- Design and evaluation of artificial receptors for the reversal of neuromuscular block. [Journal Article]
- IJInt J Pharm 2017 Oct 15; 531(2):512-520
- Applying patient friendly and cost-efficient medications in healthcare will be a real challenge in the 21st century. Sugammadex is a selective, yet expensive agent used for the post-surgical reversal...
Applying patient friendly and cost-efficient medications in healthcare will be a real challenge in the 21st century. Sugammadex is a selective, yet expensive agent used for the post-surgical reversal of neuromuscular block since 2008. A wide library of cyclodextrin-based follow-ups, having potentially similar affinity towards target aminosteroid type neuromuscular blocking agents has been established. Almost 20 compounds were assessed with respect to in vitro affinity against three commonly applied drugs. Based on the capillary electrophoretic screening, carboxymethylated and sulfobutylated gamma-cyclodextrin derivatives have the potential to be promising lead molecules for their affinity towards pipecuronium was identical or even superior to Sugammadex. Carboxymethylated gamma-cyclodextrin showed efficient and complete reversal of the pipecuronium induced neuromuscular block in an ex vivo rat diaphragm experiment.
- A novel experimental model of acute respiratory distress syndrome in pig. [Journal Article]
- PRPhysiol Res 2016 Dec 22; 65(Supplementum 5):S643-S651
- Acute respiratory distress syndrome (ARDS) is severe medical condition occurring in critically ill patients and with mortality of 33-52 % is one of the leading causes of death in critically ill patie...
Acute respiratory distress syndrome (ARDS) is severe medical condition occurring in critically ill patients and with mortality of 33-52 % is one of the leading causes of death in critically ill patients. To better understand pathophysiology of ARDS and to verify novel therapeutical approaches a reliable animal model is needed. Therefore we have developed modified lavage model of ARDS in the pig. After premedication (ketamine and midazolam) 35 healthy pigs were anesthetized (propofol, midazolam, morphin, pipecuronium) and orotracheally intubated and ventilated. Primary ARDS was induced by repeated cycles of lung lavage with a detergent Triton X100 diluted in saline (0.03 %) heated to 37 °C preceded by pre-oxygenation with 100 % O(2). Single cycle included two subsequent lavages followed by detergent suction. Each cycle was followed by hemodynamic and ventilation stabilization for approx. 15 min, with eventual administration of vasopressors according to an arterial blood pressure. The lavage procedure was repeated until the paO(2)/FiO(2) index after stabilization remained below 100 at PEEP 5 cm H(2)O. In 33 pigs we have achieved the desired degree of severe ARDS (PaO(2)/FiO(2)<100). Typical number of lavages was 2-3 (min. 1, max. 5). Hemodynamic tolerance and the need for vasopressors were strongly individual. In remaining two animals an unmanageable hypotension developed. For other subjects the experimental ARDS stability was good and allowed reliable measurement for more than 10 h. The present model of the ARDS is clinically relevant and thus it is suitable for further research of the pathophysiology and management of this serious medical condition.
- Implications of Fibroblast growth factor/Klotho system in glucose metabolism and diabetes. [Review]
- CGCytokine Growth Factor Rev 2016; 28:71-7
- Diabetes mellitus, especially type 2 diabetes, remains the dominant metabolic disease worldwide, with an expected increase in prevalence of over 50% in the next 20 years. Our knowledge about the path...
Diabetes mellitus, especially type 2 diabetes, remains the dominant metabolic disease worldwide, with an expected increase in prevalence of over 50% in the next 20 years. Our knowledge about the pathophysiology of type 2 diabetes continues to be incomplete, with unmet medical need for new therapies. The characterization of the fibroblast growth factor (FGF) family and the discovery of endocrine FGFs provided new information on the mechanisms of regulation and homeostasis of carbohydrate metabolism. More specifically, FGF19 and FGF21 signaling pathways have been linked to different glucose metabolic processes, including hepatic glucose synthesis, glycogen synthesis, glucose uptake, and insulin sensitivity, among others, and these molecules have been further related to the pathophysiology of diabetes mellitus. In-depth comprehension of these growth factors may bring to light new potential therapeutic targets for the treatment of diabetes mellitus.
- Reversal of Pipecuronium-Induced Moderate Neuromuscular Block with Sugammadex in the Presence of a Sevoflurane Anesthetic: A Randomized Trial. [Randomized Controlled Trial]
- A&AAnesth Analg 2015; 121(2):373-80
- CONCLUSIONS: Sugammadex adequately and rapidly reverses pipecuronium-induced moderate NMB during sevoflurane anesthesia. Once the train-of-four count has spontaneously returned to 2 responses following pipecuronium administration, a dose of 2.0 mg/kg of sugammadex is sufficient to reverse the NMB.
- Intravenous dextromethorphan/quinidine inhibits activity of dura-sensitive spinal trigeminal neurons in rats. [Journal Article]
- EJEur J Pain 2015; 19(8):1086-94
- CONCLUSIONS: It is evident that the observed DM/Q-induced suppression of trigeminal neuron excitability can lead to a reduction in nociceptive transmission from meninges to higher centres of the brain. Since the same mechanism is believed to underlie the pharmacodynamics of many well-known antimigraine drugs, results of the present study enable us to anticipate the potential efficacy of DM/Q in migraine.
