Evaluation of diagnostic relevance of mRNA levels in peripheral blood: predictive value for mortality in hemodialysis patients.

In clinical practice, diagnosis and risk prediction are usually based on the analysis of serum or plasma proteins whereas gene expression analysis is not used on a routine basis. In order to compare the diagnostic and predictive relevance of serum protein and peripheral blood mRNA levels, we determined cytokine levels of end-stage renal failure patients undergoing hemodialysis. These patients face a high mortality mainly due to acceleration of atherosclerosis and subsequent severe vascular events.

Wheat gluten causes dendritic cell maturation and chemokine secretion.

Wheat gluten causes gut inflammation in genetically predisposed individuals. We tested the hypothesis that wheat gluten is not only a target of adaptive immunity, but also modulates the function of APC. Dendritic cells (DC) derived from the bone marrow of BALB/c mice were exposed to chymotrypsin-treated wheat gluten.

Interleukin-11 inhibits NF-kappaB and AP-1 activation in islets and prevents diabetes induced with streptozotocin in mice.

This laboratory has reported that multiple low doses of streptozotocin (MLD-STZ) similarly upregulate the T helper (Th)1-type proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in islets of both the diabetes-susceptible male and the diabetes-resistant female C57BL/6 mice and that MLD-STZ downregulates the anti-inflammatory Th2-type cytokines interleukin (IL)-4 and IL-10, as well as the anti-inflammatory Th3-type cytokine-transforming growth factor (TGF)-ss1 in islets of male, but not female, mice. Thus, diabetes is associated with a relative preponderance of local proinflammatory cytokines. Here, we investigated the effects of MLD-STZ on the anti-inflammatory cytokine IL-11 and the transcription factors nuclear factor (NF)-kappaB and activator protein (AP)-1, which are involved in gene activation of proinflammatory cytokines, and on the cytosolic kinase (IKK-alpha) of NF-kappaB inhibitor (IkappaB).

Postmarketing surveillance of adverse drug reactions: a correlational study approach using multiple data sources.

The authors performed a correlational study on nationwide spontaneous adverse drug reaction (ADR) reports related to the antioxidant thioctic acid (Thioctacid; ASTA Medica) in Germany from April 1992 to March 1995. Thioctacid was predominantly utilized by general practitioners and internists for treatment of diabetic neuropathy. The total number of treated patients was estimated using a nationwide drug prescription database (MediPlus, IMS: 362 general practitioners and internists) and pharmacy drug sales data.

Combined activation of innate and T cell immunity for recognizing immunomodulatory properties of therapeutic agents.

Complex syndromes such as atherosclerosis and type 2 diabetes are disorders that are associated with inflammatory processes involving innate and adaptive immunity. Emerging knowledge about the pathological consequences of immune imbalances in a wide range of disease settings is expected to help to identify novel therapeutic targets. However, current test systems for immunomodulatory drugs tend to be too simplistic, as they rely only on cells of the innate- or the adaptive-immune system, or they are complex, in vivo models, which are not suitable for screening purposes.

Effect of the angiotensin II receptor blocker candesartan on fibrinolysis in patients with mild hypertension.

Aim: Impaired fibrinolysis is frequently observed in patients with the metabolic syndrome. Aim of the study was to examine the short-term effect of angiotensin II receptor blockade on the fibrinolytic system.

Methods: Seventy-four patients with mild hypertension were randomly assigned to a 7-day treatment period with either 16 mg candesartan cilexetil or placebo.

Comparison of cytokine ELISpot assay formats for the detection of islet antigen autoreactive T cells. Report of the third immunology of diabetes society T-cell workshop.

The identification of sensitive assay formats capable of distinguishing islet autoreactive T cells directly ex vivo in blood is a major goal in type 1 diabetes research. Recently, much interest has been shown in the cytokine enzyme linked immunospot assay (CK ELISpot), an assay potentially capable of fulfilling these difficult criteria. To address the utility of this assay in detecting autoreactive T cells, a 'wet' workshop was organized using the same fresh blood sample and coded antigens.

