warfarin and Diabetes-Mellitus--Type-1

Involutional osteoporosis is one of common diseases related to ageing. However, it is essential for physicians to exclude possibilities that it is caused by certain background diseases or disorders, such as hypercortisolism, hyperthyroidism and type 1 diabetes mellitus. In addition, there are several diseases other than osteoporosis, that are known to be associated with low bone mineral density, although osteoporosis is usually diagnosed according to bone mineral density measurements. Thus, physicians should be prepared to appropriately evaluate how bone metabolism is impaired in the face of patients with low bone mineral density.

Topics: Anticonvulsants; Antidepressive Agents; Bone and Bones; Bone Density; Cushing Syndrome; Diabetes Mellitus, Type 1; Glucocorticoids; Humans; Hyperthyroidism; Neoplasms; Osteoporosis; Warfarin

Lisofylline (LSF, 1-(5-R-hydroxyhexyl)-3,7-dimethylxanthine) is an anti-inflammatory agent that protects beta-cells from Th1 cytokine-induced dysfunction and reduces the onset of Type 1 diabetes in non-obese diabetic (NOD) mice. Due to its low potency, poor oral bioavailability, and short half-life, the widespread clinical utility of LSF may be limited. Our goal has been to develop new agents based on the LSF structural motif that resolve the potency and pharmacokinetic liabilities of LSF. In this study, we have generated a focused library of LSF analogs that maintain the side chain (5-R-hydroxyhexyl) constant, while substituting a variety of nitrogen-containing heterocyclic substructures for the xanthine moiety of LSF. This library includes the xanthine-like (5-aza-7-deazaxanthine), as well as non-xanthine-like skeletons. The LSF analogs were evaluated in a pancreatic beta-cell line for the effects on apoptosis protection and insulin release. The metabolic stability of selected compounds was also tested.

Topics: Animals; Apoptosis; Cell Line; Chemoprevention; Cytokines; Diabetes Mellitus, Type 1; Drug Evaluation, Preclinical; Hypoglycemic Agents; Insulin; Insulin Secretion; Insulin-Secreting Cells; Mice; Molecular Structure; Pentoxifylline; Stereoisomerism

We examined the plasma protein binding of an acidic drug (warfarin bound to albumin) and a basic drug [lidocaine (lignocaine) bound to alpha 1-acid glycoprotein] in 15 patients with insulin-dependent diabetes mellitus (IDDM) and 15 matched controls. We also examined protein binding of warfarin and lidocaine in 30 patients with non-insulin-dependent diabetes (NIDDM) and 25 controls. Compared with control, the binding of both warfarin (98.81 +/- 0.02 vs 98.57 +/- 0.03%, mean +/- SEM) and of lidocaine (69 +/- 2 vs 58 +/- 2%) was significantly reduced in IDDM. This group had lower concentrations of both albumin and alpha 1-acid glycoprotein (AAG), achieving statistical significance vs control for albumin only. In the patients with NIDDM, who had a similar level of glycosylated haemoglobin, while there was no significant difference in the binding of lidocaine there was a significant increase in warfarin binding compared with the control population (99.01 +/- 0.03 vs 98.82 +/- 0.04%). This study suggests that binding of both acidic and basic drugs is altered in both IDDM and NIDDM.

Topics: Adolescent; Adult; Aged; Blood Proteins; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dialysis; Female; Glycated Hemoglobin; Humans; Lidocaine; Male; Middle Aged; Protein Binding; Warfarin

Topics: Adult; Constriction; Diabetes Mellitus, Type 1; Heparin; Humans; Ileum; Immunosuppressive Agents; Jejunum; Methods; Middle Aged; Pancreas; Pancreas Transplantation; Pancreatic Ducts; Pancreatic Fistula; Postoperative Complications; Warfarin