bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatty Acid Methyl Ester Synthesis over Fe3+‐Vanadyl Phosphate Catalysts
Authors: Li Hui , Xie Wenlei 
Published: May 2008

AbstractA heterogeneous acid catalyst, Fe3+‐vanadyl phosphate, prepared by the isomorphous substitution of some VO3+ groups in vanadyl phosphate with trivalent metal Fe3+, was found to be active for the transesterification of soybean oil with methanol. When the transesterification reaction was carried out with a molar ratio of methanol to oil of 30:1, a reaction temperature of 473 K, a reaction time of 3 h and a catalyst amount of 5 wt%, the maximum conversion of soybean oil was 61.3%. Moreover, the catalytic activity of this catalyst was not significantly affected by the presence of free fatty acids and water in the reactants, and it also exhibits catalytic activity towards the esterification of free fatty acids with methanol. Further, it was shown that the spent catalyst could be easily reactivated by calcination at 773 K in air. There was very little change in the catalytic activity of the regenerated catalyst, even after five cycles.
Negative regulation of multifunctional Ca2+/calmodulin‐dependent protein kinases: physiological and pharmacological significance of protein phosphatases
Authors: Ishida A , Sueyoshi N , Shigeri Y , Kameshita I 
Published: May 2008

Multifunctional Ca2+/calmodulin‐dependent protein kinases (CaMKs) play pivotal roles in intracellular Ca2+ signaling pathways. There is growing evidence that CaMKs are involved in the pathogenic mechanisms underlying various human diseases. In this review, we begin by briefly summarizing our knowledge of the involvement of CaMKs in the pathogenesis of various diseases suggested to be caused by the dysfunction/dysregulation or aberrant expression of CaMKs. It is widely known that the activities of CaMKs are strictly regulated by protein phosphorylation/dephosphorylation of specific phosphorylation sites. Since phosphorylation status is balanced by protein kinases and protein phosphatases, the mechanism of dephosphorylation/deactivation of CaMKs, corresponding to their ‘switching off’, is extremely important, as is the mechanism of phosphorylation/activation corresponding to their ‘switching on’. Therefore, we focus on the regulation of multifunctional CaMKs by protein phosphatases. We summarize the current understanding of negative regulation of CaMKs by protein phosphatases. We also discuss the biochemical properties and physiological significance of a protein phosphatase that we designated as Ca2+/calmodulin‐dependent protein kinase phosphatase (CaMKP), and those of its homologue CaMKP‐N. Pharmacological applications of CaMKP inhibitors are also discussed. These compounds may be useful not only for exploring the physiological functions of CaMKP/CaMKP‐N, but also as novel chemotherapies for various diseases.British Journal of Pharmacology (2008) 154, 729–740; doi:10.1038/bjp.2008.127; published online 5 May 2008
Src kinase‐targeted anti‐inflammatory activity of davallialactone from Inonotus xeranticus in lipopolysaccharide‐activated RAW264.7 cells
Authors: Lee Y G , Lee W M , Kim J Y , Lee J Y , Lee I‐K , Yun B‐S , Rhee M H , Cho J Y 
Published: May 2008

Background and purpose:Mushrooms are popular both as food and as a source of natural compounds of biopharmaceutical interest. Some mushroom‐derived compounds such as β‐glucan have been shown to be immunostimulatory; this study explores the anti‐inflammatory properties of hispidin analogues derived from the mushroom, Inonotus xeranticus. We sought to identify the molecular mechanism of action of these hispidin analogues by determining their effects on lipopolysaccharide (LPS)‐mediated inflammatory responses in a macrophage cell line.Experimental approach:The production of inflammatory mediators was determined by Griess assay, reverse transcription‐PCR and ELISA. The inhibitory effect of davalliactone on LPS‐induced activation of signalling cascades was assessed by western blotting, immunoprecipitation and direct kinase assay.Key results:In activated RAW264.7 cells, davallialactone strongly downregulated LPS‐mediated inflammatory responses, including NO production, prostaglandin E2 release, expression of proinflammatory cytokine genes and cell surface expression of co‐stimulatory molecules. Davallialactone treatment did not alter cell viability or morphology. Davallialactone was found to exert its anti‐inflammatory effects by inhibiting a signalling cascade that activates nuclear factor kappa B via PI3K, Akt and IKK, but not mitogen‐activated protein kinases. Treatment with davallialactone affected the phosphorylation of these signalling proteins, but not their level of expression. These inhibitory effects were not due to the interruption of toll‐like receptor 4 binding to CD14. In particular, davallialactone strongly inhibited the LPS‐induced phosphorylation and kinase activity of Src, implying that Src may be a potential pharmacological target of davallialactone.Conclusions and implications:Our data suggest that davallialactone, a small molecule found in edible mushrooms, has anti‐inflammatory activity. Davallialactone can be developed as a pharmaceutically valuable anti‐Src kinase agent.British Journal of Pharmacology (2008) 154, 852–863; doi:10.1038/bjp.2008.136; published online 5 May 2008
Rapamycin affects early fracture healing in mice
Authors: Holstein J H , Klein M , Garcia P , Histing T , Culemann U , Pizanis A , Laschke M W , Scheuer C , Meier C , Schorr H , Pohlemann T , Menger M D 
Published: May 2008