- Bisphenol a in chronic kidney disease. [Journal Article]
- IJInt J Nephrol 2013; 2013:437857
- Phenols are uremic toxins of intestinal origin formed by bacteria during protein metabolism. Of these molecules, p-cresol is the most studied and has been associated with renal function impairment an...
Phenols are uremic toxins of intestinal origin formed by bacteria during protein metabolism. Of these molecules, p-cresol is the most studied and has been associated with renal function impairment and vascular damage. Bisphenol A (BPA) is a molecule with structural similarity with phenols found in plastic food and beverage containers as well as in some dialyzers. BPA is considered an environmental toxicant based on animal and cell culture studies. Japanese authorities recently banned BPA use in baby bottles based on observational association studies in newborns. BPA is excreted in urine and uremic patients present higher serum levels, but there is insufficient evidence to set cut-off levels or to link BPA to any harmful effect in CKD. However, the renal elimination and potential exposure during dialysis warrant the monitoring of BPA exposure and the design of observational studies in which the potential health risks of BPA for end-stage renal disease patients are evaluated.
- Identification of a potent endothelium-derived angiogenic factor. [Journal Article]
- PlosPLoS One 2013; 8(7):e68575
- The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosp...
The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up4U) from the secretome of human endothelial cells. The angiogenic effect of the endothelial secretome was partially reduced after incubation with alkaline phosphatase and abolished in the presence of suramin. In one fraction, purified to homogeneity by reversed phase and affinity chromatography, Up4U was identified by MALDI-LIFT-fragment-mass-spectrometry, enzymatic cleavage analysis and retention-time comparison. Beside a strong angiogenic effect on the yolk sac membrane and the developing rat embryo itself, Up4U increased the proliferation rate of endothelial cells and, in the presence of PDGF, of vascular smooth muscle cells. Up4U stimulated the migration rate of endothelial cells via P2Y2-receptors, increased the ability of endothelial cells to form capillary-like tubes and acts as a potent inducer of sprouting angiogenesis originating from gel-embedded EC spheroids. Endothelial cells released Up4U after stimulation with shear stress. Mean total plasma Up4U concentrations of healthy subjects (N=6) were sufficient to induce angiogenic and proliferative effects (1.34 ± 0.26 nmol L(-1)). In conclusion, Up4U is a novel strong human endothelium-derived angiogenic factor.
- [Evaluation of muscle relaxant requirement for hospital anesthesia]. [Journal Article]
- VMVoen Med Zh 2013; 334(3):20-6
- The rationale for cost-effectiveness of modern muscle relaxants (MR) administration in general anesthesia was evaluated. New MRs are more expensive than traditionally used pipecuronium and succinylch...
The rationale for cost-effectiveness of modern muscle relaxants (MR) administration in general anesthesia was evaluated. New MRs are more expensive than traditionally used pipecuronium and succinylcholine. However, the old MRs are often required as a block reversion with anticholinesterase medicines at the end of surgery, the longer artificial lung ventilation and observation in patients during recovery in intensive care unit. It was found that the district military hospital had done an annual average of about 900 general anesthesia assisted with artificial ventilation and muscle relaxation. About 2% of all anesthesias accrue to short-term anesthesia, the 27% to medium-term and 71% to long-term. 81% of the medium-term anesthesia accrue small hospitals. According to cost/effectiveness the most optimal muscle relaxants administration scheme for short-term (up to 30 min) anesthesia was mivacurium, for the operation of medium duration (30-120 min)--rocuronium, for long-term (120 min)--pipecuronium. An electronic form of annual report, which allows to obtain the necessary data for calculation of annual muscle relaxants demand and costs both in hospital and in the whole of the armed forces quickly, was developed.
- [Residual neuromuscular blockade after muscle relaxants administration in neurosurgical patients]. [Journal Article]
- ARAnesteziol Reanimatol 2012 Jul-Aug; (4):73-6
- The paper analyzes the incidence of residual neuromuscular blockade (NMB) after pipecuronium and rocuronium administration in 124 neurosurgical patients. We analyzed neuromuscular conductance with TO...
The paper analyzes the incidence of residual neuromuscular blockade (NMB) after pipecuronium and rocuronium administration in 124 neurosurgical patients. We analyzed neuromuscular conductance with TOF-Watch SX Residual NMB incidence after neuromuscular blocking agents administration in neurosurgical patients is 87.7%. Use of pipecuronium accompanied by a greater incidence and duration of residual NMB in comparison with rocuronium. Sugammadex administration is effective method of residual NMB reversal and can restore NMC in 3-5 minutes.
New Search Next
- [Ketamine versus propofol during one-lung ventilation in thoracic surgery]. [Clinical Trial]
- ARAnesteziol Reanimatol 2012 May-Jun; (3):14-8
- A comparative analysis of gas, the metabolic rate, pressor, resistive and volumetric characteristics of pulmonary blood flow, central and intracardiac hemodynamics in patients undergoing thoracic sur...
A comparative analysis of gas, the metabolic rate, pressor, resistive and volumetric characteristics of pulmonary blood flow, central and intracardiac hemodynamics in patients undergoing thoracic surgery was conducted. 2 methods of anesthesia maintenance: on the basis of ketamine - fentanyl - pipecuronium and propofol - fentanyl - pipecuronim were compared. Invasive monitoring system PiCCOplus for the behaviour of the transpulmonary thermodilution (TT) in combination with VoLEF for the pulmonary thermodilution (PT) the change of ventilation mode ALV - OLV - ALV was used. OLV lasted for more than 1.5 hours.