Morphine metabolism, transport and brain disposition

The chemical structures of morphine and its metabolites are closely related to the clinical effects of drugs (analgesia and side-effects) and to their capability to cross the Blood Brain Barrier (BBB). Morphine-6-glucuronide (M6G) and Morphine-3-glucuronide (M3G) are both highly hydrophilic, but only M6G can penetrate the BBB; accordingly, M6G is considered a more attractive analgesic than the parent drug and the M3G. Several hypotheses have been made to explain these differences. In this review we will discuss recent advances in the field, considering brain disposition of M6G, UDP-glucoronosyltransferases (UGT) involved in morphine metabolism, UGT interindividual variability and transport proteins

The elevation in circulating anti-angiogenic factors is independent of markers of neutrophil activation in preeclampsia

Background - Severe preeclampsia is associated with increased neutrophil activation and elevated serum soluble endoglin (sEng) and soluble Flt-1 (sFlt-1) in the maternal circulation. To dissect the contribution of systemic inflammation and anti-angiogenic factors in preeclampsia, we investigated the relationships between the circulating markers of neutrophil activation and anti-angiogenic factors in severe preeclampsia or systemic inflammatory state during pregnancy. Methods and results - Serum sEng, sFlt-1, placenta growth factor, interleukin-6 (IL-6), calprotectin, and plasma a-defensins concentrations were measured by ELISA in 88 women of similar gestational age stratified as: severe preeclampsia (sPE, n = 45), maternal systemic inflammatory response (SIR, n = 16) secondary to chorioamnionitis, pyelonephritis or appendicitis; and normotensive controls (CRL, n = 27). Neutrophil activation occurred in sPE and SIR, as a-defensins and calprotectin concentrations were two-fold higher in both groups compared to CRL (P < 0.05 for each). IL-6 concentrations were highest in SIR (P < 0.001), but were higher in sPE than in CRL (P < 0.01). sFlt-1 (P < 0.001) and sEng (P < 0.001) were ˜20-fold higher in sPE compared to CRL, but were not elevated in SIR. In women with sPE, anti-angiogenic factors were not correlated with markers of neutrophil activation (a-defensins, calprotectin) or inflammation (IL-6). Conclusions - Increased systemic inflammation in sPE and SIR does not correlate with increased anti-angiogenic factors, which were specifically elevated in sPE indicating that excessive systemic inflammation is unlikely to be the main contributor to severe preeclampsia

The Effects of Sevoflurane Anesthesia and Cardiopulmonary Bypass on Renal Function in Cyanotic and Acyanotic Children Undergoing Cardiac Surgery

Background: There are few data on the effects of anesthesia and cardiopulmonary bypass (CPB) on perioperative renal function in children with cyanotic congenital heart disease undergoing open heart surgery. This study aims to investigate the perioperative renal function in cyanotic versus acyanotic children undergoing sevoflurane anesthesia for open heart surgery. Methods: After receiving ethical committee approval, 12 acyanotic patients (preoperative oxygen saturation: SaO(2) > 85%) and 12 cyanotic children (SaO(2) < 85%) were included. Sevoflurane was administered at concentration levels of 2% before CPB and 1-2% during CPB after standard anesthesia induction. Inorganic fluoride, electrolytes, creatinine, urea nitrogen in serum and urine samples, and N-acetyl-beta-D-glucosaminidase (NAG) in urine samples were measured before induction, before CPB, during CPB, after CPB, at the end of surgery, and at 24th h postoperatively. Results: The levels of serum uric acid levels were higher in the cyanotic group (p < 0.05). There were no differences in the levels of serum creatinine and urine creatinine, urea nitrogen, and electrolytes between the two groups. Serum inorganic fluoride levels were always higher in the acyanotic group than in the cyanotic group, but these differences between the groups reached statistical significance at two measurement times (before CPB and end of surgery) (p < 0.05). Urinary inorganic fluoride levels increased with time in both groups. Although urinary NAG increased significantly after the CPB in the cyanotic group, the differences between the two groups did not reach statistical significance. Conclusions: We have concluded that renal function was not affected during open heart surgery with sevoflurane anesthesia, in both cyanotic and acyanotic children.WoSScopu