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The inherent short lifespan of Zea mays (maize, corn) pollen hinders crop improvement and challenges the hybrid seed production required to produce food, fuel, and feed. Decades of scientific effort on maize pollen storage technology have been unable to deliver a widely accessible protocol that works for liters of pollen at a hybrid seed production scale. Here we show how suppressing the pollen cellular respiration rate through refrigeration and optimizing gas exchange within the storage environment are the critical combination of factors for maintaining pollen viability in storage. The common practice of preserving maize pollen by mixing the pollen with talcum powder is critically examined using pollen tube germination testing, electron microscopy of pollen-silk (stigma) interaction, and test pollinations in production environments. These techniques lead to mixing maize pollen collected for storage with anti-clumping carrier compounds, including microcrystalline cellulose. These carriers improve stored pollen flowability during pollination and enable increased seed sets to be obtained from stored pollen. Field testing in maize seed production demonstrates that a wide range of pollen volumes can be stored for up to seven days using low-cost, globally available materials and that stored pollen can achieve seed-set equivalency to fresh pollen. Investigation of Zea mays (maize, corn) pollen cellular respiration and pollen-silk (stigma) interactions leads to the development of an accessible protocol that can preserve maize pollen viability for up to seven days at a hybrid seed production scale.

There were no significant differences in the area under the curve of unmetabolized (R)-[11C]verapamil in plasma between the elderly and young group, both for baseline scans and scans after ABCB1 inhibition. [...]tariquidar plasma concentrations at the time of the PET scan were not significantly different between the two groups.

Background At the human blood-brain barrier (BBB) high levels of efflux transporters, such as P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), are expressed, which restrict the brain distribution of many drugs. Methods Seven patients diagnosed with a neuroepithelial tumor and elected for neurosurgery underwent a 60-min dynamic [11C]tariquidar brain...

For the therapeutic dose a significant decrease (-39 ± 18%) in the influx rate constant of 11C-erlotinib from blood into hepatocytes was found, whereas the efflux rate constant from hepatocytes into gall bladder and bile duct remained unchanged. Active uptake transport of erlotinib into the liver may account for variability...

We assessed the pharmacokinetics (PK), tolerability and safety of tariquidar (TQD), a P-glycoprotein (Pgp) inhibitor, after intravenous administration of single ascending doses. Employed doses were up to 4-fold higher than in previous clinical trials in cancer patients and are capable of inhibiting Pgp at the blood-brain barrier. Fifteen male healthy volunteers were randomized to receive single intravenous doses of TQD at 4, 6 or 8 mg/kg body weight and underwent blood sampling for over 24 h. TQD concentrations were determined in plasma samples with high-performance liquid chromatography mass spectrometry. No dose-limiting toxicities of TQD were observed. The area under the plasma concentration-time curve from start until 24 h after the end of infusion was positively correlated with an administered TQD dose (r = 0.8981, p < 0.0001). Moreover, we found a positive correlation for volume of distribution at steady state (r = 0.7129, p = 0.0004) with TQD dose. Dose dependency of volume of distribution at steady state points to non-linear PK of TQD, which was in all likelihood caused by transporter saturation at high TQD doses. Acceptable safety and tolerability as well as dose-linear increases in plasma exposure support the future use of TQD at doses up to 8 mg/kg to inhibit Pgp at the human blood-brain barrier.

This study aimed to test whether [ 18 F]fluoro- D -glucose (FDG) uptake of tumours measured by positron emission tomography (PET) can be used as surrogate marker to define the optimal biological dose (OBD) of mTOR inhibitors in vivo . Everolimus at 0.05, 0.5, 5 and 15 mg kg −1 per day was administered to gastric cancer xenograft-bearing mice for 23 days and FDG uptake of tumours was measured using PET from day 1 to day 8. To provide standard comparators for FDG uptake, tumour volume, S6 protein phosphorylation, Ki-67 staining and everolimus blood levels were evaluated. Everolimus blood levels increased in a dose-dependent manner but antitumour activity of everolimus reached a plateau at doses ⩾5 mg kg −1 per day (tumour volume treated vs control (T/C): 51% for 5 mg kg −1 per day and 57% for 15 mg kg −1 per day). Correspondingly, doses ⩾5 mg kg −1 per day led to a significant reduction in FDG uptake of tumours. Dose escalation above 5 mg kg −1 per day did not reduce FDG uptake any further (FDG uptake T/C: 49% for 5 mg kg −1 per day and 52% for 15 mg kg −1 per day). Differences in S6 protein phosphorylation and Ki-67 index reflected tumour volume and changes in FDG uptake but did not reach statistical significance. In conclusion, FDG uptake might serve as a surrogate marker for dose finding studies for mTOR inhibitors in (pre)clinical trials.

