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M Haap

Publications and source records attributed to M Haap.

At least 19 recordsLinked to original sources
PubMed2006

Association of serum phosphate levels with glucose tolerance, insulin sensitivity and insulin secretion in non-diabetic subjects.

BACKGROUND: Hypophosphatemia is associated with impaired glucose tolerance and insulin resistance in primary hyperparathyroidism. However, little is known about the association between serum phosphate and glucose metabolism in healthy subjects. METHODS: We measured fasting serum phosphate levels (SP, normal range 2.6-4.5 mg/dl) and serum calcium (S-Ca, normal range 2.1-2.6 mmol/l) in 881 non-diabetic subjects (341 male/540 female, age: 38+/-1 years, body mass index 25.9+/-0.2 kg/m(2) (mean+/-standard error of the mean). An oral glucose tolerance test (OGTT) with determination of glucose and insulin every 30 min was performed in all subjects. Insulin secretion and insulin sensitivity (IS) were estimated from the OGTT using validated indices. Furthermore, we tested whether serum phosphate predicts glucose tolerance in 115 subjects during a lifestyle intervention program (LIP). RESULTS: Serum phosphate was negatively correlated with 2-h blood glucose levels independent of age, gender and percent body fat (r=-0.13, P<0.0001). This association remained significant after additional adjustment for S-Ca, creatinine and parathyroid hormone. Serum phosphate was positively correlated with IS (r=0.10, P=0.0006), but not with insulin secretion. This was independent of age, gender, percent body fat, S-Ca and serum creatinine. In the subjects taking part in the LIP low serum phosphate levels at baseline were associated with higher postprandial glucose levels. CONCLUSIONS: In non-diabetic subjects, low serum phosphate levels are associated with high 2-h blood glucose levels and reduced IS. Whether low serum phosphate levels are a cause or a consequence of low IS and impairment of glucose tolerance needs to be tested in further studies.

Adult↗
PubMed2006

Beta cell function, insulin resistance and plasma adiponectin concentrations are predictors for the change of postprandial glucose in non-diabetic subjects at risk for type 2 diabetes.

Insulin resistance, impaired insulin secretion, and low adiponectin levels have been shown to be predictors for type 2 diabetes. However, it is not yet clear whether these associations (1) are independent of changes in body weight, or (2) are valid for changes in glucose tolerance in the prediabetic state. Sixty-two non-diabetics (50 with normal glucose tolerance) aged 41 +/- 11 years, BMI 30.5 +/- 5.3 kg/m2 (mean +/- SD) were studied twice with a standard oral glucose tolerance test (oGTT, mean follow-up time 3.0 +/- 1.8 years (mean +/- SD) [range 0.5-6.5 years]). Insulin sensitivity and insulin secretion were estimated from oGTT using validated indices. Two-hour blood glucose during oGTT deteriorated over time (baseline 2 h glucose 6.32 +/- 0.21 VS. follow-up 2 h glucose 7.14 +/- 0.22 mM, p < 0.001) while the percentage body fat did not change (32.7 +/- 1.2 VS. 32.6 +/- 1.2%, p = 0.46). Follow-up 2 h blood glucose was predicted by adiponectin (p = 0.01), baseline insulin sensitivity (p = 0.02) and baseline insulin secretion relative to insulin sensitivity (p = 0.03) independent of sex, age, baseline 2 h blood glucose or change in percentage body fat. Our results suggest that low adiponectin levels, insulin resistance and low beta cell function predict the continuous deterioration of glucose tolerance in early prediabetic states, independent of changes in adiposity. Therefore, the early influence of these parameters should be the subject of future prevention programs to prevent deterioration of glucose tolerance.

Adiponectin↗
PubMed2005

Genetic determinants of insulin action in polycystic ovary syndrome.

