Pharmacol Rep
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Target controlled infusion (TCI) devices are increasingly used in clinical practice. These devices unquestionably aid optimization of drug dosage. ⋯ One has to realize the limitation of this approach: these models may be less accurate when applied to patients in extreme clinical conditions: in intensive care units, with a considerable loss of blood, severe hypothermia or temporary changes in the composition of plasma, e.g., hypoalbuminemia. In the future, data obtained under these "extreme" clinical circumstances, may be used to modify the dosage algorithms of propofol TCI systems to match the clinical scenario.
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The animal models are pivotal for understanding the characteristics of acute renal failure (ARF) and development of effective therapy for its optimal management. Since the etiology for induction of renal failure is multifold, therefore, a large number of animal models have been developed to mimic the clinical conditions of renal failure. Glycerol-induced renal failure closely mimics the rhabdomyolysis; ischemia-reperfusion-induced ARF simulate the hemodynamic changes-induced changes in renal functioning; drug-induced such as gentamicin, cisplatin, NSAID, ifosfamide-induced ARF mimics the renal failure due to clinical administration of respective drugs; uranium, potassium dichromate-induced ARF mimics the occupational hazard; S-(1,2-dichlorovinyl)-L-cysteine-induced ARF simulate contaminated water-induced renal dysfunction; sepsis-induced ARF mimics the infection-induced renal failure and radiocontrast-induced ARF mimics renal failure in patients during use of radiocontrast media at the time of cardiac catheterization. Since each animal model has been created with specific methodology, therefore, it is essential to describe the model in detail and consequently interpret the results in the context of a specific model.
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Clinical Trial
Pharmacokinetics and pharmacodynamics of propofol in patients undergoing abdominal aortic surgery.
Available propofol pharmacokinetic protocols for target-controlled infusion (TCI) were obtained from healthy individuals. However, the disposition as well as the response to a given drug may be altered in clinical conditions. The aim of the study was to examine population pharmacokinetics (PK) and pharmacodynamics (PD) of propofol during total intravenous anesthesia (propofol/fentanyl) monitored by bispectral index (BIS) in patients scheduled for abdominal aortic surgery. ⋯ The BIS index was linked to the effect site concentrations through a sigmoidal E(max) model with EC(50) = 2.19 mg/l. The body weight, age, blood pressure and gender were not identified as statistically significant covariates for all PK/PD parameters. The population PK/PD model was successfully developed to describe the time course and variability of propofol concentration and BIS index in patients undergoing surgery.
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Paroxysmal sleep disorders in children are important from both pathophysiological and clinical point of view. Correct diagnosis is crucial for further management. The aim of the present study was to identify peripheral markers of paroxysmal sleep disorders in children, which could improve diagnostics of these disorders. We compared serum levels of several putative biomarkers of neurological disorders, such as S100B protein, neuron specific enolase (NSE), orexin A, adiponectin, and insulin-like growth factor 1 (IGF-1) in pediatric patients suffering from sleep disturbances with those who additionally to parasomnia revealed also epilepsy. ⋯ Out of the five putative biomarkers measured, blood concentration of S100B and orexin A may be helpful in differentiating parasomnic pediatric patients with and without epilepsy.
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Restraint stress (RS) markedly increases interleukin 1-β (IL-1β) generation in brain structures involved in hypothalamic-pituitary adrenocortical (HPA) axis regulation. The IL-1β-induced transient stimulation of HPA axis activity was parallel in time and magnitude to respective changes in regulation of HPA activity. In the present experiment the expression of neuron al and inducible nitric oxide synthase (nNOS and iNOS) were investigated in prefrontal cortex, hippocampus and hypothalamus in response to acute restraint stress in control and prior repeatedly restrained rats. ⋯ These results indicate that during restraint stress nNOS regulate formation of low amount of NO and the high-output generation of NO is effected by inducible isoform of nitric oxide synthase. Prior repeated stress significantly enhances the homotypic stress-induced nNOS and iNOS responses.