Biomedical subjects

H van Goor

Publications and source records attributed to H van Goor.

At least 55 records · Page 3Linked to original sources

PubMed2001

ACE inhibition preserves heparan sulfate proteoglycans in the glomerular basement membrane of rats with established adriamycin nephropathy.

The gradual onset of the antiproteinuric effects of ACE inhibition suggests that structural effects on the glomerular basement membrane (GBM) may be involved in their renoprotective action. To test this hypothesis, we studied the effects of lisinopril (5 mg/kg/24 h) on proteinuria, focal glomerulosclerosis (FGS) and glomerular heparan sulfate (HS) proteoglycan (HSPG) GBM staining in rats with established Adriamycin nephrosis. Treatment was started 6 weeks after disease induction. As expected, lisinopril reduced blood pressure, proteinuria and the FGS score. In control rats, Adriamycin nephrosis was associated with significantly impaired GBM staining for both HSPG core protein (assessed from BL-31 staining) and HS staining (assessed from JM-403 staining) 12 weeks after disease induction. In rats treated with lisinopril (5 mg/kg/24 h) GBM staining was significantly better preserved for HS as well as for HSPG core protein. These data suggest that structural effects on the GBM, improving glomerular permselectivity, may be involved in the renoprotective effects of ACE inhibition in proteinuria-induced renal damage.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2001

Hyperlipidemia and atherosclerosis associated with liver disease in ferrochelatase-deficient mice.

Erythropoietic protoporphyria (EPP) is an inherited disorder of heme synthesis caused by deficiency of the mitochondrial enzyme ferrochelatase. EPP in humans is associated with liver disease, hypertriglyceridemia, and a low level of high density lipoprotein (HDL) cholesterol. To explore consequences of ferrochelatase deficiency in lipid metabolism, we have analyzed hepatic lipid content and plasma lipoprotein levels in chow-fed BALB/c mice homozygous ( fch/fch) or heterozygous ( fch/1) for a point mutation in the ferrochelatase gene and in wild-type controls (1/1). Livers of fch/fch mice show bile duct proliferation and biliary fibrosis, but bile formation is not impaired. The free cholesterol content of fch/fch livers is significantly increased when compared with fch/1 and 1/1 livers. Plasma cholesterol in fch/fch mice (9.9 +/- 6.4 mM) is elevated when compared with fch/1 and 1/1 mice (2.9 +/- 0.2 and 2.5 +/- 0.3 mM, respectively), because of an increased cholesterol content in the very low density lipoprotein-sized fractions, whereas HDL cholesterol is reduced. The ratio of cholesteryl ester to free cholesterol is 4.3 +/- 0.6, 3.3 +/- 0.3, and 0.3 +/- 0.1 in the plasma of 1/1, fch/1, and fch/fch mice, respectively. The latter is not due to reduced lecithin:cholesterol acyltransferase activity in plasma of fch/fch mice but to the presence of lipoprotein-X (Lp-X), a particle composed of bile-type lipids usually seen only in cholestatic conditions. Expression of mdr2, essential for biliary phospholipid/cholesterol secretion, is increased in fch/fch livers. In spite of this, biliary phospholipid/cholesterol secretion is reduced relative to that of bile salts. It is postulated that an inability of bile salts to stimulate lipid secretion adequately leads to formation of Lp-X in this noncholestatic condition. Distinct atherosclerotic lesions were found in aged fch/fch mice.Thus, ferrochelatase deficiency in mice leads to liver disease associated with altered hepatic lipid metabolism, a characteristic hyperlipidemia, and development of atherosclerosis.-Bloks, V. W., T. Plösch, H. van Goor, H. Roelofsen, J. Baller, R. Havinga, H. J. Verkade, A. van Tol, P. L. M. Jansen, and F. Kuipers. Hyperlipidemia and atherosclerosis associated with liver disease in ferrochelatase-deficient mice. J. Lipid Res. 2001. 42: 41;-50.

Animals↗

PubMed2001

Distribution of cytoskeletal proteins, integrins, leukocyte adhesion molecules and extracellular matrix proteins in plastic-embedded human and rat kidneys.