INTRODUCTION: Insulin resistance is associated with both type 2 diabetes (T2 D) and polycystic ovary syndrome (PCOS). There is an association of T2 D with several polymorphisms in candidate genes related to insulin resistance. However, there is limited information about the association of these polymorphisms with PCOS. METHODS: 57 non-diabetic women with PCOS and a control group of 567 healthy non-diabetic women underwent an oral glucose tolerance test (OGTT). They were genotyped for the polymorphisms Gly972Arg in IRS-1, Gly1057Asp in IRS-2, SNP 43, 44, and 45 in CAPN10, Pro12Ala in PPAR(gamma)2, C-512 T in FOXC2, and T45 G in adiponectin. RESULTS: Women with PCOS had higher 2-h blood glucose levels (6.5 +/- 0.2 vs. 6.0 +/- 0.06 mmol/l, p = 0.03) compared to control women, higher fasting insulin (79 +/- 7 vs. 53 +/- 2 pmol/l, p = 0.02), and a lower insulin sensitivity estimated from the OGTT (12.4 +/- 1.1 vs. 19.1 +/- 0.5 U, p = 0.0001). More homozygous G allele carriers of the T45 G polymorphism in the adiponectin gene were found in women with PCOS compared to controls (13.2 % vs. 2.6 %, p = 0.008). In women with PCOS, G-allele carriers had lower fasting insulin levels than TT carriers (61 +/- 9 vs. 88 +/- 10, p = 0.02) in contrast to controls (p = 0.03 for interaction genotype x PCOS). The other polymorphisms were distributed equally among women with PCOS and controls (all p > 0.5). SUMMARY: We found a higher prevalence of the T45 G polymorphism in the adiponectin gene in women with PCOS compared to controls. This was not associated with a more insulin resistant phenotype in PCOS, however. Other frequent polymorphisms in genes related to insulin resistance and type 2 diabetes showed no association with PCOS.

Adiponectin↗
PubMed2005

Elevated serum GGT concentrations predict reduced insulin sensitivity and increased intrahepatic lipids.

Elevated serum gamma-glutamyltransferase (GGT) concentrations have been related to features of the metabolic syndrome as well as increased risk of cardiovascular and liver disease. More recently, elevated GGT levels were shown to predict development of type 2 diabetes in a longitudinal study from Korea. The aim of the present study was to test the hypothesis that serum GGT is associated with glucose tolerance, insulin sensitivity and beta-cell function in a healthy, non-diabetic Caucasian population from the Tübingen family study. Insulin sensitivity was estimated by oGTT (n = 850) or measured by hyperinsulinemic euglycemic clamp (n = 245), respectively. A subgroup (n = 70) underwent additional determination of intrahepatic lipid content using 1H magnetic resonance spectroscopy. Serum GGT was positively correlated with two-hour glucose during oGTT (r = 0.15, p < 0.0001) and negatively correlated with insulin sensitivity from oGTT (r = -0.31, p < 0.0001) and clamp (r = -0.27, p < 0.0001). The relationship between GGT and insulin sensitivity remained significant after adjusting for sex, age, BMI, and AST using multivariate regression analysis. Inclusion of serum triglyceride levels as a parameter of lipid metabolism kept the relationship significant in the oGTT group (p < 0.0001), but not in the smaller clamp group (p = 0.11). Additionally, serum GGT was positively correlated with hepatic lipid content (r = 0.49, p < 0.001) independent of sex, age, BMI, AST or serum triglycerides. There was no significant correlation between GGT and the index for beta-cell function after adjusting for age, sex, BMI and insulin sensitivity (p = 0.74). In conclusion, elevated serum GGT levels predict glucose intolerance probably via insulin resistance rather than beta-cell dysfunction. This may be primarily related to hepatic insulin resistance and increased intrahepatic lipids. The association observed between elevated hepatic lipids and reduced insulin sensitivity might explain the increased diabetes risk observed in subjects with elevated serum GGT concentrations. In the absence of overt liver disease, elevated serum GGT concentrations may point the clinician to incipient disturbances in the glucose metabolism.

Adolescent↗
PubMed2005

Early carotid atherosclerosis in overweight non-diabetic individuals is associated with subclinical chronic inflammation independent of underlying insulin resistance.

