High-sensitivity MALDI-MRM-MS imaging of moxifloxacin distribution in tuberculosis-infected rabbit lungs and granulomatous lesions

MALDI-MSI is a powerful technology for localizing drug and metabolite distributions in biological tissues. To enhance our understanding of tuberculosis (TB) drug efficacy and how efficiently certain drugs reach their site of action, MALDI-MSI was applied to image the distribution of the second-line TB drug moxifloxacin at a range of time points after dosing. The ability to perform multiple monitoring of selected ion transitions in the same experiment enabled extremely sensitive imaging of moxifloxacin within tuberculosis-infected rabbit lung biopsies in less than 15 min per tissue section. Homogeneous application of a reference standard during the matrix spraying process enabled the ion-suppressing effects of the inhomogeneous lung tissue to be normalized. The drug was observed to accumulate in granulomatous lesions at levels higher than that in the surrounding lung tissue from 1.5 h postdose until the final time point. MALDI-MSI moxifloxacin distribution data were validated by quantitative LC/MS/MS analysis of lung and granuloma extracts from adjacent biopsies taken from the same animals. Drug distribution within the granulomas was observed to be inhomogeneous, and very low levels were observed in the caseum in comparison to the cellular granuloma regions. In this experiment the MALDI-MRM-MSI method was shown to be a rapid and sensitive method for analyzing the distribution of anti-TB compounds and will be applied to distribution studies of additional drugs in the future.     

Psychological colloquia as exercises in impression management.

Outlines 6 strategies observed by the present author that are used to create a positive image by colloquia speakers. The intent of "impression management" is to convince the audience that the speaker is a successful "scientist." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of mechanical versus thermal removal of gutta-percha on the quality of the apical seal following post space preparation

The objective of this study was to compare the effects of a flame-heated endodontic plugger, an electrically-heated endodontic spreader, Peeso reamers, and GPX burs on the apical seal when gutta-percha was removed from the root canal for post space preparation. Eighty-nine human canines were instrumented and obturated with gutta-percha and sealer to a standardized working length of 15 mm. An 11-mm segment of gutta-percha was removed from the roots in each of the four experimental groups of 20 teeth to simulate post space preparation. The teeth were immersed in India ink for 7 days and rendered transparent. The extent of linear dye leakage was measured with a stereomicroscope. There was no statistically significant difference in linear dye leakage among any of the experimental groups when 4 mm of gutta-percha remained.     

Inhibitory effect of pregnancy on counterregulatory hormone responses to hypoglycemia in awake rat

Intensive insulin treatment during diabetic pregnancy is complicated by maternal hypoglycemia. To investigate whether pregnancy may contribute as an independent hypoglycemia risk factor, awake pregnant rats that were near term underwent stepped insulin hypoglycemic (3.4 and 2.3 mM) clamp studies in the fasted and nonfasted states. In the fasted state, the glucagon response to hypoglycemia was completely suppressed in the pregnant rats (P < 0.01). Epinephrine, but not norepinephrine, was also diminished by approximately 70-75% at both hypoglycemic steps, and more exogenous glucose was needed to maintain hypoglycemia during pregnancy. To avoid the potential confounding effect of increased ketone levels (beta-hydroxybutyrate was approximately 170% higher in the pregnant rats), experiments were repeated in the nonfasting state when ketosis was eliminated in both groups. The nonfasted pregnant rats continued to show near complete suppression of the glucagon response, even at glucose levels of 2.3 mM. In contrast, a brisk response occurred in nonpregnant controls when glucose fell to 3.4 mM. Although epinephrine levels in the pregnant rats were also markedly suppressed during the milder hypoglycemic stimulus, they approached values seen in nonpregnant controls when glucose was lowered further to 2.3 mM. We concluded that in the rat, pregnancy markedly suppresses glucagon responses to hypoglycemia. The release of epinephrine, but not norepinephrine, is also blunted, especially during mild hypoglycemia. These findings suggest that pregnancy may impair glucose counterregulation by inhibiting glucagon and epinephrine release during hypoglycemia.     

Intracellular cations and hypertension in blacks

OBJECTIVE: To evaluate the effectiveness of a fetal monitoring education program in increasing nurses' knowledge and clinical skills. DESIGN: Multicenter randomized control trial. SETTING: Twelve hospitals in eastern Ontario, Canada. PARTICIPANTS: One hundred nine volunteer registered nurses randomly assigned, within each hospital, to an experimental (n = 47) or control (n = 62) group. Ninety-six nurses (40 in the experimental group and 56 in the control group) completed the 6-month follow-up (88% retention). INTERVENTIONS: The experimental group participated in a 1-day fetal monitoring workshop and a review session 6 months later. MAIN OUTCOME MEASURES: Performance on a 45-item knowledge test and a 25-item skills checklist. The passing score was at least 75% correct on each test. RESULTS: The percentage of nurses in the experimental group passing both the knowledge and the clinical skills tests after the workshop was significantly higher (p < 0.01) than that of the nurses in the control group: 68.1% versus 6.5%, respectively. A large difference between the groups remained at the 6-month follow-up (experimental, 45%; control, 6.5%). The performance of the nurses in the experimental group improved to an 85% pass rate after they attended the 6-month review session. CONCLUSION: This comprehensive, research-based program is effective in increasing fetal monitoring knowledge and clinical skills.     

Fetal branch pulmonary arterial vascular impedance during the second half of pregnancy

OBJECTIVE: Our purpose was to establish normal physiologic parameters in the fetal proximal and distal branch pulmonary arterial vascular impedance during the second half of pregnancy and to analyze relationships between proximal and distal pulmonary arterial blood velocity waveforms. STUDY DESIGN: In this cross-sectional study 100 uncomplicated singleton pregnancies were studied by pulsed color Doppler techniques between 18 and 41 weeks of gestation (median 30 weeks). Both right and left proximal (immediately after the bifurcation of the main pulmonary artery) and distal (beyond the first bifurcation of the branch pulmonary artery) pulmonary artery blood velocity waveforms were recorded and pulsatility index values were calculated. Peak systolic velocities and time-to-peak-velocity intervals were measured. Time-to-peak-velocity intervals were also analyzed at the level of aortic and pulmonary valves and at the ductus arteriosus. Right and left pulmonary artery diameters and right lung length were measured. RESULTS: In both right and left proximal and distal pulmonary arteries pulsatility index values decreased (p < 0.0001) and the peak systolic velocities (p < 0.003) and time-to-peak-velocity intervals (p < 0.0001) increased during the second half of pregnancy. In the proximal pulmonary arteries the pulsatility index values decreased linearly until 34 to 35 weeks of gestation and in the distal pulmonary arteries until 31 weeks of gestation. Thereafter they remained unchanged. In pulmonary arteries time-to-peak-velocity intervals were shorter (p < 0.01) than at the pulmonary valve level. There were no significant differences between the right or left pulmonary arteries in the pulsatility index values, peak systolic velocities, time-to-peak-velocity intervals, or pulmonary artery diameters. In the proximal pulmonary arteries the pulsatility index values (p < 0.02) and peak systolic velocities (p < 0.0001) were higher and time-to-peak-velocity intervals (p < 0.0001) were longer than in the distal pulmonary arteries. There was a 2.5-fold increase in pulmonary artery diameters and right lung length. CONCLUSIONS: Fetal branch pulmonary arterial vascular impedance decreases significantly during the second half of pregnancy. The linear decrease in vascular impedance during the second trimester and in the beginning of the third trimester may be related to the growth of the lung and the increase in the number of resistance vessels. During the latter part of the third trimester pulmonary vascular impedance does not decrease further.