Relationship between IL-6, leptin and adiponectin and variables of fibrinolysis in overweight and obese hypertensive patients.

Impaired fibrinolysis is a common finding in obese humans. This condition is now considered as an established risk factor for thromboembolic complications. Furthermore, obesity is characterized by a specific pattern of circulating concentrations of fat-cell products interleukin-6 (IL-6), leptin, and adiponectin.

Different heat shock protein 60 species share pro-inflammatory activity but not binding sites on macrophages.

In a study of seven different hsp60 species, we found that all mammalian and microbial proteins shared the property of eliciting an inflammatory response in mouse macrophages. In all cases, TNFalpha production was induced by 0.1 microM concentrations of hsp60.

Fibre consumption, metabolic effects and prevention of complications in diabetic patients: epidemiological evidence.

The EURODIAB Complications Study, a clinic based epidemiological project including 3250 individuals with type 1 diabetes from 31 European centres analysed the natural dietary fibre intake and possible benefits for patients with diabetes. The mean intake of natural dietary fibre in the cohort of patients with type 1 diabetes was 17.3 g/day for all centres with a centre range of 13.

Generation of hydroxyl radicals mediated by streptozotocin in pancreatic islets of mice in vitro.

Type I diabetes is considered a multifactorial autoimmune process initiated by an environmental factor. There is evidence that reactive oxygen species are involved in destructing insulin-producing beta-cells. In mice, reactive oxygen species and nitric monoxide contribute to beta-cell damage in the non-obese diabetic strain developing spontaneously diabetes and in diabetes induced with multiple low doses of streptozotocin.

Clinical trials for drugs against diabetic neuropathy: can we combine scientific needs with clinical practicalities?

Diabetic neuropathy is a chronic progressive disease accounting for considerable morbidity and reduced quality of life among patients with diabetes. Accumulating evidence suggests that the clinical and neurophysiological markers used to assess neuropathy not only predict the development of neuropathic foot ulceration, one of the most common causes for hospital admission and lower limb amputations, but are also predictors of increased mortality in diabetic patients. In addition to metabolic control, drug treatment of both incipient and clinically manifest diabetic neuropathy will be necessary for the years to come.

Molecular target structures in alloxan-induced diabetes in mice.

Type 1 diabetes results from irreversible damage of insulin-producing beta-cells. In laboratory animals, diabetes can be induced with alloxan (ALX), a 2,4,5,6-tetraoxopyrimidine. ALX is a potent generator of reactive oxygen species (ROS), which can mediate beta-cell toxicity.

Heat shock protein 60 elicits abnormal response in macrophages of diabetes-prone non-obese diabetic mice.

Heat shock protein 60 (hsp60) is a target antigen in autoimmune diabetes and injections of human hsp60 for tolerance induction were found to protect non-obese diabetic (NOD) mice, an animal model of human type 1 diabetes, from disease development. We tested whether innate immune cells of NOD mice exhibit an abnormal response to extracellular hsp60. Bone marrow derived macrophages (BMM) were grown from NOD, C57BL/6J, non-obese non-diabetic (NON) mice, and NOD-related congenic variants differing in the Idd-3, Idd-10/18, or major histocompatibility complex (MHC) region.

Insulin resistance and the metabolic syndrome-a challenge of the new millennium.

The term metabolic syndrome is used for describing a cluster of cardiovascular risk factors comprising abdominal obesity, glucose intolerance/type 2 diabetes mellitus, dyslipidaemia and hypertension. A concomitant presentation of all components of the syndrome is rare, therefore, in the view of most experts three out of the four main components are sufficient for defining the syndrome. Another recently identified component of high clinical significance is the impairment of the fibrinolytic system which is now frequently mentioned in extended definitions.

Effect of acarbose on weight maintenance after dietary weight loss in obese subjects.

Aims: Acarbose is a well established antidiabetic drug and is known to exert a modest weight-lowering effect. The aim of this study was to assess the potential of acarbose to improve weight maintenance after a substantial weight loss by dietary measures in obese subjects.

