Biomedical subjects

T Kunt

Publications and source records attributed to T Kunt.

29 records · Page 2Linked to original sources

PubMed1999

Alpha-lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products.

Advanced glycation end products (AGEs) have been identified as relevant mediators of late diabetic complications such as atherosclerotic disease. The endothelial migration of monocytes is one of the first steps in atherogenesis and monocyte-endothelial interaction itself is linked to the expression of adhesion molecules like vascular cell adhesion molecule-1 (VCAM-1). Recently, stimulation of VCAM-1 by AGEs has been demonstrated. Since endothelial stimulation by AGEs is followed by generation of oxygen free radicals with subsequent activation of nuclear transcription factor kappaB, we investigated the influence of alpha-lipoic acid on the expression of VCAM-1 and monocyte adherence to endothelial cells in vitro by means of cell-associated chemiluminescence assays and quantitative reverse transcriptase polymerase chain reaction using a constructed recombinant RNA standard. We found that alpha-lipoic acid was able to decrease the number of VCAM-1 transcripts from 41. 0+/-11.2 to 9.5+/-4.7 RNA copies per cell in AGE-stimulated cell cultures. Furthermore, expression of VCAM-1 was suppressed in a time- and dose-dependent manner by alpha-lipoic acid as shown by chemiluminescence endothelial cell assay. Pretreatment of endothelial cells with 0.5 mM or 5 mM alpha-lipoic acid reduced AGE-induced endothelial binding of monocytes from 22.5+/-2.9% to 18. 3+/-1.9% and 13.8+/-1.8% respectively. Thus, we suggest that extracellularly administered alpha-lipoic acid reduces AGE-albumin-induced endothelial expression of VCAM-1 and monocyte binding to endothelium in vitro. These in vitro results may contribute to the understanding of a potential antioxidative treatment of atherosclerosis.

Antioxidants↗

PubMed1998

Biological activity of C-peptide on the skin microcirculation in patients with insulin-dependent diabetes mellitus.

19 insulin-dependent diabetes mellitus (IDDM) patients participated in a randomized double-blind crossover investigation to investigate the impact of human C-peptide on skin microvascular blood flow. The investigation was also carried out with 10 healthy volunteers. Blood pressure, heart rate, blood sugar, and C-peptide levels were monitored during a 60-min intravenous infusion period of C-peptide (8 pmol kg-1 min-1) or saline solution (154 mmol liter-1 NaCl), and 30 min after stopping the infusion. During the same time period, capillary blood cell velocity (CBV), laser Doppler flux (LDF), and skin temperature were assessed in the feet. In the verum arm, C-peptide levels increased after starting infusion to reach a maximum of 2.3+/-0.2 nmol liter-1 after 45 min, but remained below 0. 15 nmol liter-1 during the saline treatment. Baseline CBV was lower in diabetic patients compared with healthy subjects (147+/-3.6 vs. 162+/-4.2 micron s-1; P < 0.01). During C-peptide administration, CBV in IDDM patients increased progressively from 147+/-3.6 to 167+/-3.7 micron s-1; P < 0.001), whereas no significant change occurred during saline infusion or in healthy subjects. In contrast to the CBV measurements, the investigation of LDF, skin temperature, blood pressure, heart rate, or blood sugar did not demonstrate any significant change during the study. Replacement of human C-peptide in IDDM patients leads to a redistribution in skin microvascular blood flow levels comparable to levels in healthy subjects by increasing the nutritive CBV relative to subpapillary arteriovenous shunt flow.

Adult↗

PubMed1998

Is there an ectopic secretion of monomeric calcitonin in the human being?

