Feasibility of Nurse-Led Advance Care Planning Before Pre-cardiac Procedures: A Descriptive Study.

Background Shared decision-making is important for deciding whether to perform surgery, especially high-risk surgery, or end-of-life care in cases of serious complications after the surgery. In shared decision-making, surgeons should be aware of patients' values. Therefore, advance care planning (ACP) before the surgery is important. In Japan, the feasibility of ACP, particularly preoperative nurse-led ACP, is yet to be evaluated. Methodology This retrospective, single-center, descriptive study included all adult candidates for open-heart or thoracic aortic surgery and transcutaneous aortic valve implantation (TAVI) referred by their surgeon for a nurse-led preoperative ACP between April 1, 2020 and December 31, 2021. The nurse conducted semi-structured interviews with patients regarding goals of care, unacceptable conditions, undesired procedures, advance directives, and their surrogates and documented them. The content of these interviews and their influence on decision-making were retrospectively investigated. Results Sixty-four patients (median age, 82 years; Society of Thoracic Surgeons (STS) score, 7.9; EuroSCORE II, 4.2; JapanSCORE, 7.0) were included (open-heart or thoracic aortic surgery 24, TAVI 40). Among them, 63 (98.4%), 56 (87.5%), and 13 (20.3%) patients articulated their goals of care, unacceptable conditions, and undesired procedures. Only one (1.6%) had a written advance directive. Although all of the patients could designated their surrogate, only 11 (17.2%) had shared their values disclosed in the pre-procedure ACP communication with their surrogates. Two patients who planned to undergo open-heart surgery disclosed their wish not to undergo the surgery only to the nurses but could not tell their surgeon; thereafter, the surgery was canceled. Three patients died after the procedure; however, the patients' value disclosed in ACP was not used for the end-of-life decision. Conclusion Nurse-led ACP can be implemented before high-risk cardiac procedures. It may have an impact on the decision-making of surgery although the ACP content may not be utilized for the end-of-life discussion after the procedures between surgeons and the family member.

Immune-Mediated Non-Infectious Periaortitis After Aortic Graft Replacement Surgery: A Case Report Highlighting the Need for Immunosuppressive Therapy.

BACKGROUND A non-infectious inflammatory reaction against replaced aortic graft for aortic dissection often manifests as fever, malaise, and peri-graft effusion. It usually lasts less than 1 month and subsides spontaneously without immunosuppressive treatment. CASE REPORT A 49-year-old man underwent ascending aorta and total arch replacement for acute thoracic aortic dissection. He had fever, malaise, nausea, and elevated serum C-reactive protein for 1 month postoperatively. Pathological examination of the aorta revealed no aortitis, and repeated blood cultures were negative. We also noted periaortic graft fluid collection, and a small amount of pleural and pericardial effusions. We suspected post-pericardiotomy syndrome. Colchicine and prednisolone were administered, with an excellent clinical response. Three weeks after discontinuation of a 7-week prednisolone treatment, the same symptoms recurred and gradually worsened. Prednisolone was restarted 6 months after the first surgery, with good clinical response. Thereafter, he developed left-sided weakness and dysarthria, being diagnosed as ischemic stroke. Contrast-enhanced computed tomography revealed fluid collection with contrast leak around the aortic grafts, suggesting peel dehiscence, and thrombus formation in anastomotic pseudoaneurysm. He underwent surgical repair. He was diagnosed with non-infectious periaortitis, likely due to an immune reaction to the grafts, based on an excellent clinical response to immunosuppressive therapy. CONCLUSIONS We report a case of non-infectious periaortitis around a thoracic aortic graft, probably with an immune-mediated mechanism, requiring immunosuppressive treatment. When fever persists after aortic graft replacement surgery, non-infectious periaortitis should be considered and immunosuppressive treatment should be considered to prevent critical complications of anastomotic pseudoaneurysm and graft dehiscence.

Validation study of EuroSCORE II for dialysis patients: A single-center study in Japan.

