Quantification of voriconazole in plasma by liquid chromatography-tandem mass spectrometry

A convenient liquid chromatography-tandem mass spectrometry method for the quantification of the triazole antifungal agent voriconazole in plasma samples is described. Fenbuconazole is used as an internal standard. After protein precipitation, automated solid-phase extraction is applied. Electrospray ionization in the positive mode is used and the following mass transitions are recorded: voriconazole, 350 -> 127; and fenbuconazol, 337 -> 125. The analytical run time is 4 min. The response was linear from 78 to 5000 mu g/L. The total coefficient of variation (n=16) was 12.6% for a low-concentration pool (143 mu g/L), 4.7% for a medium-concentration pool (419 mu g/L), and 5.0% for a high-concentration pool (4304 mu g/L). The method is proposed for future investigations that should be performed to test the hypothesis that therapeutic drug monitoring of voriconazole is clinically useful

Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine

These studies investigated the absorption and metabolic conversion of lisdexamfetamine dimesylate (LDX), a prodrug stimulant that requires conversion to d-amphetamine for activity. Oral absorption of LDX was assessed in rat portal and jugular blood, and perfusion of LDX into isolated intestinal segments of anesthetized rats was used to assess regional absorption. Carrier-mediated transport of LDX was investigated in Caco-2 cells and Chinese hamster ovary (CHO) cells expressing human peptide transporter-1 (PEPT1). LDX metabolism was studied in rat and human tissue homogenates and human blood fractions. LDX was approximately10-fold higher in portal blood versus systemic blood. LDX and d-amphetamine were detected in blood following perfusion of the rat small intestine but not the colon. Transport of LDX in Caco-2 cells had permeability apparently similar to cephalexin and was reduced with concurrent PEPT1 inhibitor. Affinity for PEPT1 was also demonstrated in PEPT1-transfected CHO cells. LDX metabolism occurred primarily in whole blood (rat and human), only with red blood cells. Slow hydrolysis in liver and kidney homogenates was probably due to residual blood. The carrier-mediated absorption of intact LDX, likely by the high-capacity PEPT1 transporter, and subsequent metabolism to d-amphetamine in a high-capacity system in blood (ie, red blood cells) may contribute to the consistent, reproducible pharmacokinetic profile of LDX

Eclosion

Eclosion is also a metaphor for my journey through Fashion Design, going through ups and downs in my schooling as I\u27ve learned, molded and refined my perspective as a designer

Electrothermal simulation of large-area semiconductor devices

The lateral charge transport in thin-film semiconductor devices is affected by the sheet resistance of the various layers. This may lead to a non-uniform current distribution across a large-area device resulting in inhomogeneous luminance, for example, as observed in organic light-emitting diodes. The resistive loss in electrical energy is converted into thermal energy via Joule heating, which results in a temperature increase inside the device. On the other hand, the charge transport properties of the device materials are also temperature-dependent, such that we are facing a two-way coupled electrothermal problem. It has been demonstrated that adding thermal effects to an electrical model significantly changes the results. We present a mathematical model for the steady-state distribution of the electric potential and of the temperature across one electrode of a large-area semiconductor device, as well as numerical solutions obtained using the finite element method

Specialization and Integration of Brain Responses to Object Recognition and Location Detection

Visual information in the brain is processed by two distinct pathways, the dorsal and the ventral visual streams, which operate in a parallel and distributed manner. While the dorsal stream, associated with locating objects in space, extends from the occipital towards the parietal lobe, the ventral stream, associated with recognizing objects, projects from occipital to the temporal lobes (Ungerleider & Mishkin, 1982). This division of labor evidenced from lesion studies in monkeys may be rather reductionistic in the context of humans where the experience-driven knowledge base is rich and may prompt neural integration (Mesalum, 2008). The present fMRI study investigated the specialization and integration of dorsal and ventral streams in eighteen healthy adult volunteers using two simple tasks of object recognition and location detection. The stimuli consisted of grays-cale photographs of common household objects presented in a blocked design format. In the object recognition task, the participants named an object from four choices, and in the location detection task, they located the position of a given object relative to a cross pre-sented on the screen. While the location detection task elicited greater activation in the dorsal visual stream (precuneus, right angular gyrus, superior parietal lobule), recognizing objects showed greater activation in several cortical (left inferior frontal gyrus) and subcortical (bilateral thalami) areas previously found to be associated with tasks of object recognition. Although there were no differences found in functional connectivity between the two tasks, we found preliminary evidence for a group of regions, such as frontal and parietal cortex, working together in this task. Overall, the results of this study indicate the existence of specialized modules for object recognition and location detection, and possible interactions between areas beyond the visual cortex that may play a role in such tasks

Imaging diagnosis: ultrasonographic appearance of small bowel metastasis from canine mammary carcinoma

A 10-year-old entire female Beagle dog was evaluated for an acute history of lethargy, anorexia, and diarrhea. Mammary tumors were detected during physical examination. Ultrasonographic scanning revealed the presence of a unique pattern of multiple, well-defined and well-marginated hypoechoic nodules in the muscularis layer of the jejunum. These nodules were not associated with changes in the rest of the normal intestinal layering and were not causing signs of intestinal obstruction. Mammary carcinoma metastases to the intestinal muscularis layer were diagnosed based on histopathological examination

Efficacy of lisdexamfetamine dimesylate throughout the day in children and adolescents with attention-deficit/hyperactivity disorder:results from a randomized, controlled trial

Lisdexamfetamine dimesylate (LDX) is a long-acting, prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder (ADHD). This randomized placebo-controlled trial of an optimized daily dose of LDX (30, 50 or 70 mg) was conducted in children and adolescents (aged 6–17 years) with ADHD. To evaluate the efficacy of LDX throughout the day, symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners’ Parent Rating Scale-Revised (CPRS-R) at 1000, 1400 and 1800 hours following early morning dosing (0700 hours). Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference treatment, but the study was not designed to support a statistical comparison between LDX and OROS-MPH. The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107). At baseline, CPRS-R total scores were similar across treatment groups. At endpoint, differences (active treatment − placebo) in least squares (LS) mean change from baseline CPRS-R total scores were statistically significant (P < 0.001) throughout the day for LDX (effect sizes: 1000 hours, 1.42; 1400 hours, 1.41; 1800 hours, 1.30) and OROS-MPH (effect sizes: 1000 hours, 1.04; 1400 hours, 0.98; 1800 hours, 0.92). Differences in LS mean change from baseline to endpoint were statistically significant (P < 0.001) for both active treatments in all four subscales of the CPRS-R (ADHD index, oppositional, hyperactivity and cognitive). In conclusion, improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening (1800 hours)

Adverse event reporting in studies of penetrating acupuncture during pregnancy: a systematic review

Background - Acupuncture within pregnancy has frequently been investigated, often with finding this to be more effective than standard care. However, the adverse event severity, types and occurrence are unclear. Objective - To investigate the quality of reporting adverse events and to attempt to identify occurrence, type and severity of adverse events in acupuncture and non-acupuncture groups. Results - Overall quality of reporting of adverse events was poor, with information describing the adverse events often lacking in detail. A number of trends were noted: adverse events occurring within a treatment session was 3%-17% in the acupuncture groups and 4-25% in the non-acupuncture groups. The percentage of women affected by an adverse event was between 14%-17% in the acupuncture groups and 15-19% in non-acupuncture groups. Conclusions - Adverse event reporting within acupuncture trials is generally poor. The trends noted were that adverse events do occur, but would appear to be largely minor and comparable to non-acupuncture related interventions