ABSTRACT
Mesenchymal stem cells (MSCs) have attracted a great deal of interest as a therapeutic tool for renal fibrosis. Although both adipose-derived and bone marrow-derived MSCs (ADSCs and BMSCs, respectively) suppress renal fibrosis, which of these two has a stronger therapeutic effect remains unclear. This study aimed to compare the antifibrotic effects of ADSCs and BMSCs extracted from adipose tissue and bone marrow derived from the same rats. When cultured in serum-containing medium, ADSCs had a more potent inhibitory effect than BMSCs on renal fibrosis induced by ischemia-reperfusion injury in rats. ADSCs and BMSCs cultured in serum-free medium were equally effective in suppressing renal fibrosis. Mice infused with ADSCs (serum-containing or serum-free cultivation) had a higher death rate from pulmonary embolism than those infused with BMSCs. In vitro, mRNA levels of tissue factor, tumor necrosis factor-α-induced protein 6 and prostaglandin E synthase were higher in ADSCs than in BMSCs, while that of vascular endothelial growth factor was higher in BMSCs than in ADSCs. Although ADSCs had a stronger antifibrotic effect, these findings support the consideration of thromboembolism risk in clinical applications. Our results emphasize the importance of deciding between ADSCs and BMSCs based upon the target disease and culture method.
Subject(s)
Mesenchymal Stem Cells , Vascular Endothelial Growth Factor A , Rats , Mice , Animals , Vascular Endothelial Growth Factor A/metabolism , Bone Marrow , Mesenchymal Stem Cells/metabolism , Fibrosis , Adipose Tissue/metabolism , Bone Marrow Cells , Cell DifferentiationABSTRACT
Noroviruses (NoVs) are one of the major causes of acute viral gastroenteritis in humans. Virus-like particles (VLPs) without genomes that mimic the capsid structure of viruses are promising vaccine candidates for the prevention of NoVs infection. To produce large amounts of recombinant protein, including VLPs, the silkworm-expression vector system (silkworm-BEVS) is an efficient and powerful tool. In this study, we constructed a recombinant baculovirus that expresses VP1 protein, the major structural protein of NoV GII.4. Expression analysis showed that the baculovirus-infected silkworm pupae expressed NoV VP1 protein more efficiently than silkworm larval fat bodies. We obtained about 4.9 mg of purified NoV VP1 protein from only five silkworm pupae. The purified VP1 protein was confirmed by dynamic light scattering and electron microscopy to form VLPs of approximately 40 nm in diameter. Antisera from mice immunized with the antigen blocked NoV VLPs binding to histo-blood group antigens of pig gastric mucin and also blocked NoV infection in intestinal epithelial cells derived from human induced pluripotent stem (iPS) cells. Our findings demonstrated that NoV VLP eliciting protective antibodies could be obtained in milligram quantities from a few silkworm pupae using the silkworm-BEVS.
Subject(s)
Artificial Virus-Like Particles , Bombyx , Caliciviridae Infections , Gastroenteritis , Norovirus , Animals , Humans , Mice , Antibodies , Antibodies, Viral , Bombyx/chemistry , Bombyx/metabolism , Caliciviridae Infections/prevention & control , Capsid Proteins/genetics , Norovirus/genetics , Norovirus/immunology , Pupa , Swine , Artificial Virus-Like Particles/immunologyABSTRACT
New µ3-hydroxido/oxido bridged trinuclear uranyl(VI) complexes with 3,5-di-t-butyl-N-salicylidene-2-aminophenolato (dbusap2-) ligands, Et3NH[(UO2)3(µ3-OH)(dbusap)3] (Et3NH[1]) and (Et3NH)2[(UO2)3(µ3-O)(dbusap)3] ((Et3NH)2[2]) were synthesized and characterized. Single-crystal X-ray structures of both complexes were determined. The oxygen atom on µ3-hydroxido center in [1]- is sp3 hybridized with an average U-(µ3-O)-U bond angle of 109.7(5)°; the µ3-oxido atom in [2]2- is sp2 hybridized with an average U-(µ3-O)-U bond angle of 118.0(10)°. U-(µ3-O) distances in [1]- are long (average of 2.43(1) Å) compared with those in [2]2- (average of 2.23(2) Å). The optimized geometries of the [(UO2)3(µ3-OH)]5+ core in [(UO2)3(µ3-OH)(sap)3]- and the [(UO2)3(µ3-O)]4+ core in [(UO2)3(µ3-O)(sap)3]2- (where sap = N-salicylidene-2-aminophenolato) from density functional theory (DFT) calculations resemble those in [1]- and [2]2-, respectively. The U-(µ3-O) bond in [2]2- is significantly shorter than that in [1]-, because of the greater negative charge on the central µ3-oxido. A reversible structural conversion between [2]2- and [1]- was conducted by protonation and deprotonation of the µ3-oxido/hydroxido group. The activation enthalpy and entropy of the proton self-exchange reaction between [1]- and [2]2- determined from the temperature dependence of 1H NMR coalescence are ΔH⧧ = 23 ± 2 kJ mol-1 and ΔS⧧ = -77 ± 5 J K-1 mol-1.
