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| 2. |
- Graf, W, et al.
(författare)
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The influence of early postoperative intraperitoneal chemotherapy on human wound healing.
- 1994
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Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 57:3, s. 394-400
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Tidskriftsartikel (refereegranskat)abstract
- Cell ingrowth, hydroxyproline accumulation, and mRNA expression of collagen I were measured in two polytetrafluoroethylene grafts implanted subcutaneously at the time of colorectal cancer surgery to evaluate the influence of early postoperative chemotherapy on human wound healing. Eleven patients treated with intraperitoneal 5-fluorouracil and intravenous folinic acid Days 1-6 after operation were compared with 15 patients who underwent surgery alone. At 1 week, chemotherapy-treated patients had accumulated less hydroxyproline (mean 0.35 +/- 0.33 micrograms/cm) compared with untreated patients (mean 0.73 +/- 0.37 micrograms/cm, P < 0.05). By 2 weeks, the hydroxyproline content had increased sixfold in the chemotherapy group (P < 0.01) and threefold in the nonchemotherapy group (P < 0.01) and there was no difference between the groups. Cell and connective tissue ingrowth and total RNA content did not differ between the groups at any point in time, but at 1 week the mRNA expression of collagen I was higher in the chemotherapy group (P < 0.05). These results indicate that collagen accumulation in human subjects is reduced during a short course of postoperative chemotherapy and normalizes after the end of treatment.
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| 3. |
- Lepistö, J, et al.
(författare)
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Effects of homodimeric isoforms of platelet-derived growth factor (PDGF-AA and PDGF-BB) on wound healing in rat.
- 1992
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Ingår i: Journal of Surgical Research. - 0022-4804 .- 1095-8673. ; 53:6, s. 596-601
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor (PDGF) has been suggested to have a significant role in wound healing. The present work was aimed at studying the effects of PDGF-AA and PDGF-BB homodimers on developing granulation tissue in rats. Subcutaneously implanted hollow cylindrical cellulose sponges were used as an inductive matrix for the ingrowth of granulation tissue. Fifty microliters of solutions containing 0, 5, 50, or 500 ng of PDGF-AA or PDGF-BB homodimers was injected daily into the sponges; 7 days after implantation the granulation tissue in the sponge cylinders was analyzed. Five hundred nanograms of PDGF-BB stimulated significantly the accumulation of collagen, indicated by the elevated hydroxyproline content of the sponge (+34%, P < 0.001). Similarly, the amounts of RNA-ribose, nitrogen, hexosamines, and uronic acids were significantly higher, reflecting a PDGF-BB-induced increase in the accumulation of RNA, protein, and glycosaminoglycans. Analyses of wound fluid showed no essential changes in the composition of different cell types after PDGF-BB-treatment. The PDGF-AA-treatment increased significantly the mean amount of RNA but there were no significant changes in other parameters. In vitro both PDGF-AA and PDGF-BB increased significantly the number of rat granulation tissue derived fibroblasts in culture at concentrations of 10 and 30 ng/ml. This proliferative effect resulted in a lowered level of protein synthesis per cell. To conclude, PDGF-BB accelerates granulation tissue formation both in vitro and in vivo, whereas PDGF-AA is effective in vitro but it is clearly less effective in vivo.
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| 4. |
- Roxvall, Lennart, et al.
(författare)
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Trypsin-induced vascular permeability and leukocyte accumulation in hamster cheek pouch: the role of complement activation.
- 1990
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Ingår i: The Journal of surgical research. - : Elsevier BV. - 0022-4804. ; 49:6, s. 504-13
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Tidskriftsartikel (refereegranskat)abstract
- Trypsin-induced acute inflammation was studied in hamster cheek pouch using intravital microscopy, correlative histology, and electron microscopy. Vascular permeability changes were monitored with intravital fluoroscopy, after intravenous injection of FITC-dextran (Mw 150,000), by counting the number of FITC-dextran leakages around the vessels. The number of extravasated polymorphonuclear leukocytes (PMNLs) was calculated by a histological technique. A dose-dependent increase in the number of FITC-dextran leakages, as well as the number of accumulated PMNLs, was found when trypsin was locally deposited in concentrations of 0.25-2.5 microM (15 microliters during 5 min). Local deposition of autologous serum treated with trypsin at final concentrations of 0.25-2.5 microM caused an increase in vascular permeability as equally pronounced as that of pure trypsin, but only a moderate PMNL accumulation which was not dose dependent. Trypsin at a 25 microM concentration resulted in numerous microbleedings and cessation of flow. The electron microscopy demonstrated inflammatory events (PMNL adhesion, diapedesis, and interstitial infiltration) in all treatment groups but they were more pronounced after trypsin exposure. Trypsin did not cause disintegration, cellular lysis, or increased mast cell degranulation. The permeability changes induced by trypsin (2.5 microM) and trypsinated serum (2.5 microM) were significantly suppressed by the addition of the chelating agent potassium-EDTA to the reaction mixture, indicating a calcium- or magnesium-dependent mechanism. Pretreatment of the animals with cobra venom factor (CVF), by which the plasma C3 concentration was reduced to less than 10%, inhibited the vascular leakages almost completely. The trypsin-induced accumulation of PMNLs was significantly reduced by potassium-EDTA as well as by pretreatment with CVF (P less than 0.01). These findings indicate a central role of complement activation in trypsin-induced acute inflammation in the hamster cheek pouch.
