Detection of modafinil in human urine by gas chromatography-mass spectrometry

The main purpose of this study was to detect and quantify modafinil in human urine by gas chromatography–mass spectrometry (GC–MS). Urinary samples were collected from three healthy male volunteers following oral administration of a clinical dose (100 mg) of modafinil (Provigil^®). Urine specimens were extracted with t-butylmethyl ether (TBME) prior to GC–MS analysis. The results demonstrate that the chromatographic characteristics and the mass spectrum of the unchanged parent drug extracted from urine samples were identical to that obtained from the authentic standard. The times for the unchanged modafinil to reach peak concentration in the urine of the three volunteers were at 2 h (6.14 μg/mL), 4 h (9.93 μg/mL) and 8 h (3.58 μg/mL), respectively. Total clearance occurred in approximately 48–72 h with 2–5% eliminated through urine as unchanged modafinil. The present study demonstrates that modafinil is detectable in the absence of hydrolysis and derivatization steps.     

CD44 crosslinking-mediated matrix metalloproteinase-9 relocation in breast tumor cells leads to enhanced metastasis

CD44 plays a major role in multiple physiological processes, including cell-cell adhesion, cell-substrate interaction, lymphocyte homing, and tumor metastasis. It has been reported that highly expressed CD44 in certain types of tumors is associated with the hematogenic spread of tumor cells. The ability of CD44 to bind hyaluronan has been shown to correlate with tumor cell invasiveness, and it is likely that this ability may enhance tumor cell migration at several points during metastasis. However, the mechanism as to how CD44 stimulates metastasis remains unknown. The human breast tumor cell line, MDA-MB-435s, was used to investigate the effect of antibody-mediated CD44 crosslinking on the cellular level and localization of matrix metalloproteinase-9 (MMP-9). Confocal microscopy and immunocytochemical analyses were performed to demonstrate colocalization of CD44 and MMP-9 after CD44 crosslinking. Furthermore, the CD44-MMP-9 complex was purified by immunoprecipitation. G8 myoblast monolayers were employed to evaluate the invasiveness of human breast tumor cells after CD44 crosslinking in the presence or absence of protease inhibitors. CD44 crosslinking augmented the level of MMP-9 in the membrane of human breast tumor cells and clustering of CD44 serves as an MMP-9 docking molecule allowing MMP-9 to retain its concentrated proteolytic activity on the cell surface. Furthermore, crosslinking of CD44 enhances the ability of breast tumor cells to invade G8 myoblast monolayers and migrate through the basal membranes which was inhibited in the presence of anti-MMP-9 antibody or the MMP inhibitors GM6001 or 1,10-phenanthroline. This study demonstrates for the first time that CD44 crosslinking leads to an enhanced level and relocation of MMP-9 in human breast tumor cells accompanied by increased tumor invasion and metastasis.     

Leptin effects on food and water intake in lines of chickens selected for high or low body weight

There is an association between autonomic nervous system output and obesity. The sympathetic nervous system stimulates lipid metabolism and regulates food intake and, hence, body weight. Leptin, produced by adipocytes in proportion to their size, has been shown to directly stimulate the satiety center. In the experiment reported here, food and water intake were compared after intracerebroventricular administration of human recombinant leptin to lines of chickens that had undergone divergent selection for over 45 generations from a common White Rock base population for high (HWS) or low (LWS) body weight at 8 weeks-of-age. Leptin caused a linear decrease in food intake in chickens from the LWS line whereas no effect was observed in those from the HWS line. The HWS chickens tended to have reduced water intake post leptin administration. Others reported that leptin decreased food intake in both broiler and Leghorn chickens. Leptin concentration in the central nervous system may not contribute directly to the difference of body weight between HWS and LWS chickens.     

Effects of 16, 16-dimethyl prostaglandin E2 on alkaline secretion in isolated canine gastric mucosa

An isolated fundic mucosal preparation of dog stomach which is capable of exhibiting an alkaline secretion is described. A stable secretion was established 40 min to 1 hr after the mucosa was pretreated with the H₂-antagonist cimetidine to block spontaneous acid output. Alkaline secretion decreased when Ca²⁺ was removed from the nutrient solution. This secretion was stimulated by dibutyryl cyclic GMP, but was not altered by acetylcholine, carbachol, or 16,16-dimethyl PGE₂. Alkaline secretion from a similar antral mucosal preparation was stimulated by 16,16-dimethyl PGE₂. We conclude that the 16,16-dimethyl PGE₂-stimulated bicarbonate secretion previously demonstrated inin vivo canine fundic mucosa is not the result of a direct effect of PG on gastric mucosal cells and that an intact blood circulation or cholinergic innervation is required for this action to occur.     

