Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C NMR of urinary menthol glucuronide.

Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose. Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin-coupled multiplet components within each (13)C resonance by (13)C NMR. The [U-(13)C]glucuronide isotopomer derived via direct pathway conversion of [U-(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway metabolism of [U-(13)C]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C-isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.     

The multiple drug resistance gene,MDR1: Expression at the protein and RNA levels

A comparison of three different approaches to detect MDR₁ expression in myeloid leukemia cells was undertaken. With respect to the 4 different antibodies studied, a high proportion of false positive reactions were detected. Substantial discordance between MDR₁ expression as indicated by Northern blot analysis, PCR, and immunohistochemistry was found. These findings complicate the clinical interpretation of data derived from these methods.     

Motor vehicle rollover and static stability: an exposure study.

OBJECTIVES: This study examined vehicle rollovers in terms of site-specific exposure and speeds of vehicles of varying stability. METHODS: Fifty-one rollover sites in two states were visited at the same time of day and day of week as the rollover. A sample of vehicles moving in the same direction as the rollover were observed, and vehicle-specific data were obtained from identification numbers. RESULTS: Low stability, exacerbated by the addition of passengers, increased the risk of rollover. Speed was not correlated with stability and is not a confounder. CONCLUSIONS: Rollovers could be substantially reduced if motor vehicles were manufactured with a static stability of 1.2 or greater.     

Effects of 1-week head-down tilt bed rest on bone formation and the calcium endocrine system.

To understand the potential early responses of human bone and the calcium endocrine system to spaceflight, we studied 8 healthy men, aged 35-44 years before, during, and after bed rest in a -6 degrees head-down tilt model for microgravity. Based on a novel single-dose labeling schedule, average rates of bone formation in the iliac crest were reduced in 6, unchanged in 1, and increased in 1 following the bed rest period. The decrease was greatest for subjects whose daily walking miles were highest (r = -0.762, p less than 0.05, n = 7). Before a measurable increase in ionized serum calcium the sixth bed rest day, there was increased excretion of urinary calcium and sodium, evident the first 2 bed-rest days and parallel for the entire week (r = 0.92, p less than 0.001). Reduced excretion of phosphorus and 3', 5' cyclic adenosine monophosphate on the first and second bed rest days was followed by an increase in serum phosphorus by the sixth bed rest day. Depressed serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D were manifest by the sixth and seventh bed rest days. The similarity of the response of bone and the calcium endocrine system of healthy men after only 7 days to results of longer term bed rest studies emphasizes the responsiveness of the adult human skeleton to biomechanical stimuli induced by changes in activity and/or position.     

The efficacy of nasal septal surgery.

Nasal septal deformity is a frequent clinical entity, and septoplasty comprises one of the most common procedures performed by otolaryngologists today. Its efficacy seems intuitive, however the literature reveals relatively few papers confirming its utility. In this study, all patients undergoing septal reconstruction (excluding septorhinoplasty) at three major teaching hospitals in Vancouver during the years 1988 to 1990 were reviewed retrospectively in a two-pronged study. Information was collected concerning symptoms, physical findings and surgical technique. In the second phase, patients were contacted by telephone in a blinded fashion. Data was collected concerning patient satisfaction regarding various parameters including initial and ultimate symptom resolution, acceptance of nasal packing and postoperative complications. The following conclusions may be drawn: 1) Septoplasty was successful in relieving nasal obstruction in 70.5% of patients. 2) Turbinate surgery including outfracturing appears to significantly improve the outcome of surgery. 3) Rhinitis, including allergy, congestion, postnasal drip and rhinorrhea did not significantly affect success in relieving nasal obstruction. 4) Nasal packing did not significantly affect the outcome, but was the most frequently complained of aspect of the surgery. Therefore, we do not feel nasal packing is necessary.     

