The cumulative impact and associated costs of multiple health conditions on employee productivity.

Objective: This study investigates and provides comparative data on the relative contributions of multiple physical and psychological health conditions on work productivity.

Methods: A total of 667 employees from the headquarters office of a multinational consumer goods manufacturing firm in Germany completed a purpose-designed self-report questionnaire addressing the presence of 13 common health conditions, and associated absenteeism and presenteeism. Adjustments for comorbidity and self-report bias were made using an innovative approach.

Differences in protein and energy metabolism following portal versus systemic administration of insulin in diabetic dogs.

Aims/hypothesis: In non-diabetic people, insulin levels in the liver are two-fold higher than those in the systemic circulation. In contrast, patients with type 1 diabetes have similar hepatic and systemic insulin levels because insulin is administered peripherally. The aim of this study was to compare the effects of systemic (SI) and pre-portal (PI) insulin administration on energy, glucose and protein metabolism in chronic insulin-dependent ketosis-prone diabetic dogs.

Effects of fatty acids on hepatic amino acid catabolism and fibrinogen synthesis in young healthy volunteers.

Increased synthesis rate of fibrinogen, an independent risk factor for cardiovascular disease, was recently reported in obese insulin-resistant female adolescents with chronic elevated nonesterified fatty acids (NEFA). It is unknown whether a short-term change of NEFA concentrations controls hepatic fibrinogen synthesis. Therefore, 10 healthy male volunteers (24.

In vitro stimulation by islet antigen facilitates the detectability of beta-cell reactive cells in diabetes-prone BB/OK rats.

It has been supposed that beta-cell destruction in man and animals is due to autoreactive T-cells. We used the [51Cr]-release assay to identify the presence of beta-cell reactive cells in the spleen of diabetes-prone BB/OK rats before and after diabetes manifestation as well as in long-term normoglycaemic rats with a reduced diabetes risk of 3%. Splenic mononuclear cells (MNCs) obtained from diabetes-resistant LEW.

Glucagon-like peptide-1 has no insulin-like effects in insulin-dependent diabetic dogs maintained normoglycemic and normoinsulinemic.

A pharmacological concentration of glucagon-like peptide-1 (GLP-1) in the insulin-deficient state clearly decreases the blood glucose level. Therefore, this study was designed to evaluate a putatively relevant effect of the gastrointestinal peptide as an adjuvant to insulin replacement therapy. GLP-1 (GLP-1(7-36) amide 10 pmol x kg(-1) x min(-1)) was infused intravenously over 8 hours in nine fasting, C-peptide-negative diabetic dogs.

Estimation of urea production rate with [15N2]urea and [13C]urea to measure catabolic rates in diabetes mellitus.

For verifying catabolic states in insulin-dependent patients and dogs the method estimating urea production rates with 13C and with doubly 15N labeled urea, respectively, has been established. For a fast steady state of urea tracer dilution, a prime of 600 times the continuous infusion rate had to be injected. Urea was isolated from plasma samples by protein precipitation and cation exchange chromatography with a consecutive derivatization of the dried urea fraction (trimethylsilyl derivatives).

Estimation of urea production rate with [(15)n(2)]urea and [(13)c]urea to measure catabolic rates in diabetes mellitus.

Abstract For verifying catabolic states in insulin-dependent patients and dogs the method estimating urea production rates with (13)C and with doubly (15)N labeled urea, respectively, has been established. For a fast steady state of urea tracer dilution, a prime of 600 times the continuous infusion rate had to be injected. Urea was isolated from plasma samples by protein precipitation and cation exchange chromatography with a consecutive derivatization of the dried urea fraction (trimethylsilyl derivatives).

Blood glucose lowering and glucagonostatic effects of glucagon-like peptide I in insulin-deprived diabetic dogs.

To establish potential effects of glucagon-like peptide I (GLP-I) on blood glucose control in insulin-deficient states, GLP-I [GLP-I(7-36) amide; 10 pmol x kg(-1) x min(-1)] was infused intravenously in six fasting, canine C-peptide-negative, chronically diabetic dogs for 8 h. Blood samples were saved for the analysis of hormones, metabolites, and turnover rates of glucose (6-(3)H-glucose), alanine (U-(14)C-alanine), and urea ((15)N(2)-urea) starting 22 h after the last subcutaneous dose of exogenous insulin. Circulating plasma GLP-I levels rose under infusion from 2.

