Comparison of semi-quantitative and visual assessment of early MRI signal evolution in acute ischaemic stroke.

Background: The evaluation of DWI/FLAIR mismatch in ischaemic stroke patients with unknown, time from onset can determine the treatment strategy. This approach is based on, visual assessment and may be subject to insufficient inter-rater agreement. Objective: To compare the inter-rater agreement of visual evaluation of FLAIR MRI and proposed region of interest (ROI) semiquantitative method in large vessel occlusion (LVO) strokes. Methods: Five readers have analysed MRIs of 104 patients obtained within six hours of the onset of stroke symptoms resulting from LVO visually and semi-quantitatively. For the semiquantitative analysis, a ROI method was used to obtain relative signal intensity compared to the unaffected side. Cut-off values of 1.15 and 1.10 were tested. The analysis yielded FLAIR-positive (abnormal) and negative (normal) findings. Percentage agreement and Fleiss kappa coefficients were calculated. Results: The visual agreement of 5/5 readers and ≥ 4/5 readers occurred in 31% and 59% of cases respectively. Semi-quantitative evaluation using a cut-off value of 1.15 increased the agreements to 67% and 88% respectively. The agreement of visual evaluation was fair. The semi-quantitative method utilising the cut-off of 1.15 had moderate agreement although it increased the number of FLAIR-negative results compared to the visual evaluation. A low cut-off value of 1.10 didn't improve the agreement significantly. Conclusion: The inter-rater agreement of visual evaluation of FLAIR in patients with short-duration large vessel occlusion stroke was fair. The high cut-off value of semiquantitative evaluation increased the agreement although it changed the proportion of FLAIR positive and negative results.

Pilot study trialling a new ambulatory method for the clinical assessment of regional gastrointestinal transit using multiple electromagnetic capsules.

BACKGROUND: Gastrointestinal (GI) motor disorders often involve several regions of the GI tract. Therefore, easy and safe assessment of whole gut and regional motility is valuable for more precise diagnosis. 3D-Transit is a novel method for ambulatory evaluation of total and regional gastrointestinal transit times (GITT) based on the anatomical localization of ingestible electromagnetic capsules. The main purpose of this study was to test the performance of the 3D-Transit system. METHODS: Twenty healthy volunteers each ingested three electromagnetic capsules over a period of two consecutive days. Standard radio-opaque markers (ROM) were also ingested to assess the agreement between total GITT obtained with both methods. KEY RESULTS: Investigations were well-tolerated and three capsules could be tracked simultaneously with minimal data loss (Capsule 1: median: 0.2% of time (range 0-25.3%). Region specific contraction patterns were identified and used for computation of total and regional GITT in all subjects. Inter-observer agreement was 100% for total GITT (median variation 0%) but less for regional GITT. Day-to-day and diurnal variations were significant for total and regional GITT. Total GITT assessed by 3D-Transit capsules were moderately well-correlated to those assessed with standard ROM (Spearman's rho = 0.7). CONCLUSIONS & INFERENCES: 3D-transit is a well-tolerated and minimal invasive ambulatory method for assessment of GI motility. By providing both total and regional transit times, the 3D-Transit system holds great promise for future clinical studies of GI function in health and disease.

Positivity for islet cell autoantibodies in patients with monogenic diabetes is associated with later diabetes onset and higher HbA1c level.

AIMS: Islet cell autoantibodies are associated with autoimmune insulitis and belong to the diagnostic criteria of type 1 diabetes mellitus. However, growing evidence suggests that autoantibodies are present in other types of diabetes. Here, we focus on the autoantibody incidence in Czech patients with maturity-onset diabetes of the young and analyse their functional relevance in terms of diabetes onset and control. METHODS: Autoantibodies against glutamic acid decarboxylase (GAD) 65 and protein tyrosine phosphatase islet antigen 2 (IA-2) were measured in a cohort of 28 Czech patients with maturity-onset diabetes of the young, all confirmed by genetic testing. Selected clinical data were correlated to the status and kinetics of autoantibodies. RESULTS: One quarter of patients with maturity-onset diabetes of the young examined (7/28; 25%) was positive for GAD or IA-2 autoantibodies. GAD autoantibodies were more prevalent (7/7) than IA-2 autoantibodies (1/7). The incidence of autoantibodies did not correlate with human leukocyte antigen status. The patients who were positive for the autoantibodies developed diabetes later than those who were autoantibody-negative, but had worse glycaemic control (increased HbA1c ). Expression of autoantibodies decreased with any improvement of diabetes compensation. Only one patient did not correspond to the above and displayed signs of combined signs of maturity-onset diabetes of the young and Type 1 diabetes. CONCLUSIONS: The data suggest transient but highly prevalent islet cell autoantibody expression in Czech patients with maturity-onset diabetes of the young. The autoantibodies were found in patients with delayed diabetes onset, and in times of insufficient diabetes control. As improvement of glycaemic control was associated with a decrease in levels of autoantibodies, their presence may reflect the kinetics of ß-cell destruction induced by causes other than autoimmune ones.