BACKGROUND: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II is a predictive model for in-hospital mortality after cardiac surgery. Although it has good performance among the general population undergoing cardiac surgery, it has not been validated among dialysis patients, who have a higher rate of mortality after cardiac surgery. This study aimed to evaluate the performance of the model in predicting in-hospital mortality in maintenance dialysis patients undergoing cardiac surgery. METHODS: This retrospective, single-center study included adult patients on maintenance dialysis who underwent open cardiac surgery at our institution. Calibration performance of EuroSCORE II for in-hospital death was determined based on the comparison between expected and observed mortalities for low- (EuroSCORE II <4 %), intermediate- (4-8 %), and high-risk (>8 %) groups. The area under receiver operating characteristic curve (AUROC) was investigated to determine the model's discrimination performance. RESULTS: A total of 163 patients (male, 73.6 %; median age, 70 years; median dialysis vintage, 9 years; median EuroSCORE II, 3.3 %) were included. The mortality rate was 9.2 %. The observed mortality rates (vs. mean expected mortality) rates were 2.1 % (vs. 2.4 %), 7.5 % (vs. 5.5 %), and 34.5 % (vs. 21.1 %) in the low-, intermediate-, and high-risk groups, respectively. Its AUROC was 0.825 (95 % confidence interval, 0.711-0.940). CONCLUSIONS: Although EuroSCORE II model adequately estimated in-hospital mortality in the low-and intermediate-risk groups (EuroSCORE II <8 %), it underestimated in-hospital mortality in the high-risk group (EuroSCORE II >8 %) among maintenance dialysis patients. The discrimination performance of the model for in-hospital death was good among maintenance dialysis patients.

Successful Conservative Management of Emphysematous Cystitis With Pneumoperitoneum: A Case Report and Literature Review.

Emphysematous cystitis is a rare type of urinary tract infection that is characterized by the accumulation of gas within the walls and lumen of the urinary bladder. In rarer instances, pneumoperitoneum may accompany emphysematous cystitis. When pneumoperitoneum is suspected through imaging studies in patients with emphysematous cystitis, surgical abdominal exploration is frequently performed considering the possibility of bladder perforation or coexistence of intestinal perforation. We successfully managed a case of emphysematous cystitis accompanied with pneumoperitoneum conservatively. A 90-year-old woman hospitalized with a gastric ulcer developed abrupt lower abdominal pain and hematuria. Contrast-enhanced CT revealed gas within the bladder wall, which was consistent with emphysematous cystitis, and pneumoperitoneum. No obvious bowel or bladder perforation was observed in the CT scan. Regarding her high surgical risk and clinical stability, surgical abdominal exploration was not performed, and she was managed conservatively with urethral catheter placement and antibiotics. She recovered with the treatment, and CT imaging obtained on day 18 demonstrated resolution of the bladder wall emphysema and no signs of pneumoperitoneum. We performed a literature review using MEDLINE and Japana Centra Revuo Medicina Web and confirmed 13 previously reported cases of emphysematous cystitis and pneumoperitoneum. Based on the review of these 13 cases and our case, it is difficult to predict the presence of bladder perforation solely based on peritoneal signs in physical findings or ascites on CT scans. Therefore, it would be preferable to perform surgical abdominal exploration to make a definite diagnosis and select an appropriate treatment. However, the fact that at least eight out of the 10 cases managed conservatively survived suggests that there is a specific clinical entity among patients who present with emphysematous cystitis and pneumoperitoneum that can be safely managed conservatively. Further accumulation of cases and research is necessary to determine which cases can be treated conservatively.

Spontaneous Recovery of Hemophagocytic Lymphohistiocytosis Due to Primary Epstein-Barr Virus Infection in an Adult Patient.