OBJECTIVE: To study the distribution of cytoskeletal proteins (actin, alpha-actinin, vinculin, beta-tubulin, keratin, vimentin, desmin), adhesion molecules for cell-matrix interations (very later antigens [VLA1-61, beta1, beta2 [CD18], vitronectin receptor [alphavbeta3], CD 11b), leukocyte adhesion molecules (ICAM-1) and extracellular matrix proteins (collagen IV, fibronectin, laminin, vitronectin) in human and rat kidneys by using a superior processing and immunohistochemical staining technique. STUDY DESIGN: Human and rat kidneys were fixed in 2% paraformaldehyde, dehydrated in acetone and processed in a new, low-toxic glycol, methacrylate mixture, especially developed for immunohistochemistry. Both the glomeruli and the interstitial areas were carefully examined and scored semiquantitatively. RESULTS: Immunostained plastic sections showed excellent morphology combined with remarkably well preserved antigenicity. CONCLUSION: The above mentioned provides an excellent tool for the accurate localization of a wide variety of antigens at the light microscopic level.

Animals↗

PubMed2000

Nitric oxide production and nitric oxide synthase expression in acute human renal allograft rejection.

BACKGROUND: Nitric oxide (NO) is produced by nitric oxide synthases (NOS), which are either constitutively expressed in the kidney or inducible, in resident and infiltrating cells during inflammation and allograft rejection. NO is rapidly degraded to the stable end products nitrite and nitrate, which can be measured in serum and urine, and may serve as noninvasive markers of kidney allograft rejection. METHODS: Total nitrite and nitrate levels (NOx) were measured in serum and urine thrice weekly after an overnight fast in 18 consecutive patients following renal cadaveric transplantation. Inducible NOS (iNOS) and endothelial NOS (eNOS) expression was immunochemically determined in renal biopsy specimens with or without acute rejection (AR). RESULTS: Serum NOx levels increased days before AR and were significantly higher at the moment of AR (27+/-12.4 micromol/L) compared with recipients with an uncomplicated course (13+/-7.6 micromol/L), but not compared with recipients with cyclosporine (CsA) toxicity (20+/-13.0 micromol/L). Urinary NOx levels were significantly lower during AR (20+/-13.6 micromol/mmol creatinine) compared with an uncomplicated course (64+/-25.2 micromol/mmol creatinine) or CsA toxicity (53.8+/-28.3 micromol/mmol creatinine). Interstitial and glomerular iNOS expression was significantly increased in biopsy specimens showing AR. Unexpectedly, glomerular eNOS expression was significantly decreased in patients with AR. CONCLUSIONS: This study reports differences in NOx levels in serum and urine, which may help discriminate AR episodes from an uncomplicated course or CsA toxicity. As expected, renal iNOS expression is increased in acute allograft rejection. The decrease in glomerular eNOS expression suggests an intriguing link between acute and chronic rejection.

Adult↗

PubMed2000

Lack of endothelial nitric oxide synthase aggravates murine accelerated anti-glomerular basement membrane glomerulonephritis.

Nitric oxide (NO) radicals generated by endothelial nitric oxide synthase (eNOS) are involved in the regulation of vascular tone. In addition, NO radicals derived from eNOS inhibit platelet aggregation and leukocyte adhesion to the endothelium and, thus, may have anti-inflammatory effects. To study the role of eNOS in renal inflammation, the development of accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was examined in mice lacking a functional gene for eNOS and compared with wild-type (WT) C57BL/B6j mice. WT C57BL/6j mice (n = 12) and eNOS knockout (-/-) mice (n = 12) were immunized intraperitoneally with sheep IgG (0.2 mg in complete Freund's adjuvant). At day 6.5 after immunization, mice received a single i.v. injection of sheep anti-mouse GBM (1 mg in 200 microl PBS). Mice were sacrificed at day 1 and 10 after induction of the disease. All WT mice survived until day 10, whereas 1 eNOS-/- mouse died and 2 more became moribund, requiring sacrifice. At day 10, eNOS-/- mice had higher levels of blood urea nitrogen than WT mice (P < 0.02), although proteinuria was comparable. Immunofluorescence microscopy documented similar IgG deposition in both WT and eNOS-/- mice, but eNOS-/- mice had more extensive glomerular staining for fibrin at day 10 (P < 0.007). At day 10, light microscopy demonstrated that eNOS-/- mice had more severe glomerular thrombosis (P < 0.003) and influx of neutrophils (P < 0. 006), but similar degrees of overall glomerular endocapillary hypercellularity and crescent formation. In conclusion, accelerated anti-GBM glomerulonephritis is severely aggravated in eNOS-/- mice, especially with respect to glomerular capillary thrombosis and neutrophil infiltration. These results indicate that NO radicals generated by eNOS play a protective role during renal inflammation.

