Truncus arteriosus communis in a midtrimester fetus: comparison of prenatal ultrasound and MRI with postmortem MRI and autopsy

Different techniques are used in fetal cardiology, and their accuracy has been demonstrated on several occasions. Color Doppler US has proved to be a reliable and valuable tool in the diagnosis of fetal cardiac abnormalities. Magnetic resonance imaging (MRI) of the fetal heart has, so far, played no role in prenatal diagnostics. We report on a truncus arteriosus communis diagnosed prenatally during a screening ultrasound at 22 weeks of gestation. In addition to real-time ultrasound and color Doppler echocardiography, fetal MRI was performed. Fetal echocardiography arose suspicion of a type I common trunk. Fetal MR showed solely a widened vessel coursing retrocardially and additionally an inhomogeneous fluid distribution of the lung not shown on prenatal US. After termination of pregnancy at 23 weeks of gestation, MR fetography and autopsy were performed, and both found a type II common trunk. MR autopsy of the heart was very reliable in this case and could be an alternative when fetal pathology is not available for different reasons. Postmortem MRI was also able to demonstrate the inhomogeneous fluid distribution in the lung, which was confirmed by autopsy. Fetal and postmortem MR was reliable in the detection of an inhomogeneous fluid distribution in the lung not shown on prenatal US, providing a relevant additional finding to US. Therefore, MRI should be used more often in fetal cardiology, although it still must be further developed.     

Comparison of plasma responses in human subjects after the ingestion of 3R,3R'-zeaxanthin dipalmitate from wolfberry (Lycium barbarum) and non-esterified 3R,3R'-zeaxanthin using chiral high-performance liquid chromatography

Age-related macular degeneration (AMD) is one of the most common eye diseases of elderly individuals. It has been suggested that lutein and zeaxanthin may reduce the risk for AMD. Information concerning the absorption of non-esterified or esterified zeaxanthin is rather scarce. Furthermore, the formation pathway of meso (3R,3'S)-zeaxanthin, which does not occur in plants but is found in the macula, has not yet been identified. Thus, the present study was designed to assess the concentration of 3R,3R'-zeaxanthin reached in plasma after the consumption of a single dose of native 3R,3'R-zeaxanthin palmitate from wolfberry (Lycium barbarum) or non-esterified 3R,3'R-zeaxanthin in equal amounts. In a randomised, single-blind cross-over study, twelve volunteers were administered non-esterified or esterified 3R,3'R-zeaxanthin (5 mg) suspended in yoghurt together with a balanced breakfast. Between the two intervention days, a 3-week depletion period was inserted. After fasting overnight, blood was collected before the dose (0 h), and at 3, 6, 9, 12, and 24 h after the dose. The concentration of non-esterified 3R,3'R-zeaxanthin was determined by chiral HPLC. For the first time, chiral liquid chromatography-atmospheric pressure chemical ionisation-MS was used to confirm the appearance of 3R,3'R-zeaxanthin in pooled plasma samples. Independent of the consumed diet, plasma 3R,3'R-zeaxanthin concentrations increased significantly (P=0.05) and peaked after 9-24 h. Although the concentration curves were not distinguishable, the respective areas under the curve were distinguishable according to a two-sided F and t test (P=0.05). Thus, the study indicates an enhanced bioavailability of 3R,3'R-zeaxanthin dipalmitate compared with the non-esterified form. The formation of meso-zeaxanthin was not observed during the time period studied.     

Impaired regulation of renal K+ elimination in the sgk1-knockout mouse

Serum- and glucocorticoid-regulated kinase 1 (Sgk1) contributes to Na+ reabsorption in the aldosterone-sensitive distal nephron. Sgk1-knockout (sgk1-/-) and littermate wild-type mice (sgk1+/+) were used to test the importance of Sgk1 in renal elimination of K+ . Intravenous application of K+ load under anesthesia increased plasma K+ concentration by 1.3 to 1.4 mM in both sgk1-/- (n = 6) and sgkl+/+ (n = 7) mice. However, the increase of absolute and fractional renal K+ excretion observed in sgk1+/+ was significantly blunted in sgk1-/- animals. Both groups of mice decreased or increased renal K+ excretion to a similar extent after a low (<0.03%) or high (5%) K+ diet for 6 d, respectively. In sgk1+/+, plasma K+ concentration was not significantly modified by either high or low K+ diet. In sgk1-/-, however, high K+ diet enhanced plasma K+ concentration by about 1.6 mM, despite an excessive increase of plasma aldosterone concentration reaching values about sixfold higher than in sgk1+/+. Electrophysiological and immunohistochemical studies under high K+ diet indicated that reduced epithelial Na+ channel ENaC and/or Na+/K+-ATPase activity in the aldosterone-sensitive distal nephron accounted for the impaired response in sgk1-/- and that an enhanced apical abundance of renal outer medullary K+ channel ROMK partly compensated for the defect. The acute and chronic regulation of renal K+ elimination involves Sgk1.     

