Antimicrobial pharmacokinetics and dosing in critically ill adults receiving prolonged intermittent renal replacement therapy: A systematic review.

Prolonged intermittent renal replacement therapy (PIRRT) is gaining popularity as a renal replacement modality in intensive care units, but there is a relative lack of guidance regarding antimicrobial clearance and dosing when compared with other modalities. The objectives of this systematic review were to: (1) identify and describe the pharmacokinetics (PK) of relevant antimicrobials used in critically ill adults receiving PIRRT, (2) evaluate the quality of evidence supporting these data, and (3) propose dosing recommendations based on the synthesis of these data. A search strategy for multiple databases was designed and executed to identify relevant published evidence describing the PK of antimicrobials used in critically ill adults receiving PIRRT.

[Effect of steroid therapy on intraocular pressure].

Glucocorticosteroids are key anti-inflammatory agents in the treatment of ophthalmic and systemic inflammatory diseases. However, prolonged use may result in an increase in intraocular pressure followed by a potentially vision -threatening ocular complication as glaucomatous neuropathy ultimately leading to blindness. Steroid therapy can increase intraocular pressure not only with ophthalmic preparations, but also with other routes of administration such as inhalational, intranasal and systemic.

Therapeutic Drug Monitoring of Vancomycin in Adult Patients with Methicillin-Resistant Bacteremia or Pneumonia.

Background: Vancomycin remains widely used for methicillin-resistant (MRSA) infections; however, treatment failure rates up to 50% have been reported. At the authors' institution, monitoring of trough concentration is the standard of care for therapeutic drug monitoring of vancomycin. New guidelines support use of the ratio of 24-hour area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) as the pharmacodynamic index most likely to predict outcomes in patients with MRSA-associated infections.

Lio-A Personal Robot Assistant for Human-Robot Interaction and Care Applications.

Lio is a mobile robot platform with a multi-functional arm explicitly designed for human-robot interaction and personal care assistant tasks. The robot has already been deployed in several health care facilities, where it is functioning autonomously, assisting staff and patients on an everyday basis. Lio is intrinsically safe by having full coverage in soft artificial-leather material as well as collision detection, limited speed and forces.

Rational design and synthesis of substrate-product analogue inhibitors of α-methylacyl-coenzyme A racemase from Mycobacterium tuberculosis.

2,2-Bis(4-isobutylphenyl)propanoyl-CoA and 2,2-bis(4-t-butylphenyl)propanoyl-CoA are rationally designed, gem-disubstituted substrate-product analogues that competitively inhibit α-methylacyl-coenzyme A racemase from Mycobacterium tuberculosis with Ki values of 16.9 ± 0.6 and 21 ± 4 μM, respectively, exceeding the enzyme's affinity for the substrate by approximately 5-fold.

Effect of changes in food groups intake on magnesium, zinc, copper, and selenium serum levels during 2 years of dietary intervention.

Background: Essential elements in serum are related to specific changes in food groups intake.

Objective: To address the effect of 2-year food intake changes in an intervention study on serum concentrations of magnesium, zinc, copper, and selenium.

Method: Two hundred thirty-one participants, a subgroup of the Dietary Intervention Randomized Control Trial (DIRECT) study (age = 52 years; body mass index = 32.

Binding kinetics and affinities of heterodimeric versus homodimeric HIV-1 reverse transcriptase on DNA-DNA substrates at the single-molecule level.

During viral replication, HIV-1 reverse transcriptase (RT) plays a pivotal role in converting genomic RNA into proviral DNA. While the biologically relevant form of RT is the p66-p51 heterodimer, two recombinant homodimer forms of RT, p66-p66 and p51-p51, are also catalytically active. Here we investigate the binding of the three RT isoforms to a fluorescently labeled 19/50-nucleotide primer/template DNA duplex by exploiting single-molecule protein-induced fluorescence enhancement (SM-PIFE).

Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet.

Background: Trials comparing the effectiveness and safety of weight-loss diets are frequently limited by short follow-up times and high dropout rates.

Methods: In this 2-year trial, we randomly assigned 322 moderately obese subjects (mean age, 52 years; mean body-mass index [the weight in kilograms divided by the square of the height in meters], 31; male sex, 86%) to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non-restricted-calorie.

Results: The rate of adherence to a study diet was 95.

Establishing schedules for repeated doses of strontium and for concurrent chemotherapy in hormone-resistant patients with prostate cancer: measurement of blood and urine strontium levels.

Strontium-89 (Sr-89) alone or with concurrent chemotherapy has a role in the treatment of patients with prostate cancer (PCP). The schedules for repeated doses of Sr-89 or for concurrent chemotherapy is undetermined. The objective of this study was to measure the effective half-life (Te) of Sr-89 using a detector available in a nuclear research facility.

Uptake of ingested uranium after low "acute intake".

The uptake of uranium, ingested as a soluble compound, was studied by monitoring the uranium level in urine by inductively coupled plasma mass spectrometry and through measurement of an isotopic tracer. The high sensitivity of this method allows measurement of uranium levels in urine samples from each voiding, therefore more detailed biokinetic studies are possible. To simulate low "acute intake," five volunteers with "normal" levels (5-15 ng L(-1)) of uranium in urine ingested a grapefruit drink spiked with 100 microg of uranium (235U/238U = 0.

Uranium in urine--normalization to creatinine.

