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H A Prins

Publications and source records attributed to H A Prins.

At least 19 recordsLinked to original sources
PubMed2005

The effect of oral administration of L-arginine on anal resting pressure and anodermal blood flow in healthy volunteers.

BACKGROUND: Topical application of L-arginine, the precursor of nitric oxide, reduces anal resting pressure without significant side effects and may therefore be of benefit in the treatment of anal fissure. This in vivo study investigated the effect of orally administered L-arginine on anal resting pressure and anodermal blood flow in healthy volunteers. METHODS: Eight healthy volunteers took 3 sachets of Arginaid (Novartis Consumer Health, Breda, The Netherlands) containing 15 g L-arginine on a daily basis, for 7 days. At the start of the experiment (day 0) and on days 3 and 7, plasma levels of L-arginine, anal resting pressures and anodermal blood flow were determined. RESULTS: Arginine plasma levels increased from 107.0+/-8.6 micromol/l (day 0) to 283.7+/-44.0 micromol/l on day 3 (p< 0.01) and remained elevated at day 7 (157.3+/-19.6 micromol/l, p<0.05). Anodermal blood flow and anal resting pressures were similar on days 0, 3 and 7. CONCLUSIONS: Oral administration of 15 g arginine in healthy volunteers on a daily basis increased arginine plasma levels but had no influence on anodermal blood flow and anal resting pressure.

Administration, Oral↗
PubMed2004

High plasma arginine concentrations in critically ill patients suffering from hepatic failure.

OBJECTIVE: In physiological conditions, the liver plays an important role in the regulation of plasma arginine concentrations by taking up large amounts of arginine from the hepatic circulation. When hepatic failure is present, arginine metabolism may be disturbed. Therefore, we hypothesized high arginine plasma concentrations in critically ill patients suffering from hepatic failure. DESIGN: We prospectively collected blood samples from a cross-section of intensive care unit patients. SETTING: Surgical intensive care unit of a Dutch university medical center. SUBJECTS: A total of 52 critically ill patients with clinical evidence of dysfunction of more than two organs were recruited. MEASUREMENTS: Plasma arginine concentrations were determined by HPLC. We identified correlations of arginine concentrations with organ failure scores and laboratory variables by univariate and multiple regression analyses. RESULTS: High plasma arginine concentrations were found in critically ill patients developing organ failure. Patients who were in the highest quartile of plasma arginine concentrations had significantly lower fibrinogen concentrations, higher lactic acid concentrations, and longer prothrombin time. Stepwise multiple regression analysis showed that concentrations of arginine were independently associated with the presence of hepatic failure (P=0.03) and renal failure (P=0.048). In addition, lactic acid proved to be an independent determinant of plasma arginine concentration (P=0.014). CONCLUSIONS: Critically ill patients who suffer from hepatic failure have elevated plasma arginine concentrations. Additional arginine in the treatment of these patients can be harmful, and therefore should not be used as a standard nutritional regimen until further evaluation.

Adolescent↗
PubMed2001

Major liver resection results in a changed plasma amino acid pattern as reflected by a decreased Fischer ratio which improves by bactericidal/permeability increasing protein.

BACKGROUND/AIMS: Major liver resection results in a high morbidity and mortality, and endotoxin plays a role in post-resection hepatic failure. Severe hepatic failure as seen in hepatitis and cirrhosis may be accompanied by hepatic encephalopathy and is characterized by a typical plasma amino acid pattern reflected by a decreased Fischer ratio. This study was performed to evaluate the plasma amino acid pattern in patients undergoing major liver surgery receiving placebo or the endotoxin-neutralizing agent bactericidal/permeability-increasing protein (rBPI21). PATIENTS AND METHODS: Forty-eight patients were randomized in this phase II, dose escalation, multicenter trial. Plasma amino acid profiles were determined preoperatively, and on the first (day 1) and third (day 3) postoperative day. RESULTS: In the placebo group the Fischer ratio decreased significantly on both postoperative days. Administration of rBPI21 also resulted in a decreased Fischer ratio on day 1, but not on day 3. Highly elevated alanine plasma levels were observed on day 1 in placebo-treated patients, whereas rBPI21 prevented this elevation. Plasma alanine levels on day 1 correlated with the duration of post-resection hepatic failure. CONCLUSIONS: Major liver resection results in a decreased Fischer ratio and a rise in plasma alanine levels. Plasma levels of alanine on the first postoperative day correlated with the duration of the post-resection hepatic failure. rBPI21 improved the Fischer ratio and prevented the rise of plasma alanine levels.