ABSTRACT
Heparin-induced thrombocytopenia (HIT) is still a relatively uncommon condition and it is not well known how to administer argatroban during continuous hemodiafiltration (CHDF). A 72-year-old man required CHDF with heparin because of the oliguria and hyperpotassemia directly after the open repair of a juxtarenal abdominal aortic aneurysm. As the postoperative blood platelet count dropped and there was a thrombus in the CHDF circuit, HIT was suspected and nafamostat mesilate, but not heparin, was immediately administered for CHDF. As heparin-platelet factor 4 complex was positive, we diagnosed him with HIT and started argatroban while monitoring the activated clotting time (ACT), resulting in no further obstruction of the CHDF and an increase in the platelets. There was no disadvantage for administering nafamostat mesilate which we have commonly used instead of heparin, we should have used argatroban once we suspected HIT. It may be important to consider the history of heparin especially in administering heparin and it may be useful to monitor the ACT when initially starting argatroban for patients with HIT.
ABSTRACT
OBJECTIVE: Vitamin B2 (riboflavin) reportedly has an antioxidant effect through superoxide dismutase (SOD) activation. However, the effect of riboflavin on abdominal aortic aneurysm (AAA) has never been investigated. In the present study, we examined the hypothesis that riboflavin has a protective effect on AAA formation in an experimental rat model. METHODS: The AAA model, which was induced with intraluminal elastase and extraluminal calcium chloride, was created in 36 rats. The 36 rats were divided into a riboflavin group (group R; 25 mg/kg/d), and control group (carboxymethyl cellulose). Riboflavin administration by gastric gavage once per day was started at 3 days before aneurysm preparation. On day 3, SOD activity in aneurysm walls was assayed. On day 7, reactive oxygen species (ROS) levels were semiquantified by dihydroethidium staining, and the oxidation product of DNA produced by ROS, 8-hydroxydeoxyguanosine (8-OHdG), was measured by immunohistochemical staining. Histopathologic examination (hematoxylin/eosin and elastica Van Gieson staining) was performed on day 28, and the AAA dilatation ratio was calculated to evaluate the protective effect of riboflavin. RESULTS: On day 3, SOD activity was significantly increased in aneurysm walls by riboflavin administration (370 ± 204 U/mL in normal, 334 ± 86 U/mL in control, 546 ± 143 U/mL in group R; P = .021). On day 7, ROS levels and 8-OHdG-positive cells in aneurysm walls were significantly decreased by riboflavin treatment (ROS levels: 1.0 ± 0.1 in normal, 4.5 ± 0.4 in control, 3.1 ± 0.5 in group R, P < .01; 8-OHdG-positive cells: 30 ± 2 cells in normal, 148 ± 20 cells in control, 109 ± 15 cells in group R, P < .01). Riboflavin treatment significantly reduced matrix metalloproteinase (MMP)-9 messenger RNA expression in aneurysm walls (relative expression: MMP-9: 0.4 ± 0.7 in normal, 2.6 ± 1.3 in control, 0.5 ± 0.3 in group R, P < .01). On day 28, the aortic walls were less dilated and had higher elastin content in group R than in control (dilatation ratio: 194.9% ± 10.9% in control, 158.6% ± 2.5% in group R; P <.01). CONCLUSIONS: Riboflavin treatment prevents AAA formation in a rat model through an antioxidant effect and might be a potent pharmacologic agent for AAA treatment in clinical practice.
