Arachidonic acid stimulates glucose uptake in 3T3-L1 adipocytes by increasing GLUT1 and GLUT4 levels at the plasma membrane: Evidence for involvement of lipoxygenase metabolites and peroxisome proliferator-activated receptor

Exposure of insulin-sensitive tissues to free fatty acids can impair glucose disposal through inhibition of carbohydrate oxidation and glucose transport. However, certain fatty acids and their derivatives can also act as endogenous ligands for peroxisome proliferator-activated receptor gamma (PPARgamma ), a nuclear receptor that positively modulates insulin sensitivity. To clarify the effects of externally delivered fatty acids on glucose uptake in an insulin-responsive cell type, we systematically examined the effects of a range of fatty acids on glucose uptake in 3T3-L1 adipocytes. Of the fatty acids examined, arachidonic acid (AA) had the greatest positive effects, significantly increasing basal and insulin-stimulated glucose uptake by 1.8- and 2-fold, respectively, with effects being maximal at 4 h at which time membrane phospholipid content of AA was markedly increased. The effects of AA were sensitive to the inhibition of protein synthesis but were unrelated to changes in membrane fluidity. AA had no effect on total cellular levels of glucose transporters, but significantly increased levels of GLUT1 and GLUT4 at the plasma membrane. While the effects of AA were insensitive to cyclooxygenase inhibition, the lipoxygenase inhibitor, nordihydroguaiaretic acid, substantially blocked the AA effect on basal glucose uptake. Furthermore, adenoviral expression of a dominant-negative PPARgamma mutant attenuated the AA potentiation of basal glucose uptake. Thus, AA potentiates basal and insulin-stimulated glucose uptake in 3T3-L1 adipocytes by a cyclooxygenase-independent mechanism that increases the levels of both GLUT1 and GLUT4 at the plasma membrane. These effects are at least partly dependent on de novo protein synthesis, an intact lipoxygenase pathway and the activation of PPARgamma with these pathways having a greater role in the absence than in the presence of insulin.

Estimation of body water compartments in cirrhosis by multiple-frequency bioelectrical-impedance analysis

Estimation of total body water by measuring bioelectrical impedance at a fixed frequency of 50 kHz is useful in assessing body composition in healthy populations. However, in cirrhosis, the distribution of total body water between the extracellular and intracellular compartments is of greater clinical importance. We report an evaluation of a new multiple-frequency bioelectrical-impedance analysis technique (MFBIA) that may quantify the distribution of total body water in cirrhosis. In 21 cirrhotic patients and 21 healthy control subjects, impedance to the Row of current was measured at frequencies ranging from 4 to 1012 kHz. These measurements were used to estimate body water compartments and then compared with total body water and extracellular water determined by isotope methodology. In cirrhotic patients, extracellular water and total body water (as determined by isotope methods) were well predicted by MFBIA (r = 0.73 and 0.89, respectively).;However, the 95% confidence intervals of the limits of agreement between MFBIA and the isotope methods were +/- 14% and +/-9% for cirrhotics (extracellular water and total body water, respectively) and +/-9% and +/-9% for cirrhotics without ascites. The 95% confidence intervals estimated from the control group were +/-10% and +/-5% for extracellular water and total body water, respectively. Thus, despite strong correlations between MFBIA and isotope measurements, the relatively large limits of agreement with accepted techniques suggest that the MFBIA technique requires further refinement before it can be routinely used to determine the nutritional assessment of individual cirrhotic patients. Nutrition 2001,17.31-34. (C)Elsevier Science Inc. 2001.

Effect of probe stimulus intensity on the dissociation between autonomic orienting and secondary probe reaction time

Information processing accounts propose that autonomic orienting reflects the amount of resources allocated to process a stimulus. However, secondary task reaction time (RT), a supposed measure of processing resources, has shown a dissociation from autonomic orienting. The present study tested the hypothesis that secondary task RT reflects a serial processing mechanism. Participants (N = 24) were presented with circle and ellipse shapes and asked to count the number of longer-than-usual presentations of one shape (task-relevant) and to ignore presentations of a second shape (task-irrelevant). Concurrent with the counting task, participants performed a secondary RT task to an auditory probe presented at either a high or low intensity and at two different probe positions following shape onset (50 and 300 ms). Electrodermal orienting was larger during task-relevant shapes than during task-irrelevant shapes, but secondary task RT to the high-intensity probe was slower during the latter. In addition, an underadditive interaction between probe stimulus intensity and probe position was found in secondary RT. The findings are consistent with a serial processing model of secondary RT and suggest that the notion of processing stages should be incorporated into current information-processing models of autonomic orienting.

