Stability of mycophenolate mofetil in an extemporaneously compounded oral liquid

The stability of mycophenolate mofetil in an extemporaneously prepared 100-mg/mL oral liquid was studied. The contents of 80 250-mg capsules of mycophenolate mofetil were combined with sterile water for irrigation and cherry-flavored syrup to produce 200 mL of suspension. Six 1-mL samples were analyzed immediately, and the rest of the suspension was poured into 12 2-oz amber polyethylene terephthalate [corrected] G(PETG) bottles; six bottles were stored at 23-25 degrees C and six at 2-8 degrees C. Samples were removed on days 14, 21, 28, 35, 49, 63, 92, and 121 for analysis by high-performance liquid chromatography; pH was measured initially and at each sampling time. The pH of the suspension was initially 6.1 and remained unchanged throughout the study. The suspension retained more than 90% of its initial drug concentration for 121 days at 23-25 and 2-8 degrees C. There was no detectable change in color or odor and no visible microbial growth in any sample. Mycophenolate mofetil in a 100-mg/mL oral liquid prepared with cherry-flavored vehicle and stored in amber PETG bottles was stable for 121 days at 23-25 and 2-8 degrees C.     

Ventricular pressure slope and bileaflet mechanical heart valve closure

The maximum left ventricular pressure slope (dP/dt) value has been used by several investigators as the criterion for studying mitral valve closure. In this article, the relationship between the ventricular pressure slope (dP/dt) and the leaflet closing behavior of bileaflet mechanical heart valves (BMV) is investigated. Two current BMVs, the St. Jude Medical 29 mm and CarboMedics 29 mm, installed in the mitral position of a mock circulatory pulsatile flow loop were used as the study model. Under simulated physiologic pressures and flow conditions, the experiment was conducted at 70, 90, and 120 beats/min with corresponding flow rates of 5.0, 6.0, and 7.5 liters/min, respectively. A laser sweeping technique was used to monitor the leaflet closing motion within the last 3 degrees excursion at valve closure. A modified dual beam laser sweeping technique system was used to register the difference of leaflet/housing impact time between the two BMV closing leaflets in asynchronous closure. Common BMV asynchronous closures were found in both BMVs at all three heart rates tested. The second closing leaflet was found to always close at higher velocity than the first. Simultaneous measurements of the ventricular pressure (Pv) and the leaflet closing time showed that Pv exhibited three stage characteristics. In the first stage, Pv gradually increased as the ventricle was filled. A sudden rise of Pv occurred immediately after closing of the first leaflet. The maximum dp/dt occurred in the third stage after closure of both BMV leaflets. The BMV closing behavior and the corresponding Pv pattern were found to depend strongly upon valve type and heart rate. The time averaged ventricular pressure slope (dp/dt) values at 70, 90, and 120 beats/min were about 40, 70, and 150 mmHg/sec for the St. Jude Medical valve and 40, 105, and 205 for the CarboMedics valve during the first closing stage. The maximum dp/dt values were 2670, 4350, and 5000 mmHg/sec for the St. Jude Medical valve and 1210, 2530, and 3210 mmHg/sec for the CarboMedics valve at the three heart rates tested, respectively. The study showed that the left ventricular pressure patterns (dP/dt) at valve closure were the result of valve operation under given driving conditions. The dp/dtmax cannot be used as the criterion for studying BMV closure.     

Glucagon-like peptide-1 can reverse the age-related decline in glucose tolerance in rats

Wistar rats develop glucose intolerance and have a diminished insulin response to glucose with age. The aim of this study was to investigate if these changes were reversible with glucagon-like peptide-1 (GLP-1), a peptide that we have previously shown could increase insulin mRNA and total insulin content in insulinoma cells. We infused 1.5 pmol/ kg-1.min-1 GLP-1 subcutaneously using ALZET microosmotic pumps into 22-mo-old Wistar rats for 48 h. Rat infused with either GLP-1 or saline were then subjected to an intraperitoneal glucose (1 g/kg body weight) tolerance test, 2 h after removing the pump. 15 min after the intraperitoneal glucose, GLP-1-treated animals had lower plasma glucose levels (9.04+/-0.92 mmol/liter, P < 0.01) than saline-treated animals (11.61+/-0.23 mmol/liter). At 30 min the plasma glucose was still lower in the GLP-1-treated animals (8.61+/-0.39 mmol/liter, P < 0.05) than saline-treated animals (10.36+/-0.43 mmol/liter). This decrease in glucose levels was reflected in the higher insulin levels attained in the GLP-1-treated animals (936+/-163 pmol/liter vs. 395+/-51 pmol/liter, GLP-1 vs. saline, respectively, P < 0.01), detected 15 min after glucose injection. GLP-1 treatment also increased pancreatic insulin, GLUT2, and glucokinase mRNA in the old rats. The effects of GLP-1 were abolished by simultaneous infusion of exendin [9-39], a specific antagonist of GLP-1. GLP-1 is therefore able to reverse some of the known defects that arise in the beta cell of the pancreas of Wistar rats, not only by increasing insulin secretion but also by inducing significant changes at the molecular level.     