Effects of the platelet-activating factor antagonist BN 52021 on anti-islet cytotoxicity of mononuclear cells and serum from type 1 (insulin-dependent) diabetic patients.

The effect of platelet-activating factor (PAF) antagonist BN 52021 (0.06-2.5 mM) on the cytotoxic activity of mononuclear cells (MNC) from newly diagnosed type 1 diabetic patients against 51Cr-labeled Langerhans islets from neonatal rats was investigated in a 6-hour cytotoxicity test.

Beta cell destruction of pancreatic islets transplanted into diabetic BB/OK rats may be reflected by increased antibody-mediated anti-islet cytotoxicity.

Neonatal rat pancreatic islets can be affected in vitro by ADCC mediated by serum and mononuclear cells from diabetic BB/OK rats or complement-dependent antibody-mediated cytotoxicity (C'AMC) of BB rat serum as revealed by enhanced 51Cr-release. Using a syngeneic islet transplantation system in BB/OK rats this study addressed the question whether the destruction of islets of Langerhans in vivo is reflected by the appearance of ADCC or C'AMC in vitro. The frequency of the appearance of enhanced anti-islet ADCC in newly diagnosed diabetic BB/OK rats amounted to 33% whereas ADCC was not detectable in long-term diabetic rats with a diabetes duration in a range between 50 and 90 days.

Autologous mixed lymphocyte reaction in newly diagnosed type-1 diabetes.

The autologous mixed lymphocyte reaction (AMLR) represents activation, proliferation and differentiation of T cells in response to signals from autologous non-T cells. Deteriorations in AMLR have been reported in many autoimmune diseases and in diseases with a derangement in T cell regulatory function. We have studied AMLR in 23 newly diagnosed Type-1 diabetic patients and 32 healthy subjects.

Ciamexone suppressed anti-islet ADCC of mononuclear cells and serum from type 1 (insulin-dependent) diabetic patients.

ADCC (Antibody-dependent cellular cytotoxicity) against xenogenic islets has frequently been found in newly diagnosed Type 1 (insulin-dependent) diabetics suggesting that when combined with autologous serum in vitro, the destruction of islet cells caused by mononuclear cells (MNC) reflects islet destruction in vivo. In this study the ability of Ciamexone to suppress the anti-islet ADCC in vitro was investigated. We selected both ADCC positive and ADCC negative subjects from a group of Type 1 diabetics.

Persistence of anti-islet ADCC after manifestation of type-1 (insulin-dependent) diabetes.

ADCC (antibody-dependent cellular cytotoxicity) against xenogenic islets in vitro has frequently been found with mononuclear blood cells and heat inactivated autologous serum from newly diagnosed Type-1 diabetics. Anti-islet ADCC, as measured by enhanced 51Cr-release of islets after a 6h-incubation, leads to functional alteration of islets such as a decrease in insulin content and in leucine incorporation. In a follow-up investigation over at least three years it was demonstrated that anti-islet ADCC in vitro disappears, if there is no more C-peptide secretion in vivo.

Effect of lymphocytes and serum from probands before and after manifestation of type 1 (insulin-dependent) diabetes on rat islets in vitro.

In a two-year follow-up study neonatal rat islets have been shown to be affected in vitro by lymphocytes and complement-inactivated serum obtained from newly diagnosed Type 1 (insulin-dependent) diabetic patients and probands who are at high risk for developing the disease. The effect was measured by 51Cr-release of the islets treated with the proband's serum after a 6 h-incubation with lymphocytes of the same donor. Nineteen newly diagnosed diabetic patients, 23 persons at risk and 11 control probands were studied.

Phagocytic activity of blood cells in diabetic risk probands and newly diagnosed type 1 diabetics.

The phagocytic activity of granulocytes and mononuclear blood cells was compared in probands at risk for insulin-dependent Type 1 diabetes mellitus and in newly diagnosed diabetics before and during short-term insulin treatment. Healthy persons without family history of Type 1 diabetes were used as controls. Furthermore, the relationship between phagocytic activity and the proportion on monocytes in the granulocyte- and mononuclear blood cell fractions was estimated.

Cell-mediated immune reactions against islets of Langerhans in diabetes-prone BB rats.

The intact pancreatic islet can be destroyed by antibody-dependent cell-mediated cytotoxicity (ADCC). T cell-mediated cytotoxicity (CMC) might additionally be important in the pathogenesis of IDDM. However, in vitro alterations of islets due to CMC have so far not been demonstrated.