Animals↗

PubMed2000

The antiadhesive agent sodium hyaluronate increases the proliferation rate of human peritoneal mesothelial cells.

OBJECTIVE: Evaluating the influence of sodium hyaluronate on the proliferation rate of attached and nonattached human peritoneal mesothelial cells to elucidate whether this is a possible mechanism of action in peritoneal tissue repair. DESIGN: Controlled laboratory experiment. SETTING: A university hospital. PATIENT(S): Five patients undergoing colorectal surgery for noninfectious reasons. INTERVENTION(S): Human peritoneal mesothelial cells were harvested from patients undergoing a laparotomy for noninfectious reasons. Cells, both nonattached and attached, were incubated for 4 and 24 hours with different concentrations of sodium hyaluronate. Thereafter, the cell proliferation rate was measured by XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-car boxanilide) colorimetric assay. To mimic peritoneal injury, the cells were exposed to tumor necrosis factor alpha and/or lipopolysaccharide and were incubated immediately or after 24 hours of exposure to 0% or 0.2% sodium hyaluronate. Afterward, the cell proliferation rate was measured. MAIN OUTCOME MEASURE(S): Proliferation rate measured by XTT assay. RESULT(S): Sodium hyaluronate significantly increased the proliferation rate of mesothelial cells, both in a nonattached (P<.005) and attached (P<.001) state. Exposure of the mesothelial cells to tumor necrosis factor alpha and/or lipopolysaccharide diminished the cells' proliferation rate. However, incubation of these exposed cells with 0.2% sodium hyaluronate significantly increased the proliferation rate, regardless of whether the sodium hyaluronate was added immediately (P<.001) or after 24 hours (P<.001). CONCLUSION(S): Sodium hyaluronate increases the proliferation rate of human peritoneal mesothelial cells, both attached and nonattached, under normal conditions and after stimulation with tumor necrosis factor alpha and/or lipopolysaccharide.

Cell Adhesion↗

PubMed2000

Hepatic lipid accumulation, altered very low density lipoprotein formation and apolipoprotein E deposition in apolipoprotein E3-Leiden transgenic mice.

BACKGROUND/AIM: Apolipoprotein (apo) E-deficiency leads to hepatic steatosis and impaired Very Low Density Lipoprotein (VLDL)-triglyceride production rates in mice. A mutant apoE isoform, apoE3-Leiden, is associated with a dominantly inherited form of dysbetalipoproteinemia in humans. The aim of this study was to evaluate the effects of APOE*3-Leiden expression on hepatic lipid content, VLDL formation and liver morphology in mice. METHODS: Comparison of lipid parameters and liver morphology in mouse strains with different expression of the APOE*3-Leiden transgene with and without co-expression of human APOCI. RESULTS: Hepatic triglyceride content was increased to maximally 233% of control values, depending on hepatic APOE*3-Leiden expression. Hepatic secretion of VLDL-associated triglycerides was impaired (-20%) in high-expressing transgenics, with a concomitant increase from 1.6 to 8.1 of the apoB48/ apoB100 ratio in newly-formed VLDL. Hepatocytes of the transgenic mice contained characteristic inclusions, up to 20 microm in diameter, in numbers dependent on APOE*3-Leiden expression and independent of APOCI expression. These inclusions contained material positively reacting with antihuman apoE antibodies. Immunogold-labeling confirmed the presence of apoE3-Leiden within these inclusions and also revealed the presence of the mutant protein on sinusoidal membranes, in multivesicular bodies and in peroxisomes, i.e., a distribution pattern similar to that of endogenous apoE in rodents. Nascent VLDL particles associated with the Golgi apparatus were also labeled. CONCLUSION: This study has demonstrated that introduction of human apoE3-Leiden in mice, in addition to its reported effects on lipolysis and lipoprotein clearance, leads to hepatic deposition of the mutant apolipoprotein, development of fatty liver and to altered hepatic VLDL secretion. The latter findings are consistent with a role of apoE in the regulation of intrahepatic lipid metabolism.

