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Search Results: 1 - 10 of 267 matches for " Siamak Djafarzadeh "
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Effect of Remifentanil on Mitochondrial Oxygen Consumption of Cultured Human Hepatocytes
Siamak Djafarzadeh, Madhusudanarao Vuda, Jukka Takala, Stephan M. Jakob
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0045195
Abstract: During sepsis, liver dysfunction is common, and failure of mitochondria to effectively couple oxygen consumption with energy production has been described. In addition to sepsis, pharmacological agents used to treat septic patients may contribute to mitochondrial dysfunction. This study addressed the hypothesis that remifentanil interacts with hepatic mitochondrial oxygen consumption. The human hepatoma cell line HepG2 and their isolated mitochondria were exposed to remifentanil, with or without further exposure to tumor necrosis factor-α (TNF-α). Mitochondrial oxygen consumption was measured by high-resolution respirometry, Caspase-3 protein levels by Western blotting, and cytokine levels by ELISA. Inhibitory κBα (IκBα) phosphorylation, measurement of the cellular ATP content and mitochondrial membrane potential in intact cells were analysed using commercial ELISA kits. Maximal cellular respiration increased after one hour of incubation with remifentanil, and phosphorylation of IκBα occurred, denoting stimulation of nuclear factor κB (NF-κB). The effect on cellular respiration was not present at 2, 4, 8 or 16 hours of incubation. Remifentanil increased the isolated mitochondrial respiratory control ratio of complex-I-dependent respiration without interfering with maximal respiration. Preincubation with the opioid receptor antagonist naloxone prevented a remifentanil-induced increase in cellular respiration. Remifentanil at 10× higher concentrations than therapeutic reduced mitochondrial membrane potential and ATP content without uncoupling oxygen consumption and basal respiration levels. TNF-α exposure reduced respiration of complex-I, -II and -IV, an effect which was prevented by prior remifentanil incubation. Furthermore, prior remifentanil incubation prevented TNF-α-induced IL-6 release of HepG2 cells, and attenuated fragmentation of pro-caspase-3 into cleaved active caspase 3 (an early marker of apoptosis). Our data suggest that remifentanil increases cellular respiration of human hepatocytes and prevents TNF-α-induced mitochondrial dysfunction. The results were not explained by uncoupling of mitochondrial respiration.
Increasing mean arterial blood pressure in sepsis: effects on fluid balance, vasopressor load and renal function
Thiago Corrêa, Madhusudanarao Vuda, Jukka Takala, Siamak Djafarzadeh, Eliézer Silva, Stephan Jakob
Critical Care , 2013, DOI: 10.1186/cc12495
Abstract: Twenty-four anesthetized and mechanically ventilated pigs were randomly assigned (n = 8 per group) to a septic control group (Septic-CG) without resuscitation until death or one of two groups in which resuscitation was performed after 12 hours of untreated sepsis for 48 hours, targeting MAP between 50 and 60 mmHg (Low-MAP) or between 75 and 85 mmHg (High-MAP).MAP at the end of resuscitation was 56+/-13 mmHg (mean+/-SD) and 76+/-17 mmHg respectively, for Low-MAP and High-MAP groups. One animal each in High- and Low-MAP groups, and all animals in the septic control group died [median survival time: 21.8 hours (inter-quartile range: 16.3-27.5 hours). Norepinephrine was administered to all animals of the High-MAP group [0.38 (0.21-0.56) mcg/kg/min], and to three animals of the Low-MAP group [0.00 (0.00-0.25) mcg/kg/min; p=0.009]. The High-MAP group had a more positive fluid balance (3.3+/-1.0 ml/kg/h vs. 2.3+/-0.7 ml/kg/h; p=0.001). Inflammatory markers, skeletal muscle ATP content and hemodynamics other than MAP did not differ between Low- and High-MAP groups. The incidence of acute kidney injury (AKI) after 12 hours of untreated sepsis was, respectively for Low- and High-MAP groups, 50% (4/8) and 38% (3/8), and in the end of the study 57% (4/7) and 0% (p=0.026). In Septic-CG, maximal isolated skeletal muscle mitochondrial Complex I, State 3 respiration increased from 1357+/-149 pmol/s/mg to 1822+/-385 pmol/s/mg, (p=0.020). In High- and Low-MAP groups, permeabilized skeletal muscle fibers Complex IV-state 3 respiration increased during resuscitation (p=0.003).The MAP targets during resuscitation did not alter the inflammatory response, nor affected skeletal muscle ATP content and mitochondrial respiration. While targeting a lower MAP was associated with increased incidence of AKI, targeting a higher MAP resulted in increased net positive fluid balance and vasopressor load during resuscitation. The long-term effects of using lower MAP targets on kidney function and whet
