ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov.

Apolipoprotein AII (apoAII) transgenic (apoAIItg) mice exhibit several traits associated with the insulin resistance (IR) syndrome, including IR, obesity, and a marked hypertriglyceridemia. Because treatment of the apoAIItg mice with rosiglitazone ameliorated the IR and hypertriglyceridemia, we hypothesized that the hypertriglyceridemia was due largely to overproduction of very low density lipoprotein (VLDL) by the liver, a normal response to chronically elevated insulin and glucose. We now report in vivo and in vitro studies that indicate that hepatic fatty acid oxidation was reduced and lipogenesis increased, resulting in a 25% increase in triglyceride secretion in the apoAIItg mice. In addition, we observed that hydrolysis of triglycerides from both chylomicrons and VLDL was significantly reduced in the apoAIItg mice, further contributing to the hypertriglyceridemia. This is a direct, acute effect, because when mouse apoAII was injected into mice, plasma triglyceride concentrations were significantly increased within 4 h. VLDL from both control and apoAIItg mice contained significant amounts of apoAII, with ϳ4 times more apoAII on apoAIItg VLDL. ApoAII was shown to transfer spontaneously from high density lipoprotein (HDL) to VLDL in vitro, resulting in VLDL that was a poorer substrate for hydrolysis by lipoprotein lipase. These results indicate that one function of apoAII is to regulate the metabolism of triglyceride-rich lipoproteins, with HDL serving as a plasma reservoir of apoAII that is transferred to the triglyceride-rich lipoproteins in much the same way as VLDL and chylomicrons acquire most of their apoCs from HDL.More than 95% of plasma apolipoprotein AII (apoAII) 2 is associated with high density lipoproteins (HDLs) where it is the second most abundant protein comprising ϳ20% of the HDL total protein mass (1). Studies of the physiologic effects of apoAII have focused on reverse cholesterol transport and antioxidant functions, mechanisms through which HDLs are believed to protect against atherosclerosis (2, 3). Most but not all of these studies suggest that increased apoAII impaired both of these processes and promoted atherosclerosis (4 -8). Additional evidence for other physiologic effects of apoAII has come from genetic studies in both humans and mice, which suggest a role for apoAII in triglyceride and free fatty acid metabolism (8 -10). Subsequently, studies of genetically modified mice carrying a transgene for either human or mouse apoAII (3, 11-21), as well as apoAII knockout mice (22), confirmed a complex metabolic role for apoAII, including a rather profound effect on plasma triglyceride concentrations.Hypertriglyceridemia is an integral component of the phenotype of several disease states, including type 2 diabetes, familial combined hyperlipidemia, and the metabolic syndrome, and it is likely to be one of several contributing factors underlying the increased atherosclerosis associated with these complex diseases. Hypertriglyceridemia has been demonstrated to be an independent risk factor ...

Neuraxial anesthesia, as the standard of care for Cesarean deliveries, is associated with decreased blood loss. However, parturients with inherited bleeding disorders are at increased risk for epidural hematomas. A small retrospective study has shown that parturients with known factor deficiencies can safely undergo neuraxial anesthesia once the specific factors are replenished. We present a patient who had a considerably increased risk of peripartum bleeding from an unspecified inherited bleeding disorder and was provided a successful neuraxial anesthetic without complications. We discuss the multidisciplinary approach among the surgeons, anesthesiologists, hematologist, and nursing staff to maximize patient safety and comfort.

Neuraxial anesthesia, as the standard of care for Cesarean deliveries, is associated with decreased blood loss. However, parturients with inherited bleeding disorders are at increased risk for epidural hematomas. A small retrospective study has shown that parturients with known factor deficiencies can safely undergo neuraxial anesthesia once the specific factors are replenished. We present a patient who had a considerably increased risk of peripartum bleeding from an unspecified inherited bleeding disorder and was provided a successful neuraxial anesthetic without complications. We discuss the multidisciplinary approach among the surgeons, anesthesiologists, hematologist, and nursing staff to maximize patient safety and comfort.