bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hemoperfusion with polymyxin B-immobilized fibers reduced the number of CD16+CD14 + monocytes in patients with septic shock
Authors: Tsujimoto Hironori , Ono Satoshi , Hiraki Shuichi , Majima Takashi , Kawarabayashi Nobuaki , Sugasawa Hidekazu , Kinoshita Manabu , Hiraide Hoshio , Mochizuki Hidetaka 
Published: June 2007

Background: CD16 +CD14+ monocytes dramatically increase in number in patients with severe infection. Hemoperfusion with PMX-F (direct hemoperfusion with polymyxin B immobilized fibers) has been reported to be a safe and effective treatment for patients with septic shock, although the molecular mechanism that accounts for its effectiveness is still unclear. The purpose of this study was to quantify the number of CD16+CD14+ monocytes in patients with an intra-abdominal infection and to evaluate the effects of PMX-F treatment on clinical parameters and leukocyte surface antigen expression in these patients. Materials and Methods : Seventeen septic patients who had an intra-abdominal infection were enrolled in this study; 7 of these patients received PMX-F treatment. Peripheral blood samples were obtained immediately after admission, and were also collected from the above 7 patients before, during, and immediately after their PMX-F treatment. The expression of CD14, CD16, and Toll-like receptor (TLR)-4 on these patients' monocytes was evaluated using flow cytometry. In addition, lipopolysaccharide (LPS)-induced production of TNF-α and IL-1β by these cells was measured by ELISA. Results: Monocytic expression of CD16 and TLR-4 was significantly greater in septic patients than in healthy controls, and their proportion of CD16+CD14 + monocytes was similarly elevated. LPSinduced production of TNF-α and IL-1β by peripheral blood mononuclear cells (PBMCs) of septic patients was significantly reduced compared to controls. Furthermore, there was a reduction in the proportion of CD 16+CD 14+ monocytes during PMX-F treatment, and in the expression of TLR-4 on monocytes after PMX-F treatment. Conclusions: These results showed that the number of peripheral blood CD16+CD14 + monocytes and monocytic TLR-4 expression were markedly increased, and the production of pro-inflammatory cytokines in response to LPS significantly reduced in patients with sepsis. PMX-F treatment was found to be effective in reducing the number of CD 16+CD 14+ monocytes and in decreasing the monocytic expression of TLR-4 in patients with septic shock.
Lipoprotein-bound endotoxin exerts an immunomodulatory effect on hepatocytes through the lipid A domain of LPS
Authors: Behzad Kasravi F. , Lee Diana H. , Weisgraber Karl , Harris Hobart W. 
Published: June 2007

Background: We have previously shown that chylomicron (CM)-bound lipopolysaccharide (LPS) inhibits the host innate immune response by rendering hepatocytes tolerant to pro-inflammatory cytokine stimulation. However, LPS is a complex macromolecule containing both lipid and carbohydrate domains. We hypothesized that just as lipid A confers the toxicity of LPS, it is also responsible for the immunoregulatory effect on hepatocytes. Methods: We pretreated primary rat hepatocytes for 2 h with a series of CM-LPS complexes in which the endotoxin moiety varied in its structure and/or toxicity. Subsequently, the cells were stimulated with a mixture of pro-inflammatory cytokines. Nitric oxide production was measured as an indicator of hepatocellular activation. Results: All pretreatments wherein the CM-bound complex contained the lipid A moiety readily inhibited the hepatocellular cytokine response, including CM bound to lipid A alone. In contrast, CM-LPS complexes containing detoxified LPS, which lacks the lipid A domain, had no effect on the hepatocellular response to cytokines. Conclusions: The lipid A domain of the LPS macromolecule is both sufficient and essential for the CM-mediated induction of cytokine tolerance in hepatocytes. However, this process is independent of the specific endotoxic activity of the lipid A moiety.
Cardiovasc Pharmacol Therapeut 6(1):57-63, 2001 Low-Dose ACE with Alphaor Beta-Adrenergic Receptor Inhibitors Have Beneficial SHR Cardiovascular Effects
Authors: Varagic Jasmina , Susic Dinko , Frohlich Edward D. 
Published: June 2007

