Relation between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women

BACKGROUND: On the basis of observations in rodents, leptin is thought to play a key role in the regulation of energy expenditure and food intake, but less is known of its influence on ingestive behavior and energy balance in humans. OBJECTIVE: We examined the effect in women of a chronic energy deficit on plasma leptin concentrations and self-reported appetite and explored possible relations between leptin and appetite sensations. DESIGN: Twelve healthy women (body mass index, in kg/m2: 23-37) participated in a metabolic ward study in which 3 wk of neutral energy balance was followed by 12 wk of energy deficit (energy intake reduced by 2 MJ/d and energy expenditure increased by 0.8 MJ/d). Body weight and composition were monitored, fasting leptin concentrations were measured 4 times, and feelings of hunger, fullness, desire to eat, and prospective consumption were monitored hourly throughout the day on 7 selected days. RESULTS: Adiposity-adjusted leptin decreased by 54% after 1 wk of a moderate energy deficit and remained low after 6 and 12 wk. Leptin was associated with self-reported hunger, desire to eat, and prospective consumption (range of r: -0.6 to -0.7, P < 0.01). The greatest hunger increase coincided with the largest percentage drop in circulating leptin and the lowest final leptin concentration. The relation between leptin and hunger was not influenced by amount of weight or body fat loss. CONCLUSIONS: These findings support the idea that leptin is a physiologic regulator of hunger during energy deficits in humans; the role of leptin in the long-term regulation of food intake warrants further study.     

Minimum-phase calibration of sampling oscilloscopes

We describe an algorithm for determining the minimum phase of a linear time-invariant response function from its magnitude. The procedure is based on Kramers-Kronig relations in combination with auxiliary direct measurements of the desired phase response. We demonstrate that truncation of the Hilbert transform gives rise to large errors in estimated phase, but that these errors may be approximated using a small number of basis functions. As an example, we obtain a minimum-phase calibration of a sampling oscilloscope in the frequency domain. This result rests on data obtained by an electrooptic sampling (EOS) technique in combination with a swept-sine calibration procedure. The EOS technique yields magnitude and phase information over a broad bandwidth, yet has degraded uncertainty estimates from dc to approximately 1 GHz. The swept-sine procedure returns only the magnitude of the oscilloscope response function, yet may be performed on a fine frequency grid from about 1 MHz to several gigahertz. The resulting minimum-phase calibration spans frequencies from dc to 110 GHz, and is traceable to fundamental units. The validity of the minimum-phase character of the oscilloscope response function at frequencies common to both measurements is determined as part of our analysis. A full uncertainty analysis is provided.     

Review article: olestra and its gastrointestinal safety

Olestra is a fat substitute made from sucrose and vegetable oil. Olestra is neither digested nor absorbed, and therefore adds no calories or fat to the diet. Because the gut is the only organ that is exposed to olestra, the potential for olestra to affect gastrointestinal structure and function, and the absorption of nutrients from the gut, has been investigated. Histological evaluations performed after long-term feeding studies have shown no indications that olestra causes injury to the gastrointestinal mucosa. Olestra is not metabolized by the colonic microflora, and has no meaningful effects on the metabolic function of these organisms. Studies of gastrointestinal transit have shown that the consumption of olestra with food does not affect gastric emptying, or small or large bowel transit times. Olestra does not affect the absorption of macronutrients, water-soluble vitamins or minerals. It causes a dose-responsive decrease in the availability of the fat-soluble vitamins A, D, E and K; however, this potentially adverse effect is offset by the addition of vitamins to olestra-containing foods. Olestra has no consistent effect on the amount of total bile acids excreted in the faeces, and therefore probably has no significant effect on bile acid absorption. The occurrence of gastrointestinal symptoms, including diarrhoea, loose stools, gas and abdominal cramping, after consumption of olestra under ordinary snacking conditions is comparable to that following consumption of triglyceride-containing snacks.     

Regulation of Mg2+ homeostasis by insulin in perfused rat livers and isolated hepatocytes

Several recent studies demonstrate that adrenergic receptor stimulation evokes marked changes in Mg2+ homeostasis. As insulin counter-regulates many of the metabolic consequences of adrenergic receptor stimulation, we evaluated the potential influence of insulin on Mg2+ movements in response to adrenergic stimulation. The data demonstrate that insulin is able to block the Mg2+ efflux from perfused rat livers stimulated by isoproterenol or 8-Br-cAMP, but has little or no effect on epinephrine or phenylephrine induced Mg2+ efflux. Thus, evidence is provided demonstrating that there are redundant adrenergic pathways regulating Mg2+ efflux from liver tissue. One of these pathways, the beta-adrenergic component, is selectively blocked by insulin. Furthermore, these findings may provide a cellular explanation for hypomagnesemia associated with diabetes.     

Effect of noninvasive positive pressure ventilation on mortality in patients admitted with acute respiratory failure: a meta-analysis

