Echinochrome A Reverses Kidney Abnormality and Reduces Blood Pressure in a Rat Model of Preeclampsia.

We aimed to observe the effects of Echinochrome A (Ech A) on systemic changes using a rat model of preeclampsia. The results showed that an infusion of angiotensin II (Ang II) through an osmotic pump (1 µg/kg/min) on GD 8 increased systolic and diastolic blood pressures and reduced fetal weight and placental weight. The diameters of the glomeruli were expended and glomeruli capillaries were diminished. No change was observed in the heart and liver in the Ang II group, but epithelial structures were disrupted in the uterus. Ech A treatment on GD 14 (100 µg/µL) through the jugular vein reduced systolic and diastolic blood pressures and reversed glomerulus alterations, but the fetal or placental parameters were unaffected. Ech A only partly reversed the effect on the uterus. The mRNA expression of TNF-α was increased and IL-10 and VEGF were reduced in the uterus of the Ang II group, while Ech A restored these changes. A similar trend was observed in the kidney, liver, and heart of this group. Furthermore, Bcl-2 was reduced and Bcl-2/Bax ratios were significantly reduced in the kidney and heart of the Ang II group, while Ech A reversed these changes. We suggest that Ech A modulates inflammation and apoptosis in key systemic organs in Ang II-induced rat preeclampsia and preserves kidney and uterus structures and reduces blood pressure.

Comparative analysis of the hydrogen sulphide pathway in internal thoracic artery and radial artery.

OBJECTIVES: The molecular basis supporting the superiority of the left internal thoracic artery (LITA) as a bypass conduit is limited. This study was conducted to compare the expression and localization of hydrogen sulphide synthesizing enzymes in LITA and radial artery (RA). METHODS: Nineteen patients who underwent coronary artery bypass grafting using LITA and RA were enrolled. The remnant LITA and RA were collected to measure the expression levels of 3 hydrogen sulphide-producing enzymes: cystathionine ß-synthase, cystathionine γ-lyase and 3-mercaptopyruvate sulphurtransferase using quantitative real-time polymerase chain reaction. Expression levels of these enzymes in the LITA and RA were compared in each subject. The expression and localization patterns of the enzymes were also analysed by immunohistochemistry. RESULTS: The mRNA expression of the cystathionine ß-synthase was greater in the LITA than in the RA (P = 0.033), whereas the expression levels of the other 2 enzymes did not significantly differ between the 2 arteries. The immunohistochemistry analysis demonstrated greater expression of the cystathionine ß-synthase in the LITA than in the RA (P = 0.006). This protein was present in both tunica intima and tunica media of the LITA, although it was present only in the tunica media of the RA. Localization patterns of the other 2 enzymes were not different between LITA and RA. CONCLUSIONS: Expression levels of the mRNA and protein of cystathionine ß-synthase were significantly greater in LITA than in the RA. These findings might be a factor that affects the superior patency rate of LITA.

A beta3-adrenergic-leptin-melanocortin circuit regulates behavioral and metabolic changes induced by chronic stress.

BACKGROUND: Obesity has been associated with an increased risk of developing several psychiatric illnesses, including major depression and posttraumatic stress disorder. Likewise, these stress-related disturbances are associated with a higher rate of obesity; yet, the neurobiological mechanisms linking obesity and stress remain incompletely understood. METHODS: Following exposure to chronic social defeat stress (CSDS), mice were given free access to either regular chow or a Western-style diet high in triglycerides and cholesterol. Comprehensive metabolic and behavioral testing was then conducted. RESULTS: Mice subjected to CSDS and then fed a high-fat diet for 30 days display severe behavioral deficits accompanied by redistribution of body fat. Stressed mice have decreased adipose tissue as well as decreased serum leptin levels compared with control mice. Pharmacological inhibition of beta(3)-adrenergic signaling during CSDS normalizes these metabolic abnormalities but worsens behavioral symptoms. Furthermore, mice subjected to CSDS display central leptin resistance including reduced expression of pro-opiomelanocortin in hypothalamus. Administration of a central melanocortin agonist worsens stress-induced behavioral deficits, while mice lacking the melanocortin-4 receptor display attenuated symptoms. CONCLUSIONS: These results indicate that chronic signaling through beta(3)-adrenergic receptors during social stress is an adaptive response that improves behavioral function. However, these responses come at the expense of central leptin resistance and melanocortin signaling alterations that contribute to significant and long-lasting metabolic abnormalities.