Background and purpose:The immunosuppressive drug rapamycin (RAPA) prevents rejection in organ transplantation by inhibiting interleukin‐2‐stimulated T‐cell division. Rapamycin has also been suggested to possess strong anti‐angiogenic activities linked to a decrease in production of vascular endothelial growth factor (VEGF). Angiogenesis and VEGF are thought to play a crucial role in fracture healing and as osteoporotic and traumatic fractures are common complications in immunosuppressed, organ transplantation patients, we conducted this study to analyze the effect of rapamycin treatment on bone repair.Experimental approach:We investigated the effect of rapamycin treatment on bone repair in a murine closed femur fracture model using radiological, histomorphometric, immunohistochemical, biomechanical and protein biochemical analyses.Key results:X‐ray analyses demonstrated that rapamycin treatment inhibits callus formation after two weeks of fracture healing. The radiologically observed lack of callus formation was confirmed by histomorphometric analyses, which revealed a significantly diminished callus size and a reduced amount of bone formation when compared with vehicle‐treated controls. Biomechanical testing further demonstrated that rapamycin significantly reduces torsional stiffness of the callus. Interestingly, this effect was associated with decreased vessel formation; a diminished proliferation of osteoblasts, endothelial cells and periosteal cells; and a reduced VEGF expression in hypertrophic chondrocytes. After five weeks treatment, however, the negative impact of rapamycin on fracture healing was overcome.Conclusions and implications:Thus, rapamycin initially delays fracture healing, most probably by inhibiting cell proliferation and neovascularization in the callus. These undesirable effects should be considered when rapamycin is administered to patients sustaining bone fractures.British Journal of Pharmacology (2008) 154, 1055–1062; doi:10.1038/bjp.2008.167; published online 5 May 2008
Rimonabant in rats with a metabolic syndrome: good news after the depression
Authors: Di Marzo V , Szallasi A 
Published: May 2008

The synthetic cannabinoid CB1 receptor antagonist rimonabant (sold in the United Kingdom under the brand name Acomplia) was reported to improve the profile of cardiovascular risk factors in obese patients with the metabolic syndrome, a cluster of metabolic disorders that often precedes the onset of type II diabetes. Rimonabant is shown in the current issue of British Journal of Pharmacology to attenuate weight gain in Zucker rats, an experimental model of insulin resistance. Neutrophil and monocyte counts were lowered by rimonabant administration. Both platelet activation (by ADP) and aggregation (in response to thrombin) were inhibited. Circulating pro‐inflammatory cytokine levels (monocyte chemotactic protein 1, MCP1 and Regulated upon Activation, Normal T‐cell Expressed and Secreted, RANTES) were also reduced. Furthermore, fibrinogen levels returned to normal. These favourable anti‐inflammatory and anti‐thrombotic actions imply for rimonabant a peripheral, direct action on some cardiovascular risk factors.British Journal of Pharmacology (2008) 154, 915–917; doi:fn1; published online 5 May 2008
Key Role of Platelet Procoagulant Activity in Tissue Factor‐and Collagen‐Dependent Thrombus Formation in Arterioles and Venules In Vivo Differential Sensitivity to Thrombin Inhibition
Authors: Kuijpers Marijke J.E. , Munnix Imke C.A. , Cosemans Judith M.E.M. , Vlijmen Bart J. Van , Reutelingsperger Chris P.M. , Egbrink Mirjam G.A. Oude , Heemskerk Johan W.M. 
Published: May 2008