Animals↗

PubMed2000

Hyaluronic acid-based agents do not affect anastomotic strength in the rat colon, in either the presence or absence of bacterial peritonitis.

BACKGROUND: Hyaluronic acid (HA) agents reduce postsurgical adhesion formation. The effect of their perioperative administration on early anastomotic healing is unknown. This study investigated the influence of two HA-containing agents on the development of strength in colonic anastomosis during the first postoperative week, both in normal rats and in rats with bacterial peritonitis. METHODS: In 90 male Wistar rats a 1-cm segment was resected from the descending colon and an end-to-end anastomosis was constructed. In 108 rats a bacterial peritonitis was induced using caecal ligation and puncture (CLP). Some 24 h after CLP the abdomen was reopened, the caecum was taken out and, after resection of a 1-cm segment, an anastomosis was made. Animals in both groups were randomized to receive either an HA-carboxymethylcellulose (CMC) bioresorbable membrane, 0.4 per cent HA solution or no treatment. One-third of each group was killed at day 1, 3 and 7 after operation. Cultures were taken from the abdominal cavity for microbiological analysis in half of the animals. Subsequently, both bursting pressure and breaking strength were determined as parameters for anastomotic strength. RESULTS: No differences in anastomotic bursting pressure or breaking strength were found between the experimental groups and their controls. In addition, there was no significant difference in the number of bacteria cultured from the abdominal cavity between rats treated with HA and controls. CONCLUSION: Neither HA-CMC bioresorbable membrane nor 0.4 per cent HA solution interferes with the development of early anastomotic strength in the colon, and can therefore be safely used to prevent intra-abdominal adhesion formation after performing bowel anastomosis.

Adjuvants, Immunologic↗

PubMed2000

Estrogen worsens incipient hypertriglyceridemic glomerular injury in the obese Zucker rat.

BACKGROUND: The obese Zucker rat (OZR) is a model of glomerulosclerosis and renal failure in the setting of hyperlipidemia, hyperinsulinemia, and obesity. Our prior work in OZRs has shown that ovariectomy attenuates glomerulosclerosis, while added estrogen worsens it. To investigate the mechanism of estrogen's effects on glomerular disease in this model, we evaluated the effects of ovariectomy and estrogen supplementation on seven-week peripubertal OZRs. At this time point, rats exhibit no overt histologic glomerular disease, but are just beginning to show elevated urinary albumin excretion. METHODS: Female OZRs fed ad libitum were ovariectomized at four weeks, with or without estrogen supplementation to raise estrogen levels to just below those of preoestral adults (mean 16.5 pg/mL). Sham-operated controls were included. RESULTS: Ovariectomy normalized albuminuria, lowered total and very low-density lipoprotein triglycerides, and reduced glomerular fibronectin expression. Estrogen supplementation worsened albuminuria and raised total/very low-density lipoprotein triglycerides and total cholesterol. Estrogen-supplemented rats exhibited enhanced glomerular deposition of apo A-IV and apo B, increased glomerular expression of desmin and type IV collagen, and increased interstitial macrophage deposition. CONCLUSION: Estrogen may be permissive for the early development of renal disease in OZRs and may act by increasing triglyceride-rich lipoproteins, which then bind to glomerular cells and initiate or accelerate glomerulosclerosis.

Albuminuria↗

PubMed2000

Recent clinical developments in pathophysiology, epidemiology, diagnosis and treatment of intra-abdominal adhesions.

