Search

The fatty acid profile and mineral composition (calcium, magnesium, sodium, phosphorus, potassium, iron, zinc, manganese, silicon, boron, cadmium, chromium, nickel, aluminium, copper, and lead) by Inductively Coupled Plasma-Atomic Emission Spectometry (ICP-AES) and the proximate composition of the body and legs of edible frog (Rana esculenta) were investigated. The fatty acids occurring in the highest proportions in both the body and leg of frogs were mystiric acid (C14:0, 1.13-2.30%), palmitic acid (C16:0, 19.76-23.23%), stearic acid (C18:0, 3.61-6.29%), palmitoleic acid (C16:1, 7.06-13.08%), oleic acid (C18:1n-9 cis, 10.83-16.71%), linoleic acid (C18:2n-6, 6.44-6.71%), γ-linolenic (C18:3n-6, 0.13-0.27%), linolenic (C18:3n-3, 2.32-3.37%), cis-11,14,17-eicosatrienoic acid (C20:3n-3, 4.71-7.72%), cis-5,8,11,14,17-eicosapentaenoic acid (C20:5n-3, 3.96-6.05%) and cis-4,7,10,13,16,19-docosahexaenoic acid (C22:6n-, 2.77-6.67%). Among the minerals determined, potassium was found to be highest, followed by phosphorus. Calcium, aluminium, cadmium, copper, lead, chromium, nickel, boron, silicon and zinc are found to be lower than the potential toxicity levels. [ABSTRACT FROM AUTHOR]

Abstract: The starting compound for the synthesis of 16,17-secoandrostane derivatives with the 4-en-3-on, 1,4-dien-3-on, 4,6-dien-3-on, and 1,4,6-trien-3-on systems was 3β-hydroxy-17-methyl-16,17-secoandrost-5-en-16-nitrile-17-one (1), the Oppenauer oxidation of which yielded the corresponding 4-en-3-one derivative 2. Dehydrogenation of compound 2 with the aid of 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil) gave the three products: 17-methyl-16,17-secoandrosta-1,4-dien-3,17-dione-16-nitrile (3), 17-methyl-16,17-secoandrosta-4,6-dien-3,17-dione-16-nitrile (4), and 17-methyl-16,17-secoandrosta-1,4,6-trien-3,17-dione-16-nitrile (5). On the other hand, epoxidation of compound 2 resulted in a mixture of α and β isomers of 4,5-epoxy-17-methyl-16,17-secoandrosta-3,17-dione-16-nitrile (6 and 7). Opening of the oxirane rings of the mixture of 6 and 7 by the action of formic acid yielded the 4-hydroxy-4-en derivative 8. Antiaromatase activity and in vitro cytotoxicity against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, human breast adenocarcinoma ER−, MDA-MB-231, and prostate cancer PC3) of selected compounds were evaluated. Compound 2 exhibited a relatively strong inhibition of aromatase and extremely potent cytotoxicity against PC3 cells. Compound 8 showed satisfactory cytotoxicity against MCF-7 cells. [Copyright &y& Elsevier]

Abstract: The elastic scattering of 6He on 208Pb has been measured at laboratory energies of 14, 16, 18 and 22 MeV. These data were analyzed using phenomenological Woods–Saxon form factors and optical model calculations. A semiclassical polarization potential was used to study the effect of the Coulomb dipole polarizability. Evidence for long range absorption, partially arising from Coulomb dipole polarizability, is reported. The energy variation of the optical potential was found to be consistent with the dispersion relations which connect the real and imaginary parts of the potential. [Copyright &y& Elsevier]

Abstract: The key reaction 12 in nuclear astrophysics is difficult to be performed experimentally at low energy because of the Coulomb barrier. But it is different if we use its inverse reaction 16 because the cross-section of 16 is almost 100 times larger than the cross-section of 12 at the same center of mass energy based on our study. In the present work, we study the angular distributions and total cross-sections of 16 which are induced by polarized photon using the resonance theory of low energy reaction. The differential cross-sections as well as E1 and E2 transition cross-sections at low nuclear astrophysics energies are also calculated. The feature of the future Shanghai Laser Electron Gamma Source (SLEGS) facility, a low energy -ray beam line with a high photon flux, is presented. The experiments of 16 are simulated with a time projection chamber (TPC) and a realistic SLEGS layout. The lowest , which can be obtained from the simulation, is 0.8MeV with the 20–30% uncertainty for the one-month beam time of SLEGS. The extracted factors of 12 and their statistical uncertainties from the simulation are compared with the existing data and some theoretical calculations. It is shown that the promising 16 experiment at SLEGS can largely reduce the statistical uncertainties of the 12 experiment at low energies. [Copyright &y& Elsevier]