ABSTRACTObjective: Blood coagulation and platelet activation are mutually dependent processes, but contribute differently to venous and arterial thrombosis. We investigated the interplay of these processes in vivo in a mouse model of arteriolar and venular thrombus formation.Methods: Thrombus formation was studied by intravital (fluorescence) microscopy after topical application of FeCl3 on mouse mesenteric microvessels.Results: Both in arterioles and venules, the thrombus‐forming process relied on tissue factor‐factor VII(a) interaction, collagen exposure, and glycoprotein VI–mediated platelet activation. Arterial thrombus formation was impaired by mild thrombin inhibition or platelet inhibition, while venous thrombosis was only suppressed by strong thrombin inhibition or by mild thrombin inhibition together with platelet inhibition. Phosphatidylserine‐exposing platelets were present in thrombi of both vessel types, as detected with fluorescently labeled annexin A5. Injection of annexin A5 to shield exposed phosphatidylserine abolished thrombus formation in arterioles and venules, while mutant M1234‐annexin A5 was ineffective. Arterial and venous thrombus formations were only slightly affected in mice carrying the factor V Leiden mutation, suggesting insensitivity to factor Va inactivation.Conclusions: In this microvascular model, the formation of both arterial and venous thrombi relies on collagen‐induced platelet activation and tissue factor–induced thrombin generation. Activated, phosphatidylserine‐exposing platelets play a key role in thrombus growth in arterioles and venules.
Inflammatory and Hemodynamic Changes in the Cerebral Microcirculation of Aged Rats after Global Cerebral Ischemia and Reperfusion
Authors: Ritter Leslie , Funk Janet , Schenkel Lori , Tipton Alicia , Downey Kate , Wilson Jonathan , Coull Bruce , Mcdonagh Paul 
Published: May 2008

ABSTRACTEffects of aging on inflammation and blood flow in the brain are unclear. Young (three to six months) and aged (19–22 months) male Brown Norway Fisher rats were used to compare (i) leukocyte function in nonischemic conditions and (ii) leukocyte function and hemodynamic changes after ischemia‐reperfusion (I‐R). In nonischemic studies, polymorphonuclear (PMN) CD11b expression and reactive oxygen species (ROS) production were measured with flow cytometry and PMN chemotaxis was measured with a Boyden chamber (+/‐fMLP). In I‐R studies, ischemia was induced by bilateral carotid artery occlusion and hypotension (20 minutes). During early reperfusion (30 minutes), leukocyte adhesion and rolling and blood‐shear rates were measured using fluorescence microscopy. During late reperfusion (48 hours), mortality, neurological function, and leukocyte infiltration were measured. Stimulated PMN chemotaxis was increased in nonischemic aged rats (p < 0.05). In early reperfusion, there was a significant increase in leukocyte rolling and adhesion in the cerebral microcirculation and a significant decrease in shear rate in aged rats, compared to the young (p < 0.05). During late reperfusion, neurologic function was worse in aged vs. young rats (p < 0.05). These findings suggest that increased intravascular PMN adhesion and vascular dysfunction may contribute to poor neurologic outcome after cerebral I‐R in the aged brain.
Critical Role of FcR γ‐Chain, LAT, PLCγ2 and Thrombin in Arteriolar Thrombus Formation upon Mild, Laser‐Induced Endothelial Injury In Vivo
Authors: Kalia Neena , Auger Jocelyn M. , Atkinson Ben , Watson Steve P. 
Published: May 2008

ABSTRACTObjective: The role of collagen receptor complex GPVI‐FcR γ‐chain, PLCγ2 and LAT in laser‐induced thrombosis is unclear. Controversy surrounds whether collagen is exposed in this model or whether thrombosis is dependent on thrombin. This study hypothesized that collagen exposure plays a critical role in thrombus formation in this model, which was tested by investigating contributions of FcR γ‐chain, LAT, PLCγ2 and thrombin.Methods: Thrombi were monitored using intravital microscopy in anesthetized wild‐type and FcR γ‐chain, LAT and PLCγ2 knockout mice. Hirudin (thrombin inhibitor) was administered to wild‐type and FcR γ‐chain knockout mice.Results: Significantly reduced thrombus formation was observed in FcR γ‐chain and PLCγ2 knockouts with a greater decrease observed in LAT knockouts. Dramatic reduction was observed in wild‐types treated with hirudin, with abolished thrombus formation only observed in FcR γ‐chain knockouts treated with hirudin.Conclusions: GPVI‐FcR γ‐chain, LAT and PLCγ2 are essential for thrombus generation and stability in this laser‐induced model of injury. More importantly, a greater role for LAT was identified, which may reflect a role for it downstream of a second matrix protein receptor. However, inhibition of platelet activation by matrix proteins and thrombin generation are both required to maximally prevent thrombus formation.
Peritubular Capillary Loss Is Ameliorated by Ramipril or Valsartan Treatment
Authors: Zhang Bin , Chen Nan , Shi Wei , Wang Weiming , Shi Hao , Yu Haijin 
Published: May 2008