Postsurgical intra-abdominal adhesions pose a significant medical problem in the Western world, and in the past decade progress has been made in understanding their pathophysiology. The early balance between fibrin formation and degradation in the peritoneal cavity during and after surgery seems to be a major determinant of adhesion formation. Postsurgical inhibition of fibrinolytic activity severely impairs fibrin breakdown. Adhesive small-bowel obstruction, inadvertent enterotomy at reoperation, prolonged operative time dividing adhesions, increased clinical workload and high financial costs are important adhesion-related problems discussed in this review. The cumulative risk of adhesive small-bowel obstruction after (sub)total colectomy is 11% within 1 year, increasing to 30% at 10 years. One of five patients undergoing reoperation suffers from inadvertent enterotomy, resulting in significant postoperative morbidity and mortality. Roughly 3% of all surgical admissions are associated with intra-abdominal adhesions. Clinical prospective trials have recently been designed to investigate the efficacy of barrier membranes and gels in the reduction of abdominal and pelvic adhesions and prevention of long-term morbidity, e.g., adhesive bowel obstruction and infertility in women. Early results are promising and contribute to the increased interest among clinicians in postsurgical adhesion formation and its consequences.

Abdomen↗

PubMed1999

Apolipoprotein E participates in the regulation of very low density lipoprotein-triglyceride secretion by the liver.

ApoE-deficient mice on low fat diet show hepatic triglyceride accumulation and a reduced very low density lipoprotein (VLDL) triglyceride production rate. To establish the role of apoE in the regulation of hepatic VLDL production, the human APOE3 gene was introduced into apoE-deficient mice by cross-breeding with APOE3 transgenics (APOE3/apoe-/- mice) or by adenoviral transduction. APOE3 was expressed in the liver and, to a lesser extent, in brain, spleen, and lung of transgenic APOE3/apoe-/- mice similar to endogenous apoe. Plasma cholesterol levels in APOE/apoe-/- mice (3.4 +/- 0.5 mM) were reduced when compared with apoe-/- mice (12.6 +/- 1.4 mM) but still elevated when compared with wild type control values (1.9 +/- 0.1 mM). Hepatic triglyceride accumulation in apoE-deficient mice was completely reversed by introduction of the APOE3 transgene. The in vivo hepatic VLDL-triglyceride production rate was reduced to 36% of control values in apoE-deficient mice but normalized in APOE3/apoe-/- mice. Hepatic secretion of apoB was not affected in either of the strains. Secretion of (3)H-labeled triglycerides synthesized from [(3)H]glycerol by cultured hepatocytes from apoE-deficient mice was four times lower than by APOE3/apoe-/- or control hepatocytes. The average size of secreted VLDL particles produced by cultured apoE-deficient hepatocytes was significantly reduced when compared with those of APOE3/apoe-/- and wild type mice. Hepatic expression of human APOE3 cDNA via adenovirus-mediated gene transfer in apoE-deficient mice resulted in a reduction of plasma cholesterol depending on plasma apoE3 levels. The in vivo VLDL-triglyceride production rate in these mice was increased up to 500% compared with LacZ-injected controls and correlated with the amount of apoE3 per particle. These findings indicate a regulatory role of apoE in hepatic VLDL-triglyceride secretion, independent from its role in lipoprotein clearance.

Animals↗

PubMed1999

Perianal ulcer.

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Crohn Disease↗

PubMed1999

Bile diversion in rats leads to a decreased plasma concentration of linoleic acid which is not due to decreased net intestinal absorption of dietary linoleic acid.

Decreased bile secretion into the intestine has been associated with low plasma concentrations of essential fatty acids (EFA) in humans. We studied the mechanism behind this relationship by determining the status and absorption of the major dietary EFA, linoleic acid (LA), in control and 1-week bile-diverted rats. The absorption of LA was quantified by a balance method and by measuring plasma concentrations of [13C]LA after its intraduodenal administration. Absolute and relative concentrations of LA in plasma were decreased in bile-diverted rats (P<0.01 and P<0.001, respectively). Fecal excretion of LA was increased at least 20-fold in bile-diverted rats (0.72+/-0.11 vs. 0.03+/-0.00 mmol/day; P<0.0001). Due to increased chow ingestion by bile-diverted rats, net intestinal absorption of LA was similar between bile-diverted and control rats (1.96+/-0.14 vs. 1.91+/-0.07 mmol/day, respectively; P>0.05). After intraduodenal administration of [13C]LA, plasma concentrations were approximately 3-4-fold lower in bile-diverted rats for at least 6 h (P<0.001). Plasma concentrations of both [12C]arachidonic acid and [13C]arachidonic acid were increased in bile-diverted rats (P<0.05). We conclude that decreased plasma concentrations of LA in 1-week bile-diverted rats are not due to decreased net intestinal absorption of LA, but may be related to increased metabolism of LA.