Abstract: The ternary [Li+][MPPip+][NTf2 −] ionic liquid, obtained by dissolution of solid lithium bis(trifluoromethanesulfonyl)imide (LiNTf2) in liquid N-methyl-N-propylpiperidinium bis(trifluoromethanesulfonyl)imide (MPPipNTf2), was used as an electrolyte, and stable at the lithium or graphite-lithium anodes. The graphite-lithium (C6Li) anode showed good cyclability and Coulombic efficiency in the presence of a molecular additive (10wt.% of vinylene carbonate, VC) to the ionic liquid. The electrode showed ca. 90% of its initial discharge capacity after 100 cycles. The addition of ethylene carbonate (EC) does not improve the cyclability of the anode to the same degree as that observed in the case of vinylene carbonate. [Copyright &y& Elsevier]

Prophylactic HPV vaccination provides an opportunity to profoundly affect cervical cancer incidence worldwide. The quadrivalent HPV VLP 6, 11, 16, 18 vaccine (Gardasil®) and the bivalent HPV VLP 16, 18 vaccine (Cervarix®) are effective for prevention of HPV infection and cervical precancerous lesions. The quadrivalent vaccine is also effective for prevention of vulvar and vaginal lesions and genital warts. With the introduction of the vaccines general issues have to be raised such as optimal age for vaccination, duration of protection after vaccination, impact on cervical cancer screening, vaccination of males and feasibility of application to developing countries. The prospects of a vaccine which will protect against the most common viral sexually transmitted infection and thereby, protect against the complications of HPV infection such as cervical cancer is extremely appealing. The success of HPV vaccination as a major public health prevention opportunity, however, will entirely depend on efficient infrastructures to deliver the vaccines and on the acceptance by individuals, parents and health care providers. [ABSTRACT FROM AUTHOR]

Abstract: The 11β-hydroxylation product of 16,17α-epoxyprogesterone (EP), 11β-hydroxy-16,17α-epoxyprogesterone (HEP), is an important intermediate for many anti-inflammatory drugs. To understand the hydroxylation characteristics of the 11β-hydroxylase from filamentous fungus Absidia coerulea IBL02, the 11β-hydroxylation process, the purification results and some characteristics of the enzyme (protein P450) from mycelia were first reported in this paper. When the feeding time of the substrate was set at 27h and the biotransformation time was for 42h after fermentation optimization in the whole-cell bioconversion, a satisfied yield of about 4g/l with above 85% biotransformation rate was achieved. We found the 11β-hydroxylase biosynthesis in cell cultivation could be induced by adding analogs of the substrate, and an about three-fold increase in enzymatic amount was achieved by adding progesterone as inducer for about 4h. Experimental results showed that Ca2+ and Fe2+ could greatly enhance the enzymatic activity, but Mg2+, Mn2+, Cu2+, and Zn2+ could inhibit it. After the optimization of the purification conditions, the 11β-hydroxylase (protein P450) with a single band on SDS-PAGE was obtained and estimated to be a MW of about 60kDa, giving a maximum absorbance at 448nm in reduced carbon monoxide difference spectra. [Copyright &y& Elsevier]

Abstract: The rotational motions of the biamphiphilic polyenes (bolapolyenes) dimethyl all-(E)-octacosa-10,12,14,16,18-pentaenedioate (DE28:5) and dimethyl all-(E)-tetratriaconta-13,15,17,19,21-pentaenedioate (DE34:5), with head-to-head distances of 34 and 42Å, respectively, have been examined by fluorescence anisotropy methods. The membrane-spanning bolapolyenes, which contain a central emitting pentaene group tethered to two methoxycarbonyl opposite polar heads by symmetric C8 (DE28:5) and C11 (DE34:5) polymethylene chains, were dispersed in lipid bilayers of DPPC or DMPC, and the stationary and picosecond-resolved emission was recorded as a function of temperature. In fluid-phase DMPC bilayers, three relaxation times could be determined, assigned to fast (0.2 and 2ns) single-bond isomerization processes localized on the alkyl chains, and to whole-molecule oscillations (∼11ns), respectively. The anisotropy decay parameters were further analyzed in terms of a diffusive model for wobbling in a Gaussian ordering potential, to assess the anchoring effect of the symmetric polar heads. In this way, the average rotational diffusion constant of the bolapolyenes, D ⊥, could be estimated as 0.022–0.026rad2 ns−1 (DMPC bilayers, 35°C), a value that is only 1/3 of that corresponding to the related pentaene fatty acid spanning a single membrane monolayer. In contrast, the amplitude of the equilibrium orientational distribution (θ half-cone∼50°) is very similar for both the transmembrane and the single-headed polyenes. The reorientational oscillations of the central emitting group in the bolapolyenes necessarily would produce large-amplitude (2–5Å) and very fast (ns) translational motions of the polar heads. [Copyright &y& Elsevier]