Drug interactions in human neuropathic pain pharmacotherapy

The effects of 0.3 mg/kg methylphenidate (MPH) and expectancy regarding medication on the performance and task persistence of 60 boys with attention deficit hyperactivity disorder (ADHD) were investigated. In a balanced-placebo design, boys in 4 groups (received placebo/drug crossed with told placebo/drug) completed the task in success and failure conditions. Medication improved participants' task persistence following failure. Participants' task performance was not affected by whether they thought they had received medication or placebo. Children made internal attributions for success and made external attributions for failure, regardless of medication or expectancy. These findings confirm previous reports that it is the pharmacological activity of MPH that affects ADHD children's self-evaluations and persistence. The results contradict anecdotal reports that MPH causes dysfunctional attributions and confirm previous studies showing that medication does not produce adverse effects on the causal attributions of children with ADHD.     

Changes in mRNA for metabotropic glutamate receptors after transient cerebral ischaemia

Using a rat 4-vessel occlusion model of cerebral ischaemia we studied the changes in the mRNA level for the metabotropic receptor subtypes mGluR1 alpha, mGluR1 beta, mGluR2, mGluR3, mGluR4, and mGluR5 by means of in situ hybridization with oligonucleotides. After 24 hours of reperfusion the mRNA levels were significantly increased for mGluR2 and mGluR4 while it was significantly decreased for mGluR5. These results suggest that vulnerable neurones react to an increased extracellular glutamate concentration by differential regulation of the mRNA for metabotropic glutamate receptor subtypes which perhaps reflects the different pre- or postsynaptic location and different involvement in ischaemic neurodegeneration.     

Retinopathy in African Americans and whites with insulin-dependent diabetes mellitus

BACKGROUND: The development and progression of diabetic retinopathy in African Americans with insulin-dependent diabetes mellitus is not known. METHODS: Two hundred subjects with insulin-dependent diabetes mellitus with duration of diabetes 16 years or less at first visit were studied; 58 were African Americans and 142 were whites. All had gradable stereoscopic color fundus photographs (seven standard fields) from at least two visits (mean time between first and second visit was 4.1 years). Subjects with hemoglobinopathy or proliferative retinopathy or subjects who had evidence of treatment for proliferative retinopathy at first visit were excluded. Masked grading of photographs was conducted using the modified Airlie House classification scheme. RESULTS: African Americans were older, heavier, had higher systolic blood pressure (all P < .05), and marginally higher hemoglobin A1 (HbA1) values (P = .06) than the whites at first visit. African Americans had a lower rate of two steps or more progression from preexistent retinopathy (19%) than whites (43%). Progression to proliferative retinopathy or treatment was similar by race. Multivariate analysis predicting development oe progression of retinopathy, while controlling for length of follow-up, found higher HbA1 (odds ratio [OR] = 2.15), longer duration of insulin-dependent diabetes mellitus (OR = 1.69), higher serum creatinine concentration (OR = 1.59), and white race (OR = 2.62) to be independent risk factors. CONCLUSIONS: These data suggest a previously unsuspected reduction in the adjusted risk for development and progression of retinopathy in African Americans. The reason for this apparently reduced risk are not known.     

Pair-rule expression patterns of even-skipped are found in both short- and long-germ beetles

Now that the genes controlling embryonic patterning have been identified in several model organisms, long-standing questions concerning the evolution of developmental systems are open to investigation. Examination of the expression of even-skipped in a variety of insects reveals that Insect germ-type designations apparently do not reflect the variations in the mechanisms of segmentation evident throughout insect phylogeny.