"Spot samples" of urine are routinely used to monitor occupational exposure to uranium and other toxic heavy metals, such as mercury, lead, and cadmium. In the present work, it was shown that diurnal variations in the uranium concentration in different urine samples from the same individual could be quite large. However, these variations were in correlation to the creatinine level of the same samples, with values of R = 0.

Inductively coupled plasma mass spectrometry as a simple, rapid, and inexpensive method for determination of uranium in urine and fresh water: comparison with LIF.

A simple method, based on inductively coupled plasma mass spectrometry, for determination of uranium in urine at levels that indicate occupational exposure, is presented. Sample preparation involves a fifty-fold dilution of the urine by nitric acid (2% HNO3) and no other chemical treatment or separation. The analysis itself is completed in under 3 min.

Phenylethylamine and tyramine are mixed-acting sympathomimetic amines in the brain.

On the helical strip of a capacitance vessel, the pulmonary artery of the rabbit, phenylethylamine (PEA) and tyramine act solely via displacement of noradrenaline from their storage sites and this effect is inhibited by desmethylimipramine (DMI). In contrast, on a resistance vessel, the perfused central ear artery of the rabbit, PEA enhances stimulation induced contractions in 0.2-0.

(-)Deprenyl and (-)1-phenyl-2-propylaminopentane, [(-)PPAP], act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons.

The activity of the catecholaminergic neurons in the rat brain is enhanced significantly 30 min after the subcutaneous injection of very small doses of (-)deprenyl (threshold doses: 0.01 mg/kg for noradrenergic neurons and 0.025 mg/kg for dopaminergic neurons).

Electrophysiological actions of a new antiarrhythmic drug, bisaramil, on isolated heart preparations.

Electrophysiological effects of bisaramil--a new antiarrhythmic drug under clinical trial--were investigated on isolated heart preparations, at a concentration range of 2.3-23 x 10(-6) M. Bisaramil dose dependently decreased the maximum rate of depolarization (Vmax), action potential amplitude (APA) and overshoot (OS) both in auricle and in papillary muscle of guinea-pig heart.

[Electrophysiologic study of the anti-arrhythmic mechanism of action of phosphocreatine in acute myocardial ischemia and reperfusion].

To determine the possible application of exogenous phosphocreatine (ePC) to protect the ischemic myocardium from reperfusion abnormalities in cardiac rhythm, the antiarrhythmic and antifibrillatory activities of the agent were studied in an acute myocardial ischemia model and reperfusion-induced cardiac damage. It was shown that ePC produced a pronounced antifibrillatory effect in acute coronary occlusion and subsequent reperfusion. The agent substantially increased the threshold of electric ventricular fibrillation and the frequency of spontaneous defibrillation.

Trends and developments in radioprotection: the effect of nicotinamide on DNA repair.

Recent studies point to the naturally occurring molecules in expression of radiation damage and in protection. DNA repair was shown to be one of the parameters that can be modified to attain improved protection. The need for a natural compound that can enhance DNA repair in order to improve cellular protection focused our attention on nicotinamide (NA).

Inhibition of human lymphocyte stimulation by visible light and phthalocyanine photosensitization: mitogen and wavelength dependency.

Mitogenic stimulation of human peripheral blood lymphocytes is inhibited by phthalocyanine photosensitization using visible light. The mechanism of inhibition was studied using stimulating agents differing in their mode of action. Stimulation by the plant lectin phytohemagglutinin (PHA) was the least sensitive to inhibition by photosensitization, followed by the tumor promoter phorbol myristate acetate (PMA) and the calcium ionophore A23187.

Combined action of phthalocyanine photosensitization and gamma-radiation on mammalian cells.

The response of Chinese hamster cells and human lymphocytes to the combined action of photosensitization by chloroaluminium phthalocyanine tetrasulfonate and gamma-radiation was studied using colony-forming ability and [3H]thymidine incorporation following mitogenic stimulation respectively, as endpoints. The action of both treatments was usually additive regardless of the sequence of application. However, in human lymphocytes irradiated at low temperature, the photosensitization interacted synergistically with the subsequent ionizing radiation; in this experiment the initial photosensitization reduced the yield of micronuclei produced by gamma-radiation.

Modification of the cardiac transmembrane potentials and currents by polyamines.

Spermine up to 10(-5) M increased the resting potential (RP) and maximum rate of rise (Vmax) of the action potential (AP) and accelerated the initial (20, 50%) repolarization in isolated guinea-pig and cat atria. These effects were not modified by pindolol (4 X 10(-7) M) or atropine (3 X 10(-7) M) but were prevented by indomethacin (10(-6) M). The right papillary muscle of guinea-pig only showed the acceleration of repolarization while the other parameters were not changed.

Effect of light fluence rate on mammalian cells photosensitization by chloroaluminium phthalocyanine tetrasulphonate.

Phthalocyanines are photosensitizers evaluated for use in photodynamic therapy of cancer. As such, the dependence of the bioresponse on the light fluence rate may be of clinical importance. The effect of the fluence rate of white light from 0.

Blockage of the fast sodium current by dimethindene in frog auricular fibres.

The effect of dimethindene (DMI) on action potential and fast inward Na current (INa) of frog atrial fibres was studied using double sucrose gap voltage-clamp technique. DMI reduced the amplitude and maximum rate of rise of the action potentials without altering the resting membrane potential. The drug inhibited the fast Na conductance in a concentration-dependent manner, without changing the reversal potential.