Overweight in children and young adults is an increasing problem in Western industrialized countries with potential impact on cardiovascular morbidity. Whether early arterial wall thickening in these subjects mainly results from the often associated insulin resistance syndrome or from increased subclinical chronic inflammation probably triggered by adipose tissue is still under discussion. We therefore determined insulin sensitivity index (ISI) by performing an euglycaemic hyperinsulinaemic glucose clamp (insulin infusion rate 1 mU/kg/min) and high-sensitivity C-reactive protein (hsCRP) levels in relation to the intima-media thickness (IMT) at the common carotid artery (high resolution ultrasound; 13 MHz) in 81 young (age 33 +/- 1 years), moderately overweight subjects. To reduce the number of confounding variables, subjects with disturbances in glucose metabolism (75 g oral glucose tolerance test) and hypertension were excluded. As expected, higher BMI was positively correlated with increased IMT (r = 0.358; p = 0.001). After multiple regression analysis, hsCRP levels independently correlated to IMT (r = 0.251; p = 0.03), even after adjusting for age, sex, BMI, ISI, LDL cholesterol and smoking as cofactors. However, taking all above listed factors into account, glucose-clamp assessed insulin sensitivity was not correlated with IMT. Thus, overweight might trigger inflammatory mechanisms leading to vascular wall hypertrophy independent of the insulin resistance syndrome already early in life.

Adult↗
PubMed2004

Serum adiponectin levels predict the effect of short-term dietary interventions on insulin sensitivity in humans.

AIMS/HYPOTHESIS: Fat-rich diets can acutely induce insulin resistance. Data from adiponectin knock-out mice suggest that this effect might be increased in the absence of adiponectin. In the present study we tested whether plasma adiponectin concentrations influence changes in insulin sensitivity induced by a short-term dietary intervention in humans. METHODS: We analysed data from 27 healthy, non-obese men with normal glucose tolerance. These men ate a diet high in fat and a diet high in carbohydrates for three days each. RESULTS: The high-fat diet induced a significant drop in insulin sensitivity (determined by euglycaemic-hyperinsulinaemic clamp) compared to baseline (0.100+/-0.009 vs 0.083+/-0.007 micro mol.kg(-1).min(-1).(pmol.l(-1)), p=0.01). The drop in insulin sensitivity was more pronounced in subjects with low serum adiponectin (0.094+/-0.011 vs 0.077+/-0.010 micro mol.kg(-1).min(-1).(pmol.l(-1)), p=0.02) than in subjects with high serum adiponectin (0.103+/-0.011 vs 0.090+/-0.040 micro mol.kg(-1).min(-1).(pmol.l(-1)), p=0.16). In the whole group the high-carbohydrate, low-fat diet did not cause an increase in insulin sensitivity (0.095+/-0.007 vs 0.102+/-0.009 micro mol.kg(-1).min(-1).(pmol.l(-1)), p=0.06). However, insulin sensitivity was significantly increased in the subgroup with low serum adiponectin levels (0.084+/-0.013 vs 0.099+/-0.018 micro mol.kg(-1).min(-1).(pmol.l(-1)), p=0.01). In an additional multivariate analysis post-intervention insulin sensitivity was predicted by pre-intervention insulin sensitivity ( p<0.001) and adiponectin concentrations ( p=0.001). CONCLUSIONS/INTERPRETATION: These data indicate that the reduction in insulin sensitivity achieved by a short-term high-fat diet is more pronounced in non-obese subjects with low serum adiponectin. Thus it is possible that the restriction of dietary fat and a diet high in carbohydrates might be particularly effective in subjects with low adiponectin such as obese or Type 2 diabetic individuals.

Adiponectin↗
PubMed2004

[Reduced insulin effect in subclinical fatty liver].

BACKGROUND AND OBJECTIVE: Steatosis of the liver is known to be associated with impaired insulin action and is considered to be a feature of the metabolic syndrome. In the present study we addressed the question whether liver fat content, as measured by proton MR spectroscopy ( (1)H MRS), in healthy subjects without clinical signs (hepatomegaly, elevation of transaminases) of relevant liver disease correlates with whole-body insulin sensitivity. METHODS: 21 (18 males and 3 females, age 35 +/- 11 years) non-diabetic subjects underwent the euglycemic-hyperinsulinemic clamp test for determination of whole body insulin action. Liver fat content was measured by means of proton MR spectroscopy ( (1)H MRS). Lipid content was calculated as percentage share of the lipid signal in relation to the entire signal of the spectrum (water and lipid signals). Clinically relevant steatosis of the liver was ruled out by standard magnetic resonance imaging (MRI). Subjects with a history of alcohol intake of more than 40 g/d were excluded from analysis. RESULTS: In a single correlation analysis percentage liver fat strongly correlated with insulin sensitivity index (ISI) (r = 0.7, p = 0.001). After adjusting for the effects of percentage body fat (PFAT) percentage liver fat remained an independent determinant of ISI (p = 0.01). CONCLUSION: Our results suggest that liver fat content is an important predictor of whole-body insulin sensitivity in healthy subjects. The correlation of liver fat content with insulin sensitivity was found in the absence of clinical steatosis and was independent of body fat content.