Background: There are no data regarding the prolonged effect of alpha-I adrenergic receptor antagonists on ventricular collagen content and coronary hemodynamics in spontaneously hypertensive rats (SHR). This study, therefore, was designed to determine the effects of chronic treatment with the alpha-I adrenergic receptor inhibitor doxazosin on SHR systemic and regional (especially coronary) hemodynamics, cardiovascular mass, and ventricular collagen. The effects of the combination of doxazosin with low-dose angiotensin-converting enzyme inhibitor were studied versus the alpha-I antagonist alone. These effects were compared with those of a beta-I adrenergic receptor inhibitor. Methods and Results: Systemic and regional hemodynamics (radionuclide-labeled microspheres), left and right ventricular weight, hydroxyproline concentration, and aortic weight were measured at age 35 weeks. Doxazosin reduced arterial pressure and total peripheral resistance without changing left ventricular mass and collagen content, whereas monotherapies with the beta-l antagonist metoprolol or a subdepressor dose of the ACE inhibitor enalapril were effective in reducing left ventricular mass and hydroxyproline without altering pressure. Doxazosin combined with the same low-dose ACE inhibitor reduced left ventricular mass and hydroxyproline without potentiating the hypotensive effect of doxazosin. By contrast, the combination of beta-I antagonist with the low-dose ACE inhibitor reduced pressure, unlike either agent alone. Aortic weight index was significantly reduced only by doxazosin whether when used alone or with the ACE inhibitor. Low-dose ACE inhibitor with doxazosin or the beta-I receptor antagonist as well as doxazosin alone decreased renal vascular resistance. Conclusion: These data show that the low subdepressor dose ACE inhibitor with an alphaor beta-adrenergic receptor antagonist provides beneficial cardiovascular effects in SHR.
Different Isoforms of Tocopherols Enhance Nitric Oxide Synthase Phosphorylation and Inhibit Human Platelet Aggregation and Lipid Peroxidation: Implications in Therapy with Vitamin E
Authors: Li Dayuan , Saldeen Tom , Romeo Francesco , Mehta Jawahar L. 
Published: June 2007

Background: oc-Tocopherol has received much attention in the primary and secondary prevention of coronary artery disease. Absence of other isoforms, such as y- and &-tocopherol, in commercial preparations of vitamin E may account for the inconsistent results of clinical trials. Since platelet aggregation is intimately involved in thrombogenesis, the relative effects of ox-, y-, and 6-tocopherol and their combination were examined on human platelet aggregation, lipid peroxidation, and constitutive nitric oxide synthase (cNOS) activity. Methods and Results: Human platelets were incubated with the three different isoforms of tocopherol and their combination for 30 minutes, and then ADP-induced platelet aggregation measured. All three isoforms of tocopherol markedly and similarly decreased platelet aggregation in a concentration (120-480,uM)-dependent manner. All three tocopherols also decreased the level of the lipid peroxidation product, malondialdehyde (MDA), and increased NO release (P < 0.05 vs control). These isoforms of tocopherol did not affect cNOS protein expression, but enhanced cNOS phosphorylation in platelets. The combination of three tocopherols in a concentration found in nature was more potent than oc-, y-, or 6-tocopherol alone in this regard. Conclusion: These observations suggest that all three major isoforms of tocopherol have a similar effect on human platelet aggregation. The three isoforns appear to attenuate platelet aggregation at least in part via a decrease in free radical generation and an increase in platelet cNOS activity. The combination of tocopherols has a synergistic platelet inhibitory effect. Future clinical trials should concentrate on the combination of these three isoforms of tocopherols.
Activation of ATP-Sensitive Potassium Channels in Hypoxic Cardiac Failure Is not Mediated by Adenosine-1 Receptors in the Isolated Rat Heart
Authors: Reffelmann Thorsten , Skobel Erik C. , Kammermeier Helmut , Hanrath Peter , Schwarz Ernst R. 
Published: June 2007