Abstract: Docosahexaenoic acid (DHA; C22:6 n −3) is an abundant fatty acid in fish phospholipids. In the present study, we employed liquid chromatography–ultraviolet spectrometry–tandem mass spectrometry and dissociated rainbow trout (Oncorhynchus mykiss) brain cells to determine whether fish utilize endogenous DHA to produce the recently uncovered novel lipid mediators termed the resolvins and protectins, generated by mammalian cells [Serhan CN, Hong S, Gronert K, et al. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med 2002; 196:1025–37; Hong S, Gronert K, Devchand P, Moussignac R-L, Serhan, CN. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. J Biol Chem 2003;278:14677–87]. Trout brain cells biosynthesize a range of recently identified di- and tri-hydroxy-containing bioactive products from endogenous sources of DHA when challenged in vitro. We identified neuroprotectin D1, resolvin D5, resolvin D1 and resolvin D2 from trout brain cells. Each compound was identified on the basis of its characteristic physical chemical properties that included MS, MS–MS, UV spectra and chromatographic behavior. The monohydroxy products from DHA, signatures of DHA conversion by lipoxygenases, were also identified. These included both 14S-hydroxy-docosahexaenoic acid and 17S-hydroxy-docosahexaenoic acid. The biosynthesis of these novel bioactive lipid mediators, namely resolvins and protectins, by fish cells provides the first evidence for the conservation of these structures from fish to humans as chemical signals in diverse biological systems. [Copyright &y& Elsevier]

Background: Although the detrimental effect of hyperkalemia on coronary endothelium has been reported, there is no direct evidence regarding the effect of hyperkalemic exposure on nitric oxide (NO) release from the coronary endothelium. In addition, it is unclear whether nicorandil, a KATP channel opener, used as hyperpolarizing cardioplegia or added in hyperkalemic cardioplegic solution may protect endothelial function during cardiac surgery. The present study was designed to clarify NO release and the function of endothelium-derived hyperpolarizing factor (EDHF) in coronary circulation with respect to the effect of hyperkalemia and nicorandil. Methods: Nitric oxide was measured by using a NO-specific electrode, and EDHF-mediated relaxation was investigated in a myograph. Substance P- and calcium ionophore A23187-induced NO release was compared in porcine left circumflex coronary arteries before and after 1-hour exposure to 20 mM potassium (K+) at 37°C. In coronary microarteries (diameter 200 to 450 μm), precontracted with U46619, in the presence of indomethacin (7 μM), NG-nitro-L-arginine (300 μM), and oxyhemoglobin (20 μM), EDHF-mediated relaxation was induced by bradykinin (−10 to −6.5 log M) after incubation with Krebs (control) or 20 mM K+ with or without 10 μM nicorandil at 37°C for 1 hour. Results: Neither substance P (58.8 ± 5.0 versus 66.2 ± 7.2 nmol/L) nor A23187 (86.6 ± 9.0 versus 82.4 ± 9.2 nmol/L in control) induced NO release was altered by hyperkalemic exposure (p > 0.05). In contrast, EDHF-mediated relaxation was decreased from 84.2% ± 3.8% to 42.3% ± 6.0% (p < 0.001) that was partially restored by nicorandil (50.7% ± 5.5%, p < 0.05). Conclusions: Exposure to potassium at 20 mM does not affect NO release but impairs EDHF-mediated relaxation in coronary arteries. Supplementation of nicorandil in hyperkalemic cardioplegia may provide a protective effect on EDHF-related endothelial function. [Copyright &y& Elsevier]

Background: International normalized ratio (INR) self-management can significantly reduce INR fluctuations, bleeding, and thromboembolic events compared with INR control managed by general practitioners. However, even patients with INR self-management may have an increased risk of bleeding if their INR value is above 3.5. This study evaluated the compliance, clinical complications, and survival of patients after mechanical heart valve replacement with low-dose INR self-management compared with conventional-dose anticoagulation. Methods: Group 1 (n = 908) received low-dose anticoagulation with a target INR range of 1.8 to 2.8 for aortic valve replacement and 2.5 to 3.5 for mitral or double valve replacement. Group 2 (n = 910) received conventional-dose anticoagulation with a target INR range of 2.5 to 4.5 for all heart valve prostheses. Results: In groups 1 and 2, 76% and 75% of INR values, respectively, were in the target range. Results did not differ according to schooling and age. The rate of thromboembolic events per patient year was 0.18% in group 1 and 0.40% in group 2 (p = 0.210). The rate of bleeding complications was 0.74% for group 1 and 1.20% for group 2 (p = 0.502). In most patients with clinically relevant bleeding, these complications occurred although their measured INR values were below 3.5. The survival rate did not differ between the study groups (p = 0.495). Conclusions: Low-dose INR self-management is a promising tool to achieve low hemorrhagic complications without increasing the risk of thromboembolic complications. INR self-management is applicable for all patients in whom permanent anticoagulation therapy is indicated. Even INR values below 3.5 can bear the risk of bleeding complications. [Copyright &y& Elsevier]