Adult↗
PubMed2003

Glucose oversupply increases Delta9-desaturase expression and its metabolites in rat skeletal muscle.

AIM/HYPOTHESIS: Previous studies have shown that prolonged glucose infusion causes insulin resistance and triglyceride accumulation in rat skeletal muscle. In this study, we investigated a possible relationship between insulin resistance and the composition of different accumulated lipid fractions in rat skeletal muscle. METHODS: Continuous glucose infusion was carried out in rats for 7 days. Lipids were extracted from skeletal muscle, separated by thin layer chromatography and fatty acid composition of phospholipids, triglycerides, diglycerides, free fatty acids and cholesterol esters fractions was analysed by gas chromatography. Delta9-Desaturase mRNA was measured by real time polymerase chain reaction. The enzyme activity was measured in the microsomal fractions. RESULTS: Prolonged glucose infusion (5 days) increased the relative content of palmitoleic acid (16:1 N7) several-fold (2.3- to 5.8-fold) in four out of five lipid fractions and enhanced oleic acid (18:1 N9) two-fold in three lipid fractions suggesting increased Delta9-desaturase activity while the content of several polyunsaturated fatty acids was reduced. In parallel, Delta9-Desaturase mRNA contents and enzyme activities in skeletal muscle were increased 10-fold, 75-fold, 2.6-fold and 7.7-fold after 2 and 5 days of glucose infusion, respectively. CONCLUSION/INTERPRETATION: Our results suggest that long-term glucose oversupply induces a rapid increase in Delta9-desaturase expression and enzyme activity in skeletal muscle which leads to fast and specific changes in fatty acid metabolism possibly contributing to the insulin resistance in this animal model.

Animals↗
PubMed2003

Insulin-like effect of low-dose leptin on glucose transport in Langendorff rat hearts.

BACKGROUND: In a murine myotube cell line (C 2 C 12 myotubes), leptin at low physiological concentrations (1 ng/ml) has been shown to stimulate glucose transport and glycogen synthesis. The aim of the present study was to test whether an analogous leptin effect on glucose transport is detectable in the heart. METHODS AND RESULTS: We used the isolated Langendorff rat heart preparation with hemodynamic function control. Using polymerase chain reaction (RT-PCR), a 346- and 375-base fragment indicative for the short and long leptin receptor isoform was detected in the rat heart. Glucose transport rates were calculated using equimolar double tracer perfusion with the non-metabolizable glucose analog 3-O-methylglucose (3-O-MG) and the non-transportable tracer mannitol and two-compartimental modeling. 3-O-MG uptake at a perfusate glucose concentration of 11 mM was measured over 15 minutes in control hearts, hearts perfused with insulin (10 mU/ml), leptin (1 ng/ml) or insulin (10 mU/ml) plus leptin (1 ng/ml; n = 8 in each group). The basal 3-O-MG transport rate of 0,7351 +/- 0,051 micro mol/min/g wet weight was increased 4.18 fold with insulin, 2.69 fold with leptin, and 4.2 fold with leptin plus insulin. Simultaneous monitoring of hemodynamic function revealed a minor and transient effect of leptin on left ventricular pressure, which was strongly augmented in coperfusion with insulin. CONCLUSIONS: The data suggest that leptin at low physiological concentrations is able to exert a partial insulin like effect on glucose uptake. We speculate that the effect might be mediated by both leptin receptor isoforms. This leptin effect is additive to the effect of insulin and might therefore contribute to the insulin independent basal glucose supply of the heart. It can not be completely excluded that the observed leptin effect on glucose transport is secondary to altered myocardial function.

Animals↗
PubMed2002

Prolonged glucose infusion into conscious rats inhibits early steps in insulin signalling and induces translocation of GLUT4 and protein kinase C in skeletal muscle.