Norepinephrine to increase blood pressure in endotoxaemic pigs is associated with improved hepatic mitochondrial respiration
Tomas Regueira, Bertram B?nziger, Siamak Djafarzadeh, Sebastian Brandt, Jose Gorrasi, Jukka Takala, Philipp M Lepper, Stephan M Jakob
Critical Care , 2008, DOI: 10.1186/cc6956
Abstract: Thirteen anaesthetized pigs received endotoxin (Escherichia coli lipopolysaccharide B0111:B4; 0.4 μg/kg per hour) and were subsequently randomly assigned to norepinephrine treatment or placebo for 10 hours. Norepinephrine dose was adjusted at 2-hour intervals to achieve 15 mmHg increases in mean arterial blood pressure up to 95 mmHg. Systemic (thermodilution) and hepatosplanchnic (ultrasound Doppler) blood flow were measured at each step. At the end of the experiment, hepatic mitochondrial oxygen consumption (high-resolution respirometry) and citrate synthase activity (spectrophotometry) were assessed.Mean arterial pressure (mmHg) increased only in norepinephrine-treated animals (from 73 [median; range 69 to 81] to 63 [60 to 68] in controls [P = 0.09] and from 83 [69 to 93] to 96 [86 to 108] in norepinephrine-treated animals [P = 0.019]). Cardiac index and systemic oxygen delivery (DO2) increased in both groups, but significantly more in the norepinephrine group (P < 0.03 for both). Cardiac index (ml/min per·kg) increased from 99 (range: 72 to 112) to 117 (110 to 232) in controls (P = 0.002), and from 107 (84 to 132) to 161 (147 to 340) in norepinephrine-treated animals (P = 0.001). DO2 (ml/min per·kg) increased from 13 (range: 11 to 15) to 16 (15 to 24) in controls (P = 0.028), and from 16 (12 to 19) to 29 (25 to 52) in norepinephrine-treated animals (P = 0.018). Systemic oxygen consumption (systemic VO2) increased in both groups (P < 0.05), whereas hepatosplanchnic flows, DO2 and VO2 remained stable. The hepatic lactate extraction ratio decreased in both groups (P = 0.05). Liver mitochondria complex I-dependent and II-dependent respiratory control ratios were increased in the norepinephrine group (complex I: 3.5 [range: 2.1 to 5.7] in controls versus 5.8 [4.8 to 6.4] in norepinephrine-treated animals [P = 0.015]; complex II: 3.1 [2.3 to 3.8] in controls versus 3.7 [3.3 to 4.6] in norepinephrine-treated animals [P = 0.09]). No differences were observed in citrate s
Effects of TLR Agonists on the Hypoxia-Regulated Transcription Factor HIF-1α and Dendritic Cell Maturation under Normoxic Conditions
Rolf Spirig,Siamak Djafarzadeh,Tomas Regueira,Sidney G. Shaw,Christophe von Garnier,Jukka Takala,Stephan M. Jakob,Robert Rieben,Philipp M. Lepper
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010983
Abstract: Dendritic cells (DC) are professional antigen presenting cells that represent an important link between innate and adaptive immunity. Danger signals such as toll-like receptor (TLR) agonists induce maturation of DC leading to a T-cell mediated adaptive immune response. In this study, we show that exogenous as well as endogenous inflammatory stimuli for TLR4 and TLR2 induce the expression of HIF-1α in human monocyte-derived DC under normoxic conditions. On the functional level, inhibition of HIF-1α using chetomin (CTM), YC-1 and digoxin lead to no consistent effect on MoDC maturation, or cytokine secretion despite having the common effect of blocking HIF-1α stabilization or activity through different mechanisms. Stabilization of HIF-1α protein by hypoxia or CoCl2 did not result in maturation of human DC. In addition, we could show that TLR stimulation resulted in an increase of HIF-1α controlled VEGF secretion. These results show that stimulation of human MoDC with exogenous as well as endogenous TLR agonists induces the expression of HIF-1α in a time-dependent manner. Hypoxia alone does not induce maturation of DC, but is able to augment maturation after TLR ligation. Current evidence suggests that different target genes may be affected by HIF-1α under normoxic conditions with physiological roles that differ from those induced by hypoxia.