Adult↗
PubMed2001

Low arginine plasma levels do not aggravate renal blood flow after experimental renal ischaemia/reperfusion.

BACKGROUND: Ischaemic renal dysfunction is present in many clinical settings, including cardiovascular surgery. Renal hypoperfusion seems to be the most important pathophysiologic mechanism. Arginine plasma levels are rate limiting for NO synthesis, and low arginine plasma levels are seen after major vascular surgery. OBJECTIVE: to establish the effects of low arginine plasma levels on renal blood flow after renal ischaemia/reperfusion. DESIGN: Wistar rats were used in this unilateral renal ischaemia/reperfusion model. After 70 min of ischaemia, the kidney was reperfused for 150 min. Arginase infusion was used to lower arginine plasma levels. Blood flow measurement was performed at the end of the experiment using radiolabelled microspheres. Additional experiments were performed for histopathology. RESULTS: Arginase efficiently decreased arginine plasma levels to about 50% of normal. There was a lower blood flow in the ischaemic kidney than the contralateral (non-ischaemic) kidney. Lowering arginine plasma levels did not reduce renal blood flow in the ischaemic kidney. Renal histopathology was not influenced by lowered arginine plasma levels. CONCLUSIONS: Lowering arginine plasma levels did not affect blood flow or histology following renal ischaemia and reperfusion.

Animals↗
PubMed2001

Arginase release from red blood cells: possible link in transfusion induced immune suppression?

Arginine stimulates lymphocyte function and is degraded by arginase, an enzyme that is abundantly present in red blood cells. Arginase impairs lymphocyte function and responses in vitro. Leakage of arginase from stored red blood cells may be involved in the lymphocyte dysfunction associated in allogenic blood transfusion. In the present study, arginase activity was determined in bags of red cells stored for transfusion. Buffy coat depleted red blood cells were obtained routinely from four healthy donors and stored in bags for a maximum period of five weeks at 4 degrees C. The bags were sampled for determination of arginase, lactate dehydrogenase, and potassium. In addition, a random sample of 36 bags of red blood cells about to be transfused to patients were studied. Levels of arginase, lactate dehydrogenase, and potassium showed a time dependent increase in the bags of the four donors. This time dependent increase in arginase activity could be confirmed in the additional bags sampled (P < 0.0001, r = 0.78). The results for the first time show that arginase is released from red blood cells during storage for transfusion. Arginase infusion may play an important role in the immune suppression observed after blood transfusion.

Arginase↗
PubMed2000

High plasma levels of arginine and liver arginase in Kupffer-cell-depleted rats after partial hepatectomy.

BACKGROUND/AIMS: The remnant liver after partial hepatectomy releases arginase into the plasma, which is a reliable indicator of hepatocellular damage. Little information is available on how this release affects arginine plasma levels. We hypothesized that Kupffer cells after partial hepatectomy may prevent further hepatocellular damage, contributing to lower arginase release. The aim of the study was to evaluate the role of Kupffer cells in plasma arginase activity and arginine plasma levels after partial hepatectomy. METHODS: Wag/Rij rats (n=72, 250-275 g) were randomly assigned to receive 1 ml liposome-encapsulated dichloromethylene-diphosphonate in order to eliminate Kupffer cells (DMDP, n=24), 1 ml liposome encapsulated-phosphate buffered saline (PBS, n=24) or 1 ml NaCl 0.9% (NaCl, n=24) intravenously. Forty-eight hours later, all rats had a two-third liver resection. Rats were killed at 0, 24, 48 and 96 h after partial hepatectomy. RESULTS: Arginase plasma activity was higher in the DMDP-treated group compared to NaCl and PBS (both p<0.01, p<0.05, p<0.01 and p<0.05 for 0, 24, 48 and 96 h after partial hepatectomy respectively). Arginine plasma levels increased, but were lower in the DMDP group compared to NaCl and PBS (both p<0.05, 24 h after hepatectomy). CONCLUSION: The study showed that Kupffer cell depletion results in a higher arginase release from the remnant liver after partial hepatectomy, indicating a hepatocellular protective function of Kupffer cells. Despite this arginase release, arginine plasma levels were increased after partial hepatectomy.

Amino Acids↗
PubMed2000

Low arginine plasma levels in patients after thoracoabdominal aortic surgery.