INTRODUCTION: Persistent detectable calcitonin (CT) values can be frequently observed after treatment of medullary thyroid carcinomas (MTCs). Apart from residual C cells or incomplete tumor extirpation, ectopic CT production should be taken into account. CT determination in patients without MTC and after total thyroidectomy should reveal to what extent, apart from the C cells, other neuroendocrine cells show a relevant CT production. OBJECTIVES: The objective of this study was to find out whether ectopic CT production can be detected using an assay specifically recognizing the monomeric form of CT. METHODS: The CT serum values were obtained from 94 healthy individuals and 64 patients who had undergone total thyroidectomy and radioiodine therapy because of follicular or papillary carcinoma. RESULTS: In the group of thyroidectomized patients, the CT values were below the detection limit of the assay. In the tested patients, there was neither a physiological (C cell) nor a pathological (MTC cell) secretion of monomeric CT. CONCLUSION: A relevant ectopic monomeric CT production could be excluded because the patients were without detectable CT concentration. For this reason, postoperative CT concentrations of the monomeric form in MTC patients can be traced either to remaining C cells or to tumor cells. For a differentiation of these two possibilities further diagnostics is necessary.

Adult↗

PubMed1998

Cholesterol granuloma of the maxillary sinus: six cases from the same region.

It is common to find cholesterol granuloma in the mastoid antrum and air cells of the temporal bone, but it is very rare in paranasal sinuses. In the development of this pathology, the key factor is the presence of a closed cavity containing exudate and blood. Six cases of cholesterol granuloma of the maxillary sinus are presented from six years' study in our hospital. According to the main symptoms, clinical findings, and radiological appearance (except the destruction of the antrum wall in some patients), the pathology was similar to chronic maxillary sinusitis. All the patients were treated with radical operative techniques. In this study, we reviewed the literature and our cases, and could not detect any findings to explain why this pathology had occurred frequently in our district. We strongly recommend that investigations should be carried out on all specimens obtained from paranasal sinus surgery, because the cholesterol granuloma in the maxillary antrum could be mistaken for chronic sinusitis.

Adult↗

PubMed1998

Skin microcirculation in patients with type I diabetes with and without neuropathy after neurovascular stimulation.

1. Neurovascular inflammation is impaired in patients suffering from diabetic neuropathy. The aim of our study was to evaluate the distribution of nutritive and total skin blood flow in diabetic patients with and without neuropathy after neurovascular stimulation with acetylcholine. 2. Twenty patients with Type I diabetes, 10 with and 10 without neuropathy, and 10 age-matched non-diabetic control subjects, underwent microvascular investigations before and after neurovascular stimulation by intracutaneous application of acetylcholine. The capillary blood cell velocity in the nailfold of the hallux was measured by videophotometric capillaroscopy, and the total skin microcirculation in the same area by laser Doppler flowmetry. 3. The increase in total skin blood flow was significantly impaired in the group of neuropathic diabetic patients compared with the non-neuropathic diabetic patients (17.5 +/- 8.3 versus 51.0 +/- 16.2; P < 0.05) and the non-diabetic subjects (17.5 +/- 8.3 versus 67.8 +/- 19.7; P < 0.01). The increase in capillary blood flow was not significantly impaired in Type I diabetes patients with neuropathy. 4. The ratio between capillary blood flow and total skin perfusion decreased significantly in the control group (from 0.82 +/- 0.15 to 0.47 +/- 0.11; P < 0.05) and in the Type I diabetes patients without neuropathy (from 0.79 +/- 0.12 to 0.43 +/- 0.12; P < 0.05), whereas the decrease in the neuropathic group was statistically insignificant (from 1.05 +/- 0.19 to 0.72 +/- 0.16). 5. Diminished total skin perfusion in the foot after intracutaneous stimulation with acetylcholine in Type I diabetes patients is associated with diabetic neuropathy, indicating a disturbance in the neurovascular reflex arc. This impaired neurovascular response is caused by a diminished total and subpapillary blood flow and not by a diminished nutritive capillary flow. There is no evidence of a diminished nutritive capillary blood flow during neurogenic inflammation in Type I diabetes patients suffering from diabetic neuropathy.

Acetylcholine↗

PubMed1998

The influence of advanced glycation endproducts (AGE) on the expression of human endothelial adhesion molecules.