ABSTRACTObjective: To identify the preservation of peritubular capillaries conferred by ramipril or valsartan treatment as an additional mechanism for their renoprotection.Methods: The effect of ramipril or valsartan on peritubular capillaries was investigated in a remnant kidney model using male Sprague‐Dawley rats sacrificed post‐operatively at 3, 6 and 12 weeks respectively. Peritubular capillaries and tubulointerstitial hypoxia in untreated remnant kidney rats (n = 26), remnant kidney rats treated with ramipril (n = 22, 0.5 mg/kg/day), valsartan (n = 22, 30 mg/kg/day) or amlodipine (n = 22, 30 mg/kg/day) and sham‐operated rats (n = 22) were assessed by CD141 and HIF‐1α staining.Results: Ramipril or valsartan significantly preserved the peritubular capillaries as well as renal function (p < 0.01). Tubulointerstitial hypoxia and tubular TGF‐β expression were noted well before the development of tubulointerstitial damage. The gentler slope of the relationship between HIF‐1α scores and peritubular capillary density in individual rats was noted in both ramipril‐treated and valsartan‐treated groups compared to the untreated remnant kidney group (p < 0.05).Conclusions: Amelioration of peritubular capillary loss and subsequent tubular hypoxia by ramipril or valsartan treatment should be interpreted as an alternative type of their renoprotection, one which also implies a novel focus for clinical intervention.
The Origin of the Biphasic Flow Response to Local Heat in Skin
Authors: Widmer R. Jay , Laurinec Jennifer E. , Young Missy F. , Mohiuddin M. Waqar , Laine Glen A. , Quick Christopher M. 
Published: May 2008

ABSTRACTObjective: Although it is well established that the application of local heat causes a biphasic increase in skin blood flow, the responsible microvessels have not been identified.Methods: A bifurcating network of arterioles (1st–5th orders, 60–15 μm, n = 10 per group) of the intact, unanesthetized, translucent bat wing were visualized on a transparent heat plate via intravital microscopy. Similar to previous bat wing studies, plate temperature was set at 25°C for 10 min then increased to 37°C for 20 min. Vessel diameter and red blood cell velocity were recorded and used to calculate resistance and blood flow.Results: The average flow response in arterioles was biphasic (p = 0.02) and proportional to the temporal decrease in total resistance calculated from 1st–5th order arterioles. Metarteriole (i.e., 5th order arteriole) resistance had the greatest impact on total resistance (−67.0 ± 20.7%) and exhibited a biphasic trend that was opposed by temporal changes in resistance of 1st–4th order arterioles.Conclusion: Metarterioles are not only necessary but sufficient to explain the origin of the biphasic flow response in skin blood flow.
Aortic Valve Replacement through a Mini Lateral Thoracotomy with High Thoracic Epidural Anesthesia
Authors: Francesco Siclari , Stefanos Demertzis , Romano Mauri , Tiziano Cassina , Giovanni Pedrazzini , Tiziano Moccetti 
Published: May 2008

Background Minimally invasive aortic valve surgery is usually performed through a right parasternal incision or a modification of partial sternotomy. We explored the feasibility of using a videoassisted small right lateral thoracotomy (RLT) to approach the aortic valve. Methods From August 2003 to December 2004, 12 patients with aortic stenosis (9) or regurgitation (3) underwent an aortic valve replacement through an 8 cm RLT in the 4th intercostal space. There were 4 men and 8 women with a mean age of 61 years (range 30–79 years). Nine mechanical and 3 biologic prostheses were implanted. Endotracheal narcosis was combined with high thoracic epidural anesthesia. Transesophageal echocardiographic monitoring was performed in all cases. Cannulation was done via the right femoral artery and vein and right jugular vein. The video-assisted operation was performed in moderate hypothermia (30°C) and in cardioplegic arrest. Transthoracic aortic clamping was used in all cases. Results Mean operation, perfusion, and clamping times were 223 minutes, 132 minutes, and 73 minutes, respectively. There was no mortality. One patient required conversion to sternotomy due to discovery of a calcium fragment entrapped in a mechanical prosthesis. One patient developed a groin seroma that was treated surgically. All patients, except one were extubated in the operative room and transferred to the intermediate care unit after 6 hours; all had an uneventful recovery. Conclusions Aortic valve replacement through an RLT is feasible and safe. Operative time, perfusion, and cross-clamping times are only marginally longer than a conventional operation, and recovery is rapid.
External Reshaping of the Left Ventricle in Off-Pump Surgery
Authors: Prapas Sotirios N. , Protogeros Demetrios A. , Kotsis Vassilios N. , Panagiotopoulos Ioannis A. , Raptis Ioannis P. , Danou Fotini N. , Linardakis Ioannis N. , Karatza Dimitra C. , Anagnostopoulos Constantinos E. 
Published: May 2008