BACKGROUND Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening systemic hyperinflammatory condition. Most adult HLH cases are secondary to infection, malignancy, and rheumatic diseases. Epstein-Barr virus (EBV) infection is the most frequent cause of infection-induced HLH. Early treatment with dexamethasone, etoposide, and cyclosporine is generally recommended for adult patients with HLH. However, this treatment regimen was established based on pediatric clinical trial data; thus, its efficacy and validity in adults remain unclear. Because little is known about the disease course of untreated adult EBV-associated HLH (EBV-HLH), we report a case of an adult patient who recovered from EBV-HLH spontaneously without specific treatment and discuss potential treatment strategies. CASE REPORT A 34-year-old man presented to the emergency department with a 7-day history of fever, headache, and sore throat. The main laboratory test abnormalities were elevated liver enzymes, hyperbilirubinemia, hypertriglyceridemia, and hyperferritinemia. Serologic tests confirmed acute primary EBV infection. He was diagnosed with EBV-HLH based on the HLH-2004 diagnostic criteria and the HLH probability calculator (HScore). Because he was clinically stable, we did not initiate immunosuppressive/cytotoxic treatment targeting HLH. High-grade fever persisted, but the abnormalities in his laboratory data improved spontaneously, and he did not develop major organ failure. His fever resolved on day 29 without HLH-specific treatment. CONCLUSIONS In clinically stable adult patients with EBV-HLH without major organ failure, it might be an acceptable alternative to observe the patient for several weeks before initiating HLH-specific treatment. Further research is required to better predict the subset of patients who can be safely observed without treatment.

Acute Lower Extremity Arterial Thrombosis Associated with Osimertinib-Induced Erythrocytosis.

BACKGROUND Osimertinib is an oral third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) approved as first-line therapy for advanced non-small cell lung cancer (NSCLC) with positive EGFR mutation. Rashes, nail toxicity, and diarrhea are common adverse events. Hematological adverse effects, including anemia, thrombocytopenia, and lymphocytopenia, have been reported. However, erythrocytosis has not been reported as an adverse event. To the best of our knowledge, we report the first case of acute lower extremity thrombosis presumably caused by osimertinib-induced erythrocytosis. CASE REPORT A 70-year-old man with epidermal EGFR-mutant advanced NSCLC presented with acute left sural pain. The patient's left foot was cold, and peripheral arterial Doppler signals were absent. He had developed erythrocytosis of unknown etiology during osimertinib therapy. Hemoglobin (Hb) and hematocrit were 22.6 g/dL and 62.5%, respectively. Contrast-enhanced computed tomography showed thrombotic occlusion of the popliteal artery. Other than erythrocytosis, there was no possible cause of arterial thrombosis. Osimertinib was discontinued immediately because the NSCLC started to resist treatment and was presumed to be the cause of erythrocytosis. He received endovascular treatment (EVT). Following serial EVT and debridement, his fourth toe was amputated for necrosis. Erythrocytosis persisted 8 months during osimertinib therapy. Hb levels decreased to 15.4 mg/dL due to blood loss complicated with catheter thrombectomy and remained normal for 20 months after osimertinib discontinuation. The patient died of cancer progression. CONCLUSIONS This case suggests the erythrocytosis was possibly caused by osimertinib. We may need to monitor Hb levels during osimertinib therapy and be alert to thrombosis once Hb starts to rise.

Role of a rapid response system and code status discussion as determinants of prognosis for critical inpatients: An observational study in a Japanese urban hospital.

ABSTRACT: Rapid response systems (RRS) have been introduced worldwide to reduce unpredicted in-hospital cardiac arrest (IHCA) and in-hospital mortality. The role of advance care planning (ACP) in the management of critical patients has not yet been fully determined in Japan.We retrospectively assessed the characteristics of all inpatients with unpredicted IHCA in our hospital between 2016 and 2018. Yearly changes in the number of RRS activations and the incidence of unpredicted IHCA with or without code status discussion were evaluated from 2014 to 2018. Hospital standardized mortality ratios were assessed from the data reported in the annual reports by the National Hospital Organization.A total of 81 patients (age: 70.9 ±â€Š13.3 years) suffered an unpredicted IHCA and had multiple background diseases, including heart disease (75.3%), chronic kidney disease (25.9%), and postoperative status (cardiovascular surgery, 18.5%). Most of the patients manifested non-shockable rhythms (69.1%); survival to hospital discharge rate was markedly lower than that with shockable rhythms (26.8% vs 72.0%, P < .001). The hospital standardized mortality ratios was maintained nearly constant at approximately 50.0% for 3 consecutive years. The number of cases of RRS activation markedly increased from 75 in 2014 to 274 patients in 2018; conversely, the number of unpredicted IHCA cases was reduced from 40 in 2014 to 18 in 2018 (P < .001). Considering the data obtained in 2014 and 2015 as references, the RRS led to a reduction in the relative risk of unpredicted IHCA from 2016 to 2018 (ie, 0.618, 95% confidence interval 0.453-0.843). The reduction in unpredicted IHCA was attributed partly to the increased number of patients who had discussed the code status, and a significant correlation was observed between these parameters (R2 = 0.992, P < .001). The reduction in the number of patients with end-stage disease, including congestive heart failure and chronic renal failure, paralleled the incidence of unpredicted IHCA.Both RRS and ACP reduced the incidence of unpredicted IHCA; RRS prevents progression to unpredicted IHCA, whereas ACP decreases the number of patients with no code status discussion and thus potentially reducing the patient subgroup progressing to an unpredicted IHCA.

