Elevated endothelin 1 levels in critical illness.
Explore the source record for details and available documents.
Critical Illness↗
Biomedical subjects
K H Usadel
Publications and source records attributed to K H Usadel.
Elevated endothelin levels in patients with hyperlipoproteinemia.
We determined lipoproteins, apolipoproteins, and endothelin in 98 patients (58 female and 40 male, age 18-72 years) with hyperlipidemia (plasma cholesterol > 2.5 g/l and/or triglycerides > 2.0 g/l) and in 50 healthy subjects (20 female, 30 male, age 19-68 years). In patients with hyperlipidemia endothelin levels were elevated compared to healthy controls. Patients with plasma cholesterol above 2.5 g/l had higher endothelin and lipoprotein(a) concentrations than patients with plasma cholesterol levels less than 2.5 g/l. A positive correlation was found between the concentrations of endothelin and apolipoprotein B (r = 0.2137; P < 0.013). Smoking patients with lipoprotein (a) above 300 mg/l had higher endothelin levels than both nonsmoking patients with lipoprotein (a) above 300 mg/l and smokers with normal lipoprotein(a). In smokers endothelin correlated positively with Lp(a) (r = 0.709; P < 0.01). No correlation was found between endothelin and triglycerides nor between endothelin and age or sex. The results suggest that the vasoconstrictor endothelin contributes to the increased vasal tone in hyperlipidemia. Because endothelin also has mitogenic properties, it may play a relevant role in the development of premature atherosclerosis in patients with hyperlipidemia.
Adolescent↗
T lymphocytes, CD68-positive cells and vascularisation in thyroid carcinomas.
Immunohistochemical detection and quantification of CD3- and CD45RO-positive lymphocytes and CD68-positive cells in 75 thyroid carcinomas of follicular cell origin revealed rising levels for these parameters associated with dedifferentiation. A parallel trend towards reduction of vascularisation, determined as CD31-positive blood vessels, with decreasing differentiation became evident, statistically only significant when well-differentiated follicular and anaplastic carcinomas were compared. Positive correlations could be demonstrated between the density of CD68-, CD3-, and CD45RO-positive cells as well as between the density of CD68-, and CD3-, and CD45RO-positive cells and vascularisation. These correlations were expected, as the interaction of CD68-positive cells and T lymphocytes results in the production of angiogenesis factors, ultimately leading to better vascularisation of the tumour. Nevertheless, the tumour cells themselves are variously capable of producing angiogenic substances. The obvious lack of positive correlation between the density of tumour-infiltrating cells determined in this study and vascularisation, despite reduced vascularisation in less differentiated tumours that contained increasing numbers of tumour-infiltrating cells, seems to be due to functional heterogeneity of morphologically similar tumours.
Antibodies, Monoclonal↗
Elevated endothelin-1 levels after cigarette smoking.
The effect of short-term nicotine consumption on endothelin-1 (ET-1) levels was studied in 10 male healthy smokers. Volunteers smoked in random order on 3 separate days a low-tar cigarette or a high-tar cigarette, or were studied without having smoked (no-cigarette experiment). ET-1, corticotropin, and cortisol levels, heart rate, and blood pressure were determined before and 1, 3, 5, 10, 20, and 30 minutes after smoking. In contrast to results obtained after smoking a low-tar cigarette or not smoking, smoking a high-tar cigarette resulted in a significant increase in ET-1 levels within 10 minutes, followed by an increase in corticotropin levels within 20 minutes after smoking. Thirty minutes after smoking, cortisol levels were higher after a high-tar cigarette compared with a low-tar cigarette or no smoking. Increases in heart rate and systolic blood pressure were likewise higher after smoking a high-tar cigarette than after smoking a low-tar cigarette. In conclusion, it is tempting to speculate that ET-1 may indeed act as the long-searched-for link between vasopressin and corticotropin-releasing hormone (CRH) and thus play an essential role in the stimulation of the hypothalamic-pituitary-adrenal axis. In addition, these results suggest that the increase in the level of ET-1, a powerful vasoconstrictor and mitogen, may play an important part in the disease mechanisms of atherosclerosis arising from smoking.