Trypanocidal effect of alpha',beta'-epoxyketones indicates that trypanosomes are particularly sensitive to inhibitors of proteasome trypsin-like activity

Previous studies have shown that the proteasome of Trypanosoma brucei is a candidate for novel chemotherapy of African sleeping sickness. In this study, two potent and highly selective alpha',beta'-epoxyketones peptide proteasome inhibitors, epoxomicin and YU101, have been tested for their trypanocidal activities in vitro using culture-adapted bloodstream forms of T. brucei. Both inhibitors displayed promising anti-trypanosomal activities with ED(50) and ED(90) values in the low to mid nanomolar range. Based on MIC values, epoxomicin exhibited a selectivity index approaching those of commercially available drugs. Enzymatic analyses of proteasomal peptidase activities revealed that, compared with mammalian cells, trypanosomes are particular sensitive to inhibition of the trypsin-like activity of the proteasome. In conclusion, the data suggests that proteasome inhibitors targeting the trypsin-like activity are the rational choice for future anti-trypanosomal drug development.     

Cryopreserved rat, dog and monkey hepatocytes: measurement of drug metabolizing enzymes in suspensions and cultures

Metabolism in fresh and cryopreserved (CP) rat, dog and monkey hepatocyte suspensions and cultures was measured using midazolam (CYP3A), tolbutamide (CYP2C), dextromethorphan (CYP2D) and p-nitrophenol (glucuronosyl S-transferases (UGT), sulphotransferases (ST)). CYP3A, CYP2C9, CYP2D6, UGT and ST enzyme functions in fresh and CP rat, dog and monkey hepatocyte suspensions were retained - CP rat hepatocytes lost some CYP2C activity but this was restored by adding NADPH or by placing the cells in culture, suggesting that the enzyme was still functional. Phase 2 activities were equivalent in fresh and CP hepatocyte suspensions. In some cases, incubation conditions increased the rate of metabolism, possibly reflecting de novo cofactor synthesis. However, this effect was substrate and species dependent and was not always the same in fresh and CP cells. CYP3A, CYP2C, CYP2D, UGT and ST activities at 24 hours of culture of rat and monkey hepatocytes were not compromised by cryopreservation. CYP3A, CYP2D but not CYP2C were lower in 24-hour cultures of CP dog hepatocytes than in fresh cells. Despite being lower than fresh cells, UGT activity in dog CP hepatocytes did not decrease from 0 to 24 hours of culture. Species-specific metabolism of p-nitrophenol could be demonstrated in both CP cell suspensions and cultures. In conclusion, these data suggest that the enzyme characteristics of fresh and CP hepatocytes from each species and under specific incubation conditions should be considered when carrying out metabolism studies of new compounds.     

Vacation at moderate and low altitude improves perceived health in individuals with metabolic syndrome

BACKGROUND: Recent data suggest that vacation may improve cardiovascular health, an effect possibly moderated by altitude. The aim of the present study was to study the effect of a 3-week vacation at moderate and low altitude on perceived health in individuals with increased cardiovascular risk. METHODS: Seventy-two overweight males, both occupationally active and retired (mean age=56.6 +/- 7.2 years), with signs of metabolic syndrome were randomly assigned to identical sojourns at either moderate (1,700 m) or low (300 m) altitude and engaged in four 3- to 4-h heart-rate-controlled hiking tours per week. Perceived health was measured 2 weeks before vacation, at the beginning and end of vacation, and 7 weeks after vacation. RESULTS: Fitness, recreational ability, positive and negative mood and social activities improved during vacation, independent of altitude and occupational status, although the day-to-day improvement in quality of sleep was delayed at moderate altitude. During the follow-up examinations, improvements in all reported aspects of health except for social activities were maintained. In comparison to retired individuals, active individuals showed a greater long-term improvement in social activities. CONCLUSION: Vacation positively affects perceived health independent of altitude or occupational status in generally inactive overweight males.