Subject(s)
Antioxidants/administration & dosage , Aorta, Abdominal/drug effects , Aortic Aneurysm, Abdominal/prevention & control , Enzyme Activators/administration & dosage , Riboflavin/administration & dosage , Superoxide Dismutase/metabolism , 8-Hydroxy-2'-Deoxyguanosine , Administration, Oral , Animals , Aorta, Abdominal/enzymology , Aorta, Abdominal/pathology , Aortic Aneurysm, Abdominal/chemically induced , Aortic Aneurysm, Abdominal/enzymology , Aortic Aneurysm, Abdominal/pathology , Calcium Chloride , DNA Damage , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Dilatation, Pathologic , Disease Models, Animal , Enzyme Activation , Extracellular Signal-Regulated MAP Kinases/metabolism , Inflammation Mediators/metabolism , Male , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Oxidative Stress/drug effects , Pancreatic Elastase , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Time FactorsABSTRACT
PURPOSE: To demonstrate the protective effect of glucagon-like peptide 1 (GLP-1) signaling on the cardiovascular system, we conducted this study to show that the GLP-1 receptor analog (lixisenatide) could inhibit abdominal aortic aneurysm (AAA) development in rats. METHODS: Lixisenatide was injected subcutaneously 7 days after aneurysm preparation. We evaluated reactive oxygen species (ROS) expression by dihydroethidium staining and 8-hydroxydeoxyguanosine (8-OHdG; the oxidation product of DNA) by immunohistochemical staining. We also analyzed the effect of GLP-1 signaling on the inflammatory response. Histopathological examination was done on day 28, and the AAA dilatation ratio was calculated. RESULTS: On day 14, ROS expression and 8-OHdG-positive cells in the aneurysm walls were seen to have been significantly decreased by lixisenatide treatment. Western blot analysis showed decreased ERK expression. There was significantly reduced tumor necrosis factor-α mRNA expression in the aneurysm walls and CD68-positive cell infiltration in the aneurysm walls. On day 28, it was evident that the lixisenatide had dramatically reduced aneurysm development in the rats. CONCLUSION: GLP-1 elevation inhibits AAA development in rats through its anti-oxidant and anti-inflammatory effects. Thus, GLP-1 could be a potent pharmacological target for AAA treatment.
Subject(s)
Aortic Aneurysm, Abdominal/genetics , Aortic Aneurysm, Abdominal/prevention & control , Glucagon-Like Peptide 1/pharmacology , Glucagon-Like Peptide 1/physiology , Signal Transduction/physiology , Animals , Anti-Inflammatory Agents , Antioxidants , Aortic Aneurysm, Abdominal/metabolism , Disease Models, Animal , Glucagon-Like Peptide 1/administration & dosage , Glucagon-Like Peptide-1 Receptor/physiology , Injections, Subcutaneous , Male , Molecular Targeted Therapy , Peptides/administration & dosage , Peptides/pharmacology , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolismABSTRACT
A 49-year-old male was referred to our hospital for cardiomegaly and severe aortic regurgitation. He had been diagnosed with osteogenesis imperfecta (OI) due to his history of multiple fractures in childhood and blue sclera. Aortic valve replacement(AVR) was performed via femoral cannulation and full sternotomy, with the opening of the sternum limited to a width of 6-7 cm in order to protect the brittle sternum and thorax. After weaning the patient off cardiopulmonary bypass, the sternum was closed using titanium plates. He subsequently recovered without excessive bleeding or other complications, and the healing of the sternum 3 months after the surgery was satisfactory. Cardiovascular surgery has been reported to be associated with high morbidity and mortality in patients with OI due to their friability of tissue and bleeding tendency. In the present case, AVR was performed successfully in a patient with OI using various surgical techniques.
Subject(s)
Aortic Valve Insufficiency/surgery , Osteogenesis Imperfecta/complications , Aortic Valve Insufficiency/diagnostic imaging , Aortic Valve Insufficiency/etiology , Heart Valve Prosthesis Implantation , Humans , Imaging, Three-Dimensional , Male , Middle Aged , Tomography, X-Ray Computed , UltrasonographyABSTRACT
A 72-year-old female presented with congestive heart failure. Ultrasound cardiogram revealed billowing mitral leaflets and severe mitral regurgitation. We diagnosed her with Barlow's disease and performed mitral valve repair. The posterior leaflet was large, and the leaflet height was more than 26 mm. Leaflet height reduction was necessary in order to prevent systolic anterior movement (SAM). The middle scallop was resected in a" W" shape, and its center vertex was designed to have a height of 18 mm, which was the final height of the posterior leaflet. SAM and major leaks were not seen by transesophageal echocardiography after weaning the patient from cardiopulmonary bypass. The use of a W-shaped resection is a simple technique that can be used to reduce the volume and height of the posterior mitral leaflet.