Objective: We investigated whether blood pressure profile early in pregnancy was associated with the development of pre-eclampsia in patientswith gestational diabetesmellitus(GDM).Methods: A retrospective longitudinal database study of 1664 GDM subjects was performed. Systolic and diastolic blood pressure measurements were taken bi-weekly during the first and second trimesters. GDM patients who developed pre-eclampsia were compared to GDM patients who did not. Subjects were further stratified by maternal age, parity, race, prepregnancy body mass index (BMI) and weight gain during pregnancy. Logistic regression was performed to identify the net effect of each factor on the development of pre-eclampsia.Results: Overall, 167 1664 (10%) GDM patientsdeveloped pre-eclampsia.GDM patients who developed pre-eclampsia were more obese, gained more weight during pregnancy and had more severe GDM in comparison to GDM patients who did not. Although all mean blood pressure measurements were within the normal range, significantly higher systolic and diastolic valueswere recorded in the GDM patientswho developed pre-eclampsia throughout the first and the second trimesters of pregnancy. Logistic regression revealed that higher parity (p=0.04), maternal age (p=0.03) and pre-pregnancy BMI (p=0.03) were all contributing factors to pre-eclampsia. In contrast, weight gain during pregnancy and race were not related.Conclusion: In GDM patients, higher blood pressure readings early in pregnancy, even prior to GDM diagnosis, were associated with the subsequent development of pre-eclampsia.

In this multicenter, four-year observational study of women with a history of cesarean section and a singleton gestation, a trial of labor was associated with a higher risk of symptomatic uterine rupture in the mother and hypoxic–ischemic encephalopathy in the infant than was elective cesarean delivery, although the absolute risks of these complications were low. The findings from this study should help inform women about their choices regarding the type of delivery after a prior cesarean section. The findings from this study should help inform women about their choices regarding the type of delivery after a prior cesarean section. The overall rate of cesarean delivery in the United States has risen dramatically, from 5 percent of all deliveries in 1970 to a high of 26 percent in 2002. 1 Efforts to reduce the number of cesarean births, although initially successful, failed to achieve the U.S. Public Health Service goals, set in 1990. These goals included achieving an overall rate of cesarean delivery of 15 percent, and a rate of vaginal birth after previous cesarean section of 35 percent of deliveries after previous cesarean sections, by the year 2000. 2 The Healthy People 2010 report published in 2000 proposes a target rate . . .

Objective: Objective: We sought to evaluate birth weight diversity and pregnancy outcome in women with two consecutive pregnancies complicated with gestational diabetes mellitus (GDM).Methods: A retrospective longitudinal study of 389 patients with two consecutive GDM pregnancies was assessed for pregnancy outcome and fetal weight diversity. Since there is a tendency towards repetition or moderate increase in fetal weight in subsequent non-diabetic pregnancies, consecutive GDM pregnancies were stratified into three categories. They consisted of: an increase in birth weight of more than 250 g between GDM pregnancies for the same gestational age at delivery, and considered significant; an increase in birth weight of more than 100 g but less than 250 g; and a decrease in birth weight in the second GDM pregnancy compared to the index pregnancy. Any change in birth weight of up to 100 g between the two pregnancies was considered comparable.Results: The mean interval between the two diabetic pregnancies was 3 years. The change in weight above the biologically expected weight was evaluated. In 181 389(46%), an elevation in birth weight between pregnancies was recorded and from this group only 125 181 (69%) had significant increases in birth weight (>250 g) with a mean of 531±49 g. Furthermore, 130 389 (33.4%) had decreased fetal weight between the two pregnancies (mean 373±31 g). In 78 389(20.1%), birth weight changes were considered similar (>100 g). Fasting plasma glucose (FBG) and pre-pregnancy body mass index (BMI) were significantly elevated in the second pregnancy (FBG 97±15 vs. 102±4.7 mg dl; BMI 25.9±4.7 vs. 27±6.7 kg m2, respectively; p=0.02). No difference was found in the mean maternal weight gain during pregnancy, gestational age at delivery, mean blood glucose, macrosomia or large-for-gestationalage rates. No difference in neonatal outcome (neonatal intensive care unit admission, the need for respiratory support, stillbirth rate or shoulder dystocia) was found between the two pregnancies.Conclusion: In GDM patients, owing to the role of glycemic control and environmental factors, an expected increase in birth weight between pregnancies cannot be predicted.