OBJECTIVE: Thoracoabdominal aortic surgery is a high-risk procedure and associated with a significant morbidity and mortality. Ischemia reperfusion of visceral organs and lower extremities is one of the most important determinants of this morbidity. Arginine is the precursor of nitric oxide and arginine plasma levels are important in maintaining organ blood flow. Furthermore, arginine is important in wound healing and the immune system. Because of increased utilization of arginine, low arginine plasma levels could be expected after thoracoabdominal aortic surgery. We therefore measured arginine plasma levels in these patients. DESIGN: Six patients with thoracoabdominal aortic aneurysm were included in this study. SETTING: University Hospital Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands. SUBJECTS: Six patients undergoing thoracoabdominal aortic surgery. INTERVENTION: Plasma levels of arginine were measured by high-performance liquid chromatography. RESULTS: Very low arginine plasma levels were seen on the first postoperative day. From day 1 arginine slowly increased, but did not reach normal plasma levels on day 6. CONCLUSIONS: A significant decrease of arginine plasma levels was found and because of the fact that arginine has multiple functions, it may be important to keep these arginine plasma levels at normal or even higher levels in patients undergoing major vascular surgery. European Journal of Clinical Nutrition (2000) 54, 615-617.

Aged↗
PubMed2000

Bactericidal/permeability-increasing protein preserves leukocyte functions after major liver resection.

OBJECTIVE: To analyze postoperative leukocyte functions in patients undergoing hemihepatectomy, and to assess the effect of treatment with the endotoxin-neutralizing agent bactericidal/permeability-increasing protein (rBPI21). SUMMARY BACKGROUND DATA: Extensive liver resection is associated with a high incidence of infectious complications. Because elimination of pathogenic microorganisms occurs mainly by leukocytes, this increased rate of infections is most likely due to an impaired function of these cells. Endotoxin, translocated from the gut into the systemic circulation as a result of increased gut permeability and reduced hepatic clearance function after major liver resection, may play an important role in the impairment of posthepatectomy leukocyte function. METHODS: To investigate whether hemihepatectomy results in impaired leukocyte functions and to determine the role of endotoxin in this process, leukocyte oxidative burst and leukocyte antigen expression were studied in three groups of patients: patients undergoing a hemihepatectomy and receiving rBPI21 treatment, patients undergoing hemihepatectomy and receiving placebo, and as an extra control group patients undergoing other major abdominal surgeries. Blood samples were collected before surgery, 2 hours after surgery, and at days 1, 2, 5, and 7. Phorbol myristate acetate-stimulated oxidative burst was measured using dihydrorhodamine, and leukocyte surface expression of the antigens CD11b, CD16, and CD14 was investigated by indirect immunofluorescence. Both oxidative burst and membrane surface expression were quantified by flow cytometry. An indication of the antiendotoxin effect of rBPI21 treatment was provided by assessment of plasma lipopolysaccharide binding protein (LBP) levels by enzyme-linked immunosorbent assay. RESULTS: The oxidative burst in the hemihepatectomized patients receiving placebo and the controls increased 2 hours after surgery, whereas it decreased in the rBPI21-treated patients, resulting in significant differences between the groups. On day 1, neutrophil CD11b expression and monocyte CD14 expression in the rBPI21-treated patients and controls were significantly lower than in the placebo group. At 2 hours, CD16 expression in the placebo-treated patients was significantly higher than in the rBPI21-treated patients and controls. On day 5 and day 7, plasma LBP levels were significantly higher in the placebo-treated patients compared with the rBPI21-treated patients. CONCLUSIONS: The results of this study show that patients undergoing major liver resection have an increased activation of leukocytes compared with those undergoing other major abdominal surgery. This enhanced activation may contribute to the increased risk of infection in these patients. Administration of the endotoxin-neutralizing agent rBPI21 to hemihepatectomy patients was shown to reduce plasma LBP levels, to preserve leukocyte functions partially, and to reduce leukocyte activation to the level of other, nonhepatic abdominal surgery.

Acute-Phase Proteins↗
PubMed2000

The effect of mild endotoxemia during low arginine plasma levels on organ blood flow in rats.