Subject(s)
Cardiac Surgical Procedures/methods , Mitral Valve Insufficiency/surgery , Mitral Valve Prolapse/surgery , Mitral Valve/surgery , Sutures , Aged , Female , Humans , Mitral Valve/physiopathology , Mitral Valve Prolapse/physiopathologyABSTRACT
A 72-year-old woman was diagnosed with bladder cancer (cT3bN0M0). After 2 cycles of GC (gemcitabineï¼cisplatin) neoadjuvant chemotherapy, the patient underwent a cystectomy and ileal conduit construction. Pathological findings showed urothelial carcinoma, high grade, G2ï¼G3, pT3a, INFß, ly0, v1. Six months after the operation, metastases to the liver, lung, left adrenal gland, rib, multiple lymph nodes, and peritoneum were revealed. Under palliative care, she suffered from palpitation and general fatigue. Electrocardiogram findings showed a complete atrioventricular block, while echocardiography and computed tomography revealed cardiac metastasis. We diagnosed her with complete atrioventricular block due to cardiac metastasis from bladder cancer. She died 7 days after onset of the complete atrioventricular block without use of a pacemaker.
Subject(s)
Atrioventricular Block/etiology , Heart Neoplasms/secondary , Urinary Bladder Neoplasms/pathology , Aged , Atrioventricular Block/physiopathology , Electrocardiography , Fatal Outcome , Female , HumansABSTRACT
BACKGROUND: Although drug-eluting stents (DES) reduce restenosis, the best strategy for DES implantation in small vessels has not been established. PURPOSE: We investigated the clinical usefulness of low-pressure implantation of a 2.5-mm DES for small vessels less than 2.5mm in diameter. METHODS: In 118 patients, a 2.5-mm DES was implanted for small vessels less than 2.5mm in diameter between 2007 and 2009 in our hospital. The patients were divided into two groups by initial deployment pressure: low-pressure (LP; n=46) and nominal-pressure (NP; n=72). RESULTS: Patients with impaired glucose tolerance were more frequent (p=0.02) and the target vessel diameter was significantly smaller (p=0.01) in the LP group than in the NP group. A smaller minimum lumen diameter (MLD) was obtained (LP: 2.22±0.27mm vs. NP: 2.34±0.26mm, p=0.02) after DES implantation with a smaller balloon-to-artery ratio (p=0.03) in the LP group. However, at mid-term follow-up (7.7±3.9 months), MLD (p=0.55) and the binary restenosis rate (LP: 2.6% vs. NP: 11.1%, p=0.12) were not significantly different between the LP and NP groups. Furthermore, by Kaplan-Meier analysis, the incidence of major adverse cardiac events was not different between the groups during the long-term follow-up (32.4±8.6 months). CONCLUSION: The present study indicates that low-pressure implantation of 2.5-mm DES for very small vessels may be feasible with regard to short- and long-term clinical outcomes.
Subject(s)
Coronary Disease/surgery , Drug-Eluting Stents , Percutaneous Coronary Intervention/methods , Aged , Coronary Angiography , Coronary Disease/diagnostic imaging , Coronary Disease/pathology , Coronary Restenosis/prevention & control , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Feasibility Studies , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVE: Dipeptidyl peptidase-4 (DPP-4) inhibitor, a novel antidiabetic drug, has a cardioprotective effect on ischemia-reperfusion injury through an antioxidant effect. However, the effect of DPP-4 inhibitor on aneurysm formation has not been investigated. We aimed to test the hypothesis that the DPP-4 inhibitor, alogliptin, attenuates vascular oxidative stress and thus inhibits abdominal aortic aneurysm (AAA) formation. METHODS: AAAs were created with intraluminal elastase and extraluminal calcium chloride in 36 male rats. Rats were divided into three groups: a low dose of alogliptin group (group LD; 1 mg/kg/d), a high-dose group (group HD; 3 mg/kg/d), and a control group (group C, water). Alogliptin was administered by gastric gavage once daily beginning 3 days before surgery. On day 7 after aneurysm preparation, reactive oxygen species (ROS) expression was semiquantified by dihydroethidium staining, and the oxidation product of DNA produced by ROS, 8-hydroxydeoxyguanosine (8-OHdG), was measured by immunohistochemical staining. Blood glucose concentrations were measured. Hematoxylin and eosin and elastica Van Gieson stainings were performed on day 28, and the AAA dilatation ratio was calculated. RESULTS: On day 7 (six in each group), dihydroethidium staining of the aneurysm wall showed a reduced level of ROS expression (4.6 ± 0.6 in group C, 2.7 ± 0.3 in group LD, and 1.7 ± 0.5 in group HD; P < .0001) and showed fewer 8-OHdG-positive cells in alogliptin-treated samples (138.1 ± 7.4 cells in group C, 102.5 ± 4.5 cells in group LD, and 66.1 ± 4.5 cells in group HD; P < .0001) The treatment significantly reduced messenger RNA expression of matrix metalloproteinases (MMPs) in aneurysm walls (relative expression: MMP-2: 2.1 ± 0.4 in group C, 1.3 ± 0.3 in group LD, and 0.9 ± 0.2 in group HD; P < .001; MMP-9: 2.0 ± 0.5 in group C, 0.3 ± 0.3 in group LD, and 0.3 ± 0.2 in group HD; P < .001). On day 28 (six in each group), the aortic wall in groups LD and HD was less dilated (dilatation ratio: 199.2% ± 11.8% in group C, 159.6% ± 2.8% in group LD, and 147.1% ± 1.9% in group HD; P < .02 group C vs HD) and had higher elastin content than in group C. The difference in blood glucose levels among the three groups was not significant. CONCLUSIONS: The DPP-4 inhibitor, alogliptin, attenuates aneurysm formation and expansion dose-dependently in a rat AAA model via an antioxidative action.
Subject(s)
Antioxidants/administration & dosage , Aorta, Abdominal/drug effects , Aortic Aneurysm, Abdominal/prevention & control , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/administration & dosage , Oxidative Stress/drug effects , Piperidines/administration & dosage , Uracil/analogs & derivatives , 8-Hydroxy-2'-Deoxyguanosine , Administration, Oral , Animals , Aorta, Abdominal/enzymology , Aorta, Abdominal/pathology , Aortic Aneurysm, Abdominal/chemically induced , Aortic Aneurysm, Abdominal/enzymology , Aortic Aneurysm, Abdominal/genetics , Aortic Aneurysm, Abdominal/pathology , Blood Glucose/drug effects , Blood Glucose/metabolism , Calcium Chloride , DNA Damage , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Dilatation, Pathologic , Disease Models, Animal , Dose-Response Relationship, Drug , Gene Expression Regulation, Enzymologic/drug effects , Male , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Pancreatic Elastase , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Time Factors , Uracil/administration & dosageABSTRACT
OBJECTIVE: Abdominal aortic aneurysms (AAAs) are associated with oxidative stress and inflammatory response. We investigated the hypothesis that the known antioxidant ascorbic acid, which can also promote elastin and collagen production by smooth muscle cells, would prevent AAA formation in a rat model. METHODS: An intraluminal elastase and extraluminal calcium chloride-induced rat AAA model was used, and the animals were divided into three groups: control (group C, n = 18), the aorta wrapped with a saline-impregnated gelatin hydrogel sheet (group G, n = 18), and the aorta wrapped with a gelatin hydrogel sheet incorporating ascorbic acid (group A, n = 18). Wrapping of the sheet was completed at the end of treatment for AAA creation. The aortic dilatation ratio was measured, and aortic tissues were further examined for oxidative stress and oxidative DNA damage using biochemical and histologic techniques. RESULTS: Aortic dilatation at both 4 and 8 weeks was inhibited in group A (dilatation ratio [%] at 4 weeks: 186.2 ± 21.8 in group C, 152.3 ± 10.2 in group G, 126.8 ± 11.6 in group A; P < .0001; dilatation ratio [%] at 8 weeks: 219.3 ± 37.5 in group C, 194.0 ± 11.6 in group G, 145.7 ± 8.3 in group A; P = .0002). Elastin and collagen content were significantly preserved in group A (elastin, P = .0015; collagen, P < .0001). The messenger RNA expressions of matrix metalloproteinase (MMP)-9, monocyte chemotactic protein-1, interleukin-1ß, and tissue necrosis factor-α (P = .0024, P < .0001, P < .0001, and P < .0001, respectively) were downregulated in group A (P = .0024), whereas tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 were both upregulated in group A (TIMP-1, P = .0014; TIMP-2, P < .0001). Gelatin zymography showed activities of pro-MMP-2, MMP-2, and MMP-9 were significantly suppressed in group C (P < .0001 for each). Reactive oxygen species expression and 8-hydroxydeoxyguanosine and cluster of differentiation 68 staining were significantly suppressed in group A (reactive oxygen species expression, P < .0001; 8-hydroxydeoxyguanosine-positive cells, P < .0001; cluster of differentiation 68 positive cells, P < .0001). CONCLUSIONS: Controlled release of ascorbic acid using gelatin hydrogel sheet-attenuated AAA formation through antioxidant and anti-inflammatory effect, regulation of MMP-2, TIMP-1, and TIMP-2, and preserving elastin and collagen in this animal model.