Basophil activation can predict clinical sensitivity in patients after venom immunotherapy.

OBJECTIVE: At present, no reliable in vitro test is available to monitor the success of specific venom immunotherapy (VIT) in preventing insect venom anaphylaxis. We investigated usefulness of the basophil activation test (BAT) in predicting the outcome of sting challenge in bee venom-allergic patients after VIT. PATIENTS AND METHODS: Twenty-one patients with bee venom anaphylaxis at the end of VIT and 6 control participants were enrolled. BAT (flow-cytometric evaluation of allergen-induced expression of CD63), skin testing, and specific immunoglobulin (Ig) E determination were performed prior to sting challenge. RESULTS: Five of the 21 patients (23.8%) reacted to sting challenge. At a bee venom concentration of 100 ng/mL, the mean proportion of basophils expressing CD63 was 56% in reactors and 13.2% in nonreactors (P = .0321). Four of the 5 reactors had positive results and 14 of the 16 nonreactors had negative results. Thus, using 18.4% and 21.6% (receiver operating characteristic curve analysis) as the cutoff for expression of the CD63 marker, the positive and the negative predictive values were 67% and 93%, respectively, and specificity and sensitivity for BAT were 80% and 83%, respectively. However, at a concentration of 1000 ng/mL, no significant differences in basophil activation were observed between reactors and nonreactors. CONCLUSION: We found BAT to be a helpful tool in predicting the clinical sensitivity of bee venom-allergic patients after VIT (correlation between BAT at submaximal venom concentration and sting challenge).

Colonic movements in healthy subjects as monitored by a Magnet Tracking System.

The Magnet Tracking System (MTS) is a minimally-invasive technique of continuous evaluation of gastrointestinal motility. In this study, MTS was used to analyse colonic propulsive dynamics and compare the transit of a magnetic pill with that of standard radio-opaque markers. MTS monitors the progress in real time of a magnetic pill through the gut. Ten men and 10 women with regular daily bowel movements swallowed this pill and 10 radio-opaque markers at 8 pm. Five hours of recordings were conducted during 2 following mornings. Origin, direction, amplitude and velocity of movements were analysed relative to space-time plots of the pill trajectory. Abdominal radiographs were taken to compare the progress of both pill and markers. The magnetic pill lay idle for 90% of its sojourn in the colon; its total retrograde displacement accounted for only 20% of its overall movement. Analysis of these movements showed a bimodal distribution of velocities: around 1.5 and 50 cm min(-1), the latter being responsible for 2/3 of distance traversed. There were more movements overall and more mass movements in males. Net hourly forward progress was greater in the left than right colon, and greater in males. The position of the magnetic pill correlated well with the advancement of markers. MTS showed patterns and propulsion dynamics of colonic segments with as yet unmet precision. Detailed analysis of slow and fast patterns of colonic progress makes it possible to specify the motility of colonic segments, and any variability in gender. Such analysis opens up promising avenues in studies of motility disorders.

Pycnogenol efficiency on glycaemia, motor nerve conduction velocity and markers of oxidative stress in mild type diabetes in rats.

The aim of this study was to describe the effects of Pycnogenol at various doses on preprandial and postprandial glucose levels, the levels of thiobarbituric acid reactive substances (TBARs) and N-acetyl-beta-d-glucosaminidase (NAGA) and on motor nerve conduction velocity (MNCV) in streptozotocin (STZ)-induced diabetic rats. Pycnogenol treatment (10, 20, 50 mg/kg body weight (b.w.)/day) lasted for 8 weeks after induction of diabetes. Pycnogenol significantly decreased elevated levels of preprandial glycaemia in treated animals at all doses. At doses of 10 mg/kg b.w./day and 20 mg/kg b.w./day it significantly decreased elevated levels of postprandial glycaemia compared with diabetic non-treated animals. Pycnogenol failed to induce a significant decrease of postprandial glycaemia at a dose of 50 mg/kg b.w./day. Pycnogenol improved significantly the impaired MNCV at doses of 10 and 20 mg/kg b.w./day compared with non-treated animals. The levels of TBARs were elevated in diabetic rats. The levels of NAGA increased gradually despite the treatment. Pycnogenol failed to affect the increased levels of TBARs and NAGA. Pycnogenollowered the elevated levels of glycaemia and reduced the decline in motor nerve conduction velocity in STZ-induced diabetic rats. The effect of Pycnogenol on postprandial glycaemic levels and MNCV was not dose-dependent.