AIMS/HYPOTHESIS: Previous studies on diabetic patients have shown that hyperglycaemia increases glucose uptake in an apparently insulin-independent manner. However, the molecular mechanism has not been clarified. METHODS: We studied rats receiving continuous glucose infusion to address this question. In this animal model, rats accommodate systemic glucose oversupply and rapidly develop insulin resistance. RESULTS: Glucose infusion increased both plasma glucose and insulin concentrations to peak after one day. In spite of continuous glucose infusion normoglycaemia was reached after 5 days while insulin concentrations remained higher. Focusing our studies in day 2 (hyperglycaemia/hyperinsulinaemia) and day 5 (normoglycaemia/hyperinsulinaemia) we found, particularly in day 5, that the early steps of the insulin signalling cascade in skeletal muscle of glucose-infused rats were not more activated when compared to control animals as assessed by a comparable phosphorylation of the insulin receptor, IRS-1 and PKB and by an unaltered IRS-1-associated Ptd(Ins) 3' kinase activity. Continuous glucose infusion induced GLUT4 protein expression and translocation to the plasma membrane while neither expression nor translocation of GLUT1 was affected. Translocation of PKC- betaI, - betaII (> threefold) and -alpha, -theta (to a lesser extent) to the plasma membrane was significantly induced after 2 days but not after 5 days of glucose infusion when normoglycaemia was reached. CONCLUSIONS/INTERPRETATION: Our data support the hypothesis that continuous glucose infusion induces translocation of GLUT4 while the early steps of the insulin signalling cascade were not increased. These effects could be mediated by activation of PKC.

Animals↗
PubMed2002

Evidence for greater oxidative substrate flexibility in male carriers of the Pro 12 Ala polymorphism in PPARgamma2.

The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma2 (PPARgamma2) gene is associated with reduced type 2 diabetes risk and increased insulin sensitivity. It is possible that the oxidative shift from lipid to glucose as a fuel is more efficient in Ala allele carriers. To test this hypothesis, we examined carbohydrate and lipid oxidation by indirect calorimetry in lean, glucose tolerant subjects with (X/Ala, n = 25) and without the Pro12Ala polymorphism (Pro/Pro, n = 73) basally and after insulin stimulation during a 2-hour eugylcaemic hyperinsulinaemic clamp. Insulin sensitivity was non-significantly greater in X/Ala (0.13 +/- 0.01 micromol/kg/min/pM) than in Pro/Pro (0.12 +/- 0.01 micromol/kg/min/pM, p = 0.27). Basally, there were no lipid nor carbohydrate oxidation differences between the groups. Interestingly, the decrease in lipid oxidation during insulin stimulation was significantly greater in male X/Ala (- 0.51 +/- 0.06 mg/kg/min) than in male Pro/Pro (- 0.35 +/- 0.04 mg/kg/min, p = 0.03). No difference was observed in females. Analogously, the change in carbohydrate oxidation in male X/Ala (1.34 +/- 0.2 mg/kg/min) was significantly greater than in male Pro/Pro (1.03 +/- 0.12 mg/kg/min, p = 0.05). The respiratory quotient increased more, but not significantly more, in male X/Ala (0.11 +/- 0.01) than in male Pro/Pro subjects (0.08 +/- 0.01, p = 0.08) but similarly in females. These results indicate that the mechanism by which the Ala allele improves insulin sensitivity might involve enhanced suppression of lipid oxidation permitting more efficient (predominantly non-oxidative) glucose disposal. It is unclear why this could be demonstrated only in males, although gender differences in substrate oxidation are well documented.

Adult↗
PubMed2002

Erythropoietin-mediated decrease of the redox-sensitive transcription factor NF-kappaB is inversely correlated with the hemoglobin level.