Portal and Mesenteric Vein Thrombosis Associated with Hyperthyroidism.

BACKGROUND Non-malignant and non-cirrhotic portal and mesenteric vein thrombosis is rare. It has been reported that the hyperthyroid state is associated with increased risks of venous thrombosis due to increases in levels of various coagulation and anti-fibrinolytic factors. Particularly, changes in levels of these factors are also reported in cases of portal and mesenteric vein thrombosis. Although hyperthyroidism is not known as a risk factor for portal and mesenteric vein thrombosis, it might be an underlying pathogenesis of hyperthyroidism-associated portal and mesenteric vein thrombosis. CASE REPORT A 59-year-old Japanese man with a history of Grave's disease presented with acute portal and mesenteric vein thrombosis and hyperthyroidism. Anticoagulation therapy was initiated and the dose of antithyroid drug was increased. He underwent various tests to identify causes of portal and mesenteric vein thrombosis. However, all test results were within normal range except for hyperthyroidism. Therefore, we discontinued anticoagulation therapy after normalization of thyroid hormone status. After 3 years, he experienced recurrence of portal vein thrombosis concomitant with hyperthyroidism. CONCLUSIONS Hyperthyroidism might be associated with portal vein thrombosis. Thyroid function tests should be performed in cases of portal and mesenteric vein thrombosis in the absence of other risk factors.

Nasogastric Tubes Can Cause Intramural Hematoma of the Esophagus.

BACKGROUND Intramural hematoma of the esophagus (IHE), a rare manifestation of acute mucosal injuries of the esophagus, can be caused by trauma such as endoscopic surgeries. Coagulation disorders increase the risk of IHE. The most common location of IHE is in the distal esophagus. The characteristic clinical triad of manifestations comprises acute retrosternal pain, odynophagia or dysphagia, and hematemesis. It is important to distinguish IHE from other acute conditions such as acute coronary syndrome, aortic dissection, and pulmonary embolism. CASE REPORT An 84-year-old male was scheduled for coil embolization for an endoleak after endovascular aneurysm repair. For this reason, he was taking aspirin and warfarin. A nasogastric tube had been inserted during surgery and subsequently removed without any problems reported. Postoperatively, he experienced chest pain and hematemesis of sudden onset. Urgent esophagogastroduodenoscopy demonstrated a large, dark red, non-pulsatile, submucosal, esophageal mass in the area of the mid-esophagus with a little oozing. He was diagnosed as having an IHE; other possible diagnoses were excluded by contrast-enhanced computed tomography and aortography. He was treated with fasting, a proton pump inhibitor, and cessation of anti-thrombotic drugs; he recovered completely. The bleeding spot in the esophagus was in the area of the mid-esophagus, which was around the second natural constriction site. It was possible that the nasogastric tube had contact with the esophageal wall at this second natural constriction, and caused intramural esophageal bleeding. CONCLUSIONS Nasogastric tubes are not generally recognized as a cause of IHE. However, they can cause them, especially when a patient is taking anti-thrombotic drugs.

Can folate replacement induce lymphoma progression?

A 43-year-old Japanese man with a low haemoglobin level of 1.3 g/dL and multiorgan dysfunction syndrome (MODS) was admitted to our hospital. He was diagnosed with folate deficiency, which was initially attributed to his malnutrition. He was transfused with several units of packed red blood cells and treated with folate, thiamine and vitamin B12 supplements; he showed a prompt haematological response and recovery from MODS. However, 3 weeks after the initial recovery, he had a relapse of pancytopenia and developed high-grade fever along with rapidly enlarging, generalised lymphadenopathy. Bone marrow biopsy revealed hemophagocytosis, and lymph node biopsy revealed peripheral T-cell lymphoma, not otherwise specified. Folate supplementation may have promoted lymphoma progression.