Success of Maternal and Child Health Pipeline Training Programs: Alumni Survey Results

Maternal and Child Health Journal - The Maternal and Child Health (MCH) Pipeline Training Program, promotes development of a diverse health workforce by training undergraduate students from...     

Aerosol delivery to non-ventilated infants by metered dose inhaler: Should a valved spacer be used?

In a randomized double-blind cross-over study on 20 spontaneously breathing, oxygen-dependent preterm infants who had received positive pressure ventilation for respiratory distress syndrome, we tested the hypothesis that the one-way non-rebreathing valves of aerosol spacer devices might impair rather than enhance the delivery of aerosols to small infants by metered dose inhalers (MDI). Ten infants were given 2 doses (200 μg/dose) of MDI albuterol through a neonatal Aerochamber® 4 h apart. At random sequence, one dose was delivered with the non-rebreathing valve of the Aerochamber® in place; for the other dose, the valve had been removed. The experiment was repeated on another ten infants using a different spacer device (Babyhaler®) with or without its one-way inspiratory valve removed. During the first hour following aerosol administration, use of the non-valved spacers was associated with a significantly greater degree of tachycardia in both groups, and also lower transcutaneous carbon dioxide tension in the Aerochamber® group. All infants showed a reduction in respiratory system resistance and an improvement in functional residual capacity following albuterol treatment. In both groups, maximum reduction in respiratory system resistance, recorded 30 min after aerosol delivery, was significantly greater following the use of the non-valved spacers (Aerochamber®: 51.2 ± 3.1% vs. 35.0 ± 2.8%, P < 0.0001; Babyhaler®: 38.8 ± 2.3% vs. 19.2 ± 1.4%, P < 0.0001) than following the use of the spacers with a valve. The findings provide indirect evidence supporting our hypothesis and suggest that when the MDI is used to deliver therapeutic aerosols to non-ventilated newborns or small infants, a spacer device without a non-rebreathing valve should be used. Pediatr. Pulmonol. 1997; 24:204–212. © 1997 Wiley-Liss, Inc.     

Polymorphisms at the LDLR locus may be associated with ischemic cerebrovascular disease independent of lipid profile

The low-density lipoprotein receptor (LDLR) gene has been reported to be associated with cerebral infarction. This study aimed to explore 2 genetic LDLR variants, rs688 and rs5925, for their potential roles in cerebral infarction. This genetic association study was conducted within an isolated Taiwanese population; 815 ischemic stroke patients (431 with atherothrombotic stroke and 384 with lacunar infarction) and 430 normal controls were enrolled. There was no significant difference in the genetic frequency of rs688 and rs5925 between the control group and overall ischemic stroke, atherothrombotic stroke, or lacunar infarct groups. However, when analyzing the association between the haplotypes related to rs688 and rs5925 and cerebral ischemic stroke, the most common haplotype allele CT was used as the reference allele, and the haplotype TC associated with a 65% increased risk of overall ischemic stroke, 72% increased risk of atherothrombotic stroke, and 70% increased risk of lacunar infarction; this indicated a synergistic effect between these 2 single-nucleotide polymorphisms. The LDLR analysis based on the haplotypes rs688 and rs5925 was conducted in a Taiwanese population and provided preliminary evidence suggesting that genetic polymorphisms of LDLR are associated with cerebral infarction.     

Measurement of foot placement and its variability with inertial sensors

Gait parameters such as stride length, width, and period, as well as their respective variabilities, are widely used as indicators of mobility and walking function. Foot placement and its variability have thus been applied in areas such as aging, fall risk, spinal cord injury, diabetic neuropathy, and neurological conditions. But a drawback is that these measures are presently best obtained with specialized laboratory equipment such as motion capture systems and instrumented walkways, which may not be available in many clinics and certainly not during daily activities. One alternative is to fix inertial measurement units (IMUs) to the feet or body to gather motion data. However, few existing methods measure foot placement directly, due to drift associated with inertial data. We developed a method to measure stride-to-stride foot placement in unconstrained environments, and tested whether it can accurately quantify gait parameters over long walking distances. The method uses ground contact conditions to correct for drift, and state estimation algorithms to improve estimation of angular orientation. We tested the method with healthy adults walking over-ground, averaging 93 steps per trial, using a mobile motion capture system to provide reference data. We found IMU estimates of mean stride length and duration within 1% of motion capture, and standard deviations of length and width within 4% of motion capture. Step width cannot be directly estimated by IMUs, although lateral stride variability can. Inertial sensors measure walks over arbitrary distances, yielding estimates with good statistical confidence. Gait can thus be measured in a variety of environments, and even applied to long-term monitoring of everyday walking.