs function in liver parenchymal and sinusoidal cells. In this study, the endocytic activity in sinusoidal endothelial cells in the rats with biliary obstruction was measured by plasma clearance of radiolabeled formaldehyde-treated bovine serum albumin. The endocytic activity in hepatocytes was also measured with asialofetuin. The clearance of asialofetuin significantly decreased after 1 week of biliary obstruction and the clearance was reduced to 42% of the controls at 4 weeks. In contrast, the clearance of formaldehyde-treated bovine serum albumin was essentially unchanged until 4 weeks of biliary obstruction. The maximal removal rate which was assessed by kinetic analysis of injected protein for formaldehyde-treated bovine serum albumin showed no significant decrease at 2 weeks compared with the controls, while that for asialofetuin was significantly decreased to 50% of the controls. These results suggest that the endocytosis of formaldehyde-treated bovine serum albumin in endothelial cells is maintained until the advanced stage of biliary obstruction, whereas the endocytic activity for asialofetuin in hepatocytes is impaired earlier.

ISSN:0014-312X    

DOI:10.1159/000129458

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Selective portal vein occlusion prior to aggressive hepatic resection is now an alternative way to decrease postoperative morbidity and mortality rates. However, the detailed changes in the hepatic energy status and DNA synthesis rate in both portal vein ligated (PVL) and nonligated (PVNL) lobes of the liver are not clear. In rats, the portal branch that supplies 70% of the liver volume was ligated, and changes in arterial ketone body ratio (AKBR), liver weight, histology, DNA synthesis rate and adenine nucleotides of the PVL and PVNL liver lobes were determined before and 1, 2, 4 and 7 days after portal vein ligation, and compared with those in sham-operated rats. The weight of the PVL lobes decreased, while that of the PVNL lobes increased depending on time. The DNA synthesis rates of the PVNL lobes were significantly higher than those in sham-operated control liver during the first 4 days with the maximal value on the 2nd day, while those of PVL lobes were essentially similar to the control values. Energy charge (EC) in both PVL and PVNL lobes significantly decreased on day 1 and recovered gradually, but with less extent in the regenerating PVNL lobes. The concentrations of total adenine nucleotides (TAN) in both the PVL and PVNL lobes were essentially similar during the first 2 days, but became significantly lower in PVL lobes after day 4. A decrease in EC preceded an increase in DNA synthesis only in the PVNL lobes, in contrast to the PVL lobes. Mitosis of hepatocytes on day 2 and subsequently enlarged lobules with an increased number of hepatocytes were histologic features in the PVNL liver. The AKBR was not correlated with hepatic energy charge of the liver. In conclusion, PVNL liver regenerates preceded by a decrease in EC and a subsequent increase in DNA synthesis keeping TAN constant, while PVL liver becomes atrophic, with a similar change in EC of the PVNL liver but ultimately decreased TAN without any change in DNA synthesis. AKBR is not a parameter reflecting the hepatic EC after portal branch ligation.

ISSN:0014-312X    

DOI:10.1159/000129459

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Hepatocytes transplanted some days prior to vascularized allografts were shown to have the potential to prolong allograft survival in the rat. In the present study, hepatocytes and small bowel allografts were transplanted simultaneously in a Lewis (donor)-Brown Norway (recipient) rat model. 8–15 × 106 liver cells were injected into the spleen of small bowel recipients. The administration of at least 10 mg cyclosporine A (CyA)&slash;kg over 3 days was necessary to prevent early rejection of hepatocytes. In groups simultaneously receiving hepatocytes, small bowel grafts and 10 mg CyA/kg over 3 days, a significant mitigation of rejection and a prolongation of survival was achieved, compared to groups receiving solely small bowel grafts and 10 mg CyA/kg over 3 days. We conclude that simultaneously transplanted hepatocytes exert a protective effect on a grafted organ from the same donor, provided that early rejection of hepatocytes is prevented by sufficient immunosuppressi

ISSN:0014-312X    

DOI:10.1159/000129460

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Nine anesthetized and mechanically ventilated test pigs were intracavally infused with a 10% allogeneic bone marrows suspension at a dose of 100 mg/kg over 5 min; 9 control pigs received saline. The cardiac index decreased slightly in the fat embolism animals. Left ventricular stroke work remained unchanged in both groups, whereas right ventricular stroke work rose in the fat embolism animals. Mean arterial pressure remained stationary in the test group but rose in the controls. Pulmonary capillary wedge pressure and central venous pressure rose slightly in the test group. After infusion of the bone marrow suspension, mean pulmonary arterial pressure, pulmonary vascular resistance, pulmonary shunt and alveoloarterial oxygen tension difference increased immediately and remained elevated throughout the study period. Simultaneously, arterial and mixed venous oxygen tension and hemoglobin oxygen saturation decreased. Arterial carbon dioxide tension and hematocrit remained stationary. The fat embolism animals developed gradual fever. In conclusion, increased mean pulmonary arterial pressure, pulmonary vascular resistance, pulmonary shunt and alveoloarterial oxygen tension difference proved to be useful early indicators of experimental fat embolism.

ISSN:0014-312X    

DOI:10.1159/000129461

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Controversy exists concerning the optimal pO2 of the perfusate during isolated limb perfusion (ILP) with melphalan. Therefore we studied the implications of hyperbaric oxygen tensions in the perfusate. In 12 consecutive patients, subcutaneous pO2 (Continucath 1000®), tissue and tumor pH, and blood gas values were monitored throughout the ILP procedure. ILP started with an oxygen flow through the bubble oxygenator which was set routinely at one half of the flow of the perfusate; 30 min before the end of ILP, the oxygen flow was tripled. Mean arterial pO2 before and during ILP (before and after increasing the oxygen supply) was 19.4, 25.5 and 49.4 kPa, respectively. Mean subcutaneous pO2 values before, during (before and after increasing the oxygen supply), and post-ILP, were 7.4,10.1, 16.3, and 9.1 kPa, respectively. Tissue pH values in the subcutis and muscle decreased during routine oxygen supply (p = 0.001); muscle pH moved towards starting values after increase of the oxygen supply (p = 0.011). In 4 patients, tumor pH was recorded showing a rise after increasing the oxygen supply (from 7.10 to 7.22; p = 0.11). In conclusion, high pO2 in the perfusate improves muscle pH during ILP. However, a concomitant rise in tumor pH may unfavorably influence the therapeutic effect of ILP, as it has been shown that low pH increases the cytotoxicity of melphalan

ISSN:0014-312X    

DOI:10.1159/000129462

出版商:S. Karger AG    

年代:1996

数据来源: Karger