Animals↗

PubMed1999

Prevention of intra-abdominal abscesses and adhesions using a hyaluronic acid solution in a rat peritonitis model.

HYPOTHESIS: Hyaluronic acid (HA)-based bioresorbable membrane and 0.4% HA solution reduce intraabdominal adhesion and abscess formation in a rat peritonitis model. DESIGN: Randomized laboratory experiment. SETTING: A university hospital. INTERVENTIONS: In 72 male Wistar rats, a bacterial peritonitis was induced using the cecal ligation and puncture model. Animals were randomized to receive isotonic sodium chloride solution (group 1), HA-carboxymethylcellulose bioresorbable membrane (group 2), or 0.4% HA solution (group 3). Half of each group were killed at day 7 and half at day 21, and adhesions were scored in a blind fashion. The presence and sizes of intra-abdominal abscesses were noted. Cultures were taken for bacterial analysis. MAIN OUTCOME MEASURES: Intra-abdominal adhesions and abscesses. RESULTS: The median severity of adhesions was significantly lower in group 3 compared with group 1 rats at day 7 (II [range, I-IV] vs IV [range, I-IV], respectively; P=.02) and at day 21 (II [range, I-III vs IV [range, II-IV], respectively; P=.02). There was no significant difference between group 2 and group 1 rats on either day. At day 7, abscesses larger than 2 cm were found in 6 of 12 group 1 rats and in 4 of 12 group 2 rats, but in 0 of 11 group 3 rats (P=.01). At day 21, 0 of 11 group 3 rats had an intra-abdominal abscess, in contrast to 4 (33%) of 12 group 1 rats and 5 (45%) of 11 group 2 rats. All cultures of abscesses revealed polymicrobial flora. CONCLUSION: Adhesion and abscess formation are reduced using a 0.4% HA solution, and not HA-carboxymethylcellulose bioresorbable membrane, in a rat model of generalized bacterial peritonitis.

Abdominal Abscess↗

PubMed1999

Transposition of the rectus abdominis muscle for complicated pouch and rectal fistulas.

PURPOSE: Operative repair for complicated pouch and rectal fistulas is often difficult. We present our experience with ten consecutive patients operated on for complicated pouch and rectal fistulas by transposition of the rectus abdominis muscle. METHODS: Ten patients with high and complex pouch and rectal fistulas were treated with the interposition of a vascularized rectus abdominis muscle flap. All patients received standard bowel preparation and antibiotics. All were diverted by a temporary ileostomy. RESULTS: Causes of fistulas included Crohn's disease (n = 3), previous rectal surgery (n = 5), anal atresia (n = 1), and sphincter repair (n = 1). Three patients had a third recurrence. The procedure was performed in combination with a plastic surgeon. All fistulas healed. No special postoperative care was required. There were no cosmetic or functional complaints caused by transposition of the rectus abdominis muscle. CONCLUSIONS: Transposition of the rectus abdominis muscle is a suitable technique in treatment of fistulas between the rectum or ileal pouch and the vagina or urinary system, with no obvious side effects and excellent clinical outcome.

Adult↗

PubMed1999

Role and localization of urokinase receptor in the formation of new microvascular structures in fibrin matrices.