Suppression of keratinocyte growth and differentiation by transforming growth factor beta 1 involves multiple signaling pathways

Transforming growth factor beta1 treatment of keratinocytes results in a suppression of differentiation, an induction of extracellular matrix production, and a suppression of growth. In this study we utilized markers specific for each of these functions to explore the signaling pathways involved in mediating these transforming-growth-factor-beta1-induced activities. In the first instance, we found that the induction of extracellular matrix production (characterized by 3TP-Lux reporter activity) was induced in both keratinocytes and a keratinocyte-derived carcinoma cell line, SCC25, in a dose-dependent manner. Furthermore, transforming growth factor beta1 also suppressed the differentiation-specific marker gene, transglutaminase type 1, in both keratinocytes and SCC25 cells. In contrast, transforming growth factor beta1 inhibited proliferation of keratinocytes but did not cause growth inhibition in the SCC25 cells. Transforming-growth-factor-beta1-induced growth inhibition of keratinocytes was characterized by decreases in DNA synthesis, accumulation of hypophosphorylated Rb, and the inhibition of the E2F:Rb-responsive promoter, cdc2, and an induction of the p21 promoter. When the negative regulator of transforming growth factor beta1 signaling, SMAD7, was overexpressed in keratinocytes it could prevent transforming-growth-factor-beta1-induced activation of the 3TP-Lux and the p21 promoter. SMAD7 could also prevent the suppression of the transglutaminase type 1 by transforming growth factor beta1 but it could not inhibit the repression of the cdc2 promoter. These data indicate that the induction of 3TP-Lux and p21 and the suppression of transglutaminase type 1 are mediated by a different proximate signaling pathway to that regulating the suppression of the cdc2 gene. Combined, these data indicate that the regulation of transforming growth factor beta1 actions are complex and involve multiple signaling pathways.

Early diagnosis of lymphedema using multiple frequency bioimpedance

Multiple frequency bioelectrical impedance analysis (MFBIA) has previously been shown to provide accurate relative measures of lymphedema in the upper limb of patients (1). This paper reports the results of a three year prospective study to evaluate the efficacy of MFBIA to predict the early onset of lymphedema in patients following treatment for breast cancer. Bioelectrical impedance measurements and circumferential measurements of each upper limb were recorded in healthy control subjects (n=60) to determine the normal range of the ratio (dominant/non-dominant) of extracellular and total limb volumes respectively. Patients undergoing surgery for the treatment of breast cancer were recruited as the study group; MFBIA and circumferential measurements were recorded pre-surgery, one month post-surgery and then at two month intervals for 24 months. One hundred and two patients were recruited into the study. Twenty patients developed lymphedema in the 24 months follow up period of this study. In each of these 20 cases MFBIA predicted the onset of the condition up to 10 months before the condition could be clinically diagnosed. Estimates of the sensitivity and specificity were both approximately 100%. At the time of detection by MFBIA, only one of the patients returned a positive test result from the total limb volumes determined from the circumferential measures. These results confirmed the suitability of the MFBIA technique as a reliable diagnostic procedure for the early detection of lymphedema.

Multiple impacts of the HIV/AIDS epidemic on the aged in rural Uganda

This paper reports research conducted among theaged residents of a rural, Southwestern Ugandanvillage. It documents their knowledge ofHIV/AIDS, their perceptions of their own riskof infection, and the multiple impacts of thecurrent HIV/AIDS epidemic on their lives. Mostolder individuals have a sound understanding ofthe sexual transmission of HIV, and someconsider themselves to be at risk of infectionthrough having multiple sexual partners. Theyattempt to limit their children's exposure toHIV, but many of these children have left thevillage to live in urban areas of relativelyhigh HIV prevalence. The loss of adult childrendeprives the aged of any support these childrenmight have provided as their parents'capabilities declined with advancing age.Female-headed households were more affected inthis way than were male-headed households. TheAIDS epidemic has increased the number ofburials taking place in the village, and theiraccumulated costs, both in time and money, andcreated new hardships for the aged, who alsohave to cope with grief that accompaniescontinuing deaths among their children andtheir contemporaries' children.

