Genetic and environmental influences on serum oxylipins, endocannabinoids, bile acids and steroids.

Lipid bioactivity is a result of direct action and the action of lipid mediators including oxylipins, endocannabinoids, bile acids and steroids. Understanding the factors contributing to biological variation in lipid mediators may inform future approaches to understand and treat complex metabolic diseases. This research aims to determine the contribution of genetic and environmental influences on lipid mediators involved in the regulation of inflammation and energy metabolism. This study recruited 138 monozygotic (MZ) and dizygotic (DZ) twins aged 18-65 years and measured serum oxylipins, endocannabinoids, bile acids and steroids using liquid chromatography mass-spectrometry (LC-MS). In this classic twin design, the similarities and differences between MZ and DZ twins are modelled to estimate the contribution of genetic and environmental influences to variation in lipid mediators. Heritable lipid mediators included the 12-lipoxygenase products 12-hydroxyeicosatetraenoic acid [0.70 (95% CI: 0.12,0.82)], 12-hydroxyeicosatetraenoic acid [0.73 (95% CI: 0.30,0.83)] and 14­hydroxy-docosahexaenoic acid [0.51 (95% CI: 0.07,0.71)], along with the endocannabinoid docosahexaenoy-lethanolamide [0.52 (95% CI: 0.15,0.72)]. For others such as 13-hydroxyoctadecatrienoic acid and lithocholic acid the contribution of environment to variation was stronger. With increased understanding of lipid mediator functions in health, it is important to understand the factors contributing to their variance. This study provides a comprehensive analysis of lipid mediators and extends pre-existing knowledge of the genetic and environmental influences on the human lipidome.

Embolic stroke in a woman with mitral valve prolapse who used oral contraceptives.

A case of angiographically-documented embolism is presented in a patient using oral contraceptives (OC) with marked mitral valve prolapse (MVP) and an atrial thrombus. OC use has been shown to decrease levels of antithrombin III and increase platelet coagulant activity. This increased coagulability may increase the risk of intra-atrial thrombus formation and subsequent cerebral embolism in patients with MVP. We believe that MVP, especially when redundant valve leaflets are recognized, may be a relative contraindication to OC use.

PIP: A 21-year old women taking oral contraceptives suffered thromboembolic stroke associated with mitral valve prolapse. She had been using an unspecified oral contraceptive for 3 months postpartum, and had smoked a pack a day for 5 years. She complained of sudden right orbital headache, left-sided weakness and pain. Clinical exam showed left sided anopsia, facial paralysis, tongue protrusion, parietal sensory deficit, and loss of position sense. Computed tomography suggested a lesion near the right middle cerebral artery; and cerebral angiography revealed an 8 x 2 mm filling defect in that artery. A midsystolic click without a murmur was evident in the cardiac exam. Thickened, redundant mitral valve leaflets with marked prolapse, and a mass on the atrial side of the posterior leaflet appeared on the echocardiogram. The atrial thrombus was considered the source of the apparent embolism in the cerebral artery. Oral contraceptives have been found to increase the risk of thrombotic stroke and venous thromboembolism. Therefore, women with known mitral valve prolapse or leaflets may be advised not to use the pill.

Norepinephrine-induced hypertension in Guillain Barré syndrome.

Systemic haemodynamics, plasma catecholamine levels and diurnal variation of arterial pressure were studied in a 20-year-old patient with hypertension during Guillain Barré syndrome after complete resolution of the illness. Transient arterial hypertension during the course of Guillain Barré syndrome is characterized by an increased total peripheral resistance associated with elevated circulating norepinephrine levels, suggesting an over-activity of the sympathetic nervous system as the underlying mechanism of the elevated blood pressure.