Association of code status discussion with invasive procedures among advanced-stage cancer and noncancer patients.

BACKGROUND: Code status discussion is associated with a decrease in invasive procedures among terminally ill cancer patients. We investigated the association between code status discussion on admission and incidence of invasive procedures, cardiopulmonary resuscitation (CPR), and opioid use among inpatients with advanced stages of cancer and noncancer diseases. METHODS: We performed a retrospective cohort study in a single center, Ito Municipal Hospital, Japan. Participants were patients who were admitted to the Department of Internal Medicine between October 1, 2013 and August 30, 2015, with advanced-stage cancer and noncancer. We collected demographic data and inquired the presence or absence of code status discussion within 24 hours of admission and whether invasive procedures, including central venous catheter placement, intubation with mechanical ventilation, and CPR for cardiac arrest, and opioid treatment were performed. We investigated the factors associated with CPR events by using multivariate logistic regression analysis. RESULTS: Among the total 232 patients, code status was discussed with 115 patients on admission, of which 114 (99.1%) patients had do-not-resuscitate (DNR) orders. The code status was not discussed with the remaining 117 patients on admission, of which 69 (59%) patients had subsequent code status discussion with resultant DNR orders. Code status discussion on admission decreased the incidence of central venous catheter placement, intubation with mechanical ventilation, and CPR in both cancer and noncancer patients. It tended to increase the rate of opioid use. Code status discussion on admission was the only factor associated with the decreased use of CPR (P<0.001, odds ratio =0.03, 95% CI =0.004-0.21), which was found by using multivariate logistic regression analysis. CONCLUSION: Code status discussion on admission is associated with a decrease in invasive procedures and CPR in cancer and noncancer patients. Physicians should be educated about code status discussion to improve end-of-life care.

What is the true definition of a "Do-Not-Resuscitate" order? A Japanese perspective.

BACKGROUND: Japan has no official guidelines for do-not-resuscitate (DNR) orders. Therefore, we investigated the effect of DNR orders on physician decision making in relation to performing noncardiopulmonary resuscitation (CPR) and CPR procedures. METHODS: A case-scenario-based questionnaire that included a case of advanced cancer, a case of advanced dementia, and a case of nonadvanced heart failure was administered to physicians. The questions determined whether physicians would perform different non-CPR procedures and CPR procedures in the presence or absence of DNR orders. The number of non-CPR procedures each physician would perform and the number of physicians who would perform each non-CPR and CPR procedure in the absence and presence of DNR ocrders were compared. Physicians from three Japanese municipal acute care hospitals participated. RESULTS: We analyzed 111 of 161 (69%) questionnaires. Physicians would perform significantly fewer non-CPR procedures in the presence of DNR orders than in the absence of DNR orders for all three case scenarios (median [interquartile range] percentages: Case 1: 72% [45%-90%] vs 100% [90%-100%]; Case 2: 55% [36%-72%] vs 91% [63%-100%]; Case 3: 78% [55%-88%] vs 100% [88%-100%]). Fewer physicians would perform non-CPR and CPR procedures in the presence of DNR orders than in the absence of DNR orders. However, considerable numbers of physicians would perform electric shock treatment for ventricular fibrillation in the presence of DNR orders (Case 1: 26%; Case 2: 16%; Case 3: 20%). CONCLUSION: DNR orders affect physician decision making about performing non-CPR procedures. Although some physicians would perform CPR for ventricular fibrillation in the presence of DNR orders, others would not. Therefore, a consensus definition for DNR orders should be developed in Japan, otherwise DNR orders may cause harm.

Amoebiasis masquerading as inflammatory bowel disease.