Effect of fluid resuscitation on mortality and organ function in experimental sepsis models
Sebastian Brandt, Tomas Regueira, Hendrik Bracht, Francesca Porta, Siamak Djafarzadeh, Jukka Takala, José Gorrasi, Erika Borotto, Vladimir Krejci, Luzius B Hiltebrand, Lukas E Bruegger, Guido Beldi, Ludwig Wilkens, Philipp M Lepper, Ulf Kessler, Stephan M Jakob
Critical Care , 2009, DOI: 10.1186/cc8179
Abstract: 48 pigs were randomized to continuous endotoxin infusion, fecal peritonitis, and a control group (n = 16 each), and each group further to two different basal rates of volume supply for 24 hours [moderate-volume (10 ml/kg/h, Ringer's lactate, n = 8); high-volume (15 + 5 ml/kg/h, Ringer's lactate and hydroxyethyl starch (HES), n = 8)], both supplemented by additional volume boli, as guided by urinary output, filling pressures, and responses in stroke volume. Systemic and regional hemodynamics were measured and tissue specimens taken for mitochondrial function assessment and histological analysis.Mortality in high-volume groups was 87% (peritonitis), 75% (endotoxemia), and 13% (controls). In moderate-volume groups mortality was 50% (peritonitis), 13% (endotoxemia) and 0% (controls). Both septic groups became hyperdynamic. While neither sepsis nor volume resuscitation strategy was associated with altered hepatic or muscle mitochondrial complex I- and II-dependent respiration, non-survivors had lower hepatic complex II-dependent respiratory control ratios (2.6 +/- 0.7, vs. 3.3 +/- 0.9 in survivors; P = 0.01). Histology revealed moderate damage in all organs, colloid plaques in lung tissue of high-volume groups, and severe kidney damage in endotoxin high-volume animals.High-volume resuscitation including HES in experimental peritonitis and endotoxemia increased mortality despite better initial hemodynamic stability. This suggests that the strategy of early fluid management influences outcome in sepsis. The high mortality was not associated with reduced mitochondrial complex I- or II-dependent muscle and hepatic respiration.Severe sepsis and septic shock are major causes of death in intensive care patients [1,2]. Most deaths from septic shock can be attributed to either cardiovascular or multiorgan failure [3]. The causes of organ dysfunction and failure are unclear, but inadequate tissue perfusion, systemic inflammation, and direct metabolic changes at the cellular level
Evolutions and Future Directions of Surgical Robotics: A Review  [PDF]
Siamak Najarian, Elnaz Afshari
International Journal of Clinical Medicine (IJCM) , 2012, DOI: 10.4236/ijcm.2012.32017
Abstract: Although the robotics firstly appeared as an entertainment form, its capabilities have continuously advanced from the world’s first industrial robot to the surgical robotic systems which are today capable of performing many surgical maneuvers unaided. However, these surgical robots are not autonomous systems; they are designed to complete a surgeon’s abilities and converting surgeon’s movements into incredibly steady and accurate robotic movements that finally manipulate surgical instruments to assist delicate operations. This novel type of surgery is carried out in the form of minimally invasive surgical procedure and has offered valuable alternatives to enhance traditional open surgery approach. Although the surgical robotic systems began as external robots, technological progresses are directing the surgical robotic systems to endoluminal robots which consist of doing surgical maneuvers by navigating of robot through lumens of human body. Here, we will briefly review different applications of robotic systems in various fields of medicine. Then, we will discuss minimally invasive surgical systems and their role in progressing of minimally invasive surgery as a modern surgery method. By thoroughly investigating a considerable amount of published materials about the minimally invasive surgical technologies, we will study the recent research activities and commercially available samples of surgical robotic systems.
The Relation between Freeway Average Speed and Speed Noise  [PDF]
Bahar Zarin, Siamak Ardekani
Journal of Transportation Technologies (JTTs) , 2015, DOI: 10.4236/jtts.2015.52009

Many factors affect the vehicular fuel consumption rate. The most significant traffic-related ones are speed, number of stops, speed noise, and acceleration noise (acceleration standard deviation). Fuel consumption models for both urban and highway traffic are used to evaluate the effect of these factors. Previous literature shows the speed and the acceleration of vehicles as well as the aerodynamic effects are the most commonly used variables in the highway fuel consumption mo dels. However, most existing models are based on the average or cruising speed and the effect of speed variation is by-and-large ignored. Incorporating the speed noise as a variable in the prediction models seems impractical because measuring it is cumbersome. However, knowing the relation between speed and speed noise may allow including the effect of speed noise in the model indirectly. To that end, this study examines the relation between speed and speed noise. The resulting mathematical relation is used to incorporate the speed noise effects in the fuel consumption model.