Adrenocorticotropic Hormone↗
Rat liver injury induced by hypoxic ischemia and reperfusion: protective action by somatostatins is independent from changes in glucose metabolism.
Changes in glucose metabolism mediated by natural somatostatin and two derivatives (octreotide, 008) were studied in hypoxic ischemic cell injury of the isolated perfused rat liver. The tested somatostatin and its analogues were previously shown to exert protective actions in liver damage induced by hypoxic ischemia and reperfusion. In isolated perfused livers of rats starved for 24 hours and unstarved rats flow rate was reduced and oxygen supply interrupted for 180 min. Then the livers were normoxically reperfused for 30 min. Glucose and lactate concentration, as well as LDH and GLDH activity, were determined in the effluent. In starved and unstarved rat livers hypoxic ischemia resulted in a substantial enzyme release. In livers harvested from unstarved rats hepatic glucose release was noticed which ceased towards prolonged low flow ischemia. In livers harvested from starved rats containing low hepatic glycogen concentration only minimal hepatic glucose release was present. In starved and unstarved rats pretreatment with somatostatin, octreotide, and 008 significantly reduced LDH and GLDH release (p < 0.001). In unstarved rats natural somatostatin and octreotide pretreatment resulted in a substantial output of glucose during the hypoxic ischemic perfusion period (p < 0.001), whereas livers with 008 pretreatment did not show any difference in glucose release compared to controls. In livers harvested from starved rats neither somatostatin nor octreotide nor 008 pretreatment led to a difference in glucose output observed in controls. Natural somatostatin and octreotide cause a strong hepatic glucose release even under hypoxic ischemic conditions in rat livers with filled glycogen stores. The protective action of natural somatostatin, octreotide, and 008 is not mediated by changes in glucose metabolism, and is not related to endocrine activity.
Amino Acid Sequence↗
The influence of iodine on the intensity of the intrathyroidal autoimmune process in Graves' disease.
Several lines of evidence support an etiological role of iodine for the initiation and perpetuation of autoimmune thyroid disease. However, varying relapse rates after increased iodine supplementation have been reported for Graves' disease. Furthermore the effects of iodine on the intensity of human autoimmune thyroiditis have previously only been investigated by indirect parameters and actions of iodine on thyroid function and a possible enhancement of the intrathyroidal autoimmune process in Graves' disease are difficult to separate in previous studies. Moreover lymphocytic thyroiditis in animal models has always been induced by considerably higher iodine doses as those used in in vivo studies. Therefore we investigated the effect of low and high iodine concentrations on the intensity of the intrathyroidal autoimmune process in Graves' disease. The intensity of intrathyroidal infiltration by lymphocytes, memory T cells, plasma cells and antigen presenting cells was determined by quantitative immunohistologic methods in 38 Graves' disease patients. 12 patients received additional preoperative iodine (group II) and 26 were treated with thiourelene antithyroid drugs only (group I). Urinary and intrathyroidal iodine concentrations were determined by a modified cer arsenite method in both groups. Application of high iodine doses in group II induced a significant increase of kappa and lambda positive plasma cells and interdigitating reticulum cells. This was not observed for activated T cells. There was no correlation between the extent of intrathyroidal infiltration by activated T cells, plasma cells and antigen presenting cells, and intrathyroidal or urinary iodine or intrathyroidal iodine concentrations in group I.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effect of 1-year treatment with nitrendipine versus enalapril on urinary albumin and alpha 1-microglobulin excretion in microalbuminuric patients with type 1 diabetes mellitus. A randomized, single-blind comparative study.