Background: Hypoxic cardiac failure is accompanied by action potential shortening, which in part might be a consequence of opening of cardiac ATP-sensitive potassium channels (KMp channels). Coupling of the adenosine-1 receptor (A-1 receptor) to these channels has been described; however, the interaction of A-I-receptors and KMP channels in different models of ischemia is still under debate. The hypothesis as to whether A-1 receptors are involved in hypoxic K,, channel-activation in the saline-perfused rat heart was tested. Methods and Results: Pharmacologic modulation of the KTP channel by Glibenclamide (inhibitor) and Rimalkalim (activator) and of the A-1 receptor by R(-)-N6-(1-methyl-2-phenylethyl)-adenosine (R(-)-PIA, agonist) and 1,3-diethyl-3,7-dihydro-8-phenyl-purine-2,6-dione (DPX, antagonist) at different oxygen tensions (95% 02 and 20% 02) was performed in isolated Langendorff-rat hearts. Peak systolic pressure (PSP, intraventricular balloon), duration of monophasic action potential (epicardial suction electrode, time to 67% of repolarization: MAP67%), coronary flow, and heart rate (HR) were registered. Hypoxic perfusion resulted in a significant reduction of PSP (from 106 ±1 to 56 ± mmHg, P < 0.005) and shortening of MAP67% (from 37 ± to 25 ± ms, P < 0.005). With application of 1 pM Glibenclamide, MAP67% returned to normoxic values and PSP increased to 78 ± mmHg (P < 0.005 vs hypoxia). In normoxia, 2 pM Rimalkalin resulted in reduction of MAP67%/ and PSP, which was reversed by Glibenclamide. Application of 0.1 pM R(-)-PIA in normoxia resulted in a decrease of HR (from 235 ±6/min to 75 +41/min, P < 0.005), which was accompanied by an increase of PSP from 96 ± to 126 ± mmHg (P < 0.05) without changes in MAP67%. These effects were reversible by 1 MM DPX and remained unaffected by application of 1 PM Glibenclamide. Application of 1 pM DPX in hypoxia had no effect on the measured parameters. Conclusion: In isolated rat hearts, the K,p channel-system is activated in hypoxic cardiac failure and contributes to action potential shortening and reduced contractile performance. These effects seem to be independent of the A- I receptor in this model.
Treatment of Diabetic Microangiopathy and Edema with HR (Paroven, Venoruton; 0-(β-hydroxyethyl)-rutosides): A Prospective, Placebo-Controlled, Randomized Study
Authors: Incandela L. , Cesarone M. R. , DeSanctis M. T. , Belcaro G. , Dugall M. , Acerbi G. 
Published: June 2007

This study was planned to demonstrate in a prospective, placebo-controlled, randomized study, whether HR (Paroven, Venoruton; 0-(P-hydroxyethyl)-rutosides), is effective in improving the microcirculation in subjects with diabetic microangiopathy and neuropathy. Patients with severe diabetic microangiopathy, neuropathy and edema, patients with microangiopathy, without neuropathy, and 20 healthy subjects were included. Microangiopathy was defined by laser Doppler flowmetry and capillary filtration (rate of ankle swelling (RAS)). Inclusion criteria were: increase in resting flux (RF) and RAS, a decrease in venoarteriolar response (VAR), and alterations in flux increase with temperature. The 2 groups of patients and the control group were randomized in a treatment sub-group which received HR (1 g, twice daily for 6 months); those in the placebo group received similar treatment. Results: Groups were comparable; there were no drop-outs. There were no differences in the treatment and placebo groups at inclusion. Treatment was well tolerated; no adverse effects were reported. No variations were observed in healthy subjects at 6 months. In both groups of patients, significant decreases (P < 0.05) in RF and RAS were observed in the active treatment groups. The decrease in RAS was associated with a decrease in edema (P < 0.05) in both treatment groups. The decrease in RF and the increase in VAR were associated with a proportional decrease in RAS (P < 0.05). In patients without neuropathy, the variations in RF, VAR, and RAS were larger (P < 0.05) at 6 months. The variations in healthy subjects were limited and not significant. Conclusion: The decrease in capillary filtration and edema with HR is associated with symptomatic improvement. The action on edema is beneficial for the evolution of neuropathy. The effects of HR on flux, RAS, and edema are important in early stages of microangiopathy to avoid progression to clinical stages.
The Role of Approximate Entropy in Predicting Ventricular Defibrillation Threshold
Authors: Hamzei Ali , Ohara Toshihiko , Kim Young-Hoon , Lee Moon-Hyoung , Voroshilovski Olga , Lin Shien-Fong , Weiss James N. , Chen Peng-Sheng , Karagueuzian Hrayr S. 
Published: June 2007