OBJECTIVE: Arginine is the sole precursor in the generation of the vasodilating agent nitric oxide. Arginine plasma levels are low in situations associated with endotoxemia such as major trauma, sepsis, and experimental obstructive jaundice. The aim of the study was to evaluate hemodynamics at low arginine plasma levels during a low-grade endotoxemia. DESIGN: Randomized, placebo-controlled animal laboratory investigation. SUBJECTS: Male Wistar rats (n = 29), anesthetized. INTERVENTIONS: Rats were randomly assigned to receive (at t = 0 mins) an intravenous infusion of 1.5 mL of 0.9% NaCl (SAL, n = 12) or 1.5 mL of an arginase (3200 IU) solution (ASE, n = 17) over a 20-min period. After the SAL or ASE infusion, rats were randomly assigned to receive an intravenous endotoxin (lipopolysaccharide [LPS], 150 microg/kg in 1.0 mL of 0.9% NaCl; ASE/LPS, n = 10 and SAL/LPS, n = 6) challenge or a control infusion (1.0 mL of 0.9% NaCl; ASE/SAL, n = 7 and SAL/SAL, n = 6) at t = 30 mins. MEASUREMENTS AND MAIN RESULTS: Organ blood flow was measured at t = 270 mins, using radiolabeled microspheres. At this time point, arginine plasma levels were lower in the ASE-treated rats (ASE/SAL vs. SAL/SAL and ASE/LPS vs. SAL/LPS, both p < .005, respectively). Cardiac output, mean arterial pressure, and therefore total peripheral resistance were similar for all groups. In the LPS-treated animals (SAL/LPS and ASE/LPS), cardiac output was maintained by a higher heart rate compensating the lower stroke volume. Organ blood flow to the small intestine and splanchnic blood flow was lower in the ASE/LPS-treated rats (both p < .05 when compared with other groups). Total liver blood flow was similar for all groups; the lower splanchnic blood flow was compensated for by a higher hepatic arterial blood flow. CONCLUSION: The present study shows that low arginine plasma levels do not influence organ blood flow, whereas, during a low-grade endotoxemia, low arginine plasma levels result in reduced blood flow to the small intestine.

Animals↗
PubMed1999

Impaired leukocyte phagocytosis in patients undergoing hemihepatectomy for liver metastases.

Patients undergoing partial hepatectomy have an increased susceptibility to infection. To investigate whether this increased risk is related to impaired leukocyte function, we studied polymorphonuclear leukocyte (PMN) phagocytosis in patients undergoing a hemihepatectomy because of liver metastasis (LM, n = 11) and in patients undergoing major abdominal surgery because of abdominal malignancy (AM, n = 8). Eight healthy volunteers (HVs) served as controls. Leukocyte suspensions were incubated with fluorescein isothiocyanate-labeled Staphylococcus aureus, and phagocytosis was measured by flow cytometry. Preoperative PMN phagocytosis, in the presence of autologous plasma, was significantly less in patients with LM compared with patients with AM or HVs. This impaired phagocytosis was potentially restored in the presence of normal plasma. The decreased phagocytic capacity of PMNs from patients with LM was not related to levels of known plasma opsonins or phenotypic changes of PMNs. Rather, it was related to a deficiency of unidentified plasma factors. After surgery, the phagocytic capacity of PMNs of patients with AM decreased by approximately 30%, which correlated with decreasing levels of immunoglobulin G and C3. In conclusion, patients with LM had a decreased PMN phagocytic capacity before surgery. This impairment in phagocytosis disappeared 1 week after surgery. We propose that the presence of LM leads to a deficiency of factor(s) in the blood that impairs PMN phagocytic capacity.

Case-Control Studies↗
PubMed1999

Reduced arginine plasma levels are the drive for arginine production by the kidney in the rat.

In bile duct ligated rats, arginase (ASE) release from damaged hepatocytes results in low arginine (ARG) levels despite maximal renal ARG production. Plasma ARG levels were restored by reducing gut-derived endotoxemia that lowered circulating ASE activity although maintaining increased renal production. From this it was not clear if the higher renal ARG production was induced by the low grade endotoxemia or the low arginine plasma levels. The separate and combined influence of both factors on ARG metabolism was studied in the rat. Male Wistar rats received either bovine liver ASE, to lower ARG levels, or saline (SAL). Following the ASE or SAL infusion, rats were randomized to receive a low dose endotoxin (LPS) or SAL infusion. In ASE/SAL- and ASE/LPS-treated rats, ARG levels were lower compared with SAL/SAL (p<.005) and SAL/LPS (p<.005). The increased ARG production by the kidneys and gut proved to be independent of LPS but related to reduced ARG plasma levels (both p<.05 when compared with SAL/SAL and SAL/LPS). Metabolism of related amino acids was not explanatory. The study concluded that a low grade endotoxemia did not influence the metabolism of ARG by the gut, kidney, and liver. Reductions in ARG plasma by ASE treatment, irrespective a low dose endotoxin, were the drive for ARG production by the gut and the kidney.