In order to compare the long-term effects of nitrendipine (CAS 39562-70-4) and enalapril (CAS 75847-73-3) on variables of glomerular and tubular function in type 1 diabetes mellitus, a single-blind, randomised comparative 1-year study was carried out in microalbuminuric patients (6 women, 14 men, age, 30-58 years, duration of diabetes, 3-41 years, HbA1 sigma 5.5-10%). 10 patients were treated with 20 mg/d nitrendipine, 10 patients were treated with 10 mg/d enalapril. On the average, urinary albumin excretion was decreased by 38 +/- 4% by nitrendipine (p < 0.01 vs. before treatment) and by 21 +/- 8% by enalapril (p < 0.05 vs. before treatment). The excretion of alpha 1-microglobulin decreased by 35 +/- 10% and by 39 +/- 9%, respectively (p < 0.05 vs. before treatment). Creatine clearance rose by 20 +/- 30% during nitrendipine treatment (p < 0.05 vs. before treatment) but was unchanged during enalapril treatment. Total kidney volume decreased by 23 +/- 4% (p < 0.01) and by 14 +/- 6% (p < 0.05), respectively. Blood pressure fell by 8 +/- 1% systolic and by 13 +/- 1% (diastolic) in nitrendipine-treated patients (both p < 0.01) and by 10 +/- 1% and 13 +/- 1% in enalapril-treated patients (both p < 0.01). Thus, nitrendipine long-term treatment of microalbuminuric type 1 diabetic appeared to be as effective as the treatment with enalapril in preventing or postponing the progression of diabetic nephropathy.
Adult↗
Somatic pain threshold and reactive hyperemia in autonomic diabetic neuropathy and silent myocardial ischemia.
In 31 patients with coronary artery disease (autonomic neuropathy, n = 11; diabetes without neuropathy, n = 10; silent myocardial ischemia without diabetes, n = 10) difference in somatic pain threshold and plethysmographically determined reactive hyperemia induced by forearm skeletal muscle ischemia was investigated. There was no difference in reactive hyperemia after passive maximum forearm ischemia in the three groups indicating identical vascular reactivity. After symptom-limited ischemic work however, reactive hyperemia was significantly higher in patients with silent myocardial ischemia as compared to diabetic patients. Exercise time was longer in patients with silent myocardial ischemia (153 +/- 51 s) as in patients with diabetic neuropathy (139 +/- 45 s) and diabetics without neuropathy (120 +/- 45 s). Pain as a cause of termination of symptom-limited ischemic forearm exercise occurred less frequently in patients with diabetic neuropathy (2/11) and patients with silent myocardial ischemia (3/10) as compared to patients with diabetes without neuropathy (9/10). In conclusion, patients with silent myocardial ischemia have a higher ischemic tolerance in the working forearm as compared to diabetic patients with and without neuropathy. There is a quantitative difference in ischemic tolerance between patients with silent myocardial ischemia and patients with diabetic neuropathy.
Autonomic Nervous System Diseases↗
[Significance of increased endothelin level for development of sequelae of diabetes mellitus].
In order to gain insight into the potential role of endothelin, a 21 amino acid peptide produced by endothelial cells, in the development of complications of diabetes mellitus, basal plasma endothelin levels were measured in 152 patients with diabetes mellitus (83 patients with type 1 diabetes mellitus, 69 patients with type 2 diabetes mellitus) and compared to those in 50 healthy controls. Blood was drawn at 8.00 a.m. under resting conditions and endothelin was determined after prior extraction by a sensitive radioimmunoassay. Endothelin levels were increased in patients with diabetes mellitus in comparison to controls (controls 0.9 +/- 0.1 pg/ml, type 1 diabetes mellitus 1.7 +/- 0.1, type-2-diabetes mellitus 2.0 +/- 0.1 pg/ml, p < 0.01 vs controls). 60% of patients with type 1 diabetes mellitus and elevated endothelin levels > 2.5 pg/ml (highest value measured in a control subject) had arterial hypertension with blood pressure > 140/90 mm Hg (p < 0.05 vs patients with normal endothelin levels). A reduced creatinine clearance (< 60 ml/min) was detected in 30% of patients with type 1 diabetes mellitus with elevated endothelin levels > 2.5 pg/ml, but only in 7% of patients with endothelin levels < 2.5 pg/ml (p < 0.05). In patients with type 1 diabetes mellitus and elevated endothelin levels diabetic retinopathy and peripheral neuropathy (p < 0.05) were more prevalent than in patients with normal endothelin values. 62% of patients with elevated endothelin levels had insufficient metabolic control (HbA1 concentrations above 10%). Positive correlations were found between endothelin and human atrial natriuretic peptide levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Rat liver injury induced by hypoxic ischemia and reperfusion: protective action by somatostatin and two derivatives.