Background Dyskinetic areas of the lateral and inferior left ventricular (LV) wall are frequently encountered in patients with coronary artery disease. In clinical practice, all of the techniques described for the restoration of shape and function of the LV require cardiopulmonary bypass. A new technique of LV external reshaping that aims to obtain a near-normal ventricular conical shape is described. This technique is performed during an off-pump coronary artery bypass graft (CABG) operation. It is used mainly on the inferior and lateral walls of the ventricle, but also on the anterolateral wall when warranted. This technique can be considered an alternative to classic aneurysmectomy in high-risk cases. Methods All patients underwent total arterial revascularization without aortic manipulation. Intraoperative transesophageal echocardiography was used in all cases to define the dilated akinetic/dyskinetic area. This area was effectively plicated using interrupted mattress sutures reinforced with Teflon felt or pericardial strips. This technique allows near normalization of the geometry of the ventricle and LV end-diastolic volume reduction. In cases of preexisting mitral regurgitation (MR), a reduction of the MR was observed after lateral wall restoration. From September 2002 to April 2005, the external reshaping technique was applied on 56 cases among 949 off-pump CABG cases (5.9%). A detailed transthoracic echocardiogram was obtained preoperatively. The mean ejection fraction of all enrolled patients was 31.2 ± 7%. The location of the plication was: lateral wall in 22, inferior wall in 16, and anterolateral wall in 18. The average number of coronary anastomoses was 2.6. Twelve patients were found to have 2–3 + MR. All patients were followed up during a period of 35 months. Results One patient died due to severe right ventricular dysfunction. Seven patients developed atrial fibrillation, and one had ventricular tachycardia. During the follow-up period, we observed a reduction of left ventricular end-diastolic diameter and a parallel augmentation of ejection fraction (mean 42.2 ± 4%). The ventricular cavity's architecture was normalized. Among the 12 patients with MR, an improvement of regurgitation was noted in 10 (from 2–3+ to 1–2+). One patient died during the follow-up period, and 1 patient required reoperation due to persistent severe MR. Conclusions The external reshaping of the LV during beating heart surgery is technically feasible, has promising results, and can be performed without major complications.
Percutaneous Subxiphoid Access to the Epicardium Using a Miniature Crawling Robotic Device
Authors: Ota Takeyoshi , Patronik Nicholas A. , Riviere Cameron N. , Zenati Marco A. 
Published: May 2008

Background To expand minimally invasive beating-heart surgery, we have developed a miniature 2-footed crawling robot (Heart-Lander) that navigates on the epicardium. This paradigm obviates mechanical stabilization and lung deflation, and avoids the access limitations of current approaches. We tested the locomotion of the device on a beating porcine heart accessed through a closed-chest subxiphoid approach. Methods HeartLander consists of 2 modules that are connected by an extensible midsection. It adheres to the epicardium using suction pads. Locomotion and turning are accomplished by moving the 2 modules in an alternating fashion using wires that run through the midsection between them. After a preliminary test with a plastic beating-heart model, we performed a porcine study in vivo. The device was inserted into the pericardial space through a subxiphoid incision, while the test was observed using a left thoracoscopy. The blood pressure and electrocardiogram were monitored, and vacuum pressure and driving forces on the wires were recorded. Results HeartLander traveled across the anterior and lateral surfaces of the beating heart without restriction, including locomotion forward, backward, and turning. The vacuum pressure was kept below 450 mm Hg at all times. The average maximum force during elongation was 1.86 ± 0.97 N, and during retraction was 1.24 ± 0.33 N. No adverse hemodynamic or electrophysiologic events were noted during the trial. No epicardial damage was found on the excised heart after the porcine trial. Conclusions The current HeartLander prototype demonstrated safe and successful locomotion on a beating porcine heart through a closed-chest subxiphoid approach.