NMDA Receptor Activation Triggers Voltage Oscillations, Plateau Potentials and Burstinq in Neonatal Rat Lumbar Motoneurons ln Vitro

Whole-cell recordings of lumbar motoneurons in the intact neonatal rat spinal cord in vitro were undertaken to examine the effects of Kmethyl-D-aspartate (NMDA) receptor activation on membrane behaviour. Bath application of NMDA induced rhythmic voltage oscillations of 5.9 ± 2.1 mV (SD) at a frequency of 4.4 ± 1.5 Hz. Amplitude, but not frequency, of the voltage oscillations was membrane potential-dependent. Voltage oscillations could recruit action potentials and/or plateau potentials with or without superimposed bursting. Blockade of synaptic transmission with tetrodotoxin (TTX) sometimes resulted in a loss of oscillatory activity which could then be restored by increasing the NMDA concentration. After application of TTX, the trajectory of NMDA-induced oscillations was similar to the trajectory induced in the presence of intact synaptic networks, although the mean oscillation duration was longer and the oscillation frequency was slower (1.8 ± 1.1 Hz). Current ramps delivered after bath application of NMDA demonstrated bistable membrane properties which may underlie the plateau potentials. Injection of intracellular current pulses could initiate, entrain and terminate individual plateau potentials. The results suggest that membrane depolarization produced by oscillations may activate other intrinsic conductances which generate plateau potentials, thereby providing the neuron with enhanced voltage sensitivity, compared to that produced by NMDA receptor activation alone. These oscillatory events may have a role in the regulation of motor output in a variety of rhythmic behaviours including locomotion.     

The influence of continuous passive motion on outcome in total knee arthroplasty

All primary condylar total knee replacement arthroplasties (TKAs) performed from 1977 to 1984 at the authors' institution were divided into two groups based on the use of continuous passive motion (CPM) in the immediate postoperative period. The control group consisted of 73 patients who were treated with 95 TKAs without postoperative CPM. The average age was 65.4 years. The study group consisted of 38 patients who had 51 TKAs in which CPM was used postoperatively. The mean patient age was 62.8 years. The most common diagnoses in both groups were osteoarthritis and rheumatoid arthritis. Range of motion (ROM) was recorded preoperatively, at discharge, at three months, one year, two years, and at the last follow-up visit. There were no statistically significant differences in the ROM between the two groups at any of these time periods. At two years, the mean flexion and extension in the study group were 99 degrees and -4 degrees, respectively, compared to 103 degrees and -5 degrees in the control group. The average hospital stay was 11.2 days in the study group, whereas it was 15.1 days in control group. In the control group, there was one superficial infection, no deep infections, and four pulmonary emboli compared with three superficial infections, two deep infections, and no pulmonary emboli in the study group. There was no difference in the transfusion requirements between the two groups. CPM is advocated by the authors to help achieve discharge ROM earlier, but the protocol has been changed to begin CPM on the second postoperative day to allow the wound to stabilize.     

Cultural considerations for Canadians in the diagnosis of brain death

PURPOSE: This articles explores cultural perceptions and values related to brain death and organ donation from both a Western and non-Western perspective. SOURCE: Anthropological literature review of the historical concept of brain death in Canada using Eastern culture as a comparison. Principal findings: Although the concept of brain death and concomitant organ donation have become widely practiced in Western nations such as Canada, from a cross-cultural point of view these concepts and practices can be deeply troubling and may hold profoundly different meaning to people new to Canada. CONCLUSIONS: Canada has a deep commitment and obligation to respect diversity as reflected in the Canadian Charter of Rights and Freedoms. Therefore, healthcare workers have an obligation to respect cultural differences. To truly respect cultural differences we must first explore our own culturally formulated belief systems and then consider how our views may interface with other cultures. Our findings call for a greater analysis of the cultural influences on the concept of brain death and organ donation as a means of building a better understanding and respect for cultural diversity.     

The striatal-enriched protein tyrosine phosphatase gates long-term potentiation and fear memory in the lateral amygdala.

BACKGROUND: Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized. METHODS: Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation. RESULTS: STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala (LA) disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a biphasic activation of ERK1/2 in the LA with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning. CONCLUSIONS: Together, these data imply a role for STEP in experience-dependent plasticity and suggest that STEP modulates the activation of ERK1/2 during amygdala-dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as posttraumatic stress disorder (PTSD), panic, and anxiety disorders.