Natural somatostatin and two synthetic derivatives (octreotide, 008) were tested for their ability to prevent hypoxic ischemic cell injury of the isolated perfused rat liver. The cyclic octapeptide octreotide is known to have endocrine and cytoprotective activities, whereas the cyclic hexapeptide 008 exerts protective actions without any endocrine effects. In isolated perfused rat livers flow rate was reduced and oxygen supply interrupted for 180 min. Then the livers were normoxically reperfused for 30 min. LDH and GLDH activity as well as Ca2+ concentration was determined in the effluent. Hypoxic ischemia led to a substantial enzyme release from the liver and to a strong Ca2+ influx. Pretreatment with somatostatin, octreotide and 008 significantly reduced LDH and GLDH release (P < 0.001). The somatostatins significantly increased the Ca(2+)-influx into the hypoxic, ischemic perfused rat liver (P < 0.001). Ca(2+)-influx is known to be an essential factor in the final common pathway of cell death induced by hypoxic ischemia. Even though the administration of the somatostatins was associated with an enhanced Ca(2+)-influx, the somatostatins reduced hypoxic ischemic liver injury.
Amino Acid Sequence↗
Screening for thyroid disorders in a working population.
Subclinical thyroid disorders have received increasing attention in recent years due to refined laboratory methods and a stronger emphasis on the role of preventive medicine. We performed a screening for thyroid-stimulating hormone (TSH) on 6884 persons in a working population. In cases in which TSH was not within the normal range we also measured the levels of triiodothyronine (T3), thyroxine (T4), and thyroxine-binding globulin (TBG). All persons who did not present with exclusion criteria or other nonthyroidal illnesses (n = 59) and the controls (n = 39) were submitted to thyrotropin-releasing hormone (TRH)-testing. Additionally, sonography of the thyroid was performed on 120 persons (59 subjects with abnormal hormone levels and 61 controls) to determine thyroid size and rule out morphological abnormalities. Based on the TRH test and T3, T4, and TBG measurements we found a prevalence of 0.03% (2/6884) for overt hyperthyroidism, 0.33% (23/6884) for subclinical hypothyroidism, 0.09% (6/6884) for subclinical hypothyroidism, and 0.015% (1/6884) for overt hypothyroidism in the healthy population. In subjects with overt or subclinical hyperthyroidism the prevalence of goiters (thyroid volume > 18 ml in women, > 25 ml in men) was 28%. Of this group 48% had structural abnormalities. All persons with goiters and/or structural abnormalities were over 35 years of age. Among the euthyroid, 20% had thyroid enlargement, and the same proportion presented with structural abnormalities. There were no differences between the two age groups. In the group with overt/subclinical hypothyroidism 47% presented with structural abnormalities of the thyroid; however, none presented with thyroid enlargement. Thyroid nodules were found only in older persons (> 35 years) with euthyroidism or hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
HLA-DR3 and HLA-DR5 confer risk for autoantibody positivity against the thyroperoxidase (mic-TPO) antigen in healthy blood donors.