Using Theory to Understand the Multiple Determinants of Low Participation in Worksite Health Promotion Programs

Low participation at the employee or worksite level limits the potential public health impact of worksite-based interventions. Ecological models suggest that multiple levels of influence operate to determine participation patterns in worksite health promotion programs. Most investigations into the determinants of low participation study the intrapersonal, interpersonal, and institutional influences on employee participation. Community- and policy-level influences have not received attention, nor has consideration been given to worksite-level participation issues. The purpose of this article is to discuss one macrosocial theoretical perspective—political economy of health—that may guide practitioners and researchers interested in addressing the community- and policy-level determinants of participation in worksite health promotion programs. The authors argue that using theory to investigate the full spectrum of determinants offers a more complete range of intervention and research options for maximizing employee and worksite levels of participation.

Valproic acid has temporal variability in urinary clearance of metabolites

The reasons for the intra- and interindividual variability in the clearance of valproic acid (VPA) have not been completely characterized. The aim of this study was to examine day-night changes in the clearance of 3-oxo-valproate (3-oxo-VPA), 4-hydroxy-valproate (4-OH-VPA), and valproic acid glucuronides under steady state. Six diurnally active healthy male volunteers ingested 200 mg sodium valproate 12 hourly, at 0800 and 2000, for 28 days. On the last study day, two sequential 12-h urine samples were collected commencing at 2000 the evening before. Plasma samples were obtained at the end of each collection. Following alkaline hydrolysis, urine was analyzed for concentrations of VPA, 3-oxo-VPA, and 4-OH-VPA. A separate aliquot was assayed for creatinine (CR). The plasma concentrations of VPA, 3-oxo-VPA, 2-en-VPA, and CR were determined. The analysis of VPA and its metabolites was performed by CC-MS. There was an increase in plasma 3-oxo-VPA concentration at 0800, sampling as compared to 2000 sampling (p < .05). The urinary excretion of 3-oxo-VPA and VPA glucuronides were decreased between 2000 and 0800, compared to between 0800, and 2000, by 30% and 50% respectively (p < .05). These results indicate a nocturnal decrease in renal clearance of 3-oxo-VPA rather than a decrease in the beta -oxidation of VPA at night. These differences were not explained by differences between the sampling periods in CR excretion. These results indicate the importance of collecting samples of 24-h duration when studying metabolic profiles of VPA.

Multiple bifurcations in atom optics

We report the observation of multiple bifurcations in a nonlinear Hamiltionian system: laser-cooled atoms in a standing wave with single-frequency intensity modulation. We provide clear evidence of the occurrence of bifurcations by analyzing the atomic momentum distributions.

Fluorescence spectrum of a two-level atom driven by a multiple modulated field

We investigate the fluorescence spectrum of a two-level atom driven by a multiple amplitude-modulated field. The driving held is modeled as a polychromatic field composed of a strong central (resonant) component and a large number of symmetrically detuned sideband fields displaced from the central component by integer multiples of a constant detuning. Spectra obtained here differ qualitatively from those observed for a single pair of modulating fields [B. Blind, P.R. Fontana, and P. Thomann, J. Phys. B 13, 2717 (1980)]. In the case of a small number of the modulating fields, a multipeaked spectrum is obtained with the spectral features located at fixed frequencies that are independent of the number of modulating fields and their Rabi frequencies. As the number of the modulating fields increases, the spectrum ultimately evolves to the well-known Mellow triplet with the sidebands shifted from the central component by an effective Rabi frequency whose magnitude depends on the initial relative phases of the components of the driving held. For equal relative phases, the effective Rabi frequency of the driving field can be reduced to zero resulting in the disappearance of fluorescence spectrum, i.e., the atom can stop interacting with the field. When the central component and the modulating fields are 180 degrees out of phase, the spectrum retains its triplet structure with the sidebands located at frequencies equal to the sum of the Rabi frequencies of the component of the driving field. Moreover, we shaw that the frequency of spontaneous emission can be controlled and switched from one frequency to another when the Rabi frequency or initial phase of the modulating fields are varied.