Changes in angiogenesis and expression of extracellular matrix-degrading enzymes have been substantiated during progression of solid tumours, whereas information on haematological tumours remains circumstantial. In this study, 57 biopsies of mycosis fungoides (MF), a haematological tumour of T-cell lineage, were investigated immunohistochemically for the extent of angiogenesis, and by in situ hybridisation for the expression of matrix metalloproteinases 2 (MMP-2, collagenase A) and 9 (MMP-9, collagenase B). The biopsies we grouped according to the stage of progression: patch-->plaque-->nodular (most advanced). The extent of angiogenesis, as microvessel area, of MF lesions as a whole was significantly higher than that of normal uninjured skin, used as a control. When the stages of MF progression were compared, the values of MF patch stage overlapped that of control skin, while values were significantly higher in the plaque stage and even higher in the nodular stage. In these stages, microvessels were widely scattered in the tumour tissue, in close association with tumour cells, and they frequently displayed arborisation and microaneurysmatic dilation. In contrast, in the patch stage microvessels were irregularly distributed around the tumour aggregates, and arborisation or dilated structures were only rarely seen. The expression of MMP-2 and MMP-9 mRNAs underwent significant upregulation in relation to advancing stage. Indeed, the upstaging was significantly associated with higher proportions of lesions positive for each mRNA or for both, and with lesions with the greatest intensity of expression for each mRNA. Besides tumour cells, the MMP-2 mRNA was expressed by microvascular endothelial cells of intratumour and peri-tumour vessels, and by fibroblasts which were especially abundant in the stroma adjacent to the tumour nodules. The MMP-9 mRNA was found to be present in a subset of tissue macrophages which were more frequently located in close vicinity to the tumour nodules. In contrast, in control skin, a weak positivity for the MMP-2 mRNA in very few microvascular endothelial cells and no signal for the MMP-9 mRNA were observed. These in situ data suggest that angiogenesis and degradation of the extracellular matrix occur simultaneously during MF progression. They imply that interaction between tumour cells and their microvasculature are all the more likely to occur during progression, occasionally with the contribution of tumour-associated stromal cells.     

Factors contributing to the development of chronic rejection in heterotopic rat heart transplantation

To monitor the low back risk imposed by asymmetric postures at workplaces, a method using angular velocity sensors was studied. According to a simple model analysis, trunk rotation could be calculated from the angular velocities measured at both the waist and shoulder and from the inclination of each angular velocity sensor. We thus developed a new detector consisting of an angular velocity sensor (ENC-05D, Murata, Japan) for detecting angular velocity and an acceleration sensor (ADXL05, Analog Devices, USA) for measuring inclination. The precision of the angular velocity sensor was high as the correlation coefficient between the output of the sensor and the true value was 0.9996. When the detectors were affixed to a subject and compared with data measured by a Vicon System 370 (Oxford Metrics, UK), the correlation coefficients between the two methods were 0.949 and 0.815 during model tasks of box transfer and box lifting, respectively. In a model of lifting boxes at different rates, the mean and standard deviation increased according to the task speed. This method was shown to be of practical use for monitoring trunk rotation.     

Endothelial barrier dysfunction and oxidative stress: roles for nitric oxide?

Endothelial dysfunction has an important role to play in the pathophysiology of human vascular disease. The maintenance of barrier function is critical to the role of vascular endothelium in cardiovascular haemostasis and this function can be compromised by inflammatory mediators, cytokines or oxidants. Under conditions of oxidative stress a variety of reactive oxygen species (ROS) may be generated, which increase the permeability of the endothelial monolayer to fluid, macromolecules and inflammatory cells. The endothelium-derived nitric oxide radical (NO), whose physiological actions include effects on vascular smooth muscle, is normally inactivated by the superoxide radical anion. While large amounts of NO have cytotoxic potential, it is now becoming clear that combinations of NO with ROS can produce either cytotoxic or cytoprotective effects, depending on the relative amounts of each which are present in the target cell or its environment at a particular time. The contribution of NO to oxidant-mediated endothelial barrier dysfunction can be assessed in vitro in endothelial monolayers grown on porous membrane supports. In this model, using hydrogen peroxide (H2O2) as the oxidant, H2O2-induced losses of barrier function can be enhanced or partially offset by NO donor drugs, depending on the concentration of NO donor used. Furthermore, the injurious or cytoprotective effects of these agents appear to be determined by the quantity of NO generated. Since NO is administered clinically by inhalation in conditions such as pulmonary hypertension or the adult respiratory distress syndrome, which are themselves associated with generation of ROS, it is likely that low concentrations of NO may protect the pulmonary vascular endothelium while high concentrations might be expected to combine with ROS to yield intermediates capable of causing further endothelial injury or loss of barrier function.     

A humanized form of a CD4-specific monoclonal antibody exhibits decreased antigenicity and prolonged plasma half-life in rhesus monkeys while retaining its unique biological and antiviral properties

Certain monoclonal antibodies (MAbs) directed against CD4 can efficiently block HIV-1 replication in vitro. To explore CD4-directed passive immunotherapy for prevention or treatment of AIDS virus infection, we previously examined the biological activity of a nondepleting CD4-specific murine MAb, mu5A8. This MAb, specific for domain 2 of CD4, blocks HIV-1 replication at a post-gp120-CD4 binding step. When administered to normal rhesus monkeys, all CD4+ target cells were coated with antibody, yet no cell clearance or measurable immunosuppression occurred. However, strong anti-mouse Ig responses rapidly developed in all monkeys. In the present study, we report a successfully humanized form of mu5A8 (hu5A8) that retains binding to both human and monkey CD4 and anti-AIDS virus activity. When administered intravenously to normal rhesus monkeys, hu5A8 bound to all target CD4+ cells without depletion and showed a significantly longer plasma half-life than mu5A8. Nevertheless, an anti-hu5A8 response directed predominantly against V region determinants did eventually appear within 2 to 4 weeks in most animals. However, when hu5A8 was administered to rhesus monkeys chronically infected with the simian immunodeficiency virus of macaques, anti-hu5A8 antibodies were not detected. Repeated administration of hu5A8 in these animals resulted in sustained plasma levels and CD4+ cell coating with humanized antibody for 6 weeks. These studies demonstrate the feasibility of chronic administration of CD4-specific MAb as a potential means of treating or preventing HIV-1 infection.