Advanced glycation endproducts (AGEs) possibly play a dominant role in the pathogenesis of macrovascular disease in diabetes. Recent studies could demonstrate that glycated albumin (AGE-BSA) was able to stimulate vascular cell adhesion molecule-1 (VCAM.1) on endothelial cells. The aim of this study was to find out if AGE-BSA was not only able to enhance the expression of vascular cell adhesion molecule-1, but also of intercellular adhesion molecule-1 (ICAM-1) and E-Selectin on human endothelial cells. Stimulation of endothelial cells with AGE-BSA for six hours predominantly increased the expression of VCAM-1, but ICAM-1 and E-Selectin were also upregulated as shown by immunoilluminometric assay (ILMA).

Albumins↗

PubMed1998

Microvascular skin blood flow following the ingestion of 75 g glucose in healthy individuals.

It is expected that microvascular blood flow might be affected by blood glucose, blood insulin and C-peptide levels. In our investigation skin microvascular blood flow (LDF) was measured using laser doppler fluxometry at skin temperatures of 37 degrees C and 44 degrees C during a 75 g oral glucose load (OGT) or water in ten healthy volunteers (6 male, 4 female, age: 28.1+/-4.0) who had fasted overnight. The transcutaneous oxygen tension (tcPO2) was measured using a transcutaneous oxygen electrode at a temperature of 44 degrees C. The microvascular response to acetylcholine was investigated before the start of the ingestion period and after 30 minutes. In addition, the capillary blood cell velocity (CBV) was measured using dynamic capillaroscopy. During OGT an increase in LDF could be observed at 37 degrees C (180%, p < 0.005) but only a slight increase was observed at 44 degrees C (86%, n.s.). The microvascular response to acetylcholine increased by 164% (p < 0.05) and the TcPO2 values increased by 30% (p < 0.01) during the OGT investigation. No significant changes in the microvascular measurements could be observed during the water experiment. No significant changes could be observed in the CBV measurements in any phase of the investigation. Plasma C-peptide and insulin levels exhibited an association with the LDF measurements at 37 degrees C (r = 0.22, p < 0.05; r = 0.30, p < 0.05; respectively), whereas blood sugar values showed an association with the TcPO2 measurements (r = 0.39, p < 0.01). After the ingestion of glucose a sophisticated modulation of microvascular blood flow was found in healthy volunteers. Further studies are necessary to investigate the role of a disturbed postprandial blood sugar control, insulin and C-peptide secretion in the development of microvascular dysfunction, especially in IDDM.

Acetylcholine↗

PubMed1998

New aspects on biological activity of C-peptide in IDDM patients.

C-peptide, which is released from the pancreatic beta cells into the circulation in amounts equimolar with insulin, fulfills an important function in the assembly of the two-chain insulin structure, but has otherwise been considered to be biologically inactive. However, during the last few years several experimental and clinical studies have demonstrated that replacement of C-peptide in patients with insulin-dependent diabetes mellitus elicits several physiological effects. Thus, during short-term substitution of C-peptide (1-3 h) decreased glomerular hyperfiltration, augmented whole body and skeletal muscle glucose utilisation, improved autonomic nerve function and a redistribution of microvascular skin blood flow could be observed. In addition, replacement of C-peptide during a period of 1-3 months has been shown to improve renal function as well as autonomic and sensory nerve function in IDDM patients. The mechanisms behind these effects remain unclear, but recent investigations have indicated that an increase in Na+K+ATPase activity and a stimulation of the endothelial nitric oxide synthase may contribute to the observed physiological effects of C-peptide. Not only the intact C-peptide molecule, but also fragments from the C-terminal and mid-portion of the molecule have been shown to exert biological effects. Further research will be necessary to evaluate the underlying mechanism and the clinical impact of C-peptide replacement in IDDM patients.

C-Peptide↗

PubMed1998

Establishment of a quantitative RT-pCR for detection of vascular cell adhesion molecule-1 transcripts in endothelial cells after stimulation with advanced glycation endproducts.

