Dexamethasone inhibition of interferon-alpha 2-induced stimulation of cortisol and growth hormone secretion in chronic myeloproliferative syndrome

This study investigated the acute effects of interferon-alpha 2 (IFN-alpha 2) on hormonal secretion in adult patients affected by a chronic myeloproliferative syndrome and tried to shed some light on the mechanism by which IFN-alpha 2 stimulates cortisol and GH secretion in humans. We compared the pattern of IFN-alpha 2-induced cortisol and GH release with that elicited after the same challenge given subsequent to pretreatment with dexamethasone (Dex). We studied eight patients affected by a chronic myeloproliferative syndrome (thrombocythemia) who had been selected for treatment with IFN-alpha 2. Four sets of experiments were performed: 1) 2 mL iv saline was given at 0800 h in eight cases; 2) 3 x 10(6) IU iv IFN-alpha 2 was given at 0800 h in eight cases; 3) 3 x 10(6) IU iv IFN-alpha 2 was given at 0800 h after pretreatment with 1.5 mg Dex (1 mg at midnight the previous night and 0.5 mg at 0700 h on the day of the test) in six cases; and 4) 2 mL iv saline was given at 0800 h after the same Dex pretreatment in four cases. Cortisol and GH were measured in plasma samples drawn at 30-min intervals between 0800 and 1300 h. Acute iv administration of IFN-alpha 2 stimulated the release of both cortisol and GH in each patient with a significant increment vs. control values, as assessed by areas under the curve. The administration of Dex significantly decreased basal plasma cortisol secretion and abolished cortisol response to IFN-alpha 2 administration. These data suggest that the stimulatory action of IFN-alpha 2 on cortisol release is mediated via a modulation of the activity of the hypothalamic-pituitary axis rather than through a direct effect at the level of the adrenal cortex. After Dex plus saline administration, no significant effect was observed on plasma GH levels, which remained low. Dex administration significantly decreased GH response to IFN-alpha 2. These data suggest that a hypothalamic or pituitary stimulation (or both) is involved in the mechanism of IFN-alpha 2-induced GH secretion. It remains to be established whether IFN-alpha 2 directly stimulates pituitary somatotropic cells or whether the cytokine exerts a stimulatory action on GH secretion by indirectly modulating the hypothalamic or pituitary activity. In conclusion, acute iv administration of IFN-alpha 2 represents a potent stimulus for cortisol and GH secretion in adult human subjects.(ABSTRACT TRUNCATED AT 400 WORDS)     

Neonatal androgen and estrogen treatments masculinize the size of motoneurons in the rat spinal nucleus of the bulbocavernosus

Electrically-assisted transdermal delivery (EATDD) is the facilitated transport of compounds across the skin using an electromotive force. It has been extensively explored as a potential means for delivering peptides and other hydrophilic, acid-labile or orally unstable products of biotechnology. The predominant mechanism for delivery is iontophoresis, although electroosmosis and electroporation have also been investigated. The focus of this review is to put these different mechanisms in perspective and relate them to the drug and skin model system being investigated.     

The posterior operative approach for cervical radiculopathy

Cervical disc disease includes acute herniation and chronic disc degeneration with secondary changes in the associated bone. The latter may lead to the spectrum of cervical spondylitic stenosis, which is considered to be multilevel and may be more of a bony disease. Clinically, cervical disc disorders can be divided into several disorders. The disorder of true cervical radiculopathy is associated with lateral compression of the nerve root. When this condition is due to a lateral soft disc herniation or lateral bony stenosis, the posterior cervical laminoforaminotomy is commonly used. It is a procedure that works extremely well in the vast majority of patients and there is no risk of spinal instability; therefore, no fusion is required. The details of operative care have been described. In patients who have persistent radicular problems after a failed anterior cervical interspace procedure, the posterior cervical laminoforaminotomy with posterior wiring and fusion is a simple and effective operative option.     

ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes

Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.     

Application of the recurrent multilayer perceptron in modelingcomplex process dynamics

A nonlinear dynamic model is developed for a process system, namely a heat exchanger, using the recurrent multilayer perceptron network as the underlying model structure. The perceptron is a dynamic neural network, which appears effective in the input-output modeling of complex process systems. Dynamic gradient descent learning is used to train the recurrent multilayer perceptron, resulting in an order of magnitude improvement in convergence speed over a static learning algorithm used to train the same network. In developing the empirical process model the effects of actuator, process, and sensor noise on the training and testing sets are investigated. Learning and prediction both appear very effective, despite the presence of training and testing set noise, respectively. The recurrent multilayer perceptron appears to learn the deterministic part of a stochastic training set, and it predicts approximately a moving average response of various testing sets. Extensive model validation studies with signals that are encountered in the operation of the process system modeled, that is steps and ramps, indicate that the empirical model can substantially generalize operational transients, including accurate prediction of instabilities not in the training set. However, the accuracy of the model beyond these operational transients has not been investigated. Furthermore, online learning is necessary during some transients and for tracking slowly varying process dynamics. Neural networks based empirical models in some cases appear to provide a serious alternative to first principles models.     