Background: Hemostatic effects of the protease inhibitor aprotinin in cardiac surgery are well described, and recent evidence suggests an antithrombotic mechanism of aprotinin through inhibition of thrombin-mediated platelet activation. We hypothesized that aprotinin provides hemostasis while reducing vascular thrombosis by attenuating protease-dependent platelet function. Methods: Rabbits (3 to 4 kg) underwent carotid artery thrombosis induced by electrical current. Treatment animals (n = 8) received aprotinin by a 100,000-KIU bolus followed by a continuous infusion (25,000 KIU/h). Control animals (n = 8) received crystalloid solution. Thrombus weight and time to thrombotic occlusion were determined. Platelet aggregation was examined in response to protease-dependent (thrombin) and protease-independent (adenosine diphosphate, ADP) platelet agonists. Platelet thrombin protease-activated receptor (PAR) expression was analyzed by Western blot. Ear bleeding time and abdominal incisional bleeding were measured at baseline and serially. Results: Thrombus weight was decreased by aprotinin (6.1 ± 1.1 mg versus 10.8 ± 1.5 mg, aprotinin versus control, p < 0.05). Time to thrombotic occlusion was prolonged in the aprotinin group (17.4 ± 1.0 minutes versus 8.3 ± 1.3 minutes, p < 0.001). Rabbit platelet expression of thrombin PARs was demonstrated by Western blot analysis, and was not altered by aprotinin therapy. Platelet aggregation due to thrombin was decreased by aprotinin therapy (59.2% ± 3.0% versus 95.8% ± 1.5%, p < 0.001), whereas protease-independent, ADP-induced platelet aggregation was unchanged with aprotinin. Incisional bleeding was not different between groups. In the aprotinin group, bleeding time was unchanged at baseline and then reduced for the duration of the experiment (35.0 ± 4.7 seconds versus 76.8 ± 6.4 seconds, p < 0.05). Conclusions: While providing hemostatic effects, aprotinin attenuates vascular thrombosis in part by inhibition of PAR activation, resulting in the prevention of thrombin-induced platelet aggregation. [Copyright &y& Elsevier]

Angiotensin-converting enzyme inhibitors have been shown to prolong survival and decrease infarct size in patients after acute coronary syndromes. Now there is evidence to suggest that angiotensin-converting enzyme inhibition is beneficial in coronary artery bypass patients. This review will summarize the beneficial effects of angiotensin-converting enzyme inhibition in patients with ischemic heart disease and provide evidence to show that the routine use of angiotensin-converting enzyme inhibition in coronary artery bypass patients can improve clinical outcomes. [Copyright &y& Elsevier]

Background: Radial artery grafts are used for coronary artery bypass grafting (CABG), and postoperative antispasm therapy with diltiazem is performed widely. Some investigators have warned that diltiazem administration after cardiac surgery is harmful to renal function. We designed a retrospective study to investigate the renal and hemodynamic effects of the postoperative administration of diltiazem in patients undergoing CABG. Methods: Subjects were 90 consecutive CABG patients. All were treated with diltiazem during surgery (a 0.1 mg/kg bolus injection followed by continuous infusion at 2 μg · kg−1 · min−1). In the 50 patients (diltiazem group) with a radial artery graft, intravenous diltiazem administration was continued until the oral intake of diltiazem (90 mg/d) was begun to avoid graft spasms. In the remaining 40 patients without a radial artery graft, diltiazem was not continued postoperatively (control group). Postoperative renal function, assessed by serum creatinine level and creatinine clearance, and hemodynamic variables (heart rate, arterial pressure, pulmonary wedge pressure, cardiac index, left ventricular stroke work index) was compared between the two groups. Results: Renal function: Serum creatinine concentrations on postoperative days 1 through 7 were lower, and the endogenous creatinine clearance in the early postoperative period was higher in diltiazem group than in control group, although the differences were not significant. Hemodynamics: Heart rate was lower in diltiazem group than in the control group, but blood pressure, pulmonary wedge pressure, cardiac index, left ventricular stroke work index, and urinary output were similar between the groups. Conclusions: Our results confirmed that intravenous diltiazem treatment in patients undergoing CABG is not harmful to renal function. [Copyright &y& Elsevier]

Since its clinical introduction, the anaphylactic potential of aprotinin has been a major concern. World wide, its use is expanding so there is an increased chance that patients have reexposure from various sources. The risk of anaphylaxis is approximately 2.8% in reexposed patients. From 1963 to 2003, 124 cases of aprotinin-induced anaphylaxis were reported in 61 publications. Eleven patients died. The reexposure interval was less than 3 months in 72% (38 of 53 patients). This review looks at the profile of patients at risk so preventive measures may be taken. Past and future exposures have to be taken into account before any aprotinin administration. [Copyright &y& Elsevier]

