Insulinomimetic effect on glucose transport by epidermal growth factor when combined with a major histocompatibility complex class I-derived peptide

Peptides derived from the alpha 1-region of the murine H-2Dk molecule enhance glucose uptake in rat adipose cells above the maximum obtained with insulin stimulation alone (Stagsted, J., Reaven, G. M., Hansen, T., Goldstein, A., and Olsson, L. (1990) Cell 62, 297-307). We now describe that epidermal growth factor (EGF) in combination with the same peptides, Dk-(61-85) and Dk-(62-85), stimulates cellular glucose uptake 5-7 times over the basal level, i.e. to 30-50% of the maximal insulin effect. EGF alone increased glucose uptake by only approximately 50% above basal and the peptide alone by 100% above basal. Maximal effect of EGF and peptide was reached in 10-20 min with 30 microM peptide (EC50 10-15 microM) and 50 nM EGF (EC50 1-2 nM). The effect of EGF and peptide on glucose uptake was additive to that of insulin and peptide until the maximal level attained with insulin and peptide was reached. The combined effect of EGF plus peptide on glucose transport was associated with a recruitment of GLUT4 molecules to the plasma membrane. However, the phosphatidylinositol (PI) kinase which is activated by insulin was not activated by EGF plus peptide. Thus, the effect of EGF plus peptide on glucose uptake seems independent of the activity status of the insulin receptor. 125I-Labeled EGF bound specifically to rat adipose cells with an apparent affinity of approximately 2 nM and Bmax approximately 5 x 10(3). However, the major histocompatibility complex (MHC) peptides did not affect EGF-stimulated internalization of EGF receptor, in contrast to their effect on the insulin receptors. Transforming growth factor alpha had an effect similar to EGF on glucose uptake. Three other peptides derived from other parts of murine MHC class I had no effect on glucose uptake in combination with EGF. Thus, EGF in combination with certain MHC class I-derived peptides is insulinomimetic concerning glucose transport and this effect is independent of the insulin receptor activity.     

A cost comparison of balloon angioplasty and stenting versus endarterectomy for the treatment of carotid artery stenosis

PURPOSE: Percutaneous transluminal angioplasty with stenting (PTAS) of the carotid artery has been advocated as an alternative treatment for high-grade stenosis. Rationale for this approach includes less morbidity, shorter recovery, and lower cost when compared with carotid endarterectomy (CEA). METHODS: The clinical results and hospital charges of patients who underwent elective treatment for carotid stenosis were reviewed. During a concurrent 14-month period, 218 patients were admitted 229 times for 234 procedures for the treatment of 239 carotid bifurcation stenoses, 109 by PTAS and 130 by CEA. Hospital charges were reviewed for each hospitalization and were categorized according to radiology, operating room, cardiac catheterization laboratory, and all other hospital charges. RESULTS: The combined incidence of postprocedure strokes and deaths were: PTAS, eight strokes (7.7%) and one death (0.9%); CEA, two strokes (1.5%) and two deaths (1.5%). Total hospital charges per admission for the two groups were $30,140 for PTAS and $21,670 for CEA. The average postprocedure length of stay for PTAS was 2.9 days (median, 2 days) and for CEA was 3.1 days (median, 3 days). Cardiac catheterization laboratory charges for the PTAS group were $12,968, whereas the operating room charges for the CEA group were $4263. When hospitalizations that were extended by complications were excluded, the average total charges for the PTAS group (n = 84) dropped to $24,848 (mean length of stay, 1.9 days) and for the CEA group (n = 111) to $19,247 (mean length of stay, 2.6 days). CONCLUSIONS: After evaluating hospital charges, PTAS for the treatment of carotid stenosis cannot currently be justified on the basis of reduced costs alone. With future cost-containing measures, total hospital charges can be reduced in both groups.     

Trends and variations in neonatal length of in-hospital stay in Canada

The objectives of this study were to evaluate the possible mechanisms involved in prolongation of bleeding time in pre-eclamptic patients receiving a magnesium sulfate infusion to prevent convulsions. Eighteen pre-eclamptic patients near term or at term (4 cases 33 to 35 weeks; the remainder > 36 weeks) were studied. Fifteen of them received magnesium sulfate infusion; 3 did not and served as controls. Bleeding time (modified Ivy method with Surgicutt), platelet count, platelet aggregation pattern, as well as serum arachidonic acid metabolites [thromboxane B2 (TxB2) and 6-Keto-prostaglandin F1 alpha (6-Keto-PGF1 alpha)] werde done on admission to the labor floor (before magnesium infusion) and repeated at discontinuation of the infusion, 12-24 hours postpartum; the controls received the second test 24 hours postpartum. Thirteen of 15 patients receiving magnesium sulfate had an increase in bleeding time from an average of 6 minutes 31 seconds to 11 minutes 56 seconds, an 82% rise (p < 0.004). In 2 there was a decrease. Among the 3 controls the averages were 6 minutes 38 seconds and 6 minutes 3 seconds. The total magnesium given ranged from 52.5 to 145 grams. Platelet counts averaged 251,000/mm3 (range 145,000-519,000). Platelet aggregation pattern done in 11 patients and was normal and unchanged after magnesium in 10 of the patients with increased bleeding time and one control. TxB2 and 6-Keto-PGF1 alpha levels did not change significantly either after magnesium administration (688 and 135 pgm/ml, to 654 and 117) or in controls (695 and 230 pgm/ml, to 445 and 225). Likewise, the ratio of these 2 substances did not change in either group (6.3 to 6.6, and 4.2 to 2.2). There was no correlation between duration of infusion or total magnesium given and directions of small changes observed. This study confirms a prior preliminary observation that magnesium sulfate infusion, as currently used to prevent eclamptic convulsions, induces a significant prolongation of bleeding time. This effect is mediated neither by changes in platelets count or aggregation pattern, nor by changing the level or ratios of serum arachidonic acid metabolites (TxB2 and 6-Keto-PGF1 alpha). Further studies are needed to clarify the mechanism of this clinically important observation of increased bleeding following magnesium sulfate infusion.     