Background: The role of myocardial tissue mass on ventricular defibrillation threshold (DFT) is unclear. We hypothesized that changes in tissue mass modulate DFT by changing ventricular fibrillation (VF) wavefront regularity (entropy). Methods and Results: The right ventricles (RV) of seven farm pigs were isolated, superfused and perfused through the right coronary artery with oxygenated Tyrode's solution at 37 The epicardial surface was stained with the voltage sensitive dye, di-4-ANEPPS, and activation wavefront numbers (AWN) during VF were determined from the optical maps using a CCD camera (96 x 96 pixels over a 3.5 x 3.5 cm area). The RV mass was progressively reduced by sequential cutting of 1 to 2 g of tissue (approximately 12 cuts in total) distal to the perfusion site. After each cut, VF was reinduced, optical maps obtained, and the 50% probability of successful DFT50 determined using an up-down algorithm. After each cut, the approximate entropy (ApEn) was also computed using 5 seconds of VF data obtained with a bipolar electrode and a pseudo-electrocardiogram. Tissue mass reduction of up to one third of the RV mass (ie, from 48.4 ± 4.25 g to 34 ± 4.7 g) caused little or no change in the DFT, ApEn or AWN. However, further progressive reduction of the RV mass near the critical mass of VF resulted in a significant (P < 0.05) progressive decrease in all three measured parameters. DFT energy was reduced by 27% (1.47 ± 0.34 J vs. 1.02 ± 0.14 J). There was a significant (P < 0.01) correlation between the DFT and ApEn, which significantly further increased (P < 0.001) near the critical mass. In a separate series of 6 isolated RVs, the ApEn correlated well with the Kolmogorov-Sinai (K-S) entropy, the standard method of calculating entropy. Conclusion: Tissue mass reduction significantly reduces DFT when the mass reduction increases VF wavefront regularity.
Cocaine Produces Cardiac Hypertrophy by Protein Kinase C Dependent Mechanisms
Authors: Henning Robert J. , Li Yongxiang 
Published: June 2007

Background: Chronic cocaine users can have as much as a 69% increase in left ventricular muscle mass without associated increases in arterial blood pressure, heart rate, renin, aldosterone, or cortisol. We determined whether cocaine directly increases cardiomyocyte protein content and whether protein kinase C is important in this process.Methods and Results: Adult rat cardiomyocytes were isolated and grown in cultures. In Series I experiments, cocaine, 10-8to 10-6M, or vehicle, in the absence or presence of phentolamine or metoprolol, was added to each culture and the cells were subsequently harvested. In Series II, cocaine, 10-6M, cocaine, 10-6M, plus bisindolylmaleimide, 10-6M, a protein kinase C inhibitor, or vehicle were added to each culture and the cells subsequently harvested. We determined the total protein content, the content of α-myosin and fetal β-myosin heavy-chain protein, and the presence of protein kinase C isoforms in the cardiomyocyte soluble and particulate fractions. Protein kinase C translocation from the soluble to particulate fraction is indicative of activation. In Series III, we determined the cocaine effects on ERK, SAPK/JNK, and p38. In Series I, cocaine, 10-8to 10-6M, dose-dependently increased myocyte protein content by as much as 28%±2% (P < .001) and fetal,β-myosin heavy-chain protein content by 80% ± 2% (P < .001). Neither phentolamine nor metoprolol inhibited this process. In Series II, we determined that ventricular myocytes contain alpha (α), beta (β), delta (δ), epsilon (ε), and zeta (ξ) protein kinase C isoforms. Cocaine, 10-6M, caused a 45 ± 5% increase (P<.001) in protein kinase Cα in the particulate fraction. The addition of a protein kinase C inhibitor to the myocyte cultures prevented the cocaine-induced translocation of protein kinase Cα and limited the increase in β-myosin heavy-chain protein content by >75% (P<.001). However, cocaine did not increase the phosphorylation of ERK, SAPK/JNK or p38 in Series III.Conclusions: Cocaine increases adult cardiomyocyte protein content by protein kinase Cα-dependent mechanisms, and this process can contribute to the cardiac hypertrophy and cardiomyopathy that results from chronic cocaine use.
Effect of Fenofibrate on Serum Inflammatory Markers in Patients With High Triglyceride Values
Authors: Tsimihodimos Vasilis , Kostoula Angeliki , Kakafika Anna , Bairaktari Eleni , Tselepis Alexandros D. , Mikhailidis Dimitri P. , Elisaf Moses 
Published: June 2007