Subject(s)
Antioxidants/administration & dosage , Aorta, Abdominal/drug effects , Aortic Aneurysm, Abdominal/prevention & control , Ascorbic Acid/administration & dosage , Drug Carriers , Gelatin/chemistry , Animals , Antioxidants/chemistry , Aorta, Abdominal/metabolism , Aorta, Abdominal/pathology , Aortic Aneurysm, Abdominal/chemically induced , Aortic Aneurysm, Abdominal/diagnosis , Aortic Aneurysm, Abdominal/genetics , Aortic Aneurysm, Abdominal/metabolism , Ascorbic Acid/chemistry , Calcium Chloride , Chemistry, Pharmaceutical , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Collagen/metabolism , DNA Damage/drug effects , Delayed-Action Preparations , Dilatation, Pathologic , Disease Models, Animal , Elastin/metabolism , Gene Expression Regulation , Hydrogels , Inflammation Mediators/metabolism , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Male , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Oxidative Stress/drug effects , Pancreatic Elastase , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Time Factors , Tissue Inhibitor of Metalloproteinase-1/genetics , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tissue Inhibitor of Metalloproteinase-2/genetics , Tissue Inhibitor of Metalloproteinase-2/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
A 66-year-old man was diagnosed as lung cancer. We performed right upper lobectomy and lymphnode dissection. On the 1st postoperative day, a chest radiograph showed an opacification in the right upper lung field. Computed tomography (CT) showed a stenosis of the middle lobe bronchus and infiltrative shadow of the middle lobe on the 3rd postoperative day. Fiber optic bronchoscopic examination also revealed a bend and stenosis of the middle lobe bronchus, but tortion was not demonstrated. On the 6th postoperative day, chest radiographic findings was worsened. Torsion of the middle lobe was suspected, and rethoracotomy was performed on the 7th postoperative day. The right middle lobe was not rotated, but the lobar pedicle bend toward cranial. The middle lobe was highly congested necessitating lobectomy.
Subject(s)
Lung/blood supply , Lung/diagnostic imaging , Pneumonectomy/adverse effects , Aged , Humans , Lung Neoplasms/surgery , Male , Postoperative Complications , RadiographyABSTRACT
The atom-transfer carbonylation reaction of various alkyl iodides thereby leading to carboxylic acid esters was effectively accelerated by the addition of transition-metal catalysts under photoirradiation conditions. By using a combined Pd/hν reaction system, vicinal C-functionalization of alkenes was attained in which α-substituted iodoalkanes, alkenes, carbon monoxide, and alcohols were coupled to give functionalized esters. When alkenyl alcohols were used as acceptor alkenes, three-component coupling reactions, which were accompanied by intramolecular esterification, proceeded to give lactones. Pd-dimer complex [Pd(2)(CNMe)(6)][PF(6)](2), which is known to undergo homolysis under photoirradiation conditions, worked quite well as a catalyst in these three- or four-component coupling reactions. In this metal/radical hybrid system, both Pd radicals and acyl radicals are key players and a stereochemical study confirmed the carbonylation step proceeded through a radical carbonylation mechanism.