The prevalence of circulating autoantibodies against thyroperoxidase (mic-TPO) was determined in 3,000 healthy blood donors (age range: 23 to 60 years) from the Hamburg area. Of the blood donors, 153 (5.1%) were found to have high titer of mic-TPO (> 350 IU/ml). Only two autoantibody positive subjects (0.06%) were chemically hyper- and hypothyroid, respectively. Analysis of HLA-DR specificities revealed that HLA-DR specificities DR3 and DR5 were significantly increased when compared to controls (n = 1,863). Comparison of the autoantibody-positive probands with a group of disease controls, i.e., Graves' patients and patients with lymphocytic thyroiditis, revealed a higher prevalence of HLA-DR3-positive HLA haplotypes in the disease controls when compared to autoantibody positives. Individuals with a mic-TPO level greater than 2,000 IU/ml were almost exclusively found to have one HLA-DR3 or HLA-DR5 positive HLA haplotype. We conclude that a high prevalence of high-titer mic-TPO can be found in healthy blood donors. Circulating signs of thyroid autoimmunity were associated with HLA specificities also found to be associated with autoimmune thyroid diseases.
Adult↗
Human atrial natriuretic peptide in patients with type 1 diabetes mellitus: is it related to the development of diabetic nephropathy?
There is controversy as to whether increased plasma levels of human atrial natriuretic peptide (hANP) in patients with type 1 diabetes mellitus may contribute to the development of diabetic nephropathy. Therefore, we decided to conduct two studies to examine the relationship of hANP levels to urinary albumin excretion and blood pressure. In a cross-sectional study, 83 randomly selected type 1 diabetic patients were investigated. 19 of the patients had increased urinary albumin excretion. 45 healthy volunteers served as controls. In a longitudinal study, 19 type 1 diabetic patients were examined for one year at monthly intervals. An increased risk of eventually developing diabetic nephropathy was identified in 7 out of these patients by repeatedly revealing increased urinary albumin excretion. On the average, hANP levels were increased in type 1 diabetic patients in comparison to controls (P < 0.001). In both studies, hANP levels were positively related (P < 0.05) to mean arterial blood pressure. There was no correlation between hANP levels and metabolic control. hANP levels lay within normal range irrespective of normal or elevated urinary albumin excretion provided that mean arterial blood pressure was normal. In the longitudinal study, increased urinary albumin and alpha-1-microglobulin excretion preceded the increase in both hANP levels and mean arterial blood pressure. Although hANP levels were evidently not related to the disease mechanisms of early diabetic nephropathy, it is tempting to speculate that hANP may contribute to the vicious circle connecting diabetic kidney disease to hypertension once that its levels are increased by elevated blood pressure.
Adolescent↗
Bromocriptine treatment over 12 years in acromegaly: effect on glucose tolerance and insulin secretion.
It is not known whether the beneficial effect of bromocriptine on glucose homeostasis in acromegaly is limited by a certain duration of therapy. To elucidate this problem, oral glucose tolerance tests were performed in 12 acromegaly patients before bromocriptine medication, under therapy (15.0 +/- 6.8 mg/day for 12 +/- 3 years), and during a 2-week drug withdrawal after long-term treatment. Initially altered glucose tolerance was normalized in 4 of 5 patients under bromocriptine therapy. During drug withdrawal the mean fasting glucose level and the mean glucose concentration at 120 min after oral glucose load increased from 5.05 +/- 0.61 to 5.77 +/- 0.78 mmol/l and from 5.61 +/- 2.05 to 7.55 +/- 3.05 mmol/l, respectively. A deterioration in glucose homeostasis was observed in 9 patients, and impaired glucose tolerance was ameliorated (but not to normal range) in 2 when bromocriptine was withdrawn. The proportion of alterations in glucose tolerance during drug withdrawal corresponded to that before the beginning of long-term bromocriptine treatment. Impaired glucose tolerance, observed in 2 patients under bromocriptine treatment, seemed to be compensated because a distinct elevation of glycosylated hemoglobin A1c was not observed. Bromocriptine led to a significant decrease in basal as well as glucose-stimulated insulin levels, and growth hormone secretion during oral glucose load was reduced in all 12 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Acromegaly↗
Development of thyroid gland volume during the first 3 months of life in breast-fed versus iodine-supplemented and iodine-free formula-fed infants.
