Insulin signaling in the adipocyte

Mammalian adipose tissue serves a number of functions, including storage of nutrients for periods of fasting and control of organismal metabolism. Critical to these functions is the capacity of the fat cell to respond to insulin with a significant increase in glucose uptake. It is now generally recognized that the major site of action of insulin in this tissue is the mobilization of a pool of latent, intracellular transport proteins. Nonetheless, the precise signaling pathways which mediate the insulin-stimulated increase in glucose transport remain uncertain. In recent years, the serine/threonine protein kinase Akt/PKB has emerged as an important candidate signaling molecule. Considerable current effort is being directed at trying to definitively establish whether Akt/PKB is an important intermediate in insulin signaling to glucose transport in muscle and fat.     

Atrial natriuretic peptide in the preterm infant. Lack of correlation with natriuresis and diuresis

We assessed the relation of atrial natriuretic peptide (ANP) to renal function on postnatal day 2 and day 5 in preterm infants. Plasma ANP concentration was measured by radioimmunoassay in two groups of preterm infants: group 1, gestational age less than 30 weeks, n = 10; and group 2, gestational age 30-34 weeks, n = 11. The identity of the immunoreactivity as ANP-28 was confirmed by HPLC. Plasma ANP was significantly higher in group 1 than in group 2 on day 2 and day 5 (p < 0.01) and ANP concentration decreased by day 5 in both groups (group 1, p < 0.01; group 2, p < 0.02). The results showed no correlation between plasma ANP concentration and urinary sodium excretion or creatinine clearance, which may be due to a blunted renal response to ANP, but other factors may be involved also. We conclude that preterm infants are able to release large amounts of ANP, but a high plasma ANP concentration does not correlate directly with renal regulation of sodium and water balance.     

Left ventricular remodeling after pulmonary autograft aortic valve replacement: evaluation with color-Doppler echocardiography and magnetic resonance imaging

The superior hemodynamic performance of the pulmonary autograft in aortic position is expected to reflect complete regression of hypertrophy and improved ventricular function. We evaluated and compared early and midterm transthoracic color-Doppler echocardiography (TTE) and magnetic resonance imaging (MRI) assessment concerning left ventricular (LV) function, LV mass regression, and performance of the semilunar valves. A total of 42 consecutive patients, mean age 36 +/- 6 years (range 15 to 56 years), were studied. TTE and MRI were performed preoperatively, at discharge, and at 6 and 12 months postoperatively. Left ventricular diameters and function and LV wall thickness and mass were assessed. There was no early and one late postoperative death. Maximum and mean LV outflow gradients were significantly reduced (p = 0.0001 and p = 0.0001, respectively). There was a significant reduction in left ventricular mass to near normal for all patients (p = 0.001) seen after 6 months. This was paralleled by significant reductions in the interventricular septum and posterior wall thickness, but difference was slight during further follow-up. There was a strong correlation between the results obtained by TTE and MRI for LV mass and ejection fraction (r = 0.86 and 0. 87, respectively). The pulmonary autograft operation gives excellent results that are translated into greater, rapid, and near complete regression of LV hypertrophy. Magnetic resonance imaging is a sensitive and noninvasive methodology that provides reliable visualization and quantification of ventricular performance.     

Pumpless extracorporeal lung assist using an arterio-venous shunt. Applications and limitations

We report the use of a pumpless extracorporeal lung assist (PECLA) in 70 patients with severe pulmonary failure of various causes. The device was used under rescue conditions in patients with preserved cardiac function. By establishing a shunt between femoral artery and vein using the arterio-venous pressure gradient as the driving force for the blood flow through the oxygenator, PECLA proved to be extremely effective in terms of oxygenation and carbon dioxide removal.     