ABSTRACT
OBJECTIVE: An ideal pharmaceutical treatment for abdominal aortic aneurysm (AAA) is to prevent aneurysm formation and development (further dilatation of pre-existing aneurysm). Recent studies have reported that oxidative stress with reactive oxygen species (ROS) is crucial in aneurysm formation. We hypothesized that edaravone, a free-radical scavenger, would attenuate vascular oxidative stress and inhibit AAA formation and development. METHODS: An AAA model induced with intraluminal elastase and extraluminal calcium chloride was created in 42 rats. Thirty-six rats were divided three groups: a low-dose (group LD; 1 mg/kg/d), high-dose (group HD; 5 mg/kg/d), and control (group C, saline). Edaravone or saline was intraperitoneally injected twice daily, starting 30 minutes before aneurysm preparation. The remaining six rats (group DA) received a delayed edaravone injection (5 mg/kg/d) intraperitoneally, starting 7 days after aneurysm preparation to 28 days. AAA dilatation ratio was calculated. Pathologic examination was performed. ROS expression was semi-quantified by dihydroethidium staining and the oxidative product of DNA induced by ROS, 8-hydroxydeoxyguanosine (8-OHdG), by immunohistochemical staining. RESULTS: At day 7, ROS expression and 8-OHdG-positive cells in aneurysm walls were decreased by edaravone treatment (ROS expression: 3.0 ± 0.5 in group LD, 1.7 ± 0.3 in group HD, and 4.8 ± 0.7 in group C; 8-OHdG-positive cells: 106.2 ± 7.8 cells in group LD, 64.5 ± 7.7 cells in group HD, and 136.6 ± 7.4 cells in group C; P < .0001), compared with group C. Edaravone treatment significantly reduced messenger RNA expressions of cytokines and matrix metalloproteinases (MMPs) in aneurysm walls (MMP-2: 1.1 ± 0.5 in group LD, 0.6 ± 0.1 in group HD, and 2.3 ± 0.4 in group C; P < .001; MMP-9: 1.2 ± 0.1 in group LD, 0.2 ± 0.6 in group HD, and 2.4 ± 0.2 in group C; P < .001). At day 28, aortic walls in groups LD and HD were less dilated, with increased wall thickness and elastin content than those in group C (dilatation ratio: 204.7% ± 16.0% in group C, 156.5% ± 6.6% in group LD, 136.7% ± 2.0% in group HD; P < .0001). Delayed edaravone administration significantly prevented further aneurysm dilatation, with increased elastin content (155.2% ± 2.9% at day 7, 153.1% ± 11.6% at day 28; not significant). CONCLUSIONS: Edaravone inhibition of ROS can prevent aneurysm formation and expansion in the rat AAA model. Free-radical scavenger edaravone might be an effective pharmaceutical agent for AAA in clinical practice.
Subject(s)
Antipyrine/analogs & derivatives , Aorta, Abdominal/drug effects , Aortic Aneurysm, Abdominal/prevention & control , Free Radical Scavengers/pharmacology , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , 8-Hydroxy-2'-Deoxyguanosine , Animals , Antipyrine/administration & dosage , Antipyrine/pharmacology , Aorta, Abdominal/metabolism , Aorta, Abdominal/pathology , Aortic Aneurysm, Abdominal/chemically induced , Aortic Aneurysm, Abdominal/genetics , Aortic Aneurysm, Abdominal/metabolism , Aortic Aneurysm, Abdominal/pathology , Apoptosis/drug effects , Biomarkers/metabolism , Calcium Chloride , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Dilatation, Pathologic , Disease Models, Animal , Disease Progression , Drug Administration Schedule , Edaravone , Elastin/metabolism , Free Radical Scavengers/administration & dosage , Gene Expression Regulation , Immunohistochemistry , Injections, Intraperitoneal , Interleukin-1beta/genetics , Male , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , Pancreatic Elastase , Rats , Rats, Sprague-Dawley , Time Factors , Tumor Necrosis Factor-alpha/geneticsABSTRACT
The straightforward synthesis of isochromene derivatives and related cyclic ethers is achieved by the rhodium-catalyzed oxidative coupling of α,α-disubstituted benzyl and allyl alcohols with alkynes. The hydroxy groups effectively act as the key function for the regioselective C-H bond cleavage.