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| 5. |
- Andersson, Christer, et al.
(författare)
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Acute-phase proteins in response to tumor growth.
- 1993
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Ingår i: The Journal of surgical research. - : Elsevier BV. - 0022-4804. ; 55:6, s. 607-14
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Tidskriftsartikel (refereegranskat)abstract
- This study has evaluated the relationship between tumor growth and induction of acute-phase proteins. It has also determined whether an intact cellular immunity is obligatory for a fully expressed acute-phase plasma protein response in the presence of a highly antigenic tumor. Quantitatively, acute-phase responses (protein synthesis, plasma concentrations, hepatic RNA content, anorexia) were proportional to tumor burden. Anti-inflammatory drugs (indomethacin 1 micrograms/g body wt, dexamethasone 0.5 micrograms/g body wt) had no direct effect on the attenuation of the systemic acute-phase responses, but did affect them indirectly by decreasing tumor growth. Immune suppression (cyclosporine A at 20 or 60 micrograms/g body wt) had no effect on either acute-phase reactions or local tumor growth. In endotoxin-stimulated (lipopolysaccharide) normal mice, immune suppression aggravated anorexia and caused high mortality, while dexamethasone partly reversed these effects in endotoxin-stimulated mice. Plasma levels of acute-phase proteins correlated to circulating levels of IL-6 in untreated tumor-bearing mice, but this relationship was not obvious in either drug-treated tumor-bearing or endotoxin-stimulated mice. Tumor tissue induced the synthesis of different acute-phase proteins compared to endotoxin. However, disintegrated normal liver tissue induced the synthesis of serum amyloid protein to the same extent as the growing tumor. This effect was primarily associated with the mitochondrial/lysosomal and microsomal liver cell fractions. In conclusion, the overall acute-phase protein response is not a modulating factor of tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 6. |
- Andersson, Christer, et al.
(författare)
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Identification of tissue sites for increased albumin degradation in sarcoma-bearing mice.
- 1991
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Ingår i: The Journal of surgical research. - 0022-4804. ; 50:2, s. 156-62
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Tidskriftsartikel (refereegranskat)abstract
- Plasma albumin concentration declines in both experimental and clinical cancer. Previous investigations have demonstrated that this is partly explained by increased breakdown of albumin. The present study has identified the tissue sites for increased albumin degradation in a nonmetastasizing sarcoma mouse (C57/BL6J) model. Results have been compared to nontumor-bearing animals either freely fed or food restricted (pair-weighed) so that their body composition was similar to tumor-bearing animals. Tumor-bearing mice had increased albumin degradation (0.13 +/- 0.02 mg/hr/g bw) compared to both freely fed (0.09 +/- 0.007) and pair-weighed control animals (0.05 +/- 0.008). Radioactivity from circulating [3H]raffine aldehyde labeled albumin appeared with maximum peak values in lysosomes isolated from both tumor and nontumor tissues at 48 hr following iv injection. The intralysosomal accumulation of radioactivity was two- to threefold higher in tumor tissue compared to liver tissue, although the specific activity of protease(s) for albumin degradation measured in vitro was not higher in tumor tissue (30.4 +/- 3.6 mg/hr/g tissue) compared to normal liver tissue (36.9 +/- 1.7). Accounting for the entire tumor the proteolytic capacity for albumin breakdown was however much larger in the tumor (161.6 +/- 32.6 mg/organ) compared to both normal liver (37.5 +/- 2.3) and tumor-host liver (56.4 +/- 2.8). Pepstatin inhibited 78 +/- 6% of the proteolytic activity in the tumor measured by 125I-labeled undenatured mouse albumin as the substrate. Leupeptin inhibited 49 +/- 6%. There was a significantly decreased breakdown of albumin in both skeletal muscles and the gastrointestinal tract from tumor-bearing animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 7. |
- Gelin, Johan, 1948, et al.