The aim of this study was to determine the effect of rh-EPO on the redox-sensitive transcription factor (NF-kappaB) in vivo and in vitro. Ten patients (7 female, 3 male), mean age 69.2 +/- 11 years, with end-stage renal failure and anemia prior to initiation of regular hemodialysis were enrolled and divided into 2 groups (group A "good responder", 7 patients and group B "poor responder", 3 patients) in accordance to the response to rh-EPO therapy. Nuclear binding activity of NF-kappaB was determined in ex vivo isolated mononuclear cells before, 4 and 8 weeks after onset of regular hemodialysis and rh-EPO therapy by electrophoretic mobility shift assays (EMSA). In group A, a reduction of NF-KB binding activity from 100% to 56 +/- 6% was observed within the first four weeks of rh-EPO treatment, while mean hemoglobin rose from 8.2 +/- 0.4 g/dl to 11.1 +/- 0.2 g/dl. However, this effect was abrogated after another 4 weeks of treatment when NF-kappaB signal increased back to 85.2 +/- 10.6% despite consistent mean hemoglobin level of 11.3 +/- 0.4 g/dl. Group B demonstrated a slight increase of NF-kappaB signal from 100% to 129 +/- 18.5%, while mean hemoglobin only moderately rose from 7.6 +/- 0.3 g/dl to 8.3 +/- 0.1 g/dl within the first 4 weeks, and it further rose to 180 +/- 45% after 8 weeks of treatment, while mean hemoglobin (9.5 +/- 0.1 g/dl) remained low. The NF-kappaB binding activity differed significantly when comparing both groups (p = 0.007). Binding activity of Oct-1, serving as control, did not change notably in either group (p = 0.34). In vitro studies showed that rh-EPO did not directly affect NF-KB binding activity in THP-1 cells. However, coincubation of THP-1 cells with erythrocytes led to a reduction of NF-kappaB binding activity only in THP-1 cells with a hemoglobin level adjusted to 11 g/dl compared to 8 g/dl in the presence of rh-EPO. In vivo and in vitro data implicate a complex interaction between rh-EPO, stimulated RBC and the redox-sensitive transcription factor NF-kappaB in mononuclear cells.

Aged↗
PubMed2001

Effects of intravenous and dietary lipid challenge on intramyocellular lipid content and the relation with insulin sensitivity in humans.

An increased intramyocellular lipid (IMCL) content, as quantified by (1)H-magnetic resonance spectroscopy ((1)H-MRS), is associated with reduced insulin sensitivity. At present, it is unclear which factors determine IMCL formation and how rapidly IMCL accumulation can be induced. We therefore studied the impact of hyperinsulinemia and elevated circulating nonesterified fatty acid (NEFA) levels on IMCL formation and insulin sensitivity. We further evaluated the influence of a high-fat diet on IMCL storage. In the infusion protocol, 12 healthy male subjects underwent a 6-h hyperinsulinemic-euglycemic glucose clamp with concomitant infusion of Intralipid plus heparin. IMCL was quantified by (1)H-MRS in soleus (SOL) and tibialis anterior (TA) muscle at baseline and then every hour. IMCL levels started to increase significantly after 2 h, reaching a maximum of 120.8 +/- 3.4% (SOL) and 164.2 +/- 13.8% (TA) of baseline after 6 h (both P < 0.05). In parallel, the glucose infusion rate (GIR) decreased progressively, reaching a minimum of 60.4 +/- 5.4% of baseline after 6 h. Over time, the GIR was strongly correlated with IMCL in TA (r = -0.98, P < or = 0.003) and SOL muscle (r = -0.97, P < or = 0.005). In the diet protocol, 12 male subjects ingested both a high-fat and low-fat diet for 3 days each. Before and after completion of each diet, IMCL levels and insulin sensitivity were assessed. After the high-fat diet, IMCL levels increased significantly in TA muscle (to 148.0 +/- 16.9% of baseline; P = 0.005), but not in SOL muscle (to 114.4 +/- 8.2% of baseline; NS). Insulin sensitivity decreased to 83.3 +/- 5.6% of baseline (P = 0.033). There were no significant changes in insulin sensitivity or IMCL levels after the low-fat diet. The effects of the high-fat diet showed greater interindividual variation than those of the infusion protocol. The data from the lipid infusion protocol suggest a functional relationship between IMCL levels and insulin sensitivity. Similar effects could be induced by a high-fat diet, thereby underlining the physiological relevance of these observations.

Adult↗
PubMed1997

[Effects of leukocyte depletion on the storage quality of whole blood].