Hematopoietic stem cell transplantation for infantile osteopetrosis

Infantile osteopetrosis is a lethal disorder resulting from a severe defect in the ability of osteoclasts to resorb bone. The only therapy shown to be capable of providing lasting benefit is allogeneic hematopoietic stem cell transplantation (HCT). We report the outcome of 10 patients with infantile malignant osteopetrosis treated with HCT from an HLA A, B, DRB1 matched (n=6) or A or B locus mismatched (n=4) family member or unrelated donor at the University of Minnesota between 1978 and 1997. Eight of 10 patients achieved primary engraftment; secondary graft failure was seen in two patients. Five of 10 patients survive; three with full or partial donor chimerism and two with autologous hematological recovery. Transient or partial donor chimerism can be sufficient to correct the hematological manifestations of osteopetrosis. We recommend early referral for consideration of HCT with a related or unrelated donor as neurosensory manifestations of osteopetrosis are generally not reversible. Donor engraftment may be easier to achieve early in the course of the disease.     

Molecular recognition with C-clamp porphyrins: synthesis, structural, and complexation studies

The cholesterolaemic effect of 2 hypercholesterolaemic diets was tested in 12 rat inbred strains. Diet I is a commercial diet supplemented with 2.0% (w/w) cholesterol and 5.0% (w/w) olive oil; diet II is identical to diet I with addition of 0.5% (w/w) sodium cholate. Strains with the highest plasma cholesterol response after diet I (BN and LEW) also had the highest cholesterol response after diet II (hyperresponders, mean response > 3.5 mmol/l). In the strains DA, SHR, BC, WAG, LOU, PVG and BUF the strain mean cholesterol response remained below 1.3 mmol/l after both diets (hyporesponders). Strains F344 and OM had an intermediate cholesterol response after both diets (normoresponders, mean response between 1.3 and 3.5 mmol/l). Only in the strains LOU, PVG and SHR there appeared to be a significant higher cholesterol response after diet II when compared with the cholesterol response after diet I. In the strain WKY this difference was of a borderline significance (P = 0.052) and this strain turned from a normoresponder after diet I into a hyperresponder after diet II. Liver cholesterol levels as measured after feeding diet II for two weeks also appeared to be strain-specific. No correlation was found between the plasma cholesterol response after diet II and the liver cholesterol levels. Changes in plasma phospholipid and triglyceride levels have been measured for both diet I and diet II. For group means a correlation between the cholesterol response and the change in phospholipid levels was found (r = 0.86 for diet I, P < 0.001 and r = 0.76 for diet II, P < 0.01). No such correlation was found for triglyceride levels.     

Minimum-Energy Translational Trajectory Generation for Differential-Driven Wheeled Mobile Robots

Mobile robots can be used in many applications, such as exploration, search and rescue, reconnaissance, security, and cleaning. Mobile robots usually carry batteries as their energy source and their operational time is restricted by the finite energy available from the batteries. Therefore, energy constraints are critical to the service time of mobile robots. This paper investigates the minimum-energy control problem for translational trajectory generation, which minimizes the energy drawn from the batteries. Optimal control theory is used to find the optimal velocity trajectory in analytic form. To demonstrate energy efficiency obtainable, we performed simulations of minimum-energy velocity control and compared the results with loss-minimization control and energy-optimal trapezoidal velocity profiles. Simulation results showed that significant energy savings can be achieved, of up to 9% compared with loss-minimization control and up to 10% compared with energy-optimal trapezoidal velocity profile. We also performed an actual robot experiment using Pioneer 3-AT platform to show the validity of the proposed minimum-energy velocity control. The experimental results revealed that the proposed minimum-energy velocity control can save the battery energy up to 10% compared with loss-minimization control. Categories (3): Robot control, (5): RobotMotion Planning     

An accurate and practical buffer allocation model for the buffer cache based on marginal gains

A new dynamic buffer allocation strategy based on the notion of marginal gains is presented for the buffer cache that is used by the operating system to store frequently accessed disk blocks in main memory, and the performance of the proposed strategy is compared with those of previous allocation strategies. In the proposed strategy, marginal gain values are predicted by exploiting functions that approximate the expected number of buffer hits per unit time. Experimental results from both trace-driven simulation and an actual implementation in the FreeBSD operating system show that the proposed strategy accurately predicts the marginal gain values for various workloads resulting in significantly improved buffer hit ratios.