A 60-year-old Japanese man presented with bloody diarrhoea. He stated that he had been diagnosed with ulcerative colitis (UC) 3 years prior, but discontinued follow-up care as treatment was ineffective. One year later, he came to our hospital with anorexia and weight loss. The abdomen was soft and flat without tenderness. Laboratory tests were unremarkable; faecal culture and Clostridium difficile toxin were negative. Findings and biopsy from a subsequent colonoscopy reconfirmed his diagnosis of UC. Neither mesalazine, which was initially prescribed, nor additional treatments improved his symptoms. Repeat colonoscopy, performed 5 months later, demonstrated similar findings in the same area. Although the pathology remained consistent with UC, multiple treatment failures suggested ongoing occult infection. Additional testing revealed positive Entamoeba histolytica antibody. 14 days of metronidazole dramatically improved his symptoms. He has remained asymptomatic after 2 years.

Evaluation of the toxicity of stress-related aldehydes to photosynthesis in chloroplasts.

Aldehydes produced under various environmental stresses can cause cellular injury in plants, but their toxicology in photosynthesis has been scarcely investigated. We here evaluated their effects on photosynthetic reactions in chloroplasts isolated from Spinacia oleracea L. leaves. Aldehydes that are known to stem from lipid peroxides inactivated the CO(2) photoreduction to various extents, while their corresponding alcohols and carboxylic acids did not affect photosynthesis. alpha,beta-Unsaturated aldehydes (2-alkenals) showed greater inactivation than the saturated aliphatic aldehydes. The oxygenated short aldehydes malondialdehyde, methylglyoxal, glycolaldehyde and glyceraldehyde showed only weak toxicity to photosynthesis. Among tested 2-alkenals, 2-propenal (acrolein) was the most toxic, and then followed 4-hydroxy-(E)-2-nonenal and (E)-2-hexenal. While the CO(2)-photoreduction was inactivated, envelope intactness and photosynthetic electron transport activity (H(2)O --> ferredoxin) were only slightly affected. In the acrolein-treated chloroplasts, the Calvin cycle enzymes phosphoribulokinase, glyceraldehyde-3-phosphate dehydrogenase, fructose-1,6-bisphophatase, sedoheptulose-1,7-bisphosphatase, aldolase, and Rubisco were irreversibly inactivated. Acrolein treatment caused a rapid drop of the glutathione pool, prior to the inactivation of photosynthesis. GSH exogenously added to chloroplasts suppressed the acrolein-induced inactivation of photosynthesis, but ascorbic acid did not show such a protective effect. Thus, lipid peroxide-derived 2-alkenals can inhibit photosynthesis by depleting GSH in chloroplasts and then inactivating multiple enzymes in the Calvin cycle.

Delivery may affect arterial elasticity in women.

BACKGROUND: Estrogen is considered to be cardioprotective, but estrogen replacement therapy for postmenopausal women has not shown results for either primary or secondary cardiovascular event prevention. During normal pregnancy, women have significantly higher levels of estrogen and it may be endogenous estrogen that helps prevent atherosclerosis. METHODS AND RESULTS: The present cross-sectional study examined the association between pregnancy followed by delivery and clinical atherosclerosis using the brachial-ankle pulse wave velocity (PWV). A total of 2,560 women undergoing annual health screening at the Institute of Hyogo Prefecture Health Promotion Association in Japan were recruited. Pregnancy history (the age of menarche/menopause and the number of gravida/para), conventional coronary risk factors, and brachial-ankle PWV were recorded. Multivariate linear regression by stepwise selection analysis demonstrated that women who had 1 or more deliveries had a significantly lower PWV, independent of age and other conventional coronary risk factors. CONCLUSIONS: Pregnancy followed by delivery may decrease arterial stiffness and prevent the progress of atherosclerosis in women. The contribution of such a pregnancy followed by delivery-related decrease in arterial stiffness to the reduction of cardiovascular disease in women should be further evaluated.

Endothelial lipase gene polymorphism is associated with acute myocardial infarction, independently of high-density lipoprotein-cholesterol levels.