BACKGROUND: According to the German Guidelines for Hemotherapy, preoperative autologous blood donations can be stored and transfused as whole blood. In contrast to the storage of blood components, however, storage of whole blood results in deterioration of the biological quality due to contamination with leukocytes and platelets. In this study we examined the influence of prestorage leukocyte depletion on the quality of filtered whole blood donations during storage. MATERIAL AND METHODS: Whole blood was donated by healthy volunteers (n = 14,500 ml, 70 ml CPDA-1) and was filtered using an integrated whole blood filter system (Leukotrap A1, Fa.Pall, Dreieich, Germany). The leukocyte-depleted whole blood units were then stored for up to 49 days. Several hematological and biochemical parameters indicative of the quality of blood donations were determined during storage. RESULTS: Our data indicate a quality of leukocyte-depleted whole blood donations comparable to buffy-coat-free red blood cell units. CONCLUSIONS: The Leukotrap A1 whole blood filter system is an interesting option for hospitals lacking the technical capacity to separate whole blood into components. The clinical suitability remains to be investigated by means of clinical studies.

Adult↗
PubMed1991

Selenium as a protector of diastolic function during oxidant stress.

Interventional studies yielded conflicting results on reperfusion injury. They are unable to discriminate between lesions due to ischemia or to additional damage during reoxygenation. Since reactive oxygen metabolites have been implicated as a major cause of reperfusion injury, 375 nmol/min of hydrogen peroxide was infused in a Langendorff rat heart preparation as a model of oxidant stress without previous ischemic contractile dysfunction. Impaired endogenous defense was remodeled, using selenium-deficient hearts with reduced glutathione peroxidase activity. Measurements of hemodynamic parameters demonstrate increased myocardial susceptibility to oxidant stress in hearts with decreased antioxidant defense. Defined concentrations of hydrogen peroxide produce isolated impairment of active and passive diastolic properties of the ventricle in this model.

Animals↗
PubMed1989

Nitroglycerin and isosorbide dinitrate stimulation of glutathione disulfide efflux from perfused rat liver.

Nitroglycerin (GTN) and isosorbide dinitrate (ISD) are metabolized by glutathione S-transferase to nitrite with production of GSSG from GSH. Infusion of organic nitrates into perfused rat liver led to efflux of GSSG in the bile and nitrite in the perfusate. Biliary GSSG increased more rapidly than did nitrite release as GTN infusion rate was increased, indicating that GSSG reducing capacity was being exceeded. Rapid GTN-induced oxidation of GSH may be the mechanism of tissue GSH depletion by GTN and other alkylnitrates. Such depletion of glutathione may reduce nitrite production from organic nitrates and underlie tolerance to these drugs.

Animals↗
PubMed1989

Diastolic dysfunction of perfused rat hearts induced by hydrogen peroxide. Protective effect of selenium.

Oxidant substances such as hydrogen peroxide are postulated to cause cardiac dysfunction and injury in a number of pathological conditions. Selenium is an essential nutrient which serves as an oxidant defense through the selenoenzyme glutathione peroxidase. This enzyme metabolizes hydrogen peroxide; its activity in rat heart is reduced to 5% of control by selenium deficiency. Left ventricular function of selenium-deficient and control rat hearts was studied in a Langendorff preparation under isovolumic conditions. A stabilization period of 20 min was followed by a 70 min infusion of hydrogen peroxide at 375 or 1500 nmol/min. When no hydrogen peroxide was infused, perfusion for 90 min had no effect on systolic or diastolic function and no effect of selenium deficiency was detected. Hydrogen peroxide infusion into selenium-deficient hearts at 375 nmol/min led to impaired isovolumic relaxation and a substantial increase in end-diastolic pressure after 45 min which worsened progressively until the experiment was terminated. By contrast no effect was observed on systolic contractile function as assessed by peak pressure or developed pressure. Infusion of this dose of hydrogen peroxide into control hearts had no significant effect on diastolic or systolic function. However, infusion of 1500 nmol hydrogen peroxide/min into control hearts caused diastolic dysfunction after 30 min without affecting systolic function. These results indicate that hydrogen peroxide injury to the perfused rat heart is manifested by diastolic dysfunction before systolic dysfunction occurs. Selenium deficiency lowers the dose of hydrogen peroxide needed to cause diastolic dysfunction. This suggests that the selenoenzyme glutathione peroxidase protects the heart against hydrogen peroxide injury.

Animals↗