The spontaneous development of thyroid gland volume (TGV) during the first 3 months of life was studied in entirely breast-fed infants (n = 21) and compared to those fed an iodine-supplemented formula (n = 19), an iodine-free formula (n = 5), or partially breast-fed in addition to an iodine-free (n = 4) or an iodine-supplemented formula (n = 16). The TGV of the infants and their mothers was determined sonographically in addition to their urinary iodine concentrations 5-7 days postpartum and 3 months later. In ten additional lactating mothers the breast milk concentrations of thyroid hormones and iodine were determined. It was shown that at 3 months of age an infant consuming about 1000 ml breast milk per day receives about 2 micrograms thyroid hormones and 55 micrograms iodine per day. At the end of their first week of life the infants showed a TGV between 0.28 and 1.5 ml (median 0.61 ml) and a urinary iodine concentration between 0.03 and 16.3 micrograms/dl (median 3.0 micrograms/dl). At 3 months of age the TGV of the breast-fed infants had decreased by a median of 0.24 ml (= -34%; median of percentage changes) whereas those fed a formula without iodine had increased by a median of 0.26 ml (= +50%; median of percentage changes). Those receiving an iodine-supplemented formula showed a TGV reduction of 0.14 ml (= +2%; median of percentage changes). The TGV development of the partially breast-fed infants lay between those being exclusively breast or formula fed.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Mechanisms of hepatotoxicity caused by dacarbazine in rats.
Possible risks of fatal dacarbazine hepatotoxicity have not been studied systematically. We therefore asked whether dacarbazine hepatotoxicity is influenced by the dose or mode of application, by dacarbazine light-decay products, by prior liver damage or by an induction of dacarbazine metabolism. 22 Sprague-Dawley rats were treated with 4.5 mg and 200 mg dacarbazine/kg bodyweight i.p. and i.v., with dacarbazine light-decay products and with 4.5 mg and 200 mg dacarbazine/kg bodymass after previous galactosamine and ethanol treatment. Serum alanine aminotransferase, cholinesterase and white blood cell and platelet numbers were measured and liver histology was evaluated. Dose-dependent dacarbazine hepatotoxicity could be demonstrated by histology. The mode of application, dacarbazine light-decay products and acute liver damage did not influence dacarbazine hepatotoxicity. However 200 mg dacarbazine/kg bodymass after ethanol pretreatment caused significant serological changes and a significant leucodepression. The increased hepato- and myelotoxicity after induction of hepatic microsomal enzymes should be reason to exclude ethanol and drugs that induce hepatic microsomal enzymes prior to treatment with dacarbazine.
Alanine Transaminase↗
Rapid and simple subtyping of the HLA-DRB3 gene in Graves' disease by using temperature-gradient gel electrophoresis.
A HLA-DRB3-subtyping system that uses TGGE for analyzing DRB3 alleles was developed. The polymorphic second exon of the HLA-DRB3 gene was amplified from four homozygous typing cell lines, 223 healthy individuals, and 102 patients with Graves' disease by using the PCR. The PCR products were electrophoresed in a temperature gradient from 35 degrees C to 70 degrees C, and the resulting fragments were visualized by silver staining. Four DRB3 alleles (HLA-DRB3*0101, *0201, *0202, and *0301) were distinguished from one another by the migration of the corresponding homoduplex with the exception that DRB3*0201 was indistinguishable from DRB3*0202. The latter two alleles, however, were resolved by the artificial heteroduplexing approach. Arginine in position 74 of the DRB3 gene product (i.e., HLA-DRB3*0101) was significantly more frequent in Graves' patients than in controls. The relative risk conferred by the presence of the DRB3*0101 was 15.8 (p < or = 0.001). The presence of arginine in position 74 contributed to an etiologic fraction of 75% in our study population. The PCR-TGGE technique is a simple, nonisotopic method, which may be useful in rapid screening of large populations for HLA disease markers.
Alleles↗