(författare)
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The role of the adrenals in the acute phase response to interleukin-1 and tumor necrosis factor-alpha.
- 1993
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Ingår i: The Journal of surgical research. - 0022-4804. ; 54:1, s. 70-8
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the role of the adrenals, particularly the glucocorticoids, in the acute phase response following daily injections for 5 days of recombinant human interleukin-1 alpha,beta and tumor necrosis factor-alpha (TNF alpha). Adult weight-stable freely fed or pair-fed (to cytokine-injected mice) mice (C57Bl/6J) with and without adrenals were used. Adrenalectomized animals showed a sensitivity to both IL-1 alpha and -1 beta (40 ng IL-1/day) greater than 10-fold higher than that of normal mice (420 ng IL-1/day) in regard to mortality and anorexia. Microscopic examination of tissue specimens from adrenalectomized IL-1 alpha,beta-injected mice did not reveal any histologic alterations in lung, kidney, liver, brain, or gastrointestinal tract to explain the mortality. This mortality was not prevented by physiologic replacement doses of hydrocortisone (10-20 micrograms/day); however, a pharmacological dose of 2.5 mg hydrocortisone/day abolished completely the increased toxicity to IL-1 alpha,beta and the anorectic response to IL-1 alpha,beta and TNF alpha. Increased toxicity (mortality) was not observed in adrenalectomized animals with TNF alpha at the dose interval used (450 ng TNF alpha/day and lower). The hepatic acute phase response (liver weight and RNA and liver protein content) was increased by both IL-1 alpha,beta and TNF alpha in a glucocorticoid-independent way. The cytokine-induced alterations of plasma concentrations of acute phase proteins (serum amyloid P, transferrin, complement C3) were significantly dependent on glucocorticoids, while the decline in plasma albumin was not.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 8. |
- Nordvall, Gunnar, et al.
(författare)
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Analogs of the Muscarinic Agent 2'‑Methylspiro(1‑azabicyclo[2.2.2]octane)‑3,4'‑[1,3]dioxolane (AF30) : Synthesis and Pharmacology
- 1992
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 35:9, s. 1541-1550
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Tidskriftsartikel (refereegranskat)abstract
- A number of tetrahydrofuran analogues of 2'-methylspiro[1-azabicyclo[2.2.2]octane-3,4'-[1,3]dioxolane] ( 1) have been prepared with the aim to obtain information about the relative importance of each of the oxygens in 1 for efficacy and for selectivity. In addition, the dimethyl and deamethyl doguea of 1 &re prepared. The new compounds were compared to cis- and trans-1 with regard to their ability to displace (-)-[3H]-3-quinuclidinyl benzilate ((-)-[3H]QNB) from muscarinic receptors in cerebral cortex, heart, parotid gland, and urinary bladder from guinea pigs. Functioinal studies were made on isolated guinea pig bladder and ileum. The new compounds exhibited both lower affmity and efficacy thancis-1.Aconformational studywasperformed,and the effects of steric and electronic factors on the biological activity of the compounds are discussed.
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| 9. |
- Roxvall, L, et al.
(författare)
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Anti-inflammatory agents inhibit leukocyte accumulation and vascular leakage induced by trypsin and trypsin-digested serum in hamster cheek pouch.
- 1993
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Ingår i: The Journal of surgical research. - : Elsevier BV. - 0022-4804. ; 54:3, s. 207-11
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Tidskriftsartikel (refereegranskat)abstract
- In the present study we investigated the effect of nordihydroguaiaretic acid (NDGA), indomethacin, and cortisone on trypsin-induced acute inflammation in the hamster cheek pouch. Permeability changes, evaluated by fluorescence microscopy after injection of FITC-dextran (MW 150,000), induced by trypsin (2.5 microM) and trypsinated serum (2.5 microM) were significantly suppressed by pretreatment with NDGA (20 mg/kg) and indomethacin (20 mg/kg). Pretreatment with cortisone (40 mg/kg) reduced the permeability changes induced by trypsinated serum but had no significant effect on trypsin-induced leakages. Accumulation of polymorphonuclear leukocytes, as calculated by a whole tissue histological technique, induced by trypsin or trypsinated serum, was significantly reduced by pretreatment with cortisone, NDGA, or indomethacin. These results indicate a role of both cyclooxygenase and lipoxygenase products in trypsin-induced acute inflammation in the hamster cheek pouch.
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