Animals↗
PubMed1999

Is major liver surgery associated with an increased systemic inflammatory response? A prospective comparison of hemihepatectomy and other major abdominal surgery.

AIMS/BACKGROUND: Extensive liver resection is associated with a higher morbidity and mortality than other major abdominal surgery. Because the liver is responsible for the clearance of pathogenic particles as well as the clearance and degradation of several inflammatory mediators, the high rate of complications after liver surgery may be due to an enhanced or prolonged inflammatory response. The objective of this prospective study was to investigate whether major liver resection is associated with an enhanced systemic inflammatory response. METHODS: The course of various inflammatory parameters was studied in 12 patients undergoing a hemihepatectomy and the results were compared with those of 12 patients undergoing other major abdominal surgery. RESULTS: After hemihepatectomy, the plasma levels of IL-6, IL-8, sPLA2 and elastase were similar to the levels after other major abdominal surgery, though the hepatectomized patients showed higher levels of lactoferrin, possibly due to impaired hepatic clearance. In addition, the hemihepatectomized patients showed signs of impaired liver function, as was indicated by increased plasma bilirubin and ASAT levels, whereas the other patients did not. CONCLUSIONS: The inflammatory response associated with major liver resection is not significantly different from that after other major abdominal surgery, and therefore does not explain the increased complication rate that is seen after major liver resection. We infer that the most important factor in the development of complications after liver resection may be the hepatic failure itself.

Abdomen↗
PubMed1998

Use of a mixture of medium-chain triglycerides and longchain triglycerides versus long-chain triglycerides in critically ill surgical patients: a randomized prospective double-blind study.

Twenty critically-ill surgical patients who needed total parenteral nutrition were randomly enrolled in a double-blind study comparing two intravenous fat emulsions: one containing a mixture of 50% medium-chain triglycerides and 50% long-chain triglycerides and another containing 100% longchain triglycerides. The purpose of this study was to investigate metabolic and biochemical differences between both emulsions with special reference to liver enzymes. After a baseline period of 24 h with only glucose and NaCl infusion, the lipid emulsion was added continuously during 24 h over 5 days. The parenteral nutrition was administered in mixture bags containing amino-acids, glucose and lipids together. Two-thirds of the non-protein calories were administered as glucose 40% and one third as either long-chain triglycerides or a mixture of medium-chain triglycerides and long-chain triglycerides. The total amount of non-protein calories received was the measured energy expenditure during the baseline period plus 10% and was fixed during the study. Plasma substrate concentrations, energy expenditure, and nitrogen balance were determined and arterial blood samples were taken. No toxic effects or complications attributable to one of the two emulsions were observed. There was no significant difference in energy expenditure, nitrogen balance, liver function tests, carnitine, transferrin, pre-albumin, albumin, cholesterol, triglycerides and free fatty acids. The only parameter that showed a different pattern of reaction between the two emulsions was serum bilirubin concentration. In this study no evidence of any advantageous effect of a mixture of medium-chain triglycerides and long-chain triglycerides was seen.

Adult↗
PubMed1998

Paradoxical changes in organ blood flow after arginase infusion in the non-stressed rat.

Arginine (ARG) is the precursor of nitric oxide (NO), a potent vasodilator. Arginase (ASE) is released following hepatocellular damage, resulting in low plasma ARG levels. The effect of ASE infusion on hemodynamics was studied. Rats received a 20 min ASE or saline infusion, and systemic hemodynamics and organ blood flow were studied, at 30 and 270 min, using radiolabeled microspheres. Compared with control, ASE resulted (30 min) in 1) undetectable ARG levels; 2) higher mean arterial pressure and total peripheral resistance (both p < .05); 3) higher blood flow to the heart, kidneys, stomach, small intestine (all p < .05), and spleen (p < .001); and 4) lower vascular resistance in the heart, kidneys, stomach, and small intestine (all p < .05) and in the spleen (p < .005). At 270 min, ASE rats had similar organ blood flow and higher nitrate levels in urine and plasma (both p < .05) compared with control. We conclude that ASE reduces ARG levels with simultaneous increase in mean arterial pressure and total peripheral resistance. Higher nitrate production, suggesting higher NO formation in the presence of low ARG plasma levels, is paradoxical but could explain the higher blood flow in some organs. The increased total peripheral resistance during higher nitrate formation suggests regional differences in dependency of NO production on plasma ARG levels.

Animals↗