Sex Difference in Capillary Reperfusion After Transient Middle Cerebral Artery Occlusion in Diabetic Mice.

Background: Type 2 diabetes (DM2) exacerbates stroke injury, reduces efficacy of endovascular therapy, and worsens long-term functional outcome. Sex differences exist in stroke incidence, response to therapy, poststroke microvascular dysfunction, and functional recovery. In this study, we tested the hypotheses that poor outcome after stroke in the setting of DM2 is linked to impaired microvascular tissue reperfusion and that male and female DM2 mice exhibit different microvascular reperfusion response after transient middle cerebral artery occlusion (MCAO).

GPR39 Knockout Worsens Microcirculatory Response to Experimental Stroke in a Sex-Dependent Manner.

No current treatments target microvascular reperfusion after stroke, which can contribute to poor outcomes even after successful clot retrieval. The G protein-coupled receptor GPR39 is expressed in brain peri-capillary pericytes, and has been implicated in microvascular regulation, but its role in stroke is unknown. We tested the hypothesis that GPR39 plays a protective role after stroke, in part due to preservation of microvascular perfusion.

Soluble Epoxide Hydrolase Blockade after Stroke Onset Protects Normal but Not Diabetic Mice.

Soluble epoxide hydrolase (sEH) is abundant in the brain, is upregulated in type 2 diabetes mellitus (DM2), and is possible mediator of ischemic injury via the breakdown of neuroprotective epoxyeicosatrienoic acids (EETs). Prophylactic, pre-ischemic sEH blockade with 4-[[-4-[[(tricyclo[3.3.

Mechanism of protection by soluble epoxide hydrolase inhibition in type 2 diabetic stroke.

Inhibition of soluble epoxide hydrolase (sEH) is a potential target of therapy for ischemic injury. sEH metabolizes neuroprotective epoxyeicosatrienoic acids (EETs). We recently demonstrated that sEH inhibition reduces infarct size after middle cerebral artery occlusion (MCAO) in type 1 diabetic mice.

Role of soluble epoxide hydrolase in exacerbation of stroke by streptozotocin-induced type 1 diabetes mellitus.

Hyperglycemia worsens stroke, yet rigorous glycemic control does not improve neurologic outcome. An alternative is to target downstream molecular mediator(s) triggered by hyperglycemia but independent of prevailing glycemia. Soluble epoxide hydrolase (sEH) is a potential mediator of injury via its metabolism of neuroprotective epoxyeicosatrienoic acids (EETs).

Dichloroacetate stabilizes the intraoperative acid-base balance during liver transplantation.

Lactic acidosis occurs during orthotopic liver transplantation (OLT), especially during the anhepatic and early postreperfusion phases. Dichloroacetate (DCA) inhibits pyruvate dehydrogenase kinase-1, indirectly activating mitochondrial pyruvate dehydrogenase. This, in turn, markedly reduces systemic lactate production and, to a lesser extent, increases hepatic lactate uptake.

Managing intergenerational differences in academic anesthesiology.

Purpose Of Review: Common definitions for workplace generations are the silent generation (born 1925-1945), the baby boomer generation (1946-1962), generation X (1963-1981), and generation Y (1982-2000). Distinct motivational and value perceptions stereotype generations. This review defines the characteristics of workplace generations today and provides insight into how differences influence the workplace environment.

Volume replacement therapy during major orthopedic surgery using Voluven (hydroxyethyl starch 130/0.4) or hetastarch.

Background: The purpose of this study was to test the equivalence of efficacy and compare the safety of the 6% hydroxyethyl starches (HES) Voluven (HES 130/0.4; Fresenius Kabi, Bad Homburg, Germany) and hetastarch (HES 670/0.75 in saline) for intravascular volume replacement therapy during major orthopedic surgery.

Effect of short-term drinking water exposure to dichloroacetate on its pharmacokinetics and oral bioavailability in human volunteers: a stable isotope study.

Dichloroacetic acid (DCAA) is a by-product of drinking water disinfection, is a known rodent hepatocarcinogen, and is also used therapeutically to treat a variety of metabolic disorders in humans. We measured DCAA bioavailability in 16 human volunteers (eight men, eight women) after simultaneous administration of oral and iv DCAA doses. Volunteers consumed DCAA-free bottled water for 2 weeks to wash out background effects of DCAA.

Mechanism of dichloroacetate-induced hypolactatemia in humans with or without cirrhosis.

Dichloroacetate (DCA) has been used as an experimental treatment for lactic acidosis because it lowers plasma lactic acid concentration. Three potential mechanisms could underlie the hypolactatemic action of DCA, but the dominant mechanism in vivo remains unclear. This study tested whether DCA-induced hypolactatemia occurs via decreased lactate production, increased lactate clearance, or decreased rate of glycolysis in healthy humans and in patients with end-stage cirrhosis.