Advanced glycation endproducts (AGE) are supposed to increase endothelial expression of adhesion molecules like vascular cell adhesion molecule-1 (VCAM-1) by inducing an intracellular stress with subsequent activation of nuclear transcription factor NF-kappa-B. Quantitative analysis of VCAM-1-transcription has not been demonstrated concerning this topic. Thus, the aim of this study was to establish quantitative reverse transcription polymerase chain reaction (RT-PCR) assays using a spacer gene in order to measure the amounts of specific mRNA for VCAM-1 in human umbilical vein endothelial cells (HUVEC) which were stimulated with AGE-albumin (AGE-BSA). A recombinant RNA-standard was synthesized and used as internal RT-PCR standard. The amount of VCAM-1-mRNA in unstimulated HUVEC was found to be 2.2 +/- 2.7 copies per cell. After stimulation with AGE-BSA, mRNA-levels were elevated to 38.9 +/- 10.9 copies per cell. Positive controls (stimulated with lipopolysaccharide) revealed mRNA-levels of 78.7 +/- 27.5 copies per cell. We conclude that quantitative RT-PCR using the spacer gene technique is a valid and reliable method for the measurement of small amounts of specific

Cells, Cultured↗

PubMed1978

[Complaints in the lumbosacral region and their management with Dolo-Neurobion].

Many patients complaining of acute pain in the lumbosacral area suffer from affections of intrapelvic organs (urinary bladder, prostate glands, female genital-organs). The routine diagnosis in such cases is described. In 53 own patients the analgesic and anti-inflammatory effect of Dolo-Neurobion has been evaluated. It is a combination drug consisting of the neurotropic vitamins B1, B6 and B12 and the analgesic metamizole. The treatment was started parenterally in the recommended doses and continued orally. If there were definite signs of infection in the pelvic area, additional antibiotics were administered after bacteriological tests. Dolo-Neurobion showed good or excellent results in 77,4% and moderate effects in 15,1% of the patients. There were no major side-effects or intolerance.

Aminopyrine↗

PubMedDate not supplied

Effects of C-peptide on microvascular blood flow and blood hemorheology.

Beside functional and structural changes in vascular biology, alterations in the rheologic properties of blood cells mainly determines to an impaired microvascular blood flow in patients suffering from diabetes mellitus. Recent investigations provide increasing evidence that impaired C-peptide secretion in type 1 diabetic patients might contribute to the development of microvascular complications. C-peptide has been shown to stimulate endothelial NO secretion by activation of the Ca2+ calmodolin regulated enzyme eNOS. NO himself has the potency to increase cGMP levels in smooth muscle cells and to activate Na+K+ATPase activity and therefore evolves numerous effects in microvascular regulation. In type 1 diabetic patients, supplementation of C-peptide was shown to improve endothelium dependent vasodilatation in an NO-dependent pathway in different vascular compartments. In addition, it could be shown that C-peptide administration in type 1 diabetic patients, results in a redistribution of skin blood flow by increasing nutritive capillary blood flow in favour to subpapillary blood flow. Impaired Na+K+ATPase in another feature of diabetes mellitus in many cell types and is believed to be a pivotal regulator of various cell functions. C-peptide supplementation has been shown to restore Na+K+ATPase activity in different cell types during in vitro and in vivo investigations. In type 1 diabetic patients, C-peptide supplementation was shown to increase erythrocyte Na+K+ATPase activity by about 100%. There was found a linear relationship between plasma C-peptide levels and erythrocyte Na+K+ATPase activity. In small capillaries, microvascular blood flow is increasingly determined by the rheologic properties of erythrocytes. Using laser-diffractoscopie a huge improvement in erythrocyte deformability could be observed after C-peptide administration in erythrocytes of type 1 diabetic patients. Inhibition of the Na+K+ATPase by Obain completely abolished the effect of C-peptide on erythrocyte deformability. In conclusion, C-peptide improves microvascular function and blood flow in type 1 diabetic patients by interfering with vascular and rheological components of microvascular blood flow.

Animals↗