Lorazepam-valproate interaction: studies in normal subjects and isolated perfused rat liver

Valproate (VPA) has been shown to interact with all the major antiepileptic drugs (AEDs) through two mechanisms of action: displacement from albumin binding sites and inhibition of drug metabolism. More recently, evidence showed that VPA inhibits the elimination of drugs metabolized by glucuronide conjugation. Lorazepam (LZP), which is primarily eliminated by conjugation with glucuronic acid, is administered concurrently with VPA both in treatment of epilepsy and in patients treated with VPA for psychiatric disorders. Therefore, a significant drug interaction is likely. We investigated such interaction both in in vitro isolated perfused rat liver (IPRL) and in normal subjects. LZP [2 mg, intravenous (i.v.) bolus] was administered to 8 normal volunteers before and after chronic dosing with VPA. In 6 of 8 subjects, VPA significantly decreased LZP plasma clearance by an average of 40% (p < 0.05) and increased LZP concentrations by decreasing formation clearance of the LZP glucuronide. In the IPRL studies, VPA also significantly decreased formation of LZP glucuronide (from 0.72 +/- 0.14 to 0.22 +/- 0.15 ml/h/kg, p < 0.05), indicating that IPRL is a useful tool for evaluation of the effect of VPA on drugs eliminated by glucuronide conjugation.     

Enhancing echo cancellation via estimation of delay

The advent of packetized audio transmission, such as voice over IP (VoIP), has resulted in challenging requirements for echo cancellation technology. One key aspect of this technology is the need to characterize, quickly and accurately, the echo paths in the transmission media. Echo paths consist of a constant time delay with no echo signal and active regions in which the echo signal is present. When an adaptive filter echo cancellation algorithm is used, its performance can be greatly increased, and its complexity can be reduced if it is only applied to the active regions. This requires an algorithm to estimate the constant delay and locate the active regions. Traditionally, delay estimation has been based on direct application of cross-correlation. This method has poor performance because the input signals are highly correlated and has a high implementation cost because many cross-correlation lags have to be computed for longer time delays. The delay estimation addressed in this paper has two major advantages over the traditional methods. The first is that it has improved performance because the input signals are processed to have less correlation. The second is that the implementation cost is significantly reduced because fewer cross-correlation lags are computed, and an efficient method to estimate lags is created.     

Human interface: a case study

Complex instruments, even those used only by "gurus" still need reasonable human interfaces. There are elements that need to be considered in any interface: consistency, intuitiveness, obviousness, utility, and ease of use. Even "gurus" shouldn't have to learn the ins and outs of strange operations; most of them probably don't want to learn it, either. Their focus is to use the instrument, not to become an expert on it. This article discusses a case study on human interfaces in instruments.     

"What is in a word? No versus Yes differentially engage the lateral orbitofrontal cortex": Correction.

Reports an error in "What is in a word? No versus Yes differentially engage the lateral orbitofrontal cortex" by Nelly Alia-Klein, Rita Z. Goldstein, Dardo Tomasi, Lei Zhang, Stephanie Fagin-Jones, Frank Telang, Gene-Jack Wang, Joanna S. Fowler and Nora D. Volkow (Emotion, 2007[Aug], Vol 7[3], 649-659). The supplemental materials link should appear as follows: http://dx.doi.org/10.1037/1528-3542.7.3.649.supp. (The following abstract of the original article appeared in record 2007-11660-018.) The words "No" and "Yes" are involved in conditioning to prohibit or encourage behavior, respectively. The authors, therefore, hypothesized that these words would be attributed to endogenous valence, activating neuronal circuits involved with valence and emotional control. Functional MRI (fMRI) at 4 Tesla was used to record regional brain activity while participants were exposed to emphatic vocalizations of the words. Results showed that No and Yes were associated with opposite brain-behavior responses; while No was negatively valenced, produced slower response times, and evoked a negative signal in the right lateral orbitofrontal cortex (OFC), Yes was positively valenced, produced faster response times, and evoked a positive signal in a contiguous region of the OFC. Attribution of negative valence to No and trait anger control were associated with increased responsivity of the OFC to No. Inasmuch as sensitivity to the prohibitive command No develops during childhood through interaction with primary caregivers as the first social objects, our findings may implicate the lateral OFC in the neurobiology of emotion regulation and subsequent social development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)