Short-term dietary intake of C18:1 trans fatty acids decreases the function of cellular immunity in healthy young men.

AIM: In this study, we tested the impact of short-term intake of increased amounts of C18:1 trans fatty acids (TFAs) on parameters of cellular and humoral immunity in healthy young men. METHODS: Twenty-seven healthy young men were subsequently exposed to a standard diet for 7 days and an experimental TFA-enriched diet for 4 days. The mean energy content of these diets was 2,453 and 2,455 kcal/day, with 10, 35 and 55% of energy from proteins, fats and carbohydrates, respectively. Standard diet contained about 0.8 g and experimental diet 10.4 g TFAs. Plasma levels of C18:1 TFAs and immunological parameters were measured. RESULTS: The 4-day increased consumption of C18:1 TFAs led to a significant decrease in mitogen-induced CD69 expression on CD8+ T cells as well as decreased phagocytic activity on neutrophils. After returning to the participants' habitual diet (1 week after the end of the experimental diet), we observed a significant decrease in the mean level of circulating immune complexes. Concentrations of plasma immunoglobulins remained unchanged throughout the study. CONCLUSIONS: Acute impact of higher dietary C18:1 TFA intake on phagocytosis and cell-mediated immunity seems to be suppressive. This finding differs from results describing proinflammatory effects associated with long-term exposure to TFAs.

Single parameter wrist ultrasonography as a first-line screening examination in suspected carpal tunnel syndrome patients.

UNLABELLED: Carpal tunnel syndrome (CTS) is the most common form of peripheral nerve entrapment. Electromyography with selected nerve conduction studies (NCS) is an accepted diagnostic tool in CTS patients. Ultrasonography presents a widely available and low cost investigation method and its position in CTS diagnostics needs further clarification with concrete recommendations for clinical practice. A prospective study of 37 patients with 74 wrists (59 wrists with suspected CTS) was done. Normative data were obtained from a control group of 25 healthy persons (50 wrists) age and sex matched. All persons underwent ultrasonographic examination (median nerve cross-sectional area at carpal tunnel entrance measurement--CSA) and median NCS studies (distal motor and sensory latency measurement--DML and DSL). RESULTS: CSA has a sensitivity of 93% (CI 84-97%) and specificity of 96% (CI 87-99%) in our patients group. Conventional first-line NCS studies results in our patients groupare as follows: DML sensitivity 58% (CI 45-69%) and specificity 100% (CI 93-100%); DSL sensitivity 88% (CI 78-94%) and specificity 94% (CI 84-98%). CONCLUSION: We recommend the use of single-parameter wrist ultrasonography as a first-line screening laboratory method in suspected CTS diagnosis (Ref. 14). Full Text (Free, PDF) www.bmj.sk.

[Allergen challenge used to diagnose food allergy--oral allergy syndrome]. / Expozicní test ve stanovení diagnózy potravinové alergie-- orální alergický syndrom.

Food allergy is an immune mediated unwanted side effect to food. All types of hypersensitivity can be involved; the most prevalent is IgE mediated one. The diagnosis is based on the history, skin tests with allergens and detection of specific IgE. These procedures are not highly predictive for clinical reactivity to food allergens, true clinical reactivity can be confirmed by allergen challenge. Oral allergy syndrome is represented by mostly subjective symptoms in oral cavity, usually triggered by fruit or vegetable allergens, cross-reacting with pollen allergens. This cross-reactivity is based on protein homology and immunologic similarity. To confirm the diagnosis of food allergy, the ,,golden standard" is the double blind placebo controlled food challenge. The basic features of this test are discussed, particularly in the diagnosis of the oral allergy syndrome. Controlled food challenge is a useful test for patient's diagnosis confirmation, evaluation of other diagnostic tests or evaluation of food allergenicity.

HLA DRB1, DQB1 and insulin promoter VNTR polymorphisms: interactions and the association with adult-onset diabetes mellitus in Czech patients.