Background: Treatment of postoperative pulmonary hypertension with intravenous (IV) pulmonary vasodilators is hampered by the lack of selectivity. Inhaled nitric oxide produces selective pulmonary vasodilation; however, it requires a special device, and weaning can cause rebound. Oral sildenafil is a phosphodiesterase type V inhibitor. Sildenafil can produce sustained pulmonary vasodilatation in patients with hypoxic or primary pulmonary hypertension; however, experience with postoperative pulmonary hypertension is limited. We report our initial experience with eight patients who received oral sildenafil as adjunctive therapy for postoperative pulmonary hypertension Methods: We reviewed the charts of eight adult patients with postoperative pulmonary hypertension who received oral sildenafil (25 to 50 mg) to facilitate weaning of IV (milrinone, nitroglycerine, and sodium nitroprusside) and inhaled (nitric oxide) pulmonary vasodilators. Hemodynamic data were recorded before and 30 and 60 minutes after the initial dose of sildenafil. Results: After the initial dose of sildenafil, mean pulmonary artery pressure was reduced by 20% and 22% at 30 and 60 minutes, respectively (p < 0.05). Pulmonary vascular resistance index decreased by 49% and 44% at 30 and 60 minutes, respectively (p < 0.05). Sildenafil had no clinically significant effects on cardiac index, mean arterial pressure, or systemic vascular resistance. Subsequent doses of sildenafil were administered at regular intervals, allowing successful weaning of concomitant pulmonary vasodilators. Conclusions: Oral sildenafil is an effective agent for treatment of postoperative pulmonary hypertension and can be used to facilitate weaning of inhaled and IV pulmonary vasodilators. [Copyright &y& Elsevier]

Background: Many retrospective studies report increased postoperative infection after allogenic blood transfusion. To investigate this phenomenon, we prospectively studied 232 patients undergoing cardiac surgery.Methods: Patients were screened daily for evidence of culture positive infections. Wounds were examined daily and defined on the ASEPSIS score. Chest radiographs and white cell counts and differentials were recorded on days 1, 2, and 4. The use of blood products was monitored blindly and independently. Patients were grouped according to transfusion status and compared using χ2 or Fisher''s test. Logistic regression analyses were performed to identify predictors of transfusion and infection.Results: Of 232 patients, 116 (50%) received blood product transfusion. Patients receiving blood had lower preoperative hemoglobin, were older, with a greater proportion of urgent/emergency or revision surgery, and were higher risk. Despite this, there were no differences in the frequency of chest infection (20% versus 15%, p = 0.38), urinary infection (3.5% versus 5.3%, p = 0 0.75), wound infection (3.5% versus 8.0%, p = 0.16), or overall infection (28% versus 30%, p = 0.89) comparing the transfused versus untransfused groups. There was no evidence to suggest that administration of blood products was associated with infection (odds ratio 0.92, p = 0.77).Conclusions: The administration of blood per se did not lead to increased postoperative infection. Clinicians should reconsider withholding blood transfusion in patients solely owing to concerns of predisposition to infection. [Copyright &y& Elsevier]

The discovery in 1989 of sildenafil, a highly selective inhibitor of phosphodiesterase-5 (PDE-5), was the result of extensive research on chemical agents targeting PDE-5 that might potentially be useful in the treatment of coronary heart disease. Initial clinical studies on sildenafil in the early 1990s were not promising with respect to its antianginal potential. However, the incidental discovery of its antiimpotence effect led to its approval of for the treatment of erectile dysfunction. Thereafter, several reports of adverse cardiac events in patients on sildenafil raised concerns about its safety in cardiovascular disorders. Novel therapeutic indications are emerging for sildenafil with the recent discovery that PDE-5 is expressed in various other tissues such as the arterial vasculature, including pulmonary and coronary arteries, venous vasculature, skeletal muscles, platelets, and visceral and tracheobronchial muscles. In this review we briefly summarize the pharmacology of sildenafil and the current available evidence on its potential therapeutic applications in cardiovascular disorders. [Copyright &y& Elsevier]

Background: Perioperative pulmonary hypertension remains a clinical challenge. The phosphodiesterase enzyme type III inhibitor milrinone produces pulmonary vasodilation but lacks selectivity. Sildenafil, a phosphodiesterase enzyme type V inhibitor, can also induce relaxation of the pulmonary vasculature; however, only the oral formulation is presently available. This study evaluated the effects of a new intravenous sildenafil analogue—UK 343-664—compared with milrinone during acute pulmonary hypertension in a porcine model of thromboxane-induced pulmonary hypertension.Methods: After acute pulmonary hypertension, 24 adult swine were randomized to 3 groups. Group 1 (n = 9) received an intravenous dose of 500 μg of UK 343-664, group 2 (n = 8) received milrinone 50 mg/kg, and group 3 (n = 7) received 10 mL of normal saline solution. All agents were administered for more than 5 minutes. Data were recorded continuously for 30 minutes.Results: Both milrinone and UK 343-664 partially reversed thromboxane-induced pulmonary hypertension, with a notable decrease in mean pulmonary artery pressure and pulmonary vascular resistance and a concomitant increase in cardiac output. In addition, milrinone improved right ventricular contractility but produced marked systemic vasodilatation. In contrast, the administration of UK 343-664 was associated with pulmonary vasodilatation, without appreciable changes in systemic arterial pressure or vascular resistance.Conclusions: Milrinone and UK 343-664 were equally effective as pulmonary vasodilators; however, only UK 343-664 exhibited a high degree of pulmonary selectivity. Potential uses for this new phosphodiesterase enzyme type V inhibitor warrant further study. [Copyright &y& Elsevier]