A Statistical Comparison of Traffic Measurements from the Moving versus Stationary Observer Methods  [PDF]
Fadi Alhomaidat, Siamak Ardekani
Journal of Transportation Technologies (JTTs) , 2015, DOI: 10.4236/jtts.2015.54019
Abstract: Data of traffic flow, speed and density are required for planning, designing, and modelling of traffic stream for all parts of the road system. Specialized equipments such as stationary counts are used to record volume and speed; but they are expensive, difficult to set up, and require periodic maintenance. The moving observer method was proposed in 1954 by Wardrop and Charlesworth to estimate these variables inexpensively. Basically, the observer counts the number of vehicles overtaken, the number of vehicles passed, and the number of vehicles encountered while traveling in the opposite direction. The trip time is reported for both travel directions. Additionally, the length of road segment is measured. These variables are then used in estimating speeds and volumes. In a westbound direction from Interstate Highway 30 (I-30) in the DFW area, this study examined the accuracy and feasibility of this method by comparing it with stationary observer method as the standard method for such counts. The statistical tests were used to test the accuracy. Results show that this method provides accurate volume and speed estimates when compared to the stationary method for the road segment with three lanes per direction, especially when several runs are taken.
The Effect of Tool Construction and Cutting Parameters on Surface Roughness and Vibration in Turning of AISI 1045 Steel Using Taguchi Method  [PDF]
Rogov Vladimir Aleksandrovich, Ghorbani Siamak
Modern Mechanical Engineering (MME) , 2014, DOI: 10.4236/mme.2014.41002

This paper presents an experimental investigation focused on identifying the effects of cutting conditions and tool construction on the surface roughness and natural frequency in turning of AISI1045 steel. Machining experiments were carried out at the lathe using carbide cutting insert coated with TiC and two forms of cutting tools made of AISI 5140 steel. Three levels for spindle speed, depth of cut, feed rate and tool overhang were chosen as cutting variables. The Taguchi method L9 orthogonal array was applied to design of experiment. By the help of signal-to-noise ratio and analysis of variance, it was concluded that spindle speed has the significant effect on the surface roughness, while tool overhang is the dominant factor affecting natural frequency for both cutting tools. In addition, the optimum cutting conditions for surface roughness and natural frequency were found at different levels. Finally, confirmation experiments were conducted to verify the effectiveness and efficiency of the Taguchi method in optimizing the cutting parameters for surface roughness and natural frequency.

Disfunción mitocondrial en sepsis, impacto y posible papel regulador del factor inducible por hipoxia (HIF-1alfa)
Regueira,T.; Andresen,M.; Djafarzadeh,S.;
Medicina Intensiva , 2009,
Abstract: there is a direct correlation between the development of the multiple organ dysfunction syndrome (mods) and the elevated mortality associated with sepsis. the mechanisms responsible for mods development are being studied, however, the main efforts regarding mods evaluation have focused on oxygen delivery optimization and on the modulation of the characteristic inflammatory cascade of sepsis, all with negative results. recent studies have shown that there is development of tissue acidosis, even when there are normal oxygen conditions and limited presence of tissue cellular necrosis or apoptosis, which would indicate that cellular energetic dysfunction may be a central element in mods pathogenesis. mitochondrias are the main source of cellular energy, central regulators of cell death and the main source for reactive oxygen species. several mechanisms contribute to mitochondrial dysfunction during sepsis, that is blockage of pyruvate entry into the krebs cycle, oxidative phosphorylation substrate use in other enzymatic complexes, enzymatic complex inhibition and membrane damage mediated by oxidative stress, and reduction in mitochondrial content. hypoxia-inducible factor-1a (hif-1a) is a nuclear transcription factor with a central role in the regulation of cellular oxygen homeostasis. its induction under hypoxic conditions is associated to the expression of hundreds of genes that coordinate the optimization of cellular oxygen delivery and the cellular energy metabolism. hif-1a can also be stabilized under normoxic condition during inflammation and this activation seems to be associated with a prominent pro-inflammatory profile, with lymphocytes dysfunction, and to a reduction in cellular oxygen consumption. further studies should establish a role for hif-1a as a therapeutic target.
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