Effect of calcineurin inhibitor therapy on P-gp expression and function in lymphocytes of renal transplant patients: a preliminary evaluation

Cyclosporine and tacrolimus are substrates and potent inhibitors of the multidrug transporter, P-glycoprotein, in vitro. The authors have investigated the effect of chronic therapy with these and other immunosuppressive drugs on the expression and function of P-glycoprotein in T lymphocytes. Using a P-gp antibody, the authors studied the level of expression of P-gp in CD4 and CD8 T cells over a period of time in renal transplant patients. For comparison, a group of healthy volunteers and patients who did not receive any calcineurin inhibitors but were maintained on mycophenolate mofetil was included. The P-gp expression on lymphocytes from these two groups remained constant (over several months' time). However, patients who were started on tacrolimus or cyclosporine had an initial decline in expression of P-gp on CD4 T cells. Patients who were initiated on calcineurin therapy on day 1 posttransplant also had a decrease in expression of P-gp on CD4 T lymphocytes. This preliminary analysis suggests that the calcineurin inhibitors might be modulating the expression and function of transporters in lymphocytes, thus changing not only the drug concentration but also the apparent efficacy of these drugs. Further understanding and elucidation of such effects would be important in understanding the relationship between pharmacokinetics and pharmacodynamics of these and other drugs, especially for immunosuppressive and anti-AIDS therapy.     

The economic burden of depression in the United States: how did it change between 1990 and 2000?

BACKGROUND: The economic burden of depression was estimated to be 43.7 billion dollars in 1990. A subsequent study reported a cost burden of 52.9 billion dollars using revised prevalence data and a refined workplace cost estimation approach. The objective of the current report is to provide a 10-year update of these estimates using the same methodological framework. METHOD: Using a human capital approach, we developed prevalence-based estimates of 3 major cost categories: (1) direct costs, (2) mortality costs arising from depression-related suicides, and (3) costs associated with depression in the workplace. Cost-of-illness estimates from 1990 were updated to reflect the experience in 2000 using current epidemiologic data and publicly available population, wage, and cost information. RESULTS: Whereas the treatment rate of depression increased by over 50%, its economic burden rose by only 7%, going from 77.4 billion dollars in 1990 (inflation-adjusted dollars) to 83.1 billion dollars in 2000. Of the 2000 total, 26.1 billion dollars (31%) were direct medical costs, 5.4 billion dollars (7%) were suicide-related mortality costs, and 51.5 billion dollars (62%) were workplace costs. CONCLUSION: The economic burden of depression remained relatively stable between 1990 and 2000, despite a dramatic increase in the proportion of depression sufferers who received treatment. Future research will incorporate additional costs associated with depression sufferers, including the excess costs of their coexisting psychiatric and medical conditions and attention to the role of painful conditions as a driver of these costs.     

Extracorporeal lung support and endovascular stent in traumatic aortic rupture and severe lung failure

Blunt thoracic injury in association with aortic rupture represents a life-threatening situation. Surgical repair used to be the preferred method of treatment. Because most patients are multiple trauma patients including head injuries, bone fractures and respiratory failure, urgent surgical procedures portend excessively high morbidity and mortality rates. Delay in operative management bears the risk of exsanguinating hemorrhage, secondary complications, prolonged hospital stay with increased costs. We present here an alternative treatment protocol including pumpless extracorporal lung assist and endovascular aortic stent graft placement in a 20-year old traffic accident victim. This procedure may be an especially useful treatment option in managing patients with complex lung and aortic pathology primarily not suitable for transportation or surgery.     

Psychosocial correlates of physical activity and sedentary leisure habits in young adolescents: the Teens Eating for Energy and Nutrition at School study

BACKGROUND: Low levels of physical activity (PA) and highly sedentary leisure habits (SLH) in youth may establish behavioral patterns that will predispose youth to increased chronic disease risk in adulthood. The purpose of this paper was to examine associations of demographic and psychosocial factors with self-reported PA and SLH in young adolescents. METHODS: A general linear mixed model predicted self-reported PA and SLH in the spring from demographic and psychosocial variables measured the previous fall in 3798 seventh grade students. RESULTS: PA and SLH differed by race, with Caucasian students reporting among the highest PA and lowest SLH. Perceptions of higher academic rank or expectations predicted higher PA and lower SLH. Depressive symptomatology predicted higher SLH scores but not PA. Higher self-reported value of health, appearance, and achievement predicted higher PA and lower SLH in girls. Girls who reported that their mothers had an authoritative parenting style also reported higher PA and lower SLH. CONCLUSIONS: Determinants of PA and SLH appear to differ from each other, particularly in boys. Development of effective programs to increase PA and/or decrease SLH in young adolescents should be based on a clear understanding of the determinants of these behaviors.