Fibrin or a fibrinous exudate can facilitate angiogenesis in many pathological conditions. In vitro, the outgrowth of capillary-like structures in fibrin can be mimicked by exposing human microvascular endothelial cells (hMVECs) to an angiogenic growth factor and tumor necrosis factor (TNF)-alpha. Urokinase-type plasminogen activator (u-PA) and plasmin activities are required for this angiogenic process. This study focuses on the role and localization of the u-PA receptor (u-PAR) in newly formed microvascular structures. The u-PAR-blocking monoclonal antibody (MAb) H-2 completely inhibited the formation of capillary-like tubular structures induced by exposure of hMVECs to basic fibroblast growth factor and TNF-alpha. This was accompanied by a several-fold increase in u-PA accumulation in the conditioned medium. The effect of MAb H-2 was not caused by blocking cellular activation by u-PA/u-PAR interaction, as the amino-terminal fragment (ATF) of u-PA, which also activates u-PAR, prevented tube formation. In addition, the inhibition by MAb H-2 was not due to an effect of the antibody on u-PAR-vitronectin binding. These data show that inhibition of tube formation can be caused not only by inhibition of u-PA or plasmin activities but also by unavailability of the u-PAR for cell-bound proteolysis. Immunohistochemical analysis showed that in in vitro angiogenesis u-PAR and u-PA were localized on the invading, tube-forming hMVECs and not on the endothelial cells that are located on top of the fibrin matrix. u-PAR and u-PA were also prominently expressed on endothelial cells of neovessels present in an atherosclerotic plaque. These data may give more insight into the role of u-PAR in repair-associated angiogenesis.

Antibodies, Monoclonal↗

PubMed1999

Bilateral thoracoscopic splanchnicectomy in patients with chronic pancreatitis.

BACKGROUND: Intractable pain, the most prominent feature of chronic pancreatitis, causes the patient great disability, and its treatment poses a difficult problem for gastroenterologist and surgeon alike. The main goal of treatment is to provide sufficient and lasting pain relief without the use of opiates. Conservative management, including stopping alcohol consumption, dietary measures, pancreatic enzyme suppletion and analgesics, is discussed. When these measures fail, surgery is often unavoidable. Indications, effect on pain relief, morbidity and mortality of drainage and resection procedures are described. Bilateral thoracoscopic splanchnicectomy, a newly developed operation to alleviate pain irrespective of the type of anatomic abnormality, is outlined in more detail. Early encouraging results of pain relief in patients with chronic pancreatitis after thoracoscopic splanchnicectomy are presented.

Abdominal Pain↗

PubMed1999

Imaging experimental intraabdominal abscesses with 99mTc-PEG liposomes and 99mTc-HYNIC IgG.

OBJECTIVE: To evaluate the accuracy of technetium-99m-labeled polyethylene glycol-coated liposomes (99mTc-PEG liposomes) and technetium-99m-labeled nonspecific human immunoglobulin G (99mTc-HYNIC IgG) for the scintigraphic detection of experimental intraabdominal abscesses in comparison with that of a standard agent, gallium-67 citrate. BACKGROUND: Scintigraphic imaging techniques can be very useful for the rapid and accurate localization of intraabdominal abscesses. Two newly developed radiolabeled agents, 99mTc-PEG liposomes and 99mTc-HYNIC IgG, have shown to be excellent agents for imaging experimental focal infection, but have not yet been studied in the detection of abdominal abscesses. METHODS: Intraabdominal abscesses were induced in 42 rats using the cecal ligation and puncture technique. Seven days later, randomized groups of rats received 99mTc-PEG liposomes, 99mTc-HYNIC IgG, or 67Ga citrate intravenously. The rats were imaged up to 24 hours after the injection. The biodistribution of the radiolabel was determined by counting dissected tissues ex vivo. Macroscopic intraabdominal abnormalities and focal uptake on the images were independently scored on a semiquantitative scale. RESULTS: 99mTc-PEG liposomes provided the earliest scintigraphic visualization of the abscess (as soon as 2 hours after the injection vs. 4 hours for the other two agents). Liposomes, IgG, and gallium all showed similarly high absolute uptake in the abscess. Focal uptake of liposomes and gallium correlated best with the extent of the macroscopic abnormalities. CONCLUSIONS: 99mTc-PEG liposomes and 99mTc-HYNIC IgG performed at least as well as the standard agent, 67Ga citrate, in the detection of experimental intraabdominal abscesses, with obvious advantages such as lower radiation exposure and more favorable physical properties. Of the two technetium agents, the liposomes seemed to be superior, providing the earliest diagnostic image and the best correlation with the inflammatory abnormalities. In addition, the preferential localization of radiolabeled PEG liposomes holds promise for targeted delivery of liposome-encapsulated drugs.

Abdominal Abscess↗