Subject(s)
Alkynes/chemistry , Benzopyrans/chemistry , Benzopyrans/chemical synthesis , Benzyl Compounds/chemistry , Ethers, Cyclic/chemistry , Ethers, Cyclic/chemical synthesis , Propanols/chemistry , Rhodium/chemistry , Catalysis , Hydrogen Bonding , Molecular Structure , Oxidation-Reduction , StereoisomerismABSTRACT
Patients who undergo thoracic aortic surgery with deep hypothermia frequently have postoperative respiratory failure as a complication. Severe lung injury in these patients results in a fatal outcome. A specific neutrophil elastase inhibitor, sivelestat sodium hydrate, is an innovative therapeutic drug for acute lung injury. We evaluated the protective effects of sivelestat sodium hydrate on severe lung injury after thoracic aortic surgery with deep hypothermia. From January 2002 to July 2007, 71 consecutive patients underwent thoracic aortic surgery with deep hypothermia. Of these patients, 22 had postoperative respiratory failure with PaO2/FiO2 ratios of less than 150. They were randomly assigned to one of two groups. The first group (Group S, n = 10) was administered sivelestat sodium hydrate continuously at 0.2 mg/kg/h until weaning from mechanical ventilation; the second group (Group C, n = 12) was not administered sivelestat sodium hydrate. The groups were comparable with respect to clinical data. There were no significant differences between the two groups in age, operation duration, total cardiopulmonary bypass time, circulatory ischemia time, cardiac arrest time, intraoperative blood loss, and total transfusion volume. The improvement of pulmonary function was observed in the both groups, but more marked in Group S by statistical analysis using analysis of variance for repeated measurements. Especially, in the early phase, pulmonary function improvement was more marked in Group S. The duration of mechanical ventilation, the length of stay in the intensive care unit, and the length of hospital stay were shorter in Group S, but not significantly. Sivelestat sodium hydrate is a specific neutrophil elastase inhibitor that improves pulmonary function in patients with severe postoperative respiratory failure following thoracic aortic surgery with deep hypothermia. The drug may shorten the duration of postoperative ventilation, intensive care unit stay, and hospital stay.
Subject(s)
Aorta, Thoracic/surgery , Glycine/analogs & derivatives , Hypothermia, Induced/adverse effects , Leukocyte Elastase/antagonists & inhibitors , Lung/drug effects , Respiratory Insufficiency/drug therapy , Serine Proteinase Inhibitors/therapeutic use , Sulfonamides/therapeutic use , Vascular Surgical Procedures/adverse effects , Aged , Aged, 80 and over , Chi-Square Distribution , Female , Glycine/administration & dosage , Glycine/therapeutic use , Hospital Mortality , Humans , Hypothermia, Induced/mortality , Infusions, Parenteral , Intensive Care Units , Japan , Length of Stay , Leukocyte Elastase/metabolism , Lung/physiopathology , Male , Respiration, Artificial , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/etiology , Respiratory Insufficiency/physiopathology , Serine Proteinase Inhibitors/administration & dosage , Severity of Illness Index , Sulfonamides/administration & dosage , Time Factors , Treatment Outcome , Vascular Surgical Procedures/mortality , Ventilator WeaningABSTRACT
The indication for aortic valve replacement (AVR) combined left ventricular (LV) plasty in the patient with aortic valve stenosis (AS) complicated by ischemic heart disease is controversial. We describe a case of AS with ischemic heart disease of a patient who underwent a successful surgical treatment, AVR combined with the endoventricular patch technique. The patient was an 82-year-old woman who suffered from heart failure, New York Heart Association (NYHA) class III. The heart failure derived from AS and ischemic heart disease with severely compromised LV function. She underwent AVR combined with the endoventricular patch technique and the postoperative course was uneventful. She has been well with NYHA class I for about 5 years after the operation without heart failure.
Subject(s)
Aortic Valve Stenosis/surgery , Heart Valve Prosthesis Implantation , Heart Ventricles/surgery , Myocardial Ischemia/surgery , Pericardium/transplantation , Ventricular Dysfunction, Left/surgery , Aged, 80 and over , Aortic Valve Stenosis/complications , Aortic Valve Stenosis/diagnosis , Female , Heart Failure/etiology , Heart Failure/surgery , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Humans , Myocardial Ischemia/complications , Myocardial Ischemia/diagnosis , Myocardial Ischemia/physiopathology , Radiography , Treatment Outcome , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology , Ventricular Function, LeftABSTRACT
A 39-year-old woman with familial homozygous hypercholesterolemia had supravalvular and valvular aortic stenosis. Modified Nick's procedure and aortic valve replacement was performed to relieve both the supravalvular and annular stenoses. At surgery, the ascending aorta was found to be narrowing at the level of the sinotubular junction, which was compatible with congenital supravalvular aortic stenosis. Histological examination of the aortic cusps showed sclerotic change due to hypercholesterolemia. These findings indicated that familial homozygous hypercholesterolemia caused valvular aortic stenosis and exacerbated congenital supravalvular aortic stenosis.