Background: Atherosclerosis is the leading cause of death in developed countries. Although the mechanisms that underlie this process are not well defined, it has been proposed that atherosclerosis is mainly an inflammatory disease. In this context, a number of inflammatory markers have been studied for their ability to predict future cardiovascular events in asymptomatic individuals or patients with established atherosclerotic disease. Methods and Results: The aim of our study was to evaluate the effect of micronized fenofibrate on serum inflammatory markers, such as C-reactive protein, fibrinogen, and plasma platelet-activating factor acetylhydrolase (PAF-AH) in patients with high triglyceride values. An analysis of baseline values revealed that hypertriglyceridemic patients (n = 58) exhibit an atherogenic phenotype, characterized not only by elevated lipid values but also by high concentrations of serum inflammatory markers. Along with the improvement in serum lipid profile (reduction in triglycerides and total cholesterol, low-density lipoprotein, and nonhigh-density lipoprotein-cholesterol, with a concomitant increase in high-density lipoprotein-cholesterol levels), fenofibrate administration significantly reduced the values of serum inflammatory markers by 34%, 9.5%, and 24.8% for C-reactive protein, fibrinogen, and plasma PAF-AH, respectively. However, with the exception of PAF-AH, these reductions in inflammatory markers were not correlated with the changes in lipid values. Conclusions: In addition to its well-known hypolipidemic effects, fenofibrate may also possess significant anti-inflammatory properties that can contribute its antiatherogenic effect.
Compliance by Referring Physicians With Recommendations on Heart Failure Therapy from a Tertiary Center
Authors: Rocca Hans Peter Brunner-La , Capraro J. , Kiowski W. 
Published: June 2007

Background: We tested the assumption that general practitioners do not use medication as recommended and do not follow recommendations made by heart failure specialists. Methods: The study included 193 stable patients referred to and subsequently seen at our heart failure clinic between 1995 and 2001 with an ejection fraction of 40% or less. They had 1906 visits (1661 with structured follow-up). Recommendations by heart failure specialists regarding medication influencing prognosis and adherence of referring physicians to them were recorded. Results: Ninety-six percent of patients were taking angiotensin-converting enzyme (ACE) inhibitor/angiotensin-II receptor blocker (ARB) when referred. The prescription rate of β-blockers and spironolactone increased after publication of large trials (more than 80% in 2001). Doses were inappropriate for both ACE-inhibitors/ARBs (55% ± 30% of target dose) and β-blockers (29% ± 24%). Recommendations were followed closely for dose reduction/discontinuation of all drugs (82%) and start/uptitration of spironolactone (78%). Adherence was less ( P < .01) for start/uptitration of ACE inhibitors/ARBs (62%) and β-blockers (48%). Recommendations regarding single-step start/uptitration were more successful (ACE-inhibitors/ARBs, 70%; β-blockers, 63%; single-step of both, 67%) than multiplestep uptitration (ACE inhibitors/ARBs, 48%; β-blocker, 38%; P < .001). This was particularly true if recommendations concerned multiple-step uptitration of both drugs (25%, P < .001). There was no difference between general practitioners and cardiologists. Conclusions: Although penetration of drugs beneficial in heart failure was high upon referral, doses were lower than recommended, and recommendations regarding changes were insufficiently adhered to by the referring physicians. Simple, one-step recommendations were better implemented and may be combined with direct prescriptions during control visits to guarantee adequate medical therapy.
Online cognitive engagement of boys with ADHD
Authors: Whirley Kristen S. , Lorch Elizabeth Pugzles , Lemberger Clarese C. , Milich Richard 
Published: June 2007

The present study was designed to examine the role that attentional problems may play in accounting for difficulties in story comprehension experienced by children with ADHD. A secondary task methodology was used to examine whether or not online variations in cognitive engagement with a televised story were related to the continuity of central or incidental information. Twenty-two 9- to 11-year-old boys with ADHD and 36 of their nonreferred peers watched a television program and responded to auditory probes presented at preselected points during continuous sequences of central or incidental information. The reaction times to the probes for nonreferred boys showed the expected linear increase in cognitive engagement (i.e., the RTs increased) as central, plot-relevant sequences continued. In contrast, boys with ADHD showed the expected increase in RTs relatively late in the central sequences. The results were discussed in terms of how delays in engaging with central information may contribute to the academic difficulties experienced by boys with ADHD.
Boredom proneness and sleep disorders as predictors of adult attention deficit scores
Authors: Kass Steven J. , Wallace J. Craig , Vodanovich Stephen J. 
Published: June 2007

This study examined the extent to which boredom proneness and sleep disturbances were related to attention deficit scores in college-aged adults. In a sample of 148 college students, Attention scores on the Adult Behavior Checklist were best predicted by Boredom Proneness (BP) subscale scores, which assess one’s inability to maintain internal stimulation and feelings of constraint, and scores on the Epworth Daytime Sleepiness Scale and Athens Insomnia Scale ( R 2 = .57). Hyperactivity scores were best predicted by the BP subscales, which assess one’s need for a stimulating environment, the perception of time passing slowly, and feelings of constraint, and the Epworth Scale ( R 2 = .51). The findings contribute to the understanding of the symptomatology of attention deficit in adults and provide further evidence of the validity of this measure.