Both the human leucocyte antigen (HLA) DRB1 and the HLA DQB1 gene loci play a role in the development and progression of autoimmune diabetes mellitus (T1DM). Similarly, the insulin promoter variable number tandem repeats (INS-VNTR) polymorphism is also involved in the pathogenesis of diabetes mellitus (DM). We studied the association between each of these polymorphisms and DM diagnosed in patients older than age 35 years. Furthermore, we analysed possible interactions between HLA DRB1/DQB1 and INS-VNTR polymorphisms. Based on C-peptide and GADA levels we were able to distinguish three types of diabetes: T1DM, latent autoimmune diabetes in adults (LADA) and T2DM. INS-VNTR was genotyped indirectly by typing INS-23HphI A/T polymorphism. The genotype and allele frequencies of INS-23HphI did not differ between each of the diabetic groups and group of healthy subjects. We did, however, observe an association between the INS-23HphI alleles, genotypes and C-peptide secretion in all diabetic patients: A allele frequency was 86.2% in the C-peptide-negative group vs. 65.4% in the C-peptide-positive group (P(corr.) < 0.005); AA genotype was found to be 72.4% in the C-peptide-negative group vs. 42.6% in the C-peptide-positive groups (P(corr.) < 0.01). The HLA genotyping revealed a significantly higher frequency of HLA DRB1*03 allele in both T1DM and LADA groups when compared to healthy subjects: T1DM (25.7%) vs. control group (10.15%), odds ratio (OR) = 3.06, P < 0.05; LADA (27.6%) vs. control (10.15%), OR = 3.37, P < 0.01. The simultaneous presence of both HLA DRB1*04 and INS-23HphI AA genotype was detected in 37.5% of the T1DM group compared to only 9.2% of the healthy individuals group (OR = 5.9, P(corr.) < 0.007). We summarize that in the Central Bohemian population of the Czech Republic, the INS-23HphI A allele appears to be associated with a decrease in pancreatic beta cell secretory activity. HLA genotyping points to at least a partial difference in mechanism, which leads to T1DM and LADA development as well as a more diverse genetic predisposition in juvenile- and adult-onset diabetes. The simultaneous effect of HLA and INS-VNTR alleles/genotypes predispose individuals to an increased risk of diabetes development.

KCNJ11 E23K polymorphism and diabetes mellitus with adult onset in Czech patients.

In this work, we studied the association of the E23K polymorphism of the Kir6.2 ATP-sensitive potassium channels in 212 Czech patients with diabetes mellitus who were diagnosed after the age of 35. Patients were classified into T1DM, LADA and T2DM groups based on C-peptide and GADA levels. Carriers of the predisposing Kir6.2 E23K K allele showed no increased risk of either type of diabetes mellitus development. On the other hand, we found a correlation between E23K SNP of the KCNJ11 gene and C-peptide levels, which may be considered a measure of pancreatic beta-cell activity, although this correlation was not statistically significant. In conclusion, we failed to confirm the Kir6.2 E23K as a genetic marker for T1DM, LADA and T2DM in the Central Bohemian population of the Czech Republic.

Impaired cognitive functions in mild traumatic brain injury patients with normal and pathologic magnetic resonance imaging.

INTRODUCTION: Mild traumatic brain injury (MTBI) is a common neurological (neurotraumatological) diagnosis. As well as different subjective symptoms, many patients develop neuropsychological dysfunction with objective impairment of attention, memory and certain executive functions. Magnetic resonance imaging (MRI) is not routinely used in MTBI patients despite its proven greater sensitivity and specificity in comparison with computed tomography (CT). METHODS: The patient group consisted of 30 persons with MTBI and the control group consisted of 30 sex- and age-matched healthy volunteers. Both groups underwent neurological examination, neuropsychological testing (including the Postconcussion Symptoms Scale questionnaire, PCSS) and brain MRI (the patient group within 96 h after injury). RESULTS: The analyzed groups did not differ significantly in terms of sex, age, or level or duration of education. MRI pathological findings (traumatic and nonspecific) were present in nine patients. Traumatic lesions were found in seven patients. Nonspecific white matter lesions were found in five healthy controls. There were significant differences between MTBI patients and controls in terms of subjective symptoms (PCSS) and selected neuropsychological tests. Statistically significant neuropsychological differences were found between MTBI patients with true traumatic lesions and MTBI patients with nonspecific lesions. CONCLUSION: There is evidence that MTBI patients with true traumatic MRI lesions are neuropsychologically different from MTBI patients with nonspecific MRI lesions or normal brain MRI. These results support the hypothesis that some acute MTBI signs and symptoms have a real organic basis which can be detected by selected new MRI modalities.