Genetic control of diabetes induction by complete Freund's adjuvant combined with subdiabetogenic doses of streptozotocin in Lewis rats--evidence for transient cytotoxicity against beta cells.

The non-specific activation of the immune system by administration of complete Freund's adjuvant (CFA) was examined in two congenic Lewis rat strains LEW. 1A (RT1a) and LEW. 1W (RT1u) as a possible mean of amplification of the specific immune response, directed to pancreatic beta cells induced by multiple non-diabetogenic injections of streptozotocin (STZ).

Measurement of insulin during isolation and purification from animal pancreas. A comparison of radioimmunoassay, radioreceptor assay and in-vivo bioassay.

For the purpose of monitoring the yield of the insulin extraction procedure from animal pancreas three methods of insulin determination were compared, i.e. the mouse convulsion test, a radioreceptor assay (RRA) on rat fat cells and a radioimmunoassay (RIA) which was especially laid out for high insulin concentrations.

The frequency of islet cell surface antibodies and antibody-dependent cell-mediated cytotoxicity (ADCC) of mononuclear cells in HLA-typed patients with high diabetes risk.

To evaluate the significance of ICSA as a prognostic marker for the development of type I diabetes we investigated 66 subjects with first degree relatives of type I (47) and type II (9) diabetes as well as subjects with anamnestical data suggestive of diabetes. Patients were studied for glucose tolerance (oGTT) and IRI-response, ICSA (indirect fluorescence of living rat islet cell suspensions), ADCC (specific 51Cr-release of serum pretreated neonatal rat islets elicited by mononuclear cells) and HLA-antigens. 23 subjects revealed normal glucose tolerance, 17 impaired glucose tolerance and 26 had a prevoius abnormality.

Effect of antibody-mediated crosslinking of insulin on its bioactivity and receptor binding.

Precipitating anti-insulin antibodies or anti-insulin IgG/anti-IgG complexes bind insulin in a highly aggregated form and thus should preferably be capable of inducing receptor aggregation, which has recently been suggested to be a precondition for insulin bioactivity. We, therefore, studied the influence of antibody-mediated crosslinking of insulin on the glucose conversion into CO2 in rat fat cells and glycogen synthesis in rat liver cells. As far as possible receptor-bound insulin was measured in parallel.

Impaired hormonal regulation of lipolysis and the interference with adenosine in adipose tissue from hyperglycemic sand rats in vitro.

Sand rats (Psammomys obesus) developed in response to different food intake various states of hyperglycemia and hyperinsulinism. 12 normo- and 10 hyperglycemic animals were selected by means of a weekly control of plasma glucose and plasma insulin over a period of 12 weeks after separation from the mother. During this time also the development of body weight gain was checked.

Antibody-dependent cell-mediated cytotoxicity of mononuclear cells against Langerhans islets of Wistar rats in normal man and in patients at diabetes risk.

Antibody-dependent cell-mediated cytotoxicity against pancreatic islets was investigated in 13 newly diagnosed insulin-dependent diabetics, in 38 patients at high risk for the disease and in 20 age-matched healthy controls. For this purpose 51Cr-labeled neonatal rat pancreatic islets incubated with the specific anti-rat islet cell antiserum 339 or with serum of the lymphocyte donors were used as targets. The antibody-mediated cytotoxic activity of mononuclear cells was evaluated from the specific chromium release after 6 h exposure of pretreated islets to the effector cells.

Protection of insulin secretion by magnesium during islet culture: independence of cAMP/or insulin accumulation.

Pancreatic rat islets cultured for 12 days maintained their insulin content and biosynthesis when cultivated at 10 mmol/l glucose. The glucose-induced insulin secretion investigated in a subsequent incubation period was, however, reduced. At a Mg++ concentration of 5.

Carp insulin: amino acid sequence, biological activity and structural properties.

The amino acid sequence of insulin of carp (Cyprinus carpio) has been determined and correlated with its biological activity in a fat-cell test and its structural properties as measured by circular dichroism and sedimentation analysis. The amino acid sequence of carp insulin displays some unusual features: the B chain is longer at the N terminus by two residues as compared with mammalian insulins and there are substitutions of the charged residues, found in most insulins at positions B21 and B22, by proline and threonine respectively. On the other hand, all amino acid residues essential for biological activity and for the association of insulin monomers are the same in carp insulin.