Background: The purpose of this paper was to evaluate myocardial and pulmonary effects of aqueous oxygen (AO) delivered directly into the pulmonary circulation in acute hypoxia.Methods: Six calves (2 months old, 68.0 ± 2.2 kg) after general anesthesia, mechanical ventilation, and median sternotomy underwent total right heart bypass using fixed flow with continuous pressure and blood gas measurements in carotid and femoral arteries, left atrium, the coronary sinus and PA. Measurements of systemic and PA pressures and O2 saturations; myocardial O2 atrioventricular (AV) differences; and O2 extraction were made. After base line measurements, hypoxic ventilation reducing the mean arterial PO2 from 277 ± 102 mm Hg to 47 ± 4 mm Hg (p < 0.0005) was maintained for 30 minutes. Without changes in the hypoxic ventilation (mean arterial PO2 = 49 ± 11 mm Hg) 3 ml/min of hyperbaric aqueous oxygen (AO = oxygen diluted in saline solution) was administered into the PA for 30 minutes. Pulmonary blood flow was maintained during the entire experiment (3.7 ± 0.3 L/min).Results: Hypoxic ventilation significantly raised (p < 0.05) the systolic (30 ± 7 vs 21 ± 4 mm Hg), diastolic (20 ± 6 vs 12 ± 3 mm Hg), and mean (23 ± 7 vs 15 ± 3 mm Hg) PA pressure; PA/systemic pressure ratio for systolic (0.37 ± 0.08 vs 0.25 ± 0.06) and mean (0.56 ± 0.19 vs 0.29 ± 0.11) pressures; and pulmonary vascular resistance (PVR) (5.63 ± 1.06 vs 3.53 ± 0.75 U). Aqueous oxygen (AO) infusion significantly reduced (p < 0.05) the values obtained with hypoxic ventilation; systolic (23 ± 5 vs 30 ± 7 mm Hg), diastolic (11 ± 4 vs 20 ± 6 mm Hg), and mean (14 ± 3 vs 23 ± 7 mm Hg) PA pressure; PA/systemic pressure ratio for systolic (0.25 ± 0.05 vs 0.37 ± 0.08) and mean pressures (0.29 ± 0.12 vs 0.56 ± 0.19); and PVR (3.41 ± 1.01 vs 5.63 ± 1.06 U). AO infusion in the pulmonary circulation did not influence the myocardial O2 atrioventricular (AV) difference or the O2 extraction.Conclusions: Infusion of hyperbaric AO solution into the PA can completely reverse the negative effects of acute hypoxia on the pulmonary circulation without affecting the myocardial metabolism. [Copyright &y& Elsevier]

Statins have been proven to prevent or delay ischemic events in patients at risk for atherosclerotic coronary disease. Increasing evidence suggests that statin therapy is also beneficial to patients undergoing coronary revascularization. In this review statin therapy will be shown to improve vein graft patency, minimize recurrent ischemic events, and decrease the need for repeat revascularization procedures in patients who have undergone coronary artery bypass grafting. [Copyright &y& Elsevier]

: BackgroundRapamycin is an immunosuppressive agent which also exhibits marked antiproliferative properties. Rapamycin coated stents have been demonstrated to suppress restenosis in experimental and clinical studies of percutaneous coronary catheter intervention. We investigated whether rapamycin can reduce neointima formation in a mouse model of vein graft disease.: MethodsC57BL6J mice underwent interposition of the inferior vena cava from isogenic donor mice into the common carotid artery using a previously described cuff technique. In the treatment group, 100 μg or 200 μg of rapamycin was applied locally in pluronic gel. The control group did not receive local treatment. Grafts were harvested at 1, 2, 4, and 6 weeks and underwent morphometric analysis as well as immunohistochemical analysis.: ResultsIn grafted veins without treatment (controls), median intimal thickness was 9.6 (6.4 to 29)μm, 11.9 (7.9 to 39.9)μm, 46.6 (12.4 to 57.7)μm, and 57.5 (32.5 to 71.1)μm after 1, 2, 4, and 6 weeks, respectively. Treatment with 100 μg or 200 μg rapamycin showed a dose dependant reduction of intimal thickness. In the 200 μg rapamycin treatment group the intimal thickness was 4.3 (3.4 to 5.6)μm, 3.8 (3.2 to 6.3)μm, 17.1 (4.8 to 63)μm, and 33.9 (11.3 to 80.3)μm after 1, 2, 4, and 6 weeks, respectively. This difference of intimal thickness of 200 μg treated animals compared with controls was statistically significant at 1 and 2 weeks. Immunohistochemically the reduction of intimal thickness was associated with a decreased amount of infiltration of CD-8 positive cells and a decreased amount of metallothionein positive cells in the rapamycin treated grafts.: ConclusionsWe conclude that perivascular application of rapamycin inhibits neointimal hyperplasia of vein grafts in a mouse model. These results suggest that rapamycin may have a therapeutic potential for the treatment of vein graft disease. [Copyright &y& Elsevier]