Magnet Tracking: a new tool for in vivo studies of the rat gastrointestinal motility.

Digestive motility was studied in the rat using a miniaturized version of the Magnet Tracking system which monitored the progression of a small magnetic pill through the entire digestive tract. The dynamics of movement was followed and three-dimensional (3-D) images of digestive tract were generated. After a retention period in the stomach and rapid passage through duodenum, the magnet progressed along the small intestine with gradually decreasing speed and longer stationary periods. It remained in the caecum for variable intervals. In the colon, periods of progress alternated with long quiescent periods. Gastric activity oscillated at 5-6 min(-1). In the small intestine, two frequency domains coexisted, showing independent modulations and proximo-distal gradients (40 to >32 and 28 to >20 min(-1)). Caecal oscillations were of 1.5 min(-1). The data allowed the magnet location and calculation of gastric and small intestinal transit times (58 +/- 36 and 83 +/- 14 min respectively), both significantly prolonged by oleate administration (243 +/- 130 and 170 +/- 45 min respectively). Magnet Tracking is a non-invasive tool to study the in vivo spatial and temporal organization of gastrointestinal motility in the rat.

[Contemporary view on mild brain injuries in adult population]. / Nácrt súcasného pohl'adu na problematiku l'ahkých poranení mozgu so zameraním na dospelú populáciu.

Mild brain injury is one of the most common neurological a neurotraumatological diagnoses. The pathophysiological basis of mild brain injury is frequently a diffuse axonal damage of variable degree. In the acute phase of mild brain injury we have to identify 1% of patients who will undergo neurosurgery because of vital need. The analysis of patient's personal history, screening of risk factors, neuropsychological testing and imaging methods (CT, MRI) are irreplaceable in the diagnostic process of mild brain injury. Though the mild brain injury is currently considered as an irrelevant traumatic event, approximately 10% of patients develop the so-called post-concussion syndrome.

Magnetic pill tracking: a novel non-invasive tool for investigation of human digestive motility.

A new minimally invasive technique allowing for anatomical mapping and motility studies along the entire human digestive system is presented. The technique is based on continuous tracking of a small magnet progressing through the digestive tract. The coordinates of the magnet are calculated from signals recorded by 16 magnetic field sensors located over the abdomen. The magnet position, orientation and trajectory are displayed in real time. Ten young healthy volunteers were followed during 34 h. The technique was well tolerated and no complication was encountered. The information obtained was 3-D configuration of the digestive tract and dynamics of the magnet displacement (velocity, transit time, length estimation, rhythms). In the same individual, repeated examination gave very reproducible results. The anatomical and physiological information obtained corresponded well to data from current methods and imaging. This simple, minimally invasive technique permits examination of the entire digestive tract and is suitable for both research and clinical studies. In combination with other methods, it may represent a useful tool for studies of GI motility with respect to normal and pathological conditions.

Chronic toxic neuropathy after organophosphorus poisoning in quails (Coturnix coturnix japponica).

Peripheral neuropathy was induced by the long-term administration of organo-phosphorus compounds (phtalimid/phosmet) in quails (Coturnix coturnix japponica). After 4 weeks, the first symptoms of organophosphorus (OPC) poisoning (apathy, diarrhea) were present. During the second month of a daily administration of the toxic substance using the probe, an apparent clinical autonomic and peripheral neuropathy with ataxia had developed. Toxic disturbance of the nervous system was confirmed by the examination of spinal and cortical somatosensory evoked potentials (SEP) after tibial nerve stimulation. The prolongation of the peripheral conduction time (wave P6 and N9 represent the response from the ischiadic nerve and the entry of the stimulus to spinal cord, respectively) confirmed a peripheral nerve lesion. We suggest that these clinical and electrophysiological changes, displayed by the disturbed nervous system, are caused by either slowing or stoppage of the axonal flow, transport of proteins and other substances, as well as by axon demyelination (Tab. 1, Fig. 1, Ref. 22).

An acute toxic neuropathy caused by organo-phosphate poisoning in hens.