Design: Randomised, double-blind, placebo-controlled trial of the effect of acarbose on weight change over a 6-month follow-up period.

Insulin Lispro in pregnancy--retrospective analysis of 33 cases and matched controls.

Aims/hypothesis: To evaluate if the application of Lispro insulin in pregnancy increases the risk for malformations or unusual pregnancy courses.

Methods: Diabetes specialists were contacted in Germany and Austria and asked to report women with diabetes who had been treated with Lispro during pregnancy. Furthermore they were asked to report another pregnant diabetic woman treated with regular insulin with similar HbA1c and age for each Lispro case.

Time- and frequency-domain estimation of early diabetic cardiovascular autonomic neuropathy.

The risk related to cardiovascular autonomic neuropathy dysautonomia should lead to a specific assessment of this complication of diabetes. The aim of this study was to estimate the accuracy of a battery of blood pressure (BP) and heart rate (HR) variability indexes obtained in different subgroups of diabetic subjects classified according to the conventional laboratory autonomic function tests (Ewing scores). Blood pressure was measured continuously at the finger level with a Finapres monitor while subjects were in the supine position and again while they were standing.

Nutrient intakes as predictors of body weight in European people with type 1 diabetes.

Background: Overweight and obesity are also found among persons with type 1 diabetes.

Objective: The present study examined which nutrients predict the body mass index (BMI), the waist-to-hip ratio (WHR) and the waist circumference (WC) of European persons with type 1 diabetes.

Design: Cross-sectional, clinic-based study (EURODIAB Complications Study).

The receptor for heat shock protein 60 on macrophages is saturable, specific, and distinct from receptors for other heat shock proteins.

Previous studies have shown that human heat shock protein (hsp) 60 elicits a strong proinflammatory response in cells of the innate immune system with CD14, Toll-like receptor (TLR) 2, and TLR4 as mediators of signaling, but probably not of binding. In the present study, we directly demonstrate binding of hsp60 to the macrophage surface and find the binding receptor for hsp60 different from the previously described common receptor for several other heat shock proteins, including hsp70, hsp90, and gp96. Fluorescence-labeled human hsp60 bound to cell surfaces of the murine macrophage lines J774 A.

Effects of leptin on the differentiation and metabolism of human adipocytes.

Background: Leptin is an adipose protein regulating food intake in the hypothalamus. Animal studies have suggested that leptin also acts in an auto-/paracrine fashion on adipose cell function.

Objective: The aim of this study was to investigate the effects of leptin on the differentiation and metabolism of cultured human adipocytes.

Dominant role of intercellular adhesion molecule-1 in the pathogenesis of autoimmune diabetes in non-obese diabetic mice.

Intercellular adhesion molecule (ICAM)-1 is involved in forming the immunological synapse. The contribution of ICAM-1 to immune responses is not critical because mice with a disrupted ICAM-1 gene do not have grossly abnormal immune reactivity. Here we report on the surprising finding that diabetes-prone NOD mice with a disrupted ICAM-1 gene (ICAM-1(-/-)) are completely protected from disease development.

Undiagnosed diabetes mellitus and metabolic control assessed by HbA(1c) among residents of nursing homes.

Aims/hypothesis: Diabetes prevalence and diabetes care in residents of nursing homes is a neglected area of research although the growing number of elderly people with diabetes represents a growing challenge for health care in most countries. In this study, we used HbA(1c) measurement to estimate the percentage of residents with undiagnosed diabetes and the quality of metabolic control of subjects with known diabetes in nursing homes.

Methods: All 41 nursing homes in the county of Heinsberg in Northrhine-Westfalia were asked to complete a structured questionnaire on the prevalence of known diabetes among all residents.

Pertussis in Germany: regional differences in management and vaccination status of hospitalized cases.

The incidence of pertussis requiring hospitalization in children younger than 16 years was estimated by the use of an active surveillance-system. Of special interest were differences between West and East Germany following different vaccination strategies before reunification. In 1997 and 1998, 754 pertussis cases required a total of 11,151 hospital inpatient days.