: BackgroundSildenafil (Pfizer Pharmaceuticals, Sandwich, Kent, UK) has been associated with pulmonary vasorelaxation. A more potent Sildenafil analogue (UK 343-664 [Pfizer Pharmaceuticals]) has been developed, but its effects in vivo have not been studied. This study evaluated the effects of UK 343-664 (Pfizer) during acute pulmonary hypertension.: MethodsFourteen adult swine were anesthetized with 1 minimum alveolar concentration isoflurane and were mechanically ventilated with an FIO2 of 50%. End tidal CO2 was maintained between 32 and 36 mm Hg. Micromanometer tipped catheters were placed in the ascending aorta, pulmonary artery, and right ventricle. Pulmonary flow was measured with a perivascular probe using transit time ultrasound. Pulmonary hypertension was induced with a continuous infusion of the thromboxane analogue U46619. Animals were randomized into two groups. Group 1 (n = 9) received 500 μg of UK 343-664 (Pfizer) intravenously for more than 2 minutes. Group 2 (n = 5) served as the control group. Data were recorded continuously for 60 minutes. Statistical analyses were performed with the analysis of variance and t tests. A p less than 0.05 was considered significant.: ResultsPulmonary hypertension was achieved in all animals. The administration of UK 343-664 (Pfizer) was associated with a significant decrease in pulmonary artery pressure (30.3%; p < 0.05) and pulmonary vascular resistance (42%; p < 0.05) with mild systemic vasodilatation. These effects were partially maintained at 30 minutes (a 17.3% and 39% decrease, respectively; p < 0.05).: ConclusionsThe administration of UK 343-664 (Pfizer) was associated with predominant pulmonary vasodilatation without systemic hypotension. This may represent a significant advance in the treatment of acute pulmonary hypertension. Potential clinical implications for this new phosphodiesterase enzyme type V (PDEV) inhibitor merit further study. [Copyright &y& Elsevier]

Statin therapy prevents the first occurrence and recurrence of coronary events and reduces cardiovascular and general mortality in patients with coronary artery disease. These compounds modulate a variety of processes involved in the pathophysiology of arteriosclerosis and vascular graft disease by lipid-dependent and lipid-independent (pleiotropic) mechanisms. As a result, statins produce angiographic and clinical benefits in patients undergoing coronary bypass surgery. We review the present knowledge about the effects of statins on this pathologic condition and the evidence supporting an early treatment initiation. [Copyright &y& Elsevier]

A new kind of sandwich-like bis[2,3,9,10,16,17,23,24-octakis(octyloxy)phthalocyaninato] samarium complex Sm[Pc*]2(Pc*=Pc(OC8H17)8) is used as film-forming material. Pure Sm[Pc*]2 and mixture of Sm[Pc*]2 and octadecanol(OA) deposited from both pure water and 10-4M Cd2+ subphases are investigated. It is found that a mixture of 1:3 Sm[Pc*]2:OA forms an excellent material for the fabrication of the gas-sensing Langmuir-Blodgett (LB) film by studying the film-forming characteristics. A new gas sensor has been fabricated by incorporating the multilayer LB film into the gate electrode of a metal-oxide-semiconductor field effect transistor, forming an array of charge-flow transistor. On the application of a gate voltage (VGS), greater than the threshold voltage (VTH), a delay was observed in the response of the drain current. This is due to the time taken for the resistive gas-sensing film to charge up to VGS. This delay characteristic was found to depend on the concentration of NO2. Results are presented showing that the device can detect reversibly the concentration of NO2 gas down to 5 ppm at room temperature. [ABSTRACT FROM PUBLISHER]

: BackgroundThis study determines whether controlled reperfusion or diazoxide improves intramyocyte Na+ homeostasis using a porcine model of severe ischemia-reperfusion injury.: MethodsThree groups (n = 10 pigs per group) had 75 minutes of left anterior descending artery occlusion during bypass. Group 1 had no treatment (control group), group 2 had controlled reperfusion (500 mL warm cardioplegia) (controlled reperfusion group), and group 3 had diazoxide (50 μmol/L before left anterior descending artery occlusion) (diazoxide group). Biopsies were taken from the left anterior descending artery region before ischemia and at 3, 5, and 10 minutes postreperfusion. Intra-myocyte Na+ and water contents were determined using atomic absorption spectroscopy, and Na+ concentrations were calculated.: ResultsIntra-myocyte Na+ increased for the diazoxide group pigs at 3-minutes postreperfusion (21.9 ± 2.9 vs 34.0 ± 3.4 μmol/mL; p = 0.02), but decreased to 19.9 ± 3.2 μmol/mL at 10 minutes postreperfusion (p = 1.0 vs baseline). At 10 minutes postreperfusion, intra-myocyte Na+ in the controlled reperfusion group was lower than baseline (22.3 ± 2.7 vs 17.2 ± 3.1 μmol/mL; p < 0.001). Intra-myocyte Na+ at 10 minutes postreperfusion for the diazoxide and controlled reperfusion groups was lower than for the control group (p < 0.05).: ConclusionsDiazoxide and controlled reperfusion improved intra-myocyte Na+ homeostasis after severe ischemia-reperfusion injury. [Copyright &y& Elsevier]