OBJECTIVE: Organophosphorus compounds can induce an acute toxic peripheral neuropathy. In hens, the acute peripheral neuropathy was induced by poisoning with organo-phosphorus compound (OPC)--tri-ortho-cresyl phosphate (TOCP). METHODS: In the course of an acute TOCP-induced toxic neuropathy in hens the activity of following enzymes was analysed: asparaginase, glutaminase, glutamat-dehydrogenase, AMP and adenosine deaminases and 5'nucleotidase; ALT (SGPT), AST (SGOT) and proteins levels were estimated. RESULTS: A decrease in activity of all analysed enzymes was observed; the amount of proteins was increased. CONCLUSION: The biochemical changes display the slowing or stoppage in axonal transport of proteins. The disturbance of axoplasmic flow and the axonal demyelination may be considered as an attribute of peripheral neuropathy. (Tab. 1, Fig. 1, Ref. 32.).

Sympathetic skin response: review of the method and its clinical use.

Sympathetic skin response (SSR) represents a potential generated in skin sweat glands; it originates by activation of the reflex arch with different kinds of stimuli. The potential of rapid habituation after repeated stimuli is formed by biphasic or triphasic slow wave activity with relatively stable latency and variable amplitude. In healthy subjects younger than 60 years of age the response is always present in all extremities. SSR is most frequently used in diagnosing the functional impairment of non-myelinated postganglionic sudomotor sympathetic fibers in peripheral neuropathies. In this study a more complex and informative view on the anatomical and physiological substrates of SSR, its character, normal values and technique are presented, focusing on problems in evaluation of the response and factors that have influence on it. Based on personal experience normative latency and amplitude values of SSR in a group of 20 healthy individuals (x +/- SD), upper extremities: 1.48 +/- 0.80 sec., 444 +/- 167 microV, respectively; lower extremities: 2.06 +/- 0.93 sec., 203 +/- 87.4 microV, respectively) and recommendations for qualitative evaluation preference--the presence or absence of the response--over quantitative evaluation of latency and amplitude of the response in practical clinical use of the method are presented. (Tab. 1, Fig. 2, Ref. 148.).

Polymorphism of INS VNTR is associated with glutamic acid decarboxylase antibodies and postprandial C-peptide in patients with onset of diabetes after 35 years of age.

Variability in the number of tandem repeats of the insulin gene (INS VNTR) is probably involved in the genetic regulation of insulin secretion. The aim of this study was to investigate the association of INS VNTR polymorphism with the presence of glutamic acid decarboxylase antibodies (GADA) and C-peptide levels in patients with the onset of diabetes after 35 years of age. We investigated 117 patients, median of age 63 (range 40-83) years, median of diabetes duration 8 (range 1-30) years; 31 GADA-positive and 86 GADA-negative subjects. INS VNTR polymorphism was typed indirectly using - 23HphI (T/A) polymorphism, which is in complete linkage disequilibrium with INS VNTR. The I/I, I/III and III/III genotypes were found in 22 (71 %), 8 (26 %), 1 (3 %) GADA-positive individuals and in 39 (45 %), 35 (41 %), 12 (14 %) GADA-negative individuals, respectively. The Class I allele and the genotype I/I were significantly associated with the presence of GADA (OR=2.72, CI 95 %=1.29-5.73 and OR=2.95, CI 95 %=1.22-7.13). The presence of Class III allele was significantly associated with a higher level of postprandial C-peptide in GADA-positive subjects, even when regarding the duration of diabetes. Our results of INS VNTR polymorphism in patients with the onset of diabetes after 35 years of age confirm the association of Class I INS VNTR with autoimmune diabetes and the protective effect of Class III INS VNTR on the insulin secretion in GADA-positive subjects.

Effect of high glucose concentrations on expression of ELAM-1, VCAM-1 and ICAM-1 in HUVEC with and without cytokine activation.

Diabetes mellitus is associated with an increased prevalence of endothelial dysfunction and development of atherosclerotic vascular diseases. We demonstrate here that hyperglycemia results in the expression of adhesion molecules on endothelial cells in vitro. Incubation of human umbilical vein endothelial cells (HUVEC) in a culture medium with 11.0 mM, 16.5 mM and 22.0 mM glucose concentrations induced the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial-leukocyte adhesion molecule-1 (ELAM-1). This effect was detectable after 24 h incubation of HUVEC with a high glucose concentration. The effect of high glucose concentration on TNF-alpha induced expression of ELAM-1, VCAM-1 and ICAM-1 was negligible, if at all. These results show that even a short-term exposure of endothelial cells (ECs) to high glucose concentration leads to their activation associated with increased expression of adhesion molecules such as ELAM-1, VCAM-1 and ICAM-1.