BACKGROUND: Endothelial lipase (EL) is a major determinant of high-density lipoprotein-cholesterol (HDL-C) metabolism and promotes monocytes recruitment. The local expression of EL could influence atherogenesis directly, in addition to its systemic role in HDL metabolism. The EL gene has a common 584C/T polymorphism, but it is unclear whether this polymorphism is associated with HDL-C levels or acute myocardial infarction (AMI). METHODS AND RESULTS: A case-control study of 107 AMI patients and 107 control subjects was conducted. T allele frequency was lower in the AMI group than in controls (0.18 vs 0.26, p<0.05). No significant association was found between the 584C/T polymorphism and HDL-C levels. Multivariate regression analyses showed that the association of the T allele with AMI was statistically significant and independent of other risk factors when age, sex, hypertension, hypercholesterolemia, and diabetes mellitus were included in the analyses (odds ratio (OR), 0.52; 95% confidence interval (95% CI) 0.28-0.98; p=0.04). However, when smoking status was included, the association of the T allele with AMI did not remain statistically significant (OR, 0.61; 95% CI 0.32-1.18; p=0.14). CONCLUSIONS: The 584C/T polymorphism of the EL gene was associated with AMI independently of HDL-C levels and thus may be involved in the pathogenesis of AMI.

Protection against photooxidative injury of tobacco leaves by 2-alkenal reductase. Detoxication of lipid peroxide-derived reactive carbonyls.

Degradation of lipid peroxides leads to the formation of cytotoxic 2-alkenals and oxenes (collectively designated reactive carbonyls). The novel NADPH-dependent oxidoreductase 2-alkenal reductase (AER; EC 1.3.1.74) from Arabidopsis (Arabidopsis thaliana), which is encoded by the gene At5g16970, catalyzes the reduction of the alpha,beta-unsaturated bond of reactive carbonyls, and hence is presumed to function in antioxidative defense in plants. Here we show that Arabidopsis AER (At-AER) has a broad substrate spectrum to biologically relevant reactive carbonyls. Besides 2-alkenals, the enzyme recognized as substrates the lipid peroxide-derived oxenes 9-oxo-octadeca-(10E),(12Z)-dienoic acid and 13-oxo-octadeca-(9E),(11Z)-dienoic acid, as well as the potent genotoxin 4-oxo-(2E)-nonenal, altogether suggesting AER has a key role in the detoxification of reactive carbonyls. To validate this conclusion by in vivo studies, transgenic tobacco (Nicotiana tabacum) plants that had 100- to 250-fold higher AER activity levels than control plants were generated. The engineered plants exhibited significantly less damage from either (1) the exogenously administered 4-hydroxy-(2E)-nonenal, (2) treatment with methyl viologen plus light, or (3) intense light. We further show that the At-AER protein fused with the Aequorea victoria green fluorescent protein localizes in cytosol and the nucleus in Bright-Yellow 2 cells. These results indicate that reactive carbonyls mediate photooxidative injury in leaf cells, and At-AER in the cytosol protects the cells by reducing the alpha,beta-unsaturated bond of the photoproduced reactive carbonyls.

PI 3-kinase-Akt-p70 S6 kinase in hypertrophic responses to leukemia inhibitory factor in cardiac myocytes.

Leukemia inhibitory factor (LIF) is a member of interleukin-6 related cytokines, which induces cardiac hypertrophy through glycoprotein (gp) 130. In this study, the role of phosphatidylinositol (PI) 3-kinase, Akt/protein kinase B (Akt/PKB), and p70 S6 kinase activation in LIF-induced hypertrophic responses such as stimulation of protein synthesis, atrial natriuretic peptide (ANP) gene expression, and reorganization of actin filaments into sarcomeric units was investigated in cultured cardiac myocytes. Treatment of cells with LIF resulted in sequential activation of PI 3-kinase, Akt/PKB, and p70 S6 kinase. Using inhibitors for PI 3-kinase and p70 S6 kinase activation, and adenovirus-mediated expression of dominant negative mutants of PI 3-kinase and Akt/PKB, we showed that PI 3-kinase activation was essential for stimulation of protein synthesis, ANP gene expression, and sarcomeric reorganization induced by LIF, while Akt/PKB activation was indispensable for ANP expression and stimulation of protein synthesis, but not for sarcomeric reorganization. Activation of p70 S6 kinase was necessary for stimulation of protein synthesis, but not for ANP gene expression or sarcomeric reorganization. These results indicated the essential role of PI 3-kinase-Akt/PKB-p70 S6 kinase pathway in the LIF-induced hypertrophic responses in cardiac myocytes.