: BackgroundThe serine protease inhibitor aprotinin has been successfully used to reduce blood loss in patients undergoing cardiac operations. We studied aprotinin for its ability to modulate leukocyte–endothelial cell interactions after ischemia and reperfusion.: MethodsThe effects of aprotinin on leukocyte–endothelial cell interactions were observed by intravital microscopy in the rat mesenteric microcirculation and immunohistochemical analysis. The inflammatory cascade (leukocyte rolling, firm adherence, and transmigration) was studied after thrombin stimulation and after hemorrhage and reperfusion.: ResultsIntravenous bolus administration of aprotinin treatment (20,000 U/kg) significantly reduced leukocyte rolling from 55 ± 8 to 17 ± 3 cells/min (p < 0.01) and adherent cells from 12 ± 2 to 7 ± 1.4 cells (p < 0.05) along the venous endothelium of the rat mesentery after thrombin activation. In addition, aprotinin pretreatment significantly inhibited transmigration of leukocytes from 11.3 ± 1.2 to 6.0 ± 1.1 cells (p < 0.05) through the microvascular endothelial wall. Similarly, aprotinin decreased leukocyte–endothelium interaction after hemorrhagic shock. Moreover, immunohistochemistry demonstrated that aprotinin significantly attenuated P-selectin expression by the intestinal vascular endothelium.: ConclusionsOur data demonstrate that aprotinin potently inhibits recruitment of leukocytes in the microvasculature by interfering with endothelial cell–polymorphonuclear neutrophil interaction, and is a potent endothelial protective agent in clinically relevant doses. Thus, aprotinin pretreatment may be useful for primary prevention of inflammatory tissue injury mediated by ischemia–reperfusion injury such as shock, trauma, open heart operation, or other extensive vascular surgical procedures. [Copyright &y& Elsevier]

Different assay technologies are available that allow ligand occupancy of G protein coupled receptors to be converted into robust functional assay signals. Of particular interest are universal screening systems such that activation of any GPCR can be detected with a common assay end point. The promiscuous G protein Gα16 and chimeric G proteins are broadly used tools for setting up almost universal assay systems. Many efforts focused on making G proteins more promiscuous, however no attempts have been made to make promiscuos G proteins more sensitive by interfering with their cellular protein distribution. As a model system, we used a promiscuous G protein α[sub q] subunit, that lacks the highly conserved six amino acid N-terminal extension and bears four residues of α[sub i] sequence at its C-terminus replacing the corresponding α[sub q] sequence (referred to as Δ6qi4). When expressed in COS7 cells, Δ6qi4 undergoes palmitoylation at its N-terminus. Cell fractionation and immunoblotting analysis indicated localization in the particulate and cytosolic fraction. Interestingly, introduction of a consensus site for N-terminal myristoylation (the resulting mutant referred to as Δ6qi4myr) created a protein that was dually acylated and exclusively located in the particulate fraction. As a measure of G protein activation δ6qi4 and σ6qi4myr were coexpressed (in CHO cells) with a series of different Gi/o coupled receptors and ligand induced increases in intracellular Ca[sup 2+] release were determined with the FLIPR™ technology (Fluorescence plate imaging reader from Molecular Devices Corp.). All of the receptors interacted more efficiently with δ6qi4myr as compared with δ6qi4. It could be shown that increased functional responses of agonist activated GPCRs are due to the higher content of δ6qi4myr in the plasma membrane. Our results indicate that manipulation of subcellular localization of G... [ABSTRACT FROM AUTHOR]

Background. Blood transfusions have been linked to increased morbidity and mortality. Bleeding during and after cardiac operations and the hemodilution effects of cardiopulmonary bypass commonly result in blood transfusions. Because we could not find any studies evaluating the effects of transfusion on long-term survival after cardiac operation, we sought to determine these effects.Methods. We studied 1,915 patients who underwent first-time isolated coronary artery bypass operations between July 6, 1994 and December 31, 1997 at our institution. Patients with transfusions were compared with those who had not been transfused. Long-term survival data were obtained from the United States Social Security Death Index. Groups were compared by Cox proportional hazard models, Kaplan-Meier survival plots, and hazard functions.Results. Six hundred forty-nine of 1,915 study patients (34%) received a transfusion during their hospitalization. Transfused patients were older, smaller, and more likely to be female, and had more comorbidity. Transfused patients also had twice the 5-year mortality (15% vs 7%) of nontransfused patients. After correction for comorbidities and other factors, transfusion was still associated with a 70% increase in mortality (risk ratio = 1.7; 95% confidence interval = 1.4 to 2.0; p = 0.001). By multivariate analysis, transfusion, peripheral vascular disease, chronic obstructive pulmonary disease, New York Heart Association functional class IV, and age were significant predictors of long-term mortality.Conclusions. We found that blood transfusions during or after coronary artery bypass operations were associated with increased long-term mortality. [Copyright &y& Elsevier]