Improved resistance to ischemia and reperfusion, but impaired protection by ischemic preconditioning in patients with type 1 diabetes mellitus: a pilot study.

Background: In patients with type 1 diabetes mellitus (T1DM), cardiovascular events are more common, and the outcome following a myocardial infarction is worse than in nondiabetic subjects. Ischemic or pharmacological preconditioning are powerful interventions to reduce ischemia reperfusion (IR)-injury. However, animal studies have shown that the presence of T1DM can limit these protective effects.

Differential effects of sulfonylurea derivatives on vascular ATP-sensitive potassium channels.

Sulfonylurea drugs exert their insulinotropic action by inhibiting ATP-sensitive potassium channels in the pancreas. However, these channels are also expressed in myocardial and vascular smooth muscle, implicating possible detrimental cardiovascular effects. Aim of the present study was to investigate the inhibitory potency of various widely used sulfonylurea drugs in resistance arteries.

Oral therapy with dipyridamole limits ischemia-reperfusion injury in humans.

Background: Adenosine receptor stimulation induces several effects that could limit ischemia-reperfusion injury. We hypothesize that treatment with the nucleoside uptake inhibitor dipyridamole increases endogenous adenosine and limits ischemia-reperfusion injury in humans.

Methods: Ischemia-reperfusion injury was studied in forearm skeletal muscle by technetium Tc 99m-labeled annexin A5 scintigraphy.

Glibenclamide depletes ATP in renal proximal tubular cells by interfering with mitochondrial metabolism.

Sulfonylurea drugs, like glibenclamide, stimulate insulin secretion by blocking ATP-sensitive potassium channels on pancreatic beta cells. Renal tubular epithelial cells possess a different class of K(ATP) channels with much lower affinities for sulfonylurea drugs, necessitating the use of micromolar glibenclamide concentrations to study these channels. Here, we describe the toxic effects of these concentrations on mitochondrial energy metabolism in freshly isolated renal proximal tubular cells.

Enhanced extracorporeal elimination of valproic acid in overdose.

The treatment of the poisoned patient has been based on three main approaches: use of supportive nonspecific therapy, if available administration of antidotes and removal of the offending drug from the body. Gastric lavage and binding of nonabsorbed drug by activated charcoal are often used in an attempt to eliminate the intoxicating agent from the body. In addition, elimination of already absorbed drug can sometimes be enhanced by the induction of brisk diuresis coupled to manipulation of urine pH (e.

Sulphonylurea drugs reduce hypoxic damage in the isolated perfused rat kidney.

Sulphonylurea drugs have been shown to protect against hypoxic damage in isolated proximal tubules of the kidney. In the present study we investigated whether these drugs can protect against hypoxic damage in a whole kidney preparation. Tolbutamide (200 microM) and glibenclamide (10 microM) were applied to the isolated perfused rat kidney prior to changing the gassing from oxygen to nitrogen for 30 min.

Induction of Ca2+ oscillations by selective, U73122-mediated, depletion of inositol-trisphosphate-sensitive Ca2+ stores in rabbit pancreatic acinar cells.

The effect of the putative inhibitor of phospholipase C activity, U73122, on the Ca2+ sequestering and releasing properties of internal Ca2+ stores was studied in both permeabilized and intact rabbit pancreatic acinar cells. U73122 dose dependently inhibited ATP-dependent Ca2+ uptake in the inositol (1,4,5)-trisphosphate-[Ins(1,4,5)P3]-sensitive, but not the Ins(1,4,5)P3-insensitive, Ca2+ store in acinar cells permeabilized by saponin treatment. In a suspension of intact acinar cells, loaded with the fluorescent Ca2+ indicator, Fura-2, U73122 alone evoked a transient increase in average free cytosolic Ca2+ concentration ([Ca2+]i,av), which was largely independent of external Ca2+.

[A single blood pressure reading during check-up for hypertension leads to a change in management more often than multiple readings].

Objective: To define the number of blood pressure readings necessary during a patient's visit to serve as a correct reference for patient management.

Design: Observational study.

Setting: Outpatient clinic in the Netherlands.